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Curcuma longa and Curcumin have been documented to have a wide spectrum of pharmacological effects, including anti- Acanthamoeba activity. Hence, this study sought to explore the anti-adhesion activity of C. longa extract and Curcumin against Acanthamoeba triangularis trophozoites and cysts in plastic and contact lenses. Our results showed that C. longa extract and Curcumin significantly inhibited the adhesion of A. triangularis trophozoites and cysts to the plastic surface, as investigated by the crystal violet assay (P < 0.05). Also, an 80–90% decrease in adhesion of trophozoites and cysts to the plastic surface was detected following the treatment with C. longa extract and Curcumin at 1/2 × MIC, compared to the control. In the contact lens model, approximately 1 log cells/mL of the trophozoites and cysts was reduced when the cells were treated with Curcumin, when compared to the control. Pre-treatment of the plastic surface with Curcumin at 1/2-MIC reduced 60% and 90% of the adhesion of trophozoites and cysts, respectively. The reduction in 1 Log cells/mL of the adhesion of A. triangularis trophozoites was observed when lenses were pre-treated with both the extract and Curcumin. Base on the results obtained from this study, A. triangularis trophozoites treated with C. longa extract and Curcumin have lost strong acanthopodia, thorn-like projection pseudopodia observed by scanning electron microscope. This study also revealed the therapeutic potentials of C. longa extract and Curcumin, as such, have promising anti-adhesive potential that can be used in the management/prevention of A. triangularis adhesion to contact lenses. Image 1 [ABSTRACT FROM AUTHOR]

Observational study. The brachial plexus neurodynamic test (BPNT), based on previous neurodynamic tests, is considered a clinically meaningful tool to objectively assess brachial plexus extensibility. This novel test's psychometric properties have yet to be determined. The primary study aim was to assess the inter- and intrarater reliability and accuracy of the BPNT, which biases the median nerve and brachial plexus, among clinicians of various professional experience levels and geographic US regions. The secondary study aim was to determine if professional experience or geographic region affects the accuracy levels of this test. In phase 1, inter-rater reliability and accuracy was determined. About 307 participants attending neural mobilization conferences and courses were instructed in the BPNT and asked to score 7 different videos of 14 possible test levels. In phase 2, intrarater reliability was determined via scoring the same test videos twice. High inter-rater intraclass correlation coefficient (range, 0.98-0.99) and accuracy (range, 0.88-0.94) levels were determined for all clinical experience levels and geographic regions. Intrarater intraclass correlation coefficient values were high (range, 0.96-1.0) among all participants. One-way analysis of variance indicated no significant differences on test accuracy based on professional clinical experience (F = 0.104; P =.958) and geographic region (F = 0.416; P =.416) among all 307 participants. Excellent inter- and intrarater reliability and accuracy levels may allow clinicians to correctly identify BPNT positions regardless of their professional experience or geographic location. The BPNT can reliably and accurately quantify outcomes in neural mobility scoring. • The study assessed reliability as well as accuracy of the brachial plexus neurodynamic test (BPNT), based on existing scales that bias the median nerve and brachial plexus. • The scale uses a 0/5 to 5/5 grading system designed to simplify data collection during testing for restricted neurodynamics. • High inter-rater reliability (0.98-0.99) and accuracy (0.88-0.94) levels were determined for all clinical experience levels and geographic regions. • High intrarater reliability (0.96-1.0) levels were determined for all participants. • The BPNT can reliably and accurately quantify outcomes in neural mobility scoring. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Fungi cause serious life-threatening infections in immunocompromised individuals and current treatments are now complicated by toxicity issues and the emergence of drug resistant strains. Consequently, there is a need for development of new antifungal drugs. Inosine monophosphate dehydrogenase (IMPDH), a key component of the de novo purine biosynthetic pathway, is essential for growth and virulence of fungi and is a potential drug target. In this study, a high-throughput screen of 114,000 drug-like compounds against Cryptococcus neoformans IMPDH was performed. We identified three 3-((5-substituted)-1,3,4-oxadiazol-2-yl)thio benzo[ b ]thiophene 1,1-dioxides that inhibited Cryptococcus IMPDH and also possessed whole cell antifungal activity. Analogs were synthesized to explore the SAR of these hits. Modification of the fifth substituent on the 1,3,4-oxadiazole ring yielded compounds with nanomolar in vitro activity, but with associated cytotoxicity. In contrast, two analogs generated by substituting the 1,3,4-oxadiazole ring with imidazole and 1,2,4-triazole gave reduced IMPDH inhibition in vitro, but were not cytotoxic. During enzyme kinetic studies in the presence of DTT, nucleophilic attack of a free thiol occurred with the benzo[ b ]thiophene 1,1-dioxide. Two representative compounds with substitution at the 5 position of the 1,3,4-oxadiazole ring, showed mixed inhibition in the absence of DTT. Incubation of these compounds with Cryptococcus IMPDH followed by mass spectrometry analysis showed non-specific and covalent binding with IMPDH at multiple cysteine residues. These results support recent reports that the benzo[ b ]thiophene 1,1-dioxides moiety as PAINS (pan-assay interference compounds) contributor. [ABSTRACT FROM AUTHOR]

