Metabolic Footprint, towards Understanding Type 2 Diabetes beyond Glycemia

Type 2 diabetes (T2D) heterogeneity is a major determinant of complications risk and treatment response. Using cluster analysis, we aimed to stratify glycemia within metabolic multidimensionality and extract pathophysiological insights out of metabolic profiling. We performed a cluster analysis to stratify 974 subjects (PREVADIAB2 cohort) with normoglycemia, prediabetes, or non-treated diabetes. The algorithm was informed by age, anthropometry, and metabolic milieu (glucose, insulin, C-peptide, and free fatty acid (FFA) levels during the oral glucose tolerance test OGTT). For cluster profiling, we additionally used indexes of metabolism mechanisms (e.g., tissue-specific insulin resistance, insulin clearance, and insulin secretion), non-alcoholic fatty liver disease (NAFLD), and glomerular filtration rate (GFR). We found prominent heterogeneity within two optimal clusters, mainly representing normometabolism (Cluster-I) or insulin resistance and NAFLD (Cluster-II), at higher granularity. This was illustrated by sub-clusters showing similar NAFLD prevalence but differentiated by glycemia, FFA, and GFR (Cluster-II). Sub-clusters with similar glycemia and FFA showed dissimilar insulin clearance and secretion (Cluster-I). This work reveals that T2D heterogeneity can be captured by a thorough metabolic milieu and mechanisms profiling-metabolic footprint. It is expected that deeper phenotyping and increased pathophysiology knowledge will allow to identify subject's multidimensional profile, predict their progression, and treat them towards precision medicine.publishersversionpublishe

Laparoscopic management of a cavitated noncommunicating rudimentary uterine horn of a unicornuate uterus: a case report

<p>Abstract</p> <p>Introduction</p> <p>A unicornuate uterus with a rudimentary horn is the most uncommon uterine anomaly of the female genital tract. It has an estimated frequency of one in 100,000 among the fertile female population. This anomaly results from the abnormal maturation of one Müllerian duct with the normal development of the contralateral one.</p> <p>Case presentation</p> <p>We report here the case of a 14-year-old Caucasian girl who came to our hospital with intense dysmenorrhea. Imaging techniques revealed a unicornuate uterus with a rudimentary horn and a large hematosalpinx. We performed a laparoscopic removal of this uterine anomaly without any complication in the postoperative period.</p> <p>Conclusion</p> <p>In our case report, we demonstrate that laparoscopy is the best approach for the treatment of IIb Müllerian abnormalities. Laparoscopy resulted in anatomical and reproductive results equivalent to those offered by a laparotomic approach, but with the additional advantages of minimally invasive surgery, such as better cosmetic results and postoperative period, which are essential for very young patients.</p

SLP Seed Grants 1

Seed Grants are funded with programme-attributed funds. Their purpose is to support researchers and their partners during the crucial initial planning and consultation phases needed to develop larger project proposals. Allocated on a competitive basis, once the proposals are finalized, the consortia are supported to obtain project restricted funding

Influence of a virtual exercise program throughout pregnancy during the covid-19 pandemic on perineal tears and episiotomy rates: A randomized clinical trial

The complications associated with COVID-19 confinement (impossibility of grouping, reduced mobility, distance between people, etc.) influence the lifestyle of pregnant women with important associated complications regarding pregnancy outcomes. Therefore, perineal traumas are the most common obstetric complications during childbirth. The aim of the present study was to examine the influence of a supervised virtual exercise program throughout pregnancy on perineal injury and episiotomy rates during childbirth. A randomized clinical trial design (NCT04563065) was used. Data were collected from 98 pregnant women without obstetric contraindications who attended their prenatal medical consultations. Women were randomly assigned to the intervention (IG, N = 48) or the control group (CG, N = 50). A virtual and supervised exercise program was conducted from 8–10 to 38–39 weeks of pregnancy. Significant differences were found between the study groups in the percentage of episiotomies, showing a lower episiotomy rate in the IG (N = 9/12%) compared to the CG (N = 18/38%) (χ2 (3) = 4.665; p = 0.031) and tears (IG, N = 25/52% vs. CG, N = 36/73%) (χ2 (3) = 4.559; p = 0.033). A virtual program of supervised exercise throughout pregnancy during the current COVID-19 pandemic may help reduce rates of episiotomy and perineal tears during delivery in healthy pregnant women

Dynamics of Particles Deposition on a Disordered Substrate: II. Far-from Equilibrium Behavior. -

The deposition dynamics of particles (or the growth of a rigid crystal) on a disordered substrate at a finite deposition rate is explored. We begin with an equation of motion which includes, in addition to the disorder, the periodic potential due to the discrete size of the particles (or to the lattice structure of the crystal) as well as the term introduced by Kardar, Parisi, and Zhang (KPZ) to account for the lateral growth at a finite growth rate. A generating functional for the correlation and response functions of this process is derived using the approach of Martin, Sigga, and Rose. A consistent renormalized perturbation expansion to first order in the non-Gaussian couplings requires the calculation of diagrams up to three loops. To this order we show, for the first time for this class of models which violates the the fluctuation-dissipation theorem, that the theory is renormalizable. We find that the effects of the periodic potential and the disorder decay on very large scales and asymptotically the KPZ term dominates the behavior. However, strong non-trivial crossover effects are found for large intermediate scales.Comment: 52 pages & 17 Figs in uucompressed file. UR-CM 94-090

Alternative glacial-interglacial refugia demographic hypotheses tested on Cephalocereus columna-trajani (Cactaceae) in the intertropical Mexican drylands

