Contractile dysfunction and increased deposition of O-linked β-N-acetyl-d-glucosamine (O-GlcNAc) in cardiac proteins are a hallmark of the diabetic heart. However, whether and how this posttranslational alteration contributes to lower cardiac function remains unclear. Using a refined β-elimination/Michael addition with tandem mass tags (TMT)–labeling proteomic technique, we show that CpOGA, a bacterial analog of O-GlcNAcase (OGA) that cleaves O-GlcNAc in vivo, removes site-specific O-GlcNAcylation from myofilaments, restoring Ca2+ sensitivity in streptozotocin (STZ) diabetic cardiac muscles. We report that in control rat hearts, O-GlcNAc and O-GlcNAc transferase (OGT) are mainly localized at the Z-line, whereas OGA is at the A-band. Conversely, in diabetic hearts O-GlcNAc levels are increased and OGT and OGA delocalized. Consistent changes were found in human diabetic hearts. STZ diabetic hearts display increased physical interactions of OGA with α-actin, tropomyosin, and myosin light chain 1, along with reduced OGT and increased OGA activities. Our study is the first to reveal that specific removal of O-GlcNAcylation restores myofilament response to Ca2+ in diabetic hearts and that altered O-GlcNAcylation is due to the subcellular redistribution of OGT and OGA rather than to changes in their overall activities. Thus, preventing sarcomeric OGT and OGA displacement represents a new possible strategy for treating diabetic cardiomyopathy.
Pigmented lesions of the nail unit are commonly encountered in the clinical setting. Yet, they often present a unique challenge to clinicians because of a broad differential diagnosis or unfamiliarity with clinical and histopathologic features. A wide variety of causes exist ranging from benign lesions such as subungual hemorrhage to malignant lesions such as subungual melanoma. Identifying the underlying cause is key to appropriate management and follow-up in these patients. Although emerging clinical tools such as dermoscopy can be very useful in evaluation of these lesions, histopathologic analysis remains the gold standard. In this review, we discuss and provide a summary of important clinical and histopathological concepts of pigmented lesions of the nail unit with special focus on longitudinal melanonychia, melanotic macule, melanocytic nevus, subungual melanoma, along with discussion of some nonmelanocytic lesions.
Study Design:Retrospective cohort study.Objectives:Adult spinal deformity (ASD) surgery encompasses a wide variety of spinal disorders and is associated with a morbidity rate between 20% and 80%. The utilization of spinal surgery has increased and this trend is expected to continue. To effectively deal with an increasing patient volume, identifying variables associated with patient discharge destination can expedite placement and reduce length of stay.Methods:The 2013-2014 American College of Surgeons National Surgical Quality Improvement Program database was queried using Current Procedural Terminology and International Classification of Diseases, Ninth Revision diagnosis codes relevant to ASD. Patients were divided based on discharge destination. Bivariate and multivariate logistic regression analyses were employed to identify predictors for patient discharge destination and hospital length of stay.Results:A total of 4552 patients met inclusion criteria, of which 1102 (24.2%) had non-home discharge. Multivariate regression revealed total relative value unit (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 1.00-1.01); female sex (OR = 1.54, 95% CI = 1.32-1.81); American Indian, Alaska Native, Asian, Native Hawaiian, or Pacific Islander versus black race (OR = 0.52, 95% CI = 0.35-0.78, P = .002); age ≥65 years (OR = 3.72, 95% CI = 3.19-4.35); obesity (OR = 1.18, 95% CI = 1.01-1.38, P = .034); partially/totally functionally dependent (OR = 2.11, 95% CI = 1.49-2.99); osteotomy (OR = 1.42, 95% CI = 1.12-1.80, P = .004) pelvis fixation (OR = 2.38, 95% CI = 1.82-3.11); operation time ≥4 hours (OR = 1.74, 95% CI = 1.47-2.05); recent weight loss (OR = 7.66, 95% CI = 1.52-38.65; P = .014); and American Society of Anesthesiologists class ≥3 (OR = 1.80, 95% CI = 1.53-2.11) as predictors of non-home discharge. P values were <.001 unless otherwise noted. Additionally, multivariate regression found non-home discharge to be a significant variable in prolonged length of stay.Conclusions:The authors suggest these results can be used to inform patients preoperatively of expected discharge destination, anticipate patient discharge needs postoperatively, and reduce health care costs and morbidity associated with prolonged LOS.
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