Better understanding how multidrug-resistant (MDR) bacteria can evade current and novel antibiotics requires a better understanding of the chemical biology of antibiotic action. This necessitates using new tools and techniques to advance our knowledge of bacterial responses to antibiotics, ideally in live cells in real time, to selectively investigate bacterial growth, division, metabolism, and resistance in response to antibiotic challenge. In this review, we discuss the preparation and biological evaluation of fluorescent antibiotics, focussing on how these reporters and assay methods can help elucidate resistance mechanisms. We also examine the potential utility of such probes for real-time in vivo diagnosis of infections. [ABSTRACT FROM AUTHOR]

Statin therapy is a mainstay of cardiovascular disease (CVD) prevention, but research shows that statin therapy alone is insufficient for preventing incident CVD and mortality. Combining statin medication with increased physical activity (PA) can lower mortality risk more than either statin or PA alone. However, PA levels often remain the same and may even decline following statin prescription. Additional information is needed to identify how to increase PA among statin users and determine the minimal length of an intervention (i.e., intervention dose) necessary to increase PA. The study aims to identify the required dose of a behavior change technique (BCT) intervention to increase PA among individuals on primary prevention statin therapy who have an elevated risk for cardiovascular disease (CVD). The study will utilize the modified time-to-event continual reassessment method (TiTE-CRM) in 42 participants. We expect insights relating to dose-efficacy models and BCTs (Behavior Change Techniques) to improve PA in adults at risk for CVD. This trial will also examine potential mechanisms of action (MoAs) for interventions to increase PA, identify any effect a PA intervention may have on medication adherence, and determine whether participants respond uniformly to their respective behavioral interventions. This trial was approved by the Northwell Health Institutional Review Board (IRB) and all participants will complete informed consent. The trial results will be published in a peer-reviewed journal. All publications resulting from this series of personalized trials will follow the CONSORT reporting guidelines. This trial is registered on www.ClinicalTrials.gov (Number NCT05273723). [ABSTRACT FROM AUTHOR]

The discovery of new antibiotics is crucial if we are to avoid a future in which simple infections once again lead to death. New antibiotics were traditionally discovered by analyzing extracts from cultured soil-derived microbes. However, in the last few years only a few new antibiotic classes have been identified using this method. Attempts to apply target-based screening approaches to antibiotic discovery have also proven to be unproductive. In this article, we describe how DNA sequencing and bioinformatic techniques are revolutionizing natural product discovery leading to new natural product antibiotics sourced from both cultivated and uncultivated microbes. New chemical structures are also being ‘crowd sourced’ from chemists around the world, and ‘forgotten’ antibiotics repositioned for clinical trials after chemical or biochemical modification of the original natural product. Collectively such approaches have the potential to revamp antibiotic lead discovery and re-invigorate the antibiotic pipeline. [ABSTRACT FROM AUTHOR]

The aerial parts of the endemic Australian plant Eremophila debilis (Myoporaceae) contain 3% dry weight of the biologically active 5,6,7,3′,4′,5′-hexamethoxyflavone, which had its structured confirmed using X-ray crystal crystallography. The presence of significant levels of the polypharmacologically active 5,6,7,3′,4′,5′-hexamethoxyflavone in the edible parts of the plant has potential implications for its use as a food and bush medicine. [ABSTRACT FROM AUTHOR]

