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Objectives: Computed tomography (CT) has long been the gold standard in diagnosing patients with suspected small bowel obstruction (SBO). Recently, point‐of‐care ultrasound (POCUS) has demonstrated comparable test characteristics to CT imaging for the diagnosis of SBO. Our primary objective was to estimate the annual national cost saving impact of a POCUS‐first approach for the evaluation of SBO. Our secondary objectives were to estimate the reduction in radiation exposure and emergency department (ED) length of stay (LOS). Methods: We created and ran 1000 trials of a Monte Carlo simulation. The study population included all patients presenting to the ED with abdominal pain who were diagnosed with SBO. Using this simulation, we modeled the national annual cost savings in averted advanced imaging from a POCUS‐first approach for SBO. The model assumes that all patients who require surgery or have non‐diagnostic POCUS exams undergo CT imaging. The model also conservatively assumes that a subset of patients with diagnostic POCUS exams undergo additional confirmatory CT imaging. We used the same Monte Carlo model to estimate the reduction in radiation exposure and total ED bed hours saved. Results: A POCUS‐first approach for diagnosing SBO was estimated to save a mean (±SD) of $30.1 million (±8.9 million) by avoiding 143,000 (±31,000) CT scans. This resulted in a national cumulative decrease of 507,000 bed hours (±268,000) in ED LOS. The reduction in radiation exposure to patients could potentially prevent 195 (±56) excess annual cancer cases and 98 (±28) excess annual cancer deaths. Conclusions: If adopted widely and used consistently, a POCUS‐first algorithm for SBO could yield substantial national cost savings by averting advanced imaging, decreasing ED LOS, and reducing unnecessary radiation exposure in patients. Clinical decision tools are needed to better identify which patients would most benefit from CT imaging for SBO in the ED. [ABSTRACT FROM AUTHOR]

Objectives: The transpapillary drainage by endoscopic retrograde cholangiopancreatography (ERCP‐D) cannot be performed without fluoroscopy, and there are many situations in which fluoroscopy is required even in endoscopic ultrasound‐guided drainage (EUS‐D). Previous studies have compared the efficacy, but not the radiation exposure of EUS‐D and ERCP‐D. While radiation exposure in ERCP‐D has been previously evaluated, there is a paucity of information regarding radiation doses in EUS‐D. This study aimed to assess radiation exposure in EUS‐D compared with that in ERCP‐D. Methods: This retrospective single‐center cohort study included consecutive patients who underwent EUS‐D and ERCP‐D between October 2017 and March 2019. The air kerma (AK, mGy), kerma‐area product (KAP, Gycm2), fluoroscopy time (FT, min), and procedure time (PT, min) were assessed. The invasive probability weighting method was used to qualify the comparisons. Results: We enrolled 372 and 105 patients who underwent ERCP‐D and EUS‐D, respectively. The mean AK, KAP, and FT in the EUS‐D group were higher by 53%, 28%, and 27%, respectively, than those in the ERCP‐D group, whereas PT was shorter by approximately 11% (AK, 135.0 vs. 88.4; KAP, 28.1 vs. 21.9; FT, 20.4 vs. 16.0; PT, 38.7 vs. 43.5). The sub‐analysis limited to biliary drainage cases showed the same trend (AK, 128.3 vs. 90.9; KAP, 27.0 vs. 22.2; FT, 16.4 vs. 16.1; PT, 32.5 vs. 44.4). Conclusions: This is the first study to assess radiation exposure in EUS‐D compared with that in ERCP‐D. Radiation exposure was significantly higher in EUS‐D than in ERCP‐D, despite the shorter procedure time. [ABSTRACT FROM AUTHOR]

