ABSTRACT
Dysfunction of virus-specific CD4+ T cells in chronic human infections is poorly understood. We performed genome-wide transcriptional analyses and functional assays of CD4+ T cells specific for human immunodeficiency virus (HIV) from HIV-infected people before and after initiation of antiretroviral therapy (ART). A follicular helper T cell (TFH cell)-like profile characterized HIV-specific CD4+ T cells in viremic infection. HIV-specific CD4+ T cells from people spontaneously controlling the virus (elite controllers) robustly expressed genes associated with the TH1, TH17 and TH22 subsets of helper T cells. Viral suppression by ART resulted in a distinct transcriptional landscape, with a reduction in the expression of genes associated with TFH cells, but persistently low expression of genes associated with TH1, TH17 and TH22 cells compared to the elite controller profile. Thus, altered differentiation is central to the impairment of HIV-specific CD4+ T cells and involves both gain of function and loss of function.
Subject(s)
Anti-HIV Agents/therapeutic use , Gene Expression/drug effects , HIV Infections/drug therapy , HIV Infections/immunology , Th1 Cells/pathology , Th17 Cells/pathology , Gene Expression Profiling , HIV Infections/virology , Humans , Receptors, CXCR5/metabolism , Th1 Cells/cytology , Th1 Cells/immunology , Th17 Cells/cytology , Th17 Cells/immunology , Viral Load/drug effects , Virus Replication/drug effectsABSTRACT
BACKGROUND: In early atherosclerosis, circulating LDLs (low-density lipoproteins) traverse individual endothelial cells by an active process termed transcytosis. The CANTOS trial (Canakinumab Antiinflammatory Thrombosis Outcome Study) treated advanced atherosclerosis using a blocking antibody for IL-1ß (interleukin-1ß); this significantly reduced cardiovascular events. However, whether IL-1ß regulates early disease, particularly LDL transcytosis, remains unknown. METHODS: We used total internal reflection fluorescence microscopy to quantify transcytosis by human coronary artery endothelial cells exposed to IL-1ß. To investigate transcytosis in vivo, we injected wild-type and knockout mice with IL-1ß and LDL to visualize acute LDL deposition in the aortic arch. RESULTS: Exposure to picomolar concentrations of IL-1ß induced transcytosis of LDL but not of albumin by human coronary artery endothelial cells. Surprisingly, expression of the 2 known receptors for LDL transcytosis, ALK-1 (activin receptor-like kinase-1) and SR-BI (scavenger receptor BI), was unchanged or decreased. Instead, IL-1ß increased the expression of the LDLR (LDL receptor); this was unexpected because LDLR is not required for LDL transcytosis. Overexpression of LDLR had no effect on basal LDL transcytosis. However, knockdown of LDLR abrogated the effect of IL-1ß on transcytosis rates while the depletion of Cav-1 (caveolin-1) did not. Since LDLR was necessary but overexpression had no effect, we reasoned that another player must be involved. Using public RNA sequencing data to curate a list of Rab (Ras-associated binding) GTPases affected by IL-1ß, we identified Rab27a. Overexpression of Rab27a alone had no effect on basal transcytosis, but its knockdown prevented induction by IL-1ß. This was phenocopied by depletion of the Rab27a effector JFC1 (synaptotagmin-like protein 1). In vivo, IL-1ß increased LDL transcytosis in the aortic arch of wild-type but not Ldlr-/- or Rab27a-deficient mice. The JFC1 inhibitor nexinhib20 also blocked IL-1ß-induced LDL accumulation in the aorta. CONCLUSIONS: IL-1ß induces LDL transcytosis by a distinct pathway requiring LDLR and Rab27a; this route differs from basal transcytosis. We speculate that induction of transcytosis by IL-1ß may contribute to the acceleration of early disease.
