Category: Nevin Manimala

BMC Nephrol. 2023 Apr 5;24(1):89. doi: 10.1186/s12882-023-03145-x.

ABSTRACT

BACKGROUND: The KBindER (K⁺ Binders in Emergency Room and hospitalized patients) clinical trial is the first head-to-head evaluation of oral potassium binders (cation-exchange resins) for acute hyperkalemia therapy.

METHODS: Emergency room and hospitalized patients with a blood potassium level ≥ 5.5 mEq/L are randomized to one of four study groups: potassium binder drug (sodium polystyrene sulfonate, patiromer, or sodium zirconium cyclosilicate) or nonspecific laxative (polyethylene glycol). Exclusion criteria include recent bowel surgery, ileus, diabetic ketoacidosis, or anticipated dialysis treatment within 4 h of treatment drug. Primary endpoints include change in potassium level at 2 and 4 h after treatment drug. Length of hospital stay, next-morning potassium level, gastrointestinal side effects and palatability will also be analyzed. We are aiming for a final cohort of 80 patients with complete data endpoints (20 per group) for comparative statistics including multivariate adjustment for kidney function, diabetes mellitus, congestive heart failure, metabolic acidosis, renin-angiotensin-aldosterone system inhibitor prescription, and treatment with other agents to lower potassium (insulin, albuterol, loop diuretics).

DISCUSSION: The findings from our study will inform decision-making guidelines on the role of oral potassium binders in the treatment of acute hyperkalemia.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04585542 . Registered 14 October 2020.

PMID:37016309 | DOI:10.1186/s12882-023-03145-x

BMC Nephrol. 2023 Apr 4;24(1):88. doi: 10.1186/s12882-023-03123-3.

ABSTRACT

BACKGROUND: Arteriovenous fistula (AVF) is the gold standard vascular access for effective hemodialysis. There is a growing interest in AVF creations performed by nephrologists to help reduce vascular surgeons’ workload and enhance the timely treatment of patients with end-stage renal disease (ESRD). However, little is known about the feasibility and effectiveness of this approach in the low-resource settings. We examined the AVF surgical success and failure rates and associated predictors as well as early complications of AVF creations by a trained nephrologist with supports from vascular surgeons in Vietnam.

METHODS: A prospective cohort study was conducted on all adult ESRD patients at the Hemodialysis Department of Thong Nhat Hospital between April 2018 and October 2020. Information on demographic characteristics, comorbidities, and AVF creations was collected using a standardized questionnaire. All patients were followed up until 18 weeks post-surgery.

RESULTS: Among 100 patients with a mean age of 61.22 ± 17.11 years old, male accounted for 54%. Common causes of ESRD included hypertension (57%) and diabetes (32%). Just more than half (52%) of them reported having an AVF creation prior to ESRD. The successful first-time AVF creation rate was 98% (13/99, 95%CI: 8.74-21.18%). The primary and secondary AVF failure rates were 13.13% (13/99, 95%CI: 8.74-21.18%) and 16.87% (14/83, 95%CI: 10.32-26.25%), respectively. Early complications included bleeding (1%) and early thrombosis of the anastomosis (2%). There was a statistically significant association between age and primary AVF failure (P = 0.005) and between operation time and secondary AVF failure (P = 0.038).

CONCLUSIONS: AVF creations performed by well-trained and skilled interventional nephrologists with supports from vascular surgeons can result in favorable short- and long-term outcomes. It is important to follow up older patients and those with a long operation time to detect AVF failures. A standardized AVF creation training program and practice for nephrologists is needed to increase successful rates.

PMID:37016300 | DOI:10.1186/s12882-023-03123-3

BMC Bioinformatics. 2023 Apr 4;24(1):127. doi: 10.1186/s12859-023-05250-y.

ABSTRACT

BACKGROUND: Characterizing the topology of gene regulatory networks (GRNs) is a fundamental problem in systems biology. The advent of single cell technologies has made it possible to construct GRNs at finer resolutions than bulk and microarray datasets. However, cellular heterogeneity and sparsity of the single cell datasets render void the application of regular Gaussian assumptions for constructing GRNs. Additionally, most GRN reconstruction approaches estimate a single network for the entire data. This could cause potential loss of information when single cell datasets are generated from multiple treatment conditions/disease states.

