Interplay between inflammatory bowel disease therapeutics and the gut microbiome reveals opportunities for novel treatment approaches.

Inflammatory bowel disease (IBD) is a complex heterogeneous disorder defined by recurring chronic inflammation of the gastrointestinal tract, attributed to a combination of factors including genetic susceptibility, altered immune response, a shift in microbial composition/microbial insults (infection/exposure), and environmental influences. Therapeutics generally used to treat IBD mainly focus on the immune response and include non-specific anti-inflammatory and immunosuppressive therapeutics and targeted therapeutics aimed at specific components of the immune system. Other therapies include exclusive enteral nutrition and emerging stem cell therapies. However, in recent years, scientists have begun to examine the interplay between these therapeutics and the gut microbiome, and we present this information here. Many of these therapeutics are associated with alterations to gut microbiome composition and functionality, often driving it toward a "healthier profile" and preclinical studies have revealed that such alterations can play an important role in therapeutic efficacy. The gut microbiome can also improve or hinder IBD therapeutic efficacy or generate undesirable metabolites. For certain IBD therapeutics, the microbiome composition, particularly before treatment, may serve as a biomarker of therapeutic efficacy. Utilising this information and manipulating the interactions between the gut microbiome and IBD therapeutics may enhance treatment outcomes in the future and bring about new opportunities for personalised, precision medicine.

Sustainable Management of the African Great Lake Coastal Areas: Motivations and Perspectives of Community Citizen Scientists.

The long-term sustainability of the African Great Lakes is strongly connected to the management and monitoring of their coastal areas. Yet, the communities that live in these areas are rarely involved in monitoring and have limited influence on key management issues. Furthermore, regulatory activities and knowledge sharing in these transnational ecosystems are strongly limited by funding and infrastructure limitations. Citizen science has great potential to advance both scientific and public understanding of the state of the environment. However, there remains a limited understanding of participants' motivations and expectations, especially in developing countries, where citizen science has great potential to complement regulatory monitoring. The present study explores the motivations of citizen scientists in villages along Lake Tanganyika's northern coast and their potential to take a more active role in lake management. Motivations were examined through qualitative interviews, focus groups, and quantitative surveys with 110 citizen scientists and 110 non-citizen scientists from participating villages. Key motivational factors identified were the desire to contribute to scientific research and local knowledge, as well as aspects of financial compensation. The results confirm that participation in citizen science provides many benefits to participants beyond their role as data aggregators and final knowledge users. However, the incentives to participation varied to those typically considered in citizen science programs conducted in developed countries. To create sustainable long-term community based environmental monitoring, these motivations should be incorporated in the program design and participant recruitment.

Quality care close to home: Objectives and early outcomes of a second paediatric heart transplant service in Australia.

AIM: We describe the experience of a new paediatric heart transplant (HT) centre in Australia. New South Wales offers quaternary paediatric cardiac services including comprehensive care pre- and post-HT; however, perioperative HT care has previously occurred at the national paediatric centre or in adult centres. Internationally, perioperative HT care is highly protocol-driven and a majority of HT occurs in low volume centres. Establishing a low volume paediatric HT centre in New South Wales offers potential for quality HT care close to home. METHODS: Retrospective review of programme data for the first 12 months was undertaken. Patient selection was audited against the programme's intended initiation criteria. Longitudinal patient data on outcomes and complications were obtained from patient medical records. RESULTS: The programme's initial phase offered HT to children with non-congenital heart disease and no requirement for durable mechanical circulatory support. Eight patients met criteria for HT referral. Three underwent interstate transfer to the national paediatric centre. Five children (13-15 years, weight 36-85 kg) underwent HT in the new programme. Individual predicted 90-day mortality was 1.3-11.6%, with increased risk for recipients transplanted from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and with restrictive/hypertrophic cardiomyopathies. Survival at 90 days and for duration of follow-up is 100%. Observed programme benefits include mitigation of family dislocation and improved continuity of care within a family-centred programme. CONCLUSION: Audit of the first 12 months' activity of a second paediatric HT centre in Australia demonstrates adherence to proposed patient selection criteria and excellent 90-day patient outcomes. The programme demonstrates feasibility of care close to home, providing continuity for all patients including those requiring increased rehabilitation and psychosocial support post-transplantation.

