Pathogenic/likely pathogenic mutations identified in Vietnamese children diagnosed with autism spectrum disorder using high-resolution SNP genotyping platform.

Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.

Malignant Insulinoma Arising From Nonfunctioning Pancreatic Neuroendocrine Tumor.

Pancreatic neuroendocrine tumors are rare neoplasms characterized into nonfunctioning (NF-PNET) and functioning (F-PNET) subtypes. F-PNETs typically involve overt symptoms related to excessive hormone secretion but may rarely present first as NF-PNETs with delayed transformation. We present a patient with known NF-PNET with liver metastases who developed hypoglycemia 2 years after initial diagnosis due to malignant insulinoma. Hypoglycemia was refractory to continuous dextrose but improved temporarily after diazoxide and hepatic artery embolization. Malignant insulinomas are usually metastatic at presentation and portend poor prognosis. Hypoglycemia may be medically managed with steroids, somatostatin analogues, and diazoxide, along with therapies to reduce tumor burden.

Venom chemistry underlying the painful stings of velvet ants (Hymenoptera: Mutillidae).

Velvet ants (Hymenoptera: Mutillidae) are a family of solitary parasitoid wasps that are renowned for their painful stings. We explored the chemistry underlying the stings of mutillid wasps of the genus Dasymutilla Ashmead. Detailed analyses of the venom composition of five species revealed that they are composed primarily of peptides. We found that two kinds of mutillid venom peptide appear to be primarily responsible for the painful effects of envenomation. These same peptides also have defensive utility against invertebrates, since they were able to incapacitate and kill honeybees. Both act directly on cell membranes where they directly increase ion conductivity. The defensive venom peptides of Dasymutilla bear a striking similarity, in structure and mode of action, to those of the ant Myrmecia gulosa (Fabricius), suggesting either retention of ancestral toxins, or convergence driven by similar life histories and defensive selection pressures. Finally, we propose that other highly expressed Dasymutilla venom peptides may play a role in parasitisation, possible in delay or arrest of host development. This study represents the first detailed account of the composition and function of the venoms of the Mutillidae.

Attitudes about and practices for skin cancer prevention among patients with dermatological issues in Hanoi, Vietnam: a cross-sectional study.

BACKGROUND: Raising awareness and educating people regarding practices for skin cancer or melanoma prevention are critical in the context of the adversely increasing effects of global climate change. This study aimed to explore the knowledge, attitudes, and practices regarding skin cancer prevention and to determine the associated factors to knowledge, attitudes, and practices among dermatological patients in Vietnam. METHODS: This cross-sectional study included 590 dermatological patients between 18 and 82 years of age, who received an examination or treatment from the National Hospital of Dermatology in Hanoi, Vietnam, from September to December 2018. The respondents' attitudes on skin cancer and cancer prevention were assessed via face-to-face interviews with a structured questionnaire conducted by trained interviewers. RESULTS: Of the 590 respondents, the majority of people had correct responses to the question regarding skin cancer knowledge. Among the total participants, 39.8% thought that they were at risk of skin cancer, and 13.8% believed their occupation increased their skin cancer risk. The majority of respondents used hats (94.9%) and sunscreen skin coats (89.5%) and went into the shade (86.3%) when exposed to the sun. Women were less likely to be aware of their skin cancer risk but were more likely to practice prevention behaviors. CONCLUSION: Our results show that dermatological patients have acceptable knowledge towards skin cancer prevention, but still need to change their behavior to prevent the risk of skin cancer. This study highlights the importance of education to raise awareness regarding skin cancer in order to promote practice prevention strategies for skin cancer in Vietnam.

Complete Genome Sequences of Clinical Pandoraea fibrosis Isolates.

Pandoraea fibrosis is a newly identified Gram-negative bacterial species that was isolated from the respiratory tract of an Australian cystic fibrosis patient. The complete assembled genome sequences of two consecutive isolates (second isolate collected 11 months after antibiotic treatment) from the same individual are presented here.

Evaluating the genome and resistome of extensively drug-resistant Klebsiella pneumoniae using native DNA and RNA Nanopore sequencing.

BACKGROUND: Klebsiella pneumoniae frequently harbours multidrug resistance, and current diagnostics struggle to rapidly identify appropriate antibiotics to treat these bacterial infections. The MinION device can sequence native DNA and RNA in real time, providing an opportunity to compare the utility of DNA and RNA for prediction of antibiotic susceptibility. However, the effectiveness of bacterial direct RNA sequencing and base-calling has not previously been investigated. This study interrogated the genome and transcriptome of 4 extensively drug-resistant (XDR) K. pneumoniae clinical isolates; however, further antimicrobial susceptibility testing identified 3 isolates as pandrug-resistant (PDR). RESULTS: The majority of acquired resistance (≥75%) resided on plasmids including several megaplasmids (≥100 kb). DNA sequencing detected most resistance genes (≥70%) within 2 hours of sequencing. Neural network-based base-calling of direct RNA achieved up to 86% identity rate, although ≤23% of reads could be aligned. Direct RNA sequencing (with ∼6 times slower pore translocation) was able to identify (within 10 hours) ≥35% of resistance genes, including those associated with resistance to aminoglycosides, ß-lactams, trimethoprim, and sulphonamide and also quinolones, rifampicin, fosfomycin, and phenicol in some isolates. Direct RNA sequencing also identified the presence of operons containing up to 3 resistance genes. Polymyxin-resistant isolates showed a heightened transcription of phoPQ (≥2-fold) and the pmrHFIJKLM operon (≥8-fold). Expression levels estimated from direct RNA sequencing displayed strong correlation (Pearson: 0.86) compared to quantitative real-time PCR across 11 resistance genes. CONCLUSION: Overall, MinION sequencing rapidly detected the XDR/PDR K. pneumoniae resistome, and direct RNA sequencing provided accurate estimation of expression levels of these genes.

Rapid diagnosis of Capnocytophaga canimorsus septic shock in an immunocompetent individual using real-time Nanopore sequencing: a case report.

BACKGROUND: Rapid diagnosis and appropriate treatment is imperative in bacterial sepsis due increasing risk of mortality with every hour without appropriate antibiotic therapy. Atypical infections with fastidious organisms may take more than 4 days to diagnose leading to calls for improved methods for rapidly diagnosing sepsis. Capnocytophaga canimorsus is a slow-growing, fastidious gram-negative bacillus which is a common commensal within the mouths of dogs, but rarely cause infections in humans. C. canimorsus sepsis risk factors include immunosuppression, alcoholism and elderly age. Here we report on the application of emerging nanopore sequencing methods to rapidly diagnose an atypical case of C. canimorsus septic shock. CASE PRESENTATION: A 62 year-old female patient was admitted to an intensive care unit with septic shock and multi-organ failure six days after a reported dog bite. Blood cultures were unable to detect a pathogen after 3 days despite observed intracellular bacilli on blood smears. Real-time nanopore sequencing was subsequently employed on whole blood to detect Capnocytophaga canimorsus in 19 h. The patient was not immunocompromised and did not have any other known risk factors. Whole-genome sequencing of clinical sample and of the offending dog's oral swabs showed near-identical C. canimorsus genomes. The patient responded to antibiotic treatment and was discharged from hospital 31 days after admission. CONCLUSIONS: Use of real-time nanopore sequencing reduced the time-to-diagnosis of Capnocytophaga canimorsus in this case from 6.25 days to 19 h. Capnocytophaga canimorsus should be considered in cases of suspected sepsis involving cat or dog contact, irrespective of the patient's known risk factors.