Search

Background: Aedes aegypti transmits various arthropod-borne diseases such as dengue, posing a significant burden to public health in tropical and subtropical regions. Pyrethroid-based control strategies are effective in managing this vector; however, the development of insecticide resistance has hindered these efforts. Hence, long-term monitoring of insecticide resistance in mosquito populations is crucial for effective vector and disease control. Methodology/principal findings: In this study, we identified insecticide resistance due to a voltage-gated sodium channel (vgsc) mutation in Ae. aegypti in Taiwan between 2016 and 2023. In total, 1,761 field-caught Ae. aegypti samples from Tainan, Kaohsiung, and Pingtung were genotyped. The frequencies of S989P, V1016G, T1520I, F1534C, and D1763Y amino acid variants increased over the surveillance period. A T1520I mutation was detected for the first time and has since rapidly spread throughout Taiwan. The triple-mutant haplotype PGTFY was first documented in Ae. aegypti. Moreover, the unmutated haplotype vanished in Taiwan, suggesting that the vgsc mutations were fixed in local populations of Ae. aegypti. Five resistance-associated genotypes, SVTCD/SVTCD, SGTFY/PGTFD, SVTCD/SGTFY, PGTFD/PGTFD, and SVTCD/PGTFD, exhibited an increased frequency and accounted for 76% of the total field population. We also detected the resistant genotype SVICD/PGTFD, and its frequency increased 13-fold in the field between 2016 and 2023. Moreover, we also observed that mutations differed geographically, with S989P mainly found in Kaohsiung and V1016G in Kaohsiung and Pingtung. The frequency of T1520I was noticeably higher in Kaohsiung, and D1763Y occurred mainly in Tainan. Conclusions/significance: The emergence and expansion of mutations along with the disappearance of wild-type mosquitoes in Taiwan underscores the threat of resistance and difficulty of mosquito control in Taiwan as well as globally. This study determined the insecticide resistance status of Ae. aegypti in Taiwan, and the findings will be helpful for resistance monitoring in areas where pyrethroids are used to control Ae. aegypti. Author summary: We conducted an eight-year insecticide resistance surveillance study on vgsc mutations to monitor resistance trends and understand the role of vgsc mutations in Aedes aegypti in Taiwan. Mutations S989P, V1016G, T1520I (first documented in Taiwan), F1534C, and D1763Y were detected, and their frequencies increased over time. We observed that Ae. aegypti with resistance-associated vgsc genotypes comprised the majority of the field population in later years of surveillance, and the unmutated haplotype disappeared; all surveyed field Ae. aegypti harbored at least one vgsc mutation. Three haplotypes were first detected in Taiwan: PGTFY, PGTCD, and SVICD. This study presents the first report of PGTFY in Ae. aegypti, and determining its role in resistance and physiological effects will require further investigation. The observations in this study highlight the emergence and expansion of vgsc mutations and suggest the difficulty of vector control in Taiwan and worldwide. In addition, we found that mutations in Taiwan showed geographical differences. [ABSTRACT FROM AUTHOR]

Background Albuminuria is common and is associated with increased risks of end-stage kidney disease and cardiovascular diseases, yet its underlying mechanism remains obscure. Previous genome-wide association studies (GWAS) for albuminuria did not consider gene pleiotropy and primarily focused on European ancestry populations. This study adopted a multi-trait analysis of GWAS (MTAG) approach to jointly analyze two vital kidney traits, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) to identify and prioritize the genes associated with UACR. Methods Data from the Taiwan Biobank from 2012 to 2023 were analyzed. GWAS of UACR and eGFR were performed separately and the summary statistics from these GWAS were jointly analyzed using MTAG. The polygenic risk scores (PRS) of UACR were constructed for validation. The UACR-associated loci were further fine-mapped and prioritized based on their deleteriousness, eQTL associations and relatedness to Mendelian kidney diseases. Results MTAG analysis of the UACR revealed 15 genetic loci, including 12 novel loci. The PRS for UACR was significantly associated with urinary albumin level (P  < .001) and microalbuminuria (P  = .001–.045). A list of priority genes was generated. Twelve genes with high priority included the albumin endocytic receptor gene LRP2 and ciliary gene IFT172. Conclusions The findings of this multi-trait GWAS suggest that primary cilia play a role in sensing mechanical stimuli, leading to albumin endocytosis. The priority list of genes warrants further translational investigation to reduce albuminuria. [ABSTRACT FROM AUTHOR]

Introduction Acute metabolic decompensation in patients with inborn errors of metabolism (IEM) is a medical emergency that requires immediate renal replacement therapy (RRT) to remove the toxic substances from the [...], Background Intermittent hemodialysis (IHD) is the most efficient form of renal replacement therapy (RRT) for removing toxic substances from patients' bodies. However, the efficacy and safety of IHD in infants and young children with inborn errors of metabolism are still not clear. Methods This retrospective study included patients with urea cycle disorders, maple syrup urine disease, and methylmalonic acidemia who received IHD or non-IHD RRT at our hospital between 2001 and 2012 to remove ammonia, leucine, or methylmalonic acid. Both the efficacy and safety of the RRT were evaluated. Results Thirty-five courses of RRT, including 25 courses of IHD and ten courses of non-IHD RRT, for 15 patients were included in the analysis. Before 2006, non-IHD RRT procedures, including peritoneal dialysis (PD) and continuous venous-venous hemofiltration (CVVH), were the most often used; from 2006 onwards IHD was used. There was one procedure-unrelated death. Catheter penetration occurred in one course of IHD. The efficacy data revealed that both the median duration of dialysis and the median 50 % toxin reduction time were shorter in IHD than in non-IHD RRT. Conclusions In infants and young children with inborn errors of metabolism, IHD is safe and more efficient than non-IHD RRT at removing toxins. Keywords Renal replacement therapy Intermittent Hemodialysis * Inborn errors of metabolism * Urea cycle Disorders * Maple syrup urine disease * Methylmalonic acidemia