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Author: Grafiati
Published: 27 July 2024
Last updated: 29 July 2024

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1

Rayego-Mateos, Sandra, Jose Luis Morgado-Pascual, José Manuel Valdivielso, Ana Belén Sanz, Enrique Bosch-Panadero, Raúl R. Rodrigues-Díez, Jesús Egido, Alberto Ortiz, Emilio González-Parra, and Marta Ruiz-Ortega. "TRAF3 Modulation: Novel Mechanism for the Anti-inflammatory Effects of the Vitamin D Receptor Agonist Paricalcitol in Renal Disease." Journal of the American Society of Nephrology 31, no. 9 (July 6, 2020): 2026–42. http://dx.doi.org/10.1681/asn.2019111206.

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BackgroundCKD leads to vitamin D deficiency. Treatment with vitamin D receptor agonists (VDRAs) may have nephroprotective and anti-inflammatory actions, but their mechanisms of action are poorly understood.MethodsModulation of the noncanonical NF-κB2 pathway and its component TNF receptor–associated factor 3 (TRAF3) by the VDRA paricalcitol was studied in PBMCs from patients with ESKD, cytokine-stimulated cells, and preclinical kidney injury models.ResultsIn PBMCs isolated from patients with ESKD, TRAF3 protein levels were lower than in healthy controls. This finding was associated with evidence of noncanonical NF-κB2 activation and a proinflammatory state. However, PBMCs from patients with ESKD treated with paricalcitol did not exhibit these features. Experiments in cultured cells confirmed the link between TRAF3 and NF-κB2/inflammation. Decreased TRAF3 ubiquitination in K48-linked chains and cIAP1-TRAF3 interaction mediated the mechanisms of paricalcitol action.TRAF3 overexpression by CRISPR/Cas9 technology mimicked VDRA’s effects. In a preclinical model of kidney injury, paricalcitol inhibited renal NF-κB2 activation and decreased renal inflammation. In VDR knockout mice with renal injury, paricalcitol prevented TRAF3 downregulation and NF-κB2–dependent gene upregulation, suggesting a VDR-independent anti-inflammatory effect of paricalcitol.ConclusionsThese data suggest the anti-inflammatory actions of paricalcitol depend on TRAF3 modulation and subsequent inhibition of the noncanonical NF-κB2 pathway, identifying a novel mechanism for VDRA’s effects. Circulating TRAF3 levels could be a biomarker of renal damage associated with the inflammatory state.
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2

Banks, Mindy, and Stuart M. Sprague. "Vitamin D and Peritoneal Dialysis." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 28, no. 2_suppl (March 2008): 33–37. http://dx.doi.org/10.1177/089686080802802s06.

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Chronic kidney disease – mineral and bone disorder (CKD–MBD) is a cause of significant morbidity and mortality in patients with long-standing kidney disease. Management of secondary hyperparathyroidism includes the use of phosphorus-binding agents and treatment with activated vitamin D compounds, better referred to as vitamin D receptor agonists (VDRAs). In an effort to maximize the therapeutic response while reducing the adverse effects of calcitriol, the naturally synthesized hormone, the use of intravenous administration and several selective VDRAs have been developed. Recently, oral preparations of these selective VDRAs have become available, enabling their use in the peritoneal dialysis (PD) population. The present report reviews the data concerning the use of oral VDRAs for the treatment of hyperparathyroidism in PD patients. The data, although limited, appear to support the use of oral paricalcitol as the VDRA in PD patients. In addition, traditional teaching focuses only on therapy with VDRAs, ignoring vitamin D replacement in CKD stage 5. However, given the potential benefits of calcidiol (25-OH-D) repletion and the rampant 25-OH-D deficiency in the PD population, our opinion is that screening for and treating that deficiency should extend beyond early CKD and also include PD patients.
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3

Lim, Kenneth, Guerman Molostvov, Maria Lubczanska, Simon Fletcher, Rosemary Bland, Thomas F. Hiemstra, and Daniel Zehnder. "Impaired arterial vitamin D signaling occurs in the development of vascular calcification." PLOS ONE 15, no. 11 (November 19, 2020): e0241976. http://dx.doi.org/10.1371/journal.pone.0241976.

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Conflicting data exists as to whether vitamin D receptor agonists (VDRa) are protective of arterial calcification. Confounding this, is the inherent physiological differences between human and animal experimental models and our current fragmented understanding of arterial vitamin D metabolism, their alterations in disease states and responses to VDRa’s. Herein, the study aims to address these problems by leveraging frontiers in human arterial organ culture models. Human arteries were collected from a total of 24 patients (healthy controls, n = 12; end-stage CKD, n = 12). Cross-sectional and interventional studies were performed using arterial organ cultures treated with normal and calcifying (containing 5mmol/L CaCl2 and 5mmol/L β-glycerophosphate) medium, ex vivo. To assess the role of VDRa therapy, arteries were treated with either calcitriol or paricalcitol. We found that human arteries express a functionally active vitamin D system, including the VDR, 1α-hydroxylase and 24-hydroxylase (24-OHase) components and these were dysregulated in CKD arteries. VDRa therapy increased VDR expression in healthy arteries (p<0.01) but not in CKD arteries. Arterial 1α-OHase (p<0.05) and 24-OHase mRNA and protein expression were modulated differentially in healthy and CKD arteries by VDRa therapy. VDRa exposure suppressed Runx2 and MMP-9 expression in CKD arteries, however only paricalcitol suppressed MMP-2. VDRa exposure did not modulate arterial calcification in all organ culture models. However, VDRa reduced expression of senescence associated β-galactosidase (SAβG) staining in human aortic-smooth muscle cells under calcifying conditions, in vitro. In conclusion, maladaptation of arterial vitamin D signaling components occurs in CKD. VDRa exposure can exert vasculo-protective effects and seems critical for the regulation of arterial health in CKD.
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Morgado-Pascual, Jose L., Sandra Rayego-Mateos, Jose M. Valdivielso, Alberto Ortiz, Jesus Egido, and Marta Ruiz-Ortega. "Paricalcitol Inhibits Aldosterone-Induced Proinflammatory Factors by Modulating Epidermal Growth Factor Receptor Pathway in Cultured Tubular Epithelial Cells." BioMed Research International 2015 (2015): 1–13. http://dx.doi.org/10.1155/2015/783538.

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Chronic kidney disease is characterized by Vitamin D deficiency and activation of the renin-angiotensin-aldosterone system. Increasing data show that vitamin D receptor agonists (VDRAs) exert beneficial effects in renal disease and possess anti-inflammatory properties, but the underlying mechanism remains unknown. Emerging evidence suggests that “a disintegrin and metalloproteinase” (ADAM)/epidermal growth factor receptor (EGFR) signalling axis contributes to renal damage. Aldosterone induces EGFR transactivation regulating several processes including cell proliferation and fibrosis. However, data on tubular epithelial cells is scarce. We have found that, in cultured tubular epithelial cells, aldosterone induced EGFR transactivation via TGF-α/ADAM17. Blockade of the TGF-α/ADAM17/EGFR pathway inhibited aldosterone-induced proinflammatory gene upregulation. Moreover, among the potential downstream mechanisms, we found that TGF-α/ADAM17/EGFR inhibition blocked ERK and STAT-1 activation in response to aldosterone. Next, we investigated the involvement of TGF-α/ADAM17/EGFR axis in VDRA anti-inflammatory effects. Preincubation with the VDRA paricalcitol inhibited aldosterone-induced EGFR transactivation, TGF-α/ADAM-17 gene upregulation, and downstream mechanisms, including proinflammatory factors overexpression. In conclusion, our data suggest that the anti-inflammatory actions of paricalcitol in tubular cells could depend on the inhibition of TGF-α/ADAM17/EGFR pathway in response to aldosterone, showing an important mechanism of VDRAs action.
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5

Sprague, Stuart M., Adrian C. Covic, Jürgen Floege, Markus Ketteler, Jaco Botha, Edward M. Chong, and Anjay Rastogi. "Pharmacodynamic Effects of Sucroferric Oxyhydroxide and Sevelamer Carbonate on Vitamin D Receptor Agonist Bioactivity in Dialysis Patients." American Journal of Nephrology 44, no. 2 (2016): 104–12. http://dx.doi.org/10.1159/000447600.

