Közművelődési jelenségek és jelentések. Az ÁMK

Many classroom climate studies suffer from 2 critical problems: They (a) treat climate as a student-level (L1) variable in single-level analyses instead of a classroom-level (L2) construct in multilevel analyses; and (b) rely on manifest-variable models rather than on latent-variable models that control measurement error at L1 and L2, and sampling error in the aggregation of L1 ratings to form L2 constructs. On the basis of an analysis of 2,541 students in Grades 5 or 6 from 89 classrooms, the authors demonstrate doubly latent multilevel structural equation models that overcome both of these problems. The results show that L2 classroom climate (a higher-order factor representing classroom mastery goal orientation, challenge, and teacher caring) had positive effects on self-efficacy and achievement. The authors conclude with a discussion of related issues (e.g., the meaning of L2 constructs vs. L1 residuals, the dimensionality of climate constructs at L2) and guidelines for future research

The effect of unfiltered coffee on potential biomarkers for colonic cancer risk in healthy volunteers: a randomized trial

Background: Epidemiologic studies suggest that coffee use might protect against colorectal cancer. Inconsistencies as to the effect of coffee use and colorectal cancer between epidemiologic studies might be related to the type of coffee brew. Objective: We studied the effect of unfiltered coffee consumption on putative biomarkers for colonic cancer risk. Design: A total of 64 healthy volunteers (31 men and 33 women), with a mean age of 43 ± 11 years were randomly assigned to two groups in a crossover design, with two intervention periods of 2 weeks separated by a washout period of 8 weeks. Treatments were 1 L of cafetiere (French press) coffee daily or no coffee. At the end of each intervention period, fasting blood samples, colorectal biopsies and 48 h faeces were collected. Results: No effect of coffee on colorectal cell proliferation, assayed by estimating the Proliferating Cell Nuclear Antigen labelling index, was seen. Additionally, no effects were seen on the concentrations of faecal soluble bile acids and colorectal mucosal glutathione S-transferase activity. However, unfiltered coffee significantly increased the glutathione content in the colorectal mucosa by 8% and in plasma by 15%. Other aminothiols in plasma also increased on coffee. Conclusion: Unfiltered coffee does not influence the colorectal mucosal proliferation rate, but might increase the detoxification capacity and anti-mutagenic properties in the colorectal mucosa through an increase in glutathione concentration. Whether this effect indeed contributes to a lower colon cancer risk remains to be established

Novel developments in endoscopic mucosal imaging

Endoscopic techniques such as High-definition and optical-chromoendoscopy have had enormous impact on endoscopy practice. Since these techniques allow assessment of most subtle morphological mucosal abnormalities, further improvements in endoscopic practice lay in increasing the detection efficacy of endoscopists. Several new developments could assist in this. First, web based training tools could improve the skills of the endoscopist for enhancing the detection and classification of lesions. Secondly, incorporation of computer aided detection will be the next step to raise endoscopic quality of the captured data. These systems will aid the endoscopist in interpreting the increasing amount of visual information in endoscopic images providing real-time objective second reading. In addition, developments in the field of molecular imaging open opportunities to add functional imaging data, visualizing biological parameters, of the gastrointestinal tract to white-light morphology imaging. For the successful implementation of abovementioned techniques, a true multi-disciplinary approach is of vital importance

Novel cryoballoon 180° ablation system for treatment of Barrett's esophagus-related neoplasia:a first-in-human study