Nucleoside diphosphate-linked moiety X-type motif 15 C415T variant as a predictor for thiopurine-induced toxicity in Indian patients. Leukopenia is observed in 26%-63% of kidney transplant recipients on prophylactic valganciclovir.3-5 Induction and antiproliferative agents also cause leukopenia in this group. The first leukopenia event was classified as a possible adverse event for both valganciclovir and azathioprine, and the second leukopenia event was revised to probable adverse event with valganciclovir using Naranjo adverse drug reaction probability scale.15 In conclusion, I NUDT15 i variants have rarely been reported as a cause of drug-induced leukopenia in kidney transplant recipients. Dear Editor, Recent "in vitro" studies describe nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) enzyme to be involved in the metabolism of ganciclovir.1,2 We report severe leukopenia during therapy with valganciclovir in a recent kidney transplant recipient with I NUDT15 i genetic variation. [Extracted from the article]

Purpose: An estimated 377 million diagnostic and interventional radiological exams are performed annually in the United States and approximately 4 to 5 billion globally. All use x‐ray tubes that emit x‐rays over a broad energy band, a technology that is more than a century old. Only a small fraction of the radiation is useful for imaging while the remaining fraction either increases the radiation dose received by the patient or degrades the image. Monochromatic x‐rays can provide lower dose images in many of these radiological applications while maintaining or improving image quality. We report the development of the first monochromatic x‐ray source suitable for low‐dose, high‐quality imaging in the clinic and demonstrate its first application and performance with mammography phantoms. Methods: X‐ray fluorescence was used to generate monochromatic x‐rays with selectable energies from 18 to 60 keV. This patented technology was incorporated into a laboratory prototype of a monochromatic x‐ray mammography system. Image quality was evaluated as a function of radiation dose in standard breast phantoms using the signal‐to‐noise ratio (SNR) measured for high and low contrast masses and microcalcifications. Spatial imaging properties were assessed from these images as well as from modulation transfer function (MTF) analysis. Measurements using an iodine contrast agent were also performed. The results were compared to those obtained using a commercially available, conventional x‐ray mammography system. Results: Our prototype system reduced radiation dose by factors of five to ten times for the same SNRs as obtained from the conventional system. This performance was demonstrated in phantoms simulating a wide range of lesion sizes and microcalcifications in a variety of breast thicknesses. The high SNRs for very thick breast phantoms provide evidence that screening with less breast compression is possible while maintaining image quality. Contrast‐enhanced digital mammography (CEDM) with monochromatic x‐rays was shown to provide a simpler and more effective technique at substantially lower radiation dose. The MTF value at 20% was 9 lp/mm. Conclusions: The monochromatic x‐ray system is more sensitive for imaging a wide range of breast sizes and compositions than conventional broadband mammography. High image quality and lower dose are its hallmarks. It also makes CEDM much more effective than current methods developed for use with conventional broadband mammography systems. [ABSTRACT FROM AUTHOR]

In this work, the rapidly convergent approximation method (RCAM) followed by appropriate modifications is applied to obtain piecewise smooth solutions and conserved quantities of a Liénard‐type equation and some important nonlinear partial differential equations reducible to former one. Explicit parameter dependence of the solution has been sensibly used to determine parameter dependence of the constant of the motion as well as the domain in the parameter space for which the piecewise smooth solution is bounded. Solution of Liénard‐type equation is then used to find piecewise smooth traveling wave solutions and corresponding conserved quantities of nonlinear Schrödinger equation. These findings affirm the efficiency of the RCAM for analytical exercise of variety of nonlinear systems of ordinary/partial differential equations appear as mathematical model of physical processes. [ABSTRACT FROM AUTHOR]

