Validation of the Finnish version of the food allergy quality of life questionnaire-parent form (F-FAQLQ-PF).

AIM: Specific questionnaires about food allergy and health-related quality of life (HRQoL) have been developed and validated in several languages, but not Finnish. We aimed to validate the Finnish Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) for children under age 13 years. METHODS: The original FAQLQ-PF and Food Allergy Independent Measure (FAIM) were translated into Finnish per World Health Organisation guidelines and tested by 72 parents of children under age 13 years with suspected severe peanut or tree nut allergy who were recruited at Allergy Centre in Tampere University Hospital in Tampere, Finland. We calculated the construct validity of the questionnaire by calculating the coefficients between the two measures and used Cronbach's alpha to establish the internal consistency. RESULTS: The FAQLQ-PF showed strong correlations with domain structure and internal consistency, based on Spearman's correlations (rho) for the HRQoL questions, FAIM questions and FAIM mean values. The total questionnaire score correlated significantly with the mean FAIM (rho = 0.95, p < 0.001) and individual FAIM questions. The FAQLQ-PF and domains had good or excellent internal consistency (Cronbach's alpha >0.70). CONCLUSION: The Finnish FAQLQ-PF demonstrated good construct validity and excellent internal consistency for measuring food allergy HRQoL in children under age 13 years.

Glucose exchange parameters in a subset of physiological conditions.

The chemical exchange of labile protons of the hydroxyl groups can be exploited in a variety of magnetic resonance experiments to gain information about the groups and their physicochemical environment. The exchangeable -OH protons provide important contributions to the T2 of water signals thus contributing to the T2-weighted contrast of MRI images. This exchange can be exploited more specifically and sensitively in chemical exchange saturation transfer (CEST) or longitudinal rotating frame relaxation (T1,ρ) experiments. Since glucose is omnipresent in living organisms, it may be seen as a rather universal probe. Even though the potential was first recognized many years ago, practical use has remained scarce due to numerous challenges. The major limitation is the rather low glucose concentration in most tissues. The other obstacles are related to multiple dependencies of the exchange parameters, such as temperature, pH, and concentration of various ions that are not known in sufficient detail for glucose. Thus, we embarked on evaluating the exchange parameters of a model that included every relevant chemical site for all -OH protons in both dominant enantiomers of glucose. We have (1) obtained conventional one-dimensional proton NMR spectra of glucose solutions in suitable temperature ranges, (2) we have iterated through several exchange models with various degrees of freedom determined by the number of distinguishable -OH proton sites and compared their performance, (3) we extrapolated the parameters of the best model of physiological temperature and (4) we demonstrated the use of the parameters in virtual experiments. As the main results, (1) we have obtained the temperature dependence of exchange parameters with reliable confidence intervals in three different pH values, with two of them reaching physiological temperature, and (2) we show how the parameters can be used in virtual experiments, helping to develop new applications for glucose as an NMR/MRI probe.

Mono- and biallelic variant effects on disease at biobank scale.

Identifying causal factors for Mendelian and common diseases is an ongoing challenge in medical genetics1. Population bottleneck events, such as those that occurred in the history of the Finnish population, enrich some homozygous variants to higher frequencies, which facilitates the identification of variants that cause diseases with recessive inheritance2,3. Here we examine the homozygous and heterozygous effects of 44,370 coding variants on 2,444 disease phenotypes using data from the nationwide electronic health records of 176,899 Finnish individuals. We find associations for homozygous genotypes across a broad spectrum of phenotypes, including known associations with retinal dystrophy and novel associations with adult-onset cataract and female infertility. Of the recessive disease associations that we identify, 13 out of 20 would have been missed by the additive model that is typically used in genome-wide association studies. We use these results to find many known Mendelian variants whose inheritance cannot be adequately described by a conventional definition of dominant or recessive. In particular, we find variants that are known to cause diseases with recessive inheritance with significant heterozygous phenotypic effects. Similarly, we find presumed benign variants with disease effects. Our results show how biobanks, particularly in founder populations, can broaden our understanding of complex dosage effects of Mendelian variants on disease.

