Mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2) have been found to be a cause of Rett syndrome (RTT). In order to provide further insights into the distribution and the spectrum ...of mutations, we investigated, in addition to the whole coding sequence, a phylogenetically conserved sequence within the 3' untranslated region (3' UTR) of the MECP2 gene for 55 sporadic RTT, including 47 typical and 8 nonclassical cases. We have developed an approach based on conformation-sensitive gel electrophoresis, sequence analysis and, for the first time, Southern blot analysis. Mutation detection, including unreported gross DNA rearrangements, was achieved in 79% of classical RTT and 25% of nonclassical RTT patients. The high prevalence of recurrent mutations allows us to propose a molecular diagnosis strategy for RTT.
Aeromonas hydrophila is a gram-negative bacillus commonly found in water. It is responsible for a number of diseases in cold-blooded animals (e.g., fish, amphibians) and may be pathogenic in humans, ...causing wound infections, gastroenteritis, gas gangrene, and septicemia. Septicemia is often found in immunosuppressed patients or in patients who have suffered severe bodily injuries. We present three cases of A. hydrophila infection that occurred during the summer of 1991.
The occurrence of fever during periods of neutropenia in children with cancer presents a difficult problem for the clinician. Neutropenic patients are at high risk of potentially life-threatening ...infections. Although the principle of prompt empirical antibiotic therapy is well-established, changes in the patterns of nosocomial infections in this group of patients have necessitated continuing reappraisal of the antibiotic regimens used. This article reviews developments in this area and discusses the role of the carbapenems in the treatment of fever and infections in neutropenic children.
OBJECTIVE:Echocardiographic definitions of subclinical left atrial dysfunction based on epidemiological data remain scarce. In this population study, we derived outcome-driven thresholds for ...echocardiographic left atrial function parameters discriminating between normal and abnormal values.
METHODS:In 1306 individuals (mean age, 50.7 years; 51.6% women), we echocardiographically assessed left atrial function and LV global longitudinal strain. We derived cut-off values for left atrial emptying fraction (LAEF), left atrial function index (LAFI) and left atrial reservoir strain (LARS) to define left atrial dysfunction using receiver-operating curve threshold analysis. Main outcome was the incidence of cardiac events and atrial fibrillation (AFib) on average 8.5 years later.
RESULTS:For prediction of new-onset AFib, left atrial cut-offs yielding the best balance between sensitivity and specificity (highest Youden index) wereLAEF less than 55%, LAFI less than 40.5 and LARS less than 23%. Applying these cut-offs, abnormal LAEF, LAFI and LARS were, respectively, present in 27, 37.1 and 18.1% of the cohort. Abnormal LARS (<23%) was independently associated with higher risk for cardiac events and new-onset AFib (P ≤ 0.012). Participants with both abnormal LAEF and LARS presented a significantly higher risk to develop cardiac events (hazard ratio2.10; P = 0.014) and AFib (hazard ratio6.45; P = 0.0036) than normal counterparts. The concomitant presence of an impaired LARS and LV global longitudinal strain improved prognostic accuracy beyond a clinical risk model for cardiac events and the CHARGE-AF Risk Score for AFib.
CONCLUSION:Left atrial dysfunction based on outcome-driven thresholds predicted cardiac events and AFib independent of conventional risk factors. Screening for subclinical left atrial and LV systolic dysfunction may enhance cardiac disease prediction in the community.
Acute physical activity leads to several changes in metabolic, cardiovascular, and immune pathways. Although studies have examined selected changes in these pathways, the system-wide molecular ...response to an acute bout of exercise has not been fully characterized. We performed longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including metabolome, lipidome, immunome, proteome, and transcriptome from 36 well-characterized volunteers, before and after a controlled bout of symptom-limited exercise. Time-series analysis revealed thousands of molecular changes and an orchestrated choreography of biological processes involving energy metabolism, oxidative stress, inflammation, tissue repair, and growth factor response, as well as regulatory pathways. Most of these processes were dampened and some were reversed in insulin-resistant participants. Finally, we discovered biological pathways involved in cardiopulmonary exercise response and developed prediction models revealing potential resting blood-based biomarkers of peak oxygen consumption.
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•Time-series analysis reveals an orchestrated molecular choreography of exercise•Multi-level omic associations identify key biological processes of peak VO2•Prediction models highlight resting blood biomarkers of fitness•Exercise omics provides insights into the pathophysiology of insulin resistance
Longitudinal multi-omic analyses characterize the molecular changes associated with acute physical activity.
Four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) allows comprehensive assessment of pulmonary artery (PA) flow dynamics. Few studies have characterized longitudinal ...changes in pulmonary flow dynamics and right ventricular (RV) recovery following a pulmonary endarterectomy (PEA) for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This can provide novel insights of RV and PA dynamics during recovery. We investigated the longitudinal trajectory of 4D flow metrics following a PEA including velocity, vorticity, helicity, and PA vessel wall stiffness.
Twenty patients with CTEPH underwent pre-PEA and > 6 months post-PEA CMR imaging including 4D flow CMR; right heart catheter measurements were performed in 18 of these patients. We developed a semi-automated pipeline to extract integrated 4D flow-derived main, left, and right PA (MPA, LPA, RPA) volumes, velocity flow profiles, and secondary flow profiles. We focused on secondary flow metrics of vorticity, volume fraction of positive helicity (clockwise rotation), and the helical flow index (HFI) that measures helicity intensity.
Mean PA pressures (mPAP), total pulmonary resistance (TPR), and normalized RV end-systolic volume (RVESV) decreased significantly post-PEA (P < 0.002). 4D flow-derived PA volumes decreased (P < 0.001) and stiffness, velocity, and vorticity increased (P < 0.01) post-PEA. Longitudinal improvements from pre- to post-PEA in mPAP were associated with longitudinal decreases in MPA area (r = 0.68, P = 0.002). Longitudinal improvements in TPR were associated with longitudinal increases in the maximum RPA HFI (r=-0.85, P < 0.001). Longitudinal improvements in RVESV were associated with longitudinal decreases in MPA fraction of positive helicity (r = 0.75, P = 0.003) and minimum MPA HFI (r=-0.72, P = 0.005).
We developed a semi-automated pipeline for analyzing 4D flow metrics of vessel stiffness and flow profiles. PEA was associated with changes in 4D flow metrics of PA flow profiles and vessel stiffness. Longitudinal analysis revealed that PA helicity was associated with pulmonary remodeling and RV reverse remodeling following a PEA.
An iterative, CFD-based approach for aeroelastic computations in the frequency domain is presented. The method relies on a linearized formulation of the aeroelastic problem and a fixed-point ...iteration approach and enables the computation of the eigenproperties of each of the wet aeroelastic eigenmodes. Numerical experiments on the aeroelastic analysis and design optimization of two wing configurations illustrate the capability of the method for the fast and accurate aeroelastic analysis of aircraft configurations and its advantage over classical time-domain approaches.
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