Ceftriaxone Pharmacokinetics and Pharmacodynamic Target Attainment for Three Pediatric Patients Receiving Continuous Kidney Replacement Therapy.

Ceftriaxone is used commonly for sepsis, including in children requiring continuous kidney replacement therapy (CKRT). No reports exist of pharmacokinetic (PK) parameters for children receiving ceftriaxone on CKRT. We enrolled children admitted to our pediatric intensive care unit (PICU) who received CKRT for >24 hours and received >1 dose of ceftriaxone while on and off CKRT. We measured free ceftriaxone -concentrations from residual blood samples then used Bayesian estimation with PK modeling software to generate concentration-time profiles and determine PK parameters and the percentage of time free ceftriaxone concentrations were above 1× or 4× MIC (% fT >MIC). Three patients aged 2 to 17 years were included; all were anuric at CKRT initiation and received 50 mg/kg (max 2000 mg) ceftriaxone every 12 to 24 hours. Total ceftriaxone clearance (CL) was 0.50 to 3.67 L/hr while receiving CKRT and 0.29 to 2.71 L/hr while off, indicating CKRT provided 25% to 42% of total ceftriaxone CL. All achieved 100% fT >1× and 4× MIC using an estimated MIC (1 mg/L) for patients 1 to 2 (no culture data) and a measured MIC (0.016 mg/L) for patient 3. Therefore, CKRT contributed significantly to total ceftriaxone clearance in 3 children though the dosing strategies used in each patient attained PD targets.

Nitrogen loss in coastal sediments driven by anaerobic ammonium oxidation coupled to microbial reduction of Mn(IV)-oxide.

Coastal sediments play a central role in regulating the amount of land-derived reactive nitrogen (Nr) entering the ocean, and their importance becomes crucial in vulnerable ecosystems threatened by anthropogenic activities. Sedimentary denitrification has been identified as the main sink of Nr in marine environments, while anaerobic ammonium oxidation with nitrite (anammox) has also been pointed out as a key player in controlling the nitrogen pool in these locations. Collected evidence in the present work indicates that the microbial biota in coastal sediments from Baja California (northwestern Mexico) has the potential to drive anaerobic ammonium oxidation linked to Mn(IV) reduction (manganammox). Unamended sediment showed ammonification, but addition of vernadite (δMnO2 with nano-crystal size ∼15 Å) as terminal electron acceptor fueled simultaneous ammonium oxidation (up to ∼400 µM of ammonium removed) and production of Mn(II) with a ratio ∆[Mn(II)]/∆[NH4+] of 1.8, which is very close to the stoichiometric value of manganammox (1.5). Additional incubations spiked with external ammonium also showed concomitant ammonium oxidation and Mn(II) production, accounting for ∼30 % of the oxidized ammonium. Tracer analysis revealed that the nitrogen loss associated with manganammox was 4.2 ± 0.4 µg 30N2/g-day, which is 17-fold higher than that related to the feammox process (anaerobic ammonium oxidation linked to Fe(III) reduction, 0.24 ± 0.02 µg 30N2/g-day). Taxonomic characterization based on 16S rRNA gene sequencing revealed the existence of several clades belonging to Desulfobacterota as potential microorganisms catalyzing the manganammox process. These findings suggest that manganammox has the potential to be an additional Nr sink in coastal environments, whose contribution to total Nr losses remains to be evaluated.

Biochar mitigates the adverse effects of antimony on methanogenic activity: role as methane production-enhancer.