Diagnostic Accuracy of Symptoms, Endoscopy, and Imaging Signs of Chronic Rhinosinusitis Without Nasal Polyps Compared to Allergic Rhinitis.

Objectives The diagnosis of chronic rhinosinusitis without nasal polyps (CRSsNP) and distinguishing it from allergic rhinitis is difficult. Yet, early detection of CRSsNP is important to prevent progressive and severe chronic rhinosinusitis. Our aim was to compare diagnostic accuracy of symptoms, endoscopy, and imaging signs of CRSsNP and allergic rhinitis -only phenotypes. Setting Prospective controlled follow-up study. Participants Forty-two nonsmoking patients visiting tertiary care due to CRSsNP and 19 nonsmoking volunteer controls with allergic rhinitis filled a symptoms questionnaire and underwent nasal endoscopy off-seasonally. All CRSsNP patients underwent computed tomography scans of paranasal sinuses. All the allergic rhinitis control subjects and 14 of the CRSsNP patients underwent sinus magnetic resonance imaging. Results Radiologic Lund-Mackay score, duration of symptoms, visual analogue scale scores of symptoms, and Sinonasal Outcome Test 22 were significantly higher in the CRSsNP group compared to allergic rhinitis control group. These factors also correlated in part with each other. Endoscopic score did not correlate with other factors, nor did it differ between CRSsNP and allergic rhinitis groups. The highest area under curve value was demonstrated for visual analogue scale score of facial pain/pressure (0.93) and score ≥4/10 showed 60% sensitivity and 95% specificity for detecting CRSsNP group ( P < .001). Radiologic sign of obstructed osteomeatal complex showed 100% specificity and 38% sensitivity for detecting CRSsNP group ( P < .001). Conclusions CRSsNP phenotype could be primarily distinguished from allergic rhinitis by higher facial pain/pressure score and secondarily by radiologic sings of obstructed ostiomeatal complex and higher Lund-Mackay score. Endoscopic score has limited value in distinguishing CRSsNP from allergic rhinitis.

Pulse-echo ultrasound method for detection of post-menopausal women with osteoporotic BMD.

We lack effective diagnostics of osteoporosis at the primary health care level. An ultrasound device was used to identify subjects in the osteoporotic range as defined by DXA. A case finding strategy combining ultrasound results with DXA measurements for patients with intermediate ultrasound results is presented. INTRODUCTION: We lack effective screening and diagnostics of osteoporosis at primary health care. In this study, a pulse-echo ultrasound (US) method is investigated for osteoporosis screening. METHODS: A total of 1091 Caucasian women (aged 50-80 years) were recruited for the study and measured with US in the tibia and radius. This method measures cortical thickness and provides an estimate of bone mineral density (BMD) and density index (DI). BMD assessment of the hip was available for 988 women. A total of 888 women had one or more risk factors for osteoporosis (OP susp ), and 100 women were classified healthy. Previously determined thresholds for the DI were evaluated for assessment of efficacy of the technique to detect hip BMD at osteoporotic range (T-score at or below - 2.5). RESULTS: In the OP susp group, the application of thresholds for the DI showed that approximately 32% of the subjects would require an additional DXA measurement. The multi-site ultrasound (US) measurement-based DI showed 93.7% sensitivity and 81.6% specificity, whereas the corresponding values for single-site US measurement-based DI were 84.7 and 82.0%, respectively. The ultrasound measurements showed a high negative predictive value 97.7 to 99.2% in every age decade examined (ages 50-59, 60-69, 70-79 years). CONCLUSIONS: The study data demonstrate that a strategy of combining ultrasound measurement with added DXA measurements in cases with intermediate ultrasound results (about 30%) can be useful for identifying subjects at risk for a low bone mineral density in the osteoporotic range.

Higher mortality of adults with asthma: A 15-year follow-up of a population-based cohort.

