ABSTRACT
The evolutionary origins of Bilateria remain enigmatic. One of the more enduring proposals highlights similarities between a cnidarian-like planula larva and simple acoel-like flatworms. This idea is based in part on the view of the Xenacoelomorpha as an outgroup to all other bilaterians which are themselves designated the Nephrozoa (protostomes and deuterostomes). Genome data can provide important comparative data and help to understand the evolution and biology of enigmatic species better. Here we assemble and analyse the genome of the simple, marine xenacoelomorph Xenoturbella bocki, a key species for our understanding of early bilaterian evolution. Our highly contiguous genome assembly of X. bocki has a size of ~111 Mbp in 18 chromosome like scaffolds, with repeat content and intron, exon and intergenic space comparable to other bilaterian invertebrates. We find X. bocki to have a similar number of genes to other bilaterians and to have retained ancestral metazoan synteny. Key bilaterian signalling pathways are also largely complete and most bilaterian miRNAs are present. Overall, we conclude that X. bocki has a complex genome typical of bilaterians, which does not reflect the apparent simplicity of its body plan that has been so important to proposals that the Xenacoelomorpha are the simple sister group of the rest of the Bilateria.
ABSTRACT
Phylogenetic analyses over the last two decades have united a few small, and previously orphan clades, the nematodermatids, acoels and xenoturbelids, into the phylum Xenacoelomorpha. Some phylogenetic analyses support a sister relationship between Xenacoelomorpha and Ambulacraria (Xenambulacraria), while others suggest that Xenacoelomorpha may be sister to the rest of the Bilateria (Nephrozoa). An understanding of the cell type complements of Xenacoelomorphs is essential to assessing these alternatives as well as to our broader understanding of bilaterian cell type evolution. Employing whole organism single-cell RNA-seq in the marine xenacoelomorph worm Xenoturbella bocki, we show that Xenambulacrarian nerve nets share regulatory features and a peptidergic identity with those found in cnidarians and protostomes and more broadly share muscle and gland cell similarities with other metazoans. Taken together, these data are consistent with broad homologies of animal gland, muscle, and neurons as well as more specific affinities between Xenoturbella and acoel gut and epidermal tissues, consistent with the monophyly of Xenacoelomorpha.
Subject(s)
Phylogeny , AnimalsABSTRACT
Efferocytic clearance of apoptotic cells in general, and T cells in particular, is required for tissue and immune homeostasis. Transmembrane mucins are extended glycoproteins highly expressed in the cell glycocalyx that function as a barrier to phagocytosis. Whether and how mucins may be regulated during cell death to facilitate efferocytic corpse clearance is not well understood. Here we show that normal and transformed human T cells express a subset of mucins which are rapidly and selectively removed from the cell surface during apoptosis. This process is mediated by the ADAM10 sheddase, the activity of which is associated with XKR8-catalyzed flipping of phosphatidylserine to the outer leaflet of the plasma membrane. Mucin clearance enhances uptake of apoptotic T cells by macrophages, confirming mucins as an enzymatically-modulatable barrier to efferocytosis. Together these findings demonstrate a glycocalyx regulatory pathway with implications for therapeutic intervention in the clearance of normal and transformed apoptotic T cells.
Subject(s)
Efferocytosis , Mucins , Humans , T-Lymphocytes/metabolism , Apoptosis , Phagocytosis , ADAM10 Protein/genetics , Membrane Proteins/genetics , Membrane Proteins/metabolism , Amyloid Precursor Protein SecretasesABSTRACT
INTRODUCTION: Titrated application of positive end-expiratory pressure (PEEP) is an important part of any mechanical ventilation strategy. However, the method by which the optimal PEEP is determined and titrated varies widely. Methods for determining optimal PEEP have been assessed using a variety of different study designs and patient populations. We will conduct a scoping review to systematically identify all methods for determining optimal PEEP, and to identify the patient populations, outcomes measured and study designs used for each method. The goal will be to identify gaps in the optimal PEEP literature and identify areas where there may be an opportunity to further systematically synthesise and meta-analyse existing literature. METHODS AND ANALYSIS: Using scoping review methodology, we will generate a comprehensive search strategy based on inclusion and exclusion criteria generated using the population, concept, context framework. Five different databases will be searched (MEDLINE, EMBASE, CENTRAL, Web of Science and Scopus). Three investigators will independently screen titles and abstracts, and two investigators will independently complete full-text review and data extraction. Included citations will be categorised in terms of PEEP method, study design, patient population and outcomes measured. The methods for PEEP titration will be described in detail, including strengths and limitations. ETHICS AND DISSEMINATION: Given this is a synthesis of existing literature, ethics approval is not required. The results will be disseminated to stakeholders via presentation at local, regional and national levels, as well as publication in a high-impact critical care journal. There is also the potential to impact local clinical care protocols and inform broader clinical practice guidelines undertaken by societies.
