Usability and preliminary effectiveness of an app-based physical activity and education program for people with hip or knee osteoarthritis - a pilot randomized controlled trial.

BACKGROUND: Hip and knee osteoarthritis (OA) are highly prevalent worldwide. The guidelines recommend physical activity and education as the core treatments for osteoarthritis. Digital health has the potential to engage people in physical activity and disease management. Therefore, we conducted a pilot trial to assess the usability and preliminary effectiveness of an app-based physical activity and education program (Join2Move) compared to usual care for people with hip and/or knee OA in Germany. METHODS: A randomized controlled pilot study was conducted. Individuals with diagnosed or self-reported knee and hip OA were included. Allocation to the intervention or control group was randomized. The intervention group received the Join2Move program. The Join2Move program was previously developed as a website and evaluated in the Netherlands. For the current study, the program was translated and adapted to the German context and adjusted from a website to an app. The control group received usual care. The primary outcomes were usability and preliminary effectiveness (pain and physical functioning). Measurements were taken at baseline and at twelve weeks. The data analysis was performed using SPSS (IBM SPSS Statistics 29.0). RESULTS: Sixty participants, with a mean age of 61.9 (SD ± 7.2) years, were allocated to the intervention (n = 32) or the control group (n = 28) and included in the analysis. The majority of participants had knee OA (68%), and 12% had hip and knee OA. The dropout rate was n = 11 (18%). No adverse events were reported. Usability was rated as acceptable (mean System Usability Scale = 71.3/100) with a wide range (32.5 to 100). Statistically significant between-group differences were found only for pain (mean difference 8.52 (95% CI 1.01 to 16.04), p = 0.027). CONCLUSIONS: Join2Move demonstrated acceptable usability. The preliminary results of the pilot trial indicate the potential of a stand-alone app for the treatment of patients with hip or knee OA. However, the acceptable usability of Join2Move limits its recommendation for everyone. There appears to be room for improvement in app usability and in identifying patients for whom the app is suitable and the right time to use a stand-alone app. TRIAL REGISTRATION: German Clinical Trials Register DRKS00027164 .

A transcriptomic signature to predict adjuvant gemcitabine sensitivity in pancreatic adenocarcinoma.

BACKGROUND: Chemotherapy is the only systemic treatment approved for pancreatic ductal adenocarcinoma (PDAC), with a selection of regimens based on patients' performance status and expected efficacy. The establishment of a potent stratification associated with chemotherapeutic efficacy could potentially improve prognosis by tailoring treatments. PATIENTS AND METHODS: Concomitant chemosensitivity and genome-wide RNA profiles were carried out on preclinical models (primary cell cultures and patient-derived xenografts) derived from patients with PDAC included in the PaCaOmics program (NCT01692873). The RNA-based stratification was tested in a monocentric cohort and validated in a multicentric cohort, both retrospectively collected from resected PDAC samples (67 and 368 patients, respectively). Forty-three (65%) and 203 (55%) patients received adjuvant gemcitabine in the monocentric and the multicentric cohorts, respectively. The relationships between predicted gemcitabine sensitivity and patients' overall survival (OS) and disease-free survival were investigated. RESULTS: The GemPred RNA signature was derived from preclinical models, defining gemcitabine sensitive PDAC as GemPred+. Among the patients who received gemcitabine in the test and validation cohorts, the GemPred+ patients had a higher OS than GemPred- (P = 0.046 and P = 0.00216). In both cohorts, the GemPred stratification was not associated with OS among patients who did not receive gemcitabine. Among gemcitabine-treated patients, GemPred+ patients had significantly higher OS than the GemPred-: 91.3 months [95% confidence interval (CI): 61.2-not reached] versus 33 months (95% CI: 24-35.2); hazard ratio 0.403 (95% CI: 0.221-0.735, P = 0.00216). The interaction test for gemcitabine and GemPred+ stratification was significant (P = 0.0245). Multivariate analysis in the gemcitabine-treated population retained an independent predictive value. CONCLUSION: The RNA-based GemPred stratification predicts the benefit of adjuvant gemcitabine in PDAC patients.

