Surprising differences, hidden difficulties: findings from a teacher education pilot

Conference Theme: Education for a Global Networked SocietyPaper PresentationIn the last several years, Hong Kong has undergone significant changes in quality assurance and enhancement at the tertiary level. Within this context, the Hong Kong Institute of Education, the region's largest teacher education provider has conducted an exploration of an outcome-based approach to course design, implementation and assessment within teacher education programs. This paper reports findings from an institute-wide pilot study on OBL ...postprin

Elevating microRNA-122 in blood improves outcomes after temporary middle cerebral artery occlusion in rats.

Because our recent studies have demonstrated that miR-122 decreased in whole blood of patients and in whole blood of rats following ischemic stroke, we tested whether elevating blood miR-122 would improve stroke outcomes in rats. Young adult rats were subjected to a temporary middle cerebral artery occlusion (MCAO) or sham operation. A polyethylene glycol-liposome-based transfection system was used to administer a miR-122 mimic after MCAO. Neurological deficits, brain infarction, brain vessel integrity, adhesion molecule expression and expression of miR-122 target and indirect-target genes were examined in blood at 24 h after MCAO with or without miR-122 treatment. miR-122 decreased in blood after MCAO, whereas miR-122 mimic elevated miR-122 in blood 24 h after MCAO. Intravenous but not intracerebroventricular injection of miR-122 mimic decreased neurological deficits and brain infarction, attenuated ICAM-1 expression, and maintained vessel integrity after MCAO. The miR-122 mimic also down-regulated direct target genes (e.g. Vcam1, Nos2, Pla2g2a) and indirect target genes (e.g. Alox5, Itga2b, Timp3, Il1b, Il2, Mmp8) in blood after MCAO which are predicted to affect cell adhesion, diapedesis, leukocyte extravasation, eicosanoid and atherosclerosis signaling. The data show that elevating miR-122 improves stroke outcomes and we postulate this occurs via downregulating miR-122 target genes in blood leukocytes

Naturally Occurring Stable Calcium Isotope Ratios in Body Compartments Provide a Novel Biomarker of Bone Mineral Balance in Children and Young Adults

Serum calcium (Ca), bone biomarkers, and radiological imaging do not allow accurate evaluation of bone mineral balance (BMB), a key determinant of bone mineral density (BMD) and fracture risk. We studied naturally occurring stable (non‐radioactive) Ca isotopes in different body pools as a potential biomarker of BMB. {42}^Ca and {44}^Ca are absorbed from our diet and sequestered into different body compartments following kinetic principles of isotope fractionation; isotopically light {42}^Ca is preferentially incorporated into bone, whereas heavier {44}^Ca preferentially remains in blood and is excreted in urine and feces. Their ratio (δ^{44/42}Ca) n serum and urine increases during bone formation and decreases with bone resorption. In 117 healthy participants, we measured Ca isotopes, biomarkers, and BMD by dual‐energy X‐ray absorptiometry (DXA) and tibial peripheral quantitative CT (pQCT). {44}^Ca and 42Ca were measured by multi‐collector ionization‐coupled plasma mass‐spectrometry in serum, urine, and feces. The relationship between bone Ca gain and loss was calculated using a compartment model. δ^{44/42}Ca_{serum} and δ^{44/42}Ca_{urine} were higher in children (n = 66, median age 13 years) compared with adults (n = 51, median age 28 years; p < 0.0001 and p = 0.008, respectively). δ^{44/42}Ca_{serum} increased with height in boys (p < 0.001, R^{2} = 0.65) and was greatest at Tanner stage 4. δ^{44/42}Ca_{serum} correlated positively with biomarkers of bone formation (25‐hydroxyvitaminD [p < 0.0001, R^{2} = 0.37] and alkaline phosphatase [p = 0.009, R^{2} = 0.18]) and negatively with bone resorption marker parathyroid hormone (PTH; p = 0.03, R^{2} = 0.13). δ^{44/42}Ca_{serum} strongly positively correlated with tibial cortical BMD Z‐score (n = 62; p < 0.001, R^{2} = 0.39) but not DXA. Independent predictors of tibial cortical BMD Z‐score were δ^{44/42}Ca_{serum} (p = 0.004, β = 0.37), 25‐hydroxyvitaminD (p = 0.04, β = 0.19) and PTH (p = 0.03, β = −0.13), together predicting 76% of variability. In conclusion, naturally occurring Ca isotope ratios in different body compartments may provide a novel, non‐invasive method of assessing bone mineralization. Defining an accurate biomarker of BMB could form the basis of future studies investigating Ca dynamics in disease states and the impact of treatments that affect bone homeostasis

