The development of composites with antibacterial activity represents an important strategy to avoid side effects such as increasing bacterial resistance to antibiotics. In particular, the green ...synthesis of metal nanoparticles avoids the use of hazardous chemical compounds and introduces the intrinsic beneficial properties of plant-derived compounds. Herein, the reduction of gold salt into metal nanoparticles was provided by the action of a cationic polymer derived from tannin (Tanfloc®). Comparative activity of antibacterial agents (pure Tanfloc and Au NPs—Tanfloc) at different concentrations were evaluated in terms of the antibiofilm activity, kill-time assays and inhibition haloes confirming the antibacterial activity of the Tanfloc that is reinforced by the incorporation of reduced gold nanoparticles, resulting in the complete elimination of S. aureus from an initial concentration of 108 CFU/mL after 120 min of reaction of Au NPs + Tanfloc solution in association with strong inhibition of the biofilm formation attributed to the Tanfloc.
Aging infrastructure and growing interests in river restoration have led to a substantial rise in dam removals in the United States. However, the decision to remove a dam involves many complex ...trade-offs. The benefits of dam removal for hazard reduction and ecological restoration are potentially offset by the loss of hydroelectricity production, water supply, and other important services. We use a multiobjective approach to examine a wide array of trade-offs and synergies involved with strategic dam removal at three spatial scales in New England. We find that increasing the scale of decision-making improves the efficiency of trade-offs among ecosystem services, river safety, and economic costs resulting from dam removal, but this may lead to heterogeneous and less equitable local-scale outcomes. Our model may help facilitate multilateral funding, policy, and stakeholder agreements by analyzing the trade-offs of coordinated dam decisions, including net benefit alternatives to dam removal, at scales that satisfy these agreements.
On 25 August 2018 the interplanetary counterpart of the 20 August 2018 coronal mass ejection (CME) hit Earth, giving rise to a strong G3 geomagnetic storm. We present a description of the whole ...sequence of events from the Sun to the ground as well as a detailed analysis of the observed effects on Earth's environment by using a multi-instrumental approach.
We studied the ICME (interplanetary-CME) propagation in interplanetary space up to the analysis of its effects in the magnetosphere, ionosphere and at ground level. To accomplish this task, we used ground- and space-collected data, including data from CSES (China Seismo-Electric Satellite), launched on 11 February 2018. We found a direct connection between the ICME impact point on the magnetopause and the pattern of Earth's auroral electrojets. Using the Tsyganenko TS04 model prevision, we were able to correctly identify the principal magnetospheric current system activating during the different phases of the geomagnetic storm. Moreover, we analysed the space weather effects associated with the 25 August 2018 solar event in terms of the evaluation of geomagnetically induced currents (GICs) and identification of possible GPS (Global Positioning System) losses of lock. We found that, despite the strong geomagnetic storm, no loss of lock had been detected. On the contrary, the GIC hazard was found to be potentially more dangerous than other past, more powerful solar events, such as the 2015 St Patrick's Day geomagnetic storm, especially at latitudes higher than 60∘ in the European sector.
In nature, confrontations between conspecifics are recurrent and related, in general, due to the lack of resources such as food and territory. Adequate defence against a conspecific aggressor is ...essential for the individual's survival and the group integrity. However, repeated social defeat is a significant stressor promoting several behavioural changes, including social defence
. What would be the neural basis of these behavioural changes? To build new hypotheses about this, we here investigate the effects of repeated social stress on the neural circuitry underlying motivated social defence behaviour in male mice. We observed that animals re-exposed to the aggressor three times spent more time in passive defence during the last exposure than in the first one. These animals also show less activation of the amygdalar and hypothalamic nuclei related to the processing of conspecific cues. In turn, we found no changes in the activation of the hypothalamic dorsal pre-mammillary nucleus (PMD) that is essential for passive defence. Therefore, our data suggest that the balance between the activity of circuits related to conspecific processing and the PMD determines the pattern of social defence behaviour. Changes in this balance may be the basis of the adaptations in social defence after repeated social defeat.
Mutations in the
aquaporin AQP2 are associated with resistance to pentamidine and melarsoprol. We show that TbAQP2 but not TbAQP3 was positively selected for increased pore size from a common ...ancestor aquaporin. We demonstrate that TbAQP2's unique architecture permits pentamidine permeation through its central pore and show how specific mutations in highly conserved motifs affect drug permeation. Introduction of key TbAQP2 amino acids into TbAQP3 renders the latter permeable to pentamidine. Molecular dynamics demonstrates that permeation by dicationic pentamidine is energetically favourable in TbAQP2, driven by the membrane potential, although aquaporins are normally strictly impermeable for ionic species. We also identify the structural determinants that make pentamidine a permeant although most other diamidine drugs are excluded. Our results have wide-ranging implications for optimising antitrypanosomal drugs and averting cross-resistance. Moreover, these new insights in aquaporin permeation may allow the pharmacological exploitation of other members of this ubiquitous gene family.
In a prospective, multicenter, open‐label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) ...everolimus initiation with reduced‐exposure tacrolimus (EVR+Reduced TAC) or (iii) standard‐exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy‐proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (−3.0%; 95% CI −8.7, 2.6%; p<0.001 for noninferiority 12% margin). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m2, 97.5% CI 3.74, 13.27 mL/min/1.73 m2, p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation.
This prospective, randomized, multicenter, open‐label study in de novo liver transplant patients shows that initiation of everolimus at day 30 posttransplant facilitates tacrolimus minimization but not elimination, and results in comparable efficacy and superior renal function but increased adverse events compared to a standard tacrolimus exposure regimen.
DNA polymerase theta (Polθ), a member of the DNA polymerase family A, exhibits a polymerase C-terminal domain, a central domain, and an N-terminal helicase domain. Polθ plays important roles in DNA ...repair via its polymerase domain, regulating genome integrity. In addition, in mammals, Polθ modulates origin firing timing and MCM helicase recruitment to chromatin. In contrast, as a model eukaryote, Trypanosoma cruzi exhibits two individual putative orthologs of Polθ in different genomic loci; one ortholog is homologous to the Polθ C-terminal polymerase domain, and the other is homologous to the Polθ helicase domain, called Polθ-polymerase and Polθ-helicase, respectively. A pull-down assay using the T. cruzi component of the prereplication complex Orc1/Cdc6 as bait captured Polθ-helicase from the nuclear extract. Orc1/Cdc6 and Polθ-helicase directly interacted, and Polθ-helicase presented DNA unwinding and ATPase activities. A T. cruzi strain overexpressing the Polθ-helicase domain exhibited a significantly decreased amount of DNA-bound MCM7 and impaired replication origin firing. Taken together, these data suggest that Polθ-helicase modulates DNA replication by directly interacting with Orc1/Cdc6, which reduces the binding of MCM7 to DNA and thereby impairs the firing of replication origins.
No trial has investigated the long-term outcome of everolimus (EVR)-incorporating immunosuppression vs tacrolimus (TAC) and mycophenolate mofetil (MMF) after liver transplantation.
With a propensity ...score methodology, 178 recipients on TAC and MMF were compared to 178 patients on TAC and EVR.
At a median (interquartile range) follow-up of 45 (46.3) months, the probability of treated biopsy-proven acute rejection, graft loss, and death was 36.6% for MMF and 28.1% for EVR (P = .0891). Treated biopsy-proven acute rejection was numerically lower for EVR (3.3% vs 7.3%, P = .09), while adverse events (70.2% vs 58.9%, P = .02) and drug discontinuations (21.3% vs 11.8%, P = .01) were significantly higher with regard to hypercholesterolemia (P = .001), thrombocytopenia (P = .0062), and edema (P = .0107). Patients on MMF showed more hypertension (P = .0315), tremor (P = .0006), cytomegalovirus infection (P = .0165), and malignancies (P = .0175). EVR was associated with lesser deterioration in mean (SD) renal function at the latest follow-up (−2.2 (1.8) vs −5.1 (3.2) mL/min/1.73 m2, t = 3.6, P = .005).
The efficacy of the combination of TAC and EVR is comparable to that of TAC and MMF. Drug discontinuations and adverse events were higher for patients on EVR, but these latter showed less hypertension, cytomegalovirus infection, and renal dysfunction. The observed reduction in posttransplant malignancies for EVR requires longer follow-up to be confirmed.
•So far, no trial has investigated the long-term outcome of everolimus everolimus-incorporating immunosuppression versus tacrolimus and mycophenolate mofetil after liver transplantation.•With a propensity score methodology, 178 recipients on tacrolimus and mycophenolate mofetil were retrospectively compared to 178 patients on tacrolimus and everolimus.•Treated biopsy-proven acute rejection was numerically lower for everolimus, while adverse events and drug discontinuations were higher, in regard to hypercholesterolemia (P = .001), thrombocytopenia (P = .0062), and edema (P = .0107).•Patients on tacrolimus and mycophenolate showed more hypertension (P = .0315), tremor (P = .0006), cytomegalovirus infection (P = .0165), and malignancies (P = .0175).•Everolimus was associated with less deterioration in renal function at the latest follow-up.
Mineral deficiencies are prevalent in human populations and the improvement of the mineral content in cereal products represents a possible strategy to increase the human mineral intake. ...Nevertheless, most of the inorganic phosphorus (P
i) present in mature cereal seeds (40–80%) is stored as phytate, an anti-nutritional factor that forms complexes with minerals such as Ca, Mg, Zn and Fe reducing their bioavailability. The present study was undertaken: (i) to determine the variation in phytate and mineral concentrations in the whole grains of 84 Italian durum wheat (
Triticum durum Desf.) cultivars representative of old and modern germplasm; (ii) to estimate the magnitude of genotype
×
environment interaction effects; and (iii) to examine the interrelationships among mineral concentrations in durum wheat with the final aim to identify superior durum wheat cultivars that possess low phytate content and high concentration of mineral elements in their whole-wheat flour. The cultivars were grown in field trials during 2004–2005 at Foggia, Italy and during 2005–2006 at Foggia and Fiorenzuola d’Arda—Southern and Northern Italy. The phytate content was estimated indirectly by using a microtitre plate assay evaluating the P
i absorbance at 820
nm, while the Cu, Fe, Mn, Ca, K, Mg, Na and Zn mineral contents were determined by ICP/OES. The contents of Zn and Fe across years and locations ranged from 28.5 to 46.3
mg/kg for Zn with an average of 37.4
mg/kg and from 33.6 to 65.6
mg/kg for Fe with an average of 49.6
mg/kg. P
i grain content was between 0.46 and 0.76
mg/g showing a positive correlation with all minerals except Cu and Zn. Although breeding activity for Fe and Zn would be difficult because G
×
E interaction is prevalent, multi-location evaluation of germplasm collection help to identify superior genotypes to achieve this objective. The results here reported open the possibility of designing a specific breeding program for improving the nutritional value of durum wheat through the identification of parental lines with low-P
i and high minerals concentration in whole grains.
Flap necrosis continues to occur in skin free flap autologous breast reconstruction. Therefore, we investigated the benefits of indocyanine green angiography (ICGA) using quantitative parameters for ...the objective, perioperative evaluation of flap perfusion. In addition, we investigated the feasibility of hyperspectral (HSI) and thermal imaging (TI) for postoperative flap monitoring.
A single-center, prospective observational study was performed on 15 patients who underwent deep inferior epigastric perforator (DIEP) flap breast reconstruction (n=21). DIEP-flap perfusion was evaluated using ICGA, HSI, and TI using a standardized imaging protocol. The ICGA perfusion curves and derived parameters, HSI extracted oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) values, and flap temperatures from TI were analyzed and correlated to the clinical outcomes.
Post-hoc quantitative analysis of intraoperatively collected data of ICGA application accurately distinguished between adequately and insufficiently perfused DIEP flaps. ICG perfusion curves identified the lack of arterial inflow (n=2) and occlusion of the venous outflow (n=1). In addition, a postoperatively detected partial flap epidermolysis could have been predicted based on intraoperative quantitative ICGA data. During postoperative monitoring, HSI was used to identify impaired perfusion areas within the DIEP flap based on deoxyHb levels. The results of this study showed a limited added value of TI.
Quantitative, post-hoc analysis of ICGA data produced objective and reproducible parameters that enabled the intraoperative detection of arterial and venous congested DIEP flaps. HSI appeared to be a promising technique for postoperative flap perfusion assessment. A diagnostic accuracy study is needed to investigate ICGA and HSI parameters in real-time and demonstrate their clinical benefit.
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