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Objectives: Hyperhidrosis in pediatric patients has been understudied. Post hoc analyses of two phase 3 randomized, vehicle-controlled, 4-week trials (ATMOS-1 [NCT02530281] and ATMOS-2 [NCT02530294]) were performed to assess efficacy and safety of topical anticholinergic glycopyrronium tosylate (GT) in pediatric patients., Methods: Patients had primary axillary hyperhidrosis ≥ 6 months, average Axillary Sweating Daily Diary (ASDD/ASDD-Children [ASDD-C]) Item 2 (sweating severity) score ≥ 4, sweat production ≥ 50 mg/5 min (each axilla), and Hyperhidrosis Disease Severity Scale (HDSS) ≥ 3. Coprimary end points were ≥ 4-point improvement on ASDD/ASDD-C Item 2 (a validated patient-reported outcome) and change in gravimetrically measured sweat production at Week 4. Efficacy and safety data are shown through Week 4 for the pediatric (≥ 9 to ≤ 16 years) vs older (> 16 years) subgroups., Results: Six hundred and ninety-seven patients were randomized in ATMOS-1/ATMOS-2 (GT, N = 463; vehicle, N = 234); 44 were ≥ 9 to ≤ 16 years (GT, n = 25; vehicle, n = 19). Baseline disease characteristics were generally similar across subgroups. GT-treated pediatric vs older patients had comparable improvements in ASDD/ASDD-C Item 2 (sweating severity) responder rate, HDSS responder rate (≥ 2-grade improvement]), sweat production, and quality of life (mean change from Baseline in Dermatology Life Quality Index [DLQI]/children's DLQI), with greater improvement vs vehicle. Treatment-emergent adverse events were similar between subgroups, and most were mild, transient, and infrequently led to discontinuation., Conclusions: Topical, once-daily GT improved disease severity (ASDD/ASDD-C, HDSS), sweat production, and quality of life (DLQI), with similar findings in children, adults, and the pooled population. GT was well tolerated, and treatment-emergent adverse events were qualitatively similar between subgroups and consistent with other anticholinergics., (© 2018 The Authors. Pediatric Dermatology Published by Wiley Periodicals, Inc.)

In the aftermath of the end-Permian mass extinction, Early Triassic sediments record some of the largest Phanerozoic carbon isotopic excursions. Among them, a global Smithian-negative carbonate carbon isotope excursion has been identified, followed by an abrupt increase across the Smithian-Spathian boundary (SSB; ~250.8 Myr ago). This chemostratigraphic evolution is associated with palaeontological evidence that indicate a major collapse of terrestrial and marine ecosystems during the Late Smithian. It is commonly assumed that Smithian and Spathian isotopic variations are intimately linked to major perturbations in the exogenic carbon reservoir. We present paired carbon isotopes measurements from the Thaynes Group (Utah, USA) to evaluate the extent to which the Early Triassic isotopic perturbations reflect changes in the exogenic carbon cycle. The δ(13) Ccarb variations obtained here reproduce the known Smithian δ(13) Ccarb -negative excursion. However, the δ(13) C signal of the bulk organic matter is invariant across the SSB and variations in the δ(34) S signal of sedimentary sulphides are interpreted here to reflect the intensity of sediment remobilization. We argue that Middle to Late Smithian δ(13) Ccarb signal in the shallow marine environments of the Thaynes Group does not reflect secular evolution of the exogenic carbon cycle but rather physicochemical conditions at the sediment-water interface leading to authigenic carbonate formation during early diagenetic processes., (© 2016 John Wiley & Sons Ltd.)

The biochemical, histological and ultrastructural effects of 2,4-dinitrophenol and the calcium ionophore, A23187, on rat soleus muscle incubated in vitro have been examined to test the hypothesis that immunohistochemical techniques can be used to recognize early structural features of fibre damage. In control muscles, despite mild glycogen depletion and a mild reduction in protein synthetic rate in the central portion of the muscle, fibres throughout the muscle appear to be viable with normal cytoskeletal and contractile protein architecture, normal concentrations of high energy phosphates and no creatine kinase efflux. Dinitrophenol causes rapid creatine kinase efflux, extensive loss of immunolabelling for desmin and dystrophin, and abnormal myosin immunolabelling. Creatine kinase efflux and the changes in desmin and dystrophin are reduced by the exclusion of calcium. A23187 causes more gradual creatine kinase efflux associated with changes in myosin immunolabelling, but loss of desmin and dystrophin immunolabelling is restricted to a few of the most peripheral fibres. The results suggest that immunohistochemical methods can be used to reveal differences in the intracellular mechanisms of muscle damage. Although both dinitrophenol and A23187 may act, in part, through calcium-mediated processes, their effects on cytoskeletal proteins differ. Creatine kinase efflux after A23187 may not be due to gross sarcolemmal damage.