Geopolymer concrete is an inorganic polymer composite which has the potential to build an eco‐friendly and sustainable construction by replacing the existing conventional concrete. Herein, cement is totally replaced by mineral admixtures rich in aluminosilicates such as fly ash and is formed by the alkali activation using alkaline activator solutions, such as sodium hydroxide (NaOH) and sodium silicate (Na2SiO3). Fly ash, a waste material from industry, can be incorporated in the manufacture of geopolymer concrete. The replacement of cement by fly ash in geopolymer concrete reduces the huge energy consumption and restricts carbon dioxide emission to the atmosphere during its production. In this paper, experimental investigations have been carried out involving the variation of total aggregate content (viz., 74, 76, 78, 80, and 82%), NaOH concentration (8, 10, 12, and 14 M), and curing temperature (60, 70, 80, 90, and 100°C) on the strength of geopolymer concrete by keeping a constant alkaline liquid to fly ash ratio of 0.45 and a 24‐hour rest period. It is concluded that 76% of total aggregate content is suitable for producing geopolymer concrete without hindering the workability. Further, strength of geopolymer concrete has been found to be increased at 90°C having 12 M NaOH concentration. [ABSTRACT FROM AUTHOR]

Chronic pruritus is a difficult condition to treat and is associated with several comorbidities, including insomnia, depression, and decreased quality of life. Treatment for chronic itch includes corticosteroids, antihistamines, and systemic therapies such as naltrexone, gabapentin, UV light therapy, and immunomodulatory treatments, including azathioprine, methotrexate, and cellcept. However, some patients still remain refractory to conventional therapy. Aprepitant is a neurokinin-1 receptor antagonist approved for the prevention of chemotherapy-induced and postoperative nausea and vomiting (CINV, PONV). Recently, aprepitant has demonstrated effectiveness in several case series and open label trials in relieving pruritus for patients refractory to other treatments. Patients with pruritus associated with Sézary syndrome, mycosis fungoides, lung adenocarcinoma, breast carcinoma, sarcomas, metastatic solid tumors, chronic kidney disease, hyperuricemia, iron deficiency, brachioradial pruritus, and Hodgkin’s lymphoma have experienced considerable symptom relief with short-term use of aprepitant (up to two weeks). Due to differences in reporting and evaluation of drug effects, the mechanism of aprepitant’s role is difficult to understand based on the current literature. Herein, we evaluate aprepitant’s antipruritic effects and discuss its mechanism of action and adverse effects. We propose that aprepitant is an alternative for patients suffering from pruritus who do not obtain enough symptom relief from conventional therapy. [ABSTRACT FROM AUTHOR]

Diarylheptanoids from Alnus nepalensis leaves have been reported for promising activity against filariasis, a mosquito-borne disease, and this has prompted us to investigate its anti-malarial and safety profile using in-vitro and in-vivo bioassays. A. nepalensis leaf extracts were tested in-vitro against chloroquine-sensitive Plasmodium falciparum NF54 by measuring the parasite specific lactate dehydrogenase activity. Among all, the chloroform extract (ANC) has shown promising anti-plasmodial activity (IC50 8.06 ± 0.26 µg/mL). HPLC analysis of ANC showed the presence of diarylheptanoids. Efficacy and safety of ANC were further validated in in-vivo system using Plasmodium berghei-induced malaria model and acute oral toxicity in mice. Malaria was induced by intra-peritoneal injection of P. berghei infected red blood cells to the female Balb/c mice. ANC was administered orally at doses of 100 and 300 mg/kg/day following Peter's 4 day suppression test. Oral administration of ANC showed significant reduction of parasitaemia and increase in mean survival time. It also attributed to inhibition of the parasite induced pro-inflammatory cytokines as well as afford to significant increase in the blood glucose and haemoglobin level when compared with vehicle-treated infected mice. In-vivo safety evaluation study revealed that ANC is non-toxic at higher concentration. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The development of drugs to inhibit glioblastoma ( GBM) growth requires reliable pre-clinical models. To date, proteomic level validation of widely used patient-derived glioblastoma xenografts ( PDGX) has not been performed. In the present study, we characterized 20 PDGX models according to subtype classification based on The Cancer Genome Atlas criteria, TP53, PTEN, IDH 1/2, and TERT promoter genetic analysis, EGFR amplification status, and examined their proteomic profiles against those of their parent tumors. The 20 PDGXs belonged to three of four The Cancer Genome Atlas subtypes: eight classical, eight mesenchymal, and four proneural; none neural. Amplification of EGFR gene was observed in 9 of 20 xenografts, and of these, 3 harbored the EGFRv III mutation. We then performed proteomic profiling of PDGX, analyzing expression/activity of several proteins including EGFR. Levels of EGFR phosphorylated at Y1068 vary considerably between PDGX samples, and this pattern was also seen in primary GBM. Partitioning of 20 PDGX into high ( n = 5) and low ( n = 15) groups identified a panel of proteins associated with high EGFR activity. Thus, PDGX with high EGFR activity represent an excellent pre-clinical model to develop therapies for a subset of GBM patients whose tumors are characterized by high EGFR activity. Further, the proteins found to be associated with high EGFR activity can be monitored to assess the effectiveness of targeting EGFR. [ABSTRACT FROM AUTHOR]

