848 research outputs found

    Genome scan of Diabrotica virgifera virgifera for genetic variation associated with crop rotation tolerance

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    Crop rotation has been a valuable technique for control of Diabrotica virgifera virgifera for almost a century. However, during the last two decades, crop rotation has ceased to be effective in an expanding area of the US corn belt. This failure appears to be due to a change in the insect's oviposition behaviour, which, in all probability, has an underlying genetic basis. A preliminary genome scan using 253 amplified fragment-length polymorphism (AFLP) markers sought to identify genetic variation associated with the circumvention of crop rotation. Samples of D. v. virgifera from east-central Illinois, where crop rotation is ineffective, were compared with samples from Iowa at locations that the behavioural variant has yet to reach. A single AFLP marker showed signs of having been influenced by selection for the circumvention of crop rotation. However, this marker was not diagnostic. The lack of markers strongly associated with the trait may be due to an insufficient density of marker coverage throughout the genome. A weak but significant general heterogeneity was observed between the Illinois and Iowa samples at microsatellite loci and AFLP markers. This has not been detected in previous population genetic studies of D. v. virgifera and may indicate a reduction in gene flow between variant and wild-type beetles

    Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis

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    The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway represents a promising therapeutic target to prevent fibrosis. We have tested the effects of new pharmacological inhibitors of MRTF/SRF signalling in a preclinical model of fibrosis. CCG-222740, a novel MRTF/SRF inhibitor, markedly decreased SRF reporter gene activity and showed a greater inhibitory effect on MRTF/SRF target genes than the previously described MRTF-A inhibitor CCG-203971. CCG-222740 was also five times more potent, with an IC50 of 5 μM, in a fibroblast-mediated collagen contraction assay, was less cytotoxic, and a more potent inhibitor of alpha-smooth muscle actin protein expression than CCG-203971. Local delivery of CCG-222740 and CCG-203971 in a validated and clinically relevant rabbit model of scar tissue formation after glaucoma filtration surgery increased the long-term success of the surgery by 67% (P < 0.0005) and 33% (P < 0.01), respectively, and significantly decreased fibrosis and scarring histologically. Unlike mitomycin-C, neither CCG-222740 nor CCG-203971 caused any detectable epithelial toxicity or systemic side effects with very low drug levels measured in the aqueous, vitreous, and serum. We conclude that inhibitors of MRTF/SRF-regulated gene transcription such as CCG-222740, potentially represent a new therapeutic strategy to prevent scar tissue formation in the eye and other tissues

    Why Are There So Few Rickettsia conorii conorii-Infected Rhipicephalus sanguineus Ticks in the Wild?

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    The bacterium Rickettsia conorii conorii is the etiological agent of Mediterranean spotted fever (MSF), which is a life-threatening infectious disease that is transmitted by Rhipicephalus sanguineus, the brown dog tick. Rh. sanguineus-R. conorii conorii relationships in the wild are still poorly understood one century after the discovery of the disease. In this study, we collected naturally infected ticks from the houses of people afflicted by MSF in Algeria. Colonies of both infected and non-infected ticks were maintained in our laboratory, and we studied the effect of temperature variations on the infected and non-infected ticks. We did not observe any major differences between the biological life cycle of the infected and non-infected ticks held at 25Β°C. However, a comparatively higher mortality relative to the control group was noticed when R. conorii conorii-infected engorged nymphs and adults were exposed to a low temperature (4Β°C) or high temperature (37Β°C) for one month and transferred to 25Β°C. R. conorii conorii-infected Rh. sanguineus may maintain and serve as reservoirs for the Rickettsia if they are not exposed to cold temperatures. New populations of ticks might become infected with Rickettsiae when feeding on a bacteremic animal reservoir

    The impact of AI on radiographic image reporting – perspectives of the UK reporting radiographer population

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    Background: It is predicted that medical imaging services will be greatly impacted by AI in the future. Developments in computer vision have allowed AI to be used for assisted reporting. Studies have investigated radiologists' opinions of AI for image interpretation (Huisman et al., 2019 a/b) but there remains a paucity of information in reporting radiographers' opinions on this topic.Method: A survey was developed by AI expert radiographers and promoted via LinkedIn/Twitter and professional networks for radiographers from all specialities in the UK. A sub analysis was performed for reporting radiographers only.Results: 411 responses were gathered to the full survey (Rainey et al., 2021) with 86 responses from reporting radiographers included in the data analysis. 10.5% of respondents were using AI tools? as part of their reporting role. 59.3% and 57% would not be confident in explaining an AI decision to other healthcare practitioners and 'patients and carers' respectively. 57% felt that an affirmation from AI would increase confidence in their diagnosis. Only 3.5% would not seek second opinion following disagreement from AI. A moderate level of trust in AI was reported: mean score = 5.28 (0 = no trust; 10 = absolute trust). 'Overall performance/accuracy of the system', 'visual explanation (heatmap/ROI)', 'Indication of the confidence of the system in its diagnosis' were suggested as measures to increase trust.Conclusion: AI may impact reporting professionals' confidence in their diagnoses. Respondents are not confident in explaining an AI decision to key stakeholders. UK radiographers do not yet fully trust AI. Improvements are suggested

    Retargeted adenoviruses for radiation-guided gene delivery

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    The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment

    Cost-effectiveness of monitoring glaucoma patients in shared care: an economic evaluation alongside a randomized controlled trial

