First Documentation of the European Gut Fungus, \u3cem\u3eEphemerellomyces\u3c/em\u3e, and Other Insect Associated Endosymbionts in the Dry Creek Drainage, Boise, Idaho

Trichomycetes, a former class of obligate endosymbiotic fungi, are now recognized as an ecological group that inhabits the gut(s) of immature insects. Though the biodiversity and geographical distribution of trichomycetes are worldwide, our knowledge of the group in the Pacific Northwest is limited due to the few researchers conducting studies on them. Dry Creek drainage in Boise, Idaho was selected in the winter of 2009-10 as a potential site to find gut fungi. This initial survey provides the first account of Ephemerellomyces aquilonius, a species previously documented and studied only in Norway. Ephemerellomyces aquilonius (a monotypic genus) is a member of the Harpellales, an order of trichomycetes, and was dissected from the digestive tracts of mayflies (Ephemeroptera) collected from the creek. Amongst the various aquatic habitats surveyed and hosts recovered, gut fungi were also documented in stoneflies (Plecoptera) and black flies (Diptera: Simuliidae). Our investigation provides a significant new record of the very rare and unusual taxon, E. aquilonius, previously only known in Western Europe. The success of this brief survey demonstrates promise for further discoveries of gut fungi at this site, in Idaho and the Pacific Northwest. This disjunct distribution bridges an enormous geographical divide, although the species actually may be more widespread than earlier anticipated. Future collections and research on specimens from Dry Creek, with sequence data to be generated in our laboratory will be eagerly awaited as we place this unusual species in our expanding molecular-based phylogenies. We highlight here the morphology of E. aquilonius and some of the other endosymbionts found there

Assessing the Potential Effects of Fungicides on Nontarget Gut Fungi (Trichomycetes) and Their Associated Larval Black Fly Hosts

Fungicides are moderately hydrophobic and have been detected in water and sediment, particularly in agricultural watersheds, but typically are not included in routine water quality monitoring efforts. This is despite their widespread use and frequent application to combat fungal pathogens. Although the efficacy of these compounds on fungal pathogens is well documented, little is known about their effects on nontarget fungi. This pilot study, a field survey in southwestern Idaho from April to December 2010 on four streams with varying pesticide inputs (two agricultural and two reference sites), was conducted to assess nontarget impact of fungicides on gut fungi, or trichomycetes. Tissues of larval black flies (Diptera: Simuliidae), hosts of gut fungi, were analyzed for pesticide accumulation. Fungicides were detected in hosts from streams within agricultural watersheds but were not detected in hosts from reference streams. Gut fungi from agricultural sites exhibited decreased percent infestation, density and sporulation within the gut, and black fly tissues had elevated pesticide concentrations. Differences observed between the sites demonstrate a potential effect on this symbiotic system. Future research is needed to parse out the details of the complex biotic and abiotic relationships; however, these preliminary results indicate that impacts to nontarget organisms could have far-reaching consequences within aquatic ecosystems

The impact of induction and/or concurrent chemoradiotherapy on acute and late patient-reported symptoms in oropharyngeal cancer:Application of a mixed-model analysis of a prospective observational cohort registry

BACKGROUND The goal of this study was to comprehensively investigate the association of chemotherapy with trajectories of acute symptom development and late symptom recovery in patients with oropharyngeal cancer (OPC) by comparing symptom burden between induction chemotherapy followed by concurrent chemoradiotherapy (ICRT), concurrent chemo-radiotherapy (CRT), or radiotherapy (RT) alone.METHODS Among a registry of 717 patients with OPC, the 28-item patient-reported MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN) symptoms were collected prospectively at baseline, weekly during RT, and 1.5, 3 to 6, 12, and 18 to 24 months after RT. The effect of the treatment regimen (ICRT, CRT, and RT alone) was examined with mixed-model analyses for the acute and late period. In the CRT cohort, the chemotherapy agent relationship with symptoms was investigated.RESULTS Chemoradiation (ICRT/CRT) compared with RT alone resulted in significantly higher acute symptom scores in the majority of MDASI-HN symptoms (ie, 21 out of 28). No late symptom differences between treatment with or without chemotherapy were observed that were not attributable to ICRT. Nausea was lower for CRT with carboplatin than for CRT with cisplatin; cetuximab was associated with particularly higher scores for acute and late skin, mucositis, and 6 other symptoms. The addition of ICRT compared with CRT or RT alone was associated with a significant increase in numbness and shortness of breath.CONCLUSION The addition of chemotherapy to definitive RT for OPC patients was associated with significantly worse acute symptom outcomes compared with RT alone, which seems to attenuate in the late posttreatment period. Moreover, induction chemotherapy was specifically associated with worse numbness and shortness of breath during and after treatment.LAY SUMMARYChemotherapy is frequently used in addition to radiotherapy cancer treatment, yet the (added) effect on treatment-induced over time is not comprehensively investigatedThis study shows that chemotherapy adds to the symptom severity reported by patients, especially during treatment</p

