Why vegetable recipes are not very spicy.
Spices are aromatic plant materials that are used in cooking. Recently it was hypothesized that spice use yields a health benefit: cleansing food of parasites and pathogens before it is eaten, thereby reducing food poisoning and foodborne illnesses. In support, most spices have antimicrobial properties and use of spices in meat-based recipes is greatest in hot climates, where the diversity and growth rates of microorganisms are highest. A critical prediction of the antimicrobial hypothesis is that spices should be used less in preparing vegetables than meat dishes. This is because cells of dead plants are better protected physically and chemically against bacteria and fungi than cells of dead animals (whose immune system ceased functioning at death), so fewer spices would be necessary to make vegetables safe for consumption. We tested this corollary by compiling information on 2129 vegetable-only recipes from 107 traditional cookbooks of 36 countries. Analyses revealed that spice use increased with increasing ambient temperature, but less dramatically than in meat-based recipes. In all 36 countries, vegetable dishes called for fewer spices per recipe than meat dishes; 27 of these differences were significant. Of 41 individual spices, 38 were used less frequently in vegetable recipes; 30 of these differences were significant. Proportions of recipes that called for >1 spice and >1 extremely potent antimicrobial spice also were significantly lower for vegetable dishes. By every measure, vegetable-based recipes were significantly less spicy than meat-based recipes. Within-country analyses control for possible differences in spice plant availability and degrees of cultural independence. Results thus strongly support the antimicrobial hypothesis.


Rethinking psychopharmacotherapy: The role of treatment context and brain plasticity in antidepressant and antipsychotic interventions.
Emerging evidence indicates that treatment context profoundly affects psychopharmacological interventions. We review the evidence for the interaction between drug application and the context in which the drug is given both in human and animal research. We found evidence for this interaction in the placebo response in clinical trials, in our evolving knowledge of pharmacological and environmental effects on neural plasticity, and in animal studies analyzing environmental influences on psychotropic drug effects. Experimental placebo research has revealed neurobiological trajectories of mechanisms such as patients' treatment expectations and prior treatment experiences. Animal research confirmed that "enriched environments" support positive drug effects, while unfavorable environments (low sensory stimulation, low rates of social contacts) can even reverse the intended treatment outcome. Finally we provide recommendations for context conditions under which psychotropic drugs should be applied. Drug action should be steered by positive expectations, physical activity, and helpful social and physical environmental stimulation. Future drug trials should focus on fully controlling and optimizing such drug×environment interactions to improve trial sensitivity and treatment outcome.


Measurement-based modeling of contact forces and textures for haptic rendering.
Haptic texture represents the fine-grained attributes of an object's surface and is related to physical characteristics such as roughness and stiffness. We introduce an interactive and mobile scanning system for the acquisition and synthesis of haptic textures that consists of a visually tracked handheld touch probe. The most novel aspect of our work is an estimation method for the contact stiffness of an object based solely on the acceleration and forces measured during stroking of its surface with the handheld probe. We establish an experimental relationship between the estimated stiffness and the contact stiffness observed during compression. We also measure the height-displacement profile of an object's surface enabling us to generate haptic textures. We show an example of mapping the textures on to a coarse surface mesh obtained with an image-based technique, but the textures may also be combined with coarse surface meshes obtained by manual modeling.


Reporting of Adverse Events in Randomized Controlled Trials of Therapeutic Exercise for Hip Osteoarthritis: A Systematic Review.
The purpose of this study was to describe adverse events (AEs) and dropouts (DOs) in randomized controlled trials of therapeutic exercise for hip osteoarthritis (HOA) and to identify whether Consolidated Standards of Reporting Trials (CONSORT) guidelines were followed. The Cochrane Library, Embase, PubMed, and CINAHL databases were searched. Randomized controlled trials of therapeutic exercise for HOA published in English from January 1, 1980 to August 1, 2020 were included. Studies were excluded if other interventions were provided, if participants had previous hip arthroplasty, or if AEs and DOs for HOA participants were not reported separately. The internal validity of each study (Physiotherapy Evidence Database [PEDro] scoring) was assessed, participant and intervention characteristics were extracted, and the existence of a clear statement and reasons for AEs and DOs was reported. Descriptive statistics characterized results. Data heterogeneity prohibited the use of meta-analysis. Fourteen studies (mean PEDro score = 7.4; range = 6-10) from 10 countries were included, with 707 participants exercising. Exercise intensity was unspecified in 72.2% of exercise arms. Six studies (42.9%) included a statement of AEs, and 32 AEs were reported. All studies had a DO statement, but 29.0% of DOs occurred for unknown reasons. Six studies (42.9%) gave reasons for DOs that could be classified as AEs in 9 participants; 41 participants (5.8%) experienced exercise-related AEs. Reports of AEs were inconsistent, some DOs were potentially misclassified, and primary components of exercise interventions were frequently unreported. Despite these limitations, the overall low number of nonserious AEs suggests that the exercise-related risk of harm is minimal for individuals with HOA. Understanding the risk of harm associated with exercise for HOA can better inform safe dosing of exercise, clinical implementation, and replicability. Informative, consistent reporting of AEs, DOs, and exercise is needed. Greater use of the CONSORT harms-reporting checklist is warranted.


Increased Akt-mTOR signaling in lung epithelium is associated with respiratory distress syndrome in mice.
Pregnancy in women with diabetes is associated with a higher risk of perinatal complications. In particular, infants of diabetic mothers frequently suffer from respiratory distress syndrome (RDS), which is a leading cause of death in preterm infants and is considered to be primarily due to hyperinsulinemia in infants in response to maternal hyperglycemia. To elucidate the mechanism of how insulin signaling induces RDS, bronchoalveolar epithelium-specific Akt1 transgenic (TG) mice were generated. Akt1 overexpression in fetal lung epithelium resulted in RDS in preterm infants born by Caesarean section at embryonic day 18.5 (E18.5). The expression levels of hypoxia-inducible factor 2α (HIF-2α) and its target vascular endothelial growth factor (VEGF) were downregulated in the lung of Akt1 TG mice. Inhibition of the Akt-mammalian target of rapamycin (mTOR) signaling axis by rapamycin restored the expression of VEGF and improved the lung pathology of Akt1 TG pups. Rapamycin also attenuated the RDS phenotype in wild-type mice delivered preterm at E17.5. In cultured lung epithelial cells, insulin reduced VEGF expression and transcriptional activity of HIF-2 on VEGF promoter in an mTOR-dependent manner. Thus, aberrant activation of the Akt-mTOR pathway in lung epithelium plays a causal role in the pathogenesis of infant RDS, presumably through downregulation of HIF-2-dependent VEGF expression in the lung.


Persistent depression affects adherence to secondary prevention behaviors after acute coronary syndromes.
The persistence of depressive symptoms after hospitalization is a strong risk factor for mortality after acute coronary syndromes (ACS). Poor adherence to secondary prevention behaviors may be a mediator of the relationship between depression and increased mortality. To determine whether rates of adherence to risk reducing behaviors were affected by depressive status during hospitalization and 3 months later. Prospective observational cohort study. Three university hospitals. Five hundred and sixty patients were enrolled within 7 days after ACS. Of these, 492 (88%) patients completed 3-month follow-up. We used the Beck Depression Inventory (BDI) to assess depressive symptoms in the hospital and 3 months after discharge. We assessed adherence to 5 risk-reducing behaviors by patient self-report at 3 months. We used chi2 analysis to compare differences in adherence among 3 groups: persistently nondepressed (BDI < 10 at hospitalization and 3 months); remittent depressed (BDI > or = 10 at hospitalization; < 10 at 3 months); and persistently depressed patients (BDI > or = 10 at hospitalization and 3 months). Compared with persistently nondepressed, persistently depressed patients reported lower rates of adherence to quitting smoking (adjusted odds ratio [OR] 0.23, 95% confidence interval [95% CI] 0.05 to 0.97), taking medications (adjusted OR 0.50, 95% CI 0.27 to 0.95), exercising (adjusted OR 0.57, 95% CI 0.34 to 0.95), and attending cardiac rehabilitation (adjusted OR 0.5, 95% CI 0.27 to 0.91). There were no significant differences between remittent depressed and persistently nondepressed patients. Persistently depressed patients were less likely to adhere to behaviors that reduce the risk of recurrent ACS. Differences in adherence to these behaviors may explain in part why depression predicts mortality after ACS.


Searching for generality in the patterns of parasite abundance and distribution: ectoparasites of a South African rodent, Rhabdomys pumilio.
We studied abundance and distribution of seven ectoparasite species (fleas Chiastopsylla rossi and Dynopsyllus ellobius, a louse Polyplax arvicanthis, mites Androlaelaps fahrenholzi and Laelaps giganteus and two ticks Haemaphysalis elliptica and Hyalomma truncatum) exploiting the same populations of the rodent host Rhabdomys pumilio in South Africa. We considered three general patterns of abundance and distribution, namely (i) aggregated distribution of parasites amongst individual hosts; (ii) positive relationships between mean parasite abundance and their prevalence; and (iii) applicability of a simple epidemiological model based on mean parasite abundance and its variance to predict the observed patterns of prevalence. Our aims were to evaluate the relative role of host- versus parasite-associated factors by looking at similarity amongst different parasites in these patterns. In general, all parasites demonstrated strong similarity in each of the three patterns of abundance and distribution. However, the strength of these patterns differed amongst parasite species. We conclude that these patterns are driven mainly by hosts, but differences are caused by differences between various life-history traits of parasite species. Our results support the idea that general laws apply to parasite population ecology.


Awareness of the Food and Drug Administration's Bad Ad Program and Education Regarding Pharmaceutical Advertising: A National Survey of Prescribers in Ambulatory Care Settings.
The U.S. Food and Drug Administration's Bad Ad program educates health care professionals about false or misleading advertising and marketing and provides a pathway to report suspect materials. To assess familiarity with this program and the extent of training about pharmaceutical marketing, a sample of 2,008 health care professionals, weighted to be nationally representative, responded to an online survey. Approximately equal numbers of primary care physicians, specialists, physician assistants, and nurse practitioners answered questions concerning Bad Ad program awareness and its usefulness, as well as their likelihood of reporting false or misleading advertising, confidence in identifying such advertising, and training about pharmaceutical marketing. Results showed that fewer than a quarter reported any awareness of the Bad Ad program. Nonetheless, a substantial percentage (43%) thought it seemed useful and 50% reported being at least somewhat likely to report false or misleading advertising in the future. Nurse practitioners and physician assistants expressed more openness to the program and reported receiving more training about pharmaceutical marketing. Bad Ad program awareness is low, but opportunity exists to solicit assistance from health care professionals and to help health care professionals recognize false and misleading advertising. Nurse practitioners and physician assistants are perhaps the most likely contributors to the program.


