Assessment of circadian rhythm in pain and stiffness in rheumatic diseases according the EMA (Ecologic Momentary Assessment) method: patient compliance with an electronic diary

Background: Many researchers have used paper diaries in an attempt to capture patient experience. However, patient non-compliance with written diary protocols is a serious problem for researchers. Electronic patient experience diaries (eDiary) facilitate Ecologic Momentary Assessment (EMA) study designs by allowing the researcher to administer flexible, programmable assessments and mark each record with a time and date stamp. Objectives: The objectives of the current study were to evaluate methodological issues associated with real-time pain reports (EMA) using electronic patient experience diaries, to quantify compliance (percentage of the total number of diary reports scheduled that were actually completed), and to examine the circadian rhythm in pain and stiffness of patients with rheumatic diseases in an ecologically valid manner. Methods: In this cross-sectional study we examined 49 patients with rheumatic diseases (14 patients with rheumatoid arthritis, 18 with fibromyalgia and 17 with osteoarthritis of the knee), attending the care facilities of the Department of Rheumatology of Universita Politecnica delle Marche. All patients fulfilling the American College of Rheumatology (ACR) criteria. The assessment of pain and stiffness in all patients were repeated seven times a day (8 A.M., 10 A.M., 12 A.M., 2 P.M., 4 P.M., 6 P.M. and 8 P.M.) on seven consecutive days using an electronic diary (DataLoggerO - Pain Level Recorder). A datalogger is newly developed electronic instrument that records measurements of pain and stiffness over time. Dataloggers are small, battery-powered devices that are equipped with a microprocessor. Specific software is then used to select logging parameters (sampling intervals, start time, etc.) and view/analyse the collected data. Compliance is based on the time and date record that was automatically recorded by the devices. Results: Using the data from the electronic diary, we determined that the average verified compliance rate for pain and stiffness were 93.8 and 93.6%, respectively. The two highest compliance rates were observed in patients with rheumatoid arthritis (95.6 and 95.2%, respectively). There were no statistically significant difference in compliance between females and males or patients above or below 60 years old. Significant circadian rhytms in patients with RA and OA of the knee were detected in pain and stiffness. No rhythm in pain or stiffness was observed in subjects with fibromyalgia. Conclusions: We conclude that collection of subjective data using electronic diary in rheumatologic setting is a feasible method than can be adopted with high compliance rates across a range of patient demographic subgroups. The identification of diurnal cycles of self-reported pain and stiffness, using EMA method, has important implications for patients with respect to planning their daily activities and in developing individual therapeutic programs with respect to diurnal variability, which therefore may be more effective

A king and vassals' tale: Molecular signatures of clonal integration in Posidonia oceanica under chronic light shortage

Under unfavourable conditions, clonal plants benefit from physiological integration among ramets, sharing resources and information. Clonal integration can buffer against environmental changes and lets the plant clone work as a ‘macro’ organism. Molecular signals that regulate this phenomenon are completely unknown in marine plants. Here we present a first comprehensive study providing insights into the metabolic role of different types of ramets (i.e. apical vs. vertical) in the foundation species Posidonia oceanica. Plants were exposed to 80% diminishing irradiance level (LL) in a controlled mesocosm system. Subsequent multiscale variations in whole transcriptome expression, global DNA methylation level, photo-physiology, morphology and fitness-related traits, were explored at different exposure times. We tested the hypothesis that vertical shoots (the ‘vassals’) can provide vital resources to apical shoots (the ‘kings’) under energy shortage, thus safeguarding the whole clone survival. Whole transcriptome analysis of leaves and shoot-apical meristems (SAMs) emphasized signatures of molecular integration among ramets, which strongly correlated with higher organization-level responses. In both shoots types, the exposure to LL resulted in a growth slowdown throughout the experiment, which started from immediate signals in SAMs. In apical shoots, this was linked to an acclimative response, where they were suffering a mild stress condition, while in vertical ones it fell in a more severe stress response. Yet, they suffered from sugar starvation and showed a clear cellular stress response in terms of protein refolding and DNA repair mechanisms. Several epigenetic mechanisms modulated the observed gene-expression patterns and the cross-talk between DNA methylation and the cellular energetic status appeared to regulate shoot metabolism under LL. Synthesis. Our results demonstrate a high level of specialization of integrated ramets within seagrass clones and a ‘division of labour’ under adverse conditions. Vertical shoots appear to do ‘most of the job’ especially in terms of resource providing, whereas activated functions in apical shoots were restricted to few important processes, according to an ‘energy-saving’ strategy. The response of vertical shoots could be seen as a ‘sacrificing response’ allowing the survival of ‘the king’ that is key for ensuring propagation and population maintenance, and for the colonization of new environments