RESULTS: To better characterize single cell GRNs under different but related conditions, we propose the joint estimation of multiple networks using multiple signed graph learning (scMSGL). The proposed method is based on recently developed graph signal processing (GSP) based graph learning, where GRNs and gene expressions are modeled as signed graphs and graph signals, respectively. scMSGL learns multiple GRNs by optimizing the total variation of gene expressions with respect to GRNs while ensuring that the learned GRNs are similar to each other through regularization with respect to a learned signed consensus graph. We further kernelize scMSGL with the kernel selected to suit the structure of single cell data.

CONCLUSIONS: scMSGL is shown to have superior performance over existing state of the art methods in GRN recovery on simulated datasets. Furthermore, scMSGL successfully identifies well-established regulators in a mouse embryonic stem cell differentiation study and a cancer clinical study of medulloblastoma.

PMID:37016281 | DOI:10.1186/s12859-023-05250-y

J Periodontol. 2023 Apr 4. doi: 10.1002/JPER.22-0675. Online ahead of print.

ABSTRACT

BACKGROUND: Gingivitis is a non-specific inflammatory lesion in response to accumulation of oral biofilm and is a necessary precursor to periodontitis. Enhanced oral hygiene practices, including utilization of a dentifrice that could significantly improve plaque accumulation and gingival inflammation, is desirable to prevent and treat gingivitis and potentially prevent progression to periodontitis. This clinical study aimed to investigate the effect of a new stannous fluoride-containing dentifrice with 2.6% ethylenediamine tetra acetic acid (EDTA) as an anti-tartar agent to reduce plaque index and gingival index over a 3-month study period compared to other commercially-available fluoride-containing dentifrices.

METHODS: This double-blind, randomized controlled clinical study evaluated plaque, gingival inflammation, and sulcular bleeding in patients using one of five commercially available fluoride-containing dentifrices The dentifrices tested contained: 0.454% stannous fluoride and 2.6% EDTA (D1), 0.24% sodium fluoride (C), and 0.454% stannous fluoride (D2-D4). 150 subjects participated over a 3-month period. Co-primary endpoints were improvements in plaque index (PI) and modified gingival index (mGI) from baseline values. No professional cleaning was performed during the study period.

RESULTS: All subjects in the study demonstrated statistically significant improvements in all measures of oral hygiene over the 3-month study period. Subjects using dentifrice 1 (D1) showed statistically significantly greater reductions in PI, mGI, and modified sulcular bleeding index (mSBI) compared with all other commercially-available dentifrices tested (p<0.00001).

CONCLUSIONS: A new dentifrice with 0.454% stannous fluoride and 2.6% EDTA demonstrated significant improvements in clinical parameters associated with gingivitis compared to other sodium and stannous fluoride containing dentifrices. This article is protected by copyright. All rights reserved.

PMID:37016272 | DOI:10.1002/JPER.22-0675

Calcif Tissue Int. 2023 Apr 5. doi: 10.1007/s00223-023-01078-z. Online ahead of print.

ABSTRACT

To assess the effectiveness and safety of denosumab (Prolia®) compared to bisphosphonates (alendronate, ibandronate, risedronate, zoledronate), selective estrogen receptor modulators (SERMs; bazedoxifene, raloxifene) or placebo, for the treatment of osteoporosis in postmenopausal women (PMW). Systematic searches were run in PubMed, Embase & Cochrane Library on 27-April-2022. Randomized controlled trials (RCTs) that included osteoporotic PMW allocated to denosumab, SERMs, bisphosphonates, or placebo were eligible for inclusion. RCTs were appraised using Cochrane Risk of Bias 2.0. Bayesian network and/or pairwise meta-analyses were conducted on predetermined outcomes (i.e. vertebral/nonvertebral fractures, bone mineral density [BMD], mortality, adverse events [AEs], serious AEs (SAEs), withdrawals due to AEs, AEs caused by denosumab discontinuation). A total of 12 RCTs (k = 22 publications; n = 25,879 participants) were included in the analyses. Denosumab, reported a statistically significant increase in lumbar spine (LS) and total hip (TH) BMD, compared to placebo. Similarly, denosumab also resulted in a statistically significant increase in TH BMD compared to the raloxifene and bazedoxifene. However, relative to denosumab, alendronate, ibandronate and risedronate resulted in significant improvements in both femoral neck (FN) and LS BMD. With regards to vertebral fractures and all safety outcomes, there were no statistically significant differences between denosumab and any of the comparator. Relative to placebo, denosumab was associated with significant benefits in both LS and TH BMD. Additionally, denosumab (compared to placebo) was not associated with reductions in vertebral and nonvertebral fractures. Finally, denosumab was not associated with improvement in safety outcomes, compared to placebo. These findings should be interpreted with caution as some analyses suffered from statistical imprecision.

