Collaborative science in action: A 20 year perspective from the Health and Environmental Sciences Institute (HESI) Cardiac Safety Committee.

The Health and Environmental Sciences Institute (HESI) is a nonprofit organization dedicated to resolving global health challenges through collaborative scientific efforts across academia, regulatory authorities and the private sector. Collaborative science across non-clinical disciplines offers an important keystone to accelerate the development of safer and more effective medicines. HESI works to address complex challenges by leveraging diverse subject-matter expertise across sectors offering access to resources, data and shared knowledge. In 2008, the HESI Cardiac Safety Committee (CSC) was established to improve public health by reducing unanticipated cardiovascular (CV)-related adverse effects from pharmaceuticals or chemicals. The committee continues to significantly impact the field of CV safety by bringing together experts from across sectors to address challenges of detecting and predicting adverse cardiac outcomes. Committee members have collaborated on the organization, management and publication of prospective studies, retrospective analyses, workshops, and symposia resulting in 38 peer reviewed manuscripts. Without this collaboration these manuscripts would not have been published. Through their work, the CSC is actively addressing challenges and opportunities in detecting potential cardiac failure modes using in vivo, in vitro and in silico models, with the aim of facilitating drug development and improving study design. By examining past successes and future prospects of the CSC, this manuscript sheds light on how the consortium's multifaceted approach not only addresses current challenges in detecting potential cardiac failure modes but also paves the way for enhanced drug development and study design methodologies. Further, exploring future opportunities and challenges will focus on improving the translational predictability of nonclinical evaluations and reducing reliance on animal research in CV safety assessments.

Black-White Disparities in Asthma Hospitalizations and ED Visits Among Medicaid-Enrolled Children.

BACKGROUND AND OBJECTIVES: Asthma is a common, potentially serious childhood chronic condition that disproportionately afflicts Black children. Hospitalizations and emergency department (ED) visits for asthma can often be prevented. Nearly half of children with asthma are covered by Medicaid, which should facilitate access to care to manage and treat symptoms. We provide new evidence on racial disparities in asthma hospitalizations and ED visits among Medicaid-enrolled children. METHODS: We used comprehensive Medicaid claims data from the Transformed Medicaid Statistical Information System. Our study population included 279 985 Medicaid-enrolled children with diagnosed asthma. We identified asthma hospitalizations and ED visits occurring in 2019. We estimated differences in the odds of asthma hospitalizations and ED visits for non-Hispanic Black versus non-Hispanic white children, adjusting for sex, age, Medicaid eligibility group, Medicaid plan type, state, and rurality. RESULTS: In 2019, among Black children with asthma, 1.2% had an asthma hospitalization and 8.0% had an asthma ED visit compared with 0.5% and 3.4% of white children with a hospitalization and ED visit, respectively. After adjusting for other characteristics, the rates for Black children were more than twice the rates for white children (hospitalization adjusted odds ratio 2.45, 95% confidence interval 2.23-2.69; ED adjusted odds ratio 2.42; 95% confidence interval 2.33-2.51). CONCLUSIONS: There are stark racial disparities in asthma hospitalizations and ED visits among Medicaid-enrolled children with asthma. To diminish these disparities, it will be important to implement solutions that address poor quality care, discriminatory treatment in health care settings, and the structural factors that disproportionately expose Black children to asthma triggers and access barriers.

Characterization of c-di-AMP signaling in the periodontal pathobiont, Treponema denticola.

