Comparative Analysis of the Inhibitory Mechanism of Aß1-42 Aggregation by Diruthenium Complexes.

There is a growing interest in the search for metal-based therapeutics for protein misfolding disorders such as Alzheimer's disease (AD). A novel and largely unexplored class of metallodrugs is constituted by paddlewheel diruthenium complexes, which exhibit unusual water solubility and stability and unique coordination modes to proteins. Here, we investigate the ability of the complexes [Ru2Cl(DPhF)(O2CCH3)3]·H2O (1), [Ru2Cl(DPhF)2(O2CCH3)2]·H2O (2), and K2[Ru2(DPhF)(CO3)3]·3H2O (3) (DPhF- = N,N'-diphenylformamidinate) to interfere with the amyloid aggregation of the Aß1-42 peptide. These compounds differ in charge and steric hindrance due to the coordination of a different number of bulky ligands. The mechanisms of action of the three complexes were studied by employing a plethora of physicochemical and biophysical techniques as well as cellular assays. All these studies converge on different mechanisms of inhibition of amyloid fibrillation: complexes 1 and 2 show a clear inhibitory effect due to an exchange ligand process in the Ru2 unit aided by aromatic interactions. Complex 3 shows no inhibition of aggregation, probably due to its negative charge in solution. This study demonstrates that slight variations in the ligands surrounding the bimetallic core can modulate the amyloid aggregation inhibition and supports the use of paddlewheel diruthenium complexes as promising therapeutics for Alzheimer's disease.

The significance of metabolic alkalosis on acute decompensated heart failure: the ALCALOTIC study.

AIMS: To determine the prevalence and the impact on prognosis of metabolic alkalosis (MA) in patients admitted for acute heart failure (AHF). METHODS AND RESULTS: The ALCALOTIC is a multicenter, observational cohort study that prospectively included patients admitted for AHF. Patients were classified into four groups according to their acid-base status on admission: acidosis, MA, respiratory alkalosis, and normal pH (reference group for comparison). Primary endpoint was all-cause in-hospital mortality, and secondary endpoints included 30/90-day all-cause mortality, all-cause readmission, and readmission for HF. Associations between endpoints and acid-base alterations were estimated in a multivariate Cox regression model including sex, age, comorbidities, and Barthel index and expressed as hazard ratio (HR) with 95% confidence interval (95% CI). Six hundred sixty-five patients were included (84 years and 57% women), and 40% had acid-base alterations on admission: 188 (28%) acidosis and 78 (12%) alkalosis. The prevalence (95% CI) of MA was 9% (6.8-11.2%). Patients with MA were more women; had fewer comorbidities, better renal function, and higher left ventricle ejection fraction values; and received more treatment with oral acetazolamide during hospitalization and at discharge. MA was not associated with a higher risk of in-hospital mortality and 30/90-day all-cause mortality or readmissions but was associated with a significant increase in readmissions for HF at 30 and 90 days (adjusted HR [95% CI] 3.294 [1.397-7.767], p = 0.006 and 2.314 [1.075-4.978], p = 0.032). CONCLUSION: The prevalence of MA in patients admitted for AHF was 9%, and its presence was associated with more readmissions for HF but not with all-cause mortality.

A Diruthenium Metallodrug as a Potent Inhibitor of Amyloid-ß Aggregation: Synergism of Mechanisms of Action.