Antimony, extensively used in energy applications, poses toxicity and contamination concerns, especially in anaerobic environments where its impact on microbial activity is poorly understood. Emerging remedies, like biochar, show promise in soil and water treatment. This study investigates biochar's influence on methanogenic activity under Sb(V) and Sb(III) stress using anaerobic sludge as inoculum and lactate as the carbon source. Sb(III) and Sb(V) were introduced at varied concentrations (5-80 mg/L), with or without biochar, monitoring changes in biogas production, pH, Sb, and lactate levels over time. Experiments with Sb(V) also involved calculating mass balance and electron distribution. Results showcased the following significant enhancements: biochar notably improved COD removal and biogas production in Sb(III) spiked conditions, up to 5-fold and 2-fold increases, respectively. Sb(III) removal reached up to 99% with biochar, while in high Sb(V) concentrations, biochar reduced the adverse effect on biogas production by 96%. Adsorption capacities favored biomass (60.96 mg Sb(III)/gVSS, and 22.4 mg Sb(V)/gVSS) over biochar (3.33 mg Sb(III)/g, and 1.61 mg Sb(V)/g) for both Sb species. This study underscores biochar's potential to mitigate metalloid impact on methanogenic activity while aiding Sb removal from liquid phase, suggesting promising implications for remediation and methane production enhancement strategies.

Genomic classification and outcomes of young patients with polycythemia vera and essential thrombocythemia according to the presence of splanchnic vein thrombosis and its chronology.

To elucidate the role of splanchnic vein thrombosis (SVT) and genomic characteristics in prognosis and survival, we compared patients with polycythemia vera (PV) or essential thrombocythemia (ET) presenting SVT at diagnosis (n = 69, median age 43 years) or during follow-up (n = 21, median age 46 years) to a sex- and age-matched control group of PV/ET without SVT (n = 165, median age 48 years). The majority of patients presenting with SVT at diagnosis were classified as myeloproliferative neoplasm with heterozygous JAK2 mutation (87% of cases vs. 69% in PV/ET control group, p < 0.05), characterized by low JAK2 allele burden and no high-risk mutations. Despite this lower molecular complexity, patients presenting with SVT showed a higher risk of death (HR 3.0, 95% CI 1.5-6.0, p = 0.003) and lower event-free survival (HR 3.0, 95% CI 1.9-4.8, p < 0.001) than age- and sex-matched PV/ET controls. In patients presenting with SVT, molecular high-risk was associated with increased risk of venous re-thrombosis (HR 5.8, 95% CI 1.4-24.0, p = 0.01). Patients developing SVT during follow-up were more frequently allocated in molecular high-risk than those with SVT at diagnosis (52% versus 13%, p < 0.05). In the whole cohort of patients, molecular classification identified PV/ET patients at higher risk of disease progression whereas DNMT3A/TET2/ASXL1 mutations were associated with higher risk of arterial thrombosis. In conclusion, clinical and molecular characteristics are different in PV/ET patients with SVT, depending on whether it occurs at diagnosis or at follow-up. Molecular characterization by NGS is useful for assessing the risk of thrombosis and disease progression in young patients with PV/ET.

Ammonium loss microbiologically mediated by Fe(III) and Mn(IV) reduction along a coastal lagoon system.

Anaerobic ammonium oxidation, associated with both iron (Feammox) and manganese (Mnammox) reduction, is a microbial nitrogen (N) removal mechanism recently identified in natural ecosystems. Nevertheless, the spatial distributions of these non-canonical Anammox (NC-Anammox) pathways and their environmental drivers in subtidal coastal sediments are still unknown. Here, we determined the potential NC-Anammox rates and abundance of dissimilatory metal-reducing bacteria (Acidomicrobiaceae A6 and Geobacteraceae) at different horizons (0-20 cm at 5 cm intervals) of subtidal coastal sediments using the 15N isotope-tracing technique and molecular analyses. Sediments were collected across three sectors (inlet, transition, and inner) in a coastal lagoon system (Bahia de San Quintin, Mexico) dominated by seagrass meadows. The positive relationship between 30N2 production rates and dissimilatory Fe and Mn reduction provided evidence for Feammox's and Mnammox's co-occurrence. N loss through NC-Anammox was detected in subtidal sediments, with potential rates of 0.07-0.62 µg N g-1 day-1. NC-Anammox process in vegetated sediments tended to be higher than those in adjacent unvegetated ones. NC-Anammox rates showed a subsurface peak (between 5 and 15 cm) in the vegetated sediments but decreased consistently with depth in the adjacent bare bottoms. Thus, the presence/absence of seagrasses and sediment characteristics, particularly the availability of organic carbon and microbiologically reducible Fe(III) and Mn(IV), affected the abundance of dissimilatory metal-reducing bacteria, which mediated NC-Anammox activity and the associated N removal. An annual loss of 32.31 ± 3.57 t N was estimated to be associated with Feammox and Mnammox within the investigated area, accounting for 2.8-4.7% of the gross total import of reactive N from the ocean into the Bahia de San Quintin. Taken as a whole, this study reveals the distribution patterns and controlling factors of the NC-Anammox pathways along a coastal lagoon system. It improves our understanding of the coupling between N and trace metal cycles in coastal environments.

