Unique Hits Research Articles

A high-throughput approach to identify specific neurotoxicants/ developmental toxicants in human neuronal cell function assays.

The (developmental) neurotoxicity hazard is still unknown for most chemicals. Establishing a test battery covering most of the relevant adverse outcome pathways may close this gap, without requiring a huge animal experimentation program. Ideally, each of the assays would cover multiple mechanisms of toxicity. One candidate test is the human LUHMES cell-based NeuriTox test. To evaluate its readiness for larger-scale testing, a proof of concept library assembled by the U.S. National Toxicology Program (NTP) was screened. Of the 75 unique compounds, seven were defined as specifically neurotoxic after the hit-confirmation phase and additional ten compounds were generally cytotoxic within the concentration range of up to 20 micromolar. As complementary approach, the library was screened in the PeriTox test, which identifies toxicants affecting the human peripheral nervous system. Of the eight PeriTox hits, five were similar to the NeuriTox hits: rotenone, colchicine, diethylstilbestrol, berberine chloride, and valinomycin. The unique NeuriTox hit, methyl-phenylpyridinium (MPP+) is known from in vivo studies to affect only dopaminergic neurons (which LUHMES cells are). Conversely, the known peripheral neurotoxicant acrylamide was picked up in the PeriTox, but not in the NeuriTox assay. All of the five common hits had also been identified in the published neural crest migration (cMINC) assay, while none of them emerged as cardiotoxicant in a previous screen using the same library. These comparative data suggest that complementary in vitro tests can pick up a broad range of toxicants, and that multiple test results might help to predict organ specificity patterns.

Rational library design by functional CDR resampling

Successful antibody discovery relies on diversified libraries, where two aspects are implied, namely the absolute number of unique clones and the percentage of functional clones. Instead of pursuing the absolute quantity thresholded by current display technology, we have sought to maximize the effective diversity by improving functional clone percentage. With the combined effort of bioinformatics, structural biology, molecular immunology and phage display technology, we devised a bioinformatic pipeline to construct and validate libraries via combinatorial assembly of sequences from a database of experimentally validated antibodies. Furthermore, we showed that the libraries constructed as such yielded a significantly increased success rate against different antigen types and generated over 20-fold more unique hits per targets compared with libraries based on traditional degenerate nucleotide methods. Our study indicated that predefined CDR sequences with optimized CDR-framework compatibility could be a productive direction of functional library construction for in vitro antibody development.

Measuring activities and participation in persons with haemophilia: A systematic review of commonly used instruments.

Monitoring clinical outcome in persons with haemophilia (PWH) is essential in order to provide optimal treatment for individual patients and compare effectiveness of treatment strategies. Experience with measurement of activities and participation in haemophilia is limited and consensus on preferred tools is lacking. The aim of this study was to give a comprehensive overview of the measurement properties of a selection of commonly used tools developed to assess activities and participation in PWH. Electronic databases were searched for articles that reported on reliability, validity or responsiveness of predetermined measurement tools (5 self-reported and 4 performance based measurement tools). Methodological quality of the studies was assessed according to the COSMIN checklist. Best evidence synthesis was used to summarize evidence on the measurement properties. The search resulted in 3453 unique hits. Forty-two articles were included. The self-reported Haemophilia Acitivity List (HAL), Pediatric HAL (PedHAL) and the performance based Functional Independence Score in Haemophilia (FISH) were studied most extensively. Methodological quality of the studies was limited. Measurement error, cross-cultural validity and responsiveness have been insufficiently evaluated. Albeit based on limited evidence, the measurement properties of the PedHAL, HAL and FISH are currently considered most satisfactory. Further research needs to focus on measurement error, responsiveness, interpretability and cross-cultural validity of the self-reported tools and validity of performance based tools which are able to assess limitations in sports and leisure activities.

Ribbing disease: a systematic review.