Muscle synergies in cycling after incomplete spinal cord injury: correlation with clinical measures of motor function and spasticity

Background: After incomplete spinal cord injury (iSCI), patients suffer important sensorimotor impairments, such as abnormal locomotion patterns and spasticity. Complementary to current clinical diagnostic procedures, the analysis of muscle synergies has emerged as a promising tool to study muscle coordination, which plays a major role in the control of multi-limb functional movements.Objective: Based on recent findings suggesting that walking and cycling share similar synergistic control, the analysis of muscle synergies during cycling might be explored as an early descriptor of gait-related impaired control. This idea was split into the following two hypotheses: (a) iSCI patients present a synergistic control of muscles during cycling; (b) muscle synergies outcomes extracted during cycling correlate with clinical measurements of gait performance and/or spasticity.Methods: Electromyographic (EMG) activity of 13 unilateral lower limb muscles was recorded in a group of 10 healthy individuals and 10 iSCI subjects during cycling at four different cadences. A non-negative matrix factorization (NNMF) algorithm was applied to identify synergistic components (i.e., activation coefficients and muscle synergy vectors). Reconstruction goodness scores (VAF and r(2)) were used to evaluate the ability of a given number of synergies to reconstruct the EMG signals. A set of metrics based on the similarity between pathologic and healthy synergies were correlated with clinical scales of gait performance and spasticity.Results: iSCI patients preserved a synergistic control of muscles during cycling. The similarity with the healthy reference was consistent with the degree of the impairment, i.e., less impaired patients showed higher similarities with the healthy reference. There was a strong correlation between reconstruction goodness scores at 42 rpm and motor performance scales (TUG, 10-m test and WISCI II). On the other hand, the similarity between the healthy and affected synergies presented correlation with some spasticity symThis study was funded by the Spanish Ministry for Science and Innovation, in the framework of the project HYPER (CONSOLIDER-INGENIO 2010) "Hybrid Neuroprosthetic and Neurorobotic Devices for Functional Compensation and Rehabilitation of Motor Disorders" (Ref. CSD2009-00067) and the Spanish project ASSOCIATE (Ref. DPI2014-58431-C4-1-R).info:eu-repo/semantics/publishedVersio

Recent Region-wide Declines in Caribbean Reef Fish Abundance

Profound ecological changes are occurring on coral reefs throughout the tropics, with marked coral cover losses and concomitant algal increases, particularly in the Caribbean region. Historical declines in the abundance of large Caribbean reef fishes likely reflect centuries of overexploitation. However, effects of drastic recent degradation of reef habitats on reef fish assemblages have yet to be established. By using meta-analysis, we analyzed time series of reef fish density obtained from 48 studies that include 318 reefs across the Caribbean and span the time period 1955–2007. Our analyses show that overall reef fish density has been declining significantly for more than a decade, at rates that are consistent across all subregions of the Caribbean basin (2.7% to 6.0% loss per year) and in three of six trophic groups. Changes in fish density over the past half-century are modest relative to concurrent changes in benthic cover on Caribbean reefs. However, the recent significant decline in overall fish abundance and its consistency across several trophic groups and among both fished and nonfished species indicate that Caribbean fishes have begun to respond negatively to habitat degradation

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification