Prior Treatment with AICAR Causes the Selective Phosphorylation of mTOR Substrates in C2C12 Cells.

Metabolic stress in skeletal muscle cells causes sustained metabolic changes, but the mechanisms of the prolonged effects are not fully known. In this study, we tested C2C12 cells with the AMP-activated protein kinase (AMPK) stimulator AICAR and measured the changes in the metabolic pathways and signaling kinases. AICAR caused an acute increase in the phosphorylation of the AMPK target ULK1, the mTORC1 substrate S6K, and the mTORC2 target Akt. Intriguingly, prior exposure to AICAR only decreased glucose-6 phosphate dehydrogenase activity when it underwent three-hour recovery after exposure to AICAR in a bicarbonate buffer containing glucose (KHB) instead of Dulbecco's Minimum Essential Medium (DMEM). The phosphorylation of the mTORC1 target S6K was increased after recovery in DMEM but not KHB, although this appeared to be specific to S6K, as the phosphorylation of the mTORC1 target site on ULK1 was not altered when the cells recovered in DMEM. The phosphorylation of mTORC2 target sites was also heterogenous under these conditions, with Akt increasing at serine 473 while other targets (SGK1 and PKCα) were unaffected. The exposure of cells to rapamycin (an mTORC1 inhibitor) and PP242 (an inhibitor of both mTOR complexes) revealed the differential phosphorylation of mTORC2 substrates. Taken together, the data suggest that prior exposure to AICAR causes the selective phosphorylation of mTOR substrates, even after prolonged recovery in a nutrient-replete medium.

Quite a Pickle: A 10-Year Increase in Pickleball-Related Hand Injuries.

BACKGROUND: Pickleball popularity has significantly increased in the United States. Wrist, hand, and finger injuries are commonly seen among pickleball players and are on the rise. METHODS: The National Electronic Injury Surveillance System database was queried from 2013 to 2022 tennis- and pickleball-related injuries in the United States. Data were filtered to include wrist, hand, and finger injuries only. RESULTS: There were a total of 12 021 estimated pickleball injuries between 2013 and 2022, most commonly in white women greater than 55 years old. The most common mechanism of injury (90.5%) was a fall. The number of injuries increased by 765.6% between 2013 and 2022. The growth in the number of pickleball-related injuries was found to be statistically significant (P < .05), whereas the growth for tennis-related injuries was found to be not statistically different from 0. There was a statistical difference between the growth of the number of pickleball injuries per year and the number of tennis injuries. The wrist was the most common location of injury (70.0%) compared with the hand (10.5%) and fingers (19.5%). The most common injury diagnosis was fracture (60.3%). Overall, the most common injury was wrist fracture (50.0%). CONCLUSIONS: Hand surgeons should be aware of the increasing prevalence of pickleball-related injuries as an alternative mechanism of injury, particularly among the elderly.

Complex surgical reconstruction for spinopelvic instability caused by a giant Tarlov cyst eroding the sacrum: A case report.

Background: Tarlov cysts (TC), also known as perineural cysts are meningeal dilations of the posterior nerve root sheath that typically affect sacral nerve roots. TC are usually asymptomatic and found incidentally. We present the case of a patient with an enlarging sacral TC causing pain from spinopelvic instability secondary to extensive bone erosion. Such illustrative case is intended to increase awareness of the potential need for complex spinopelvic reconstruction in atypical instances of large TC. Case Description: A 29-year-old female presented to clinic reporting progressive bilateral sacroiliac joint pain that was essentially mechanical in nature. The patient had a normal neurological exam except for a known left drop foot with numbness in the left sural nerve distribution, both attributed to a previously resected peripheral nerve sheath tumor. Magnetic resonance imaging revealed a large multilobulated lesion with imaging characteristics consistent with TC adjacent to the left side of the sacrum, extending outward from the left S1 and S2 neural foramina and measuring 6.7 × 3.7 cm in the axial plane and and 5.6 cm in the sagittal plane. Six weeks of conservative management consisting of physical therapy and pain management was unsuccessful, and the patient reported worsening pain. Surgical reconstruction consisting of L5-S1 transforaminal lumbar interbody fusion, L4 to pelvis navigation-guided instrumentation and posterolateral fusion, and bilateral sacroiliac joint fusion was successfully performed. Outcomes: At 12 weeks follow-up appointment after surgery, the patient reported resolution of sacroiliac mechanical pain. Conclusions: Sacral TC are asymptomatic in their vast majority of cases but may occasionally cause neurological deficits secondary to mass effect. Rarely, however, giant TC can also lead to significant bone erosion or the sacrum with secondary spinopelvic instability. In this brief report, we describe a giant TC generating significant spinopelvic instability, which was successfully treated with complex spinopelvic reconstruction, leading to complete resolution of the reported axial mechanical pain.

Blast-Related Traumatic Brain Injuries Secondary to Thermobaric Explosives: Implications for the War in Ukraine.

Blast-related traumatic brain injury (bTBI) is a significant cause of wartime morbidity and mortality. In recent decades, thermobaric explosives have emerged as particularly devastating weapons associated with bTBI. With recent documentation of the use of these weapons in the war in Ukraine, clinicians and laypersons alike could benefit from an improved understanding behind the dynamic interplay between explosive weaponry, its potential for bTBI, and the subsequent long-term consequences of these injuries. Therefore, we provide a general overview of the history and mechanism of action of thermobaric weapons and their potential to cause bTBI. In addition, we highlight the long-term cognitive and neuropsychiatric sequelae following bTBI and discuss diagnostic, therapeutic, and rehabilitation strategies, with the aim of helping to guide mitigation strategies and humanitarian relief in Ukraine. Thermobaric weapons produce a powerful blast wave capable of causing bTBIs, which can be further classified from primary to quaternary injuries. When modeling the hypothetical use of thermobaric weapons in Odessa, Ukraine, we estimate that the detonation of a salvo of thermobaric rockets has the potential to affect approximately 272 persons with bTBIs. In addition to the short-term damage, patients with bTBIs can present with long-term symptoms (e.g., post-traumatic stress disorder), which incur substantial financial costs and social consequences. Although these results are jarring, history has seen radical advancements in the understanding, diagnosis, and management of bTBI. Moving forward, a better understanding of the mechanism and long-term sequelae of bTBIs could help guide humanitarian relief to those affected by the war in Ukraine.