Background Ribbing disease, or multiple diaphyseal sclerosis, is a rare benign bone dysplasia. Purpose To systematically review the literature to determine the clinical and radiological presentation of patients with Ribbing disease as well as the effects of attempted treatments. Material and Methods We considered individual patient data of patients diagnosed with Ribbing disease derived from patient reports and patient series. All stages of the review were performed by two reviewers independently. Standard descriptive statistics were used for quantitative analyses and mixed model analyses were used when appropriate Results The literature search yielded 420 unique hits of which 23 studies were included, covering a total of 40 patients of whom 29 had bilateral involvement. The mean age at diagnosis was 35 years and the mean time between diagnosis and onset of symptoms, mostly pain, was five years (range = 1-16 years). The tibial diaphysis was the most commonly involved bone in 35 of 36 patients. Non-surgical treatment consisted of non-steroidal anti-inflammatory drugs (NSAIDs), prednisone, and bisphophonates with mixed results. Surgical treatment consisted of intramedullary reaming and fenestration and was very effective to reduce pain. Conclusion The clinical presentation and imaging findings of patients with Ribbing disease are becoming more apparent. However, there is paucity of evidence on the natural disease progression and effectiveness of treatment modalities.

Database-driven screening of South African surface water and the targeted detection of pharmaceuticals using liquid chromatography - High resolution mass spectrometry

Pharmaceuticals and personal care products are released into aquatic environments, largely as a result of ineffectual removal during wastewater treatment. Here we present a screening strategy based on the use of three commercially available mass spectral databases, combined into a single searchable entity and parallelized by cluster computing. In addition to this, a targeted solid phase extraction method with Ultra High Pressure Liquid Chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC-QTOF) was used to quantify 99 pharmaceuticals in South African surface water on a national level. Limits of quantification were in the low ng/L range for the majority of the compounds and it was found that nationally both Lamotrigine and Nevirapine occurred most often. Prednisolone and Ritonavir were present at the highest average concentration; 623 and 489 ng/L respectively. It is however shown that more than 50% of the targets chosen for analysis are not detectable in any of the samples, which highlights the utility of untargeted, database driven screening; prior to the use of costly analytical standards. Untargeted screening detected 45% of the compounds detected in targeted mode, and furthermore tentatively identified a total of 4273 unique compounds across the samples. Automatically triggered MS/MS analyses yielded 92 unique hits with greater than 95% confidence. It is therefore suggested that untargeted screening should precede the targeted approach as a matter of economy and to guide the selection of targets for quantification. There is however great room for improvement in current commercial database search methodologies as a large bottleneck exists due to processing time.

P162 NHS GGC staff HIV anti-stigma campaign

IntroductionPeople living with HIV, and maintained on ARVs, can live long and healthy lives.Consequently, there is a growing cohort of people living and ageing with HIV, who are attending NHSGGC for non-HIV related conditions. However, many patients report experiencing stigma and discrimination within these services. NHSGGC responded to this by creating a HIV anti-stigma campaign.MethodsA baseline staff survey was conducted to ascertain knowledge, attitudes and training needs. These results and input from the HIV Patient Forum shaped the campaign, which consisted of: A range of materials, merchandise and activity including posters, road shows, factsheets; training, digital updates and direct messaging to service managers; A patient toolkit which empowers them to challenge stigma and discrimination; Short dramatic videos illustrating patient experience; A repeat staff survey was carried out in 2016Results4000 responses to the baseline survey; 9,325 unique website hits; 300+ staff engaged at road shows; 15 delegates attending training; 1,521 responses to the repeat survey; excellent partnership working between NHSGGC staff and members of the patient forum.DiscussionThe campaign was successful in raising HIV with non-specialist staff. However, uptake of training was low despite an expressed need. Lack of time to train in non-mandatory areas was an issue. Those that did attend training evaluated it well. Results from the repeat survey will shape future interventions for staff.

