Decoding the differential biomarkers of Rheumatoid arthritis and Osteoarthritis: A functional genomics paradigm to design disease specific therapeutics

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unidentified aetiology, chiefly affecting the synovial membranes of joints, cartilage, bone, bursa and tendon sheath. Osteoarthritis (OA) is a degenerative disorder and encompass different sets of pathogenic pathways than RA; however, it shows a medley of clinical manifestations or symptoms resembling RA. Hence, we intend to identify more disease specific biomarkers through the meta-analysis of microarray datasets that can be crucial in the differential diagnosis, disease specific treatment as well as management of both RA and OA in a typical clinical setting.     

Diseases of American lobsters (Homarus americanus): a review

The American lobster fishery is a significant economic driver in coastal communities of North America. Increasingly, the impacts of infectious disease are recognized as important components and factors in the population ecology and subsequent management of the lobster fishery. Both environmental and anthropogenic factors impact marine diseases. The review herein highlights aspects of several important bacterial, fungal and protistan diseases, including gaffkemia, shell disease, vibriosis, disease caused by species of Lagenidium, Haliphthoros and Fusarium, paramoebiasis and Bumper Car disease. As the global environment continues to change, these diseases could more severely affect both wild caught and impounded lobsters.     

A career structure for general practice.

Training for general practitioners usually provides little experience in research, business management, or dealing with chronic disease. It is these areas that could provide scope for further training after becoming a general practitioner principal and provided career goals. Formally recognised research practices, perhaps with one partner coordinating research but all participating, and district research facilitators could increase both the quality and the quantity of research in general practice. Recognising the different skills of doctors in the partnership and referring patients to the most appropriate partner will improve care for patients as well as provide career development. Further training could be aimed at filling gaps in the practice''s pool of skills. Good management skills are becoming more important as practice teams get bigger and fundholding spreads. Some doctors may wish to become full time or part time managers and the idea of accredited courses for management has been raised.     

Emergent spatial structure and pathogen epidemics: the influence of management and stochasticity in agroecosystems

Organisms susceptible to disease, from humans to crops, inevitably have spatial geometry that influence disease dynamics. Understanding how spatial structure emerges through time in ecological systems and how that structure influences disease dynamics is of practical importance for natural and human management systems. Here we use the perennial crop, coffee, Coffea arabica, along with its pathogen, the coffee leaf rust, Hemileia vastatrix, as a model system to understand how spatial structure is created in agroecosystems and its subsequent influence on the dynamics of the system. Here, we create a simple null model of the socio-ecological process of death and stochastic replanting of coffee plants on a plot. We then use spatial networks to quantify the spatial structures and make comparisons of our stochastic null model to empirically observed spatial distributions of coffee. We then present a simple model of pathogen spread on spatial networks across a range of spatial geometries emerging from our null model and show how both local and regional management of agroecosystems interact with space and time to alter disease dynamics. Our results suggest that our null model of evolving spatial structure can capture many critical features of how the spatial arrangement of plants changes through time in coffee agroecosystems. Additionally, we find small changes in management factors that can influence the scale of pathogen transmission, such as shade tree removal, and result in a rapid transition to epidemics with lattice-like spatial arrangements but not with irregular planting geometries. The results presented here may have practical implications for farmers in Latin America who are in the process of replanting and overhauling management of their coffee farms in response to a coffee leaf rust epidemic in 2013. We suggest that shade reduction in conjunction with more lattice-like planting schemes may result in coffee being more prone to epidemic-like dynamics of the coffee leaf rust in the future.     

Renal co-morbidity in patients with rheumatic diseases

Renal co-morbidity is common in patients with rheumatic disease based on regular assessment of serum and urine parameters of renal function. When patients present with both arthritis and renal abnormalities the following questions have to be addressed. Is kidney disease a complication of rheumatic disease or its management, or are they both manifestations of a single systemic autoimmune disease? Is rheumatic disease a complication of kidney disease and its management? How do rheumatic disease and kidney disease affect each other even when they are unrelated? The present review provides an overview of how to address these questions in daily practice.     

