Predictive modelling of acute Promyelocytic leukaemia resistance to retinoic acid therapy.

Acute Promyelocytic Leukaemia (APL) arises from an aberrant chromosomal translocation involving the Retinoic Acid Receptor Alpha (RARA) gene, predominantly with the Promyelocytic Leukaemia (PML) or Promyelocytic Leukaemia Zinc Finger (PLZF) genes. The resulting oncoproteins block the haematopoietic differentiation program promoting aberrant proliferative promyelocytes. Retinoic Acid (RA) therapy is successful in most of the PML::RARA patients, while PLZF::RARA patients frequently become resistant and relapse.

Noncanonical EZH2 drives retinoic acid resistance of variant acute promyelocytic leukemias.

Cancer cell heterogeneity is a major driver of therapy resistance. To characterize resistant cells and their vulnerabilities, we studied the PLZF-RARA variant of acute promyelocytic leukemia, resistant to retinoic acid (RA), using single-cell multiomics. We uncovered transcriptional and chromatin heterogeneity in leukemia cells.

Smart bracelet to assess physical activity after cardiac surgery: A prospective study.

Objectives: Little is known about the physical activity of patients after cardiac surgery. This study was designed to assess this activity using a connected bracelet.

Methods: In this prospective, monocentric study, patients scheduled for cardiac surgery were offered to wear an electronic bracelet.

PLZF limits enhancer activity during hematopoietic progenitor aging.

PLZF (promyelocytic leukemia zinc finger) is a transcription factor acting as a global regulator of hematopoietic commitment. PLZF displays an epigenetic specificity by recruiting chromatin-modifying factors but little is known about its role in remodeling chromatin of cells committed toward a given specific hematopoietic lineage. In murine myeloid progenitors, we decipher a new role for PLZF in restraining active genes and enhancers by targeting acetylated lysine 27 of Histone H3 (H3K27ac).

Regulation of the positive transcriptional effect of PLZF through a non-canonical EZH2 activity.

The transcription factor PLZF (promyelocytic leukemia zinc finger protein) acts as an epigenetic regulator balancing self-renewal and differentiation of hematopoietic cells through binding to various chromatin-modifying factors. First described as a transcriptional repressor, PLZF is also associated with active transcription, although the molecular bases underlying the differences are unknown. Here, we reveal that in a hematopoietic cell line, PLZF is predominantly associated with transcribed genes.

Polo-like-kinase 1 is a proviral host factor for hepatitis B virus replication.

Unlabelled: Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) and current treatments for chronic hepatitis B and HCC are suboptimal. Herein, we identified cellular serine/threonine Polo-like-kinase 1 (PLK1) as a positive effector of HBV replication. The aim of this study was to demonstrate the proviral role of PLK1 in HBV biosynthesis and validate PLK1 inhibition a potential antiviral strategy.

Nucleosome eviction in mitosis assists condensin loading and chromosome condensation.

Condensins associate with DNA and shape mitotic chromosomes. Condensins are enriched nearby highly expressed genes during mitosis, but how this binding is achieved and what features associated with transcription attract condensins remain unclear. Here, we report that condensin accumulates at or in the immediate vicinity of nucleosome-depleted regions during fission yeast mitosis.

XPR1 mutations are a rare cause of primary familial brain calcification.

Mutations in XPR1, a gene encoding an inorganic phosphate exporter, have recently been identified in patients with primary familial brain calcification (PFBC). Using Sanger sequencing, we screened XPR1 in 18 unrelated patients with PFBC and no SLC20A2, PDGFB, or PDGFRB mutation. XPR1 variants were tested in an in vitro physiological complementation assay and patient blood cells were assessed ex vivo for phosphate export.

Hospital audit of delayed transfusion after orthopaedic surgery.

Background And Objectives: To understand the mechanisms related to both the onset and correction of severe anaemia after orthopaedic surgery, we analysed all the full blood counts (FBCs) for patients on one orthopaedic ward during a one-year period in an academic hospital.

Methods: FBCs were screened and the medical records of those patients for whom a postoperative haemoglobin (Hb) concentration below 8 g/dL was recorded at least once were reviewed. The onset of postoperative anaemia was determined by calculating the various time intervals delineated by surgery, the time at which the transfusion threshold was reached and the time at which the lowest Hb level (nadir) and transfusion (if any) occurred.

Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications.

Sarcoglycanopathies (SGP) are a group of autosomal recessive muscle disorders caused by primary mutations in one of the four sarcoglycan genes. The sarcoglycans (α-, β-, γ-, and δ-sarcoglycan) form a tetrameric complex at the muscle membrane that is part of the dystrophin-glycoprotein complex and plays an essential role for membrane integrity during muscle contractions. We previously showed that the most frequent missense mutation in α-sarcoglycan (p.

Acute severe mitral regurgitation during first attacks of rheumatic fever: clinical spectrum, mechanisms and prognostic factors.