Iron and Parkinson's disease.
In this case presentation, a man with a diagnosis of Parkinson's disease was treated with Chelation Therapy against iron without iron serum level correlation. The patient, who suffered from motor and non-motor symptoms of the disease, showed an improved condition after the Therapy. This clinical test was evaluated with UPDRS III score. The rationale and the limits of the Therapy are discussed. This case suggests that iron-dependent oxidative stress could represent a promising therapy for this dramatic disease; the necessity to deeply study the iron metabolism in neuro-degeneration appears really significant.


Regional polysterism in the GTP-bound form of the human c-Ha-Ras protein.
The backbone 1H, 13C, and 15N resonances of the c-Ha-Ras protein [a truncated version consisting of residues 1-171, Ras(1-171)] bound with GMPPNP (a slowly hydrolyzable analogue of GTP) were assigned and compared with those of the GDP-bound Ras(1-171). The backbone amide resonances of amino acid residues 10-13, 21, 31-39, 57-64, and 71 of Ras(1-171).GMPPNP, but not those of Ras(1-171).GDP, were extremely broadened, whereas other residues of Ras(1-171).GMPPNP exhibited amide resonances nearly as sharp as those of Ras(1-171). GDP. The residues exhibiting the extreme broadening, except for residues 21 and 71, are localized in three functional loop regions [loops L1, L2 (switch I), and L4 (switch II)], which are involved in hydrolysis of GTP and interactions with other proteins. From the temperature and magnetic field strength dependencies of the backbone amide resonance intensities, the extreme broadening was ascribed to the exchange at an intermediate rate on the NMR time scale. It was shown that the Ras(1-171) protein bound with GTP or GTPgammaS (another slowly hydrolyzable analogue of GTP) exhibits the same type of broadening. Therefore, it is a characteristic feature of the GTP-bound form of Ras that the L1, L2, and L4 loop regions, but not other regions, are in a rather slow interconversion between two or more stable conformers. This phenomenon, termed a "regional polysterism", of these loop regions may be related with their multifunctionality: the GTP-dependent interactions with several downstream target groups such as the Raf and RalGDS families and also with the GTPase activating protein (GAP) family. In fact, the binding of Ras(1-171).GMPPNP with the Ras-binding domain (residues 51-131) of c-Raf-1 was shown to eliminate the regional polysterism nearly completely. It was indicated, therefore, that each target/regulator selects its appropriate conformer among those presented by the "polysteric" binding interface of Ras. As the downstream target groups exhibit no apparent sequence homology to each other, it is possible that one target group prefers a conformer different from that preferred by another group. The involvement of loop L1 in the regional polysterism might suggest that the negative regulators, GAPs, bind to the polysteric binding interface (loops L2 and L4) of Ras and cooperatively select a conformer suitable for transition of the GTPase catalytic center, involving loops L1 and L4, into the highly active state.


Ca2+-calmodulin promotes survival of pheromone-induced growth arrest by activation of calcineurin and Ca2+-calmodulin-dependent protein kinase.
The cmd1-6 allele contains three mutations that block Ca2+ binding to calmodulin from Saccharomyces cerevisiae. We find that strains containing cmd1-6 lose viability during cell cycle arrest induced by the mating pheromone alpha-factor. The 50% lethal dose (LD50) of alpha-factor for the calmodulin mutant is almost fivefold below the LD50 for a wild-type strain. The calmodulin mutants are not more sensitive to alpha-factor, as measured by activation of a pheromone-responsive reporter gene. Two observations indicate that activation of the Ca2+-calmodulin-dependent protein phosphatase calcineurin contributes to survival of pheromone-induced arrest. First, deletion of the gene encoding the calcineurin regulatory B subunit, CNB1, from a wild-type strain decreases the LD50 of alpha-factor but has no further effect on a cmd1-6 strain. Second, a dominant constitutive calcineurin mutant partially restores the ability of the cmd1-6 strain to survive exposure to alpha-factor. Activation of the Ca2+-calmodulin-dependent protein kinase (CaMK) also contributes to survival, thus revealing a new function for this enzyme. Deletion of the CMK1 and CMK2 genes, which encode CaMK, decreases the LD50 of pheromone compared with that for a wild-type strain but again has no effect in a cmd1-6 strain. Furthermore, the LD50 of alpha-factor for a mutant in which the calcineurin and CaMK genes have been deleted is the same as that for the calmodulin mutant. Finally, the CaMK and calcineurin pathways appear to be independent since the ability of constitutive calcineurin to rescue a cmd1-6 strain is not blocked by deletion of the CaMK genes.


Growth requirements and fermentation products of Fusobacterium prausnitzii, and a proposal to reclassify it as Faecalibacterium prausnitzii gen. nov., comb. nov.
Two newly isolated strains of obligately anaerobic bacteria from human faeces are shown here to be related to Fusobacterium prausnitzii, which is regarded as one of the most abundant colonizers of the human colon. These strains, along with Fusobacterium prausnitzii ATCC 27768(T) and 27766, are non-motile and produce butyrate, formate and lactate, but not hydrogen as fermentation products. A new finding is that all four strains produce D-lactate, but not L-lactate. The strains have a requirement for acetate in the growth medium and this may account for the previously reported requirement for rumen fluid. The DNA G+C content of the four strains is 47-57 mol%. Together with phylogenetic analysis based on 16S rRNA sequencing, this establishes that Fusobacterium prausnitzii strains are only distantly related to Fusobacterium sensu stricto and are more closely related to members of Clostridium cluster IV (the Clostridium leptum group). It is proposed that a new genus, Faecalibacterium gen. nov. be created; this genus should include Faecalibacterium prausnitzii gen. nov., comb. nov. ATCC 27768(T) (= NCIMB 13872(T)) (formerly Fusobacterium prausnitzii) as the type species together with ATCC 27766 and the newly isolated strains A2-165 and L2-6.


Proteins binding to kallikrein and esterase A2 in the urine of salt-sensitive and salt-resistant rats.
Iodine-labeled ([125I]) rat urinary kallikrein and rat urinary TAME esterase A2 were used as probes to look for urinary and plasma proteins that bind to these enzymes. Such proteins are presumptive enzyme inhibitors. Complexes formed with labeled enzymes were identified by polyacrylamide gel electrophoresis followed by autoradiography. Urine from young (6 weeks old) Dahl salt-sensitive (S) rats showed no, or only traces, of protein binding to kallikrein. Concomitant with the slow development of hypertension and proteinuria in S rats fed normal rat chow, one of the six kallikrein-binding proteins demonstrable in plasma was readily found in S-rat urine. This kallikrein-binding protein was called "KBP-1." R rats showed either no or much less KBP-1 in the urine, compared to S rats up to 5 months of age. A partly purified preparation of KBP-1 was shown to inhibit the TAME esterase activity of rat urinary kallikrein in the radiometric TAME assay. Urine of proteinuric S rats also contained two TAME esterase-binding proteins, TEBP-1 and TEBP-2, detected with the [125I]-esterase A2 probe. As S rats aged from 3 to 8 months, free KBP-1 disappeared from the urine in spite of increased and marked proteinuria and the continued presence of KBP-1 in plasma. Concomitant with this age-related loss of urinary KBP-1 there was a marked shift in S urinary proteins binding to [125I]-esterase A2 from TEBP-1 to TEBP-2. It was speculated that KBP-1 and TEBP-1 were the same protein detectable with either labeled kallikrein or labeled esterase A2. The concomitant disappearance of free KBP-1 (TEBP-1) and the appearance of free TEBP-2 in the urine of old, hypertensive, proteinuric S rats suggests that: 1) most of the KBP-1 (TEBP-1) is bound to enzyme(s) in old rats; or 2) KBP-1 (TEBP-1) is largely converted to TEBP-2 in old rats; or 3) both are true and that binding of KBP-1 (TEBP-1) to enzymes is associated with the generation of TEBP-2.


Hypertrophic cardiomyopathy: a review of etiology and treatment.
Hypertrophic cardiomyopathy (HCM) is a congenital cardiac disease with an estimated prevalence of 1:500 in the population. Individuals with HCM can present with clinical manifestations that include left ventricular outflow obstruction, cardiac dysrhythmias, diastolic heart failure, cardiac angina, and sudden cardiac death. Current treatments include pharmacologic intervention to reduce heart rate and ventricular contractility as well as surgery or septal alcohol ablation to reduce myocardial septal size. Implantable cardiac defibrillators are considered a treatment option in individuals with HCM who are at an increased risk for sudden cardiac death. The identification of persons at risk for complications related to HCM is important for reducing mortality and morbidity in this population. In addition, diagnosis of HCM in an individual allows the healthcare provider caring for these patients to screen, educate, and institute timely preventative measures in other members of the family. The purpose of this review is to provide clinicians caring for cardiac patients with a guide for recognition, diagnosis, prevention, and treatment of HCM.


Direct observation of chemical bond dynamics on surfaces.
The dynamics of chemisorbed species as they swing to-and-fro on their adsorption sites may be directly observed with electron-stimulated desorption. The observation of the thermal disorder in adsorbate chemical bond directions, through studies of the thermal excitation of librational modes, allows one to visualize the potential energy surfaces controlling the structure and dynamics of adsorbates on single crystal metal and semiconductor surfaces. This information may be useful in understanding surface diffusion as well as the spatial aspects of surface chemical reactions.