Anammox with alternative electron acceptors: perspectives for nitrogen removal from wastewaters.

In the context of the anaerobic ammonium oxidation process (anammox), great scientific advances have been made over the past two decades, making anammox a consolidated technology widely used worldwide for nitrogen removal from wastewaters. This review provides a detailed and comprehensive description of the anammox process, the microorganisms involved and their metabolism. In addition, recent research on the application of the anammox process with alternative electron acceptors is described, highlighting the biochemical reactions involved, its advantages and potential applications for specific wastewaters. An updated description is also given of studies reporting the ability of microorganisms to couple the anammox process to extracellular electron transfer to insoluble electron acceptors; particularly iron, carbon-based materials and electrodes in bioelectrochemical systems (BES). The latter, also referred to as anodic anammox, is a promising strategy to combine the ammonium removal from wastewater with bioelectricity production, which is discussed here in terms of its efficiency, economic feasibility, and energetic aspects. Therefore, the information provided in this review is relevant for future applications.

Ceftriaxone Pharmacokinetics and Pharmacodynamics in 2 Pediatric Patients on Extracorporeal Membrane Oxygenation Therapy.

BACKGROUND: Critically ill patients with cardiac or respiratory failure may require extracorporeal membrane oxygenation (ECMO). Antibiotics are frequently administered when the suspected cause of organ failure is an infection. Ceftriaxone, a ß-lactam antibiotic, is commonly used in patients who are critically ill. Although studies in adults on ECMO have suggested minimal impact on ceftriaxone pharmacokinetics, limited research exists on ceftriaxone pharmacokinetics/pharmacodynamics (PK/PD) in pediatric ECMO patients. We report the PK profiles and target attainment of 2 pediatric patients on ECMO who received ceftriaxone. METHODS: Ceftriaxone concentrations were measured in 2 pediatric patients on ECMO using scavenged opportunistic sampling. PK profiles were generated and individual PK parameters were estimated using measured free ceftriaxone concentrations and a published population PK model in children who are critically ill, using Bayesian estimation. RESULTS: Patient 1, an 11-year-old boy on venovenous ECMO for respiratory failure received 2 doses of 52 mg/kg ceftriaxone 12 hours apart while on ECMO and additional doses every 12 hours off ECMO. On ECMO, ceftriaxone clearance was 13.0 L/h/70 kg compared with 7.6 L/h/70 kg off ECMO, whereas the model-predicted mean clearance in children who are critically ill without ECMO support was 6.54 L/h/70 kg. Patient 2, a 2-year-old boy on venoarterial ECMO due to cardiac arrest received 50 mg/kg ceftriaxone every 12 hours while on ECMO for >7 days. Only clearance while on ECMO could be estimated (9.1 L/h/70 kg). Trough concentrations in both patients were >1 mg/L (the breakpoint for Streptococcus pneumoniae ) while on ECMO. CONCLUSIONS: ECMO increased ceftriaxone clearance above the model-predicted clearances in the 2 pediatric patients studied. Twelve-hour dosing allowed concentrations to remain above the breakpoint for commonly targeted bacteria but not 4 times the breakpoint in one patient, suggesting that precision dosing may be beneficial to ensure target attainment in children on ECMO.

