Published by Elsevier Ltd. All rights reserved.”
“Objective To

investigate if inflammatory stress increases intracellular accumulation of unmodified low-density lipoprotein (LDL) in human monocyte cell line (THP-1) macrophages by disrupting the sterol regulatory element binding proteins (SREBPs) cleavage-activating protein (SCAP)-SREBP2-mediated feedback regulation of LDL receptor.\n\nMaterials and methods THP-1 macrophages were incubated in serum-free p38 MAPK inhibitors clinical trials medium in the absence or presence of LDL alone, LDL plus lipopolysaccharide (LPS) and LPS alone, then intracellular cholesterol content, tumor necrosis factor alpha level in the supernatants, mRNA and protein expression of LDL receptor, and SREBP2 and SCAP in the treated cells were assessed by Oil

Red O staining, cholesterol enzymatic assay, enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and Western blotting analysis, respectively.\n\nResults We demonstrated that LPS enhanced transformation of THP-1 macrophages into foam cells by increased uptake of unmodified LDL as evidenced by Oil Red O staining and direct assay of intracellular cholesterol. In the absence of LPS, 25 mu g/ml LDL decreased LDL receptor mRNA and selleck screening library protein expression (p < 0.05). However, LPS enhanced LDL receptor expression, overcoming the suppression of LDL receptor induced by 25 mu g/ml LDL and inappropriately increasing LDL uptake (p < 0.05). Exposure to LPS also caused overexpression of mRNA and protein of SCAP and SREBP2 (p click here < 0.05). These observations indicate that LPS disrupts cholesterol-mediated LDL receptor feedback regulation, permitting intracellular accumulation of unmodified LDL and causing foam-cell formation.\n\nConclusion The implication of these findings is that inflammatory stress may contribute to intracellular LDL accumulation in THP-1 macrophages without previous modification of LDL.”
“The Inhibitor of Apoptosis Proteins

(IAPs) are important regulators of programmed cell death. XIAP is the most potent among them and is over-expressed in several hematological malignancies. Its activity is endogenously antagonized by SMAC/DIABLO, and also by small molecules mimicking Smac that can induce apoptosis in tumor cells. Here we describe the activity of 56 newly synthesized Smac-mimetics in human leukemic cell lines and normal CD34(+) progenitor cells. Our compounds bind to XIAP with high affinity, reduce the levels of cIAP1 and are cytotoxic at nanomolar or low micromolar concentrations. Furthermore, the Smac-mimetics synergize with Cytarabine, Etoposide and especially with TRAIL in combination treatments. Apoptosis activation was clearly detectable by the occurrence of sub G(1) apoptotic peak and the accumulation of cleaved PARP, caspase 8 and caspase 3. Interestingly, the down-regulation of XIAP sensitized Jurkat cells to drugs too, confirming the role of this protein in drug-resistance.

“
“Soda-anthraquinone kenaf bast pulp (12.5 kappa number and 32% ISO brightness) has been bleached with multi stage peroxide bleaching process.

Bleaching process was carried out in different sequences of peroxide stage without and with activator (tetraacetylethylenediamine, TAED) to about check details 80% ISO brightness. Full bleached pulp production with high brightness and viscosity and also, low chemical oxygen demand (COD) and no adsorbable organic halogens (AOX) in effluent are the aims of this study. The effects of temperature, retention time, chemical charges, TAED/peroxide ratio and alkalinity have been studied in order to maximize the brightness gain at the lowest viscosity loss. H2O2 was activated as bleaching agent under milder conditions, such as low alkalinity or low temperature, by TAED activator. Therefore, TAED charge

caused to an improvement in viscosity, pulp yield and effluent COD load. Pre-treatment with EDTA for 30 min and in acidic condition gave 2-4% gain in ISO brightness. (C) 2012 Elsevier Ltd. All rights reserved.”
“Background & Aims:Toll-like receptors (TLRs) are critical to innate immune responses. TLR4 recognises Gram-negative bacteria, whilst TLR2 recognises Gram-positive. We examined TLR expression and function in cirrhosis, and whether this is affected by antibiotic therapy.\n\nMethods: Sixty-four subjects were included (23 controls and 41 Child-Pugh C cirrhotic patients). Thirty patients were taking find more norfloxacin or trimethoprim-sulfamethoxazole as prophylaxis

