scholarly journals Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malaria

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Benson J. Ouma ◽  
Paul Bangirana ◽  
John M. Ssenkusu ◽  
Dibyadyuti Datta ◽  
Robert O. Opoka ◽  
...  
Keyword(s):  
Severe Malaria ◽  
Parental Education ◽  
Preschool Education ◽  
Kidney Injury ◽  
Malaria Episode ◽  
Enzyme Linked Immunosorbent Assay ◽  
Testing Time ◽  
Age Related ◽  
Angiopoietin 2 ◽  
The Relationship

Abstract Background Elevated angiopoietin-2 (Angpt-2) concentrations are associated with worse overall neurocognitive function in severe malaria survivors, but the specific domains affected have not been elucidated. Methods Ugandan children with severe malaria underwent neurocognitive evaluation a week after hospital discharge and at 6, 12 and 24 months follow-up. The relationship between Angpt-2 concentrations and age-adjusted, cognitive sub-scale z-scores over time were evaluated using linear mixed effects models, adjusting for disease severity (coma, acute kidney injury, number of seizures in hospital) and sociodemographic factors (age, gender, height-for-age z-score, socio-economic status, enrichment in the home environment, parental education, and any preschool education of the child). The Mullen Scales of Early Learning was used in children < 5 years and the Kaufman Assessment Battery for Children 2nd edition was used in children ≥ 5 years of age. Angpt-2 levels were measured on admission plasma samples by enzyme-linked immunosorbent assay. Adjustment for multiple comparisons was conducted using the Benjamini–Hochberg Procedure of False Discovery Rate. Results Increased admission Angpt-2 concentration was associated with worse outcomes in all domains (fine and gross motor, visual reception, receptive and expressive language) in children < 5 years of age at the time of severe malaria episode, and worse simultaneous processing and learning in children < 5 years of age at the time of severe malaria who were tested when ≥ 5 years of age. No association was seen between Angpt-2 levels and cognitive outcomes in children ≥ 5 years at the time of severe malaria episode, but numbers of children and testing time points were lower for children ≥ 5 years at the time of severe malaria episode. Conclusion Elevated Angpt-2 concentration in children with severe malaria is associated with worse outcomes in multiple neurocognitive domains. The relationship between Angpt-2 and worse cognition is evident in children < 5 years of age at the time of severe malaria presentation and in selected domains in older years.

scholarly journals Acute Kidney Injury Is Common in Pediatric Severe Malaria and Is Associated With Increased Mortality

2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Andrea L. Conroy ◽  
Michael Hawkes ◽  
Robyn E. Elphinstone ◽  
Catherine Morgan ◽  
Laura Hermann ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Severe Malaria ◽  
Clinical Importance ◽  
Kidney Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Arm Reaching ◽  
Increased Risk ◽  
Duration Of Hospitalization ◽  
Kdigo Guidelines ◽  
Stage 1

Abstract Background.  Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented. Methods.  One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay. Results.  Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm developing AKI compared with 34 (37.4%) in the placebo arm (relative risk, 1.36; 95% confidence interval [CI], 1.03–1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25% in children with AKI vs 1.9% in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5% in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P &gt; .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95% CI, .65–.95; P = .006) and 0.72 (95% CI, .57–.87; P &lt; .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P &lt; .0001 and P = .009, respectively). Conclusions.  Acute kidney injury is an underrecognized complication in young children with SM and is associated with increased mortality.

scholarly journals Biomarker Profiling in Stage 5 Chronic Kidney Disease Identifies the Relationship between Angiopoietin-2 and Atrial Fibrillation

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 269S-276S ◽  
Author(s):  
Jack Bontekoe ◽  
Justin Lee ◽  
Vinod Bansal ◽  
Mushabbar Syed ◽  
Debra Hoppensteadt ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Strong Association ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Biomarker ◽  
Angiopoietin 2 ◽  
The Relationship ◽  
Circulating Levels

Atrial fibrillation (AF) is prevalent in nearly 27% of patients with stage 5 chronic kidney disease on hemodialysis (CKD5-HD), suggesting a strong association between these 2 pathologies. It is hypothesized that the relationship between these 2 diseases may be mediated by inflammation. Angiopoietin-2 (Ang-2), a pro-inflammatory biomarker of endothelial instability, inflammation, and vascular remodeling, is elevated in CKD5-HD and AF, yet has not been evaluated in patients with concomitant AF and CKD5-HD. The aim of this study is to analyze circulating levels of inflammatory and thrombotic biomarkers in patients with concomitant AF and CKD5-HD. Plasma levels of Ang-2 were measured via sandwich enzyme-linked immunosorbent assay method in CKD5-HD patients (n = 96), patients with AF (n = 38), and controls (n = 50). Angiopoietin-2 was markedly elevated in CKD5-HD with comorbid AF as compared to CKD5-HD alone, and AF alone, respectively (13.05 ± 1.56 vs 9.57 ± 0.71 ng/mL; P = .00169; vs 2.48 ± 0.57 ng/mL; P < .0001). The results of this study suggest an additive effect of Ang-2 with coexistence of AF and CKD5-HD, which may be useful in the detection of AF within this patient population.

