Search

Purpose: To identify the risk factors of early occurrence of malnutrition in infants with severe congenital heart disease (CHD) during their first year of life. Methods and Results: Retrospective longitudinal multicentre study carried out from January 2014 to December 2020 in two tertiary care CHD centres. Four CHD hemodynamic groups were identified. Malnutrition was defined by a Waterlow score under 80% and/or the need for calorie-enriched formula. A total of 216 infants with a severe CHD, e.g., requiring cardiac surgery, cardiac catheterization, or hospitalization for heart failure during their first year of life were included in the study. Malnutrition was observed among 43% of the cohort, with the highest prevalence in infants with increased pulmonary blood flow (71%) compared to the others hemodynamic groups (pConclusion: In infants with a severe CHD, early occurrence of malnutrition during the first year of life affected a high proportion of subjects. CHD with increased pulmonary blood flow, low birthweight, heart failure, and repeated hospitalizations were risk factors for malnutrition. Further studies are required to identify optimal nutritional support in this population.

Triple-negative breast cancer (TNBC) is associated with high mortality due to the high expression of pro-inflammatory cytokines and lack of targeted therapies. N-acylethanolamine acid amidase (NAAA) is an N-terminal cysteine hydrolase that promotes inflammatory responses through the deactivation of Palmitoylethanolamide (PEA), an endogenous bioactive lipid mediator. Here, we examined NAAA expression in TNBC cells (MDA-MB-231 and MDA-MB-BrM2 cells) and the effects of NAAA inhibition on TNBC tumor growth, using a selective NAAA inhibitor AM11095 (IC50 = 20 nM). TNBC cells expressed elevated levels of full-length and splice mRNAs naaa variants. TNBC cells also express the N-acyl ethanol amides and elevated levels of the two fatty acid cores arachidonic (AA) and docosahexaenoic (DHA). PEA or AM11095 inhibited the secretion of IL-6 and IL-8, reduced the activation of the NF-kB pathway, decreased the expression of VEGF and Placental growth factor (PLGF) in TNBCs, and inhibited tumor cell migration in vitro. Using cellular magnetic resonance imaging (MRI), body images of mice administered with human MDA-MB-BrM2 cells treated with AM11095 showed a significant decrease in tumor numbers with a lower volume of tumors and increased mice survival. Mice untreated or treated with vehicle control showed a high number of tumors with high volumes in multiple organs. Thus, NAAA inhibition may constitute a potential therapeutic approach in the management of TNBC-associated inflammation and tumor growth.

Facilitators of professional development (PD) for mathematics teachers currently gain increasing attention, as their practices are crucial for the success of spreading mathematics educational ideas and innovations into schools and strengthening the professional expertise of teachers. So far, mainly two components of facilitation have been empirically researched: facilitators’ knowledge resources and facilitation moves. In this paper, we propose to develop a more comprehensive conceptual framework in order to explain facilitators’ practices and underlying decisions. For this purpose, we lift Schoenfeld’s ROG framework for teachers' decision-making (comprising resources, orientations, and goals) to the facilitator level, and add identity as a fourth component to obtain what we call the ROGI framework. We draw on data collected simultaneously in two PD projects for mathematics teachers in Germany and in Israel. Through three cases of facilitation, we illustrate how the adapted ROGI framework helps to understand processes of decision-making made by facilitators during mathematics professional development sessions.