Seasonal influenza vaccination in patients with COPD: a systematic literature review

BackgroundInfluenza is a frequent cause of exacerbations of chronic obstructive pulmonary disease (COPD). Exacerbations are associated with worsening of the airflow obstruction, hospitalisation, reduced quality of life, disease progression, death, and ultimately, substantial healthcare-related costs. Despite longstanding recommendations to vaccinate vulnerable high-risk groups against seasonal influenza, including patients with COPD, vaccination rates remain sub-optimal in this population.MethodsWe conducted a systematic review to summarise current evidence from randomised controlled trials (RCTs) and observational studies on the immunogenicity, safety, efficacy, and effectiveness of seasonal influenza vaccination in patients with COPD. The selection of relevant articles was based on a three-step selection procedure according to predefined inclusion and exclusion criteria. The search yielded 650 unique hits of which 48 eligible articles were screened in full-text.ResultsSeventeen articles describing 13 different studies were found to be pertinent to this review. Results of four RCTs and one observational study demonstrate that seasonal influenza vaccination is immunogenic in patients with COPD. Two studies assessed the occurrence of COPD exacerbations 14 days after influenza vaccination and found no evidence of an increased risk of exacerbation. Three RCTs showed no significant difference in the occurrence of systemic effects between groups receiving influenza vaccine or placebo. Six out of seven studies on vaccine efficacy or effectiveness indicated long-term benefits of seasonal influenza vaccination, such as reduced number of exacerbations, reduced hospitalisations and outpatient visits, and decreased all-cause and respiratory mortality.ConclusionsAdditional large and well-designed observational studies would contribute to understanding the impact of disease severity and patient characteristics on the response to influenza vaccination. Overall, the evidence supports a positive benefit-risk ratio for seasonal influenza vaccination in patients with COPD, and supports current vaccination recommendations in this population.

Effects of Hearing Impairment and Hearing Aid Amplification on Listening Effort: A Systematic Review.

To undertake a systematic review of available evidence on the effect of hearing impairment and hearing aid amplification on listening effort. Two research questions were addressed: Q1) does hearing impairment affect listening effort? and Q2) can hearing aid amplification affect listening effort during speech comprehension? English language articles were identified through systematic searches in PubMed, EMBASE, Cinahl, the Cochrane Library, and PsycINFO from inception to August 2014. References of eligible studies were checked. The Population, Intervention, Control, Outcomes, and Study design strategy was used to create inclusion criteria for relevance. It was not feasible to apply a meta-analysis of the results from comparable studies. For the articles identified as relevant, a quality rating, based on the 2011 Grading of Recommendations Assessment, Development, and Evaluation Working Group guidelines, was carried out to judge the reliability and confidence of the estimated effects. The primary search produced 7017 unique hits using the keywords: hearing aids OR hearing impairment AND listening effort OR perceptual effort OR ease of listening. Of these, 41 articles fulfilled the Population, Intervention, Control, Outcomes, and Study design selection criteria of: experimental work on hearing impairment OR hearing aid technologies AND listening effort OR fatigue during speech perception. The methods applied in those articles were categorized into subjective, behavioral, and physiological assessment of listening effort. For each study, the statistical analysis addressing research question Q1 and/or Q2 was extracted. In seven articles more than one measure of listening effort was provided. Evidence relating to Q1 was provided by 21 articles that reported 41 relevant findings. Evidence relating to Q2 was provided by 27 articles that reported 56 relevant findings. The quality of evidence on both research questions (Q1 and Q2) was very low, according to the Grading of Recommendations Assessment, Development, and Evaluation Working Group guidelines. We tested the statistical evidence across studies with nonparametric tests. The testing revealed only one consistent effect across studies, namely that listening effort was higher for hearing-impaired listeners compared with normal-hearing listeners (Q1) as measured by electroencephalographic measures. For all other studies, the evidence across studies failed to reveal consistent effects on listening effort. In summary, we could only identify scientific evidence from physiological measurement methods, suggesting that hearing impairment increases listening effort during speech perception (Q1). There was no scientific, finding across studies indicating that hearing aid amplification decreases listening effort (Q2). In general, there were large differences in the study population, the control groups and conditions, and the outcome measures applied between the studies included in this review. The results of this review indicate that published listening effort studies lack consistency, lack standardization across studies, and have insufficient statistical power. The findings underline the need for a common conceptual framework for listening effort to address the current shortcomings.

