Multimodal approach in the use of clinical scoring, morphological MRI and biochemical T2-mapping and diffusion-weighted imaging in their ability to assess differences between cartilage repair tissue after microfracture therapy and matrix-associated autologous chondrocyte transplantation: a pilot study

OBJECTIVE: The aim of the present pilot study is to show initial results of a multimodal approach using clinical scoring, morphological magnetic resonance imaging (MRI) and biochemical T2-relaxation and diffusion-weighted imaging (DWI) in their ability to assess differences between cartilage repair tissue after microfracture therapy (MFX) and matrix-associated autologous chondrocyte transplantation (MACT). METHOD: Twenty patients were cross-sectionally evaluated at different post-operative intervals from 12 to 63 months after MFX and 12-59 months after MACT. The two groups were matched by age (MFX: 36.0+/-10.4 years; MACT: 35.1+/-7.7 years) and post-operative interval (MFX: 32.6+/-16.7 months; MACT: 31.7+/-18.3 months). After clinical evaluation using the Lysholm score, 3T-MRI was performed obtaining the MR observation of cartilage repair tissue (MOCART) score as well as T2-mapping and DWI for multi-parametric MRI. Quantitative T2-relaxation was achieved using a multi-echo spin-echo sequence; semi-quantitative diffusion-quotient (signal intensity without diffusion-weighting divided by signal intensity with diffusion weighting) was prepared by a partially balanced, steady-state gradient-echo pulse sequence. RESULTS: No differences in Lysholm (P=0.420) or MOCART (P=0.209) score were observed between MFX and MACT. T2-mapping showed lower T2 values after MFX compared to MACT (P=0.039). DWI distinguished between healthy cartilage and cartilage repair tissue in both procedures (MFX: P=0.001; MACT: P=0.007). Correlations were found between the Lysholm and the MOCART score (Pearson: 0.484; P=0.031), between the Lysholm score and DWI (Pearson:-0.557; P=0.011) and a trend between the Lysholm score and T2 (Person: 0.304; P=0.193). CONCLUSION: Using T2-mapping and DWI, additional information could be gained compared to clinical scoring or morphological MRI. In combination clinical, MR-morphological and MR-biochemical parameters can be seen as a promising multimodal tool in the follow-up of cartilage repair.

Differences between dual X-ray absorptiometry using pencil beam and fan beam modes and their determinants in vivo and in vitro

The aim of this study was to determine the influence of individual factors on differences in bone mineral density (BMD) using dual X-ray absorptiometry pencil beam (PB) and fan beam (FB) modes in vivo and in vitro. PB.BMD and FB.BMD of 63 normal Caucasian females ages 21-80 yr were measured at the lumbar spine and hip. Residuals of the FB/PB regression were used to assess the impact of height, weight, adiposity index (AI) (= weight/height(3/2)), back tissue thickness, and PB.BMD, respectively, on FB/PB difference. The Hologic Anthropomorphic Spine Phantom (ASP) was measured using the PB and FB modes at two different levels to assess the impact of scanning mode and focus distance. The European Spine Phantom (ESP) prototype, a geometrically well-defined phantom with known vertebral densities, was measured using PB and FB modes and analyzed manually to determine the impact of bone density on FB/PB difference and automatically to determine the impact of edge detection on FB/PB difference. Population BMD results were perfectly correlated, but significantly overestimated by 1.5% at the lumbar spine and underestimated by 0.7% at the neck, 1.8% at the trochanter, and 2.0% at the total hip, respectively, when using the FB compared with PB mode. At the lumbar spine, the FB/PB residual correlated negatively with height (r = 0.34, p < 0.01) and PB.BMD (r = 0.48, p <: 0. 0001) and positively with AI (r = 0.26, p < 0.05). At the hip, residual of trochanter correlated positively with weight (r = 0.36, p < 0.01) and AI (r = 0.36, p < 0.01). The FB mode significantly increased ASP BMD by 0.7% compared with PB. Using the FB mode, increasing focus distance significantly (p < 0.001) decreased area and bone mineral content, but not BMD. By contrast, increasing focus distance significantly decreased PB.BMD by 0.7%. With the ESP, the PB mode supplied accurate projected are of the bone (AREA) results but significant underestimation of specified BMD in the manual analysis. The FB mode significantly underestimated PB. AREA by 2.9% but fitted specified BMD quite well. FB/PB overestimation was larger for the low-density (+8.7%) than for the high-density vertebra (+4. 9%). The automated analysis resulted in more than 14% underestimation of PB. AREA (low-density vertebra) and an almost 13% overestimation of PB.BMD (high-density vertebra) using FB. In conclusion, FB and PB measurements are highly correlated at the lumbar spine and hip with small but significant BMD differences related to height, adiposity, and BMD. In clinical practice, it can be erroneous to switch from one method to another, especially in women with low bone density.