BACKGROUND: Higher all-cause mortality in asthmatics has been shown previously. Polysensitization is associated with higher morbidity among asthmatic children, and allergic rhinitis and/or allergic conjunctivitis (AR/AC) are associated with higher morbidity in adult asthmatics. Little is known about the effect of AR/AC and other factors on mortality among adult asthmatics. The aim was to study mortality and its risk factors in adults with and without asthma. METHODS: We randomly selected 1648 asthmatics with age over 30 years from national registers and matched the asthma sample with one or two controls. Baseline information was obtained by a questionnaire in 1997, and the study population was linked with the death certificate information of Statistics Finland from 1997 to 2013. Overall and cause-specific survival between the groups was compared in several adjusted models. RESULTS: During a mean follow-up period of 15.6 years, 221 deaths among 1052 asthma patients and 335 deaths among 1889 nonasthmatics were observed. Cardiovascular diseases were the main cause of death in both groups. Asthma was associated with increased all-cause mortality (adjusted HR 1.25; 95% CI 1.05-1.49, P = .011) as well as mortality from chronic obstructive pulmonary disease (HR 12.0, 4.18-34.2, P < .001) and malignant neoplasms of respiratory organs (HR 2.33, 1.25-4.42, P = .008). Among asthmatics, smoking was associated with increased all-cause mortality, and self-reported AR/AC was associated with decreased mortality. Among nonasthmatics, smoking, and obesity were associated with increased all-cause mortality, whereas female gender showed an association with a decreased risk. CONCLUSIONS: Increased mortality among adult asthmatics was largely explained by the development of COPD, malignant respiratory tract neoplasms, and cardiovascular diseases. Smoking cessation is important for reduction in total mortality in both asthmatic and nonasthmatic adults. AR/AC was associated with decreased mortality only in asthmatics. Thus, studies in other populations of larger size are needed to explore further the nature of this association.

Birth decade affects the sensitization pattern and asthma risk in Finnish adult population.

We have previously shown that sensitizations to several types of allergens distinguish subjects with and without adult-onset asthma in Finland. The aim was to analyze how age affects sensitization and asthma risk. We used previous population-based case-control data (N=456) from Finnish adult asthma patients with one or two matched controls. Asthma was diagnosed based on a typical history of asthmatic symptoms and lung function tests. Allergic sensitization was determined by skin prick test (SPT) to 17 aeroallergens. Information on demographics was obtained by a questionnaire. Sensitization to more than one allergen type and the number of positive SPT reactions associated with younger age and asthma. Atopic subjects aged 65 and above were characterized by sensitization to only one to two allergens, with very few animal danders and without an association with asthma. Multiple sensitizations and animal dander sensitization are more common among Finnish asthmatic adults aged under 56 than among older asthmatics. Cohort studies are needed to understand timing of host-environmental interactions behind this.

Prediction of hip osteoporosis by DXA using a novel pulse-echo ultrasound device.

