Background. The association between bacteremia by Streptococcus gallolyticus subsp. gallolyticus (SGG) and colorectal neoplasia (CRN) is well established but the frequency of the association varies ...widely in different studies. We conducted a case-control study to assess the association between SGG bacteremia and CRN. Methods. An analysis of all SGG bacteremias was performed during the period 1988-2011. The frequency of CRN in patients with SGG bacteremia was compared with the frequency of CRN in a symptomatic control group of patients matched at a 1:2 ratio for gender and age (±3 years) without S. bovis bacteremia and personal history of CRN and with increased risk of CRN (by the presence of symptoms, signs, or test suspicious of colonic pathology or by family history of CRN). Results. One hundred nine cases of SGG bacteremia were detected (mean age, 66 years; 87% male). Colonoscopy was performed in 98 cases, diagnosing 69 cases of CRN: 57 adenomas (39 advanced adenomas) and 12 invasive carcinomas. Only 4 cases had suspected CRN before the blood culture. The prevalence of CRN was higher in patients with SGG bacteremia than in the 196 control patients (70% vs 32%; odds ratio OR, 5.1; 95% confidence interval CI, 3.0-8.6). This difference was not significant when comparing nonadvanced adenomas (19% vs 12%), but we found significant differences in advanced adenomas (40% vs 16%; OR, 3.5; 95% CI, 2.0-6.1) and invasive carcinomas (12% vs 5%; OR, 2.9; 95% CI, 1.2-6.9). Conclusions. The frequency of CRN among SGG infected patients is significantly increased compared with symptomatic age-matched controls, indicating that SGG infection is a strong indicator for underlying occult malignancy.
Novel reinforced cross‐linked lysozyme crystals containing homogeneous dispersions of single‐walled carbon nanotubes bundles (SWCNTs) are produced and characterized. The incorporation of SWCNTs ...inside lysozyme crystals gives rise to reinforced composite materials with tunable mechanical strength and electronic conductivity, while preserving the crystal quality and morphology. These reinforced crystals show increased catalytic activity at higher temperatures, being active even above the denaturation temperature. The electron transport through the crystals is linked to the content and distribution of SWCNT bundles inside the crystals. The electron conduction through the crystals is isotropic and very efficient, presenting high conductivity values up to 600 nS at very low (0.05 wt%) SWCNT concentration. To obtain these crystals, a new protocol based on the in situ crystallization of lysozyme in composite SWCNT–peptide hydrogels is developed. These peptide hydrogels are able to homogeneously disperse bundles of hydrophobic SWCNTs allowing first, the crystallization of the enzyme lysozyme and second, transferring the new properties of the inorganic component to the crystals. Taken together, these composite crystals represent an example of the versatility of proteins as biological substrates in the generation of novel functional materials, opening the door to use them in catalysis and bioelectronics at macroscale.
Novel composite materials based on the incorporation of single‐walled carbon nanotubes inside lysozyme crystals are produced. The inclusion of carbon nanotubes gives rise to crystals with tunable mechanical strength and electronic conductivity. The catalytic activity of these reinforced crystals improves at higher temperature. These crystals are obtained by an in situ lysozyme crystallization in composite peptide–carbon nanotube hydrogels.
Aims
Data on the impact of COVID‐19 in chronic heart failure (CHF) patients and its potential to trigger acute heart failure (AHF) are lacking. The aim of this work was to study characteristics, ...cardiovascular outcomes and mortality in patients with confirmed COVID‐19 infection and a prior diagnosis of heart failure (HF). Further aims included the identification of predictors and prognostic implications for AHF decompensation during hospital admission and the determination of a potential correlation between the withdrawal of HF guideline‐directed medical therapy (GDMT) and worse outcomes during hospitalization.
Methods and results
Data for a total of 3080 consecutive patients with confirmed COVID‐19 infection and follow‐up of at least 30 days were analysed. Patients with a previous history of CHF (n = 152, 4.9%) were more prone to the development of AHF (11.2% vs. 2.1%; P < 0.001) and had higher levels of N‐terminal pro brain natriuretic peptide. In addition, patients with previous CHF had higher mortality rates (48.7% vs. 19.0%; P < 0.001). In contrast, 77 patients (2.5%) were diagnosed with AHF, which in the vast majority of cases (77.9%) developed in patients without a history of HF. Arrhythmias during hospital admission and CHF were the main predictors of AHF. Patients developing AHF had significantly higher mortality (46.8% vs. 19.7%; P < 0.001). Finally, the withdrawal of beta‐blockers, mineralocorticoid receptor antagonists and angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant increase in in‐hospital mortality.
Conclusions
Patients with COVID‐19 have a significant incidence of AHF, which is associated with very high mortality rates. Moreover, patients with a history of CHF are prone to developing acute decompensation after a COVID‐19 diagnosis. The withdrawal of GDMT was associated with higher mortality.
