The mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) is the physical contact site between the ER and the mitochondria and plays a vital role in the regulation of calcium signaling, bioenergetics, and inflammation. Disturbances in these processes and dysregulation of the ER and mitochondrial homeostasis contribute to the pathogenesis of diabetic retinopathy (DR). However, few studies have examined the impact of diabetes on the retinal MAM and its implication in DR pathogenesis. In the present study, we investigated the proteomic changes in retinal MAM from Long Evans rats with streptozotocin-induced long-term Type 1 diabetes. Furthermore, we performed in-depth bioinformatic analysis to identify key MAM proteins and pathways that are potentially implicated in retinal inflammation, angiogenesis, and neurodegeneration. A total of 2664 unique proteins were quantified using IonStar proteomics-pipeline in rat retinal MAM, among which 179 proteins showed significant changes in diabetes. Functional annotation revealed that the 179 proteins are involved in important biological processes such as cell survival, inflammatory response, and cellular maintenance, as well as multiple disease-relevant signaling pathways, e.g., integrin signaling, leukocyte extravasation, PPAR, PTEN, and RhoGDI signaling. Our study provides comprehensive information on MAM protein changes in diabetic retinas, which is helpful for understanding the mechanisms of metabolic dysfunction and retinal cell injury in DR.

Background: Neurological complications (NCs) are increasingly recognized as contributors to adverse outcomes in hospitalized cancer populations, yet their burden and associated disparities in patients with head and neck cancer (HNC) remain poorly characterized. This study evaluated the association between NCs and hospital outcomes in HNC and examined sociodemographic disparities. Methods: A retrospective cross-sectional study was conducted using the 2021 National Inpatient Sample, a nationally representative database of U.S. hospitalizations. Adult patients with a primary diagnosis of HNC were included. NCs were identified using ICD-10-CM codes. Survey-weighted multivariable regression models assessed associations with outcomes. Results: Among 57,615 weighted HNC hospitalizations, corresponding to 11,523 unweighted discharges, 6320 (unweighted n = 1328; 11%) had at least one NC. NCs were independently associated with higher hospital charges (adjusted geometric mean ratio [aGMR], 1.38, 95% CI 1.26–1.51), longer length of stay (aGMR, 1.25, 95% CI 1.17–1.34), and increased in-hospital mortality (aOR 2.42, 95% CI 1.96–2.98). NCs were also associated with higher odds of hospital-acquired complications (aOR 1.92), septicemia (1.90), fluid and electrolyte disorders (1.65), COVID-19 infection (1.66), and emergency department admission (1.33). Disparities were observed, with Hispanic and Other race patients incurring higher charges and Black and Hispanic patients experiencing longer hospital stays; Medicaid and self-pay patients had higher mortality compared with those on Medicare. Conclusions: NCs are associated with worse outcomes and increased healthcare utilization among hospitalized HNC patients; however, given NIS limitations, including lack of cancer stage, treatment history, performance status, and brain metastasis data, these findings should be interpreted as non-causal associations. Early NC recognition and disparity-focused interventions may improve inpatient cancer care.

Krabbe disease (KD) is a lysosomal storage disorder characterized by severe peripheral demyelination caused by mutations in galactosylceramidase (GALC), leading to the accumulation of galactosylceramide and psychosine. Although psychosine toxicity is central to KD pathology, additional mechanisms likely contribute to myelin dysfunction. Because Schwann cells (SCs) play a critical role in myelin maintenance, and GALC deficiency disrupts lysosomal function, we hypothesized that autophagy is altered in SCs during KD progression. Using a SC‐specific Galc conditional knockout ( Galc SC cKO) mouse model, we identified early changes in autophagy‐related protein levels and increased autophagosome abundance during the pre‐symptomatic phase, prior to detectable myelin abnormalities. To assess whether autophagy contributes to disease progression, we selectively deleted Atg7 , an essential regulator of canonical autophagy, in SCs. Atg7 deletion alone did not affect myelin or behavior, but its loss in Galc SC cKO mice markedly worsened disease severity. Atg7‐Galc SC cKO mice exhibited significantly thinner myelin and pronounced deficits in motor performance and nerve conduction, accompanied by altered steady‐state levels of autophagy‐associated proteins and functional decline. Notably, Atg7 deletion in Galc SC cKO mice did not further increase macrophage abundance, suggesting that the worsened myelin phenotype occurs without additional macrophage recruitment at this stage. Together, these findings demonstrate that autophagy‐associated changes occur early in KD and ATG7‐dependent pathways play a protective role during disease progression. Modulating ATG7‐dependent pathways may therefore warrant further investigation as a strategy to support myelin maintenance in KD and related lysosomal disorders.