Pulse-echo ultrasonometry can be used as a pre-screen for hip osteoporosis before dual-energy x-ray absorptiometry (DXA), potentially allowing DXA to be avoided for the majority of post-menopausal women. Pulse-echo ultrasound measures of tibia cortical thickness are also associated with radiographically confirmed prior fractures, independent of femoral neck bone mineral density. INTRODUCTION: To estimate how well a pulse-echo ultrasound device discriminates those who have from those who do not have hip osteoporosis (femoral neck bone mineral density [BMD] or total hip BMD T-score ≤ -2.5), and to estimate the association of pulse-echo ultrasound measures with prevalent (radiographically confirmed) clinical fractures. METHODS: Five hundred fifty-five post-menopausal women age 50 to 89 had femoral neck and total hip BMD measured by dual-energy x-ray absorptiometry (DXA), and pulse-echo ultrasound measures of distal radius, proximal tibia, distal tibia cortical thickness, and multi- and single-site density indices (DI). Using previously published threshold ultrasound values, we estimated the proportion of women who would avoid a follow-up DXA after pulse-echo ultrasonometry, and the sensitivity and specificity of this for the detection of hip osteoporosis. Logistic regression models were used to estimate the associations of pulse-echo ultrasound measures with radiographically confirmed clinical fractures within the prior 5 years. RESULTS: Using multi-site and single-site DI measures, follow-up DXA could be avoided for 73 and 69 % of individuals, respectively, while detecting hip osteoporosis with 80-82 % sensitivity and 81 % specificity. Radiographically confirmed prior fracture was associated with ultrasound measures of single-site DI (odds ratio (OR) 1.55, 95 % confidence interval (CI). 1.06 to 2.26) and proximal tibia cortical thickness (OR 1.47, 95 % CI 1.10 to 1.96), adjusted for age, body mass index, and femoral neck BMD. CONCLUSIONS: Pulse-echo ultrasonometry can be used as an initial screening test for hip osteoporosis. Prospective studies of how well pulse-echo ultrasound measures predict subsequent clinical fractures are warranted.

Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone.

PURPOSE: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessment by PE ultrasound. METHODS: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. RESULTS: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R(2) ≥ 0.493, p < 0.01 and R(2) ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%-16.4%) was about 6% in the cortical thickness assessment in vitro. CONCLUSIONS: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated in vivo, the relationship between radial SOS and cortical porosity can be utilized and a porosity based radial SOS estimate could be implemented to determine cortical thickness. This would constitute a step toward individualized quantitative ultrasound diagnostics of osteoporosis.

Hospitalizations due to allergic reactions in Finnish and Swedish children during 1999-2011.

BACKGROUND: Several authors have reported on allergic reactions that resulted in presentation to the emergency department. However, studies of the secular trend of hospitalizations for paediatric allergic reactions, including anaphylaxis, are scarce. The aim of this study was to describe the secular trends of hospitalizations for allergic reactions, including anaphylaxis, among children aged 0-19 years in Finland and Sweden, and to establish the trend of prescribed epinephrine auto-injectors (EAI) among paediatric populations. METHODS: Using national databases, we identified hospitalizations between 1999 and 2011 with the primary diagnosis of allergic reaction per International Classification of Diseases, 10th Revision. RESULTS: Hospitalizations for allergic reactions totalled 1987 in Finland and 5433 in Sweden. Incidence rates increased in both countries. In Finland, the incidence of admission was 7.8 per 100 000 person-years at the start of the study period and 15.8 at the end of the study period. The corresponding numbers among Swedish children were 13.7 and 31.8 per 100 000 person-years. In Finland, 60% of children hospitalized were aged under 10 years. In Sweden, this proportion was somewhat lower, at 48%. Most hospitalizations occurred between May and September. The prevalence of EAI prescriptions in Finland increased by fourfold during the study period. In Sweden, such an increase was not identified. CONCLUSIONS: The incidence of allergic reactions leading to hospitalizations between 1999 and 2011 increased in Finland and Sweden among children aged 0 to 19 years. In Finland, the incidence was lower throughout the study period compared to Sweden. Younger children constituted the majority of hospitalized children.

GWAS for executive function and processing speed suggests involvement of the CADM2 gene.

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

New method for point-of-care osteoporosis screening and diagnostics.

