Differential Regulation of RGS-2 by Constant and Oscillating PTH Concentrations

PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system. PTH was administered intermittently (4 min/h, 10⁻⁷ M) or continuously at an equivalent cumulative dose (6.6 × 10⁻⁹ M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor. In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13 and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling.     

Onychomycosis caused by Fusarium solani in a woman with diabetes

A case of untreated fusarial onychomycosis leading to serious consequences is reported. Fusarium solani is a widespread fungus and an occasional human pathogen. It usually invades rapidly in immunocompromised hosts, and often results in a poor outcome despite treatment. We report a woman with diabetes mellitus who had untreated fusarial infection of the nails, which developed into subcutaneous fusariosis, superinfected by bacteria, and then evolved into osteomyelitis that subsequently resulted in septic shock. Early management of mycotic nails in immunocompromised hosts is crucial to prevent life‐threatening disease.     

Functioning and disability 6–15 years after traumatic brain injuries in northern Sweden

Objectives –  To assess long‐term functioning and disability after traumatic brain injury (TBI). Material and methods –  Individuals (n = 88) in Norrbotten, northern Sweden, who had been transferred for neurosurgical care were assessed with internationally established TBI outcome measures 6–15 years post‐injury. Results –  There was an improvement in overall outcome from discharge from inpatient rehabilitation to follow‐up. Many individuals had a high degree of motor and cognitive functioning, which enabled them to live independently in their own home without assistance, but there remained a disability related to community reintegration and social participation. This affected their productivity and to some degree their marital stability. The remaining disability and reduced productivity were related to the age at injury and the injury severity. Conclusions –  Our data showed that individuals with a TBI can achieve and maintain a high degree of functioning many years after the injury. Increasing age and a greater injury severity contributed to their long‐term disability.