against bacterial peritonitis and 11 were not. In a second study, 8 patients were examined before and after commencement of antibiotics. Monocyte expression of TLR2 and 4 was determined by How cytometry. Monocytes from the patients with paired samples were stimulated using TLR ligands and TNF-alpha production measured.\n\nResults: Patients not taking antibiotics had significantly decreased TLR4 expression compared with controls (0.74 vs. 1.0, p = 0.009) selleck products and patients receiving antibiotics (0.74 vs. 0.98, p = 0.02). There were no differences with regard to TLR2. In the patients with paired samples, TLR4 expression increased (0.74-1.49, p = 0.002) following antibiotic use, whilst again, there was no change in TLR2 expression (0.99 vs. 0.92, p = 0.20). TLR4-dependent TNF-alpha production increased following antibiotic use (1077 vs. 3620 pg/mL, p < 0.05), whilst TLR2-dependent production was unchanged.\n\nConclusions: TLR4 expression is decreased in patients with Child-Pugh C cirrhosis, but is restored by antibiotics targeting enteric Gram-negative bacteria. TLR4-dependent cytokine production also increases significantly following antibiotic therapy.

). The study has a particular focus on the plant as grown in Africa. The onion is a monocotyledonous, allogamous, and entomophilous plant, with a one-year production cycle for bulb production, and a two-year production cycle for seeds. The onion is one of the most significant vegetables in the ARN-509 concentration world because of its use as both a food and a medicine. Literature. Twenty-eight morphological markers, linked to seed, leaf, flower and bulb traits, were identified as the most discriminant phenotypical criteria. Biochemical and molecular markers were also developed to characterize

genetic variations between and within onion varieties. Previous studies examining West Africa onion varieties showed that only six enzyme systems are polymorphic. However, only twenty-four

isozymes have been used to compare the onion to other Allium species. This low number of polymorphic biochemical markers makes it more difficult to determine the genetic diversity of onions. On the other hand, molecular markers at DNA level, EGFR inhibitor such as RAPD, RFLP, AFLP, SSR, are very useful to analyze diversity at varietal and species level, using cultivated and spontaneous forms, and to analyze the level of introgression between the onion and the other species of the genus. Conclusions. Selumetinib cell line Genetic diversity analysis showed an important variability between and within Africa

onion landraces. It would be useful to combine in situ and ex situ conservation, using these genetic resources to improve the production and the appropriate use of African onion cultivars.”
“The possibility to visualize and image the arrangement of proteins within the cell at the molecular level has always been an attraction for scientists in biological research. In particular, for signalling molecules such as GPCRs (G-protein-coupled receptors), the existence of protein aggregates such as oligomers or clusters has been the topic of extensive debate. One of the reasons for this lively argument is that the molecular size is below the diffraction-limited resolution of the conventional microscopy, precluding the direct visualization of protein super-structures. On the other hand, new super-resolution microscopy techniques, such as the PALM (photoactivated localization microscopy), allow the limit of the resolution power of conventional optics to be broken and the localization of single molecules to be determined with a precision of 10-20 nm, close to their molecular size. The application of super-resolution microscopy to study the spatial and temporal organization of GPCRs has brought new insights into receptor arrangement on the plasma membrane.

The light sensitive drug sepantronium was sufficiently stable under all relevant analytical conditions. Finally, the assay was successfully used to determine plasma drug levels in mice after administration of sepantronium bromide by continuous infusion from subcutaneously implanted osmotic pumps. (C)

2014 Elsevier B.V. All rights reserved.”
“Cichoric acid extract (CAE) from Echinacea purpurea L. was used to investigate the anti-arthritic effect by using collagen-induced arthritis (CIA) rat model. The hind paw swelling volume and the body weight were measured and recorded. All the drug solutions were administered orally to rats for a total of 28 days. On day 28, the rats were anaesthetized and decapitated. The thymus and spleen were weighed for the determination selleck compound of the organ index.

The concentration selleck kinase inhibitor of tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE-2) in the serum was measured using commercially available ELISA kits. Total and phosphor-NF-kappa B and Cox-2 protein expression in synovial tissues were determined by histological slides quantification and western blot analysis. Our data showed that administration of all doses of CAE (8, 16, and 32 mg/kg) significantly decreased the paw swelling, restored body weight gain and decreased the organ index of the thymus and spleen compared with that of the CIA group. CAE (8, 16, and 32 mg/kg) treatment significantly reduced the levels of TNF alpha, IL-1 beta and PGE-2 in serum compared with the CIA group. Histopathological analysis demonstrated that CAE has obvious anti-arthritic activity. In addition, CAE (32 mg/kg) significantly decreased the levels of nuclear factor-kappa B (NF-kappa B), TNF alpha and cyclooxygenase 2 (Cox-2) in synovium tissues of the ankle joint compared with the CIA group. Furthermore, CAE administration

significantly decreased the protein expression of phosphor-NF-kappa B and Cox-2 in synovium tissues of the knee joint compared with the CIA group. The results suggest that the anti-inflammatory activity of CAE may account for its anti-arthritic effect, and CAE could be a potential therapeutic drug for the treatment of rheumatoid arthritis (RA).”
“The expression and distribution of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p-STAT3), and vascular endothelial growth factor Sapitinib (VEGF), as well as eosinophil infiltration in nasal polyps was detected to examine their roles and correlations in the nasal polyp pathogenesis. Using the streptavidin-biotin-peroxidase (SP) method, immunohistochemistry was performed on conventional paraffin sections of 30 surgery-resected polypous specimens and 10 inferior turbinate tissues that were resected during nasal septum deflection correction to detect the expression of STAT3, p-STAT3, and VEGF, as well as eosinophil infiltration. The rates of STAT3-, p-STAT3-, and VEGF-positive expression in the mucosal epithelium and glands of nasal polyps were 66.

“
“P>The aim of this study was to investigate the quality of communication and master impressions for the fabrication

of cobalt chromium removable partial dentures (RPDs) in general dental practice in England, Ireland and Wales in 2009. Two hundred and ten questionnaires were distributed to 21 laboratories throughout England, Ireland and Wales. Information was collected regarding the quality of written communication and selection of master impression techniques for cobalt chromium partial dentures in general dental practice. One Selleck P505-15 hundred and forty-four questionnaires were returned (response rate = 68%). Alginate was the most popular impression material being used in 58% of cases (n = 84), while plastic stock trays were the most popular impression tray, being used in 31% of cases (n = 44). Twenty-four per cent (n = 35) of impressions were not adequately disinfected. Opposing casts were provided in 81% of cases (n = 116). Written instructions were described as being SHP099 chemical structure ‘clear’ in 31% of cases (n = 44). In 54% of cases (n = 76), the technician was asked

to design the RPD. Based on the findings of this study, written communication for cobalt chromium RPDs by general dental practitioners is inadequate. This finding is in breach of relevant contemporary legal and ethical guidance. There are also concerns in relation to the fabrication process for this form of prosthesis, particularly, in relation to consideration of occlusal schemes.”
“Certified nursing assistants (CNAs) are an integral part of the care team in most hospitals. The chief nursing officer at a community hospital in Florida developed a program of communication, education, and accountability to highlight the role of the CNA as a team member. This easy-to-implement initiative resulted in increased understanding about the

CNA role in delivering high-quality patient care and increases in patient WZB117 cost satisfaction with responsiveness of staff to call lights.”
“Monosubstituted gamma(4)-residues (gamma(4)Leu, gamma(4)Ile, and gamma(4)Val) form helices even in short homooligomeric sequences. C-14 helix formation is established by X-ray diffraction in homooligomeric (gamma)(n) tetra-, hexa- and decapeptide sequences demonstrating the high propensity of gamma residues, with proteinogenic side chains, to adopt locally folded conformations.”
“The combination of dynamic pH junction, sweeping (using borate complexation), and large volume sample stacking (LVSS) is investigated as three consecutive steps for on-line focusing in the sensitive quantitation of urinary nucleosides by CE-UVD. A low conductivity aqueous sample matrix free from borate and a high conductivity BGE (containing borate, pH 9.25) are needed to fulfill the required conditions for dynamic pH junction, LVSS, and sweeping.