SUMMARY: Due to the lack of diagnostics in primary health care, over 75% of osteoporotic patients are not diagnosed. A new ultrasound method for primary health care is proposed. Results suggest applicability of ultrasound method for osteoporosis diagnostics at primary health care. INTRODUCTION: We lack effective screening and diagnostics of osteoporosis at primary health care. In this study, a new ultrasound (US) method is proposed for osteoporosis diagnostics. METHODS: A total of 572 Caucasian women (age 20 to 91 years) were examined using pulse-echo US measurements in the tibia and radius. This method provides an estimate of bone mineral density (BMD), i.e. density index (DI). Areal BMD measurements at the femoral neck (BMD(neck)) and total hip (BMD(total)) were determined by using axial dual-energy X-ray absorptiometry (DXA) for women older than 50 years of age (n = 445, age = 68.8 ± 8.5 years). The osteoporosis thresholds for the DI were determined according to the International Society for Clinical Densitometry (ISCD). Finally, the FRAX questionnaire was completed by 425 participants. RESULTS: Osteoporosis was diagnosed in individuals with a T-score -2.5 or less in the total hip or femoral neck (n = 75). By using the ISCD approach for the DI, only 28.7% of the subjects were found to require an additional DXA measurement. Our results suggest that combination of US measurement and FRAX in osteoporosis management pathways would decrease the number of DXA measurements to 16% and the same treatment decisions would be reached at 85.4% sensitivity and 78.5% specificity levels. CONCLUSIONS: The present results demonstrate a significant correlation between the ultrasound and DXA measurements at the proximal femur. The thresholds presented here with the application to current osteoporosis management pathways show promise for the technique to significantly decrease the amount of DXA referrals and increase diagnostic coverage; however, these results need to be confirmed in future studies.

Sensitization pattern affects the asthma risk in Finnish adult population.

BACKGROUND: There is a large global variation in the sensitization pattern and its association with allergic diseases. In temperate and tropical urban environments, mite monosensitization can be the predominant cause of allergic airway diseases, whereas in other environments, polysensitization is more typical. Sensitization to mite allergens associates with asthma. However, it is suggested that mite sensitization might play a minor role in Northern Europe. The aim of the study was to analyze how sensitization pattern affects the asthma risk in Finnish adults, with a special focus on mites. METHODS: A population-based case-control data (N = 523) from Finnish adult asthma patients with one or two matched controls were used. Asthma was diagnosed based on a typical history of asthmatic symptoms and lung function tests. The allergic sensitization was determined based on skin prick test (SPT) of five mites, three molds, and nine other aeroallergens. Information on demographics was obtained by a questionnaire. RESULTS: The proportion of sensitization to any allergen was 55% in the asthma group and 39% in the control group (P = 0.001, OR 2.06, 95% CI = 1.35-3.14). Sensitization to animal dander, pollen, or Aspergillus fumigatus was associated with asthma. Polysensitization to more than one allergen types and the number of SPT-positive reactions associated with asthma, whereas sensitization to only one allergen type was not associated with asthma. CONCLUSIONS: The large number of sensitizations to several types of allergens distinguishes subjects with asthma. Mite sensitization had little independent association with asthma in Finland.

Predation by signal crayfish Pacifastacus leniusculus on fish eggs and its consequences for coregonid recruitment.

The character and magnitude of predation by the invasive, ectothermic Pacifastacus leniusculus, a crayfish widely introduced to Europe and Japan from North America, on the eggs of coregonid fishes, vendace Coregonus albula and whitefish Coregonus lavaretus were examined by experimentation, modelling and field data. The present results showed that P. leniusculus has the potential to be very efficient predator of fish eggs under winter conditions, but the predation by P. leniusculus did not significantly decrease production of coregonid larvae during the years with a high P. leniusculus population in the study lake. Hence, the mortality caused by the novel invertebrate predator appeared to compensate for other yet unexplored mortality factors instead of having an additive effect on the present salmonids.

Ultrasound backscatter measurements of intact human proximal femurs--relationships of ultrasound parameters with tissue structure and mineral density.