Seasonally and spatially varying demand elasticities would provide important information to seafood producers and marketers as well as policy makers. We analyzed the effects of season and space on (i) demand (translation effects) and (ii) price as well as expenditure elasticities of demand (scaling effects) for 13 finfish species in the United States. The paper used market-level scanner data for 52 U.S. markets. Results suggest that not only the quantity demanded, but also the demand elasticities vary across species, seasons, and geography; not only does the degree of competition among finfish products vary considerably over space, but substituting products themselves change. These results highlight the importance of studying consumer demand behavior at species level, across seasons and geography, particularly as it sheds important light on some important policy issues such as the potential substitution between catfish and tilapia in the U.S. markets. [ABSTRACT FROM AUTHOR]

A genotype 'Sujata' developed earlier at CSIR-CIMAP from its parent 'Sampada' is considered to be the latex-less variety of Papaver somniferum. These two genotypes are contrasting in terms of latex and stem strength. Earlier we have carried out microarray analysis to identify differentially expressing genes from the capsules of the two genotypes. In this study, the peduncles of the two genotypes were compared for the anatomy revealing less number of laticifers in the cortex and vascular bundles. One of the important cell wall-related genes (for laccase) from the microarray analysis showing significantly higher expression in 'Sampada' capsule was taken up for further characterization in the peduncle here. It was functionally characterized through transient overexpression and RNAi suppression in 'Sujata' and 'Sampada'. The increase in acid insoluble lignin and total lignin in overexpressed tissue of 'Sujata', and comparable decrease in suppressed tissue of 'Sampada', along with corresponding increase and decrease in the transcript abundance of laccase confirm the involvement of laccase in lignin biosynthesis. Negligible transcript in phloem compared to the xylem tissue localized its expression in xylem tissue. This demonstrates the involvement of P. somniferum laccase in lignin biosynthesis of xylem, providing strength to the peduncle/stem and preventing lodging. [ABSTRACT FROM AUTHOR]

Ursolic acid ( UA) is the most important bioactive phytoconstituent of Eucalyptus × hybrida Maiden leaves and exhibits anticancer, antimutagenic, anti-inflammatory, antioxidative, and antiprotozoal activities. In this study, microwave-assisted extraction technique was employed for rapid isolation of UA from the leaves of Eucalyptus × hybrida and simultaneously HPLC-diode array method was developed for the quantification of UA. Effects of several experimental parameters on the extraction efficiencies of UA, such as type and volume of extraction solvents, microwave power and extraction time, were evaluated. The optimal extraction conditions were found to be 20 mL of a mixture of chloroform/methanol, 60:40; liquid-to-material ratio, 4:1; preleaching time, 10 min; microwave power, 600 W; temperature, 50°C; and microwave irradiation time, 5 min. Under the optimum conditions, the yield of UA was found to be 1.95 ± 0.08% in the dry leaves of Eucalyptus × hybrida. The results showed that microwave-assisted extraction is a more rapid extraction method with higher yield and lower solvent consumptions than the conventional method. It is a faster, convenient, and appropriate method and it may be used for rapid isolation and quantification of UA and other important phytoconstituents present in the leaves of Eucalyptus × hybrida. [ABSTRACT FROM AUTHOR]