Background The novel 180 degrees cryoballoon (CbAS (180) ) enables semicircumferential treatment over a length of 3cm per application. This first-in-human study evaluates its feasibility, efficacy, and safety for the treatment of Barrett's esophagus (BE) neoplasia. Methods This multicenter study consisted of dose-finding and extension phases. Dose-finding started with the lowest dose possible (1.0mm/s). For each dose, six patients were treated circumferentially over a 3-cm length. The dose was increased until the median BE regression was >= 60% without serious adverse events (SAEs). In the extension phase, the dose was confirmed in 19 new patients. The outcomes were technical success, BE regression after one treatment, and SAEs. Results 25 patients (median Prague C0M3) were included (6 dose-finding/19 extension). In two patients, the CbAS (180) could not be applied because of unstable balloon positioning. The technical success rate was 96% (22/23). In the six dose-finding patients, the starting dose resulted in median BE regression of 94% (95% confidence interval [CI] 60%-97%) without SAEs and was thus considered effective. Overall median BE regression was 80% (95%CI 60%-90%). Conclusion Single-session CbAS (180) seems feasible, safe, and effective, and is a promising technique for the treatment of patients with BE neoplasia

A novel cryoballoon ablation system for eradication of dysplastic Barrett's esophagus:a first-in-human feasibility study

BACKGROUND:  Endoscopic cryoablation for Barrett's esophagus (BE) might offer advantages over heat-based ablation. Focal cryoballoon ablation has been promising for short-segment BE, whereas the novel 90°-swipe cryoballoon ablation system (CbSAS90) ablates larger areas in a single step (90° over 3 cm). The system allows for dose adjustment. CbSAS90 has been feasible and safe in animal and pre-esophagectomy studies. This is the first clinical study to assess feasibility, safety, and efficacy of CbSAS90 for eradication of dysplastic BE. METHODS:  In this prospective study in dysplastic BE patients, dose finding started with semi-circumferential treatment at 0.8 mm/s (dose 1). The dose was escalated by reducing speed by 0.1 mm/s in six patients until BE surface regression was ≥ 80 % without complications ("effective dose"). The effective dose was subsequently confirmed with circumferential treatment in 12 new patients. Post-procedural pain (0 - 10) and dysphagia (0 - 4) were evaluated. Outcomes were feasibility, safety, and BE surface regression. RESULTS:  25 patients were included, with technically successful treatment in 92 % (95 %CI 73 % - 99 %). Median (95 %CI) BE surface regression was 78 % (50 % - 85 %) for dose 1 and 85 % (55 % - 95 %) for dose 2 (0.7 mm/s), which was defined as the effective dose. Circumferential treatment resulted in 93 % (88 % - 96 %) regression. Two of 12 patients with circumferential treatment developed strictures that required dilation. Median pain and dysphagia scores were low (0 - 3 and 0, respectively). CONCLUSIONS: CbSAS90 was feasible and effective for ablating larger BE areas. The optimal dose for circumferential treatment that balances safety and efficacy requires further evaluation

PPS, a Large Multidomain Protein, Functions with Sex-Lethal to Regulate Alternative Splicing in Drosophila

Alternative splicing controls the expression of many genes, including the Drosophila sex determination gene Sex-lethal (Sxl). Sxl expression is controlled via a negative regulatory mechanism where inclusion of the translation-terminating male exon is blocked in females. Previous studies have shown that the mechanism leading to exon skipping is autoregulatory and requires the SXL protein to antagonize exon inclusion by interacting with core spliceosomal proteins, including the U1 snRNP protein Sans-fille (SNF). In studies begun by screening for proteins that interact with SNF, we identified PPS, a previously uncharacterized protein, as a novel component of the machinery required for Sxl male exon skipping. PPS encodes a large protein with four signature motifs, PHD, BRK, TFS2M, and SPOC, typically found in proteins involved in transcription. We demonstrate that PPS has a direct role in Sxl male exon skipping by showing first that loss of function mutations have phenotypes indicative of Sxl misregulation and second that the PPS protein forms a complex with SXL and the unspliced Sxl RNA. In addition, we mapped the recruitment of PPS, SXL, and SNF along the Sxl gene using chromatin immunoprecipitation (ChIP), which revealed that, like many other splicing factors, these proteins bind their RNA targets while in close proximity to the DNA. Interestingly, while SNF and SXL are specifically recruited to their predicted binding sites, PPS has a distinct pattern of accumulation along the Sxl gene, associating with a region that includes, but is not limited to, the SxlPm promoter. Together, these data indicate that PPS is different from other splicing factors involved in male-exon skipping and suggest, for the first time, a functional link between transcription and SXL–mediated alternative splicing. Loss of zygotic PPS function, however, is lethal to both sexes, indicating that its role may be of broad significance

