RESUMEN
Skeletal muscle insulin resistance is a major contributor to type-2 diabetes (T2D). Pioglitazone is a potent insulin sensitizer of peripheral tissues by targeting peroxisome proliferator-activated receptor gamma. Pioglitazone has been reported to protect skeletal muscle cells from lipotoxicity by promoting fatty acid mobilization and insulin signaling. However, it is unclear whether pioglitazone increases insulin sensitivity through changes in protein-protein interactions involving protein phosphatase 2A (PP2A). PP2A regulates various cell signaling pathways such as insulin signaling. Interaction of the catalytic subunit of PP2A (PP2Ac) with protein partners is required for PP2A specificity and activity. Little is known about PP2Ac partners in primary human skeletal muscle cells derived from lean insulin-sensitive (Lean) and obese insulin-resistant (OIR) participants. We utilized a proteomics method to identify PP2Ac interaction partners in skeletal muscle cells derived from Lean and OIR participants, with or without insulin and pioglitazone treatments. In this study, 216 PP2Ac interaction partners were identified. Furthermore, 26 PP2Ac partners exhibited significant differences in their interaction with PP2Ac upon insulin treatments between the two groups. Multiple pathways and molecular functions are significantly enriched for these 26 interaction partners, such as nonsense-mediated decay, metabolism of RNA, RNA binding, and protein binding. Interestingly, pioglitazone restored some of these abnormalities. These results provide differential PP2Ac complexes in Lean and OIR in response to insulin/pioglitazone, which may help understand molecular mechanisms underpinning insulin resistance and the insulin-sensitizing effects of pioglitazone treatments, providing multiple targets in various pathways to reverse insulin resistance and prevent and/or manage T2D with less drug side effects.
RESUMEN
A malignant peripheral nerve sheath tumor (MPNST) is an aggressive tumor that can arise from the malignant transformation of benign neurofibromas in patients with neurofibromatosis type 1 (NF1). MPNST occurs in 2% of patients with NF1, contributing to significant mortality in these patients. Here, we report the case of a 67-year-old female with a known history of neurofibromatosis type 1 who was referred to general surgery after the discovery of a large left-sided adrenal mass on CT imaging five months earlier. Lab workup revealed elevated urine catecholamines, concerning pheochromocytoma. As pheochromocytoma is also common in those with NF-1, appropriate medical management followed by surgical resection was performed. The final pathology report revealed an MPNST.
RESUMEN
BACKGROUND: Ventral hernia repair is a common procedure with reported 15% to 37% morbidity and 0.3% to 1.4% mortality rates. This study examines the 30-day morbidity and mortality of open and laparoscopic ventral hernia repair in veterans, along with the impact of body mass index on these outcomes. METHODS: The Veterans Affairs Surgical Quality Improvement Program was queried for all ventral hernia repairs during the period 2008 to 2015. In this retrospective analysis, we compared outcomes of open ventral hernia repair versus laparoscopic ventral hernia repair and among different body mass index classes. RESULTS: A total of 19,883 patients were identified (92.6% male, mean age 59.7, 53.1% obese, and 71.6% with American Society of Anesthesiologists class ≥III). There were 95 (0.5%) mortalities, and complications occurred in 1,289 (6.5%) patients. Open ventral hernia repair was performed in 60.2%; 14.5% were recurrent, and 3.3% were performed as an emergency operation. When compared with open ventral hernia repair, the laparoscopic ventral hernia repair group had higher mean body mass index, less patients with American Society of Anesthesiologists class ≥III, fewer emergency operations, longer operative time, less complications, decreased mortality, and shorter duration of stay. Body mass index 35.00 to 49.99 was predictive of overall complications in the open ventral hernia repair group. CONCLUSION: Ventral hernia repair can be performed in the veteran population with outcomes comparable to those in the private sector. Morbid obesity has a negative impact on ventral hernia repair outcomes that is most prominent following open surgery. Laparoscopic ventral hernia repair may offer superior outcomes when compared to open ventral hernia repair and may be considered.