Assessment of nutritional status in children with kidney diseases-clinical practice recommendations from the Pediatric Renal Nutrition Taskforce

In children with kidney diseases, an assessment of the child’s growth and nutritional status is important to guide the dietary prescription. No single metric can comprehensively describe the nutrition status; therefore, a series of indices and tools are required for evaluation. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists who develop clinical practice recommendations (CPRs) for the nutritional management of children with kidney diseases. Herein, we present CPRs for nutritional assessment, including measurement of anthropometric and biochemical parameters and evaluation of dietary intake. The statements have been graded using the American Academy of Pediatrics grading matrix. Statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs based on the clinical judgment of the treating physician and dietitian. Audit and research recommendations are provided. The CPRs will be periodically audited and updated by the PRNT

Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

Calcium isotope ratios in blood and urine: A new biomarker for the diagnosis of osteoporosis

We assessed the potential of Calcium (Ca) isotope fractionation measurements in blood (δ44/42CaBlood) and urine (δ44/42CaUrine) as a new biomarker for the diagnosis of osteoporosis. One hundred post-menopausal women aged 50 to 75 years underwent dual-energy X-ray absorptiometry (DXA), the gold standard for determination of bone mineral density. After exclusion of women with kidney failure and vitamin D deficiency (<25 nmol/l) 80 women remained in the study. Of these women 14 fulfilled the standard diagnostic criteria for osteoporosis based on DXA. Both the δ44/42CaBlood (p < 0.001) and δ44/42CaUrine (p = 0.004) values were significantly different in women with osteoporosis (δ44/42CaBlood: −0.99 ± 0.10‰, δ 44/42CaUrine: +0.10 ± 0.21‰, (Mean ± one standard deviation (SD) n = 14) from those without osteoporosis (δ44/42CaBlood: −0.84 ± 0.14‰, δ44/42CaUrine: +0.35 ± 0.33‰, (SD), n = 66). This corresponded to the average Ca concentrations in morning spot urine samples ([Ca]Urine) which were higher (p = 0.041) in those women suffering from osteoporosis ([Ca]Urine-Osteoporosis: 2.58 ± 1.26 mmol/l, (SD), n = 14) than in the control group ([Ca]Urine-Control: 1.96 ± 1.39 mmol/l, (SD), n = 66). However, blood Ca concentrations were statistically indistinguishable between groups ([Ca]Blood, control: 2.39 ± 0.10 mmol/l (SD), n = 66); osteoporosis group: 2.43 ± 0.10 mmol/l (SD, n = 14) and were also not correlated to their corresponding Ca isotope compositions. The δ44/42CaBlood and δ44/42CaUrine values correlated significantly (p = 0.004 to p = 0.031) with their corresponding DXA data indicating that both Ca isotope ratios are biomarkers for osteoporosis. Furthermore, Ca isotope ratios were significantly correlated to other clinical parameters ([Ca]Urine, ([Ca]Urine/Creatinine)) and biomarkers (CRP, CTX/P1NP) associated with bone mineralization and demineralization. From regression analysis it can be shown that the δ44/42CaBlood values are the best biomarker for osteoporosis and that no other clinical parameters need to be taken into account in order to improve diagnosis. Cut-off values for discrimination of subjects suffering from osteoporosis were − 0.85‰ and 0.16‰ for δ44/42CaBlood and δ44/42CaUrine, respectively. Corresponding sensitivities were 100% for δ44/42CaBlood and ~79% for δ44/42CaUrine. Apparent specificities were ~55% for δ44/42CaBlood and ~71%. The apparent discrepancy in the number of diagnosed cases is reconciled by the different methodological approaches to diagnose osteoporosis. DXA reflects the bone mass density (BMD) of selected bones only (femur and spine) whereas the Ca isotope biomarker reflects bone Ca loss of the whole skeleton. In addition, the close correlation between Ca isotopes and biomarkers of bone demineralization suggest that early changes in bone demineralization are detected by Ca isotope values, long before radiological changes in BMD can manifest on DXA. Further studies are required to independently confirm that Ca isotope measurement provide a sensitive, non-invasive and radiation-free method for the diagnosis of osteoporosis

Chronic Kidney Disease and Coronary Artery Disease: JACC State-of-the-Art Review

Chronic kidney disease (CKD) is a major risk factor for coronary artery disease (CAD). As well as their high prevalence of traditional CAD risk factors, such as diabetes and hypertension, persons with CKD are also exposed to other nontraditional, uremia-related cardiovascular disease risk factors, including inflammation, oxidative stress, and abnormal calcium-phosphorus metabolism. CKD and end-stage kidney disease not only increase the risk of CAD, but they also modify its clinical presentation and cardinal symptoms. Management of CAD is complicated in CKD patients, due to their\ua0likelihood of comorbid conditions and potential for side effects during interventions. This summary of the Kidney\ua0Disease: Improving Global Outcomes (KDIGO) Controversies Conference on CAD and CKD (including end-stage\ua0kidney disease and\ua0transplant recipients) seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and\ua0treatment of CAD in CKD and to identify knowledge gaps, areas of controversy, and\ua0priorities for research

Bone Mineral Density and Vascular Calcification in Children and Young Adults With CKD 4 to 5 or on Dialysis

Introduction: Older adults with chronic kidney disease (CKD) can have low bone mineral density (BMD) with concurrent vascular calcification. Mineral accrual by the growing skeleton may protect young people with CKD from extraosseous calcification. Our hypothesis was that children and young adults with increasing BMD do not develop vascular calcification. Methods: This was a multicenter longitudinal study in children and young people (5–30 years) with CKD stages 4 to 5 or on dialysis. BMD was assessed by tibial peripheral quantitative computed tomography (pQCT) and lumbar spine dual-energy X-ray absorptiometry (DXA). The following cardiovascular imaging tests were undertaken: cardiac computed tomography for coronary artery calcification (CAC), ultrasound for carotid intima media thickness z-score (cIMTz), pulse wave velocity z-score (PWVz), and carotid distensibility for arterial stiffness. All measures are presented as age-adjusted and sex-adjusted z-scores. Results: One hundred participants (median age 13.82 years) were assessed at baseline and 57 followed up after a median of 1.45 years. Trabecular BMD z-score (TrabBMDz) decreased (P = 0.01), and there was a nonsignificant decrease in cortical BMD z-score (CortBMDz) (P = 0.09). Median cIMTz and PWVz showed nonsignificant increase (P = 0.23 and P = 0.19, respectively). The annualized increase in TrabBMDz (ΔTrabBMDz) was an independent predictor of cIMTz increase (R2 = 0.48, β = 0.40, P = 0.03). Young people who demonstrated statural growth (n = 33) had lower ΔTrabBMDz and also attenuated vascular changes compared with those with static growth (n = 24). Conclusion: This hypothesis-generating study suggests that children and young adults with CKD or on dialysis may develop vascular calcification even as their BMD increases. A presumed buffering capacity of the growing skeleton may offer some protection against extraosseous calcification

W2S: Microscopy Data with Joint Denoising and Super-Resolution for Widefield to SIM Mapping

In fluorescence microscopy live-cell imaging, there is a critical trade-off between the signal-to-noise ratio and spatial resolution on one side, and the integrity of the biological sample on the other side. To obtain clean high-resolution (HR) images, one can either use microscopy techniques, such as structured-illumination microscopy (SIM), or apply denoising and super-resolution (SR) algorithms. However, the former option requires multiple shots that can damage the samples, and although efficient deep learning based algorithms exist for the latter option, no benchmark exists to evaluate these algorithms on the joint denoising and SR (JDSR) tasks. To study JDSR on microscopy data, we propose such a novel JDSR dataset, Widefield2SIM (W2S), acquired using a conventional fluorescence widefield and SIM imaging. W2S includes 144,000 real fluorescence microscopy images, resulting in a total of 360 sets of images. A set is comprised of noisy low-resolution (LR) widefield images with different noise levels, a noise-free LR image, and a corresponding high-quality HR SIM image. W2S allows us to benchmark the combinations of 6 denoising methods and 6 SR methods. We show that state-of-the-art SR networks perform very poorly on noisy inputs. Our evaluation also reveals that applying the best denoiser in terms of reconstruction error followed by the best SR method does not necessarily yield the best final result. Both quantitative and qualitative results show that SR networks are sensitive to noise and the sequential application of denoising and SR algorithms is sub-optimal. Lastly, we demonstrate that SR networks retrained end-to-end for JDSR outperform any combination of state-of-the-art deep denoising and SR networksComment: ECCVW 2020. Project page: \<https://github.com/ivrl/w2s

Encapsulating peritoneal sclerosis

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