Many qualitative group decisions in professional fields such as law, engineering, economics, psychology, and medicine that appear to be crisp and certain are in reality shrouded in fuzziness as a result of uncertain environments and the nature of human cognition within which the group decisions are made. In this paper we introduce an innovative approach to group decision making in uncertain situations by using amean-variance neural approach. The key idea of this proposed approach is to compute the excluded mean of individual evaluations and weight it by applying a variance influence function (VIF); this process of weighting the excluded mean by VIF provides an improved result in the group decision making. In this paper, a case study with the proposed excludedmean- variance approach is also presented. The results of this case study indicate that this proposed approach can improve the effectiveness of qualitative decision making by providing the decision maker with a new cognitive tool to assist in the reasoning process. [ABSTRACT FROM AUTHOR]

A sensitive, selective and robust densitometric high-performance thin layer chromatographic method was developed and validated for the determination of diterpenoids in the root bark of Premna integrifolia. Diterpenoids 1β,3α,8β-trihydroxy-pimara-15-ene (), 6α,11,12,16-tetrahydroxy-7-oxo-abieta-8,11,13-triene () and 2α,19-dihydroxy-pimara-7,15-diene () were used as chemical markers for the standardization of P. integrifolia plant extracts. The separation was performed on silica gel 60F high-performance thin layer chromatography plates using hexane/acetone/ethylacetate (60:20:20 v/v) as mobile phase. The quantitation of diterpenoids was carried out using densitometric reflection/absorption mode at 475 nm after post-chromatographic derivatization using vanillin-sulfuric acid reagent. A precise and accurate quantification can be performed for compounds , and in the linear working concentration range of 1-10 μg/spot with good correlations ( r=0.9985, 0.9996 and 0.9992, respectively). The method was validated for peak purity, precision, robustness, limit of detection (LOD) and quantitation (LOQ) etc., as per the International Conference on Harmonization (ICH) guidelines. Specificity of quantitation was confirmed using retention factor ( R) and spectra correlation of markers in standard and sample tracks. The method reported here is simple and reproducible which may be applied for quantitative analysis of above diterpenoids in the root bark of P. integrifolia. [ABSTRACT FROM AUTHOR]

Recently there has been a paradigm shift in the focus of aquaculture planning from a top-down to a demand-driven approach. Demand-driven planning for aquaculture development emphasizes that aquaculture development must meet the needs and priorities of stakeholders, and requires processing vast amounts of information ranging from opinions and verbalized needs from primary stakeholders to quantitative data on demand from various stakeholders. However, such an approach is rarely adopted in aquaculture development. In this review, the demand for aquaculture in Bangladesh from different stakeholders, based on an extensive literature review supplemented with an analysis of primary and secondary data, is presented. The analysis shows that gaps persist between the fish yields obtained at research stations and in farmers’ fields and that inefficiency exists among aquaculture operators in Bangladesh. Fish farmers need better technology and enabling environments to reduce yield losses and to improve efficiency in production. Aquaculture planners and policymakers also need to consider demand from different consumer groups at home and abroad. [ABSTRACT FROM AUTHOR]

Sustainable agricultural intensification is an urgent challenge for Sub-Saharan Africa. One potential solution is to rely on local farmers' knowledge for improved management of diverse on-farm resources and integration among various farm enterprises. In this article, we analyze the farm-level impact of one recent example, namely the integrated aquaculture–agriculture (IAA) technologies that have been developed and disseminated in a participatory manner in Malawi. Based on a 2004 survey of 315 respondents (166 adopters and 149 nonadopters), we test the hypothesis that adoption of IAA is associated with improved farm productivity and more efficient use of resources. Estimating a technical inefficiency function shows that IAA farms were significantly more efficient compared to nonadopters. IAA farms also had higher total factor productivity, higher farm income per hectare, and higher returns to family labor. [ABSTRACT FROM AUTHOR]