The physical and chemical properties of paddlewheel diruthenium compounds are highly dependent on the nature of the ligands surrounding the bimetallic core. Herein, we compare the ability of two diruthenium compounds, [Ru2Cl(D-p-FPhF)(O2CCH3)3]·H2O (1) (D-p-FPhF- = N,N'-bis(4-fluorophenyl)formamidinate) and K3[Ru2(O2CO)4]·3H2O (2), to act as inhibitors of amyloid aggregation of the Aß1-42 peptide and its peculiar fragments, Aß1-16 and Aß21-40. A wide range of biophysical techniques has been used to determine the inhibition capacity against aggregation and the possible mechanism of action of these compounds (Thioflavin T fluorescence and autofluorescence assays, UV-vis absorption spectroscopy, circular dichroism, nuclear magnetic resonance, mass spectrometry, and electron scanning microscopy). Data show that the most effective inhibitory effect is shown for compound 1. This compound inhibits fiber formation and completely abolishes the cytotoxicity of Aß1-42. The antiaggregatory capacity of this complex can be explained by a binding mechanism of the dimetallic units to the peptide chain along with π-π interactions between the formamidinate ligand and the aromatic side chains. The results suggest the potential use of paddlewheel diruthenium complexes as neurodrugs and confirm the importance of the steric and charge effects on the properties of diruthenium compounds.

Steric hindrance and charge influence on the cytotoxic activity and protein binding properties of diruthenium complexes.

Paddlewheel diruthenium complexes are being used as metal-based drugs. It has been proposed that their charge and steric properties determine their selectivity towards proteins. Here, we explore these parameters using the first water-soluble diruthenium complex bearing two formamidinate ligands, [Ru2Cl(DPhF)2(O2CCH3)2], and two derivatives, [Ru2Cl(DPhF)(O2CCH3)3] and K2[Ru2(DPhF)(CO3)3] (DPhF- = N,N'-diphenylformamidinate), with one formamidinate. Their protein binding properties have been assessed employing hen egg white lysozyme (HEWL). The results confirm the relationship between the type of interaction (coordinate/non-coordinate bonds) and the charge of diruthenium complexes. The crystallization medium is also a key factor. In all cases, diruthenium species maintain the M-M bond and produce stable adducts. The antiproliferative properties of these diruthenium complexes have been evaluated on an eukaryotic cell-based model. Our data show a correlation between the number of the formamidinate ligands and the anticancer activity of the diruthenium derivatives against human epithelial carcinoma cells. Increased cytotoxicity may be related to increased steric hindrance and Ru25+ core electronic density. However, the effect of increasing the lipophilicity of diruthenium species by introducing a second N,N'-diphenylformamidinate must be also considered. This work illustrates a systematic approach to shed light on the relevant properties of diruthenium compounds to design metal-based metallodrugs and diruthenium metalloenzymes.

Thick shells and medially wedged posts increase foot orthoses medial longitudinal arch stiffness: an experimental study.

BACKGROUND: Foot orthoses (FOs) are commonly prescribed devices to attenuate biomechanical deficits and improve physical function in patients with musculoskeletal disorders. It is postulated that FOs provide their effects through the production of reaction forces at the foot-FOs interface. An important parameter to provide these reaction forces is their medial arch stiffness. Preliminary results suggest that adding extrinsic additions to FOs (e.g., rearfoot posts) increases their medial arch stiffness. A better understanding of how FOs medial arch stiffness can be modulated by changing structural factors is necessary to better customise FOs for patients. The objectives of this study were to compare FOs stiffness and force required to lower the FOs medial arch in three thicknesses and two models (with and without medially wedged forefoot-rearfoot posts). METHODS: Two models of FOs, 3D printed in Polynylon-11, were used: (1) without extrinsic additions (mFO), and (2) with forefoot-rearfoot posts and a 6o medial wedge (FO6MW). For each model, three thicknesses (2.6 mm, 3.0 mm, and 3.4 mm) were manufactured. FOs were fixed to a compression plate and vertically loaded over the medial arch at a rate of 10 mm/minute. Two-way ANOVAs and Tukey post-hoc tests with Bonferroni corrections were used to compare medial arch stiffness and force required to lower the arch across conditions. RESULTS: Regardless of the differing shell thicknesses, the overall stiffness was 3.4 times greater for FO6MW compared to mFO (p < 0.001). FOs with 3.4 mm and 3.0 mm thicknesses displayed 1.3- and 1.1- times greater stiffness than FOs with a thickness of 2.6 mm. FOs with a thickness of 3.4 mm also exhibited 1.1 times greater stiffness than FOs with a thickness of 3.0 mm. Overall, the force to lower the medial arch was up to 3.3 times greater for FO6MW than mFO and thicker FOs required greater force (p < 0.001). CONCLUSIONS: An increased medial longitudinal arch stiffness is seen in FOs following the addition of 6o medially inclined forefoot-rearfoot posts, and when the shell is thicker. Overall, adding forefoot-rearfoot posts to FOs is significantly more efficient than increasing shell thickness to enhance these variables should that be the therapeutic aim.