Subject(s)
Coronary Vessels , Endothelial Cells , Interleukin-1beta , Lipoproteins, LDL , Mice, Knockout , Receptors, LDL , Signal Transduction , Transcytosis , rab GTP-Binding Proteins , Interleukin-1beta/metabolism , Animals , Humans , Receptors, LDL/genetics , Receptors, LDL/metabolism , rab GTP-Binding Proteins/metabolism , rab GTP-Binding Proteins/genetics , Endothelial Cells/metabolism , Endothelial Cells/drug effects , Lipoproteins, LDL/metabolism , Coronary Vessels/metabolism , Coronary Vessels/drug effects , Cells, Cultured , Mice, Inbred C57BL , Caveolin 1/metabolism , Caveolin 1/genetics , Aortic Diseases/metabolism , Aortic Diseases/genetics , Aortic Diseases/pathology , Disease Models, Animal , Aorta, Thoracic/metabolism , Aorta, Thoracic/drug effects , Atherosclerosis/metabolism , Atherosclerosis/genetics , Atherosclerosis/pathology , Male , MiceABSTRACT
Local translation in neurons is partly mediated by the reactivation of stalled polysomes. Stalled polysomes may be enriched within the granule fraction, defined as the pellet of sucrose gradients used to separate polysomes from monosomes. The mechanism of how elongating ribosomes are reversibly stalled and unstalled on mRNAs is still unclear. In the present study, we characterize the ribosomes in the granule fraction using immunoblotting, cryogenic electron microscopy (cryo-EM), and ribosome profiling. We find that this fraction, isolated from 5-d-old rat brains of both sexes, is enriched in proteins implicated in stalled polysome function, such as the fragile X mental retardation protein (FMRP) and Up-frameshift mutation 1 homologue. Cryo-EM analysis of ribosomes in this fraction indicates they are stalled, mainly in the hybrid state. Ribosome profiling of this fraction reveals (1) an enrichment for footprint reads of mRNAs that interact with FMRPs and are associated with stalled polysomes, (2) an abundance of footprint reads derived from mRNAs of cytoskeletal proteins implicated in neuronal development, and (3) increased ribosome occupancy on mRNAs encoding RNA binding proteins. Compared with those usually found in ribosome profiling studies, the footprint reads were longer and were mapped to reproducible peaks in the mRNAs. These peaks were enriched in motifs previously associated with mRNAs cross-linked to FMRP in vivo, independently linking the ribosomes in the granule fraction to the ribosomes associated with FMRP in the cell. The data supports a model in which specific sequences in mRNAs act to stall ribosomes during translation elongation in neurons.SIGNIFICANCE STATEMENT Neurons send mRNAs to synapses in RNA granules, where they are not translated until an appropriate stimulus is given. Here, we characterize a granule fraction obtained from sucrose gradients and show that polysomes in this fraction are stalled on consensus sequences in a specific state of translational arrest with extended ribosome-protected fragments. This finding greatly increases our understanding of how neurons use specialized mechanisms to regulate translation and suggests that many studies on neuronal translation may need to be re-evaluated to include the large fraction of neuronal polysomes found in the pellet of sucrose gradients used to isolate polysomes.
Subject(s)
Fragile X Mental Retardation Protein , Ribosomes , Animals , Female , Male , Rats , Cytoplasmic Ribonucleoprotein Granules/metabolism , Fragile X Mental Retardation Protein/genetics , Polyribosomes , Protein Biosynthesis , Ribosomes/metabolism , RNA, Messenger/metabolismABSTRACT
Human immunodeficiency virus 1 (HIV-1) exposed seronegative (HESN) individuals may have unique characteristics that alter susceptibility to HIV-1 infection. However, identifying truly exposed HESN is challenging. We utilized stored data and biospecimens from HIV-1 serodifferent couple cohorts, in which couples' HIV-1 exposures were quantified based on unprotected sex frequency and viral load of the partner with HIV-1. We compared peripheral blood gene expression between 15 HESN and 18 seroconverters prior to infection. We found PTPRC (encoding CD45 antigen) and interferon-response pathways had significantly higher expression among individuals who went on to become seropositive and thus may be a signature for increased acquisition risk.
Subject(s)
HIV Infections , HIV-1 , Humans , Interferons/genetics , Up-Regulation , Leukocyte Common AntigensABSTRACT
Health care systems worldwide have been battling the ongoing COVID-19 pandemic. Since the beginning of the COVID-19 pandemic, Lymphocytes and CRP have been reported as markers of interest. We chose to investigate the prognostic value of the LCR ratio as a marker of severity and mortality in COVID-19 infection. Between 1 March and 30 April 2020, we conducted a multicenter, retrospective cohort study of patients with moderate and severe coronavirus disease 19 (COVID-19), all of whom were hospitalized after being admitted to the Emergency Department (ED). We conducted our study in six major hospitals of northeast France, one of the outbreak's epicenters in Europe. A total of 1035 patients with COVID-19 were included in our study. Around three-quarters of them (76.2%) presented a moderate form of the disease, while the remaining quarter (23.8%) presented a severe form requiring admission to the ICU. At ED admission, the median LCR was significantly lower in the group presenting severe disease compared to that with moderate disease (versus 6.24 (3.24-12) versus 12.63 ((6.05-31.67)), p < 0.001). However, LCR was neither associated with disease severity (OR: 0.99, CI 95% (0.99-1)), p = 0.476) nor mortality (OR: 0.99, CI 95% (0.99-1)). In the ED, LCR, although modest, with a threshold of 12.63, was a predictive marker for severe forms of COVID-19.