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Background: Many patients with chronic kidney disease are prescribed vitamin D receptor agonists (VDRAs) for the management of secondary hyperparathyroidism. Oral phosphate binders may interact with, and potentially reduce the therapeutic activity of, oral VDRAs. This post hoc analysis of a Phase 3 study evaluated the pharmacodynamic effects of the iron-based phosphate binder sucroferric oxyhydroxide (SFOH) and sevelamer (SEV) carbonate on VDRA activity in dialysis patients. Methods: One thousand and fifty nine patients were randomized to SFOH 1.0-3.0 g/day (n = 710) or SEV 2.4-14.4 g/day (n = 349) for up to 52 weeks. Potential interactions of SFOH and SEV with VDRAs were assessed using serum intact parathyroid hormone (iPTH) concentrations as a pharmacodynamic biomarker. Three populations of SFOH- and SEV-treated patients were analyzed: Population 1 (n = 187), patients taking concomitant stable doses of oral VDRAs only; Population 2 (n = 250), patients taking no concomitant VDRAs; Population 3 (n = 68), patients taking concomitant stable doses of intravenous paricalcitol only. Populations were compared using a mixed-effects model to obtain the least squares mean change in iPTH from baseline to Week 52. Differences between treatment groups were also compared. Results: In Population 1, iPTH decreased from baseline to Week 52 in the SFOH group (-25.3 pg/ml) but increased in the SEV group (89.8 pg/ml) (p = 0.02). In Population 2, iPTH increased to a similar extent in both treatment groups. In Population 3, iPTH concentrations in both treatment groups decreased to a similar degree (-29.6 and -11.4 pg/ml for SFOH and SEV, respectively; p = 0.87). Conclusions: In contrast with SEV, SFOH did not appear to impact the iPTH-lowering effect of oral VDRAs.
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Cozzolino, Mario, Florjan Mehmeti, Paola Ciceri, Elisa Volpi, Andrea Stucchi, Irene Brenna, and Daniele Cusi. "The Effect of Paricalcitol on Vascular Calcification and Cardiovascular Disease in Uremia: Beyond PTH Control." International Journal of Nephrology 2011 (2011): 1–5. http://dx.doi.org/10.4061/2011/269060.

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Secondary hyperparathyroidism is a systemic disorder that associates with bone and cardiovascular disease, including arterial calcification. Treatment with calcitriol, the active form of vitamin D, reduces parathyroid hormone levels, but may result in elevations in serum calcium and phosphorus, increasing the risk of vascular calcification in dialysis patients. New vitamin D receptor activators (VDRAs) have been developed and investigated with the rationale to treat high serum PTH levels, with a reduced risk of hypercalcemia and hyperphosphatemia. Paricalcitol is a selective VDRA that suppresses PTH secretion with minimal increases on serum calcium and phosphate. Moreover, paricalcitol prevents vascular calcification in experimental models of renal failure, compared with calcitriol.
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7

Wu-Wong, J. Ruth, Yung-wu Chen, and Jerry L. Wessale. "Vitamin D receptor agonist VS-105 improves cardiac function in the presence of enalapril in 5/6 nephrectomized rats." American Journal of Physiology-Renal Physiology 308, no. 4 (February 15, 2015): F309—F319. http://dx.doi.org/10.1152/ajprenal.00129.2014.

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Vitamin D receptor (VDR) agonists (VDRAs) are commonly used to manage hyperparathyroidism secondary to chronic kidney disease (CKD). Patients with CKD experience extremely high risks of cardiovascular morbidity and mortality. Clinical observations show that VDRA therapy may be associated with cardio-renal protective and survival benefits in patients with CKD. The 5/6 nephrectomized (NX) Sprague-Dawley rat with established uremia exhibits elevated serum parathyroid hormone (PTH), hypertension, and abnormal cardiac function. Treatment of 5/6 NX rats with VS-105, a novel VDRA (0.05 and 0.5 μg/kg po by gavage), once daily for 8 wk in the presence or absence of enalapril (30 mg/kg po via drinking water) effectively suppressed serum PTH without raising serum calcium. VS-105 alone reduced systolic blood pressure (from 174 ± 6 to 145 ± 9 mmHg, P < 0.05) as effectively as enalapril (from 174 ± 6 to 144 ± 7 mmHg, P < 0.05). VS-105 improved cardiac functional parameters such as E/A ratio, ejection fraction, and fractional shortening with or without enalapril. Enalapril or VS-105 alone significantly reduced left ventricular hypertrophy (LVH); VS-105 plus enalapril did not further reduce LVH. VS-105 significantly reduced both cardiac and renal fibrosis. The lack of hypercalcemic toxicity of VS-105 is due to its lack of effects on stimulating intestinal calcium transport and inducing the expression of intestinal calcium transporter genes such as Calb3 and TRPV6. These studies demonstrate that VS-105 is a novel VDRA that may provide cardiovascular benefits via VDR activation. Clinical studies are required to confirm the cardiovascular benefits of VS-105 in CKD.
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Cianciolo, Giuseppe, Andrea Galassi, Irene Capelli, Maria Laura Angelini, Gaetano La Manna, and Mario Cozzolino. "Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy." American Journal of Nephrology 43, no. 6 (2016): 397–407. http://dx.doi.org/10.1159/000446863.

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Chronic kidney disease-mineral and bone disorder (CKD-MBD) is common in kidney transplant recipients (KTRs), where secondary hyperparathyroidism (HPTH) and post-transplantation bone disease (PTBD) are potential effectors of both graft and vascular aging. Reduced 25(OH)D levels are highly prevalent in KTRs. Experimental and clinical evidence support the direct involvement of deranged vitamin D metabolism in CKD-MBD among KTRs. This review analyzes the pathophysiology of vitamin D derangement in KTRs and its fall out on patient and graft outcome, highlighting the roles of both nutritional and active vitamin D compounds to treat PTBD, cardiovascular disease (CVD) and graft dysfunction. Fibroblast growth factor-23-parathyroid hormone (PTH)-vitamin D axis, immunosuppressive therapy and previous bone status have been associated with PTBD. Although several studies reported reduced PTH levels in KTRs receiving nutritional vitamin D, its effects on bone mineral density (BMD) remain controversial. Active vitamin D reduced PTH levels and increased BMD after transplantation, but paricalcitol treatment was not accompanied by benefits on osteopenia. Vitamin D is considered protective against CVD due to the widespread pleiotropic effects, but data among KTRs remain scanty. Although vitamin deficiency is associated with lower glomerular filtration rate (GFR) and faster estimated GFR decline and data on the anti-proteinuric effects of vitamin D receptor activation (VDRA) in KTRs sound encouraging, reports on related improvement on graft survival are still lacking. Clinical data support the efficacy of VDRA against HPTH and show promising evidence of VDRA's effect in counteracting post-transplant proteinuria. New insights are mandatory to establish if the improvement of surrogate outcomes will translate into better patient and graft outcome.
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Inaguma, Daijo, Yoshitaka Tatematsu, Naoki Okamoto, Soshiro Ogata, Hideki Kawai, Eiichi Watanabe, Yukio Yuzawa, Midori Hasegawa, and Naotake Tsuboi. "Multicentre, open-label, randomised, controlled trial to compare early intervention with calcimimetics and conventional therapy in preventing coronary artery calcification in patients with secondary hyperparathyroidism (UPCOMING): a study protocol." BMJ Open 14, no. 1 (January 2024): e076962. http://dx.doi.org/10.1136/bmjopen-2023-076962.

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IntroductionCoronary artery and heart valve calcification is a risk factor for cardiovascular death in haemodialysis patients, so calcification prevention should be started as early as possible. Treatment with concomitant calcimimetics and low-dose vitamin D receptor activators (VDRAs) is available, but not enough evidence has been obtained on the efficacy of this regimen, particularly in patients with short dialysis duration. Therefore, this study will evaluate the efficacy and safety of early intervention with upacicalcet, a calcimimetic used to prevent coronary artery calcification in this patient population.Methods and analysisThis multicentre, open-label, randomised, parallel-group controlled study will compare an early intervention group, which received upacicalcet and a low-dose VDRA, with a conventional therapy group, which received a VDRA. The primary endpoint is a change in log coronary artery calcium volume score from baseline to 52 weeks. The main inclusion criteria are as follows: (1) age 18 years or older; (2) dialysis is planned or dialysis duration is less than 60 months; (3) intact parathyroid hormone (PTH) >240 pg/mL or whole PTH level>140 pg/mL; (4) serum-corrected calcium≥8.4 mg/dL and (5) Agatston score >30. The main exclusion criteria are as follows: (1) history of parathyroid intervention or fracture in the past 12 weeks; (2) history of myocardial infarction, stroke or leg amputation in the past 12 weeks; (3) history of coronary angioplasty and (4) heart failure of New York Heart Association class III or worse.Ethics and disseminationThe study will comply with the Declaration of Helsinki and the Japanese Clinical Trials Act. The study protocol has been approved by the Fujita Health University Certified Review Board (file no. CR22-052). Written informed consent will be obtained from all participants. Study results will be presented in academic meetings and peer-reviewed academic journals.Trial registration numberjRCTs041220126.
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Tai, Sheng-Lun, Yu-Chieng Liou, Juanzhen Sun, Shao-Fan Chang, and Min-Chao Kuo. "Precipitation Forecasting Using Doppler Radar Data, a Cloud Model with Adjoint, and the Weather Research and Forecasting Model: Real Case Studies during SoWMEX in Taiwan." Weather and Forecasting 26, no. 6 (December 1, 2011): 975–92. http://dx.doi.org/10.1175/waf-d-11-00019.1.

