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Metagenomic insights into microbial drivers of organic micropollutant removal in wastewater-impacted riverbank filtration.

Organic micropollutants (OMPs) in wastewater treatment plant (WWTP) effluent pose persistent risks to aquatic ecosystems and drinking water sources. Riverbank filtration (RBF) is a nature-based treatment process, yet the compartment-specific roles of riverbed sediment and downstream soil in OMP attenuation remain poorly resolved under wastewater-impacted conditions. Here, we combined targeted chemical analysis, OMP property compilation, shotgun metagenomics, EnviPath-based biotransformation annotation, and exploratory network analysis to investigate OMP attenuation in a laboratory-scale RBF system treating real WWTP effluent for 10 months. Nineteen OMPs were monitored along a sequential sediment-soil filtration pathway. Sediment preferentially attenuated hydrophilic or charged compounds, including lidocaine, amantadine, and sotalol, whereas soil contributed more strongly to the attenuation of naproxen, atenolol, and losartan. Metagenomic profiling revealed distinct microbial communities and functional gene repertoires between sediment and soil after long-term operation. Sediment harbored higher relative abundances of genes associated with oxidative xenobiotic transformation, including cytochrome P450-related enzymes, demethylases, dehydrogenases, oxidases, and aromatic compound degradation pathways. An exploratory Spearman network further identified associations among microbial genera, EnviPath-annotated candidate biotransformation genes, and OMP removal rates, including 17 KO-OMP links supported by both correlation and pathway annotation. These findings indicate that sediment and soil develop complementary microbial functional potentials that may support compound-specific OMP attenuation. This study provides a mechanistic basis for optimizing sediment-soil configurations in wastewater-impacted RBF systems and for improving nature-based barriers against diverse OMP mixtures.

Wastewater

Genetic overlap between estimated glomerular filtration rate and cardiovascular disease identifies potential targets for cardiorenal syndrome.

Heart and kidney diseases frequently coexist, but the genetic basis of this relationship remains unclear. We analyzed genetic data from large-scale studies to investigate how kidney function (estimated glomerular filtration rate, eGFR) and six common cardiovascular diseases share genetic risk factors. Using MiXeR method, and conjunctional false discovery rate (conjFDR) to identify overlapping genetic regions, we found 478 shared genomic loci between eGFR and cardiovascular diseases. These shared genes are involved in tissue development and structure. We also identified 29 genes that could be targeted by existing medications approved by the US Food and Drug Administration, such as PRKAG2, PDE1A, and IGF1R. Among these, genetically predicted higher level of IGF1R expression is associated with a higher eGFR, which reflects good kidney function and is protective against cardiorenal diseases, such as atrial fibrillation, and myocardial infarction. These findings reveal genetic overlap between kidney function and cardiovascular diseases, highlighting potential targets for understanding and treating cardiorenal syndrome.

Humans

Common charge-shift mutation Glu65Lys in K+ channel β₁-Subunit KCNMB1: pleiotropic consequences for glomerular filtration rate and progressive renal disease.

BACKGROUND: Glomerular filtration rate (GFR) is a heritable trait, and hyperfiltration (GFR increment in remnant nephrons) may accelerate renal functional decline in chronic kidney disease (CKD). Mesangial and vascular smooth myocytes control GFR by contraction, dependent on voltage-gated Ca(2+) influx, which is controlled by the regulatory β₁-subunit (KCNMB1) of large-conductance heteromeric K+ ('BK') channels. KCNMB1 gain-of-function variant Glu65Lys results in generalized vasorelaxation and thus protection against systemic hypertension. Here we asked whether the Glu65Lys variant influences GFR, in the basal state or during progressive renal decline. METHODS: We explored Glu65Lys effects on GFR in three populations spanning two ethnicities and two diseases (hypertension and nephrosclerosis). GFR was either estimated (eGFR from serum creatinine) or directly measured (iothalamate clearance). RESULTS: The 65Lys variant was relatively common, occurring on ∼5-10% of chromosomes in different biogeographic ancestry groups, and 65Lys carriers exhibited higher eGFR in two primary care populations: extreme BP values in Kaiser clinics (p = 0.029, accounting for ∼0.2% of trait variance), or treated hypertensives in VA clinics (p = 0.017, accounting for ∼0.9% of trait variance). In blacks with progressive renal disease (NIDDK AASK), 65Lys carriers displayed a steeper slope in GFR chronic decline (p = 0.030, accounting for ∼0.4% of trait variance), and Glu65Lys genotype also predicted time of onset of renal failure (log rank p = 0.019). CONCLUSIONS: Common KCNMB1 gain-of-function variant Glu65Lys influences GFR, and 65Lys carriers exhibit not only elevated baseline GFR, but also more rapid GFR decline (and consequent development of renal failure) in CKD. The results suggest that profiling patients at Glu65Lys can assist in gauging renal prognosis as well as selection of rational therapy in hypertension with progressive renal disease.