Renal co-morbidity in patients with rheumatic diseases

Renal co-morbidity is common in patients with rheumatic disease based on regular assessment of serum and urine parameters of renal function. When patients present with both arthritis and renal abnormalities the following questions have to be addressed. Is kidney disease a complication of rheumatic disease or its management, or are they both manifestations of a single systemic autoimmune disease? Is rheumatic disease a complication of kidney disease and its management? How do rheumatic disease and kidney disease affect each other even when they are unrelated? The present review provides an overview of how to address these questions in daily practice.     

Common crossroads in diabetes management

The prevalence and impact of type 2 diabetes are reaching epidemic proportions in the United States. Data suggest that effective management can reduce the risk for both microvascular and macrovascular complications of diabetes. In treating patients with diabetes, physicians must be prepared not only to tailor the initial treatment to the individual and his or her disease severity but also to advance treatment as necessary and in step with disease progression. The majority of patients with diabetes are not at goal for glycated hemoglobin A1C, fasting plasma glucose, or postprandial plasma glucose levels. Although lifestyle changes based on improved diet and exercise practices are basic elements of therapy at every stage, pharmacologic therapy is usually necessary to achieve and maintain glycemic control. Oral antidiabetic agents may be effective early in the disease but, eventually, they are unable to compensate as the disease progresses. For patients unable to achieve glycemic control on 2 oral agents, current guidelines strongly urge clinicians to consider the initiation of insulin as opposed to adding a third oral agent. Recent research suggests that earlier initiation of insulin is more physiologic and may be more effective in preventing complications of diabetes. Newer, longer-lasting insulin analogs and the use of simplified treatment plans may overcome psychological resistance to insulin on the part of physicians and patients. This article summarizes the risks associated with uncontrolled fasting and postprandial hyperglycemia, briefly reviews the various treatment options currently available for type 2 diabetes, presents case vignettes to illustrate crossroads encountered when advancing treatment, and offers guidance to the osteopathic physician on the selection of appropriate treatments for the management of type 2 diabetes.     

Downy mildew (Plasmopara viticola) epidemics on grapevine under climate change

As climate is a key agro‐ecosystem driving force, climate change could have a severe impact on agriculture. Many assessments have been carried out to date on the possible effects of climate change (temperature, precipitation and carbon dioxide concentration changes) on plant physiology. At present however, likely effects on plant pathogens have not been investigated deeply. The aim of this work was to simulate future scenarios of downy mildew (Plasmopara viticola) epidemics on grape under climate change, by combining a disease model to output from two general circulation models (GCMs). Model runs corresponding to the SRES‐A2 emissions scenario, characterized by high projections of both population and greenhouse gas emissions from present to 2100, were chosen in order to investigate impacts of worst‐case scenarios, among those currently available from IPCC. Three future decades were simulated (2030, 2050, 2080), using as baseline historical series of meteorological data collected from 1955 to 2001 in Acqui Terme, an important grape‐growing area in the north‐west of Italy. Both GCMs predicted increase of temperature and decrease of precipitation in this region. The simulations obtained by combining the disease model to the two GCM outputs predicted an increase of the disease pressure in each decade: more severe epidemics were a direct consequence of more favourable temperature conditions during the months of May and June. These negative effects of increasing temperatures more than counterbalanced the effects of precipitation reductions, which alone would have diminished disease pressure. Results suggested that, as adaptation response to future climate change, more attention would have to be paid in the management of early downy mildew infections; two more fungicide sprays were necessary under the most negative climate scenario, compared with present management regimes. At the same time, increased knowledge on the effects of climate change on host–pathogen interactions will be necessary to improve current predictions.     

