Mitochondrial DNA Haplogroup JT is Related to Impaired Glycaemic Control and Renal Function in Type 2 Diabetic Patients

The association between mitochondrial DNA (mtDNA) haplogroup and risk of type 2 diabetes (T2D) is undetermined and controversial. This study aims to evaluate the impact of the main mtDNA haplogroups on glycaemic control and renal function in a Spanish population of 303 T2D patients and 153 healthy controls. Anthropometrical and metabolic parameters were assessed and mtDNA haplogroup was determined in each individual. Distribution of the different haplogroups was similar in diabetic and healthy populations and, as expected, T2D patients showed poorer glycaemic control and renal function than controls. T2D patients belonging to the JT haplogroup (polymorphism m.4216T>C) displayed statistically significant higher levels of fasting glucose and HbA(1c) than those of the other haplogroups, suggesting a poorer glycaemic control. Furthermore, diabetic patients with the JT haplogroup showed a worse kidney function than those with other haplogroups, evident by higher levels of serum creatinine, lower estimated glomerular filtration rate (eGFR), and slightly higher (although not statistically significant) urinary albumin-to-creatinine ratio. Our results suggest that JT haplogroup (in particular, change at position 4216 of the mtDNA) is associated with poorer glycaemic control in T2D, which can trigger the development of diabetic nephropathy

Painlev\'e-Gullstrand synchronizations in spherical symmetry

A Painlev\'e-Gullstrand synchronization is a slicing of the space-time by a family of flat spacelike 3-surfaces. For spherically symmetric space-times, we show that a Painlev\'e-Gullstrand synchronization only exists in the region where $(dr)^2 \leq 1$, $r$ being the curvature radius of the isometry group orbits ($2$-spheres). This condition says that the Misner-Sharp gravitational energy of these 2-spheres is not negative and has an intrinsic meaning in terms of the norm of the mean extrinsic curvature vector. It also provides an algebraic inequality involving the Weyl curvature scalar and the Ricci eigenvalues. We prove that the energy and momentum densities associated with the Weinberg complex of a Painlev\'e-Gullstrand slice vanish in these curvature coordinates, and we give a new interpretation of these slices by using semi-metric Newtonian connections. It is also outlined that, by solving the vacuum Einstein's equations in a coordinate system adapted to a Painlev\'e-Gullstrand synchronization, the Schwarzschild solution is directly obtained in a whole coordinate domain that includes the horizon and both its interior and exterior regions.Comment: 16 page

Role of IL-36 Cytokines in the Regulation of Angiogenesis Potential of Trophoblast Cells

IL-36 cytokines (the agonists IL-36α, IL-36β, IL-36γ, and the antagonist IL-36Ra) are expressed in the mouse uterus and associated with maternal immune response during pregnancy. Here, we characterize the expression of IL-36 members in human primary trophoblast cells (PTC) and trophoblastic cell lines (HTR-8/SVneo and JEG-3) and upon treatment with bacterial and viral components. Effects of recombinant IL-36 on the migration capacity of trophoblastic cells, their ability to interact with endothelial cells and the induction of angiogenic factors and miRNAs (angiomiRNAs) were examined. Constitutive protein expression of IL-36 (α, β, and γ) and their receptor (IL-36R) was found in all cell types. In PTC, transcripts for all IL-36 subtypes were found, whereas in trophoblastic cell lines only for IL36G and IL36RN. A synthetic analog of double-stranded RNA (poly I:C) and lipopolysaccharide (LPS) induced the expression of IL-36 members in a cell-specific and time-dependent manner. In HTR-8/SVneo cells, IL-36 cytokines increased cell migration and their capacity to interact with endothelial cells. VEGFA and PGF mRNA and protein, as well as the angiomiRNAs miR-146a-3p and miR-141-5p were upregulated as IL-36 response in PTC and HTR-8/SVneo cells. In conclusion, IL-36 cytokines are modulated by microbial components and regulate trophoblast migration and interaction with endothelial cells. Therefore, a fundamental role of these cytokines in the placentation process and in response to infections may be expected

Role of the employment status and education of mothers in the prevalence of intestinal parasitic infections in Mexican rural schoolchildren