Purpose To evaluate the impact of COVID-19 pandemic on functional urology procedures in France. Methods A prospective study was conducted within 11 secondary and tertiary referral centers in France. Patients aged > 18 years who were diagnosed with a functional urology disease before the national lockdown (March 17th, 2020) and who required a surgery were included. Study period went from March 17th to September 30th 2020. The included interventions were listed according to the guidelines for functional urology enacted by the French Association of Urology and delay of reoperation was compared to the guidelines’ delay. The primary outcome was the number of procedures left unscheduled at the end of the study period. Descriptive statistics were performed. Results From March 17th 2020 to September 3 rd 2020, 1246 patients with a previous diagnosis of a functional urological disease requiring a surgery were included. The mean follow-up was 140.4 days (± 53.4). Overall, 316 interventions (25.4%) were maintained whereas 74 (5.9%) were canceled, 848 (68.1%) postponed and 8 patients (0.6%) died. At the end of the follow-up, 184 patients (21.7%) were still not rescheduled. If the intervention was postponed, the mean delay between the initial and final date was 85.7 days (± 64.4). Conclusion Overall, more than two thirds of interventions had to be postponed and the mean delay between the initial and final date was about three months.

To evaluate the outcomes of ureteral reimplantation (UR) after failure of endoscopic treatment for symptomatic vesicoureteral reflux (VUR) in renal transplant recipients. We conducted a monocentric retrospective study that included all renal transplant recipients with failure of Deflux™ as first-line treatment of VUR from January 2007 to December 2020. Failure of Deflux™ was defined by: VUR on retrograde cystography and at least one acute pyelonephritis of the renal graft. The preferred surgical treatment was native ureteropyelostomy (NPUS) in the recent years. If the native ureter could not be used, ureteroneocystostomy (UNC) was performed. The primary outcome was the clinical efficacy of UR defined as the absence of acute graft pyelonephritis during follow-up. Out of 1565 kidney transplantations, 119 (7.6%) had symptomatic VUR treated with bulking agent. 35 (29.4%) had Deflux™ failure and were addressed to UR: 21/35 (60%) NPUS and 14/35 (40%) UNC. The median estimated blood loss, operative time, and length of stay were 120 mL, 90 min, and 7 days, respectively. After a median follow-up of 7.1 (IQR 4.1–9.8) years, UR was clinically successful in a total of 32 patients (91.4%): 20 (95.2%) and 12 (85.7%) patients in the NPUS and UNC groups, respectively (p = 0.55). Three (8.5%) high-grade complications have been reported. No nephrectomy of native kidney was required in the NPUS group. After failure of Deflux™ for VUR of renal graft, surgical treatment with native ureteropyelostomy or ureteroneocystostomy is associated to a high success rate and few high-grade complications.

Three-dimensional (3-D) printed models are increasingly used to enhance understanding of complex anatomy in congenital heart disease. To assess feasibility and accuracy of 3-D printed models obtained from cardiac CT scans in young children with complex congenital heart diseases. We included children with conotruncal heart anomalies who were younger than 2 years and had a cardiac CT scan in the course of their follow-up. We used cardiac CT scan datasets to generate 3-D models. To assess the models’ accuracy, we compared four diameters for each child between the CT images and the printed models, including the largest diameters (Dmax) of ventricular septal defects and aortic annulus and their minimal diameters (Dmin). We obtained images from 14 children with a mean age of 5.5 months (range 1–24 months) and a mean weight of 6.7 kg (range 3.4–14.5 kg). We generated 3-D models for all children. Mean measurement difference between CT images and 3-D models was 0.13 mm for Dmin and 0.12 mm for Dmax for ventricular septal defect diameters, and it was 0.16 mm for Dmin and −0.13 mm for Dmax for aortic annulus diameter, indicating a non-clinically significant difference. Three-dimensional printed models could be feasibly generated from cardiac CT scans in a small pediatric population with complex congenital heart diseases. This technique is highly accurate and reliably reflects the same structural dimensions when compared to CT source images.

In this paper I explore the question of what counts as successful implementation of a mathematics professional development (PD) project at scale. Two kinds of upscale are presented and differentiated from one another: upscale of settings and upscale of values, and the link between this differentiation and how success may be defined is discussed. As part of the discussion, three models of taking a PD project to scale are described, namely replication, adaptation and reproduction, and these are tied to the degree of professional autonomy of teachers within the PD. The examination of these ideas draws on data from two PD projects for secondary mathematics teachers in Israel, that are now years after their pilot phase and still being implemented. The first project is aimed at supporting mathematics teachers in teaching mathematically at-risk students and in helping these students to succeed in high-stakes exams. The second project is aimed at enhancing mathematics teachers' reflection on their teaching practices, using classroom video as a tool. Both projects were implemented at scale across Israel, and reviewing results from these implementations enables some general insights to be gained regarding the success of scaled-up PD projects. The crucial role of PD facilitators in successful implementations is highlighted.