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Abstract The quantitative precipitation forecast (QPF) capability of the Variational Doppler Radar Analysis System (VDRAS) is investigated in the Taiwan area, where the complex topography and surrounding oceans pose great challenges to accurate rainfall prediction. Two real cases observed during intensive operation periods (IOPs) 4 and 8 of the 2008 Southwest Monsoon Experiment (SoWMEX) are selected for this study. Experiments are first carried out to explore the sensitivity of the retrieved fields and model forecasts with respect to different background fields. All results after assimilation of the Doppler radar data indicate that the principal kinematic and thermodynamic features recovered by the VDRAS four-dimensional variational data assimilation (4DVAR) technique are rather reasonable. Starting from a background field generated by blending ground-based in situ measurements (radiosonde and surface mesonet station) and reanalysis data over the oceans, VDRAS is capable of capturing the evolution of the major precipitation systems after 2 h of simulation. The model QPF capability is generally comparable to or better than that obtained using only in situ observations or reanalysis data to prepare the background fields. In a second set of experiments, it is proposed to merge the VDRAS analysis field with the Weather Research and Forecasting Model (WRF), and let the latter continue with the following model integration. The results indicate that through this combination, the performance of the model QPF can be further improved. The accuracy of the predicted 2-h accumulated rainfall turns out to be significantly higher than that generated by using VDRAS or WRF alone. This can be attributed to the assimilation of meso- and convective-scale information, embedded in the radar data, into VDRAS, and to better treatment of the topographic effects by the WRF simulation. The results illustrated in this study demonstrate a feasible extension for the application of VDRAS in other regions with similar geographic conditions and observational limitations.
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Stratos, Ioannis, Svenja Schleese, Ingmar Rinas, Brigitte Vollmar, and Thomas Mittlmeier. "Effect of Calcitriol and Vitamin D Receptor Modulator 2 on Recovery of Injured Skeletal Muscle in Wistar Rats." Biomedicines 11, no. 9 (September 7, 2023): 2477. http://dx.doi.org/10.3390/biomedicines11092477.

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Muscle injuries often result in functional limitations due to insufficient healing. This study assessed the influence of calcitriol and vitamin D Receptor Modulator 2 (VDRM2) on muscle regeneration in male Wistar rats following open blunt muscle injury. The injured left soleus muscle of the rats was treated for the first four days after trauma with local injections of either calcitriol, VDRM2, or a 10% ethanol solution (control). Although muscle strength significantly decreased post-injury, all groups showed gradual improvement but did not achieve full recovery. By the 14th day, calcitriol-treated rats significantly outperformed the control group in the incomplete tetanic force, with VDRM2-treated rats showing muscle strength values that fell between the control and calcitriol groups. Similar trends were observed in complete tetanic contractions and were confirmed histologically via muscle cell width quantification. Additionally, histological analysis showed increased cellular turnover on the fourth postoperative day in the calcitriol group, as indicated by elevated cell proliferation rates and fewer apoptotic cells. VDRM2-treated animals showed only an increased proliferative activity on day 4 after injury. No noticeable differences between the groups for CAE-positive cells or visible muscle tissue area were found. In conclusion, predominantly calcitriol positively influenced post-trauma muscle recovery, where VDRM2 had substantially lower biological activity.
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Inaguma, Daijo, Eri Ito, Shigehisa Koide, Kazuo Takahashi, Hiroki Hayashi, Midori Hasegawa, and Yukio Yuzawa. "Combination Therapy with Renin-Angiotensin System Blockers and Vitamin D Receptor Activators for Predialysis Patients Is Associated with the Incidence of Cardiovascular Events after Dialysis Initiation: A Multicenter Nonrandomized Prospective Cohort Study." Cardiorenal Medicine 8, no. 1 (November 3, 2017): 71–81. http://dx.doi.org/10.1159/000479894.

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Background: Several human studies reported that the combined use of renin-angiotensin system blockers (RASBs) and vitamin D receptor activators (VDRAs) resulted in decreased urinary protein excretion. However, it is unknown whether this combination therapy influences the incidence of cardiovascular (CV) events in dialysis patients. Methods: The study was a multicenter nonrandomized prospective cohort analysis including 1,518 patients. Patients were classified into 4 groups based on medications prescribed before dialysis initiation: those who did not receive RASBs or oral VDRAs (N group), those receiving only RASBs, those receiving only VDRAs, and those receiving a combination of RASBs and VDRAs (RD group). CV events after dialysis initiation were compared using the log-rank test. Factors contributing to the incidence of CV events were examined using multivariate Cox proportional hazard regression analysis. Results: Significant differences were observed in the incidence of CV events and all-cause mortality between the 4 groups (p = 0.021 and p = 0.001, respectively). Cox proportional hazard analysis revealed that the incidence of CV events was significantly lower in the RD group than in the N group (hazard ratio [HR] = 0.65, 95% confidence interval [CI]: 0.50-0.86, p = 0.002). Multivariate analysis revealed that the incidence of CV events was significantly lower in the RD group than in the N group (HR = 0.66, 95% CI: 0.47-0.93, p = 0.016). Conclusion: Combination therapy with RASBs and VDRAs in patients before dialysis initiation was associated with a reduction in CV events during maintenance dialysis.
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Lim, Eunha, and Juanzhen Sun. "A Velocity Dealiasing Technique Using Rapidly Updated Analysis from a Four-Dimensional Variational Doppler Radar Data Assimilation System." Journal of Atmospheric and Oceanic Technology 27, no. 7 (July 1, 2010): 1140–52. http://dx.doi.org/10.1175/2010jtecha1300.1.

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Abstract A Doppler velocity dealiasing algorithm is developed within the storm-scale four-dimensional radar data assimilation system known as the Variational Doppler Radar Analysis System (VDRAS). The innovative aspect of the algorithm is that it dealiases Doppler velocity at each grid point independently by using three-dimensional wind fields obtained either from an objective analysis using conventional observations and mesoscale model output or from a rapidly updated analysis of VDRAS that assimilates radar data. This algorithm consists of three steps: preserving horizontal shear, global dealiasing using reference wind from the objective analysis or the VDRAS analysis, and local dealiasing. It is automated and intended to be used operationally for radar data assimilation using numerical weather prediction models. The algorithm was tested with 384 volumes of radar data observed from the Next Generation Weather Radar (NEXRAD) for a severe thunderstorm that occurred during 15 June 2002. It showed that the algorithm was effective in dealiasing large areas of aliased velocities when the wind from the objective analysis was used as the reference and that more accurate dealiasing was achieved by using the continuously cycled VDRAS analysis.
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Sun, Juanzhen, Mingxuan Chen, and Yingchun Wang. "A Frequent-Updating Analysis System Based on Radar, Surface, and Mesoscale Model Data for the Beijing 2008 Forecast Demonstration Project." Weather and Forecasting 25, no. 6 (December 1, 2010): 1715–35. http://dx.doi.org/10.1175/2010waf2222336.1.

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Abstract The Variational Doppler Radar Analysis System (VDRAS) was implemented in Beijing, China, and contributed to the Beijing 2008 Forecast Demonstration Project (B08FDP) in support of the Beijing Summer Olympics. VDRAS is a four-dimensional variational data assimilation system that produces frequently updated analyses using Doppler radar radial velocities and reflectivities, surface observations, and mesoscale model data. The system was tested in real time during the B08FDP pretrials in the summers of 2006 and 2007 and run during the Olympics to assist the 0–6-h convective weather nowcasting. This paper provides a description of the upgraded system and its Beijing implementation, an evaluation of the system performance using data collected during the pretrials, and its utility on convective weather nowcasting through two case studies. Verification of VDRAS wind against a wind profiler shows that the analyzed wind is reasonably accurate with a smaller RMS difference for 2006 than for 2007 due to better radar data coverage in 2006. The analyzed cold pools in three convective episodes are compared with surface observations at selected stations. The result shows good agreement between the analysis and the observations. The two case studies demonstrate the role that VDRAS could play in nowcasting convective initiation.
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Cozzolino, Mario, and Diego Brancaccio. "VDRAs versus calcimimetics: better safe than sorry?" Kidney International 74, no. 7 (October 2008): 966. http://dx.doi.org/10.1038/ki.2008.363.

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Chang, Shao-Fan, Yu-Chieng Liou, Juanzhen Sun, and Sheng-Lun Tai. "The Implementation of the Ice-Phase Microphysical Process into a Four-Dimensional Variational Doppler Radar Analysis System (VDRAS) and Its Impact on Parameter Retrieval and Quantitative Precipitation Nowcasting." Journal of the Atmospheric Sciences 73, no. 3 (February 9, 2016): 1015–38. http://dx.doi.org/10.1175/jas-d-15-0184.1.