This study describes the syntheses of di, tetra and hexa deuterated analogues of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome inhibitor MCC950. In di and tetra deuterated analogues, deuteriums were incorporated into the 1,2,3,5,6,7-hexahydro- s -indacene moiety, whereas in the hexa deuterated MCC950 deuteriums were incorporated into the 2-(furan-3-yl)propan-2-ol moiety. The di deuterated MCC950 analogue was synthesised from 4-amino-3,5,6,7-tetrahydro- s -indacen-1(2 H )-one 5 . Tetra deuterated analogues were synthesised in 10 chemical steps starting with 5-bromo-2,3-dihydro-1 H -inden-1-one 9 , whereas the hexa deuterated analogue was synthesised in four chemical steps starting with ethyl-3-furoate 24 . All of the compounds exhibited similar activity to MCC950 (IC 50  = 8 nM). These deuterated analogues are useful as internal standards in LC-MS analyses of biological samples from in vivo studies. [ABSTRACT FROM AUTHOR]

The first synthesis of octapeptin C4 was achieved using a combination of solid phase synthesis and off-resin cyclisation. Octapeptin C4 displayed antibiotic activity against multi-drug resistant, NDM-1 and polymyxin-resistant Gram-negative bacteria, with moderate activity against Staphylococcus aureus . The linear analogue of octapeptin C4 was also prepared, which showed reduced activity. [ABSTRACT FROM AUTHOR]

Highlights: [•] A new digitoxigenin xyloside was isolated from E. australe v. integrifolium. [•] It exhibited nM activity in an assay designed to identify ICRAC channel inhibitors. [•] It inhibited Ca2+ driven expression of IL-2/luciferase in Jurkat T-cell lines. [Copyright &y& Elsevier]

Abstract: In light of past research being targeted to find specific particles which may be similar to gunshot residue (GSR), this project was formulated to detect any possible particulate by random particle fallout onto substrates at firework displays and to assess the impact this may have on GSR evidence. Firework residue was collected at a display site, from amongst spectators as well as from the author''s hair 90min after the display. SEM–EDX analysis has detected such particulate in all three scenarios, with the firework particle population at large providing a solid ground for discrimination from GSR. Wind dispersal was found to decrease the particle population and subsequently, the latter''s discriminatory power. Some particles, if treated individually were found to be indistinguishable from GSR. Findings also include residues which may mimic strontium based GSR as well as GSR which may be mixed with that from previous firings. The continuous changes made to primer and propellant compositions by manufacturers also call for greater consideration when classifying particles as originating from pyrotechnic devices. Furthermore, authorities such as police forces should be made more aware about the incidence of such particle transfer in firework related periods. [Copyright &y& Elsevier]

Abstract: Marine habitats are naturally patchy and anthropogenic disturbance can further fragment them. Many marine animals are sessile as adults or obligate inhabitants of particular habitats, so populations living in isolated patches of habitat are linked largely by dispersal of planktonic larvae. Theoretically, larvae are more likely to find and settle into large patches of habitat than small patches, thus small habitat patches may experience a more discontinuous supply of recruits resulting in small populations with unusual size- or age-structures or odd sex ratios — conditions where Allee effects on reproductive success are likely. We tested this hypothesis for the Caribbean spotted spiny lobster (Panulirus guttatus), an obligate inhabitant of coral patch reefs whose mating dynamics are size-dependent. We found that P. guttatus were less abundant on small reefs where their size structure and per capita reproductive success were significantly more variable, particularly among large females that are susceptible to sperm limitation that diminishes fertilization rates. These results are indicative of Allee effects and provide a mechanistic understanding of how size-dependent mating dynamics influence reproductive success in ways that alter population dynamics in patchy habitats. [Copyright &y& Elsevier]

Summary: Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA), or standard chow (SC) diets. Despite having reduced food intake and a low rate of weight gain equivalent to the SC group, HF/BCAA rats were as insulin resistant as HF rats. Pair-feeding of HF diet to match the HF/BCAA animals or BCAA addition to SC diet did not cause insulin resistance. Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1Ser307 and by accumulation of multiple acylcarnitines in muscle, and it was reversed by the mTOR inhibitor, rapamycin. Our findings show that in the context of a dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance. [Copyright &y& Elsevier]

