Although islet transplantation for individuals with type 1 diabetes has been shown to yield superior blood glucose control, it remains inadequate for long-term control. This is partly due to islet injuries and stresses that can lead to beta cell loss. Inhibition of excess IL-1b activity might minimize islet injuries, thus preserving function. The IL-1 receptor antagonist (IL-1Ra), an endogenous inhibitor of IL-1b, protects islets from cytokine-induced necrosis and apoptosis. Therefore, an imbalance between IL-1b and IL-1Ra might influence the courses of allogeneic and autoimmune responses to islets. Our group previously demonstrated that the circulating serine-protease inhibitor human alpha-1-antitrypsin (hAAT), the levels of which increase in circulation during acute-phase immune responses, exhibits anti-inflammatory and islet-protective properties, as well as immunomodulatory activity. In the present study, we sought to determine whether the pancreatic islet allograft-protective activity of hAAT was mediated by IL-1Ra induction. Our results demonstrated that hAAT led to a 2.04-fold increase in IL-1Ra expression in stimulated macrophages and that hAAT-pre-treated islet grafts exhibited a 4.851-fold increase in IL-1Ra transcript levels, which were associated with a moderate inflammatory profile. Unexpectedly, islets that were isolated from IL-1Ra-knockout mice and pre-treated with hAAT before grafting into wild-type mice yielded an increase in intragraft IL-1Ra expression that was presumably derived from infiltrating host cells, albeit in the absence of hAAT treatment of the host. Indeed, hAAT-pre-treated islets generated hAAT-free conditioned medium that could induce IL-1Ra production in cultured macrophages. Finally, we demonstrated that hAAT promoted a distinct phosphorylation and nuclear translocation pattern for p65, a key transcription factor required for IL-1Ra expression.
We examined the game characteristics of badminton and the physiological and metabolic responses in highly trained male junior players. Players from a Badminton England accredited Performance Centre (n = 10, age: 14.0 ± 1.2 y, height: 1.69 ± 0.06 m, body mass: 59.1 ± 5.0 kg) completed a 20-m shuttle run test (V˙O2max: 64 ± 7 mL·kg−1·min−1) and a simulated ability-matched competitive singles badminton game consisting of two 12-min games with a 2-min break wearing the COSMED K5 metabolic system with notational analysis. In five games, 427 points were contested with a rally time of 5.7 ± 3.7 s, a rest time of 11.2 ± 5.9 s, shots per rally of 5.6 ± 3.6, work density of 0.50 ± 0.21, an effective playing time of 32.3 ± 8.4%, and shots frequency of 1.04 ± 0.29. During badminton play, heart rate was 151 ± 12 b·min−1 (82 ± 10% of maximum heart rate), oxygen uptake was 39.2 ± 3.9 mL·kg−1·min−1 (62 ± 7% of V˙O2max), and energy expenditure was 11.2 ± 1.1 kcal·min−1 with a post-game blood lactate of 3.33 ± 0.83 mmol·L−1. Compared to adult badminton play, the physiological responses of junior badminton are lower and may be due to the shorter rally durations. Male junior badminton players should be exposed to training methodologies which include rally durations in excess of what they encounter during match play so as to develop greater consistency. Our observations on game characteristics and physiological responses during junior badminton can be used to inform training practice.
In this case report, we describe a unique long-term complication from undiagnosed mandibular osteomyelitis. A 53-year-old female who underwent a dental extraction complicated by chronic postoperative odontogenic infection and cutaneous parotid fistula formation 2 years earlier presented with acute mental status change, gradual unilateral facial nerve palsy (House-Brackmann score V), and nontraumatic dislocation of the condylar head into the middle cranial fossa. The patient's chronic mandibular osteomyelitis led to glenoid fossa erosion, middle cranial fossa penetration, and temporal lobe abscess formation. A combined middle cranial fossa approach through a burr hole placed in the squamous temporal bone near the zygomatic root and intraoral mandibular approach to ipsilateral condylar head was performed to complete partial mandibulectomy, including condylectomy. The patient was treated with 6 weeks of meropenem perioperatively. Four months after the surgery, the patient had complete resolution of skull base osteomyelitis, parotid fistula, and neurologic deficits and full recovery of facial nerve function (House-Brackmann score of I).
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