Differences between recent and historical records of upperspecies limits in the northern European Alps

Are there differences in historical and recent upper range limits of vascular plants and are such differences more pronounced in individual species groups? The limits of 1103 plants of the Northern Alps are compared to range limits in the mid-19th century. The comparison is based on two surveys. The first survey was conducted by Otto Sendtner in 1848–1853, the second in 1991–2008 during a habitat inventory. To our knowledge this is the first comparative studies reaching back to the end of the “Little Ice Age” and comprising an almost entire regional flora covering the complete range of habitats. During the recent survey, most species were found at higher elevations. Even though the differences fit well with the expected shifts due to climate warming we cannot exclude effects of sampling bias. However, we assume that the relative differences between species groups can be safely interpreted. The differences in upper limits between both surveys were significantly larger among forest species. The most important reason is probably discontinued pasture and mowing, which may have amplified possible warming effects. Nitrogen deposits may have contributed to this effect by placing competitive species in a more advantageous position.

Perceptual and processing differences between physical and dichorhinic odor mixtures

Perceptual integration of sensory input from our two nostrils has received little attention in comparison to lateralized inputs for vision and hearing. Here, we investigated whether a binary odor mixture of eugenol and l-carvone (smells of cloves and caraway) would be perceived differently if presented as a mixture in one nostril (physical mixture), vs. the same two odorants in separate nostrils (dichorhinic mixture). In parallel, we investigated whether the different types of presentation resulted in differences in olfactory event-related potentials (OERP). Psychophysical ratings showed that the dichorhinic mixtures were perceived as more intense than the physical mixtures. A tendency for shift in perceived quality was also observed. In line with these perceptual changes, the OERP showed a shift in latencies and amplitudes for early (more "sensory") peaks P1 and N1 whereas no significant differences were observed for the later (more "cognitive") peak P2. The results altogether suggest that the peripheral level is a site of interaction between odorants. Both psychophysical ratings and, for the first time, electrophysiological measurements converge on this conclusion.

A Dose-Response Strategy Reveals Differences between Normal-Weight and Obese Men in Their Metabolic and Inflammatory Responses to a High-Fat Meal.

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (net iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h, P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h, P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068.

Differences Between Monetary and Multidimensional Poverty in the Lao PDR: Implications for Targeting of Poverty Reduction Policies and Interventions

This study compares monetary and multidimensional poverty measures for the Lao People’s Democratic Republic. Using household data of 2007/2008, we compare the empirical outcomes of the country’s current official monetary poverty measure with those of a multidimensional poverty measure. We analyze which population subgroups are identified as poor by both measures and thus belong to the category of the poorest of the poor; and we look at which subgroups are identified as poor by only one of the measures and belong either to the category of the income-poor (identified as poor only by the monetary measure) or to that of the overlooked poor (identified as poor only by the multidimensional poverty measure). Furthermore, we examined drivers of these differences using a multinomial regression model and found that monetary poverty does not capture the multiple deprivations of ethnic minorities, who are only identified as poor when using a multidimensional poverty measure. We conclude that complementing the monetary poverty measure with a multidimensional poverty index would enable more effective targeting of poverty reduction efforts.

Genetics of male nuptial colour divergence between sympatric sister species of a Lake Victoria cichlid fish

The hypothesis of sympatric speciation by sexual selection has been contentious. Several recent theoretical models of sympatric speciation by disruptive sexual selection were tailored to apply to African cichlids. Most of this work concludes that the genetic architecture of female preference and male trait is a key determinant of the likelihood of disruptive sexual selection to result in speciation. We investigated the genetic architecture controlling male nuptial colouration in a sympatric sibling species pair of cichlid fish from Lake Victoria, which differ conspicuously in male colouration and female mating preferences for these. We estimated that the difference between the species in male nuptial red colouration is controlled by a minimum number of two to four genes with significant epistasis and dominance effects. Yellow colouration appears to be controlled by one gene with complete dominance. The two colours appear to be epistatically linked. Knowledge on how male colouration segregates in hybrid generations and on the number of genes controlling differences between species can help us assess whether assumptions made in simulation models of sympatric speciation by sexual selection are realistic. In the particular case of the two sister species that we studied a small number of genes causing major differences in male colouration may have facilitated the divergence in male colouration associated with speciation.