Abstract: Pathogens can profoundly impact the ecology of the organisms they infect through changes in host behavior that influence demographic processes. For example, juvenile Caribbean spiny lobsters (Panulirus argus Latreille) infected with the PaV1 virus (Panulirus argus Virus 1) are avoided by their normally social conspecifics, which alters local spatial distributions and presumably rates of disease transmission. PaV1 infections are nearly always lethal, but prior to succumbing to the disease, infection may impact other host dynamics (e.g., movement, growth, or survival) that effect transmission of the virus. We used mark-recapture surveys and laboratory studies to determine the impact of PaV1 infection on lobster movement and physiological condition, and in turn, the effect of condition on susceptibility to infection. Significantly more healthy lobsters were recaptured than heavily diseased lobsters in 5-d mark-recapture surveys, indicating either greater emigration or greater mortality of infected lobsters. Results of a laboratory bioassay suggest that lobsters with early-stage infections moved at an equivalent rate to healthy lobsters, however, as infection progressed, lobsters inoculated with PaV1 moved less than healthy lobsters ultimately remaining sedentary. Infected lobsters captured in nature also had significantly lower hemolymph (blood) serum protein values, indicating poor physiological condition. However, poor condition did not predispose lobsters to greater risk of infection because prevalence was not different between starved lobsters and healthy lobsters challenged with PaV1. Although lobsters infected with PaV1 eventually become sedentary and of poor nutritional condition, during the early stages of infection they remain active and are thus capable of dispersing the virus throughout the population. [Copyright &y& Elsevier]

Abstract: The use of artificial structures to enhance marine animal populations, or as an aid to fishing, is widespread and increasing. While most investigators have studied the efficacy of artificial structure by measuring population abundance of the target species, or by comparison of the resulting community structure with that of natural communities, the effect of habitat enhancement on the processes creating such patterns is largely unknown. We enhanced density with the addition of artificial structures to examine the effect of local population density on the population dynamics (e.g., movement, mortality, and nutritional condition) of juvenile Caribbean spiny lobster (Panulirus argus) at natural and habitat-manipulated sites in the Florida Keys (USA). We artificially enhanced lobster density using small, scattered crevice-bearing structures that mimicked the natural shelters sought by juvenile lobsters. Enhanced density had no measurable effect on juvenile lobster mortality from predation or nutritional condition (as measured by hemolymph refractive index), but it increased the short-term residency of juvenile lobsters. The gregarious nature of spiny lobsters coupled with access to abundant prey may make them robust to high population density. [Copyright &y& Elsevier]

Abstract: Natural products have played a pivotal role in antibiotic drug discovery with most antibacterial drugs being derived from a natural product or natural product lead. However, the rapid onset of resistance to most antibacterial drugs diminishes their effectiveness considerably and necessitates a constant supply of new antibiotics for effective treatment of infections. The natural product templates of actinonin, pleuromutilin, ramoplanin and tiacumicin B, which are compounds undergoing clinical evaluation, represent templates not found in currently marketed antibacterial drugs. In addition, the new templates present in the recently discovered lead antibacterials arylomycin, GE23077, mannopeptimycin, muraymycin/caprazamycin, nocathiacin and ECO-0501, are discussed. Despite extensive efforts to identify antibiotic leads from molecular targets, only the peptide deformylase inhibitor LBM-415 is currently in clinical trials. It is proposed that new antibacterial assays which combine cell-based screening with molecular targets could offer better prospects for lead discovery. [Copyright &y& Elsevier]

Abstract: The mevalonate-independent pathway (MIP) is an interesting avenue for antimicrobial lead discovery. Here, we present a unified enantioselective synthesis of all four stereoisomers of 2-C-methyltetrol. These are useful building blocks of many bioactive natural products, including 2-C-methylerythritol phosphate (MEP) of the MIP biosynthetic pathway. [Copyright &y& Elsevier]

Abstract: A new benzopyrroloisoquinoline alkaloid, fistulosine (1), was isolated from the stem-bark of Ficus fistulosa (Moraceae) collected in Singapore, along with three known phenanthroindolizidine alkaloids, (−)-13aα-antofine (2), (−)-14β-hydroxyantofine (3) and (−)-13aα-secoantofine (4). (−)-13aα-Antofine (2) accounted for the antifungal activity against Aspergillus fumigatus and Candida albicans originally observed in the crude alkaloid extract. [Copyright &y& Elsevier]

Abstract: A workshop held in Halifax, Nova Scotia, Canada, brought together marine policy makers, resource users and experts to discuss spatial planning in the marine environment. Participants explored concepts of ocean zoning and learned from other jurisdictions and related integrated management initiatives. An ocean user perspectives panel featured plenary addresses on the significance of ocean zoning to various sectors. Discussions at the workshop emphasized the need for involving all key players and clearly defining terms used in the spatial planning process. [Copyright &y& Elsevier]