This paper presents a motion control strategy for a rigid and constraint consistent formation that can be modeled by a directed graph whose each vertex represents individual agent kinematics and each of directed edges represents distance constraints maintained by an agent, called follower, to its neighbouring agent. A rigid and constraint consistent graph is called persistent graph. A persistent graph is minimally persistent if it is persistent, and no edge can be removed without losing its persistence. An acyclic (free of cycles in its sensing pattern) minimally persistent graph of Leader-Follower structure has been considered here which can be constructed from an initial Leader-Follower seed (initial graph with two vertices, one is Leader and another one is First Follower and one edge in between them is directed towards Leader) by Henneberg sequence (a procedure of growing a graph) containing only vertex additions. A set of nonlinear optimization-based decentralized control laws for mobile autonomous point agents in two dimensional plane have been proposed. An infinitesimal deviation in formation shape created continuous motion of Leader is compensated by corresponding continuous motion of other agents fulfilling the shortest path criteria. [ABSTRACT FROM AUTHOR]

The article focuses on mutations in the β-globin locus in population of Saudi Arabia's Eastern Province and presents diagrams for the same. Topics discussed include mutations leading to β-thalassemia; attribution to consanguineous marriages rate; and collection of peripheral blood samples. Other topics include purification of amplicons using QIAquick PCR Purification Kit; verification of HBB:c.93-21_96del mutation; and use of sequencing to identify mutations.

Abstract: Inadequate maternal intake of omega-3-fatty acids (ω3 FAs) causes adverse neurodevelopmental outcome in the progeny; however, their molecular mechanism of action is obscure. Since ω3 FAs are known to inhibit neuronal apoptosis during neuro-degeneration, we investigated their possible contribution in regulating neuronal apoptosis during brain development. Using rat model of hypothyroidism-induced neuronal apoptosis, we provide evidence for anti-apoptotic role of ω3 FAs during cerebellar development. ω3 FAs were supplemented as a mixture of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to pregnant and lactating rats, and primary hypothyroidism was induced by administering methimazole. The cerebella from postnatal day 16 (d16) pups were isolated, and studies on apoptosis were conducted. We observed that ω3 FA-supplementation significantly reduced DNA fragmentation and caspase-3 activation in developing cerebellum of hypothyroid pups. The protection provided by ω3 FAs was associated with their ability to prevent increases in the level of pro-apoptotic basal cell lymphoma protein-2 (Bcl-2)-associated X protein (Bax) in the cerebellum during thyroid hormone (TH) deficiency. ω3 FAs increased the levels of anti-apoptotic proteins like Bcl-2 and Bcl-extra large (Bcl-xL), known to be repressed in hypothyroidism. ω3 FAs also restored levels of cerebellar phospho (p)-AKT, phospho-extracellular regulated kinase (p-ERK) and phospho-c-Jun N-terminal kinase (p-JNK), which were altered by hypothyroid insults, without interfering with the expression of TH responsive gene, myelin basic protein (mbp). Taken together, these results supplement an insight into the molecular mechanism of action of ω3 FAs in developing brain that involves regulation of apoptotic signaling pathways under stress. [Copyright &y& Elsevier]