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    Background. Population aging increases the number of glaucoma patients which leads to higher workloads of glaucoma specialists. If stable glaucoma patients were monitored by optometrists and ophthalmic technicians in a glaucoma follow-up unit (GFU) rather than by glaucoma specialists, the specialists' workload and waiting lists might be reduced. We compared costs and quality of care at the GFU with those of usual care by glaucoma specialists in the Rotterdam Eye Hospital (REH) in a 30-month randomized clinical trial. Because quality of care turned out to be similar, we focus here on the costs. Methods. Stable glaucoma patients were randomized between the GFU and the glaucoma specialist group. Costs per patient year were calculated from four perspectives: those of patients, the Rotterdam Eye Hospital (REH), Dutch healthcare system, and society. The outcome measures were: compliance to the protocol; patient satisfaction; stability according to the practitioner; mean difference in IOP; results of the examinations; and number of treatment changes. Results. Baseline characteristics (such as age, intraocular pressure and target pressure) were comparable between the GFU group (n = 410) and the glaucoma specialist group (n = 405). Despite a higher number of visits per year, mean hospital costs per patient year were lower in the GFU group (€139 vs. €161). Patients' time and travel costs were similar. Healthcare costs were significantly lower for the GFU group (€230 vs. €251), as were societal costs (€310 vs. €339) (p < 0.01). Bootstrap-, sensitivity- and scenario-analyses showed that the costs were robust when varying hospital policy and the duration of visits and tests. Conclusion. We conclude that this GFU is cost-effective and deserves to be considered for implementation in other hospitals

    Strong signature of natural selection within an FHIT intron implicated in prostate cancer risk

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    Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, resequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's Ο‡2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's Ο‡2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (Ο€ = 0.0072, Tajima's D= 3.31, 14 SNPs) and the Japanese (Ο€ = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. Β© 2008 Ding et al

    Patient attitudes toward using computers to improve health services delivery

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    BACKGROUND: The aim of this study was to examine the acceptability of point of care computerized prompts to improve health services delivery among a sample of primary care patients. METHODS: Primary data collection. Cross-sectional survey. Patients were surveyed after their visit with a primary care provider. Data were obtained from patients of ten community-based primary care practices in the spring of 2001. RESULTS: Almost all patients reported that they would support using a computer before each visit to prompt their doctor to: "do health screening tests" (92%), "counsel about health behaviors (like diet and exercise)" (92%) and "change treatments for health conditions" (86%). In multivariate testing, the only variable that was associated with acceptability of the point of care computerized prompts was patient's confidence in their ability to answer questions about their health using a computer (beta = 0.39, p = .001). Concerns about data security were expressed by 36.3% of subjects, but were not related to acceptability of the prompts. CONCLUSIONS: Support for using computers to generate point of care prompts to improve quality-oriented processes of care was high in our sample, but may be contingent on patients feeling familiar with their personal medical history

    Validity of a self-reported measure of familial history of obesity

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    <p>Abstract</p> <p>Background</p> <p>Familial history information could be useful in clinical practice. However, little is known about the accuracy of self-reported familial history, particularly self-reported familial history of obesity (FHO).</p> <p>Methods</p> <p>Two cross-sectional studies were conducted. The aims of study 1 was to compare self-reported and objectively measured weight and height whereas the aims of study 2 were to examine the relationship between the weight and height estimations reported by the study participants and the values provided by their family members as well as the validity of a self-reported measure of FHO. Study 1 was conducted between 2004 and 2006 among 617 subjects and study 2 was conducted in 2006 among 78 participants.</p> <p>Results</p> <p>In both studies, weight and height reported by the participants were significantly correlated with their measured values (study 1: r = 0.98 and 0.98; study 2: r = 0.99 and 0.97 respectively; p < 0.0001). Estimates of weight and height for family members provided by the study participants were strongly correlated with values reported by each family member (r = 0.96 and 0.95, respectively; p < 0.0001). Substantial agreement between the FHO reported by the participants and the one obtained by calculating the BMI of each family members was observed (kappa = 0.72; p < 0.0001). Sensitivity (90.5%), specificity (82.6%), positive (82.6%) and negative (90.5%) predictive values of FHO were very good.</p> <p>Conclusion</p> <p>A self-reported measure of FHO is valid, suggesting that individuals are able to detect the presence or the absence of obesity in their first-degree family members.</p

    Validation of self-reported anthropometrics in the Adventist Health Study 2

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    <p>Abstract</p> <p>Background</p> <p>Relying on self-reported anthropometric data is often the only feasible way of studying large populations. In this context, there are no studies assessing the validity of anthropometrics in a mostly vegetarian population. The objective of this study was to evaluate the validity of self-reported anthropometrics in the Adventist Health Study 2 (AHS-2).</p> <p>Methods</p> <p>We selected a representative sample of 911 participants of AHS-2, a cohort of over 96,000 adult Adventists in the USA and Canada. Then we compared their measured weight and height with those self-reported at baseline. We calculated the validity of the anthropometrics as continuous variables, and as categorical variables for the definition of obesity.</p> <p>Results</p> <p>On average, participants underestimated their weight by 0.20 kg, and overestimated their height by 1.57 cm resulting in underestimation of body mass index (BMI) by 0.61 kg/m<sup>2</sup>. The agreement between self-reported and measured BMI (as a continuous variable), as estimated by intraclass correlation coefficient, was 0.97. The sensitivity of self-reported BMI to detect obesity was 0.81, the specificity 0.97, the predictive positive value 0.93, the predictive negative value 0.92, and the Kappa index 0.81. The percentage of absolute agreement for each category of BMI (normoweight, overweight, and obese) was 83.4%. After multivariate analyses, predictors of differences between self-reported and measured BMI were obesity, soy consumption and the type of dietary pattern.</p> <p>Conclusions</p> <p>Self-reported anthropometric data showed high validity in a representative subsample of the AHS-2 being valid enough to be used in epidemiological studies, although it can lead to some underestimation of obesity.</p
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