Advancing models of neural development with biomaterials.

Human pluripotent stem cells have emerged as a promising in vitro model system for studying the brain. Two-dimensional and three-dimensional cell culture paradigms have provided valuable insights into the pathogenesis of neuropsychiatric disorders, but they remain limited in their capacity to model certain features of human neural development. Specifically, current models do not efficiently incorporate extracellular matrix-derived biochemical and biophysical cues, facilitate multicellular spatio-temporal patterning, or achieve advanced functional maturation. Engineered biomaterials have the capacity to create increasingly biomimetic neural microenvironments, yet further refinement is needed before these approaches are widely implemented. This Review therefore highlights how continued progression and increased integration of engineered biomaterials may be well poised to address intractable challenges in recapitulating human neural development.

Interplay of the Tfb1 pleckstrin homology domain with Rad2 and Rad4 in transcription coupled and global genomic nucleotide excision repair.

Transcription-coupled repair (TCR) and global genomic repair (GGR) are two subpathways of nucleotide excision repair (NER). The TFIIH subunit Tfb1 contains a Pleckstrin homology domain (PHD), which was shown to interact with one PHD-binding segment (PB) of Rad4 and two PHD-binding segments (PB1 and PB2) of Rad2 in vitro. Whether and how the different Rad2 and Rad4 PBs interact with the same Tfb1 PHD, and whether and how they affect TCR and GGR within the cell remain mysterious. We found that Rad4 PB constitutively interacts with Tfb1 PHD, and the two proteins may function within one module for damage recognition in TCR and GGR. Rad2 PB1 protects Tfb1 from degradation and interacts with Tfb1 PHD at a basal level, presumably within transcription preinitiation complexes when NER is inactive. During a late step of NER, the interaction between Rad2 PB1 and Tfb1 PHD augments, enabling efficient TCR and GGR. Rather than interacting with Tfb1 PHD, Rad2 PB2 constrains the basal interaction between Rad2 PB1 and Tfb1 PHD, thereby weakening the protection of Tfb1 from degradation and enabling rapid augmentation of their interactions within TCR and GGR complexes. Our results shed new light on NER mechanisms.

Engineered matrices reveal stiffness-mediated chemoresistance in patient-derived pancreatic cancer organoids.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its fibrotic and stiff extracellular matrix. However, how the altered cell/extracellular-matrix signalling contributes to the PDAC tumour phenotype has been difficult to dissect. Here we design and engineer matrices that recapitulate the key hallmarks of the PDAC tumour extracellular matrix to address this knowledge gap. We show that patient-derived PDAC organoids from three patients develop resistance to several clinically relevant chemotherapies when cultured within high-stiffness matrices mechanically matched to in vivo tumours. Using genetic barcoding, we find that while matrix-specific clonal selection occurs, cellular heterogeneity is not the main driver of chemoresistance. Instead, matrix-induced chemoresistance occurs within a stiff environment due to the increased expression of drug efflux transporters mediated by CD44 receptor interactions with hyaluronan. Moreover, PDAC chemoresistance is reversible following transfer from high- to low-stiffness matrices, suggesting that targeting the fibrotic extracellular matrix may sensitize chemoresistant tumours. Overall, our findings support the potential of engineered matrices and patient-derived organoids for elucidating extracellular matrix contributions to human disease pathophysiology.

Constitutive knockout of interleukin-6 ameliorates memory deficits and entorhinal astrocytosis in the MRL/lpr mouse model of neuropsychiatric lupus.

