Furosemide stress test (FST) is a novel functional biomarker for predicting severe acute kidney injury (AKI); however, pediatric studies are limited.
Children 3 months to 18 years of age admitted to ...the intensive care unit (ICU) of a tertiary care hospital from Nov 2019 to July 2021 were screened and those who developed AKI stage 1 or 2 within 7 days of admission underwent FST (intravenous furosemide 1 mg/kg). Urine output was measured hourly for the next 6 h; a value > 2 ml/kg within the first 2 h was deemed furosemide responsive. Other biomarkers like plasma neutrophil gelatinase-associated lipocalin (NGAL) and proenkephalin (PENK) were also evaluated.
Of the 480 admitted patients, 51 developed AKI stage 1 or 2 within 7 days of admission and underwent FST. Nine of these patients were furosemide non-responsive. Thirteen (25.5%) patients (eight of nine from FST non-responsive group) developed stage 3 AKI within 7 days of FST, nine (17.6%) of whom (seven from non-responsive group) required kidney support therapy (KST). FST emerged as a good biomarker for predicting stage 3 AKI and need for KST with area-under-the-curve (AUC) being 0.93 ± 0.05 (95% CI 0.84-1.0) and 0.96 ± 0.03 (95% CI 0.9-1.0), respectively. FST outperformed NGAL and PENK in predicting AKI stage 3 and KST; however, the combination did not improve the diagnostic accuracy.
Furosemide stress test is a simple, inexpensive, and robust biomarker for predicting stage 3 AKI and KST need in critically ill children. Further research is required to identify the best FST cut-off in children.
Abstract
The impact of mole fraction variation on the RF/DC performance of GaAs
1−
x
Sb
x
‐based FinFET has been examined in this study. Changing the Sb mole fraction has substantial effect on the ...electronic band parameters of GaAs, which directly affects the device performance. Electrical properties of the device including electron density and mobility fluctuation are investigated as a function of Sb mole fraction. Additionally, device DC performance parameters such as the
I
ON
/
I
OFF
ratio, threshold voltage, transconductance, and device node capacitance, such as
C
gg
and
C
ds
, are studied using a technology computer‐aided design (TCAD) simulator. The mole fraction dependence of the gate capacitance dictates the application of the proposed FinFET in the RF and high‐frequency domains. A detailed investigation of the figures of merits such as intrinsic gain, intrinsic delay, dynamic power dissipation, power delay product, energy dissipation, and unity gain bandwidth reveals that GaAsSb can be a potential material for realization of low‐power analog and digital circuits. The proper tuning of the mole fraction can help to optimize the device performance.
Invasive placentation and cancer development shares many similar molecular and epigenetic pathways. Paternally expressed, growth promoting genes (SNRPN, PEG10 and MEST) which are known to play ...crucial role in tumorogenesis, are not well studied during placentation. This study reports for the first time of the impact of gestational-age, pathological conditions and folic acid supplementation on dynamic nature of DNA and histone methylation present at their differentially methylated regions (DMRs). Here, we reported the association between low DNA methylation/H3K27me3 and higher expression of SNRPN, PEG10 and MEST in highly proliferating normal early gestational placenta. Molar and preeclamptic placental villi, exhibited aberrant changes in methylation levels at DMRs of these genes, leading to higher and lower expression of these genes, respectively, in reference to their respective control groups. Moreover, folate supplementation could induce gene specific changes in mRNA expression in placental cell lines. Further, MEST and SNRPN DMRs were observed to show the potential to act as novel fetal DNA markers in maternal plasma. Thus, variation in methylation levels at these DMRs regulate normal placentation and placental disorders. Additionally, the methylation at these DMRs might also be susceptible to folic acid supplementation and has the potential to be utilized in clinical diagnosis.
