Histamine Derived from Probiotic Lactobacillus reuteri Suppresses TNF via Modulation of PKA and ERK Signaling

Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC) separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H2 receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases

Development of the Listening Self-Efficacy Questionnaire (LSEQ)

Objective: Listening self-efficacy refers to the beliefs, or confidence, that listeners have in their capability to successfully listen in specific situations, which may influence audiologic rehabilitation outcomes. The objective of this study was to develop and validate the Listening Self-Efficacy Questionnaire (LSEQ), which quantifies listening self-efficacy in a variety of situations where the goal of the listener is to understand speech. Study Sample: Older listeners with hearing loss (N = 169) participated in the study. Design: A factor analysis showed that the LSEQ has three subscales, with beliefs about listening capabilities relating to the following situations: (1) dialogue in quiet, (2) focusing attention on a single source, and (3) complex auditory scenes. Internal consistency reliability was excellent (Chronbach\u27s α \u3e .80). Results: The validity of the LSEQ was demonstrated by comparing the LSEQ scores to audiologic measures, responses on questionnaires, and to the scores for reference groups of younger and older listeners with normal hearing. Conclusion: The findings indicate that the LSEQ is a valid and reliable measure of listening self-efficacy with good potential for use in clinical and research settings

Health Care Policy and Congenital Heart Disease: 2020 Focus on Our 2030 Future

The congenital heart care community faces a myriad of public health issues that act as barriers toward optimum patient outcomes. In this article, we attempt to define advocacy and policy initiatives meant to spotlight and potentially address these challenges. Issues are organized into the following 3 key facets of our community: patient population, health care delivery, and workforce. We discuss the social determinants of health and health care disparities that affect patients in the community that require the attention of policy makers. Furthermore, we highlight the many needs of the growing adults with congenital heart disease and those with comorbidities, highlighting concerns regarding the inequities in access to cardiac care and the need for multidisciplinary care. We also recognize the problems of transparency in outcomes reporting and the promising application of telehealth. Finally, we highlight the training of providers, measures of productivity, diversity in the workforce, and the importance of patient– family centered organizations in advocating for patients. Although all of these issues remain relevant to many subspecialties in medicine, this article attempts to illustrate the unique needs of this population and highlight ways in which to work together to address important opportunities for change in the cardiac care community and beyond. This article provides a framework for policy and advocacy efforts for the next decade

Replacing underperforming protected areas achieves better conservation outcomes

Protected areas vary enormously in their contribution to conserving biodiversity, and the inefficiency of protected area systems is widely acknowledged(1-3). However, conservation plans focus overwhelmingly on adding new sites to current protected area estates(4). Here we show that the conservation performance of a protected area system can be radically improved, without extra expenditure, by replacing a small number of protected areas with new ones that achieve more for conservation. Replacing the least cost-effective 1% of Australia's 6,990 strictly protected areas could increase the number of vegetation types that have 15% or more of their original extent protected from 18 to 54, of a maximum possible of 58. Moreover, it increases markedly the area that can be protected, with no increase in overall spending. This new paradigm for protected area system expansion could yield huge improvements to global conservation at a time when competition for land is increasingly intense