The purpose of this study was to test the association between a self-report measure of 24-hour adherence to antihypertensive medication and blood pressure (BP) among African Americans. The primary analysis included 3558 Jackson Heart Study participants taking antihypertensive medication who had adherence data for at least one study examination. Nonadherence was defined by self-report of not taking one or more prescribed antihypertensive medications, identified during pill bottle review, in the past 24 hours. Nonadherence and clinic BP were assessed at Exam 1 (2000–2004), Exam 2 (2005–2008), and Exam 3 (2009–2013). Associations of nonadherence with clinic BP and uncontrolled BP (systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg) were evaluated using unadjusted and adjusted linear and Poisson repeated measures regression models. The prevalence of nonadherence to antihypertensive medications was 25.4% at Exam 1, 28.7% at Exam 2, and 28.5% at Exam 3. Nonadherence was associated with higher systolic BP (3.38 mm Hg) and diastolic BP (1.47 mm Hg) in fully adjusted repeated measures analysis. Nonadherence was also associated with uncontrolled BP (prevalence ratio = 1.26; 95% confidence interval = 1.16–1.37). This new self-report measure may be useful for identifying nonadherence to antihypertensive medication in future epidemiologic studies. [ABSTRACT FROM AUTHOR]

An abstract of the article "Comparison of blood pool and extracellular gadolinium contrast for functional MR evaluation of vascular thoracic outlet syndrome," by Ruth P. Lim., Mary T. Bruno, Andrew B. Rosenkrantz, and colleagues is presented.

An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile ?click? chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structure-activity relationships or conjugated to fluorophores to generate fluorescent probes. Such probes can report bacteria and their location in a sample in real time. Modelling of the structures bound to the cognate 50S ribosome target demonstrates binding to the same site as linezolid is possible. The fluorescent probes were successfully used to image Gram-positive bacteria using confocal microscopy. [ABSTRACT FROM AUTHOR]

Natural products possess a significant role in anticancer therapy and many currently-used anticancer drugs are of natural origin. Cerberin (CR), a cardenolide isolated from the fruit kernel of Cerbera odollam, was found to potently inhibit cancer cell growth (GI50 values < 90 nM), colony formation and migration. Significant G2/M cell cycle arrest preceded time- and dose-dependent apoptosis-induction in human cancer cell lines corroborated by dose-and time-dependent PARP cleavage and caspase 3/7 activation, in addition to reduced Bcl-2 and Mcl-1 expression. CR potently inhibited PI3K/AKT/mTOR signalling depleting polo-like kinase 1 (PLK-1), c-Myc and STAT-3 expression. Additionally, CR significantly increased the generation of reactive oxygen species (ROS) producing DNA double strand breaks. Preliminary in silico biopharmaceutical assessment of CR predicted >60% bioavailability and rapid absorption; doses of 1-10 mg/kg CR were predicted to maintain efficacious unbound plasma concentrations (>GI50 value). CR's potent and selective anti-tumour activity, and its targeting of key signalling mechanisms pertinent to tumourigenesis support further preclinical evaluation of this cardiac glycoside. [ABSTRACT FROM AUTHOR]

This analysis of the global clinical antibacterial pipeline was done in support of the Global Action Plan on Antimicrobial Resistance. The study analysed to what extent antibacterial and antimycobacterial drugs for systemic human use as well as oral non-systemic antibacterial drugs for Clostridium difficile infections were active against pathogens included in the WHO priority pathogen list and their innovativeness measured by their absence of cross-resistance (new class, target, mode of action). As of July 1, 2018, 30 new chemical entity (NCE) antibacterial drugs, ten biologics, ten NCEs against Mycobacterium tuberculosis, and four NCEs against C difficile were identified. Of the 30 NCEs, 11 are expected to have some activity against at least one critical priority pathogen expressing carbapenem resistance. The clinical pipeline is dominated by derivatives of established classes and most development candidates display limited innovation. New antibacterial drugs without pre-existing cross-resistance are under-represented and are urgently needed, especially for geographical regions with high resistance rates among Gram-negative bacteria and M tuberculosis. [ABSTRACT FROM AUTHOR]