The microbiome of a brownfield highly polluted with mercury and arsenic.

Abandoned brownfields represent a challenge for their recovery. To apply sustainable remediation technologies, such as bioremediation or phytoremediation, indigenous microorganisms are essential agents since they are adapted to the ecology of the soil. Better understanding of microbial communities inhabiting those soils, identification of microorganisms that drive detoxification process and recognising their needs and interactions will significantly improve the outcome of the remediation. With this in mind we have carried out a detailed metagenomic analysis to explore the taxonomic and functional diversity of the prokaryotic and eukaryotic microbial communities in soils, several mineralogically distinct types of pyrometallurgic waste, and groundwater sediments of a former mercury mining and metallurgy site which harbour very high levels of arsenic and mercury pollution. Prokaryotic and eukaryotic communities were identified, which turned out to be more diverse in the surrounding contaminated soils compared to the pyrometallurgic waste. The highest diversity loss was observed in two environments most contaminated with mercury and arsenic (stupp, a solid mercury condenser residue and arsenic-rich soot from arsenic condensers). Interestingly, microbial communities in the stupp were dominated by an overwhelming majority of archaea of the phylum Crenarchaeota, while Ascomycota and Basidiomycota fungi comprised the fungal communities of both stump and soot, results that show the impressive ability of these previously unreported microorganisms to colonize these extreme brownfield environments. Functional predictions for mercury and arsenic resistance/detoxification genes show their increase in environments with higher levels of pollution. Our work establishes the bases to design sustainable remediation methods and, equally important, to study in depth the genetic and functional mechanisms that enable the subsistence of microbial populations in these extremely selective environments.

Effect of Equatorial Ligand Substitution on the Reactivity with Proteins of Paddlewheel Diruthenium Complexes: Structural Studies.

The paddlewheel [Ru2Cl(O2CCH3)4] complex was previously reported to react with the model protein hen egg white lysozyme (HEWL), forming adducts with two diruthenium moieties bound to Asp101 and Asp119 side chains upon the release of one acetate. To study the effect of the equatorial ligands on the reactivity with proteins of diruthenium compounds, X-ray structures of the adducts formed when HEWL reacts with [Ru2Cl(D-p-FPhF)(O2CCH3)3] [D-p-FPhF = N,N'-bis(4-fluorophenyl)formamidinate] under different conditions were solved. [Ru2Cl(D-p-FPhF)(O2CCH3)3] is bonded through their equatorial positions to the Asp side chains. Protein binding occurs cis or trans to D-p-FPhF. Lys or Arg side chains or even main-chain carbonyl groups can coordinate to the diruthenium core at the axial site. Data help to understand the reactivity of paddlewheel diruthenium complexes with proteins, providing useful information for the design of new artificial diruthenium-containing metalloenzymes with potential applications in the fields of catalysis, biomedicine, and biotechnology.

Effective bioremediation of soil from the Burgan oil field (Kuwait) using compost: A comprehensive hydrocarbon and DNA fingerprinting study.