Black or African American

Genome-wide association study of estimated glomerular filtration rate using repeated measurements in the Taiwan Biobank.

BACKGROUND: Chronic kidney disease (CKD) is a major global public health issue, with genetic factors playing a significant role in kidney function. Although genome-wide association studies (GWAS) have identified numerous loci associated with estimated glomerular filtration rate (eGFR), most studies relied on a single time-point measurement, which limits the capacity to account for within-individual measurement variability. METHODS: We performed a repeated-measurement GWAS in the prospective Taiwan Biobank (Taiwanese ancestry; n = 25,004) using two repeated creatinine-based eGFR measurements. Repeated eGFR values were analyzed using a linear mixed-effects model with a subject-specific random intercept and time-varying covariates, providing a more precise estimate of eGFR level. Identified loci underwent functional annotation (expression quantitative trait locus, deleteriousness prediction, and epigenetic markers) and were compared with results from a single-measurement GWAS. RESULTS: Six loci associated with eGFR were identified, including four previously reported regions (1q22, 4q21.1, 11p14.1, and 17q21.2) and two additional loci (6p21.32 and 15q24.2). Functional annotation implicated several candidate genes-such as MUC1/EFNA1, SHROOM3, HLA-DQB1, MPPED2, NRG4, and PGAP3/FBXL20-in the regulation of kidney function. CONCLUSION: Incorporating repeated eGFR measurements into GWAS may improve phenotypic precision for identifying genetic associations with kidney function. This study identified eGFR-associated loci and biologically plausible candidate genes in a Taiwanese population, which require further replication and functional validation.

Chronic kidney disease

Glaucoma filtering surgery combined with phacoemulsification in the era of new aqueous humor filtration devices: A systematic review.

We evaluate the efficacy and safety of filtering glaucoma surgeries combined with phacoemulsification (PCE)-including new aqueous humor drainage devices-compared to standalone procedures. We performed a systematic search up to March 23, 2025, including all comparative studies assessing trabeculectomy (TRAB), non-penetrating deep sclerectomy (NPDS), Xen® Gel Stent (XEN), or Preserflo® MicroShunt (PMS) combined with PCE, versus the same surgery alone. Key exclusion criteria include inadequate follow-up (less than 12-month), absence of a defined success criterion, more than 50% of loss to follow-up at 12-month, and lens extraction performed without PCE. Main outcome was surgical success at ≥ 12 months. Secondary outcomes included intraocular pressure (IOP) reduction, decrease in hypotensive medications, and rates of complications. A total of 27 studies were included for analysis. Among studies comparing TRAB/PCE with standalone TRAB, half reported similar success rates, while others favored standalone TRAB, particularly using strict IOP thresholds. Safety profiles were comparable. For NPDS/PCE, data mostly showed equivalent outcomes versus standalone NPDS, with comparable safety. In studies on XEN/PCE and PMS/PCE, results suggested similar rates of surgical success, efficacy in IOP and medication reduction, and safety compared to their stand-alone procedures. Small differences occasionally favored standalone procedures under stricter success definitions. Current evidence suggests that combined filtering glaucoma surgery provides long-term efficacy and safety comparable to standalone, though some subgroups and outcome thresholds may slightly favor standalone approaches. The limited availability of high-quality prospective trials underscores the need for further large-scale robust studies.

