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

Design of a high power production target for the Beam Dump Facility at CERN

The Beam Dump Facility (BDF) project is a proposed general-purpose facility at CERN, dedicated to beam dump and fixed target experiments. In its initial phase, the facility is foreseen to be exploited by the Search for Hidden Particles (SHiP) experiment. Physics requirements call for a pulsed 400 GeV/c proton beam as well as the highest possible number of protons on target (POT) each year of operation, in order to search for feebly interacting particles. The target/dump assembly lies at the heart of the facility, with the aim of safely absorbing the full high intensity Super Proton Synchrotron (SPS) beam, while maximizing the production of charmed and beauty mesons. High-Z materials are required for the target/dump, in order to have the shortest possible absorber and reduce muon background for the downstream experiment. The high average power deposited on target (305 kW) creates a challenge for heat removal. During the BDF facility Comprehensive Design Study (CDS), launched by CERN in 2016, extensive studies have been carried out in order to define and assess the target assembly design. These studies are described in the present contribution, which details the proposed design of the BDF production target, as well as the material selection process and the optimization of the target configuration and beam dilution. One of the specific challenges and novelty of this work is the need to consider new target materials, such as a molybdenum alloy (TZM) as core absorbing material and Ta2.5W as cladding. Thermo-structural and fluid dynamics calculations have been performed to evaluate the reliability of the target and its cooling system under beam operation. In the framework of the target comprehensive design, a preliminary mechanical design of the full target assembly has also been carried out, assessing the feasibility of the whole target system.Comment: 17 pages, 18 figure

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

Carbapenemases; High-risk clones; Whole genome sequencingCarbapenemasas; Clones de alto riesgo; Secuenciación del genoma completoCarbapenemases; Clons d'alt risc; Seqüenciació del genoma sencerObjectives: CARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain. Methods: In total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis. Results: In total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5). Conclusion: This study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3.This research was supported by grants from the Instituto de Salud Carlos III (numbers PI18CIII/00030 and PI21CIII/00039). It was also supported by Plan Nacional de I + D + i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía y Competitividad, Spanish Network for Research in Infectious Diseases (grants RD16CIII/0004/0002, RD16/0016/0001, RD16/0016/0003, RD16/0016/0004, RD16/0016/0006, RD16/0016/0007, RD16/0016/0008, RD16/0016/0010, and RD16/0016/0011). Cofinanced by the European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligent Growth 2014–2020. CIBER – Consorcio Centro de Investigación Biomédica en Red (CB21/13/00095, CB21/13/00012, CB21/13/00049, CB21/13/00054, CB21/13/00055, CB21/13/00068, CB21/13/00081, CB21/13/00084, and CB21/13/00099) (CIBERINFEC) and Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU also supported this work

Regional grey matter microstructural changes and volume loss according to disease duration in multiple sclerosis patients

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER, "Otra manera de hacer Europa", "Investing in your future"); Red Española de Esclerosis Múltiple (REEM - RD16/0015/0002, RD16/0015/0003, RD12/0032/0002, RD12/0060/01-02); TEVA Spain; Fundación Merck Salud (Ayudas Merck de Investigación 2017); Proyecto Societat Catalana Neurologia 2017; CIBERNED program (Program 1, Alzheimer Disease and SIGNAL study); National Institutes of Health (NIA grants 1R01AG056850-01A1, R21AG056974, R01AG061566;, Fundació La Marató de TV3 (20142030, 20141210); Fundació Catalana Síndrome de Down; Fundació Víctor Grífols i Lucas; Generalitat de Catalunya (SLT006/17/00119); Universitat de Barcelona (APIF Pre-doctoral grant); Hospital Clinic Emili Letang).The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease duration. Additionally, we investigated the relationship between GM changes with disease severity. We studied 54 healthy controls and 247 MS patients classified regarding disease duration: MS1 (less than 5 years, n = 67); MS2 (5-15 years, n = 107); and MS3 (more than15 years, n = 73). We compared GM mean diffusivity (MD), fractional anisotropy (FA) and volume between groups, and estimated their clinical associations. Regional modifications in diffusion measures (MD and FA) and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in deep GM and left precuneus. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes in MD and volume extended to more than 80% of regions in MS3 group. Conversely, increments in FA, with very low effect size, were observed in the parietal cortex and thalamus in MS1 and MS2 groups, and extended to the frontal lobe in the later group. MD and GM changes were associated with white matter lesion load and with physical and cognitive disability. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage

Wax worm saliva and the enzymes therein are the key to polyethylene degradation by Galleria mellonella

Plastic degradation by biological systems with re-utilization of the by-products could be a future solution to the global threat of plastic waste accumulation. Here, we report that the saliva of Galleria mellonella larvae (wax worms) is capable of oxidizing and depolymerizing polyethylene (PE), one of the most produced and sturdy polyolefin-derived plastics. This effect is achieved after a few hours’ exposure at room temperature under physiological conditions (neutral pH). The wax worm saliva can overcome the bottleneck step in PE biodegradation, namely the initial oxidation step. Within the saliva, we identify two enzymes, belonging to the phenol oxidase family, that can reproduce the same effect. To the best of our knowledge, these enzymes are the first animal enzymes with this capability, opening the way to potential solutions for plastic waste management through bio-recycling/up-cycling