Chicken adaptive response to low energy diet: main role of the hypothalamic lipid metabolism revealed by a phenotypic and multi-tissue transcriptomic approach.

BACKGROUND: Production conditions of layer chicken can vary in terms of temperature or diet energy content compared to the controlled environment where pure-bred selection is undertaken. The aim of this study was to better understand the long-term effects of a 15%-energy depleted diet on egg-production, energy homeostasis and metabolism via a multi-tissue transcriptomic analysis. Study was designed to compare effects of the nutritional intervention in two layer chicken lines divergently selected for residual feed intake. RESULTS: Chicken adapted to the diet in terms of production by significantly increasing their feed intake and decreasing their body weight and body fat composition, while their egg production was unchanged. No significant interaction was observed between diet and line for the production traits. The low energy diet had no effect on adipose tissue and liver transcriptomes. By contrast, the nutritional challenge affected the blood transcriptome and, more severely, the hypothalamus transcriptome which displayed 2700 differentially expressed genes. In this tissue, the low-energy diet lead to an over-expression of genes related to endocannabinoid signaling (CN1R, NAPE-PLD) and to the complement system, a part of the immune system, both known to regulate feed intake. Both mechanisms are associated to genes related polyunsaturated fatty acids synthesis (FADS1, ELOVL5 and FADS2), like the arachidonic acid, a precursor of anandamide, a key endocannabinoid, and of prostaglandins, that mediate the regulatory effects of the complement system. A possible regulatory role of NR1H3 (alias LXRα) has been associated to these transcriptional changes. The low-energy diet further affected brain plasticity-related genes involved in the cholesterol synthesis and in the synaptic activity, revealing a link between nutrition and brain plasticity. It upregulated genes related to protein synthesis, mitochondrial oxidative phosphorylation and fatty acid oxidation in the hypothalamus, suggesting reorganization in nutrient utilization and biological synthesis in this brain area. CONCLUSIONS: We observed a complex transcriptome modulation in the hypothalamus of chicken in response to low-energy diet suggesting numerous changes in synaptic plasticity, endocannabinoid regulation, neurotransmission, lipid metabolism, mitochondrial activity and protein synthesis. This global transcriptomic reprogramming could explain the adaptive behavioral response (i.e. increase of feed intake) of the animals to the low-energy content of the diet.

Multi-tissue transcriptomic study reveals the main role of liver in the chicken adaptive response to a switch in dietary energy source through the transcriptional regulation of lipogenesis.

BACKGROUND: Because the cost of cereals is unstable and represents a large part of production charges for meat-type chicken, there is an urge to formulate alternative diets from more cost-effective feedstuff. We have recently shown that meat-type chicken source is prone to adapt to dietary starch substitution with fat and fiber. The aim of this study was to better understand the molecular mechanisms of this adaptation to changes in dietary energy sources through the fine characterization of transcriptomic changes occurring in three major metabolic tissues - liver, adipose tissue and muscle - as well as in circulating blood cells. RESULTS: We revealed the fine-tuned regulation of many hepatic genes encoding key enzymes driving glycogenesis and de novo fatty acid synthesis pathways and of some genes participating in oxidation. Among the genes expressed upon consumption of a high-fat, high-fiber diet, we highlighted CPT1A, which encodes a key enzyme in the regulation of fatty acid oxidation. Conversely, the repression of lipogenic genes by the high-fat diet was clearly associated with the down-regulation of SREBF1 transcripts but was not associated with the transcript regulation of MLXIPL and NR1H3, which are both transcription factors. This result suggests a pivotal role for SREBF1 in lipogenesis regulation in response to a decrease in dietary starch and an increase in dietary PUFA. Other prospective regulators of de novo hepatic lipogenesis were suggested, such as PPARD, JUN, TADA2A and KAT2B, the last two genes belonging to the lysine acetyl transferase (KAT) complex family regulating histone and non-histone protein acetylation. Hepatic glycogenic genes were also down-regulated in chickens fed a high-fat, high-fiber diet compared to those in chickens fed a starch-based diet. No significant dietary-associated variations in gene expression profiles was observed in the other studied tissues, suggesting that the liver mainly contributed to the adaptation of birds to changes in energy source and nutrients in their diets, at least at the transcriptional level. Moreover, we showed that PUFA deposition observed in the different tissues may not rely on transcriptional changes. CONCLUSION: We showed the major role of the liver, at the gene expression level, in the adaptive response of chicken to dietary starch substitution with fat and fiber.