Outcomes of surgical treatment of non-metastatic gastric cancer in patients aged 70 and older:A systematic review and meta-analysis

The optimal surgical treatment strategy for gastric cancer in older patients needs to be carefully evaluated due to increased vulnerability of older patients. We performed a database search for randomized controlled trials (RCTs) and cohort studies that included patients ≥70 years with potentially resectable stage I-III gastric cancer. Postoperative and survival outcomes were compared between groups undergoing 1) gastrectomy vs conservative treatment (best supportive care or non-operative treatment), 2) minimally invasive (MIG) vs open gastrectomy (OG), or 3) extended vs limited lymphadenectomy. When possible, results were pooled using risk ratios (RR). Thirty-one studies were included. Six retrospective studies compared overall survival (OS) between gastrectomy (N = 2332) and conservative treatment (N = 246). Longer OS was reported in the gastrectomy group in all studies, but study quality was low and meta-analysis was not feasible. Eighteen cohort studies compared MIG (N = 3626) and OG (N = 5193). MIG was associated with fewer complications (pooled RR 0.68, 95% confidence interval 0.54–0.84). OS was not different between the groups. Two RCTs and five cohort studies compared outcomes between extended (N = 709) and limited lymphadenectomy (N = 1323). Complication rates were comparable between the groups. Two cohort studies found longer OS or cancer-specific survival after extended lymphadenectomy. No quality of life (QoL) or functional outcomes were reported. In older patients with gastric cancer, there is low-quality evidence for better OS after gastrectomy vs conservative treatment. Compared to OG, MIG was associated with less postoperative morbidity. The evidence to support extended lymphadenectomy is limited. QoL and functional outcomes should be addressed in future studies

Fluorescence-Guided Visualization of Soft-Tissue Sarcomas by Targeting Vascular Endothelial Growth Factor A:A Phase 1 Single-Center Clinical Trial

Resection of soft-tissue sarcoma (STS) is accompanied by a high rate of tumor-positive surgical margins (14%-34%), which potentially lead to decreased disease-free survival. Vascular endothelial growth factor A is overexpressed in malignant tumors, including STS, and can be targeted with bevacizumab-800CW during fluorescence-guided surgery for real-time tumor detection. In this phase 1 clinical trial, we determined the feasibility, safety, and optimal dose of bevacizumab-800CW for fluorescence-guided surgery in STS for in vivo and ex vivo tumor detection. Methods: Patients with a histopathologic diagnosis of STS were included. In the dose-escalation phase, patients received bevacizumab-800CW intravenously 3 d before surgery (10, 25, and 50 mg; n = 8). In the subsequent dose-expansion phase, 7 additional patients received bevacizumab800CW at the optimal dose. Fluorescence images were obtained in vivo and ex vivo during all stages of standard care. The optimal dose was determined by calculating in vivo and ex vivo tumor-to-background ratios (TBR) and correlating these results with histopathology. Results: Fifteen patients with STS completed this study. All tumors could be visualized during in vivo and ex vivo imaging. The optimal bevacizumab-800CW dose proved to be 10 mg, with a median in vivo TBR of 2.0 (+/- 0.58) and a median ex vivo TBR of 2.67 (+/- 1.6). All 7 tumor-positive margins could be observed in real time after surgical resection. Conclusion: GS using 10 mg of bevacizumab-800CW is feasible and safe for intraoperative imaging of STS, potentially allowing tumor detection and margin assessment during surgery. An additional follow-up phase 2 study is needed to confirm the diagnostic accuracy

