Along with positive SARS-CoV-2 RNA in nasopharyngeal swabs, viral RNA was detectable at high concentration for >3 weeks in fecal samples from 12 mildly symptomatic and asymptomatic children with ...COVID-19 in Seoul, South Korea. Saliva also tested positive during the early phase of infection. If proven infectious, feces and saliva could serve as transmission sources.
Both glucose and free fatty acids (FFAs) are used as fuel sources for energy production in a living organism. Compelling evidence supports a role for excess fatty acids synthesized in intramuscular ...space or dietary intermediates in the regulation of skeletal muscle function. Excess FFA and lipid droplets leads to intramuscular accumulation of lipid intermediates. The resulting downregulation of the insulin signaling cascade prevents the translocation of glucose transporter to the plasma membrane and glucose uptake into skeletal muscle, leading to metabolic disorders such as type 2 diabetes. The mechanisms underlining metabolic dysfunction in skeletal muscle include accumulation of intracellular lipid derivatives from elevated plasma FFAs. This paper provides a review of the molecular mechanisms underlying insulin-related signaling pathways after excess accumulation of lipids.
Osteogenesis imperfecta (OI) is a heterogenous group of genetic disorders of bone fragility. OI type V is an autosomal-dominant disease characterized by calcification of the forearm interosseous ...membrane, radial head dislocation, a subphyseal metaphyseal radiodense line, and hyperplastic callus formation; the causative mutation involved in this disease has not been discovered yet. Using linkage analysis in a four-generation family and whole-exome sequencing, we identified a heterozygous mutation of c.−14C>T in the 5′-untranslated region of a gene encoding interferon-induced transmembrane protein 5 (IFITM5). It completely cosegregated with the disease in three families and occurred de novo in five simplex individuals. Transfection of wild-type and mutant IFITM5 constructs revealed that the mutation added five amino acids (Met-Ala-Leu-Glu-Pro) to the N terminus of IFITM5. Given that IFITM5 expression and protein localization is restricted to the skeletal tissue and IFITM5 involvement in bone formation, we conclude that this recurrent mutation would have a specific effect on IFITM5 function and thus cause OI type V.
Rotor syndrome is caused by digenic loss-of-function variants in SLCO1B1 and SLCO1B3 but only a few studies have reported co-occurring inactivating variants from both genes. A rotor syndrome-causing ...long interspersed element-1 (LINE-1) insertion in SLCO1B3 had been reported to be highly prevalent in the Japanese population but there has been no additional report. In spite of its known association with various human diseases, LINE-1 is hard to detect with current sequencing technologies. In this study, we aimed to devise a method to screen the LINE-1 insertion variant and investigate the frequency of this variant in various populations. A chimeric sequence, that was generated by concatenating the reference sequence at the junction and a part of inserted LINE-1 sequence, was searched from 725 raw sequencing data files. In cases containing the chimeric sequence, confirmatory long-range PCR and gap-PCR were performed. In total, 95 (13.1%) of 725 patients were positive for the chimeric sequence, and all were confirmed to have the SLCO1B3 LINE-1 insertion by PCR-based tests. The same chimeric sequence was searched from the 1000 Genomes Project data repository and the carrier frequency was remarkably high in the East Asian populations (10.1%), especially in Southern Han Chinese (18.5%), but almost absent in other populations. This SLCO1B3 LINE-1 insertion should be screened in a population-specific manner under suspicion of Rotor syndrome and the methods proposed in this study would enable this in a simple way.
Abstract
Background
Positive results from real-time reverse-transcription polymerase chain reaction (rRT-PCR) in recovered patients raise concern that patients who recover from coronavirus disease ...2019 (COVID-19) may be at risk of reinfection. Currently, however, evidence that supports reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reported.
Methods
We conducted whole-genome sequencing of the viral RNA from clinical specimens at the initial infection and at the positive retest from 6 patients who recovered from COVID-19 and retested positive for SARS-CoV-2 via rRT-PCR after recovery. A total of 13 viral RNAs from the patients’ respiratory specimens were consecutively obtained, which enabled us to characterize the difference in viral genomes between initial infection and positive retest.
Results
At the time of the positive retest, we were able to acquire a complete genome sequence from patient 1, a 21-year-old previously healthy woman. In this patient, through the phylogenetic analysis, we confirmed that the viral RNA of positive retest was clustered into a subgroup distinct from that of the initial infection, suggesting that there was a reinfection of SARS-CoV-2 with a subtype that was different from that of the primary strain. The spike protein D614G substitution that defines the clade “G” emerged in reinfection, while mutations that characterize the clade “V” (ie, nsp6 L37F and ORF3a G251V) were present at initial infection.