Human and avian running on uneven ground: a model-based comparison.

Birds and humans are successful bipedal runners, who have individually evolved bipedalism, but the extent of the similarities and differences of their bipedal locomotion is unknown. In turn, the anatomical differences of their locomotor systems complicate direct comparisons. However, a simplifying mechanical model, such as the conservative spring-mass model, can be used to describe both avian and human running and thus, provides a way to compare the locomotor strategies that birds and humans use when running on level and uneven ground. Although humans run with significantly steeper leg angles at touchdown and stiffer legs when compared with cursorial ground birds, swing-leg adaptations (leg angle and leg length kinematics) used by birds and humans while running appear similar across all types of uneven ground. Nevertheless, owing to morphological restrictions, the crouched avian leg has a greater range of leg angle and leg length adaptations when coping with drops and downward steps than the straight human leg. On the other hand, the straight human leg seems to use leg stiffness adaptation when coping with obstacles and upward steps unlike the crouched avian leg posture.

Bio-inspired swing leg control for spring-mass robots running on ground with unexpected height disturbance.

We proposed three swing leg control policies for spring-mass running robots, inspired by experimental data from our recent collaborative work on ground running birds. Previous investigations suggest that animals may prioritize injury avoidance and/or efficiency as their objective function during running rather than maintaining limit-cycle stability. Therefore, in this study we targeted structural capacity (maximum leg force to avoid damage) and efficiency as the main goals for our control policies, since these objective functions are crucial to reduce motor size and structure weight. Each proposed policy controls the leg angle as a function of time during flight phase such that its objective function during the subsequent stance phase is regulated. The three objective functions that are regulated in the control policies are (i) the leg peak force, (ii) the axial impulse, and (iii) the leg actuator work. It should be noted that each control policy regulates one single objective function. Surprisingly, all three swing leg control policies result in nearly identical subsequent stance phase dynamics. This implies that the implementation of any of the proposed control policies would satisfy both goals (damage avoidance and efficiency) at once. Furthermore, all three control policies require a surprisingly simple leg angle adjustment: leg retraction with constant angular acceleration.

Pleiotropic effects of polymorphism of the gene diacylglycerol-O-transferase 1 (DGAT1) in the mammary gland tissue of dairy cows.

Microarray analysis was used to identify genes whose expression in the mammary gland of Holstein-Friesian dairy cows was affected by the nonconservative Ala to Lys amino acid substitution at position 232 in exon VIII of the diacylglycerol-O-transferase 1 (DGAT1) gene. Mammary gland biopsies of 9 homozygous Ala cows, 13 heterozygous cows (Ala/Lys), and 4 homozygous Lys cows in midlactation were taken. Microarray ANOVA and factor analysis for multiple testing methods were used as statistical methods to associate the expression level of the genes present on Affymetrix bovine genome arrays (Affymetrix Inc., Santa Clara, CA) with the DGAT1 gene polymorphism. The data was also analyzed at the level of functional modules by gene set enrichment analysis. In this small-scale experimental setting, DGAT1 gene polymorphism did not modify milk yield and composition significantly, although expected changes occurred in the yields of C14:0, cis-9 C16:1, and long-chain fatty acids. Diacylglycerol-O-transferase 1 gene polymorphism affected the expression of 30 annotated genes related to cell growth, proliferation, and development, remodeling of the tissue, cell signaling and immune system response. Furthermore, the main affected functional modules were related to energy metabolism (lipid biosynthesis, oxidative phosphorylation, electron transport chain, citrate cycle, and propanoate metabolism), protein degradation (proteosome-ubiquitin pathways), and the immune system. We hypothesize that the observed differences in transcriptional activity reflect counter mechanisms of mammary gland tissue to respond to changes in milk fatty acid concentration or composition, or both.

AnnotQTL: a new tool to gather functional and comparative information on a genomic region.

