Effects of interleukin-15 on autophagy regulation in the skeletal muscle of mice.

This study aimed to evaluate the role of skeletal muscle-derived interleukin (IL)-15 in the regulation of skeletal muscle autophagy using IL-15 knockout (KO) and transgenic (TG) mice. Male C57BL/6 wild-type (WT), IL-15 KO, and IL-15 TG mice were used in this study. Changes in muscle mass, forelimb grip strength, succinate dehydrogenase (SDH) activity, gene and protein expression levels of major regulators and indicators of autophagy, comprehensive gene expression, and DNA methylation in the gastrocnemius muscle were analyzed. Enrichment pathway analyses revealed that the pathology of IL-15 gene deficiency was related to the autophagosome pathway. Moreover, although IL-15 KO mice maintained gastrocnemius muscle mass, they exhibited a decrease in autophagy induction. IL-15 TG mice exhibited a decrease in gastrocnemius muscle mass and an increase in forelimb grip strength and SDH activity in skeletal muscle. In the gastrocnemius muscle, the ratio of phosphorylated adenosine monophosphate-activated protein kinase α (AMPKα) to total AMPKα and unc-51-like autophagy activating kinase 1 and Beclin1 protein expression were higher in the IL-15 TG group than in the WT group. IL-15 gene deficiency induces a decrease in autophagy induction. In contrast, IL-15 overexpression could improve muscle quality by activating autophagy induction while decreasing muscle mass. The regulation of IL-15 in autophagy in skeletal muscles may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.NEW & NOTEWORTHY IL-15 gene deficiency can decrease autophagy induction. However, although IL-15 overexpression induced a decrease in muscle mass, it led to an improvement in muscle quality. Based on these results, understanding the role of IL-15 in regulating autophagy pathways within skeletal muscle may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.

A Three-Dimensional Anterior and Middle Cranial Fossa Model for Skull Base Surgical Training with Two Layers of the Colored Dura Mater.

BACKGROUND: Adequate epidural procedures and anatomical knowledge are essential for the technical success of skull base surgery. We evaluated the usefulness of our three-dimensional (3D) model of the anterior and middle cranial fossa as a learning tool in improving knowledge of anatomy and surgical approaches, including skull base drilling and dura matter peeling techniques. METHODS: Using a 3D printer, a bone model of the anterior and middle cranial fossa was created based on multi-detector row computed tomography data, incorporating artificial cranial nerves, blood vessels, and dura mater. The artificial dura mater was painted using different colors, with 2 pieces glued together to allow for the simulation of peeling the temporal dura propria from the lateral wall of the cavernous sinus. Two experts in skull base surgery and 1 trainee surgeon operated on this model and 12 expert skull base surgeons watched the operation video to evaluate this model subtlety on a scale of 1 to 5. RESULTS: A total of 15 neurosurgeons, 14 of whom were skull base surgery expert, evaluated, scoring 4 or higher on most of the items. The experience of dural dissection and 3D positioning of important structures, including cranial nerves and blood vessels, was similar to that in actual surgery. CONCLUSIONS: This model was designed to facilitate teaching anatomical knowledge and essential epidural procedure-related skills. It was shown to be useful for teaching essential elements of skull-base surgery.

'Hook' Shape Lister Tubercle Is Associated with a Greater Incidence of Extensor Pollicis Longus Tendon Rupture after Distal Radius Fracture.

Background: A rupture of the extensor pollicis longus (EPL) tendon located close to the Lister tubercle is an uncommon complication of distal radius fractures. This study aimed to determine whether the size and shape of Lister tubercle in patients with EPL rupture differs from a matched group of patients with distal radius fractures without EPL rupture. Methods: We identified 15 patients with EPL rupture (3.5%) out of 426 with distal radius fractures treated conservatively at our hospital over 4 years. Out of the remaining 411 patients with distal radius fractures without EPL rupture, we selected patients using simple random sampling and pseudo-randomised them such that their age, sex and fracture type were matched with patients exhibiting EPL rupture. The size and shape of the Lister tubercle and the size of the EPL groove were measured in both groups using computed tomographic scans and compared. Results: There was no difference in the size of the Lister tubercle or the EPL groove between both groups. A 'hook'-shaped Lister tubercle was noted in 8 out of 15 patients with EPL rupture but in only 1 out of 15 matched patients without EPL rupture. Conclusions: A 'hook'-shaped Lister tubercle was seen more often in patients with EPL rupture following distal radius fracture. Level of Evidence: Level III (Therapeutic).

