Neighborhood Environmental Health and Premature Death From Cardiovascular Disease.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death in the United States and disproportionately affects racial/ethnic minority groups. Healthy neighborhood conditions are associated with increased uptake of health behaviors that reduce CVD risk, but minority neighborhoods often have poor food access and poor walkability. This study tested the community-driven hypothesis that poor access to food at the neighborhood level and poor neighborhood walkability are associated with racial disparities in premature deaths from CVD. METHODS: We examined the relationship between neighborhood-level food access and walkability on premature CVD mortality rates at the census tract level for the city of Atlanta using multivariable logistic regression models. We produced maps to illustrate premature CVD mortality, food access, and walkability by census tract for the city. RESULTS: We found significant racial differences in premature CVD mortality rates and geographic disparities in food access and walkability among census tracts in Atlanta. Improved food access and walkability were associated with reduced overall premature CVD mortality in unadjusted models, but this association did not persist in models adjusted for census tract population composition and poverty. Census tracts with high concentrations of minority populations had higher levels of poor food access, poor walkability, and premature CVD mortality. CONCLUSION: This study highlights disparities in premature CVD mortality and neighborhood food access and walkability at the census tract level in the city of Atlanta. Improving food access may have differential effects for subpopulations living in the same area. These results can be used to calibrate neighborhood-level interventions, and they highlight the need to examine race-specific health outcomes.

Genomic analysis of seven mycobacteriophages identifies three novel species with differing phenotypic stabilities.

Recently, case studies have been published regarding the application of mycobacteriophage (MP) therapy (MPT) in patients with multi-antibiotic-resistant infections. A major limitation in the development of MPT is the paucity of therapeutically useful MP. As there are approximately 10,000 MP that have yet to be sequenced, it is possible that characterization of this cohort would increase the repertoire of useful MP. This study aims to contribute to such a strategy, by characterizing a cohort of 7 mycobacteriophages. Sequencing analyses revealed that the MP have unique sequences, and subsequent gene annotation revealed differences in gene organization. Notably, MP LOCARD has the largest genome and operons encoding for glycosyltransferases. Taxonomic analysis executed with VIRIDIC, Gegenees and VICTOR revealed that LOCARD belongs to a different genus than the other phages and is the foundational member of one of three novel species identified in this study. LOCARD, LOCV2, and LOCV5 were selected as representative members of their species and subjected to phenotypic analyses to compare their stability under biologically and industrially relevant conditions. Again LOCARD stood out, as it was unaffected by the typical temperatures (37 °C) and salinity (0.9%) experienced in mammals, while the viability of LOCV2 and LOCV5 was significantly reduced. LOCARD was also tolerant to pH 10, low levels of antiviral detergent and was the least impacted by a single freeze-thaw cycle. When all these results are considered, it indicates that LOCARD in particular, has potential therapeutic and/or diagnostics applications, given its resilience towards physiological and storage conditions.

Alginate-Encapsulated Mycobacteriophage: A Potential Approach for the Management of Intestinal Mycobacterial Disease.

Encapsulated medication is a common method of administering therapeutic treatments. As researchers explore alternative therapies, it is likely that encapsulation will remain a feature of these novel treatments, particularly when routes of delivery are considered. For instance, alginate-encapsulation is often favoured where gastric digestion poses an obstacle. When exposed to cations (namely Ca2+), alginate readily forms gels that are resilient to acidic conditions and readily dissociate in response to mid-range pH. This action can be extremely valuable for the encapsulation of phages. The efficient delivery of phages to the intestine is important when considering mycobacteriophage (MP) therapy (or MP prophylaxis) for disseminated mycobacterial infections and chronic gastroenteritis conditions. This study presents the design and in vitro validation of an alginate-encapsulated MP capable of releasing phages in a pH-dependent manner. Ultimately, it is shown that encapsulated phages pretreated with simulated gastric fluid (SGF) are capable of releasing viable phages into simulated intestinal fluid (SIF) and thereby reducing the mycobacterial numbers in spiked SIF by 90%. These findings suggest that alginate encapsulation may be a viable option for therapeutic and prophylactic approaches to the management of intestinal mycobacterial disease, such as Johne's disease.