Subject(s)
Positive-Pressure Respiration , Respiration, Artificial , Humans , Positive-Pressure Respiration/methods , Critical Care , Research Design , Bibliometrics , Review Literature as TopicABSTRACT
BACKGROUND: Chest pain is a common cause for emergency department (ED) presentations. After myocardial infarction (MI) has been ruled out by means of electrocardiography and troponin testing, decisions around anatomic or functional testing may be informed by clinical risk scores. We conducted a systematic review to synthesize evidence of the prognostic performance of chest pain risk scores among ED patients who have had MI ruled out by means of a high-sensitivity troponin assay. METHODS: We queried multiple databases from inception to May 17, 2022. We included studies that quantified risk of 30-day major adverse cardiac events (MACE), at different cutoffs of clinical risk scores, among adult patients who had MI ruled out by means of a high-sensitivity troponin assay. Prognostic performance of each score was synthesized and described, but meta-analysis was not possible. RESULTS: Six studies met inclusion criteria. Short-term MACE risk among patients who had MI ruled out by means of high-sensitivity cardiac troponin assays was very low. The HEART score, with a cutoff of 3 or less, predicted a very low risk of MACE among the greatest proportion of patients. Other scores had lower sensitivity or classified fewer patients as low risk. CONCLUSIONS: The HEART score with a cutoff value of 3 or less accurately identified the greatest number of patients at low risk of 30-day MACE. However, MACE risk among patients who have MI ruled out by means of high-sensitivity troponin testing is sufficiently low that clinical risk stratification or noninvasive testing may be of little additional value in identifying patients with coronary disease.
Subject(s)
Acute Coronary Syndrome , Myocardial Infarction , Adult , Humans , Myocardial Infarction/complications , Chest Pain/etiology , Risk Factors , Troponin , Emergency Service, Hospital , Electrocardiography , Risk Assessment , Acute Coronary Syndrome/complicationsABSTRACT
BACKGROUND: Hyperfunctioning or hot nodules are thought to be rarely malignant. As such, current guidelines recommend that hot nodules be excluded from further malignancy risk stratification. The objective of this systematic review and meta-analysis is to compare the malignancy risk in hot nodules and non-toxic nodules in observational studies. METHODS: Ovid MEDLINE Daily and Ovid MEDLINE, EMBASE, Scopus, and Web of Science databases were searched. Observational studies which met all of the following were included: (1) use thyroid scintigraphy for nodule assessment, (2) inclusion of both hyperfunctioning and non-functioning nodules based on scintigraphy, (3) available postoperative histopathologic nodule results, (4) published up to November 12, 2020 in either English or French. The following data was extracted: malignancy outcomes include malignancy rate, mapping of the carcinoma within the hot nodule, inclusion of microcarcinomas, and presence of gene mutations. RESULTS: Among the seven included studies, overall incidence of malignancy in all hot thyroid nodules ranged from 5 to 100% in comparison with non-toxic nodules, 3.8-46%. Odds of malignancy were also compared between hot and non-toxic thyroid nodules, separated into solitary nodules, multiple nodules and combination of the two. Pooled odds ratio (OR) of solitary thyroid nodules revealed a single hot nodule OR of 0.38 (95% confidence interval (CI) 0.25, 0.59), toxic multinodular goiter OR of 0.51 (95% CI 0.34, 0.75), and a combined hot nodule OR of 0.45 (95% CI 0.31, 0.65). The odds of malignancy are reduced by 55% in hot nodules; however, the incidence was not zero. CONCLUSIONS: Odds of malignancy of hot nodules is reduced compared with non-toxic nodules; however, the incidence of malignancy reported in hot nodules was higher than expected. These findings highlight the need for further studies into the malignancy risk of hot nodules.
