The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study

<p>Introduction: Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.</p> <p>Patients and Methods: 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.</p> <p>Results: 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).</p> <p>Conclusions: This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.</p&gt

Complexity within an oil palm monoculture: The effects of habitat variability and rainfall on adult dragonfly (Odonata) communities

Recent expansion of oil palm agriculture has resulted in loss of forest habitat and forest-dependent species. However, large numbers of species – particularly insects – can persist within plantations. This study focuses on Odonata (dragonflies and damselflies): a charismatic indicator taxon, and a potentially valuable pest control agent. We surveyed adult Odonata populations biannually over three years within an industrial oil palm plantation in Sumatra, Indonesia. We assessed the effects of rainfall (including an El Niño Southern Oscillation-associated drought), the role of roadside ditches, and the importance of understory vegetation on Odonata populations. To assess the impacts of vegetation we took advantage of a long-term vegetation management experiment that is part of the Biodiversity and Ecosystem Function in Tropical Agriculture (BEFTA) Programme. We found 41 Odonata species, and communities varied between plantation core and roadside edge microhabitats, and between seasons. Abundance was significantly related to rainfall levels four months before surveys, probably indicating the importance of high water levels in roadside ditches for successful larval development. We found no significant effect of the BEFTA understory vegetation treatments on Odonata abundance, and only limited effects on community composition, suggesting that local understory vegetation structure plays a relatively unimportant role in determining communities. Our findings highlight that there are large numbers of Odonata species present within oil palm plantations, and suggest that their abundance could potentially be increased by maintaining or establishing waterbodies. As Odonata are predators, this could bring pest control benefits, in addition to enhancing biodiversity within intensive agricultural landscapes.This work was funded by The Isaac Newton Trust Cambridge, Golden Agri Resources, and the Natural Environment Research Council [grant number NE/P00458X/1]

Onset and window of SARS-CoV-2 infectiousness and temporal correlation with symptom onset: a prospective, longitudinal, community cohort study.

BACKGROUND: Knowledge of the window of SARS-CoV-2 infectiousness is crucial in developing policies to curb transmission. Mathematical modelling based on scarce empirical evidence and key assumptions has driven isolation and testing policy, but real-world data are needed. We aimed to characterise infectiousness across the full course of infection in a real-world community setting. METHODS: The Assessment of Transmission and Contagiousness of COVID-19 in Contacts (ATACCC) study was a UK prospective, longitudinal, community cohort of contacts of newly diagnosed, PCR-confirmed SARS-CoV-2 index cases. Household and non-household exposed contacts aged 5 years or older were eligible for recruitment if they could provide informed consent and agree to self-swabbing of the upper respiratory tract. The primary objective was to define the window of SARS-CoV-2 infectiousness and its temporal correlation with symptom onset. We quantified viral RNA load by RT-PCR and infectious viral shedding by enumerating cultivable virus daily across the course of infection. Participants completed a daily diary to track the emergence of symptoms. Outcomes were assessed with empirical data and a phenomenological Bayesian hierarchical model. FINDINGS: Between Sept 13, 2020, and March 31, 2021, we enrolled 393 contacts from 327 households (the SARS-CoV-2 pre-alpha and alpha variant waves); and between May 24, 2021, and Oct 28, 2021, we enrolled 345 contacts from 215 households (the delta variant wave). 173 of these 738 contacts were PCR positive for more than one timepoint, 57 of which were at the start of infection and comprised the final study population. The onset and end of infectious viral shedding were captured in 42 cases and the median duration of infectiousness was 5 (IQR 3-7) days. Although 24 (63%) of 38 cases had PCR-detectable virus before symptom onset, only seven (20%) of 35 shed infectious virus presymptomatically. Symptom onset was a median of 3 days before both peak viral RNA and peak infectious viral load (viral RNA IQR 3-5 days, n=38; plaque-forming units IQR 3-6 days, n=35). Notably, 22 (65%) of 34 cases and eight (24%) of 34 cases continued to shed infectious virus 5 days and 7 days post-symptom onset, respectively (survival probabilities 67% and 35%). Correlation of lateral flow device (LFD) results with infectious viral shedding was poor during the viral growth phase (sensitivity 67% [95% CI 59-75]), but high during the decline phase (92% [86-96]). Infectious virus kinetic modelling suggested that the initial rate of viral replication determines the course of infection and infectiousness. INTERPRETATION: Less than a quarter of COVID-19 cases shed infectious virus before symptom onset; under a crude 5-day self-isolation period from symptom onset, two-thirds of cases released into the community would still be infectious, but with reduced infectious viral shedding. Our findings support a role for LFDs to safely accelerate deisolation but not for early diagnosis, unless used daily. These high-resolution, community-based data provide evidence to inform infection control guidance. FUNDING: National Institute for Health and Care Research

