Duusismail4923

Matrix-assisted laser desorption/ ionization (MALDI) is a soft ionization technique for introducing wide range of analytes into a mass spectrometer (MS). MALDI MS is a powerful tool in drug discovery research and development, providing a high-throughput molecular analysis technique in both preclinical and clinical systems. In particular, MALDI MS is invaluable in the study of peptides and proteins that drive all biological functions. This technology is label-free, provides high specificity in molecular identification, and is high-throughput. MALDI MS has been used in biomarker discovery and quantitation in virtually all tissues, serum, plasma, CSF, and urine for diagnostics, patient stratification, and monitoring drug efficacy. Other applications include characterization of biological drugs, spatial mapping of biomarkers and drugs in tissues, drug screening, and toxicological assessment.Bispecific antibodies combine the specificity of two antibodies into one molecule. During the past two decades, advancement in protein engineering enabled the development of more than 100 bispecific formats, three of which are approved by the FDA for clinical use. In parallel to protein engineering methods, advancement in conjugation chemistries have spurred the use of chemical engineering approaches to generate bispecific antibodies. Wnt cancer Herein, we review selected chemical strategies employed to generate bispecific antibodies that cannot be made using protein engineering methods.Patient-reported outcomes (PROs) are quantitative assessments of a patient's perspective on their health and are derived directly from the patient, as opposed to clinician interpretation. PROs can serve as unique tools to improve health care providers' understanding of the patient's daily lived experience and highlight salient domains that are specific to children with chronic kidney disease (CKD). As such, PROs fill an important gap in achieving optimal health and well-being for children with CKD. However, several knowledge gaps remain in the implementation of PROs within both the clinical and research realms. This review provides a broad overview of PRO development, implementation for children with CKD, and highlights future directions and challenges.This cross-sectional study provides preliminary findings from one of the first functional brain imaging studies in children with chronic kidney disease (CKD). The sample included 21 children with CKD (ages, 14.4 ± 3.0 y) and 11 healthy controls (ages, 14.5 ± 3.4 y). Using functional magnetic resonance imaging during a visual-spatial working memory task, findings showed that the CKD group and healthy controls invoked similar brain regions for encoding and retrieval phases of the task, but significant group differences were noted in the activation patterns for both components of the task. For the encoding phase, the CKD group showed lower activation in the posterior cingulate, anterior cingulate, precuneus, and middle occipital gyrus than the control group, but more activation in the superior temporal gyrus, middle frontal gyrus, middle temporal gyrus, and the insula. For the retrieval phase, the CKD group showed underactivation for brain systems involving the posterior cingulate, medial frontal gyrus, occipital lobe, and middle temporal gyrus, and greater activation than the healthy controls in the postcentral gyrus. Few group differences were noted with respect to disease severity. These preliminary findings support evidence showing a neurologic basis to the cognitive difficulties evident in pediatric CKD, and lay the foundation for future studies to explore the neural underpinnings for neurocognitive (dys)function in this population.An increasing amount of literature has indicated that chronic kidney disease (CKD) is associated with cognitive deficits that increase with worsening disease severity. Although abnormalities in brain structure have been widely documented, few studies to date have examined the functioning of brain areas associated with the specific cognitive domains affected by CKD (namely, attention and executive functions). Furthermore, few studies have examined functional connectivity among CKD youth who are relatively early in the course of the disease. The present study used functional magnetic resonance imaging to examine the resting state connectivity in 67 youth with CKD (mean age, 17 y) and 58 age-matched healthy controls. Using seed-based multiple regression, decreased connectivity was observed within the anterior cingulate portion of the default mode network. In addition, decreased connectivity within the dorsolateral prefrontal cortex, paracingulate gyrus, and frontal pole were correlated significantly with disease severity. These data indicate that connectivity deficits in circuits implementing attentional processes may represent an early marker for cognitive decline in CKD.Pediatric chronic kidney disease (CKD) is associated with deficits in neurocognitive functioning, ranging from mild to severe, and correlated with the severity of kidney disease. Clinical variables that are associated with neurocognitive deficits include lower kidney function, hypertension, proteinuria, and metabolic acidosis. Commonly reported neurocognitive difficulties include academic underachievement and deficits in attention regulation and executive function as well as somewhat lower intellectual abilities compared with peer and normative data. Although often mild, these neurocognitive deficits may have broad implications for quality of life and likely contribute to both poorer high school graduation rates and long-term underemployment in the adult CKD population. The presence of neurocognitive deficits in predialytic CKD has been well characterized, but further longitudinal research is warranted to describe cognitive changes as children progress from