An innovative combination of metagenomic profiling of microbial communities and GC-MS & Pyrolysis-GC-MS fingerprinting methods were used to assess the biodegradation of contaminated soil from the Burgan oil field in Kuwait. The soil was treated with (sludge) compost in microcosms to evaluate the feasibility of this material for bioremediation purposes. The most favourable trial showed a > 80% decrease in TPH, thereby indicating strong potential for full-scale application using a cost-effective technology and thus in line with the principles of the circular economy. The microbial study showed that compost addition enhanced the organic matter and nutrient content of the soil. However, the microorganisms in the compost did not seem to play a relevant role in bioremediation, meaning that compost amendments serve as a biostimulation rather than a bioaugmentation approach. The chemical study of the distinct oil fractions revealed rapidly biodegraded compounds (alkanes, alkyl-aromatics, etc.) and others that were much more refractory (hopanes, benzohopanes, etc.). Of note, although heavy fractions are usually considered recalcitrant to biodegradation, we observed incipient degradation of the asphaltene fraction by means of double-shot thermodesorption and pyrolysis. Finally, chemical fingerprinting also revealed that the treated soil contained some of the compounds found in the compost, such as coprostanol, cholesterol, and plant sterols. This observation would support the use of these compounds as proxies to monitor the effects of compost and to adjust dosages in real-scale bioremediation treatments.

Metagenomic Mining for Esterases in the Microbial Community of Los Rueldos Acid Mine Drainage Formation.

Acid mine drainage (AMD) systems are extremely acidic and are metal-rich formations inhabited by relatively low-complexity communities of acidophiles whose enzymes remain mostly uncharacterized. Indeed, enzymes from only a few AMD sites have been studied. The low number of available cultured representatives and genome sequences of acidophiles inhabiting AMDs makes it difficult to assess the potential of these environments for enzyme bioprospecting. In this study, using naïve and in silico metagenomic approaches, we retrieved 16 esterases from the α/ß-hydrolase fold superfamily with the closest match from uncultured acidophilic Acidobacteria, Actinobacteria (Acidithrix, Acidimicrobium, and Ferrimicrobium), Acidiphilium, and other Proteobacteria inhabiting the Los Rueldos site, which is a unique AMD formation in northwestern Spain with a pH of ∼2. Within this set, only two polypeptides showed high homology (99.4%), while for the rest, the pairwise identities ranged between 4 and 44.9%, suggesting that the diversity of active polypeptides was dominated not by a particular type of protein or highly similar clusters of proteins, but by diverse non-redundant sequences. The enzymes exhibited amino acid sequence identities ranging from 39 to 99% relative to homologous proteins in public databases, including those from other AMDs, thus indicating the potential novelty of proteins associated with a specialized acidophilic community. Ten of the 16 hydrolases were successfully expressed in Escherichia coli. The pH for optimal activity ranged from 7.0 to 9.0, with the enzymes retaining 33-68% of their activities at pH 5.5, which was consistent with the relative frequencies of acid residues (from 54 to 67%). The enzymes were the most active at 30-65°C, retaining 20-61% of their activity under the thermal conditions characterizing Los Rueldos (13.8 ± 0.6°C). The analysis of the substrate specificity revealed the capacity of six hydrolases to efficiently degrade (up to 1,652 ± 75 U/g at pH 8.0 and 30°C) acrylic- and terephthalic-like [including bis(2-hydroxyethyl)-terephthalate, BHET] esters, and these enzymes could potentially be of use for developing plastic degradation strategies yet to be explored. Our assessment uncovers the novelty and potential biotechnological interest of enzymes present in the microbial populations that inhibit the Los Rueldos AMD system.

Dolutegravir plus rilpivirine: benefits beyond viral suppression: DORIPEX retrospective study.