BACKGROUND: Neuropsychiatric lupus (NPSLE) describes the cognitive, memory, and affective emotional burdens faced by many lupus patients. While NPSLE's pathogenesis has not been fully elucidated, clinical imaging studies and cerebrospinal fluid (CSF) findings, namely elevated interleukin-6 (IL-6) levels, point to ongoing neuroinflammation in affected patients. Not only linked to systemic autoimmunity, IL-6 can also activate neurotoxic glial cells the brain. A prior pre-clinical study demonstrated that IL-6 can acutely induce a loss of sucrose preference; the present study sought to assess the necessity of chronic IL-6 exposure in the NPSLE-like disease of MRL/lpr lupus mice. METHODS: We quantified 1308 proteins in individual serum or pooled CSF samples from MRL/lpr and control MRL/mpj mice using protein microarrays. Serum IL-6 levels were plotted against characteristic NPSLE neurobehavioral deficits. Next, IL-6 knockout MRL/lpr (IL-6 KO; n = 15) and IL-6 wildtype MRL/lpr mice (IL-6 WT; n = 15) underwent behavioral testing, focusing on murine correlates of learning and memory deficits, depression, and anxiety. Using qPCR, we quantified the expression of inflammatory genes in the cortex and hippocampus of MRL/lpr IL-6 KO and WT mice. Immunofluorescent staining was performed to quantify numbers of microglia (Iba1 +) and astrocytes (GFAP +) in multiple cortical regions, the hippocampus, and the amygdala. RESULTS: MRL/lpr CSF analyses revealed increases in IL-17, MCP-1, TNF-α, and IL-6 (a priori p-value < 0.1). Serum levels of IL-6 correlated with learning and memory performance (R2 = 0.58; p = 0.03), but not motivated behavior, in MRL/lpr mice. Compared to MRL/lpr IL-6 WT, IL-6 KO mice exhibited improved novelty preference on object placement (45.4% vs 60.2%, p < 0.0001) and object recognition (48.9% vs 67.9%, p = 0.002) but equivalent performance in tests for anxiety-like disease and depression-like behavior. IL-6 KO mice displayed decreased cortical expression of aif1 (microglia; p = 0.049) and gfap (astrocytes; p = 0.044). Correspondingly, IL-6 KO mice exhibited decreased density of GFAP + cells compared to IL-6 WT in the entorhinal cortex (89 vs 148 cells/mm2, p = 0.037), an area vital to memory. CONCLUSIONS: The inflammatory composition of MRL/lpr CSF resembles that of human NPSLE patients. Increased in the CNS, IL-6 is necessary to the development of learning and memory deficits in the MRL/lpr model of NPSLE. Furthermore, the stimulation of entorhinal astrocytosis appears to be a key mechanism by which IL-6 promotes these behavioral deficits.

Benchmarking a universal smoking machine adaptor for tobacco product testing.

SIGNIFICANCE: Characterisation of tobacco product emissions is an important step in assessing their impact on public health. Accurate and repeatable emissions data require that a leak-tight seal be made between the smoking or vaping machine and the mouth-end of the tobacco product being tested. This requirement is challenging because of the variety of tobacco product mouth-end geometries being puffed on by consumers today. We developed and tested a prototype universal smoking machine adaptor (USMA) that interfaces with existing machines and reliably seals with a variety of tobacco product masses and geometries. METHODS: Emissions were machine-generated using the USMA and other available adaptors for a variety of electronic cigarettes (n=7 brands), cigars (n=4), cigarillos (n=2), a heated tobacco product, and a reference cigarette (1R6F), and mainstream total particulate matter (TPM) and nicotine were quantified. Data variability (precision, n≥10 replicates/brand) for all products and error (accuracy) from certified values (1R6F) were compared across adaptors. RESULTS: TPM and nicotine emissions generated using the USMA were accurate, precise and agreed with certified values for the 1R6F reference cigarette. Replicate data indicate that USMA repeatability across all tobacco products tested generally meets or exceeds that from the comparison adaptors and extant data. CONCLUSION: The USMA seals well with a variety of combustible tobacco products, e-cigarettes with differing geometries and plastic-tipped cigarillos. Variability for all measures was similar or smaller for the USMA compared with other adaptors.

Universal smoking machine adaptor for tobacco product testing.

