Home Care Workers Providing Person-Centered Care to People With Dementia.

Person-centered care for people living with dementia has been associated with improved functional ability and quality of life, yet little is known about person-centered care in the home settings. Our objective was to explore home care worker perspectives on providing person-centered care for their clients living with dementia. Using secondary qualitative analysis of 22 semi-structured interviews with home care workers, we identified themes related to the Dementia Initiative's person-centered dementia care framework (Initiative, 2013). We found that home care workers acknowledged their client's personhood while also advocating for their needs. However, home care workers encountered barriers to providing person-centered care, including role limitations and challenging dynamics with other home care workers and family caregivers. This analysis can inform further approaches to better integrate home care workers in person-centered healthcare teams and improve how the needs of people living with dementia are identified and met in the home.

"It shouldn't be like this": Family caregivers navigating insurance for family members with dementia.

BACKGROUND: Almost 11.3 million family caregivers of people with dementia must navigate the health insurance landscape to meet the complex medical and long-term care needs of their family members. This study explores factors that influence family caregivers' decisions about insurance and how these choices affect the care and support people with dementia receive. METHODS: Semi-structured interviews were conducted from June 2022 to January 2023 with 15 family caregivers of people with dementia dual eligible for Medicaid and Medicare and enrolled in home-based primary care in New York City. A set of open-ended questions were asked exploring caregivers' perspectives on navigating insurance plans. Interviews were recorded, transcribed, and analyzed using thematic analysis with both deductive and inductive coding. RESULTS: Analysis revealed three major themes: (1) challenges of Medicaid enrollment, (2) making do with existing insurance, and (3) mistrust of the insurance system. Initial enrollment in Medicaid compounded the stress of adjusting to caregiving. The enrollment process was impacted by clinical factors, financial factors, and input from providers and social workers; however, caregivers could not identify a centralized system for obtaining insurance information and support. Once Medicaid was in place, participants described advocating on behalf of their family member within the constraints of their current insurance plans (Medicare and Medicaid) and ensuring they had the necessary knowledge to understand their family member's coverage. Participants voiced a need for ongoing vigilance to ensure their family members received needed care and support. CONCLUSION: The challenges family caregivers experience when navigating insurance for their family members with dementia contribute to caregiver burden. Robust and centralized professional support for family members both immediately after a family member's dementia diagnosis and as the disease progresses could increase caregivers' capacity to make insurance decisions that best support their family members with dementia.

Photoreduction of Anthracenes Catalyzed by peri-Xanthenoxanthene: a Scalable and Sustainable Birch-Type Alternative.

The typical Birch reduction transforms arenes into cyclohexa-1,4-dienes by using alkali metals, an alcohol as a proton source, and an amine as solvent. Capitalizing on the strong photoreductive properties of peri-xanthenoxanthene (PXX), herein we report the photocatalyzed "Birch-type" reduction of acenes by employing visible blue light irradiation at room temperature in the presence of air. Upon excitation at 405 or 460 nm in the presence of a mixture of N,N-diisopropylethylamine (DIPEA) and trifluoromethanesulfonimide (HNTf2 ) in DMSO, PXX photocatalyzes the selective reduction of full-carbon acene derivatives (24-75 %). Immobilization of PXX onto polydimethylsiloxane (PDMS) beads (PXX-PDMS) allowed the use of the catalyst in heterogeneous batch reactions, giving 9-phenyl-9,10-dihydroanthracene in high yield (68 %). The catalyst could easily be recovered and reused, with no notable drop in performance observed after five reaction cycles. Integration of the PXX-PDMS beads into a microreactor enabled the reduction of acenes under continuous-flow conditions, thereby validating the sustainability and scalability of this heterogeneous-phase approach.

The Need for Stability in Paid Dementia Care: Family Caregiver Perspectives.

