Large-scale recording of neuronal activity in freely-moving mice at cellular resolution.

Current methods for recording large-scale neuronal activity from behaving mice at single-cell resolution require either fixing the mouse head under a microscope or attachment of a recording device to the animal's skull. Both of these options significantly affect the animal behavior and hence also the recorded brain activity patterns. Here, we introduce a different method to acquire snapshots of single-cell cortical activity maps from freely-moving mice using a calcium sensor called CaMPARI. CaMPARI has a unique property of irreversibly changing its color from green to red inside active neurons when illuminated with 400 nm light. We capitalize on this property to demonstrate cortex-wide activity recording without any head fixation, tethering, or attachment of a miniaturized device to the mouse's head. Multiple cortical regions were recorded while the mouse was performing a battery of behavioral and cognitive tests. We identified task-dependent activity patterns across motor and somatosensory cortices, with significant differences across sub-regions of the motor cortex and correlations across several activity patterns and task parameters. This CaMPARI-based recording method expands the capabilities of recording neuronal activity from freely-moving and behaving mice under minimally-restrictive experimental conditions and provides large-scale volumetric data that are currently not accessible otherwise.

Risk of pancreatic cancer in individuals with celiac disease in the United States: A population-based matched cohort study.

BACKGROUND: Celiac disease (CD) has been associated with gastrointestinal malignancies. However, the magnitude of the risk of pancreatic cancer (PC) associated with CD is much less clear, and risks have not been estimated from large populations. AIM: To assess the risk of PC in CD patients. METHODS: We conducted a population-based, multicenter, propensity score-matched cohort study with consecutive patients diagnosed with CD using the TriNeTx research network platform. We examined the incidence of PC in patients with CD compared with a matched cohort of patients without CD (non-CD, controls). Each patient in the main group (CD) was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects. The incidence of PC was estimated using a Cox proportional hazards model with a hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 389980 patients were included in this study. Among them, 155877 patients had a diagnosis of CD, and the remaining 234103 individuals without CD were considered a control cohort. The mean duration of follow-up for patients in the CD and control cohorts was 5.8 ± 1.8 and 5.9 ± 1.1 years, respectively. During the follow-up, 309 patients with CD developed PC, whereas 240 patients developed PC in the control group (HR = 1.29; 95%CI: 1.09-1.53). In the secondary analyses in the first year after diagnosis of CD, patients with CD were at a significant increase in risk for PC; 151 patients with CD had an incidence of PC compared with 96 incidences of PC among the patients in the non-CD control group (HR = 1.56; 95%CI: 1.20-2.01) and sensitivity analysis showed similar magnitude to the one generated in the primary and secondary analysis. CONCLUSION: Patients with CD are at increased risk of PC. Risk elevation persists beyond the first year after diagnosis to reference individuals without CD from the general population.

Indistinct retinal outer layers in the walls of the idiopathic full-thickness macular hole - A potential predictive biomarker for surgical outcomes.

Purpose: To evaluate the absence of external limiting membrane (ELM) and ellipsoid zone (indistinct retinal outer layers, I-ROL) in the walls of idiopathic full-thickness macular holes (FTMHs) circumferentially on optical coherence tomography (OCT) and its correlation with surgical outcome. Methods: In this retrospective observational study, OCT images of patients undergoing vitrectomy for FTMHs with at least 3-months of postoperative follow-up were analyzed for preoperative circumferential extent of I-ROL. Derived macular hole indices such as hole form factor (HFF), macular hole index (MHI), tractional hole index (THI), and hole diameter ratio (HDR) were also calculated. The circumferential extent of I-ROL was correlated with derived hole indices as well as anatomical closure, foveal architecture, and restoration of ELM following surgery. Results: All nine eyes (eight patients) with FTMH (mean size: 610.11 ± 122.95 microns) in the study showed I-ROL in ≥1 quadrant. The mean HFF, MHI, THI, and HDR values were 0.72 ± 0.09, 0.35 ± 0.05, 0.71 ± 0.24, and 0.53 ± 0.14, respectively. All eyes achieved type-1 hole closure with improvement in best-corrected visual acuity to 0.58 ± 0.32 LogMAR from 0.81 ± 0.26 LogMAR. Regular foveal architecture was achieved in six eyes. Out of these, five eyes had I-ROL in ≥2 quadrants, and one eye had I-ROL in <2 quadrants (P = 0.0476). Restoration of ELM was seen in aforementioned six eyes (complete = 5, partial = 1). Out of the five eyes with complete ELM restoration, four had a circumferential extent of I-ROL in ≥2 quadrants (P = 0.0476). Complete restoration of ELM was associated with the complete restoration of the ellipsoid zone in three eyes. Conclusion: Preoperative circumferential extent of I-ROL in FTMH walls can be a potential predictive OCT marker for the type of closure, postoperative foveal architecture, and ELM restoration.