MMP-1 and -3 haplotype is associated with congenital anomalies of the kidney and urinary tract

Congenital anomalies of the kidney and urinary tract (CAKUT) are a common cause of progressive chronic kidney disease that may lead to end-stage renal disease and renal replacement therapy in childhood. Altered expression or activity of matrix metalloproteinases (MMPs) have been found in CAKUT. The MMP-1, -3, and -8 polymorphisms studied here are located in the gene promoters and alter expression. Our aim was to investigate associations of MMP polymorphisms, solely and in haplotypes, with CAKUT in children. A case-control study with 101 pediatric patients and 281 controls was performed. The MMP-1 (-1607 1G/2G), -3 (5A/6A), and -8 (-799 C/T) genotypes were determined by PCR-restriction fragment length polymorphism. We found statistically significant associations of MMP-3 5A/6A polymorphism (p LT 0.0001) and 1G(-1607)-6A haplotype, with no preferences for MMP-8 -799C or T alleles, with CAKUT (OR = 2.93, 95 % CI 1.43-5.98, adjusted for gender, p = 0.003) and with obstructive uropathies in a subgroup of patients (OR = 4.57, 95 % CI 2.74-7.61, adjusted for gender, p LT 0.0001). MMP-3 genotypes and MMP-3 and -1 haplotypes encompassing either MMP-8 -799C or T alleles were associated with CAKUT and obstructive uropathies in pediatric patients. Still, functional and association studies are needed to elucidate evident roles of MMPs in CAKUT

Suicide by pesticide ingestion in Nepal and the impact of pesticide regulation

Abstract Background Nepal recorded 5754 suicides in 2018–19 - a high number for a relatively small country. Over 24% of these suicides were by poisoning, most by ingestion of highly concentrated agricultural pesticides. Nepal has actively regulated pesticides to reduce their health impacts since 2001. We aimed to analyse Nepal’s history of pesticide regulation, pesticides responsible for poisonings, and relate them to national suicide rates. Methods Information on pesticide regulation was collected from the Plant Quarantine and Pesticide Management Centre of the Ministry of Agriculture and Livestock Development. National data on suicides from 1980 to 2019 were obtained from the National Statistical Bureau and Nepal Police. Data on the pesticides responsible for self-poisoning and pesticide suicides over time were obtained from a systematic literature review. Results As of June 2020, 171 pesticides were registered for use in Nepal, of which one was extremely hazardous (WHO Class Ia), one other highly hazardous (WHO Class Ib), and 71 moderately hazardous (WHO Class II). Twenty-four pesticides have been banned since 2001, with eight (including five WHO Class I compounds) banned in 2019. Although the suicide rate has increased more than twelve-fold since 1980, particularly for hanging (15-fold increase from 1980 to 2018), fatal pesticide self-poisoning has increased by 13-fold. Methyl-parathion is reported to be the key pesticide responsible for pesticide self-poisoning in Nepal, despite being banned in 2006. Conclusion The full effect of the recent pesticide policy reform in Nepal remains to be seen. Our analysis shows a continuing increase in suicide numbers, despite bans of the most important pesticide in 2006. This may indicate smuggling across the border and the use of the brand name (Metacid) for pesticides in general making it difficult to identify the responsible pesticide. More information is required from forensic toxicology labs that identify the individual compounds found. The effect of recent bans of common suicide pesticides needs to be monitored over the coming years. Evidence from other Asian countries suggests that HHPs bans will lead to a marked reduction in suicides, as well as fewer cases of occupational poisoning

Comprehensive RNA-Seq Expression Analysis of Sensory Ganglia with a Focus on Ion Channels and GPCRs in Trigeminal Ganglia

The specific functions of sensory systems depend on the tissue-specific expression of genes that code for molecular sensor proteins that are necessary for stimulus detection and membrane signaling. Using the Next Generation Sequencing technique (RNA-Seq), we analyzed the complete transcriptome of the trigeminal ganglia (TG) and dorsal root ganglia (DRG) of adult mice. Focusing on genes with an expression level higher than 1 FPKM (fragments per kilobase of transcript per million mapped reads), we detected the expression of 12984 genes in the TG and 13195 in the DRG. To analyze the specific gene expression patterns of the peripheral neuronal tissues, we compared their gene expression profiles with that of the liver, brain, olfactory epithelium, and skeletal muscle. The transcriptome data of the TG and DRG were scanned for virtually all known G-protein-coupled receptors (GPCRs) as well as for ion channels. The expression profile was ranked with regard to the level and specificity for the TG. In total, we detected 106 non-olfactory GPCRs and 33 ion channels that had not been previously described as expressed in the TG. To validate the RNA-Seq data, in situ hybridization experiments were performed for several of the newly detected transcripts. To identify differences in expression profiles between the sensory ganglia, the RNA-Seq data of the TG and DRG were compared. Among the differentially expressed genes (> 1 FPKM), 65 and 117 were expressed at least 10-fold higher in the TG and DRG, respectively. Our transcriptome analysis allows a comprehensive overview of all ion channels and G protein-coupled receptors that are expressed in trigeminal ganglia and provides additional approaches for the investigation of trigeminal sensing as well as for the physiological and pathophysiological mechanisms of pain