SIGNIFICANCE: Historically, tobacco product emissions testing using smoking machines has largely focused on combustible products, such as cigarettes and cigars. However, the popularity of newer products, such as electronic cigarettes (e-cigarettes), has complicated emissions testing because the products' mouth-end geometries do not readily seal with existing smoking and vaping machines. The demand for emissions data on popularly used products has led to inefficient and non-standardised solutions, such as laboratories making their geometry-specific custom adaptors and/or employing flexible tubing, for each unique mouth-end geometry tested. A user-friendly, validated, universal smoking machine adaptor (USMA) is needed for testing the variety of tobacco products reflecting consumer use, including e-cigarettes, heated tobacco products, cigarettes, plastic-tipped cigarillos and cigars. METHODS: A prototype USMA that is compatible with existing smoking/vaping machines was designed and fabricated. The quality of the seal between the USMA and different tobacco products, including e-cigarettes, cigars and cigarillos, was evaluated by examining the leak rate. RESULTS: Unlike commercial, product-specific adaptors, the USMA seals well with a wide range of tobacco product mouth-end geometries and masses. This includes e-cigarettes with non-cylindrical mouth ends and cigarillos with cuboid-like plastic tips. USMA leak rates were lower than or equivalent to commercial, product-specific adaptors. CONCLUSION: This report provides initial evidence that the USMA seals reliably with a variety of tobacco product mouth-end geometries and can be used with existing linear smoking/vaping machines to potentially improve the precision, repeatability and reproducibility of machine smoke yield data. Accurate and reproducible emissions testing is critical for regulating tobacco products.

A Library of Elastin-like Proteins with Tunable Matrix Ligands for In Vitro 3D Neural Cell Culture.

Hydrogels with encapsulated cells have widespread biomedical applications, both as tissue-mimetic 3D cultures in vitro and as tissue-engineered therapies in vivo. Within these hydrogels, the presentation of cell-instructive extracellular matrix (ECM)-derived ligands and matrix stiffness are critical factors known to influence numerous cell behaviors. While individual ECM biopolymers can be blended together to alter the presentation of cell-instructive ligands, this typically results in hydrogels with a range of mechanical properties. Synthetic systems that allow for the facile incorporation and modulation of multiple ligands without modification of matrix mechanics are highly desirable. In the present work, we leverage protein engineering to design a family of xeno-free hydrogels (i.e., devoid of animal-derived components) consisting of recombinant hyaluronan and recombinant elastin-like proteins (ELPs), cross-linked together with dynamic covalent bonds. The ELP components incorporate cell-instructive peptide ligands derived from ECM proteins, including fibronectin (RGD), laminin (IKVAV and YIGSR), collagen (DGEA), and tenascin-C (PLAEIDGIELTY and VFDNFVL). By carefully designing the protein primary sequence, we form 3D hydrogels with defined and tunable concentrations of cell-instructive ligands that have similar matrix mechanics. Utilizing this system, we demonstrate that neurite outgrowth from encapsulated embryonic dorsal root ganglion (DRG) cultures is significantly modified by cell-instructive ligand content. Thus, this library of protein-engineered hydrogels is a cell-compatible system to systematically study cell responses to matrix-derived ligands.

Effects of captions on viewers' perceptions of images depicting human-primate interaction.

Promoting human contact with wildlife can be harmful to animal conservation and welfare by exposing animals to unsafe situations and driving demand for wildlife tourism and exotic pets. Conservationists and researchers justifiably use social media to raise awareness, but professionals posting pictures of themselves with animals can have unintended negative consequences for conservation. Though the International Union for Conservation of Nature Best Practice Guidelines for Responsible Images of Non-Human Primates suggests researchers and animal professionals provide context in captions of images of humans interacting with primates, there is little research investigating whether this approach is effective. We investigated whether informative captions affect viewers' desires to have primates as pets and attitudes toward wildlife conservation. Using 4 mock Instagram posts depicting human-gorilla and human-slender loris interactions, we surveyed 2977 respondents to assess the effect of captions on viewers' perceptions of the images and primate conservation. Likert scale response data were analyzed with ordered probit regression models. Captions clearly contextualizing an image as research resulted in a significantly higher agreement that posts depicted wildlife research (gorilla ß = 0.28 [SE 0.06], p < 0.001; loris ß = 0.18 [0.06], p = 0.002), but such captions resulted in no significant difference in responses regarding viewers' desires to own primates as pets or questions regarding the primates' conservation statuses. Although most participants agreed the primates were endangered, more than 56% and 59%, respectively, stated they would have a gorilla or loris as a pet, that they would make good pets, or both, further supporting the conclusion that captions do not minimize harmful impacts of images of human-primate interactions.