DNA methylation dynamics in a coastal foundation seagrass species under abiotic stressors

DNA methylation (DNAm) has been intensively studied in terrestrial plants in response to environmental changes, but its dynamic changes in a temporal scale remain unexplored in marine plants. The seagrass Posidonia oceanica ranks among the slowest-growing and longest-living plants on Earth, and is particularly vulnerable to sea warming and local anthropogenic pressures. Here, we analysed the dynamics of DNAm changes in plants collected from coastal areas differentially impacted by eutrophication (i.e. oligotrophic, Ol; eutrophic, Eu) and exposed to abiotic stressors (nutrients, temperature increase and their combination). Levels of global DNAm (% 5-mC) and the expression of key genes involved in DNAm were assessed after one, two and five weeks of exposure. Results revealed a clear differentiation between plants, depending on environmental stimuli, time of exposure and plants' origin. % 5-mC levels were higher during the initial stress exposure especially in Ol plants, which upregulated almost all genes involved in DNAm. Contrarily, Eu plants showed lower expression levels, which increased under chronic exposure to stressors, particularly to temperature. These findings show that DNAm is dynamic in P. oceanica during stress exposure and underlined that environmental epigenetic variations could be implicated in the regulation of acclimation and phenotypic differences depending on local conditions

Fast and Accurate Multivariate Gaussian Modeling of Protein Families: Predicting Residue Contacts and Protein-Interaction Partners

In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our method aims at extracting such constraints from rapidly accumulating sequence data, and thereby at inferring protein structure and function from sequence information alone. Recently, global statistical inference methods (e.g. direct-coupling analysis, sparse inverse covariance estimation) have achieved a breakthrough towards this aim, and their predictions have been successfully implemented into tertiary and quaternary protein structure prediction methods. However, due to the discrete nature of the underlying variable (amino-acids), exact inference requires exponential time in the protein length, and efficient approximations are needed for practical applicability. Here we propose a very efficient multivariate Gaussian modeling approach as a variant of direct-coupling analysis: the discrete amino-acid variables are replaced by continuous Gaussian random variables. The resulting statistical inference problem is efficiently and exactly solvable. We show that the quality of inference is comparable or superior to the one achieved by mean-field approximations to inference with discrete variables, as done by direct-coupling analysis. This is true for (i) the prediction of residue-residue contacts in proteins, and (ii) the identification of protein-protein interaction partner in bacterial signal transduction. An implementation of our multivariate Gaussian approach is available at the website http://areeweb.polito.it/ricerca/cmp/cod

Does Warming Enhance the Effects of Eutrophication in the Seagrass Posidonia oceanica?

En prens

Does Warming Enhance the Effects of Eutrophication in the Seagrass Posidonia oceanica?

Seagrass meadows are disappearing at rates comparable to those reported for mangroves, coral reefs, and tropical rainforests. One of the main causes of their decline is the so-called cultural eutrophication, i.e., the input of abnormal amounts of nutrients derived from human activities. Besides the impact of eutrophication at a local scale, the occurrence of additional stress factors such as global sea warming may create synergisms in detriment of seagrass meadows’ health. In the present study, we aimed to evaluate if plants undergoing chronic cultural eutrophication and plants growing in relatively pristine waters are more (or less) sensitive to heat stress, nutrient load and the combination of both stressors. To address this question, a mesocosm experiment was conducted using Posidonia oceanica collected from two environments with different nutrients load history. Plants were exposed in controlled conditions to high nutrient concentrations, increased temperature and their combination for 5 weeks, to assess the effect of the single stressors and their interaction. Our results revealed that plants experiencing chronic cultural eutrophication (EU) are more sensitive to further exposure to multiple stressors than plants growing in oligotrophic habitats (OL). OL and EU plants showed different morphological traits and physiological performances, which corroborates the role of local pressures in activating different strategies in response to global environmental changes. EU-plants appeared to be weaker during the treatments, showing the greatest percentage of mortality, particularly under increased temperature. Temperature and nutrient treatments showed opposite effects when tested individually and an offset response when combined. The activation of physiological strategies with high energetic expenses to cope with excess of nutrients and other stressors, could affect plants present and future persistence, particularly under eutrophic conditions. Our results represent a step forward in understanding the complex interactions that occur in natural environments. Moreover, unraveling intraspecific strategies and the role of local acclimation/adaptation in response to multiple stressors could be crucial for seagrass conservation strategies under a climate change scenario

Effects of Current and Future Summer Marine Heat Waves on Posidonia oceanica: Plant Origin Matters?

