Association of heavy metals exposure with lower blood pressure in the population aged 8-17 years: a cross-sectional study based on NHANES.

Background: The existing evidence regarding the joint effect of heavy metals on blood pressure (BP) in children and adolescents is insufficient. Furthermore, the impact of factors such as body weight, fish consumption, and age on their association remains unclear. Methods: The study utilized original data from the National Health and Nutrition Examination Survey, encompassing 2,224 children and adolescents with complete information on 12 urinary metals (barium, cadmium, cobalt, cesium, molybdenum, lead, antimony, thallium, tungsten, uranium, mercury and arsenic), BP, and core covariates. Various statistical methods, including weighted multiple logistic regression, linear regression, and Weighted Quantile Sum regression (WQS), were employed to evaluate the impact of mixed metal exposure on BP. Sensitivity analysis was conducted to confirm the primary analytical findings. Results: The findings revealed that children and adolescents with low-level exposure to lead (0.40 µg/L, 95%CI: 0.37, 0.42), mercury (0.38 µg/L, 95%CI: 0.35, 0.42) and molybdenum (73.66 µg/L, 95%CI: 70.65, 76.66) exhibited reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP). Conversely, barium (2.39 µg/L, 95%CI: 2.25, 2.54) showed a positive association with increased SBP. A 25th percentile increase in the WQS index is significantly associated with a decrease in SBP of 0.67 mmHg (95%CI, -1.24, -0.10) and a decrease in DBP of 0.59 mmHg (95% CI, -1.06, -0.12), which remains statistically significant even after adjusting for weight. Furthermore, among individuals who consume fish, heavy metals have a more significant influence on SBP. A 25 percentile increase in the WQS index is significantly associated with a decrease of 3.30 mmHg (95% CI, -4.73, -1.87) in SBP, primarily attributed to mercury (27.61%), cadmium (27.49%), cesium (17.98%), thallium (8.49%). The study also identified a declining trend in SBP among children aged 10-17, whereas children aged 11-18 exhibited lower levels of systolic and diastolic blood pressure, along with a reduced risk of hypertension. Conclusion: Some heavy metals demonstrate an inverse association with the BP of children and adolescents, particularly notable in groups with fish consumption and older children and adolescents. Future studies are warranted to validate these findings and delve deeper into the interplay of heavy metals.

A nomogram to predict 28-day mortality in neonates with sepsis: a retrospective study based on the MIMIC-III database.

Background: Sepsis is the second-leading cause of death in neonates. We established a predictive nomogram to identify critically ill neonates early and reduce the time to treatment. Methods: It is a retrospective case-control study based on the MIMIC-III database. The study population comprised 924 neonates diagnosed with sepsis. Results: Neonates with sepsis included in the MIMIC-III database were enrolled, including 880 surviving neonates and 44 neonates who died. In the derivation dataset, stepwise regression and the Lasso algorithm were employed to select predictive variables, and the neonatal sequential organ failure assessment score (nSOFA) was calculated simultaneously. Bootstrap resampling was utilized to perform internal validation. The results indicated that the Lasso algorithm displayed superior discrimination, sensitivity, and specificity relative to stepwise regression and nSOFA scores. After 500 bootstrap resampling tests, the area under the receiver operating characteristic curve (AUC) of the Lasso algorithm was 0.912 (95% CI: 0.870-0.977). The nomogram based on the Lasso algorithm outperformed stepwise regression and nSOFA scores in terms of calibration and the clinical net benefit. This nomogram can assist in prognosticating neonatal severe sepsis and aid in guiding clinical practice while concurrently improving patient outcomes. Conclusions: The established nomogram revealed that jaundice, corticosteroid use, weight, serum calcium, inotropes and base excess are all important predictors of 28-day mortality in neonates with sepsis. This nomogram can facilitate the early identification of neonates with severe sepsis. However, it still requires further modification and external validation to make it widely available.

Novel compound heterozygous CCDC40 mutations in a familial case of primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by motile ciliary dysfunction and impaired ultrastructure. Despite numerous studies, the genetic basis for about 30% of PCD cases remains to be elucidated. Here, we present the identification and functional analysis of two novel mutations in the gene encoding coiled-coil domain-containing protein 40 (CCDC40), which are found in a familial case of PCD. These novel CCDC40 mutations, NM_017950.4: c.2236-2delA and c.2042_2046delTCACA, NP_060420.2: p.(Ile681fs), were identified by whole-exome sequencing (WES). Sanger sequencing was then performed to confirm the WES results and determine the CCDC40 gene sequences of the proband's parents. The c.2042_2046delTCACA mutation disrupts the reading frame of the protein and is therefore predicted to produce a non-functional protein. Using a minigene assay with the pcDNA3.1(+) plasmid, we further investigated the potential pathogenic effects of the c.2236-2delA mutation and found that this mutation leads to formation of a truncated protein via splicing disruption. Thus, in summary, we identified two mutations of the CCDC40 gene that can be considered pathogenic compound heterozygous mutations in a case of familial PCD, thereby expanding the known mutational spectrum of the CCDC40 gene in this disease.