Health-related quality of life questionnaires in individuals with haemophilia: a systematic review of their measurement properties.

The evaluation of health related quality of life (HRQOL) is essential for a full assessment of the influence of an illness on patients' lives. The aim of this paper is to critically appraise and compare the measurement properties of HRQOL questionnaires studied in haemophilia. Bibliographic databases (Embase, Medline, Cinahl and PsycInfo) were searched for articles evaluating measurement properties of HRQOL questionnaires in haemophilia. Articles were excluded that did not report HRQOL measurement properties, or when <50% of the study population had haemophilia. The methodological quality of the selected studies was evaluated using the COSMIN checklist. The measurement properties of the HRQL questionnaires were rated as 'positive', 'indeterminate' or 'negative', accompanied by levels of evidence. The search resulted in 1597 unique hits, of which 22 studies were included. These articles evaluated three questionnaires for children (CHO-KLAT, Haemo-QoL and one unnamed measure) and five for adults (Hemofilia-QoL, Haemophilia Well-Being Index, HAEMO-QoL-A, Haem-A-QoL, and SF-36). The CHO-KLAT was the paediatric measure that showed the strongest measurement properties in high-quality studies. The Haemophilia Well-Being Index and HAEMO-QoL-A performed best among the adult measures. None of the studies reported measurement error and responsiveness. Our findings suggest that there is no need for new disease-specific HRQOL questionnaires for haemophilia, but rather that additional research is necessary to document the measurement properties of the currently available questionnaires, specifically focusing on the structural validity, measurement error and responsiveness of these questionnaires.

Prevalence of the Use of Opioids for Treatment of Pain in Persons with a Cognitive Impairment Compared with Cognitively Intact Persons: A Systematic Review.

To describe the prevalence of opioid use in persons with a cognitive impairment compared with cognitively intact persons and to explore factors associated with opioid prescription. A search was made in PubMed (Medline), Embase, Cochrane, Central, Cinahl, PsychInfo and Web of Science and additional articles were identified by manual search of reference lists. Titles and abstracts were screened and eligible articles reviewed in full-text. A citation check was performed on the included articles for a complete search. Risk of bias of the included studies was assessed using an appropriate tool. The search yielded 610 unique hits and an additional 33 records were identified via reference checking. After screening, 23 studies were included. A citation tracking was performed for these 23 articles using Web of Science, which yielded an additional 421 articles for a second screening. After the second screening, 24 studies were included. Opioid use was divided into three classes: weak, strong, and weak and strong combined. In several articles there were more than one study conclusion on different opioid classes or in a different setting. Analysis was performed on the prevalence of opioid use (prescription rates) and the dosage of opioids. The 24 studies yielded a total of 35 study conclusions related to prescription rates and dosage. Of these, four showed a higher use of opioids in persons with a cognitive impairment, 14 an equal distribution, and 17 showed lower opioid use in cognitively impaired persons. This systematic review provides evidence for general undertreatment of pain with opioids in persons with a cognitive impairment.

Characterization and optimization of a thin direct electron detector for fast imaging applications

Direct electron detectors are increasingly used to explore the dynamics of macromolecules in real space and real time using transmission electron microscopy. The purpose of this work is to optimize the most suitable detector configuration of a thin silicon detector by Monte Carlo Simulations. Several simulations were performed to achieve an advanced detector geometry that reduces significantly the background signal due to backscattered electrons resulting in an enhanced imaging performance of the detector. Utilizing DEPFET (DEpleted P-channel Field Effect Transistor) technology and the novel ideas for the optimized detector geometry, a unique direct hit electron detector is currently being produced.

The quality of information about sickle cell disease on the Internet for youth.