Pathobionts associated with periodontitis, such as Treponema denticola, must possess numerous sensory transduction systems to adapt to the highly dynamic subgingival environment. To date, the signaling pathways utilized by T. denticola to rapidly sense and respond to environmental stimuli are mainly unknown. Bis-(3'-5') cyclic diadenosine monophosphate (c-di-AMP) is a nucleotide secondary messenger that regulates osmolyte transport, central metabolism, biofilm development, and pathogenicity in many bacteria but is uncharacterized in T. denticola. Here, we studied c-di-AMP signaling in T. denticola to understand how it contributes to T. denticola physiology. We demonstrated that T. denticola produces c-di-AMP and identified enzymes that function in the synthesis (TDE1909) and hydrolysis (TDE0027) of c-di-AMP. To investigate how c-di-AMP may impact T. denticola cellular processes, a screening assay was performed to identify putative c-di-AMP receptor proteins. This approach identified TDE0087, annotated as a potassium uptake protein, as the first T. denticola c-di-AMP binding protein. As potassium homeostasis is critical for maintaining turgor pressure, we demonstrated that T. denticola c-di-AMP concentrations are impacted by osmolarity, suggesting that c-di-AMP negatively regulates potassium uptake in hypoosmotic solutions. Collectively, this study demonstrates T. denticola utilizes c-di-AMP signaling, identifies c-di-AMP metabolism proteins, identifies putative receptor proteins, and correlates c-di-AMP signaling to osmoregulation.

Reducing the Risk of Pre-Eclampsia in Women with Polycystic Ovary Syndrome Using a Combination of Pregnancy Screening, Lifestyle, and Medical Management Strategies.

Polycystic ovary syndrome (PCOS) is a multisystem disorder that presents with a variety of phenotypes involving metabolic, endocrine, reproductive, and psychological symptoms and signs. Women with PCOS are at increased risk of pregnancy complications including implantation failure, miscarriage, gestational diabetes, fetal growth restriction, preterm labor, and pre-eclampsia (PE). This may be attributed to the presence of specific susceptibility features associated with PCOS before and during pregnancy, such as chronic systemic inflammation, insulin resistance (IR), and hyperandrogenism, all of which have been associated with an increased risk of pregnancy complications. Many of the features of PCOS are reversible following lifestyle interventions such as diet and exercise, and pregnant women following a healthy lifestyle have been found to have a lower risk of complications, including PE. This narrative synthesis summarizes the evidence investigating the risk of PE and the role of nutritional factors in women with PCOS. The findings suggest that the beneficial aspects of lifestyle management of PCOS, as recommended in the evidence-based international guidelines, extend to improved pregnancy outcomes. Identifying high-risk women with PCOS will allow targeted interventions, early-pregnancy screening, and increased surveillance for PE. Women with PCOS should be included in risk assessment algorithms for PE.

Diversity of antimicrobial-resistant bacteria isolated from Australian chicken and pork meat.

Antimicrobial-resistant bacteria are frequently isolated from retail meat and may infect humans. To determine the diversity of antimicrobial-resistant bacteria in Australian retail meat, bacteria were cultured on selective media from raw chicken (n = 244) and pork (n = 160) meat samples obtained from all four major supermarket chains in the ACT/NSW, Australia, between March and June 2021. Antimicrobial susceptibility testing (AST) was performed for 13 critically and 4 highly important antibiotics as categorised by the World Health Organization (WHO) for a wide range of species detected in the meat samples. A total of 288 isolates underwent whole-genome sequencing (WGS) to identify the presence of antimicrobial resistance (AMR) genes, virulence genes, and plasmids. AST testing revealed that 35/288 (12%) of the isolates were found to be multidrug-resistant (MDR). Using WGS data, 232/288 (81%) of the isolates were found to harbour resistance genes for critically or highly important antibiotics. This study reveals a greater diversity of AMR genes in bacteria isolated from retail meat in Australia than previous studies have shown, emphasising the importance of monitoring AMR in not only foodborne pathogenic bacteria, but other species that are capable of transferring AMR genes to pathogenic bacteria.

The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease.