Conclusions
Reinfection with a genetically distinct SARS-CoV-2 strain may occur in an immunocompetent patient shortly after recovery from mild COVID-19. SARS-CoV-2 infection may not confer immunity against a different SARS-CoV-2 strain.
We conducted serial whole-genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results highlight possible SARS-CoV-2 reinfection with a genetically distinct SARS-CoV-2 strain in patients shortly after recovery from mild coronavirus disease 2019 (COVID-19).
Aims
Nocturnal acid breakthrough has been considered an unmet need of proton‐pump inhibitors. Tegoprazan, a novel potassium‐competitive acid blocker, is expected to show improved properties for this ...unmet need. This study was aimed to compare night‐time acid suppression by tegoprazan with that by vonoprazan or esomeprazole, and to explore the effect of CYP2C19 phenotypes on acid‐suppressive effects.
Methods
A randomized, open‐label, 3‐period, 6‐sequence crossover study was conducted. A single oral dose of tegoprazan 50 mg, vonoprazan 20 mg or esomeprazole 40 mg was administered at night in each period. Continuous intragastric pH was monitored at baseline and after each dosing.
Results
Sixteen healthy subjects (6 CYP2C19 extensive metabolizers, 5 intermediate metabolizers, 5 poor metabolizers) completed the study. After a single dose of tegoprazan, intragastric pH increased more rapidly to over 4 at approximately 1 hour compared to the other treatments, and elevated intragastric pH was maintained stably at night. Tegoprazan exhibited night‐time acid suppression for slightly but not significantly longer than vonoprazan, and greater than esomeprazole; % time at pH ≥ 4 at night was 66.0%, 60.5% and 36.1% for tegoprazan, vonoprazan and esomeprazole, respectively. Night‐time acid suppression by tegoprazan and vonoprazan was not dependent on CYP2C19 phenotypes, while that by esomeprazole tended to be influenced by CYP2C19 phenotypes.
Conclusion
Tegoprazan produced more rapid, potent and well sustained night‐time acid suppression vs. vonoprazan or esomeprazole when administered at night. Furthermore, tegoprazan showed no CYP2C19 phenotype dependency in acid suppression. It suggests the potential of tegoprazan, especially in preventing nocturnal acid breakthrough.
Abstract
Sarcopenia is characterized by decreased skeletal muscle mass and function with age. Aged muscles have altered lipid compositions; however, the role and regulation of lipids are unknown. ...Here we report that FABP3 is upregulated in aged skeletal muscles, disrupting homeostasis via lipid remodeling. Lipidomic analyses reveal that FABP3 overexpression in young muscles alters the membrane lipid composition to that of aged muscle by decreasing polyunsaturated phospholipid acyl chains, while increasing sphingomyelin and lysophosphatidylcholine. FABP3-dependent membrane lipid remodeling causes ER stress via the PERK-eIF2α pathway and inhibits protein synthesis, limiting muscle recovery after immobilization. FABP3 knockdown induces a young-like lipid composition in aged muscles, reduces ER stress, and improves protein synthesis and muscle recovery. Further, FABP3 reduces membrane fluidity and knockdown increases fluidity in vitro, potentially causing ER stress. Therefore, FABP3 drives membrane lipid composition-mediated ER stress to regulate muscle homeostasis during aging and is a valuable target for sarcopenia.
Reliable biomarkers are required to evaluate and manage pancreatic ductal adenocarcinoma. Circulating tumor cells and circulating tumor DNA are shed into blood and can be relatively easily obtained ...from minimally invasive liquid biopsies for serial assays and characterization, thereby providing a unique potential for early diagnosis, forecasting disease prognosis, and monitoring of therapeutic response. In this review, we provide an overview of current technologies used to detect circulating tumor cells and circulating tumor DNA and describe recent advances regarding the multiple clinical applications of liquid biopsy in pancreatic ductal adenocarcinoma.
This review provides an overview of current technologies used to detect circulating tumor cells and circulating tumor DNA and recent advances regarding the multiple clinical applications of liquid biopsy in pancreatic ductal adenocarcinoma. Recent studies focusing on the diagnostic, prognostic, and predictive aspects of circulating tumor cells and circulating tumor DNA in pancreatic ductal adenocarcinoma are also discussed.
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