Adolescence is a vulnerable time for teens with sickle cell disease (SCD). Although there is evidence to support the use of web-based education to promote self-management skills in patients with chronic illnesses, the quality of SCD-related information on the Internet has not been assessed. A website review was conducted to appraise the quality, content, accuracy, readability, and desirability of online information for the adolescents with SCD. Relevant keywords were searched on the most popular search engines. Websites meeting predetermined criteria were reviewed. The quality of information was appraised using the validated DISCERN tool. Two physicians independently rated website completeness and accuracy. Readability of the sites was documented using the simple measure of gobbledygook (SMOG) scores and the Flesch Reading Ease (FRE). The website features considered desirable by youth were tracked. Search results yielded >600 websites with 25 unique hits meeting criteria. The overall quality of the information was "fair" and the average DISCERN rating score was 50.1 (±9.3, range 31.0-67.5). Only 12 of 25 (48%) websites had scores >50. The average completeness score was 20 of 29 (±5, range 12-27). No errors were identified. The mean SMOG score was 13.04 (±2.80, range 10.21-22.85) and the mean FRE score was 46.05 (±11.47; range 17.50-66.10), suggesting that the material was written well beyond the acceptable reading level for patient education. The websites were text-heavy and lacked the features that appeal to youth (chat, games, videos, etc.). Given the paucity of high-quality health information available for the teens with SCD, it is essential that additional online resources be developed.

Eye movements in patients with Whiplash Associated Disorders: a systematic review.

BackgroundMany people with Whiplash Associated Disorders (WAD) report problems with vision, some of which may be due to impaired eye movements. Better understanding of such impaired eye movements could improve diagnostics and treatment strategies.This systematic review surveys the current evidence on changes in eye movements of patients with WAD and explains how the oculomotor system is tested.MethodsNine electronic data bases were searched for relevant articles from inception until September 2015. All studies which investigated eye movements in patients with WAD and included a healthy control group were screened for inclusion. Qualifying studies were retrieved and independently assessed for methodological quality using the Methodology Checklists provided by the Scottish Intercollegiate Guidelines Network.ResultsFourteen studies out of 833 unique hits were included. Ten studies reported impaired eye movements in patients with WAD and in four studies no differences compared to healthy controls were found. Different methods of eye movement examination were used in the ten studies: in five studies, the smooth pursuit neck torsion test was positive, in two more the velocity and stability of head movements during eye-coordination tasks were decreased, and in another three studies the cervico-ocular reflex was elevated.ConclusionsOverall the reviewed studies show deficits in eye movement in patients with WAD, but studies and results are varied. When comparing the results of the 14 relevant publications, one should realise that there are significant differences in test set-up and patient population. In the majority of studies patients show altered compensatory eye movements and smooth pursuit movements which may impair the coordination of head and eyes.

Title, Description, and Subject are the Most Important Metadata Fields for Keyword Discoverability

A Review of:&#x0D; Yang, L. (2016). Metadata effectiveness in internet discovery: An analysis of digital collection metadata elements and internet search engine keywords. College &amp; Research Libraries, 77(1), 7-19. http://doi.org/10.5860/crl.77.1.7 &#x0D; &#x0D; Objective – To determine which metadata elements best facilitate discovery of digital collections.&#x0D; &#x0D; Design – Case study.&#x0D; &#x0D; Setting – A public research university serving over 32,000 graduate and undergraduate students in the Southwestern United States of America. &#x0D; &#x0D; Subjects – A sample of 22,559 keyword searches leading to the institution’s digital repository between August 1, 2013, and July 31, 2014. &#x0D; &#x0D; Methods – The author used Google Analytics to analyze 73,341 visits to the institution’s digital repository. He determined that 22,559 of these visits were due to keyword searches. Using Random Integer Generator, the author identified a random sample of 378 keyword searches. The author then matched the keywords with the Dublin Core and VRA Core metadata elements on the landing page in the digital repository to determine which metadata field had drawn the keyword searcher to that particular page. Many of these keywords matched to more than one metadata field, so the author also analyzed the metadata elements that generated unique keyword hits and those fields that were frequently matched together. &#x0D; &#x0D; Main Results – Title was the most matched metadata field with 279 matched keywords from searches. Description and Subject were also significant fields with 208 and 79 matches respectively. Slightly more than half of the results, 195 keywords, matched the institutional repository in one field only. Both Title and Description had significant match rates both independently and in conjunction with other elements, but Subject keywords were the sole match in only three of the sampled cases. &#x0D; &#x0D; Conclusion – The Dublin Core elements of Title, Description, and Subject were the most frequently matched fields in keyword searches. Academic librarians should focus on these elements when creating records in digital repositories to optimize traffic to their site from search engines.