Background And Aim Of The Study: The study aim was to describe the clinical spectrum and mechanism of acute severe mitral regurgitation (MR) observed during first episodes of rheumatic fever (RF), and to identify prognostic factors related to the short-term outcome.

Methods: Since 1990, 44 patients (mean age 9.2 +/- 0.

Resident versus staff anesthesiologist performance: coracoid approach to infraclavicular brachial plexus blocks using a double-stimulation technique.

Objectives: Infraclavicular brachial plexus block with double stimulation (ICB) is a safe technique for upper-limb anesthesia. However, the experience of learning this technique by anesthesiology residents has not been reported. The aim of this study was to compare staff with resident anesthesiologists in the performance of ICB.

Relationships between left ventricular morphology, diastolic function and oxygen carrying capacity and maximal oxygen uptake in children.

Little attention has been paid to children with respect to factors controlling maximal oxygen uptake (V.O (2max)). This study was therefore specifically designed to examine the potential relationships between cardiac size, diastolic function and O (2) carrying capacity with maximal aerobic capacity.

Cardiovascular responses to endurance training in children: effect of gender.

Background: The aim of the present study was to determine in healthy children the effect of a well-controlled endurance training programme on cardiac function at maximal exercise and to define whether gender affects the training-induced cardiovascular response. The contribution of factors potentially involved in those adaptations such as cardiac dimensions and diastolic and systolic function was also investigated.

Methods: Thirty-five l0-11-year-old children took part in this study: 19 children (10 girls and nine boys) were assigned to participate in a 13-week endurance training programme (3 x 1 h week-1, intensity: > 80% HR max), and 16 (seven girls and nine boys) served as a control group.

Physical training increases heart rate variability in healthy prepubertal children.

Background: The aim of the present study was to evaluate the effect of an endurance training program on heart rate variability (HRV) in prepubertal healthy children and to determine the relationships between HRV components and training-induced cardiac adaptations.

Methods: Nineteen prepubertal children (aged 10-11 years old) took part in this study: 12 children were assigned to participate in a 13-week endurance training program (3 x 1 h week-1; intensity, > 80% HRmax) and 7 children served as a control group. Before and after the 13-week study period, all the children were tested for maximal oxygen uptake (V O(2max)), HRV was measured by spectral and time domain analysis of 5 h night ECG recordings, and left ventricular (LV) cardiac morphology and function were assessed by means of Doppler-Echocardiography.

Central and peripheral cardiovascular adaptations to exercise in endurance-trained children.

Stroke volume (SV) response to exercise depends on changes in cardiac filling, intrinsic myocardial contractility and left ventricular afterload. The aim of the present study was to identify whether these variables are influenced by endurance training in pre-pubertal children during a maximal cycle test. SV, cardiac output (Doppler echocardiography), left ventricular dimensions (time-movement echocardiography) as well as arterial pressure and systemic vascular resistances were assessed in 10 child cyclists (VO2max: 58.

Effect of aerobic training and detraining on left ventricular dimensions and diastolic function in prepubertal boys and girls.

Purpose: The purpose of this study was to determine the effect of an aerobic training program on the left ventricular (LV) cardiac morphology and function of prepubertal children.

Methods: Twenty-nine 10-11 year old boys and girls (TG) participated in a 13-week running program (3 x 1 h/week, intensity: > 80% HRmax), 26, of the same age, served as a control group (CG). M-mode, 2-dimensional and pulsed-wave Doppler analyses were performed, during resting conditions, before and after the training period (T) as well as, for TG only, after 2 months of detraining (D).

Pathogens isolated during treatment failures in otitis.

Objectives: A prospective study in the Paris region to evaluate the clinical and bacteriologic epidemiology of acute otitis media in infants in whom oral antibiotic therapy resulted in clinical failure.

Methods: The study included 186 children with a mean age of 17.5 +/- 13.

Wuchereria bancrofti filariasis in French Polynesia: age-specific patterns of microfilaremia, circulating antigen, and specific IgG and IgG4 responses according to transmission level.

The age-specific patterns of microfilaremia, Og4C3 antigenemia, anti-Brugia malayi IgG and IgG4 were assessed in 3 villages of low, medium and high transmission level for Wuchereria bancrofti filariasis. The prevalence rates for each of the 4 markers were clearly age dependent and their patterns strongly associated with the transmission level. The antigenemia prevalence rate was consistently higher than the microfilaremia prevalence rate, in all age groups.

The anterior perineal approach for pull-through operations in high imperforate anus.

Recent widespread interest in a new approach to imperforate anus is ample testimony to the difficulty of the classical operations and to the unsatisfactory results. In the early seventies, Mollard began to use an anterior perineal approach to high imperforate anus as an alternative to the sacrococcygeal pull-through. It entails a semicircular retroscrotal incision allowing direct access and visualization of the urethra and puborectalis sling.