Clinical Characteristics and Outcomes of Patients with Primary and Secondary Myelofibrosis According to the Genomic Classification Using Targeted Next-Generation Sequencing.

Myelofibrosis (MF) is a heterogeneous disease regarding its mutational landscape, clinical presentation, and outcomes. The aim of our work is to evaluate the genomic classification of MF considering whether it is primary or secondary. One-hundred seventy-five patients, 81 with primary MF (PMF) and 94 with secondary MF (SMF) were hierarchically allocated into eight molecular groups. We found that TP53 disruption/aneuploidy (n = 16, 9%) was more frequent (12% versus 6%) and showed higher allele burden (57% versus 15%, p = 0.01) in SMF than in PMF, and was associated with shorter survival (median 3.5 years). Mutations in chromatin/spliceosome genes (n = 72, 41%) represented the most frequent genomic group in PMF. Homozygous JAK2 mutation (n = 40, 23%) was enriched with old patients with SMF after long-standing polycythemia vera, whereas MF with heterozygous JAK2 mutation (n = 22, 13%) was similarly distributed among PMF and SMF. MF with CALR mutation (n = 19, 11%) predominated in post-essential thrombocythemia MF. The remaining genomic groups were infrequent. TP53 disruption, chromatin/spliceosome mutation, and homozygous JAK2 mutation were associated with significantly shorter survival and higher risk of progression. In conclusion, genomic classification reveals different pathogenic pathways between PMF and SMF and provides relevant information regarding disease phenotype and outcomes.

Genomic insights of Leclercia adecarboxylata strains linked to an outbreak in public hospitals in Mexico.

BACKGROUND: Leclercia adecarboxylata is a bacteria closely related to Escherichia coli according to its biochemical characteristics and is commonly considered non-pathogenic although a growing number of publications classify it as an emerging pathogen. Fosfomycin resistance is a common trait for L. adecarboxylata encoded by fosALA gene. OBJECTIVE: To analyze genomic traits of sixteen L. adecarboxylata strains isolated from blood culture and a bottle of total parenteral nutrition. METHODS: Twenty-eight L. adecarboxylata strains isolated from blood culture and a bottle of total parenteral nutrition were identified biochemically with a Vitek ® automated system. The strains were phenotyped by their growth on Eosin Methylene Blue agar or MacConkey agar plates. Additionally, Pulsed field gel electrophoresis (PFGE) was performed to establish the clonal relationship. The genomic DNA of sixteen strains was obtained using a Qubit ® dsDNA HS Assay Kit and sequenced on an Illumina ® MiSeq instrument. Draft genomes were assembled using PROKKA and Rast. Assemblies were submitted to Resfinder and PathogenFinder from the Center for Genomic Epidemiology in order to find resistance genes and pathogenic potential. IslandViewer4 was also used to find Pathogenicity and Phage Islands. For identification of the fosA gene, manual curation and Clustal analysis was performed. A novel FosA variant was identified. Finally, phylogenetic analysis was performed using VAMPhyRE software and Mega X. RESULTS: In this paper, we report the genomes of sixteen strains of Leclercia adecarboxylata causing an outbreak associated with parenteral nutrition in public hospitals in Mexico. The genomes were analyzed for genetic determinants of virulence and resistance. A high pathogenic potential (pathogenicity index 0.82) as well as multiple resistance genes including carbapenemics, colistin and efflux pumps were determined. Based on sequence analysis, a new variant of the fosALA gene was described. Finally, the outbreak was confirmed by establishing the clonal relationship among the sixteen genomes obtained. CONCLUSIONS: Commensal strains of L. adecarboxylata may acquire genetic determinants that provide mechanisms of host damage and go unnoticed in clinical diagnosis. L. adecarboxylata can evolve in a variety of ways including the acquisition of resistance and virulence genes representing a therapeutic challenge in patient care.