Do We Need Updated Guidelines on the Use of Insulin Pump Therapy in Type 2 Diabetes? A Review of National and International Practice Guidelines.

Continuous subcutaneous insulin infusion (CSII) is used less for type 2 than for type 1 diabetes because of inconsistencies in evidence of effectiveness. We reviewed published guidelines on intensive insulin therapy in type 2 diabetes to assess whether updating of guidance is needed with respect to evidence used and recommendations for CSII in diabetes management. A literature review was performed to identify published national and international guidelines on type 2 diabetes management. Searches were performed using PubMed, Cochrane Library, and Embase databases, and websites of national health care agencies, reimbursement agencies, and professional associations. Searches were limited to articles published in English between 2004 and 2014 and 1666 unique hits were identified, of which 22 were reviewed following screening. Only 6 of the 22 guidelines identified from North and South America, Western Europe, Greece, and Israel provided specific recommendations on intensive insulin therapy and the role of CSII, and only 1 provided information on the grade of evidence supporting recommendations. Quality appraisal based on the AGREE II tool suggested that published guidelines may have limitations in terms of search methodology and evidence grading, and findings were of mixed rigor and clarity. Only 3 guidelines described the population for whom CSII may be appropriate. Guidelines need to improve the evidence base, rigor, clarity, and grading of evidence associated with recommendations on intensive insulin therapy in type 2 diabetes. Future updates may benefit from considering recent evidence on the efficacy of CSII in poorly controlled patients on MDI.

Effects of Exercise Therapy on Balance Capacity in Chronic Stroke: Systematic Review and Meta-Analysis.

The purpose of this systematic review and meta-analysis was to investigate the effects of exercise training on balance capacity in people in the chronic phase after stroke. Furthermore, we aimed to identify which training regimen was most effective. Electronic databases were searched for randomized controlled trials evaluating the effects of exercise therapy on balance capacity in the chronic phase after stroke. Studies were included if they were of moderate or high methodological quality (PEDro score ≥4). Data were pooled if a specific outcome measure was reported in at least 3 randomized controlled trials. A sensitivity analysis and consequent subgroup analyses were performed for the different types of experimental training (balance and/or weight-shifting training, gait training, multisensory training, high-intensity aerobic exercise training, and other training programs). Forty-three randomized controlled trials out of 369 unique hits were included. A meta-analysis could be conducted for the Berg Balance Scale (28 studies, n=985), Functional Reach Test (5 studies, n=153), Sensory Organization Test (4 studies, n=173), and mean postural sway velocity (3 studies, n=89). A significant overall difference in favor of the intervention group was found for the Berg Balance Scale (mean difference 2.22 points (+3.9%); 95% confidence interval [CI], 1.26-3.17; P<0.01; I(2)=52%), Functional Reach Test (mean difference=3.12 cm; 95% CI, 0.90-5.35; P<0.01; I(2)=74%), and Sensory Organization Test (mean difference=6.77 (+7%) points; 95% CI, 0.83-12.7; P=0.03; I(2)=0%). Subgroup analyses of the studies that included Berg Balance Scale outcomes demonstrated a significant improvement after balance and/or weight-shifting training of 3.75 points (+6.7%; 95% CI, 1.71-5.78; P<0.01; I(2)=52%) and after gait training of 2.26 points (+4.0%; 95% CI, 0.94-3.58; P<0.01; I(2)=21, whereas no significant effects were found for other training regimens. This systematic review and meta-analysis showed that balance capacities can be improved by well-targeted exercise therapy programs in the chronic phase after stroke. Specifically, balance and/or weight-shifting and gait training were identified as successful training regimens.

New Insights on Eggplant/Tomato/Pepper Synteny and Identification of Eggplant and Pepper Orthologous QTL.

Eggplant, pepper, and tomato are the most exploited berry-producing vegetables within the Solanaceae family. Their genomes differ in size, but each has 12 chromosomes which have undergone rearrangements causing a redistribution of loci. The genome sequences of all three species are available but differ in coverage, assembly quality and percentage of anchorage. Determining their syntenic relationship and QTL orthology will contribute to exploit genomic resources and genetic data for key agronomic traits. The syntenic analysis between tomato and pepper based on the alignment of 34,727 tomato CDS to the pepper genome sequence, identified 19,734 unique hits. The resulting synteny map confirmed the 14 inversions and 10 translocations previously documented, but also highlighted 3 new translocations and 4 major new inversions. Furthermore, each of the 12 chromosomes exhibited a number of rearrangements involving small regions of 0.5–0.7 Mbp. Due to high fragmentation of the publicly available eggplant genome sequence, physical localization of most eggplant QTL was not possible, thus, we compared the organization of the eggplant genetic map with the genome sequence of both tomato and pepper. The eggplant/tomato syntenic map confirmed all the 10 translocations but only 9 of the 14 known inversions; on the other hand, a newly detected inversion was recognized while another one was not confirmed. The eggplant/pepper syntenic map confirmed 10 translocations and 8 inversions already detected and suggested a putative new translocation. In order to perform the assessment of eggplant and pepper QTL orthology, the eggplant and pepper sequence-based markers located in their respective genetic map were aligned onto the pepper genome. GBrowse in pepper was used as reference platform for QTL positioning. A set of 151 pepper QTL were located as well as 212 eggplant QTL, including 76 major QTL (PVE ≥ 10%) affecting key agronomic traits. Most were confirmed to cluster in orthologous chromosomal regions. Our results highlight that the availability of genome sequences for an increasing number of crop species and the development of “ultra-dense” physical maps provide new and key tools for detailed syntenic and orthology studies between related plant species.

Systematic Analysis of Intracellular-targeting Antimicrobial Peptides, Bactenecin 7, Hybrid of Pleurocidin and Dermaseptin, Proline–Arginine-rich Peptide, and Lactoferricin B, by Using Escherichia coli Proteome Microarrays

Antimicrobial peptides (AMPs) act either through membrane lysis or by attacking intracellular targets. Intracellular targeting AMPs are a resource for antimicrobial agent development. Several AMPs have been identified as intracellular targeting peptides; however, the intracellular targets of many of these peptides remain unknown. In the present study, we used an Escherichia coli proteome microarray to systematically identify the protein targets of three intracellular targeting AMPs: bactenecin 7 (Bac7), a hybrid of pleurocidin and dermaseptin (P-Der), and proline-arginine-rich peptide (PR-39). In addition, we also included the data of lactoferricin B (LfcinB) from our previous study for a more comprehensive analysis. We analyzed the unique protein hits of each AMP in the Kyoto Encyclopedia of Genes and Genomes. The results indicated that Bac7 targets purine metabolism and histidine kinase, LfcinB attacks the transcription-related activities and several cellular carbohydrate biosynthetic processes, P-Der affects several catabolic processes of small molecules, and PR-39 preferentially recognizes proteins involved in RNA- and folate-metabolism-related cellular processes. Moreover, both Bac7 and LfcinB target purine metabolism, whereas LfcinB and PR-39 target lipopolysaccharide biosynthesis. This suggested that LfcinB and Bac7 as well as LfcinB and PR-39 have a synergistic effect on antimicrobial activity, which was validated through antimicrobial assays. Furthermore, common hits of all four AMPs indicated that all of them target arginine decarboxylase, which is a crucial enzyme for Escherichia coli survival in extremely acidic environments. Thus, these AMPs may display greater inhibition to bacterial growth in extremely acidic environments. We have also confirmed this finding in bacterial growth inhibition assays. In conclusion, this comprehensive identification and systematic analysis of intracellular targeting AMPs reveals crucial insights into the intracellular mechanisms of the action of AMPs.