An evaluation of the PacBio RS platform for sequencing and de novo assembly of a chloroplast genome.
Second generation sequencing has permitted detailed sequence characterisation at the whole genome level of a growing number of non-model organisms, but the data produced have short read-lengths and biased genome coverage leading to fragmented genome assemblies. The PacBio RS long-read sequencing platform offers the promise of increased read length and unbiased genome coverage and thus the potential to produce genome sequence data of a finished quality containing fewer gaps and longer contigs. However, these advantages come at a much greater cost per nucleotide and with a perceived increase in error-rate. In this investigation, we evaluated the performance of the PacBio RS sequencing platform through the sequencing and de novo assembly of the Potentilla micrantha chloroplast genome. Following error-correction, a total of 28,638 PacBio RS reads were recovered with a mean read length of 1,902 bp totalling 54,492,250 nucleotides and representing an average depth of coverage of 320× the chloroplast genome. The dataset covered the entire 154,959 bp of the chloroplast genome in a single contig (100% coverage) compared to seven contigs (90.59% coverage) recovered from an Illumina data, and revealed no bias in coverage of GC rich regions. Post-assembly the data were largely concordant with the Illumina data generated and allowed 187 ambiguities in the Illumina data to be resolved. The additional read length also permitted small differences in the two inverted repeat regions to be assigned unambiguously. This is the first report to our knowledge of a chloroplast genome assembled de novo using PacBio sequence data. The PacBio RS data generated here were assembled into a single large contig spanning the P. micrantha chloroplast genome, with a higher degree of accuracy than an Illumina dataset generated at a much greater depth of coverage, due to longer read lengths and lower GC bias in the data. The results we present suggest PacBio data will be of immense utility for the development of genome sequence assemblies containing fewer unresolved gaps and ambiguities and a significantly smaller number of contigs than could be produced using short-read sequence data alone.


A probabilistic characterization of the health benefits of reducing methyl mercury intake in the United States.
We developed a probabilistic model to characterize the plausible distribution of health and economic benefits that would accrue to the U.S. population following reduction of methyl mercury (MeHg) exposure. MeHg, a known human developmental neurotoxicant, may increase fatal heart attack risks. Model parameters reflect current understanding of the relationships between MeHg intake, health risks, and societal valuation of these risks. The expected monetary value of the annual health benefits generated by a 10% reduction in U.S. population exposure to MeHg for one year is $860 million; 80% of this is associated with reductions in fatal heart attacks and the remainder with IQ gains. The plausible distribution of the benefits is quite broad with 5th and 95th percentile estimates of approximately $50 million and $3.5 billion, respectively. The largest source of uncertainty is whether epidemiological associations between MeHg exposure and fatal heart attacks reflect causality. The next largest sources of uncertainty concern the slope of the relationship between maternal MeHg exposure and reduced intelligence among children and whether this relationship exhibits a threshold. Our analysis suggests that the possible causal relationship between MeHg exposure and fatal heart attacks should be better characterized, using additional epidemiological studies and formally elicited expert judgment.


Goal neglect, fluid intelligence and processing speed: Manipulating instruction load and inter-stimulus interval.
Goal maintenance is the process where task rules and instructions are kept active to exert their control on behavior. When this process fails, an individual may ignore a rule while performing the task, despite being able to describe it after task completion. Previous research has suggested that the goal maintenance system is limited by the number of concurrent rules which can be maintained during a task, and that this limit is dependent on an individual's level of fluid intelligence. However, the speed at which an individual can process information may also limit their ability to use task rules when the task demands them. In the present study, four experiments manipulated the number of instructions to be maintained by younger and older adults and examined whether performance on a rapid letter-monitoring task was predicted by individual differences in fluid intelligence or processing speed. Fluid intelligence played little role in determining how frequently rules were ignored during the task, regardless of the number of rules to be maintained. In contrast, processing speed predicted the rate of goal neglect in older adults, where increasing the presentation rate of the letter-monitoring task increased goal neglect. These findings suggest that goal maintenance may be limited by the speed at which it can operate.


Homogeneous and heterogeneous catalysis: bridging the gap through surface organometallic chemistry.
Surface organometallic chemistry is an area of heterogeneous catalysis which has recently emerged as a result of a comparative analysis of homogeneous and heterogeneous catalysis. The chemical industry has often favored heterogeneous catalysis, but the development of better catalysts has been hindered by the presence of numerous kinds of active sites and also by the low concentration of active sites. These factors have precluded a rational improvement of these systems, hence the empirical nature of heterogeneous catalysis. Catalysis is primarily a molecular phenomenon, and it must involve well-defined surface organometallic intermediates and/or transition states. Thus, one must be able to construct a well-defined active site, test its catalytic performance, and assess a structure-activity relationship, which will be used, in turn-as in homogeneous catalysis-to design better catalysts. By the transfer of the concepts and tools of molecular organometallic chemistry to surfaces, surface organometallic chemistry can generate well-defined surface species by understanding the reaction of organometallic complexes with the support, which can be considered as a rigid ligand. This new approach to heterogeneous catalysis can bring molecular insight to the design of new catalysts and even allow the discovery of new reactions (Ziegler-Natta depolymerization and alkane metathesis). After more than a century of existence, heterogeneous catalysis can still be improved and will play a crucial role in solving current problems. It offers an answer to economical and environmental problems faced by industry in the production of molecules (agrochemicals, petrochemicals, pharmaceuticals, polymers, basic chemicals).


Halogen bonding in halocarbon-protein complexes: a structural survey.
Halogen bonding has been extensively described in the context of a variety of self-assembled supramolecular systems and efficiently utilized in the rational design of materials with specific structural properties. However, it has so far received only little recognition for its possible role in the stabilization of small molecule-protein complexes. In this tutorial review, we provide a few examples of halogen bonds occurring between small halogen-substituted ligands and their biological substrates. Examples were drawn from a diverse set of compounds, ranging from chemical additives and possible environmental agents such as triclosan to pharmacologically active principles such as the volatile anesthetic halothane or HIV-1 reverse transcriptase inhibitors or a subset of non-steroidal anti-inflammatory drugs (NSAIDs) that are halogen-substituted. The crystal structures presented here, where iodine, bromine, or chlorine atoms function as halogen bonding donors and a variety of electron rich sites, such as oxygen, nitrogen and sulfur atoms, as well as aromatic π-electron systems, function as halogen bonding acceptors, prove how halogen bonds can occur in biological systems and provide a class of highly directional stabilizing contacts that can be exploited in the process of rational drug design.


Elucidating the 'Jekyll and Hyde' nature of PXR: the case for discovering antagonists or allosteric antagonists.
The pregnane X receptor belongs to the nuclear hormone receptor superfamily and is involved in the transcriptional control of numerous genes. It was originally thought that it was a xenobiotic sensor controlling detoxification pathways. Recent studies have shown an increasingly important role in inflammation and cancer, supporting its function in abrogating tissue damage. PXR orthologs and PXR-like pathways have been identified in several non-mammalian species which corroborate a conserved role for PXR in cellular detoxification. In summary, PXR has a multiplicity of roles in vivo and is being revealed as behaving like a "Jekyll and Hyde" nuclear hormone receptor. The importance of this review is to elucidate the need for discovery of antagonists of PXR to further probe its biology and therapeutic applications. Although several PXR agonists are already reported, virtually nothing is known about PXR antagonists. Here, we propose the development of PXR antagonists through chemical, genetic and molecular modeling approaches. Based on this review it will be clear that antagonists of PXR and PXR-like pathways will have widespread utility in PXR biology and therapeutics.


Multifunctional hydrogel coatings on the surface of neural cuff electrode for improving electrode-nerve tissue interfaces.
Recently, implantable neural electrodes have been developed for recording and stimulation of the nervous system. However, when the electrode is implanted onto the nerve trunk, the rigid polyimide has a risk of damaging the nerve and can also cause inflammation due to a mechanical mismatch between the stiff polyimide and the soft biological tissue. These processes can interrupt the transmission of nerve signaling. In this paper, we have developed a nerve electrode coated with PEG hydrogel that contains poly(lactic-co-glycolic) acid (PLGA) microspheres (MS) loaded with anti-inflammatory cyclosporin A (CsA). Micro-wells were introduced onto the electrode in order to increase their surface area. This allows for loading a high-dose of the drug. Additionally, chemically treating the surface with aminopropylmethacrylamide can improve the adhesive interface between the electrode and the hydrogel. The surface of the micro-well cuff electrode (MCE) coated with polyethylene glycol (PEG) hydrogel and drug loaded PLGA microspheres (MS) were characterized by SEM and optical microscopy. Additionally, the conductive polymers, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT/PSS), were formed on the hydrogel layer for improving the nerve signal quality, and then characterized for their electrochemical properties. The loading efficiencies and release profiles were investigated by High Performance Liquid Chromatography (HPLC). The drug loaded electrode resulted in a sustained release of CsA. Moreover, the surface coated electrode with PEG hydrogel and CsA loaded MP showed a significantly decreased fibrous tissue deposition and increased axonal density in animal tests. We expect that the developed nerve electrode will minimize the tissue damage during regeneration of the nervous system. The nerve electrodes are used for interfacing with the central nervous system (CNS) or with the peripheral nervous system (PNS). The interface electrodes should facilitate a closed interconnection with the nerve tissue and provide for selective stimulation and recording from multiple, independent, neurons of the neural system. In this case, an extraneural electrodes such as cuff and perineural electrodes are widely investigated because they can completely cover the nerve trunk and provide for a wide interface area. In this study, we have designed and prepared a functionalized nerve cuff electrode coated with PEG hydrogel containing Poly lactic-co-glycol acid (PLGA) microspheres (MS) loaded with cyclosporine A (CsA). To our knowledge, our findings suggest that surface coating a soft-hydrogel along with an anti-inflammatory drug loaded MS can be a useful strategy for improving the long-term biocompatibility of electrodes.


Fibromyalgia: present to future.
There has been a dramatic increase in our understanding of fibromyalgia throughout the past 14 years since the publication of the 1990 American College of Rheumatology classification criteria. Before 1990, and for most of the 20th century, fibromyalgia was considered to be predominantly a muscle disorder; now the critical abnormality is described as "central sensitization." However, central sensitization has to have an initial genesis and nociceptive stimuli from painful foci in muscle are increasingly recognized as being relevant to the development of fibromyalgia. Clinicians also recognize an association between the initiation of fibromyalgia and chronic psychologic stressors and inflammatory disorders. It has been more difficult to understand how two such apparently diverse events could affect central pain physiology. However, some clues are emerging from the role of diverse stimuli in activating glial cells and the role of disordered cytokine networks. Some predictions about future developments in fibromyalgia are ventured based on the current state of knowledge.


