Effect of riboflavin deficiency on development of the cerebral cortex in Slc52a3 knockout mice

Riboflavin transporter 3 (RFVT3), encoded by the SLC52A3 gene, is important for riboflavin homeostasis in the small intestine, kidney, and placenta. Our previous study demonstrated that Slc52a3 knockout (Slc52a3−/−) mice exhibited neonatal lethality and metabolic disorder due to riboflavin deficiency. Here, we investigated the influence of Slc52a3 gene disruption on brain development using Slc52a3−/− embryos. Slc52a3−/− mice at postnatal day 0 showed hypoplasia of the brain and reduced thickness of cortical layers. At embryonic day 13.5, the formation of Tuj1+ neurons and Tbr2+ intermediate neural progenitors was significantly decreased; no significant difference was observed in the total number and proliferative rate of Pax6+ radial glia. Importantly, the hypoplastic phenotype was rescued upon riboflavin supplementation. Thus, it can be concluded that RFVT3 contributes to riboflavin homeostasis in embryos and that riboflavin itself is required during embryonic development of the cerebral cortex in mice

Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway.

BACKGROUND: Although an increasing number of histone demethylases have been identified and biochemically characterized, their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. We investigated the role of KDM5B, a JmjC histone demethylase, in human carcinogenesis. Quantitative RT-PCR and microarray analyses were used to examine the expression profiles of histone demethylases in clinical tissue samples. We also examined the functional effects of KDM5B on the growth of cancer cell lines treated with small interfering RNAs (siRNAs). Downstream genes and signal cascades induced by KDM5B expression were identified from Affymetrix Gene Chip experiments, and validated by real-time PCR and reporter assays. Cell cycle-dependent characteristics of KDM5B were identified by immunofluorescence and FACS. RESULTS: Quantitative RT-PCR analysis confirmed that expression levels of KDM5B are significantly higher in human bladder cancer tissues than in their corresponding non-neoplastic bladder tissues (P < 0.0001). The expression profile analysis of clinical tissues also revealed up-regulation of KDM5B in various kinds of malignancies. Transfection of KDM5B-specific siRNA into various bladder and lung cancer cell lines significantly suppressed the proliferation of cancer cells and increased the number of cells in sub-G1 phase. Microarray expression analysis indicated that E2F1 and E2F2 are downstream genes in the KDM5B pathway. CONCLUSIONS: Inhibition of KDM5B may affect apoptosis and reduce growth of cancer cells. Further studies will explore the pan-cancer therapeutic potential of KDM5B inhibition.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Clinical implication of children's depression rating scale‐revised score: Linking the children's depression rating scale‐revised score and clinical global impression using patients data from clinical trials

Abstract Background and Aims The Children's Depression Rating Scale‐Revised (CDRS‐R) score has been widely used to assess the severity of major depression in children and adolescents; however, the clinical implications of changes in the CDRS‐R score remain unclear. We evaluated these clinical implications by assessing the relationship between changes in the CDRS‐R score and changes in the Clinical Global Impression of Improvement (CGI‐I), in clinical research on major depression. Methods We used data from four clinical trials involving two antidepressants and evaluated the relationship between CDRS‐R score changes and the CGI‐I score using the equipercentile linking method. Results CDRS‐R score changes corresponding to a minimally improved (score of 3) CGI‐I score was approximately 14 points. Conclusion Our findings from the linking analyses are useful for interpreting the clinical implications of changes in the CDRS‐R score

Computed Tomography Fluoroscopy-guided Biopsy of Lung Nodules: Comparison of the Step-wise and Realtime Techniques