ABSTRACT: Switching dual therapy with dolutegravir (DTG) plus rilpivirine (RPV) was assessed in the SWORD-1 and SWORD-2 studies. Real-life data regarding the immunological impact of this approach on CD4+ and CD8+ T lymphocyte counts and the CD4/CD8 ratio are scarce. We evaluated this strategy on the basis of clinical practice data.A multicentric retrospective cohort study.Treatment-experienced virologically suppressed HIV-1-infected patients who were switched to DTG plus RPV were included. Using different models for paired data, we evaluated the efficacy and immune status in terms of CD4+ and CD8+ T-cell counts and CD4/CD8 ratio at 24 and 48 weeks of treatment.The study population comprised of 524 patients from 34 centers in Spain. Men accounted for 76.9% of patients, with a median age of 53 years. Patients receiving DTG plus RPV reached weeks 24 and 48 in 99.4% and 83.8% of cases, respectively, with only three (0.57%) virological failures. We found a significant decrease in CD8+ T-cell count (log OR -40) at week 24 and an increase in CD4+ T-cell count at week 48 (log OR +22.8). In acquired immunodeficiency syndrome-diagnosed patients, we found a significant increase in the CD4+ T-cell count at week 48 (log OR = 41.7, P = .0038), but no significant changes in the CD8+ T-cell count (log OR = -23.4, P = .54). No differences were found in the CD4/CD8 ratio between the acquired immunodeficiency syndrome subgroup and sex or age.In patients with controlled treatment, dual therapy with DTG plus RPV slightly improved the immune status during the first 48 weeks after switching, not only in terms of CD4+ T-cell count but also in terms of CD8+ T-cell count, with persistently high rates of viral control.

Bacterial inoculant-assisted phytoremediation affects trace element uptake and metabolite content in Salix atrocinerea.

Natural plant-associated microorganisms are of critical importance to plant growth and survival in field conditions under toxic concentrations of trace elements (TE) and these plant-microbial processes can be harnessed to enhance phytoremediation. The total bacterial diversity from grey willow (Salix atrocinerea) on a brownfield heavily-polluted with lead (Pb) and arsenic (As) was studied through pyrosequencing. Culturable bacteria were isolated and in vitro tested for plant growth-promotion (PGP) traits, arsenic (As) tolerance and impact on As speciation. Two of the most promising bacterial strains - the root endophyte Pantoea sp. AV62 and the rhizospheric strain Rhodococcus erythropolis AV96 - were inoculated in field to S. atrocinerea. This bioaugmentation resulted in higher As and Pb concentrations in both, roots and leaves of bacterial-inoculated plants as compared to non-inoculated plants. In consequence, bacterial bioaugmentation also affected parameters related to plant growth, oxidative stress, the levels of phytochelatins and phenylpropanoids, together with the differential expression of genes related to these tolerance mechanisms to TE in leaves. This study extends our understanding about plant-bacterial interactions and provides a solid basis for further bioaugmentation studies aiming to improve TE phytoremediation efficiency and predictability in the field.

Ultrasound-assisted synthesis of water-soluble monosubstituted diruthenium compounds.

The elusive monosubstituted diruthenium complexes [Ru2Cl(DAniF)(O2CMe)3] (1), [Ru2Cl(DPhF)(O2CMe)3] (2), [Ru2Cl(D-p-CNPhF)(O2CMe)3] (3), [Ru2Cl(D-o-TolF)(O2CMe)3] (4), [Ru2Cl(D-m-TolF)(O2CMe)3] (5), [Ru2Cl(D-p-TolF)(O2CMe)3] (6) and [Ru2Cl(p-TolA)(O2CMe)3] (7) have been synthesized using for the first time ultrasound-assisted synthesis to carry out a substitution reaction in metal-metal bonded dinuclear compounds (DAniF- = N,N'-bis(4-anisyl)formamidinate; DPhF- = N,N'-diphenylformamidinate; D-p-CNPhF- = N,N'-bis(4-cyanophenyl)formamidinate; D-o/m/p-TolF- = N,N'-bis(2/3/4-tolyl)formamidinate; p-TolA- = N-4-tolylamidate). This is a simpler and greener method than the tedious procedures described in the literature, and it has permitted to obtain water-soluble complexes with good yields in a short period of time. A synthetic study has been implemented to find the best experimental conditions to prepare compounds 1-7. Two different types of ligands, formamidinate and amidate, have been used to check the generality of the method for the preparation of monosubstituted complexes. Five new compounds (2-6) have been obtained using a formamidinate ligand, the synthesis of the previously described compound 1 has been improved, and an unprecedented monoamidate complex has been achieved (7). The crystal structures of compounds 3 and 7 have been solved by single crystal X-ray diffraction. These compounds show the typical paddlewheel structure with three acetate ligands and one formamidinate (3) or amidate (7) bridging ligand at the equatorial positions. The axial positions are occupied by the chloride ligand giving rise to one-dimensional polymer structures that were previously unknown for monosubstituted compounds.