0%); inadequate blinding (4.9%); and duplicative publication (4.4%). Overall, 20.2% of all published medical research has an identified methodological flaw, with RCTs having as many limitations as non-RCTs.Steen,

R. G., Dager, S. R. Evaluating the evidence for evidence-based medicine: are randomized clinical trials less flawed than other forms of peer-reviewed medical research?”
“Background: VS-6063 Leveraging professionalism has been put forward as a strategy to drive improvement of patient care. We investigate professionalism as a factor influencing the uptake of quality improvement activities by physicians and nurses working in European hospitals. Objective: To (i) investigate the reliability and validity of data yielded by using the self-developed professionalism measurement tool for physicians and nurses, (ii) describe their levels of professionalism displayed, and (iii) quantify the extent to which professional attitudes would predict professional behaviors. Tariquidar Transmembrane Transporters inhibitor Methods and Materials: We designed and deployed survey instruments amongst 5920 physicians and nurses working in European hospitals. This was conducted under the cross-sectional multilevel study “Deepening Our Understanding of Quality

Improvement in Europe” (DUQuE). We used psychometric and generalized linear mixed modelling techniques to address the aforementioned objectives. Results: In all, 2067 (response rate 69.8%) physicians and 2805 nurses (94.8%) representing 74 hospitals in 7 European countries participated. The professionalism instrument revealed five subscales of professional attitude and one scale for professional behaviour with moderate to high internal consistency and reliability. Physicians

and nurses display equally high professional attitude sum scores (11.8 and 11.9 respectively out of 16) but seem to have different perceptions towards separate professionalism aspects. Lastly, professionals displaying higher levels Dibutyryl-cAMP datasheet of professional attitudes were more involved in quality improvement actions (physicians: b = 0.019, P smaller than 0.0001; nurses: b = 0.016, P smaller than 0.0001) and more inclined to report colleagues’ underperformance (physicians – odds ratio (OR) 1.12, 95% CI 1.01-1.24; nurses – OR 1.11, 95% CI 1.01-1.23) or medical errors (physicians – OR 1.14, 95% CI 1.01-1.23; nurses – OR 1.43, 95% CI 1.22-1.67). Involvement in QI actions was found to increase the odds of reporting incompetence or medical errors. Conclusion: A tool that reliably and validly measures European physicians’ and nurses’ commitment to professionalism is now available. Collectively leveraging professionalism as a quality improvement strategy may be beneficial to patient care quality.”
“To find the effect of field-to-field variation in pesticide residue levels in Chinese cabbage and spinach, two residue datasets each were obtained from eight test fields in different years.

All rights reserved.”
“The C2-WW-HECT-type ubiquitin ligases Smurf1 and Smurf2 play a critical role in embryogenesis and adult bone homeostasis via regulation of bone morphogenetic protein, Wnt, and RhoA signaling pathways. The intramolecular interaction between C2 and HECT domains autoinhibits the ligase activity of Smurf2. However, the role of the Smurf1 C2 domain remains elusive. Here, we show that the C2-HECT autoinhibition mechanism is not observed in Smurf1, and instead its C2 domain functions in substrate selection. The Smurf1

C2 domain exerts a key role in localization to the plasma membrane and endows Smurf1 with differential activity toward RhoA versus Smad5 and Runx2. Crystal structure INCB018424 clinical trial analysis reveals that the Smurf1 C2 domain possesses a typical anti-parallel beta-sandwich fold. Examination of the sulfate-binding site analysis reveals two key lysine residues, Lys-28 and Lys-85, within the C2 domain that are important for Smurf1 localization at the plasma membrane, regulation on cell migration, and robust ligase activity check details toward RhoA, which further supports a Ca(2+)-independent localization mechanism for Smurf1. These findings demonstrate a previously unidentified role of the Smurf1 C2 domain in substrate selection and cellular localization.”
“We studied homing and differentiation fate of transplanted bone marrow

mononuclears after non-selective intracoronary injection on day 30 after acute myocardial infarction in rats. Mononuclear cells migrated to the cicatrix zone where they differentiated into fibroblasts and myofibroblasts. Mononuclear cells