Humans

Diurnal differences in the effects of heat exposure on renal function: A randomized controlled crossover trial.

High temperature is a major risk factor for kidney injury, and population exposure to nighttime heat is increasing as the climate warms. However, whether renal responses to heat exposure differ between daytime and nighttime remains unclear. Forty-one healthy adults participated in a randomized crossover experiment conducted in a controlled laboratory setting. Participants were exposed to heat (32°C during daytime; 30°C during nighttime) and thermoneutral conditions (26°C) for 8 h. Blood and urine samples were collected before and after each exposure to examine various renal biomarkers reflecting glomerular filtration function, tubular injury, and early kidney stress. Heat exposure affected both blood and urinary biomarkers of kidney function, with notable diurnal differences in renal responses. Daytime heat exposure primarily affected blood markers of glomerular filtration, increasing creatinine by 7.67% (95% CI: 4.73%-10.61%) and cystatin C by 3.05% (95% CI: 0.17%-5.93%), while reducing estimated glomerular filtration rate by 0.05% (95% CI: 0.02%-0.08%). In contrast, nighttime heat exposure predominantly elevated urinary biomarkers of early kidney stress, including insulin-like growth factor-binding protein 7 (58.40%, 95% CI: 27.66%-89.14%), kidney injury molecule-1 (47.25%, 95% CI: 18.91%-75.59%), and tissue inhibitor of metalloproteinases-2 (51.88%, 95% CI: 22.26%-81.51%). Moreover, increases in insulin-like growth factor-binding protein 7 were significantly greater at night than during the day. Sleep-related parameters, including sleep quality, duration, and heart rate variability, partially mediated nighttime heat effects on renal responses. These results indicated that heat exposure induced different diurnal patterns in renal responses.

Humans

Natural, safety immunomodulatory derivatives of lactobacillus biofilms promote diabetic wound healing by metabolically regulating macrophage phenotype and alleviating local inflammation.

INTRODUCTION: Long-term inflammatory microenvironment further impairs the healing process of diabetic wounds. Many studies have shown that Lactobacillus can regulate immune function and promote injured tissue repair. However, the immunomodulatory function and safety of Lactobacillus biofilm (LB) on wounds need further investigation. OBJECTIVES: In this present research, we proposed a "bacteria-free biofilm derivative therapy" and successfully extracted Lactobacillus biofilm derivatives (LBDs) by ultrasonic separation and filtration technology for the natural and safe treatment of diabetic wounds. METHODS: The study first cultured Lactobacillus anaerobically and extracted LBDs using ultrasound separation combined with filtration technology. LBDs were characterized via scanning electron microscopy, Concanavalin A fluorescence staining, and protein gel electrophoresis. In vivo diabetic wound model, wound closure rates were dynamically monitored, and tissue sections were analyzed using hematoxylin-eosin and immunofluorescence staining to evaluate LBDs' healing effects. An in vitro macrophage inflammation model was established, employing immunofluorescence, flow cytometry, and Western blotting techniques to explore the molecular mechanisms underlying LBDs' effects on macrophage phenotypes. Furthermore, whole-genome sequencing and proteomics of LBDs-treated macrophages were performed to further elucidate the intrinsic molecular mechanisms through which LBDs regulate macrophage phenotypes. RESULTS: LBDs were effectively extracted utilizing ultrasonic separation coupled with filtration technology. Studies revealed that LBDs modulate the systemic metabolic reprogramming in wound-site macrophages, suppress JAK-STAT1 signaling pathway, alleviate the local inflammatory microenvironment, promote neovascularization and ultimately accelerate wound healing. CONCLUSION: The LBDs retains most bioactive components of the LB. As a natural, safe and immunomodulatory agent, LBDs promote diabetic wound healing by metabolically reprogramming macrophage phenotypes and improving the local immune microenvironment, offering promising potential for regenerative applications in diabetic wound management.

Wound Healing

Biological characterization and genome analysis of Bacillus thuringiensis GX0003935 with biocontrol activity against Meloidogyne enterolobii.