A utilization distribution for the global population of Cape Vultures (Gyps coprotheres) to guide wind energy development.

The rapid development of wind energy in southern Africa represents an additional threat to the already fragile populations of African vultures. The distribution of the vulnerable Cape Vulture Gyps coprotheres overlaps considerably with wind energy development areas in South Africa, creating conflicts that can hinder both vulture conservation and sustainable energy development. To help address this conflict and aid in the safe placement of wind energy facilities, we map the utilization distribution (UD) of this species across its distributional range. Using tracking data from 68 Cape Vultures collected over the last 20 years, we develop a spatially explicit habitat use model to estimate the expected UDs around known colonies. Scaling the UDs by the number of vultures expected to use each of the colonies, we estimate the Cape Vulture population utilization distribution (PUD) and determine its exposure to wind farm impacts. To complement our results, we model the probability of a vulture flying within the rotor sweep area of a wind turbine throughout the species range and use this to identify areas that are particularly prone to collisions. Overall, our estimated PUD correlates well with reporting rates of the species from the Southern African Bird Atlas Project, currently used to assess potential overlap between Cape Vultures and wind energy developments, but it adds important benefits, such as providing a spatial gradient of activity estimates over the entire species range. We illustrate the application of our maps by analyzing the exposure of Cape Vultures in the Renewable Energy Development Zones (REDZs) in South Africa. This application is a scalable procedure that can be applied at different planning phases, from strategic, nationwide planning to project-level assessments.

Water reclamation from anodizing wastewaters by removing reactive silica with adsorption and precipitation methods.

Water stress is a current environmental menace mainly driven by over exploitation of aquifers, which is triggering poor water quality with high concentration of minerals in extracted groundwater. Particularly, silica is widespread in natural water supplies due to weathering processes of silicates occurring in contact with water, light, air, and other factors. However, due to groundwater over extraction the concentration of silica has increased during the last years in aquifer reservoirs from Aguascalientes State (México). In this context, it is very important to note that the removal of silica compounds from water is challenging and different methods can be used to avoid embedding problems in different industries. In the present work, the removal of reactive silica from synthetic solutions as well as from real wastewaters from an industrial anodizing process was studied using adsorption and chemical precipitation methods. Twelve commercial materials of different nature were used for adsorption tests, while seven precipitant agents were applied in the precipitation experiments. Adsorption tests were performed in batch systems with constant stirring at 30 °C and at different pH values (7 and 9). Precipitation experiments were carried out in batch systems and the best conditions for silica removal were found using an L9 orthogonal array of the Taguchi method employing molar ratio, pH of wastewater, stirring time and temperature as experimental factors. Adsorption results showed that Ferrolox (Iron (III) hydroxide-base adsorbent) was the most efficient sorbent for reactive silica removal from synthetic solutions and the anodizing wastewater. Also, the reactive silica adsorption was higher at pH 9 as compared to that measured at pH 7 and the adsorbed quantity at pH 9 was 16.22 and 11.25 mg/g for the synthetic solution and anodizing wastewater, respectively. According to molecular simulation, the main interaction between Ferrolox and silica species was related to the formation of hydroxo-complexes and to the interaction of Fe with oxygen of silica species. Additionally, magnesium chloride was the best precipitating reagent for reactive silica achieving up to 87% removal. According to ANOVA analysis of Taguchi method, pH was the most influential factor during the precipitation of reactive silica with a variance value of 81.42, while values lower than 3 were obtained for the rest of parameters. Overall, the present work is reporting for the first time the removal of reactive silica from anodizing wastewaters with promising results that can be implemented at full scale for water reclamation, which may significantly contribute to manage water reservoir in the region sustainably.