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Abstract The microphysical process of a cloud-scale model used by a four-dimensional Variational Doppler Radar Analysis System (VDRAS) is extended from its original warm rain parameterization scheme to a cold rain process containing ice and snow. The development of the adjoint equations for the additional control variables related to ice physics is accomplished by utilizing the existing four-dimensional variational (4DVar) minimization framework employed by VDRAS. Experiments are conducted to examine the accuracy of the new 4DVar system with the ice physics scheme implemented and to explore the impact of the ice-phase process on numerical simulations, parameter retrievals, and the model’s quantitative precipitation nowcasting (QPN) capability. It is shown that the ice-phase microphysical process can significantly alter the kinematic and thermodynamic structure of deep convection and provide a better description of the contents of the hydrometeors. During the 4DVar minimization, using the VDRAS-predicted freezing level after the previous assimilation cycle to replace the true but unknown 0°C line is found to be a feasible approach for separating the rain and snow and, at the same time, allowing the 4DVar minimization algorithm to converge to an optimal solution. A real case study from intensive observation period 8 of the 2008 Southwest Monsoon Experiment shows that, with the added ice-phase process, VDRAS is more capable of capturing the actual evolution of the reflectivity field than the original scheme. The model’s QPN skill is also improved significantly. Thus, the benefits of adding the ice-phase process into a 4DVar radar data assimilation system on the convective-scale weather analysis and forecast are demonstrated.
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Vickery, B. H., Z. Avnur, M. Uskokovic, and S. Peleg. "New tissue-selective vit D receptor modulators (VDRMs)." Bone 27, no. 4 (October 2000): 11. http://dx.doi.org/10.1016/s8756-3282(00)80032-0.

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Wu-Wong, J. Ruth, Masaki Nakane, Gerard D. Gagne, Kristin A. Brooks, and William T. Noonan. "Comparison of the Pharmacological Effects of Paricalcitol and Doxercalciferol on the Factors Involved in Mineral Homeostasis." International Journal of Endocrinology 2010 (2010): 1–8. http://dx.doi.org/10.1155/2010/621687.

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Vitamin D receptor agonists (VDRAs) directly suppress parathyroid hormone (PTH) mRNA expression. Different VDRAs are known to have differential effects on serum calcium (Ca), which may also affect serum PTH levels since serum Ca regulates PTH secretion mediated by the Ca-sensing receptor (CaSR). In this study, we compared the effects of paricalcitol and doxercalciferol on regulating serum Ca and PTH, and also the expression of PTH, VDR, and CaSR mRNA. The 5/6 nephrectomized (NX) Sprague-Dawley rats on a normal or hyperphosphatemia-inducing diet were treated with vehicle, paricalcitol, or doxercalciferol for two weeks. Both drugs at the tested doses (0.042–0.33 g/kg) suppressed PTH mRNA expression and serum PTH effectively in the 5/6 NX rats, but paricalcitol was less potent in raising serum Ca than doxercalciferol. In pig parathyroid cells, paricalcitol and the active form of doxercalciferol induced VDR translocation from the cytoplasm into the nucleus, suppressed PTH mRNA expression and inhibited cell proliferation in a similar manner, although paricalcitol induced the expression of CaSR mRNA more effectively. The multiple effects of VDRAs on modulating serum Ca, parathyroid cell proliferation, and the expression of CaSR and PTH mRNA reflect the complex involvement of the vitamin D axis in regulating the mineral homeostasis system.
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Zupcic, Ana, Nejla Latic, Mhaned Oubounyt, Alice Ramesova, Geert Carmeliet, Jan Baumbach, Maria L. Elkjaer, and Reinhold G. Erben. "Ablation of Vitamin D Signaling in Cardiomyocytes Leads to Functional Impairment and Stimulation of Pro-Inflammatory and Pro-Fibrotic Gene Regulatory Networks in a Left Ventricular Hypertrophy Model in Mice." International Journal of Molecular Sciences 25, no. 11 (May 29, 2024): 5929. http://dx.doi.org/10.3390/ijms25115929.

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The association between vitamin D deficiency and cardiovascular disease remains a controversial issue. This study aimed to further elucidate the role of vitamin D signaling in the development of left ventricular (LV) hypertrophy and dysfunction. To ablate the vitamin D receptor (VDR) specifically in cardiomyocytes, VDRfl/fl mice were crossed with Mlcv2-Cre mice. To induce LV hypertrophy experimentally by increasing cardiac afterload, transverse aortic constriction (TAC) was employed. Sham or TAC surgery was performed in 4-month-old, male, wild-type, VDRfl/fl, Mlcv2-Cre, and cardiomyocyte-specific VDR knockout (VDRCM-KO) mice. As expected, TAC induced profound LV hypertrophy and dysfunction, evidenced by echocardiography, aortic and cardiac catheterization, cardiac histology, and LV expression profiling 4 weeks post-surgery. Sham-operated mice showed no differences between genotypes. However, TAC VDRCM-KO mice, while having comparable cardiomyocyte size and LV fibrosis to TAC VDRfl/fl controls, exhibited reduced fractional shortening and ejection fraction as measured by echocardiography. Spatial transcriptomics of heart cryosections revealed more pronounced pro-inflammatory and pro-fibrotic gene regulatory networks in the stressed cardiac tissue niches of TAC VDRCM-KO compared to VDRfl/fl mice. Hence, our study supports the notion that vitamin D signaling in cardiomyocytes plays a protective role in the stressed heart.
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Lopez, Ignacio, Francisco J. Mendoza, Escolastico Aguilera-Tejero, Jose Perez, Fatima Guerrero, David Martin, and Mariano Rodriguez. "Response to ‘VDRAs versus calcimimetics: better safe than sorry?’." Kidney International 74, no. 7 (October 2008): 966–67. http://dx.doi.org/10.1038/ki.2008.368.

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Her, Qoua, Thomas Kent, Yuji Samizo, Aleksandra Slavkovic, Yury Vilk, and Sengwee Toh. "Automatable Distributed Regression Analysis of Vertically Partitioned Data Facilitated by PopMedNet: Feasibility and Enhancement Study." JMIR Medical Informatics 9, no. 4 (April 23, 2021): e21459. http://dx.doi.org/10.2196/21459.

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Background In clinical research, important variables may be collected from multiple data sources. Physical pooling of patient-level data from multiple sources often raises several challenges, including proper protection of patient privacy and proprietary interests. We previously developed an SAS-based package to perform distributed regression—a suite of privacy-protecting methods that perform multivariable-adjusted regression analysis using only summary-level information—with horizontally partitioned data, a setting where distinct cohorts of patients are available from different data sources. We integrated the package with PopMedNet, an open-source file transfer software, to facilitate secure file transfer between the analysis center and the data-contributing sites. The feasibility of using PopMedNet to facilitate distributed regression analysis (DRA) with vertically partitioned data, a setting where the data attributes from a cohort of patients are available from different data sources, was unknown. Objective The objective of the study was to describe the feasibility of using PopMedNet and enhancements to PopMedNet to facilitate automatable vertical DRA (vDRA) in real-world settings. Methods We gathered the statistical and informatic requirements of using PopMedNet to facilitate automatable vDRA. We enhanced PopMedNet based on these requirements to improve its technical capability to support vDRA. Results PopMedNet can enable automatable vDRA. We identified and implemented two enhancements to PopMedNet that improved its technical capability to perform automatable vDRA in real-world settings. The first was the ability to simultaneously upload and download multiple files, and the second was the ability to directly transfer summary-level information between the data-contributing sites without a third-party analysis center. Conclusions PopMedNet can be used to facilitate automatable vDRA to protect patient privacy and support clinical research in real-world settings.
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Galassi, Andrea, Antonio Bellasi, Sara Auricchio, Sergio Papagni, and Mario Cozzolino. "Which Vitamin D in CKD-MBD? The Time of Burning Questions." BioMed Research International 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/864012.

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Vitamin D is a common treatment against secondary hyperparathyroidism in renal patients. However, the rationale for the prescription of vitamin D sterols in chronic kidney disease (CKD) is rapidly increasing due to the coexistence of growing expectancies close to unsatisfactory evidences, such as (1) the lack of randomized controlled trials (RCTs) proving the superiority of any vitamin D sterol against placebo on patients centered outcomes, (2) the scanty clinical data on head to head comparisons between the multiple vitamin D sterols currently available, (3) the absence of RCTs confirming the crescent expectations on nutritional vitamin D pleiotropic effects even in CKD patients, (4) the promising effects of vitamin D receptors activators (VDRA) against proteinuria and myocardial hypertrophy in diabetic CKD cohorts, and (5) the conflicting data on the impact on mortality of VDRA versus calcimimetic centered regimens to control CKD-MBD. The present review arguments these issues focusing on the opened questions that nephrologists should consider dealing with the prescription of nutritional vitamin D or VDRA and with the choice of a VDRA versus a calcimimetic based regimen in CKD-MBD patients.
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Milovanova, Ludmila Yu, Vladimir D. Beketov, Svetlana Yu Milovanova, Marina V. Taranova, Vasilii V. Kozlov, Anastasiia I. Pasechnik, Vladimir A. Reshetnikov, Tatiana V. Androsova, and Mikhail V. Kalashnikov. "Effect of vitamin D receptor activators on serum Klotho levels in 3b–4 stages chronic кidney disease patients: a prospective randomized study." Terapevticheskii arkhiv 93, no. 6 (June 15, 2021): 679–84. http://dx.doi.org/10.26442/00403660.2021.06.000854.

