Explore the vast range of titles available.

Microglia become progressively activated and seemingly dysfunctional with age, and genetic studies have linked these cells to the pathogenesis of a growing number of neurodegenerative diseases. Here we report a striking buildup of lipid droplets in microglia with aging in mouse and human brains. These cells, which we call ‘lipid-droplet-accumulating microglia’ (LDAM), are defective in phagocytosis, produce high levels of reactive oxygen species and secrete proinflammatory cytokines. RNA-sequencing analysis of LDAM revealed a transcriptional profile driven by innate inflammation that is distinct from previously reported microglial states. An unbiased CRISPR–Cas9 screen identified genetic modifiers of lipid droplet formation; surprisingly, variants of several of these genes, including progranulin (GRN), are causes of autosomal-dominant forms of human neurodegenerative diseases. We therefore propose that LDAM contribute to age-related and genetic forms of neurodegeneration.Microglia in the aging hippocampus accumulate lipid droplets, and are functionally impaired and inflamed. Lipid droplet formation in microglia is regulated by genes linked to neurodegeneration such as progranulin.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Although major categories of ageing damage have been identified—such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function 1 —these deleterious processes interact with extraordinary complexity within and between organs, and a comprehensive, whole-organism analysis of ageing dynamics has been lacking. Here we performed bulk RNA sequencing of 17 organs and plasma proteomics at 10 ages across the lifespan of Mus musculus , and integrated these findings with data from the accompanying Tabula Muris Senis 2 —or ‘Mouse Ageing Cell Atlas’—which follows on from the original Tabula Muris 3 . We reveal linear and nonlinear shifts in gene expression during ageing, with the associated genes clustered in consistent trajectory groups with coherent biological functions—including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Notably, these gene sets show similar expression across tissues, differing only in the amplitude and the age of onset of expression. Widespread activation of immune cells is especially pronounced, and is first detectable in white adipose depots during middle age. Single-cell RNA sequencing confirms the accumulation of T cells and B cells in adipose tissue—including plasma cells that express immunoglobulin J—which also accrue concurrently across diverse organs. Finally, we show how gene expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to the ageing of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of ageing, providing a foundation from which to track systemic sources of declining health at old age. Bulk RNA sequencing of organs and plasma proteomics at different ages across the mouse lifespan is integrated with data from the Tabula Muris Senis , a transcriptomic atlas of ageing mouse tissues, to describe organ-specific changes in gene expression during ageing.

The mental health of Hmong Americans has been studied since their arrival in the United States. The purpose of this metasynthesis is to utilize a qualitative approach to analyze academic journal article studies that assess mental health issues in Hmong Americans. Forty-eight published articles from 1983 to 2012 were chosen for analysis. Each of the selected articles focused on Hmong participants and contained findings relevant to the psychological well-being of Hmong Americans. Results of this study revealed several common themes: trends in research, depression, anxiety, adjustment issues, family issues, substance abuse, other mental health concerns, factors linked to mental health, help seeking behavior and perceptions, effectiveness of mental health treatments, strengths and resiliency, and supportive factors. Keywords: adjustment, anxiety, depression, family issues, Hmong, mental health, metasynthesis, resiliency, treatment effectiveness.

Student awareness, usage, and perception of academic support programs were examined among 55 Hmong college students at a large, public western university. Twenty-eight students had participated in one or more ASPs while 27 students had not participated in any ASPs. Those who had participated found the programs to be supportive with an average rating of 7.39 out of 10 (10 being most supportive). The majority of students who did not participate in ASPs reported that they were not aware of ASPs and their services. Results also show that the majority of Hmong college students perceived a lack of time to study, poor study habits, lack of money, lack of motivation, lack of direction on career goals, and poor time management to be obstacles for them in higher education. Based on the findings, it seems ASPs were not able to reach some Hmong students with their outreach efforts. However, those that they were able to reach found academic support services helpful, especially with financial concerns and direction on career goals. Keywords: Hmong, postsecondary education, higher education barriers, academic support programs

