The pathological hallmarks of Parkinson's disease (PD) are degeneration of dopamine (DA) neurons of the substantia nigra (SN) and the presence of alpha-synuclein (α-syn)-rich Lewy bodies in DA cells that remain. To model these aspects of the disease, we previously showed that high titer (5.1×10exp12 gp/ml) AAV1/2 driven expression of A53T α-syn in the SN of rats caused nigrostriatal pathology including a loss of DA neurons, but also with toxicity in the GFP control group. In the current study, we evaluate the effects of two lower titers by dilution of the vector (1∶3 [1.7×10exp12] and 1∶10 [5.1×10exp11]) to define a concentration that produced pathology specific for α-syn. In GFP and empty vector groups there were no behavioural or post-mortem changes at 3 or 6 weeks post-administration at either vector dose. Dilution of the AAV1/2 A53T α-syn (1∶3) produced significant paw use asymmetry, reductions in striatal tyrosine hydroxylase (TH), and increases in DA turnover at 3 weeks in the absence of overt pathology. By 6 weeks greater evidence of pathology was observed and included, reductions in SN DA neurons, striatal DA, TH and DA-transporter, along with a sustained behavioural deficit. In contrast, the 1∶10 AAV1/2 A53T α-syn treated animals showed normalization between 3 and 6 weeks in paw use asymmetry, reductions in striatal TH, and increased DA turnover. Progression of dopaminergic deficits using the 1∶3 titer of AAV1/2 A53Tα-syn provides a platform for evaluating treatments directed at preventing and/or reversing synucleinopathy. Use of the 1∶10 titer of AAV1/2 A53T α-syn provides an opportunity to study mechanisms of endogenous compensation. Furthermore, these data highlight the need to characterize the titer of vector being utilized, when using AAV to express pathogenic proteins and model disease process, to avoid producing non-specific effects.

No abstract

No abstract

Inappropriate antibiotic prescriptions are associated with an increase in healthcare costs and a decrease in the quality of care. The aim of this study was to measure the clinical and economic impact of rapid microbiological reporting on the specimens most frequently processed by the Microbiology Laboratory. The Vitek® 2 system (bioMérieux) was used for identification and susceptibility testing. Only hospitalized patients with bacterial infections were included. Two groups were established, a historical control group (results available the day following the analysis) and an intervention group (results available the same day of the analysis). Specimens studied and the median length of time from the introduction of the microorganism in the Vitek® 2 until microbiological report were as follows: wound and abscess (control = 23.5 h, intervention = 9.5 h, p < 0.001), blood (control = 23.5 h, intervention = 9.2 h, p < 0.001), and urine (control = 23.4 h, intervention = 9.3 h, p < 0.001). Outcome parameters were hospital stay and mortality rates. Hospital costs were calculated. The mortality rates did not differ significantly between the two groups. Faster reporting of identification and antimicrobial susceptibility results was associated with a significant reduction in hospital stay and in overall costs for those patients from whom wound, abscess, and urine specimens were analyzed. However, the antimicrobial results of blood culture isolates did not lead to significant clinical or financial benefits.