Marine heat waves (MHWs), prolonged discrete anomalously warm water events, have been increasing significantly in duration, intensity and frequency all over the world, and have been associated with a variety of impacts including alteration of ecosystem structure and function. This study assessed the effects of current and futureMHWs on the Mediterranean seagrass Posidonia oceanica performance, also testing the importance of the thermal environment where the plant lives. The effects of current MHWs were studied through a mensurative experiment in a cold and in a warm site (West and North-West Sardinia, Italy, respectively). Future MHWs effects were tested through a manipulative experiment using P. oceanica shoots collected fromthe cold and warmsites and transplanted in a common garden in front of a power plant (North-West Sardinia): here plants were exposed to heat longer in duration and stronger in intensity than the natural MHWs of the last 20 years, resembling the future scenario. Morphological (total # of leaves, maximum leaf length, and percentage of total necrotic leaf length per shoot) and biochemical variables (leaf proteins, carbohydrates, and lipids) were considered. Plants had similar sublethal responses in both the experiments for most of the variables, revealing that current and future MHWs had similar effect types, but different in magnitude depending on the intensity of the waves: in general, the number of leaves, the maximum leaf length and lipid content decreased, while the leaf necrosis and carbohydrates increased. However, also the origin of the plants affected the results, corroborating the hypothesis that the thermal context the plants live affects their tolerance to the heat. Overall, this study provided evidence about the importance of biochemical variations, such as carbohydrate and lipid levels, as potentially good indicators of seagrass heat stress

Comparison of relativity theories with observer-independent scales of both velocity and length/mass

We consider the two most studied proposals of relativity theories with observer-independent scales of both velocity and length/mass: the one discussed by Amelino-Camelia as illustrative example for the original proposal (gr-qc/0012051) of theories with two relativistic invariants, and an alternative more recently proposed by Magueijo and Smolin (hep-th/0112090). We show that these two relativistic theories are much more closely connected than it would appear on the basis of a naive analysis of their original formulations. In particular, in spite of adopting a rather different formal description of the deformed boost generators, they end up assigning the same dependence of momentum on rapidity, which can be described as the core feature of these relativistic theories. We show that this observation can be used to clarify the concepts of particle mass, particle velocity, and energy-momentum-conservation rules in these theories with two relativistic invariants.Comment: 21 pages, LaTex. v2: Andrea Procaccini (contributing some results from hia Laurea thesis) is added to the list of authors and the paper provides further elements of comparison between DSR1 and DSR2, including the observation that both lead to the same formula for the dependence of momentum on rapidit

Effects of Current and Future Summer Marine Heat Waves on Posidonia oceanica: Plant Origin Matters?

Marine heat waves (MHWs), prolonged discrete anomalously warm water events, have been increasing significantly in duration, intensity and frequency all over the world, and have been associated with a variety of impacts including alteration of ecosystem structure and function. This study assessed the effects of current and future MHWs on the Mediterranean seagrass Posidonia oceanica performance, also testing the importance of the thermal environment where the plant lives. The effects of current MHWs were studied through a mensurative experiment in a cold and in a warm site (West and North-West Sardinia, Italy, respectively). Future MHWs effects were tested through a manipulative experiment using P. oceanica shoots collected from the cold and warm sites and transplanted in a common garden in front of a power plant (North-West Sardinia): here plants were exposed to heat longer in duration and stronger in intensity than the natural MHWs of the last 20 years, resembling the future scenario. Morphological (total # of leaves, maximum leaf length, and percentage of total necrotic leaf length per shoot) and biochemical variables (leaf proteins, carbohydrates, and lipids) were considered. Plants had similar sublethal responses in both the experiments for most of the variables, revealing that current and future MHWs had similar effect types, but different in magnitude depending on the intensity of the waves: in general, the number of leaves, the maximum leaf length and lipid content decreased, while the leaf necrosis and carbohydrates increased. However, also the origin of the plants affected the results, corroborating the hypothesis that the thermal context the plants live affects their tolerance to the heat. Overall, this study provided evidence about the importance of biochemical variations, such as carbohydrate and lipid levels, as potentially good indicators of seagrass heat stress.En prens