ABSTRACT
PURPOSE: To perform a scoping review of the evidence for therapeutic interventions to manage functional impairments associated with Rett syndrome (RTT) throughout the lifespan. METHODS: MEDLINE, EMBASE, PsycINFO, CENTRAL, CINAHL, Scopus and Index to Chiropractic Literature were searched systematically up to December 2019. Two investigators independently reviewed all search results and extracted those that met the inclusion criteria. Human and animal model studies pertaining to therapies that increase functional ability or treat RTT-associated symptoms in all age groups were included. Relevant studies were grouped into intervention categories and rated using the Oxford Centre of Evidence Based Medicine Levels of Evidence. Demographics of participants, interventions, and outcomes were summarized. RESULTS: Ninety-one articles representing 88 studies met the inclusion criteria, of which 80 were human clinical studies and eight were studies using animal models. Study designs were primarily case series and only six studies involved participants above the age of 40. CONCLUSION: A small number of rigorously studied rehabilitation interventions have been published. Published studies aim to address a wide variety of functional impairments. Research regarding implementation of therapies for older patients with RTT is lacking and requires further exploration.
Subject(s)
Rett Syndrome , Animals , Humans , LongevityABSTRACT
BACKGROUND: Treatment of hypoxemic respiratory failure (HRF) and ARDS is complex. Standardized management of HRF and ARDS may improve adherence to evidence-informed practice and improve outcomes. RESEARCH QUESTION: What is the effect of standardized treatment compared with usual care on survival of patients with HRF and ARDS? STUDY DESIGN AND METHODS: MEDLINE, EMBASE, Cochrane, CINAHL, Scopus, and Web-of-Science were searched (inception to 2018). Included studies were randomized clinical trials or quasi-experimental studies that examined the effect of standardized treatment (care-protocol, care-pathway, or bundle) compared with usual treatment among mechanically ventilated adult patients admitted to an ICU with HRF or ARDS. Study characteristics, pathway components, and patient outcomes were abstracted independently by two reviewers. RESULTS: From 15,932 unique citations, 14 studies were included in the systematic review (three randomized clinical trials and 11 quasi-experimental studies). Twelve studies (including 5,767 patients) were included in the meta-analysis. Standardized management of HRF was associated with a 23% relative reduction in mortality (relative risk, 0.77; 95% CI, 0.65-0.91; I2, 70%; P = .002). In studies targeting patients with ARDS (n = 8), a 21% pooled mortality reduction was observed (relative risk, 0.79; 95% CI, 0.71-0.88; I2, 3.1%). Standardized management was associated with increased 28-day ventilator-free days (weighted mean difference, 3.48 days; 95% CI, 2.43-4.54 days; P < .001). Standardized management was also associated with a reduction in tidal volume (weighted mean difference, -1.80 mL/kg predicted body weight; 95% CI, -2.80 to -0.80 mL/kg predicted body weight; P < .001). Meta-regression demonstrated that the reduction in mortality was associated with provision of lower tidal volume (P = .045). INTERPRETATION: When compared with usual treatment, standardized treatment of patients with HRF and ARDS is associated with increased ventilator-free days, lower tidal volume ventilation, and lower mortality. ICUs should consider the use of standardized treatment to improve the processes and outcomes of care for patients with HRF and ARDS. CLINICAL TRIAL REGISTRATION: PROSPERO; No.: CRD42019099921; URL: www.crd.york.ac.uk/prospero/.