Efectos de los pies de foto sobre la percepción del público de imágenes de la interacción humano-primate Resumen La promoción del contacto humano con la fauna puede ser dañina para la conservación y el bienestar animal al exponer a la fauna a situaciones poco seguras e incrementar la demanda por el turismo de fauna y las mascotas exóticas. Los conservacionistas y los investigadores usan con justificación las redes sociales para generar conciencia, pero los profesionales que publican imágenes de sí mismos con los animales pueden generar sin intención consecuencias negativas para la conservación. Aunque la Guía de Buenas Prácticas de la Unión Internacional para la Conservación de la Naturaleza para la Obtención Responsable de Imágenes de Primates No Humanos sugiere que los investigadores y profesionales de fauna proporcionen contexto en los pies de foto de las imágenes de humanos interactuando con primates, hay muy poca investigación sobre si esta estrategia es efectiva. Investigamos si los pies de foto informativos afectan el deseo del público de tener primates como mascotas y la actitud hacia la conservación de la fauna. Usamos cuatro publicaciones simuladas de Instagram representando interacciones humano-gorila y humano-loris para encuestar a 2,977 respondientes y estudiar el efecto de los pies de foto sobre la percepción del público de las imágenes y la conservación de primates. Analizamos los datos de respuesta de escala Likert con modelos de regresión probit ordenada. Los pies de foto que contextualizaban con claridad una imagen como trabajo de investigación resultaron en mayor aceptación de que las publicaciones representaban investigación sobre la fauna (gorila ß = 0.28 [SE 0.06], p < 0.001; loris ß = 0.18 [0.06], p = 0.002), pero dichos textos resultaron en una diferencia no significativa en las respuestas con respecto al deseo del público de tener primates como mascota o preguntas sobre el estado de conservación de los primates. Mientras que la mayoría de los participantes estuvo de acuerdo en que los primates están en peligro de extinción, más del 56% y 59%, respectivamente, afirmaron que tendrían un gorila o un loris como mascota, que serían buenas mascotas, o ambas. Esto suma a la conclusión de que los pies de foto no minimizan el impacto dañino de las imágenes de interacciones humano-primate.

"If you respect me, you are respecting my culture": methods and recommendations for personalizing a TBI transitional care intervention.

OBJECTIVE: Despite research, national legislation, and clinical guidelines supporting transitional care, there is minimal benefit from existing transitional care interventions for racial/ethnic minorities with traumatic brain injury (TBI) discharged home from acute hospital care. Existing TBI transitional care interventions are not tailored to address the needs/preferences of patients from various racial/ethnic minority groups. The purpose of this study was to describe use of personalization to tailor a TBI transitional care intervention for various racial/ethnic groups. DESIGN: Following preliminary intervention manual development, a qualitative descriptive study was conducted using eight focus groups with 40 English-and Spanish-speaking participants (12 patients, 12 caregivers, and 16 providers). RESULTS: Three personalization-related themes emerged: 1) what is important to me, 2) finding someone to deliver the intervention who can adapt to my needs, and 3) respect over culture. Findings informed personalization strategies within our final manual. CONCLUSIONS: We recommend researchers who wish to use personalization to tailor interventions to consider: 1) allowing stakeholders to dictate what is most important and 2) implementing an iterative intervention development process with input from diverse stakeholders. Findings have implications for informing the development of transitional care interventions to increase the likelihood that interventions are inclusive of needs and preferences of various races/ethnicities.

Elucidation of proteostasis defects caused by osteogenesis imperfecta mutations in the collagen-α2(I) C-propeptide domain.