The differentiation of resident intestinal macrophages from blood monocytes depends upon signals from the macrophage colony-stimulating factor receptor (CSF1R). Analysis of genome-wide association studies (GWAS) indicates that dysregulation of macrophage differentiation and response to microorganisms contributes to susceptibility to chronic inflammatory bowel disease (IBD). Here, we analyzed transcriptomic variation in monocyte-derived macrophages (MDM) from affected and unaffected sib pairs/trios from 22 IBD families and 6 healthy controls. Transcriptional network analysis of the data revealed no overall or inter-sib distinction between affected and unaffected individuals in basal gene expression or the temporal response to lipopolysaccharide (LPS). However, the basal or LPS-inducible expression of individual genes varied independently by as much as 100-fold between subjects. Extreme independent variation in the expression of pairs of HLA-associated transcripts (HLA-B/C, HLA-A/F and HLA-DRB1/DRB5) in macrophages was associated with HLA genotype. Correlation analysis indicated the downstream impacts of variation in the immediate early response to LPS. For example, variation in early expression of IL1B was significantly associated with local SNV genotype and with subsequent peak expression of target genes including IL23A, CXCL1, CXCL3, CXCL8 and NLRP3. Similarly, variation in early IFNB1 expression was correlated with subsequent expression of IFN target genes. Our results support the view that gene-specific dysregulation in macrophage adaptation to the intestinal milieu is associated with genetic susceptibility to IBD.

Renal artery stenosis stenting with unmasking and embolisation of a renal arteriovenous fistula.

A man in his 70s was presented to the emergency department with uncontrollable hypertension and worsening renal function on a background of atherosclerosis-related bilateral renal artery stenosis. Following progressive deterioration in renal function and refractory hypertension, the patient was referred to interventional radiology for consideration of renal artery stenting. Following stenting of the right renal artery, a large renal arteriovenous fistula became apparent, which required emergent embolisation. Both procedures were successful, with excellent clinical and radiological responses.

Comparative genomics and phenotypic studies to determine site-specificity of Escherichia coli in the lower gastrointestinal tract of humans.

Escherichia coli (E. coli) is an important commensal in the human gut; however, it is unknown whether strains show site-specificity in the lower gut. To investigate this, we assessed genotypic and phenotypic differences in 37 clone pairs (two strains with very similar multiple locus variable-number-tandem-repeat analysis [MLVA] profiles) of E. coli isolated from mucosal biopsies of two different gut locations (terminal ileum and rectum). The clone pairs varied at the genomic level; single nucleotide polymorphisms (SNPs) were common, multiple nucleotide polymorphisms (MNPs) were observed but less common, and few indels (insertions and deletions) were detected. The variation was higher in clone pairs that are associated with non-human-associated sequence types (ST) compared to human-associated STs, such as ST95, ST131, and ST73. No gene(s) with non-synonymous mutations were found to be commonly associated with either the terminal ileum or the rectal strains. At the phenotypic level, we identified the metabolic signatures for some STs. Rectum strains of some STs showed consistently higher metabolic activity with particular carbon sources. Clone pairs belonging to specific STs showed distinct growth patterns under different pH conditions. Overall, this study showed that E. coli may exhibit genomic and phenotypic variability at different locations in the gut. Although genomics did not reveal significant information suggesting the site-specificity of strains, some phenotypic studies have suggested that strains may display site-specificity in the lower gut. These results provide insights into the nature and adaptation of E. coli in the lower gut of humans. To the best of our knowledge, no study has investigated or demonstrated the site-specificity of commensal E. coli in the human gut.

"Older People Want to Be in Their Own Homes": A Service Evaluation of Patient and Carer Feedback after Pathfinder Responded to Their Emergency Calls.

OBJECTIVE: Older people experience high rates of adverse outcomes following emergency department (ED) presentation. There is growing evidence to support alternative care pathways for certain types of emergency medical services (EMS) calls. Pathfinder is one such service and targets patients aged 65 years and over, whose presenting issues can be safely managed at home by immediate paramedic, occupational therapy, and/or physiotherapy interventions. The aim of this service evaluation was to understand how older people feel about being treated at home as a result of EMS calls and to understand their experiences of the Pathfinder service. METHODS: This was a thematic analysis of open-ended responses recorded from telephone interviews during routine service evaluation with service users (patients or their next-of-kin). RESULTS: Of 573 service users, telephone interviews were conducted with 429 (75%). Five primary themes were identified: (1) professionalism of the multidisciplinary clinical team; (2) "the right service, in the right place, at the right time"; (3) role of Pathfinder in "getting the ball rolling"; (4) lasting effects of the experience on the patient and his or her next-of-kin; (5) value of skilled communication with the older person. CONCLUSION: Older people and their next-of-kin voiced a clear preference for hospital avoidance, and strongly valued the opportunity to be treated in their homes at the time of an EMS call rather than default conveyance to the ED. They appreciated the importance of a skilled multidisciplinary team with a follow-up service that effectively positions itself between the acute hospital and community services.

Development of a Screencast-Based Flipped Classroom to Enrich Learning and Reduce Faculty Time Requirements in an Animal Welfare Master's Degree.

A new distance learning Master of Science (MSc) degree in Animal Welfare Science, Ethics and Law was established in 2016 within the Centre for Animal Welfare at the University of Winchester, UK. Our program recruited students worldwide, with enrollments increasing dramatically since its inception in 2016. However, despite rapid growth, our MSc has had only one full-time equivalent faculty member. With further projected sharp increases in student numbers, significant programmatic change was required for the MSc to remain viable. After consultation with our students and program team, we decided to transition to a flipped classroom teaching model. Piloting a screencast-based flipped classroom in one course, our objectives were to provide a more enriched, engaging, and effective student learning experience and to increase student satisfaction while concurrently saving staff time in future years. We aimed to provide a series of enriched screencast videos of short (∼20-minute) durations, with contents clearly signposted. The new teaching model was well received. Within our 2021 program survey, 100% of respondents expressed a wish to see our screencast-based flipped classroom approach continued, and 71%-86% wished to see it implemented in various additional courses. This model has greatly enriched students' learning experiences, increasing student engagement and satisfaction while also freeing staff time to engage in discussion fora and additional live sessions. Learning and achievement outcomes also appear positive. We plan to steadily integrate this model across additional courses, although initial time investment will be significant. Hence, this new model will be implemented over several semesters.

Racialized economic segregation and potentially preventable hospitalizations among Medicaid/CHIP-enrolled children.

OBJECTIVE: To examine geographic variation in preventable hospitalizations among Medicaid/CHIP-enrolled children and to test the association between preventable hospitalizations and a novel measure of racialized economic segregation, which captures residential segregation within ZIP codes based on race and income simultaneously. DATA SOURCES: We supplement claims and enrollment data from the Transformed Medicaid Statistical Information System (T-MSIS) representing over 12 million Medicaid/CHIP enrollees in 24 states with data from the Public Health Disparities Geocoding Project measuring racialized economic segregation. STUDY DESIGN: We measure preventable hospitalizations by ZIP code among children. We use logistic regression to estimate the association between ZIP code-level measures of racialized economic segregation and preventable hospitalizations, controlling for sex, age, rurality, eligibility group, managed care plan type, and state. DATA EXTRACTION METHODS: We include children ages 0-17 continuously enrolled in Medicaid/CHIP throughout 2018. We use validated algorithms to identify preventable hospitalizations, which account for characteristics of the pediatric population and exclude children with certain underlying conditions. PRINCIPAL FINDINGS: Preventable hospitalizations vary substantially across ZIP codes, and a quarter of ZIP codes have rates exceeding 150 hospitalizations per 100,000 Medicaid-enrolled children per year. Preventable hospitalization rates vary significantly by level of racialized economic segregation: children living in the ZIP codes that have the highest concentration of low-income, non-Hispanic Black residents have adjusted rates of 181 per 100,000 children, compared to 110 per 100,000 for children in ZIP codes that have the highest concentration of high-income, non-Hispanic white residents (p < 0.01). This pattern is driven by asthma-related preventable hospitalizations. CONCLUSIONS: Medicaid-enrolled children's risk of preventable hospitalizations depends on where they live, and children in economically and racially segregated neighborhoods-specifically those with higher concentrations of low-income, non-Hispanic Black residents-are at particularly high risk. It will be important to identify and implement Medicaid/CHIP and other policies that increase access to high-quality preventive care and that address structural drivers of children's health inequities.

