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Integrated primary care for home-dwelling older adults with mild cognitive impairment in China: a hybrid effectiveness-implementation trial protocol

1 month ago
BACKGROUND: With China’s rapidly aging population, addressing the health management of mild cognitive impairment (MCI) in community settings has become crucial for dementia prevention. This study focuses on developing an integrated primary care intervention (IPC) within primary care system to support home-dwelling older adults with MCI and explore the underlying barriers based on the Consolidated Framework for Implementation Research (CFIR) to the implementation and further scale up of the IPC...
Shasha Yuan

Multimodal mass spectrometry imaging for plaque- and region-specific neurolipidomics in Alzheimer's disease mouse models

1 month ago
The progressive accumulation of amyloid beta (Aβ) plaques is a hallmark of Alzheimer's disease (AD). However, the biochemical mechanisms of their formation and the consequences associated with plaque formation remain elusive. In female 5xFAD and APP^(NL-G-F) mice, we map region-specific, plaque-associated lipids with large molecular coverage including isomers. We describe a multimodal framework that integrates matrix assisted laser desorption/ionization with laser-induced postionization...
Timothy J Trinklein

Prime editing of the beta(1) adrenoceptor in the brain restores physiological REM sleep in a mouse model of Alzheimer's disease

1 month ago
Prime editing offers versatile genome modifications with therapeutic potential; yet its use to modulate neural circuitry remains underexplored. Here, we used adeno-associated viral vectors to deliver prime editors into the mouse brain and introduced the naturally occurring Adrb1^(A187V) variant of the β1-adrenergic receptor, linked to short sleep in humans and mice. Editing reached up to 28.1% in the cortex six months after intracerebroventricular injection and increased excitability of...
Desirée Böck

White matter hyperintensity regression: Fact or artifact?

1 month ago
White matter hyperintensities (WMH) are an MRI-based biomarker associated with aging, Alzheimer's disease, and vascular dementia. Although the volume of WMH typically increases over time (growth) for individuals, WMH volume in some cases can also decrease (regress). This suggests the presence of active brain injury recovery mechanisms. Whether WMH regression reflects a true biological phenomenon or results from imaging artifacts or measurement errors, however, remains controversial. Here, we...
Ahmed A Bahrani

Platelet-bioengineered hiPSC-sEVs achieve targeted repair of fibrotic sinoatrial node in preclinical SND models

1 month ago
Sinus node dysfunction, a prevalent arrhythmia in aging populations, is characterized by fibrosis and loss of pacemaker activity, necessitating pacemaker implantation. Current therapies fail to reverse the underlying pathology. Small extracellular vesicles derived from human induced pluripotent stem cells possess regenerative potential but lack targeted delivery. Here, we engineer platelet membrane-fused vesicles that synergistically combine collagen targeting for ischemic injury homing with...
Hanfeng Liu

Inhibiting the formation of neutrophil extracellular traps to prevent the recurrence of post-operative glioblastoma

1 month ago
Glioblastoma (GBM) is a highly malignant tumor with a high postoperative recurrence rate. It is crucial to develop innovative and effective approaches to prevent its recurrence. Herein, we focus on the important roles of neutrophil extracellular traps (NETs) in the progression of GBM in mice and patients. Neutrophils accumulate around the surgical cavity and release NETs to promote the proliferation and migration of postoperative residual GBM cells. Injection of a hydrogel loaded with copper...
Yaobao Han

Predicting the demand of elderly care beds by a novel recursive grey Gompertz model: case studies of Jiangsu and Shanghai, China

1 month ago
CONCLUSIONS: The RGGM model introduces a memory factor into its objective function, which assigns a greater weight to newer observations. This mechanism ensures the priority of new information during the modeling process, enhancing the model's adaptability. Furthermore, the model's structural parameters are solved recursively with each new observation, allowing the parameters to inherit information from previous data points. This recursive approach effectively improves prediction accuracy....
Xiaojun Guo

The expectations and influencing factors to choose institutional elder care for older person in the context of future disability: an empirical analysis in China based on Anderson's health behavior model

1 month ago
CONCLUSION: Affected by a variety of factors, the older person's low acceptance of institutional care remains consistent even when future disability is considered. This situation provides the background and ideas for China's current research on promoting social care services. For example, the nursing institutions should consider factors such as the age, education leveland income of the older person when designing elderly care services. The government can lower the threshold for the older person...
Yuanyuan Heng

Hospitalizations for cardiovascular events and risk for all cause and cardiovascular mortality in elderly patients with atrial fibrillation treated with oral anticoagulants: beyond preventing thromboembolism

1 month ago
CONCLUSIONS: Hospitalizations for CVEs in elderly AF/AFL OAC treated patients increased the risk for all cause and CV mortality within 12 months from admission for AF/AFL. Hospitalization for HF bared the highest risk, but the residual stroke/TIA/SE risk was noteworthy.
Matteo Candeloro

Molecular mechanisms underlying p62-dependent secretion of the Alzheimer-associated ubiquitin variant UBB(+1)

1 month ago
UBB^(+1), a ubiquitin variant protein resulting from a frameshift in the ubiquitin-B gene, is a pathological hallmark of Alzheimer disease (AD). At the cellular level, UBB^(+1) disrupts the ubiquitin-proteasome system while inducing autophagy. Notably, UBB^(+1) itself is secreted via autophagosome-like vesicles. Here, we demonstrate that UBB^(+1) can be removed from the cell by degradative and secretory autophagy. Sequestosome 1 (SQSTM1)/p62 functions as a pivotal ubiquitin receptor for...
Ajay R Wagh

IL-27 promotes Treg cell expression of CD122 and fitness at homeostasis

1 month ago
Regulatory T (Treg) cells express high levels of the IL-27R, and in the setting of infection and autoimmunity, the cytokine IL-27 promotes Treg cell activities that mitigate tissue pathology. However, IL-27 appears dispensable for Treg cell development and maintenance as lineage-specific depletion of the IL-27R on Treg cells does not impact these populations at steady state. In contrast, when mice were generated in which the Treg compartment comprised a mix of IL-27R-sufficient and -deficient...
Zachary R Lanzar

Dual Regulatory Roles of USP10 in Tau Pathology and Neuronal Fate During Alzheimer's Disease Progression

1 month ago
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by neuronal cell death, brain atrophy, and cognitive decline. Aggregation of Tau protein in neurons is a critical factor in the pathogenesis of AD. Tau aggregates increase as the disease progresses and contribute to neuronal cell death. This study investigated the role of ubiquitin-specific protease 10 (USP10) in Tau pathology and neuronal viability in AD. We found that the expression of USP10 was reduced in the...
Masahiko Takahashi