Subject(s)
Patient Care Management , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/therapy , Humans , Mortality , Patient Care Management/methods , Patient Care Management/standards , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/mortality , Respiratory Insufficiency/mortalityABSTRACT
BACKGROUND: Medical therapy and/or endoscopic balloon dilation with intralesional therapies are options for the treatment of small bowel fibrostenotic Crohn's disease (CD). AIM: To perform a systematic review summarising evidence for efficacy of systemic and endoscopic intralesional medical therapy in established small bowel strictures in adult CD patients. METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL and Scopus was conducted. Primary outcomes were rates of surgical resection and repeat endoscopic dilation. Pooled event rates from random effects models across studies with 95% confidence intervals were reported. RESULTS: Ten studies describing systemic medical therapy and eight studies of intralesional injection were included. One randomised controlled trial each for systemic therapy and intrastricture injection were identified. Only observational studies were found for systemic biologic therapies, which exclusively included tumour necrosis factor (TNF) antagonists, while intralesional therapies all involved corticosteroids except for one study that evaluated infliximab. Pooled event rates for surgical resection after systemic and intralesional therapy were 28.3% (95% CI: 18.2%-41.3%) and 18.5% (95% CI: 8.3%-36.2%), respectively over a median follow-up of 23 months (range 5.5-105.8), and 21.8 months (range 5-47). Risk of repeat endoscopic balloon dilation in those with intralesional therapy was 58.3% (95% CI: 36.6%-77.3%) over a median follow-up of 21.8 months (range 5-47). CONCLUSIONS: There are no favoured therapies for patients with stricturing small bowel CD. Data are lacking for ustekinumab and vedolizumab. No endoscopic intralesional medications provided a clear benefit for prevention of repeat EBD or surgery.
Subject(s)
Crohn Disease/drug therapy , Intestinal Obstruction/drug therapy , Adrenal Cortex Hormones/administration & dosage , Combined Modality Therapy/statistics & numerical data , Constriction, Pathologic/complications , Constriction, Pathologic/drug therapy , Constriction, Pathologic/epidemiology , Constriction, Pathologic/surgery , Crohn Disease/complications , Crohn Disease/epidemiology , Crohn Disease/surgery , Dilatation/methods , Dilatation/statistics & numerical data , Endoscopy, Gastrointestinal/methods , Endoscopy, Gastrointestinal/statistics & numerical data , Fibrosis/complications , Fibrosis/drug therapy , Fibrosis/epidemiology , Fibrosis/surgery , Humans , Infusions, Intralesional , Intestinal Obstruction/complications , Intestinal Obstruction/epidemiology , Intestinal Obstruction/surgery , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/immunologyABSTRACT
BACKGROUND: Patients with chronic noncancer pain (CNCP) present unique challenges to emergency department (ED) care providers and administrators. Their conditions lead to frequent ED visits for pain relief and symptom management and are often poorly addressed with costly, low-yield care. A systematic review has not been performed to inform the management of frequent ED utilizing patients with CNCP. Therefore, we synthesized the available evidence on interventional strategies to improve care-associated outcomes for this patient group. METHODS: We searched Medline, EMBASE, CINAHL, CENTRAL, SCOPUS, and Web of Science from database inception to June 2018 for eligible interventional studies aimed at reducing frequent ED utilization among adult patients with CNCP. Articles were assessed in duplicate in accordance with methodologic recommendations from the Cochrane Handbook for Systematic Reviews of Interventions. Outcomes of interest were the frequency of subsequent ED visits, type and amount of opioids administered in the ED and prescribed at discharge, and costs. Methodologic quality was assessed using the Cochrane Risk of Bias in Non-Randomized Studies of Interventions and Risk of Bias tools for nonrandomized and randomized studies, respectively. RESULTS: Thirteen studies including 1,679 patients met the inclusion criteria. Identified interventions implemented pain policies (n = 4), individualized care plans (n = 5), ED care coordination (n = 2), chronic pain management pathways (n = 1), and behavioral health interventions (n = 1). All of the studies reported a decrease in ED visit frequency following their respective interventions. These reductions were especially pronounced in studies whose interventions were focused around individualized care plans and primary care involvement. Interventions implementing opioid restriction and pain management policies were largely successful in reducing the amounts of opioid medications administered and prescribed in the ED. CONCLUSIONS: Multifaceted interventions, especially those employing individualized care plans, can successfully reduce subsequent ED visits, ED opioid administration and prescription, and care-associated costs for frequent ED utilizing patients with CNCP.