Public perceptions of pharmacogenomic services in Ireland - Are people with chronic disease more likely to want service availability than those without? A questionnaire study.

Background: As pharmacogenomic services begin to emerge in primary care, the insight of the public is crucial for its integration into clinical practice. Objectives: To establish perceptions of pharmacogenomics (awareness, understanding, openness to availability, perceived benefits and concerns, willingness to pay, and service setting) and investigate if they differ between those with and without chronic disease(s). Methods: An anonymous, online questionnaire generated using Qualtrics® and circulated via social media and posters placed in eight participating community pharmacies was conducted with Irish adults. The questions were designed to consider existing literature on patient perceptions of pharmacogenomics. Descriptive statistics were used to summarize questionnaire responses. Chi-square test was used to compare categorical variables, while independent sample t-test and one-way ANOVA were used to compare the mean values of two (with and without chronic disease) and three groups (multimorbidity (two or more chronic conditions) and polypharmacy (prescribed four or more regular medicines) (MMPP), a single chronic disease, and those without existing medical conditions) respectively Logistic regression was used to evaluate age and gender adjusted associations of chronic disease(s) with responses. A p-value <0.05 was considered statistically significant. Results: A total of 421 responses were received, 30% (n = 120) of whom reported having a chronic disease. Overall, respondents reported low awareness (44%, n = 166) and poor knowledge (55%, n = 212) of pharmacogenomics. After explaining pharmacogenomics to respondents, patients with chronic disease(s) were 2.17 times more likely (p < 0.001) to want pharmacogenomic services availability than those without existing conditions, adjusted for age and gender (driven by preferences of those with MMPP than those with single chronic disease). Respondents demonstrated a high level of interest and noted both the potential benefits and downsides of pharmacogenomic testing. Willingness-to-pay was not associated with having a chronic disease and respondents were more positive about primary care (community pharmacy or general practice) rather than hospital-based pharmacogenomics implementation. Conclusion: The Irish public in general and those with chronic disease in particular are strongly supportive of pharmacogenomic testing, highlighting an unmet need for its incorporation in medicines optimization. These data underline the need for more research on the implementation of community-based pharmacogenomics services for MMPP patients and ubiquitous pharmacogenomics education programs.

Setting Preconception Care Priorities in Australia Using a Delphi Technique.

Preconception health affects fertility, pregnancy, and future health outcomes but public awareness of this is low. Our aims were to rank priorities for preconception care (PCC), develop strategies to address these priorities, and establish values to guide future work in preconception healthcare in Australia. A Delphi technique involved two rounds of online voting and mid-round workshops. Inputs were a scoping review of PCC guidelines, a priority setting framework and existing networks that focus on health. During July and August, 2021, 23 multidisciplinary experts in PCC or social care, including a consumer advocate, completed the Delphi technique. Ten priority areas were identified, with health behaviors, medical history, weight, and reproductive health ranked most highly. Six strategies were identified. Underpinning values encompassed engagement with stakeholders, a life course view of preconception health, an integrated multi-sectorial approach and a need for large scale collaboration to implement interventions that deliver impact across health care, social care, policy and population health. Priority populations were considered within the social determinants of health. Health behaviors, medical history, weight, and reproductive health were ranked highly as PCC priorities. Key strategies to address priorities should be implemented with consideration of values that improve the preconception health of all Australians.

Review article: the future of microbiome-based therapeutics.

BACKGROUND: From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic. AIM: This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development. METHODS: Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical interventions. Key literature was identified through Pubmed searches with the following key words, 'microbiome', 'microbiome biomarkers', 'probiotics', 'prebiotics', 'synbiotics', 'faecal microbiota transplant', 'live biotherapeutics', 'microbiome mimetics' and 'postbiotics'. RESULTS: Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, rationally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics. CONCLUSIONS: Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation.

Nutrition policy: developing scientific recommendations for food-based dietary guidelines for older adults living independently in Ireland.