Cognitive Factors Mediate the Relation Between Age and Flight Path Maintenance in General Aviation

2016 ◽  
Vol 6 (2) ◽  
pp. 81-90 ◽  
Author(s):  
Kathleen Van Benthem ◽  
Chris M. Herdman
Keyword(s):  
Cognitive Functioning ◽  
Flight Path ◽  
General Aviation ◽  
Cognitive Factors ◽  
Pilot Performance ◽  
Pilot Error ◽  
Age Related ◽  
And Performance ◽  
Relationship Of ◽  
The Relationship

Abstract. Identifying pilot attributes associated with risk is important, especially in general aviation where pilot error is implicated in most accidents. This research examined the relationship of pilot age, expertise, and cognitive functioning to deviations from an ideal circuit trajectory. In all, 54 pilots, of varying age, flew a Cessna 172 simulator. Cognitive measures were obtained using the CogScreen-AE ( Kay, 1995 ). Older age and lower levels of expertise and cognitive functioning were associated with significantly greater flight path deviations. The relationship between age and performance was fully mediated by a cluster of cognitive factors: speed and working memory, visual attention, and cognitive flexibility. These findings add to the literature showing that age-related changes in cognition may impact pilot performance.

The relationship between brain structure and general psychopathology in preadolescents

2020 ◽  
Author(s):  
Louise Mewton ◽  
Briana Lees ◽  
Lindsay Squeglia ◽  
Miriam K. Forbes ◽  
Matthew Sunderland ◽  
...  
Keyword(s):  
Mental Disorders ◽  
Surface Area ◽  
Brain Structure ◽  
Parental Education ◽  
Mental Illnesses ◽  
General Psychopathology ◽  
Control Approach ◽  
Cortical Volume ◽  
Subcortical Regions ◽  
The Relationship

Categorical mental disorders are being recognized as suboptimal targets in clinical neuroscience due to poor reliability as well as high rates of heterogeneity within, and comorbidity between, mental disorders. As an alternative to the case-control approach, recent studies have focused on the relationship between neurobiology and latent dimensions of psychopathology. The current study aimed to investigate the relationship between brain structure and psychopathology in the critical preadolescent period when psychopathology is emerging. This study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study® (n = 11,721; age range = 9-10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area. Higher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, and parental education. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There was evidence of a relationship between externalizing psychopathology and frontal regions of the cortex that was independent of general psychopathology. The current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. The widespread and pervasive relationships between general psychopathology and brain structure may reflect cognitive dysfunction that is a feature across a range of mental illnesses.

MiR-125a-5p Alleviates Dysfunction and Inflammation of Pentylenetetrazol- induced Epilepsy Through Targeting Calmodulin-dependent Protein Kinase IV (CAMK4)

2019 ◽  
Vol 16 (4) ◽  
pp. 365-372 ◽  
Author(s):  
Qishuai Liu ◽  
Li Wang ◽  
Guizhen Yan ◽  
Weifa Zhang ◽  
Zhigang Huan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Target Gene ◽  
Luciferase Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Factor ◽  
Dependent Protein Kinase ◽  
Expression Levels ◽  
Dependent Protein ◽  
Polymerase Chain ◽  
The Relationship

Background: MicroRNAs (miRNA) are known to play a key role in the etiology and treatment of epilepsy through controlling the expression of gene. However, miR-125a-5p in the epilepsy is little known. Epilepsy in rat models was induced by Pentylenetetrazol (PTZ) and miR- 125a-5p profiles in the hippocampus were investigated in our experiment. Also, the relationship between miR-125a-5p and calmodulin-dependent protein kinase IV (CAMK4) was identified and the related mechanism was also illustrated. Methods: The miR-125a-5p mRNA expression levels were evaluated by quantitative real time polymerase chain reaction (qRT-PCR). Western Blot (WB) was used to analyze the CAMK4 protein expression levels. Seizure score, latency and duration were determined based on a Racine scale. The enzyme-linked immunosorbent assay (ELISA) was used to analyze the inflammatory factor expression. The relationship between miR-125a-5p and CAMK4 was detected through dual luciferase assay. Results: Downregulation of miR-125a-5p was observed in the hippocampus of PTZ-induced epilepsy rats. The overexpression of miR-125a-5p attenuated seizure and decreased inflammatory factor level in the hippocampus of PTZ-induced rats. The miR-125a-5p alleviated epileptic seizure and inflammation in PTZ-induced rats by suppressing its target gene, CAMK4. Conclusion: miR-125a-5p may represent a novel therapeutic treatment for PTZ-induced epilepsy by preventing the activation of CAMK4.

