A glial circadian gene expression atlas reveals cell type and disease-specific reprogramming in response to amyloid pathology or aging.

While circadian rhythm disruption may promote neurodegenerative disease, how aging and neurodegenerative pathology impact circadian gene expression patterns in different brain cell types is unknown. Here, we used translating ribosome affinity purification methods to define the circadian translatomes of astrocytes, microglia, and bulk cerebral cortex, in healthy mouse brain and in the settings of amyloid-beta plaque pathology or aging. Our data reveal that glial circadian translatomes are highly cell type-specific and exhibit profound, context-dependent reprogramming of rhythmic transcripts in response to amyloid pathology or aging. Transcripts involved in glial activation, immunometabolism, and proteostasis, as well as nearly half of all Alzheimer Disease (AD)-associated risk genes, displayed circadian oscillations, many of which were altered by pathology. Amyloid-related differential gene expression was also dependent on time of day. Thus, circadian rhythms in gene expression are cell- and context dependent and provide important insights into glial gene regulation in health, AD, and aging.

Care integration goes Beyond Co-Location: Creating a Medical Home.

How to successfully integrate mental health and primary care remains a critically important question given the continued morbidity and early mortality of people with serious mental illness. This study investigated integration in a community mental health center (MHC) primarily treating people with SMI in a large, urban northeastern city where an on-site primary care center (PCC) was opened resulting in co-located mental health and primary care services being provided. Using focus groups and online surveys this study asked participants about their thoughts and interactions with the on-site PCC. Participants included staff from clinical, non-clinical, and leadership roles in the mental health center (MHC; PCC staff; and MHC clients who did not use the on-site PCC). MHC staff also offered their thoughts about and experiences with the on-site PCC one year and two years after the on-site PCC opened through an on-line survey. In both methods, staff reported limited awareness and expectations of the PCC in the first year. Staff indicated that successful care integration goes beyond co-location and peer health navigation can enhance integration. Finally, staff discussed desires for enhancing care integration and co-located services into a medical home that included communicating across medical records and providers at different agencies. Our results suggest that, in addition to the previously researched three C's of care integration (consultation, coordination, and collaboration), two more C's were essential to successful care integration: co-location and communication. Communication across medical records and providers at different agencies was an essential component of care integration, and co-location added increased ability to communicate across providers.

At-home urine estrone-3-glucuronide quantification predicts oocyte retrieval outcomes comparably with serum estradiol.

Objective: To investigate the feasibility of monitoring urine estrone-3-glucuronide (E3G) with an at-home device during gonadotropin stimulation for in vitro fertilization and oocyte cryopreservation. Design: Prospective, observational cohort study. Setting: Private fertility clinic. Patients: Thirty patients undergoing stimulation with a gonadotropin-releasing hormone antagonist protocol for in vitro fertilization or oocyte cryopreservation. Interventions: Daily collection of the first urine in the morning during stimulation and analysis performed at home by each patient with the Mira Fertility Tracker. Main Outcome Measures: Primary outcomes were correlation of urine E3G and serum estradiol (E2) concentrations on the day of trigger to the number of total and metaphase 2 oocytes (MII). Secondary outcomes of interest were the correlation of matched E3G and E2 measurements and the daily trends of E3G and E2 during stimulation. Results: Both urine E3G and serum E2 concentrations on the day of trigger significantly correlated with retrieval outcomes to a similar extent, with E3G demonstrating slightly higher correlation to the number of MII oocytes than that demonstrated by E2 (r = 0.485 vs. 0.391, respectively). The Pearson correlation coefficient for matched E3G and E2 levels was 0.761. The correlation coefficients of determination for daily trends of E3G and E2 during stimulation were 0.7066 and 0.6102, respectively. Conclusions: Measured on the day of trigger, urine E3G monitoring during gonadotropin stimulation was comparable with serum E2 for predicting oocyte retrieval outcomes. Matched daily samples confirmed good correlation of urine E3G and serum E2. The option of at-home estrogen monitoring with devices such as Mira offers an alternative to traditional serum monitoring that may improve patient experience. Clinical Trial Registration Number: NCT05493202.

Geometric control of human stem cell morphology and differentiation.

During tissue morphogenesis, stem cells and progenitor cells migrate, proliferate, and differentiate, with striking changes in cell shape, size, and acting mechanical stresses. The local cellular function depends on the spatial distribution of cytokines as well as local mechanical microenvironments in which the cells reside. In this study, we controlled the organization of human adipose derived stem cells using micro-patterning technologies, to investigate the influence of multi-cellular form on spatial distribution of cellular function at an early stage of cell differentiation. The underlying role of cytoskeletal tension was probed through drug treatment. Our results show that the cultivation of stem cells on geometric patterns resulted in pattern- and position-specific cell morphology, proliferation and differentiation. The highest cell proliferation occurred in the regions with large, spreading cells (such as the outer edge of a ring and the short edges of rectangles). In contrast, stem cell differentiation co-localized with the regions containing small, elongated cells (such as the inner edge of a ring and the regions next to the short edges of rectangles). The application of drugs that inhibit the formation of actomyosin resulted in the lack of geometrically specific differentiation patterns. This study confirms the role of substrate geometry on stem cell differentiation, through associated physical forces, and provides a simple and controllable system for studying biophysical regulation of cell function.

Rotational stability of toric soft contact lenses during natural viewing conditions.

PURPOSE: To compare objectively the rotational stability of two differently designed toric soft contact lenses over a range of natural viewing conditions using a novel infrared, video-based technique. METHODS: Two contact lenses using different methods of stabilization were assessed: Accelerated Stabilization Design (ACUVUE ADVANCE for ASTIGMATISM) and Lo-Torque Design (B&L SofLens Toric). Four tasks involving saccades were performed: settling time with free viewing, reading, visual search, and execution of large versional tasks. Lens position (degrees of rotation) was continuously recorded with a head mounted, infrared, video-based system and a digital photo slit-lamp in 20 adult subjects. All measurements were obtained from the left eye under binocular viewing conditions with contact lenses on both eyes. RESULTS: The ACUVUE lens was significantly more stable during the settling time and large saccadic versional tasks than the SofLens. For the two other tasks (reading, visual search), performance was similar. CONCLUSION: The ACUVUE design was superior in stability for two of the four conditions tested. This resulted in a more stable lens immediately after insertion as well as during some visual tasks involving either naturally occurring or programmed large versional eye movements. Both lens designs provided acceptable performance in terms of induced astigmatism produced by off-axis rotation.