Modelling Associations between Public Understanding,Engagement and Forest Conditions in the Inland Northwest,USA

Opinions about public lands and the actions of private non-industrial forest owners in the western United States play important roles in forested landscape management as both public and private forests face increasing risks from large wildfires, pests and disease. This work presents the responses from two surveys, a random-sample telephone survey of more than 1500 residents and a mail survey targeting owners of parcels with 10 or more acres of forest. These surveys were conducted in three counties (Wallowa, Union, and Baker) in northeast Oregon, USA. We analyze these survey data using structural equation models in order to assess how individual characteristics and understanding of forest management issues affect perceptions about forest conditions and risks associated with declining forest health on public lands. We test whether forest understanding is informed by background, beliefs, and experiences, and whether as an intervening variable it is associated with views about forest conditions on publicly managed forests. Individual background characteristics such as age, gender and county of residence have significant direct or indirect effects on our measurement of understanding. Controlling for background factors, we found that forest owners with higher self-assessed understanding, and more education about forest management, tend to hold more pessimistic views about forest conditions. Based on our results we argue that self-assessed understanding, interest in learning, and willingness to engage in extension activities together have leverage to affect perceptions about the risks posed by declining forest conditions on public lands, influence land owner actions, and affect support for public policies. These results also have broader implications for management of forested landscapes on public and private lands amidst changing demographics in rural communities across the Inland Northwest where migration may significantly alter the composition of forest owner goals, understanding, and support for various management actions.     

Role of hereditary factors in weight loss and its maintenance

The prevalence of obesity is increasing worldwide at an alarming rate in both developed and developing countries. Obesity is a chronic complex disease of multifactorial origin resulting from a long-term positive energy balance, in which both genetic and environmental factors are involved. Genetically prone individuals are the first to accumulate fat in the present obesogenic environment. Obesity increases the risks of type 2 diabetes, hypertension, cardiovascular disease, dyslipidemia, arthritis, and several cancers and reduces the average life expectancy. Implementation of effective strategies in prevention and management of obesity should become an important target in health care systems. Weight changes throughout life depend on the interaction of behavioral, genetic and environmental factors. Weight loss in response to weight management shows a wide range of interindividual variation which is largely influenced by genetic determinants. The strong control of weight loss by genotype was confirmed by twin and family studies. Recently, special attention has been paid to nutritional, hormonal, psychobehavioral and genetic factors which can predict the response to weight reduction programme. In this article currently available data on the role of obesity candidate gene polymorphisms in weight loss and maintenance are reviewed. It is believed that an elucidation of the genetic component in the prognosis of weight management could assist in the development of more effective and individually tailored therapeutic strategies.     

Stem cell therapy in coronavirus disease 2019: current evidence and future potential

The end of 2019 saw the beginning of the coronavirus disease 2019 (COVID-19) pandemic that soared in 2020, affecting 215 countries worldwide, with no signs of abating. In an effort to contain the spread of the disease and treat the infected, researchers are racing against several odds to find an effective solution. The unavailability of timely and affordable or definitive treatment has caused significant morbidity and mortality. Acute respiratory distress syndrome (ARDS) caused by an unregulated host inflammatory response toward the viral infection, followed by multi-organ dysfunction or failure, is one of the primary causes of death in severe cases of COVID-19 infection. Currently, empirical management of respiratory and hematological manifestations along with anti-viral agents is being used to treat the infection. The quest is on for both a vaccine and a more definitive management protocol to curtail the spread. Researchers and clinicians are also exploring the possibility of using cell therapy for severe cases of COVID-19 with ARDS. Mesenchymal stromal cells are known to have immunomodulatory properties and have previously been used to treat viral infections. This review explores the potential of mesenchymal stromal cells as cell therapy for ARDS.     

Spontaneous tumours of pet dog as models for human cancers: searching for adequate guidelines.

