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To better describe the genetic diversity of hantaviruses associated with human illness in South America, we screened blood samples from febrile patients in Chapare Province in central Bolivia during 2008-2009 for recent hantavirus infection. Hantavirus RNA was detected in 3 patients, including 1 who died. Partial RNA sequences of small and medium segments from the 3 patients were most closely related to Andes virus lineages but distinct (<90% nt identity) from reported strains. A survey for IgG against hantaviruses among residents of Chapare Province indicated that 12.2% of the population had past exposure to >1 hantaviruses; the highest prevalence was among agricultural workers. Because of the high level of human exposure to hantavirus strains and the severity of resulting disease, additional studies are warranted to determine the reservoirs, ecologic range, and public health effect of this novel strain of hantavirus. [ABSTRACT FROM AUTHOR]

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A letter to the editor is presented regarding the use of the hepatic venous pressure gradient (HVPG) method to estimate portal hypertension (PHT) liver cirrhosis complication.

The article presents a case study on the diagnosis of secondary hypertension which causes miscarriage during the first trimester of pregnancy. Differential diagnosis of uncontrolled arterial hypertension (AHT) includes testing for hypertension, pregnancy-related ATH, and pre-eclampsia or secondary aetiology. It suggests that PHA diagnosis must be considered to prevent severe pregnancy complications.

Abstract Background Anthropogenic habitat modifications have led to the extinction of many species and have favoured the expansion of others. Nonetheless, the possible role of humans as a diversifying force in vertebrate evolution has rarely been considered, especially for species with long generation times. We examine the influence that humans have had on the colonization and phenotypic and genetic differentiation of an insular population of a long-lived raptor species, the Egyptian vulture (Neophron percnopterus). Results The morphological comparison between the Canarian Egyptian vultures and the main and closest population in Western Europe (Iberia) indicated that insular vultures are significantly heavier (16%) and larger (about 3%) than those from Iberia. Bayesian and standard genetic analyses also showed differentiation (FST = 0.11, p < 0.01). The inference of changes in the effective size of the Canarian deme, using two likelihood-based Bayesian approaches, suggested that the establishment of this insular population took place some 2500 years ago, matching the date of human colonization. This is consistent with the lack of earlier fossils. Conclusions Archaeological remains show that first colonizers were Berber people from northern Africa who imported goats. This new and abundant food source could have allowed vultures to colonize, expand and adapt to the island environment. Our results suggest that anthropogenic environmental change can induce diversification and that this process may take place on an ecological time scale (less than 200 generations), even in the case of a long-lived species.

Abstract Background The molecular events and evolutionary forces underlying lethal mutagenesis of virus (or virus extinction through an excess of mutations) are not well understood. Here we apply for the first time phylogenetic methods and Partition Analysis of Quasispecies (PAQ) to monitor genetic distances and intra-population structures of mutant spectra of foot-and-mouth disease virus (FMDV) quasispecies subjected to mutagenesis by base and nucleoside analogues. Results Phylogenetic and PAQ analyses have revealed a highly dynamic variation of intrapopulation diversity of FMDV quasispecies. The population diversity first suffers striking expansions in the presence of mutagens and then compressions either when the presence of the mutagenic analogue was discontinued or when a mutation that decreased sensitivity to a mutagen was selected. The pattern of mutations found in the populations was in agreement with the behavior of the corresponding nucleotide analogues with FMDV in vitro. Mutations accumulated at preferred genomic sites, and dn/ds ratios indicate the operation of negative (or purifying) selection in populations subjected to mutagenesis. No evidence of unusually elevated genetic distances has been obtained for FMDV populations approaching extinction. Conclusion Phylogenetic and PAQ analysis provide adequate procedures to describe the evolution of viral sequences subjected to lethal mutagenesis. These methods define the changes of intra-population structure more precisely than mutation frequencies and Shannon entropies. PAQ is very sensitive to variations of intrapopulation genetic distances. Strong negative (or purifying) selection operates in FMDV populations subjected to enhanced mutagenesis. The quantifications provide evidence that extinction does not imply unusual increases of intrapopulation complexity, in support of the lethal defection model of virus extinction.