Older adults (≥65 years) are the fastest growing population group. Thus, ensuring nutritional well-being of the 'over-65s' to optimise health is critically important. Older adults represent a diverse population - some are fit and healthy, others are frail and many live with chronic conditions. Up to 78% of older Irish adults living independently are overweight or obese. The present paper describes how these issues were accommodated into the development of food-based dietary guidelines for older adults living independently in Ireland. Food-based dietary guidelines previously established for the general adult population served as the basis for developing more specific recommendations appropriate for older adults. Published international reports were used to update nutrient intake goals for older adults, and available Irish data on dietary intakes and nutritional status biomarkers were explored from a population-based study (the National Adult Nutrition Survey; NANS) and two longitudinal cohorts: the Trinity-Ulster and Department of Agriculture (TUDA) and the Irish Longitudinal Study on Ageing (TILDA) studies. Nutrients of public health concern were identified for further examination. While most nutrient intake goals were similar to those for the general adult population, other aspects were identified where nutritional concerns of ageing require more specific food-based dietary guidelines. These include, a more protein-dense diet using high-quality protein foods to preserve muscle mass; weight maintenance in overweight or obese older adults with no health issues and, where weight-loss is required, that lean tissue is preserved; the promotion of fortified foods, particularly as a bioavailable source of B vitamins and the need for vitamin D supplementation.

Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment.

Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that manifests in genetically susceptible women following a range of negative exposures to nutritional and environmental factors related to contemporary lifestyle. The hypothesis that PCOS phenotypes are derived from a mismatch between ancient genetic survival mechanisms and modern lifestyle practices is supported by a diversity of research findings. The proposed evolutionary model of the pathogenesis of PCOS incorporates evidence related to evolutionary theory, genetic studies, in utero developmental epigenetic programming, transgenerational inheritance, metabolic features including insulin resistance, obesity and the apparent paradox of lean phenotypes, reproductive effects and subfertility, the impact of the microbiome and dysbiosis, endocrine-disrupting chemical exposure, and the influence of lifestyle factors such as poor-quality diet and physical inactivity. Based on these premises, the diverse lines of research are synthesized into a composite evolutionary model of the pathogenesis of PCOS. It is hoped that this model will assist clinicians and patients to understand the importance of lifestyle interventions in the prevention and management of PCOS and provide a conceptual framework for future research. It is appreciated that this theory represents a synthesis of the current evidence and that it is expected to evolve and change over time.

A narrative review of the role of gastrointestinal dysbiosis in the pathogenesis of polycystic ovary syndrome.

Diet-induced gastrointestinal dysbiosis has been hypothesized to play a significant role in stimulating an increase in gastrointestinal permeability and activating systemic inflammation in women with polycystic ovary syndrome (PCOS). We reviewed the current proof-of-concept studies on the proposed mechanism of dysbiosis in the pathogenesis of PCOS. A literature search was performed to identify articles on changes in the intestinal microbiome (dysbiosis) and increased intestinal mucosal permeability involving lipopolysaccharide (LPS), LPS-binding protein (LPS-BP), and zonulin. We also searched for systematic reviews and meta-analyses that synthesized the results of studies on the therapeutic effects of prebiotics, probiotics, or synbiotics in women with PCOS. Our search was confined to human studies between 2012 and 2021 using the PubMed, Scopus, and Cochrane databases. Thirty-one studies met the inclusion criteria (14 microbiota, 1 LPS, 1 LPS-BP, 1 LPS and LPS-BP, 5 zonulin, 9 systematic reviews). Our analysis revealed that most studies reported reduced alpha diversity and dysbiosis in women with PCOS. Preliminary studies suggest that LPS, LPS-BP, and zonulin may be involved in the pathophysiology of increased intestinal permeability. Treatment of PCOS with prebiotics, probiotics, and synbiotics appears to have a range of beneficial effects on metabolic and biochemical profiles. This review highlights the need for continued research into the pathophysiological mechanisms of dysbiosis and the clinical efficacy of prebiotics, probiotics, and synbiotics in women with PCOS.

Early probiotic supplementation with B. infantis in breastfed infants leads to persistent colonization at 1 year.

BACKGROUND: Recent studies have reported a dysfunctional gut microbiome in breastfed infants. Probiotics have been used in an attempt to restore the gut microbiome; however, colonization has been transient, inconsistent among individuals, or has not positively impacted the host's gut. METHODS: This is a 2-year follow-up study to a randomized controlled trial wherein 7-day-old infants received 1.8 × 1010 colony-forming unit Bifidobacterium longum subsp. infantis (B. infantis) EVC001 (EVC) daily for 21 days or breast milk alone (unsupplemented (UNS)). In the follow-up study, mothers (n = 48) collected infant stool at 4, 6, 8, 10, and 12 months postnatal and completed the health-diet questionnaires. RESULTS: Fecal B. infantis was 2.5-3.5 log units higher at 6-12 months in the EVC group compared with the UNS group (P < 0.01) and this relationship strengthened with the exclusion of infants who consumed infant formula and antibiotics. Infants in the EVC group had significantly higher Bifidobacteriaceae and lower Bacteroidaceae and Lachnospiraceae (P < 0.05). There were no differences in any health conditions between the two groups. CONCLUSIONS: Probiotic supplementation with B. infantis within the first month postnatal, in combination with breast milk, resulted in stable colonization that persisted until at least 1 year postnatal. IMPACT: A dysfunctional gut microbiome in breastfed infants is common in resource-rich nations and associated with an increased risk of immune diseases. Probiotics only transiently exist in the gut without persistent colonization or altering the gut microbiome. This is the first study to show that early probiotic supplementation with B. infantis with breast milk results in stable colonization of B. infantis and improvements to the gut microbiome 1 year postnatal. This study addresses a key gap in the literature whereby probiotics can restore the gut microbiome if biologically selected microorganisms are matched with their specific food in an open ecological niche.

Prevalence, diversity and genetic structure of Escherichia coli isolates from septic tanks.

The present study investigated the diversity and genetic structure of Escherichia coli isolates from 100 septic tanks in the Canberra region, Australia. The physicochemical characteristics of the septic tanks were determined to examine the extent to which environmental factors might influence E. coli prevalence, diversity and population structure. The results of this study indicated that the temperature of the septic tank could explain some of the variation observed in the number of E. coli isolates recovered per septic tank, whereas pH was an important driver of E. coli diversity. Conductivity, pH and household size had a significant impact on E. coli population structure, and household size significantly affected the probability of detecting human-associated E. coli lineages [sequence types (STs) 69, 73, 95 and 131] in septic tanks. Phylogroup A and B1 strains were not randomly distributed among septic tanks, and the strong negative association between them may indicate intraspecific competition. The findings of this study suggest that the combination of environmental factors and intraspecific interactions may influence the distribution and genetic structure of E. coli in the environment.

A Preliminary Investigation into Ridden Water Submersion Training as an Adjunct to Current Condition Training Protocols in Performance Horses.

This observational study aimed to elucidate the effects of RWST on the cardiovascular and musculoskeletal systems of horses and concurrently determine whether RWST limits distal limb temperature increases previously reported during gallop training on land. A group of 15 clinically sound international event horses were recruited, and heart rate (HR), speed (km/h) and thermal images of the distal limb were analysed at set intervals during RWST training. Intervals of RWST produced a total mean HRmax value of 65.18 ± 3.76%, which is within the parameters for increased aerobic stamina. Mean HR increased significantly (p < 0.01) while mean distal limb temperature decreased significantly (p < 0.01) between warm-up and RWST, which contrasts with positive correlations previously reported during gallop training on land. These preliminary results suggest that RWST can be classed as a moderate submaximal intensity exercise in elite international event horses whilst restricting an increase in temperature of the distal limb that is commonly associated with tendon rupture. Horses competing at very elite levels of eventing only represent a small percentage of the total performance population; therefore, further research is needed to ascertain the physiological effects of RWST in non-elite performance horses, as well as horses competing across various equestrian disciplines.