Mapping Crohn's Disease Pathogenesis with Mycobacterium paratuberculosis: A Hijacking by a Stealth Pathogen.

Mycobacterium avium ssp. paratuberculosis (MAP) has been implicated in the development of Crohn's disease (CD) for over a century. Similarities have been noted between the (histo)pathological presentation of MAP in ruminants, termed Johne's disease (JD), and appearances in humans with CD. Analyses of disease presentation and pathology suggest a multi-step process occurs that consists of MAP infection, dysbiosis of the gut microbiome, and dietary influences. Each step has a role in the disease development and requires a better understanding to implementing combination therapies, such as antibiotics, vaccination, faecal microbiota transplants (FMT) and dietary plans. To optimise responses, each must be tailored directly to the activity of MAP, otherwise therapies are open to interpretation without microbiological evidence that the organism is present and has been influenced. Microscopy and histopathology enables studies of the mycobacterium in situ and how the associated disease processes manifest in the patient e.g., granulomas, fissuring, etc. The challenge for researchers has been to prove the relationship between MAP and CD with available laboratory tests and methodologies, such as polymerase chain reaction (PCR), MAP-associated DNA sequences and bacteriological culture investigations. These have, so far, been inconclusive in revealing the relationship of MAP in patients with CD. Improved and accurate methods of detection will add to evidence for an infectious aetiology of CD. Specifically, if the bacterial pathogen can be isolated, identified and cultivated, then causal relationships to disease can be confirmed, especially if it is present in human gut tissue. This review discusses how MAP may cause the inflammation seen in CD by relating its known pathogenesis in cattle, and from examples of other mycobacterial infections in humans, and how this would impact upon the difficulties with diagnostic tests for the organism.

A mixed-methods evaluation of a health-promoting café located in a small health service in rural Victoria, Australia.

INTRODUCTION: Residents of rural areas internationally typically experience chronic disease risk profiles worse than city dwellers. Poor diet, a key driver of chronic disease, has been associated with unhealthy food environments, and rural areas often experience limited access to healthy, fresh and affordable food. OBJECTIVE: This study aimed to evaluate the first three years of a health promoting social enterprise café established in a small rural health service. DESIGN: A mixed-methods evaluation study. Quantitative sales data, surveys and key informant interviews that included both quantitative and qualitative responses. FINDINGS: Three years of sales data were included; 111customer surveys and five key informant interviews were conducted. Food and beverages on displayed and sold consistently met or exceeded the healthy criteria set by policy. Stakeholders supported the traffic light system, the social enterprise model and rated the likelihood of sustainability of the café as high. DISCUSSION: Customers used the 'traffic light' system to inform food choices, placed value on the warmth of the staff and on the welcoming environment created through the social enterprise model. Resources remain tight although all stakeholders are committed to the sustainability of the YarriYak café. CONCLUSION: The study shows the acceptability, feasibility and sustainability of a health promoting social enterprise café in a rural area.

Putting Crohn's on the MAP: Five Common Questions on the Contribution of Mycobacterium avium subspecies paratuberculosis to the Pathophysiology of Crohn's Disease.

For decades, Mycobacterium avium subspecies paratuberculosis (MAP) has been linked to the pathogenesis of Crohn's disease. Despite many investigations and research efforts, there remains no clear unifying explanation of its pathogenicity to humans. Proponents argue Crohn's disease shares many identical features with a granulomatous infection in ruminants termed Johne's disease and similarities with ileo-cecal tuberculosis. Both are caused by species within the Mycobacterium genus. Sceptics assert that since MAP is found in individuals diagnosed with Crohn's disease as well as in healthy population controls, any association with CD is coincidental. This view is supported by the uncertain response of patients to antimicrobial therapy. This report aims to address the controversial aspects of this proposition with information and knowledge gathered from several disciplines, including microbiology and veterinary medicine. The authors hope that this discussion will stimulate further research aimed at confirming or refuting the contribution of MAP to the pathogenesis of Crohn's disease and ultimately lead to advanced targeted clinical therapies.