Salivary microRNA 155, 146a/b and 203: A pilot study for potentially non-invasive diagnostic biomarkers of periodontitis and diabetes mellitus.
Dysregulated expression of MicroRNAs (miRNAs) plays substantial role in the initiation and progression of both diabetes and periodontitis. The aim of the present study was to validate four miRNAs in saliva as potential predictive biomarkers of periodontal disease among patients with and without diabetes mellitus (DM). MiRNAs were extracted from the saliva of 24 adult subjects with DM and 29 healthy controls. Each group was subdivided into periodontally healthy or having periodontitis. In silico analysis identified 4 miRNAs (miRNA 155, 146 a/b and 203) as immune modulators. The expression of miRNAs-146a/b, 155, and 203 was tested using quantitative PCR. The expression levels in the study groups were compared to explore the effect of diabetes on periodontal status and vice versa. In our cohort, the four miRNAs expression were higher in patients with periodontitis and/or diabetes. miRNA-155 was the most reliable predictors of periodontitis among non-diabetics with an optimum cut-off value of < 8.97 with accuracy = 82.6%. MiRNA 146a, on the other hand, was the only reliable predictor of periodontitis among subjects with diabetes with optimum cut-off value of ≥11.04 with accuracy = 86.1%. The results of the present study concluded that MiRNA-146a and miRNA155 in saliva provide reliable, non-invasive, diagnostic and prognostic biomarkers that can be used to monitor periodontal health status among diabetic and non-diabetic patients.


Characterization of the multigene family coding for HMW glutenin subunits in wheat using cDNA clones.
cDNA clones encoding wheat HMW glutenin subunits have been isolated from a cDNA bank made to poly A(+) RNA from developing wheat endosperm var. Chinese Spring. One such clone, pTag 1290, has enabled us to identify the HMW glutenin mRNA species. The DNA sequence of this clone has been partially determined and it contains several tandem DNA repeats. The sequence is discussed in relation to the generation of the HMW glutenin subunit gene family. Analysis of the organization of the HMW glutenin sequences in the wheat genome revealed that the genes encoding HMW glutenin subunits exist in low copy number and are located on the long arm of each of the homoeologous group 1 chromosomes.


An exploratory propensity score matched comparison of second-generation and first-generation baroreflex activation therapy systems.
Baroreflex activation therapy (BAT) is a device-based therapy for patients with treatment-resistant hypertension. In a randomized, controlled trial, the first-generation system significantly reduced blood pressure (BP) versus sham. Although an open-label validation study of the second-generation system demonstrated similar BP reductions, controlled data are not presently available. Therefore, this investigation compares results of first- and second-generation BAT systems. Two cohorts of first-generation BAT system patients were generated with propensity matching to compare against the validation group of 30 second-generation subjects. The first cohort was drawn from the first-generation randomized trial sham group and the second cohort from the active therapy group. Safety and efficacy were compared for the second-generation group relative to the first generation. At 6 months, second-generation BAT outperformed first-generation sham systolic BP reduction by 20 ± 28 mm Hg (mean ± standard deviation, P = .008), while BP reduction in first- and second-generation active groups was similar. At 12 months, efficacy was comparable between all three groups after the sham group had received 6 months of therapy; 47% of second-generation patients achieved goal systolic BP of 140 mm Hg or less after 12 months, comparable to 50% of patients at goal in the first-generation group (P > .999). Implant procedure time, system/procedural safety, and pulse generator longevity improved with the second-generation system. Propensity-matched cohort analysis of the first- and second-generation BAT systems suggests similar therapeutic benefit and superior BP reduction of the second-generation system relative to sham control. Implantation procedure duration and perioperative safety were improved with the second-generation device. These findings should be validated in a prospective randomized trial.


Selected pharmacokinetic issues of the use of antiepileptic drugs and parenteral nutrition in critically ill patients.
To conduct a systematic review for the evidence supporting or disproving the reality of parenteral nutrition- antiepileptic drugs interaction, especially with respect to the plasma protein-binding of the drug. The articles related to the topic were identified through Medline and PubMed search (1968-Feburary 2010) for English language on the interaction between parenteral nutrition and antiepileptic drugs; the search terms used were anti-epileptic drugs, parenteral nutrition, and/or interaction, and/or in vitro. The search looked for prospective randomized and nonrandomized controlled studies; prospective nonrandomized uncontrolled studies; retrospective studies; case reports; and in vitro studies. Full text of the articles were then traced from the Universiti Sains Malaysia (USM) library subscribed databases, including Wiley-Blackwell Library, Cochrane Library, EBSCOHost, OVID, ScienceDirect, SAGE Premier, Scopus, SpringerLINK, and Wiley InterScience. The articles from journals not listed by USM library were traced through inter library loan. There were interactions between parenteral nutrition and drugs, including antiepileptics. Several guidelines were designed for the management of illnesses such as traumatic brain injuries or cancer patients, involving the use of parenteral nutrition and antiepileptics. Moreover, many studies demonstrated the in vitro and in vivo parenteral nutrition -drugs interactions, especially with antiepileptics. There was no evidence supporting the existence of parenteral nutrition-antiepileptic drugs interaction. The issue has not been studied in formal researches, but several case reports and anecdotes demonstrate this drug-nutrition interaction. However, alteration in the drug-free fraction result from parenteral nutrition-drug (i.e. antiepileptics) interactions may necessitate scrupulous reassessment of drug dosages in patients receiving these therapies. This reassessment may be particularly imperative in certain clinical situations characterized by hypoalbuminemia (e.g., burn patients).


Ventilation during steady-state exercise in patients with chronic obstructive pulmonary disease. A preliminary study.
In this preliminary study 20 patients with chronic obstructive pulmonary disease (COPD) walked on the treadmill until symptoms limited further exercise. When minute volume exceeded 60% of the predicted maximum breathing capacity the arterial carbon dioxide partial pressure was frequently low, thus indicating hyperventilation; the arterial oxygen partial pressure also declined on exercise. In only 2 patients was there alveolar hypoventilation. Although other factors may be operative, the hyperventilation in some patients with COPD may be induced by an exertional decline in alveolar oxygen partial pressure. In 4 patients the exercise tidal volume exceeded the resting inspiratory capacity, indicating a decline in functional residual capacity and increased work of breathing. It is concluded that there is a need further to assess patients with COPD in respect of the association between exertional dyspnoea, alveolar ventilation and lung mechanics.


Paraspinal sinuses? Do remember renal tuberculosis.
Approximately 4%-8% of patients with pulmonary tuberculosis develop clinically significant genitourinary infection. In the case being reported, a 30-year-old female, admitted with right-sided back swelling, local pain and low-grade fever. The swelling gradually increased in size over a period of 6 months and had burst spontaneously forming a pus discharging with associated localised pain and fever bringing the patient to the hospital. X-ray lumbar spine, chest and kidney ureter bladder showed no abnormalities. Ultrasound findings were suggestive of pyonephrosis with a posterior paraspinal abscess with a sinus tract within the posterior paraspinal region. CT findings were more conclusive in suggesting the sinus tract origin. Finding of tuberculous kidney and upper ureteric stricture with sinus tract opening in the posterior paraspinal region was made on CT. Right nephrectomy was done. Histopathologically proved it to be tuberculous kidney.


Long-Term Effect of Docosahexaenoic Acid Feeding on Lipid Composition and Brain Fatty Acid-Binding Protein Expression in Rats.
Arachidonic (AA) and docosahexaenoic acid (DHA) brain accretion is essential for brain development. The impact of DHA-rich maternal diets on offspring brain fatty acid composition has previously been studied up to the weanling stage; however, there has been no follow-up at later stages. Here, we examine the impact of DHA-rich maternal and weaning diets on brain fatty acid composition at weaning and three weeks post-weaning. We report that DHA supplementation during lactation maintains high DHA levels in the brains of pups even when they are fed a DHA-deficient diet for three weeks after weaning. We show that boosting dietary DHA levels for three weeks after weaning compensates for a maternal DHA-deficient diet during lactation. Finally, our data indicate that brain fatty acid binding protein (FABP7), a marker of neural stem cells, is down-regulated in the brains of six-week pups with a high DHA:AA ratio. We propose that elevated levels of DHA in developing brain accelerate brain maturation relative to DHA-deficient brains.


The influence of bis-EMA vs bis GMA on the degree of conversion and water susceptibility of experimental composite materials.
The aim of this work was to assess the influence of the bis-EMA content on the degree of conversion (DC) and its effect on the water sorption and solubility. In a polytetrafluorethylene (PTFE) mould, 30 samples (Ø = 5 mm, height = 2 mm) of four experimental dental composite resins were cured for 10 s, 20 s and 40 s. The DC was analysed by Fourier Transform (FT)-Raman spectroscopy. To analyse sorption and solubility, six samples (Ø = 15 mm and thickness = 1 mm) of each composite (n = 72) were stored in water at 37°C for different storage periods: 24 h, 7 days and 30 days. When cured for 20 or 40 s the DC increased with the increasing content of bis-EMA. However, the presence of 15 wt% of bis-GMA did not affect the DC, except when cured with 10 s irradiation time. This study also found a correlation between the content of bis-EMA and the reduced values for sorption and solubility, for all storage times used, when the materials were cured with 20 s. The DC of mixtures with higher content of bis-EMA is affected by the presence of bis-GMA at lower energy density delivered from the curing device, suggesting that the restrictions caused by the presence of hydrogen bonds is dependent of the irradiation time used.