<p><b>Background:</b> Intestinal parasitic infections are a public health problem in developing countries such as Mexico. As a result, two governmental programmes have been implemented: a) "National Deworming Campaign" and b) "Opportunities" aimed at maternal care. However, both programmes are developed separately and their impact is still unknown. We independently investigated whether a variety of socio-economic factors, including maternal education and employment levels, were associated with intestinal parasite infection in rural school children.</p> <p><b>Methods:</b> This cross-sectional study was conducted in 12 rural communities in two Mexican states. The study sites and populations were selected on the basis of the following traits: a) presence of activities by the national administration of albendazole, b) high rates of intestinal parasitism, c) little access to medical examination, and d) a population having less than 2,500 inhabitants. A total of 507 schoolchildren (mean age 8.2 years) were recruited and 1,521 stool samples collected (3 per child). Socio-economic information was obtained by an oral questionnaire. Regression modelling was used to determine the association of socio-economic indicators and intestinal parasitism.</p> <p><b>Results:</b> More than half of the schoolchildren showed poliparasitism (52%) and protozoan infections (65%). The prevalence of helminth infections was higher in children from Oaxaca (53%) than in those from Sinaloa (33%) (p < 0.0001). Giardia duodenalis and Hymenolepis nana showed a high prevalence in both states. Ascaris lumbricoides, Trichuris trichiura and Entamoeba hystolitica/dispar showed low prevalence. Children from lower-income families and with unemployed and less educated mothers showed higher risk of intestinal parasitism (odds ratio (OR) 6.0, 95% confidence interval (CI) 1.6–22.6; OR 4.5, 95% CI 2.5–8.2; OR 3.3, 95% CI 1.5–7.4 respectively). Defecation in open areas was also a high risk factor for infection (OR 2.4, 95% CI 2.0–3.0).</p> <p><b>Conclusion:</b> Intestinal parasitism remains an important public health problem in Sinaloa (north-western Mexico) and Oaxaca (south-eastern Mexico). Lower income, defecation in open areas, employment status and a lower education level of mothers were the significant factors related to these infections. We conclude that mothers should be involved in health initiatives to control intestinal parasitism in Mexico.</p&gt

In silico selection and in vitro evaluation of new molecules that inhibit the adhesion of Streptococcus mutans through Antigen I/II

Streptococcus mutans is the main early colonizing cariogenic bacteria because it recognizes salivary pellicle receptors. The Antigen I/II of S. mutans is one of the most important adhesins in this process, is involved in the adhesion to the tooth surface and the bacterial co-aggregation in the early stage of biofilm formation. However, this protein has not been used as a target in a virtual strategy search for inhibitors. Based on the predicted binding affinities, drug-like properties and toxicity, molecules were selected and evaluated for their ability to reduce S. mutans adhesion. A virtual screening of 883,551 molecules was conducted, cytotoxicity analysis on fibroblast cells, S. mutans adhesion studies, scanning electron microscopy analysis for bacterial integrity and molecular dynamics simulation were also performed. We have found three molecules (ZI-187, ZI-939, ZI-906) without cytotoxic activity, which inhibited about 90% the adhesion of S. mutans to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates

Variable order Mittag-Leffler fractional operators on isolated time scales and application to the calculus of variations

We introduce new fractional operators of variable order on isolated time scales with Mittag-Leffler kernels. This allows a general formulation of a class of fractional variational problems involving variable-order difference operators. Main results give fractional integration by parts formulas and necessary optimality conditions of Euler-Lagrange type.Comment: This is a preprint of a paper whose final and definite form is with Springe

LSPM J1112+7626: detection of a 41-day M-dwarf eclipsing binary from the MEarth transit survey

We report the detection of eclipses in LSPM J1112+7626, which we find to be a moderately bright (I_C = 12.14 +/- 0.05) very low-mass binary system with an orbital period of 41.03236 +/- 0.00002 days, and component masses M_1 = 0.395 +/- 0.002 Msol and M_2 = 0.275 +/- 0.001 Msol in an eccentric (e = 0.239 +/- 0.002) orbit. A 65 day out of eclipse modulation of approximately 2% peak-to-peak amplitude is seen in I-band, which is probably due to rotational modulation of photospheric spots on one of the binary components. This paper presents the discovery and characterization of the object, including radial velocities sufficient to determine both component masses to better than 1% precision, and a photometric solution. We find that the sum of the component radii, which is much better-determined than the individual radii, is inflated by 3.8 +0.9 -0.5 % compared to the theoretical model predictions, depending on the age and metallicity assumed. These results demonstrate that the difficulties in reproducing observed M-dwarf eclipsing binary radii with theoretical models are not confined to systems with very short orbital periods. This object promises to be a fruitful testing ground for the hypothesized link between inflated radii in M-dwarfs and activity.Comment: 23 pages, 11 figures, 12 tables, emulateapj format. Accepted for publication in Ap

Comparison of flipped learning and traditional lecture method for teaching digestive system diseases in undergraduate medicine: A prospective non-randomized controlled trial

Introduction: This study examined the effects of a large-scale flipped learning (FL) approach in an undergraduate course of Digestive System Diseases. Methods: This prospective non-randomized trial recruited 404 students over three academic years. In 2016, the course was taught entirely in a Traditional Lecture (TL) style, in 2017 half of the course (Medical topics) was replaced by FL while the remaining half (Surgical topics) was taught by TL and in 2018, the whole course was taught entirely by FL. Academic performance, class attendance and student’s satisfaction surveys were compared between cohorts. Results: Test scores were higher in the FL module (Medical) than in the TL module (Surgical) in the 2017 cohort but were not different when both components were taught entirely by TL (2016) or by FL (2018). Also, FL increased the probability of reaching superior grades (scores >7.0) and improved class attendance and students’ satisfaction. Conclusion: The holistic FL model is more effective for teaching undergraduate clinical gastroenterology compared to traditional teaching methods and has a positive impact on classroom attendances