Foot Function Index for Arabic-speaking patients (FFI-Ar): translation, cross-cultural adaptation and validation study.

BACKGROUND: Foot Function Index (FFI) is a valid and reliable outcome measure, which is widely used to measure the foot and ankle functional level and disorders. Until now, no validated Arabic version of the FFI is available. This study was conducted at a tertiary care hospital in Riyadh, Saudi Arabia. The purpose of this project was to translate and adapt the FFI into Arabic and to evaluate its psychometric properties of validity and reliability. METHODS: The study consisted of two phases. The first phase was the translation and cultural adaptation of the FFI to Arabic. The next phase involved, testing the psychometric properties of the Arabic version of the FFI on a sample of 50 consecutive participants which included internal consistency, test-retest reliability, floor and ceiling effects and construct validity. RESULTS: The mean age of the study participants was 38 ± 12.94 years. Both the genders were evenly enrolled with 50% of the participants as male and 50% as female. Majority of them complained of plantar fasciopathy (32%) followed by pes planus (22%) and ankle sprain (18%). The scores of FFI-Ar were normally distributed, confirmed by a significant Shapiro-Wilk test. The mean value of FFI-Ar total score was 47.73 ± 19.85. There were no floor or ceiling effects seen in any of the subscales and total score. The internal consistency was good with the Cronbach's alpha value of 0.882, 0.936 and 0.850 for the pain, disability and activity limitation subscales, respectively. The reproducibility of the FFI-Ar was analysed by intra-class correlation coefficient which revealed good to excellent test-retest reliability. A significant correlation was found between FFI-Ar and SF-36 and numeric rating scale (NRS) confirming its construct validity. CONCLUSION: The FFI-Arabic version showed good validity and reliability in patients with foot and ankle problems. This tool can be used in usual practice and research for analysing foot and ankle disorders in Arabic-speaking people.

Evaluation and validation of a robust single cell RNA-amplification protocol through transcriptional profiling of enriched lung cancer initiating cells.

BACKGROUND: Although profiling of RNA in single cells has broadened our understanding of development, cancer biology and mechanisms of disease dissemination, it requires the development of reliable and flexible methods. Here we demonstrate that the EpiStem RNA-Amp™ methodology reproducibly generates microgram amounts of cDNA suitable for RNA-Seq, RT-qPCR arrays and Microarray analysis. RESULTS: Initial experiments compared amplified cDNA generated by three commercial RNA-Amplification protocols (Miltenyi µMACS™ SuperAmp™, NuGEN Ovation® One-Direct System and EpiStem RNA-Amp™) applied to single cell equivalent levels of RNA (25-50 pg) using Affymetrix arrays. The EpiStem RNA-Amp™ kit exhibited the highest sensitivity and was therefore chosen for further testing. A comparison of Affymetrix array data from RNA-Amp™ cDNA generated from single MCF7 and MCF10A cells to reference controls of unamplified cDNA revealed a high degree of concordance. To assess the flexibility of the amplification system single cell RNA-Amp™ cDNA was also analysed using RNA-Seq and high-density qPCR, and showed strong cross-platform correlations. To exemplify the approach we used the system to analyse RNA profiles of small populations of rare cancer initiating cells (CICs) derived from a NSCLC patient-derived xenograft. RNA-Seq analysis was able to identify transcriptional differences in distinct subsets of CIC, with one group potentially enriched for metastasis formation. Pathway analysis revealed that the distinct transcriptional signatures demonstrated in the CIC subpopulations were significantly correlated with published stem-cell and epithelial-mesenchymal transition signatures. CONCLUSIONS: The combined results confirm the sensitivity and flexibility of the RNA-Amp™ method and demonstrate the suitability of the approach for identifying clinically relevant signatures in rare, biologically important cell populations.

Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer.

Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor with early dissemination and dismal prognosis, accounts for 15-20% of lung cancer cases and ∼200,000 deaths each year. Most cases are inoperable, and biopsies to investigate SCLC biology are rarely obtainable. Circulating tumor cells (CTCs), which are prevalent in SCLC, present a readily accessible 'liquid biopsy'. Here we show that CTCs from patients with either chemosensitive or chemorefractory SCLC are tumorigenic in immune-compromised mice, and the resultant CTC-derived explants (CDXs) mirror the donor patient's response to platinum and etoposide chemotherapy. Genomic analysis of isolated CTCs revealed considerable similarity to the corresponding CDX. Most marked differences were observed between CDXs from patients with different clinical outcomes. These data demonstrate that CTC molecular analysis via serial blood sampling could facilitate delivery of personalized medicine for SCLC. CDXs are readily passaged, and these unique mouse models provide tractable systems for therapy testing and understanding drug resistance mechanisms.