Single-cell and spatial omics: exploring hypothalamic heterogeneity.

Elucidating the complex dynamic cellular organization in the hypothalamus is critical for understanding its role in coordinating fundamental body functions. Over the past decade, single-cell and spatial omics technologies have significantly evolved, overcoming initial technical challenges in capturing and analyzing individual cells. These high-throughput omics technologies now offer a remarkable opportunity to comprehend the complex spatiotemporal patterns of transcriptional diversity and cell-type characteristics across the entire hypothalamus. Current single-cell and single-nucleus RNA sequencing methods comprehensively quantify gene expression by exploring distinct phenotypes across various subregions of the hypothalamus. However, single-cell/single-nucleus RNA sequencing requires isolating the cell/nuclei from the tissue, potentially resulting in the loss of spatial information concerning neuronal networks. Spatial transcriptomics methods, by bypassing the cell dissociation, can elucidate the intricate spatial organization of neural networks through their imaging and sequencing technologies. In this review, we highlight the applicative value of single-cell and spatial transcriptomics in exploring the complex molecular-genetic diversity of hypothalamic cell types, driven by recent high-throughput achievements.

Systemic inflammation attenuates the repair of damaged brains through reduced phagocytic activity of monocytes infiltrating the brain.

In this study, we examined how systemic inflammation affects repair of brain injury. To this end, we created a brain-injury model by stereotaxic injection of ATP, a damage-associated molecular pattern component, into the striatum of mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS-ip). An analysis of magnetic resonance images showed that LPS-ip reduced the initial brain injury but slowed injury repair. An immunostaining analysis using the neuronal marker, NeuN, showed that LPS-ip delayed removal of dead/dying neurons, despite the fact that LPS-ip enhanced infiltration of monocytes, which serve to phagocytize dead cells/debris. Notably, infiltrating monocytes showed a widely scattered distribution. Bulk RNAseq analyses showed that LPS-ip decreased expression of genes associated with phagocytosis, with PCR and immunostaining of injured brains confirming reduced levels of Cd68 and Clec7a, markers of phagocytic activity, in monocytes. Collectively, these results suggest that systemic inflammation affects properties of blood monocytes as well as brain cells, resulting in delay in clearing damaged cells and activating repair processes.

Family-centered decision making: A culturally responsive collaborative approach among Asians living in the United States.

OBJECTIVE: Compared to Western cultures, self-determination needs are expressed and pursued differently in Asian cultures, where interdependence and achieving greater good for the group are prioritized. To accommodate these needs, we propose the use of family-centered decision making (FCDM) to complement the shared decision-making (SDM) practice, fostering collaborative psychiatric care for Asian individuals residing in the United States. METHOD: This article synthesizes various literature to outline the similarities and differences between SDM and FCDM, discuss implementation steps, challenges associated with implementation, potential solutions, and future research considerations. RESULTS: Our review suggests that FCDM is more responsive to and inclusive of Asian cultural experience, better reflecting these cultures' expression of self-determination. We propose a five-step framework for FCDM implementation in psychiatric rehabilitation for Asian and Asian American individuals, while identifying three further practical considerations: logistical difficulties, intrafamilial differences, and making the decision to use FCDM or not. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Given the heterogeneity of Asian individuals in the United States, we urge providers to allow flexibility in practicing FCDM. We outline the important components for providers to help individuals with psychiatric disabilities distinguish between the characteristics of FCDM and SDM, evaluate the potential pros and cons of utilizing FCDM, and then initiate FCDM if appropriate or requested by the individuals. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Elder mistreatment experiences, perceptions, and help-seeking behaviors of Asian American older adults.

This study examined the experiences and the perceptions of elder mistreatment (EM), as well as help-seeking knowledge and behaviors, particularly about Adult Protective Services (APS), among community samples of Asian American older adults, including Koreans, Chinese, and others (N = 288). Approximately 27% of the study participants experienced at least one EM incident in the past year. Between 27% and 38% of the participants reported that they were likely to seek help from APS for different types of EM. Significant differences were found across the three Asian groups in their perceptions toward EM and intention to seek help from APS in the event of EM. However, many Asian American older adults in the study did not know about APS prior to participating in the study (75.5%) and other formal sources of help (66.3%). Implications for helping professionals, particularly APS and community-based organizations serving Asian Americans, are discussed.

