Increased MCHC*RDW-SD interaction values: indicators of neurological impairment in lead-poisoned children
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ABSTRACT:
SUBMITTER: Ying Q
PROVIDER: S-EPMC10908253 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:IntroductionThe prognostic significance of red cell distribution width-SD (RDW-SD) as a promising inflammatory biomarker in individuals with non-ischemic dilated cardiomyopathy (DCM) and varying glycemic status remains unexplored.Research design and methodsPatients hospitalized for DCM in Fuwai Hospital from 2006 to 2021 were retrospectively included. The primary outcome encompassed all-cause mortality and heart transplantations. The multivariable Cox regression was used to evaluate the association between RDW-SD and outcomes in the overall DCM population, and among patients with normoglycemia (NG), pre-diabetes mellitus (pre-DM) and DM.ResultsAmong 1,102 patients with DCM, the median age was 48 years and 23.5% were women. In the overall DCM cohort, the RDW-SD was independently associated with the primary outcome (adjusted HR 1.29, 95% CI 1.15 to 1.45, p<0.001, per SD increase). When stratifying patients with glycemic status, the RDW-SD exhibited an independent association with outcome in patients with DCM with pre-DM and DM, the adjusted HRs were 1.48 (95% CI 1.21 to 1.79, p<0.001) and 1.30 (95% CI 1.06 to 1.60, p=0.011) per SD increase, respectively. However, in patients with DCM and NG, the prognostic value of RDW-SD was insignificant, with an adjusted HR of 1.20 per SD increase (95% CI: 0.97 to 1.48, p=0.101).ConclusionsRDW-SD was independently associated with the outcome in patients with DCM with pre-DM and DM, suggesting potential individualized therapeutic targets for this subset of patients with DCM.
| S-EPMC11575278 | biostudies-literature
Project description:Lead poisoning caused by lead pollution seriously affects people's health. Lactic acid bacteria has been shown to be useful for biological scavenging of lead. In this experiment, Sprague-Dawley (SD) rats were treated with 200 mg/L of lead acetate solution daily to induce chronic lead poisoning, and oral Limosilactobacillus fermentum (L. fermentum) SCHY34 to study its mitigation effects and mechanisms on rat neurotoxicity. The L. fermentum SCHY34 showed competent results on in vitro survival rate and the lead ion adsorption rate. Animal experiments showed that L. fermentum SCHY34 maintained the morphology of rat liver, kidney, and hippocampi, reduced the accumulation of lead in the blood, liver, kidney, and brain tissue. Further, L. fermentum SCHY34 alleviated the lead-induced decline in spatial memory and response capacity of SD rats, and also regulated the secretion of neurotransmitters and related enzyme activities in the brain tissue of rats, such as glutamate (Glu), monoamine oxidase (MAO), acetylcholinesterase (AchE), cyclic adenosine monophosphate (cAMP), and adenylate cyclase (AC). In addition, the expression of genes related to cognitive capacity, antioxidation, and anti-apoptotic in rat brain tissues were increased L. fermentum SCHY34 treatment, such as brain-derived neurotrophic factor (BDNF), c-fos, c-jun, superoxide dismutase (SOD)1/2, Nuclear factor erythroid 2-related factor 2 (Nrf2), and B-cell lymphoma 2 (Bcl-2), and so on. L. fermentum SCHY34 showed a great biological scavenging and potential effect on alleviating the toxicity of lead ions.
| S-EPMC9094495 | biostudies-literature
Project description:Biallelic variants in NADH (nicotinamide adenine dinucleotide (NAD) + hydrogen (H))-ubiquinone oxidoreductase 1 alpha subcomplex 13 have been linked to mitochondrial complex I deficiency, nuclear type 28, based on three affected individuals from two families. With only two families reported, the clinical and molecular spectrum of NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13-related diseases remains unclear. We report 10 additional affected individuals from nine independent families, identifying four missense variants (including recurrent c.170G > A) and three ultra-rare or novel predicted loss-of-function biallelic variants. Updated clinical-radiological data from previously reported families and a literature review compiling clinical features of all reported patients with isolated complex I deficiency caused by 43 genes encoding complex I subunits and assembly factors are also provided. Our cohort (mean age 7.8 ± 5.4 years; range 2.5-18) predominantly presented a moderate-to-severe neurodevelopmental syndrome with oculomotor abnormalities (84%), spasticity/hypertonia (83%), hypotonia (69%), cerebellar ataxia (66%), movement disorders (58%) and epilepsy (46%). Neuroimaging revealed bilateral symmetric T2 hyperintense substantia nigra lesions (91.6%) and optic nerve atrophy (66.6%). Protein modeling suggests missense variants destabilize a critical junction between the hydrophilic and membrane arms of complex I. Fibroblasts from two patients showed reduced complex I activity and compensatory complex IV activity increase. This study characterizes NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13-related disease in 13 individuals, highlighting genotype-phenotype correlations.
