Different intensities of glycaemic control for pregnant women with pre-existing diabetes.
The optimal glycaemic control target in pregnant women with pre-existing diabetes is unclear, although there is a clear link between high glucose concentrations and adverse birth outcomes. To assess the effects of different intensities of glycaemic control in pregnant women with pre-existing type 1 or type 2 diabetes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2012). We included randomised controlled trials comparing different glycaemic control targets in pregnant women with pre-existing diabetes. Two review authors assessed trial eligibility and risk of bias, and extracted data. We included three trials all in women with type 1 diabetes (223 women and babies), and all with a high risk of bias. Two trials compared very tight (3.33 to 5.0 mmol/L fasting blood glucose (FBG)) with tight-moderate (4.45 to 6.38) glycaemic control targets, with one trial of 22 babies reporting no perinatal deaths or serious perinatal morbidity. In the same trial, there were two birth defects in the very tight and none in the tight-moderate group with no significant differences in caesarean section between groups (risk ratio 0.92, 95% confidence interval (CI) 0.49 to 1.73). In these two trials glycaemic control was not significantly different between the very tight and tight-moderate groups by the third trimester, although one trial of 22 women found significantly less maternal hypoglycaemia in the tight-moderate group.In a trial of 60 women and babies comparing tight (≤ 5.6 mmol/L FBG); moderate (5.6 to 6.7); and loose (6.7 to 8.9) glycaemic control targets, there were two neonatal deaths in the loose and none in the tight or moderate groups. There were significantly fewer women with pre-eclampsia, fewer caesareans and fewer birthweights greater than 90th centile in the combined tight-moderate compared with the loose group. In a very limited body of evidence, few differences in outcomes were seen between very tight and tight-moderate glycaemic control targets in pregnant women with pre-existing type 1 diabetes, including actual glycaemic control achieved. There is evidence of harm (increased pre-eclampsia, caesareans and birthweights greater than 90th centile) for 'loose' control (FBG above 7 mmol/L). Future trials comparing interventions, rather than glycaemic control targets, may be more feasible particularly for pregnant women with type 2 diabetes.


The degradation of L-histidine, imidazolyl-L-lactate and imidazolylpropionate by Pseudomonas testosteroni.
1. Imidazol-5-ylpropionate and imidazol-5-yl-lactate are degraded by Pseudomonas testosteroni via inducible pathways. 2. Growth on either compound as the sole source of carbon results in the induction of the enzymes for histidine catabolism. 3. The pathway of histidine degradation in this organism, a non-fluorescent Pseudomonad, is shown to be the same as that operating in Pseudomonas fluorescens and Pseudomonas putida. It consists of the successive formation of urocanate, imidazol-4-on-5-ylpropionate, N-formimino-l-glutamate, N-formyl-l-glutamate and glutamate. 4. Whole cells of P. testosteroni accumulate urocanate in the reaction mixture when incubated with imidazolylpropionate, but only after an adaptive lag period which is removed by previous growth on imidazolylpropionate as the source of carbon. 5. Imidazolyl-lactate is oxidized to imidazolylpyruvate, which then gives rise to histidine by specific transamination with l-glutamate. 6. Cells grown on histidine, urocanate or imidazolylpropionate are also able to degrade imidazolyllactate. 7. Mutants lacking urocanase are unable to grow on imidazolylpropionate, imidazolyl-lactate, histidine or urocanate. One with impaired histidase activity cannot utilize histidine or imidazolyl-lactate, but grows normally on imidazolylpropionate or urocanate. A mutant unable to grow on imidazolylpropionate is indistinguishable from the wild-type with respect to growth on histidine, imidazolyl-lactate or urocanate. 8. Thus it is established that imidazolyl-lactate is metabolized via histidine whereas imidazolylpropionate enters the histidine degradation pathway after conversion into urocanate.


Automated segmentation of mouse brain images using extended MRF.
We introduce an automated segmentation method, extended Markov random field (eMRF), to classify 21 neuroanatomical structures of mouse brain based on three dimensional (3D) magnetic resonance images (MRI). The image data are multispectral: T2-weighted, proton density-weighted, diffusion x, y and z weighted. Earlier research (Ali, A.A., Dale, A.M., Badea, A., Johnson, G.A., 2005. Automated segmentation of neuroanatomical structures in multispectral MR microscopy of the mouse brain. NeuroImage 27 (2), 425-435) successfully explored the use of MRF for mouse brain segmentation. In this research, we study the use of information generated from support vector machine (SVM) to represent the probabilistic information. Since SVM in general has a stronger discriminative power than the Gaussian likelihood method and is able to handle nonlinear classification problems, integrating SVM into MRF improved the classification accuracy. The eMRF employs the posterior probability distribution obtained from SVM to generate a classification based on the MR intensity. Secondly, the eMRF introduces a new potential function based on location information. Third, to maximize the classification performance, the eMRF uses the contribution weights optimally determined for each of the three potential functions: observation, location and contextual functions, which are traditionally equally weighted. We use the voxel overlap percentage and volume difference percentage to evaluate the accuracy of eMRF segmentation and compare the algorithm with three other segmentation methods--mixed ratio sampling SVM (MRS-SVM), atlas-based segmentation and MRF. Validation using classification accuracy indices between automatically segmented and manually traced data shows that eMRF outperforms other methods.


Hydrogenated ZnO core-shell nanocables for flexible supercapacitors and self-powered systems.
Although MnO2 is a promising material for supercapacitors (SCs) due to its excellent electrochemical performance and natural abundance, its wide application is limited by poor electrical conductivity. Inspired by our results that the electrochemical activity and electrical conductivity of ZnO nanowires were greatly improved after hydrogenation, we designed and fabricated hydrogenated single-crystal ZnO@amorphous ZnO-doped MnO2 core-shell nanocables (HZM) on carbon cloth as SC electrodes, showing excellent performance such as areal capacitance of 138.7 mF/cm(2) and specific capacitance of 1260.9 F/g. Highly flexible all-solid-state SCs were subsequently assembled with these novel HZM electrodes using polyvinyl alcohol/LiCl electrolyte. The working devices achieved very high total areal capacitance of 26 mF/cm(2) and retained 87.5% of the original capacitance even after 10 000 charge/discharge cycles. An integrated power pack incorporating series-wound SCs and dye-sensitized solar cells was demonstrated for stand-alone self-powered systems.


ortho-Phenylene oligomers with terminal push-pull substitution.
ortho-Phenylenes are an emerging class of helical oligomers and polymers. We have synthesized a series of push-pull-substituted o-phenylene oligomers (dimethylamino/nitro) up to the octamer. Conformational analysis of the hexamer using a combination of low-temperature NMR spectroscopy and ab initio predictions of (1)H NMR chemical shifts indicates that, like other o-phenylenes, they exist as compact helices in solution. However, the substituents are found to have a significant effect on their conformational behavior: the nitro-functionalized terminus is 3-fold more likely to twist out of the helix. Protonation of the dimethylamino group favors the helical conformer. UV/vis spectroscopy indicates that the direct charge-transfer interaction between the push-pull substituents attenuates quickly compared to other conjugated systems, with no significant charge-transfer band for oligomers longer than the trimer. On protonation of the dimethylamino group, significant bathochromic shifts with increasing oligomer length are observed: the effective conjugation length is 9 repeat units, more than twice that of the parent oligomer. This behavior may be rationalized through examination of the frontier molecular orbitals of these compounds, which exhibit greater delocalization after protonation, as shown by DFT calculations.


Tuning the SERS activity and plasmon-driven reduction of p-nitrothiophenol on a Ag@MoS2 film.
The combination of plasmonic metal nanostructures with semiconductors has been widely applied in plasmon-driven photocatalysis. Here, a uniform Ag@MoS2 hybrid film is fabricated by depositing MoS2 onto a thin Ag film via the pulsed laser deposition (PLD) technique. The thickness and crystallinity of MoS2 can be adjusted by controlling the PLD deposition time and temperature, respectively. With the assistance of surface-enhanced Raman scattering (SERS) analysis, the Raman enhancement uniformity of the substrate and plasmon-driven reaction of p-nitrothiophenol (PNTP) dimerizing into p,p'-dimercaptobenzene (DMAB) are carefully studied on Ag@MoS2 film substrates with different MoS2 crystallinities. The Raman enhancement decreases with increased MoS2 thickness, due to the weakened electromagnetic field enhancement as suggested by finite-difference time-domain (FDTD) simulations. The increased crystallinity of MoS2 can efficiently accelerate the hot electron transfer process, resulting in the enhancement of SERS activity and the improved efficiency of the plasmon-driven reaction. This study may pave the way for the design of other uniform metal-semiconductor hybrids for use as SERS substrates and photocatalysts.


Pharmacologic treatment of downstream of tyrosine kinase 7 congenital myasthenic syndrome.
Congenital myasthenic syndromes (CMSs) are increasingly recognized as causes of muscle fatigue and weakness. However, treatment of individual syndromes has been described only in small case series. To analyze the information published thus far concerning the effect of pharmacologic treatment of one of the most common subtypes of CMS, downstream of tyrosine kinase 7 (DOK7) CMS. In a search of the PubMed database, we found 16 publications describing the response to medication in 122 individuals with DOK7 deficiency. The last search was performed August 15, 2013. If more than 1 article had been published by the same group, a comparison of the participants in the studies was made, and data appearing more than once were excluded. Positive effects were observed in 6 of 66 patients who received an acetylcholinesterase inhibitor, 65 of 69 patients who received ephedrine or salbutamol, 18 of 29 who were given 3,4-diaminopyridine, and 13 of 16 individuals who received a combination of these drugs. Our analysis found no evidence that age at disease onset, age at treatment start, drug dosage, or mutation type influenced treatment results. The magnitude of treatment effect with ephedrine or salbutamol seems to increase gradually, peaking after approximately 6 to 8 months. Treatment with acetylcholinesterase inhibitors resulted in worsened conditions for most patients. This analysis suggests that (1) ephedrine or salbutamol is the first choice of treatment in DOK7 CMS; (2) 3,4-diaminopyridine may provide additional benefi; (3) it is never too late to initiate treatment; and (4) in contrast to acquired myasthenia gravis, treatment with acetylcholinesterase inhibitors should be avoided in DOK7 CMS.