Subject(s)
Analgesics, Opioid , Chronic Pain , Emergency Service, Hospital , Pain Management , Adult , Analgesics, Opioid/therapeutic use , Chronic Pain/drug therapy , Humans , Patient DischargeABSTRACT
OBJECTIVE: Our goal was to perform a systematic review of the literature to demonstrate the prevalence of cardiac abnormalities identified using cardiac investigations in patients with mitochondrial myopathy (MM). METHODS: This systematic review surveys the available evidence for cardiac investigations in MM from a total of 21 studies including 825 participants. Data were stratified by genetic mutation and clinical syndrome. RESULTS: We identified echocardiogram and ECG as the principal screening modalities that identify cardiac structural (29%) and conduction abnormalities (39%) in various MM syndromes. ECG abnormalities were more prevalent in patients with m.3243A>G mutations than other gene defects, and patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) had a higher prevalence of ECG abnormalities than patients with other clinical syndromes. Echocardiogram abnormalities were significantly more prevalent in patients with m.3243A>G or m.8344A>G mutations compared with other genetic mutations. Similarly, MELAS and MERRF had a higher prevalence compared with other syndromes. We observed a descriptive finding of an increased prevalence of ECG abnormalities in pediatric patients compared with adults. CONCLUSIONS: This analysis supports the presence of a more severe cardiac phenotype in MELAS and myoclonic epilepsy with ragged red fibres syndromes and with their commonly associated genetic mutations (m.3243A>G and m.8344A>G). This provides the first evidence basis on which to provide more intensive cardiac screening for patients with certain clinical syndromes and genetic mutations. However, the data are based on a small number of studies. We recommend further studies of natural history, therapeutic response, pediatric participants, and cardiac MRI as areas for future investigation.
ABSTRACT
Macrocyclic lactone treatments for livestock can have detrimental effects on the arthropod populations in livestock faeces. For the last twenty years, avoidance of these products has been a standard recommendation on livestock farms that are managed for wildlife by the Royal Society for Protection of Birds (RSPB). However, the continued decline in the populations of birds (in particular the red-billed chough Pyrrhocorax pyrrhocorax) that are dependent on dung invertebrates on islands in the Inner Hebrides of Scotland prompted us to investigate the effects of livestock treatments that are commonly used on these islands. We conducted a replicated field plot study over two years to quantify the effects of livestock treatments containing copper, deltamethrin and triclabendazole on invertebrate density in pooled, artificial faecal pats on the island of Islay. We found that the density of arthropod larvae was significantly reduced by the triclabendazole and deltamethrin treatments in both years and by as much as 86% when the treatments were combined. Copper-containing boluses did not consistently affect abundance of arthropod larvae. These results suggest that veterinary treatment of livestock might contribute to a reduction in the food supply of chough.
Subject(s)
Diptera/physiology , Larva/drug effects , Pyrethrins/adverse effects , Triclabendazole/adverse effects , Animals , Antiplatyhelmintic Agents/adverse effects , Cattle , Feces , Hebrides , Insecticides/adverse effects , Islands , Passeriformes/growth & development , ScotlandABSTRACT
BACKGROUND: Electronic health records (EHRs) are increasing in popularity across national and international healthcare systems. Despite their augmented availability and use, the quality of electronic health records is problematic. There are various reasons for poor documentation quality within the EHR, and efforts have been made to address these areas. Previous systematic reviews have assessed intervention effectiveness within the outpatient setting or within paper documentation. This systematic review aims to assess the effectiveness of different interventions seeking to improve EHR documentation within an inpatient setting. METHODS: We will employ a comprehensive search strategy that encompasses four distinct themes: EHR, documentation, interventions, and study design. Four databases (MEDLINE, EMBASE, CENTRAL, and CINAHL) will be searched along with an in-depth examination of the grey literature and reference lists of relevant articles. A customized hybrid study quality assessment tool has been designed, integrating components of the Downs and Black and Newcastle-Ottawa Scales, into a REDCap data capture form to facilitate data extraction and analysis. Given the predicted high heterogeneity between studies, it may not be possible to standardize data for a quantitative comparison and meta-analysis. Thus, data will be synthesized in a narrative, semi-quantitative manner. DISCUSSION: This review will summarize the current level of evidence on the effectiveness of interventions implemented to improve inpatient EHR documentation, which could ultimately enhance data quality in administrative health databases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017083494.