| S-EPMC11832047 | biostudies-literature
Project description:Background:The aim of the study was to determine a survival prognostic value of selected blood morphological rates of patients, operated on due to non-small cell lung cancer (NSCLC). Methods:The study was conducted on 532 patients, surgically treated due to NSCLC, in stages IA-IIIA, 174 females and 358 males, mean age 63.6 years (36-84 years) were included in the study. Blood parameters and clinical factors were included in statistical analysis, in order to determine potential prognostic values of red blood cell distribution width-standard deviation (RDW-SD), mean corpuscular volume (MCV) of red cell and hemoglobin. Factors contained: age, sex, smoking history, histopathological diagnosis, T category, N category, age-adjusted Charlson Comorbidity Index (CCI), number of lymphocytes, neutrophils, monocytes, platelets, the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR), kind of surgery, patient survival. Results:The univariate analysis revealed a dependence of the value of RDW-SD and CCI values, the number of monocytes, NLR and PLR values, neoplasia stage and the overall survival. The multivariate analysis confirmed that not only N2 category and the value of CCI above 4 are negative prognostication factors, but also RDW-SD above 43 fL (P=0.00007) and PLR above 138 (P=0.001) are such negative factors of survival prognosis. Conclusions:RDW-SD is an independent and significant prognostic factor of patients' survival operated on due to NSCLC.
| S-EPMC7138985 | biostudies-literature
Project description:Controlling residential lead hazards is critical for case management of lead poisoned children. To attain this goal, permanent relocation of the family is sometimes necessary or advisable for many reasons, including poor housing conditions; extensive lead hazards; lack of abatement resources, landlord compliance and local enforcement capacity; and family eviction. During 1996-1998, the Kennedy Krieger Institute implemented a unique capitated program for case management of Baltimore City children with blood lead concentrations (PbB) >19 microg/dL. The Program provided financial, housing, and social work assistance to facilitate relocation as a means of providing safer housing. Nearly half of the Program families relocated with direct assistance, and 28% relocated on their own. The Program evaluation examined the costs and benefits of relocation. Average relocation cost per child was relatively inexpensive (<1,500 dollars). Average relocation time of 5 months (range <2 months to >12 months) was less than the 8-month average time to complete lead hazard control work in 14 city and state programs funded by U.S. HUD. Relocation was associated with (1) a statistically significant decrease in dust lead loadings on floors, windowsills and window troughs that persisted for one year, and (2) statistically significantly greater decreases in children's PbB compared to children who did not relocate from untreated homes. Children relocated to housing that met current Federal residential dust lead standards had statistically significant decreases in blood lead levels. Visual inspection did not consistently identify relocation houses with dust lead levels below current Federal standards, indicating that dust testing should be an essential component of future programs. This will require additional resources for dust testing and possibly cleaning and repairs but is expected to yield additional benefits for children. The findings support recent U.S. CDC case management recommendations suggesting that permanent relocation to safer housing is a viable means to reduce children's lead exposure. The benefits of relocation notwithstanding, 40% of families moved at least twice. Research is needed to better understand how to expedite relocation and encourage families to remain in safe housing. Relocation does not negate owners' and health authorities' responsibilities to address lead hazards in the child's original house in order to protect future occupants.
| S-EPMC2258327 | biostudies-other
Project description:Smoking and lead (Pb) exposure increased oxidative stress in human body, and people with some gene variants may be susceptible to Pb and smoking via oxidative stress. The aim of this study is to evaluate oxidative stress by measuring thiobarbituric acid reactive substances (TBARS) and the relationship of lipid peroxidation markers in Pb workers with different gene polymorphisms (rs4673 and rs1050450) in both smokers and nonsmokers. Blood samples were collected from 267 Pb workers who received their annual health examination in the Kaohsiung Medical University Hospital. Glutathione peroxidase 1 (GPx-1) rs1050450 and cytochrome B-245 Alpha Chain (CYBA) rs4673 single-nucleotide polymorphisms (SNP) were analyzed by specific primer-probes using Real-Time PCR methods. The interaction between blood Pb and smoking increased serum levels of TBARS and the ratio of oxidative low-density lipoprotein and low-density lipoprotein (oxLDL/LDL). Analysis of workers with rs1050450 SNPs showed higher blood Pb levels in the workers with CC genotype than those with CT genotype. Smokers had significantly higher blood Pb, alanine transaminase (ALT), TBARS, and OxLDL levels than nonsmokers. TBARS increased 0.009 nmol/mL when blood Pb increased one µg/dL in smokers compared to nonsmokers. The ratio of OxLDL/LDL increased 0.223 when blood Pb increased one µg/dL in smokers compared to nonsmokers. TBARS levels and the ratio of OxLDL/LDL were positively correlated and interacted between blood Pb and smoking after the adjustment of confounders, suggesting that smoking cessation is an important issue in the Pb-exposed working environment.