Mycobacterium avium ssp. paratuberculosis and Crohn's Disease-Diagnostic Microbiological Investigations Can Inform New Therapeutic Approaches.

Mycobacterium avium ssp. paratuberculosis (MAP) is the cause of Johne's disease (JD), which is a chronic infectious gastrointestinal disease of ruminants and is often fatal. In humans, MAP has been associated with Crohn's disease (CD) for over a century, without conclusive evidence of pathogenicity. Numerous researchers have contributed to the subject, but there is still a need for evidence of the causation of CD by MAP. An infectious aetiology in CD that is attributable to MAP can only be proven by bacteriological investigations. There is an urgency in resolving this question due to the rising global incidence rates of CD. Recent papers have indicated the "therapeutic ceiling" may be close in the development of new biologics. Clinical trial outcomes have demonstrated mild or inconsistent improvements in therapeutic interventions over the last decades when compared with placebo. The necessity to revisit therapeutic options for CD is becoming more urgent and a renewed focus on causation is essential for progress in identifying new treatment options. This manuscript discusses newer interventions, such as vaccination, FMT, dietary remediation and gut microbiome regulation, that will become more relevant as existing therapeutic options expire. Revisiting the MAP theory as a potential infectious cause of CD, rather than the prevailing concept of an "aberrant immune response" will require expanding the current therapeutic programme to include potential new alternatives, and combinations of existing treatments. To advance research on MAP in humans, it is essential for microbiologists and medical scientists to microscopically detect CWDM and to biologically amplify the growth by directed culture.

Initial assessment of the efficacy of food recovery policies in US States for increasing food donations and reducing waste.

In this paper, we examine the primary impact of two categories of food recovery policies on food donation and the secondary impact on food safety, food waste, and food insecurity in U.S. states. As one method of food recovery, food donation can reduce food waste while mitigating food insecurity, and it can be promoted in U.S. states through strong liability protection policies that provide legal protection to food donors and through tax incentivization policies that financially reward food donors via deductions and/or credits. To provide an initial evaluation of the effects of these policies, we coded each state's food recovery policies in 2012 and 2018 and compared strong policies versus weak policies. Using data from multiple sources, we found that states with stronger liability protection policies had more food donations, and states that provide tax incentivization had more food waste. Although our analyses were correlational, rather than causal, and were reliant upon limited data, our results demonstrate that the current food recovery policy landscape in U.S. states does relate to important food waste outcomes. We discuss the implications of these findings for crafting more effective policies that encourage food recovery.

Task-related and task-unrelated thoughts in runners and equestrians: Measurement issues in evaluations of thought content.

Much of the thought content and mind-wandering literature examines self-reported thought content's relationship with performance criteria in limited ways. Furthermore, retrospective reports about thought content may be influenced by the quality of one's performance. We explored these method issues in a cross-sectional study of individuals competing in a trail race and an equestrian event. Our results demonstrated that self-reports of thought content differed based on the performance context: whereas runners' task-related and task-unrelated thoughts were negatively correlated, equestrians' thought content showed no relationship. Moreover, equestrians in general reported fewer task-related and task-unrelated thoughts than runners. Finally, objective performance predicted task-unrelated thought (but not task-related thought) among runners, and an exploratory mediation test suggested the effect was partially mediated by performance awareness. We discuss the applied implications of this research for human performance practitioners.

Epsilonproteobacteria in humans, New Zealand.

Using PCR-denaturing gradient gel electrophoresis, we examined 49 fecal samples from healthy volunteers and 128 diarrhea specimens to assess the distribution of Epsilonproteobacteria that might be routinely overlooked. Our results suggest that certain taxa that are not routinely examined for could account for a proportion of diarrhea of previously unknown etiology.

Evolution of biomarker research in autoimmunity conditions for health professionals and clinical practice.