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Background. High risk of cardiovascular events is among leading problems in chronic kidney disease (CKD). Serum Klotho is supposed to be cardio- and nephroprotective; modification of its levels may be important in CKD. Aim. To evaluate the impact of vitamin D receptor activators (VDRA) on Klotho serum levels in CKD 3b4 stages patients. Materials and methods. Study included 90 CKD 3b4 stages patients who had elevated serum levels of parathyroid hormone (PTH). From them, 47 patients (group 1) started to treat with the selective VDRA (zemplar 1 mcg/day), and 43 patients (group 2) started to treat with non-selective VDRA (alfacalcidol 0.25 mcg/day). At baseline and after 12 months we conducted routine examination, serum Klotho measurement, and broad cardiovascular examination. Results. The patients who managed to maintain a target serum PTH level, had higher Klotho serum level (p=0.037) at the end of the study. Patients who used selective VDRA significantly more often reached the target PTH level (p=0.032), had higher serum Klotho levels (p=0.037), and glomerular filtration rate (eGFR) level (p=0.048) than patients who used non-selective VDRA. In addition, patients treated with alfacalcidol more than 6 months, more often had hypercalcemia (p=0.047) and hyperphosphatemia (p=0.035). Group 2 showed higher: pulse wave velocity (p=0.051), left ventricular myocardial mass index (p=0.033), and more advanced heart valve calcification (p=0.038). Conclusion. Successful parathyroid hormone level control with vitamin D receptor activators was associated with higher serum Klotho, selective agents having shown greater effect. Long-term treatment with selective vitamin D receptor activators may contribute to cardiovascular calcification prevention by modifying Klotho levels.
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Kwon, Hye-Joo. "Vitamin D Receptor Signaling Regulates Craniofacial Cartilage Development in Zebrafish." Journal of Developmental Biology 7, no. 2 (June 22, 2019): 13. http://dx.doi.org/10.3390/jdb7020013.

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Vitamin D plays essential roles in supporting the skeletal system. The active form of vitamin D functions through the vitamin D receptor (VDR). A hereditary vitamin-D-resistant rickets with facial dysmorphism has been reported, but the involvement of VDR signaling during early stages of craniofacial development remains to be elucidated. The present study investigated whether VDR signaling is implicated in zebrafish craniofacial cartilage development using a morpholino-based knockdown approach. Two paralogous VDR genes, vdra and vdrb, have been found in zebrafish embryos. Loss-of-vdra has no discernible effect on cartilage elements, whereas loss-of-vdrb causes reduction and malformation of craniofacial cartilages. Disrupting both vdra and vdrb leads to more severe defects or complete loss of cartilage. Notably, knockdown of vdrb results in elevated expression of follistatin a (fsta), a bone morphogenetic protein (BMP) antagonist, in the adjacent pharyngeal endoderm. Taken together, these findings strongly indicate that VDR signaling is required for early craniofacial cartilage development in zebrafish.
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Law, Samantha P. L., Prudence N. Gatt, Stephen D. Schibeci, Fiona C. McKay, Steve Vucic, Prue Hart, Scott N. Byrne, et al. "Expression of CYP24A1 and other multiple sclerosis risk genes in peripheral blood indicates response to vitamin D in homeostatic and inflammatory conditions." Genes & Immunity 22, no. 4 (June 23, 2021): 227–33. http://dx.doi.org/10.1038/s41435-021-00144-6.

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AbstractAlthough genetic and epidemiological evidence indicates vitamin D insufficiency contributes to multiple sclerosis (MS), and serum levels of vitamin D increase on treatment with cholecalciferol, recent metanalyses indicate that this vitamin D form does not ameliorate disease. Genetic variation in genes regulating vitamin D, and regulated by vitamin D, affect MS risk. We evaluated if the expression of vitamin D responsive MS risk genes could be used to assess vitamin D response in immune cells. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and people with MS treated with dimethyl fumarate. We assayed changes in expression of vitamin D responsive MS risk (VDRMS) genes in response to treatment with 25 hydroxy vitamin D in the presence or absence of inflammatory stimuli. Expression of CYP24A1 and other VDRMS genes was significantly altered in PBMCs treated with vitamin D in the homeostatic and inflammatory models. Gene expression in MS samples had similar responses to controls, but lower initial expression of the risk genes. Vitamin D treatment abrogated these differences. Expression of CYP24A1 and other MS risk genes in blood immune cells indicate vitamin D response and could enable assessment of immunological response to vitamin D in clinical trials and on therapy.
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Zupanič, Katja. "Poplavljen arhiv Mestne občine Ptuj ob naravni ujmi julija 2019 ali Kako smo uspešno rešili pisno kulturno dediščino mesta Ptuj iz 90. let 20 stoletja." Moderna arhivistika 2022 (5), no. 2 (October 2022): 326–36. http://dx.doi.org/10.54356/ma/2022/rwiu6800.

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Julija 2019 popoldan se je nad Ptujem in okolico razbesnelo hudo neurje z nalivi, ki je povzročilo močne poplave. Poplavilo je tudi središče mesta in številne objekte. Voda je tako vdrla tudi v kletne prostore arhiva Mestne občine Ptuj (MOP). Ko je bilo ugotovljeno, da gre za najdragocenejše gradivo, ki ima status arhivskega (A), to so zapisniki sej mestnega sveta ter drugi pomembni zapisniki iz obdobja začetka devetdesetih let 20. st., so nemudoma sledili ukrepi za zavarovanje gradiva.
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Lundwall, Kristina, Gun Jörneskog, Stefan H. Jacobson, and Jonas Spaak. "Paricalcitol, Microvascular and Endothelial Function in Non-Diabetic Chronic Kidney Disease: A Randomized Trial." American Journal of Nephrology 42, no. 4 (2015): 265–73. http://dx.doi.org/10.1159/000441364.

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Background: Vitamin D deficiency, sympathetic activation and endothelial dysfunction are associated with increased cardiovascular risk in patients with chronic kidney disease (CKD). Studies have so far failed to establish the role of vitamin D and vitamin D receptor activator (VDRA) treatment in moderate CKD. This trial was designed to assess whether VDRA treatment can ameliorate sympathetic activation and macro- and microvascular dysfunction in non-diabetic patients with moderate CKD. Methods: We conducted a randomized controlled double-blind trial using placebo, 1 or 2 μg of paricalcitol, a VDRA, for 3 months. We assessed muscle sympathetic nerve activity (MSNA) by microneurography, pulse wave velocity (PWV) by tonometry, flow mediated vasodilatation (FMD) by brachial ultrasound, skin microcirculation assessed by iontophoresis and capillary blood velocity (CBV) by videophotometric capillaroscopy. Results: Thirty-six patients with a mean age of 65 years and mean estimated glomerular filtration rate of 40 ml/min/1.73 m2 were included. We found a significant decline in endothelial function after 3 months, except in the group receiving 2 μg of paricalcitol. The higher dose (2 μg) seemed to attenuate the decline in microvascular endothelial function, assessed by iontophoresis of acetylcholine (p = 0.06 for all groups, p = 0.65 for the 2 μg group) and for FMD (p = 0.006 for all groups, p = 0.54 for the 2 μg group). We found a borderline significance (p = 0.05) for improved CBV in the treated groups. We found no significant changes between treatments in MSNA, PWV or albuminuria. Conclusions: Endothelial function declined significantly over 3 months in patients with moderate CKD, and this decline could be ameliorated by VDRA treatment (NCT01204528).
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Yaghoobi, Mohammad Mehdi, and Azadeh Samare Gholami. "Association of rs4516035 Polymorphism with Osteoporosis in the Southeastern Iranian Population: A Case-Control Study." Journal of Research in Health Sciences 24, no. 1 (March 18, 2024): e00603. http://dx.doi.org/10.34172/jrhs.2024.138.