Subject(s)
COVID-19 , Humans , C-Reactive Protein/metabolism , SARS-CoV-2/metabolism , Pandemics , Retrospective Studies , Lymphocytes/metabolism , Emergency Service, HospitalABSTRACT
This study aimed to compare continuous glucose monitoring (CGM) in cystic fibrosis (CF) according to pancreatic exocrine status.CGM and oral glucose tolerance testing (OGTT) were realized annually over five years in people with CF (pwCF) aged≥10 years without cystic fibrosis-related diabetes (CFRD). CGM parameters in patients with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and newly diagnosed CFRD were compared according to presence of pancreatic sufficiency (PS) or insufficiency (PI).Overall, 547 OGTTs and 501 CGMs were performed in 147 CF patients, comprising 122 PI and 25 PS. In PS patients, 84% displayed NGT, 12% IGT, and 4% CFRD vs. 58%, 32%, and 10% (p=0.05) in PI. Among participants displaying normal OGTT, time in glucose range (70-140 mg/dl) was significantly increased, 97% (93, 99) vs. 92% (85, 96), p<0.001, and time above glucose range > 140 mg/dl significantly decreased, 1% (0, 2) % vs. 6% (2, 13), in patients with PS compared to those with PI. No significant differences were highlighted in patients with IGT.CGM revealed significant different glucose tolerance abnormalities in PI versus PS, which were undetected by standard 2-hour OGTT glucose.
Subject(s)
Cystic Fibrosis , Diabetes Mellitus , Exocrine Pancreatic Insufficiency , Glucose Intolerance , Blood Glucose , Blood Glucose Self-Monitoring , Cystic Fibrosis/complications , Diabetes Mellitus/diagnosis , Exocrine Pancreatic Insufficiency/complications , Glucose , Glucose Intolerance/diagnosis , HumansABSTRACT
Soybean (Glycine max (L.) Merr.) is among the most valuable crops based on its nutritious seed protein and oil. Protein quality, evaluated as the ratio of glycinin (11S) to ß-conglycinin (7S), can play a role in food and feed quality. To help uncover the underlying differences between high and low protein soybean varieties, we performed differential expression analysis on high and low total protein soybean varieties and high and low 11S soybean varieties grown in four locations across Eastern and Western Canada over three years (2018-2020). Simultaneously, ten individual differential expression datasets for high vs. low total protein soybeans and ten individual differential expression datasets for high vs. low 11S soybeans were assessed, for a total of 20 datasets. The top 15 most upregulated and the 15 most downregulated genes were extracted from each differential expression dataset and cross-examination was conducted to create shortlists of the most consistently differentially expressed genes. Shortlisted genes were assessed for gene ontology to gain a global appreciation of the commonly differentially expressed genes. Genes with roles in the lipid metabolic pathway and carbohydrate metabolic pathway were differentially expressed in high total protein and high 11S soybeans in comparison to their low total protein and low 11S counterparts. Expression differences were consistent between East and West locations with the exception of one, Glyma.03G054100. These data are important for uncovering the genes and biological pathways responsible for the difference in seed protein between high and low total protein or 11S cultivars.