Efficacy of Invasive and Non-Invasive Brain Modulation Interventions for Addiction.
It is important to find new treatments for addiction due to high relapse rates despite current interventions and due to expansion of the field with non-substance related addictive behaviors. Neuromodulation may provide a new type of treatment for addiction since it can directly target abnormalities in neurocircuits. We review literature on five neuromodulation techniques investigated for efficacy in substance related and behavioral addictions: transcranial direct current stimulation (tDCS), (repetitive) transcranial magnetic stimulation (rTMS), EEG, fMRI neurofeedback and deep brain stimulation (DBS) and additionally report on effects of these interventions on addiction-related cognitive processes. While rTMS and tDCS, mostly applied at the dorsolateral prefrontal cortex, show reductions in immediate craving for various addictive substances, placebo-responses are high and long-term outcomes are understudied. The lack in well-designed EEG-neurofeedback studies despite decades of investigation impedes conclusions about its efficacy. Studies investigating fMRI neurofeedback are new and show initial promising effects on craving, but future trials are needed to investigate long-term and behavioral effects. Case studies report prolonged abstinence of opioids or alcohol with ventral striatal DBS but difficulties with patient inclusion may hinder larger, controlled trials. DBS in neuropsychiatric patients modulates brain circuits involved in reward processing, extinction and negative-reinforcement that are also relevant for addiction. To establish the potential of neuromodulation for addiction, more randomized controlled trials are needed that also investigate treatment duration required for long-term abstinence and potential synergy with other addiction interventions. Finally, future advancement may be expected from tailoring neuromodulation techniques to specific patient (neurocognitive) profiles.


Maternal Multiple Micronutrient Supplementation Stabilizes Mitochondrial DNA Copy Number in Pregnant Women in Lombok, Indonesia.
The Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) in Lombok, Indonesia showed that maternal multiple micronutrients (MMN), as compared with iron and folic acid (IFA), reduced fetal loss, early infant mortality, and low birth weight. Mitochondria play a key role during pregnancy by providing maternal metabolic energy for fetal development, but the effects of maternal supplementation during pregnancy on mitochondria are not fully understood. The aim of this study was to assess the impact of MMN supplementation on maternal mitochondrial DNA copy number (mtDNA-CN). We used archived venous blood specimens from pregnant women enrolled in the SUMMIT study. SUMMIT was a cluster-randomized double-blind controlled trial in which midwives were randomly assigned to distribute MMN or IFA to pregnant women. In this study, we selected 108 sets of paired baseline and postsupplementation samples (MMN = 54 and IFA = 54). Maternal mtDNA-CN was determined by real-time quantitative polymerase chain reaction in baseline and postsupplementation specimens. The association between supplementation type and change in mtDNA-CN was performed using rank-based estimation for linear models. In both groups, maternal mtDNA-CN at postsupplementation was significantly elevated compared with baseline (P < 0.001). The regression revealed that the MMN group had lower postsupplementation mtDNA-CN than the IFA group (β = -4.63, P = 0.003), especially for women with mtDNA-CN levels above the median at baseline (β = -7.49, P = 0.007). This effect was rapid, and observed within 33 d of initiation of supplementation (β = -7.39, P = 0.017). Maternal MMN supplementation rapidly stabilized mtDNA-CN in pregnant women who participated in SUMMIT, indicating improved mitochondrial efficiency. The data provide a mechanistic basis for the beneficial effects of MMN on fetal growth and survival, and support the transition from routine IFA to MMN supplementation.This trial was registered at www.isrctn.com as ISRCTN34151616.


Effect of Body Mass Index on Blood Transfusion in Total Hip and Knee Arthroplasty.
Perioperative blood management remains a challenge during total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of this study was to systematically examine the relationship between body mass index (BMI) and perioperative blood transfusion during THA and TKA while attempting to resolve conflicting results in previously published studies. The authors retrospectively evaluated 2399 patients, 896 of whom underwent THA and 1503 of whom underwent TKA. Various outcome variables were assessed for their relationship to BMI, which was stratified using the World Health Organization classification scheme (normal, <25 kg/m(2); overweight, 25-30 kg/m(2); obese, >30 kg/m(2)). Among patients undergoing THA, transfusion rates were 34.8%, 27.6%, and 21.9% for normal, overweight, and obese patients, respectively (P=.002). Among patients undergoing TKA, transfusion rates were 17.3%, 11.4%, and 8.3% for normal, overweight, and obese patients, respectively (P=.002). Patients with an elevated BMI have decreased rates of blood transfusion following both THA and TKA. This same cohort also loses a significantly decreased percentage of estimated blood volume. No trends were identified for a relationship between BMI and deep venous thrombosis, pulmonary embolism, myocardial infarction, discharge location, length of stay, 30-day readmission rate, and preoperative hemoglobin level. Elevated BMI was significantly associated with increased estimated blood loss in patients undergoing THA and those undergoing TKA. There was a statistically significant trend toward increased deep surgical-site infection in patients undergoing THA (P=.043). Patients with increased BMI have lower rates of blood transfusion and lose a significantly smaller percentage of estimated blood volume following THA and TKA. [Orthopedics.2016; 39(5):e844-e849.].


Iron homeostasis in plants - a brief overview.
Iron plays a crucial role in biochemistry and is an essential micronutrient for plants and humans alike. Although plentiful in the Earth's crust it is not usually found in a form readily accessible for plants to use. They must therefore sense and interact with their environment, and have evolved two different molecular strategies to take up iron in the root. Once inside, iron is complexed with chelators and distributed to sink tissues where it is used predominantly in the production of enzyme cofactors or components of electron transport chains. The processes of iron uptake, distribution and metabolism are overseen by tight regulatory mechanisms, at the transcriptional and post-transcriptional level, to avoid iron concentrations building to toxic excess. Iron is also loaded into seeds, where it is stored in vacuoles or in ferritin. This is important for human nutrition as seeds form the edible parts of many crop species. As such, increasing iron in seeds and other tissues is a major goal for biofortification efforts by both traditional breeding and biotechnological approaches.


Consistency and quality check of survey data in India.
Reliability of survey responses on topics such as utilization of health facilities by mother and child has long been a subject of concern. This paper explores consistency of responses from the same individuals over time on utilization of health services involving child delivery and child care. A sub-sample survey was carried out by an independent monitoring agency in 13 states as a part of a larger Coverage Evaluation Survey of all states of India in 2009 by UNICEF, to recheck the responses to improve data quality. Our randomly chosen sub-sample consisted of 510 questionnaires regarding mothers and 497 regarding children. Differences of responses were noted and conveyed to field agencies to rectify recurring errors. Statistical analysis was conducted to find consistency of responses. Matching between the original and rechecked responses varied. Generally, however, the overall match was greater than 90%. Findings suggest that response inconsistencies and the manner in which they are resolved are shown to have important implications for the overall estimate of indicators of utilization of health facilities. The monitoring exercise has, therefore, addressed the quality and consistency issue, which needs further consideration in large-scale surveys. Otherwise, it poses a validity threat to data quality and results on which national policy is framed.


Analysis of the Tribolium homeotic complex: insights into mechanisms constraining insect Hox clusters.
The remarkable conservation of Hox clusters is an accepted but little understood principle of biology. Some organizational constraints have been identified for vertebrate Hox clusters, but most of these are thought to be recent innovations that may not apply to other organisms. Ironically, many model organisms have disrupted Hox clusters and may not be well-suited for studies of structural constraints. In contrast, the red flour beetle, Tribolium castaneum, which has a long history in Hox gene research, is thought to have a more ancestral-type Hox cluster organization. Here, we demonstrate that the Tribolium homeotic complex (HOMC) is indeed intact, with the individual Hox genes in the expected colinear arrangement and transcribed from the same strand. There is no evidence that the cluster has been invaded by non-Hox protein-coding genes, although expressed sequence tag and genome tiling data suggest that noncoding transcripts are prevalent. Finally, our analysis of several mutations affecting the Tribolium HOMC suggests that intermingling of enhancer elements with neighboring transcription units may constrain the structure of at least one region of the Tribolium cluster. This work lays a foundation for future studies of the Tribolium HOMC that may provide insights into the reasons for Hox cluster conservation.


Calcium Signals in the Plant Nucleus: Origin and Function.
The universality of calcium as an intracellular messenger depends on the dynamics of its spatial and temporal release from calcium stores. Accumulating evidence over the past two decades supports an essential role for nuclear calcium signalling in the transduction of specific stimuli into cellular responses. This review focusses on mechanisms underpinning changes in nuclear calcium concentrations and discusses what is known so far, about the origin of the nuclear calcium signals identified, primarily in the context of microbial symbioses and abiotic stresses.


Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague.
Yersinia pestis, one of history's deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y. pestis virulence factors, F1 and LcrV, demonstrated variable levels of protection in primate pneumonic plague models. As the most likely mode of exposure in biological attack with Y. pestis is by aerosol, this raises a question of whether this parenteral vaccine will adequately protect humans against pneumonic plague. In the present study we evaluated two distinct mucosal delivery platforms for the intranasal (IN) administration of LcrV and F1 vaccine proteins, a live bacterial vector, Lactobacillus plantarum, and a Tobacco Mosaic Virus (TMV) based delivery platform. IN administration of L. plantarum expressing LcrV, or TMV-conjugated to LcrV and F1 (TMV-LcrV+TMV-F1) resulted in the similar induction of high titers of IgG antibodies and evidence of proinflammatory cytokine secretion. However, only the TMV-conjugate delivery platform protected against subsequent lethal challenge with Y. pestis. TMV-LcrV+TMV-F1 co-vaccinated mice had no discernable morbidity and no mortality, while mice vaccinated with L. plantarum expressing LcrV or rLcrV+rF1 without TMV succumbed to infection or were only partially protected. Thus, TMV is a suitable mucosal delivery platform for an F1-LcrV subunit vaccine that induces complete protection against pneumonic infection with a lethal dose of Y. pestis in mice.


Effects of social network diversity on mortality, cognition and physical function in the elderly: a longitudinal analysis of the Chicago Health and Aging Project (CHAP).
Having a larger social network has been shown to have beneficial effects on health and survival in adults, but few studies have evaluated the role of network diversity, in addition to network size. We explore whether social network diversity is associated with mortality, cognition and physical function among older black and white adults. Data are obtained from the Chicago Health and Aging Project, a longitudinal, population-based study of adults aged 65 years and older at baseline. Using Cox proportional hazards regression, we estimate the hazard of mortality by network diversity (n=6497). The association between network diversity and cognition (n=6560) and physical function (n=6561) is determined using generalised estimating equations. Models were adjusted for age, gender, race, socioeconomic status, marital status and health-related variables. In fully adjusted models, elderly with more diverse social networks had a lower risk of mortality (HR=0.93, p<0.01) compared with elderly with less diverse networks. Increased diversity in social networks was also associated with higher global cognitive function (coefficient=0.11, p<0.001) and higher physical function (coefficient=0.53, p<0.001). Social networks are particularly important for older adults as they face the greatest threats to health and depend on network relationships, more than younger individuals, to meet their needs. Increasing diversity, and not just increasing size, of social networks may be essential for improving health and survival among older adults.


