Gut microbiome derived short chain fatty acids: Promising strategies in necrotising enterocolitis.

Necrotising enterocolitis (NEC) is a devastating condition that poses a significant risk of morbidity and mortality, particularly among preterm babies. Extensive research efforts have been directed at identifying optimal treatment and diagnostic strategies but results from such studies remain unclear and controversial. Among the most promising candidates are prebiotics, probiotics and their metabolites, including short chain fatty acids (SCFAs). Such metabolites have been widely explored as possible biomarkers of gut health for different clinical conditions, with overall positive effects on the host observed. This review aims to describe the role of gut microbiome derived SCFAs in necrotising enterocolitis. Until now, information has been conflicting, with the primary focus on the main three SCFAs (acetic acid, propionic acid, and butyric acid). While numerous studies have indicated the relationship between SCFAs and NEC, the current evidence is insufficient to draw definitive conclusions about the use of these metabolites as NEC biomarkers or their potential in treatment strategies. Ongoing research in this area will help enhance both our understanding of SCFAs as valuable indicators of NEC and their practical application in clinical settings.

Methodological challenges in neonatal microbiome research.

Following microbial colonization at birth, the gut microbiome plays a vital role in the healthy development of human neonates and impacts both health and disease in later life. Understanding the development of the neonatal gut microbiome and how it interacts with the neonatal host are therefore important areas of study. However, research within this field must address a range of specific challenges that impact the design and implementation of research methods. If not considered ahead of time, these challenges have the potential to introduce biases into studies, negatively affecting the relevance, reproducibility, and impact of any findings. This review outlines the nature of these challenges and points to current and future solutions, as outlined in the literature, to assist researchers in the early stages of study design.

Systematic whole-genome sequencing reveals an unexpected diversity among actinomycetoma pathogens and provides insights into their antibacterial susceptibilities.

Mycetoma is a neglected tropical chronic granulomatous inflammatory disease of the skin and subcutaneous tissues. More than 70 species with a broad taxonomic diversity have been implicated as agents of mycetoma. Understanding the full range of causative organisms and their antibiotic sensitivity profiles are essential for the appropriate treatment of infections. The present study focuses on the analysis of full genome sequences and antibiotic inhibitory concentration profiles of actinomycetoma strains from patients seen at the Mycetoma Research Centre in Sudan with a view to developing rapid diagnostic tests. Seventeen pathogenic isolates obtained by surgical biopsies were sequenced using MinION and Illumina methods, and their antibiotic inhibitory concentration profiles determined. The results highlight an unexpected diversity of actinomycetoma causing pathogens, including three Streptomyces isolates assigned to species not previously associated with human actinomycetoma and one new Streptomyces species. Thus, current approaches for clinical and histopathological classification of mycetoma may need to be updated. The standard treatment for actinomycetoma is a combination of sulfamethoxazole/trimethoprim and amoxicillin/clavulanic acid. Most tested isolates had a high IC (inhibitory concentration) to sulfamethoxazole/trimethoprim or to amoxicillin alone. However, the addition of the ß-lactamase inhibitor clavulanic acid to amoxicillin increased susceptibility, particularly for Streptomyces somaliensis and Streptomyces sudanensis. Actinomadura madurae isolates appear to have a particularly high IC under laboratory conditions, suggesting that alternative agents, such as amikacin, could be considered for more effective treatment. The results obtained will inform future diagnostic methods for the identification of actinomycetoma and treatment.

Methylsulfonylmethane and Sesame Seed Oil Improve Dyslipidemia and Modulate Polyunsaturated Fatty Acid Metabolism in Two Mouse Models of Diabetes.

The objective of this study was to identify alterations in lipids and polyunsaturated fatty acid (PUFA) metabolism in both the streptozotocin (STZ)-induced type 1 diabetic (T1D) mouse and the mutant db/db type 2 diabetic (T2D) mouse to establish a biological signature for the evaluation of natural products with purported lipid-altering activity. Eight-week-old male C57BL/6J mice were randomized to nondiabetic group or STZ-induced diabetic groups (n = 10/group). STZ-induced diabetic mice and 6-week-old male db/db mice (n = 10/group) were randomized to the following groups: (1) diabetic control, no treatment, (2) methylsulfonylmethane (MSM) treatment, (3) sesame seed oil (SSO) treatment, and (4) MSM+SSO combination treatment. Clinical parameters measured included weights, blood glucose, serum lipid panels, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection of free fatty acids in serum, liver, brain, and eyes. Blood glucose significantly decreased after 4 weeks of MSM treatment in T1D mice. Serum PUFA levels were significantly reduced in T2D mice compared with control mice. In contrast, treatment with SSO reversed this effect in T2D mice, exhibiting serum PUFA levels comparable to control mice. Serum triglycerides were significantly increased in both diabetic models compared to nondiabetic control, mimicking diabetes in people. High-density lipoprotein (HDL) was significantly increased in T1D receiving MSM+SSO and all T2D treatment groups. A corresponding significant decrease in non-HDL cholesterol was seen in T2D mice in all treatment groups. MSM+SSO treatment's effects on HDL and non-HDL cholesterol and PUFA metabolism could lead to improved clinical outcomes in diabetics by improving the lipid profile.

