Mediterranean Diet and White Matter Hyperintensity Change over Time in Cognitively Intact Adults

Current evidence on the impact of Mediterranean diet (MeDi) on white matter hyperintensity (WMH) trajectory is scarce. This study aims to examine whether greater adherence to MeDi is associated with less accumulation of WMH. This population-based longitudinal study included 183 cognitively intact adults aged 20–80 years. The MeDi score was obtained from a self-reported food frequency questionnaire; WMH was assessed by 3T MRI. Multivariable linear regression was used to estimate the effect of MeDi on WMH change. Covariates included socio-demographic factors and brain markers. Moderation effects by age, gender, and race/ethnicity were examined, followed by stratification analyses. Among all participants, WMH increased from baseline to follow-up (mean difference [follow-up-baseline] [standard deviation] = 0.31 [0.48], p < 0.001). MeDi adherence was negatively associated with the increase in WMH (β = −0.014, 95% CI = −0.026–−0.001, p = 0.034), adjusting for all covariates. The association between MeDi and WMH change was moderated by age (young group = reference, p-interaction[middle-aged × MeDi] = 0.075, p-interaction[older × MeDi] = 0.037). The association between MeDi and WMH change was observed among the young group (β = −0.035, 95% CI = −0.058–−0.013, p = 0.003), but not among other age groups. Moderation effects by gender and race/ethnicity did not reach significance. Greater adherence to MeDi was associated with a lesser increase in WMH over time. Following a healthy diet, especially at younger age, may help to maintain a healthy brain.     

Educational attainment polygenic scores,socioeconomic factors,and cortical structure in children and adolescents

Genome‐wide polygenic scores for educational attainment (PGS‐EA) and socioeconomic factors, which are correlated with each other, have been consistently associated with academic achievement and general cognitive ability in children and adolescents. Yet, the independent associations of PGS‐EA and socioeconomic factors with specific underlying factors at the neural and neurocognitive levels are not well understood. The main goals of this study were to examine the unique contributions of PGS‐EA and parental education to cortical structure and neurocognitive skills in children and adolescents, and the associations among PGS‐EA, cortical structure, and neurocognitive skills. Participants were typically developing 3‐ to 21‐year‐olds (53% male; N = 391). High‐resolution, T1‐weighted magnetic resonance imaging data were acquired, and cortical thickness (CT) and surface area (SA) were measured. PGS‐EA were computed based on the EA3 genome‐wide association study of educational attainment. Participants completed executive function, vocabulary, and episodic memory tasks. Higher PGS‐EA and parental education were independently and significantly associated with greater total SA and vocabulary. Higher PGS‐EA was significantly associated with greater SA in the left medial orbitofrontal gyrus and inferior frontal gyrus, which was associated with higher executive function. Higher parental education was significantly associated with greater SA in the left parahippocampal gyrus after accounting for PGS‐EA and total brain volume. These findings suggest that education‐linked genetics may influence SA in frontal regions, leading to variability in executive function. Associations of parental education with cortical structure in children and adolescents remained significant after controlling for PGS‐EA, a source of genetic confounding.     

Isolated breast parenchymal changes following COVID-19 vaccine booster

Ipsilateral transient axillary lymphadenopathy is well-documented following COVID-19 mRNA vaccine administration. Recently, rare mammographic findings of breast tissue changes with co-existing lymphadenopathy have been documented. Current literature on isolated ipsilateral true breast parenchymal changes on diagnostic mammography in symptomatic patients following COVID-19 mRNA vaccine administration is limited. This is one of the first case reports that demonstrates isolated ipsilateral focal asymmetry 5 days after administration of COVID-19 mRNA vaccine followed by complete resolution of symptoms and focal asymmetry confirmed on follow up magnetic resonance imaging. These findings warrant the development of guidelines to reduce unnecessary invasive procedures as part of the workup for possible malignancy.     

