Cross-Cultural Adaptation and Validation of the Finnish Version of the Michigan Hand Outcomes Questionnaire

Background and Aims: Michigan Hand Outcomes Questionnaire is a widely used patient-reported outcome measure in hand surgery. The aim of this study was to translate and validate the Michigan Hand Outcomes Questionnaire into Finnish for Finnish patients with hand problems following international standards and guidelines. Material and Methods: The original English Michigan Hand Outcomes Questionnaire was translated into Finnish. Altogether, 115 patients completed the Finnish Michigan Hand Outcomes Questionnaire, and reference outcomes: Disabilities of the Arm and Shoulder, EQ-5D 3L and pain intensity on a visual analog scale. Grip and key pinch forces were measured. After 1-2 weeks, 63 patients completed the Finnish Michigan Hand Outcomes Questionnaire the second time. The Michigan Hand Outcomes Questionnaire was analyzed for internal consistency, repeatability, correlations with the reference outcomes, and factor analysis. Results: Cronbach's alpha ranged from 0.90 to 0.97 in all the Michigan Hand Outcomes Questionnaire subscales, showing high internal consistency. The intraclass correlation coefficient showed good to excellent test-retest reliability ranging from 0.66 to 0.91 in all the Michigan Hand Outcomes Questionnaire subscales. In factor analysis, the structure with six subscales was not confirmed. All the subscales correlated with Disabilities of the Arm and Shoulder score, and five subscales correlated with EQ-5D index. Conclusion: The Finnish version of the Michigan Hand Outcomes Questionnaire showed similar properties compared to the original English version and thus can be used as patient-reported outcome measure for Finnish patients with hand problems.Peer reviewe

Efflux Protein Expression in Human Stem Cell-Derived Retinal Pigment Epithelial Cells

Retinal pigment epithelial (RPE) cells in the back of the eye nourish photoreceptor cells and form a selective barrier that influences drug transport from the blood to the photoreceptor cells. At the molecular level, ATP-dependent efflux transporters have a major role in drug delivery in human RPE. In this study, we assessed the relative expression of several ATP-dependent efflux transporter genes (MRP1, -2, -3, -4, -5, -6, p-gp, and BCRP), the protein expression and localization of MRP1, MRP4, and MRP5, and the functionality of MRP1 efflux pumps at different maturation stages of undifferentiated human embryonic stem cells (hESC) and RPE derived from the hESC (hESC-RPE). Our findings revealed that the gene expression of ATP-dependent efflux transporters MRP1, -3, -4, -5, and p-gp fluctuated during hESC-RPE maturation from undifferentiated hESC to fusiform, epithelioid, and finally to cobblestone hESC-RPE. Epithelioid hESC-RPE had the highest expression of MRP1, -3, -4, and P-gp, whereas the most mature cobblestone hESC-RPE had the highest expression of MRP5 and MRP6. These findings indicate that a similar efflux protein profile is shared between hESC-RPE and the human RPE cell line, ARPE-19, and suggest that hESC-RPE cells are suitable in vitro RPE models for drug transport studies. Embryonic stem cell model might provide a novel tool to study retinal cell differentiation, mechanisms of RPE -derived diseases, drug testing and targeted drug therapy

Protein Trafficking or Cell Signaling : A Dilemma for the Adaptor Protein TOM1

Lysosomal degradation of ubiquitinated transmembrane protein receptors (cargo) relies on the function of Endosomal Sorting Complex Required for Transport (ESCRT) protein complexes. The ESCRT machinery is comprised of five unique oligomeric complexes with distinct functions. Target of Myb1 (TOM1) is an ESCRT protein involved in the initial steps of endosomal cargo sorting. To exert its function, TOM1 associates with ubiquitin moieties on the cargo via its VHS and GAT domains. Several ESCRT proteins, including TOLLIP, Endofin, and Hrs, have been reported to form a complex with TOM1 at early endosomal membrane surfaces, which may potentiate the role of TOM1 in cargo sorting. More recently, it was found that TOM1 is involved in other physiological processes, including autophagy, immune responses, and neuroinflammation, which crosstalk with its endosomal cargo sorting function. Alteration of TOM1 function has emerged as a phosphoinositide-dependent survival mechanism for bacterial infections and cancer progression. Based on current knowledge of TOM1-dependent cellular processes, this review illustrates how TOM1 functions in coordination with an array of protein partners under physiological and pathological scenarios.Peer reviewe

The structural validity of the Finnish version of the Disabilities of the Arm, Shoulder and Hand:a Rasch model analysis

Abstract Introduction: The construct validity of the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) has previously been questioned. The purpose of this study was to evaluate the measurement properties of the Finnish version of the DASH for assessing disability in patients with hand complaints using Rasch Measurement Theory. Methods: A cohort of 193 patients with typical hand and wrist complaints were recruited at a surgery outpatient clinic. The DASH scores were analysed using the Rasch model for differential item functioning, unidimensionality, fit statistics, item residual correlation, coverage/targeting and reliability. Results: In the original DASH questionnaire, the item response thresholds were disordered for 2 of 30 of the items. The item fit was poor for 9 of 30 of the items. Unidimensionality was not supported. There was substantial residual correlation between 87 pairs of items. Item reduction (chi square 95, degrees of freedom 50, p < 0.001) and constructing two testlets led to unidimensionality (chi square 0.64, degrees of freedom 4, p = 0.96). Person separation index was 0.95. The testlets had good fit with no differential item functioning towards age or gender. Conclusion: Unidimensionality of the original Finnish version of the DASH was not supported, meaning the questionnaire seems to gauge traits other than disability alone. Hence, the clinician must be careful when trying to measure change in patients’ scores. Item reduction or the creation of testlets did not lead to good alternatives for the original Finnish DASH. Differential item functioning showed that the original Finnish scale exhibits minor response bias by age in one item. The original Finnish DASH covers different levels of ability well among typical hand surgery patients

Smoking as risk factor for carpal tunnel syndrome:a birth cohort study

Abstract Background: Our aim was to determine whether maternal smoking and offspring’s own smoking affect the offspring’s risk for carpal tunnel syndrome (CTS). Method: The study sample consisted of the Northern Finland Birth Cohort 1966 (N = 8703). Information on maternal smoking was collected from the participants’ mothers. At 31 years, information on smoking, body mass index, socioeconomic status, and long‐term illnesses were collected, combined with data of CTS diagnoses from the Care Register for Health Care (1997–2016). Results: Maternal smoking was not associated with increased risk of CTS in offspring. Before the age of 31 years, smoking ≤10 pack years (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.11–2.15) and >10 pack years (HR = 1.90; 95% CI = 1.20–3.01) among women, and >10 pack years (HR = 1.89; 95% CI = 1.14–3.12) among men was associated with CTS compared with nonsmokers. Conclusions: In this birth cohort, offsprings’ own smoking was associated with CTS; however, maternal smoking was not