Design, synthesis and biological evaluation of 4-piperidin-4-yl-triazole derivatives as novel histone deacetylase inhibitors.
Histone deacetylase is an important member of epigenetics and a well validated target for anti-cancer drug discovery. In this study, we designed and synthesized a series of twenty-one novel hydroxamic acid-based histone deacetylase inhibitors with 4-piperidin-4-yl-triazole as the core skeleton. Most target compounds displayed excellent inhibition rates toward histone deacetylases at the concentration of 1 μM. Among them, the inhibition rates of two compounds MH1-18 and MH1-21 exceeded 90%. Furthermore, these two compounds selectively inhibited the activity of histone deacetylase 6 with low IC50 values. The high potency of them toward histone deacetylase 6 was rationalized by molecular docking studies. We found that MH1-18 and MH1-21 moderately inhibited the proliferation of four human cancer cell lines SGC-7901, NCI-H226, MCF-7, and HL-60. However, MH1-21 showed potent efficacy in suppressing the migration of MCF-7 cells. Results obtained in the current study shed light on designing potent HDAC6 inhibitors as anti-cancer agents.


Successful treatment with Ipilimumab and Interleukin-2 in two patients with metastatic melanoma and systemic autoimmune disease.
Two patients were treated with immunotherapy for metastatic malignant melanoma (MM) despite suffering from systemic autoimmune disease, i.e., ulcerative colitis (UC) and Behcets disease (BD), respectively. Both patients benefitted from the treatment. The patient with UC achieved partial remission of all measurable parameters after treatment with Ipilimumab, while the patient with BD achieved a complete remission of MM after treatment with Interleukin-2 (IL-2) and Interferon-α (IFN-α). Moreover, no aggravation of symptoms related to the autoimmune diseases was seen during treatment, in contrast, clinical indications of improvement were observed. These two cases illustrate that the presence of autoimmune disease does not necessarily predict increased autoimmune toxicity in connection with immunotherapy. They also raise the question of whether autoimmune disease should continue to be an absolute exclusion criterion for treatment of MM with immunotherapy. Consequently, given the poor prognosis of refractory MM, immunotherapies need to be taken into consideration even in cases of autoimmune comorbidity due to the potential long-term benefit that these therapies offer to MM patients.


A method for radioligand binding assays using a robotic workstation.
Radioligand binding assays provide a powerful tool for screening drug candidates at many receptors. We present a method utilizing a robotic workstation, the Biomek 1000, which automates the tedious and repetitive tasks of these assays. First, the robot handles the serial dilution of up to 8 drugs with 11 concentrations per drug. The sequential addition of diluting buffer, non-radioactively labeled ligand, radioactive ligand, and finally the tissue homogenate or membrane preparation, is fully automated. A novel rack design allows the use of tubes with a maximum capacity of 2 ml, providing a total assay volume of 1 ml. Final filtration on a Brandel cell harvester outfitted with a uniquely designed head allows for processing of 48 samples simultaneously from the rack holder. We have employed this method for the determination of equilibrium dissociation constants (Kds) for drugs at the 5 human muscarinic acetylcholine receptor subtypes expressed in cultured cells, as well as histamine H1, dopamine D2, serotonin 5HT1A, alpha 1- and alpha 2-adrenergic receptors in human brain tissue homogenates. Our results compare favorably with manual methods reported for these receptors, and exhibit a very high degree of reproducibility and throughput, with a minimum of operator input.


How do mindfulness-based cognitive therapy and mindfulness-based stress reduction improve mental health and wellbeing? A systematic review and meta-analysis of mediation studies.
Given the extensive evidence base for the efficacy of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT), researchers have started to explore the mechanisms underlying their therapeutic effects on psychological outcomes, using methods of mediation analysis. No known studies have systematically reviewed and statistically integrated mediation studies in this field. The present study aimed to systematically review mediation studies in the literature on mindfulness-based interventions (MBIs), to identify potential psychological mechanisms underlying MBCT and MBSR's effects on psychological functioning and wellbeing, and evaluate the strength and consistency of evidence for each mechanism. For the identified mechanisms with sufficient evidence, quantitative synthesis using two-stage meta-analytic structural equation modelling (TSSEM) was used to examine whether these mechanisms mediate the impact of MBIs on clinical outcomes. This review identified strong, consistent evidence for cognitive and emotional reactivity, moderate and consistent evidence for mindfulness, rumination, and worry, and preliminary but insufficient evidence for self-compassion and psychological flexibility as mechanisms underlying MBIs. TSSEM demonstrated evidence for mindfulness, rumination and worry as significant mediators of the effects of MBIs on mental health outcomes. Most reviewed mediation studies have several key methodological shortcomings which preclude robust conclusions regarding mediation. However, they provide important groundwork on which future studies could build.


Prognostic models for chronic kidney disease: a systematic review and external validation.
Accurate risk prediction is needed in order to provide personalized healthcare for chronic kidney disease (CKD) patients. An overload of prognosis studies is being published, ranging from individual biomarker studies to full prediction studies. We aim to systematically appraise published prognosis studies investigating multiple biomarkers and their role in risk predictions. Our primary objective was to investigate if the prognostic models that are reported in the literature were of sufficient quality and to externally validate them. We undertook a systematic review and appraised the quality of studies reporting multivariable prognosis models for end-stage renal disease (ESRD), cardiovascular (CV) events and mortality in CKD patients. We subsequently externally validated these models in a randomized trial that included patients from a broad CKD population. We identified 91 papers describing 36 multivariable models for prognosis of ESRD, 50 for CV events, 46 for mortality and 17 for a composite outcome. Most studies were deemed of moderate quality. Moreover, they often adopted different definitions for the primary outcome and rarely reported full model equations (21% of the included studies). External validation was performed in the Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners trial (n = 788, with 160 events for ESRD, 79 for CV and 102 for mortality). The 24 models that reported full model equations showed a great variability in their performance, although calibration remained fairly adequate for most models, except when predicting mortality (calibration slope >1.5). This review shows that there is an abundance of multivariable prognosis models for the CKD population. Most studies were considered of moderate quality, and they were reported and analysed in such a manner that their results cannot directly be used in follow-up research or in clinical practice.


Contribution of TonB- and Feo-mediated iron uptake to growth of Salmonella typhimurium in the mouse.
We examined the role of iron(II) and iron(III) uptake, mediated by FeoB and TonB, respectively, in infection of the mouse by Salmonella typhimurium. The S. typhimurium feoB gene, encoding a homolog of an Escherichia coli cytoplasmic membrane iron(II) permease, was cloned, and a mutant was generated by allelic exchange. In addition, an S. typhimurium tonB mutant was constructed. Together these two mutations inactivate all known iron uptake systems of S. typhimurium. We examined the abilities of these mutants to grow in vitro and in different compartments of the host. Mutants in feoB were outcompeted by the wild type during mixed colonization of the mouse intestine, but the feoB mutation did not attenuate S. typhimurium for oral or intraperitoneal infection of mice. The tonB mutation attenuated S. typhimurium for infection of mice by the intragastric route but not the intraperitoneal route, and the mutant was recovered in lower numbers from the Peyer's patches and mesenteric lymph nodes than the wild type. These results indicate that TonB-mediated iron uptake contributes to colonization of the Peyer's patches and mesenteric lymph nodes but not the liver and spleen of the mouse. The tonB feoB double mutant, given intraperitoneally, was able to infect the liver and spleen at wild-type doses, indicating that additional iron acquisition systems are used during growth at systemic sites of infection.


Host Range of Fusarium Dieback and Its Ambrosia Beetle (Coleoptera: Scolytinae) Vector in Southern California.
The polyphagous shot hole borer (PSHB) is an invasive ambrosia beetle that forms a symbiosis with a new, as-yet-undescribed Fusarium sp., together causing Fusarium dieback on avocado and other host plants in California and Israel. In California, PSHB was first reported on black locust in 2003 but there were no records of fungal damage until 2012, when a Fusarium sp. was recovered from the tissues of several backyard avocado trees infested with PSHB in Los Angeles County. The aim of this study was to determine the plant host range of the beetle-fungus complex in two heavily infested botanical gardens in Los Angeles County. Of the 335 tree species observed, 207 (62%), representing 58 plant families, showed signs and symptoms consistent with attack by PSHB. The Fusarium sp. was recovered from 54% of the plant species attacked by PSHB, indicated by the presence of the Fusarium sp. at least at the site of the entry hole. Trees attacked by PSHB included 11 species of California natives, 13 agriculturally important species, and many common street trees. Survey results also revealed 19 tree species that function as reproductive hosts for PSHB. Additionally, approximately a quarter of all tree individuals planted along the streets of southern California belong to a species classified as a reproductive host. These data suggest the beetle-disease complex potentially may establish in a variety of plant communities locally and worldwide.


Prospective Evaluation of the Accuracy of MDCT Angiography for Living Kidney Donor.
In donor nephrectomy, it is important to understand the exact anatomy of the blood vessels during minimally invasive surgery. We prospectively analyzed the accuracy of the vessel structures obtained by use of 64-row multi-detector computed tomography (MDCT) angiography compared with the actual vessel structure observed during surgery. We analyzed 238 patients who underwent donor nephrectomy from July 2007 to August 2010. Before the operation, MDCT angiography was performed, and after the operation, the surgeons themselves wrote the protocol. The ipsilateral artery, the number of veins, the association with the run of the hilar vessel, and other vascular anomalies in computed tomography (CT) angiography and in the donor protocol were summarized. Among 238 patients, nephrectomy was performed on the left side in 199 patients. The accuracy of MDCT for the artery and the vein was 93.3% and 92.4%, respectively. Accuracy did not differ significantly on the left and right sides (artery: p=0.124; vein: p=0.174). In 199 patients, the CT findings for the lumbar vein were compared with the surgical findings. The overall accuracy was shown to be 84.9%, and the accuracy of the group drained to the inferior vena cava (54%) was significantly different (p<0.01) from that of the group drained to the renal vein (98.6%). Thus, it may be necessary to pay close attention to the interpretation of the findings for the lumbar vein. MDCT angiography is important for understanding the exact anatomy of blood vessels before minimally invasive surgery. We showed that 64-channel MDCT has high accuracy in the main vessel and hilar vessels. However, close attention to the interpretation of the CT findings for the lumbar vein may be required.