Meloidogyne enterolobii is a highly aggressive root-knot nematode, and reduced availability of chemical nematicides increases the need for effective biocontrol alternatives. We characterized Bacillus thuringiensis GX0003935 in terms of nematicidal activity, stability, biocontrol efficacy, and genome features. The culture broth and filtrate caused more than 97% corrected mortality of second-stage juveniles within 48 h, whereas bacterial suspension showed limited activity, suggesting that extracellular factors substantially contribute to nematicidal activity. The culture filtrate retained high nematicidal activity after exposure to UV irradiation, heat treatment, broad pH range, and prolonged storage, and the strain maintained stable activity during serial passaging. Furthermore, protease sensitivity assays, ammonium sulfate precipitation, and polarity characterization collectively suggested a composite active system involving proteinaceous and non-proteinaceous components. In pot trials, culture broth and filtrate reduced galling by approximately 74%. Genome sequencing combined with ANI/dDDH analyses confirmed GX0003935 as B. thuringiensis. Multiple candidates (proteases, chitinases, and toxin proteins) and secondary metabolite biosynthetic gene clusters were revealed, while known nematicidal Cry toxins were not detected. RT-qPCR results confirmed that the expression of these candidate genes at different growth stages. B. thuringiensis GX0003935 exhibits stable, extracellular-factor-associated nematicidal activity and effectively suppresses M. enterolobii in water spinach, indicating its potential as a biocontrol candidate.

Bacillus thuringiensis

Mutations in filamentous bacteriophages spark eco-evolutionary feedbacks in Pseudomonas aeruginosa.

Microbial populations strongly shape their environment, which can re-route adaptation toward organism-generated fitness optima. However, the conditions that promote these eco-evolutionary feedbacks are unclear. Here, we used experimental evolution to test whether high population density, by strengthening niche construction, drives eco-evolutionary feedbacks in the bacterial pathogen Pseudomonas aeruginosa (Pa) MPAO1. We tested for adaptation to organism-modified environments by measuring the relative performance of ancestral and endpoint populations in filtrate generated by each evolutionary line sampled across generations. Contrary to expectations, we found that endpoint populations had higher performance than the ancestral strain in filtrate across nearly all evolutionary lines regardless of population density. This was caused by the emergence of hyperactive filamentous bacterio(phage) mutants during experimental passaging that inhibited the ancestral strain but not endpoint populations in modified media. Hyperactive phages emerged from one of two avirulent prophages in MPAO1's genome (Pf4 or Pf6). Hyperactive phages drove the evolution of phage resistance in bacterial populations via mutations in the type IV pilus (TIVP), the phage's binding receptor. In a follow-up experiment, we showed that these TIVP mutations pleiotropically reduced motility and conferred resistance to a TIVP-targeting virulent phage, both of which are important traits for Pa infection and treatment. Overall, this work suggests that filamentous phage evolution can drive eco-evolutionary feedbacks in bacterial populations, causing phenotypic and genetic changes that would not be anticipated from adaptation to the extrinsic environment alone.

Pseudomonas aeruginosa

FOXC2 and WT1 regulate transcriptional reprogramming during the podocyte response to injury.

Transcriptional reprogramming has an important role in kidney glomerular disease. Using in vivo murine models of podocyte injury, we studied the roles of the FOXC2 and WT1 transcription factors (TFs) in podocyte injury. Podocytes are a crucial cell type of glomeruli, the filtration units of each nephron. Podocyte injury is often the incipient event leading to chronic kidney disease. It is well established that the TFs FOXC2 and WT1 are required in podocytes to maintain the glomerular filtration barrier. Their role in the response to injury is less well understood. Here, we tested the hypothesis that FOXC2 and WT1 act together to mediate transcriptional reprogramming in response to podocyte injury. Similarly to that of WT1, genome-wide FOXC2 binding to target genes is dynamic during the course of injury, initially increasing, but late in injury there is a dramatic decrease in FOXC2 expression and in its binding to target genes. Podocyte-specific inactivation of FoxC2 or Wt1 in adult mice limits the transcriptional response to injury. Correlating FOXC2 and WT1 ChIP-seq analyses demonstrated that they co-bind many genes expressed in podocytes. Thus, reprogramming the transcriptome involves dynamic changes in the binding of FOXC2 and WT1 to their target genes during a reparative injury response.