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Background: Genetic polymorphisms are known to play a crucial role in the development of osteoporosis. Vitamin D3 regulates bone homeostasis through the vitamin D receptor (VDR). Reduced VDR activity increases osteoporosis risk. Study Design: A case-control study. Methods: This case-control study investigated the potential association between six single-nucleotide polymorphisms (SNPs) within the VDR gene (rs11568820, rs4516035, rs2228570, rs1544410, rs7975232, and rs731236) and the occurrence of osteoporosis in Kerman province. The genotypes of the SNPs were analyzed using polymerase chain reaction-restriction fragment length polymorphism, tetra primer amplification refractory mutation system-PCR, and sequencing in two groups of osteoporosis patients (n=40) and controls (n=42). Additionally, the levels of calcium and vitamin D3 in the serum of the patients were measured, and the in silico analysis of the VDR structure and interaction was performed using I-TASSER, ProSA, PROCHECK, GeneMANIA, GTEx, and GPS 6.0. Results: None of the patients exhibited calcium or vitamin D3 deficiencies. Among the six SNPs, only the T allele in rs4516035, which leads to a shorter variant called VDRA, showed a significant association with susceptibility to osteoporosis (odds ratio=3.061, P=0.007). The in silico analysis demonstrated that the 3D structure, expression, and post-transcriptional modification of VDRA are distinct from those of the more extended variant, VDRB1. VDRB1 is upregulated in sun-exposed skin, and its interactions with its partners differ from those of VDRA. Conclusion: Despite adequate vitamin D levels, the VDRA variant, which has lower activity, could increase the predisposition to osteoporosis in the studied population. These findings clarify the importance of genetic screening for personalized medicine and the effectiveness of prevention and treatment strategies.
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Stavenuiter, Andrea W. D., Karima Farhat, Marc Vila Cuenca, Margot N. Schilte, Eelco D. Keuning, Nanne J. Paauw, Pieter M. ter Wee, Robert H. J. Beelen, and Marc G. Vervloet. "Protective Effects of Paricalcitol on Peritoneal Remodeling during Peritoneal Dialysis." BioMed Research International 2015 (2015): 1–12. http://dx.doi.org/10.1155/2015/468574.

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Peritoneal dialysis (PD) is associated with structural and functional alterations of the peritoneal membrane, consisting of fibrosis, angiogenesis, and loss of ultrafiltration capacity. Vitamin D receptor activation (VDRA) plays an important role in mineral metabolism and inflammation, but also antiangiogenic and antifibrotic properties have been reported. Therefore, the effects of active vitamin D treatment on peritoneal function and remodeling were investigated. Rats were either kept naïve to PDF exposure or daily exposed to 10 mL PDF and were treated for five or seven weeks with oral paricalcitol or vehicle control. Non-PDF-exposed rats showed no peritoneal changes upon paricalcitol treatment. Paricalcitol reduced endogenous calcitriol but did not affect mineral homeostasis. However, upon PDF exposure, loss of ultrafiltration capacity ensued which was fully rescued by paricalcitol treatment. Furthermore, PD-induced ECM thickening was significantly reduced and omental PD-induced angiogenesis was less pronounced upon paricalcitol treatment. No effect of paricalcitol treatment on total amount of peritoneal cells, peritoneal leukocyte composition, and epithelial to mesenchymal transition (EMT) was observed. Our data indicates that oral VDRA reduces tissue remodeling during chronic experimental PD and prevents loss of ultrafiltration capacity. Therefore, VDRA is potentially relevant in the prevention of treatment technique failure in PD patients.
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Chong-Eun Kim and Gun-Woo Moon. "Input-Voltage Feedforward (IVFF) Circuit Minimizing Current Stress of Voltage-Doubler Rectified Asymmetrical Half-Bridge (VDRAHB) Converter." IEEE Transactions on Industrial Electronics 55, no. 5 (May 2008): 2222–24. http://dx.doi.org/10.1109/tie.2007.896553.

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James, Bryan D., Brian Caffo, Walter F. Stewart, David Yousem, Christos Davatzikos, and Brian S. Schwartz. "Genetic Risk Factors for Longitudinal Changes in Structural MRI in Former Organolead Workers." Journal of Aging Research 2011 (2011): 1–11. http://dx.doi.org/10.4061/2011/362189.

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This study examined associations between polymorphisms in three genes, apolipoprotein E (APOE), angiotensin converting enzyme (ACE), and vitamin D receptor (VDR), and longitudinal change in brain volumes and white matter lesions (WML) as well as effect modification by cardiovascular factors and tibia lead concentrations. Two MRIs, an average of 5 years apart, were obtained for 317 former organolead workers and 45 population-based controls. Both regions-of-interest and voxel-wise analyses were conducted.APOEε3/ε4andε4/ε4genotypes were associated with less decline in white matter volumes. There was some evidence of interaction between genetic polymorphisms and cardiovascular risk factors (ACEand high-density lipoprotein;VDRand diabetes) on brain volume decline. TheVDR FokIff genotype was associated with an increase in WML (no association forAPOEorACE). This study expands our understanding of how genetic precursors of dementia and cardiovascular diseases are related to changes in brain structure.
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Cozzolino, M., S. Pasho, C. Crovetto, and E. Missaglia. "Trattamento dell'iperparatiroidismo secondario: calciomimetici, attivatori selettivi del recettore della vitamina D (VDRAs) o terapia combinata?" Giornale di Clinica Nefrologica e Dialisi 19, no. 3-4 (July 1, 2007): 28–33. http://dx.doi.org/10.33393/gcnd.2007.1518.

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Cozzolino, M., S. Pasho, C. Crovetto, and E. Missaglia. "Trattamento dell'iperparatiroidismo secondario: calciomimetici, attivatori selettivi del recettore della vitamina D (VDRAs) o terapia combinata?" Giornale di Tecniche Nefrologiche e Dialitiche 19, no. 3-4 (July 2007): 28–33. http://dx.doi.org/10.1177/039493620701903-406.

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Sun, Juanzhen, and Hongli Wang. "Radar Data Assimilation with WRF 4D-Var. Part II: Comparison with 3D-Var for a Squall Line over the U.S. Great Plains." Monthly Weather Review 141, no. 7 (July 1, 2013): 2245–64. http://dx.doi.org/10.1175/mwr-d-12-00169.1.

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Abstract The Weather Research and Forecasting Model (WRF) four-dimensional variational data assimilation (4D-Var) system described in Part I of this study is compared with its corresponding three-dimensional variational data assimilation (3D-Var) system using a Great Plains squall line observed during the International H2O Project. Two 3D-Var schemes are used in the comparison: a standard 3D-Var radar data assimilation (DA) that is the same as the 4D-Var except for the exclusion of the constraining dynamical model and an enhanced 3D-Var that includes a scheme to assimilate an estimated in-cloud humidity field. The comparison is made by verifying their skills in 0–6-h quantitative precipitation forecast (QPF) against stage-IV analysis, as well as in wind forecasts against radial velocity observations. The relative impacts of assimilating radial velocity and reflectivity on QPF are also compared between the 4D-Var and 3D-Var by conducting data-denial experiments. The results indicate that 4D-Var substantially improves the QPF skill over the standard 3D-Var for the entire 6-h forecast range and over the enhanced 3D-Var for most forecast hours. Radial velocity has a larger impact relative to reflectivity in 4D-Var than in 3D-Var in the first 3 h because of a quicker precipitation spinup. The analyses and forecasts from the 4D-Var and 3D-Var schemes are further compared by examining the meridional wind, horizontal convergence, low-level cold pool, and midlevel temperature perturbation, using analyses from the Variational Doppler Radar Analysis System (VDRAS) as references. The diagnoses of these fields suggest that the 4D-Var analyzes the low-level cold pool, its leading edge convergence, and midlevel latent heating in closer resemblance to the VDRAS analyses than the 3D-Var schemes.
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Na, Songqing, Yanfei Ma, Jingyong Zhao, Clint Schmidt, Qing Q. Zeng, Srinivasan Chandrasekhar, William W. Chin, and Sunil Nagpal. "A Nonsecosteroidal Vitamin D Receptor Modulator Ameliorates Experimental Autoimmune Encephalomyelitis without Causing Hypercalcemia." Autoimmune Diseases 2011 (2011): 1–14. http://dx.doi.org/10.4061/2011/132958.

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Vitamin D receptor (VDR) agonists are currently the agents of choice for the treatment of psoriasis, a skin inflammatory indication that is believed to involve an autoimmune component. 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active metabolite of vitamin D, has shown efficacy in animal autoimmune disease models of multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and type I diabetes. However, the side effect of 1,25-(OH)2D3and its synthetic secosteroidal analogs is hypercalcemia, which is a major impediment in their clinical development for autoimmune diseases. Hypercalcemia develops as a result of the action of VDR agonists on the intestine. Here, we describe the identification of a VDR modulator (VDRM) compound A that was transcriptionally less active in intestinal cells and as a result exhibited less calcemic activityin vivothan 1,25-(OH)2D3. Cytokine analysis indicated that the VDRM not only modulated the T-helper cell balance from Th1 to Th2 effector function but also inhibited Th17 differentiation. Finally, we demonstrate that the oral administration of compound A inhibited the induction and progress of experimental autoimmune encephalomyelitis in mice without causing hypercalcemia.
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Zhang, Guifu, Juanzhen Sun, and Edward A. Brandes. "Improving Parameterization of Rain Microphysics with Disdrometer and Radar Observations." Journal of the Atmospheric Sciences 63, no. 4 (April 1, 2006): 1273–90. http://dx.doi.org/10.1175/jas3680.1.