early stage CKD to kidney replacement therapy. Such studies should include both cognitive and neuroimaging evaluations to better inform the impact of CKD progression on neurocognitive outcomes.Chronic kidney disease (CKD) mineral bone disorder has long-term effects on skeletal integrity and growth. Abnormalities in serum markers of mineral metabolism are evident early in pediatric CKD. Bone deformities, poor linear growth, and high rates of fractures are common in children with CKD. Newer imaging modalities such as high-resolution peripheral quantitative computed tomography shows promise in assessing bone mineral density more comprehensively and predicting incident fractures. A lack of large-scale studies that provide a comprehensive assessment of bone histology and correlations with serum biomarkers has contributed to the absence of evidence-based guidelines and suboptimal management of CKD mineral bone disorder in children with CKD.Over the past 2 decades, cardiovascular (CV) disease has been recognized as one of the most important complications of chronic kidney disease (CKD) and one of the leading causes of death in children with advanced CKD and in young adults who developed CKD during childhood. CV abnormalities develop early and progress during the course of CKD in children. Characterization of the prevalence and evolution of CV disease risk factors in progressive CKD is one of the primary aims of the Chronic Kidney Disease in Children study. In this review, we summarize up-to-date findings from the Chronic Kidney Disease in Children study with a focus on traditional and CKD-related CV risk factors and early subclinical markers of cardiac and vascular structure and function. We also discuss the effect of CV risk factors on progression of CKD.Congenital anomalies of the kidney and urinary tract are the leading cause of chronic kidney disease in children. Noninvasive imaging biomarkers that predict chronic kidney disease progression in early infancy are needed. We performed a pilot study nested in the prospective Chronic Kidney Disease in Children cohort study to determine the association between renal parenchymal area (RPA) on first post-natal renal ultrasound and change in estimated glomerular filtration rate (eGFR) in children with congenital anomalies of the kidney and urinary tract. Among 14 participants, 78.6% were males, the median age at the time of the ultrasound was 3.4 months (interquartile range, 1.3-7.9 mo), and the median total RPA z-score at baseline was -1.01 (interquartile range, -2.39 to 0.52). After a median follow-up period of 7.4 years (interquartile range, 6.8-8.2 y), the eGFR decreased from a median of 49.4 mL/min per 1.73 m2 at baseline to 29.4 mL/min per 1.73 m2, an annual eGFR percentage decrease of -4.68%. Lower RPA z-scores were correlated weakly with a higher annual decrease in eGFR (Spearman correlation, 0.35; 95% confidence interval, -0.25 to 0.76). This pilot study shows the feasibility of obtaining RPA from a routine ultrasound and suggests that a lower baseline RPA may be associated with a greater decrease in eGFR over time. Further studies with larger patient cohorts are needed to confirm this association.Serum creatinine and level of proteinuria, as biomarkers of chronic kidney disease (CKD) progression, inadequately explain the variability of glomerular filtration rate decline, and are late markers of glomerular filtration rate decline. Recent studies have identified plasma and urine biomarkers at higher levels in children with CKD and also associate independently with CKD progression, even after adjustment for serum creatinine and proteinuria. These novel biomarkers represent diverse biologic pathways of tubular injury, tubular dysfunction, inflammation, and tubular health, and can be used as a liquid biopsy to better characterize CKD in children. In this review, we highlight the biomarker findings from the Chronic Kidney Disease in Children cohort, a large longitudinal study of children with CKD, and compare results with those from other pediatric CKD cohorts. The biomarkers in focus in this review include plasma kidney injury molecule-1, monocyte chemoattractant protein-1, fibroblast growth factor-23, tumor necrosis factor receptor-1, tumor necrosis factor receptor-2, soluble urokinase plasminogen activator receptor, and chitinase-3-like protein 1, as well as urine epidermal growth factor, α-1 microglobulin, kidney injury molecule-1, monocyte chemoattractant protein-1, and chitinase-3-like protein 1. Blood and urine biomarkers improve our ability to prognosticate CKD progression and may improve our understanding of CKD pathophysiology. Further research is required to establish how these biomarkers can be used in the clinical setting to improve the clinical management of CKD.Chronic kidney disease (CKD) progression is typically characterized as either time to a clinically meaningful event (such as dialysis or transplant), or longitudinal changes in kidney function. This review describes pediatric kidney disease progression using these two distinct frameworks by reviewing and discussing data from the Chronic Kidney Disease in Children study. We first describe new equations to estimate glomerular filtration rate (GFR) for patients younger than age 25 years, and how the average of serum creatinine-based and cystatin C-based GFR equations yield valid estimates than either alone. Next, we present a life course description of CKD onset to kidney replacement therapy, prediction models based on clinical measurements, and show the importance of diagnosis (broadly classified as nonglomerular and glomerular in origin), GFR level, and proteinuria on progression. Literature on longitudinal GFR in children and young adults are reviewed and new data are presented to characterize nonlinear changes in estimated GFR in patients younger than age 25 years.