Paid caregivers (e.g., home health aides, home care workers) provide essential care to people with dementia living at home; this study explored family caregiver perspectives on the role and impact of paid caregivers in home-based dementia care. We conducted semi-structured interviews with family caregivers (n = 15) of people with advanced dementia who received long-term paid care at home in New York between October 2020 and December 2020. We found that given the vulnerability resulting from advanced dementia, family caregivers prioritized finding the "right" paid caregivers and valued continuity in the individual providing care. The stable paid care that resulted improved outcomes for both the person with advanced dementia (e.g., eating better) and their family (e.g., ability to work). Those advocating for high quality, person-centered dementia care should partner with policymakers and home care agencies to promote the stability of well-matched paid caregivers for people with advanced dementia living at home.

Stoichiometric Post-Modification of Hydrogel Microparticles Dictates Neural Stem Cell Fate in Microporous Annealed Particle Scaffolds.

Microporous annealed particle (MAP) scaffolds are generated from assembled hydrogel microparticles (microgels). It has been previously demonstrated that MAP scaffold are porous, biocompatible, and recruit neural progenitor cells (NPCs) to the stroke cavity after injection into the stroke core. Here, the goal is to study NPC fate inside MAP scaffolds in vitro. To create plain microgels that can later be converted to contain different types of bioactivities, the inverse electron-demand Diels-Alder reaction between tetrazine and norbornene is utilized, which allows the post-modification of plain microgels stoichiometrically. As a result of adhesive peptide attachment, NPC spreading leads to contractile force generation which can be recorded by tracking microgel displacement. Alternatively, non-adhesive peptide integration results in neurosphere formation that grows within the void space of MAP scaffolds. Although the formed neurospheres do not impose a contractile force on the scaffolds, they are seen to continuously transverse the scaffolds. It is concluded that MAP scaffolds  can be engineered to either promote neurogenesis or enhance stemness depending on the chosen post-modifications of the microgels, which can be key in modulating their phenotypes in various applications in vivo.

"I Am the Home Care Agency": The Dementia Family Caregiver Experience Managing Paid Care in the Home.

As the locus of long-term care in the United States shifts from institutions to the community, paid caregivers (i.e., home health aides, personal care attendants) are providing more hands-on care to persons with dementia living at home. Yet, little is known about how family caregivers engage with paid caregivers. We conducted in-depth, semi-structured interviews (n = 15) with family caregivers, of persons living at home with severe dementia, and enriched our findings with data from a second cohort of family caregivers of persons with dementia (n = 9). Whether paid caregivers were hired privately or employed via a Medicaid-funded agency, family caregivers reported that they needed to manage paid caregivers in the home. Core management tasks were day-to-day monitoring and relationship building with family caregivers; training paid caregivers and coordinating care with homecare agencies was also described. In order to support family caregivers of individuals with dementia at home, it is important consider their preferences and skills in order to effectively manage paid caregivers. Support of efforts to build a high-quality paid caregiving workforce has the potential to improve not only care delivered to persons with dementia, but the experiences of their family caregivers.

Microfluidics for Microswimmers: Engineering Novel Swimmers and Constructing Swimming Lanes on the Microscale, a Tutorial Review.

This paper provides an updated review of recent advances in microfluidics applied to artificial and biohybrid microswimmers. Sharing the common regime of low Reynolds number, the two fields have been brought together to take advantage of the fluid characteristics at the microscale, benefitting microswimmer research multifold. First, microfluidics offer simple and relatively low-cost devices for high-fidelity production of microswimmers made of organic and inorganic materials in a variety of shapes and sizes. Microscale confinement and the corresponding fluid properties have demonstrated differential microswimmer behaviors in microchannels or in the presence of various types of physical or chemical stimuli. Custom environments to study these behaviors have been designed in large part with the help of microfluidics. Evaluating microswimmers in increasingly complex lab environments such as microfluidic systems can ensure more effective implementation for in-field applications. The benefits of microfluidics for the fabrication and evaluation of microswimmers are balanced by the potential use of microswimmers for sample manipulation and processing in microfluidic systems, a large obstacle in diagnostic and other testing platforms. In this review various ways in which these two complementary technology fields will enhance microswimmer development and implementation in various fields are introduced.

Rapid Fabrication of Membrane-Integrated Thermoplastic Elastomer Microfluidic Devices.

Leveraging the advantageous material properties of recently developed soft thermoplastic elastomer materials, this work presents the facile and rapid fabrication of composite membrane-integrated microfluidic devices consisting of FlexdymTM polymer and commercially available porous polycarbonate membranes. The three-layer devices can be fabricated in under 2.5 h, consisting of a 2-min hot embossing cycle, conformal contact between device layers and a low-temperature baking step. The strength of the FlexdymTM-polycarbonate seal was characterized using a specialized microfluidic delamination device and an automated pressure controller configuration, offering a standardized and high-throughput method of microfluidic burst testing. Given a minimum bonding distance of 200 µm, the materials showed bonding that reliably withstood pressures of 500 mbar and above, which is sufficient for most microfluidic cell culture applications. Bonding was also stable when subjected to long term pressurization (10 h) and repeated use (10,000 pressure cycles). Cell culture trials confirmed good cell adhesion and sustained culture of human dermal fibroblasts on a polycarbonate membrane inside the device channels over the course of one week. In comparison to existing porous membrane-based microfluidic platforms of this configuration, most often made of polydimethylsiloxane (PDMS), these devices offer a streamlined fabrication methodology with materials having favourable properties for cell culture applications and the potential for implementation in barrier model organ-on-chips.

Microporous annealed particle hydrogel stiffness, void space size, and adhesion properties impact cell proliferation, cell spreading, and gene transfer.

Designing scaffolds for polyplex-mediated therapeutic gene delivery has a number of applications in regenerative medicine, such as for tissue repair after wounding or disease. Microporous annealed particle (MAP) hydrogels are an emerging class of porous biomaterials, formed by annealing microgel particles to one another in situ to form a porous bulk scaffold. MAP gels have previously been shown to support and enhance proliferative and regenerative behaviors both in vitro and in vivo. Therefore, coupling gene delivery with MAP hydrogels presents a promising approach for therapy development. To optimize MAP hydrogels for gene delivery, we studied the effects of particle size and stiffness as well as adhesion potential on cell surface area and proliferation and then correlated this information with the ability of cells to become transfected while seeded in these scaffolds. We find that the void space size as well as the presentation of integrin ligands influence transfection efficiency. This work demonstrates the importance of considering MAP material properties for guiding cell spreading, proliferation, and gene transfer. STATEMENT OF SIGNIFICANCE: Microporous annealed particle (MAP) hydrogels are an emerging class of porous biomaterials, formed by annealing spherical microgels together in situ, creating a porous scaffold from voids between the packed beads. Here we investigated the effects of MAP physical and adhesion properties on cell spreading, proliferation, and gene transfer in fibroblasts. Particle size and void space influenced spreading and proliferation, with larger particles improving transfection. MAP stiffness was also important, with stiffer scaffolds increasing proliferation, spreading, and transfection, contrasting studies in nonporous hydrogels that showed an inverse response. Last, RGD ligand concentration and presentation modulated spreading similar to non-MAP hydrogels. These findings reveal relationships between MAP properties and cell processes, suggesting how MAP can be tuned to improve future design approaches.

Pathways Governing Polyethylenimine Polyplex Transfection in Microporous Annealed Particle Scaffolds.