Modulation of the gut microbiome with nisin.

Nisin is a broad spectrum bacteriocin used extensively as a food preservative that was identified in Lactococcus lactis nearly a century ago. We show that orally-ingested nisin survives transit through the porcine gastrointestinal tract intact (as evidenced by activity and molecular weight determination) where it impacts both the composition and functioning of the microbiota. Specifically, nisin treatment caused a reversible decrease in Gram positive bacteria, resulting in a reshaping of the Firmicutes and a corresponding relative increase in Gram negative Proteobacteria. These changes were mirrored by the modification in relative abundance of pathways involved in acetate, butyrate (decreased) and propionate (increased) synthesis which correlated with overall reductions in short chain fatty acid levels in stool. These reversible changes that occur as a result of nisin ingestion demonstrate the potential of bacteriocins like nisin to shape mammalian microbiomes and impact on the functionality of the community.

Numerous Angiomatous Lesions in an Infant.

A 3-month-old infant presented with bright red macules, papules, and plaques that appeared at birth and grew in size and number. What is your diagnosis?

Pedagogy of teaching with large datasets: Designing and implementing effective data-based activities.

Integrating the use of large datasets into our teaching provides critical and unique opportunities to build students' skills and conceptual knowledge. Here, we discuss the core components needed to develop effective activities based on large datasets, which align with the 5E learning cycle. Data-based activities should be structured around a relevant question, use authentic publicly accessible data, be scaffolded to include choice, and involve discussion of the results. It is important that the software that is used to manipulate, analyze and/or visualize the data is accessible for students. There are a range of strategies to reduce the barriers of working with large datasets through pre-organizing and pre-scripting code for analyses, using online cloud-based versions of software, and reducing opportunities for error in syntax. Resources exist for learning open-source software (e.g., Data Carpentry) as well as for support and professional development in teaching with large datasets (Project EDDIE).

Citizen scientist monitoring accurately reveals nutrient pollution dynamics in Lake Tanganyika coastal waters.

Several studies in Lake Tanganyika have effectively employed traditional methods to explore changes in water quality in open waters; however, coastal monitoring has been restricted and sporadic, relying on costly sample and analytical methods that require skilled technical staff. This study aims in validating citizen science water quality collected data (nitrate, phosphate and turbidity) with those collected and measured by professional scientists in the laboratory. A second objective of the study is to use citizen scientist data to identify the patterns of seasonal and spatial variations in nutrient conditions and forecast potential changes based on expected changes in population and climate (to 2050). The results showed that the concentrations of nitrate and phosphate measured by citizen scientists nearly matched those established by professional scientists, with overall accuracy of 91% and 74%, respectively. For total suspended solids measured by professional and turbidity measured by citizen scientists, results show that, using 14 NTU as a cut-off, citizen scientist measurements of Secchi tube depth to identify lake TSS below 7.0 mg/L showed an accuracy of 88%. In both laboratory and citizen scientist-based studies, all measured water quality variables were significantly higher during the wet season compared to the dry season. Climate factors were discovered to have a major impact on the likelihood of exceeding water quality restrictions in the next decades (2050), which could deteriorate lake conditions. Upscaling citizen science to more communities on the lake and other African Great Lakes would raise environmental awareness, inform management and mitigation activities, and aid long-term decision-making.

Tear Trough Filler Techniques Utilizing Hyaluronic Acid: A Systematic Review.