There is significant clinical need for new antifungal agents to manage infections with pathogenic species such as Cryptococcus neoformans Because the purine biosynthesis pathway is essential for many metabolic processes, such as synthesis of DNA and RNA and energy generation, it may represent a potential target for developing new antifungals. Within this pathway, the bifunctional enzyme adenylosuccinate (ADS) lyase plays a role in the formation of the key intermediates inosine monophosphate and AMP involved in the synthesis of ATP and GTP, prompting us to investigate ADS lyase in C. neoformans. Here, we report that ADE13 encodes ADS lyase in C. neoformans. We found that an ade13Δ mutant is an adenine auxotroph and is unable to successfully cause infections in a murine model of virulence. Plate assays revealed that production of a number of virulence factors essential for dissemination and survival of C. neoformans in a host environment was compromised even with the addition of exogenous adenine. Purified recombinant C. neoformans ADS lyase shows catalytic activity similar to its human counterpart, and its crystal structure, the first fungal ADS lyase structure determined, shows a high degree of structural similarity to that of human ADS lyase. Two potentially important amino acid differences are identified in the C. neoformans crystal structure, in particular a threonine residue that may serve as an additional point of binding for a fungal enzyme-specific inhibitor. Besides serving as an antimicrobial target, C. neoformans ADS lyase inhibitors may also serve as potential therapeutics for metabolic disease; rather than disrupt ADS lyase, compounds that improve the stability the enzyme may be used to treat ADS lyase deficiency disease. [ABSTRACT FROM AUTHOR]

Over the last four decades the HIV pandemic and advances in medical treatments that also cause immunosuppression have produced an ever-growing cohort of individuals susceptible to opportunistic pathogens. Of these, AIDS patients are particularly vulnerable to infection by the encapsulated yeast Cryptococcus neoformans. Most commonly found in the environment in purine-rich bird guano, C. neoformans experiences a drastic change in nutrient availability during host infection, ultimately disseminating to colonize the purine-poor central nervous system. Investigating the consequences of this challenge, we have characterized C. neoformans GMP synthase, the second enzyme in the guanylate branch of de novo purine biosynthesis. Weshow that in the absence of GMP synthase, C. neoformans becomes a guanine auxotroph, the production of key virulence factors is compromised, and the ability to infect nematodes and mice is abolished. Activity assays performed using recombinant protein unveiled differences in substrate binding between the C. neoformans and human enzymes, with structural insights into these kinetic differences acquired via homology modeling. Collectively, these data highlight the potential of GMP synthase to be exploited in the development of new therapeutic agents for the treatment of disseminated, life-threatening fungal infections. [ABSTRACT FROM AUTHOR]

Abstract: Background: The study objective was to explore the effect of music as an adjunct to local anesthesia on pain and anxiety during first-trimester surgical abortion. Secondary outcomes included patient satisfaction and coping. Study Design: We conducted a randomized controlled pilot study of 26 women comparing music and local anesthesia to local anesthesia alone. We assessed pain, anxiety and coping with 11-point verbal numerical scales. Patient satisfaction was measured via a 4-point Likert scale. Results: In the music group, we noted a trend toward a faster decline in anxiety postprocedure (p=.065). The music group reported better coping than the control group (mean±S.D., 8.5±2.3 and 6.2±2.8, respectively; p<.05). Both groups reported similarly high satisfaction scores. There were no group differences in pain. Conclusions: Music as an adjunct to local anesthesia during surgical abortion is associated with a trend toward less anxiety postprocedure and better coping while maintaining high patient satisfaction. Music does not appear to affect abortion pain. [Copyright &y& Elsevier]

Abstract: The rise of antibiotic resistance is of great clinical concern. One approach to reducing the development of resistance is to co-administer two or more antibiotics with different modes of action. However, it can be difficult to control the distribution and pharmacokinetics of two drugs to ensure both concentrations remain within the range of therapeutic efficacy whilst avoiding adverse effects. Hybrid drugs, where two drugs are linked together with a flexible linker, have been explored, but the resultant large, flexible molecules can have poor bioavailability. We have developed a chimeric approach using click chemistry where the pharmacophores of two drugs are overlapped into a single smaller, more drug-like molecule. Design and selection of compounds were assisted by in silico structural docking. We prepared a series of compounds that include candidates showing activity against the targets of both trimethoprim; dihydrofolate reductase, and ciprofloxacin; DNA gyrase and topoisomerase IV. The resultant triazole containing molecules show modest, but broad spectrum activities against drug sensitive and resistant Gram-negative and Gram-positive bacteria, with no observable cytotoxicity. [Copyright &y& Elsevier]

