The cytoplasmic tail of the rabies virus G protein is an essential domain controlling death/survival in human neuronal cells

Poster presentation

Tumour ADC measurements in rectal cancer: effect of ROI methods on ADC values and interobserver variability

OBJECTIVES: To assess the influence of region of interest (ROI) size and positioning on tumour ADC measurements and interobserver variability in patients with locally advanced rectal cancer (LARC). METHODS: Forty-six LARC patients were retrospectively included. Patients underwent MRI including DWI (b0,500,1000) before and 6-8 weeks after chemoradiation (CRT). Two readers measured mean tumour ADCs (pre- and post-CRT) according to three ROI protocols: whole-volume, single-slice or small solid samples. The three protocols were compared for differences in ADC, SD and interobserver variability (measured as the intraclass correlation coefficient; ICC). RESULTS: ICC for the whole-volume ROIs was excellent (0.91) pre-CRT versus good (0.66) post-CRT. ICCs were 0.53 and 0.42 for the single-slice ROIs versus 0.60 and 0.65 for the sample ROIs. Pre-CRT ADCs for the sample ROIs were significantly lower than for the whole-volume or single-slice ROIs. Post-CRT there were no significant differences between the whole-volume ROIs and the single-slice or sample ROIs, respectively. The SDs for the whole-volume and single-slice ROIs were significantly larger than for the sample ROIs. CONCLUSIONS: ROI size and positioning have a considerable influence on tumour ADC values and interobserver variability. Interobserver variability is worse after CRT. ADCs obtained from the whole tumour volume provide the most reproducible results. Key Points • ROI size and positioning influence tumour ADC measurements in rectal cancer • ROI size and positioning influence interobserver variability of tumour ADC measurements • ADC measurements of the whole tumour volume provide the most reproducible results • Tumour ADC measurements are more reproducible before, rather than after, chemoradiation treatment • Variations caused by ROI size and positioning should be taken into account when using ADC as a biomarker for tumour response

Tumour ADC measurements in rectal cancer: effect of ROI methods on ADC values and interobserver variability

OBJECTIVES: To assess the influence of region of interest (ROI) size and positioning on tumour ADC measurements and interobserver variability in patients with locally advanced rectal cancer (LARC). METHODS: Forty-six LARC patients were retrospectively included. Patients underwent MRI including DWI (b0,500,1000) before and 6-8 weeks after chemoradiation (CRT). Two readers measured mean tumour ADCs (pre- and post-CRT) according to three ROI protocols: whole-volume, single-slice or small solid samples. The three protocols were compared for differences in ADC, SD and interobserver variability (measured as the intraclass correlation coefficient; ICC). RESULTS: ICC for the whole-volume ROIs was excellent (0.91) pre-CRT versus good (0.66) post-CRT. ICCs were 0.53 and 0.42 for the single-slice ROIs versus 0.60 and 0.65 for the sample ROIs. Pre-CRT ADCs for the sample ROIs were significantly lower than for the whole-volume or single-slice ROIs. Post-CRT there were no significant differences between the whole-volume ROIs and the single-slice or sample ROIs, respectively. The SDs for the whole-volume and single-slice ROIs were significantly larger than for the sample ROIs. CONCLUSIONS: ROI size and positioning have a considerable influence on tumour ADC values and interobserver variability. Interobserver variability is worse after CRT. ADCs obtained from the whole tumour volume provide the most reproducible results. Key Points • ROI size and positioning influence tumour ADC measurements in rectal cancer • ROI size and positioning influence interobserver variability of tumour ADC measurements • ADC measurements of the whole tumour volume provide the most reproducible results • Tumour ADC measurements are more reproducible before, rather than after, chemoradiation treatment • Variations caused by ROI size and positioning should be taken into account when using ADC as a biomarker for tumour response

Role of the urinary concentrating process in the renal effects of high protein intake