The present study aimed to compare the step-wise and real-time techniques for computed tomography (CT) fluoroscopy-guided biopsy of lung nodules. It included 72 consecutive patients (50 men, 22 women; mean age: 71.8 years; range: 45–89 years) with lung nodules. Between March 2017 and April 2019, 72 CT fluoroscopy-guided biopsy procedures were performed using either the step-wise (n = 34) or real-time technique (n = 38). The diagnostic accuracy was 97.1% for biopsies performed using the step-wise technique and 94.7% for those performed using the real-time technique (p = 0.39). The mean CT dose index was 48.8 ± 16.9 mGy/s for the step-wise method and 59.9 ± 25.6 mGy/s for the real-time method; the dose length product was 1956 ± 729 mGy and 2613 ± 1300 mGy for the two techniques, respectively (p < 0.05). There was a significant difference in mean exposure time (81 ± 43 s for the step-wise technique and 162 ± 120 s for the real-time technique; p < 0.05). The mean lung nodule size was also significantly different (29.9 ± 17.6 mm for the step-wise method and 17.8 ± 12.2 mm for the real-time method; p < 0.01). Of the 34 step-wise procedures, 11 (32.4%) resulted in pneumothorax, as did 24 of 38 (63.2%) real-time procedures (p < 0.01). The real-time technique is particularly useful in patients with small nodules. The CT dose, exposure time, and incidence of pneumothorax were significantly lower when the step-wise technique was applied to CT fluoroscopy-guided biopsy of lung nodules

Filling the Upper Pole with the Pectoralis Major Muscle Flap in Profunda Femoris Artery Perforator Flap Breast Reconstruction

Background and Objectives: Among many donor site options for autologous breast reconstruction, the use of the profunda femoris artery perforator (PAP) flap has become common in patients who are not suitable for the gold standard procedure, the deep inferior epigastric artery perforator flap. However, its limited volume has precluded its wide use in breast reconstruction. The aim of this report was to demonstrate the effectiveness of a method in which the anatomical position of the pectoralis major muscle was adjusted to augment the volume of the superior pole of the breast during PAP flap transfer. A comparison was made with a conventional PAP flap breast reconstruction. Materials and Methods: Fifty-nine consecutive cases where unilateral autologous breast reconstruction was performed using the vertically designed PAP flap were retrospectively reviewed. Conventional PAP flap transfer was performed in 36 patients (Group 1), and PAP flap transfer with pectoralis major muscle augmentation was performed in 23 patients (Group 2). Results: The patient satisfaction at 12 months postoperatively was statistically greater in Group 2, with the pectoralis major muscle augmentation, than in Group 1 [23/36 (64%) vs. 22/23 (96%), p = 0.005]. There were no significant differences in postoperative complication rates at the reconstructed site [2/36 (5.6%) vs. 0/23 (0%), p = 0.52]. Conclusions: Higher patient satisfaction could be achieved with pectoralis major muscle augmentation in PAP flap breast reconstruction without increasing the postoperative complication rate at the reconstructed site

Filling the Upper Pole with the Pectoralis Major Muscle Flap in Profunda Femoris Artery Perforator Flap Breast Reconstruction

Background and Objectives: Among many donor site options for autologous breast reconstruction, the use of the profunda femoris artery perforator (PAP) flap has become common in patients who are not suitable for the gold standard procedure, the deep inferior epigastric artery perforator flap. However, its limited volume has precluded its wide use in breast reconstruction. The aim of this report was to demonstrate the effectiveness of a method in which the anatomical position of the pectoralis major muscle was adjusted to augment the volume of the superior pole of the breast during PAP flap transfer. A comparison was made with a conventional PAP flap breast reconstruction. Materials and Methods: Fifty-nine consecutive cases where unilateral autologous breast reconstruction was performed using the vertically designed PAP flap were retrospectively reviewed. Conventional PAP flap transfer was performed in 36 patients (Group 1), and PAP flap transfer with pectoralis major muscle augmentation was performed in 23 patients (Group 2). Results: The patient satisfaction at 12 months postoperatively was statistically greater in Group 2, with the pectoralis major muscle augmentation, than in Group 1 [23/36 (64%) vs. 22/23 (96%), p = 0.005]. There were no significant differences in postoperative complication rates at the reconstructed site [2/36 (5.6%) vs. 0/23 (0%), p = 0.52]. Conclusions: Higher patient satisfaction could be achieved with pectoralis major muscle augmentation in PAP flap breast reconstruction without increasing the postoperative complication rate at the reconstructed site

Riboflavin transporters RFVT/SLC52A mediate translocation of riboflavin, rather than FMN or FAD, across Plasma Membrane

