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Food insecurity affected 10.2% of US households throughout 2021. Individuals living in food insecure households face higher probability of chronic disease. Food insecurity among individuals with symptomatic heart failure is likely common, but underreported and underappreciated in this patient population. A questionnaire was implemented at our clinic to assess food security and enroll patients in the Food4Health Clinic, which provides healthy food at no cost to eligible patients. The Food4Health Clinic is designed like a grocery store, offering fresh produce, high quality protein, and whole grains to eligible patients at no cost (Figure). A questionnaire (Figure) was developed (7 questions: 5 related to demographics and 2 for food security screening) to assess food security in our HF clinic and screen patients for eligibility in the Food4Health Clinic. This pilot project includes patients with low income, who screened positive for food insecurity, and had the ability to carry/transport groceries to their home. 61 questionnaires were completed in HF patients (32 white, 24 female, average age 60 years) visiting our clinic, who agreed to participate in the screening process, between May and October 2022. 31 patients (9 white, 14 female, average age 54 years) had food insecurity and were enrolled in the Food4Health Clinic. Only 14 referred patients made a visit to the program. Around 50% of patients with symptomatic HF suffer from food insecurity. Non-White patients were more likely to have food insecurity. A concerted effort should be made to screen and manage food insecurity in patients with HF. [ABSTRACT FROM AUTHOR]

The most widely used fluorophore in glioma-resection surgery, 5-aminolevulinic acid (5-ALA), is thought to cause the selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumour cells. Here we show that the clinical detection of PpIX can be improved via a microscope that performs paired stimulated Raman histology and two-photon excitation fluorescence microscopy (TPEF). We validated the technique in fresh tumour specimens from 115 patients with high-grade gliomas across four medical institutions. We found a weak negative correlation between tissue cellularity and the fluorescence intensity of PpIX across all imaged specimens. Semi-supervised clustering of the TPEF images revealed five distinct patterns of PpIX fluorescence, and spatial transcriptomic analyses of the imaged tissue showed that myeloid cells predominate in areas where PpIX accumulates in the intracellular space. Further analysis of external spatially resolved metabolomics, transcriptomics and RNA-sequencing datasets from glioblastoma specimens confirmed that myeloid cells preferentially accumulate and metabolize PpIX. Our findings question 5-ALA-induced fluorescence in glioma cells and show how 5-ALA and TPEF imaging can provide a window into the immune microenvironment of gliomas., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Loss-of-function mutations in MEGF10 lead to a rare and understudied neuromuscular disorder known as MEGF10-related myopathy. There are no treatments for the progressive respiratory distress, motor impairment, and structural abnormalities in muscles caused by the loss of MEGF10 function. In this study, we deployed cellular and molecular assays to obtain additional insights about MEGF10-related myopathy in juvenile, young adult, and middle-aged Megf10 knockout (KO) mice. We found fewer muscle fibers in juvenile and adult Megf10 KO mice, supporting published studies that MEGF10 regulates myogenesis by affecting satellite cell differentiation. Interestingly, muscle fibers do not exhibit morphological hallmarks of atrophy in either young adult or middle-aged Megf10 KO mice. We next examined the neuromuscular junction (NMJ), in which MEGF10 has been shown to concentrate postnatally, using light and electron microscopy. We found early and progressive degenerative features at the NMJs of Megf10 KO mice that include increased postsynaptic fragmentation and presynaptic regions not apposed by postsynaptic nicotinic acetylcholine receptors. We also found perisynaptic Schwann cells intruding into the NMJ synaptic cleft. These findings strongly suggest that the NMJ is a site of postnatal pathology in MEGF10-related myopathy. In support of these cellular observations, RNA-seq analysis revealed genes and pathways associated with myogenesis, skeletal muscle health, and NMJ stability dysregulated in Megf10 KO mice compared to wild-type mice. Altogether, these data provide new and valuable cellular and molecular insights into MEGF10-related myopathy., (© 2024. The Author(s).)

Age-induced degeneration of the neuromuscular junction (NMJ) is associated with motor dysfunction and muscle atrophy. While the impact of aging on the NMJ presynapse and postsynapse is well-documented, little is known about the changes perisynaptic Schwann cells (PSCs), the synaptic glia of the NMJ, undergo during aging. Here, we examined PSCs in young, middle-aged, and old mice in three muscles with different susceptibility to aging. Using light and electron microscopy, we found that PSCs acquire age-associated cellular features either prior to or at the same time as the onset of NMJ degeneration. Notably, we found that aged PSCs fail to completely cap the NMJ even though they are more abundant in old compared with young mice. We also found that aging PSCs form processes that either intrude into the synaptic cleft or guide axonal sprouts to innervate other NMJs. We next profiled the transcriptome of PSCs and other Schwann cells (SCs) to identify mechanisms altered in aged PSCs. This analysis revealed that aged PSCs acquire a transcriptional pattern previously shown to promote phagocytosis that is absent in other SCs. It also showed that aged PSCs upregulate unique pro-inflammatory molecules compared to other aged SCs. Interestingly, neither synaptogenesis genes nor genes that are typically upregulated by repair SCs were induced in aged PSCs or other SCs. These findings provide insights into cellular and molecular mechanisms that could be targeted in PSCs to stave off the deleterious effects of aging on NMJs., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Amyotrophic Lateral Sclerosis (ALS) is a currently incurable disease that causes progressive motor neuron loss, paralysis and death. Skeletal muscle pathology occurs early during the course of ALS. It is characterized by impaired mitochondrial biogenesis, metabolic dysfunction and deterioration of the neuromuscular junction (NMJ), the synapse through which motor neurons communicate with muscles. Therefore, a better understanding of the molecules that underlie this pathology may lead to therapies that slow motor neuron loss and delay ALS progression. Kruppel Like Factor 15 (KLF15) has been identified as a transcription factor that activates alternative metabolic pathways and NMJ maintenance factors, including Fibroblast Growth Factor Binding Protein 1 (FGFBP1), in skeletal myocytes. In this capacity, KLF15 has been shown to play a protective role in Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), however its role in ALS has not been evaluated. Here, we examined whether muscle-specific KLF15 overexpression promotes the health of skeletal muscles and NMJs in the SOD1 G93A ALS mouse model. We show that muscle-specific KLF15 overexpression did not elicit a significant beneficial effect on skeletal muscle atrophy, NMJ health, motor function, or survival in SOD1 G93A ALS mice. Our findings suggest that, unlike in mouse models of DMD and SMA, KLF15 overexpression has a minimal impact on ALS disease progression in SOD1 G93A mice., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The sarcomere is the basic contractile unit of muscle, composed of repeated sets of actin thin filaments and myosin thick filaments. During muscle development, sarcomeres grow in size to accommodate the growth and function of muscle fibers. Failure in regulating sarcomere size results in muscle dysfunction; yet, it is unclear how the size and uniformity of sarcomeres are controlled. Here we show that the formin Diaphanous is critical for the growth and maintenance of sarcomere size: Dia sets sarcomere length and width through regulation of the number and length of the actin thin filaments in the Drosophila flight muscle. To regulate thin filament length and sarcomere size, Dia interacts with the Gelsolin superfamily member Flightless I (FliI). We suggest that these actin regulators, by controlling actin dynamics and turnover, generate uniformly sized sarcomeres tuned for the muscle contractions required for flight., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)