Intracellular collagen assembly begins with the oxidative folding of ∼30-kDa C-terminal propeptide (C-Pro) domains. Folded C-Pro domains then template the formation of triple helices between appropriate partner strands. Numerous C-Pro missense variants that disrupt or delay triple-helix formation are known to cause disease, but our understanding of the specific proteostasis defects introduced by these variants remains immature. Moreover, it is unclear whether or not recognition and quality control of misfolded C-Pro domains is mediated by recognizing stalled assembly of triple-helical domains or by direct engagement of the C-Pro itself. Here, we integrate biochemical and cellular approaches to illuminate the proteostasis defects associated with osteogenesis imperfecta-causing mutations within the collagen-α2(I) C-Pro domain. We first show that "C-Pro-only" constructs recapitulate key aspects of the behavior of full-length Colα2(I) constructs. Of the variants studied, perhaps the most severe assembly defects are associated with C1163R C-Proα2(I), which is incapable of forming stable trimers and is retained within cells. We find that the presence or absence of an unassembled triple-helical domain is not the key feature driving cellular retention versus secretion. Rather, the proteostasis network directly engages the misfolded C-Pro domain itself to prevent secretion and initiate clearance. Using MS-based proteomics, we elucidate how the endoplasmic reticulum (ER) proteostasis network differentially engages misfolded C1163R C-Proα2(I) and targets it for ER-associated degradation. These results provide insights into collagen folding and quality control with the potential to inform the design of proteostasis network-targeted strategies for managing collagenopathies.

Advances in the diagnosis, pathogenesis and treatment of neuropsychiatric systemic lupus erythematosus.

PURPOSE OF REVIEW: Diagnosing and treating neuropsychiatric systemic lupus erythematosus (NPSLE) remains challenging as the pathogenesis is still being debated. In this review, we discuss studies evaluating recent advances in diagnostic methods, pathogenic mediators and potential treatments. RECENT FINDINGS: Screening tools used for neurodegenerative diseases were found to be both sensitive and moderately specific for cognitive dysfunction in NPSLE. Neuroimaging can be used to distinguish systemic lupus erythematosus (SLE) patients from healthy controls, but further refinement is needed to differentiate between lupus patients with and without neuropsychiatric manifestations. Elevated levels of specific molecules in the cerebrospinal fluid and/or serum, as well as the presence of certain autoantibodies, have been identified as potential biomarkers in attempts to facilitate a more accurate and objective diagnosis. Among such autoantibodies, anti-NR2 and anti-ribosomal P autoantibodies also have a pathogenic role, although newer studies demonstrate that blood-brain barrier damage may not always be required as previously believed. These and other observations, together with new evidence for disease attenuation after microglial modulation, suggest direct involvement of the central nervous system in NPSLE pathogenesis. SUMMARY: Neuropsychiatric involvement of SLE includes a variety of symptoms that impact quality of life and patient prognosis. There have been recent advances in improving the diagnosis of NPSLE as well as in dissecting the underlying pathogenesis. The attenuation of neuropsychiatric disease in mouse models demonstrates the potential for targeted therapies, which are based on a clearer understanding of the pathogenesis of NPSLE. Further assessment of these treatments is required in NPSLE patients, as well as the potential use of neuroimaging to distinguish between SLE patients with or without neuropsychiatric manifestations.

Asymmetrical selection maintains heritable phenotypic variation between two subspecies of Monardella villosa.

PREMISE: Monardella villosa is an evolutionarily young species complex distributed across a large geographic range. Our goal was to determine whether the phenotypic difference between two subspecies of M. villosa was heritable and whether the alternative phenotypes were adaptive to their respective local habitats. METHODS: We collected seeds from 25 populations of M. villosa, 14 from subspecies franciscana, which grows closer to the coast, and 11 from subspecies villosa, which has a larger and more inland geographic distribution. We reciprocally transplanted the two subspecies into their respective habitats and compared plant germination, post-emergence survival, and growth. We used linear mixed models to quantify the effects of genotype and environment to determine whether subspecies were locally adapted and whether leaf traits that distinguish these subspecies were genetically based. RESULTS: Plants of both subspecies grown at the coastal site had significantly lower survival and biomass than the inland site. The subspecies were not locally adapted; however, the coastal subspecies franciscana did have a home site advantage. We also found that distinctive leaf morphological traits were genetically based, with high broad-sense heritability of traits. CONCLUSIONS: The two subspecies of Monardella villosa were not locally adapted to their respective habitat, but rather we found that selection for local genotypes may be stronger at the coastal site. Despite the lack of evidence for local adaptation in the strict sense, the subspecies had heritable variation in several leaf phenotypes, indicating that heterogeneous selection imposes an adaptive trade-off for leaf trichome production within this species.

A kainate receptor subunit promotes the recycling of the neuron-specific K+-Cl- co-transporter KCC2 in hippocampal neurons.