Despite impressive improvement in long-term survival, adults with congenital heart disease (CHD) remain exposed to a significant cardiovascular morbidity over lifetime. Thromboembolic events (TE) are a major issue. Specific anatomic groups have been shown a particular high risk of TE, including cyanotic heart disease and Fontan circulation. Many intercurrent clinical factors add a substantial risk such as intracardiac medical devices, atrial arrhythmia, endocarditis, or pregnancy. Nevertheless, what is unknown exceeds what is known, especially regarding the management of this heterogenous patient population. Anticoagulation decision should always be individualized weighing balanced with the alternative risk of hemorrhagic complications. In this review, we aim to synthetize existing literature on TE in adults with CHD, discuss management issues, highlight gaps in knowledge, and intend to suggest high priority research.

While the prevalence of breast cancer metastasis in the brain is significantly higher in triple negative breast cancers (TNBCs), there is a lack of novel and/or improved therapies for these patients. Monoacylglycerol lipase (MAGL) is a hydrolase involved in lipid metabolism that catalyzes the degradation of 2-arachidonoylglycerol (2-AG) linked to generation of pro- and anti-inflammatory molecules. Here, we targeted MAGL in TNBCs, using a potent carbamate-based inhibitor AM9928 (hMAGL IC50 = 9 nM) with prolonged pharmacodynamic effects (46 h of target residence time). AM9928 blocked TNBC cell adhesion and transmigration across human brain microvascular endothelial cells (HBMECs) in 3D co-cultures. In addition, AM9928 inhibited the secretion of IL-6, IL-8, and VEGF-A from TNBC cells. TNBC-derived exosomes activated HBMECs resulting in secretion of elevated levels of IL-8 and VEGF, which were inhibited by AM9928. Using in vivo studies of syngeneic GFP-4T1-BrM5 mammary tumor cells, AM9928 inhibited tumor growth in the mammary fat pads and attenuated blood brain barrier (BBB) permeability changes, resulting in reduced TNBC colonization in brain. Together, these results support the potential clinical application of MAGL inhibitors as novel treatments for TNBC.

Background Sarcopenia is defined by a loss of muscle strength associated to a decrease in skeletal muscle mass. Ageing greatly contributes to sarcopenia as may many other factors such as cancer or androgen deprivation therapies (ADT). This cohort study aims to evaluate (1) the prevalence of muscle disorders and sarcopenia in older patients before initiation of intermediate to high risk prostate cancer treatment with ADT and radiotherapy, and (2) the occurrence and/or aggravation of muscle disorders and sarcopenia at the end of cancer treatment. Methods This cohort study is monocentric and prospective. The primary objectives are to determine the risk factor of sarcopenia prevalence and to study the relationship between ADT and sarcopenia incidence, in patients 70 years and older with histologically proven localized or locally advanced prostate cancer, addressed to a geriatrician (G8 score ≤14) for comprehensive geriatric assessment (CGA) in Marseille University Hospital. Secondary objectives encompass, measurement of sarcopenia clinical criteria along prostate oncological treatment; evaluation of the quality of life of patients with sarcopenia; evaluation of the impact of socio-behavioral and anthropological factors on sarcopenia evolution and incidence; finally the evaluation of the impact of ADT exposure on sarcopenia. Sarcopenia prevalence was estimated to be between 20 and 30%, therefore the study will enroll 200 patients. Discussion The current guidelines for older patients with prostate cancer recommend a pelvic radiotherapy treatment associated to variable duration (6 to 36 months) of ADT. However ADT impacts muscle mass and could exacerbate the risks of sarcopenia. Our study intends to assess the specific effect of ADT on sarcopenia incidence and/or worsening as well as to estimate sarcopenia prevalence in this population. The results of this cohort trial will lead to a better understanding of sarcopenia prevalence and incidence necessary to further elaborate a prevention plan. Trial registration The protocol was registered to the French drug and device regulation agency under the number 2019-A02319-48, before beginning the study (11/12/2019). The ClinicalTrials.gov identifier is NCT04484246, registration on the ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04484246).