The optimal imaging window for dysplastic colorectal polyp detection using c-Met targeted fluorescence molecular endoscopy

Fluorescence molecular endoscopy (FME) is an emerging technique that has the potential to improve the 22% colorectal polyp detection miss-rate. We determined the optimal dose-to-imaging interval and safety of FME using EMI-137, a c-Met-targeted fluorescent peptide, in a population at high risk for colorectal cancer. Methods: We performed in vivo FME and quantification of fluorescence by multidiameter single-fiber reflectance/single-fiber fluorescence spectroscopy in 15 patients with a dysplastic colorectal adenoma. EMI-137 was intravenously administered (0.13 mg/kg) at a 1-, 2- or 3-h dose-to-imaging interval (n = 3 patients per cohort). Two cohorts were expanded to 6 patients on the basis of target-to-background ratios. Fluorescence was correlated to histopathology and c-Met expression. EMI-137 binding specificity was assessed by fluorescence microscopy and in vitro experiments. Results: FME using EMI-137 appeared to be safe and well tolerated. All dose-to-imaging intervals showed significantly higher fluorescence in the colorectal lesions than in surrounding tissue, with a target-to-background ratio of 1.53, 1.66, and 1.74 for the 1-, 2-, and 3-h cohorts, respectively, and a mean intrinsic fluorescence of 0.035 vs. 0.023 mm-1 (P < 0.0003), 0.034 vs. 0.021 mm-1 (P < 0.0001), and 0.033 vs. 0.019 mm-1 (P < 0.0001), respectively. Fluorescence correlated with histopathology on a macroscopic and microscopic level, with significant c-Met overexpression in dysplastic mucosa. In vitro, a dose-dependent specific binding was confirmed. Conclusion: FME using EMI-137 appeared to be safe and feasible within a 1- to 3-h dose-to-imaging interval. No clinically significant differences were observed among the cohorts, although a 1-h dose-to-imaging interval was preferred from a clinical perspective. Future studies will investigate EMI-137 for improved colorectal polyp detection during screening colonoscopies

Implementation of population screening for colorectal cancer by repeated fecal occult blood test in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is the third most prevalent type of cancer in the world. Its prognosis is closely related to the disease stage at the time of diagnosis. Early detection of symptomless CRC or precursor lesions through population screening could reduce CRC mortality. However, screening programs are only effective if enough people are willing to participate. This study aims to asses the uptake of a second round of fecal occult blood test (FOBt) based screening and to explore factors that could potentially increase this uptake.</p> <p>Methods and design</p> <p>Two years after the first screening round, 10.000 average risk persons, aged 50 to 75, will again receive an invitation to participate in immunohistochemical FOBt (iFOBt) based screening. Eligible persons will be recruited through a city population database. Invitees will be randomized to receive either an iFOBt with a faeces collection paper or an iFOBt without a collection paper. The iFOBts will be analyzed in a specialized laboratory at the Academic Medical Centre. Positive iFOBts will be followed by a consultation at our outpatient clinic and, in the absence of contra-indications and after informed consent, by a colonoscopy. The primary outcome measure is the participation rate. Secondary outcome measures are the effect of the addition of a collection paper on the participation rate, reasons for participation and non-participation, measures of informed choice and psychological consequences of screening and measures of psychological and physical burden associated with the iFOBt and the colonoscopy. Another secondary outcome measure is the diagnostic yield of the program.</p> <p>Discussion</p> <p>In order to implement population screening for colorectal cancer in the Netherlands, information is needed on the uptake of repeated rounds of FOBt-based screening and on factors that could potentially increase this uptake in the future since effectiveness of such a program depends on the willingness of persons to participate. This study will provide information on the actual uptake and perception of a second round of iFOBt-based screening. The results of this study will contribute to the future implementation of a national colorectal screening program in the Netherlands.</p> <p>Trial registration</p> <p>Dutch Trial register: NTR1327</p