Nursing Care of Patients With Cirrhosis: The LiverHope Nursing Project

Cirrhosis is a complex disease that is associated with disturbances in different organs besides the liver, including kidneys, heart, arterial circulation, lungs, gut, and brain. As a consequence, patients develop a number of complications that result in frequent hospital admissions and high morbidity and mortality. Patients with cirrhosis require constant and rigorous monitoring both in and outside the hospital. In this context, the role of nurses in the care of patients with cirrhosis has not been sufficiently emphasized and there is very limited information about nursing care of patients with cirrhosis compared with other chronic diseases. The current article provides a review of nursing care for the different complications of patients with cirrhosis. Nurses with specific knowledge on liver diseases should be incorporated into multidisciplinary teams managing patients with cirrhosis, both inpatient and outpatient. Conclusion: Nurses play an important role in the management and prevention of complications of the disease and improvement in patients’ quality of life and bridge the gap between clinicians and families, between primary care and hospital care, and provide medical education to patients and caregivers

Reconstruction of the equation of state for the cyclic universes in homogeneous and isotropic cosmology

We study the cosmological evolutions of the equation of state (EoS) for the universe in the homogeneous and isotropic Friedmann-Lema\^{i}tre-Robertson-Walker (FLRW) space-time. In particular, we reconstruct the cyclic universes by using the Weierstrass and Jacobian elliptic functions. It is explicitly illustrated that in several models the universe always stays in the non-phantom (quintessence) phase, whereas there also exist models in which the crossing of the phantom divide can be realized in the reconstructed cyclic universes.Comment: 29 pages, 8 figures, version accepted for publication in Central European Journal of Physic

Screening of cosmological constant for De Sitter Universe in non-local gravity, phantom-divide crossing and finite-time future singularities

We investigate de Sitter solutions in non-local gravity as well as in non-local gravity with Lagrange constraint multiplier. We examine a condition to avoid a ghost and discuss a screening scenario for a cosmological constant in de Sitter solutions. Furthermore, we explicitly demonstrate that three types of the finite-time future singularities can occur in non-local gravity and explore their properties. In addition, we evaluate the effective equation of state for the universe and show that the late-time accelerating universe may be effectively the quintessence, cosmological constant or phantom-like phases. In particular, it is found that there is a case in which a crossing of the phantom divide from the non-phantom (quintessence) phase to the phantom one can be realized when a finite-time future singularity occurs. Moreover, it is demonstrated that the addition of an $R^2$ term can cure the finite-time future singularities in non-local gravity. It is also suggested that in the framework of non-local gravity, adding an $R^2$ term leads to possible unification of the early-time inflation with the late-time cosmic acceleration.Comment: 42 pages, no figure, version accepted for publication in General Relativity and Gravitatio

The Search for Supersymmetry at the Tevatron Collider

We review the status of searches for Supersymmetry at the Tevatron Collider. After discussing the theoretical aspects relevant to the production and decay of supersymmetric particles at the Tevatron, we present the current results for Runs Ia and Ib as of the summer of 1997. To appear in the book "Perspectives in Supersymmetry", edited by G.L. Kane, World Scientific.Comment: 84 pages with 31 figures imbedded using psfig.tex. Uses sprocl.st

The two-component system BvrR/BvrS essential for Brucella abortus virulence regulates the expression of outer membrane proteins with counterparts in members of the Rhizobiaceae

The Brucella BvrR/BvrS two-component regulatory system is homologous to the ChvI/ChvG systems of Sinorhizobium meliloti and Agrobacterium tumefaciens necessary for endosymbiosis and pathogenicity in plants. BvrR/BvrS controls cell invasion and intracellular survival. Probing the surface of bvrR and bvrS transposon mutants with monoclonal antibodies showed all described major outer membrane proteins (Omps) but Omp25, a protein known to be involved in Brucella virulence. Absence of Omp25 expression was confirmed by two-dimensional electrophoresis of envelope fractions and by gene reporter studies. The electrophoretic analysis also revealed reduction or absence in the mutants of a second set of protein spots that by matrix-assisted laser desorption ionization MS and peptide mass mapping were identified as a non-previously described Omp (Omp3b). Because bvrR and bvrS mutants are also altered in cell-surface hydrophobicity, permeability, and sensitivity to surf ace-targeted bactericidal peptides, it is proposed that BvrR/BvrS controls cell envelope changes necessary to transit between extracellular and intracellular environments. A genomic search revealed that Omp25 (Omp3a) and Omp3b belong to a family of Omps of plant and animal cell-associated alpha-Proteobacteria, which includes Rhizobium leguminosarum RopB and A. tumefaciens AopB. Previous work has shown that RopB is not expressed in bacteroids, that AopB is involved in tumorigenesis, and that dysfunction of A. tumetaciens ChvI/ChvG alters surface properties. It is thus proposed that the BvrR/BvrS and Omp3 homologues of the cell-associated a-Proteobacteria play a role in bacterial surface control and host cell interactions