Activation of the sympathetic nervous system causes pronounced metabolic changes that are mediated by multiple adrenergic receptor subtypes. Systemic treatment with β2-adrenergic receptor agonists results in multiple beneficial metabolic effects, including improved glucose homeostasis. To elucidate the underlying cellular and molecular mechanisms, we chronically treated wild-type mice and several newly developed mutant mouse strains with clenbuterol, a selective β2-adrenergic receptor agonist. Clenbuterol administration caused pronounced improvements in glucose homeostasis and prevented the metabolic deficits in mouse models of β-cell dysfunction and insulin resistance. Studies with skeletal muscle-specific mutant mice demonstrated that these metabolic improvements required activation of skeletal muscle β2-adrenergic receptors and the stimulatory G protein, Gs. Unbiased transcriptomic and metabolomic analyses showed that chronic β2-adrenergic receptor stimulation caused metabolic reprogramming of skeletal muscle characterized by enhanced glucose utilization. These findings strongly suggest that agents targeting skeletal muscle metabolism by modulating β2-adrenergic receptor-dependent signaling pathways may prove beneficial as antidiabetic drugs., In this study, the authors demonstrated that agents targeting skeletal muscle metabolism by modulating β2-adrenergic receptor-dependent signaling may prove beneficial as novel antidiabetic drugs.

Percutaneous closure of sinus venosus atrial septal defects (ASD) using covered stent implantation is a new and promising minimally invasive technique. New imaging tools are used to ensure preoperative anatomical characterization and preoperative guidance, which are key procedural success factors. Here we will describe and analyze these recent developments. Sinus venosus ASDs present a wide variety of anatomical features which must be described and analyzed using various imaging tools, including 3D technology. Percutaneous closure is challenging, but can hasten clinical recovery compared to the gold-standard conventional open-heart surgery. The feasibility of percutaneous closure relies on precise preoperative anatomical study and on real-time guidance using a multimodal fusion imaging process. Three-dimensional modeling of sinus venosus ASD is essential to understand the large anatomical panel encountered in this pathology. Multimodal fusion imaging guidance is very useful for performing sinus venosus ASD percutaneous closure in selected patients.

In our center, until 2018, MRI-targeted biopsy was underused. Since January 2018, we systematically performed MRI-targeted biopsy for suspicious PI-RADS ≥ 3 lesions in accordance to the recent guidelines. We hypothesized that the implementation of systematic prebiopsy MRI would increase the detection rate (DR) of prostate cancer (PCa) without increasing DR of clinically insignificant PCa (insignPCa). A retrospective study including consecutive men who underwent prostate biopsy for suspicion of PCa in our center between January 2017 and December 2018 was conducted. Combined biopsies were performed for suspicious MRI and systematic biopsies for nonsuspicious MRI. The primary outcome was to compare the DR of PCa per year. Secondary outcomes included DRs of clinically significant PCa (csPCa) and insignPCa between both years and outcomes of targeted vs systematic biopsies. A total of 306 men (152 in 2017 and 154 in 2018) were included. Respectively, median (IQR) age was 69 (63–75) vs 70 (65–76) years (p = 0.29) and median (IQR) PSA density was 0.17 (0.13–0.28) vs 0.17 (0.11–0.26) (p = 0.24). There was a significant increase in prebiopsy MRI performed (120 [78.9%] vs 143 [92.8%]; p