Abstract: Nitrous oxide (N2O) is one of the major greenhouse gases emitted from soils, where it is mainly produced by nitrification and denitrification. It is well known that rates of N2O release from soils are mainly determined by the availability of substrates and oxygen, but N2O source apportioning, highly needed to advance N2O mitigation strategies, still remains challenging. In this study, using an automated soil incubation system, the N2O site preference, i.e. the intramolecular 15N distribution, was analyzed to evaluate the progression in N2O source processes following organic soil amendment. Biogas fermentation residue (BGR; originating from food waste fermentation) was applied to repacked grassland soil cores and compared to ammonium sulfate (AS) application, both at rates equivalent to 160kgNH4 +–Nha−1, and to unamended soil (control). The soil cores were incubated in a helium–oxygen atmosphere with 20kPa O2 for 43 days at 80% water-filled pore space. 43-day cumulative N2O emissions were highest with BGR treated soil accounting for about 1.68kgN2O–Nha−1 while application of AS caused much lower fluxes of c. 0.23kgN2O–Nha−1. Also, after BGR application, carbon dioxide (CO2) fluxes showed a pronounced initial peak with steep decline until day 21 whereas with ammonium addition they remained at the background level. N2O dual isotope and isotopomer analysis of gas samples collected from BGR treated soil indicated bacterial denitrification to be the main N2O generating process during the first three weeks when high CO2 fluxes signified high carbon availability. In contrast, in the second half after all added labile carbon substrates had been consumed, nitrification, i.e. the generation of N2O via oxidation of hydroxylamine, gained in importance reaching roughly the same N2O production rate compared to bacterial denitrification as indicated by N2O SP. Overall in this study, bacterial denitrification seemed to be the main N2O forming process after application of biogas residues and fluxes were mainly driven by available organic carbon. [Copyright &y& Elsevier]

Abstract: The synthesis of the chiral core structure of the lissoclimide class of anti-tumour agents containing three rings, including a chiral succinimide subunit and an exocyclic double bond, has been investigated. The compound 7 was obtained, without the use of any protecting groups for the alcohol at C-12, via an asymmetric boron-mediated aldol addition as the key step to install the chiral centres of the rare succinimido methanol moiety. This was followed by a sequence of lactonisation, microwave-assisted amidation and imidation reactions. [ABSTRACT FROM AUTHOR]

Abstract: Study Objective: To determine the associations between postoperative cognitive dysfunction (POCD) and plasma concentrations of stable nitric oxide products [nitric oxide index (NOi)]. Design: Prospective study. Setting: Academic hospital. Patients: 28 ASA physical status I, II, and III physical status patients undergoing major non-cardiac surgery. Interventions: Cognitive assessment was performed preoperatively and postoperatively at 4 days (early) and 6 weeks (late). Measurements: Serial measurements of plasma NOi were recorded. Main Results: Early POCD with a deficit in one cognitive domain was present in 18 patients (64%), and in 8 patients (28%) with deficits in two or more cognitive domains. Late POCD was evident in three patients (20%) who had a deficit in one domain. Eight patients were lost to late follow-up. There was no difference in baseline or subsequent serum concentrations of NOi between those who showed early and late POCD and those who showed no POCD. Conclusion: Factors other than nitric oxide-mediated injury is responsible for POCD following major non-cardiac surgery. [Copyright &y& Elsevier]

Abstract: Bioassay-guided isolation using an MRSA whole cell assay yielded four novel benzophenone dimers, microsphaerins A–D (1–4), from two Singapore isolates of the soil anamorph Microsphaeropsis sp. The structures of 1–4 were elucidated on the basis of spectral data and the structures of 1 and 4 were confirmed by X-ray crystallographic analyses. [Copyright &y& Elsevier]

Abstract: We examined the histopathological and hematological response of the Caribbean spiny lobster to experimentally induced infections with Panulirus argus Virus 1 (PaV1). The fixed phagocytes in the hepatopancreas were the primary sites of PaV1 infection in spiny lobsters. Fixed phagocytes were activated in early infections. However, as the disease progressed, the fixed phagocytes became infected and eventually lysed. Infected cells were subsequently observed in the hepatopancreas, gill, heart, hindgut, glial cells around the ventral nerves, and in the cuticular epidermis and foregut. In advanced infections, spongy connective tissues were heavily infected, as were glial cells around the optic nerves. The structure of the hepatopancreas was significantly altered as the disease progressed. The hemal sinuses among the hepatopancreatic tubules filled with massive amounts of cellular aggregates, including infected circulating hemocytes and spongy connective tissues. Atrophy of the hepatopancreatic tubules occurred in the late stage of viral infection. The virus caused significant decreases in total hemocyte counts and significantly altered several constituents in the hemolymph lysates of diseased lobsters, including: glucose, phosphorus, and triglycerides. [Copyright &y& Elsevier]