Synthesis and characterization of bioconjugates of S-layer proteins.
The self-assembling proteins that form crystalline surface layers (S-layers) on many microbial species have found numerous applications due to their nanostructured nature. To devise a new method to construct surface displays that exploit S-layer self-assembly activity and nanostructural properties, we have constructed polymer bioconjugates of S-layer proteins. The conjugates formed are similar in function to the monomer alkanethiols that form self-assembled monolayers (SAMs) on gold surfaces. However, the self-assembly is driven by the protein "headgroup" that positions polymer-tethered endgroups on a surface. This paper examines the integration of protein purification, conjugation, and surface assembly that has led to the development of this new method for the formation of nanostructured surfaces. Purified S-layer proteins from Lactobacillus brevis were conjugated with small molecule probes and polymers using amine-based reactions. To keep multiple labeling of protein amine groups to acceptable levels, the conjugations were performed at pH 6.5, allowing for limited yields (24-39%) as determined by mass spectrometry and SDS-polyacrylamide gel electrophoresis. As the presence of high levels of unlabeled S-layer proteins is undesired, we have developed a protocol for further purification that employs monomeric avidin affinity chromatography. The surface self-assembly of the polymer bioconjugates onto amine-terminated microspheres was studied using epi-fluorescence, confocal, and scanning electron microscopy. The surfaces obtained exhibited homogeneous distributions of tethered molecules. Also, in cases where the modular assembly of two distinct types of tethered endgroups was accomplished, there was no evidence for phase separation in the surfaces. The modular assembly method will provide a potential route to controlling surface display density as the starting assembly conditions guide displayed endgroup concentrations in mixed molecular monolayers.


Molecular characterization of myosin IB from the lower eukaryote Entamoeba histolytica, a human parasite.
The complete amino acid sequence of the Entamoeba histolytica unconventional myosin IB (Eh-myosin IB) is reported. Sequencing of overlapping cDNA fragments reveals a single open reading frame which predicts a 130 kDa protein of 1049 aa. Eh-myosin IB presents the three characteristics domains of myosins I subclass 1. This protein presents homology with myosins IB from other amoebae, but striking homologies with vertebrate unconventional myosins were also observed. The predicted actin and ATP-binding sites are located in the head domain. The heavy chain phosphorylation region is homologous to metazoan myosins I with an acidic residue present at the phosphorylation site. In the neck domain, an IQ motif indicates potential binding of calmodulin to the myosin I heavy chain. In the tail of Eh-myosin IB the three characteristic regions of myosin I are found. A putative membrane binding domain a very short domain rich in alanine and proline we demonstrate to be functional for actin binding, and the src-homology 3 domain. The Entamoeba histolytica myosin IB is the first unconventional myosin so far described in a lower eukaryote.


Characterisation of community structure of bacteria in parallel mesophilic and thermophilic pilot scale anaerobe sludge digesters.
The aim of the present work was to compare the microbial communities of a mesophilic and a thermophilic pilot scale anaerobe sludge digester. For studying the communities cultivation independent chemotaxonomical methods (RQ and PLFA analyses) and T-RFLP were applied. Microbial communities of the mesophilic and thermophilic pilot digesters showed considerable differences, both concerning the species present, and their abundance. A Methanosarcina sp. dominated the thermophilic, while a Methanosaeta sp. the mesophilic digester among Archaea. Species diversity of Bacteria was reduced in the thermophilic digester. Based on the quinone patterns in both digesters the dominance of sulphate reducing respiratory bacteria could be detected. The PLFA profiles of the digester communities were similar though in minor components characteristic differences were shown. Level of branched chain fatty acids is slightly lower in the thermophilic digester that reports less Gram positive bacteria. The relative ratio of fatty acids characteristic to Enterobacteriaceae, Bacteroidetes and Clostridia shows differences between the two digesters: their importance generally decreased under thermophilic conditions. The sulphate reducer marker (15:1 and 17:1) fatty acids are present in low quantity in both digesters.


Enhanced Azidolysis by the Formation of Stable Ser-His Catalytic Dyad in a Glycoside Hydrolase Family 10 Xylanase Mutant.
Glycoside hydrolases require carboxyl groups as catalysts for their activity. A retaining xylanase from Streptomyces olivaceoviridis E-86 belonging to glycoside hydrolase family 10 possesses Glu128 and Glu236 that respectively function as acid/base and nucleophile. We previously developed a unique mutant of the retaining xylanase, N127S/E128H, whose deglycosylation is triggered by azide. A crystallographic study reported that the transient formation of a Ser-His catalytic dyad in the reaction cycle possibly reduced the azidolysis reaction. In the present study, we engineered a catalytic dyad with enhanced stability by site-directed mutagenesis and crystallographic study of N127S/E128H. Comparison of the Michaelis complexes of N127S/E128H with pNP-X2 and with xylopentaose showed that Ser127 could form an alternative hydrogen bond with Thr82, which disrupts the formation of the Ser-His catalytic dyad. The introduction of T82A mutation in N127S/E128H produces an enhanced first-order rate constant (6 times that of N127S/E128H). We confirmed the presence of a stable Ser-His hydrogen bond in the Michaelis complex of the triple mutant, which forms the productive tautomer of His128 that acts as an acid catalyst. Because the glycosyl azide is applicable in the bioconjugation of glycans by using click chemistry, the enzyme-assisted production of the glycosyl azide may contribute to the field of glycobiology.


Developmental and regional expression of thyroid hormone receptor genes during Xenopus metamorphosis.
A characteristic feature of the obligatory control of amphibian metamorphosis by thyroid hormones is the early acquisition of response of tadpole tissues to these hormones well before the latter are secreted, with 'exponentially' increasing hormonal sensitivity upon the onset of metamorphosis. We have therefore analyzed the expression of the two thyroid hormone receptor genes (TR alpha and beta) before, during and after metamorphosis in Xenopus tadpoles and froglets. Using non-cross-hybridizing cRNA probes for 5' and 3' sequences of Xenopus TR alpha and beta transcripts for RNAase protection assays, the two mRNAs can be detected in tadpoles as early as stage 39. Their concentration increases abruptly at stage 44 and continues to increase differentially at the onset of metamorphosis (stage 55) and through metamorphic climax at stages 58-62, after which they decline upon completion of metamorphosis at stage 66. Quantitative densitometric scanning of autoradiograms showed that, although the concentration of TR beta transcripts is about 1/30th of that of TR alpha mRNA at stages 44-48, depending on the region, it accumulates 3-10 times more rapidly than does the alpha isoform during further development. A substantial proportion of the increase in TR beta mRNA is localized to the head region of tadpoles. Using the hormone-binding domain (HBD) and 3' end of Xenopus TR alpha cRNA as probe for in situ hybridization, the highest concentration of TR transcripts in stage 44 tadpoles is seen in the brain and spinal cord. High concentrations of mRNA are also present in the intestinal epithelium and tail tip, tissues programmed for regression. At later stages (55 onwards), strong hybridization signals are also exhibited by hindlimb buds. This pattern persists through metamorphic climax, after which TR mRNAs decline in all tissues to low levels in froglets at stage 66. In developing froglets, TR transcripts were detected in large amounts in the cytoplasm of stage 1 and 2 oocytes but the rate of their accumulation did not increase with further oocyte growth. This observation raises the possibility that the response to thyroid hormones at early stages of tadpoles (42-44) may be due to TR synthesized on maternally derived mRNA. Exposure of tadpoles at premetamorphic stages (48-52) to exogenous thyroid hormone (T3) substantially enhanced the accumulation of TR mRNA, especially that of TR beta message, which could explain the accelerated increase in sensitivity of tadpoles to thyroid hormones at the onset of natural metamorphosis.(ABSTRACT TRUNCATED AT 400 WORDS)


Robot-mediated interviews--how effective is a humanoid robot as a tool for interviewing young children?
Robots have been used in a variety of education, therapy or entertainment contexts. This paper introduces the novel application of using humanoid robots for robot-mediated interviews. An experimental study examines how children's responses towards the humanoid robot KASPAR in an interview context differ in comparison to their interaction with a human in a similar setting. Twenty-one children aged between 7 and 9 took part in this study. Each child participated in two interviews, one with an adult and one with a humanoid robot. Measures include the behavioural coding of the children's behaviour during the interviews and questionnaire data. The questions in these interviews focused on a special event that had recently taken place in the school. The results reveal that the children interacted with KASPAR very similar to how they interacted with a human interviewer. The quantitative behaviour analysis reveal that the most notable difference between the interviews with KASPAR and the human were the duration of the interviews, the eye gaze directed towards the different interviewers, and the response time of the interviewers. These results are discussed in light of future work towards developing KASPAR as an 'interviewer' for young children in application areas where a robot may have advantages over a human interviewer, e.g. in police, social services, or healthcare applications.


Self-Reported Hedonism Predicts 12-Month Weight Loss After Roux-en-Y Gastric Bypass.
Research regarding psychological risk factors for reduced weight loss after bariatric surgery has yielded mixed results, especially for variables measured prior to surgery. More profound personality factors have shown better promise and one such factor that may be relevant in this context is time perspective, i.e., the tendency to focus on present or future consequences. The aim of this study was to investigate the predictive value of time perspective for 12-month weight loss after Roux-en-Y gastric bypass surgery. A total of 158 patients were included and completed self-report instruments prior to surgery. Weight loss was measured after 12 months by medical staff. Background variables as well as self-reported disordered eating, psychological distress, and time perspective were analyzed with regression analysis to identify significant predictors for 12-month weight loss. The mean BMI loss at 12 months was 14 units, from 45 to 30 kg/m2. Age, sex, and time perspective could significantly predict weight loss but only male sex and self-reported hedonism were independent risk factors for reduced weight loss in the final regression model. In this study, self-reported hedonistic time perspective proved to be a better predictor for 12-month weight loss than symptoms of disordered eating and psychological distress. It is possible that a hedonistic tendency of focusing on immediate consequences and rewards is analogous to the impaired delay discounting seen in previous studies of bariatric surgery candidates. Further studies are needed to identify whether these patients may benefit from extended care and support after surgery.


