SAPFIR: A webserver for the identification of alternative protein features.

BACKGROUND: Alternative splicing can increase the diversity of gene functions by generating multiple isoforms with different sequences and functions. However, the extent to which splicing events have functional consequences remains unclear and predicting the impact of splicing events on protein activity is limited to gene-specific analysis. RESULTS: To accelerate the identification of functionally relevant alternative splicing events we created SAPFIR, a predictor of protein features associated with alternative splicing events. This webserver tool uses InterProScan to predict protein features such as functional domains, motifs and sites in the human and mouse genomes and link them to alternative splicing events. Alternative protein features are displayed as functions of the transcripts and splice sites. SAPFIR could be used to analyze proteins generated from a single gene or a group of genes and can directly identify alternative protein features in large sequence data sets. The accuracy and utility of SAPFIR was validated by its ability to rediscover previously validated alternative protein domains. In addition, our de novo analysis of public datasets using SAPFIR indicated that only a small portion of alternative protein domains was conserved between human and mouse, and that in human, genes involved in nervous system process, regulation of DNA-templated transcription and aging are more likely to produce isoforms missing functional domains due to alternative splicing. CONCLUSION: Overall SAPFIR represents a new tool for the rapid identification of functional alternative splicing events and enables the identification of cellular functions affected by a defined splicing program. SAPFIR is freely available at https://bioinfo-scottgroup.med.usherbrooke.ca/sapfir/ , a website implemented in Python, with all major browsers supported. The source code is available at https://github.com/DelongZHOU/SAPFIR .

Lead breakage and vocal cord paralysis following blunt neck trauma in a patient with vagal nerve stimulator.

Patients with medically intractable seizures who are not candidates for epilepsy surgery are left with few options. Vagal nerve stimulation therapy is often a viable alternative for these patients and can have a positive impact on quality of life. Rarely complications may occur. We report a case of mild blunt neck trauma resulting in VNS malfunction and delayed vocal cord paralysis. A systematic review of the literature on VNS malfunction, self-inflicted injuries, vagal nerve injury, and common side effects including voice changes was performed. Only a handful of relevant publications were found. Symptoms following VNS dysfunction include pain, dyspnea, and dysphonia. These symptoms are usually nonspecific, and in many cases, do not help differentiate from vagal nerve traction, lead breakage, or pulse generator malfunction. In our case, lead fracture and visible traction injury to the left vagus nerve were seen during surgical exploration. The vocal cord function completely recovered after revision of the leads. Prompt medical attention including appropriate diagnostic studies and early surgical exploration is necessary in cases of delayed vocal cord dysfunction and can help prevent long-term complications such as neuroma formation. The authors present a unique case of reversible vocal cord injury from blunt neck trauma leading to left vagus nerve damage.

Statin's cost-effectiveness: a Canadian analysis of commonly prescribed generic and brand name statins.

BACKGROUND: Generic statins may be considered as a compelling treatment option for managing dyslipidemia, due to their reduced cost, compared to their brand name equivalent. However, further assessment is needed to determine whether using a particular generic statin is more cost-effective relative to other brand-name statins. OBJECTIVE: The purpose of this study is to compare the cost-effectiveness of the most commonly prescribed statins in Canada with respect to 1) lowering low-density lipoprotein cholesterol level (LDL-C) and 2) achieving National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goal. METHODS: The study was conducted from the perspective of Canadian payers over a 1-year time horizon. Clinical data were obtained from the STELLAR trial (n=2268) in which patients received fixed doses of rosuvastatin, atorvastatin, simvastatin and pravastatin. Brand and generic drug costs were based on wholesale acquisition costs. Relative cost-effectiveness was assessed using the net monetary benefit approach (NMB), which allows probabilistic cost-effectiveness comparison of the various treatment options over a wide range of willingness-to-pay (WTP) values for a unit of clinical effect. RESULTS: Rosuvastatin 10mg was the most cost-effective statin over the largest range of WTP values. Pravastatin 10mg was cost-effective when the clinical outcomes had little or no monetary value. Rosuvastatin 20 mg was more cost-effective at the highest end of the WTP spectrum. CONCLUSION: The result of this analysis provides evidence that prescribing generic statins in Canada does not necessarily translate into the most cost-effective option for treating dyslipidemia; especially as the monetary value of 1% decrease in LDL-C or patients achieving NCEP ATP III target increases.