Abstract: Development of post-transcriptional gene silencing (PTGS) agents for therapeutic purposes is an immense challenge in modern biology. Established technologies used to knockdown a specific target RNA and its cognate protein: antisense, ribozyme, RNAi, all conditionally depend upon an initial, critical annealing event of the PTGS ligand to a target RNA. In this review we address the nature of the bottlenecks, emphasizing the biocomplexity of target RNA structure, that currently limit PTGS therapeutic development. We briefly review existing and emerging technologies designed to release these constraints to realize the potential of PTGS agents in gene based therapies. [Copyright &y& Elsevier]

Abstract: This paper outlines the rationale and design of the Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project, in which detailed biologic profiling of three hundred and fifty obese individuals (body mass index (BMI): 30–50 kg/m2) will be conducted as they lose weight via seven distinct interventions. These profiles will be compared to those of fifty normal, healthy, control participants (BMI: 18.5–24.9 kg/m2). The interventions include the following: Roux-en-Y gastric bypass surgery, dietary interventions of differing macronutrient composition and diverse pharmacologic interventions. Outcome variables include eight conventional metabolites and CRP measured by standard clinical chemistry techniques, twenty hormones of energy balance and fuel homeostasis measured by radioimmunoassay (RIA) or by enzyme-linked Immunosorbent assay (ELISA), ten pro- and anti-inflammatory cytokines measured using Luminex xMAP® technology, one hundred and one intermediary metabolites measured by targeted mass-spectrometry-based methods, and physiologic variables such as body composition measured by dual energy X-ray absorptiometry (DEXA), air displacement plethysmography, and abdominal computerized tomography (CT), insulin sensitivity measured by intravenous glucose tolerance test (IV-GTT) and metabolic rate measured by indirect calorimetry. Results from this study will expand our knowledge of the biology of obesity and weight regulation and may lead to targeted strategies for its treatment and control. [Copyright &y& Elsevier]

Abstract: Several long-term sets of hourly nitrate concentration data were obtained through deployment of a nitrate sensor in an upper reach of the River Taw, a small moorland-fed river in the South West of the UK. Examination of the data obtained during periods of low flow and the absence of rainfall in the catchment revealed the presence of marked diurnal cycles, which were in concert and negatively correlated with diurnal cycles in water temperature. After verifying that these cycles were natural, an intensive 90-h field monitoring campaign was conducted, in which river water was sampled hourly and immediately analysed in the laboratory for molybdate-reactive phosphorus (P), nitrate, nitrite, ammonium, and pH. Coincident measurements of water temperature, river discharge and solar energy were also taken at, or close to, the site. All measurements revealed diurnal patterns and all patterns were concerted. The cycles of P, nitrate, nitrite, and discharge had two maxima and minima per 24 h, while the cycle of water temperature had one, with a maximum at 20.00 and a minimum at 08.00. The amplitudes of the cycles of P and nitrate were each about 30% of the mean values, while the amplitude of the nitrite cycle was as great as 80% of the mean value on occasions. Both biological and physical mechanisms for the cycling could operate through water temperature and/or incident radiation to account for the observed phenomenon, but there remains uncertainty of which is the more important. The observations have important implications for both the accuracy of pollution assessment in rivers and the physiological rhythms of riverine organisms. [Copyright &y& Elsevier]

A high throughput screen against POLO-like kinase 1 (Plk1), an anti-cancer target, identified an active extract from the fungus Arachniotus punctatus. Bioassay guided fractionation led to the isolation of the new natural product, gymnastatin N (1) and the known compound aranorosinol A (2) with IC50 values of 13 and 118μM, respectively. A 12′-hydroxy analog of gymnastatin N, 3, was also isolated as a minor component. Gymnastatin N (1) was found to be a 52:48 mixture of (1S,6′R) and (1R,6′R) diastereomers, by synthesis of the four possible diastereomers and comparison of the optical rotation and chiral HPLC profile of each diastereoisomer with the natural product. Analogues of 1 were synthesized and evaluated against the Plk1 assay and these SAR studies suggested that the diene and free carboxylic acid moieties might be responsible for its bioactivity. [Copyright &y& Elsevier]

Three compounds, 2,3-dihydroxy-4-methoxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran (1), 8-methoxy-2-methyl-2-(4-methyl-3-pentenyl)-2H-1-benzopyran-6-ol (2) and 4-methoxy-3-(3-methyl-2-butenyl)-benzoic acid (3), have been isolated from Wigandia urens. The structures of compounds 1, 2 and 3 were determined from spectroscopic data and showed activity in a CCR5 assay with IC50 values of 33, 46 and 26 μM respectively. [Copyright &y& Elsevier]