Background and Aims: Alcohol-associated liver disease (ALD) is a leading cause of liver-related mortality worldwide, with limited treatment options beyond abstinence and liver transplantation. Chronic alcohol consumption has been linked to magnesium (Mg 2+ ) deficiency, which can influence liver disease progression. The mechanisms underlying Mg 2+ homeostasis dysregulation in ALD remain elusive. This study aimed to investigate the role of the Mg 2+ transporter Cyclin M4 (CNNM4) in ALD by analyzing its expression patterns in patients with ALD and preclinical animal models., Approach and Results: In this study, CNNM4 is upregulated in the liver of both patients with ALD and animal models. CNNM4 overexpression triggers Mg 2+ homeostasis dysregulation, linked to ALD progression. We propose a novel therapeutic approach for ALD treatment using N -acetylgalactosamine silencing RNA technology to specifically modulate Cnnm4 expression in the liver, improving mitochondrial function and alleviating endoplasmic reticulum stress. Notably, silencing Cnnm4 restores protein isoaspartyl methyltransferase (PCMT1) activity, essential for repairing ethanol-induced protein damage. Enhancing mitochondrial activity through Cnnm4-dependent mechanisms increases S -adenosylmethionine levels, crucial for PCMT1 function, highlighting the interconnected roles of mitochondrial health and protein homeostasis in ALD treatment., Conclusions: These findings shed light on the dysregulation of Mg 2+ homeostasis in ALD, providing a promising therapeutic approach targeting CNNM4. N -acetylgalactosamine si Cnnm4 therapy boosts the repair processes of ethanol-damaged proteins through the upregulation of PCMT1 activity., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The prevailing belief that antibiotic resistance mechanisms emerged with human antibiotic use has been challenged. Evidence indicates that some antibiotic resistance genes (ARGs) have a long evolutionary history, predating the advent of antibiotics in human medicine, thereby demonstrating that resistance is an ancient phenomenon. Despite extensive surveys of resistance elements in environments impacted by human activity, limited data are available from remote and pristine habitats. This minireview aims to compile the most relevant research on the origins and evolution of ARGs in these habitats, which function as reservoirs for ancient resistance mechanisms. These studies indicate that ancient ARGs functionally similar to modern resistance genes, highlighting the general role of natural antimicrobial substances in fostering the evolution and exchange of diverse resistance mechanisms through horizontal gene transfer over time. This minireview underscores that antibiotic resistance was present in ancestral microbial communities and emphasizes the ecological role of antibiotics and resistance determinants. Understanding ancient ARGs is crucial for predicting and managing the evolution of antibiotic resistance. Thus, these insights provide a foundational basis for developing new antibiotics and strategies for microbial resistance management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Agudo and Reche.)