BACKGROUND: Hyaluronic acid soft-tissue augmentation fillers are commonly injected into multiple areas of the face, including the tear trough. Despite well-documented risks, there is no standardized, evidence-based approach to inject filler in this area, be it using a hypodermic needle or a microcannula. The authors, therefore, sought to establish a preference between the two methods to facilitate progression toward standardization and prevention of adverse events. METHODS: This is a systematic review of articles discussing hyaluronic acid tear trough injection techniques performed in vivo and related outcomes. Searches were conducted across The Cochrane Library, PubMed, Scopus, Web of Science, and Embase to yield relevant articles published before February of 2020. All selected articles incorporated discrete patient cases and were analyzed by a variety of variables assessing evidence strength, outcomes, technique, and patient safety. RESULTS: After appraisal, 42 articles met eligibility criteria: 20 using needles, 12 using cannulas, and 10 focusing on adverse events. Level III was the most commonly awarded evidence grade, corresponding to retrospective, nonexperimental descriptive studies. There were no statistically significant differences in reported aesthetic results, patient satisfaction, or incidence of adverse events across the needle-based and cannula-based articles. Some technique trends, such as targeted anatomical plane and needle position, emerged in subsequent articles. CONCLUSION: Given that there were no statistically significant differences in patient safety or outcomes, an evidence-based preference for needle or cannula injection into the tear trough cannot be made at this time. Current inconsistencies make tear trough injection procedures difficult to replicate, making standardization based on avoidance of adverse events not feasible.

Community monitoring of coliform pollution in Lake Tanganyika.

Conventional water quality monitoring has been done for decades in Lake Tanganyika, under different national and international programs. However, these projects utilized monitoring approaches, which were temporally limited, labour intensive and costly. This study examines the use of citizen science to monitor the dynamics of coliform concentrations in Lake Tanganyika as a complementary method to statutory and project-focused measurements. Persons in five coastal communities (Kibirizi, Ilagala, Karago, Ujiji and Gombe) were trained and monitored total coliforms, faecal coliforms and turbidity for one year on a monthly basis, in parallel with professional scientists. A standardized and calibrated Secchi tube was used at the same time to determine turbidity. Results indicate that total and faecal coliform concentrations determined by citizen scientists correlated well to those determined by professional scientists. Furthermore, citizen scientist-based turbidity values were shown to provide a potential indicator for high FC and TC concentrations. As a simple tiered approach to identify increased coliform loads, trained local citizen scientists could use low-cost turbidity measurements with follow up sampling and analysis for coliforms, to inform their communities and regulatory bodies of high risk conditions, as well as to validate local mitigation actions. By comparing the spatial and temporal dynamics of coliform concentrations to local conditions of infrastructure, population, precipitation and hydrology in the 15 sites (3 sites per community) over 12 months, potential drivers of coliform pollution in these communities were identified, largely related to precipitation dynamics and the land use.

Impact of nisin on Clostridioides difficile and microbiota composition in a faecal fermentation model of the human colon.

AIMS: Nisin is a bacteriocin with a broad spectrum of activity against Gram-positive bacteria. The aims were to assess nisin activity against Clostridioides difficile in a complex microbial environment and determine the minimum inhibitory concentration at which C. difficile growth is suppressed whilst having minimal impact on the faecal microbiota. METHODS AND RESULTS: Faecal slurries were prepared from fresh faecal samples and spiked with C. difficile (106  CFU per ml). Nisin was added to each fermentation at a range of concentrations from 0 to 500 µM. Following 24 h, 16S rRNA gene sequencing was performed, and the presence of viable C. difficile was assessed. There was no viable C. difficile detected in the presence of 50-500 µM nisin. There was a decrease in the diversity of the microbiota in a nisin dose-dependent manner. Nisin predominantly depleted the relative abundance of the Gram-positive bacteria whilst the relative abundance of Gram-negative bacteria such as Escherichia Shigella and Bacteroides increased. CONCLUSIONS: Using an ex vivo model of the colon, this study demonstrates the ability of purified nisin to selectively deplete C. difficile in a faecal microbial environment and establishes the minimum concentration at which this occurs whilst having a minimal impact on the composition of the microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: This study opens up the potential to use nisin as a therapeutic for clostridial gut infections.

Langerhans Cells as Morphologic Mimickers of Atypical Melanocytes on Reflectance Confocal Microscopy: A Case Report and Review of the Literature.

Pagetoid spread of melanocytes in the epidermis is a common indicator of melanocytic atypia, both histopathologically and with reflectance confocal microscopy (RCM). Specifically on RCM, large, bright, atypical dendritic and/or roundish cells are characteristic of melanoma. However, intraepidermal Langerhans cells (ILC) create the potential for diagnostic ambiguity on RCM. We describe one case of a pigmented facial lesion that was initially diagnosed as lentigo maligna (LM) due to numerous atypical perifollicular dendritic cells on RCM. Additionally, we present the findings of a literature review for similar reported cases conducted by searching the following terms on PubMed: reflectance confocal microscopy, RCM, lentigo maligna, melanoma, Langerhans cells, dendritic cells, and atypical cells. In our case, the lesion was determined to be a solar lentigo on histopathology. Immunohistochemistry (IHC) with CD1a identified the atypical-appearing cells as ILC, as it did in 54 reported cases of benign lesions (benign melanocytic nevus, Sutton/halo nevus, labial melanotic macule, and solar lentigo) misdiagnosed as malignant on RCM (melanoma, lip melanoma, lentigo maligna, and LM melanoma). According to our case and the literature, both ILC and atypical melanocytes can present with atypical-appearing dendritic and/or roundish cells under RCM. Currently, there is no method to distinguish the two without IHC. Therefore, the presence of pagetoid cells should continue to alert the confocalist of a potential neoplastic process, prompting biopsy, histopathologic diagnosis, and IHC differentiation.

Reflectance confocal microscopy evaluation of pigmented lesions on tattooed skin.

The evaluation of pigmented lesions on tattooed skin poses a diagnostic challenge for dermatologists, as a nevus may be partially or completely obscured by tattoo pigment. Because of incidences of melanoma arising from tattooed skin, the current gold standard is to biopsy these lesions. Reflectance confocal microscopy (RCM) is a noninvasive imaging modality used in the diagnosis and management of skin diseases that may allow for diagnosis, while preserving the tattoo design. Retrospective chart review was conducted to identify pigmented lesions on or near tattooed skin that were evaluated with RCM. Confocal characteristics and diagnoses were recorded and analyzed. Nineteen lesions from 15 patients were retrospectively reviewed. Tattoo pigment did not hinder evaluation and diagnosis of pigmented lesions on RCM. About 94.7% of lesions were diagnosed as benign melanocytic nevi by an expert confocal reader. One lesion was confocally diagnosed as melanocytic nevus with atypia but was found to be an inflamed melanocytic nevus on histology. Tattoo pigment particles were differentiated from other hyper-refractile entities by an expert confocal reader based on size, morphology, and clinical correlation. RCM may provide a solution to the diagnostic challenge of pigmented lesions on or near tattooed skin.

Increased winter drownings in ice-covered regions with warmer winters.

Winter activities on ice are culturally important for many countries, yet they constitute a high safety risk depending upon the stability of the ice. Because consistently cold periods are required to form stable and thick ice, warmer winters could degrade ice conditions and increase the likelihood of falling through the ice. This study provides the first large-scale assessment of winter drowning from 10 Northern Hemisphere countries. We documented over 4000 winter drowning events. Winter drownings increased exponentially in regions with warmer winters when air temperatures neared 0°C. The largest number of drownings occurred when winter air temperatures were between -5°C and 0°C, when ice is less stable, and also in regions where indigenous traditions and livelihood require extended time on ice. Rates of drowning were greatest late in the winter season when ice stability declines. Children and adults up to the age of 39 were at the highest risk of winter drownings. Beyond temperature, differences in cultures, regulations, and human behaviours can be important additional risk factors. Our findings indicate the potential for increased human mortality with warmer winter air temperatures. Incorporating drowning prevention plans would improve adaptation strategies to a changing climate.

A database of chlorophyll and water chemistry in freshwater lakes.

Measures of chlorophyll represent the algal biomass in freshwater lakes that is often used by managers as a proxy for water quality and lake productivity. However, chlorophyll concentrations in lakes are dependent on many interacting factors, including nutrient inputs, mixing regime, lake depth, climate, and anthropogenic activities within the watershed. Therefore, integrating a broad scale dataset of lake physical, chemical, and biological characteristics can help elucidate the response of freshwater ecosystems to global change. We synthesized a database of measured chlorophyll a (chla) values, associated water chemistry variables, and lake morphometric characteristics for 11,959 freshwater lakes distributed across 72 countries. Data were collected based on a systematic review examining 3322 published manuscripts that measured lake chla, and we supplemented these data with online repositories such as The Knowledge Network for Biocomplexity, Dryad, and Pangaea. This publicly available database can be used to improve our understanding of how chlorophyll levels respond to global environmental change and provide baseline comparisons for environmental managers responsible for maintaining water quality in lakes.