Synaptic inhibition depends on a transmembrane gradient of chloride, which is set by the neuron-specific K+-Cl- co-transporter KCC2. Reduced KCC2 levels in the neuronal membrane contribute to the generation of epilepsy, neuropathic pain, and autism spectrum disorders; thus, it is important to characterize the mechanisms regulating KCC2 expression. In the present study, we determined the role of KCC2-protein interactions in regulating total and surface membrane KCC2 expression. Using quantitative immunofluorescence in cultured mouse hippocampal neurons, we discovered that the kainate receptor subunit GluK2 and the auxiliary subunit Neto2 significantly increase the total KCC2 abundance in neurons but that GluK2 exclusively increases the abundance of KCC2 in the surface membrane. Using a live cell imaging assay, we further determined that KCC2 recycling primarily occurs within 1-2 h and that GluK2 produces an ∼40% increase in the amount of KCC2 recycled to the membrane during this time period. This GluK2-mediated increase in surface recycling translated to a significant increase in KCC2 expression in the surface membrane. Moreover, we found that KCC2 recycling is enhanced by protein kinase C-mediated phosphorylation of the GluK2 C-terminal residues Ser-846 and Ser-868. Lastly, using gramicidin-perforated patch clamp recordings, we found that the GluK2-mediated increase in KCC2 recycling to the surface membrane translates to a hyperpolarization of the reversal potential for GABA (EGABA). In conclusion, our results have revealed a mechanism by which kainate receptors regulate KCC2 expression in the hippocampus.

Neto2 is a KCC2 interacting protein required for neuronal Cl- regulation in hippocampal neurons.

KCC2 is a neuron-specific K(+)-Cl(-) cotransporter that is essential for Cl(-) homeostasis and fast inhibitory synaptic transmission in the mature CNS. Despite the critical role of KCC2 in neurons, the mechanisms regulating its function are not understood. Here, we show that KCC2 is critically regulated by the single-pass transmembrane protein neuropilin and tolloid like-2 (Neto2). Neto2 is required to maintain the normal abundance of KCC2 and specifically associates with the active oligomeric form of the transporter. Loss of the Neto2:KCC2 interaction reduced KCC2-mediated Cl(-) extrusion, resulting in decreased synaptic inhibition in hippocampal neurons.

SMARCB1 (INI1)-deficient sinonasal carcinoma manifesting as oral lesions: A report of two cases.

BACKGROUND: Sinonasal carcinomas represent a rare group of malignancies, accounting for less than 5% of all head and neck cancers and a worldwide incidence of less than 1 case per 100 000 inhabitants annually. Despite the restricted anatomical location, sinonasal carcinomas harbor some of the most histologically and molecularly diverse groups of tumors. SMARCB1 (INI1)-deficient sinonasal carcinomas are locally aggressive tumors commonly detected late, leading to devastating morbidity and mortality. CASE REPORT: We present two cases of SMARCB1-deficient sinonasal carcinoma involving the oral cavity and presenting as progressive radiolucent lesions with local swelling associated with maxillary dentition and alveolar bone. Both cases were initially considered odontogenic in origin and involved the destruction of the left anterior maxilla. CONCLUSION: Given the rarity and the variable presentation of these tumors, they pose a challenge for head and neck surgeons, dentists, and pathologists due to the potential overlapping features with odontogenic and non-odontogenic inflammatory and neoplastic lesions. These cases highlight the importance of a multidisciplinary team and include SMARCB1-deficient sinonasal carcinomas in the differential diagnosis of destructive lesions of the maxilla.

Strategies for Effective Dentist-Patient Communication: A Literature Review.