Aging is the single greatest cause of disease and death worldwide, and so understanding the associated processes could vastly improve quality of life. While the field has identified major categories of aging damage such as altered intercellular communication, loss of proteostasis, and eroded mitochondrial function, these deleterious processes interact with extraordinary complexity within and between organs. Yet, a comprehensive analysis of aging dynamics organism-wide is lacking. Here we performed RNA-sequencing of 17 organs and plasma proteomics at 10 ages across the mouse lifespan. We uncover previously unknown linear and non-linear expression shifts during aging, which cluster in strikingly consistent trajectory groups with coherent biological functions, including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Remarkably, these gene sets are expressed similarly across tissues, differing merely in age of onset and amplitude. Especially pronounced is widespread immune cell activation, detectable first in white adipose depots in middle age. Single-cell RNA-sequencing confirms the accumulation of adipose T and B cells, including immunoglobulin J-expressing plasma cells, which also accrue concurrently across diverse organs. Finally, we show how expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to aging of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of aging, thereby providing a foundation to track systemic sources of declining health at old age. Footnotes * https://twc-stanford.shinyapps.io/maca/

Microglia become progressively activated and seemingly dysfunctional with age, and genetic studies have linked these cells to the pathogenesis of a growing number of neurodegenerative diseases. Here we report a striking buildup of lipid droplets in microglia with aging in mouse and human brains. These cells, which we call lipid droplet-accumulating microglia (LAM), are defective in phagocytosis, produce high levels of reactive oxygen species, and secrete pro-inflammatory cytokines. RNA sequencing analysis of LAM revealed a transcriptional profile driven by innate inflammation distinct from previously reported microglial states. An unbiased CRISPR-Cas9 screen identified genetic modifiers of lipid droplet formation; surprisingly, variants of several of these genes, including progranulin, are causes of autosomal dominant forms of human neurodegenerative diseases. We thus propose that LAM contribute to age-related and genetic forms of neurodegeneration.

To identify risk factors for intraocular pressure (IOP) increases during hemodialysis (HD) in the early postoperative period following pars plana vitrectomy (PPV). Comparisons of 36 vitrectomized eyes of 22 diabetics undergoing maintenance HD with those of 138 eyes of 69 nonoperated patients. Serial IOPs were measured before PPV, after PPV/before dialysis, and during dialysis. Serum osmolarity and blood pressure were also recorded. In 20 of 36 operated eyes (55.6%) and 18 of 138 nonoperated eyes (13.0%) IOP was increased (> or =4 mm Hg) during HD. In the operated group, marked increases (> or =7 mm Hg) were noted in 9 eyes and ocular pain in 5 eyes. Eyes with pre-existing outflow obstruction and/or acute postoperative outflow compromise carried high risks. No correlation with changes in serum osmolarity or blood pressure was found. Monitoring of IOP during HD seems warranted when diabetics with pre-existing outflow obstruction and/or postoperative outflow compromise, undergo HD following PPV.

To identify risk factors for intraocular pressure (IOP) increases during hemodialysis (HD) in the early postoperative period following pars plana vitrectomy (PPV). Comparisons of 36 vitrectomized eyes of 22 diabetics undergoing maintenance HD with those of 138 eyes of 69 nonoperated patients. Serial IOPs were measured before PPV, after PPV/before dialysis, and during dialysis. Serum osmolarity and blood pressure were also recorded. In 20 of 36 operated eyes (55.6%) and 18 of 138 nonoperated eyes (13.0%) IOP was increased (> or =4 mm Hg) during HD. In the operated group, marked increases (> or =7 mm Hg) were noted in 9 eyes and ocular pain in 5 eyes. Eyes with pre-existing outflow obstruction and/or acute postoperative outflow compromise carried high risks. No correlation with changes in serum osmolarity or blood pressure was found. Monitoring of IOP during HD seems warranted when diabetics with pre-existing outflow obstruction and/or postoperative outflow compromise, undergo HD following PPV.