Role of the urinary concentrating process in the renal effects of high protein intake. High protein diet is known to increase glomerular filtration rate (GFR) and induce kidney hypertrophy. The mechanisms underlying these changes are not understood. Since the mammalian kidney comprises different nephron segments located in well-delineated zones, it is conceivable that the hypertrophy does not affect all kidney zones and all nephron segments uniformly. The present experiments were designed to study the chronic effects of high or low isocaloric protein diets (HP = 32% or LP = 10% casein, respectively) on kidney function and morphology in Sprague-Dawley rats. HP diet induced significant increases in kidney mass, GFR, free water clearance, and maximum urine concentrating ability. Kidney hypertrophy was characterized by: 1. a preferential increase in thickness of the inner stripe of the outer medulla (IS) (+ 54%, P < 0.001, while total kidney height, from cortex to papillary tip, increased only by 18%); 2. a marked hypertrophy of the thick ascending limbs (TAL) in the inner stripe (+40% epithelium volume/unit tubular length, P < 0.05) but not in the outer stripe nor in the cortex; 3. an increase in heterogeneity of glomeruli between superficial (S) and deep (D) nephrons (D/S = 1.47 in HP vs. 1.17 in LP, P < 0.05). In contrast, normal kidney growth with age and kidney hypertrophy induced by uninephrectomy were not accompanied by preferential enlargement of IS structures. The morphologic changes induced by high protein intake parallel those we previously reported in rats fed a normal diet (25% protein) but in which the operation of the urine concentrating mechanism was chronically stimulated by ADH infusion or by reduction in water intake. This similarity and the dramatic increase in free water reabsorption induced by HP diet suggest that high protein intake affects kidney function and morphology by increasing the level of operation of the urine concentrating process. The preferential increase in TAL epithelium disclosed in this study, and the recent demonstration by others of a decreased salt concentration in the early distal tubule of HP rats raises the possibility that the protein-induced increase in GFR is mediated by a depression of tubuloglomerular feedback resulting from an increased salt transport in the medullary TAL in relation with an increase in free water generation

Strengthening Peer Mentoring Relationships for New Mothers: A Qualitative Analysis

(1) Background: The transition to motherhood can be challenging, especially for first-time mothers, and can accompany maternal distress. Social support—such as that offered by peers— can be important in assisting mothers to manage such distress. Although primiparous mothers often seek out and value peer support programs, few researchers have investigated factors that may influence the strength of relationships in non-professional maternal peer support programs. Insight into these factors can be key to enhancing the success of future peer support interventions. (2) Methods: Reflexive thematic analysis was applied to data gathered from 36 semi-structured interviews conducted with 14 primiparous mothers and 17 peer mentors in a peer support program. (3) Results: Four themes related to successful mentorship were identified: expectations of peer relationship, independence of peer mentor, contact, and similarities. (4) Conclusions: For primiparous mothers who are developing their support network, these factors appear important for promoting close and effective peer support relationships. Interventions that harness the dynamics between these factors may contribute to more successful peer support relationships and mental health outcomes for participants

Statins, but not proprotein convertase subtilisin-kexin type 9 inhibitors, lower chemerin in hypercholesterolemia via low-density lipoprotein receptor upregulation

Hypercholesterolemia is characterized by elevated low-density lipoprotein (LDL)-cholesterol levels and an increased risk of cardiovascular disease. The adipokine chemerin is an additional risk factor. Here we investigated whether cholesterol-lowering with statins or proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) affects chemerin. Both statins and PCKS9i lowered plasma LDL-cholesterol, triglycerides and total cholesterol in hypercholesterolemic patients, and increased high-density lipoprotein (HDL)-cholesterol. Yet, only statins additionally reduced chemerin and high-sensitivity C-reactive protein (hsCRP). Applying PCSK9i on top of statins did not further reduce chemerin. Around 20% of chemerin occurred in the HDL2/HDL3 fractions, while &gt;75% was free. Statins lowered both HDL-bound and free chemerin. Pull-down assays revealed that chemerin binds to the HDL-component Apolipoprotein A-I (ApoA-I). The statins, but not PCSK9i, diminished chemerin secretion from HepG2 cells by upregulating LDL receptor mRNA. Furthermore, chemerin inhibited HDL-mediated cholesterol efflux via its chemerin chemokine-like receptor 1 in differentiated macrophages. In conclusion, statins, but not PCSK9i, lower circulating chemerin by directly affecting its release from hepatocytes. Chemerin binds to ApoA-I and inhibits HDL-mediated cholesterol efflux. Statins prevent this by lowering HDL-bound chemerin. Combined with their anti-inflammatory effect evidenced by hsCRP suppression, this represents a novel cardiovascular protective function of statins that distinguishes them from PCSK9i.</p