West Nile virus (WNV) is a flavivirus responsible for causing febrile illness and severe neurological diseases, with an increasing impact on human health around the world. However, there is still no adequate therapeutic treatment available to struggle WNV infections. Therefore, there is an urgent need to develop new techniques to accelerate the discovery of drugs against this pathogen. The main protein implicated in the replication of WNV is the non-structural protein 5 (NS5). This multifunctional protein contains methyltransferase (MTase) activity involved in the capping formation at the 5'-end of RNA and the methylation of internal viral RNA residues, both functions being essential for viral processes, such as RNA translation and escape from the innate immune response. We have developed a straightforward luminescence-based assay to monitor the MTase activity of the WNV NS5 protein with potential for high-throughput screening. We have validated this method as a sensitive and suitable assay for the identification of WNV MTase inhibitors assessing the inhibitory effect of the broad MTase inhibitor sinefungin, a natural nucleoside analog of the universal methyl donor S-adenosyl methionine (SAM). The screening of a small series of purine derivatives identified an adenosine derivative as a dose-dependent inhibitor of the MTase activity. The antiviral efficacy of this compound was further confirmed in WNV infections, displaying a measurable antiviral effect. This result supports the utility of this novel method for the screening of inhibitors against WNV MTase activity, which can be of special relevance to the discovery and development of therapeutics against WNV., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Introduction: Ammonia is a pathogenic factor implicated in the progression of metabolic-associated steatotic liver disease (MASLD). The contribution of the glutaminase 1 (GLS) isoform, an enzyme converting glutamine to glutamate and ammonia, to hepatic ammonia build-up and the mechanisms underlying its upregulation in metabolic-associated steatohepatitis (MASH) remain elusive., Methods: Multiplex transcriptomics and targeted metabolomics analysis of liver biopsies in dietary mouse models representing the whole spectra of MASLD were carried out to characterize the relevance of hepatic GLS during disease pathological progression. In addition, the acute effect of liver-specific GLS inhibition in hepatic ammonia content was evaluated in cultured hepatocytes and in in vivo mouse models of diet-induced MASLD. Finally, the regulatory mechanisms of hepatic GLS overexpression related to the lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4) axis were explored in the context of MASH., Results: In mouse models of diet-induced MASLD, we found that augmented liver GLS expression is closely associated with the build-up of hepatic ammonia as the disease progresses from steatosis to steatohepatitis. Importantly, the acute silencing/pharmacological inhibition of GLS diminishes the ammonia burden in cultured primary mouse hepatocytes undergoing dedifferentiation, in steatotic hepatocytes, and in a mouse model of diet-induced steatohepatitis, irrespective of changes in ureagenesis and gut permeability. Under these conditions, GLS upregulation in the liver correlates positively with the hepatic expression of TLR4 that recognizes LPS. In agreement, the pharmacological inhibition of TLR4 reduces GLS and hepatic ammonia content in LPS-stimulated mouse hepatocytes and hyperammonemia animal models of endotoxemia., Conclusions: Overall, our results suggest that the LPS/TLR4 axis regulates hepatic GLS expression promoting liver ammonia build-up as steatotic liver disease progresses to steatohepatitis., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Drug-induced liver injury (DILI) is a significant cause of acute liver failure (ALF) and liver transplantation in the Western world. Acetaminophen (APAP) overdose is a main contributor of DILI, leading to hepatocyte cell death through necrosis. Here, we identified that neddylation, an essential post-translational modification involved in the mitochondria function, was upregulated in liver biopsies from patients with APAP-induced liver injury (AILI) and in mice treated with an APAP overdose. MLN4924, an inhibitor of the neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8)-activating enzyme (NAE-1), ameliorated necrosis and boosted liver regeneration in AILI. To understand how neddylation interferes in AILI, whole-body biotinylated NEDD8 ( bio NEDD8) and ubiquitin ( bio UB) transgenic mice were investigated under APAP overdose with and without MLN4924. The cytidine diphosphate diacylglycerol (CDP-DAG) synthase TAM41, responsible for producing cardiolipin essential for mitochondrial activity, was found modulated under AILI and restored its levels by inhibiting neddylation. Understanding this ubiquitin-like crosstalk in AILI is essential for developing promising targeted inhibitors for DILI treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nowadays, chronic kidney disease (CKD) prevalence keeps increasing worldwide. The management of these patients usually requires renal replacement therapy (RRT). However, the complexity of patients' profiles comprises a great challenge to overcome. During the last decades, CKD units have been developed to offer multidisciplinary and coordinated attention to patients, helping in the decision-making of the RRT. Nevertheless, there is a huge variability in the performance and organization of care practice, implying an existing necessity to homogenize the RRT modality chosen. We propose a test composed of two parts: one to be completed by the medical staff (to evaluate contraindications for the different RRT techniques) and another by the patient or nursing staff (to consider patients' preferences). In this sense, it would be possible to have a common and useful tool to complement patient education in RRT, as well as sharing decision-making in the ACKD units taking into account patient preferences., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

Background: Patients with chronic kidney disease (CKD) are more prone to cardiovascular disease (CVD) risks, including CVD-derived sudden death. Additionally, patients with CKD also develop lipid metabolism abnormalities. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i) are drugs capable of reducing CVD risk in patients with CKD, but their efficacy is scarcely assessed in transplant patients., Case Presentation: Here, we report a case of a 74-year-old man undergoing nephrology follow-up for a cadaver donor kidney transplant. The patient described an atorvastatin allergic reaction after an acute coronary syndrome. Because the patient had a very high risk for CVD, alirocumab was substituted for atorvastatin. The patient showed a well-tolerated and effective response and stable everolimus levels., Conclusion: PCSK9i may be considered a pharmacologic option for treating lipid metabolism disorder and reducing low-density lipoprotein cholesterol in transplant recipients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)