Animals

Genome analysis and antagonistic activity of Streptomyces sp. strain J36 against Phytophthora cactorum.

The Phytophthora blight of Panax notoginseng, caused by Phytophthora cactorum, is a devastating oomycete disease. Biocontrol strategies hold immense potential for inhibiting the spread of P. cactorum. We isolated 72 actinobacteria from soil and screened their antagonistic activity against P. cactorum. Both strain J36 and its cell-free filtrate exhibited strong antagonistic activity against P. cactorum and were therefore selected. Based on the 16S rRNA gene phylogenetic tree, strain J36 formed a well supported subclade with Streptomyces zaomyceticus NRRL B-2038 (bootstrap value 100%). However, because 16S rRNA sequences often lack sufficient resolution for species-level discrimination, we performed multilocus sequence analysis (MLSA) using three housekeeping genes (rpoB, recA, and atpD). The MLSA results consistently placed strain J36 within the same cluster as S. zaomyceticus NRRL B-2038, with a bootstrap support of 99%, indicating a close phylogenetic relationship. To further clarify the taxonomic status, we calculated the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain J36 and the type strain of S. zaomyceticus NBC-00415T. The ANI value was 90.91% and the dDDH value was 39.30%, both well below the accepted thresholds for species demarcation (ANI&#x202f;<&#x202f;95%, dDDH < 70%). These genomic indices therefore strongly support that strain J36 represents a novel species within the genus Streptomyces. Through whole-genome sequencing and CAZymes analysis, a total of 98 carbohydrate-active enzymes (CAZymes) were detected, including 2 cellulase and 2 &#x3b2;-1,3-glucanases. The cell-free filtrate, which exhibited strong antagonistic activity against P. cactorum, also showed high activities of cellulase and &#x3b2;-1,3-glucanase, suggesting that these enzymes may be involved in its anti-oomycete activity. These findings suggest that J36 has potential as a biocontrol candidate, although further in vivo evaluation is needed to confirm its efficacy against Phytophthora blight of P. notoginseng.

Panax notoginseng

Cellular Recovery and Therapeutic Rechallenge After Cancer Therapy-Induced Kidney Injury: Mechanistic Insights and Clinical Implications.

Cancer therapy-related acute kidney injury has become an increasingly common challenge as modern treatments prolong survival and increase exposure to potentially nephrotoxic therapies. Decisions regarding therapeutic rechallenge have relied on normalizing serum creatinine and recovering estimated glomerular filtration rate, despite growing evidence that biochemical recovery does not necessarily indicate restoration of kidney integrity or resilience. In this review, we propose biological kidney recovery as a conceptual framework that integrates mechanisms of kidney injury and repair (adaptive and maladaptive) with emerging biomarkers and therapeutic rechallenge. We first summarize the distinct mechanisms of kidney injury induced by platinum-based chemotherapy, immune checkpoint inhibitors, and vascular endothelial growth factor pathway inhibitors, highlighting how these differences influence subsequent repair. We then discuss the cellular and metabolic processes underlying adaptive repair, the transition to maladaptive remodeling, and current approaches for assessing biological recovery through pathology, biomarkers, and multi-omics technologies. Finally, we present a practical framework for individualized therapeutic rechallenge based on an integrated assessment of kidney-, tumor-, and patient-related factors and outline future directions for precision onco-nephrology. By shifting the focus from filtration alone to biological recovery, this framework enables more informed therapeutic rechallenge aimed at preserving both oncologic efficacy and long-term kidney health.

Humans

Polygenic Risk Scores Predicting Estimated GFR Validated With Iohexol Clearance.