Associations between neighborhood walkability and walking following residential relocation: Findings from Alberta's Tomorrow Project.

Introduction: Cross-sectional studies consistently find that the neighborhood built environment (e.g., walkability) is associated with walking. However, findings from the few existing longitudinal residential relocation studies that have estimated associations between changes in neighborhood built characteristics and walking are equivocal. The study objective was to estimate whether changes in neighborhood walkability resulting from residential relocation were associated with leisure, transportation, and total walking levels among adults. Methods: This study included longitudinal data from the "Alberta's Tomorrow Project"-a province-wide cohort study (Alberta, Canada). The analysis included data collected at two time points (i.e., baseline and follow-up) from 5,977 urban adults. The International Physical Activity Questionnaire (IPAQ) captured self-reported walking. We estimated neighborhood walkability, an index capturing intersection, destination, and population counts for the 400 m Euclidean buffer around participants' homes. Using household postal codes reported at baseline and follow-up, we categorized participants into three groups reflecting residential relocation ("non-movers:" n = 5,679; "movers to less walkability:" n = 164, and; "movers to more walkability:" n = 134). We used Inverse-Probability-Weighted Regression Adjustment to estimate differences [i.e., average treatment effects in the treated (ATET)] in weekly minutes of leisure, transportation, and total walking at follow-up between residential relocation groups, adjusting for baseline walking, sociodemographic characteristics, and walkability. The median time between baseline and follow-up was 2-years. Results: The three residential relocation groups mainly included women (61.6-67.2%) and had a mean age of between 52.2 and 55.7 years. Compared to "non-movers" (reference group), weekly minutes of transportation walking at follow-up was significantly lower among adults who moved to less walkable neighborhoods (ATET: -41.34, 95 CI: -68.30, -14.39; p < 0.01). We found no other statistically significant differences in walking between the groups. Discussion: Our findings suggest that relocating to less walkable neighborhoods could have detrimental effects on transportation walking to the extent of adversely affecting health. Public health strategies that counteract the negative impacts of low walkable neighborhoods and leverage the supportiveness of high walkable neighborhoods might promote more walking.

'Carbon-Monoxide-Releasing Molecule-2 (CORM-2)' Is a Misnomer: Ruthenium Toxicity, Not CO Release, Accounts for Its Antimicrobial Effects.

Carbon monoxide (CO)-releasing molecules (CORMs) are used to deliver CO, a biological 'gasotransmitter', in biological chemistry and biomedicine. CORMs kill bacteria in culture and in animal models, but are reportedly benign towards mammalian cells. CORM-2 (tricarbonyldichlororuthenium(II) dimer, Ru2Cl4(CO)6), the first widely used and commercially available CORM, displays numerous pharmacological, biochemical and microbiological activities, generally attributed to CO release. Here, we investigate the basis of its potent antibacterial activity against Escherichia coli and demonstrate, using three globin CO sensors, that CORM-2 releases negligible CO (<0.1 mol CO per mol CORM-2). A strong negative correlation between viability and cellular ruthenium accumulation implies that ruthenium toxicity underlies biocidal activity. Exogenous amino acids and thiols (especially cysteine, glutathione and N-acetyl cysteine) protected bacteria against inhibition of growth by CORM-2. Bacteria treated with 30 µM CORM-2, with added cysteine and histidine, exhibited no significant loss of viability, but were killed in the absence of these amino acids. Their prevention of toxicity correlates with their CORM-2-binding affinities (Cys, Kd 3 µM; His, Kd 130 µM) as determined by 1H-NMR. Glutathione is proposed to be an important intracellular target of CORM-2, with CORM-2 having a much higher affinity for reduced glutathione (GSH) than oxidised glutathione (GSSG) (GSH, Kd 2 µM; GSSG, Kd 25,000 µM). The toxicity of low, but potent, levels (15 µM) of CORM-2 was accompanied by cell lysis, as judged by the release of cytoplasmic ATP pools. The biological effects of CORM-2 and related CORMs, and the design of biological experiments, must be re-examined in the light of these data.