This paper reports on a study conducted within VIDEO-LM (Viewing, Investigating and Discussing Environments of Learning Mathematics), a video-based professional development project for secondary mathematics teachers that aims to enhance reflection on practice. The study explored VIDEO-LM sessions where Israeli teachers watched an 8th grade geometry lesson from Japan. We analyzed teachers’ discussions around this lesson and characterized main themes and reflection types. Findings suggest that watching the Japanese lesson, using the VIDEO-LM framework, led to productive discussions among teachers. The fact that the videotaped lesson was culturally “far” from the teachers’ reality provoked them to re-see everyday aspects of their practice, revealing some dissonances which promoted reflective thoughts and actions.

There have recent reports in the literature of increased rates of bladder recurrence (BR) after radical nephroureterectomy (RNU) when diagnostic flexible ureteroscopy (DFU) was performed before RNU. The technical heterogeneity of DFU was a major bias in these studies. Our purpose was to evaluate the impact of a standardized DFU technique before RNU on the risk of BR. A retrospective monocenter study including patients who underwent RNU for upper tract urothelial carcinoma (UTUC) between 2005 and 2017. 171 patients were identified. 78 patients were excluded owing to a history of bladder cancer before RNU or neo-adjuvant/adjuvant chemotherapy. 93 included patients were stratified according to pre-RNU ureteroscopy (DFU + 70 patients) or no pre-RNU ureteroscopy (DFU—23 patients). The standardized DFU technique consisted of systematic ureteral sheath (ch9–10), flexible ureteroscopy, biopsy, and drainage with a mono-J/bladder catheter to avoid contact of contaminated urine of the upper tract with the bladder. Epidemiological, initial staging, and postoperative tumoral characteristics were similar in both groups. Mean follow-up was 35 months [2–166], 47(50%) BR occurred with 41(87%) in the DFU + group, and pre-RNU–DFU was an independent predictive factor of BR (OR = 4[1.4–11.9], P = 0.01) (Cox regression model). The characteristics of BR were similar in both groups, although BR occurred earlier in DFU + (427 days vs. 226 days (P = 0.07)). Bladder recurrence after diagnostic ureteroscopy + nephroureterectomy was high despite technical precautions to avoid contact of bladder mucosa with contaminated urine from the upper urinary tract. Post-DFU endovesical instillation should be investigated.

Background The classical functions of the skeleton encompass locomotion, protection and mineral homeostasis. However, cell-specific gene deletions in the mouse and human genetic studies have identified the skeleton as a key endocrine regulator of metabolism. The bone-specific phosphatase, Phosphatase, Orphan 1 (PHOSPHO1), which is indispensable for bone mineralisation, has been recently implicated in the regulation of energy metabolism in humans, but its role in systemic metabolism remains unclear. Here, we probe the mechanism underlying metabolic regulation by analysing Phospho1 mutant mice. Results Phospho1−/− mice exhibited improved basal glucose homeostasis and resisted high-fat-diet-induced weight gain and diabetes. The metabolic protection in Phospho1−/− mice was manifested in the absence of altered levels of osteocalcin. Osteoblasts isolated from Phospho1−/− mice were enriched for genes associated with energy metabolism and diabetes; Phospho1 both directly and indirectly interacted with genes associated with glucose transport and insulin receptor signalling. Canonical thermogenesis via brown adipose tissue did not underlie the metabolic protection observed in adult Phospho1−/− mice. However, the decreased serum choline levels in Phospho1−/− mice were normalised by feeding a 2% choline rich diet resulting in a normalisation in insulin sensitivity and fat mass. Conclusion We show that mice lacking the bone mineralisation enzyme PHOSPHO1 exhibit improved basal glucose homeostasis and resist high-fat-diet-induced weight gain and diabetes. This study identifies PHOSPHO1 as a potential bone-derived therapeutic target for the treatment of obesity and diabetes.