A gene transfer vector-cell line system for complete functional complementation of adenovirus early regions E1 and E4.
The improvements to adenovirus necessary for an optimal gene transfer vector include the removal of virus gene expression in transduced cells, increased transgene capacity, complete replication incompetence, and elimination of replication-competent virus that can be produced during the growth of first-generation adenovirus vectors. To achieve these aims, we have developed a vector-cell line system for complete functional complementation of both adenovirus early region 1 (E1) and E4. A library of cell lines that efficiently complement both E1 and E4 was constructed by transforming 293 cells with an inducible E4-ORF6 expression cassette. These 293-ORF6 cell lines were used to construct and propagate viruses with E1 and E4 deleted. While the construction and propagation of AdRSV beta gal.11 (an E1-/E4- vector engineered to contain a deletion of the entire E4 coding region) were possible in 293-ORF6 cells, the yield of purified virus was depressed approximately 30-fold compared with that of E1- vectors. The debilitation in AdRSV beta gal.11 vector growth was found to correlate with reduced fiber protein and mRNA accumulation. AdCFTR.11A, a modified E1-/E4- vector with a spacer sequence placed between late region 5 and the right inverted terminal repeat, efficiently expressed fiber and grew with the same kinetic profile and virus yield as did E1- vectors. Moreover, purified AdCFTR.11A yields were equivalent to E1- vector levels. Since no overlapping sequences exist in the E4 regions of E1-/E4- vectors and 293-ORF6 cell lines, replication-competent virus cannot be generated by homologous recombination. In addition, these second-generation E1-/E4- vectors have increased transgene capacity and have been rendered virus replication incompetent outside of the new complementing cell lines.


Scientific advances and challenges in safety evaluation of food packaging materials: Workshop proceedings.
Packaging is an indispensable component of the food manufacturing and food supply process. This scientific workshop was convened to bring together scientists from government, academia, and industry to discuss the state of the science regarding the safety of food packaging, prompted by rapidly advancing research to improve food packaging that continues to impact packaging technology, toxicology, exposure, risk assessment, and sustainability. The opening session focused on scientific challenges in the safety assessment of food packaging materials. Experts discussed migration of contaminant residues from food packaging, presented emerging analytical methods for safety evaluation, and highlighted the use of improved exposure assessment models and new packaging technologies. The workshop then focused on recycled packaging and sustainability. Experts also discussed application of recycled materials in food packaging, recycling processes, identification of contaminant residues from recycled packaging, and challenges in safety assessment of recycled materials. The workshop concluded with panel discussions that highlighted the challenges and research gaps in food packaging. Overall, there is a need to better understand and define "contaminants in food packaging" for developing appropriate testing methods needed to establish the significance of the migration levels of these contaminants and conduct appropriate safety assessments in this rapidly evolving field.


Plasmodium falciparum infection and clinical indicators in relation to net coverage in central Côte d'Ivoire.
Sleeping under a net, particularly a long-lasting insecticidal net (LLIN), is associated with reduced malaria morbidity and mortality, but requires high coverage and adherence. In this study, parasitologically confirmed Plasmodium falciparum infection and a clinical indicator (i.e. fever) were measured among children in three villages of central Côte d'Ivoire (Bozi, N'Dakonankro and Yoho) and associations with net coverage explored. In Bozi and Yoho, LLINs were provided by the national malaria control programme, prior to the study and an additional catch-up coverage was carried out in Bozi. In N'Dakonankro, no net intervention was conducted. Three cross-sectional surveys were carried out; two in the dry season (February 2010 and November 2011) and one in the rainy season (May 2012). Among 897 children aged <15 years, P. falciparum infection was determined by microscopy and a rapid diagnostic test (RDT). Fever was defined as an axillary temperature ≥37.5°C. A questionnaire was administered to obtain demographic data and net usage. The proportion of children infected with P. falciparum according to microscopy in the third survey was 74%, 81% and 82% in Yoho, N'Dakonankro and Bozi, respectively. Meanwhile, 46% of the children in N'Dakonankro, 44% in Bozi and 33% in Yoho slept under a net. The risk of P. falciparum infection did not differ between net-sleepers and non-net-sleepers. Fewer children had parasitaemia ≥1,000 parasites/μl of blood in Bozi in the third compared to the first survey. Fever was poorly correlated with P. falciparum infection. The risk of P. falciparum infection did not depend on the village of residence, presence of fever or sleeping under LLIN the night before the survey. Conversely, it was higher in the rainy season and among older children. In an area where P. falciparum is highly prevalent, the use of nets was associated with significantly lower levels of parasitaemia. The apparent lack of effect on P. falciparum infection and fever might be explained by the relatively low net coverage in Bozi and Yoho and the relatively short period (<2 years) during which the impact of nets was measured.


Risk factors for the elimination of endurance horses from competition.
To identify risk factors such as signalment, previous competition miles completed, ride characteristics, and physical examination variables associated with the elimination of horses during endurance competitions. Retrospective observational study. Veterinary records for 3,493 endurance horse competition starts. Records were requested of all sanctioned 2007 endurance horse competitions in the United States. Only rides that provided data from all horses were included. The horse's signalment, previous endurance competition record, specific ride characteristics, weight division (ie, based on rider's weight with tack), and physical examination variables throughout the ride were included for analysis. Examination variables were separated into abnormalities occurring prior to the start of the ride, during the first half of the ride, and during the second half of the ride. Multivariate logistic regression was used to identify risk factors for overall elimination and elimination subcategories (lameness and metabolic). Specific breeds, the heavyweight division, and distance of the ride were all associated with an increased risk of elimination. A variety of examination variables prior to the start of the ride and during the ride were associated with elimination and included heart rate, cardiac recovery index, and abnormal gastrointestinal sounds. Results suggested that specific risk factors were associated with elimination of horses from endurance competitions. These factors may be used to help identify horses at higher risk for elimination and prevent morbidity associated with competition.


Two common chromosome 8q24 variants are associated with increased risk for prostate cancer.
Two variants (rs1447295/DG8S737) of chromosome 8q24 were recently reported to be associated with increased risk of prostate cancer (PC). To confirm this finding, we genotyped and compared the frequencies of these polymorphisms among 1,121 Caucasian men with PC (435 men with familial PC, 491 men with sporadic PC, and 195 men with aggressive PC) to 545 population-based controls. For the single nucleotide polymorphism marker rs1447295, frequencies of the minor allele (A) were 10.3% in controls, 11.9% in sporadic cases, 16.7% in familial cases, and 17.2% in aggressive cases. Compared with controls, the A allele was significantly more common in both familial PC [odds ratios (OR), 1.93; 95% confidence intervals (95% CI), 1.37-2.72; P = 0.0004] and aggressive PC (OR, 1.87; 95% CI, 1.28-2.74; P = 0.0005) but not for sporadic PC (OR, 1.16; 95% CI, 0.85-1.58; P = 0.25). Although the A allele was more frequent in aggressive PC cases when compared with controls, the allele frequencies were similar among cases with high- and low-grade PC (Gleason grades <7 and >/=7, respectively). For the microsatellite marker DG8S737, the -8 allele was significantly more frequent in familial PC (OR, 1.68; 95% CI, 1.09-2.60; P = 0.031), whereas the -10 allele was more frequent in aggressive PC (OR, 2.85; 95% CI, 1.52-5.36; P = 0.0004). Haplotype analysis showed significant differences in haplotype frequencies between the familial PC (P = 0.006) and aggressive PC (P = 0.005) cases versus controls. The -8/A haplotype showed the strongest association with familial PC (P = 0.008), whereas the -10/A haplotype was most strongly associated with aggressive PC (P = 0.00005). These results further confirm the importance of these two polymorphic variants (rs1447295 and DG8S737) as risk factors for PC. However, the mechanism explaining this increased risk has not yet been established.


Prefrontal over-activation during walking in people with mobility deficits: Interpretation and functional implications.
Control of walking by the central nervous system includes contributions from executive control mechanisms, such as attention and motor planning resources. Executive control of walking can be estimated objectively by recording prefrontal cortical activity using functional near infrared spectroscopy (fNIRS). The primary objective of this study was to investigate group differences in prefrontal/executive control of walking among young adults, older adults, and adults post-stroke. Also assessed was the extent to which walking-related prefrontal activity fits existing cognitive frameworks of prefrontal over-activation. Participants included 24 adults post-stroke with moderate to severe walking deficits, 15 older adults with mild gait deficits, and 9 young healthy adults. Executive control of walking was quantified as oxygenated hemoglobin concentration in the prefrontal cortex measured by fNIRS. Three walking tasks were assessed: typical walking, walking over obstacles, and walking while performing a verbal fluency task. Walking performance was assessed by walking speed. There was a significant effect of group for prefrontal activity (p < 0.001) during typical and obstacles walking tasks, with young adults exhibiting the lowest level of prefrontal activity, followed by older adults, and then adults post-stroke. In young adults the prefrontal activity during typical walking was much lower than for the verbal fluency dual-task, suggesting substantial remaining prefrontal resources during typical walking. However, in older and post-stroke adults these remaining resources were significantly less (p < 0.01). Cumulatively, these results are consistent with prefrontal over-activation in the older and stroke groups, which was accompanied by a steeper drop in walking speed as task complexity increased to include obstacles (p < 0.05). There is a heightened use of prefrontal/executive control resources in older adults and post-stroke adults during walking. The level of prefrontal resource utilization, particularly during complex walking tasks like obstacle crossing, may approach the ceiling of available resources for people who have walking deficits. Prior cognitive research has revealed that prefrontal over-activation combined with limited prefrontal resources can lead to poor cognitive performance. The present study suggests a similar situation influences walking performance. Future research should further investigate the extent to which prefrontal over-activation during walking is linked to adverse mobility outcomes.


