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Background The effect of different dosing regimens of cholecalciferol supplementation on bone biomarkers has not been studied in children with chronic kidney disease (CKD). Methods This is a post hoc analysis of a multi-center randomized controlled trial which included children with CKD stages 2-4 with vitamin D deficiency (25-hydroxy vitamin D (25OHD) < 30 ng/ml) randomized 1:1:1 to receive an equivalent dose of oral cholecalciferol as daily, weekly or monthly treatment. Markers of bone formation (bone alkaline phosphatase (BAP), procollagen I N terminal peptide (PINP)), bone resorption (tartarate-resistant acid phosphatase 5b (TRAP), C terminal telopeptide (CTX)), and osteocyte markers (intact fibroblast growth factor 23 (iFGF23), sclerostin) and soluble klotho were measured at baseline and after 3 months of intensive replacement therapy. The change in biomarkers and ratio of markers of bone formation to resorption were compared between treatment arms. BAP and TRAP were expressed as age- and sex-specific z-scores. Results 25OHD levels increased with cholecalciferol supplementation, with 85% achieving normal levels. There was a significant increase in the BAP/TRAP ratio (p = 0.04), iFGF23 (p = 0.004), and klotho (p = 0.002) with cholecalciferol therapy, but this was comparable across all three therapy arms. The BAPz was significantly higher in the weekly arm (p = 0.01). The change in 25OHD ([DELTA]25OHD) inversely correlated with [DELTA]PTH (r = - 0.4, p < 0.001). Conclusions Although cholecalciferol supplementation was associated with a significant increase in bone formation, the three dosing regimens of cholecalciferol supplementation have a comparable effect on the bone biomarker profile, suggesting that they can be used interchangeably to suit the patient's needs and optimize adherence to therapy. Graphical abstract, Author(s): Nivedita Kamath [sup.1] , Arpana Iyengar [sup.1] , Hamsa V. Reddy [sup.1] , Jyoti Sharma [sup.2] , Jyoti Singhal [sup.2] , Sudha Ekambaram [sup.3] , Susan Uthup [sup.4] , [...]

Wolfram syndrome is characterised by insulin-dependent diabetes (IDDM), diabetes insipidus (DI), optic atrophy, sensorineural deafness and neurocognitive disorders. The DIDMOAD acronym has been recently modified to DIDMOAUD suggesting the rising awareness of the prevalence of urinary tract dysfunction (UD). End stage renal disease is the commonest cause of mortality in Wolfram syndrome. We present a case series with main objective of long term follow up in four children having Wolfram syndrome with evaluation of their urodynamic profile. A prospective follow up of four genetically proven children with Wolfram syndrome presenting to a tertiary care pediatric diabetes clinic in Pune, India was conducted. Their clinical, and urodynamic parameters were reviewed. IDDM, in the first decade, was the initial presentation in all the four children (three male and one female). Three children had persistent polyuria and polydipsia despite having optimum glycemic control; hence were diagnosed to have DI and treated with desmopressin. All four patients entered spontaneous puberty. All patients had homozygous mutation in WFS1 gene; three with exon 8 and one with exon 6 novel mutations. These children with symptoms of lower urinary tract malfunction were further evaluated with urodynamic studies; two of them had hypocontractile detrusor and another had sphincter-detrusor dyssynergia. Patients with hypocontractile bladder were taught clean intermittent catheterization and the use of overnight drain. We report a novel homozygous deletion in exon 6 of WFS-1 gene. The importance of evaluation of lower urinary tract malfunction is highlighted by our case series. The final bladder outcome in our cases was a poorly contractile bladder in three patients. [ABSTRACT FROM AUTHOR]

This study investigates the determinants of gold price movements in India by “multiple regression models” using Monthly time series data from 2019 to 2024. The key variables used include Sensex, the BSE stock exchange index price movement, Exchange Rate, Crude oil price movement, Inflation and Global Bond, based on the correlation coefficient, reveal a significant positive relationship between gold price movements and other factors of price movement. Sensex index of BSE, Indian stocks market, Gpld man sach global multi-sector bond funds, and Crude Oil monthly data from MCX index. The Exchange rate between INR and USD only revealed positive relationships. The determinants, whose correlation factors were more than 0.5 were found to have a positive association with gold price movements. Conversely, Goldman Sachs bonds and inflation revealed a less than 0.5 correlation factor showing a less significant positive relationship with gold price movements. These results have significant policy implications for gold producers and investors, as Sensex, crude oil, exchange rate and bond price movement are important sources of information as the determinants of gold price movement. [ABSTRACT FROM AUTHOR]

Profitability, and efficient Working Capital Management are hand to hand to make an organisation successful. Proper allocation of cash flows increases liquidity and simultaneously increases profitability. The purpose of this study is to develop the research on the relationship between Working Capital Management and efficiency by investigating how it is affected by different factors. A quantitative method will be applied in objectivism and positivism and deductive theory was used to approach the subject. Data is collectedrelated to working capital cash management credit management and efficiency ratio to confirm, how fast a company turns purchased products into profit, with Gross Profit Margin as the measure of Profitability. The data analysed is financial information from 2019-21, collected from a secondary source, Annual Reports of the companies. Correlation analysesand descriptive statistics will be used to analyse the relationship between Working Capital Management and gross profit is compared between the different company groups. Theprofitability, and the sensitivity to determinants of Working Capital Management is analysed. [ABSTRACT FROM AUTHOR]

Aims: The prevalence of vitamin D deficiency is high in children with chronic kidney disease (CKD). However, current dosing recommendations are based on limited pharmacokinetic (PK) data. This study aimed to develop a population PK model of colecalciferol that can be used to optimise colecalciferol dosing in this population. Methods: Data from 83 children with CKD were used to develop a population PK model using a nonlinear mixed effects modelling approach. Serum creatinine and type of kidney disease (glomerular vs. nonglomerular disease) were investigated as covariates, and optimal dosing was determined based on achieving and maintaining 25‐hydroxyvitamin D (25(OH)D) concentration of 30–48 ng/mL. Results: The time course of 25(OH)D concentrations was best described by a 1‐compartment model with the addition of a basal concentration parameter to reflect endogenous 25(OH)D production from diet and sun exposure. Colecalciferol showed wide between‐subject variability in its PK, with total body weight scaled allometrically the only covariate included in the model. Model‐based simulations showed that current dosing recommendations for colecalciferol can be optimised using a weight‐based dosing strategy. Conclusion: This is the first study to describe the population PK of colecalciferol in children with CKD. PK model informed dosing is expected to improve the attainment of target 25(OH)D concentrations, while minimising the risk of overdosing. [ABSTRACT FROM AUTHOR]

Background The optimal treatment regimen for correcting 25-hydroxyvitamin D (25OHD) deficiency in children with chronic kidney disease (CKD) is not known. We compared cholecalciferol dosing regimens for achieving and maintaining 25OHD concentrations ≥30 ng/mL in children with CKD stages 2–4. Methods An open-label, multicentre randomized controlled trial randomized children with 25OHD concentrations <30 ng/mL in 1:1:1 to oral cholecalciferol 3000 IU daily, 25 000 IU weekly or 100 000 IU monthly for 3 months (maximum three intensive courses). In those with 25OHD ≥30 ng/mL, 1000 IU cholecalciferol daily (maintenance course) was given for up to 9 months. Primary outcome was achieving 25OHD ≥30 ng/mL at the end of intensive phase treatment. Results Ninety children were randomized to daily (n  = 30), weekly (n  = 29) or monthly (n  = 31) treatment groups. At the end of intensive phase, 70/90 (77.8%) achieved 25OHD ≥30 ng/mL; 25OHD concentrations were comparable between groups (median 44.3, 39.4 and 39.3 ng/mL for daily, weekly and monthly groups, respectively; P = 0.24) with no difference between groups for time to achieve 25OHD ≥30 ng/mL (P = 0.28). There was no change in calcium, phosphorus and parathyroid hormone, but fibroblast growth factor 23 (P = 0.002) and klotho (P = 0.001) concentrations significantly increased and were comparable in all treatment groups. Irrespective of dosing regimen, children with glomerular disease had 25OHD concentrations lower than non-glomerular disease (25.8 versus 41.8 ng/mL; P = 0.007). One child had a 25OHD concentration of 134 ng/mL, and 5.5% had hypercalcemia without symptoms of toxicity. Conclusion Intensive treatment with oral cholecalciferol as daily, weekly or monthly regimens achieved similar 25OHD concentrations between treatment groups, without toxicity. Children with glomerular disease required higher doses of cholecalciferol compared with those with non-glomerular disease. [ABSTRACT FROM AUTHOR]