Differential effects of pre-exercise on cancer cachexia-induced muscle atrophy in fast- and slow-twitch muscles.

We hypothesized that pre-exercise may effectively prevent cancer cachexia-induced muscle atrophy in both fast- and slow-twitch muscle types. Additionally, the fast-twitch muscle may be more affected by cancer cachexia than slow-twitch muscle. This study aimed to evaluate the effects of pre-exercise on cancer cachexia-induced atrophy and on atrophy in fast- and slow-twitch muscles. Twelve male Wistar rats were randomly divided into sedentary and exercise groups, and another 24 rats were randomly divided into control, pre-exercise, cancer cachexia induced by intraperitoneal injections of ascites hepatoma AH130 cells, and pre-exercise plus cancer cachexia groups. We analyzed changes in muscle mass and in gene and protein expression levels of major regulators and indicators of muscle protein degradation and synthesis pathways, angiogenic factors, and mitochondrial function in both the plantaris and soleus muscles. Pre-exercise inhibited muscle mass loss, rescued protein synthesis, prevented capillary regression, and suppressed hypoxia in the plantaris and soleus muscles. Pre-exercise inhibited mitochondrial dysfunction differently in fast- and slow-twitch muscles. These results suggested that pre-exercise has the potential to inhibit cancer-cachexia-induced muscle atrophy in both fast- and slow-twitch muscles. Furthermore, the different progressions of cancer-cachexia-induced muscle atrophy in fast- and slow-twitch muscles are related to differences in mitochondrial function.

Preventive effects of medium-chain triglycerides supplementation on the oxidative capacity in skeletal muscle under cachectic condition.

Cachexia is a multifactorial condition characterized by muscle mass loss and induces metabolic dysfunction of the skeletal muscles. The preventive effects of medium-chain triglycerides (MCT) supplementation on the oxidative capacity in skeletal muscle under cachectic condition were investigated in the present study. ICR mice were randomly divided into four groups; control, lipopolysaccharide (LPS), LPS plus long-chain triglycerides (LCT) and LPS plus MCT supplementation. LCT and MCT oil were administered to the LPS + LCT and LPS + MCT groups orally (5.0 g/kg body weight/day) by a catheter for one week. Cachexia was induced in the LPS, LPS + LCT, and LPS + MCT groups via LPS injection (7.5 mg/kg body weight, i.p.) after the supplementation. LPS induced a reduction of ketone bodies concentration in blood plasma. LPS also induced a decrease in succinate dehydrogenase activity and PGC-1α expression level in tibialis anterior muscles. Meanwhile, MCT supplementation suppressed a decrease in ketone bodies concentration and succinate dehydrogenase activity. In addition, MCT supplementation increased the level of citrate synthase activity in the muscles. These results suggested the preventive effect of MCT supplementation on oxidative capacity in skeletal muscle and the involvements of ketone bodies regulation under cachectic condition.

Nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy mimicking rapid-onset Guillain-Barré syndrome: a case report.

Nivolumab, an anti-programmed death-1-specific monoclonal antibody, has demonstrated a durable response and effect on overall survival and has become one of the standard treatments for patients with advanced melanoma. Reported herein is a case of nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy, in which an 85-year-old woman with stage IV melanoma developed grade 1 paresthesia 2 weeks after the initial dose of nivolumab was administered. With continued treatment, the neurological deficiency deteriorated rapidly, mimicking Guillain-Barré syndrome, causing such a dramatic decrease in her activities of daily living that she could no longer function in daily life. Thus, nivolumab treatment was discontinued. A course of intravenous immunoglobulin infusion yielded a dramatic clinical improvement; in particular, improved motor control was observed within a few days. Her initial presentation was suggestive of acute inflammatory demyelinating polyradiculoneuropathy, a subtype of Guillain-Barré syndrome; however, the good response to steroids and exacerbation 8 weeks after the onset were suggestive of chronic inflammatory demyelinating polyradiculoneuropathy induced by nivolumab. This is the first case of Guillain-Barré syndrome-like autoimmune polyradiculoneuropathy induced by programmed death-1/programmed death-ligand 1 inhibitors. Although neurological adverse events related to nivolumab are rare, they can become severe, requiring early diagnosis and intervention. Intravenous immunoglobulin may be considered as an effective initial treatment for patients who develop acute autoimmune nervous system disorders due to nivolumab.