Central role for MCP-1/CCL2 in injury-induced inflammation revealed by in vitro, in silico, and clinical studies

The translation of in vitro findings to clinical outcomes is often elusive. Trauma/hemorrhagic shock (T/HS) results in hepatic hypoxia that drives inflammation. We hypothesize that in silico methods would help bridge in vitro hepatocyte data and clinical T/HS, in which the liver is a primary site of inflammation. Primary mouse hepatocytes were cultured under hypoxia (1% O 2) or normoxia (21% O2) for 1-72 h, and both the cell supernatants and protein lysates were assayed for 18 inflammatory mediators by Luminex™ technology. Statistical analysis and data-driven modeling were employed to characterize the main components of the cellular response. Statistical analyses, hierarchical and k-means clustering, Principal Component Analysis, and Dynamic Network Analysis suggested MCP-1/CCL2 and IL-1α as central coordinators of hepatocyte-mediated inflammation in C57BL/6 mouse hepatocytes. Hepatocytes from MCP-1-null mice had altered dynamic inflammatory networks. Circulating MCP-1 levels segregated human T/HS survivors from non-survivors. Furthermore, T/HS survivors with elevated early levels of plasma MCP-1 post-injury had longer total lengths of stay, longer intensive care unit lengths of stay, and prolonged requirement for mechanical ventilation vs. those with low plasma MCP-1. This study identifies MCP-1 as a main driver of the response of hepatocytes in vitro and as a biomarker for clinical outcomes in T/HS, and suggests an experimental and computational framework for discovery of novel clinical biomarkers in inflammatory diseases. © 2013 Ziraldo et al

Non-Compliance with Growth Hormone Treatment in Children Is Common and Impairs Linear Growth

BACKGROUND: GH therapy requires daily injections over many years and compliance can be difficult to sustain. As growth hormone (GH) is expensive, non-compliance is likely to lead to suboptimal growth, at considerable cost. Thus, we aimed to assess the compliance rate of children and adolescents with GH treatment in New Zealand. METHODS: This was a national survey of GH compliance, in which all children receiving government-funded GH for a four-month interval were included. Compliance was defined as ≥ 85% adherence (no more than one missed dose a week on average) to prescribed treatment. Compliance was determined based on two parameters: either the number of GH vials requested (GHreq) by the family or the number of empty GH vials returned (GHret). Data are presented as mean ± SEM. FINDINGS: 177 patients were receiving GH in the study period, aged 12.1 ± 0.6 years. The rate of returned vials, but not number of vials requested, was positively associated with HVSDS (p < 0.05), such that patients with good compliance had significantly greater linear growth over the study period (p<0.05). GHret was therefore used for subsequent analyses. 66% of patients were non-compliant, and this outcome was not affected by sex, age or clinical diagnosis. However, Maori ethnicity was associated with a lower rate of compliance. INTERPRETATION: An objective assessment of compliance such as returned vials is much more reliable than compliance based on parental or patient based information. Non-compliance with GH treatment is common, and associated with reduced linear growth. Non-compliance should be considered in all patients with apparently suboptimal response to GH treatment

Risk factors and vectors for SARS-CoV-2 household transmission: a prospective, longitudinal cohort study