Gross tumour volume delineation in anal cancer on T2-weighted and diffusion-weighted MRI - Reproducibility between radiologists and radiation oncologists and impact of reader experience level and DWI image quality

Abstract Purpose To assess how gross tumour volume (GTV) delineation in anal cancer is affected by interobserver variations between radiologists and radiation oncologists, expertise level, and use of T2-weighted MRI (T2W-MRI) vs. diffusion-weighted imaging (DWI), and to explore effects of DWI quality. Methods and materials We retrospectively analyzed the MRIs (T2W-MRI and b800-DWI) of 25 anal cancer patients. Four readers (Senior and Junior Radiologist; Senior and Junior Radiation Oncologist) independently delineated GTVs, first on T2W-MRI only and then on DWI (with reference to T2W-MRI). Maximum Tumour Diameter (MTD) was calculated from each GTV. Mean GTVs/MTDs were compared between readers and between T2W-MRI vs. DWI. Interobserver agreement was calculated as Intraclass Correlation Coefficient (ICC), Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD). DWI image quality was assessed using a 5-point artefact scale. Results Interobserver agreement between radiologists vs. radiation oncologists and between junior vs. senior readers was good–excellent, with similar agreement for T2W-MRI and DWI (e.g. ICCs 0.72–0.94 for T2W-MRI and 0.68–0.89 for DWI). There was a trend towards smaller GTVs on DWI, but only for the radiologists (P = 0.03–0.07). Moderate-severe DWI-artefacts were observed in 11/25 (44%) cases. Agreement tended to be lower in these cases. Conclusion Overall interobserver agreement for anal cancer GTV delineation on MRI is good for both radiologists and radiation oncologists, regardless of experience level. Use of DWI did not improve agreement. DWI artefacts affecting GTV delineation occurred in almost half of the patients, which may severely limit the use of DWI for radiotherapy planning if no steps are undertaken to avoid them

Outcomes and potential impact of a virtual hands-on training program on MRI staging confidence and performance in rectal cancer

Objectives: To explore the potential impact of a dedicated virtual training course on MRI staging confidence and performance in rectal cancer. // Methods: Forty-two radiologists completed a stepwise virtual training course on rectal cancer MRI staging composed of a pre-course (baseline) test with 7 test cases (5 staging, 2 restaging), a 1-day online workshop, 1 month of individual case readings (n = 70 cases with online feedback), a live online feedback session supervised by two expert faculty members, and a post-course test. The ESGAR structured reporting templates for (re)staging were used throughout the course. Results of the pre-course and post-course test were compared in terms of group interobserver agreement (Krippendorf’s alpha), staging confidence (perceived staging difficulty), and diagnostic accuracy (using an expert reference standard). // Results: Though results were largely not statistically significant, the majority of staging variables showed a mild increase in diagnostic accuracy after the course, ranging between + 2% and + 17%. A similar trend was observed for IOA which improved for nearly all variables when comparing the pre- and post-course. There was a significant decrease in the perceived difficulty level (p = 0.03), indicating an improved diagnostic confidence after completion of the course. // Conclusions: Though exploratory in nature, our study results suggest that use of a dedicated virtual training course and web platform has potential to enhance staging performance, confidence, and interobserver agreement to assess rectal cancer on MRI virtual training and could thus be a good alternative (or addition) to in-person training. // Clinical relevance statement: Rectal cancer MRI reporting quality is highly dependent on radiologists’ expertise, stressing the need for dedicated training/teaching. This study shows promising results for a virtual web-based training program, which could be a good alternative (or addition) to in-person training. // Key Points: • Rectal cancer MRI reporting quality is highly dependent on radiologists’ expertise, stressing the need for dedicated training and teaching. • Using a dedicated virtual training course and web-based platform, encouraging first results were achieved to improve staging accuracy, diagnostic confidence, and interobserver agreement. • These exploratory results suggest that virtual training could thus be a good alternative (or addition) to in-person training