Small bowel diverticulitis - Spectrum of CT findings and review of the literature.

PURPOSE: To review the CT findings and complications of small bowel diverticulitis (SBD) and discuss clinical presentations and outcomes. METHODS: A text search of radiology reports within our health system for cases of small bowel diverticulitis yielded 95 cases. All cases were reviewed by an abdominal radiologist with equivocal cases reviewed by a second abdominal radiologist for consensus. Retrospective analysis of CT imaging findings was performed on 67 convincing cases of SBD. RESULTS: Small bowel diverticulitis most often affected the jejunum (58%) and the duodenum (26%). The most common imaging feature was peridiverticular inflammation manifested by peridiverticular edema, diverticular wall thickening, bowel wall thickening, and fascial thickening. Edema was typically seen along the mesenteric border of the bowel with relative sparing of the anti-mesenteric side. When a prior CT was available, the affected diverticulum was identified in 95% of cases. Fecalized content within the affected diverticulum was observed in 51% of cases. Perforation (6%) and abscess (6%) were the most common complications. CONCLUSION: Small bowel diverticulitis is an uncommon cause of abdominal pain which can mimic an array of abdominal pathologies, although the reported mortality rate of 40-50% may no longer be accurate. The "fecalized diverticulum" sign can be helpful in identifying the culprit diverticulum and aid diagnosing SBD. Findings of perforation and or abscess formation are critical as they may impact management.

A longitudinal residential relocation study of changes in street layout and physical activity.

Few longitudinal residential relocation studies have explored associations between urban form and physical activity, and none has used the Space Syntax theory. Using a Canadian longitudinal dataset (n = 5944), we estimated: (1) differences in physical activity between non-movers, and those relocating to neighbourhoods with less or more integrated street layouts, and; (2) associations between changes in street layout integration exposure and differences in physical activity. Adjusting for covariates, we found relative to non-movers, those who moved to more integrated neighbourhoods undertook significantly (p < .05) more leisure walking (27.3 min/week), moderate-intensity (45.7 min/week), and moderate-to-vigorous intensity physical activity (54.4 min/week). Among movers, a one-unit increase in the relative change in street integration exposure ([Street integration at follow-up-street integration at baseline]/street integration at baseline) was associated with a 7.5 min/week increase in leisure walking. Our findings suggest that urban design policies that improve neighbourhood street integration might encourage more physical activity in adults.

Isolation of L-form Bacteria from Urine using Filtration Method.

Transition of bacteria to the L-form state is thought to play a possible role in immune evasion and bacterial persistence during treatment with cell wall-targeting antibiotics. However, isolation and handling of L-form bacteria is challenging, mainly due to their high sensitivity to changes in osmolarity. Here, we describe detailed protocols for the preparation of L-form medium, isolation of L-forms from urine using a filtration method, detection of L-forms in urine samples by phase contrast microscopy and induction of L-forms in vitro. The exact requirements for survival and growth of L-forms may vary from strain to strain. Therefore, the methods presented here are intended to act as basic guidelines for establishing L-form protocols within individual laboratories, rather than as precise instructions. The filtration method can lead to a reduction in the number of L-forms in a sample and should not be used for quantification. However, it is the only method used so far for effective separation of cell wall-deficient variants from their walled counterparts and for identification of bacterial strains, which are capable of L-form switching in patients with urinary tract infections. The filtration method has the potential to be adapted for the isolation of L-forms from patients with other categories of bacterial infections and from environmental samples.

A scoping review on the relations between urban form and health: a focus on Canadian quantitative evidence. / Examen de la portée sur les associations entre aménagement urbain et santé : les données quantitatives canadiennes.