did not differentiate into cardiomyocytes, endothelial cells, or smooth muscle cells of vascular media. Stimulation of angiogenesis and reparation of the myocardium was observed under these conditions.”
“A dynamic method was Suggested to determine the variation of both refractive index and transverse sectional area of regular and/or irregular fibers during the dynamic cold drawing process. The suggested method depends on the physical principle of constant volume of the filament during Selleckchem PLX4032 the cold drawing process. The mathematical analysis of the method was given. The optical and geometrical properties of acrylic fibers with denier 2 and polypropylene c fibers were determined. One dimension optical Fourier transform was used for automatic analysis of microinterferograms. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 112: 1909-1915, 2009″
“This study was conducted to investigate effects of some plant growth regulators (PGRs) such as abscisic acid (ABA) and benzyladenine (BA), on changes of expression of some isoenzymes [superoxide dismutase (SOD), malat dehydrogenase (MDH), glutamate dehydrogenase (GDH), glucose-6-phosphate dehydrogenase (G-6-PDH)] in three vegetative organs (the root, stem, leaf) of bean (Phaseolus vulgaris L) under chilling stress.

\n\nMethods and setting An observational multicenter study based on two consecutive acute hepatitis C cohorts, retrospective then prospective, registered between 1993 and 2007, mostly in general hospitals.\n\nResults A cohort of 23 patients with occupationally transmitted hepatitis C virus (HCV) was set up. Occupational accident registration was done in 14 (61%) cases. They were mainly women (n = 14), with a mean age of 43 years. The disease was diagnosed during surveillance after exposure in 16 patients, and nine had hyperbilirubinemia. Early treatment was applied to nine of them, with eight who sustained viral response (SVR).

Fourteen underwent surveillance: spontaneous viral clearance occurred selleck compound in nine of them, with two relapses. Five patients with persistent HCV RNA 12 weeks after the diagnosis were then treated, with four SVR.\n\nConclusion Information and prevention of healthcare workers concerning occupational HCV transmission need to be improved, and all blood-exposure accidents should be registered. Spontaneous viral clearance occurred in half of the

patients. Antiviral treatment was highly effective, with a SVR of 86%. Eur J Gastroenterol Hepatol 23:515-520 (C) 2011 Wolters Kluwer Health Selleck Bucladesine vertical bar Lippincott Williams & Wilkins.”
“E1 and E2 enzymes coordinate the first steps in conjugation of ubiquitin (Ub) and ubiquitin-like proteins (Ubls). ISG15 is an interferon-alpha/beta-induced Ubl, and the E1 and E2 enzymes

for ISG15 conjugation are Ube1L and UbcH8, respectively. UbcH7 is the most closely related E2 to UbcH8, yet it does not function in ISG15 conjugation in vivo, while both UbcH7 and UbcH8 have been reported to function in Ub conjugation. Kinetic analyses of wild-type and chimeric E2s were performed to determine the basis for preferential activation of UbcH8 by Ube1L and to determine ACY-738 cell line whether UbcH8 is activated equally well by Ube1L and E1(Ub) (Ube1). K-m determinations confirmed the strong preference of Ube1L for UbcH8 over UbcH7 (a 29-fold K-m difference), similar to the preference of E1(Ub) for UbcH7 over UbcH8 (a 36- fold K-m difference). Thioester assays of chimeric E2s identified two structural elements within residues 1-39 of UbcH8 that play a major role in defining Ube1L-UbcH8 specificity: the alpha 1-helix and the beta 1-beta 2 region. The C-terminal ubiquitin fold domain (UFD) of Ube1L was required for transfer of ISG15 to UbcH8 and for binding of Ube1L to UbcH8. Replacement of the Ube1L UFD with that from E1(Ub) resulted in preferential transfer of ISG15 to UbcH7. Together, these results indicate that Ube1L discriminates between UbcH8 and closely related Ub E2s based on specific interactions between the Ube1L UFD and determinants within the N-terminal region of UbcH8.

The aim of the sustainability of healthcare innovations (SUSHI) study is to analyse sustainability and its determinants using two implementation cases.\n\nMethods: This observational study uses a mixed methods approach. The study will be performed in 14 hospitals in the Netherlands, from November 2010. For both implementation cases, the programme aspects and the effects will be evaluated by means of a follow-up measurement in 160 patients who underwent breast cancer surgery and 300 patients who underwent colonic

surgery. A policy cost-effectiveness analysis from a societal perspective will be performed prospectively for the Short Stay Programme for breast cancer surgery in 160 patients. To study determinants of sustainability key professionals in the