Evidence of neutral and adaptive genetic divergence between European trout populations sampled along altitudinal gradients

Species with a wide geographical distribution are often composed of distinct subgroups which may be adapted to their local environment. European trout (Salmo trutta species complex) provide an example of such a complex consisting of several genetically and ecologically distinct forms. However, trout populations are strongly influenced by human activities, and it is unclear to what extent neutral and adaptive genetic differences have persisted. We sampled 30 Swiss trout populations from heterogeneous environments along replicated altitudinal gradients in three major European drainages. More than 850 individuals were genotyped at 18 microsatellite loci which included loci diagnostic for evolutionary lineages and candidate markers associated with temperature tolerance, reproductive timing and immune defence. We find that the phylogeographic structure of Swiss trout populations has not been completely erased by stocking. Distinct genetic clusters corresponding to the different drainages could be identified, although nonindigenous alleles were clearly present, especially in the two Mediterranean drainages. We also still detected neutral genetic differentiation within rivers which was often associated with the geographical distance between populations. Five loci showed evidence of divergent selection between populations with several drainage-specific patterns. Lineage-diagnostic markers, a marker linked to a quantitative trait locus for upper temperature tolerance in other salmonids and a marker linked to the major histocompatibility class I gene were implicated in local adaptation and some patterns were associated with altitude. In contrast, tentative evidence suggests a signal of balancing selection at a second immune relevant gene (TAP2). Our results confirm the persistence of both neutral and potentially adaptive genetic differences between trout populations in the face of massive human-mediated dispersal.

Tritrichomonas foetus isolates from cats and cattle show minor genetic differences in unrelated loci ITS-2 and EF-1alpha

The protozoan parasite Tritrichomonas foetus is well known as an important causative agent of infertility and abortion in cattle (bovine trichomonosis). This World Organisation for Animal Health (O.I.E.) notifiable disease is thought to be under control in many countries including Switzerland. In recent studies, however, T. foetus has also been identified as an intestinal parasite that causes chronic large-bowel diarrhoea in cats. Since the feline isolates were considered indistinguishable from bovine isolates, the possibility and risk of parasite transmission from cats to cattle and vice versa has been intensively discussed in current literature. Therefore, we investigated if cat and cattle isolates are genetically distinct from each other or in fact represent identical genotypes. For this purpose, two independent genetic loci were selected that turned out to be well-suited for a PCR sequencing-based genotyping of trichomonad isolates: (i) previously published internal transcribed spacer region 2 (ITS-2) and (ii) a semi-conserved sequence stretch of the elongation factor-1 alpha (EF-1alpha) gene used for the first time in the present study. Respective comparative analyses revealed that both loci were sufficiently variable to allow unambiguous genetic discrimination between different trichomonad species. Comparison of both genetic loci confirmed that T. suis and T. mobilensis are phylogenetically very close to T. foetus. Moreover, these two genetic markers were suited to define host-specific genotypes of T. foetus. Both loci showed single base differences between cat and cattle isolates but showed full sequence identity within strains from either cat or cattle isolates. Furthermore, an additional PCR with a forward primer designed to specifically amplify the bovine sequence of EF-1alpha was able to discriminate bovine isolates of T. foetus from feline isolates and also from other trichomonads. The implications these minor genetic differences may have on the biological properties of the distinct isolates remain to be investigated.

Coordinated gene expression in adipose tissue and liver differs between cows with high or low NEFA concentrations in early lactation

Dairy cows with high and low plasma non-esterified fatty acid (NEFA) concentrations in early lactation were compared for plasma parameters and mRNA expression of genes in liver and subcutaneous adipose tissue. The study involved 16 multiparous dairy cows with a plasma NEFA concentration of >500 mumol/l [n = 8, high NEFA (HNEFA)] and <140 mumol/l [n = 8, low NEFA (LNEFA)] in the first week post-partum (pp). Blood samples, adipose and liver tissues were collected on day 1 (+1d) and at week 3 pp (+3wk). Blood plasma was assayed for concentrations of metabolites and hormones. Subcutaneous adipose and liver tissues were analysed for mRNA abundance by real-time qRT-PCR encoding parameters related to lipid metabolism. Results showed that mean daily milk yield and milk fat quantity were higher in HNEFA than in LNEFA cows (p < 0.01), and the NEB was more negative in HNEFA than in LNEFA in +3wk too (p < 0.05). HNEFA cows had slightly lower (p < 0.1) insulin concentrations than LNEFA cows across the study period, and the body condition score decreased more from +1d to +3wk in HNEFA than in LNEFA (p = 0.09). The mRNA abundance of genes in the liver related to fatty acid oxidation (carnitine palmitoyltransferase 2 and very long chain acyl-coenzyme A dehydrogenase) and ketogenesis (3-hydroxy-3-methylglutaryl-coenzyme A synthase 2) were lower in HNEFA than in LNEFA cows. No differences between the two groups were observed for mRNA expression of genes in adipose tissue. The number of calculated significant correlation coefficients (moderately strong) between parameters in the liver and in adipose tissue was nearly similar on +1d, and higher for HNEFA compared with LNEFA cows in +3wk. In conclusion, dairy cows with high compared with low plasma NEFA concentrations in early lactation show differentially synchronized mRNA expression of genes in adipose tissue and liver in +3wk that suggests a different orchestrated homeorhetic regulation of lipid metabolism.