Highly sensitive and selective colorimetric detection of Pb(ii) ions using Michelia tonkinensis seed extract capped gold nanoparticles

In this study, gold nanoparticles (AuNPs) were synthesized via a green and environmentally-friendly approach and applied as a colorimetric probe for detecting Pb²⁺ ions in aqueous solution. Instead of toxic chemicals, Michelia tonkinensis (MT) seed extract was used for reducing Au³⁺ and stabilizing the formed AuNPs. The synthesis conditions, including temperature, reaction time, and Au³⁺ ion concentration, were optimized at 90 °C, 40 min, and 1.25 mM, respectively. The physicochemical properties of the produced MT-AuNPs were assessed by means of transmission electron microscopy, X-ray diffraction, field emission scanning electron microscopy, dynamic light scattering, and Fourier-transform infrared spectroscopy. The characterization results revealed that the MT-AuNPs exhibited a spherical shape with a size of about 15 nm capped by an organic layer. The colorimetric assay based on MT-AuNPs showed excellent sensitivity and selectivity toward Pb²⁺ ions with the limit of detection value of 0.03 μM and the limit of quantification of 0.09 μM in the linear range of 50–500 μM. The recoveries of inter-day and intra-day tests were 97.84–102.08% and 98.78–102.34%, respectively. The MT-AuNPs probe also demonstrated good and reproducible recoveries (98.71–101.01%) in analyzing Pb²⁺ in drinking water samples, indicating satisfactory practicability and operability of the proposed method.

Michelia tonkinensis seed extract capped AuNPs exhibit great potential in analyzing Pb²⁺ ions in aqueous solution.     

Small-molecule eRF3a degraders rescue CFTR nonsense mutations by promoting premature termination codon readthrough

The vast majority of people with cystic fibrosis (CF) are now eligible for CF transmembrane regulator (CFTR) modulator therapy. The remaining individuals with CF harbor premature termination codons (PTCs) or rare CFTR variants with limited treatment options. Although the clinical modulator response can be reliably predicted using primary airway epithelial cells, primary cells carrying rare CFTR variants are scarce. To overcome this obstacle, cell lines can be created by overexpression of mouse Bmi-1 and human TERT (hTERT). Using this approach, we developed 2 non-CF and 6 CF airway epithelial cell lines, 3 of which were homozygous for the W1282X PTC variant. The Bmi-1/hTERT cell lines recapitulated primary cell morphology and ion transport function. The 2 F508del-CFTR cell lines responded robustly to CFTR modulators, which was mirrored in the parent primary cells and in the cell donors’ clinical response. Cereblon E3 ligase modulators targeting eukaryotic release factor 3a (eRF3a) rescued W1282X-CFTR function to approximately 20% of WT levels and, when paired with G418, rescued G542X-CFTR function to approximately 50% of WT levels. Intriguingly, eRF3a degraders also diminished epithelial sodium channel (ENaC) function. These studies demonstrate that Bmi-1/hTERT cell lines faithfully mirrored primary cell responses to CFTR modulators and illustrate a therapeutic approach to rescue CFTR nonsense mutations.     

IL-1β–dependent extravasation of preexisting lung-restricted autoantibodies during lung transplantation activates complement and mediates primary graft dysfunction

Preexisting lung-restricted autoantibodies (LRAs) are associated with a higher incidence of primary graft dysfunction (PGD), although it remains unclear whether LRAs can drive its pathogenesis. In syngeneic murine left lung transplant recipients, preexisting LRAs worsened graft dysfunction, which was evident by impaired gas exchange, increased pulmonary edema, and activation of damage-associated pathways in lung epithelial cells. LRA-mediated injury was distinct from ischemia-reperfusion injury since deletion of donor nonclassical monocytes and host neutrophils could not prevent graft dysfunction in LRA-pretreated recipients. Whole LRA IgG molecules were necessary for lung injury, which was mediated by the classical and alternative complement pathways and reversed by complement inhibition. However, deletion of Fc receptors in donor macrophages or mannose-binding lectin in recipient mice failed to rescue lung function. LRA-mediated injury was localized to the transplanted lung and dependent on IL-1β–mediated permeabilization of pulmonary vascular endothelium, which allowed extravasation of antibodies. Genetic deletion or pharmacological inhibition of IL-1R in the donor lungs prevented LRA-induced graft injury. In humans, preexisting LRAs were an independent risk factor for severe PGD and could be treated with plasmapheresis and complement blockade. We conclude that preexisting LRAs can compound ischemia-reperfusion injury to worsen PGD for which complement inhibition may be effective.