AnnotQTL is a web tool designed to aggregate functional annotations from different prominent web sites by minimizing the redundancy of information. Although thousands of QTL regions have been identified in livestock species, most of them are large and contain many genes. This tool was therefore designed to assist the characterization of genes in a QTL interval region as a step towards selecting the best candidate genes. It localizes the gene to a specific region (using NCBI and Ensembl data) and adds the functional annotations available from other databases (Gene Ontology, Mammalian Phenotype, HGNC and Pubmed). Both human genome and mouse genome can be aligned with the studied region to detect synteny and segment conservation, which is useful for running inter-species comparisons of QTL locations. Finally, custom marker lists can be included in the results display to select the genes that are closest to your most significant markers. We use examples to demonstrate that in just a couple of hours, AnnotQTL is able to identify all the genes located in regions identified by a full genome scan, with some highlighted based on both location and function, thus considerably increasing the chances of finding good candidate genes. AnnotQTL is available at http://annotqtl.genouest.org.

Robust and efficient walking with spring-like legs.

The development of bipedal walking robots is inspired by human walking. A way of implementing walking could be performed by mimicking human leg dynamics. A fundamental model, representing human leg dynamics during walking and running, is the bipedal spring-mass model which is the basis for this paper. The aim of this study is the identification of leg parameters leading to a compromise between robustness and energy efficiency in walking. It is found that, compared to asymmetric walking, symmetric walking with flatter angles of attack reveals such a compromise. With increasing leg stiffness, energy efficiency increases continuously. However, robustness is the maximum at moderate leg stiffness and decreases slightly with increasing stiffness. Hence, an adjustable leg compliance would be preferred, which is adaptable to the environment. If the ground is even, a high leg stiffness leads to energy efficient walking. However, if external perturbations are expected, e.g. when the robot walks on uneven terrain, the leg should be softer and the angle of attack flatter. In the case of underactuated robots with constant physical springs, the leg stiffness should be larger than k = 14 in order to use the most robust gait. Soft legs, however, lack in both robustness and efficiency.

Swing leg control in human running.

Humans can run within a wide range of speeds without thinking about stabilizing strategies. The leg properties seem to be adjusted automatically without need for sensory feedback. In this work, the dynamics of human running are represented by the planar spring mass model. Within this framework, for higher speeds, running patterns can be stable without control strategies. Here, potential strategies that provide stability over a broader range of running patterns are considered and these theoretical predictions are compared to human running data. Periodic running solutions are identified and analyzed with respect to their stability. The control strategies are assumed as linear adaptations of the leg parameters-leg angle, leg stiffness and leg length-during the swing phase. To evaluate the applied control strategies regarding their influence on landing behavior, two parameters are introduced: the velocity of the foot relative to the ground (ground speed matching) and the foot's angle of approach. The results show that periodic running solutions can be stabilized and that control strategies, which guarantee running stability, are redundant. For any swing leg kinematics (adaptation of the leg angle and the leg length), running stability can be achieved by adapting the leg stiffness in anticipation of the ground contact.

Lymphoma masquerading as infection.

During surgical training, medical students and residents constantly are reminded to culture every suspected tumor and send tissue for pathologic evaluation for every suspected abscess. A diagnosis of cancer can be missed easily if this procedure is not followed, delaying the diagnosis and possibly adversely affecting the patient's prognosis. The confusion also may be compounded by a sterile abscess, positive culture results or a negative biopsy specimen. Therefore it is imperative to do a biopsy and a culture on any suspect lesion. An additional workup and possible biopsy may be warranted for a nonhealing wound that has been treated appropriately. The cases of three patients with lymphoma that were treated as infectious processes are presented. In all three instances, the appropriate treatment was delayed because of a delay in diagnosis.

Oscillations of the superconducting critical current in Nb-Cu-Ni-Cu-Nb junctions.

We report on experimental studies of superconductor-ferromagnet layered structures. Strong oscillations of the critical supercurrent were observed with the thickness variation of the ferromagnet. Using known microscopic parameters of Ni, we found reasonable agreement between the period of oscillations and the decay of the measured critical current, and theoretical calculations.