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Abstract Disdrometer observations indicate that the raindrop size distribution (DSD) can be represented by a constrained-gamma (CG) distribution model. The model is used to retrieve DSDs from polarization radar measurements of reflectivity and differential reflectivity and to characterize rain microphysics and physical processes such as evaporation, accretion, and precipitation. The CG model parameterization is simplified to a single parameter for application in single-moment numerical models. This simplified parameterization is applied in the Variational Doppler Radar Analysis System (VDRAS) using Kessler-type parameterizations for model initialization and forecasting. Results are compared to those for the Marshall–Palmer (MP) DSD model. It is found that the simplified CG model parameterization better preserves the stratiform rain and produces better forecasts than the MP model parameterization.
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De Brabander, H. F., J. Vanden Bussche, K. Wille, K. Bekaert, and L. Vanhaecke. "The state of the art of residue analysis: the 6th VDRA symposium 2010." Drug Testing and Analysis 2, no. 9 (September 13, 2010): 421–23. http://dx.doi.org/10.1002/dta.164.

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Pandey, Richa, Julia Zella, Margaret Clagett-Dame, Lori A. Plum, Hector F. DeLuca, and Daniel W. Coyne. "Use of 2MD, a Novel Oral Calcitriol Analog, in Hemodialysis Patients with Secondary Hyperparathyroidism." American Journal of Nephrology 43, no. 3 (2016): 213–20. http://dx.doi.org/10.1159/000445756.

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Background: Use of existing therapies for secondary hyperparathyroidism (SHPT), such as calcitriol or paricalcitol, is frequently limited by the development of hypercalcemia. 2-Methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD; DP001) is a novel and a more potent vitamin D receptor activator (VDRA) that more selectively localizes in the parathyroid gland, and has a wider therapeutic margin in the uremic rat model than calcitriol and paricalcitol. Design, Setting, Participants, and Measurements: Hemodialysis patients were enrolled and dosed with 110, 220, 330, 440, or 550 ng of 2MD orally thrice weekly for 4 weeks. Responders were defined as patients having a ≥30% reduction in parathyroid hormone (PTH) from baseline, and were assessed at weeks 2 and 4. Results: Of 31 patients recruited, 24 completed the 4-week treatment. There was little or no reduction in PTH in the 110 and 220 ng dose cohorts. Higher dose cohorts had greater PTH suppression with more than half the patients in the 440 and 550 ng dose cohorts considered responders (≥30% PTH reduction from baseline). None had oversuppression of PTH or hypercalcemia (corrected serum calcium >10.6 mg/dl). Plasma drug concentration increased with increasing dose, and all responders achieved a 2MD concentration of ≥1.5 pg/ml. All dose levels of 2MD were well tolerated without safety concerns. Conclusions: In hemodialysis patients with SHPT, 2MD, at thrice weekly oral doses of 440 and 550 ng, is well tolerated and effectively suppresses PTH without hypercalcemia. Future studies are needed to study the long-term implications of treating ESRD patients with this novel VDRA.
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Han, Sungdam, Minkook Son, Byungjin Choi, ChulHyoung Park, Dong Ho Shin, Jong Hwan Jung, Min-Jeong Lee, et al. "Characterization of Medication Trends for Chronic Kidney Disease: Mineral and Bone Disorder Treatment Using Electronic Health Record-Based Common Data Model." BioMed Research International 2021 (November 22, 2021): 1–10. http://dx.doi.org/10.1155/2021/5504873.

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Chronic kidney disease–mineral bone disorder (CKD-MBD) is the most common complication in CKD patients. Although there is a consensus on treatment guidelines for CKD-MBD, it remains uncertain whether these treatment recommendations reflect actual practice. Therefore, the aim of this study was to investigate the CKD-MBD medication trend in real-world practice. This was a retrospective and observational study using a 12-year period database transformed into a common data model from three tertiary university hospitals. Study populations were subjects initially diagnosed as CKD. The date of diagnosis was designated as the index date. New patients were categorized year to year from 2008 to 2019 with a fixed observation period of 365 days to check the prescription of CKD-MBD medications including calcium-containing phosphate binder, noncalcium-containing phosphate binder, aluminium hydroxide, vitamin D receptor activator (VDRA), and cinacalcet. The numbers of CKD patients in the three hospitals were 7555, 2424, and 5351, respectively. The proportion for patients with CKD-MBD medication prescription decreased yearly regardless of hospital and CKD stage ( p for trend < 0.05). The use of aluminium hydroxide disappeared steadily while the use of VDRA increased annually in all settings. Despite these changes in prescription patterns, the mean value for CKD-MBD-related serologic markers was almost within target range. The proportion of the population within the target value was not significantly changed. Irrespective of hospital and CKD stage, similar trends of prescription for CKD-MBD medications were observed in real-world practice. Further research with a distributed network study may be helpful to understand medication trends in CKD-MBD treatment.
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Lin, Chia-Hao, Che-Hsien Su, Deng-Yu Tseng, Feng-Chun Ding, and Pung-Pung Hwang. "Action of Vitamin D and the Receptor, VDRa, in Calcium Handling in Zebrafish (Danio rerio)." PLoS ONE 7, no. 9 (September 19, 2012): e45650. http://dx.doi.org/10.1371/journal.pone.0045650.

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Cozzolino, Mario, and Diego Brancaccio. "Emerging role for the vitamin D receptor activator (VDRA), paricalcitol, in the treatment of secondary hyperparathyroidism." Expert Opinion on Pharmacotherapy 9, no. 6 (April 2008): 947–54. http://dx.doi.org/10.1517/14656566.9.6.947.

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Floege, Jürgen, Stuart Sprague, Adrian Covic, Anjay Rastogi, Bruce Spinowitz, Sylvain Larroque, Viatcheslav Rakov, and Markus Ketteler. "MP365SUCROFERRIC OXYHYDROXIDE DOES NOT IMPACT THE IPTH-LOWERING EFFECTS OF ORAL VDRAS OR CINACALCET: A POST HOC ANALYSIS OF A PHASE 3 STUDY." Nephrology Dialysis Transplantation 31, suppl_1 (May 2016): i461. http://dx.doi.org/10.1093/ndt/gfw190.22.

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Tai, Sheng-Lun, Yu-Chieng Liou, Juanzhen Sun, and Shao-Fan Chang. "The Development of a Terrain-Resolving Scheme for the Forward Model and Its Adjoint in the Four-Dimensional Variational Doppler Radar Analysis System (VDRAS)." Monthly Weather Review 145, no. 1 (January 1, 2017): 289–306. http://dx.doi.org/10.1175/mwr-d-16-0092.1.

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Abstract The four-dimensional Variational Doppler Radar Analysis System (VDRAS) developed at the National Center for Atmospheric Research (NCAR) is significantly improved by implementing a terrain-resolving scheme to its forward model and adjoint based on the ghost cell immersed boundary method (GCIBM), which allows the topographic effects to be considered without the necessity to rebuild the model on a terrain-following coordinate system. The new system, called IBM_VDRAS, is able to perform forward forecast and backward adjoint model integration over nonflat lower boundaries, ranging from mountains with smooth slopes to buildings with sharp surfaces. To evaluate the performance of the forward model over complex terrain, idealized numerical experiments of a two-dimensional linear mountain wave and three-dimensional leeside vortices are first conducted, followed by a comparison with a simulation by the Weather Research and Forecasting (WRF) Model. An observing system simulation experiment is also conducted with the assimilation of simulated radar data to examine the ability of IBM_VDRAS in analyzing orographically forced moist convection. It is shown that the IBM_VDRAS can retrieve terrain-influenced three-dimensional meteorological fields including winds, thermodynamic, and microphysical parameters with reasonable accuracy. The new system, with the advanced radar data assimilation capability and the GCIBM terrain scheme, has the potential to be used for studying the evolution of convective weather systems under the influence of terrain.
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44

Jacek Kozak, Krištof. "Postpostdramske reinkarnacije klasičnih tragedij: Jelinek, Hertmans, Möderndorfer." Amfiteater 9, no. 2021-2 (June 30, 2022): 114–35. http://dx.doi.org/10.51937/amfiteater-2022-1/114-135.