Historic demography changes of plant species adapted to New World arid environments could be consistent with either the Glacial Refugium Hypothesis (GRH), which posits that populations contracted to refuges during the cold-dry glacial and expanded in warm-humid interglacial periods, or with the Interglacial Refugium Hypothesis (IRH), which suggests that populations contracted during interglacials and expanded in glacial times. These contrasting hypotheses are developed in the present study for the giant columnar cactus Cephalocereus columna-trajani in the intertropical Mexican drylands where the effects of Late Quaternary climatic changes on phylogeography of cacti remain largely unknown. In order to determine if the historic demography and phylogeographic structure of the species are consistent with either hypothesis, sequences of the chloroplast regions psbA-trnH and trnT-trnL from 110 individuals from 10 populations comprising the full distribution range of this species were analysed. Standard estimators of genetic diversity and structure were calculated. The historic demography was analysed using a Bayesian approach and the palaeodistribution was derived from ecological niche modelling to determine if, in the arid environments of south-central Mexico, glacial-interglacial cycles drove the genetic divergence and diversification of this species. Results reveal low but statistically significant population differentiation (FST = 0.124, P < 0.001), although very clear geographic clusters are not formed. Genetic diversity, haplotype network and Approximate Bayesian Computation (ABC) demographic analyses suggest a population expansion estimated to have taken place in the Last Interglacial (123.04 kya, 95% CI 115.3–130.03). The species palaeodistribution is consistent with the ABC analyses and indicates that the potential area of palaedistribution and climatic suitability were larger during the Last Interglacial and Holocene than in the Last Glacial Maximum. Overall, these results suggest that C. columna-trajani experienced an expansion following the warm conditions of interglacials, in accordance with the GRH

Three red suns in the sky: A transiting, terrestrial planet in a triple M-dwarf system at 6.9 pc

We present the discovery from Transiting Exoplanet Survey Satellite (TESS) data of LTT 1445Ab. At a distance of 6.9 pc, it is the second nearest transiting exoplanet system found to date, and the closest one known for which the primary is an M dwarf. The host stellar system consists of three mid-to-late M dwarfs in a hierarchical configuration, which are blended in one TESS pixel. We use MEarth data and results from the Science Processing Operations Center data validation report to determine that the planet transits the primary star in the system. The planet has a radius of ${1.38}_{-0.12}^{+0.13}$ ${R}_{\oplus }$, an orbital period of ${5.35882}_{-0.00031}^{+0.00030}$ days, and an equilibrium temperature of ${433}_{-27}^{+28}$ K. With radial velocities from the High Accuracy Radial Velocity Planet Searcher, we place a 3σ upper mass limit of 8.4 ${M}_{\oplus }$ on the planet. LTT 1445Ab provides one of the best opportunities to date for the spectroscopic study of the atmosphere of a terrestrial world. We also present a detailed characterization of the host stellar system. We use high-resolution spectroscopy and imaging to rule out the presence of any other close stellar or brown dwarf companions. Nineteen years of photometric monitoring of A and BC indicate a moderate amount of variability, in agreement with that observed in the TESS light-curve data. We derive a preliminary astrometric orbit for the BC pair that reveals an edge-on and eccentric configuration. The presence of a transiting planet in this system hints that the entire system may be co-planar, implying that the system may have formed from the early fragmentation of an individual protostellar core.Accepted manuscrip

A mouse model for Luminal epithelial like ER positive subtype of human breast cancer

<p>Abstract</p> <p>Background</p> <p>Generation of novel spontaneous ER positive mammary tumor animal model from heterozygous NIH nude mice.</p> <p>Methods</p> <p>Using brother-sister mating with pedigree expansion system, we derived a colony of heterozygous breeding females showing ER-Positive tumors around the age of 6 months. Complete blood picture, differential leukocyte count, and serum levels of Estrogen, Alanine amino transferase (SGPT), Aspartate amino transferase (SGOT), total protein and albumin were estimated. Aspiration biopsies and microbiology were carried out. Gross pathology of the tumors and their metastatic potential were assessed. The tumors were excised and further characterized using histopathology, cytology, electron microscopy (EM), molecular markers and Mouse mammary Tumor Virus – Long Terminal Repeats (MMTV LTR) specific RT-PCR.</p> <p>Results</p> <p>The tumors originated from 2^ndor 5^thor both the mammary glands and were multi-nodulated with variable central necrosis accompanied with an accumulation of inflammatory exudate. Significant increases in estrogen, SGPT, SGOT and neutrophils levels were noticed. Histopathologically, invasive nodular masses of pleomorphic tubular neoplastic epithelial cells invaded fibro-vascular stroma, adjacent dermis and subcutaneous tissue. Metastatic spread through hematogenous and regional lymph nodes, into liver, lungs, spleen, heart and dermal lymphatics was observed. EM picture revealed no viral particles and MMTV-negativity was confirmed through MMTV LTR-specific RT-PCR. High expression of ER α, moderate to high expression of proliferating cell nuclear antigen (PCNA), moderate expression of vimentin and Cytokeratin 19 (K19) and low expression of p53 were observed in tumor sections, when compared with that of the normal mammary gland.</p> <p>Conclusion</p> <p>Since 75% of human breast cancer were classified ER-positive and as our model mimics (in most of the characteristics, such as histopathology, metastasis, high estrogen levels) the ER-positive luminal epithelial-like human breast cancer, this model will be an attractive tool to understand the biology of estrogen-dependant breast cancer in women. To our knowledge, this is the first report of a spontaneous mammary model displaying regional lymph node involvement with both hematogenous and lymphatic spread to liver, lung, heart, spleen and lymph nodes.</p

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF &lt;5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants