Comparison and transfer testing of multiplex ligation detection methods for GM plants

<p>Abstract</p> <p>Background</p> <p>With the increasing number of GMOs on the global market the maintenance of European GMO regulations is becoming more complex. For the analysis of a single food or feed sample it is necessary to assess the sample for the presence of many GMO-targets simultaneously at a sensitive level. Several methods have been published regarding DNA-based multidetection. Multiplex ligation detection methods have been described that use the same basic approach: i) hybridisation and ligation of specific probes, ii) amplification of the ligated probes and iii) detection and identification of the amplified products. Despite they all have this same basis, the published ligation methods differ radically. The present study investigated with real-time PCR whether these different ligation methods have any influence on the performance of the probes. Sensitivity and the specificity of the padlock probes (PLPs) with the ligation protocol with the best performance were also tested and the selected method was initially validated in a laboratory exchange study.</p> <p>Results</p> <p>Of the ligation protocols tested in this study, the best results were obtained with the PPLMD I and PPLMD II protocols and no consistent differences between these two protocols were observed. Both protocols are based on padlock probe ligation combined with microarray detection. Twenty PLPs were tested for specificity and the best probes were subjected to further evaluation. Up to 13 targets were detected specifically and simultaneously. During the interlaboratory exchange study similar results were achieved by the two participating institutes (NIB, Slovenia, and RIKILT, the Netherlands).</p> <p>Conclusions</p> <p>From the comparison of ligation protocols it can be concluded that two protocols perform equally well on the basis of the selected set of PLPs. Using the most ideal parameters the multiplicity of one of the methods was tested and 13 targets were successfully and specifically detected. In the interlaboratory exchange study it was shown that the selected method meets the 0.1% sensitivity criterion. The present study thus shows that specific and sensitive multidetection of GMO targets is now feasible.</p

Vitality and the course of limitations in activities in osteoarthritis of the hip or knee

<p>Abstract</p> <p>Background</p> <p>The objective of the study was to determine whether psychological and social factors predict the course of limitations in activities in elderly patients with osteoarthritis of the hip or knee, in addition to established somatic and cognitive risk factors.</p> <p>Methods</p> <p>A longitudinal cohort study with a follow-up period of three years was conducted. Patients (N = 237) with hip or knee osteoarthritis were recruited from rehabilitation centers and hospitals. Body functions, comorbidity, cognitive functioning, limitations in activities and psychological and social factors (mental health, vitality, pain coping and perceived social support) were assessed. Statistical analyses included univariate and multivariate regression analyses. Psychological and social factors were added to a previously developed model with body functions, comorbidity and cognitive functioning.</p> <p>Results</p> <p>In knee OA, low vitality has a negative impact on the course of self-reported and performance-based limitations in activities, after controlling for somatic and cognitive factors. In hip OA, psychological and social factors had no additional contribution to the model.</p> <p>Conclusion</p> <p>Low vitality predicts deterioration of limitations in activities in elderly patients with osteoarthritis of the knee, in addition to established somatic and cognitive risk factors. However, the contribution of vitality is relatively small. Results of this study are relevant for the group of patients with knee or hip OA, attending hospitals and rehabilitation centers.</p

Comorbidity, limitations in activities and pain in patients with osteoarthritis of the hip or knee

BACKGROUND: This study aims to contribute to the knowledge of the influence of comorbidity in OA. The objectives of the study were (i) to describe the prevalence of comorbidity and (ii) to describe the relationship between comorbidity (morbidity count, severity and the presence of specific diseases) and limitations in activities and pain in elderly patients with knee or hip OA using a comprehensive inventory of comorbidity. METHODS: A cross-sectional cohort study was conducted, in which 288 elderly patients with hip or knee osteoarthritis were included. Apart from demographic and clinical data, information about comorbidity, limitations in activities (WOMAC, SF-36 and timed walking test) and pain (VAS) was collected by questionnaires and tests. Statistical analyses included descriptive statistics, multivariate regression techniques, t-tests and one-way ANOVA. RESULTS: Almost all patients suffered from at least one comorbid disease, with cardiac diseases, diseases of eye, ear, nose, throat and larynx, other urogenital diseases and endocrine/metabolic diseases being most prevalent. Morbidity count and severity index were associated with more limitations in activities and with more pain. The presence of most of the moderate or severe diseases and obesity was associated with limitations in activities or with pain. CONCLUSION: The results of this study emphasize the importance of comorbidity in the rehabilitation of elderly patients with osteoarthritis of the hip or knee. Clinical practitioners should be aware of the relationship of comorbidity with functional problems in OA patients. (aut. ref.

Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene

Accuracy of physical and occupational therapists' early predictions of recovery after severe middle cerebral artery stroke

Introduction: The ability of physical therapists (PTs) and occupational therapists (OTs) to predict level of outcome accurately was investigated prospectively in 91 severely disabled stroke patients with a first-ever middle cerebral artery (MCA) stroke. Methods: Within the second and fifth week after stroke onset, 364 predictions were made by 59 PTs and 47 OTs about walking ability, dexterity, activities of daily living (ADL), need for additional care in ADL, time required to achieve independent walking ability and maximal level of ADL, and destination of discharge at six months after stroke. The functional recovery patterns of stroke patients were assessed by an independent observer. The accuracy of the therapists' predictions was compared with that of derived prediction models. In addition, the influence of characteristics of patients and therapists on the accuracy of the predictions was investigated. Results: Compared to observed outcomes at six months after stroke, therapists' lowest accuracies of prediction were found for the moment at which maximal ADL score was achieved (r(s) = 0.07; p = NS), and highest accuracy was for level of dexterity of the hemiplegic arm (r(s) = 0.78; p < 0.01). Therapists' predictions of functional outcome at six months tended to be too pessimistic. No significant differences were observed for dexterity and walking ability when the predictions by PTs and OTs were compared with those of regression models, whereas significant differences were found for the accuracies of OTs' and PTs' first prediction of destination of discharge and second predictions of outcome in ADL and need for additional care in ADL. No significant differences were found between the accuracy of PTs' and OTs' predictions, and their ability to predict functional outcome was not significantly influenced by the characteristics of patient and therapists

Course of functional status and pain in osteoarthritis of the hip or knee: A systematic review of the literature

Objective. To systematically review studies describing the course of functioning in patients with osteoarthritis (OA) of the hip or knee and identifying potential prognostic factors. Methods. A systematic search was performed. Studies involving patients with hip or knee OA, >6 months of followup, and outcome measures on functional status or pain were included. Methodologic quality was assessed using a standardized set of 11 criteria; a qualitative data analysis was performed. Results. Approximately 6,500 titles and abstracts were screened and 48 publications were considered for inclusion. Eighteen studies, 4 of which met the high methodologic quality criteria, were included. For hip OA, there was limited evidence that functional status and pain do not change during the first 3 years of followup. After 3 years, however, a worsening of functional status and pain was seen. For knee OA, there was conflicting evidence for the first 3 years and limited evidence for worsening of pain and functional status after 3 years. Furthermore, limited evidence was established for negative associations between future functional status and laxity, proprioceptive inaccuracy, age, body mass index, and knee pain intensity. In contrast, greater muscle strength, better mental health, better self-efficacy, social support, and more aerobic exercise were protective factors in the first 3 years. Conclusion. Pain and functional status in hip or knee OA seem to deteriorate slowly, with limited evidence for worsening after 3 years of followup. In specific subgroups, prognosis in the first 3 years of followup was either worse or better, as both risk factors and protective factors were identified. Prognostic factors included biomechanical factors, psychological factors, clinical factors, and treatment modalities. To strengthen the evidence, further high-quality longitudinal research on hip or knee OA functioning is needed