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Tudi za postpostdramski čas je značilno spogledovanje s ključnimi formami svetovne dramatike, kot so antične in elizabetinske tragedije, ter z njihovimi temami, ki jih aplicira na popolnoma sodobne probleme. Izmed mnogih besedil je mogoče izbrati tri: Die Schutzbefohlenen Elfriede Jelinek, Antigona v Molenbeeku Stefana Hertmansa ter Romeo in Julija sta bila begunca Vinka Möderndorferja. Poleg razmerja do antike povezuje vse tri drame še tematska rdeča nit: migracije ter z njimi povezane nesrečne usode beguncev. Izkaže se, da je edina optimistična različica te teme nastala pri Ajshilu, vse tri sodobne drame pa bi bilo mogoče brez težav uvrstiti med tragedije. Takšna je drama Jelinekove, ki je nastala po resničnem dogodku iz leta 2012, ko je skupina migrantov protestno vdrla v Votivno cerkev na Dunaju in zahtevala zase in za sebi podobne človeka dostojno azilno obravnavo. Jelinek izkaže ves etični razkroj Evrope, ki se skriva za visokoletečimi ideali človekoljubja, dejansko pa ravna prav nasprotno. V tem primeru gre za razmerje med migranti, ki so pravi tujci, in pa Evropejci. Tujca, ki je že polnopraven državljan Evrope, predstavi Hertmans, le da svojo »Antigono« zaplete še s klasično zgodbo pokopa mrtvega brata, ki je v tem primeru terorist. Ta Antigona je še vedno tujka, a tudi že državljanka Evrope. Zadnji korak v tej smeri naredi Möderndorfer, ki pa kot migrante, torej kot tujce, obravnava ekonomsko ogrožene Evropejce. Nobena od treh dram nima izhoda in slehernikova usoda se konča tragično.
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45

Zhang, Honghao, Xiaona Rao, Zeyong Guo, Xiantong Liu, Xiaoding Yu, Xingdeng Chen, Huiqi Li, Jingjing Zhang, Guangyu Zeng, and Shidong Chen. "Detailed Evolution Characteristics of an Inclined Structure Hailstorm Observed by Polarimetric Radar over the South China Coast." Atmosphere 13, no. 10 (September 25, 2022): 1564. http://dx.doi.org/10.3390/atmos13101564.

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A hailstorm with an inclined structure occurred in the western part of the South China coast on 27 March 2020. This study investigates the detailed evolution characteristics of this inclined structure using the Doppler radar data assimilation system (VDRAS) and the improved fuzzy logic hydrometeor classification algorithm (HCA). Obvious differential reflectivity (often referred to as ZDR) arc characteristics, ZDR column characteristics, and the specific differential phase (often referred to as KDP) of the column are observed using dual-polarization radar prior to hailfall. Both the ZDR column and KDP column reached their strongest intensities during the hailfall phase, with their heights exceeding the height of the −20 °C layer (7.997 km above ground level), displaying a cross-correlation coefficient (CC) valley during this phase. Meanwhile, two centers of strong reflectivity were found, with one (C1) being located at 2–4 km, and the other (C2) being located at 6–8 km. The maximum horizontal distance between the two centers is 8 km, suggesting a strongly inclined structure. This inclined structure was closely related to the interaction between upper-level divergent outflows and ambient horizontal winds. The updraft on the front edge of the hailstorm continued to increase, keeping C2 at the upper level. At the same time, large raindrops at the lower part of C2 are continuously lifted, leading to ice formation. These ice particles then fell obliquely from their high altitude, merging with C1.
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46

Bechini, Renzo, and V. Chandrasekar. "An Enhanced Optical Flow Technique for Radar Nowcasting of Precipitation and Winds." Journal of Atmospheric and Oceanic Technology 34, no. 12 (December 2017): 2637–58. http://dx.doi.org/10.1175/jtech-d-17-0110.1.

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AbstractThe atmospheric state evolution is an inherently highly complex three-dimensional problem that numerical weather prediction (NWP) models attempt to solve. Although NWP models are being successfully employed for medium- and long-range forecast, their short-duration forecast (or nowcast) capabilities are still limited because of model initialization challenges. On the lower end of the complexity scale, nowcasting by extrapolation of two-dimensional weather radar images has long been the most effective tool for nowcasting precipitation. Attempts are being made to take advantage of both approaches by blending extrapolation and numerical model forecasts. In this work a different approach is presented, relying on the additional Doppler radar wind information and a simplified modeling of basic physical processes. Instead of mixing the outputs of different forecasts as in blended approaches, the idea behind this study is to combine extrapolation and precipitation modeling in a new technique with a higher level of complexity with respect to conventional nowcasting methods, although still much simpler than NWP models. As a preliminary step, the Variational Doppler Radar Analysis System (VDRAS) is used to provide an initial analysis exploiting all the available dual-polarization and Doppler radar observations. The rainwater and wind fields are then advected using an optical flow technique that is subject to simplified physical interactions. As a result precipitation and wind nowcasting are obtained and are successively validated up to a 1-h lead time, showing potential improvement upon standard extrapolation.
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47

Xu, Changyi, and Xian Xiao. "Comparison of Cold Pool Characteristics of Two Distinct Gust Fronts over Bohai Sea Bay in China." Atmosphere 15, no. 3 (February 20, 2024): 247. http://dx.doi.org/10.3390/atmos15030247.

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Previous studies have demonstrated that cold pools play a pivotal role in the initiation and organization of convection, yet their influence on the evolution of gust fronts (GFs) remains inadequately understood. A destructive wind event associated with a rearward gust front (RGF; 8 grade gale after passing GF) and a prior gust front (PGF; 10 grade gale before passing GF) over the north coast of China on 10 June 2016 was analyzed. Using multiple forms of observation data, as well as the four-dimensional Variational Doppler Radar Data Assimilation System (VDRAS), we found that the depth and intensity of the cold pool in RGF are relatively shallower and weaker, leading to a correspondingly reduced strength in both outflow and convergence. In contrast, the enhanced vertical shear and boundary northeaster inflow of PGF generate intensified and more organized downdrafts, resulting in a deeper cold pool, robust outflow, and convergence. Two schematic models were proposed to explain the discrepancy between GFs and associated cold pools. We further show that there is an internal correlation between meso-γ-scale vortices (MVs) and cold pools, the collision of MVs strengthened low-level convergence and updraft between these two GFs. Moreover, the consolidation of the two cold pools exacerbates low-layer instability and rotation, generating an intense horizontal vorticity that leads to rapid convective storm intensification. These findings offer novel insights into the diversity of GFs and associated cold pools.
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48

Ito, Eri, Daijo Inaguma, Kazuo Takahashi, Hiroki Hayashi, Shigehisa Koide, Midori Hasegawa, and Yukio Yuzawa. "FP623EARLY INTRODUCTION OF INTRAVENOUS VDRA COULD BE ASSOCIATED WITH BETTER PROGNOSIS OF END-STAGE KIDNEY DISEASE PATIENTS ON HEMODIALYSIS." Nephrology Dialysis Transplantation 33, suppl_1 (May 1, 2018): i251. http://dx.doi.org/10.1093/ndt/gfy104.fp623.

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49

Murashima, Miho, Takayuki Hamano, Kazuhiko Tsuruya, Satoshi Ogata, Eiichiro Kanda, Masanori Abe, Ikuto Masakane, and Kosaku Nitta. "Performance Status (PS) as an Effect Modifier for Association Between Vitamin D Receptor Activator (VDRA) and Outcomes Among Hemodialysis Patients." Journal of the American Society of Nephrology 32, no. 10S (October 2021): 216–17. http://dx.doi.org/10.1681/asn.20213210s1216d.

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50

Di Luca, Marina, Silvio Di Stante, Hirissanti Kulurianu, Flavia Manenti, Mauro Marani, and Mauro Martello. "Attivazione dei recettori della Vitamina D nell'insufficienza renale cronica." Giornale di Clinica Nefrologica e Dialisi 25, no. 2 (May 29, 2013): 100–106. http://dx.doi.org/10.33393/gcnd.2013.1017.

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I pazienti affetti da IRC presentano fin dai primi stadi della malattia una ridotta attivazione del recettore per la Vitamina D (VDR), determinata da ridotti livelli sia di 1.25-idrossivitamina D (1.25(OH)2D3) che di 25-idrossivitamina D (25(OH)D3), con il conseguente sviluppo di anomalie del metabolismo osseo e minerale. La Vitamina D e i suoi metaboliti di sintesi, oltre a controllare l'iperparatiroidismo secondario (IPTS), esercitano numerosi effetti pleiotropici in diversi sistemi cellulari e, in particolare, sembrano giocare un ruolo fondamentale nella salute del sistema cardiovascolare e nella riduzione della mortalità, come suggerito da studi osservazionali. È stato di recente dimostrato che il paracalcitolo orale nell'IRC non solo riduce il paratormo-ne, ma è anche associato a un effetto antiproteinurico significativo, e ciò appare di particolare interesse in quanto la proteinuria è un fattore di rischio renale e cardiovascolare. I dati attuali non sono, tuttavia, sufficienti per raccomandare l'uso degli agenti attivatori dei VDR (VDRa) oltre al trattamento delle alterazioni del metabolismo minerale legate all'iperparatiroidismo secondario.
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