No abstract

Enrichment of rare circulating tumor cells (CTCs) in blood is typically achieved using antibodies to epithelial cell adhesion molecule (EpCAM), with detection using cytokeratin (CK) antibodies. However, EpCAM and CK are not expressed in some tumors and can be downregulated during epithelial-to-mesenchymal transition. A micro-fluidic system, not limited to EpCAM or CK, was developed to use multiple antibodies for capture followed by detection using CEE-Enhanced (CE), a novel in situ staining method that fluorescently labels the capture antibodies bound to CTCs. Higher recovery of CTCs was demonstrated using antibody mixtures compared to anti-EpCAM. In addition, CK-positive breast cancer cells were found in 15 of 24 samples (63%; range 1–60 CTCs), while all samples contained additional CE-positive cells (range 1–41; median = 11; P = .02). Thus, antibody mixtures against a range of cell surface antigens enables capture of more CTCs than anti-EpCAM alone and CE staining enables the detection of CK-negative CTCs.

NeuroKit2 is an open-source, community-driven, and user-friendly Python package dedicated to neurophysiological signal processing with an initial focus on bodily signals (e.g., ECG, EDA, EMG, EOG, PPG etc.). Its design philosophy is centred on user-experience and accessibility to both novice and advanced users. The package provides a consistent set of high-level functions that enable data processing in a few lines of code using validated pipelines, which we illustrate in two examples covering the most typical scenarios, such as an event-related paradigm and an interval-related analysis. The package also includes tools dedicated to specific processing steps such as rate extraction and filtering methods, offering a trade-off between efficiency and fine-tuned control to the user.Rather than focusing on specific signals, NeuroKit2 was developed to provide a comprehensive means for a simultaneous processing of a wide range of signals. Its goal is to improve transparency and reproducibility in neurophysiological research, as well as foster exploration and innovation.

More than half of older trauma patients in this study had sarcopenia, osteopenia, or both. Each factor was independently associated with increased 1-year mortality. Given the prevalent use of abdominopelvic CT in trauma centers, opportunistic screening for radiologic indicators of frailty provides an additional tool for early identification of older trauma patients at high risk for poor outcomes, with the potential for targeted interventions.

Metastasis is a complex, multistep process that begins with the epithelial-mesenchymal transition (EMT). Circulating tumor cells (CTCs) are believed to have undergone EMT and thus lack or express low levels of epithelial markers commonly used for enrichment and/or detection of such cells. However, most current CTC detection methods only target EpCAM and/or cytokeratin to enrich epithelial CTCs, resulting in failure to recognize other, perhaps more important, CTC phenotypes that lack expression of these markers. Here, we describe a population of complex aneuploid CTCs that do not express cytokeratin or CD45 antigen in patients with breast, ovarian, or colorectal cancers. These cells were not observed in healthy subjects. We show that the primary epithelial tumors were characterized by similar complex aneuploidy, indicating conversion to an EMT phenotype in the captured cells. Collectively, our study provides a new method for highly efficient capture of previously unrecognized populations of CTCs. Significance Current assays for CTC capture likely miss populations of cells that have undergone EMT. Capture and study of CTCs that have undergone EMT would allow a better understanding of the mechanisms driving metastasis.

High-fat diet and certain dietary patterns are associated with higher incidence of sporadic Alzheimer's disease (AD) and cognitive decline. However, no specific therapy has been suggested to ameliorate the negative effects of high fat/high cholesterol levels on cognition and amyloid pathology. Here we show that in 9-month-old APP23 mice, a high-fat/high-cholesterol (HF) diet provided for 4 months exacerbates the AD phenotype evaluated by behavioral, morphological, and biochemical assays. To examine the therapeutic potential of liver X receptor (LXR) ligands, APP23 mice were fed HF diet supplemented with synthetic LXR agonist T0901317 (T0). Our results demonstrate that LXR ligand treatment causes a significant reduction of memory deficits observed during both acquisition and retention phases of the Morris water maze. Moreover, the effects of T0 on cognition correlate with AD-like morphological and biochemical parameters. We found a significant decrease in amyloid plaque load, insoluble A␤ and soluble A␤ oligomers. In vitro experiments with primary glia demonstrate that Abca1 is essential for the proper lipidation of ApoE and mediates the effects of T0 on A␤ degradation by microglia. Microdialysis experiments performed on awake freely moving mice showed that T0 decreased A␤ levels in the interstitial fluid of the hippocampus, supporting the conclusion that this treatment increases A␤ clearance. The data presented conclusively shows that LXR activation in the context of a metabolic challenge has critical effects on AD phenotype progression by attenuating A␤ deposition and facilitating its clearance.

a b s t r a c tThe novel coronavirus, SARS-CO V2 responsible for COVID-19 pandemic is rapidly escalating across the globe. Burn centers gearing for the pandemic must strike a balance between contributing to the pandemic response and preserving ongoing burn care in a safe and ethical fashion. The authors of the present communication represent seven burn centers from China, Singapore, Japan, Italy, Spain, the United Kingdom (UK), and the United States (US).Each center is located at a different point along the pandemic curve and serves different patient populations within their healthcare systems. We review our experience with the virus to date, our strategic approach to burn center function under these circumstances, and lessons learned. The purpose of this communication is to share experiences that will assist with continued preparations to help burn centers advocate for optimum burn care and overcome challenges as this pandemic continues.

Improvements in outcomes for older adults sustaining burn injuries have lagged far behind those of younger patients. As this segment of the population grows, there has been an increasing interest in better understanding the epidemiology and outcomes of injury in older adults. The National Burn Repository (NBR) provides a unique opportunity to examine burn injuries on a national level. We aimed to characterize specific injury and outcome trends in older adult with burns through analysis of the NBR. We examined the records of all patients in the NBR aged 55 and older. To characterize age effects on injury and outcomes, patients were stratified into three age categories: 55 to 64 years, 65 to 74 years, and 75 years and older. Baseline characteristics, details of hospital treatment, mortality, and disposition were compared among these three age groups using χ 2 or analysis of variance. Logistic regression analysis was performed to assess the impact of age on burn mortality. A total of 180,401 patient records were available from 1991 to 2005, of which 23,180 (14%) met age inclusion criteria. Mean burn size (9.6% TBSA) and percent with inhalation injury (11.3%) did not markedly differ by age. Men predominated overall (ratio 1.4:1), although women (4290) outnumbered men (3439) in the oldest age category. Length of stay per TBSA and median hospital charges increased with increasing age category, suggesting higher resource consumption with aging. Mean number of operations per patient, however, decreased with age. Mortality rates and discharge to nonindependent status increased with age. By logistic regression, the adjusted odds ratio for mortality was 2.3 (95% CI 2.1-2.7) in the 65 to 74 age group, and 5.4 (95% CI 4.8-6.1) in the oldest group when compared with the 55 to 64 age group. Mortality rates decreased significantly after 2001 across all age groups. This analysis demonstrates age-dependent differences in resource utilization and mortality risk within the older burn population and highlights the need for a national research agenda focused on management practices and outcomes in older adult with burns.