Despite the ongoing search for "replacement" alternatives, animal models continue to play a crucial role in bio-medical research. However, both in vivo and in vitro models usually employed, such as rodents and/or cell lines, display intrinsic limits related to the specific characteristics of the biological systems used, whose management is very complex, and whose pathology, usually induced under artificial laboratory conditions, is frequently dissimilar to the studied human spontaneous disease. It has been suggested that carrying out clinical trials based on pre-clinical data obtained after a screening on animal models developing the neoplastic disease in a more similar way to human beings, as represented by spontaneous canine tumours, could accelerate the entry of new effective drugs into the clinical practice. In this paper the authors discuss the scientific foundation as well as the ethic and legal concerns related to the use of this "pet model" in comparative oncology, suggesting some "key words" as the necessary starting point for a correct approach to the matter.     

An Integrated Framework for Risk Management and Population Health

The traditional medical model of health and health policy development has focused on individuals and the role of medical care in preventing and treating disease and injury. Recent attention to health inequities and social determinants of health has raised the profile of population heath and evidence-based strategies for improving the health of whole populations. At the same time, risk science has emerged as an important new discipline for the assessment and management of risks to health. This article reviews historical developments in the fields of risk management and population health and proposes a joint population health risk management framework that integrates the key elements of both fields. Applying this integrated approach to managing population health risks will facilitate the development of evidence-based health policy. It will encourage a more systematic and comprehensive evaluation of population health issues and promote the use of a broader suite of interventions to reduce health risks and enhance population health status.     

Management of intraoral stents for radiotherapy during COVID-19 pandemic

Radiotherapy is being performed in many situations as a curative approach for head and neck cancer instead of surgery due to the current novel coronavirus disease (COVID-19) pandemic. A recent publication reported that even hypofractionation was being conducted in order to reduce the daily exposure of both patients and the medical staff involved in cancer therapies. As a result, dental teams may be requested more frequently than usual to fabricate intraoral stents (IOS). Given that IOS may be a potential source of COVID-19 contagion, the main purpose of the present correspondence is to offer a guide on how health professionals may be safely presented in the room, on the management of the IOS and also how to sanitize the stents.     

Patterns and drivers of fungal disease communities on Arabica coffee along a management gradient

Plants, including those managed by humans, are often attacked by multiple diseases. Yet, most studies focus on single diseases, even if the disease dynamics of multiple species is more interesting from a farmers’ perspective. Moreover, most studies are from single management systems, although it is valuable to understand how diseases are distributed across broad management gradients, especially in cases where less intensive management also provides biodiversity values in the landscape. To understand the spatial dynamics and drivers of diseases across such a broad management gradient, we assessed four major fungal diseases on Arabica coffee (Coffea arabica) at 60 sites in southwestern Ethiopia along a gradient from only little managed wild coffee in the forest understory to intensively managed coffee plantations. We found that environmental and management factors related to disease incidence and severity differed strongly among the four fungal diseases. Coffee leaf rust (Hemileia vastatrix) and Armillaria root rot (Armillaria mellea) were more severe in intensively managed sites, whereas coffee berry disease (Colletotrichum kahawae) and wilt disease (Gibberella xylarioides) were more severe in less managed sites. Among sites, incidence and severity of the four fungal diseases poorly correlated with each other. Within sites, however, shrubs that were severely attacked by coffee leaf rust also had high levels of berry disease symptoms. A better understanding of disease dynamics is important for providing management recommendations that benefit smallholder farmers, but also to evaluate possibilities for maintaining biodiversity values in the landscape related to shade cover complexity and wild coffee genetic variation.     

肠道菌群及其代谢产物氧化三甲胺与冠心病的关系及相关技术方法的研究进展

肠道菌群失调与冠心病密切相关。本文就肠道菌群研究的相关技术方法、冠心病患者的肠道菌群分类和功能特征以及肠道菌群代谢产物氧化三甲胺（trimethylamine-N-oxide,TMAO）与冠心病的关系进行综述。尽管鸟枪法宏基因组学可对微生物精准鉴定到属水平,并提供更多的微生物群落信息,但是16S rRNA在心血管疾病领域的应用更为广泛。研究人员已经证实冠心病患者的肠道菌群分类和功能特征发生了改变。代谢组学技术的应用发现TMAO可能具有促动脉粥样硬化的特性,推测其可能是预测心血管不良事件发生的潜在生物标志物。肠道菌群及其代谢产物TMAO可能成为心血管疾病管理和治疗的新靶点。