INTRODUCTION: Despite the accumulating Canadian evidence regarding the relations between urban form and health behaviours, less is known about the associations between urban form and health conditions. Our study aim was to undertake a scoping review to synthesize evidence from quantitative studies that have investigated the relationship between built environment and chronic health conditions, self-reported health and quality of life, and injuries in the Canadian adult population. METHODS: From January to March 2017, we searched 13 databases to identify peer-reviewed quantitative studies from all years that estimated associations between the objectively-measured built environment and health conditions in Canadian adults. Studies under-taken within urban settings only were included. Relevant studies were catalogued and synthesized in relation to their reported study and sample design, and health outcome and built environment features. RESULTS: Fifty-five articles met the inclusion criteria, 52 of which were published after 2008. Most single province studies were undertaken in Ontario (n = 22), Quebec (n = 12), and Alberta (n = 7). Associations between the built environment features and 11 broad health outcomes emerged from the review, including injury (n = 19), weight status (n = 19), cardiovascular disease (n = 5), depression/anxiety (n = 5), diabetes (n = 5), mortality (n = 4), self-rated health (n = 2), chronic conditions (n = 2), metabolic condi-tions (n = 2), quality of life (n = 1), and cancer (n = 1). Consistent evidence for associations between aggregate built environment indicators (e.g., walkability) and diabetes and weight and between connectivity and route features (e.g., transportation route, trails, pathways, sidewalks, street pattern, intersections, route characteristics) and injury were found. Evidence for greenspace, parks and recreation features impacting multiple health outcomes was also found. CONCLUSION: Within the Canadian context, the built environment is associated with a range of chronic health conditions and injury in adults, but the evidence to date has limitations. More research on the built environment and health incorporating rigorous study designs are needed to provide stronger causal evidence to inform policy and practice.

Hepatobiliary Iminodiacetic Acid Scanning Detects Previously Unknown Hepatic Metastases from Colorectal Adenocarcinoma.

A case of previously unknown metastatic colorectal adenocarcinoma presented as focal photopenia on hepatobiliary iminodiacetic acid scintigraphy. Differential diagnosis of focal photopenia and heterogenous hepatic radiotracer uptake on hepatobiliary scintigraphy is reviewed.

A thiol-reactive Ru(II) ion, not CO release, underlies the potent antimicrobial and cytotoxic properties of CO-releasing molecule-3.

Carbon monoxide (CO)-releasing molecules (CORMs), mostly metal carbonyl compounds, are extensively used as experimental tools to deliver CO, a biological 'gasotransmitter', in mammalian systems. CORMs are also explored as potential novel antimicrobial drugs, effectively and rapidly killing bacteria in vitro and in animal models, but are reportedly benign towards mammalian cells. Ru-carbonyl CORMs, exemplified by CORM-3 (Ru(CO)3Cl(glycinate)), exhibit the most potent antimicrobial effects against Escherichia coli. We demonstrate that CORM-3 releases little CO in buffers and cell culture media and that the active antimicrobial agent is Ru(II), which binds tightly to thiols. Thus, thiols and amino acids in complex growth media - such as histidine, methionine and oxidised glutathione, but most pertinently cysteine and reduced glutathione (GSH) - protect both bacterial and mammalian cells against CORM-3 by binding and sequestering Ru(II). No other amino acids exert significant protective effects. NMR reveals that CORM-3 binds cysteine and GSH in a 1:1 stoichiometry with dissociation constants, Kd, of about 5 µM, while histidine, GSSG and methionine are bound less tightly, with Kd values ranging between 800 and 9000 µM. There is a direct positive correlation between protection and amino acid affinity for CORM-3. Intracellular targets of CORM-3 in both bacterial and mammalian cells are therefore expected to include GSH, free Cys, His and Met residues and any molecules that contain these surface-exposed amino acids. These results necessitate a major reappraisal of the biological effects of CORM-3 and related CORMs.

The Microbiology of Ruthenium Complexes.

Ruthenium is seldom mentioned in microbiology texts, due to the fact that this metal has no known, essential roles in biological systems, nor is it generally considered toxic. Since the fortuitous discovery of cisplatin, first as an antimicrobial agent and then later employed widely as an anticancer agent, complexes of other platinum group metals, such as ruthenium, have attracted interest for their medicinal properties. Here, we review at length how ruthenium complexes have been investigated as potential antimicrobial, antiparasitic and chemotherapeutic agents, in addition to their long and well-established roles as biological stains and inhibitors of calcium channels. Ruthenium complexes are also employed in a surprising number of biotechnological roles. It is in the employment of ruthenium complexes as antimicrobial agents and alternatives or adjuvants to more traditional antibiotics, that we expect to see the most striking developments in the future. Such novel contributions from organometallic chemistry are undoubtedly sorely needed to address the antimicrobial resistance crisis and the slow appearance on the market of new antibiotics.

Optimisation of rocker sole footwear for prevention of first plantar ulcer: comparison of group-optimised and individually-selected footwear designs.