Biocatalyst developed with recovered iron-rich minerals enhances the biotransformation of SARS-CoV-2 antiviral drugs in anaerobic bioreactors.

The biotransformation of the SARS-CoV-2 antiviral drugs, ribavirin and tenofovir, was studied in methanogenic bioreactors. The role of iron-rich minerals, recovered from a metallurgic effluent, on the biotransformation process was also assessed. Enrichment of anaerobic sludge with recovered minerals promoted superior removal efficiency for both antivirals (97.4 % and 94.7 % for ribavirin and tenofovir, respectively) as compared to the control bioreactor lacking minerals, which achieved 58.5 % and 37.9 % removal for the same drugs, respectively. Further analysis conducted by liquid chromatography coupled to mass spectroscopy revealed several metabolites derived from the biotransformation of both antivirals. Interestingly, tracer analysis with 13CH4 revealed that anaerobic methane oxidation coupled to Fe(III) reduction occurred in the enriched bioreactor, which was reflected in a lower content of methane in the biogas produced from this system, as compared to the control bioreactor. This treatment proposal is suitable within the circular economy concept, in which recovered metals from an industrial wastewater are applied in bioreactors to create a biocatalyst for promoting the biotransformation of emerging pollutants. This strategy may be appropriate for the anaerobic treatment of wastewaters originated from hospitals, as well as from the pharmaceutical and chemical sectors.

Immobilized Nanomaterials for Environmental Applications.

Nanomaterials (NMs) have been extensively used in several environmental applications; however, their widespread dissemination at full scale is hindered by difficulties keeping them active in engineered systems. Thus, several strategies to immobilize NMs for their environmental utilization have been established and are described in the present review, emphasizing their role in the production of renewable energies, the removal of priority pollutants, as well as greenhouse gases, from industrial streams, by both biological and physicochemical processes. The challenges to optimize the application of immobilized NMs and the relevant research topics to consider in future research are also presented to encourage the scientific community to respond to current needs.

Prediction of thrombosis in post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a study on 1258 patients.

Patients with Philadelphia-negative myeloproliferative neoplasms are at high risk of thrombotic events (TEs). Predisposing factors have been identified in essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (primary MF, PMF), while yet not recognized in post PV/ET-MF (known as secondary MF, SMF). Within the 1258 SMF of the MYSEC (MYelofibrosis SECondary to PV and ET) dataset, 135 (10.7%) developed a TE at a median follow-up of 3.5 years (range, 1-21.4), with an incidence of 2.3% patients per year. Venous events accounted for two-thirds of the total. Cox multivariable analysis, supported by Fine-Gray models with death as competitive risk, showed that being on cytoreductive therapy at time of SMF evolution is associated with an absolute risk reduction of thrombosis equal to 3.3% within 3 years. Considering individually cytoreductive therapies, univariate regression model found that both conventional cytoreduction, mainly hydroxyurea, (HR 0.41, 95% CI: 0.26-0.65, p = 0.0001) and JAK inhibitors, mostly ruxolitinib, (HR 0.50, 95% CI: 0.24-1.02, p = 0.05) were associated with fewer thrombosis. Our study informs treating physicians of a non-low incidence of TEs in post PV/ET-MF and of the potential protective role of cytoreductive therapy in terms of thrombotic events.

Overall survival in the SIMPLIFY-1 and SIMPLIFY-2 phase 3 trials of momelotinib in patients with myelofibrosis.