Subject(s)
Glycine max , Soybean Proteins , Glycine max/genetics , Glycine max/metabolism , Soybean Proteins/genetics , Soybean Proteins/metabolism , Canada , Seeds/genetics , Seeds/chemistryABSTRACT
OBJECTIVE: Recent studies carried out on amyotrophic lateral sclerosis patients suggest that the disease might initiate in the motor cortex and spread to its targets along the corticofugal tracts. In this study, we aimed to test the corticofugal hypothesis of amyotrophic lateral sclerosis experimentally. METHODS: Sod1G86R and Fezf2 knockout mouse lines were crossed to generate a model that expresses a mutant of the murine Sod1 gene ubiquitously, a condition sufficient to induce progressive motor symptoms and premature death, but genetically lacks corticospinal neurons and other subcerebral projection neurons, one of the main populations of corticofugal neurons. Disease onset and survival were recorded, and weight and motor behavior were followed longitudinally. Hyper-reflexia and spasticity were monitored using electromyographic recordings. Neurodegeneration and gliosis were assessed by histological techniques. RESULTS: Absence of subcerebral projection neurons delayed disease onset, reduced weight loss and motor impairment, and increased survival without modifying disease duration. Absence of corticospinal neurons also limited presymptomatic hyper-reflexia, a typical component of the upper motoneuron syndrome. INTERPRETATION: Major corticofugal tracts are crucial to the onset and progression of amyotrophic lateral sclerosis. In the context of the disease, subcerebral projection neurons might carry detrimental signals to their downstream targets. In its entirety, this study provides the first experimental arguments in favor of the corticofugal hypothesis of amyotrophic lateral sclerosis. ANN NEUROL 2020;88:688-702.
Subject(s)
Amyotrophic Lateral Sclerosis/pathology , Brain/pathology , Interneurons/pathology , Spinal Cord/pathology , Animals , Disease Models, Animal , Mice , Mice, Transgenic , Motor Neurons/pathologyABSTRACT
BACKGROUND: In survival analysis, data can be modeled using either a multiplicative hazards regression model (such as the Cox model) or an additive hazards regression model (such as Lin's or Aalen's model). While several diagnostic tools are available to check the assumptions underpinning each type of model, there is no defined procedure to fit these models optimally. Moreover, the two types of models are rarely combined in survival analysis. Here, we propose a strategy for optimal fitting of multiplicative and additive hazards regression models in survival analysis. METHODS: This section details our proposed strategy for optimal fitting of multiplicative and additive hazards regression models, with a focus on the assumptions underpinning each type of model, the diagnostic tools used to check these assumptions, and the steps followed to fit the data. The proposed strategy draws on classical diagnostic tools (Schoenfeld and martingale residuals) and less common tools (pseudo-observations, martingale residual processes, and Arjas plots). RESULTS: The proposed strategy is applied to a dataset of patients with myocardial infarction (TRACE data frame). The effects of 5 covariates (age, sex, diabetes, ventricular fibrillation, and clinical heart failure) on the hazard of death are analyzed using multiplicative and additive hazards regression models. The proposed strategy is shown to fit the data optimally. CONCLUSIONS: Survival analysis is improved by using multiplicative and additive hazards regression models together, but specific steps must be followed to fit the data optimally. By providing different measures of the same effect, our proposed strategy allows for better interpretation of the data.
Subject(s)
Breast Neoplasms , Female , Humans , Proportional Hazards Models , Survival AnalysisABSTRACT
Objective. Preoperative imaging in primary hyperparathyroidism (PHPT) is essential for planning of parathyroidectomy-particularly for selection of a minimally invasive approach. The objective of this cohort study was to evaluate the diagnostic precision of 3D virtual neck exploration (3D-VNE), to evaluate its impact on choice of surgical approach, and to document the correlation with long-term outcomes. Methods. 235 consecutive patients with PHPT were studied (January 2014 to December 2018), with 6-month follow-up. 220 patients had a preoperative computed tomography (CT), 172 of these had a 3D-VNE based on the CT, and 226 patients had a Tc-99m sestamibi scan. Results. Sensitivity of exact, per gland, adenoma localization was 57.09% (95% CI: 50.85-63.10%) for nonspecialized radiologist interpretation of CT scan, 58.17% (95% CI: 51.99-64.10%) for Tc-99m sestamibi scan, and 90.21% (95% CI: 85.21-93.64%) for 3D-VNE, and thereby favoring 3D-VNE compared to CT scan alone (OR 34.5, 95% CI: 9.19-290.56%, P < 2.2 × 10-16) and to Tc-99m sestamibi scan (OR 16.25, 95% CI: 6.05-61.42%, P = 3.1 × 10-15). Specificity was 87.38% for CT scan, 86.36% for 3D-VNE, and 90% for Tc-99m sestamibi scan (P > .05). The cure rate was 100%. The long-term recurrence rate (RR) was 2.978%. The RR was 1.324% in the video-assisted parathyroidectomy group of 151 patients and 5.952% in the group of 84 patients with cervicotomy (P = .0459). Conclusion. CT-based 3D-VNE proved to be the most accurate localizing study in PHPT and aided in selecting patients for targeted minimally invasive parathyroidectomy, which was associated with the lower recurrence rate. 3D-VNE could be proposed as a first-line imaging study in patients with PHPT.