INTRODUCTION: Genome-wide association studies (GWAS) have identified hundreds of single nucleotide variants (SNVs) associated with estimated glomerular filtration rate (eGFR). eGFR has been used as a proxy phenotype because of the complexity and cost of measured GFR (mGFR) in large studies. Because eGFR is influenced by non-GFR factors, these GWAS results may be biased compared with a hypothetical study using mGFR. We aimed to investigate this by comparing aggregate measures of genetic effects on mGFR and eGFR. METHODS: We studied 1492 persons from the Renal Iohexol Clearance Survey (RENIS) cohort, a representative sample of the general population in Northern Norway without preexisting cardiovascular disease, kidney disease, or diabetes. We measured iohexol-clearance, and genotyping was performed with a microarray chip enriched for GFR-related SNVs. We compared the performance of 3 published polygenic risk scores (PGS) developed for creatinine-based eGFR (eGFRcr), narrow-sense heritability (h2) and the mean effect of SNVs on mGFR, eGFRcr, cystatin C-based eGFR (eGFRcys) and eGFRcr-cys. RESULTS: The performance of the PGS differed for mGFR and the 3 eGFRs, with best performance for prediction of eGFRcr (P < 0.05). However, when the beta coefficients of the SNVs in the 3 PGS were estimated in the RENIS-cohort, their magnitude was 11% to 46% greater for mGFR than for the 3 eGFR methods in 8 of 9 comparisons (P < 0.05). mGFR had higher h2 (0.47) than eGFRcr (0.21), eGFRcys (0.37), and eGFRcr-cys (0.42). CONCLUSIONS: SNVs with non-GFR effects on creatinine and cystatin-C influence GWAS results. The results of GWAS using eGFR should be validated using experimental and other more precise methods.

chronic kidney disease

Effect of levothyroxine therapy on albuminuria and glomerular function in patients with type 2 diabetes and subclinical Hypothyroidism: a randomized controlled pilot trial.

AIMS: To evaluate the effect of levothyroxine therapy on renal outcomes in patients with type 2 diabetes mellitus (T2DM) and subclinical hypothyroidism (SCH) with background SGLT2 inhibitor therapy. METHODS: In this hypothesis generating open-label, randomized controlled pilot trial, adults with T2DM and SCH were assigned (1:1) to levothyroxine or no levothyroxine therapy and followed for 6&#xa0;months. Primary outcomes were changes in urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). RESULTS: Sixty participants were randomized (30 per group); 24 and 27 completed follow-up in the treatment and control groups respectively. UACR decreased with levothyroxine (-13.09&#xa0;mg/g) and increased in controls (31.84&#xa0;mg/g). The difference was significant in per-protocol (PP)(-44.93&#xa0;mg/g; 95% CI -77.6 to -12.26; p&#xa0;=&#xa0;0.008) but insignificant in intention to treat (ITT)(-35.61&#xa0;mg/g; 95% CI -77.31 to 6.08; p&#xa0;=&#xa0;0.092). eGFR changes were statistically insignificant in both ITT(4.65&#xa0;mL/min/1.73&#xa0;m2; 95% CI -8.3 to 17.6; p&#xa0;=&#xa0;0.472) and PP(7.35&#xa0;mL/min/1.73&#xa0;m2; 95% CI -1.68 to 16.37; p&#xa0;=&#xa0;0.108). Thyroid-stimulating hormone decreased significantly in treatment arm in comparison to control arm (p&#xa0;<&#xa0;0.001) in ITT and PP. No adverse event was reported. CONCLUSIONS: Levothyroxine treatment showed trend toward improving albuminuria and eGFR without reaching statistical significance, suggesting possible renoprotective effect warranting further studies. CLINICAL TRIAL REGISTRATION: This trial is registered with Clinical Trial Registry of India (CTRI/2025/06/089606).

Humans

Kidney Outcomes in Transthyretin Amyloid Cardiomyopathy.