Subject(s)
Documentation/standards , Electronic Health Records/standards , Quality Improvement , Hospitalization , Hospitals , Humans , Program Evaluation , Research Design , Systematic Reviews as TopicABSTRACT
The Dicyemida and Orthonectida are two groups of tiny, simple, vermiform parasites that have historically been united in a group named the Mesozoa. Both Dicyemida and Orthonectida have just two cell layers and appear to lack any defined tissues. They were initially thought to be evolutionary intermediates between protozoans and metazoans but more recent analyses indicate that they are protostomian metazoans that have undergone secondary simplification from a complex ancestor. Here we describe the first almost complete mitochondrial genome sequence from an orthonectid, Intoshia linei, and describe nine and eight mitochondrial protein-coding genes from Dicyema sp. and Dicyema japonicum, respectively. The 14,247 base pair long I. linei sequence has typical metazoan gene content, but is exceptionally AT-rich, and has a unique gene order. The data we have analysed from the Dicyemida provide very limited support for the suggestion that dicyemid mitochondrial genes are found on discrete mini-circles, as opposed to the large circular mitochondrial genomes that are typical of the Metazoa. The cox1 gene from dicyemid species has a series of conserved, in-frame deletions that is unique to this lineage. Using cox1 genes from across the genus Dicyema, we report the first internal phylogeny of this group.
ABSTRACT
BACKGROUND: Childhood obesity has become a global epidemic irrespective of the socioeconomic status of a country or nation. Obesity increases the risk of various diseases in children, for example asthma, sleep apnea, bone and joint problems, type-2 diabetes, and heart problems. The existing literature informs us of the many factors associated with childhood obesity. Among these factors, maternal mental health has been found to be a strong predictor. Maternal mental health programs were implemented to address the issue of childhood obesity but with little or no improvement. It suggests systematically reviewing the literature to assess the contents of these programs and carrying out meta-analysis for the overall effect of these interventions. METHODS: The studies included in this review will be experimental designs such as randomized controlled trials (RCTs) which provide information on interventions to improve maternal mental health and its effects on childhood obesity. We plan to search MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, ERIC, CINAHL, ProQuest Dissertations and Theses Global, Scopus, and Web of Science with no restrictions as to language. Reference lists of the selected articles will also be searched for additional articles. The Cochrane EPOC Risk of Bias Tool will be used to assess the quality of studies. If the studies lend themselves to a statistical analysis, we will also carry out a meta-analysis. DISCUSSION: This review will help determine the effect of maternal health improvement programs on childhood obesity. These findings, in turn, will guide the research community on the development of related programs in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42017072737 .
Subject(s)
Maternal Health , Mental Health , Pediatric Obesity , Child , Humans , Pediatric Obesity/epidemiology , Randomized Controlled Trials as Topic , Meta-Analysis as Topic , Systematic Reviews as TopicABSTRACT
The animal groups of Orthonectida and Dicyemida are tiny, extremely simple, vermiform endoparasites of various marine animals and have been linked in the Mesozoa (Figure 1). The Orthonectida (Figures 1A and 1B) have a few hundred cells, including a nervous system of just ten cells [2], and the Dicyemida (Figure 1C) are even simpler, with â¼40 cells [3]. They are classic "Problematica" [4]-the name Mesozoa suggests an evolutionary position intermediate between Protozoa and Metazoa (animals) [5] and implies that their simplicity is a primitive state, but molecular data have shown they are members of Lophotrochozoa within Bilateria [6-9], which means that they derive from a more complex ancestor. Their precise affinities remain uncertain, however, and it is disputed whether they even constitute a clade. Ascertaining their affinities is complicated by the very fast evolution observed in their genes, potentially leading to the common systematic error of long-branch attraction (LBA) [10]. Here, we use mitochondrial and nuclear gene sequence data and show that both dicyemids and orthonectids are members of the Lophotrochozoa. Carefully addressing the effects of unequal rates of evolution, we show that the Mesozoa is polyphyletic. While the precise position of dicyemids remains unresolved within Lophotrochozoa, we identify orthonectids as members of the phylum Annelida. This result reveals one of the most extreme cases of body-plan simplification in the animal kingdom; our finding makes sense of an annelid-like cuticle in orthonectids [2] and suggests that the circular muscle cells repeated along their body [11] may be segmental in origin.