PMID:37016189 | DOI:10.1007/s00223-023-01078-z

Reprod Sci. 2023 Apr 4. doi: 10.1007/s43032-023-01230-y. Online ahead of print.

ABSTRACT

This study was aimed to identify a novel metastasis-promoting molecule and elucidate its functional and prognostic roles in cervical cancer. DDIT4 (DNA-damage-inducible transcript 4), a hypoxia-inducible gene, was identified by analyzing multiple microarray databases. The correlation between DDIT4 expression in immunohistochemistry and clinicopathological characteristics in the public database and our cohort was evaluated by statistical analysis. Transwell® assay and wound-healing assay to determine cell migration and invasion were performed. DDIT4 was knocked down using siRNA or lentiviral vectors. The potential downstream pathways of DDIT4 were explored and verified by a gene set enrichment analysis and western blotting. The in vivo metastatic capability was determined with the use of an intraperitoneal injection mouse model. In the analysis of the public database and our cohort, DDIT4 high expression was significantly related to short overall survival and lymph node metastasis in patients with early-stage cervical cancer. The knockdown of DDIT4 attenuated the migration and invasion activity of tumor cells in vitro and reduced the expression of epithelial-mesenchymal transition (EMT)-related proteins and the NF-κB pathway in cervical cancer cells. DDIT4 also promoted tumor progression in the mouse model. Our results indicate that DDIT4 can be a prognostic indicator in cervical cancer and promote lymph node metastasis, augmenting malignancy via the EMT and NF-kB pathways.

PMID:37016173 | DOI:10.1007/s43032-023-01230-y

AAPS J. 2023 Apr 4;25(3):37. doi: 10.1208/s12248-023-00806-5.

ABSTRACT

The statistical assessments needed to establish anti-drug antibody (ADA) assay cut points (CPs) can be challenging for bioanalytical scientists. Poorly established CPs that are too high could potentially miss treatment emergent ADA or, when set too low, result in detection of responses that may have no clinical relevance. We evaluated 16 validation CP datasets generated with ADA assays at Regeneron’s bioanalytical laboratory and compared results obtained from different CP calculation tools. We systematically evaluated the impact of various factors on CP determination including biological and analytical variability, number of samples for capturing biological variability, outlier removal methods, and the use of parametric vs. non-parametric CP determination. In every study, biological factors were the major component of assay response variability, far outweighing the contribution from analytical variability. Non-parametric CP estimations resulted in screening positivity in drug-naïve samples closer to the targeted rate (5%) and were less impacted by skewness. Outlier removal using the boxplot method with an interquartile range (IQR) factor of 3.0 resulted in screening positivity close to the 5% targeted rate when applied to entire drug-naïve dataset. In silico analysis of CPs calculated using different sample sizes showed that using larger numbers of individuals resulted in CP estimates closer to the CP of the entire population, indicating a larger sample size (~ 150) for CP determination better represents the diversity of the study population. Finally, simpler CP calculations, such as the boxplot method performed in Excel, resulted in CPs similar to those determined using complex methods, such as random-effects ANOVA.

PMID:37016171 | DOI:10.1208/s12248-023-00806-5

Cytokine. 2023 Apr 2;166:156194. doi: 10.1016/j.cyto.2023.156194. Online ahead of print.

ABSTRACT

INTRODUCTION: Dengue infection is generated by a complex interaction between DENV (Dengue Virus) and the host’s immune response. Interleukin-10 is an immunoregulatory cytokine during DENV infection. The objective of this study was to investigate whether genetic variants in IL-10 could be useful as a predictive and susceptibility marker in the prognosis of DENV infection, particularly with serotype 1, and in participants with dengue without warning signs.

MATERIAL AND METHODS: A study of cases (n = 365) and controls (n = 364) was carried out. Genotyping was performed by real-time PCR using TaqMan probes. Sample size power was calculated using Quanto software RESULTS: This is the first report showing the independent association of the T allele of rs1800871 (P = 0.023) and the A allele of rs1800872 (P = 0.010) with the risk of dengue infection. Statistical analysis established the genotypic association of IL-10 SNPs with DENV infection under different inheritance models. Our results also showed the association of the CC, TC, and CA haplotypes (P = 0.0064, P = 0.0032, and P = 0.0010 respectively) with infection. Furthermore, both polymorphic sites were associated with the risk of DwoWS and serotype 1 (Den-1) under different inheritance models. Finally, under the dominant model, we identified a positive correlation between IL-10 levels vs. IFN-γ and IL-8.