Heart failure in COVID‐19 patients: prevalence, incidence and prognostic implications.
Here we perform whole-exome sequencing of samples from 105 individuals with chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in Western countries. We found 1,246 somatic ...mutations potentially affecting gene function and identified 78 genes with predicted functional alterations in more than one tumor sample. Among these genes, SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7% of affected individuals. Further analysis in 279 individuals with CLL showed that SF3B1 mutations were associated with faster disease progression and poor overall survival. This work provides the first comprehensive catalog of somatic mutations in CLL with relevant clinical correlates and defines a large set of new genes that may drive the development of this common form of leukemia. The results reinforce the idea that targeting several well-known genetic pathways, including mRNA splicing, could be useful in the treatment of CLL and other malignancies.
Recent experiments have reported a novel transition to elasto-inertial turbulence in the Taylor–Couette flow of a dilute polymer solution. Unlike previously reported transitions, this newly ...discovered scenario, dubbed vortex merging and splitting (VMS) transition, occurs in the centrifugally unstable regime and the mechanisms underlying it are two-dimensional: the flow becomes chaotic due to the proliferation of events where axisymmetric vortex pairs may be either created (vortex splitting) or annihilated (vortex merging). In this paper, we present direct numerical simulations, using the finitely extensible nonlinear elastic-Peterlin (FENE-P) constitutive equation to model the polymer dynamics, which reproduce the experimental observations with great accuracy and elucidate the reasons for the onset of this surprising dynamics. Starting from the Newtonian limit and increasing progressively the fluid's elasticity, we demonstrate that the VMS dynamics is not associated with the well-known Taylor vortices, but with a steady pattern of elastically induced axisymmetric vortex pairs known as diwhirls. The amount of angular momentum carried by these elastic vortices becomes increasingly small as the fluid's elasticity increases and it eventually reaches a marginal level. When this occurs, the diwhirls become dynamically disconnected from the rest of the system and move independently from each other in the axial direction. It is shown that vortex merging and splitting events, along with local transient chaotic dynamics, result from the interactions among diwhirls, and that this complex spatio-temporal dynamics persists even at elasticity levels twice as large as those investigated experimentally.
BACKGROUNDEndothelial dysfunction is a crucial step in atherosclerosis development, and its severity is determinant for the risk of cardiovascular recurrence. Diet may be an effective strategy to ...protect the endothelium, although there is no consensus about the best dietary model. The CORonary Diet Intervention with Olive oil and cardiovascular PREVention (CORDIOPREV) study is an ongoing prospective, randomized, single-blind, controlled trial in 1,002 coronary heart disease (CHD) patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat versus Mediterranean diet) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study: to evaluate the effect of these diets on endothelial function, assessed by flow-mediated dilation (FMD) of the brachial artery. METHODS AND FINDINGSFrom the total participants taking part in the CORDIOPREV study, 805 completed endothelial function study at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids MUFAs, and <50% carbohydrates) or a low-fat diet (28% fat, 12% MUFAs, and >55% carbohydrates), with endothelial function measurement repeated after 1 year. As secondary objectives and to explore different underlying mechanisms in the modulation of endothelial function, we quantified endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) and evaluated, in 24 preselected patients, in vitro cellular processes related to endothelial damage (reactive oxygen species, apoptosis, and senescence) and endothelial repair (cell proliferation and angiogenesis), as well as other modulators (micro-RNAs miRNAs and proteins). Patients who followed the Mediterranean diet had higher FMD (3.83%; 95% confidence interval CI: 2.91-4.23) compared with those in the low-fat diet (1.16%; 95% CI: 0.80 to 1.98) with a difference between diets of 2.63% (95% CI: 1.89-3.40, p = 0.011), even in those patients with severe endothelial dysfunction. We observed higher EPC levels (group difference: 1.64%; 95% CI: 0.79-2.13, p = 0.028) and lower EMPs (group difference: -755 EMPs/μl; 95% CI: -1,010 to -567, p = 0.015) after the Mediterranean diet compared with the low-fat diet in all patients. We also observed lower intracellular reactive oxygen species (ROS) production (group difference: 11.1; 95% CI: 2.5 to 19.6, p = 0.010), cellular apoptosis (group difference: -20.2; 95% CI: -26.7 to -5.11, p = 0.013) and senescence (18.0; 95% CI: 3.57 to 25.1, p = 0.031), and higher cellular proliferation (group difference: 11.3; 95% CI: 4.51 to 13.5, p = 0.011) and angiogenesis (total master segments length, group difference: 549; 95% CI: 110 to 670, p = 0.022) after the Mediterranean diet than the low-fat diet. Each dietary intervention was associated with distinct changes in the epigenetic and proteomic factors that modulate biological process associated with endothelial dysfunction. The evaluation of endothelial function is a substudy of the CORDIOPREV study. As in any substudy, these results should be treated with caution, such as the potential for false positives because of the exploratory nature of the analyses. CONCLUSIONSOur results suggest that the Mediterranean diet better modulates endothelial function compared with a low-fat diet and is associated with a better balance of vascular homeostasis in CHD patients, even in those with severe endothelial dysfunction. CLINICAL TRIAL REGISTRATIONURL, http://www.cordioprev.es/index.php/en. clinicaltrials.gov number NCT00924937.
The drag of turbulent flows can be drastically decreased by adding small amounts of high molecular weight polymers. While drag reduction initially increases with polymer concentration, it eventually ...saturates to what is known as the maximum drag reduction (MDR) asymptote; this asymptote is generally attributed to the dynamics being reduced to a marginal yet persistent state of subdued turbulent motion. Contrary to this accepted view, we show that, for an appropriate choice of parameters, polymers can reduce the drag beyond the suggested asymptotic limit, eliminating turbulence and giving way to laminar flow. At higher polymer concentrations, however, the laminar state becomes unstable, resulting in a fluctuating flow with the characteristic drag of the MDR asymptote. Our findings indicate that the asymptotic state is hence dynamically disconnected from ordinary turbulence.
Price elasticities of energy demand have become increasingly relevant in estimating the socio-economic and environmental effects of energy policies or other events that influence the price of energy ...goods. Since the 1970s, a large number of academic papers have provided both short and long-term price elasticity estimates for different countries using several models, data and estimation techniques. Yet the literature offers a rather wide range of estimates for the price elasticities of demand for energy. This paper quantitatively summarizes the recent, but sizeable, empirical evidence to facilitate a sounder economic assessment of (in some cases policy-related) energy price changes. It uses meta-analysis to identify the main factors affecting short and long term elasticity results for energy, in general, as well as for specific products, i.e., electricity, natural gas, gasoline, diesel and heating oil.
•An updated and wider meta-analysis on price elasticities of energy demand.•Energy goods are shown to be price inelastic both in the short and long-term.•Results are relevant for a proper design and implementation of energy policies.•Our results refer to energy, as a whole, and specific energy goods.
Achieving and maintaining a high-quality response is the treatment goal for patients with newly diagnosed multiple myeloma (NDMM). The phase 3 PETHEMA/GEM2012 study, in 458 patients aged ≤65 years ...with NDMM, is evaluating bortezomib (subcutaneous) + lenalidomide + dexamethasone (VRD) for 6 cycles followed by autologous stem cell transplant (ASCT) conditioned with IV busulfan + melphalan vs melphalan and posttransplant consolidation with 2 cycles of VRD. We present grouped response analysis of induction, transplant, and consolidation. Responses deepened over time; in patients who initiated cycle 6 of induction (n = 426), the rates of a very good partial response or better were 55.6% by cycle 3, 63.8% by cycle 4, 68.3% by cycle 5, and 70.4% after induction. The complete response rate of 33.4% after induction in the intent-to-treat (ITT) population, which was similar in the 92 patients with high-risk cytogenetics (34.8%), also deepened with further treatment (44.1% after ASCT and 50.2% after consolidation). Rates of undetectable minimal residual disease (median 3 × 10−6 sensitivity) in the ITT population also increased from induction (28.8%) to transplant (42.1%) and consolidation (45.2%). The most common grade ≥3 treatment-emergent adverse events during induction were neutropenia (12.9%) and infection (9.2%). Grade ≥2 peripheral neuropathy (grouped term) during induction was 17.0%, with a low frequency of grade 3 (3.7%) and grade 4 (0.2%) events. VRD is an effective and well-tolerated regimen for induction in NDMM with deepening response throughout induction and over the course of treatment. This trial was registered at www.clinicaltrials.gov as #NCT01916252 and EudraCT as #2012-005683-10.
•VRD was effective and well tolerated before ASCT; 33.4% complete response/28.8% minimal residual disease–negative after 6 induction cycles.•Responses deepened with VRD throughout induction and over the course of treatment with few discontinuations due to toxicity.
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Marine Environmental Epigenetics Eirin-Lopez, Jose M; Putnam, Hollie M
Annual review of marine science,
01/2019, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Marine organisms' persistence hinges on the capacity for acclimatization and adaptation to the myriad of interacting environmental stressors associated with global climate change. In this context, ...epigenetics-mechanisms that facilitate phenotypic variation through genotype-environment interactions-are of great interest ecologically and evolutionarily. Our comprehensive review of marine environmental epigenetics guides our recommendations of four key areas for future research: the dynamics of wash-in and wash-out of epigenetic effects, the mechanistic understanding of the interplay of different epigenetic marks and the interaction with the microbiome, the capacity for and mechanisms of transgenerational epigenetic inheritance, and the evolutionary implications of the interaction of genetic and epigenetic features. Emerging insights in marine environmental epigenetics can be applied to critical issues such as aquaculture, biomonitoring, and biological invasions, thereby improving our ability to explain and predict the responses of marine taxa to global climate change.
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