OBJECTIVES Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB) but little is known about the clinical characteristics of those with early disease. METHODS Radionuclide bone scans, biochemical markers of bone turnover and clinical characteristics were analysed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. RESULTS We studied 222 individuals of whom 54.9% were female with average (± sem) age of 50.1± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu which was present in 141/222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%) of which 9 (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 vs. 49.8 ± 8.9, p=0.07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years vs. 59 years, p=0.25). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalised to the upper limit of normal in each centre were higher in those with lesions (0.75 ± 0.69 vs 0.42 ± 0.29; p less then 0.0001). Similar findings were observed for other biochemical markers of bone turnover but the sensitivity of ALP and other markers in detecting lesions was poor. CONCLUSIONS Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow up of this cohort will provide important information on the natural history of early PDB and its response to treatment. This article is protected by copyright. All rights reserved.  https://www.selleckchem.com/products/jsh-23.html  This article is protected by copyright. All rights reserved.BACKGROUND Coccidioides spp are dimorphic fungi endemic to parts of the United States, Mexico, Central, and South America. Infection can cause a range of disease from self-limited acute pneumonia to severe, disseminated disease. METHODS We performed a retrospective chart review of medical records of cases of culture-proven acute coccidioidomycosis at the University of California San Diego between April 1, 2015 and December 31, 2019 and described the demographics, risk factors, and outcomes of these cases. RESULTS Over the study period, fifteen evaluable cases of culture-proven acute coccidioidomycosis were identified. Of these, 87% (13/15) had traditional risk factors for coccidioidomycosis infection while two lacked known risk factors, including one patient with cirrhosis and one with chronic hepatitis C infection. Seven of fifteen (47%) had primary coccidioidomycosis of the lungs without dissemination and 7/15 (47%) disseminated disease. Of those with disseminated disease, 6/7 (86%) had either high-risk ethnicity or blood type as their only risk factor. At 90 days, 11/15 (73%) were alive, 3/15 (20%) deceased, and 1/15 (7%) lost to follow-up. Of those not alive at 90 days, 1/3 (33%) had disseminated disease and 2/3 (67%) primary coccidioidomycosis, both on immunosuppressive therapy. DISCUSSION Coccidioides spp infection occurs in a variety of hosts with varying underlying risk factors, with the majority in our cohort overall and 86% with disseminated disease lacking traditional risk factors for invasive fungal infection other than ethnicity and/or blood phenotype. Clinicians should be aware of these non-traditional risk factors in patients with coccidioidomycosis infection. This article is protected by copyright. All rights reserved.PURPOSE To achieve high resolution in imaging of short-T2 materials and tissues by using a high-performance human-sized gradient insert with strength up to 200 mT/m and 100% duty cycle. METHODS Dedicated short-T2 methodology and hardware are used, such as the pointwise encoding time reduction with radial acquisition (PETRA) technique with modulated excitation pulses, optimized radio-frequency hardware, and a high-performance gradient insert. A theoretical analysis of actual spatial resolution and SNR is provided to support the choice of scan parameters and interpretation of the results. Imaging is performed in resolution phantoms, animal specimen, and human volunteers at both conventional and maximum available gradient strengths and compared using image subtraction. RESULTS Calculations suggest that increasing gradient strength beyond conventional values considerably improves both actual resolution and SNR efficiency in short-T2 imaging. Resolution improvements are confirmed in all investigated samples, in particular 2 mm slots were resolved in a hard-plastic plate with T2 ≈ 10 μs and in vivo musculoskeletal images were acquired at isotropic 200 μm resolution. Expected improvements in signal yield are realized in fine structures benefitting from high resolution but to less extent in regions of low contrast where decay-related blurring leads to signal overlap between neighboring locations. CONCLUSION Strong gradients with high duty cycle enable short-T2 imaging at unprecedentedly high resolution, holding the potential for improving MRI of, eg, bone, tendon, lung, or teeth. Moreover, it allows direct access of tissues with T2 of tens of microseconds such as myelin or collagen. © 2020 International Society for Magnetic Resonance in Medicine.WHAT IS KNOWN AND OBJECTIVE Exenatide is widely used in the treatment of type 2 diabetes mellitus (T2DM) because of its established effect on lowering glucose and promotion of weight loss. However, therapeutic response to exenatide varies considerably among patients with T2DM. The purpose of this study was to determine which variables can predict the response to exenatide and to individualize specific therapies for patients with T2DM who need treatment with exenatide. METHODS This is a retrospective cohort study of patients with T2DM who were treated with exenatide twice daily as a part of their diabetes care for at least 12 months. Patients were categorized into two cohorts based on glycaemic response to exenatide use responders and non-responders. RESULTS AND DISCUSSION One hundred forty-eight patients met the inclusion criteria; among them, 92 responded with an HbA1C reduction ≥1.0% from baseline HbA1C and 56 did not respond to exenatide after 6 months of exenatide treatment. Binary logistic regression analysis revealed that baseline HbA1C and duration of diabetes were identified as predictors of HbA1C reduction ≥1% at 6 months (P 15.