Ultrasound reflection and backscatter parameters are related to the mechanical and structural properties of bone in vitro. However, the potential of ultrasound reflection and backscatter measurements has not been tested with intact human proximal femurs ex vivo. We hypothesize that ultrasound backscatter can be measured from intact femurs and that the measured backscattered signal is associated with cadaver age, bone mineral density (BMD) and trabecular bone microstructure. In this study, human femoral bones of 16 male cadavers (47.0±16.1 years, range: 21-77 years) were investigated using pulse-echo ultrasound measurements at the femoral neck in the antero-posterior direction and at the trochanter major in the anteroposterior and lateromedial directions. Recently introduced ultrasound backscatter parameters, independent of cortical thickness, e.g., time slope of apparent integrated backscatter (TSAB) and mean of the backscatter difference technique (MBD) were obtained and compared with the structural properties of trabecular bone samples, extracted from the locations of ultrasound measurements. Moreover, more conventional backscatter parameters, e.g., apparent integrated backscatter (AIB) and frequency slope of apparent integrated backscatter (FSAB) were analyzed. Bone mineral density of the intact femurs was evaluated using dual energy X-ray absorptiometry (DXA). AIB and MDB measured from the femoral neck correlated significantly (p<0.01) with the neck BMD (R2=0.44 and 0.45), cadaver age (R2=0.61 and 0.41) and several structural parameters, e.g., bone volume fraction (R2=0.33 and 0.39, p<0.05 and p<0.01), respectively. To conclude, ultrasound backscatter parameters, measured from intact proximal femurs, are significantly related (p<0.05) to structural properties and mineral density of trabecular bone.

Multi-site bone ultrasound measurements in elderly women with and without previous hip fractures.

UNLABELLED: About 75% of patients suffering from osteoporosis are not diagnosed. This study describes a multi-site bone ultrasound method for osteoporosis diagnostics. In comparison with axial dual energy X-ray absorptiometry (DXA), the ultrasound method showed good diagnostic performance and could discriminate fracture subjects among elderly females. INTRODUCTION: Axial DXA, the gold standard diagnostic method for osteoporosis, predicts fractures only moderately. At present, no reliable diagnostic methods are available at the primary health care level. Here, a multi-site ultrasound method is proposed for osteoporosis diagnostics. METHODS: Thirty elderly women were examined using the ultrasound backscatter measurements in proximal femur, proximal radius, proximal and distal tibia in vivo. First, we predicted the areal bone mineral density (BMD) at femoral neck by ultrasound measurements in tibia combined with specific subject characteristics (density index, DI) and, second, we tested the ability of ultrasound backscatter measurements at proximal femur to discriminate between individuals with previously fractured hips from those without fractures. Areal BMD was determined by axial DXA. RESULTS: Combined ultrasound parameters, cortical thickness at distal and proximal tibia, with age and weight of the subject, provided a significant estimate of BMD(neck) (r = 0.86, p < 0.001, n = 30). When inserted into FRAX (World Health Organization fracture risk assessment tool), the DI indicated the same treatment proposal as the BMD(neck) with 86% sensitivity and 100% specificity. The receiver operating characteristic analyses, with a combination of ultrasound parameters and patient characteristics, discriminated fracture subjects from the controls similarly as the model combining BMD(neck) and patient characteristics. CONCLUSIONS: For the first time, ultrasound backscatter measurements of proximal femur were conducted in vivo. The results indicate that ultrasound parameters, combined with patient characteristics, may provide a means for osteoporosis diagnostics.

Indoleamine 2,3-dioxygenase expression is associated with chronic rhinosinusitis with nasal polyps and antrochoanal polyps.

Chronic rhinosinusitis without and with nasal polyps (CRSwNP and CRSsNP), and antrochoanal polyps are different phenotypes with different pathomechanisms. Indoleamine 2,3-dioxygenase (IDO) is an enzyme expressed in many cells involved in the catabolism of the essential amino acid tryptophan to kynurenine. IDO might have a role in allergic airway inflammation. The aim was to evaluate if IDO expression is associated with CRSsNP, CRSwNP, or ACP. One hundred fifty specimens from the nasal cavity and sinus mucosa were immunohistochemically stained with mAb anti-IDO. The expression of epithelial and leukocyte IDO was associated with CRSwNP and ACP. The presence of ASA intolerance, asthma, atopy, smoking and use of medication did not significantly change the results. The different expression of IDO could putatively indicate the differences in the pathomechanisms of CRSsNP, CRSwNP and ACP. Further studies on the role of IDO in upper airways pathologies are required.