The major challenge in recent time, more or less in all the sectors is acquiring and retaining talent. Professional employees are found to be always on the move today for better and better opportunities. So, loyalty and commitment seem to have taken a backseat, not appreciated much either at the individual or at the organizational level. In the present paper, an attempt has been made to find out whether the employees' intent to leave the organization depends on their levels of motivational force as measured in line with Vroom's (1964) expectancy theory. In addition, another effort has been made to explore if there is any difference lies between the findings in comparison between two different sectors. The sample of the present study are the employees (n = 155) working in the Information Technology Sectors and employees (n=157) working in Academic Sectors (Technical) in different cities in India. The available data seem to indicate that there exists a significant positive relationship between employees' level of motivational force and their tenure in the job. These may be considered while deciding a strategy for retaining employees in an organization. [ABSTRACT FROM AUTHOR]

Atypical haemolytic uremic syndrome (aHUS) is a clinically and genetically heterogeneous condition caused by a complex interplay between genomic susceptibility factors and environmental influences. Pathogenic variants in the DGKE gene are recently identified in cases with infantile-onset autosomal recessive aHUS. The presence of low serum C3 levels, however, has rarely been described in cases of DGKE-associated aHUS. Molecular genetic testing was performed by a commercial next-generation sequencing (NGS) panel as well and by an in-house developed targeted NGS for DGKE gene. Copy number variations (CNVs) were computed from NGS data by calculating a normalised copy number ratio of aligned number of reads at targeted genomic regions against multiple reference regions of the same sample and multiple controls. We report here two such novel clinically relevant variants (c.727_730delTTGT and c.251_259delGCGCCTTC) in the DGKE gene, in two families of infantile aHUS with low serum C3 levels. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of information on epidemiology, diagnosis, and treatment outcomes of congenital nephrotic syndrome (CNS) in developing countries., Methods: Retrospective (2012-2017) review of case records undertaken across 12 Indian pediatric nephrology centers., Results: Sixty-five children (58% male, median birth weight 2.4 kg [interquartile range (IQR) 2.1-2.86]) were identified with CNS. Nearly half (45%) were preterm with previous history of fetal loss/sibling death in 22% and history of consanguinity in a third. No infective etiology was confirmed. Genetic reports available for 15 (23%) children identified causal mutations in 10 (8 in NPHS1 [1 novel variant], 1 in WT 1 [novel variant], and 1 in PLCE-1 gene). In addition, 1 child was clinically diagnosed as Galloway Mowat syndrome. Next-generation sequencing showed 80% yield and Sanger sequencing 20%. Albumin infusion and angiotensin-converting enzyme inhibitors were used initially in around two-third of cohort, while only 12% of children received indomethacin. Totally, 22 (34%) children were lost to follow-up after initial visit, and among the rest median follow-up was 69 days (IQR 20-180) with 18 (42%) deaths. Eight children showed partial response (including 2 with NPHS1 compound mutation), 1 complete response, and all of them were alive at last follow-up in contrast to 53% mortality among nonresponders, p = 0.004., Conclusion: This largest reported series on CNS from India revealed suboptimal management with poor outcome as well as low number of CNS being subjected to genetic evaluation., (© 2019 S. Karger AG, Basel.)