Previous studies have shown that neurokinin 1 receptor (NK1R) occurs naturally in human glioblastomas and its stimulation causes cell proliferation. In the present study we show that stimulation of NK1R in human U373 glioblastoma cells by substance P increases Akt phosphorylation by 2.5-fold, with an EC50 of 57 nM. Blockade of NK1R lowers basal phosphorylation of Akt, indicating the presence of a constitutively active form of NK1R; similar results are seen in U251 MG and DBTRG-05 glioblastoma cells. Linkage of NK1R to Akt implicates NK1R in apoptosis of glioblastoma cells. Indeed, treatment of serum-starved U373 cells with substance P reduces apoptosis by 53 ± 1% ( p < 0.05), and treatment with NK1R antagonist L-733,060 increases apoptosis by 64 ± 16% ( p < 0.01). Further, the blockade of NK1R in human glioblastoma cells with L-733,060 causes cleavage of Caspase-3 and proteolysis of poly (ADP-ribose) polymerase. Experiments designed to elucidate the mechanism of NK1R-mediated Akt phosphorylation revealed total involvement of non-receptor tyrosine kinase Src and phosphatidyl-3-kinase, a partial involvement of epidermal growth factor receptor, and no involvement of mitogen-activated protein/extracellular signal-related kinase. Taken together, the results of the present study indicate a key role for NK1R in glioblastoma apoptosis. [ABSTRACT FROM AUTHOR]

Problem Lipopolysaccharide (LPS) has been postulated to exert harmful biologic effects during pregnancy. The objective of present investigation is to measure the vaginal electrical resistance (VER) in LPS-treated normal cycling and pregnant female mice. Method of study Minimum dose (MD) of LPS (250 μg/kg body weight) was injected in pregnant female mice through i.p. route on day 0.5 of pregnancy. VER was measured during different phases of reproductive cycle in female mice, which were pre-exposed to LPS and in untreated cycling female mice. VER was also measured in control pregnant female mice (saline-treated mice) through whole pregnancy and LPS-treated female mice in early stages of pregnancy. Results Vaginal electrical resistance was significantly higher during proestrous or early estrous stage as compared with any other stages of reproductive cycle in mouse. One peak of VER was observed during peri-implantation period of pregnancy in control female mice. The significant differences in the pattern of VER were found between LPS-treated and control female mice during peri-implantation period of pregnancy, and between cycling female mice, which were pre-exposed to LPS and untreated cycling female mice during proestrus. Conclusion The presented results demonstrate, for the first time, that LPS exposure during pregnancy may be determined by measuring VER in mothers without any adverse effect on ongoing pregnancy and may help in refining the assisted reproduction techniques. [ABSTRACT FROM AUTHOR]

Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, is a cholesterol-lowering drug that may play a role in bone metabolism through a mechanism that is not fully understood. Recently, receptor activator of NF-κB ligand (RANKL), a member of the TNF superfamily, has emerged as a major mediator of bone loss via activation of osteoclastogenesis. The latter is also associated with certain cancers such as multiple myeloma and breast cancer. Whether simvastatin can modulate RANKL-induced or cancer induced osteoclastogenesis was investigated. The effect of simvastatin on RANKL signaling and consequent osteoclastogenesis was investigated. RANKL induced NF-κB activation, whereas pretreatment with simvastatin completely suppressed such activation and correlated with suppression of RANKL-induced activation of IκBα kinase, IκBα phosphorylation and IκBα degradation. Similarly, RANKL induced the differentiation of monocytic cells to osteoclasts, whereas simvastatin suppressed it. The inhibition was maximal when cells were exposed to both simvastatin and RANKL simultaneously and minimal when simvastatin was added 1 day after RANKL treatment. Simvastatin also inhibited the osteoclastogenesis induced by human breast cancer and by multiple myeloma cells. Together, our results indicate that simvastatin inhibits the RANKL-induced NF-κB activation pathway that leads to suppression of osteoclastogenesis induced by RANKL and by tumor cells, thereby suggesting its therapeutic potential in osteoporosis and in cancer-related bone loss. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In contrast to research on farming systems, research on natural resource systems seldom applies rigorous priority setting techniques, mainly due to difficulties associated with estimating research impact ex ante for such systems. This article presents a replicable approach to priority setting that addresses these difficulties. Assessment is based on multiple criteria, combining economic surplus analysis with subjective scoring, based on information drawn from a cross-country survey of expert opinion. The approach is applied to the WorldFish Center, a global agricultural research organization focusing on living aquatic resources, both farmed and wild. The exercise demonstrates the relevance of conventional evaluation techniques to fisheries research based on a practical application of its impact pathways. [ABSTRACT FROM AUTHOR]