BACKGROUND: Appropriate footwear for individuals with diabetes but no ulceration history could reduce the risk of first ulceration. However, individuals who deem themselves at low risk are unlikely to seek out bespoke footwear which is personalised. Therefore, our primary aim was to investigate whether group-optimised footwear designs, which could be prefabricated and delivered in a retail setting, could achieve appropriate pressure reduction, or whether footwear selection must be on a patient-by-patient basis. A second aim was to compare responses to footwear design between healthy participants and people with diabetes in order to understand the transferability of previous footwear research, performed in healthy populations. METHODS: Plantar pressures were recorded from 102 individuals with diabetes, considered at low risk of ulceration. This cohort included 17 individuals with peripheral neuropathy. We also collected data from 66 healthy controls. Each participant walked in 8 rocker shoe designs (4 apex positions × 2 rocker angles). ANOVA analysis was then used to understand the effect of two design features and descriptive statistics used to identify the group-optimised design. Using 200 kPa as a target, this group-optimised design was then compared to the design identified as the best for each participant (using plantar pressure data). RESULTS: Peak plantar pressure increased significantly as apex position was moved distally and rocker angle reduced (p < 0.001). The group-optimised design incorporated an apex at 52% of shoe length, a 20° rocker angle and an apex angle of 95°. With this design 71-81% of peak pressures were below the 200 kPa threshold, both in the full cohort of individuals with diabetes and also in the neuropathic subgroup. Importantly, only small increases (<5%) in this proportion were observed when participants wore footwear which was individually selected. In terms of optimised footwear designs, healthy participants demonstrated the same response as participants with diabetes, despite having lower plantar pressures. CONCLUSIONS: This is the first study demonstrating that a group-optimised, generic rocker shoe might perform almost as well as footwear selected on a patient by patient basis in a low risk patient group. This work provides a starting point for clinical evaluation of generic versus personalised pressure reducing footwear.

Lessons from the 2006 Louisiana health and population survey.

The 2005 hurricane season caused extensive damage and induced a mass migration of approximately 1.1 million people from southern Louisiana in the United States. Current and accurate estimates of population size and demographics and an assessment of the critical needs for public services were required to guide recovery efforts. Since forecasts using pre-hurricane data may produce inaccurate estimates of the post-hurricane population, a household survey in 18 hurricane-affected parishes was conducted to provide timely and credible information on the size of these populations, their demographics and their condition. This paper describes the methods used, the challenges encountered, and the key factors for successful implementation. This post-disaster survey was unique because it identified the needs of the people in the affected parishes and quantified the number of people with these needs. Consequently, this survey established new population and health indicator baselines that otherwise would have not been available to guide the relief and recovery efforts in southern Louisiana.

Podiatry services for patients with arthritis: an unmet need.

Foot problems are extremely common in patients with rheumatoid arthritis (RA). There is ample evidence that foot pain, either alone or as a comorbidity, contributes significantly to disability. Despite the high prevalence of foot disease in RA, this problem is often trivialised or underappreciated. The inequity in foot health provision for patients with rheumatic disorders in New Zealand has recently been highlighted. Expertise in dealing with foot problems is often limited among healthcare professionals, and it has been argued that better integration of podiatric services into rheumatology services would be beneficial. The aim of this paper is to highlight the major issues related to foot care for patients with arthritis and provide key recommendations that should implemented to improve access to podiatric services in New Zealand.

Clinical audit of foot problems in patients with rheumatoid arthritis treated at Counties Manukau District Health Board, Auckland, New Zealand.

BACKGROUND: At diagnosis, 16% of rheumatoid arthritis (RA) patients may have foot joint involvement, increasing to 90% as disease duration increases. This can lead to joint instability, difficulties in walking and limitation in functional ability that restricts activities of daily living. The podiatrist plays an important role in the multidisciplinary team approach to the management of foot problems. The aim of this study was to undertake a clinical audit of foot problems in patients with RA treated at Counties Manukau District Health Board. METHODS: Patients with RA were identified through rheumatological clinics run within CMDHB. 100 patients were eligible for inclusion. Specific foot outcome tools were used to evaluate pain, disability and function. Observation on foot lesions were noted and previous history of foot assessment, footwear/insoles and foot surgery were evaluated. RESULTS: The median age of the cohort was 60 (IQR: 51-64) years old with median disease duration of 15 (IQR: 7.3-25) years. Over 85% presented with foot lesions that included corns and callus over the forefoot region and lesser toe deformities. Moderate to high disability was noted. High levels of forefoot structural damage were observed. 76% had not seen a podiatrist and 77% reported no previous formal foot assessment. 40% had been seen at the orthotic centre for specialised footwear and insoles. 27% of RA patients reported previous foot surgery. A large proportion of patients wore inappropriate footwear. CONCLUSION: This clinical audit suggests that the majority of RA patients suffer from foot problems. Future recommendations include the provision of a podiatrist within the current CMDHB multidisciplinary rheumatology team to ensure better services for RA patients with foot problems.