Evolocumab in HIV-Infected Patients With Dyslipidemia: Primary Results of the Randomized, Double-Blind BEIJERINCK Study.
People living with human immunodeficiency virus (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) and are prone to statin-related adverse events from drug-drug interactions with certain antiretroviral regimens. This study sought to evaluate the efficacy and safety of evolocumab in dyslipidemic PLHIV. BEIJERINCK (EvolocumaB Effect on LDL-C Lowering in SubJEcts with Human Immunodeficiency VirRus and INcreased Cardiovascular RisK) is a randomized, double-blind, multinational trial comparing monthly subcutaneous evolocumab 420 mg with placebo in PLHIV with hypercholesterolemia/mixed dyslipidemia taking maximally-tolerated statin therapy. The primary endpoint was the percent change (baseline to week 24) in low-density lipoprotein cholesterol (LDL-C); secondary endpoints included achievement of LDL-C <70 mg/dl and percent change in other plasma lipid and lipoprotein levels. Treatment-emergent adverse events were also examined. A total of 464 patients were analyzed (mean age of 56.4 years, 82.5% male, mean duration with HIV of 17.4 years). ASCVD was documented in 35.6% of patients, and statin intolerance/contraindications to statin use were present in 20.7% of patients. Evolocumab reduced LDL-C by 56.9% (95% confidence interval: 61.6% to 52.3%) from baseline to week 24 versus placebo. An LDL-C level of <70 mg/dl was achieved in 73.3% of patients in the evolocumab group versus 7.9% in the placebo group. Evolocumab also significantly reduced other atherogenic lipid levels, including non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) (all p < 0.0001). Evolocumab was well tolerated, and treatment-emergent adverse events patient incidence was similar among evolocumab and placebo groups. Evolocumab was safe and significantly reduced lipid levels in dyslipidemic PLHIV on maximally-tolerated statin therapy. Evolocumab is an effective therapy for lowering atherogenic lipoproteins in PLHIV with high cardiovascular risk. (Safety, Tolerability & Efficacy on LDL-C of Evolocumab in Subjects With HIV & Hyperlipidemia/Mixed Dyslipidemia; NCT02833844).


The Phosphorylation and Distribution of Cortactin Downstream of Integrin α9β1 Affects Cancer Cell Behaviour.
Integrins, a family of heterodimeric adhesion receptors are implicated in cell migration, development and cancer progression. They can adopt conformations that reflect their activation states and thereby impact adhesion strength and migration. Integrins in an intermediate activation state may be optimal for migration and we have shown previously that fully activated integrin α9β1 corresponds with less migratory behaviour in melanoma cells. Here, we aimed to identify components associated with the activation status of α9β1. Using cancer cell lines with naturally occuring high levels of this integrin, activation by α9β1-specific ligands led to upregulation of fibronectin matrix assembly and tyrosine phosphorylation of cortactin on tyrosine 470 (Y470). Specifically, cortactin phosphorylated on Y470, but not Y421, redistributed together with α9β1 to focal adhesions where active β1 integrin also localises, upon integrin activation. This was commensurate with reduced migration. The localisation and phosphorylation of cortactin Y470 was regulated by Yes kinase and PTEN phosphatase. Cortactin levels influenced fibronectin matrix assembly and active β1 integrin on the cell surface, being inversely correlated with migratory behaviour. This study underlines the complex interplay between cortactin and α9β1 integrin that regulates cell-extracellular matrix interactions.


Laminar thickness alterations in the fronto-parietal cortical mantle of patients with attention-deficit/hyperactivity disorder.
Although Attention-Deficit/Hyperactivity Disorder (ADHD) was initially regarded as a disorder exclusive to childhood, nowadays its prevalence in adulthood is well established. The development of novel techniques for quantifying the thickness of the cerebral mantle allows the further exploration of the neuroanatomical profiles underlying the child and adult form of the disorder. To examine the cortical mantle in children and adults with ADHD, we applied a vertex-wise analysis of cortical thickness to anatomical brain MRI scans acquired from children with (n = 43) and without ADHD (n = 41), as well as a group of adult neurotypical individuals (n = 31), adult patients with a history of stimulant treatment (n = 31) and medication-naïve adults with ADHD (n = 24). We observed several clusters of reduced laminar cortical thickness in ADHD patients in comparison to neurotypical individuals. These differences were primarily located in the dorsal attention network, including the bilateral inferior and superior parietal cortex and a section of the frontal cortex (centered on the superior frontal and precentral gyrus bilaterally). Further laminar thickness deficits were observed in the bilateral orbitofrontal cortex and medial occipital cortex. The deficits in the cortical surface were especially pronounced in the child sample, while adult patients showed a more typical laminar thickness across the cerebral mantle. These findings show that the neuroanatomical profile of ADHD, especially the childhood form of the disorder, involves robust alterations in the cortical mantle, which are most prominent in brain regions subserving attentional processing.


Mitochondrial genotype influences the response to cold stress in the European green crab, Carcinus maenas.
Hybrid zones provide natural experiments in recombination within and between genomes that may have strong effects on organismal fitness. On the East Coast of North America, two distinct lineages of the European green crab (Carcinus maenas) have been introduced in the last two centuries. These two lineages with putatively different adaptive properties have hybridized along the coast of the eastern Gulf of Maine, producing new nuclear and mitochondrial combinations that show clinal variation correlated with water temperature. To test the hypothesis that mitochondrial or nuclear genes have effects on thermal tolerance, we first measured the response to cold stress in crabs collected throughout the hybrid zone, then sequenced the mitochondrial CO1 gene and two nuclear single nucleotide polymorphisms (SNPs) representative of nuclear genetic lineage. Mitochondrial haplotype had a strong association with the ability of crabs to right themselves at 4.5°C that was sex specific: haplotypes originally from northern Europe gave male crabs an advantage while there was no haplotype effect on righting in female crabs. By contrast, the two nuclear SNPs that were significant outliers in a comparison between northern and southern C. maenas populations had no effect on righting response at low temperature. These results add C. maenas to the shortlist of ectotherms in which mitochondrial variation has been shown to affect thermal tolerance, and suggest that natural selection is shaping the structure of the hybrid zone across the Gulf of Maine. Our limited genomic sampling does not eliminate the strong possibility that mito-nuclear co-adaptation may play a role in the differences in thermal phenotypes documented here. Linkage between mitochondrial genotype and thermal tolerance suggests a role for local adaptation in promoting the spread of invasive populations of C. maenas around the world.


The Solidarity and Health Neutrality of Physicians in War & Peace.
The wars in the Middle East have led to unprecedented threats and attacks on patients, healthcare workers, and purposeful targeting of hospitals and medical facilities. It is crucial that every healthcare provider, both civilian and military, on either side of the conflict become aware of the unique and inherent protections afforded to them under International Humanitarian Law. However, these protections come with obligations. Whereas Governments must guarantee these protections, when violated, medical providers have equal duty and obligations under the Law to ensure that they will neither commit nor assist in these violations nor take part in any act of hostility. Healthcare providers must not allow any inhuman or degrading treatment of which they are aware and must report such actions to the appropriate authorities. Failure to do so leads to risks of moral, ethical and legal consequences as well as penalties for their actions and inactions. There must be immediate recognition by all parties of the neutrality of health care workers and their rights and responsibilities to care for any sick and injured patient, regardless of their nationality, race, religion, or political point of view.


Role of arsenic and its resistance in nature.
Contamination of the environment with heavy metals has increased drastically over the last few decades. The heavy metals that are toxic include mercury, cadmium, arsenic, and selenium. Of these heavy metals, arsenic is one of the most important global environmental pollutants and is a persistent bioaccumulative carcinogen. It is a toxic metalloid that exists in two major inorganic forms: arsenate and arsenite. Arsenite disrupts enzymatic functions in cells, while arsenate behaves as a phosphate analog and interferes with phosphate uptake and utilization. Despite its toxicity, arsenic may be actively sequestered in plant and animal tissues. Various microbes interact with this metal and have shown resistance to arsenic exposure, and they appear to possess the ars operon for arsenic resistance consisting of three to five genes, i.e., arsRBC or arsRDABC, organized into a single transcriptional unit; some microbes even use it for respiration. Microbial interactions with metals may have several implications for the environment. Microbes may play a role in cycling of toxic heavy metals and in remediation of metal-contaminated sites. There is a correlation between tolerance to heavy metals and antibiotic resistance, a global problem currently threatening the treatment of infections in plants, animals, and humans. The purpose of this review is to highlight the nature and role of toxic arsenic in bacterial systems and to discuss the various genes responsible for this heavy-metal resistance in nature and the mechanisms to detoxify this element.


In-vivo transfer of mecA DNA to Staphylococcus aureus [corrected].
Staphylococcus aureus is thought to have acquired mecA DNA by horizontal transfer. DNA fingerprints made by restriction nucleases that cut certain sequences of DNA are used to compare complete genomes or particular genes between bacteria. We isolated an epidemic mecA(-) meticillin-susceptible S aureus genotype and, subsequently, a rare isogeneic mecA(+) meticillin-resistant S aureus (MRSA) genotype from a neonate who had never been in contact with MRSA. This MRSA contained mecA DNA that was identical to that in a coagulase-negative staphylococcal strain isolated from this patient, but different from other MRSA genotypes. We believe that this MRSA was formed in vivo by horizontal transfer of the mecA DNA between two staphylococcal species.


Fully switchable multiwavelength fiber laser assisted by a random mirror.
A real-time switchable and reconfigurable multiwavelength laser has been experimentally carried out. The laser cavity is based on a random distributed mirror and a novel real-time reconfigurable filter mirror structure. The proposed laser has been demonstrated to generate any combination of wavelengths at the 50 and 100 GHz International Telecommunications Union (ITU) grids specifications. By simultaneously using Er-doped fiber and Raman amplification, a 15 nm wide lasing window at the C band can be utilized to create up to 18 different lasing wavelengths into the ITU grid that can be switched automatically and in real time when desired.