Aims: The primary objective was to highlight the role of intraoperative bronchoscopic guidance during the management of central airway obstruction.Materials& Methods: A 6-month-old child presented with recurrent chest infections due to innominate artery compression of distal trachea. Aortopexy was performed under real-time bronchoscopic guidance.Results: Intraoperative bronchoscopic guidance helped in confirm a successful release of the central airway obstruction.Discussion: When operations similar to aortopexy are performed for release of airway obstructions, intraoperative bronchoscopic guidance is a valuable tool for confirming a successful outcome.Conclusion: The successful surgical management of central airway obstruction due to an innominate artery compression of the distal trachea under real-time bronchoscopic guidance in a 6-month-old child is described. [ABSTRACT FROM AUTHOR]

A simple, precise and rapid high-performance thin-layer chromatographic method has been developed for the estimation of phyllanthin ( 1) and hypophyllanthin ( 2), the important lignans of Phyllanthus species, especially Phyllanthus amarus. Separation of 1 and 2 was carried out on silica gel 60 F254 layers eluted with hexane:acetone:ethyl acetate (74:12:8), and the analytes were visualised through colour development with vanillin in concentrated sulphuric acid and ethanol. Scanning and quantification of spots was performed at 580 nm. Recoveries of 1 and 2 were 98.7 and 97.3%, respectively. The method was validated and the peak purities and limits of detection and quantification were determined. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An attempt has been made to develop a method by which to determine the chemical fingerprint of Andrographis paniculata (Acanthaceae). High-performance thin layer chromatography (HPTLC) was used to analyse hexane, chloroform, methanol and water extracts of leaves of A. paniculata. A computerised densitometer was applied to the two-dimensional spectrographic image analysis of the HPTLC plates. An HPLC equipped with a photodiode array detector was used for the analyses of these different extracts. The analyses showed that andrographolide and neoandrographolide are absent in the hexane extract but are present in greater amounts in the methanol extract as compared with the other extracts. These chromatograms may serve as a chemical fingerprint of the drug A. paniculata for quality control purposes and in the preparation of formulations based on the drug. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract Substance P receptor (SPR) and its naturally occurring splice-variant, lacking the C-terminal tail, are found in brain and spinal cord. Whether C-terminally truncated SPR desensitizes like full-length SPR is controversial. We used a multivaried approach to determine whether human SPR (hSPR) and a C-terminally truncated mutant, hSPRΔ325, differ in their desensitization and internalization. In HEK-293 cells expressing either hSPRΔ325 or hSPR, SP-induced desensitization of the two receptors was similar when measured by inositol triphosphate accumulation or by transient translocation of coexpressed PKCβII-GFP to the plasma membrane. Moreover, translocation of β-arrestin 1 or 2-GFP (βarr1-GFP or βarr2-GFP) to the plasma membrane, and receptor internalization were also similar. However, hSPR and hSPRΔ325 differ in their phosphorylation and in their ability to form β-arrestin-containing endocytic vesicles. Unlike hSPR, hSPRΔ325 is not phosphorylated to a detectable level in intact HEK293 cells, and whereas hSPR forms vesicles containing either βarr1-GFP or βarr2-GFP, hSPRΔ325 does not form any vesicles with βarr1-GFP, and forms fewer vesicles with βarr2-GFP. We conclude that truncated hSPR undergoes agonist-dependent desensitization and internalization without detectable receptor phosphorylation. [ABSTRACT FROM AUTHOR]