IMPORTANCE: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive cardiomyopathy that commonly presents with concomitant chronic kidney disease. Chronic kidney dysfunction is associated with worse outcomes, but the prognostic value of changes in kidney function over time has yet to be defined. OBJECTIVE: To assess the prognostic importance of a decline in estimated glomerular filtration rate (eGFR) in a large cohort of patients with ATTR-CM. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, observational, single-center cohort study evaluated patients diagnosed with ATTR-CM at the National Amyloidosis Centre (NAC) in the UK who underwent an eGFR baseline assessment and a follow-up assessment at 1 year between January 2000 and April 2024. Data analysis was performed in June 2024. MAIN OUTCOMES AND MEASURES: The primary outcome was the risk of all-cause mortality associated with decline in kidney function (defined as a decrease in eGFR >20%). RESULTS: Among 2001 patients, mean (SD) age was 75.5 (8.4) years, and 263 patients (13.1%) were female. The median (IQR) change in eGFR was -5 mlL/min/1.73 m2 (-12 to 1), and 481 patients (24.0%) experienced decline in kidney function. Patients who experienced decline in kidney function more often had the p.(V142I) genotype than patients with stable kidney function (99 [20.6%] vs 202 [13.3%]; P&#x2009;<&#x2009;.001) and had a more severe cardiac phenotype at baseline, as evidenced by higher median (IQR) concentrations of serum cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 2949 pg/mL [1759-5182] vs 2309 pg/mL [1146-4290]; P&#x2009;<&#x2009;.001; troponin T: 0.060 ng/mL [0.042-0.086] vs 0.052 ng/mL [0.033-0.074]; P&#x2009;<&#x2009;.001), while baseline median (IQR) kidney function was similar between the 2 groups (eGFR: 63 mL/min/1.73 m2 [51-77] vs 61 mL/min/1.73 m2 [49-77]; P&#x2009;=&#x2009;.41). Decline in kidney function was associated with a 1.7-fold higher risk of mortality (hazard ratio [HR], 1.71; 95% CI, 1.43-2.04; P&#x2009;<&#x2009;.001), with a similar risk across the 3 genotypes (wild type: HR, 1.64; 95% CI, 1.31-2.04; p.(V142I): HR, 1.70; 95% CI, 1.21-2.39; non-p.(V142I): HR, 1.51; 95% CI, 0.87-2.61) (P for interaction&#x2009;=&#x2009;.93) and the 3 NAC disease stages (stage 1: HR, 1.69; 95% CI, 1.22-2.32; stage 2: HR, 1.69; 95% CI, 1.30-2.18; stage 3: HR, 1.61; 95% CI, 1.11-2.35) (P for interaction&#x2009;=&#x2009;.97). Decline in kidney function remained independently associated with mortality after adjusting for increases in NT-proBNP and outpatient diuretic intensification (HR, 1.48; 95% CI, 1.23-2.76; P&#x2009;<&#x2009;.001). CONCLUSIONS AND RELEVANCE: In this retrospective cohort study, decline in kidney function was frequent in patients with ATTR-CM and was consistently associated with an increased risk of mortality, even after adjusting for established markers of worsening ATTR-CM. eGFR decline represents an independent marker of ATTR-CM disease progression that could guide treatment optimization in clinical practice.

Humans

Microfiltration (MF) and Ultrafiltration (UF) for Sewage and Surface Water Concentration for SARS-CoV-2 and Other Enveloped Viruses' Detection in Wastewater-Based Epidemiology (WBE).