Walking ability and all-cause mortality in older women.

In this study self-reported ability to walk 2 km and six-minute walking test (6MWT) performance were examined as predictors of all-cause mortality in 434 women, aged 63-76 years. The primary outcome measure was all-cause mortality (follow-up: 8 years). Predictors were self-reported difficulties in walking 2 km and 6-min walking distance tertiles of ≤495, 496-560 and ≥561 m, and no test result due to refusal by the physician to grant permission to perform the test or participant's inability or unwillingness to perform the test. During the follow-up, 39 participants died. Participants reporting minor (age- and body mass index-adjusted hazard ratio 2.53, 95% confidence interval 1.12-5.69) or major (7.93, 3.49-18.05) difficulties in walking 2 km had increased risk of death compared with those reporting no difficulties. Participants with no 6MWT result (6.99, 2.46-19.86) were at an increased risk of death when compared with participants who walked ≥561 m. A similar trend (2.47, 0.81-7.56) was found for participants with walking distance of ≤495 m during the 6MWT. The trends remained similar after adjustments for other confounders. In conclusion, self-reported difficulties in walking 2 km are associated with an increased risk of death in older community-dwelling women. Objectively measured walking ability gives similar results.

Technical and practical improvements in arthroscopic indentation technique for diagnostics of articular cartilage softening.

Indentation measurements have been proposed to serve as sensitive in vivo diagnostics of cartilage degeneration. However, practical difficulties have hindered the use of quantitative indentation techniques during routine arthroscopies. In this study we modified the previously commercial indentation technique by designing software for quality control of manual indentations. With the modifications, our aim was to introduce more rapid and less erroneous measurements, as well as more automatic and objective analyses. The performance of the technique was tested in situ using six bovine medial tibial plateaus. All measurements were conducted by three operators. The intraoperator reproducibility was reasonable (CV%  = 7.1%) and the interoperator reproducibility was good (intraclass correlation coefficient  = 0.976). Further, the novel technique was tested by a single operator using 10 bovine medial tibial plateaus. The indentation stiffness values determined with the arthroscopic instrument correlated significantly with the dynamic (r = 0.823) and equilibrium (r = 0.752) moduli as well as tissue water (r =  -0.830) and hydroxyproline (r = 0.776) contents. To conclude, the novel measurement technique showed good reproducibility and was found to give valuable information on cartilage properties. Most importantly, the measurements and analyses were more straightforward and automatic than those introduced in the original indentation approach.

Antegrade flow and peripheral resistance determine the level of endogenous arteriogenesis in patients with superficial femoral artery occlusion.

OBJECTIVES: Occlusion in a limb artery leads to impaired blood supply and ischaemia. Collateral artery growth (arteriogenesis) is one of the most effective natural response mechanisms to compensate this pathologic situation. However, it is unknown if clinically important features, like poor run-off, have an impact on compensatory vessel growth. METHODS: Study population of this retrospective study consisted of 70 patients who suffered from lower limb ischaemia and underwent bypass surgery because of an occlusion of the superficial femoral artery. Clinical data were collected and pre- and postoperative angiograms were reviewed. Number of collateral vessels bypassing the occluded segment was counted. Features of inflow and outflow vessels were recorded. RESULTS: The mean number of collaterals was 13 + or - 0.5 per patient. In univariate analysis, short daily walking distance, chronic critical leg ischaemia, low ankle brachial index, low number of patent calf arteries and stenosed inflow arteries predicted low number of collateral arteries. In the multivariate analysis, only the quality of inflow and the number of patent calf vessels demonstrated an independent association (P < 0.05) with the number of collaterals. CONCLUSIONS: Ankle-brachial index, grade of symptoms and daily walking capacity could be used to predict collateral density. Importantly, a good antegrade flow and peripheral runoff seem to have a significant effect on collateral density, implying an impact on the activation of arteriogenesis.