Subject(s)
Hyperparathyroidism, Primary , Parathyroid Neoplasms , Cohort Studies , Humans , Hyperparathyroidism, Primary/diagnostic imaging , Hyperparathyroidism, Primary/surgery , Neoplasm Recurrence, Local , Parathyroid Glands/diagnostic imaging , Parathyroid Glands/surgery , Parathyroid Neoplasms/diagnostic imaging , Parathyroid Neoplasms/surgery , Parathyroidectomy , Radiopharmaceuticals , Technetium Tc 99m SestamibiABSTRACT
INTRODUCTION: Long-term follow-up and management of orthodontic bonded retainers require a strong collaboration between orthodontists and general dental practitioners (GDPs). This study aimed to evaluate if Eastern French GDPs were aware of bonded retainers' complications and side effects and if they were willing to take part in their long-term follow-up. METHODS: Two-hundred and eighteen randomly selected GDPs were invited to answer an online questionnaire. The initial sections covered their experience and management with bonded retainers. In the final sections, GDPs were asked their opinion on the responsibility for long-term follow-up of patients wearing fixed retainers and on the mutual communication between orthodontists and GDPs. Statistical analysis involved descriptive statistics and Fisher exact tests. RESULTS: Response rate was 32.6% (n = 71). The vast majority of GDPs were familiar with loose retainers, but only 45.2% were willing to repair them. Respondents offering orthodontic services on a regular basis were more likely to insert retainers and repair loose or broken retainers (P < 0.001). Approximately 18.6% of GDPs were aware of third-order side effects encountered with unintentionally active retainers bonded to all 6 anterior teeth. For 88.8% of GDPs, permanent retention was justified, whereas 90% of the dentists refused to be responsible for long-term supervision of fixed retainers. In addition, 67.1% were interested in further training on orthodontic retention, and 92.9% would appreciate clinical guidelines. CONCLUSIONS: Knowledge about the harmful side effects of bonded retainers was evaluated as insufficient among surveyed GDPs. Long-term follow-up of patients wearing bonded retainers raises issues that should be addressed globally by enhancing mutual communication, practitioners' education, and patients' involvement.
Subject(s)
Dental Bonding , Orthodontic Retainers , Dentists , Humans , Orthodontic Appliance Design , Orthodontic Appliances, Fixed , Orthodontists , Professional RoleABSTRACT
The aim of this study was to produce a prognostic model to help predict posttransplant survival in patients transplanted with grade-3 acute-on-chronic liver failure (ACLF-3). Patients with ACLF-3 who underwent liver transplantation (LT) between 2007 and 2017 in 5 transplant centers were included (n = 152). Predictors of 1-year mortality were retrospectively screened and tested on a single center training cohort and subsequently tested on an independent multicenter cohort composed of the 4 other centers. Four independent pretransplant risk factors were associated with 1-year mortality after transplantation in the training cohort: age ≥53 years (P = .044), pre-LT arterial lactate level ≥4 mml/L (P = .013), mechanical ventilation with PaO2 /FiO2 ≤ 200 mm Hg (P = .026), and pre-LT leukocyte count ≤10 G/L (P = .004). A simplified version of the model was derived by assigning 1 point to each risk factor: the transplantation for Aclf-3 model (TAM) score. A cut-off at 2 points distinguished a high-risk group (score >2) from a low-risk group (score ≤2) with 1-year survival of 8.3% vs 83.9% respectively (P < .001). This model was subsequently validated in the independent multicenter cohort. The TAM score can help stratify posttransplant survival and identify an optimal transplantation window for patients with ACLF-3.
Subject(s)
Acute-On-Chronic Liver Failure , Liver Transplantation , Critical Illness , Humans , Liver Cirrhosis/surgery , Middle Aged , Prognosis , Retrospective StudiesABSTRACT
French general practitioners (GPs) are known to widely prescribe medications to treat insomnia despite their negative effects. GPs' easy access to self-medication may affect their mental representation of sleep and hypnotics, and subsequently their professional behaviour. Our aim was to examine the association between GPs' personal hypnotic drug consumption habits and their management of patients with sleep disturbances. A randomized sample of Alsatian GPs participated in a survey based on questionnaires including the Pittsburgh Sleep Quality Index, the Dysfunctional Beliefs About Sleep in 10 questions to characterize sleep, and an evaluation of their management strategies regarding sleep for both patients and themselves. Two-hundred and forty-nine GPs were included (response rate of 51%). Demographics of the GPs' samples were representative of those of the Alsatian GP population. Fifteen percent of the survey respondents met insomnia criteria. For the management of their own sleep disturbances, 14.3% of GPs were taking hypnotic drugs and 8.7% were taking anxiolytics, with greater drug consumption in the insomnia group. In a multivariate analysis, GPs who personally consumed these medications prescribed significantly more of them to patients, whereas their insomnia status had less impact. Other factors such as gender and type of practice were not associated with a higher prescription rate. Our results indicate that GPs' personal drug consumption can have a significant impact on the management of their patients, therefore suggesting that actions towards GPs' health improvement may also benefit their patients and the public.