Atypical cells on reflectance confocal microscopy may not represent melanoma: A case of axillary pigmented extramammary Paget disease.

Pigmented extramammary Paget disease (PEMPD) is a rare intraepithelial carcinoma which can clinically resemble other pigmented neoplasms. Similarities to melanoma on dermoscopy, histopathology, and reflectance confocal microscopy (RCM) increase the risk of misdiagnosis and, consequently, mismanagement. Here, we describe a case of a 67-year-old African American woman with a large, pigmented axillary patch that exhibited features of melanoma on RCM, guiding the clinician to perform an excisional biopsy. While traditional histopathology resembled melanoma, immunohistochemistry staining was performed and revealed PEMPD. We highlight an uncommon clinical presentation of PEMPD disease and identify morphologic mimickers of melanoma on RCM-as well as differentiating features.

Fusions involving BCOR and CREBBP are rare events in infiltrating glioma.

BCOR has been recognized as a recurrently altered gene in a subset of pediatric tumors of the central nervous system (CNS). Here, we describe a novel BCOR-CREBBP fusion event in a case of pediatric infiltrating astrocytoma and further probe the frequency of related fusion events in CNS tumors. We analyzed biopsy samples taken from a 15-year-old male with an aggressive, unresectable and multifocal infiltrating astrocytoma. We performed RNA sequencing (RNA-seq) and targeted DNA sequencing. In the index case, the fused BCOR-CREBBP transcript comprises exons 1-4 of BCOR and exon 31 of CREBBP. The fused gene thus retains the Bcl6 interaction domain of BCOR while eliminating the domain that has been shown to interact with the polycomb group protein PCGF1. The fusion event was validated by FISH and reverse transcriptase PCR. An additional set of 177 pediatric and adult primary CNS tumors were assessed via FISH for BCOR break apart events, all of which were negative. An additional 509 adult lower grade infiltrating gliomas from the publicly available TCGA dataset were screened for BCOR or CREBBP fusions. In this set, one case was found to harbor a CREBBP-GOLGA6L2 fusion and one case a CREBBP-SRRM2 fusion. In a third patient, both BCOR-L3MBTL2 and EP300-BCOR fusions were seen. Of particular interest to this study, EP300 is a paralog of CREBBP and the breakpoint seen involves a similar region of the gene to that of the index case; however, the resultant transcript is predicted to be completely distinct. While this gene fusion may play an oncogenic role through the loss of tumor suppressor functions of BCOR and CREBBP, further screening over larger cohorts and functional validation is needed to determine the degree to which this or similar fusions are recurrent and to elucidate their oncogenic potential.

Process Optimisation Studies and Aminonitrile Substrate Evaluation of Rhodococcus erythropolis SET1, A Nitrile Hydrolyzing Bacterium.

A comprehensive series of optimization studies including pH, solvent and temperature were completed on the nitrile hydrolyzing Rhodococcus erythropolis bacterium SET1 with the substrate 3-hydroxybutyronitrile. These identified temperature of 25 °C and pH of 7 as the best conditions to retain enantioselectivity and activity. The effect of the addition of organic solvents to the biotransformation mixture was also determined. The results of the study suggested that SET1 is suitable for use in selected organo-aqueous media at specific ratios only. The functional group tolerance of the isolate with unprotected and protected ß-aminonitriles, structural analogues of ß-hydroxynitriles was also investigated with disappointingly poor isolated yields and selectivity obtained. The isolate was further evaluated with the α- aminonitrile phenylglycinonitrile generating acid in excellent yield and ee (>99 % (S) - isomer and 50 % yield). A series of pH studies with this substrate indicated pH 7 to be the optimum pH to avoid product and substrate degradation.