Predicting self-reported functional improvement one year after primary total knee arthroplasty using pre- and postoperative patient-reported outcome measures

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No clinical difference between TiN-coated versus uncoated cementless CoCrMo mobile-bearing total knee arthroplasty; 10-year follow-up of a randomized controlled trial

Purpose: Improvement of biomechanical properties of cobalt–chromium–molybdenum (CoCrMo) implant surface and reduction of adhesive wear is achieved by titanium–nitride (TiN) coating in vitro. Less pain, higher postoperative outcome scores and a lower revision rate after TKA with a TiN-coated CoCrMo TKA compared with uncoated CoCrMo TKA after 10-year follow-up was hypothesized. Methods: In a double-blinded RCT, 101 patients received a cementless mobile-bearing CoCrMo TKA, either TiN-coated or uncoated. The primary outcome measure was the visual analogue scale (VAS) score for pain and secondary outcome measures were the Knee Society Score (KSS), Oxford Knee Score (OKS), revision rate and adverse events. Patients were assessed at 6 weeks, 6 months, 1 year, 5 years and 10 years, postoperatively. Results: 68 patients (67%) were available for 10-year follow-up. No difference was found in any of the assessed outcome measures with a mean decrease in VAS score (31.6 ± 22.9) and a mean increase in OKS (10.9 ± 8.4), KSS (29.3 ± 31.4), KSSK (26.4 ± 18.2) and KSSF (4.1 ± 22.9). Overall revision rate was 7% (coated 6% vs uncoated 8%) without additional revision procedures between 5 and 10-year follow-up. Conclusions: The in vitro potential benefits of TiN coating did not result in better clinical outcome when compared to an uncoated cementless TKA. Pain, functional outcome and revision rates were comparable after 10-year follow-up. TiN-coated cementless TKA provides comparable good long-term results, similar to uncoated cementless CoCrMo TKA. Level of evidence: Level 1, Therapeutic Study Netherlands Trial Register: NL2887/NTR3033

Osteocyte morphology in human tibiae of different bone pathologies with different bone mineral density - Is there a role for mechanosensing?

Matrix strains due to external loading are different in bones of different pathologies with different bone mineral density (BMD), and are likely sensed by the osteocytes, the putative bone mechanosensors. The mechanosensitivity of osteocytes appears to be strongly influenced by their morphology. in this study, we explored the possibility that osteocyte morphology might play a role in various bone pathologies with different BMD. Confocal laser scanning microscopy and nano-CT were used to quantitatively determine 3D morphology and alignment of osteocytes and osteocyte lacunae in human proximal tibial bone with relatively low (osteopenic), medium (osteoarthritic), and high (osteopetrotic) BMD, Osteopenic osteocytes were relatively large and round (lengths 8.9:15.6:13.4 mu m), osteopetrotic osteocytes were small and discoid shaped (lengths 5.5:11.1:10.8 mu m), and osteoarthritic osteocytes were large and elongated (lengths 8.4:17.3:12.2 mu m). Osteopenic osteocyte lacunae showed 3.5 fold larger volume and 2.2 fold larger surface area than osteciarthritic lacunae, whereas osteopetrotic lacunae were 1.9 fold larger and showed 1.5 fold larger surface area than osteoarthritic lacunae. Osteopetrotic osteocyte lacunae had lower alignment than osteopenic and osteoarthritic lacunae as indicated by their lower degree of anisotropy. The differences in 3D morphology ofosteocytes and their lacunae in long bones of different pathologies with different BMD might reflect an adaptation to matrix strain due to different external loading conditions. since direct mechanosensing of matrix strain likely occurs by the cell bodies, the differences in Moreover, osteocyte morphology and their lacunae might indicate differences in osteocyte mechanosensitivity. The exact relationship between osteocyte morphology and bone architecture, however, is complex and deserves further study. (C) 2009 Elsevier Inc. All rights reserve

Defeat stress in rodents: From behavior to molecules

Mood and anxiety disorders are prevalent conditions affecting one out of four people during lifetime. The development of high validity animal models to study these disorders has been a major challenge in the past. When considering experimental approaches for studying affective disorders, the social defeat paradigm has been shown to have etiological, predictive and face validity. Here, we explain the general principle of social defeat stress paradigms, with a strong focus on the resident-intruder model and compare different experimental settings as published to date. We discuss behavioral changes described in defeated animals as well as changes in the animal's physiological parameters. In addition, we provide an overview of the molecular adaptations that are found in animals subjected to defeat stress, with special attention to neural circuits and neuroendocrine signaling. Defeat produces specific behaviors resembling the signs and symptoms of humans with affective disorders, such as anhedonia, social avoidance, despair and anxiety. These can be linked to a wide range of physiological changes-ranging from cardiovascular changes to alterations in the immune system- or by disturbances in specific neurotransmitter systems, in particular serotonin and dopamine. The defeat stress model thus impacts on several functional domains of behavior and may mimic cardinal features of a multitude of psychiatric disorders including depression, post-traumatic stress disorder and schizophrenia. This manuscript critically reviews the core findings, strengths and limitations of the range of animal studies in this field and provides future perspectives.publisher: Elsevier articletitle: Defeat stress in rodents: From behavior to molecules journaltitle: Neuroscience & Biobehavioral Reviews articlelink: http://dx.doi.org/10.1016/j.neubiorev.2015.10.006 content_type: article copyright: Copyright © 2015 Elsevier Ltd. Published by Elsevier Ltd. All rights reserved.status: publishe

Epigenetic Genes and Emotional Reactivity to Daily Life Events:A Multi-Step Gene-Environment Interaction Study

Recent human and animal studies suggest that epigenetic mechanisms mediate the impact of environment on development of mental disorders. Therefore, we hypothesized that polymorphisms in epigenetic-regulatory genes impact stress-induced emotional changes. A multi-step, multi-sample gene-environment interaction analysis was conducted to test whether 31 single nucleotide polymorphisms (SNPs) in epigenetic-regulatory genes, i.e. three DNA methyltransferase genes DNMT1, DNMT3A, DNMT3B, and methylenetetrahydrofolate reductase (MTHFR), moderate emotional responses to stressful and pleasant stimuli in daily life as measured by Experience Sampling Methodology (ESM). In the first step, main and interactive effects were tested in a sample of 112 healthy individuals. Significant associations in this discovery sample were then investigated in a population-based sample of 434 individuals for replication. SNPs showing significant effects in both the discovery and replication samples were subsequently tested in three other samples of: (i) 85 unaffected siblings of patients with psychosis, (ii) 110 patients with psychotic disorders, and iii) 126 patients with a history of major depressive disorder. Multilevel linear regression analyses showed no significant association between SNPs and negative affect or positive affect. No SNPs moderated the effect of pleasant stimuli on positive affect. Three SNPs of DNMT3A (rs11683424, rs1465764, rs1465825) and 1 SNP of MTHFR (rs1801131) moderated the effect of stressful events on negative affect. Only rs11683424 of DNMT3A showed consistent directions of effect in the majority of the 5 samples. These data provide the first evidence that emotional responses to daily life stressors may be moderated by genetic variation in the genes involved in the epigenetic machinery

Demographic characteristics and ESM variables of the different samples.

<p>Sample I = Healthy control; Sample II = Twins from the general population; Sample III = Unaffected siblings of psychotic patients; Sample IV = Patients with psychotic disorder; Sample V = Patients with a history of a major depressive disorder currently displaying residual depressive symptoms.</p>a<p>Number of ESM reports when scores for both stressful event and NA are available,</p>b<p>number of ESM report when scores for both pleasant event and PA are available.</p