Medical abzymology has made a great contribution to the development of general autoimmunity theory: it has put the autoantibodies (Ab) as the key brick of the theory to the level of physiological functionality by providing such Ab with the ability to catalyze and mediate direct and independent cytotoxic effect on cellular and molecular targets. Natural catalytic autoantibodies (abzymes) while being a pool of canonical Abs and possessing catalytic activity belong to the new group of physiologically active substances whose features and properties are evolutionary consolidated in one functionally active biomolecule. Therefore, further studies on Ab-mediated autoAg degradation and other targeted Ab-mediated proteolysis may provide biomarkers of newer generations and thus a supplementary tool for assessing the disease progression and predicting disability of the patients and persons at risks. This chapter is a summary of current knowledge and prognostic perspectives toward catalytic Abs in autoimmunity and thus some autoimmune clinical cases, their role in pathogenesis, and the exploitation of both whole molecules and their constituent parts in developing highly effective targeted drugs of the future to come, and thus the therapeutic protocols being individualized.

Some reflections on Operation Corporate - the Falklands Campaign.

At the time of the Falklands Campaign (Operation Corporate), apart from performing clinical dentistry, the Royal Army Dental Corps (RADC) dental officer's combat role included acting as a resuscitation officer attached to a field hospital or a field ambulance. It was in that role that three dental officers from the RADC became involved in the campaign. This paper reflects their experiences in the operation.

A Mycobacterium species for Crohn's disease?

In ruminants Mycobacterium avium subspecies paratuberculosis (MAP) is the causative organism of a chronic granulomatous inflammatory bowel disease called Johne's disease (JD). Some researchers have hypothesised that MAP is also associated with Crohn's disease (CD), an inflammatory bowel disease in humans that shares some histological features of JD. Despite numerous attempts to demonstrate causality by researchers, direct microbiological evidence of MAP involvement in CD remains elusive. Importantly, it has not been possible to reliably and reproducibly demonstrate mycobacteria in the tissue of CD patients. Past attempts to visualise mycobacteria in tissue may have been hampered by the use of stains optimised for Mycobacterium tuberculosis complex (MTB) and the lack of reliable bacteriological culture media for both non-tuberculous mycobacteria (NTM) and cell-wall-deficient mycobacteria (CWDM). Here we describe a Ziehl-Neelsen (ZN) staining method for the demonstration of CWDM in resected tissue from patients with Crohn's disease, revealing the association of CWDM in situ with host tissue reactions, and posit this as a cause of the tissue inflammation. Using the ZN stain described we demonstrated the presence of CWDM in 18 out of 18 excised tissue samples from patients diagnosed as having Crohn's disease, and in zero samples out of 15 non-inflammatory bowel disease controls.

Influence of Simulation-based Training on Reflective Practice.

BACKGROUND: Simulation-based training (SBT) is often evaluated based on the transfer of specific knowledge and skills. In contrast, the degree to which reflective practice is inculcated by SBT is rarely considered. Because reflection is a pillar of adult learning theories, we sought to examine the degree to which participation in SBT was associated with increased reflective practice. METHOD: Eighty one healthcare professionals completed a survey which included the number of SBTs they participated in during the past two years, content- and administrative-related features of those SBTs, and a key aspect of reflective practice (i.e., self-appraisal). RESULTS: The number of SBTs healthcare professionals participated in during the past two years was positively associated with reflective self-appraisal. This relationship was not moderated by the inclusion of reflection components in SBTs nor by the voluntary/mandatory nature of participation in SBTs. Furthermore, the facilitator was ranked as the most important feature of the overall learning experience in SBTs. Also, no significant differences were found between the number of technical skills-based and non-technical skills-based SBTs. CONCLUSION: These findings demonstrate the importance (of evaluating) SBTs for facilitating reflective learning mindsets that healthcare practitioners can apply beyond the specific skills trained by SBTs.

Men's Preconception Health: A Primary Health-Care Viewpoint.

The purpose of this article is to theoretically explore men's preconception health as a mechanism to enhance fertility, as well as the health and well-being of the subject and his descendants. Premorbid risk factors and behaviors associated with stress, environmental toxins, excessive alcohol consumption, smoking, lack of exercise/obesity, and the use of illicit drugs are all known to affect fecundity. While there are many health clinics available to women, where advice in areas such as postnatal care of the newborn, family planning, and couples fertility is provided, there are few, if any, equivalent health clinics available to men. Additionally, getting men to attend primary health-care services has also been continuously problematic, even in the context of there being a clearly discernible need for treatment. It is argued in this article that an impetus is required to encourage men to focus on and improve their preconception health and to utilize primary health-care services to take action. An assertive men's preconception health outlook can positively influence the conjugal relationship, fathering, male self-esteem, and continued good health. Using the sometimes complex concept of preconception health as a motivating factor for healthy lifestyle adaptation has the potential to improve male fertility outcomes and general health and well-being, as well as the health of future generations.

Oxidative stress, placental ageing-related pathologies and adverse pregnancy outcomes.

Oxidative stress (OS), an imbalance between free radical generation and antioxidant defence, is recognized as a key factor in the pathogenesis of adverse pregnancy outcomes. Although OS is a common future of normal pregnancy, persistent, overwhelming OS leads to consumption and decline of antioxidants, affecting placental antioxidant capacity and reducing systems. The accumulation of OS causes damage to lipids, proteins and DNA in the placental tissue that induces a form of accelerated ageing. Premature ageing of the placenta is associated with placental insufficiency that prevents the organ meeting the needs of the foetus, and as a consequence, the viability of the foetus is compromised. This review summarizes the literature regarding the role of OS and premature placental ageing in the pathophysiology of pregnancy complications.

The Consensus from the Mycobacterium avium ssp. paratuberculosis (MAP) Conference 2017.

On March 24 and 25, 2017 researchers and clinicians from around the world met at Temple University in Philadelphia to discuss the current knowledge of Mycobacterium avium ssp. paratuberculosis (MAP) and its relationship to human disease. The conference was held because of shared concern that MAP is a zoonotic bacterium that poses a threat not only to animal health but also human health. In order to further study this problem, the conferees discussed ways to improve MAP diagnostic tests and discussed potential future anti-MAP clinical trials. The conference proceedings may be viewed on the www.Humanpara.org website. A summary of the salient work in this field is followed by recommendations from a majority of the conferees.

Phosphorylation of Izumo1 and Its Role in Male Infertility.

Izumo1 is a testis-specific gene product, whose function is essential for sperm-egg fusion. Throughout its lifespan, Izumo1 is posttranslationally modified, being both N-linked glycosylated on its extracellular domain and phosphorylated on the intracellular C-terminal tail. Within the caput regions of the rat epididymis, two phosphorylation events have been documented. However, as sperm pass through the epididymis, this cytoplasmic portion of Izumo1 has been shown to contain up to seven phosphorylation sites. Remarkably, in the rat, in correlation with these events, Izumo1 undergoes sub-cellular re-location, moving from the head/tail regions of the spermatozoa, to a predominantly equatorial segment location once they have reached the caudal end of the epididymis.

Resolution of Crohn's disease and complex regional pain syndrome following treatment of paratuberculosis.

A cohort of family members with various chronic diseases including Crohn's disease, asthma, complex regional pain syndrome, hypothyroidism, type 1 diabetes mellitus, and lymphangiomatosis and/or evidence of infection by Mycobacterium avium subsp. paratuberculosis (MAP) are described in this series of case reports. MAP was cultured from the blood of three members affected by the first five diseases and there was accompanying elevated anti-MAP IgG in two members. The patient affected by the sixth disease has a markedly elevated anti-MAP titer. The two patients affected by the first four diseases have been treated with a combination of anti-MAP antibiotics and ultraviolet blood irradiation therapy with resolution of the disease symptomatology and inability to culture MAP in post treatment blood samples. These case reports of patients with MAP infections provide supportive evidence of a pathogenic role of MAP in humans.

Evaluation of the BD ProbeTec ET system for direct detection of Mycobacterium bovis in veterinary specimens.

We describe the application of the BD ProbeTec ET direct tuberculosis system for the detection of Mycobacterium bovis in bovine and cervine lymph node tissues. Compared to traditional culture, the overall sensitivity, specificity, and positive and negative predictive values of the BD ProbeTec were 87, 100, 100, and 87%, respectively.