The Association Between Cardio-Ankle Vascular Index and Primary Idiopathic Complete Atrioventricular Block in an Elderly Population

Angiology ◽  
2021 ◽  
pp. 000331972110287
Author(s):  
Turhan Turan ◽  
Faruk Kara ◽  
Selim Kul ◽  
Muhammet Rasit Sayın ◽  
Sinan Sahin ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Atrioventricular Block ◽  
Elderly Population ◽  
Complete Atrioventricular Block ◽  
Age Related ◽  
And Gender ◽  
The Relationship ◽  
Block Frequency ◽  
Complete Atrioventricular ◽  
Relevant Factors

The most common cause of complete atrioventricular block (CAVB) is age-related fibrotic degeneration and is referred to as primary idiopathic complete atrioventricular block (iCAVB). This study aims to investigate the relationship between iCAVB and arterial stiffness using the cardio-ankle vascular index (CAVI). In this study, of 205 CAVB patients, 41 patients with iCAVB implanted with a dual-chamber permanent pacemaker and 40 age- and gender-matched controls were studied. Arterial stiffness was assessed by a VaSera VS-1000 CAVI instrument. The CAVI values of patients with iCAVB were significantly higher compared with the controls (9.63 ± 1.42 vs 8.57 ± 1.12, P < .001). Idiopathic complete atrioventricular block frequency was higher among patients with abnormal CAVI values than those with borderline and normal CAVI ( P = .04). In multivariate analysis, only CAVI was an independent predictor of iCAVB after adjusting for other relevant factors (odds ratio, 2.575; 95% CI [1.390-4.770]; P = .003). The present study demonstrated that CAVI, as a marker of arterial stiffness, was increased among elderly patients with iCAVB. Thus, we provide a possible additional mechanism linking easily measured CAVI with iCAVB.

scholarly journals Hsa-miR-494-3p attenuates gene HtrA3 transcription to increase inflammatory response in hypoxia/reoxygenation HK2 Cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qian Gong ◽  
Zhi-ming Shen ◽  
Zhe Sheng ◽  
Shi Jiang ◽  
Sheng-lin Ge
Keyword(s):  
Cardiac Surgery ◽  
Inflammatory Response ◽  
Target Gene ◽  
Kidney Injury ◽  
Human Kidney ◽  
Luciferase Reporter ◽  
The Relationship ◽  
Hk2 Cells ◽  
Dual Luciferase Reporter Assay ◽  
Hypoxia Reoxygenation

AbstractThe occurrence of cardiac surgery-associated acute kidney injury (CSA-AKI) increases hospital stay and mortality. MicroRNAs has a crucial role in AKI. This objective of the current study is to explore the function of hsa-miR-494-3p in inflammatory response in human kidney tubular epithelial (HK2) cells with hypoxia/reoxygenation. According to KDIGO standard, patients after cardiac surgery with cardiopulmonary bypass were divided into two groups: AKI (n = 10) and non-AKI patients (n = 8). HK2 were raised in the normal and hypoxia/reoxygenation circumstances and mainly treated by overexpression ofmiR-494-3p and HtrA3. The relationship between miR-494-3p and HtrA3 was determined by dual-luciferase reporter assay. Our result showed that Hsa-miR-494-3p was elevated in the serum of patients with CSA-AKI, and also induced in hypoxic reoxygenated HK2 cells. Hsa-miR-494-3p also increased a hypoxia-reoxygenation induced inflammatory response in HK2 cells. Moreover, as a target gene of miR-494-3p, overexpression of HtrA3 downregulated the hypoxia-reoxygenation induced inflammatory response in HK2 cells. Overexpression of hsa-miR-494-3p-induced inflammatory response was inhibited by overexpression of HtrA3. Collectively, we identified that hsa-miR-494-3p, a miRNA induced in both circulation of AKI patients and hypoxia-reoxygenation-treated HK2 cells, enhanced renal inflammation by targeting HtrA3, which may suggest a possible role as a new therapeutic target for CSA-AKI.