Genome expansion in early eukaryotes drove the transition from lateral gene transfer to meiotic sex.
Prokaryotes acquire genes from the environment via lateral gene transfer (LGT). Recombination of environmental DNA can prevent the accumulation of deleterious mutations, but LGT was abandoned by the first eukaryotes in favour of sexual reproduction. Here we develop a theoretical model of a haploid population undergoing LGT which includes two new parameters, genome size and recombination length, neglected by previous theoretical models. The greater complexity of eukaryotes is linked with larger genomes and we demonstrate that the benefit of LGT declines rapidly with genome size. The degeneration of larger genomes can only be resisted by increases in recombination length, to the same order as genome size - as occurs in meiosis. Our results can explain the strong selective pressure towards the evolution of sexual cell fusion and reciprocal recombination during early eukaryotic evolution - the origin of meiotic sex.


The memory function of noradrenergic activity in non-REM sleep.
There is a long-standing assumption that low noradrenergic activity during sleep reflects mainly the low arousal during this brain state. Nevertheless, recent research has demonstrated that the locus coeruleus, which is the main source of cortical noradrenaline, displays discrete periods of intense firing during non-REM sleep, without any signs of awakening. This transient locus coeruleus activation during sleep seems to occur in response to preceding learning-related episodes. In the present study, we manipulate noradrenergic activity during sleep in humans with either the α2-autoreceptor agonist clonidine or the noradrenaline reuptake inhibitor reboxetine. We show that reducing noradrenergic activity during sleep, but not during wakefulness, impairs subsequent memory performance in an odor recognition task. Increasing noradrenergic availability during sleep, in contrast, enhances memory retention. We conclude that noradrenergic activity during non-REM sleep interacts with other sleep-related mechanisms to functionally contribute to off-line memory consolidation.


[Phage therapy: a realistic weapon against multidrug resistant bacteria].
The continuous increase in antibiotic resistance among bacteria in infectious diseases associated with the lack of new antibiotics able to circumvent them are urging physicians, researchers and politicians to look for others options for treatments. Among those, phage therapy (use of natural viruses that infect bacteria, called bacteriophages) is one of the most promising approaches. In this review, we first focus on the problematic raised by multidrug resistant bacteria before addressing the main biological characteristics of bacteriophages, as well as the credibility and the relevance of phage therapy. We then introduce human applications, their potentials and limits.


Large induction of type III deiodinase expression after partial hepatectomy in the regenerating mouse and rat liver.
The deiodinase types 1 (D1) and 2 (D2) catalyze the activation of T4 to T3, whereas type 3 deiodinase (D3) catalyzes the inactivation of T3 and T4. D3 plays a key role in controlling thyroid hormone bioavailability. It is highly expressed during fetal development, but also in other processes with increased cell proliferation, e.g. in vascular tumors. Because tissue regeneration is dependent on cellular proliferation and is associated with activation of fetal genes, we evaluated deiodinase activities and mRNA expression in rat and mouse liver, as well as the local and systemic thyroid hormone status after partial hepatectomy (PH). We observed that in rats, D3 activity was increased 10-fold at 20 h and 3-fold at 48 h after PH; D3 mRNA expression was increased 3-fold at 20 h. The increase in D3 expression was associated with maximum 2- to 3-fold decreases of serum and liver T3 and T4 levels at 20 to 24 h after PH. In mice, D3 activity was increased 5-fold at 12 h, 8-fold at 24 h, 40-fold at 36 h, 15-fold at 48 h, and 7-fold at 72 h after PH. In correlation with this, D3 mRNA was highest (6-fold increase), and serum T3 and T4 were lowest at 36 h. Furthermore, as a measure for cell proliferation, 5-bromo-2'-deoxyuridine incorporation peaked at 20-24 h after PH in rats and at 36 h in mice. No significant effect on D1 activity or mRNA expression was found after PH. D2 activity was always undetectable. In conclusion, we found a large induction of hepatic D3 expression after PH that was correlated with an increased cellular proliferation and decreased serum and liver T3 and T4 levels. Our data suggest that D3 is important in the modulation of thyroid hormone levels in the regenerating liver, in which a decrease in cellular T3 permits an increase in proliferation.


Serum neurofilament light: A biomarker of neuroaxonal injury after ischemic stroke.
To explore the utility of serum neurofilament light chain (NfL) as a biomarker for primary and secondary neuroaxonal injury after ischemic stroke (IS) and study its value for the prediction of clinical outcome. We used an ultrasensitive single-molecule array assay to measure serum NfL levels in healthy controls (n = 30) and 2 independent cohorts of patients with IS: (1) with serial serum sampling at hospital arrival (n = 196), at days 2, 3, and 7 (n = 89), and up to 6 months post stroke; and (2) with standardized MRI at baseline and at 6 months post stroke, and with cross-sectional serum sampling at 6 months (n = 95). We determined the temporal profile of serum NfL levels, their association with imaging markers of neuroaxonal injury, and with clinical outcome. Patients with IS had higher serum NfL levels compared with healthy controls starting from admission until 6 months post stroke. Serum NfL levels peaked at day 7 (211.2 pg/mL [104.7-442.6], median [IQR]) and correlated with infarct volumes (day 7: partial r = 0.736, p = 1.5 × 10-15). Six months post stroke, patients with recurrent ischemic lesions on MRI (n = 19) had higher serum NfL levels compared to those without new lesions (n = 76, p = 0.002). Serum NfL levels 6 months post stroke further correlated with a quantitative measure of secondary neurodegeneration obtained from diffusion tensor imaging MRI (r = 0.361, p = 0.001). Serum NfL levels 7 days post stroke independently predicted modified Rankin Scale scores 3 months post stroke (cumulative odds ratio [95% confidence interval] = 2.35 [1.60-3.45]; p = 1.24 × 10-05). Serum NfL holds promise as a biomarker for monitoring primary and secondary neuroaxonal injury after IS and for predicting functional outcome.


Snakebite injuries treated in United States emergency departments, 2001-2004.
Venomous and nonvenomous snakes are found throughout most of the United States. While the literature on treatment is robust, there is not a current national epidemiologic profile of snakebite injuries in the United States. National estimates of such injuries treated in emergency departments (EDs) are presented along with characteristics of the affected population. Data on snakebite injuries were abstracted from the National Electronic Injury Surveillance System-All Injury Program (2001-04). Variables included age, gender, body part affected, cause, disposition, and treatment date. When available, location, intentionality of the interaction, and snake species were coded based on narrative comments. Estimates were weighted and analyzed with SPSS Complex Samples. An estimated 9873 snakebites were treated in US EDs each year between 2001 and 2004. Males were more frequently seen in the ED for snakebites than were females (males: 72.0% [95% confidence interval (CI), 68.0-75.7]; females: 28.0% [95% CI, 24.3-32.0]). Approximately 32% of patients were known to be bitten by venomous species. Overall, more than one quarter of patients were hospitalized (27.9% [95% CI, 15.9-44.2]), although 58.9% of patients with known venomous bites were hospitalized (95% CI, 41.5-74.3). While they are rare events, snakebites cause nearly 10,000 visits to EDs for treatment every year. Epidemiologic data regarding snakebites provide practicing physicians with an understanding of the population affected and can help guide public health practitioners in their prevention efforts.


Clinical and functional characterization of a novel mutation in lamin a/c gene in a multigenerational family with arrhythmogenic cardiac laminopathy.
Mutations in the lamin A/C gene (LMNA) were associated with dilated cardiomyopathy (DCM) and, recently, were related to severe forms of arrhythmogenic right ventricular cardiomyopathy (ARVC). Both genetic and phenotypic overlap between DCM and ARVC was observed; molecular pathomechanisms leading to the cardiac phenotypes caused by LMNA mutations are not yet fully elucidated. This study involved a large Italian family, spanning 4 generations, with arrhythmogenic cardiomyopathy of different phenotypes, including ARVC, DCM, system conduction defects, ventricular arrhythmias, and sudden cardiac death. Mutation screening of LMNA and ARVC-related genes PKP2, DSP, DSG2, DSC2, JUP, and CTNNA3 was performed. We identified a novel heterozygous mutation (c.418_438dup) in LMNA gene exon 2, occurring in a highly conserved protein domain across several species. This newly identified variant was not found in 250 ethnically-matched control subjects. Genotype-phenotype correlation studies suggested a co-segregation of the LMNA mutation with the disease phenotype and an incomplete and age-related penetrance. Based on clinical, pedigree, and molecular genetic data, this mutation was considered likely disease-causing. To clarify its potential pathophysiologic impact, functional characterization of this LMNA mutant was performed in cultured cardiomyocytes expressing EGFP-tagged wild-type and mutated LMNA constructs, and indicated an increased nuclear envelope fragility, leading to stress-induced apoptosis as the main pathogenetic mechanism. This study further expands the role of the LMNA gene in the pathogenesis of cardiac laminopathies, suggesting that LMNA should be included in mutation screening of patients with suspected arrhythmogenic cardiomyopathy, particularly when they have ECG evidence for conduction defects. The combination of clinical, genetic, and functional data contribute insights into the pathogenesis of this form of life-threatening arrhythmogenic cardiac laminopathy.


Rational design of reconfigurable prismatic architected materials.
Advances in fabrication technologies are enabling the production of architected materials with unprecedented properties. Most such materials are characterized by a fixed geometry, but in the design of some materials it is possible to incorporate internal mechanisms capable of reconfiguring their spatial architecture, and in this way to enable tunable functionality. Inspired by the structural diversity and foldability of the prismatic geometries that can be constructed using the snapology origami technique, here we introduce a robust design strategy based on space-filling tessellations of polyhedra to create three-dimensional reconfigurable materials comprising a periodic assembly of rigid plates and elastic hinges. Guided by numerical analysis and physical prototypes, we systematically explore the mobility of the designed structures and identify a wide range of qualitatively different deformations and internal rearrangements. Given that the underlying principles are scale-independent, our strategy can be applied to the design of the next generation of reconfigurable structures and materials, ranging from metre-scale transformable architectures to nanometre-scale tunable photonic systems.