This study objective was to evaluate hollow fiber membranes for concentration of enveloped enteric viruses in sewage and surface water samples. Microfiltration (MF, 0.2&#x2009;&#xb5;m nominal pore size) and ultrafiltration (UF, 100&#x2009;kDa molecular weight cut-off) hollow fiber membranes were compared for the concentration of the bovine respiratory syncytial virus, and the influence of initial sample volumes (1, 1.5, and 2&#x2009;L), permeate recovery rates (60%, 70% and 80% of the initial volume collected as permeate, equivalent to volumetric concentration factors of 2.5, 3.3 and 5), and backwashing was assessed. Polyethylene glycol precipitation followed by centrifugation (PEG-C) was evaluated both as a stand-alone method and as a secondary step applied to the membrane concentrate. MF and UF membranes had a similar capacity to retain pollutants and to concentrate organic matter in most parameters and conditions (p&#x2009;>&#x2009;0.05). In sewage, increasing the initial volume from 1 to 2&#x2009;L raised recovery from 20.7&#x2009;&#xb1;&#x2009;0.1% to 30.0&#x2009;&#xb1;&#x2009;0.1% with MF and from 20.8&#x2009;&#xb1;&#x2009;0.1% to 25.3&#x2009;&#xb1;&#x2009;0.1% with UF (p&#x2009;<&#x2009;0.05), whereas changes in the permeate recovery rate produced no significant differences (p&#x2009;>&#x2009;0.05). In surface water recovery did not exceed 5.5%, and every increment in the permeate recovery rate produced a significant increase (p&#x2009;<&#x2009;0.05). Backwashing had a stronger effect on RNA recovery than pore size or the remaining operational parameters, reaching 29.3&#x2009;&#xb1;&#x2009;9.3% with MF and 33.8&#x2009;&#xb1;&#x2009;13.7% with UF in sewage and nearly doubling recovery in surface water. In sewage, PEG-C alone (14.1%) was statistically similar to membrane filtration alone (12.1% to 12.3%, p&#x2009;>&#x2009;0.05), while combining both techniques raised recovery to 23.0% to 25.5%. In surface water, membranes alone recovered 0.8% against 2.4% for PEG-C (p&#x2009;<&#x2009;0.05), and the combination of UF with PEG-C reached 5.7%, making it a valid alternative, albeit more time consuming and requiring additional equipment. Recoveries are expressed as the ratio between the genome copy concentration in the concentrate and in the spiked sample; on a total genome copy basis they correspond to 4% to 9% in sewage and to about 1% in surface water.

tangential filtration

The Use of eDNA Metabarcoding to Detect and Identify Phytophthora in Water Samples.

We describe a protocol to amplify DNA barcodes of known and unknown taxa of Phytophthora and related plant pathogenic oomycetes from a range of environments. The methods focus on sampling pathogen propagules from water using in situ sampling and filtration equipment and buffers that enable efficient storage and DNA extraction for later downstream processing.

Phytophthora

Impact of renal dysfunction on immediate versus staged revascularization of non-culprit lesions in patients with ST segment elevation myocardial infarction: a pre-specified subgroup analysis of the randomized MULTISTARS AMI trial.

BACKGROUND: Renal dysfunction might affect outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD) undergoing percutaneous coronary intervention (PCI). METHODS: In MULTISTARS AMI, patients with STEMI and MVD were randomized to immediate or staged PCI of non-culprit lesions. In this pre-specified analysis, patients were stratified according to the presence of renal dysfunction at baseline, defined at an estimated glomerular filtration rate (eGFR) of 60&#xa0;ml/min/1.73 m2. Patients with an eGFR&#x2009;<&#x2009;30&#xa0;ml/min/1.73 m2 were excluded from the trial. The primary endpoint was a composite of death, non-fatal myocardial infarction, stroke, unplanned revascularization, or hospitalization for heart failure at 1&#xa0;year. RESULTS: In MULTISTARS AMI, 108 (13%) of 832 patients had renal dysfunction. The primary endpoint occurred more frequently in patients with renal dysfunction (19.4% vs. 11.2%, unadjusted HR 1.82, 95% CI 1.13-2.94), primarily driven by higher rates of death. Among patients with renal dysfunction, the rates of the primary end point were 14.5% and 24.5% in the immediate and staged PCI groups (unadjusted HR 0.55, 95% CI 0.23-1.33). There was no interaction between renal dysfunction and the randomized treatment assignment with respect to the primary end point (adjusted HR 1.30, 95% CI 0.8-2.20, pint 0.82). The occurrence of acute renal insufficiency was statistically similar in patients with renal dysfunction who underwent immediate and staged PCI (10.9% vs. 18.9%, unadjusted HR 0.61, 95% CI 0.22-1.72, pint 0.09). Renal dysfunction at baseline emerged as a strong risk factor for the development of acute renal insufficiency (adjusted HR 5.0, 95% CI 2.30-10.70, p&#x2009;<&#x2009;0.01). CONCLUSIONS: Outcomes with immediate compared to staged multivessel PCI did not appear significantly altered by the presence of renal dysfunction&#xa0;at baseline. (Supported by Boston Scientific; MULTISTARS AMI ClinicalTrials.gov number, NCT03135275).

Humans