Examining the Association between Neighbourhood Socioeconomic Disadvantage and Type 2 Diabetes Comorbidity in Serious Mental Illness.
This study examined the association between neighbourhood socioeconomic disadvantage and serious mental illness (SMI)-type 2 diabetes (T2D) comorbidity in an Australian population using routinely collected clinical data. We hypothesised that neighbourhood socioeconomic disadvantage is positively associated with T2D comorbidity in SMI. The analysis considered 3816 individuals with an SMI living in the Illawarra and Shoalhaven regions of NSW, Australia, between 2010 and 2017. Multilevel logistic regression models accounting for suburb (neighbourhood) level clustering were used to assess the association between neighbourhood disadvantage and SMI -T2D comorbidity. Models were adjusted for age, sex, and country of birth. Compared with the most advantaged neighbourhoods, residents in the most disadvantaged neighbourhoods had 3.2 times greater odds of having SMI-T2D comorbidity even after controlling for confounding factors (OR 3.20, 95% CI 1.42-7.20). The analysis also revealed significant geographic variation in the distribution of SMI -T2D comorbidity in our sample (Median Odds Ratio = 1.35) Neighbourhood socioeconomic disadvantage accounted for approximately 17.3% of this geographic variation. These findings indicate a potentially important role for geographically targeted initiatives designed to enhance prevention and management of SMI-T2D comorbidity in disadvantaged communities.


Staining and peeling of the internal limiting membrane using a fluorescent dye (Rhodamine 6 G).
To assess whether low concentrations of a fluorescent dye such as Rhodamine 6G would help the unaided human eye visualise the vitreous and the internal limiting membrane (ILM) under standard halogen illumination. The UV/Vis absorption (E) and fluorescence (I) spectra of Rhodamine 6G in water were measured and compared with Indocyanine Green (ICG). Surgery was performed in two rhesus monkeys and consisted of standard pars plana vitrectomy with halogen light source used for illumination. Rhodamine 6G was diluted in balanced salt solution (BSS). A few drops of the dye in a concentration of 0.1% (307 mOsm) were applied over the posterior pole in the air-filled globe and washed out by irrigation after 1 min. Immediately after surgery, the globes were enucleated, fixated and prepared for histological evaluation. In contrast to ICG, both the maximum of the absorption and emission of Rhodamin 6G are very much within the spectral sensitivity of the human eye. The Rhodamine 6G-BSS itself appears red in colour. Using a dye concentration of 0.1%, there was no visible red-staining of the ILM as such. As the dye was irrigated out with BSS, a marked green fluorescence of the fluid within the vitreous cavity was noted. With halogen illumination through a standard 20-gauge light pipe, the dye provided a sufficient green fluorescence to identify and safely remove the ILM and to clearly differentiate areas of peeled from non-peeled ILM. During light microscopy, eyes revealed a peeled ILM demarcation with no signs of acute retinal toxicity. The findings indicate that a fluorescent dye can be used for ILM peeling. Assuming that the fluorophore provides a high enough fluorescence quantum yield after adsorption to the ILM, much lower dye concentrations could be used compared with absorbent dyes, thereby minimising toxic effects.


Uptake Kinetics and Subcellular Compartmentalization Explain Lethal but Not Sublethal Effects of Cadmium in Two Closely Related Amphipod Species.
Eulimnogammarus cyaneus and Eulimnogammarus verrucosus, closely related amphipod species endemic to Lake Baikal, differ with respect to body size (10- to 50-fold lower fresh weights of E. cyaneus) and cellular stress response (CSR) capacity, potentially causing species-related differences in uptake, internal sequestration, and toxic sensitivity to waterborne cadmium (Cd). We found that, compared to E. verrucosus, Cd uptake rates, related to a given exposure concentration, were higher, and lethal concentrations (50%; LC50) were 2.3-fold lower in E. cyaneus (4 weeks exposure; 6 °C). Upon exposures to species-specific subacutely toxic Cd concentrations (nominal LC1; E. cyaneus: 18 nM (2.0 μg L-1); E. verrucosus: 115 nM (12.9 μg L-1); 4 weeks exposure; 6 °C), Cd amounts in metal sensitive tissue fractions (MSF), in relation to fresh weight, were similar in both species (E. cyaneus: 0.25 ± 0.06 μg g-1; E. verrucosus: 0.26 ± 0.07 μg g-1), whereas relative Cd amounts in the biologically detoxified heat stable protein fraction were 35% higher in E. cyaneus. Despite different potencies in detoxifying Cd, body size appears to mainly explain species-related differences in Cd uptake and sensitivities. When exposed to Cd at LC1 over 4 weeks, only E. verrucosus continuously showed 15-36% reduced oxygen consumption rates indicating metabolic depression and pointing to particular sensitivity of E. verrucosus to persisting low-level toxicant pressure.


Reproductive and Lifestyle Factors and Circulating sRANKL and OPG Concentrations in Women: Results from the EPIC Cohort.
Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor κB (sRANKL) and OPG concentrations in women are limited. We evaluated reproductive and lifestyle factors as potential sources of variation in circulating sRANKL and OPG concentrations in pre- and postmenopausal women. This study includes 2,016 controls [n = 1,552 (76%) postmenopausal, n = 757 (38%) using postmenopausal hormone therapy (PMH)] from a breast cancer case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Serum sRANKL was measured using an ELISA and serum OPG using an electrochemiluminescent assay. Generalized linear models were used to evaluate associations between these analytes and reproductive and lifestyle factors. Older age at blood collection was associated with lower sRANKL concentrations in postmenopausal women (P trend ≤ 0.03) and higher OPG concentrations in all women (P trend ≤ 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG (P trend ≤ 0.04). In postmenopausal non-PMH users, sRANKL concentrations were lower with longer duration of oral contraceptive use and current (vs. never) smoking (P ≤ 0.01). sRANKL concentrations were higher among women with higher BMI (P trend ≤ 0.01). The evaluated factors accounted for 12% of the variation in sRANKL concentrations and 21% of the variation in OPG concentrations. Circulating sRANKL and OPG concentrations are minimally impacted by hormone-related factors in pre- and postmenopausal women. This study suggests circulating concentrations of sRANKL and OPG are unlikely to be strongly modified by hormone-related reproductive and lifestyle factors.


Encoding of sensory prediction errors in the human cerebellum.
A central tenet of motor neuroscience is that the cerebellum learns from sensory prediction errors. Surprisingly, neuroimaging studies have not revealed definitive signatures of error processing in the cerebellum. Furthermore, neurophysiologic studies suggest an asymmetry, such that the cerebellum may encode errors arising from unexpected sensory events, but not errors reflecting the omission of expected stimuli. We conducted an imaging study to compare the cerebellar response to these two types of errors. Participants made fast out-and-back reaching movements, aiming either for an object that delivered a force pulse if intersected or for a gap between two objects, either of which delivered a force pulse if intersected. Errors (missing the target) could therefore be signaled either through the presence or absence of a force pulse. In an initial analysis, the cerebellar BOLD response was smaller on trials with errors compared with trials without errors. However, we also observed an error-related decrease in heart rate. After correcting for variation in heart rate, increased activation during error trials was observed in the hand area of lobules V and VI. This effect was similar for the two error types. The results provide evidence for the encoding of errors resulting from either the unexpected presence or unexpected absence of sensory stimulation in the human cerebellum.


Effects of gender and psychosocial factors on "friends with benefits" relationships among young adults.
Friends with benefits relationships (FWB) are a blend of friendship and physical intimacy outside of a committed romantic relationship. This study examined young adults' (n = 889) engagement in, and reactions to, a FWB relationship in the past year based on their gender, psychological distress, alcohol use, and relationship attitudes. Men (54.3%) were more likely than women (42.9%) to report at least one FWB relationship and both men and women reported that FWB relationships were associated with more positive emotional reactions than negative ones although this difference was larger for men. Greater alcohol use was related to engaging in a FWB relationship and this relationship was stronger for women. Further, thoughtfulness about relationship decisions moderated the relationship between alcohol use and engaging in FWB relationships, and again this moderation effect was stronger for women than men. Young adults with more psychological distress and who felt constrained in the FWB relationship were more likely to report negative emotional reactions. Implications for psychoeducational programs and future research are offered.


Do we need bispectral index monitoring during total intravenous anesthesia for lumbar discectomies?
The aim of this study was to investigate the effect of bispectral index (BIS) monitoring on hemodynamic parameters, drug consumption and awareness during total intravenous anesthesia (TIVA) with remifentanil and propofol in lumbar discectomies. After institutional ethical committee approval, ASAI-II 56 patients were divided as control and BIS groups. Anesthesia was induced by bolus remifentanil 1 mug/kg in both groups; propofol 2 mg/kg in was used in the control group while propofol was titrated to BIS 45- 65 values in the BIS group. Anesthesia was maintained by remifentanil and propofol infusions. Drug consumption, time to extubation and awareness were recorded. Demographic parameters were similar between the groups. Consumption of propofol was lower, and time to extubation was shorter in the BIS group; there was no difference between awareness among groups. BIS monitoring was helpful for propofol titration and decreased propofol consumption, but not enough to prevent reaction to noxious stimuli. Standard anesthesia titration considering hemodynamic parameters was enough for most ASA I-II patients for lumbar discectomies. BIS might be more helpful for patients who cannot show hemodynamic responses to noxious stimuli. More studies are needed to investigate the correlation between positioning and awareness using BIS monitoring.


Treatment of cyanide wastewater by bulk liquid membrane using tricaprylamine as a carrier.
The transport of cyanide from wastewater through a bulk liquid membrane (BLM) containing tricaprylamine (TOA) as a carrier was studied. The effect of cyanide concentration in the feed solution, TOA concentration in the organic phase, the stirring speed, NaOH concentration in the stripping solution and temperature on cyanide transport was determined through BLM. Mass transfer of cyanide through BLM was analyzed by following the kinetic laws of two consecutive irreversible first-order reactions, and the kinetic parameters (k(1), k(2), R(m)(max), t(max), J(a)(max), J(d)(max)) were also calculated. Apparently, increase in membrane entrance (k(1)) and exit rate (k(2)) constants was accompanied by a rise in temperature. The values of activation energies were obtained as 35.6 kJ/mol and 18.2 kJ/mol for removal and recovery, respectively. These values showed that both removal and recovery steps in cyanide transport is controlled by the rate of the chemical complexation reaction. The optimal reaction conditions were determined by BLM using trioctylamine as the carrier: feed phase: pH 4, carrier TOA possession ratio in organic phase: 2% (V/V), stripping phase concentration of NaOH: 1% (W/V), reaction time: 60 min, stirring speed: 250 r/min. Under the above conditions, the removal rate was up to 92.96%. The experiments demonstrated that TOA was a good carrier for cyanide transport through BLM in this study.