Subject(s)
General Practitioners/ethics , Hypnotics and Sedatives/therapeutic use , Self Medication/methods , Sleep Initiation and Maintenance Disorders/drug therapy , Substance-Related Disorders/epidemiology , Adult , Aged , Cross-Sectional Studies , Female , Humans , Hypnotics and Sedatives/pharmacology , Male , Middle AgedABSTRACT
BACKGROUND: Quality of recovery is an important component of perioperative health status. The 15-item Quality of Recovery (QoR-15) scale is a validated multidimensional questionnaire that measures postoperative quality of recovery. The aim of this study was to translate and assess the psychometric properties of a French version of the QoR-15 scale (QoR-15F) to measure postoperative recovery in French-speaking patients. METHODS: After translation into French of the original English version of the QoR-15 scale, psychometric validation of the QoR-15F scale to measure postoperative quality of recovery was performed. This psychometric validation included validity, reliability, responsiveness, and feasibility. The QoR-15F scale was administered before operation and on Postoperative day 1 in French-speaking patients. Patient-perceived global recovery assessment was measured at Postoperative day 1 using a VAS. RESULTS: We enrolled 150 patients, and 144 completed the study protocol. The completion rate of administered questionnaires was 100%. Pearson (r) correlation between postoperative QoR-15F and the global recovery assessment by the patient was 0.60 (P<0.0001). As expected, there was a significant negative correlation between QoR-15F score and duration of surgery (r=-0.29; P<0.01), duration of PACU stay (r=-0.21; P=0.01), and duration of hospital stay (r=-0.34; P<0.01). Cronbach's alpha was 0.81, split-half alpha was 0.83, and the global test-retest intra-class coefficient was 0.98 (0.95-0.99). CONCLUSIONS: The QoR-15F is a valid and reliable tool to measure postoperative quality of recovery in French-speaking patients. The psychometric properties to measure postoperative quality of recovery were similar to the seminal English version. CLINICAL TRIAL REGISTRATION: NCT03578068.
Subject(s)
Anesthesia Recovery Period , Health Status , Quality of Life , Surveys and Questionnaires/standards , Translations , France , Humans , Length of Stay/statistics & numerical data , Psychometrics , Reproducibility of ResultsABSTRACT
Biostatistics are omnipresent in the scientific and medical literature and are an essential skill for any health student. We have developed a practical training tool - GMRC Shiny stats - an interactive application specifically dedicated to medical data statistical analysis. The application has been designed to provide an analysis workflow corresponding to the usual progression of an experienced statistician during data analysis. The most common statistical analyses can be performed (descriptive statistics, inferences according to frequentist methods, survival analyses, correlation, agreement measurements, etc.). GMRC Shiny stats is intuitive and user-friendly and assists students in choosing the most appropriate statistical tests. With all these functionalities, students can learn statistical analysis by doing. Getting involved in the statistical analysis and processing of their own data is likely to improve their biostatistics skills.
Subject(s)
Biostatistics/methods , Statistics as Topic/education , Curriculum , Humans , Predictive Value of Tests , Reproducibility of Results , Research Personnel , Schools, Medical , Students, Medical , WorkflowABSTRACT
OBJECTIVES: To investigate the radiation dose exposure, image quality, and diagnostic performance of enhanced 100-kVp abdominopelvic single-energy CT protocol with tin filter (TF). METHODS: Ninety-three consecutive patients referred for a single-phase enhanced abdominopelvic CT were prospectively included after informed consent. They underwent in addition to a standard protocol (SP) an acquisition with TF. Both examinations were performed on a third-generation dual-source CT system (DSCT), in single energy, using automatic tube current modulation, identical pitch, and identical level of iterative reconstruction. Radiation metrics were compared. Size-specific dose estimates (SSDE), contrast to noise ratio (CNR), and figure of merit (FOM) were calculated. Diagnostic confidence for the assessment of a predetermined list of abdominal lesions was rated by two independent readers. RESULTS: The mean dose of the TF protocol was significantly lower (CDTI 1.56 ± 0.43 mGy vs. 8.13 ± 3.32, p < 0.001; SSDE 9.94 ± 3.08 vs. 1.93 ± 0.39, p < 0.001), with an effective dose close to 1 mSv (1.14 mSv ± 0.34; p < 0.001). TF group exhibited non-significant lower liver CNR (2.76 vs. 3.03, p = 0.56) and was more dose efficient (FOM 10.6 vs. 2.49/mSv, p < 0.001) in comparison to SP. The mean diagnostic confidence for visceral, bone, and peritoneal tumors was equivalent between both groups. CONCLUSIONS: Enhanced 100-kVp abdominopelvic CT acquired after spectral shaping with tin filtration can achieve similar diagnostic performance and CNR compared to a standard CT protocol, while reducing the radiation dose by 81%. KEY POINTS: ⢠100-kVp spectral filtration enables enhanced abdominal CT with high-dose efficiency. ⢠The radiation dose reaches the 1-mSv range. ⢠Predetermined abdominopelvic lesions can be assessed without impairing on diagnostic confidence.
Subject(s)
Abdomen/diagnostic imaging , Contrast Media/administration & dosage , Multidetector Computed Tomography/methods , Aged , Female , Humans , Liver/diagnostic imaging , Male , Prospective Studies , Radiation Dosage , Radiation Exposure , Reproducibility of ResultsABSTRACT
Identifying an infection may be difficult in the ED. Neutrophilic leukocytosis is often used in the diagnosis of infection despite its lack of specificity in situations of stress. Our objective was to study the value of each parameter of the WBC count, in particular eosinopenia, to diagnose bacterial infections in the ED. We conducted a retrospective and observational study over a period of 6 months. All patients with one of the following diagnoses were eligible: pneumonia (9.9%), pyelonephritis (26.2%), prostatitis (8.4%), appendicitis (26.2%), cholecystitis (8.4%), and diverticular sigmoiditis (5%). A total of 466 infected patients were included for statistical analysis, and a control group of 466 uninfected patients was randomly selected in the same period of time. All leukocyte count parameters were significantly modified (p < 0.001) in the infected group compared with the control group. Neutrophils and total leukocytes remain the two most suitable parameters for the diagnosis of infections in the ED. Eosinopenia represented the most efficient parameter of the WBC count for the diagnosis of urinary and biliary tract infections. Deep eosinopenia presented a specificity of 94% for the diagnosis of infection. Any modification of the WBC count associated with an elevation of CRP (> 40 mg/L) or fever (> 38.5 °C) showed a high specificity for the diagnosis of infection. A careful analysis of the WBC count remains a valuable tool for the diagnosis of infection in the ED.
Subject(s)
Bacterial Infections/diagnosis , Emergency Service, Hospital , Eosinophils/pathology , Leukocyte Count , Adult , Aged , Aged, 80 and over , Bacterial Infections/immunology , Biliary Tract Diseases/immunology , Biliary Tract Diseases/microbiology , C-Reactive Protein/analysis , Female , Humans , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Sepsis/diagnosis , Sepsis/immunology , Sepsis/microbiology , Severity of Illness Index , Urinary Tract Infections/diagnosisABSTRACT
BACKGROUND: Interval aerobic training programme with active recovery bouts (IATP-R) has shown to improve tolerance to IATP among seniors. However, data concerning its benefits for seniors' health are still limited. PURPOSE: The purpose of this study was to examine the effects of IATP-R on seniors' health status. METHODS: Sedentary volunteers (n = 60, aged ≥70 years) were randomly assigned to either IATP-R or maintained sedentary lifestyle for 9.5 weeks. IATP-R consisted of 30-minute cycling (6 × 4 minutes at first ventilatory threshold (VT1 ) intensity + 1 minute at 40% of VT1 ) twice a week. Cognitive and functional performances were assessed with the Trail Making Test (TMT-A; TMT-B); Paced Auditory Serial Addition Test (PASAT); Timed Up and Go (TUG) test; 6-Minute Walk Test (6-MWT); one-leg balance test; and the Short Physical Performance Battery (SPPB) tests, respectively. QoL and anxiety/depression status were measured by the Short Form-12 and the Goldberg's Scale, respectively. All participants were assessed at baseline and 9.5 weeks later. RESULTS: Compared to controls, IATP-R improved cognitive functions (TMT-A: +1.5% vs -21.5%; TMT-B: +0.9% vs -13.3%; PASAT: +1.4% vs -14.6%; semantic fluency: -1.1% vs +11.7%), functional performance (TUG: +5.4% vs -16.5%; 6-MWT: -3.2% vs +11.5%; SPPB: -3.2% vs +14.6%; One-leg balance: -16.3% vs +25.0%); QoL (physical health: -13.3% vs +23.1%; mental health: -7.1% vs +8.2%); and depressive symptoms (+26.3% vs -42.8%). Significant impacts were measured neither on letter modality of fluency tasks nor on anxiety score. CONCLUSION: These data showed that IATP-R is an effective training programme to improve functional and cognitive performances, mental health and well-being in sedentary seniors. Trial registration ClinicalTrials.gov NCT02263573. Registered October 1, 2014.