BACKGROUND: Despite circumstantial evidence for aerosol and fomite spread of SARS-CoV-2, empirical data linking either pathway with transmission are scarce. Here we aimed to assess whether the presence of SARS-CoV-2 on frequently-touched surfaces and residents' hands was a predictor of SARS-CoV-2 household transmission. METHODS: In this longitudinal cohort study, during the pre-alpha (September to December, 2020) and alpha (B.1.1.7; December, 2020, to April, 2021) SARS-CoV-2 variant waves, we prospectively recruited contacts from households exposed to newly diagnosed COVID-19 primary cases, in London, UK. To maximally capture transmission events, contacts were recruited regardless of symptom status and serially tested for SARS-CoV-2 infection by RT-PCR on upper respiratory tract (URT) samples and, in a subcohort, by serial serology. Contacts' hands, primary cases' hands, and frequently-touched surface-samples from communal areas were tested for SARS-CoV-2 RNA. SARS-CoV-2 URT isolates from 25 primary case-contact pairs underwent whole-genome sequencing (WGS). FINDINGS: From Aug 1, 2020, until March 31, 2021, 620 contacts of PCR-confirmed SARS-CoV-2-infected primary cases were recruited. 414 household contacts (from 279 households) with available serial URT PCR results were analysed in the full household contacts' cohort, and of those, 134 contacts with available longitudinal serology data and not vaccinated pre-enrolment were analysed in the serology subcohort. Household infection rate was 28·4% (95% CI 20·8-37·5) for pre-alpha-exposed contacts and 51·8% (42·5-61·0) for alpha-exposed contacts (p=0·0047). Primary cases' URT RNA viral load did not correlate with transmission, but was associated with detection of SARS-CoV-2 RNA on their hands (p=0·031). SARS-CoV-2 detected on primary cases' hands, in turn, predicted contacts' risk of infection (adjusted relative risk [aRR]=1·70 [95% CI 1·24-2·31]), as did SARS-CoV-2 RNA presence on household surfaces (aRR=1·66 [1·09-2·55]) and contacts' hands (aRR=2·06 [1·57-2·69]). In six contacts with an initial negative URT PCR result, hand-swab (n=3) and household surface-swab (n=3) PCR positivity preceded URT PCR positivity. WGS corroborated household transmission. INTERPRETATION: Presence of SARS-CoV-2 RNA on primary cases' and contacts' hands and on frequently-touched household surfaces associates with transmission, identifying these as potential vectors for spread in households. FUNDING: National Institute for Health Research Health Protection Research Unit in Respiratory Infections, Medical Research Council

Evaluating compliance to a low glycaemic index (GI) diet in women with polycystic ovary syndrome (PCOS)

<p>Abstract</p> <p>Background</p> <p>A low Glycaemic Index (GI) diet may decrease some long-term health risks in Polycystic Ovary Syndrome (PCOS) such as endometrial cancer. This study was performed to assess compliance to a low GI diet in women with PCOS. Food diaries prospectively collected over 6 months from women on a low GI diet or healthy eating diet were analysed retrospectively. The women were recruited for a pilot randomised control trial investigating whether a low GI diet decreased the risk of Endometrial Cancer. Nine women with PCOS completed 33 food diaries (17 from women on a low GI diet and 16 from women on a healthy eating diet) recording 3023 food items (low GI group:n = 1457; healthy eating group:n = 1566). Data was analysed using Foster-Powell international values inserted into an SPSS database as no scientifically valid established nutrition software was found. The main outcome measures were mean item GI and Glyacemic Load (GL), mean meal GL, percentage high GI foods and mean weight loss.</p> <p>Findings</p> <p>Women allocated the low GI diet had a statistically significant lower GI of food items (33.67 vs 36.91, p < 0.05), lower percentage of high GI foods (4.3% vs 12.1%, p < 0.05) and lower GL of food items and meals.</p> <p>Conclusion</p> <p>Women with PCOS on a low GI diet consumed food items with a significantly lower mean GI and GL compared to the healthy eating diet group. Longer term compliance needs evaluation in subsequent studies to ascertain that this translates to reduced long term health risks.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN86420258">ISRCTN86420258</a></p