Gene delivery using injectable hydrogels can serve as a potential method for regulated tissue regeneration in wound healing. Our microporous annealed particle (MAP) hydrogel has been shown to promote cellular infiltration in both skin and brain wounds, while reducing inflammation. Although the scaffold itself can promote healing, it is likely that other signals will be required to promote healing of hard-to-treat wounds. Gene delivery is one approach to introduce desired bioactive signals. In this study, we investigated how the properties of MAP hydrogels influence non-viral gene delivery of polyethylenimine-condensed plasmid to cells seeded within the MAP gel. From past studies, we found that gene transfer to cells seeded in tissue culture plastic differed from gene transfer to cells seeded inside hydrogel scaffolds. Since MAP scaffolds are generated from hydrogel microparticles that are approximately 100 µm in diameter, they display local characteristics that can be viewed as two-dimensional or three-dimensional to cells. Thus, we sought to study if gene transfer inside MAP scaffolds differed from gene transfer to cells seeded in tissue culture plastic. We sought to understand the roles of the endocytosis pathway, actin and microtubule dynamics, RhoGTPases, and YAP/TAZ on transfection of human fibroblasts.

Capacitive coupling synchronizes autonomous microfluidic oscillators.

Even identically designed autonomous microfluidic oscillators have device-to-device oscillation variability that arises due to inconsistencies in fabrication, materials, and operation conditions. This work demonstrates, experimentally and theoretically, that with appropriate capacitive coupling these microfluidic oscillators can be synchronized. The size and characteristics of the capacitive coupling needed and the range of input flow rate differences that can be synchronized are also characterized. In addition to device-to-device variability, there is also within-device oscillation noise that arises. An additional advantage of coupling multiple fluidic oscillators together is that the oscillation noise decreases. The ability to synchronize multiple autonomous oscillators is also a first step towards enhancing their usefulness as tools for biochemical research applications where multiplicate experiments with identical temporal-stimulation conditions are required.

Dispersible oxygen microsensors map oxygen gradients in three-dimensional cell cultures.

Phase fluorimetry, unlike the more commonly used intensity-based measurement, is not affected by differences in light paths from culture vessels or by optical attenuation through dense 3D cell cultures and hydrogels thereby minimizing dependence on signal intensity for accurate measurements. This work describes the use of phase fluorimetry on oxygen-sensor microbeads to perform oxygen measurements in different microtissue culture environments. In one example, cell spheroids were observed to deplete oxygen from the cell-culture medium filling the bottom of conventional microwells within minutes, whereas oxygen concentrations remained close to ambient levels for several days in hanging-drop cultures. By dispersing multiple oxygen microsensors in cell-laden hydrogels, we also mapped cell-generated oxygen gradients. The spatial oxygen mapping was sufficiently precise to enable the use of computational models of oxygen diffusion and uptake to give estimates of the cellular oxygen uptake rate and the half-saturation constant. The results show the importance of integrated design and analysis of 3D cell cultures from both biomaterial and oxygen supply aspects. While this paper specifically tests spheroids and cell-laden gel cultures, the described methods should be useful for measuring pericellular oxygen concentrations in a variety of biomaterials and culture formats.

Getting there is half the battle: recent advances in delivering therapeutics.

Delivery of therapeutic molecules at the right time, place and at the correct dosage is critical to improve the effectiveness of therapeutic regimens. Barriers in the body, normally needed to maintain function, often impede delivery of therapeutic payloads to their target areas. Designing innovative solutions to circumvent these environmental factors, and ensure the timely delivery of therapeutic doses, is an essential element in improving human health. Here we highlight recent studies that focus on bypassing different barriers crucial for improving therapeutic delivery, by temporarily modifying the in vivo microenvironment, re-designing therapeutic carrier vehicles to improve control characteristics and on-demand delivery, and developing convenience-based strategies to improve patient compliance and access to therapeutics.

Modeling selective elimination of quiescent cancer cells from bone marrow.