PET/MRI and Novel Targets for Breast Cancer.

Breast cancer, with its global prevalence and impact on women's health, necessitates effective early detection and accurate staging for optimal patient outcomes. Traditional imaging modalities such as mammography, ultrasound, and dynamic contrast-enhanced magnetic resonance imaging (MRI) play crucial roles in local-regional assessment, while bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) aid in evaluating distant metastasis. Despite the proven utility of 18F-FDG PET/CT in various cancers, its limitations in breast cancer, such as high false-negative rates for small and low-grade tumors, have driven exploration into novel targets for PET radiotracers, including estrogen receptor, human epidermal growth factor receptor-2, fibroblast activation protein, and hypoxia. The advent of PET/MRI, which combines metabolic PET information with high anatomical detail from MRI, has emerged as a promising tool for breast cancer diagnosis, staging, treatment response assessment, and restaging. Technical advancements including the integration of PET and MRI, considerations in patient preparation, and optimized imaging protocols contribute to the success of dedicated breast and whole-body PET/MRI. This comprehensive review offers the current technical aspects and clinical applications of PET/MRI for breast cancer. Additionally, novel targets in breast cancer for PET radiotracers beyond glucose metabolism are explored.

Nanoplastics exacerbate Parkinson's disease symptoms in C. elegans and human cells.

The increasing prevalence of nanoplastics in our environment due to the widespread use of plastics poses potential health risks that are not yet fully understood. This study examines the physiological and neurotoxic effects of these minuscule nanoplastic particles on the nematode Caenorhabditis elegans as well as on human cells. Here, we find that 25 nm polystyrene nanoplastic particles can inhibit animal growth and movement at very low concentrations, with varying effects on their surface groups. Furthermore, these nanoplastic particles not only accumulate in the digestive tract but also penetrate further into extraintestinal tissues. Such nanoplastics significantly compromise the integrity of the intestinal barrier, leading to "leaky gut" conditions and cause mitochondrial fragmentation in muscles, which possibly explains the observed movement impairments. A striking discovery was that these nanoplastics exacerbate symptoms similar to those of Parkinson's disease (PD), including dopaminergic neuronal degeneration, locomotor dysfunction, and accumulation of α-Synuclein aggregates. Importantly, our study demonstrates that the detrimental effects of nanoplastics on the aggregation of α-Synuclein extend to both C. elegans and human cell models of PD. In conclusion, our research highlights the potential health hazards linked to the physicochemical properties of nanoplastics, underlining the urgency of understanding their interactions with biological systems. ENVIRONMENTAL IMPLICATION: The escalating prevalence of nanoplastics in the environment due to widespread plastic usage raises potential health risks. Studies conducted on C. elegans indicate that even low concentrations of 25 nm polystyrene nanoplastics can impair growth and movement. These particles accumulate in the digestive system, compromising the intestinal barrier, causing "leaky gut", as well as inducing Parkinson's-like symptoms. Importantly, in both C. elegans and human cell models of Parkinson's disease, such nanoplastics penetrate tissues or cells and increase α-Synuclein aggregates. This underscores the urgent need to understand the interactions of nanoplastics with biological systems and highlights potential environmental and health consequences.

ANKS1A regulates LDL receptor-related protein 1 (LRP1)-mediated cerebrovascular clearance in brain endothelial cells.

Brain endothelial LDL receptor-related protein 1 (LRP1) is involved in the clearance of Aß peptides across the blood-brain barrier (BBB). Here we show that endothelial deficiency of ankyrin repeat and SAM domain containing 1 A (ANKS1A) reduces both the cell surface levels of LRP1 and the Aß clearance across the BBB. Association of ANKS1A with the NPXY motifs of LRP1 facilitates the transport of LRP1 from the endoplasmic reticulum toward the cell surface. ANKS1A deficiency in an Alzheimer's disease mouse model results in exacerbated Aß pathology followed by cognitive impairments. These deficits are reversible by gene therapy with brain endothelial-specific ANKS1A. In addition, human induced pluripotent stem cell-derived BBBs (iBBBs) were generated from endothelial cells lacking ANKS1A or carrying the rs6930932 variant. Those iBBBs exhibit both reduced cell surface LRP1 and impaired Aß clearance. Thus, our findings demonstrate that ANKS1A regulates LRP1-mediated Aß clearance across the BBB.