     

Bacterial disease management: challenges,experience, innovation and future prospects

Plant diseases caused by bacterial pathogens place major constraints on crop production and cause significant annual losses on a global scale. The attainment of consistent effective management of these diseases can be extremely difficult, and management potential is often affected by grower reliance on highly disease‐susceptible cultivars because of consumer preferences, and by environmental conditions favouring pathogen development. New and emerging bacterial disease problems (e.g. zebra chip of potato) and established problems in new geographical regions (e.g. bacterial canker of kiwifruit in New Zealand) grab the headlines, but the list of bacterial disease problems with few effective management options is long. The ever‐increasing global human population requires the continued stable production of a safe food supply with greater yields because of the shrinking areas of arable land. One major facet in the maintenance of the sustainability of crop production systems with predictable yields involves the identification and deployment of sustainable disease management solutions for bacterial diseases. In addition, the identification of novel management tactics has also come to the fore because of the increasing evolution of resistance to existing bactericides. A number of central research foci, involving basic research to identify critical pathogen targets for control, novel methodologies and methods of delivery, are emerging that will provide a strong basis for bacterial disease management into the future.

• Near‐term solutions are desperately needed. Are there replacement materials for existing bactericides that can provide effective disease management under field conditions?
• Experience should inform the future. With prior knowledge of bactericide resistance issues evolving in pathogens, how will this affect the deployment of newer compounds and biological controls?
• Knowledge is critical. A comprehensive understanding of bacterial pathosystems is required to not only identify optimal targets in the pathogens, but also optimal seasonal timings for deployment.
• Host resistance to effectors must be exploited, carefully and correctly. Are there other candidate genes that could be targeted in transgenic approaches? How can new technologies (CRISPR, TALEN, etc.) be most effectively used to add sustainable disease resistance to existing commercially desirable plant cultivars?
• We need an insider's perspective on the management of systemic pathogens. In addition to host resistance or reduced sensitivity, are there other methods that can be used to target these pathogen groups?
• Biological systems are variable. Can biological control strategies be improved for bacterial disease management and be made more predictable in function?

The answers to the research foci outlined above are not all available, as will become apparent in this article, but we are heading in the right direction. In this article, we summarize the contributions from past experiences in bacterial disease management, and also describe how advances in bacterial genetics, genomics and host–pathogen interactions are informing novel strategies in virulence inhibition and in host resistance. We also outline potential innovations that could be exploited as the pressures to maximize a safe and productive food supply continue to become more numerous and more complex.     

Regulation between survival, persistence, and elimination of intracellular mycobacteria: a nested equilibrium of delicate balances

This review elaborates on recent insights gained on the dynamic aspects of interactions between pathogen and the host intracellular machinery in tuberculosis infection. In addition we will also discuss the utility of adopting a systems biology approach, both for a better understanding of TB biology, and for the development of more effective ways for disease management.     

The pathogenesis of coeliac disease

Coeliac disease is a common condition and its prevalence in UK is now thought to be approximately 1:100. It is being diagnosed and treated more frequently as awareness at the primary care level has increased. Coeliac disease is a complex disorder and is frequently associated with other disease processes. The management of these patients needs to take on a holistic approach, whilst the physician needs to be aware of the rare complications.

This article gives an up-to-date review of the literature written on the pathogenesis of coeliac disease. We have attempted to paint a picture from beginning to end, whilst clarifying the grey areas in between. General epidemiological factors are reviewed before looking at genetic risk factors. We assess the sensitivity and specificity of the investigative modalities available for clinical use and comment on optimum management of these patients thereafter.

The future of coeliac disease looks promising for patients with several novel therapies on the horizon. Whilst further work is still needed to breed out the toxic epitopes from wheat, novel therapies may come from other areas such as the work aimed at restoring normal tolerance to gluten.