Low-cost, versatile, and highly reproducible microfabrication pipeline to generate 3D-printed customised cell culture devices with complex designs.

Cell culture devices, such as microwells and microfluidic chips, are designed to increase the complexity of cell-based models while retaining control over culture conditions and have become indispensable platforms for biological systems modelling. From microtopography, microwells, plating devices, and microfluidic systems to larger constructs such as live imaging chamber slides, a wide variety of culture devices with different geometries have become indispensable in biology laboratories. However, while their application in biological projects is increasing exponentially, due to a combination of the techniques, equipment and tools required for their manufacture, and the expertise necessary, biological and biomedical labs tend more often to rely on already made devices. Indeed, commercially developed devices are available for a variety of applications but are often costly and, importantly, lack the potential for customisation by each individual lab. The last point is quite crucial, as often experiments in wet labs are adapted to whichever design is already available rather than designing and fabricating custom systems that perfectly fit the biological question. This combination of factors still restricts widespread application of microfabricated custom devices in most biological wet labs. Capitalising on recent advances in bioengineering and microfabrication aimed at solving these issues, and taking advantage of low-cost, high-resolution desktop resin 3D printers combined with PDMS soft lithography, we have developed an optimised a low-cost and highly reproducible microfabrication pipeline. This is thought specifically for biomedical and biological wet labs with not prior experience in the field, which will enable them to generate a wide variety of customisable devices for cell culture and tissue engineering in an easy, fast reproducible way for a fraction of the cost of conventional microfabrication or commercial alternatives. This protocol is designed specifically to be a resource for biological labs with limited expertise in those techniques and enables the manufacture of complex devices across the µm to cm scale. We provide a ready-to-go pipeline for the efficient treatment of resin-based 3D-printed constructs for PDMS curing, using a combination of polymerisation steps, washes, and surface treatments. Together with the extensive characterisation of the fabrication pipeline, we show the utilisation of this system to a variety of applications and use cases relevant to biological experiments, ranging from micro topographies for cell alignments to complex multipart hydrogel culturing systems. This methodology can be easily adopted by any wet lab, irrespective of prior expertise or resource availability and will enable the wide adoption of tailored microfabricated devices across many fields of biology.

From Office-Based Treatment to Telehealth: Comparing Clinical Outcomes and Patient Participation in a Psychiatric Intensive Outpatient Program with a Large Transdiagnostic Sample.

Introduction: Patient participation and clinical outcomes of a precoronavirus disease 2019 (COVID-19) office-based transdiagnostic psychiatric intensive outpatient program (IOP) were compared with those of telehealth IOP during COVID-19. Materials and Methods: Weeks of enrollment, Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) assessments, and sociodemographic and clinical factors (including group track and diagnosis) were collected during pre-COVID-19 (n = 191) and during COVID-19 (n = 200). Continuous and categorical measures of GAD-7 and PHQ-9 were analyzed; potential sociodemographic and clinical covariates to scores were also explored. Results: There were no statistically significant differences in participation between time periods. Associations were observed between PHQ-9/GAD-7 score improvement and number of assessments. Significant score reductions occurred in both periods, and differences in change scores were not significant. Sociodemographic and clinical factors were not significantly different between time periods. Patients with commercial insurance had significantly higher improvement in both mean and categorical PHQ-9 scores (t = 2.77, p = 0.006; χ2 = 10.47, df = 1, p = 0.001) and GAD-7 scores (t = 2.29, p = 0.023; χ2 = 8.58, df = 1, p = 0.003) than those with public insurance. Patients with anxiety disorders had significantly greater improvements (F = 4.49, p = 0.004; χ2 = 9.15, df = 3, p = 0.027) in GAD-7 during COVID-19. Discussion: Significant improvements in PHQ-9/GAD-7 scores and measures of participation were not significantly different between telehealth and office-based IOP, nor were they greatly influenced by clinical or sociodemographic factors. Further study is needed of possible care disparities for publicly insured patients. Conclusion: Despite some limitations, telehealth IOP appears to be a clinically appropriate option for a diverse sociodemographic and diagnostically heterogeneous psychiatric population.

Stroke Induces Prolonged Changes in Lipid Metabolism, the Liver and Body Composition in Mice.

During recovery, stroke patients are at risk of developing long-term complications that impact quality of life, including changes in body weight and composition, depression and anxiety, as well as an increased risk of subsequent vascular events. The aetiologies and time-course of these post-stroke complications have not been extensively studied and are poorly understood. Therefore, we assessed long-term changes in body composition, metabolic markers and behaviour after middle cerebral artery occlusion in mice. These outcomes were also studied in the context of obesity, a common stroke co-morbidity proposed to protect against post-stroke weight loss in patients. We found that stroke induced long-term changes in body composition, characterised by a sustained loss of fat mass with a recovery of lean weight loss. These global changes in response to stroke were accompanied by an altered lipid profile (increased plasma free fatty acids and triglycerides) and increased adipokine release at 60 days. After stroke, the liver also showed histological changes indicative of liver damage and a decrease in plasma alanine aminotransferase (ALT) was observed. Stroke induced depression and anxiety-like behaviours in mice, illustrated by deficits in exploration, nest building and burrowing behaviours. When initial infarct volumes were matched between mice with and without comorbid obesity, these outcomes were not drastically altered. Overall, we found that stroke induced long-term changes in depressive/anxiety-like behaviours, and changes in plasma lipids, adipokines and the liver that may impact negatively on future vascular health.

Implementing interpersonal and social rhythm therapy for mood disorders across a continuum of care.

OBJECTIVE: Interpersonal and social rhythm therapy (IPSRT) is an evidence-based psychotherapy for mood disorders. The goal of this quality improvement initiative was to demonstrate feasibility of implementing IPSRT across the continuum of outpatient and inpatient care within an academic medical center. METHODS: A multidisciplinary work group was convened to implement IPSRT in outpatient (N=48), inpatient (N=602), and intensive outpatient (N=68) programs of an academic medical center. Quality improvement performance markers (including symptoms and group attendance rates) were collected. RESULTS: Institutional preference for group treatments required adaptation of IPSRT from an individual to group psychotherapy format. Iterative problem solving and protocol development resulted in models of group IPSRT appropriate for each level of care. Performance outcome markers were favorable, indicating feasibility of implementation. CONCLUSIONS: At a single, multisite, urban, academic medical center, IPSRT proved a feasible evidence-based psychotherapy for implementation across levels of care in routine practice.