CONCLUSION: Our results show the first independent association of the T and A alleles of the polymorphic sites rs1800871 and rs1800872, with dengue infection, particularly with Den-1, and in participants with DwoWs.

PMID:37015157 | DOI:10.1016/j.cyto.2023.156194

J Environ Manage. 2023 Apr 2;338:117853. doi: 10.1016/j.jenvman.2023.117853. Online ahead of print.

ABSTRACT

The current paper refers to the study of a new approach to optimizing the adsorptive properties of geopolymers by varying the aluminosilicate precursors from kaolin (K), metakaolin (MK), and coal fly ash (CFA) as internal synthesis factors. The simplex-augmented-centroid mixture design was applied to identify the optimal formulation from the three aluminosilicate precursors to develop a geopolymer (GP) with a distinctive structure that positively affects its dye adsorption efficiency. The variously formulated GP samples were tested for the removal of both methylene blue (MB-dye) and crystal violet dye (CV-dye) from an aqueous solution. The mathematical-statistical analysis of the experimental readings suggested that the generated special cubic models were significant, and thus the chosen approach was adequate for determining the optimum blending proportion. The optimization tools indicated that the optimal mixture from the three aluminosilicate precursors for developing a GP with high adsorption efficiency was 58% MK, 42% K, and 0% CFA. The optimized geopolymer (GP_O) was synthesized and then analyzed using a variety of physicochemical techniques, which revealed the presence of an amorphous N-A-S-H gel-rich porous structure as an influencing property on the geopolymer’s organic dye adsorption efficiency. The dependence of the adsorption mechanism of both MB-dye and CV-dye by GP_O on the adsorbent dosage, contact time, initial dye concentration, temperature, and solution pH was evaluated. The isothermic and kinetic experimental readings for MB and CV-dyes adsorption by GP_O were well fitted to the pseudo-second-order and Freundlich models, with an exothermic, favorable, and spontaneous adsorption reaction thermodynamically. The experimental studies in the lab scale on GP_O produce comparable results. From these results, it has been concluded that the accuracy and feasibility of the mixture design simulation succeeded in optimizing and developing a geopolymeric sorbent material with great potential as an excellent economical agent for removing cationic dyes from aqueous media. This point represents an added value compared to traditional non-optimized geopolymer absorbents. Besides, this geopolymer material represents a significant application possibility for water treatment and remediation of hazardous dye pollutants.

PMID:37015145 | DOI:10.1016/j.jenvman.2023.117853

Mult Scler Relat Disord. 2023 Mar 21;73:104627. doi: 10.1016/j.msard.2023.104627. Online ahead of print.

ABSTRACT

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is considered a complex multifactorial disorder. Most cases are sporadic, and familial NMOSD is assumed as a rare occurrence. However, few studies reported familial aggregation of the disorder.

OBJECTIVES: To report familial NMOSD cases in Thailand and conduct a systematic review of familial NMOSD.

METHODS: A retrospective chart review of familial NMOSD patients at the university hospital was performed. Articles related to “genetic” and “NMOSD” were systematically searched and reviewed. We included NMOSD patients whose one or more relatives were diagnosed with the same disease or multiple sclerosis (MS). Data regarding demographics, clinical features, disease outcomes, and genetic testing were collected and analyzed using descriptive statistics.

RESULTS: We identified 6 familial cases from 165 NMOSD cases (3.6%) at our hospital and gathered 77 cases from a systematic review, totaling 83 cases from 40 families. The mean (SD) age at onset was 37.2 (18.0) years. Familial NMOSD involved 1-2 generations with mainly 2 affected individuals. The most common kinship pattern was siblingship in 21 families (52.5%). Initial syndromes were mostly optic neuritis and transverse myelitis. Serum aquaporin-4 IgG was positive in 79.7% of cases. Median number of relapses was 3 (range 1-26). Median expanded disability status scale in the last visit was 2 (range 0-8). Reported human leukocyte antigens (HLA) alleles shared between familial cases were HLA-A*01 and HLA-DRB1*03.

CONCLUSION: Familial clustering of NMOSD is more common than would be expected in the general population. The demographic, clinical, and outcome profiles of familial cases were not different from sporadic cases. Certain specific HLA haplotypes were shared among familial cases. Our systematic review highlighted complex genetic predisposition to NMOSD.

PMID:37015139 | DOI:10.1016/j.msard.2023.104627