Multi-dimensional MR spectroscopy: towards a better understanding of hepatic encephalopathy.
Hepatic encephalopathy (HE) is normally diagnosed by neuropsychological (NP) tests. The goals of this study were to quantify cerebral metabolites, separate glutamate (Glu) from glutamine (Gln) in patients with minimal hepatic encephalopathy (MHE) as well as healthy subjects using the prior-knowledge fitting (ProFit) algorithm on data acquired by two-dimensional (2D) localized correlated spectroscopy (L-COSY) on two different MR scanners, and to correlate the metabolite changes with neuropsychological (NP) tests. We studied 14 MHE patients and 18 healthy controls using a GE 1.5 T Signa MR scanner. Another group of 16 MHE patients and 18 healthy controls were studied using a Siemens 1.5 T Avanto MR scanner. The following parameters were used for L-COSY: TR/TE = 2 s/30 ms, 3 × 3 × 3 cm(3) voxel size, 96 Δt(1) increments with 8 averages per Δt(1). Using the ProFit algorithm, we were able to differentiate Gln from Glu on the GE 1.5 T data in the medial frontal white/gray matter. The ratios of myo-inositol (mI), Glu, total choline, scyllo-inositol (sI), phosphoethanolamine (PE), and total N-acetyl aspartate (NAA) showed statistically significant decline in HE patients compared to healthy controls, while the ratio of Gln was significantly increased. Similar trend was seen in the ProFit quantified Siemens 1.5 T data in the frontal and occipito-parietal white/gray regions. Among the NP domain scores, motor function, cognitive speed, executive function and the global scores showed significant differences. Excellent correlations between various NP domains and metabolite ratios were also observed. ProFit based cerebral metabolite quantitation enhances the understanding and basis of the current hypothesis of MHE.


Unusual but sound minds: mental health indicators in spiritual individuals.
Previous research has linked certain types of modern spirituality, including New Age and Pagan, with either benign schizotypy or insecure attachment. While the first view emphasizes a positive aspect of spiritual believers' mental health (benign schizotypy), the second view emphasizes a negative aspect, namely the unhealthy emotional compensation associated with an insecure attachment style. This study addresses these two conflicting views by comparing a sample of modern spiritual individuals (N = 114) with a contrast group of traditional religious believers (N = 86). Measures of schizotypy and attachment style were combined with mental health scales of anxiety and depression. We further assessed death anxiety to determine whether modern spiritual beliefs fulfilled a similar function as traditional religious beliefs in the reduction of existential threat. Our results support a psychological contiguity between traditional and modern spiritual believers and reinforce the need to de-stigmatize spiritual ideas and experiences. Using hierarchical regression, we showed that unusual experiences and ideas are the major predictor of engagement in modern spiritual practices. Anxiety, depression variables, and insecure attachment were not significant predictors of spirituality or correlated with them; on the other hand, the results show that spiritual believers report high social support satisfaction and this variable predicts involvement in modern spirituality. Further, spiritual practices were negatively correlated with and negatively predicted by death anxiety scores. Overall, the results strengthen the association between modern spirituality, good mental health, and general well-being.


Corals chemically cue mutualistic fishes to remove competing seaweeds.
Corals in the genus Acropora generate much of the structural complexity upon which coral reefs depend, but they are susceptible to damage from toxic seaweeds. Acropora nasuta minimizes this damage by chemically cuing symbiotic goby fishes (Gobiodon histrio or Paragobiodon echinocephalus) to remove the toxic seaweed Chlorodesmis fastigiata. Within minutes of seaweed contact, or contact from only seaweed chemical extract, the coral releases an odor that recruits gobies to trim the seaweed and dramatically reduce coral damage that would otherwise occur. In turn, chemically defended gobies become more toxic after consumption of this noxious alga. Mutualistic gobies and corals appear to represent a marine parallel to terrestrial ant-plants, in that the host provides shelter and food in return for protection from natural enemies.


Neurodevelopment and in utero antiretroviral exposure of HIV-exposed uninfected infants.
Antiretroviral (ARV) drugs are routinely provided to HIV-infected pregnant women to prevent HIV mother-to-child transmission. Although ARV use has significantly reduced mother-to-child transmission to <2% in the United States, it remains crucial to monitor uninfected infants and children for adverse consequences of in utero ARV exposure. We studied neurodevelopmental function in HIV-exposed uninfected children who were enrolled in Pediatric AIDS Clinical Trials Group 219/219C, a multisite, prospective, cohort study. Mental and motor functioning were assessed with the Bayley Scales of Infant Development (BSID), first and second editions. ARV exposure information was collected during pregnancy or within the first years of life. Linear regression methods were used to evaluate the association of in utero ARV exposure on Mental Developmental Index and Psychomotor Developmental Index at 2 years of age, controlling for demographic factors (age, gender, and race/ethnicity) and potential confounders: test version, primary language, primary caregiver, caregiver education level, low birth weight, geographic and urban/rural location, birth year, and maternal illicit drug use. Among 1840 infants who were born between 1993 and 2006, 1694 (92%) were exposed to ARV in utero and 146 (8%) were not exposed. After controlling for confounders, children who were exposed in utero to any ARV did not have lower Mental Developmental Index and Psychomotor Developmental Index scores than unexposed children. Among low birth weight infants, significantly higher BSID scores were observed for prenatally ARV-exposed than unexposed children. Maternal illicit drug use was reported for 17% of mothers but was not associated with BSID scores. Mental and motor functioning scores were not lower for infants with in utero ARV exposure compared with no exposure. Although these results are reassuring, continued evaluation of uninfected children with in utero ARV exposure for long-term adverse outcomes is important.


Beta₂-agonists for exercise-induced asthma.
It is well known that physical exercise can trigger asthma symptoms and can induce bronchial obstruction in people without clinical asthma. International guidelines on asthma management recommend the use of beta2-agonists at any stage of the disease. At present, however, no consensus has been reached about the efficacy and safety of beta2-agonists in the pretreatment of exercise-induced asthma and exercise-induced bronchoconstriction. For the purpose of the present review, both of these conditions are referred to by the acronymous EIA, independently from the presence of an underlying chronic clinical disease. To assess the effects of inhaled short- and long-acting beta2-agonists, compared with placebo, in the pretreatment of children and adults with exercise-induced asthma (or exercise-induced bronchoconstriction). Trials were identified by electronic searching of the Cochrane Airways Group Specialised Register of Trials and by handsearching of respiratory journals and meetings. Searches are current as of August 2013. We included randomised, double-blind, placebo-controlled trials of any study design, published in full text, that assessed the effects of inhaled beta2-agonists on EIA in adults and children. We excluded studies that did not clearly state diagnostic criteria for EIA. We used standard methodological procedures as expected by The Cochrane Collaboration. We included 53 trials consisting of 1139 participants. Forty-eight studies used a cross-over design, and five were performed in accordance with a parallel-group design. Forty-five studies addressed the effect of a single beta2-agonist administration, and eight focused on long-term treatment. We addressed these two different intervention regimens as different comparisons.Among primary outcomes for short-term administration, data on maximum fall in forced expiratory volume in 1 second (FEV1) showed a significant protective effect for both short-acting beta-agonists (SABA) and long-acting beta-agonists (LABA) compared with placebo, with a mean difference of -17.67% (95% confidence interval (CI) -19.51% to -15.84%, P = 0.00001, 799 participants from 72 studies). The subgroup analysis of studies performed in adults compared with those performed in children showed high heterogeneity confined to children, despite the comparable mean bronchoprotective effect.Secondary outcomes on other pulmonary function parameters confirmed a more positive and protective effect of beta2-agonists on EIA compared with placebo. Occurrence of side effects was not significantly different between beta2-agonists and placebo.Overall evaluation of the included long-term studies suggests a beta2-agonist bronchoprotective effect for the first dose of treatment. However, long-term use of both SABA and LABA induced the onset of tolerance and decreased the duration of drug effect, even after a short treatment period. Evidence of low to moderate quality shows that beta2-agonists, both SABA and LABA, when administered in a single dose, are effective and safe in preventing EIA.Long-term regular administration of inhaled beta2-agonists induces tolerance and lacks sufficient safety data. This finding appears to be of particular clinical relevance in view of the potential for prolonged regular use of beta2-agonists as monotherapy in the pretreatment of EIA, despite the warnings of drug agencies (FDA, EMA) regarding LABA.


Alterations in erythrocyte fatty acid composition in preclinical Alzheimer's disease.
Brain and blood fatty acids (FA) are altered in Alzheimer's disease and cognitively impaired individuals, however, FA alterations in the preclinical phase, prior to cognitive impairment have not been investigated previously. The current study therefore evaluated erythrocyte FA in cognitively normal elderly participants aged 65-90 years via trans-methylation followed by gas chromatography. The neocortical beta-amyloid load (NAL) measured via positron emission tomography (PET) using ligand 18F-Florbetaben, was employed to categorise participants as low NAL (standard uptake value ratio; SUVR < 1.35, N = 65) and high NAL or preclinical AD (SUVR ≥ 1.35, N = 35) wherein, linear models were employed to compare FA compositions between the two groups. Increased arachidonic acid (AA, p < 0.05) and decreased docosapentaenoic acid (DPA, p < 0.05) were observed in high NAL. To differentiate low from high NAL, the area under the curve (AUC) generated from a 'base model' comprising age, gender, APOEε4 and education (AUC = 0.794) was outperformed by base model + AA:DPA (AUC = 0.836). Our findings suggest that specific alterations in erythrocyte FA composition occur very early in the disease pathogenic trajectory, prior to cognitive impairment. As erythrocyte FA levels are reflective of tissue FA, these alterations may provide insight into the pathogenic mechanism(s) of the disease and may highlight potential early diagnostic markers and therapeutic targets.