Alternatives to antibiotics in veterinary medicine: considerations for the management of Johne's disease.

Antibiotic resistance has become a major health concern globally, with current predictions expecting deaths related to resistant infections to surpass those of cancer by 2050. Major efforts are being undertaken to develop derivative and novel alternatives to current antibiotic therapies in human medicine. What appears to be lacking however, are similar efforts into researching the application of those alternatives, such as (bacterio)phage therapy, in veterinary contexts. Agriculture is still undoubtedly the most prominent consumer of antibiotics, with up to 70% of annual antibiotic usage attributed to this sector, despite policies to reduce their use in food animals. This not only increases the risk of resistant infections spreading from farm to community but also the risk that animals may acquire species-specific infections that subvert treatment. While these diseases may not directly affect human welfare, they greatly affect the profit margin of industries reliant on livestock due to the cost of treatments and (more frequently) the losses associated with animal death. This means actively combatting animal infection not only benefits animal welfare but also global economies. In particular, targeting recurring or chronic conditions associated with certain livestock has the potential to greatly reduce financial losses. This can be achieved by developing novel diagnostics to quickly identify ill animals alongside the design of novel therapies. To explore this concept further, this review employs Johne's disease, a chronic gastroenteritis condition that affects ruminants, as a case study to exemplify the benefits of rapid diagnostics and effective treatment of chronic disease, with particular regard to the diagnostic and therapeutic potential of phage.

Identification of novel genera and subcluster classifications for mycobacteriophages.

Aim: To identify novel genera amongst mycobacteriophages (MP) and verify a hypothesised correlation between the taxonomy set by the International Committee on Taxonomy of Viruses (ICTV) and the National Centre for Biotechnology Information (NCBI) with that of the Actinobacteriophage Database, which may help formalise subcluster assignment. Methods: A dataset of 721 MP genomes was analysed using VIRIDIC, a nucleotide alignment-based software that predicts genus assignments. Potentially novel genera were analysed using Gegenees and VICTOR, respectively. These genera were then compared to the subclusters assigned by the Actinobacteriophage Database to verify a hypothesis that one genus can be assigned to one subcluster (i.e., the genus-subcluster hypothesis). Results: Initially, when comparing the current genus classifications of the 721 MP dataset to the Actinobacteriophage database subcluster assignments, 83.3% of subclusters supported the genus-subcluster hypothesis. Following the sequential VIRIDIC, Gegenees and VICTOR analyses, a total of 20 novel genera were identified based on a ≥ 70% and ~ 50% similarity threshold for VIRIDIC and Gegenees, respectively, and a monophyletic nature in the VICTOR output. Interestingly, these criteria also appear to support the creation of 13 novel subclusters, which would increase the support for the genus-subcluster hypothesis to 97.6%. Conclusion: The link between genus and subcluster classifications appears robust, as most subclusters can be assigned a single genus and vice versa. By relating the taxonomic and clustering classification systems, they can be easily kept up to date to best reflect MP diversity, which could aid the rapid selection of related (or diverse) phages for research, therapeutic and diagnostic purposes.

Natural Transformation in Gram-Positive Bacteria and Its Biotechnological Relevance to Lactic Acid Bacteria.

Competence refers to the specialized physiological state in which bacteria undergo transformation through the internalization of exogenous DNA in a controlled and genetically encoded process that leads to genotypic and, in many cases, phenotypic changes. Natural transformation was first described in Streptococcus pneumoniae and has since been demonstrated in numerous species, including Bacillus subtilis and Neisseria gonorrhoeae. Homologs of the genes encoding the DNA uptake machinery for natural transformation have been reported to be present in several lactic acid bacteria, including Lactobacillus spp., Streptococcus thermophilus, and Lactococcus spp. In this review, we collate current knowledge of the phenomenon of natural transformation in Gram-positive bacteria. Furthermore, we describe the mechanism of competence development and its regulation in model bacterial species. We highlight the importance and opportunities for the application of these findings in the context of bacterial starter cultures associated with food fermentations as well as current limitations in this area of research.

