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Parkinson's Disease (PD) is the second most common neurodegenerative disease worldwide, affecting 1 % of the population over 65 years of age. Dopaminergic cell death in the substantia nigra and accumulation of Lewy bodies are the defining neuropathological hallmarks of the disease. Neuronal death and dysfunction have been reported in other central nervous system regions, including the retina. Symptoms of PD typically manifest only when more than 70 % of dopaminergic cells are lost, and the definitive diagnosis of PD can only be made histologically at post-mortem, with few biomarkers available.In this study, a rotenone-induced rodent model of PD was employed to investigate retinal manifestations in PD and their usefulness in assessing the efficacy of a novel therapeutic intervention with a liposomal formulation of the PPAR-γ (Peroxisome proliferator-activated receptor gamma) agonist rosiglitazone.Retinal assessment was performed using longitudinal in vivo imaging with DARC (detection of apoptosing retinal cells) and OCT (optical coherence tomography) technologies and revealed increased RGCs (Retinal Ganglion Cells) apoptosis and a transient swelling of the retinal layers at day 20 of the rotenone insult. Follow-up of this model demonstrated characteristic histological neurodegenerative changes in the substantia nigra and striatum by day 60, suggesting that retinal changes precede the "traditional" pathological manifestations of PD. The therapeutic effect of systemic administration of different formulations of rosiglitazone was then evaluated, both in the retina and the brain. Of all treatment regimen tested, sustained release administration of liposome-encapsulated rosiglitazone proved to be the most potent therapeutic strategy, as evidenced by its significant neuroprotective effect on retinal neurons at day 20, and on nigrostriatal neurons at day 60, provided convincing evidence for its potential as a treatment for PD.Our results demonstrate significant retinal changes occurring in this model of PD. We show that rosiglitazone can efficiently protect retinal neurons from the rotenone insult, and that systemic administration of liposome-encapsulated rosiglitazone has an enhanced neuroprotective effect on the retina and CNS (Central Nervous System). To our knowledge, this is the first in vivo evidence of RGCs loss and early retinal thickness alterations in a PD model. Together, these findings suggest that retinal changes may be a good surrogate biomarker for PD, which may be used to assess new treatments both experimentally and clinically. ispartof: Acta Neuropathologica Communications vol:4 issue:86 pages:1-15 ispartof: location:England status: published

Background: Pyoderma gangrenosum is a neutrophilic dermatosis of unknown etiology, with inconstant systemic associations and a variable prognosis. Aims: To study the clinical features and systemic associations of pyoderma gangrenosum and its response to treatment. Methods: All patients diagnosed to have pyoderma gangrenosum at the dermatology department of the Government Medical College, Kozhikode, from January 01, 2005 to December 31, 2014 were included in this prospective study. Results: During the 10-year study period, 61 patients were diagnosed to have pyoderma gangrenosum. A male predilection was noted. The most common clinical type was ulcerative pyoderma gangrenosum (90.2%). More than 60% of patients had lesions confined to the legs; 78.7% had a single lesion and 27.9% had systemic associations. Most patients required systemic steroids. Patients with disease resistant to steroid therapy were treated with intravenous immunoglobulin G and split-thickness skin grafts under immunosuppression induced by dexamethasone pulse therapy. All except one patient attained complete disease resolution. Limitations: The main limitation of our study was the small sample size. Conclusions: The male predilection documented by us was contrary to most previous studies. We found split-thickness skin graft to be a useful option in resistant cases. More prospective studies may enable the formulation of better diagnostic criteria for pyoderma gangrenosum and improve its management.

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We consider a MIMO fading broadcast channel and compare the achievable ergodic rates when the channel state information at the transmitter is provided by analog noisy feedback or by quantized (digital) feedback. The superiority of digital feedback is shown, with perfect or imperfect CSIR, whenever the number of feedback channel uses per channel coefficient is larger than 1. Also, we show that by proper design of the digital feedback link, errors in the feedback have a minor effect even by using very simple uncoded modulation. Finally, we show that analog feedback achieves a fraction 1 - 2F of the optimal multiplexing gain even in the presence of a feedback delay, when the fading belongs to the class of Doppler processes with normalized maximum Doppler frequency shift 0, Submitted to ISIT, January 2007. 5 pages