Janus kinase inhibitors (JAKi) approved for myelofibrosis provide spleen and symptom improvements but do not address anemia, a negative prognostic factor. Momelotinib, an inhibitor of ACVR1/ALK2, JAK1 and JAK2, demonstrated activity against anemia, symptoms, and splenomegaly in the phase 3 SIMPLIFY trials. Here, we report mature overall survival (OS) and leukemia-free survival (LFS) from both studies, and retrospective analyses of baseline characteristics and efficacy endpoints for OS associations. Survival distributions were similar between JAKi-naïve patients randomized to momelotinib, or ruxolitinib then momelotinib, in SIMPLIFY-1 (OS HR = 1.02 [0.73, 1.43]; LFS HR = 1.08 [0.78, 1.50]). Two-year OS and LFS were 81.6% and 80.7% with momelotinib and 80.6% and 79.3% with ruxolitinib then momelotinib. In ruxolitinib-exposed patients in SIMPLIFY-2, two-year OS and LFS were 65.8% and 64.2% with momelotinib and 61.2% and 59.7% with best available therapy then momelotinib (OS HR = 0.98 [0.59, 1.62]; LFS HR = 0.97 [0.59, 1.60]). Baseline transfusion independence (TI) was associated with improved survival in both studies (SIMPLIFY-1 HR = 0.474, p = 0.0001; SIMPLIFY-2 HR = 0.226, p = 0.0005). Week 24 TI response in JAKi-naïve, momelotinib-randomized patients was associated with improved OS in univariate (HR = 0.323; p < 0.0001) and multivariate (HR = 0.311; p < 0.0001) analyses. These findings underscore the importance of achieving or maintaining TI in myelofibrosis, supporting the clinical relevance of momelotinib's pro-erythropoietic mechanism of action, and potentially informing treatment decision-making.

Impact of Individual Comorbidities on Survival of Patients with Myelofibrosis.

The comorbidity burden is an important risk factor for overall survival (OS) in several hematological malignancies. This observational prospective study was conducted to evaluate the impact of individual comorbidities on survival in a multicenter series of 668 patients with primary myelofibrosis (PMF) or MF secondary to polycythemia vera (PPV-MF) or essential thrombocythemia (PET-MF). Hypertension (hazard ratio (HR) = 4.96, p < 0.001), smoking (HR = 5.08, p < 0.001), dyslipidemia (HR = 4.65, p < 0.001) and hepatitis C virus (HCV) (HR = 4.26, p = 0.015) were most adversely associated with OS. Diabetes (HR = 3.01, p < 0.001), pulmonary disease (HR = 3.13, p < 0.001) and renal dysfunction (HR = 1.82, p = 0.037) were also associated with an increased risk of death. Multivariate analysis showed that pulmonary disease (HR = 2.69, p = 0.001), smoking (HR = 3.34, p < 0.001), renal dysfunction (HR = 2.08, p = 0.043) and HCV (HR = 11.49, p = 0.001) had a negative impact on OS. When ruxolitinib exposure was included in the model, the effect of each comorbidity on survival was modified. Therefore, individual comorbidities should be taken into account in determining the survival prognosis for patients with MF.

Protease and gag diversity and drug resistance mutations among treatment-naive Mexican people living with HIV.