"Who needs an app? Fertility patients' use of a novel mobile health app".

Objective: The number of couples experiencing infertility treatment has increased, as has the number of women and men experiencing infertility treatment-related stress and anxiety. Therefore, there is a need to provide information and support to both men and women facing fertility concerns. To achieve this goal, we designed a mhealth app, Infotility, that provided men and women with tailored medical, psychosocial, lifestyle, and legal information. Methods: This study specifically examined how fertility factors (e.g. time in infertility treatment, parity), socio-demographic characteristics (e.g. gender, education, immigrant status), and mental health characteristics (e.g. stress, depression, anxiety, fertility-related quality of life) were related to male and female fertility patients' patterns of use of the Infotility app. Results: Overall, the lifestyle section of the app was the most highly used section by both men and women. In addition, women without children and highly educated women were more likely to use Infotility. No demographic, mental health or fertility characteristics were significantly associated with app use for men. Conclusion: This study shows the feasibility of a mhealth app to address the psychosocial and informational needs of fertility patients.

Examining the Diversity of Prosocial Behavior: Helping, Sharing, and Comforting in Infancy.

Prosocial behaviors are a diverse group of actions that are integral to human social life. In this study, we examined the ability of 18- and 24-month-old infants to engage in three types of other-oriented behaviors, specifically helping, sharing, and comforting. Infants in both age groups engaged in more prosocial behavior on trials in which an unfamiliar adult experimenter required aid (experimental conditions) than on those in which she did not (control conditions) across two of the three prosocial tasks (i.e., helping and sharing). The infants engaged in these behaviors with similar frequency; however, there was no correlation between the tasks. The implications for the construct of prosocial behavior and the presence of a prosocial disposition are discussed.

Can Infants Use a Nonhuman Agent's Gaze Direction to Establish Word-Object Relations?

Adopting a procedure developed with human speakers, we examined infants' ability to follow a nonhuman agent's gaze direction and subsequently to use its gaze to learn new words. When a programmable robot acted as the speaker (Experiment 1), infants followed its gaze toward the word referent whether or not it coincided with their own focus of attention, but failed to learn a new word. When the speaker was human, infants correctly mapped the words (Experiment 2). Furthermore, when the robot interacted contingently, this did not facilitate infants' word mapping (Experiment 3). These findings suggest that gaze following upon hearing a novel word is not sufficient to learn the referent of the word when the speaker is nonhuman.

Capturing expert uncertainty in spatial cumulative impact assessments.

Understanding the spatial distribution of human impacts on marine environments is necessary for maintaining healthy ecosystems and supporting 'blue economies'. Realistic assessments of impact must consider the cumulative impacts of multiple, coincident threats and the differing vulnerabilities of ecosystems to these threats. Expert knowledge is often used to assess impact in marine ecosystems because empirical data are lacking; however, this introduces uncertainty into the results. As part of a spatial cumulative impact assessment for Spencer Gulf, South Australia, we asked experts to estimate score ranges (best-case, most-likely and worst-case), which accounted for their uncertainty about the effect of 32 threats on eight ecosystems. Expert scores were combined with data on the spatial pattern and intensity of threats to generate cumulative impact maps based on each of the three scoring scenarios, as well as simulations and maps of uncertainty. We compared our method, which explicitly accounts for the experts' knowledge-based uncertainty, with other approaches and found that it provides smaller uncertainty bounds, leading to more constrained assessment results. Collecting these additional data on experts' knowledge-based uncertainty provides transparency and simplifies interpretation of the outputs from spatial cumulative impact assessments, facilitating their application for sustainable resource management and conservation.