Subject(s)
Annelida/classification , Phylogeny , Amino Acid Sequence , Animals , Annelida/anatomy & histology , Annelida/genetics , Female , Sequence AlignmentABSTRACT
INTRODUCTION: Point-of-care ultrasound (POCUS) has been suggested as an initial investigation in the management of renal colic. Our objectives were: 1) to determine the accuracy of POCUS for the diagnosis of nephrolithiasis and 2) to assess its prognostic value in the management of renal colic. METHODS: The review protocol was registered to the PROSPERO database (CRD42016035331). An electronic database search of MEDLINE, Embase, and PubMed was conducted utilizing subject headings, keywords, and synonyms that address our research question. Bibliographies of included studies and narrative reviews were manually examined. Studies of adult emergency department patients with renal colic symptoms were included. Any degree of hydronephrosis was considered a positive POCUS finding. Accepted criterion standards were computed tomography evidence of renal stone or hydronephrosis, direct stone visualization, or surgical findings. Screening of abstracts, quality assessment with the QUADAS-2 instrument, and data extraction were performed by two reviewers, with discrepancies resolved by consensus with a third reviewer. Test performance was assessed by pooled sensitivity and specificity, calculated likelihood ratios, and a summary receiver operator curve (SROC). The secondary objective of prognostic value was reported as a narrative summary. RESULTS: The electronic search yielded 627 unique titles. After relevance screening, 26 papers underwent full-text review, and nine articles met all inclusion criteria. Of these, five high-quality studies (N = 1,773) were included in the meta-analysis for diagnostic accuracy and the remaining yielded data on prognostic value. The pooled results for sensitivity and specificity were 70.2% (95% confidence interval [CI] = 67.1%-73.2%) and 75.4% (95% CI = 72.5%-78.2%), respectively. The calculated positive and negative likelihood ratios were 2.85 and 0.39. The SROC generated did not show evidence of a threshold effect. Two of the studies in the meta-analysis found that the finding of moderate or greater hydronephrosis yielded a specificity of 94.4% (95% CI = 92.7%-95.8%). Four studies examining prognostic value noted a higher likelihood of a large stone when positive POCUS findings were present. The largest randomized trial showed lower cumulative radiation exposure and no increase in adverse events in those who received POCUS investigation as the initial renal colic investigation. CONCLUSION: Point-of-care ultrasound has modest diagnostic accuracy for diagnosing nephrolithiasis. The finding of moderate or severe hydronephrosis is highly specific for the presence of any stone, and the presence of any hydronephrosis is suggestive of a larger (>5 mm) stone in those presenting with renal colic.
Subject(s)
Kidney Calculi/diagnostic imaging , Point-of-Care Systems/standards , Renal Colic/diagnostic imaging , Ultrasonography/methods , Adult , Emergency Service, Hospital/statistics & numerical data , Humans , Hydronephrosis/diagnostic imaging , Hydronephrosis/etiology , Sensitivity and Specificity , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: The prevalence of menopause in women with or at risk of chronic kidney disease is increasing globally. Although international guidelines on menopause recommend the use of postmenopausal hormone therapy with or without selective estrogen receptor modulators for control of vasomotor symptoms, the effects of these treatments on kidney function and albuminuria are unclear. Furthermore, women with chronic kidney disease are at significantly increased risk of venous thromboembolism and malignancy, well-documented adverse effects of postmenopausal hormone therapy. Our study aims to establish the effect of these treatments on kidney function and albuminuria in women, as well as determine the safety of these treatments in the chronic kidney disease population. METHODS: We will conduct a systematic review and meta-analysis addressing the effect and safety of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney outcomes in women. We plan to search for published (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), tables of contents of relevant journals) and unpublished (ongoing studies, conference proceedings) studies in all languages examining the effect of postmenopausal hormone therapy, including selective estrogen receptor modulators, on kidney function and albuminuria, as well as the risk of adverse outcomes of these treatments in women with chronic kidney disease. Two independent investigators will screen identified abstracts and select studies that examine the effect of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney outcomes in the general population or adverse outcomes in the chronic kidney disease population. Data on study population, intervention, outcomes, as well as study quality and risk of bias will be independently extracted from each eligible study. Along with descriptive presentation of data, outcome measures will be presented as meta-analyses using a random effects model. Planned subgroup analyses will be completed, and meta-regression will be performed if significant heterogeneity is noted. DISCUSSION: By examining the effects of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney function and albuminuria, the results of this systematic review and meta-analysis will inform management of postmenopausal women in the general population. Furthermore, it will evaluate the safety, including the risks of known adverse outcomes of postmenopausal hormone therapy and selective estrogen receptor modulators, in the already vulnerable chronic kidney disease population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016050651.