INTRODUCTION: In Mexico, HIV genotyping is performed in people living with HIV (PLWH) failing their first-line antiretroviral (ARV) regimen; it is not routinely done for all treatment-naive PLWH before ARV initiation. The first nationally representative survey published in 2016 reported that the prevalence of pretreatment drug mutations in treatment-naive Mexican PLWH was 15.5% to any antiretroviral drug and 10.6% to non-nucleoside reverse transcriptase inhibitors (NNRTIs) using conventional Sanger sequencing. Most reports in Mexico focus on HIV pol gene and nucleoside and non-nucleoside reverse transcriptase inhibitor (NRTI and NNRTI) drug resistance mutations (DRMs) prevalence, using Sanger sequencing, next-generation sequencing (NGS) or both. To our knowledge, NGS has not be used to detect pretreatment drug resistance mutations (DRMs) in the HIV protease (PR) gene and its substrate the Gag polyprotein. METHODS: Treatment-naive adult Mexican PLWH were recruited between 2016 and 2019. HIV Gag and protease sequences were obtained by NGS and DRMs were identified using the WHO surveillance drug resistance mutation (SDRM) list. RESULTS: One hundred PLWH attending a public national reference hospital were included. The median age was 28 years-old, and most were male. The median HIV viral load was 4.99 [4.39-5.40] log copies/mL and median CD4 cell count was 150 [68.0-355.78] cells/mm3. As expected, most sequences clustered with HIV-1 subtype B (97.9%). Major PI resistance mutations were detected: 8 (8.3%) of 96 patients at a detection threshold of 1% and 3 (3.1%) at a detection threshold of 20%. A total of 1184 mutations in Gag were detected, of which 51 have been associated with resistance to PI, most of them were detected at a threshold of 20%. Follow-up clinical data was available for 79 PLWH at 6 months post-ART initiation, seven PLWH failed their first ART regimen; however no major PI mutations were identified in these individuals at baseline. CONCLUSIONS: The frequency of DRM in the HIV protease was 7.3% at a detection threshold of 1% and 3.1% at a detection threshold of 20%. NGS-based HIV drug resistance genotyping provide improved detection of DRMs. Viral load was used to monitor ARV response and treatment failure was 8.9%.

Enhanced anaerobic treatment of synthetic protein-rich wastewater promoted by organic xerogels.

Carbon-based materials have been shown to enhance anaerobic digestion processes by promoting direct interspecies electron transfer in methanogenic consortia. However, little is known on their effects during the treatment of complex substrates, such as those derived from protein-rich wastewaters. Here, organic xerogels (OX) are tested, for the first time, as accelerators of the methanogenic activity of an anaerobic consortium treating a synthetic protein-rich wastewater. Three OX with distinct pore size distribution (10 and 1000 nm for OX-10 and OX-1000, respectively) and structural conformation (graphene oxide integration into OX-10-GO polymeric matrix) were synthesized. OX-1000 promoted the highest methane production rate (5.21 mL/g*h, 13.5% increase with respect to the control incubated without OX) among the synthesized OX. Additionally, batch bioreactors amended with OX achieved higher chemical oxygen demand (COD) removal (up to 88%) as compared to the control, which only showed 50% of COD removal. Interestingly, amendment of bioreactors with OX also triggered the production of medium-chain fatty acids, including caprylate and caproate. Moreover, OX decreased the accumulation of ammonium, derived from proteins hydrolysis, partly explained by their adsorption capacities, and probably involving their electron-accepting capacity promoting anaerobic ammonium oxidation. This is the first time that OX were successfully applied as methanogenic accelerators for the anaerobic treatment of synthetic protein-rich wastewater, increasing the methane production rate and COD removal as well as triggering the production of medium chain fatty acids and attenuating the accumulation of ammonium. Therefore, OX are proposed as suitable materials to boost the efficiency of anaerobic systems to treat complex industrial wastewaters.

Population viability assessment of an endangered raptor using detection/non-detection data reveals susceptibility to anthropogenic impacts.

As the demand for carbon-neutral energy sources increases, so does the need to understand the impacts that these technologies have on the environment. Here, we assess the potential consequences of additional mortality on an Endangered raptor recently exposed to wind farms for the first time, the Black Harrier Circus maurus, one of the world's rarest harriers. We conduct a population viability assessment using a Bayesian model integrating life-history information and annual reporting rates from detection/non-detection surveys from the South African Bird Atlas Project. Our model estimates a global population of approximately 1300 birds currently declining at 2.3% per year, and one that could collapse in under 100 years, if an average of three to five adult birds are killed annually. This level of mortality may soon exist, given the current rate of fatalities and the number of wind farms planned within the species' distribution. In addition, we find that the population is sensitive to changes in climate. Our results highlight the critical need for appropriate placement, and adaptive management of wind farms and other infrastructure causing harrier mortality. We also show how detection/non-detection data may be used to infer population dynamics and viability, when population counts are unavailable.