Taphonomy of Microbial Biosignatures in Spring Deposits: A Comparison of Modern, Quaternary, and Jurassic Examples.

On Earth, microorganisms commonly enhance mineral precipitation and mediate mineralogical and chemical compositions of resulting deposits, particularly at spring systems. However, preservation of any type of microbial fossil or chemical or textural biosignature depends on the degree of alteration during diagenesis and factors such as exposure to diagenetic fluids. Little is known about the transformation of biosignatures during diagenesis over geologic time. Ten Mile Graben, Utah, USA, hosts a cold spring system that is an exceptional site for evaluation of diagenetic alteration of biosignatures because of the presence of modern springs with actively precipitating microbial mats and a series of progressively older tufa terraces (<400 ka) preserved in the area from the same spring system. A previously undescribed Jurassic laminated carbonate unit within the upper part of the Brushy Basin Member of the Morrison Formation is also exposed in Ten Mile Graben. This research characterizes the geology of these modern and Quaternary saline, Fe-undersaturated, circumneutral Ten Mile Graben cold springs and provides the first description in the literature of the Jurassic Brushy Basin Member of the Morrison Formation carbonate deposit. Taphonomy of microbial fossils is characterized by scanning electron microscopy (SEM). The data highlight two distinct methods of biosignature formation: (1) precipitation of minerals from an undersaturated solution owing to metabolic activity of the cells and (2) mineral precipitation on charged cell surfaces that produce distinctive microbial trace fossils. Although diagenesis can destroy or severely degrade biosignatures, particularly microbial fossils, some fossils and trace fossils are preserved because entombment by Ostwald ripening limits diagenetic alteration. Recognizing spring-fed, biogenic tufas is crucial for astrobiological research and the search for life on Mars. Key Words: Biosignatures-Taphonomy-Diagenesis-Carbonates-Hot springs. Astrobiology 17, 216-230.

Pharmacological characterization of guinea pig chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2).

Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), a G protein-coupled receptor activated by prostaglandin D(2) (PGD(2)), has been identified as a receptor expressed on cell types critical to the pathogenesis of asthma. The cDNA encoding guinea pig CRTH2 was cloned and mRNA expression examined in selected tissues. Transcript profiling of guinea pig CRTH2 indicated relatively high levels of expression in bone marrow, intermediate levels in brain and relatively low levels in lung, spleen, thymus, lymph node, etc. Characterization of the molecular pharmacology of guinea pig CRTH2 revealed that guinea pig CRTH2 exhibited a greater affinity for Delta(12)-PGJ(2), a stable PGD(2) metabolite relative to human CRTH2. The CRTH2 selective agonists 13,14-dihydro-15-keto PGD(2) and Delta(12)-PGJ(2) induced the recruitment of eosinophils following intradermal administration of these ligands in guinea pigs. Chemotaxis of guinea pig eosinophils was elicited by either PGD(2) or Delta(12)-PGJ(2), and was abolished by a CRTH2-specific antagonist. These results indicate that PGD(2) and the stable metabolite, Delta(12)-PGJ(2), play important roles in CRTH2 activation in the guinea pig.

General Applications of Ultrasound in Rheumatology Practice.

A growing body of clinical and research studies have demonstrated the utility of ultrasound for providing better diagnostic and treatment decisions in patients with rheumatic diseases.

Unfinished business in the regulation of shale gas production in the United States.

With increased drilling for natural gas, toxic chemicals used to fracture wells have been introduced into the environment accompanied by allegations of injuries. This article evaluates laws and regulations governing shale gas production to disclose ideas for offering further protection to people and the environment. The aim of the study is to offer state governments ideas for addressing contractual obligations of drilling operators, discerning health risks, disclosing toxic chemicals, and reporting sufficient information to detect problems and enforce regulations. The discussion suggests opportunities for state regulators to become more supportive of public health through greater oversight of shale gas extraction.