Seasonality in antarctic airborne fungal spores.
Airborne fungal spores were monitored over periods of up to 131/2 months at three sites on Signy Island in the maritime Antarctic. Fungal spore concentrations in the air were much lower than in other parts of the world. Concentrations were very low during the austral winter but increased during the austral summer. Chlamydospores were the most abundant fungal spore type found. Spores of Cladosporium spp. were the second most frequently trapped form. All spore types samples were most abundant in the summer months, except for chlamydospores, which were most numerous during the winter. The concentration of Cladosporium spores in the air at Signy Island was compared with the concentrations of this spore type found in the air in other parts of the world. It was evident that Cladosporium loses its dominance as the most abundant component of the air spora with increasingly high latitude. The peak concentration of fungal spores occurred at two sites following the start of the thaw; at the third site, the peak occurred with the arrival of spores by long-distance transport from more northerly regions.


Genetics of warfarin sensitivity in an emergency department population with thromboembolic.
Emergency department (ED) patients with venous thromboembolism (VTE) are eventually treated with a standard dose of warfarin despite the fact that a number of patients are known to be sensitive to warfarin and may experience supra-therapeutic INRs and adverse bleeding events. Pharmacogenetics is an emerging field of medical practice that seeks to improve drug safety and efficacy in an individual patient by tailoring treatment to the patient's known genetic makeup. To identify patients with risk for warfarin sensitivity among an ED population with VTE and to assess if the warfarin sensitivity mutations were of significant enough prevalence to be of clinical significance in customizing treatment of VTE. We sought in a pilot study to identify if testing for common CYP2C9 and VKORC1 single nucleotide polymorphisms (SNPs) in patients who were likely to begin warfarin treatment was feasible in an ED setting. A prospective study that identified and enrolled patients presenting to our ED with high clinical suspicion of VTE. Those with high clinical suspicion of VTE were defined as those who had a Doppler ultrasound or computed tomography pulmonary angiography (CTPA) ordered by the primary emergency physician. Blood was taken and processed to ascertain the following SNPs: CYP2C9*2, CYP2C9*3, and VKORC1 3673. Of the 194 patients enrolled, 132 (68.0%) had at least one known warfarin sensitivity mutation and 114 (58.8%) had the most clinically significant VKORC1 3673 mutation. A majority of our patients had at least one mutation associated with the atypical metabolism of warfarin. Over half of our population had the most clinically significant VKORC1 3673 mutation. They would likely benefit from individualized warfarin dosing if ever needing anticoagulation. Our initial pilot study shows that allele frequencies of target warfarin sensitivity SNPs in our patient population are frequent enough to make initiation of personalized warfarin dosing feasible.


2-aminoethoxydiphenyl borate stimulates pulmonary C neurons via the activation of TRPV channels.
This study was carried out to determine the effect of 2-aminoethoxydiphenyl borate (2-APB), a common activator of transient receptor potential vanilloid (TRPV) type 1, 2, and 3 channels, on cardiorespiratory reflexes, pulmonary C fiber afferents, and isolated pulmonary capsaicin-sensitive neurons. In anesthetized, spontaneously breathing rats, intravenous bolus injection of 2-APB elicited the pulmonary chemoreflex responses, characterized by apnea, bradycardia, and hypotension. After perineural treatment of both cervical vagi with capsaicin to block the conduction of C fibers, 2-APB no longer evoked any of these reflex responses. In open-chest and artificially ventilated rats, 2-APB evoked an abrupt and intense discharge in vagal pulmonary C fibers in a dose-dependent manner. The stimulation of C fibers by 2-APB was attenuated but not abolished by capsazepine, a selective antagonist of the TRPV1, which completely blocked the response to capsaicin in these C fiber afferents. In isolated pulmonary capsaicin-sensitive neurons, 2-APB concentration dependently evoked an inward current that was partially inhibited by capsazepine but almost completely abolished by ruthenium red, an effective blocker of all TRPV channels. In conclusion, 2-APB evokes a consistent and distinct stimulatory effect on pulmonary C fibers in vivo and on isolated pulmonary capsaicin-sensitive neurons in vitro. These results establish the functional evidence demonstrating that TRPV1, V2, and V3 channels are expressed on these sensory neurons and their terminals.


Presence of enterotoxigenic Staphylococcus aureus in bulk tank milk from Argentine dairy farms.
Staphylococcus aureus is the most prevalent bovine mastitis pathogen in Argentina. The ability of this organism to produce enterotoxins is linked to staphylococcal food poisoning. Staphylococcal enterotoxins are low molecular weight proteins, highly resistant to heat and proteolytic enzyme activity. The aim of this study was to determine the ability to produce enterotoxins and types of enterotoxins A through E produced among 94 S. aureus isolated from bulk tank milk in Argentina by enzyme-linked immunosorbent assay. Eleven isolates (11.7 %) produced enterotoxins. Seven of them (7.4 %) produced enterotoxin C, two (2.1 %) enterotoxin D, one (1.1 %) enterotoxin B and one (1.1 %) enterotoxins C-D-E. None of the isolates produced enterotoxins A or E alone. Since presence of staphylococcal enterotoxins constitute a potential risk to public health, these findings underscore the need to control S. aureus bovine mastitis and to limit bacterial multiplication in bulk tank milk.


Re-introduction of dengue virus serotype 2 in the state of Rio de Janeiro after almost a decade of epidemiological silence.
The Asian/American genotype of dengue virus serotype 2 (DENV-2) has been introduced in Brazil through the state of Rio de Janeiro around 1990, and since then it has been spreading and evolving, leading to several waves of dengue epidemics throughout the country that cause a major public health problem. Of particular interest has been the epidemic of 2008, whose highest impact was evidenced in the state of Rio de Janeiro, with a higher number of severe cases and mortality rate, compared to previous outbreaks. Interestingly, no circulation of DENV-2 was witnessed in this region during the preceding 9-year period. By early 2010, phylogenetic analysis of the 2008 epidemic strain revealed that the outbreak was caused by a new viral lineage of the Asian/American genotype, which was pointed as responsible for the outbreak severity as well. The same scenario is repeating in 2019 in this state; however, only a few cases have been detected yet. To provide information that helps to the understanding of DENV-2 dynamics in the state of Rio de Janeiro, and thereafter contribute to public health control and prevention actions, we employed phylogenetic studies combined with temporal and dynamics geographical features to determine the origin of the current viral strain. To this effect, we analyzed a region of 1626 nucleotides entailing the Envelope/NS1 viral genes. Our study reveals that the current strain belongs to the same lineage that caused the 2008 outbreak, however, it is phylogenetically distant from any Brazilian strain identified so far. Indeed, it seemed to be originated in Puerto Rico around 2002 and has been introduced into the state in late 2018. Taking into account that no DENV-2 case was reported over the last decade in the state (representing a whole susceptible children generation), and the fact that a new viral strain may be causing current dengue infections, these results will be influential in strengthening dengue surveillance and disease control, mitigating the potential epidemiological consequences of virus spread.


Preferential binding effects on protein structure and dynamics revealed by coarse-grained Monte Carlo simulation.
The effect of preferential binding of solute molecules within an aqueous solution on the structure and dynamics of the histone H3.1 protein is examined by a coarse-grained Monte Carlo simulation. The knowledge-based residue-residue and hydropathy-index-based residue-solvent interactions are used as input to analyze a number of local and global physical quantities as a function of the residue-solvent interaction strength (f). Results from simulations that treat the aqueous solution as a homogeneous effective solvent medium are compared to when positional fluctuations of the solute molecules are explicitly considered. While the radius of gyration (Rg) of the protein exhibits a non-monotonic dependence on solvent interaction over a wide range of f within an effective medium, an abrupt collapse in Rg occurs in a narrow range of f when solute molecules rapidly bind to a preferential set of sites on the protein. The structure factor S(q) of the protein with wave vector (q) becomes oscillatory in the collapsed state, which reflects segmental correlations caused by spatial fluctuations in solute-protein binding. Spatial fluctuations in solute binding also modify the effective dimension (D) of the protein in fibrous (D ∼ 1.3), random-coil (D ∼ 1.75), and globular (D ∼ 3) conformational ensembles as the interaction strength increases, which differ from an effective medium with respect to the magnitude of D and the length scale.


GABAB receptor-mediated, layer-specific synaptic plasticity reorganizes gamma-frequency neocortical response to stimulation.
Repeated presentations of sensory stimuli generate transient gamma-frequency (30-80 Hz) responses in neocortex that show plasticity in a task-dependent manner. Complex relationships between individual neuronal outputs and the mean, local field potential (population activity) accompany these changes, but little is known about the underlying mechanisms responsible. Here we show that transient stimulation of input layer 4 sufficient to generate gamma oscillations induced two different, lamina-specific plastic processes that correlated with lamina-specific changes in responses to further, repeated stimulation: Unit rates and recruitment showed overall enhancement in supragranular layers and suppression in infragranular layers associated with excitatory or inhibitory synaptic potentiation onto principal cells, respectively. Both synaptic processes were critically dependent on activation of GABAB receptors and, together, appeared to temporally segregate the cortical representation. These data suggest that adaptation to repetitive sensory input dramatically alters the spatiotemporal properties of the neocortical response in a manner that may both refine and minimize cortical output simultaneously.


