Nuclear receptor interaction protein (NRIP, also known as DCAF6 and IQWD1) is a Ca 2+ -dependent calmodulin-binding protein.In this study, we newly identify NRIP as a Z-disc protein in skeletal muscle. NRIP-knockout mice were generated and found to have reduced muscle strength, susceptibility to fatigue and impaired adaptive exercise performance. The mechanisms of NRIP-regulated muscle contraction depend on NRIP being downstream of Ca 2+ signaling, where it stimulates activation of both 'calcineurin-nuclear factor of activated T-cells, cytoplasmic 1' (CaN-NFATc1; also known as NFATC1) and calmodulin-dependent protein kinase II (CaMKII) through interaction with calmodulin (CaM), resulting in the induction of mitochondrial activity and the expression of genes encoding the slow class of myosin, and in the regulation of Ca 2+ homeostasis through the internal Ca 2+ stores of the sarcoplasmic reticulum. Moreover, NRIP-knockout mice have a delayed regenerative capacity. The amount of NRIP can be enhanced after muscle injury and is responsible for muscle regeneration, which is associated with the increased expression of myogenin, desmin and embryonic myosin heavy chain during myogenesis, as well as for myotube formation. In conclusion, NRIP is a novel Z-disc protein that is important for skeletal muscle strength and regenerative capacity.

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BackgroundNuclear receptor interaction protein (NRIP) is a calcium/calmodulin (CaM) binding protein. Nuclear receptor interaction protein interacts with CaM to activate calcineurin and CaMKII signalling. The conventional NRIP knockout mice (global knockout) showed muscular abnormality with reduction of muscle oxidative functions and motor function defects.MethodsTo investigate the role of NRIP on neuromuscular system, we generated muscle‐restricted NRIP knockout mice [conditional knockout (cKO)]. The muscle functions (including oxidative muscle markers and muscle strength) and lumbar motor neuron functions [motor neuron number, axon denervation, neuromuscular junction (NMJ)] were tested. The laser‐captured microdissection at NMJ of skeletal muscles and adenovirus gene therapy for rescued effects were performed.ResultsThe cKO mice showed muscular abnormality with reduction of muscle oxidative functions and impaired motor performances as global knockout mice. To our surprise, cKO mice also displayed motor neuron degeneration with abnormal architecture of NMJ. Specifically, the cKO mice revealed reduced motor neuron number with small neuronal size in lumbar spinal cord as well as denervating change, small motor endplates, and decreased myonuclei number at NMJ in skeletal muscles. To explore the mechanisms, we screened various muscle‐derived factors and found that myogenin is a potential candidate that myogenin expression was lower in skeletal muscles of cKO mice than wild‐type mice. Because NRIP and myogenin were colocalized around acetylcholine receptors at NMJ, we extracted RNA from synaptic and extrasynaptic regions of muscles using laser capture microdissection and showed that myogenin expression was especially lower at synaptic region in cKO than wild‐type mice. Notably, overexpression of myogenin using intramuscular adenovirus encoding myogenin treatment rescued abnormal NMJ architecture and preserved motor neuron death in cKO mice.ConclusionsIn summary, we demonstrated that deprivation of NRIP decreases myogenin expression at NMJ, possibly leading to abnormal NMJ formation, denervation of acetylcholine receptor, and subsequent loss of spinal motor neuron. Overexpression of myogenin in cKO mice can partially rescue abnormal NMJ architecture and motor neuron death. Therefore, muscular NRIP is a novel trophic factor supporting spinal motor neuron via stabilization of NMJ by myogenin expression.

ObjectiveTo investigate the association between diabetes and latent tuberculosis infections (LTBI) in high TB incidence areas.DesignCommunity-based comparison study.SettingOutpatient diabetes clinics at 4 hospitals and 13 health centres in urban and rural townships. A community-based screening programme was used to recruit non-diabetic participants.ParticipantsA total of 2948 patients with diabetes aged older than 40 years were recruited, and 453 non-diabetic participants from the community were enrolled.Primary and secondary outcome measuresThe interferon-gamma release assay (IGRA) and the tuberculin skin test were used to detect LTBI. The IGRA result was used as a surrogate of LTBI in logistic regression analysis.ResultsDiabetes was significantly associated with LTBI (adjusted OR (aOR)=1.59; 95% CI 1.11 to 2.28) and age correlated positively with LTBI. Many subjects with diabetes also had additional risk factors (current smokers (aOR=1.28; 95% CI 0.95 to 1.71), comorbid chronic kidney disease (aOR=1.26; 95% CI 1.03 to 1.55) and history of TB (aOR=2.08; 95% CI 1.19 to 3.63)). The presence of BCG scar was protective (aOR=0.66; 95% CI 0.51 to 0.85). Duration of diabetes and poor glycaemic control were unrelated to the risk of LTBI.ConclusionThere was a moderately increased risk of LTBI in patients with diabetes from this high TB incidence area. This finding suggests LTBI screening for the diabetics be combined with other risk factors and comorbidities of TB to better identify high-risk groups and improve the efficacy of targeted screening for LTBI.

Patient: Female, 60Final Diagnosis: Acute phlegmonous esophagogastritis complicated with hypopharyngeal abscess • esophageal perforationSymptoms: Fever • painful swallowing • chest painMedication: —Clinical Procedure: Drainage • debridement • esophageal reconstructionSpecialty: SurgeryObjective:Rare diseaseBackground:Acute phlegmonous esophagogastritis is a life-threatening disease that may be combined with serious complications. We present the classical radiological and endoscopic features and treatment strategy of a middle-aged female patient suffering from acute phlegmonous esophagogastritis complicated with hypopharyngeal abscess, esophageal perforation, mediastinitis, and empyema.Case Report:A 60-year-old Taiwanese female presented at our hospital due to fever, fatigue, painful swallowing, and vague chest pain for 5 days. She had a past history of uncontrolled type 2 diabetes mellitus. On physical examination, general weakness, chest pain, odynophagia, and a fever up to 38.9°C were found. Positive laboratory findings included leukocytosis (leukocyte count of 14.58×103/μL, neutrophils 76.8%) and serum glucose 348 mg/dL (HbA1c 11.3%). A diagnosis of acute phlegmonous esophagogastritis with hypopharyngeal abscess was made based on typical computed tomography image features and clinical signs of infection. The patient received empirical antibiotic therapy initially; however, esophageal perforation with mediastinitis and empyema developed after admission. Emergency surgery with drainage and debridement was performed and antibiotics were administered. She was discharged in a stable condition on the 56th day of hospitalization. Six months later, a delayed esophageal reconstruction was performed. The patient has performed well for 9 months to date since the initial diagnosis.Conclusions:Acute phlegmonous esophagogastritis complicated with hypopharyngeal abscess and esophageal perforation is extremely rare, and requires immediate medical attention. This report serves to remind physicians of this rare entity and the potential complications that may manifest with acute phlegmonous esophagogastritis.