Gestational weight gain: Toward best practices in managing gestational weight gain in patients with obesity: Comparison of recommendations.

BACKGROUND AND AIMS: In 2009, the Institute of Medicine (IOM) issued recommendations for gestational weight gain (GWG) based on body mass index (BMI). Several studies have challenged those recommendations for women with obesity, considering them too liberal and advising more limited weight gain - or even weight loss - during pregnancy to improve maternal and neonatal outcomes. Our aim was to study how gestational weight gain in women with obesity impacted maternal and fetal complications in the Belgian population. We did this by comparing the results from two groups of patients with obesity: those who met the 2009 IOM standards and those who satisfied the stricter recommendations suggested by other authors. MATERIALS AND METHODS: This is a retrospective cohort study using data collected at the Centre d'Epidémiologie Périnatale (CEpiP) from obese (BMI ≥ 30 kg/m2) pregnant women with live singleton deliveries between 2010 and 2019 in Wallonia-Brussels Federation (n = 65,314). RESULTS: Compared to obese patients whose GWG satisfied the IOM standards, those with GWG meeting the stricter recommendations had lower rates of gestational hypertension (7.1 % vs. 10.1 %; p = 0.0059), cesarean section (22.1 % vs. 26.3 %; p = 0.0074), and macrosomia (12.0 % vs. 17.7 %; p < 0.0001). There was no significant difference in the rate of preterm delivery (6.9 % vs 5.8 %; p = 0.12) or small-for-gestational-age births (7.2 % vs. 6.2 %; p = 0.16). CONCLUSION: Gestational weight gain below that currently recommended by the IOM appears beneficial to the health of mothers with obesity and their children. These data, from our population, further challenge the standards proposed since 2009.

Utility of indium-111 platelet scintigraphy for understanding the mechanism of thrombocytopenia associated with myelodysplastic syndromes and chronic myelomonocytic leukemia.

BACKGROUND: Thrombocytopenia occurs in 60% of patients with myelodysplastic syndromes (MDS), increasing the risk of life-threatening haemorrhage in this population of mainly old patients with comorbidities. However, data are scare regarding immune thrombocytopenia (ITP) secondary to MDS. AIM: We analyzed the utility of indium-111 platelet scintigraphy (IPS) to better characterize the mechanisms of thrombocytopenia in 21 adult patients with MDS. METHODS: Adult patients with a definite diagnosis of MDS according to the international criteria who underwent IPS between 2009 and 2018 because of an increased bleeding risk were retrospectively selected. Autologous 111Indium platelet labelling was performed with a technique similar to that described previously using a standardized method. RESULTS: Platelet lifespan ≤ 6 days identified patients with peripheral platelet destruction. Taking into account the response to ITP-directed therapies after IPS, the sensitivity, specificity, and positive and negative predictive values of IPS were 100%, 84.6%, 80%, and 100%, respectively. CONCLUSION: We show that IPS can be a useful tool to identify the mechanism and guide treatment of a chronic thrombocytopenia increasing the bleeding risk in patients with MDS.

NMDA receptor membrane dynamics tunes the firing pattern of midbrain dopaminergic neurons.

KEY POINTS: NMDA receptors (NMDARs) expressed by dopamine neurons of the ventral tegmental area (VTA) play a central role in glutamate synapse plasticity, neuronal firing and adaptative behaviours. The NMDAR surface dynamics shapes synaptic adaptation in hippocampal networks, as well as associative memory. We investigated the basic properties and role of the NMDAR surface dynamics on cultured mesencephalic and VTA dopamine neurons in rodents. Using a combination of single molecule imaging and electrophysiological recordings, we demonstrate that NMDARs are highly diffusive at the surface of mesencephalic dopamine neurons. Unexpectedly, the NMDAR membrane dynamics per se regulates the firing pattern of VTA dopaminergic neurons, probably through a functional interplay between NMDARs receptors and small-conductance calcium-dependent potassium (SK) channels. ABSTRACT: Midbrain dopaminergic (DA) neurons play a central role in major physiological brain functions, and their dysfunctions have been associated with neuropsychiatric diseases. The activity of midbrain DA neurons is controlled by ion channels and neurotransmitter receptors, such as the glutamate NMDA receptor (NMDAR) and small-conductance calcium-dependent potassium (SK) channels. However, the cellular mechanisms through which these channels tune the firing pattern of midbrain DA neurons remain unclear. Here, we investigated whether the surface dynamics and distribution of NMDARs tunes the firing pattern of midbrain DA neurons. Using a combination of single molecule imaging and electrophysiological recordings, we report that NMDARs are highly diffusive at the surface of cultured midbrain DA neurons from rodents and humans. Reducing acutely the NMDAR membrane dynamics, which leaves the ionotropic function of the receptor intact, robustly altered the firing pattern of midbrain DA neurons without altering synaptic glutamatergic transmission. The reduction of NMDAR surface dynamics reduced apamin (SK channel blocker)-induced firing change and the distribution of SK3 channels in DA neurons. Together, these data show that the surface dynamics of NMDAR, and not solely its ionotropic function, tune the firing pattern of midbrain DA neurons partly through a functional interplay with SK channel function.