The effectiveness of high-quality dental care predominantly lies on the communication between dentist and patient. However, little literature has reported the importance of these "soft skills" in dental practice. The aim of this literature review is to explore strategies for effective dentist-patient communication. Dentist-patient communication is a bidirectional process involving the exchange of ideas that should be clear (easy to understand), correct (accurate), concise (to the point), complete (with essential information), and cohesive (well-organized). Effective communication empowers patients with the knowledge required to make an informed decision about their own oral health. It not only improves the dentist's efficiency and boosts patient confidence, but also alleviates patients' dental anxiety and fear, addresses patients' needs and preferences, increases patients' adherence, and enhances patient satisfaction. To enhance dentist-patient communication, dentists should take the patient-centered approach as a premise. The approach comprises understanding patients' illnesses, shared decision-making, and mindful intervention at the patient's own pace. In addition, dentists should use simple, succinct language, proper body posture, gestures, facial expressions, and eye contact when interacting with patients. Dentists should show empathy, encourage questions and feedback, employ visual aids, and give ample time to patients. Nowadays, dentists and their patients use messaging applications in their communication. This form of telecommunication is not only a convenient way of communication but also reduces the costs associated with a dentist visit. In conclusion, effective dentist-patient communication is vital for the success of dental practice. Dentists who prioritize communication and build positive relationships with their patients are more likely to achieve positive outcomes and foster the expansion of their dental practice.

Challenges in the Transition from Acute Hospital Care to Home for Spanish-Speaking Latino Patients with TBI and Families: Perspectives of Healthcare Providers and Interpreters.

Language-based disparities negatively impact patient outcomes. Spanish-speaking Latino patients with traumatic brain injury (TBI) transitioning home from acute hospital care and their families have poor TBI-related outcomes; further, they have significant difficulties navigating the healthcare system due to care fragmentation and limited provider support. These challenges are exacerbated by language barriers. There are disproportionately fewer bilingual providers and interpreters in the U.S. healthcare system for patients with TBI for whom English is not their primary language. Although Spanish-speaking Latino patients with TBI and their families communicate with healthcare providers using interpreters on a regular basis, limited research has explored the healthcare delivery perspective. The purpose of this study was to understand the perspectives of healthcare providers and interpreters regarding their experience caring for or supporting Spanish-speaking Latino patients with TBI and their families during the transition home from acute hospital care. This qualitative descriptive study included 10 bilingual (English and Spanish-speaking) participants: 7 interdisciplinary providers and 3 interpreters; findings were analyzed using rapid qualitative analysis to inform intervention adaptation. Four themes were identified: 1) language misalignment decreases health literacy and increases length of stay; 2) TBI-related cognitive impairments, coupled with language differences, make communication challenging; 3) unique social contributors to health directly decrease health equity; and 4) recommendations to improve access and justice in transitional care. There are multiple opportunities to improve transitional care support provided to Spanish-speaking Latino patients with TBI and their families in a manner that is not currently being addressed in research or in practice.

Laminin-associated integrins mediate Diffuse Intrinsic Pontine Glioma infiltration and therapy response within a neural assembloid model.

Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive and fatal pediatric brain cancer. One pre-requisite for tumor cells to infiltrate is adhesion to extracellular matrix (ECM) components. However, it remains largely unknown which ECM proteins are critical in enabling DIPG adhesion and migration and which integrin receptors mediate these processes. Here, we identify laminin as a key ECM protein that supports robust DIPG cell adhesion and migration. To study DIPG infiltration, we developed a DIPG-neural assembloid model, which is composed of a DIPG spheroid fused to a human induced pluripotent stem cell-derived neural organoid. Using this assembloid model, we demonstrate that knockdown of laminin-associated integrins significantly impedes DIPG infiltration. Moreover, laminin-associated integrin knockdown improves DIPG response to radiation and HDAC inhibitor treatment within the DIPG-neural assembloids. These findings reveal the critical role of laminin-associated integrins in mediating DIPG progression and drug response. The results also provide evidence that disrupting integrin receptors may offer a novel therapeutic strategy to enhance DIPG treatment outcomes. Finally, these results establish DIPG-neural assembloid models as a powerful tool to study DIPG disease progression and enable drug discovery.

Mobility mediates maturation: Synthetic substrates to enhance neural differentiation.

The maturation of human induced pluripotent stem cell (hiPSC)-derived neurons in 2D is dependent upon cell attachment, spreading, and pathfinding across a biomaterial substrate. In this issue of Cell Stem Cell, Álvarez et al.1 demonstrate that highly mobile supramolecular scaffolds facilitate long-term hiPSC-derived motor neuron culture, increase maturation-related phenotypes, and recapitulate disease-relevant pathologies.