multidisciplinary care processes and implementation change agents www.selleckchem.com/screening/kinase-inhibitor-library.html PP2 cell line will be interviewed using semi-structured interviews.\n\nDiscussion: The concept of sustainability is not commonly studied in implementation science. The SUSHI study will provide insight in to what extent the short-term implementation benefits have been maintained and in the determinants of long-term continuation of programme activities.”
“This systematic review identifies the factors that both support and deter patients from being willing and able to participate actively in reducing clinical errors. Specifically, we add to our understanding of the safety culture in healthcare by engaging with the call for more focus on the relational and subjective factors which enable patients’ participation (Iedema, Jorm, & Lum, 2009; Ovretveit, 2009). A systematic search of six databases, ten journals and seven healthcare organisations’ web sites resulted in the identification of 2714 studies of which 68 were included in the review. These studies investigated initiatives involving patients in safety GSK3326595 order or studies of patients’ perspectives of being actively involved in the safety of their care. The factors explored varied considerably depending on the scope, setting and context of the study. Using

thematic analysis we synthesized the data to build an explanation of why, when and how patients are likely to engage actively in helping to reduce clinical errors. The findings show that the main factors for engaging patients in their own safety can be summarised in four categories: illness; individual cognitive characteristics; the clinician patient relationship; and organisational factors. We conclude that illness and patients’ perceptions of their role and status as subordinate to that of clinicians are the most important barriers to their involvement in error reduction. In sum, patients’ fear of being labelled “difficult” and a consequent desire for clinicians’ approbation may cause them to assume a passive role as a means of actively protecting their personal safety. (C) 2012 Elsevier Ltd. All rights reserved.”
“Background: Glenoid bone deficiencies may be addressed by specialized components.

It is not unreasonable to consider that the results of these trials may provide a positive answer to the question: ‘Is it possible to improve brain development in DS?’.”
“In this work a series of nano-hydroxyapatite/poly(epsilon-caprolactone)-Pluronic-poly(epsilon-caprolactone) (n-HA/PCFC) nanocomposites has been prepared. Thermal properties of the nanocomposites are studied by thermogravimetry analysis (TGA) and differential scanning calorimetry (DSC). The TGA/DTG results reveal that thermal stability of n-HA/PCFC

nanocomposites is improved by incorporation of n-HA into polymer matrix, and the thermo-degradation temperature increased slightly with increasing HA loading. DSC results show that the glass transition temperature BI 2536 chemical structure (T(g)) changed by the addition of n-HA. Kinesin inhibitor The mechanical properties of the nanocomposites are investigated by tensile testing. The morphology for tensile-fractured surfaces of nanocomposites is observed by scanning electron microscopy. The effect of n-HA contents of nanocomposites

on tensile strength and morphology is also discussed. (C) Koninklijke Brill NV, Leiden, 2011″
“Objective: To examine the clinimetric properties and clinical applicability of published tools for ‘quantifying’ the degree of lateropulsion or pusher syndrome following stroke.\n\nData sources: Search through electronic databases (MEDLINE, EMBASE, CINAHL, Science Citation Index) with the terms lateropulsion, pushing, pusher syndrome, validity, reliability, internal consistency, JQ1 solubility dmso responsiveness, sensitivity, specificity,

posture and stroke. Databases were searched from their inception to October 2008.\n\nReview methods: Abstracts were selected by one author. A panel of experts then determined which should be included in this review. Five abstracts were reviewed and the panel agreed to omit one abstract because those authors did not write a full manuscript. The panel critiqued manuscripts according to predetermined criteria about clinical and clinimetric properties.\n\nResults: Four manuscripts referencing three tools for examining lateropulsion were found. Validity and reliability data support the clinical use of the Scale for Contraversive Pushing, the Modified Scale for Contraversive Pushing and the Burke Lateropulsion Scale. The Scale for Contraversive Pushing has the most extensive testing of clinimetric properties. The other tools show promising preliminary evidence of clinical and research utility. More testing is needed with larger, more diverse samples.\n\nReviewers’ conclusions: The Scale for Contraversive Pushing, the Modified Scale for Contraversive Pushing and the Burke Lateropulsion Scale are reliable and valid measures with good clinical applicability. Larger, more varied samples should be used to better delineate responsiveness and other clinimetric properties of these examination tools.