Velocity vector imaging to quantify left atrial function

The aim of our study was to assess the feasibility of a new image analysis, velocity vector imaging (VVI), in the assessment of left atrial volumes (LAV) and left atrial ejection fraction (LAEF). We retrospectively analysed 100 transthoracic echocardiographic findings in 71 men, and 29 women (mean age 57 ± 19.8 years). Two subgroups of patients were defined: (1) with left ventricular (LV) EF > 50%, and (2) LV EF < 50%. For the VVI method of indexed LAV assessment we used the apical four-chamber view. From the displacement of LA endocardial pixels time–volume curves were extracted which provided automatically data regarding indexed maximum LAV (LAVImax), indexed minimum LAV (LAVImin), and LAEF. LAVs and LAEF by 2-dimensional echocardiograhy (2DE) were measured by Simpson’s biplane disc summation method. Comparing LAVImax, LAVImin, and LAEF by VVI versus 2DE in the total study population, we found significant correlations: r = 0.94, P < 0.0001, r = 0.94, P < 0.0001, r = 0.79, P < 0.0001, respectively. In addition, LAVImax ≥ 40 ml/m2 was 94% sensitive and 72% specific, LAVImin ≥ 27 ml/m2 was 90% sensitive and 86% specific, and LAEF < 30% was 80% sensitive and 96% specific for the detection of LV systolic dysfunction. There were highly significant inverse associations of LAVImax and LAVImin to LVEF. LAEF was also significantly related to LV systolic function. When comparing the time required for VVI and 2DE measurements, VVI led to 62% reduction in the measurement time. In conclusion, VVI is a feasible method for the assessment of LAVs and LAEF. It provides close agreement with that measured by conventional 2DE Simpson’s biplane method with significant time saved

How well do second-year students learn physical diagnosis? Observational study of an objective structured clinical examination (OSCE)

BACKGROUND: Little is known about using the Objective Structured Clinical Examination (OSCE) in physical diagnosis courses. The purpose of this study was to describe student performance on an OSCE in a physical diagnosis course. METHODS: Cross-sectional study at Harvard Medical School, 1997–1999, for 489 second-year students. RESULTS: Average total OSCE score was 57% (range 39–75%). Among clinical skills, students scored highest on patient interaction (72%), followed by examination technique (65%), abnormality identification (62%), history-taking (60%), patient presentation (60%), physical examination knowledge (47%), and differential diagnosis (40%) (p < .0001). Among 16 OSCE stations, scores ranged from 70% for arthritis to 29% for calf pain (p < .0001). Teaching sites accounted for larger adjusted differences in station scores, up to 28%, than in skill scores (9%) (p < .0001). CONCLUSIONS: Students scored higher on interpersonal and technical skills than on interpretive or integrative skills. Station scores identified specific content that needs improved teaching

Managing Oil Palm Plantations More Sustainably: Large-Scale Experiments Within the Biodiversity and Ecosystem Function in Tropical Agriculture (BEFTA) Programme

Conversion of tropical forest to agriculture results in reduced habitat heterogeneity, and associated declines in biodiversity and ecosystem functions. Management strategies to increase biodiversity in agricultural landscapes have therefore often focused on increasing habitat complexity; however, the large-scale, long-term ecological experiments that are needed to test the effects of these strategies are rare in tropical systems. Oil palm (Elaeis guineensis Jacq.)—one of the most widespread and important tropical crops—offers substantial potential for developing wildlife-friendly management strategies because of its long rotation cycles and tree-like structure. Although there is awareness of the need to increase sustainability, practical options for how best to manage oil palm plantations, for benefits to both the environment and crop productivity, have received little research attention. In this paper we introduce the Biodiversity and Ecosystem Function in Tropical Agriculture (BEFTA) Programme: a long-term research collaboration between academia and industry in Sumatra, Indonesia. The BEFTA Programme aims to better understand the oil palm agroecosystem and test sustainability strategies. We hypothesise that adjustments to oil palm management could increase structural complexity, stabilize microclimate, and reduce reliance on chemical inputs, thereby helping to improve levels of biodiversity and ecosystem functions. The Programme has established four major components: (1) assessing variability within the plantation under business-as-usual conditions; (2) the BEFTA Understory Vegetation Project, which tests the effects of varying herbicide regimes; (3) the Riparian Ecosystem Restoration in Tropical Agriculture (RERTA) Project, which tests strategies for restoring riparian habitat; and (4) support for additional collaborative projects within the Programme landscape. Across all projects, we are measuring environmental conditions, biodiversity, and ecosystem functions. We also measure oil palm yield and production costs, in order to assess whether suggested sustainability strategies are feasible from an agronomic perspective. Early results show that oil palm plantation habitat is more variable than might be expected from a monoculture crop, and that everyday vegetation management decisions have significant impacts on habitat structure. The BEFTA Programme highlights the value of large-scale collaborative projects for understanding tropical agricultural systems, and offers a highly valuable experimental set-up for improving our understanding of practices to manage oil palm more sustainably.This work was funded by The Isaac Newton Trust Cambridge, Golden Agri Resources, ICOPE (the International Conference on Oil Palm and the Environment), and the Natural Environment Research Council [grant number NE/P00458X/1]