Citations

Abstract Although structures of vitrified supramolecular complexes have been determined at near-atomic resolution, elucidating in situ molecular structure in living cells remains a major challenge. Here, we apply a novel but simple liquid-cell technique, developed previously for real-time imaging of the dynamics at a liquid-gas interface, to image wet biological samples. With extra scattering from the liquid phase, the transmission electron micrographs show amplitude contrast comparable to that in negatively stained samples. Single-molecule domains are resolved in the protein complex GroEL imaged in buffer solution at room temperature. Moreover, various stages of virus cell entry, which are transient events with very few structural information to date, are also captured. Morphological details are reconstructed using the technique of individual particle electron tomography. These results demonstrate that this approach can be a valuable yet cost-effective technique complementary to other microscopy techniques for addressing important biological questions at the molecular level.

Objective: Sleep fragmentation determined by repetitive arousals from sleep in obstructive sleep apnea (OSA) is associated with hypertension. We aimed to quantify the independent association of arousals during rapid eye movement (REM)/non-rapid eye movement (NREM) sleep with prevalent hypertension. Methods: We included adults with 4 h of total sleep time and at least 30 min of REM sleep obtained from overnight in-laboratory polysomnography. Logistic regression models were fitted to explore the association between arousals during REM/NREM sleep and prevalent hypertension. All models controlled for OSA metrics and arousals during NREM/REM sleep, either by statistical adjustment or by stratification. Results: The sample comprised of 11 643 patients, of which 10 055 were OSA patients. Fully adjusted models demonstrated significant dose-relationships between arousal index during REM sleep (AI-REM) and prevalent hypertension (P trend = 0.002). The higher relative odds of prevalent hypertension were most evident with AI-REM > 40 events/h. In OSA patients with arousal index during NREM sleep (AI-NREM) <15 events/h, every10-unit increase in the AI-REM was associated with 18% higher odds of hypertension (odds ratio, 1.18; 95% confidence interval, 1.11–1.27) in OSA. On the contrary, AI-NREM was not a significant predictor of hypertension in any of the models. Conclusions: Our findings indicate that arousals during REM sleep are associated with prevalent hypertension. This is clinically relevant because treatment of OSA is often limited to the first half of the sleep period leaving most of sleep fragmentation during REM sleep untreated.

AbstractThere is a lack of understanding in the performance of flexible noise control (FNC) processing, which is used in digital radiography on a scanner vendor and has four parameters each involving multiple options. The aim of this study was to investigate the impact of FNC on portable chest imaging. An anthropomorphic chest phantom was imaged using a clinical chest program with 85 kV and five radiation dose levels at 40″ source‐to‐image distance with software‐based scatter reduction method. All images were processed without and with FNC. Noise analysis was performed in two regions of interest (ROI) on subtracted noise‐only images, and line profiles were generated through a lung‐rib interface. In addition, noise power spectra (NPS) analysis was performed in solid water phantoms of 10 and 20 cm thicknesses, using the same acquisition program and a range of dose levels. Last, feedback on retrospectively deidentified, reprocessed, and randomized clinical images from 20 portable chest exams was gathered from two thoracic radiologists. Noise reduction performances of FNC were demonstrated, with the level depending on specific FNC parameters, dose levels, ROI placement, and phantom sizes. Higher frequency textural patterns were revealed through the NPS analysis, which varied based on FNC parameters, dose levels, and phantom sizes. Overall, the vendor default parameter FGA0.5 yielded the highest noise reduction and textural artifacts. Radiologist feedback showed consistent preference of no FNC due to the presence of textural artifacts in the FNC‐processed images. An algorithm improvement to avoid introducing artifacts would be desired.

TREM2 is exclusively expressed by microglia in the brain and is strongly linked to the risk for Alzheimer’s disease (AD). As microglial responses modulated by TREM2 are central to AD pathogenesis, enhancing TREM2 signaling has been explored as an AD therapeutic strategy. However, the effective therapeutic window targeting TREM2 is unclear. Here, by using microglia-specific inducible mouse models overexpressing human wild-type TREM2 (TREM2-WT) or R47H risk variant (TREM2-R47H), we show that TREM2-WT expression reduces amyloid deposition and neuritic dystrophy only during the early amyloid seeding stage, whereas TREM2-R47H exacerbates amyloid burden during the middle amyloid rapid growth stage. Single-cell RNA sequencing reveals suppressed disease-associated microglia (DAM) signature and reduced DAM population upon TREM2-WT expression in the early stage, whereas upregulated antigen presentation pathway is detected with TREM2-R47H expression in the middle stage. Together, our findings highlight the dynamic effects of TREM2 in modulating AD pathogenesis and emphasize the beneficial effect of enhancing TREM2 function in the early stage of AD development.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally in tandem with the growing obesity epidemic. However, there is a lack of data on the relationship between historical weight changes 10 years ago and at present on NAFLD prevalence at the population level. Therefore, we sought to evaluate the relationship between weight classes and the prevalence of NAFLD. Methods: Data were used from the United States National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Univariate and multivariate general linear model analyses were used to obtain risk ratio (RR) estimations of NAFLD events. Results: In total, 34,486 individuals were analysed, with those who were lean at both time points as the control group. Overweight (RR: 14.73, 95%CI: 11.94 to 18.18, p < 0.01) or obese (RR: 31.51, 95%CI: 25.30 to 39.25, p < 0.01) individuals at both timepoints were more likely to develop NAFLD. Residual risk exists where previously obese individuals became overweight (RR: 14.72, 95%CI: 12.36 to 17.52, p < 0.01) or lean (RR: 2.46, 95%CI: 1.40 to 4.31, p = 0.02), and previously overweight individuals who became lean (RR 2.24, 95%CI 1.42 to 3.54, p = 0.01) had persistent elevated risk of developing NAFLD despite weight regression. Sensitivity analysis identified that a higher proportion of individuals with regression in weight class were diabetics and Mexican Americans, while fewer African Americans saw weight-class regression. Conclusions: Residual risk exists in patients who lost weight despite the smaller magnitude of effect, and targeted weight reductions should still be used to mitigate the risk of NAFLD at the population level.

Background The Woven EndoBridge (WEB) device is a novel intrasaccular flow disruptor tailored for bifurcation aneurysms. We aim to describe the degree of aneurysm occlusion at the latest follow-up, and the rate of complications of aneurysms treated with the WEB device stratified according to rupture status. Methods Our data were taken from the WorldWideWeb Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups: ruptured and unruptured. We compared clinical and radiologic outcomes of both groups. Propensity score matching (PSM) was done to match according to age, gender, bifurcation, location, prior treatment, neck, height, dome width, daughter sac, incorporated branch, pretreatment antiplatelets, and last imaging follow-up. Results The study included 676 patients with 691 intracranial aneurysms (529 unruptured and 162 ruptured) treated with the WEB device. The PSM analysis had 55 pairs. In both the unmatched (85.8% vs 84.3%, p=0.692) and matched (94.4% vs 83.3%, p=0.066) cohorts there was no significant difference in the adequate occlusion rate at the last follow-up. Likewise, there were no significant differences in both ischemic and hemorrhagic complications between the two groups. There was no documented aneurysm rebleeding after WEB device implantation. Conclusion There was no significant difference in both the radiologic outcomes and complications between unruptured and ruptured aneurysms. Our findings support the feasibility of treatment of ruptured aneurysms with the WEB device.