Single nanoparticle tracking of [Formula: see text]-methyl-d-aspartate receptors in cultured and intact brain tissue.

Recent developments in single-molecule imaging have revealed many biological mechanisms, providing high spatial and temporal resolution maps of molecular events. In neurobiology, these techniques unveiled that plasma membrane neurotransmitter receptors and transporters laterally diffuse at the surface of cultured brain cells. The photostability of bright nanoprobes, such as quantum dots (QDs), has given access to neurotransmitter receptor tracking over long periods of time with a high spatial resolution. However, our knowledge has been restricted to cultured systems, i.e., neurons and organotypic slices, therefore lacking several aspects of the intact brain rheology and connectivity. Here, we used QDs to track single glutamatergic [Formula: see text]-methyl-d-aspartate receptors (NMDAR) in acute brain slices. By delivering functionalized nanoparticles in vivo through intraventricular injections to rats expressing genetically engineered-tagged NMDAR, we successfully tracked the receptors in native brain tissue. Comparing NMDAR tracking to different classical brain preparations (acute brain slices, cultured organotypic brain slices, and cultured neurons) revealed that the surface diffusion properties shared several features and are also influenced by the nature of the extracellular environment. Together, we describe the experimental procedures to track plasma membrane NMDAR in dissociated and native brain tissue, paving the way for investigations aiming at characterizing receptor diffusion biophysics in intact tissue and exploring the physiopathological roles of receptor surface dynamics.

Silicone Granuloma in the Buttocks Incidentally Detected by 18F-FDG PET/CT 30 Years After Free Liquid Silicone Injections.

A 59-year-old transexual (male to female) patient presented with a squamous cell carcinoma of the larynx. She underwent an F-FDG PET/CT for initial staging. The examination showed high F-FDG uptake of the primary lesion and a homolateral lymphadenopathy. Incidental heterogeneous uptake of round hyperdense lesions in the gluteal muscles and subcutaneous fat was visualized. The medical history revealed secondly that the patient had had free liquid silicone injections 30 years before the examination. Although the injection of free silicone is not practised since the 1980s, this incidental finding should prompt to check the patient's medical history over several decades.

CX3CL1, a chemokine finely tuned to adhesion: critical roles of the stalk glycosylation and the membrane domain.

The multi-domain CX3CL1 transmembrane chemokine triggers leukocyte adherence without rolling and migration by presenting its chemokine domain (CD) to its receptor CX3CR1. Through the combination of functional adhesion assays with structural analysis using FRAP, we investigated the functional role of the other domains of CX3CL1, i.e., its mucin stalk, transmembrane domain, and cytosolic domain. Our results indicate that the CX3CL1 molecular structure is finely adapted to capture CX3CR1 in circulating cells and that each domain has a specific purpose: the mucin stalk is stiffened by its high glycosylation to present the CD away from the membrane, the transmembrane domain generates the permanent aggregation of an adequate amount of monomers to guarantee adhesion and prevent rolling, and the cytosolic domain ensures adhesive robustness by interacting with the cytoskeleton. We propose a model in which quasi-immobile CX3CL1 bundles are organized to quickly generate adhesive patches with sufficiently high strength to capture CX3CR1+ leukocytes but with sufficiently low strength to allow their patrolling behavior.