| S-EPMC8393757 | biostudies-literature
Project description:BackgroundAs protein interactions mediate most cellular mechanisms, protein-protein interaction networks are essential in the study of cellular processes. Consequently, several large-scale interactome mapping projects have been undertaken, and protein-protein interactions are being distilled into databases through literature curation; yet protein-protein interaction data are still far from comprehensive, even in the model organism Saccharomyces cerevisiae. Estimating the interactome size is important for evaluating the completeness of current datasets, in order to measure the remaining efforts that are required.ResultsWe examined the yeast interactome from a new perspective, by taking into account how thoroughly proteins have been studied. We discovered that the set of literature-curated protein-protein interactions is qualitatively different when restricted to proteins that have received extensive attention from the scientific community. In particular, these interactions are less often supported by yeast two-hybrid, and more often by more complex experiments such as biochemical activity assays. Our analysis showed that high-throughput and literature-curated interactome datasets are more correlated than commonly assumed, but that this bias can be corrected for by focusing on well-studied proteins. We thus propose a simple and reliable method to estimate the size of an interactome, combining literature-curated data involving well-studied proteins with high-throughput data. It yields an estimate of at least 37, 600 direct physical protein-protein interactions in S. cerevisiae.ConclusionsOur method leads to higher and more accurate estimates of the interactome size, as it accounts for interactions that are genuine yet difficult to detect with commonly-used experimental assays. This shows that we are even further from completing the yeast interactome map than previously expected.
| S-EPMC3023808 | biostudies-literature
Project description:Biallelic mutations in the DCPS gene that disrupt the decapping activity of the DcpS scavenger decapping enzyme lead to neurodevelopmental deficiencies and intellectual disability. However, how the neurogenesis defects arise in these individuals remains unknown. Here we show that cells derived from DCPS mutant individuals have a metabolic deficiency in their creatine biosynthetic pathway. The cells possess reduced levels of creatine and a corresponding elevation of the creatine precursor, guanidinoacetate (GAA), due to reduced levels of guanidinoacetate methyltransferase mRNA and protein. Importantly, the compromised neurogenesis as well as neurite outgrowth observed in DcpS mutant induced pluripotent stem cell differentiation into neurons was reversed upon supplementation of creatine monohydrate into the culture medium. These findings suggest creatine deficiency as the underlying etiology of the neurogenetic defect in DcpS mutant cells and a potential driver of the neurological deficienciesin affected individuals.
2025-05-30 | GSE274722 | GEO
Project description:AudienceThis video lecture is appropriate for emergency medical providers who are not comfortable with initial assessment of poisoned patients. Ideal learners include medical students and residents.IntroductionPoisoning is the leading cause of injury-related mortality in the United States, with more than 40,000 deaths annually.1 Of all ED injury-related visits, 2.4% are related to poisoning.2 While providers may have access to support services (poison control center, medical toxicology consulting service), they are often responsible for the initial evaluation of poisoned patients. While a large portion of poisoned patients have good outcomes regardless of the care they receive, inappropriate risk assessment and lack of knowledge about basic interventions can put patients at risk. A standardized approach as outlined in the video will help evaluate and treat the vast majority of poisoned patients.Educational objectivesBy the end of the lecture, learners should be able to: 1) initiate the evaluation of a poisoned patient, 2) identify key interventions to support airway, breathing, and circulation, 3) identify the three components of risk assessment in the poisoned patient, 4) list the four options for gastric decontamination, and 5) select standard diagnostic labs and tests commonly used in evaluating poisoned patients.Educational methodsThis is an enhanced live action greenscreen recording with video animation.Research methodsThis video has been made available for a variety of learners on social medial (Facebook and YouTube) and written feedback has been collected on YouTube.ResultsThe video has been seen over three thousand times and has received positive comments on social media (Facebook, YouTube). Comments include "dropping some tox knowledge bombs, proving yet again that #ToxRocks," and "This is an excellent talk, thank you very much, but I think it would be worth mentioning antidotes."DiscussionThe goal is to expose learners to basic concepts in approaching poisoned patients and focusses on cognitive knowledge and diagnostic frameworks. The learner may watch the on-demand video as part of a flipped classroom experience with clinical cases, or as a just-in-time resource before seeing a patient who has been poisoned.TopicsPoisoning, resuscitation, risk assessment, gastric decontamination, occult ingestion, supportive care.
| S-EPMC10334441 | biostudies-literature
Project description: Not available
| S-EPMC9968906 | biostudies-literature