Subject(s)
Cognition , Health Status , Mental Health , Physical Conditioning, Human/physiology , Physical Conditioning, Human/psychology , Physical Functional Performance , Aged , Female , Humans , Male , Physical Conditioning, Human/methods , Prospective Studies , Quality of Life , Sedentary Behavior , Time FactorsABSTRACT
OBJECTIVES: The aim of this retrospective study was to assess in maxillary canine impaction cases both the prevalence of root resorption of adjacent teeth among untreated children and adolescents, and its associated risk factors. SUBJECTS AND METHODS: Sixty subjects (mean age 12.2 years; SD 1.9; range 8-17 years) with 83 displaced maxillary canines and without any past or ongoing orthodontic treatment were included in this study. The presence of root resorption was evaluated on images from a single cone beam computed tomography (CBCT) unit. Potential risk factors were measured on the CBCT images and on panoramic reconstructions of the 3D data sets. The sample was characterized by descriptive statistics and multiple logistic regressions were performed to predict root resorption. RESULTS: Root resorption of at least one adjacent tooth was detected in 67.5 per cent of the affected quadrants. It was found that 55.7 per cent of the lateral incisors, 8.4 per cent of the central incisors, and 19.5 per cent of first premolars were resorbed. Of the detected resorptions, 71.7 per cent were considered slight, 14.9 per cent moderate, and 13.4 per cent severe. Contact between the displaced canine(s) and the adjacent teeth roots was the only identified statistically significant risk factor, all teeth being considered (odds ratio [OR] = 18.7, 95% confidence interval: 2.26-756, P < 0.01). An enlarged canine dental follicle, a peg upper lateral, or an upper lateral agenesis were not significantly associated with root resorption of adjacent teeth, nor were age nor gender. CONCLUSIONS: Root resorption of adjacent teeth was detected in more than two-thirds of a sample of sixty untreated children and adolescents.
Subject(s)
Root Resorption/etiology , Tooth, Impacted/diagnostic imaging , Adolescent , Child , Cone-Beam Computed Tomography , Cuspid/diagnostic imaging , Humans , Maxilla/diagnostic imaging , Prevalence , Retrospective Studies , Risk FactorsABSTRACT
Tritrophic interactions involving a biocontrol agent, a pathogen and a plant have been analyzed predominantly from the perspective of the biocontrol agent. We have conducted the first comprehensive transcriptomic analysis of all three organisms in an effort to understand the elusive properties of Pseudozyma flocculosa in the context of its biocontrol activity against Blumeria graminis f.sp. hordei as it parasitizes Hordeum vulgare. After inoculation of P. flocculosa, the tripartite interaction was monitored over time and samples collected for scanning electron microscopy and RNA sequencing. Based on our observations, P. flocculosa indirectly parasitizes barley, albeit transiently, by diverting nutrients extracted by B. graminis from barley leaves through a process involving unique effectors. This brings novel evidence that such molecules can also influence fungal-fungal interactions. Their release is synchronized with a higher expression of powdery mildew haustorial effectors, a sharp decline in the photosynthetic machinery of barley and a developmental peak in P. flocculosa. The interaction culminates with a collapse of B. graminis haustoria, thereby stopping P. flocculosa growth, as barley plants show higher metabolic activity. To conclude, our study has uncovered a complex and intricate phenomenon, described here as hyperbiotrophy, only achievable through the conjugated action of the three protagonists.