Identifying and Managing Pain in People with Alzheimer's Disease and Other Types of Dementia: A Systematic Review.

Background and ObjectivePain in patients with Alzheimer’s disease is a complex issue; these patients suffer from the common causes of acute and chronic pain, and some also have neuropathic or nociceptive pain. Whatever the mechanism of pain in these patients, their pain will require careful assessment and management, to insure the correct type and level of analgesia is given. The objective of this systematic review was the identification of studies that have investigated the efficacy of different analgesics on pain intensity or pain-related behavior during nursing home stay and at the end of life.MethodsA search using pain, pain treatment, and dementia MESH terms and keywords was conducted (October 15, 2015) in MEDLINE, EMBASE, PsychINFO, CINAHL, and Cochrane libraries.ResultsOur search yielded 3138 unique hits, published between 1990 and October 2015. We read titles and abstracts, identified 124 papers for full-text evaluation, and included 12 papers to reflect and synthesize the following questions: (1) Which pain assessment tools for people with dementia are responsive to change in pain intensity scores? (2) Which analgesics are efficacy-tested by controlled trials including people with dementia living in nursing homes, including at the end of life? (3) Which outcome measures have been used to identify pain, pain behavior, and/or treatment efficacy in people with dementia?ConclusionDespite increased use of analgesics, pain is still prevalent in people with dementia. Validated pain tools are available but not implemented and not fully tested on responsiveness to treatment. Official guidelines for pain assessment and treatment addressing people with dementia living in a nursing home are lacking. The efficacy of analgesic drug use on pain or neuropsychiatric behavior related to dementia has been hardly investigated.Electronic supplementary materialThe online version of this article (doi:10.1007/s40263-016-0342-7) contains supplementary material, which is available to authorized users.

Transcriptome Analysis of Scrippsiella trochoidea CCMP 3099 Reveals Physiological Changes Related to Nitrate Depletion.

Dinoflagellates are a major component of marine phytoplankton and many species are recognized for their ability to produce harmful algal blooms (HABs). Scrippsiella trochoidea is a non-toxic, marine dinoflagellate that can be found in both cold and tropic waters where it is known to produce “red tide” events. Little is known about the genomic makeup of S. trochoidea and a transcriptome study was conducted to shed light on the biochemical and physiological adaptations related to nutrient depletion. Cultures were grown under N and P limiting conditions and transcriptomes were generated via RNAseq technology. De novo assembly reconstructed 107,415 putative transcripts of which only 41% could be annotated. No significant transcriptomic response was observed in response to initial P depletion, however, a strong transcriptional response to N depletion was detected. Among the down-regulated pathways were those for glutamine/glutamate metabolism as well as urea and nitrate/nitrite transporters. Transcripts for ammonia transporters displayed both up- and down-regulation, perhaps related to a shift to higher affinity transporters. Genes for the utilization of DON compounds were up-regulated. These included transcripts for amino acids transporters, polyamine oxidase, and extracellular proteinase and peptidases. N depletion also triggered down regulation of transcripts related to the production of Photosystems I & II and related proteins. These data are consistent with a metabolic strategy that conserves N while maximizing sustained metabolism by emphasizing the relative contribution of organic N sources. Surprisingly, the transcriptome also contained transcripts potentially related to secondary metabolite production, including a homolog to the Short Isoform Saxitoxin gene (sxtA) from Alexandrium fundyense, which was significantly up-regulated under N-depletion. A total of 113 unique hits to Sxt genes, covering 17 of the 34 genes found in C. raciborskii were detected, indicating that S. trochoidea has previously unrecognized potential for the production of secondary metabolites with potential toxicity.