Riboflavin (vitamin B2) plays a role in various biochemical oxidation-reduction reactions. Flavin mononucleotide (FMN) and FAD, the biologically active forms, are made from riboflavin. Riboflavin transporters (RFVTs), RFVT1-3/Slc52a1-3, have been identified. However, the roles of human (h)RFVTs in FMN and FAD homeostasis have not yet been fully clarified. In this study, we assessed the contribution of each hRFVT to riboflavin, FMN and FAD uptake and efflux using in vitro studies. The transfection of hRFVTs increased cellular riboflavin concentrations. The uptake of riboflavin by human embryonic kidney cells transfected with hRFVTs was significantly increased, and the efflux was accelerated in a time-dependent manner. However, the uptake and efflux of FMN and FAD hardly changed. These results strongly suggest that riboflavin, rather than FMN or FAD, passes through plasma membranes via hRFVTs. Our findings could suggest that hRFVTs are involved in riboflavin homeostasis in the cells, and that FMN and FAD concentrations are regulated by riboflavin kinase and FAD synthase

Early detection of myocardial dysfunction using two-dimensional speckle tracking echocardiography in a young cat with hypertrophic cardiomyopathy

Case summary A 5-month-old intact female Scottish Fold cat was presented for cardiac evaluation. Careful auscultation detected a slight systolic murmur (Levine I/VI). The findings of electrocardiography, thoracic radiography, non-invasive blood pressure measurements and conventional echocardiographic studies were unremarkable. However, two-dimensional speckle tracking echocardiography revealed abnormalities in myocardial deformations, including decreased early-to-late diastolic strain rate ratios in longitudinal, radial and circumferential directions, and deteriorated segmental systolic longitudinal strain. At the follow-up examinations, the cat exhibited echocardiographic left ventricular hypertrophy and was diagnosed with hypertrophic cardiomyopathy using conventional echocardiography. Relevance and novel information This is the first report on the use of two-dimensional speckle tracking echocardiography for the early detection of myocardial dysfunction in a cat with hypertrophic cardiomyopathy; the myocardial dysfunction was detected before the development of hypertrophy. The findings from this case suggest that two-dimensional speckle tracking echocardiography can be useful for myocardial assessment when conventional echocardiographic and Doppler findings are ambiguous

Layer‐specific myocardial function in asymptomatic cats with obstructive hypertrophic cardiomyopathy assessed using 2‐dimensional speckle‐tracking echocardiography

Background Hypertrophic cardiomyopathy (HCM), a primary disorder of the myocardium, is the most common cardiac disease in cats. However, determination of layer‐specific myocardial function with 2D speckle‐tracking echocardiography in cats with asymptomatic HCM has not yet been reported. Objectives To quantitatively measure layer‐specific myocardial function of asymptomatic cats with HCM. Animals Ten client‐owned, asymptomatic cats with obstructive HCM and 13 healthy cats. Methods A retrospective, case‐control study. Cats underwent assessment of layer‐specific myocardial function (whole, endocardial, and epicardial) in the longitudinal and circumferential directions by using 2D speckle‐tracking echocardiography. Results Longitudinal strains were significantly lower in cats with HCM than controls in the whole (−15.5% vs −19.1%), endocardial (−18.3% vs −21.8%), and epicardial (−13.1% vs −16.8%) layers. Circumferential strains in whole and epicardial layers also were significantly lower in cats with HCM as compared with controls (−15.0% vs −20.2% and − 4.4% vs −9.4%, respectively). However, no significant difference was found between cats with HCM and controls in the global circumferential strain in the endocardial layer (−31.2% vs −34.2%). The circumferential endocardial‐to‐epicardial strain ratio was significantly higher in cats with HCM than in controls (6.1 vs 3.5). Conclusions and Clinical Importance Layer‐specific myocardial function assessed by 2D speckle‐tracking echocardiography differed in asymptomatic cats with obstructive HCM compared to controls despite their apparently normal systolic function, as determined by conventional echocardiography. The maintained endocardial circumferential strain and higher circumferential endocardial‐to‐epicardial strain ratio may reflect compensation for occult systolic dysfunction in cats with obstructive HCM