Activating Killer-Cell Immunoglobulin-Like Receptors Are Associated With the Severity of Coronavirus Disease 2019.

BACKGROUND: Etiopathogenesis of the clinical variability of the coronavirus disease 2019 (COVID-19) remains mostly unknown. In this study, we investigate the role of killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen class-I (HLA-I) interactions in the susceptibility and severity of COVID-19. METHODS: We performed KIR and HLA-I genotyping and natural killer cell (NKc) receptors immunophenotyping in 201 symptomatic patients and 210 noninfected controls. RESULTS: The NKcs with a distinctive immunophenotype, suggestive of recent activation (KIR2DS4low CD16low CD226low CD56high TIGIThigh NKG2Ahigh), expanded in patients with severe COVID-19. This was associated with a higher frequency of the functional A-telomeric activating KIR2DS4 in severe versus mild and/or moderate patients and controls (83.7%, 55.7% and 36.2%, P < 7.7 × 10-9). In patients with mild and/or moderate infection, HLA-B*15:01 was associated with higher frequencies of activating B-telomeric KIR3DS1 compared with patients with other HLA-B*15 subtypes and noninfected controls (90.9%, 42.9%, and 47.3%; P < .002; Pc = 0.022). This strongly suggests that HLA-B*15:01 specifically presenting severe acute respiratory syndrome coronavirus 2 peptides could form a neoligand interacting with KIR3DS1. Likewise, a putative neoligand for KIR2DS4 could arise from other HLA-I molecules presenting severe acute respiratory syndrome coronavirus 2 peptides expressed on infected an/or activated lung antigen-presenting cells. CONCLUSIONS: Our results support a crucial role of NKcs in the clinical variability of COVID-19 with specific KIR/ligand interactions associated with disease severity.

Effects of in situ Remediation With Nanoscale Zero Valence Iron on the Physicochemical Conditions and Bacterial Communities of Groundwater Contaminated With Arsenic.

Nanoscale Zero-Valent Iron (nZVI) is a cost-effective nanomaterial that is widely used to remove a broad range of metal(loid)s and organic contaminants from soil and groundwater. In some cases, this material alters the taxonomic and functional composition of the bacterial communities present in these matrices; however, there is no conclusive data that can be generalized to all scenarios. Here we studied the effect of nZVI application in situ on groundwater from the site of an abandoned fertilizer factory in Asturias, Spain, mainly polluted with arsenic (As). The geochemical characteristics of the water correspond to a microaerophilic and oligotrophic environment. Physico-chemical and microbiological (cultured and total bacterial diversity) parameters were monitored before and after nZVI application over six months. nZVI treatment led to a marked increase in Fe(II) concentration and a notable fall in the oxidation-reduction potential during the first month of treatment. A substantial decrease in the concentration of As during the first days of treatment was observed, although strong fluctuations were subsequently detected in most of the wells throughout the six-month experiment. The possible toxic effects of nZVI on groundwater bacteria could not be clearly determined from direct observation of those bacteria after staining with viability dyes. The number of cultured bacteria increased during the first two weeks of the treatment, although this was followed by a continuous decrease for the following two weeks, reaching levels moderately below the initial number at the end of sampling, and by changes in their taxonomic composition. Most bacteria were tolerant to high As(V) concentrations and showed the presence of diverse As resistance genes. A more complete study of the structure and diversity of the bacterial community in the groundwater using automated ribosomal intergenic spacer analysis (ARISA) and sequencing of the 16S rRNA amplicons by Illumina confirmed significant alterations in its composition, with a reduction in richness and diversity (the latter evidenced by Illumina data) after treatment with nZVI. The anaerobic conditions stimulated by treatment favored the development of sulfate-reducing bacteria, thereby opening up the possibility to achieve more efficient removal of As.