Efficacy and safety of three antibiotics (Linezolid-LZ, 0.2%; Azithromycin-AZ, 1%; Tigecycline-TG, 1%) were determined in the treatment of Pythium insidiosum keratitis in rabbits. Infection of right ...eye of 38 rabbits was induced by standard intracorneal injection of P. insidiosum zoospores (left eye, intracorneal saline). Corneal infection developed in all right eyes. One hourly eye drops of one of the three antibiotics was instilled in both eyes (3 groups of 12 rabbits each) except in controls. Half of the rabbits in each group received intracorneal injection of the respective antibiotic after 4 days of starting eye drops. Clinical scoring of eyes was done over next 3 weeks. The reduction in scores post-treatment was significant for each drug (LZ: p < 0.025, AZ: p < 0.025, TG: p < 0.01). Scores with LZ (median change of 3) was significantly (p = 0.013) higher than TG (median change of 2) and comparable (p = 0.06) to AZ (median change of 3). Reduction in clinical scores in eyes receiving intracorneal antibiotics was not significantly different from the eyes that did not receive intracorneal antibiotics (p = 0.73). While no adverse effect of LZ was seen in the control corneas, 66–100% of rabbits showed reaction to AZ and TG. Histopathology showed severe inflammation in all infected corneas and intraocular extension in some of the rabbits with poor response. The success rate was noted to be 16.7%, 25% and 50% in AZ, TG and LZ respectively (p = 0.45). LZ demonstrated superior efficacy and safety and can be considered for trial in human disease.
•Pythium insidiosum, an oomycete resembling zygomycete group of fungi, causes severe keratitis•Not amenable to antifungal treatment large number of patients require keratoplasty•The organism is susceptible in vitro to antibacterial antibiotics•In a rabbit model topical and intracorneal linezolid, azithromycin and tigecycline were compared•Linezolid showing greater safety and efficacy is recommended for therapy
•There is increased prevalence of cytomegalovirus in pediatric inflammatory bowel disease patients with acute severe colitis.•Viral burden on histopathology is not predictive of response to therapy ...or long-term outcomes.•Lymphopenia is not a reliable marker of cytomegalovirus colitis in pediatric inflammatory bowel disease.
The prevalence and significance of cytomegalovirus (CMV) colitis in pediatric acute severe colitis is unknown. The aim of this study was to determine the prevalence of CMV in colonic mucosa of children with acute severe refractory colitis and compare the clinical characteristics and outcomes of CMV positive and negative patients.
In a case-control study, colonic biopsy specimens from children with severe refractory colitis were tested for CMV, and matched with non-refractory IBD controls. We characterized CMV positive patients by assessing laboratory values, concurrent medications, and need for surgery as compared with CMV negative refractory colitis patients.
Colonic biopsies from 96 patients were evaluated for CMV; 48 with severe refractory colitis, and 48 non-refractory controls. There was an increased prevalence of CMV in severe refractory colitis 7/48 (14.6%), P < 0.0001; all were previously CMV negative. Viral DNA burden on immunohistochemistry was not predictive of response to antiviral therapy or need for surgery at 12 months. Lymphopenia was seen in all CMV positive patients, but this did not demonstrate statistical significance (P = 0.09). We did not see an association between azathioprine or infliximab use and the need for surgery at 12 months.
There is an increased prevalence of CMV in colonic biopsies of pediatric patients with severe refractory colitis. Viral burden does not predict clinical outcomes or subsequent need for colectomy.
The current study aims to evaluate the feasibility of creatine (Cr) chemical exchange saturation transfer (CEST)‐weighted MRI at 7 T in the human brain by optimizing the saturation pulse parameters ...and computing contrast using a Z‐spectral fitting approach. The Cr‐weighted (Cr‐w) CEST contrast was computed from phantoms data. Simulations were carried out to obtain the optimum saturation parameters for Cr‐w CEST with lower contribution from other brain metabolites. CEST‐w images were acquired from the brains of four human subjects at different saturation parameters. The Cr‐w CEST contrast was computed using both asymmetry analysis and Z‐spectra fitting approaches (models 1 and 2, respectively) based on Lorentzian functions. For broad magnetization transfer (MT) effect, Gaussian and Super‐Lorentzian line shapes were also evaluated. In the phantom study, the Cr‐w CEST contrast showed a linear dependence on concentration in physiological range and a nonlinear dependence on saturation parameters. The in vivo Cr‐w CEST map generated using asymmetry analysis from the brain represents mixed contrast with contribution from other metabolites as well and relayed nuclear Overhauser effect (rNOE). Simulations provided an estimate for the optimum range of saturation parameters to be used for acquiring brain CEST data. The optimum saturation parameters for Cr‐w CEST to be used for brain data were around B1rms = 1.45 μT and duration = 2 seconds. The Z‐spectral fitting approach enabled computation of individual components. This also resulted in mitigating the contribution from MT and rNOE to Cr‐w CEST contrast, which is a major source of underestimation in asymmetry analysis. The proposed modified z‐spectra fitting approach (model 2) is more stable to noise compared with model 1. Cr‐w CEST contrast obtained using fitting was 6.98 ± 0.31% in gray matter and 5.45 ± 0.16% in white matter. Optimal saturation parameters reduced the contribution from other CEST effects to Cr‐w CEST contrast, and the proposed Z‐spectral fitting approach enabled computation of individual components in Z‐spectra of the brain. Therefore, it is feasible to compute Cr‐w CEST contrast with a lower contribution from other CEST and rNOE.