Emergency Health Care Use among Sociodemographic Groups of Children Presenting to Emergency Departments for Self-Harm in Alberta.
To examine sociodemographic variations among children <18 years in (1) rates of self-harm visits to emergency departments (EDs) and (2) physician follow-up after the self-harm visit in Alberta. A retrospective, population-based cohort (2002-2011) of ED visits for self-harm by individuals <18 years was conducted using administrative databases from Alberta, Canada. Individuals were grouped by First Nations status or type of health care premium subsidy (family receipt of government subsidy, human services program subsidy, no subsidy received). Visits from 104 EDs were summarized by crude and directly standardized visit rates (DSVRs) per 100,000 individuals. Kaplan-Meier estimates for median estimated time to physician follow-up were calculated with 95% confidence intervals (CIs). During the study period, visit rates decreased with the exception of children from families receiving government-sponsored program subsidy (DSVRs 163/100,000 to 250/100,000; p=0.032). First Nations children had disproportionately fewer follow-up visits compared to other children. The median time to follow-up for First Nations children was 39 days (95% CI: 32, 48) compared to 16 days for children from families receiving no subsidy (95% CI: 14, 19), who had the shortest follow-up time after an ED visit. Sociodemographic differences were evident in ED visit rates as well as the number of and time to physician follow-up visit. The disparities experienced by First Nations children in the follow-up period highlight an opportunity for culturally-grounded risk and needs assessment in the ED to determine and facilitate timely and appropriate follow-up care.


Combinatorial Reactive Sputtering of In2S3 as an Alternative Contact Layer for Thin Film Solar Cells.
High-throughput computational and experimental techniques have been used in the past to accelerate the discovery of new promising solar cell materials. An important part of the development of novel thin film solar cell technologies, that is still considered a bottleneck for both theory and experiment, is the search for alternative interfacial contact (buffer) layers. The research and development of contact materials is difficult due to the inherent complexity that arises from its interactions at the interface with the absorber. A promising alternative to the commonly used CdS buffer layer in thin film solar cells that contain absorbers with lower electron affinity can be found in β-In2S3. However, the synthesis conditions for the sputter deposition of this material are not well-established. Here, In2S3 is investigated as a solar cell contact material utilizing a high-throughput combinatorial screening of the temperature-flux parameter space, followed by a number of spatially resolved characterization techniques. It is demonstrated that, by tuning the sulfur partial pressure, phase pure β-In2S3 could be deposited using a broad range of substrate temperatures between 500 °C and ambient temperature. Combinatorial photovoltaic device libraries with Al/ZnO/In2S3/Cu2ZnSnS4/Mo/SiO2 structure were built at optimal processing conditions to investigate the feasibility of the sputtered In2S3 buffer layers and of an accelerated optimization of the device structure. The performance of the resulting In2S3/Cu2ZnSnS4 photovoltaic devices is on par with CdS/Cu2ZnSnS4 reference solar cells with similar values for short circuit currents and open circuit voltages, despite the overall quite low efficiency of the devices (∼2%). Overall, these results demonstrate how a high-throughput experimental approach can be used to accelerate the development of contact materials and facilitate the optimization of thin film solar cell devices.


Self-Reported Suicidal Ideation as a Predictor of Suicidal Behavior Among Outpatients With Diagnoses of Psychotic Disorders.
Individuals with psychotic disorders are at high risk of suicidal behavior. The study examined whether response to item 9 of the Patient Health Questionnaire (PHQ-9), which asks about thoughts of death or self-harm, predicts suicidal behavior among outpatients with diagnoses of psychotic disorders. Electronic health records (EHRs) from seven large integrated health systems were used to identify all outpatient visits by adults with a diagnosis of schizophrenia spectrum psychosis or unspecified psychosis from January 1, 2009, to June 30, 2015, during which a PHQ-9 was completed (N=32,982 visits by 5,947 patients). Suicide attempts over the 90 days following each visit were ascertained from EHRs and insurance claims. Suicide deaths were ascertained from state death certificate files. Risk of suicide attempt within 90 days of an outpatient visit was .8% among patients reporting no thoughts of death or self-harm and 3.5% among those reporting such thoughts "nearly every day." Over 90 days of follow-up, 47% of suicide attempts occurred among those who reported any recent thoughts of death or self-harm at the sampled visit. Also, 59% of attempts occurred among those reporting thoughts of death or self-harm at the index visit or any visit in the prior year. The number of suicide deaths within 90 days (N=10) was too small to accurately assess the relationship between PHQ-9 item 9 response and subsequent suicide death. Among outpatients with psychotic disorders, response to item 9 of the PHQ-9 accurately identified those at increased short-term risk of a suicide attempt.


Arrested development of the myxozoan parasite, Myxobolus cerebralis, in certain populations of mitochondrial 16S lineage III Tubifex tubifex.
Laboratory populations of Tubifex tubifex from mitochondrial (mt)16S ribosomal DNA (rDNA) lineage III were generated from single cocoons of adult worms releasing the triactinomyxon stages (TAMs) of the myxozoan parasite, Myxobolus cerebralis. Subsequent worm populations from these cocoons, referred to as clonal lines, were tested for susceptibility to infection with the myxospore stages of M. cerebralis. Development and release of TAMs occurred in five clonal lines, while four clonal lines showed immature parasitic forms that were not expelled from the worm (non-TAM producers). Oligochaetes from TAM- and non-TAM-producing clonal lines were confirmed as lineage III based on mt16S rDNA and internal transcribed spacer region 1 (ITS1) sequences, but these genes did not differentiate these phenotypes. In contrast, random amplified polymorphic DNA analyses of genomic DNA demonstrated unique banding patterns that distinguished the phenotypes. Cohabitation of parasite-exposed TAM- and non-TAM-producing phenotypes showed an overall decrease in expected TAM production compared to the same exposure dose of the TAM-producing phenotype without cohabitation. These studies suggest that differences in susceptibility to parasite infection can occur in genetically similar T. tubifex populations, and their coexistence may affect overall M. cerebralis production, a factor that may influence the severity of whirling disease in wild trout populations.


Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6.
Binding of epidermal growth factor (EGF) to its receptor leads to receptor dimerization, assembly of protein complexes, and activation of signaling networks that control key cellular responses. Despite their fundamental role in cell biology, little is known about protein complexes associated with the EGF receptor (EGFR) before growth factor stimulation. We used a modified membrane yeast two-hybrid system together with bioinformatics to identify 87 candidate proteins interacting with the ligand-unoccupied EGFR. Among them was histone deacetylase 6 (HDAC6), a cytoplasmic lysine deacetylase, which we found negatively regulated EGFR endocytosis and degradation by controlling the acetylation status of alpha-tubulin and, subsequently, receptor trafficking along microtubules. A negative feedback loop consisting of EGFR-mediated phosphorylation of HDAC6 Tyr(570) resulted in reduced deacetylase activity and increased acetylation of alpha-tubulin. This study illustrates the complexity of the EGFR-associated interactome and identifies protein acetylation as a previously unknown regulator of receptor endocytosis and degradation.


Sarco(endo)plasmic reticulum Ca2+-ATPase-2 gene: structure and transcriptional regulation of the human gene.
The sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) belong to a family of active calcium transport enzymes encoded by the SERCA1, 2, and 3 genes. In this study, we describe the complete structure of the human SERCA2 gene and its 5 -regulatory region. The hSERCA2 gene is located in chromosome 12 position q24.1 in Contig NT_009770.8, spans 70 kb, and is organized in 21 exons intervened by 20 introns. The last two exons of the pre-mRNA produce by alternatively splicing the cardiac/slow-twitch muscle-specific SERCA2a isoform and the ubiquitous SERCA2b isoform. The sequence of the proximal 225-bp regulatory region of the SERCA2 genes is 80% G+C-rich and is conserved among human, rabbit, rat, and mouse species. It contains a TATA-like-box, an E-box/USF sequence, a CAAT-box, four Sp1 binding sites, and a thyroid hormone responsive element (TRE). There are two other conserved regulatory regions located between positions -410 to -661 bp and from -919 to -1410 bp. Among the DNA cis-elements present in these two regulatory regions there are potential binding sites for: GATA-4, -5, -6, Nkx-2.5/Csx, OTF-1, USF, MEF-2, SRF, PPAR/RXR, AP-2, and TREs. Upstream from position -1.5 kb, there is no significant homology among the SERCA2 genes cloned. In addition, the human gene has several repeated sequences mainly of the Alu and L2 type located upstream from position -1.7 kb, spanning in a continuous fashion for more than 40 kb. In this study, we report the cloning of 2.4 kb of 5-regulatory region and demonstrate that the proximal promoter region is sufficient for expression in cardiac myocytes, and the region from -225 to -1232 bp contains regulatory DNA elements which down-regulate the expression of the SERCA2 gene in neonatal cardiomyocytes.


A critical beta6-beta7 loop in the pleckstrin homology domain of ceramide kinase.
CerK (ceramide kinase) produces ceramide 1-phosphate, a sphingophospholipid with recognized signalling properties. It localizes to the Golgi complex and fractionates essentially between detergent-soluble and -insoluble fractions; however, the determinants are unknown. Here, we made a detailed mutagenesis study of the N-terminal PH domain (pleckstrin homology domain) of CerK, based on modelling, and identified key positively charged amino acid residues within an unusual motif in the loop interconnecting beta-strands 6 and 7. These residues are critical for CerK membrane association and polyphosphoinositide binding and activity. Their mutagenesis results in increased thermolability, sensitivity to proteolysis, reduced apparent molecular mass as well as propensity of the recombinant mutant protein to aggregate, indicating that this loop impacts the overall conformation of the CerK protein. This is in contrast with most PH domains whose function strongly relies on charges located in the beta1-beta2 loop.


Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system.
Ketamine is a multifunctional drug with clinical applications as an anesthetic, as a pain management medication and as a transformative fast-acting antidepressant. It is also abused as a recreational drug due to its dissociative property. Recent studies in rodents are revealing the neuronal mechanisms that mediate the complex actions of ketamine, however, its long-term impact due to prolonged exposure remains much less understood with profound scientific and clinical implications. Here, we develop and utilize a high-resolution whole-brain phenotyping approach to show that repeated ketamine administration leads to a dosage-dependent decrease of dopamine (DA) neurons in the behavior state-related midbrain regions and, conversely, an increase within the hypothalamus. Congruently, we show divergently altered innervations of prefrontal cortex, striatum, and sensory areas. Further, we present supporting data for the post-transcriptional regulation of ketamine-induced structural plasticity. Overall, through an unbiased whole-brain analysis, we reveal the divergent brain-wide impact of chronic ketamine exposure on the association and sensory pathways.