CSF chitinase 3-like 1 is associated with iron rims in patients with a first demyelinating event

2021 ◽  
pp. 135245852110100
Author(s):  
Manuel Comabella ◽  
Margareta A Clarke ◽  
Sabine Schaedelin ◽  
Mar Tintoré ◽  
Deborah Pareto ◽  
...  
Keyword(s):  
Single Molecule ◽  
Multivariable Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lesion Volume ◽  
Univariable Analysis ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Multivariable Analyses ◽  
Prognostic Implications ◽  
The Relationship

Background: Chronic active lesions with iron rims have prognostic implications in patients with multiple sclerosis. Objective: To assess the relationship between iron rims and levels of chitinase 3-like 1 (CHI3L1), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with a first demyelinating event. Methods: Iron rims were identified using 3T susceptibility-weighted imaging. Serum NfL and GFAP levels were measured by single-molecule array assays. CSF (cerebrospinal fluid) CHI3L1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Sixty-one patients were included in the study. The presence of iron rims was associated with higher T2 lesion volume and higher number of gadolinium-enhancing lesions. In univariable analysis, having ⩾2 iron rims (vs 0) was associated with increased CSF CHI3L1 levels (β = 1.41; 95% confidence interval (CI) = 1.10–1.79; p < 0.01) and serum NfL levels (β = 2.30; 95% CI = 1.47–3.60; p < 0.01). In multivariable analysis, however, only CSF CHI3L1 levels remained significantly associated with the presence of iron rim lesions (β = 1.45; 95% CI = 1.11–1.90; p < 0.01). The presence of ⩾2 iron rims was not associated with increased serum GFAP levels in univariable or multivariable analyses. Conclusion: These findings support an important contribution of activated microglia/macrophages to the pathophysiology of chronic active lesions with iron rims in patients with a first demyelinating event.

Life Course Pathways from Parental Education to Age-Related Decrements in Kidney Function Among Black and White American Adults

2021 ◽  
pp. 105291
Author(s):  
Agus Surachman ◽  
Alexis R. Santos ◽  
Jonathan K. Daw ◽  
Lacy Alexander ◽  
David M. Almeida ◽  
...  
Keyword(s):  
Life Course ◽  
Kidney Function ◽  
Parental Education ◽  
White American ◽  
Black And White ◽  
Age Related

scholarly journals Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived from poor ovarian responders

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yan Gong ◽  
Jesse Li-Ling ◽  
Dongsheng Xiong ◽  
Jiajing Wei ◽  
Taiqing Zhong ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Clinical Trial Registry ◽  
Altered Expression ◽  
Vitro Fertilization ◽  
Age Related ◽  
Tertiary Teaching ◽  
Poor Ovarian Responders

Abstract Background Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes play important roles in folliculogenesis. Altered expression of the two have been found among patients with poor ovarian response (POR). In this prospective cohort study, we have determined the expression of the GDF9 and BMP15 genes in follicle fluid (FF) and granulosa cells (GCs) derived from poor ovarian responders grouped by age, and explored its correlation with the outcome of in vitro fertilization and embryo transfer (IVF-ET) treatment. Methods A total of 196 patients with POR were enrolled from a tertiary teaching hospital. The patients were diagnosed by the Bologna criteria and sub-divided into group A (< 35 year old), group B (35–40 year old), and group C (> 40 year old). A GnRH antagonist protocol was conducted for all patients, and FF and GCs were collected after oocyte retrieval. Expression of the GDF9 and BMP15 genes in the FF and GCs was determined with enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Results Compared with group C, groups A and B had significantly more two pronuclei (2PN) oocytes and transplantable embryos, in addition with higher rates of implantation and clinical pregnancy (P <  0.05). The expression level of GDF9 and BMP15 genes in the FF and GCs differed significantly among the three groups (P <  0.05), showing a trend of decline along with age. The ratio of GDF9/BMP15 mRNA levels were similar among the three groups (P > 0.05). The relative levels of GDF9 and BMP15 proteins in GCs have correlated with the relative mRNA levels in GCs and protein concentrations in FF (P <  0.05). Conclusions For poor ovarian responders, in particular those over 40, the expression of GDF9 and BMP15 is declined along with increased age and in accompany with poorer oocyte quality and IVF outcome, whilst the ratio of GDF9/BMP15 mRNA levels remained relatively constant. Trial registration Chinese Clinical Trial Registry Center (ChiCTR1800016107). Registered on 11 May 2018.

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