Altered protein ubiquitination is associated with the pathobiology of numerous diseases; however, its involvement in glycogen metabolism and associated polyglucosan body (PB) disease has not been investigated in depth. In PB disease, excessively long and less branched glycogen chains (polyglucosan bodies, PBs) are formed, which precipitate in different tissues causing myopathy, cardiomyopathy and/or neurodegeneration. Linear ubiquitin chain assembly complex (LUBAC) is a multi-protein complex composed of two E3 ubiquitin ligases HOIL-1L and HOIP and an adaptor protein SHARPIN. Together they are responsible for M1-linked ubiquitination of substrates primarily related to immune signaling and cell death pathways. Consequently, severe immunodeficiency is a hallmark of many LUBAC deficient patients. Remarkably, all HOIL-1L deficient patients exhibit accumulation of PBs in different organs especially skeletal and cardiac muscle resulting in myopathy and cardiomyopathy with heart failure. This emphasizes LUBAC's important role in glycogen metabolism. To date, neither a glycogen metabolism-related LUBAC substrate nor the molecular mechanism are known. Hence, current reviews on LUBAC's involvement in glycogen metabolism are lacking. Here, we aim to fill this gap by describing LUBAC's involvement in PB disease. We present a comprehensive review of LUBAC structure, its role in M1-linked and other types of atypical ubiquitination, PB pathology in human patients and findings in new mouse models to study the disease. We conclude the review with recent drug developments and near-future gene-based therapeutic approaches to treat LUBAC related PB disease.
The Homeless population is the most socioeconomic underprivileged community in the United States. Cardiovascular complications are one of the leading causes of death among homeless individuals. This study highlights the major risk factors of hypertension among the homeless community in the Orlando metropolitan area, in order to provide solutions and to modify associated risk factors. Adult homeless individuals (N=167) were randomly selected during daily lunch shares at St. George Orthodox Church, Orlando Florida. Each consented participant completed a survey with inquiries about demographic, lifestyle and hypertension related risk factors. Blood pressure was measured twice using an automatic Welch Allyn Connex ProBP 2400 digital device and the readings average was calculated. The Body Mass Index (BMI) was also calculated according to the World Health Organization (WHO) criteria. Average age of participants was 42.3 ± 11 years, and 83% were men. The overall prevalence of hypertension among participants was 52% (87 out of 167). The prevalence of hypertension among individuals who reported to be homeless over one year was 73% (38 out of 52), compared to only 51.3% among those with less than one year. Among diabetic homeless, 70% suffers from hypertension. The prevalence of hypertension among smokers was 51% (48 out of 95), while hypertension according to BMI group was significantly higher in both overweight and obese groups compared to individuals with normal BMI. Hypertension was significantly prevalent among homeless receiving no assistance (75.67%) compared to those receiving both financial and social assistance (47.61%). However, financial assistance had a major effect on lowering hypertension prevalence in comparison to social assistance (58.62% and 74.41%, respectively). In conclusion, hypertension is prevalent among Orlando homeless cohort and it has surpassed the national average. Clearly, social and financial services seem to lower hypertension prevalence among homeless individuals receiving benefits. The outcome of the study supports data from other countries offering affordable and accessible health care services, and certainly, it renews the call for more resources to help the homeless communities.
BACKGROUND: Memantine is a N-methyl-D-aspartate receptor antagonist that is prominently known as an Alzheimer’s disease medication. In recent years, it has started to receive attention for pain management purposes, especially for neuropathic pain. There has been little focus on its use for nociceptive pain. We present a case where the use of memantine for nociceptive pain in a patient yielded significant associated improvement. CASE REPORT: A 49-year-old man presented with a one-year history of severe nociceptive left neck pain subsequent to a whiplash injury. The patient failed multiple first-line therapies and pursued consults with multiple specialties without symptomatic improvement. He was put on memantine with subsequent sustained resolution of his nociceptive neck pain. CONCLUSIONS: Memantine’s optimal safety profile and effectiveness in this case make it important that more human patient research be conducted to further explore its efficacy for nociceptive pain. KEY WORDS: Nociceptive pain, memantine, inflammation, chronic pain, case report
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