Unconventional rotational responses of hadronic superfluids in a neutron star caused by strong entrainment and a Sigma- hyperon gap.
I show that the usual model of the rotational response of a neutron star, which predicts rotation-induced neutronic vortices and no rotation-induced protonic vortices, does not hold (i) beyond a certain threshold of entrainment interaction strength nor (ii) in the case of nonzero Sigma(-) hyperon gap. I show that in both of these cases the rotational response involves the creation of phase windings in an electrically charged condensate. Lattices of bound states of vortices which result from these phase windings can (for a range of parameters) strongly reduce the interaction between rotation-induced vortices with magnetic-field carrying superconducting components.


Interface dipoles for tuning energy level alignment in organic thin film devices.
One of the key features of organic optoelectronic and electronic devices resides in the multilayer architecture of the device stack. The performance of the latter strongly depends on the interface quality between organic layers or at the electrode heterojunction. Apart from interface thermodynamics governing adhesion and wetting, the electronic energy levels of the organic semiconductor are affected by the interface properties in a drastic way. This mini review gives a short overview on the possibilities to adjust frontier orbital energy levels using oriented electrical dipoles at the interfaces.


Baroreceptor sensitivity of rat supraoptic vasopressin neurons involves noncholinergic neurons in the DBB.
Previous studies suggest that cholinergic neurons in the diagonal band of Broca (DBB) participate in the baroreceptor-mediated inhibition of phasic vasopressin neurons in the supraoptic nucleus (SON). To test this hypothesis, extracellular recordings were obtained from putative vasopressin SON neurons of anesthetized rats injected with the cholinergic immunotoxin 192 IgG-saporin (0.8 microg/microl) in the DBB. Baroreceptor sensitivity of neurons was tested with brief phenylephrine-induced (10 microg/10 microl iv) increases in blood pressure of at least 40 mmHg. In rats injected with vehicle or unconjugated saporin, 19 of 21 and 18 of 20 phasic neurons, respectively, were inhibited by increased blood pressure. In rats injected with 192 IgG-saporin, which significantly reduced the number of choline acetyltransferase (ChAT)-positive DBB neurons, 33 of 36 phasic neurons were inhibited. Normal rats and rats with DBB saporin injections received rhodamine bead injections into the perinuclear zone (PNZ) to retrogradely label DBB neurons, and their brains were stained for ChAT. ChAT-positive DBB neurons were not retrogradely labeled from the PNZ. Together, these results indicate that the pathway relaying baroreceptor information to the SON involves noncholinergic DBB neurons.


Demystifying the ACE polymorphism: from genetics to biology.
The angiotensin converting enzyme (ACE) I/D polymorphism has been one of the most studied genetic systems. It comprises hundreds of reports and a myriad of disease associations, including cardiovascular, metabolic, immune, cancer, aging, neurodegenerative and psychiatric diseases. Despite the wealth of information on the ACE polymorphism and the well-known functions of ACE, several questions arise. Why does the ACE polymorphism associate with so many diseases? What is its function? In this review, we summarize the current information on the ACE polymorphism and explain its function in the context of cell survival. We also provide a model to understand its role in biology and disease at the organism and population levels.


First Report of Chickpea Chlorotic Dwarf Virus Infecting Spring Chickpea in Syria.
During May 2003, a high incidence of symptoms suggestive of virus infection in spring chickpea were observed in many fields in Al-Ghab Valley, Syria, the ICARDA farm (near Aleppo, Syria), as well as in other locations in northern Syria, including the Idleb governorate. Symptoms observed were yellowing, stunting, and necrosis. A total of 1,345 chickpea samples with these symptoms (331 from Al-Ghab Valley, 269 from the ICARDA farm, and 745 from the Idleb governorate) were collected and tested for the presence of five viruses with tissue-blot immunoassay (TBIA) (4) at the Virology Laboratory of ICARDA, using the following antisera: monoclonal antibodies for Faba bean necrotic yellows virus (FBNYV, genus Nanovirus) (1); Bean leafroll virus (BLRV, family Luteoviridae) (4B10) (3); Beet western yellows virus (BWYV, genus Polerovirus, family Luteoviridae [ATCC PVAS-647, American Type Culture Collection, Manassas, VA]); and Soybean dwarf virus (SbDV, family Luteoviridae, [ATCC PVAS-650]) and polyclonal antibodies for Chickpea chlorotic dwarf virus (CpCDV, genus Mastrevirus, family Geminiviridae, provided by H. J. Vetten, BBA, Braunschweig, Germany). The most common virus present was BWYV (detected in 54.1% of samples tested), followed by CpCDV (19.2%), BLRV (10.2%), and FBNYV (5.5%). SbDV was not detected in any of the samples tested. Using immunosorbent electron microscopy, infected chickpea samples revealed low numbers of geminivirus-like particles after 15 min of incubation on CpCDV antiserum-coated grids. When CpCDV was purified from infected chickpea plants, the virus coat protein was 32 kDa with sodium dodecyl sulfate-polyacrylamide gel electrophoresis typical of CpCDV coat protein (2) and reacted strongly with CpCDV antiserum in western blots. The CpCDV vector in Syria was found to be Orosius albicinctus Distant, and is thought to be similar to Orosius orientalis (Matsumura), the reported vector of CpCDV (2). FBNYV, BWYV, and BLRV infection of chickpea have been previously reported from Syria, but to our knowledge, this is the first report of CpCDV infecting chickpea in Syria. References: (1) A. Franz et al. Ann. Appl. Biol. 128:255, 1996. (2) N. M. Horn et al. Ann. Appl. Biol. 122:467, 1993. (3) L. Katul. Characterization by serology and molecular biology of bean leaf roll virus and faba bean necrotic yellows virus. Ph.D. thesis. University of Gottingen, Germany, 1992. (4) K. M. Makkouk and A. Comeau. Eur. J. Plant Pathol. 100:71, 1994.


Serotonergic modulation of intrinsic functional connectivity.
Serotonin functions as an essential neuromodulator that serves a multitude of roles, most prominently balancing mood. Serotonergic challenge has been observed to reduce intrinsic functional connectivity in brain regions implicated in mood regulation. However, the full scope of serotonergic action on functional connectivity in the human brain has not been explored. Here, we show evidence that a single dose of a serotonin reuptake inhibitor dramatically alters functional connectivity throughout the whole brain in healthy subjects (n = 22). Our network-centrality analysis reveals a widespread decrease in connectivity in most cortical and subcortical areas. In the cerebellum and thalamus, however, we find localized increases. These rapid and brain-encompassing connectivity changes linked to acute serotonin transporter blockade suggest a key role for the serotonin transporter in the modulation of the functional macroscale connectome.


Neuroprotective potential of adenosine A2A and cannabinoid CB1 receptor antagonists in an animal model of Parkinson disease.
The development of nondopaminergic therapeutic strategies that may improve motor and nonmotor deficits, while possibly slowing down the neurodegenerative process and associated neuroinflammation,is a primary goal of Parkinson disease (PD) research. We investigated the neuroprotective and anti-inflammatory potential of combined and single treatment with adenosine A2A and cannabinoid CB1 receptor antagonists MSX-3 and rimonabant, respectively, in a rodent model of PD. Rats bearing a unilateral intrastriatal 6-hydroxydopamine lesion were treated chronically with MSX-3 (0.5or 1 mg/kg/d) and rimonabant (0.1 mg/kg/d) given as monotherapy or combined. The effects of the treatments to counteract dopaminergic cell death and neuroinflammation were assessed by immunohistochemistry for tyrosine hydroxylase and glial cell markers, respectively. Both rimonabant and MSX-3 (1 mg/kg/d) promoted dopaminergic neuron survival in the substantia nigra pars compacta (SNc) when given alone; this effect was weakened when the compounds were combined. Glial activation was not significantly affected by MSX-3 (1 mg/kg/d), whereas rimonabant seemed to increase astrocyte cell density in the SNc. Our findings demonstrate the neuroprotective potential of single treatments and suggest that glial cells might be involved in this protective effect. The results also indicate that the neuroprotective potential of combined therapy may not necessarily reflect or promote single-drug effects and point out that special care should be taken when considering multidrug therapies in PD.


Iodine-impregnated incision drape and bacterial recolonization in simulated total knee arthroplasty.
Background and purpose - Iodine-impregnated incision drapes (IIIDs) are used to prevent surgical site infection (SSI). However, there is some evidence to suggest a potential increase in SSI risk as a result of IIID use, possibly from promotion of skin recolonization. A greater number of viable bacteria in the surgical field of an arthroplasty, and surgery in general, may increase the infection risk. We investigated whether IIID use increases bacterial recolonization compared to no drape use under conditions of simulated total knee arthroplasty (TKA). Methods - 20 patients scheduled for TKA were recruited. Each patient had 1 knee randomized for draping with IIID, while the contralateral knee was left bare. The patients thus served as their own control. The operating room conditions and perioperative procedures of a TKA were simulated. Cylinder samples were collected from the skin of each knee prior to disinfection, and again on 2 occasions after skin preparation-75 min apart. Quantities of bacteria were estimated using a spread plate technique under aerobic conditions. Results - We found similar quantities of bacteria on the intervention and control knees immediately after skin disinfection and after 75 min of simulated surgery. These quantities had not increased at the end of surgery when compared to baseline, so no recolonization was detected on the draped knees or on the bare knees. Interpretation - The use of IIIDs did not increase bacterial recolonization in simulated TKA. This study does not support the hypothesis that IIIDs promote bacterial recolonization and postoperative infection risk.


Mapping Europe into local climate zones.
Cities are major drivers of environmental change at all scales and are especially at risk from the ensuing effects, which include poor air quality, flooding and heat waves. Typically, these issues are studied on a city-by-city basis owing to the spatial complexity of built landscapes, local topography and emission patterns. However, to ensure knowledge sharing and to integrate local-scale processes with regional and global scale modelling initiatives, there is a pressing need for a world-wide database on cities that is suited for environmental studies. In this paper we present a European database that has a particular focus on characterising urbanised landscapes. It has been derived using tools and techniques developed as part of the World Urban Database and Access Portal Tools (WUDAPT) project, which has the goal of acquiring and disseminating climate-relevant information on cities worldwide. The European map is the first major step toward creating a global database on cities that can be integrated with existing topographic and natural land-cover databases to support modelling initiatives.