Subject(s)
Estrogen Replacement Therapy/adverse effects , Postmenopause/drug effects , Renal Insufficiency, Chronic/complications , Albuminuria , Female , Humans , Selective Estrogen Receptor Modulators/therapeutic use , Systematic Reviews as TopicABSTRACT
Acoels are small, ubiquitous - but understudied - marine worms with a very simple body plan. Their internal phylogeny is still not fully resolved, and the position of their proposed phylum Xenacoelomorpha remains debated. Here we describe mitochondrial genome sequences from the acoels Paratomella rubra and Isodiametra pulchra, and the complete mitochondrial genome of the acoel Archaphanostoma ylvae. The P. rubra and A. ylvae sequences are typical for metazoans in size and gene content. The larger I. pulchra mitochondrial genome contains both ribosomal genes, 21 tRNAs, but only 11 protein-coding genes. We find evidence suggesting a duplicated sequence in the I. pulchra mitochondrial genome. The P. rubra, I. pulchra and A. ylvae mitochondria have a unique genome organisation in comparison to other metazoan mitochondrial genomes. We found a large degree of protein-coding gene and tRNA overlap with little non-coding sequence in the compact P. rubra genome. Conversely, the A. ylvae and I. pulchra genomes have many long non-coding sequences between genes, likely driving genome size expansion in the latter. Phylogenetic trees inferred from mitochondrial genes retrieve Xenacoelomorpha as an early branching taxon in the deuterostomes. Sequence divergence analysis between P. rubra sampled in England and Spain indicates cryptic diversity.
Subject(s)
Genome, Mitochondrial , Platyhelminths/genetics , Animals , Bayes Theorem , Gene Order , Gene Rearrangement , Genes, Mitochondrial , Genetics, Population , Genome Size , Genomics/methods , Nucleic Acid Conformation , Phylogeny , Sequence Analysis, DNA , TranscriptomeABSTRACT
Despite the near universal adaptation of gentle mechanical ventilation, surfactant use and non-invasive respiratory support, bronchopulmonary dysplasia (BPD) remains one of the most common respiratory morbidities in very low birth weight (VLBW) infants. Thus, the objective of this review was to evaluate the efficacy of intra-tracheal administration of budesonide-surfactant mixture in preventing bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants. MEDLINE, EMBASE, and PubMed were searched for randomized clinical trials in which intra-tracheal administration of budesonide-surfactant was used to prevent BPD in infants. The primary outcomes were BPD and composite outcome of death or BPD. Meta-analysis of the two clinical trials revealed that infants who received intra-tracheal instillation of budesonide-surfactant mixture demonstrated 43% reduction in the risk of BPD (RR: 0.57; 95%CI: 0.43-0.76, NNT = 5). Although mortality was not different between the groups (OR: 0.61; 95%CI: 0.34-1.04), a 40% reduction was observed in the composite outcome of death or BPD in the budesonide-surfactant group (RR: 0.60; 95%CI: 0.49-0.74, NNT = 3). Thus, this review concludes that intra-tracheal administration of budesonide-surfactant combination was associated with decreased incidence of BPD alone or composite outcome of death or BPD in VLBW infants though there is a need for larger trials before it can be recommended as a standard of care.