Arsenate-reducing bacteria affect As accumulation and tolerance in Salix atrocinerea.

Arsenic (As)-reducing bacteria are able to influence As-speciation and, in this way, change As bio-availability. In consequence, this has an impact on As uptake by plants growing on polluted soil and on the effectiveness of the phytoremediation process. To be able to efficiently utilize these bacteria for As-phytoremediation in the field, a better understanding of the plant-bacterial interactions involved in As-tolerance or toxicity is needed. In this work, seedlings of a clone of Salix atrocinerea derived from a specimen naturally growing on an As-polluted brownfield were grown under gnotobiotic conditions exposed to As, and in the presence or absence of two of its field-associated and in vitro characterized plant growth-promoting (PGP) bacteria. The inoculation with Pantoea sp., induced a moderate reduction of AsV to AsIII in the exposure medium that, together with a coordinated plant response of As uptake, chelation and sequestration, increased As accumulation in roots; which is reflected into a higher phytostabilization. However, inoculation with Rhodococcus erythropolis due to a higher disproportionate reduction of AsV to AsIII in the medium caused less As accumulation in roots that non-bioaugmented plants and despite the lower As content, the concentrations of AsIII present in the medium and the damage suffered in roots and leaves, indicated that As tolerance mechanisms (such as prevention of AsIII uptake and efflux) did not occur in time to avoid physical disturbance and plants growth reduction. Interestingly, by two different metabolic pathways -coordinated by different key transporters mediating As uptake, tolerance, distribution and vacuolar accumulation at the roots- both bacteria limited As accumulation in Salix shoots. Our results provide for the first time a detailed insight in the plant-bacterial responses and physiological changes contributing to As tolerance in S. atrocinerea, that will facilitate the design of effective strategies for exploitation of plant-associated microorganisms for phytoremediation.

Patient General Condition at Diagnosis: A Systematic Evaluation for Adults Diagnosed with Hematologic Malignancies.

Several societies have published recommendations for evaluating older adults with cancer in standard conditions. It is vital to assure a proper systematic patient condition evaluation, not only in the oldest (geriatric assessment) but in all adult patients. We have investigated the feasibility of a systematic evaluation of the general condition of all patients diagnosed with hematologic malignancies, and the degree of acceptance by the clinical team, in a prospective cohort of 182 consecutive adults, by using the ECOG performance status scale (ECOG, age 18 and over, 18+), Lee Index for Older Adults (LEE, 50+), Geriatric Assessment in Hematology (GAH, 65+), and the Comprehensive Geriatric Assessment (CGA, 75+). Clinical team acceptance was analyzed with a visual analogue scale, and the objective feasibility was calculated as the proportion of patients that could be finally evaluated with each tool. Acceptance was high, but the objective feasibility was progressively lower as the complexity of the different tools increased (ECOG 100%, LEE 99.4%, GAH 93.2%, and CGA 67.9%). LEE and GAH categories showed a weak concordance (Cohen's Kappa 0.24) that was slight between LEE and CGA (Kappa 0.18). Unexpectedly, we found no significant association between the GAH and CGA categories (p = 0.16). We confirm that a systematic evaluation of all adult patients diagnosed with hematologic malignancies is feasible in daily practice by using an age-adapted approach. Direct comparisons among the different predictive tools in regard to patients' tolerance to treatments of different intensities must be a priority research subject in the coming years.

Design and catalytic studies of structural and functional models of the catechol oxidase enzyme.

The catechol oxidase activity of three copper/bicompartmental salen derivatives has been studied. One mononuclear, [CuL] (1), one homometallic, [Cu2L(NO3)2] (2), and one heterometallic, [CuMnL(NO3)2] (3) complexes were obtained using the ligand H2L = N,N'-bis(3-methoxysalicylidene)-1,3-propanediamine through different synthetic methods (electrochemical, chemical and solid state reaction). The structural data indicate that the metal ion disposition models the active site of type-3 copper enzymes, such as catechol oxidase. In this way, their ability to act as functional models of the enzyme has been spectrophotometrically determined by monitorization of the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-di-tert-butyl-o-benzoquinone (3,5-DTBQ). All the complexes show significant catalytic activity with ratio constants (kobs) lying in the range (223-294) × 10-4 min-1. A thorough kinetic study was carried out for complexes 2 and 3, since they show structural similarities with the catechol oxidase enzyme. The greatest catalytic activity was found for the homonuclear dicopper compound (2) with a turnover value (kcat) of (3.89 ± 0.05) × 106 h-1, which it is the higher reported to date, comparable to the enzyme itself (8.25 × 106 h-1).

Wickerhamiella verensis f.a. sp. nov., a novel yeast species isolated from subsoil groundwater contaminated with hydrocarbons and from a human infection.

Yeast strains belonging to a novel anamorphic yeast species were isolated from subsoil groundwater contaminated with hydrocarbons in a metal working factory located in northern Spain, and from a human infection in the USA. Comparison of ITS sequences between the isolates revealed 0.2 % divergence between the Spanish isolates and 0.46 % divergence between those and the USA isolate. Phylogenetic analysis based on the D1/D2 domains of the LSU rRNA gene showed that these isolates belong to the Wickerhamiella clade with W. sorbophila and W. infanticola as their closest relatives. Sequence divergence between the new isolates and W. sorbophila and W. infanticola was 1.97 and 1.79 %, respectively. The isolates in the novel species are not fermentative and pseudohyphae were not produced. Sexual reproduction was not observed for individual isolates or in mixtures of isolates. Conjugation between the isolates in the novel species and close relatives W. sorbophila and W. infanticola was not observed. These data support the proposal of Wickerhamiella verensis as a novel species, with CECT 12028T as the holotype.

Expected and Unexpected Imaging Findings after 90Y Transarterial Radioembolization for Liver Tumors.

Transarterial radioembolization (TARE), also called radioembolization or selective internal radiation therapy, is an interventional radiology technique used to treat primary liver tumors and liver metastases. The aim of this therapy is to deliver tumoricidal doses of radiation to liver tumors while selecting a safe radiation dose limit for nontumoral liver and lung tissue. Hence, correct treatment planning is essential to obtaining good results. However, this treatment invariably results in some degree of irradiation of normal liver parenchyma, inducing different radiologic findings that may affect follow-up image interpretation. When evaluating treatment response, the treated area size, tumor necrosis, devascularization, and changes seen at functional MRI must be taken into account. Unlike with other interventional procedures, with TARE, it can take several months for the tumor response to become evident. Ideally, responding lesions will show reduced size and decreased enhancement 3-6 months after treatment. In addition, during follow-up, there are many imaging findings related to the procedure itself (eg, peritumoral edema, inflammation, ring enhancement, hepatic fibrosis, and capsular retraction) that can make image interpretation and response evaluation difficult. Possible complications, either hepatic or extrahepatic, also can occur and include biliary injuries, hepatic abscess, radioembolization-induced liver disease, and radiation pneumonitis or dermatitis. A complete understanding of these possible posttreatment changes is essential for correct radiologic interpretations during the follow-up of patients who have undergone TARE. ©RSNA, 2019.