Patients with many types of malignancy commonly harbor quiescent disseminated tumor cells in bone marrow. These cells frequently resist chemotherapy and may persist for years before proliferating as recurrent metastases. To test for compounds that eliminate quiescent cancer cells, we established a new 384-well 3D spheroid model in which small numbers of cancer cells reversibly arrest in G1/G0 phase of the cell cycle when cultured with bone marrow stromal cells. Using dual-color bioluminescence imaging to selectively quantify viability of cancer and stromal cells in the same spheroid, we identified single compounds and combination treatments that preferentially eliminated quiescent breast cancer cells but not stromal cells. A treatment combination effective against malignant cells in spheroids also eliminated breast cancer cells from bone marrow in a mouse xenograft model. This research establishes a novel screening platform for therapies that selectively target quiescent tumor cells, facilitating identification of new drugs to prevent recurrent cancer.

A cost-effective fluorescence mini-microscope for biomedical applications.

We have designed and fabricated a miniature microscope from off-the-shelf components and a webcam, with built-in fluorescence capability for biomedical applications. The mini-microscope was able to detect both biochemical parameters, such as cell/tissue viability (e.g. live/dead assay), and biophysical properties of the microenvironment such as oxygen levels in microfabricated tissues based on an oxygen-sensitive fluorescent dye. This mini-microscope has adjustable magnifications from 8-60×, achieves a resolution as high as <2 µm, and possesses a long working distance of 4.5 mm (at a magnification of 8×). The mini-microscope was able to chronologically monitor cell migration and analyze beating of microfluidic liver and cardiac bioreactors in real time, respectively. The mini-microscope system is cheap, and its modularity allows convenient integration with a wide variety of pre-existing platforms including, but not limited to, cell culture plates, microfluidic devices, and organs-on-a-chip systems. Therefore, we envision its widespread application in cell biology, tissue engineering, biosensing, microfluidics, and organs-on-chips, which can potentially replace conventional bench-top microscopy where long-term in situ and large-scale imaging/analysis is required.

Media additives to promote spheroid circularity and compactness in hanging drop platform.

Three-dimensional spheroid cultures have become increasingly popular as drug screening platforms, especially with the advent of different high throughput spheroid forming technologies. However, comparing drug efficacy across different cell types in spheroid culture can be difficult due to variations in spheroid morphologies and transport characteristics. Improving the reproducibility of compact, circular spheroids contributes to standardizing and increasing the fidelity of the desired gradient profiles in these drug screening three-dimensional tissue cultures. In this study we discuss the role that circularity and compaction has on spheroids, and demonstrate the impact methylcellulose (MethoCel) and collagen additives in the culture media can contribute to more compact and circular spheroid morphology. We demonstrate that improved spheroid formation is not a simple function of increased viscosity of the different macromolecule additives, suggesting that other macromolecular characteristics contribute to improved spheroid formation. Of the various macromolecular additives tested for hanging drop culture, MethoCel provided the most desirable spheroid formation. Additionally, the higher viscosity of MethoCel-containing media improved the ease of imaging of cellular spheroids within hanging drop cultures by reducing motion-induced image blur.

Multiple independent autonomous hydraulic oscillators driven by a common gravity head.

Self-switching microfluidic circuits that are able to perform biochemical experiments in a parallel and autonomous manner, similar to instruction-embedded electronics, are rarely implemented. Here, we present design principles and demonstrations for gravity-driven, integrated, microfluidic pulsatile flow circuits. With a common gravity head as the only driving force, these fluidic oscillator arrays realize a wide range of periods (0.4 s-2 h) and flow rates (0.10-63 µl min(-1)) with completely independent timing between the multiple oscillator sub-circuits connected in parallel. As a model application, we perform systematic, parallel analysis of endothelial cell elongation response to different fluidic shearing patterns generated by the autonomous microfluidic pulsed flow generation system.

Stressors and coping mechanisms associated with perceived stress in Latinos.