Optimal saturation parameters reduced contribution from other CEST effects to Cr‐weighted CEST contrast in human brain at 7 T and a proposed Z‐spectral fitting approach enabled computation of individual components in Z‐spectra. The optimum saturation parameters for Cr‐w CEST to be used for brain data were around B1rms = 1.45μT and duration of 2 seconds.
Gene editing has great potential in treating diseases caused by well-characterized molecular alterations. The introduction of clustered regularly interspaced short palindromic repeats ...(CRISPR)/CRISPR-associated protein 9 (Cas9)-based gene-editing tools has substantially improved the precision and efficiency of gene editing. The CRISPR/Cas9 system offers several advantages over the existing gene-editing approaches, such as its ability to target practically any genomic sequence, enabling the rapid development and deployment of novel CRISPR-mediated knock-out/knock-in methods. CRISPR/Cas9 has been widely used to develop cancer models, validate essential genes as druggable targets, study drug-resistance mechanisms, explore gene non-coding areas, and develop biomarkers. CRISPR gene editing can create more-effective chimeric antigen receptor (CAR)-T cells that are durable, cost-effective, and more readily available. However, further research is needed to define the CRISPR/Cas9 system's pros and cons, establish best practices, and determine social and ethical implications. This review summarizes recent CRISPR/Cas9 developments, particularly in cancer research and immunotherapy, and the potential of CRISPR/Cas9-based screening in developing cancer precision medicine and engineering models for targeted cancer therapy, highlighting the existing challenges and future directions. Lastly, we highlight the role of artificial intelligence in refining the CRISPR system's on-target and off-target effects, a critical factor for the broader application in cancer therapeutics.
While machining titanium alloys, using metalworking fluids (MWFs) helps improve the tribological properties. However, its usage is restricted considering the harmful effects on health and the ...environment under sustainable machining. Using minimum quantity lubrication (MQL) to improve machining performance without utilising an excessive amount of cutting fluid is becoming more prevalent. Pure-MQL, however, might not be adequate for machining titanium alloys. Due to their improved heat transfer capabilities, nanofluid-based lubricants are extremely popular for use in the machining of superalloys. In this direction, the efficacy of the MQL mixture can be improved by using vegetable-oil-based cutting fluid reinforced with nanoparticles. Therefore, this study compares dry, flood, MQL and nanofluid-MQL techniques while machining Ti-6Al-4V titanium alloy with textured tools. The Hexagonal Boron Nitride (hBN) nanoparticles are added to the base fluid to develop a nanofluid-MQL mixture. Machinability indicators are analysed, namely tool wear, surface roughness, power consumption, and specific cutting energy. The outcomes showcased the efficacy of nanofluid-MQL with lower surface roughness, tool wear, and specific energy requirements compared to other conditions. It is observed that combining vegetable oil and hBN nanoparticles in nanofluid-MQL reduced friction and improved cooling in the machining interfaces.
Autism spectrum disorder (ASD) is a neurodevelopmental impairment characterized by deficits in social interaction skills, impaired communication, and repetitive and restricted behaviors that are ...thought to be due to altered neurotransmission processes. The amino acid glutamate is an essential excitatory neurotransmitter in the human brain that regulates cognitive functions such as learning and memory, which are usually impaired in ASD. Over the last several years, increasing evidence from genetics, neuroimaging, protein expression, and animal model studies supporting the notion of altered glutamate metabolism has heightened the interest in evaluating glutamatergic dysfunction in ASD. Numerous pharmacological, behavioral, and imaging studies have demonstrated the imbalance in excitatory and inhibitory neurotransmitters, thus revealing the involvement of the glutamatergic system in ASD pathology. Here, we review the effects of genetic alterations on glutamate and its receptors in ASD and the role of non-invasive imaging modalities in detecting these changes. We also highlight the potential therapeutic targets associated with impaired glutamatergic pathways.
PDF