OBJECTIVE: To evaluate the relationship between causes of perceived stress and the coping mechanisms used by Latino adults with perceived stress. DESIGN, SETTING, PARTICIPANTS: This cross-sectional survey was conducted on a convenience sample of 200 Latino adults (aged ≥18 years). They were recruited from clinics, migrant camps, community events, and churches located in Charleston, S.C. This survey included questions regarding causes of perceived stress, perceived stress (Perceived Stress Scale 10), coping mechanisms (Brief COPE), and depression (Perceived Health Questionnaire 9). MEASURES: High perceived stress (PSS ≥15) was the primary outcome measure. Coping mechanisms and stressors were secondary outcomes. RESULTS: Most (92%) of the sample was born outside the United States, and 66% reported high perceived stress. Stressors associated with high perceived stress included discrimination (P=.0010), lack of insurance (P=.0193), health problems (P=.0058), and lack of money (P=.0015). The most frequently utilized coping mechanisms were self-distraction (54.77%), active coping (69.85%), positive reframing (56.78%), planning (63.82%), acceptance (57.87%), and religion (57.79%). Latinos with higher perceived stress were more likely to report discrimination (OR: 3.401; 95%CI 1.285-9.004) and health problems (OR: 2.782; 95%CI 1.088-7.111) as stressors, and to use denial as a coping mechanism (OR: 2.904; 95%CI 1.280-6.589). CONCLUSION: An increased prevalence of perceived stress among the Latinos evaluated in this study was associated with using denial as a coping mechanism, and encountering discrimination and health problems as sources of perceived stress. Most individuals responded to stressors by utilizing a variety of both adaptive and maladaptive coping mechanisms.

Microfluidic systems: a new toolbox for pluripotent stem cells.

Conventional culture systems are often limited in their ability to regulate the growth and differentiation of pluripotent stem cells. Microfluidic systems can overcome some of these limitations by providing defined growth conditions with user-controlled spatiotemporal cues. Microfluidic systems allow researchers to modulate pluripotent stem cell renewal and differentiation through biochemical and mechanical stimulation, as well as through microscale patterning and organization of cells and extracellular materials. Essentially, microfluidic tools are reducing the gap between in vitro cell culture environments and the complex and dynamic features of the in vivo stem cell niche. These microfluidic culture systems can also be integrated with microanalytical tools to assess the health and molecular status of pluripotent stem cells. The ability to control biochemical and mechanical input to cells, as well as rapidly and efficiently analyze the biological output from cells, will further our understanding of stem cells and help translate them into clinical use. This review provides a comprehensive insignt into the implications of microfluidics on pluripotent stem cell research.

Secreted CXCL12 (SDF-1) forms dimers under physiological conditions.

Chemokine CXCL12 (CXC chemokine ligand 12) signalling through CXCR (CXC chemokine receptor) 4 and CXCR7 has essential functions in development and underlies diseases including cancer, atherosclerosis and autoimmunity. Chemokines may form homodimers that regulate receptor binding and signalling, but previous studies with synthetic CXCL12 have produced conflicting evidence for homodimerization. We used bioluminescence imaging with GL (Gaussia luciferase) fusions to investigate dimerization of CXCL12 secreted from mammalian cells. Using column chromatography and GL complementation, we established that CXCL12 was secreted from mammalian cells as both monomers and dimers. Secreted CXCL12 also formed homodimers in the extracellular space. Monomeric CXCL12 preferentially activated CXCR4 signalling through Gαi and Akt, whereas dimeric CXCL12 more effectively promoted recruitment of ß-arrestin 2 to CXCR4 and chemotaxis of CXCR4-expressing breast cancer cells. We also showed that CXCR7 preferentially sequestered monomeric CXCL12 from the extracellular space and had minimal effects on dimeric CXCL12 in cell-based assays and an orthotopic tumour xenograft model of human breast cancer. These studies establish that CXCL12 secreted from mammalian cells forms homodimers under physiological conditions. Since monomeric and dimeric CXCL12 have distinct effects on cell signalling and function, our results have important implications for ongoing efforts to target CXCL12 pathways for therapy.