ANA Webinars: Implementation of a conference-based virtual networking event

OBJECTIVE: To describe the design and implementation of a virtual network event at the American Neurological Association (ANA) annual meeting led by the Junior and Early Career Member (JECM) Committee. METHODS: We designed a one-hour virtual networking session featuring three 15-minute small group meetings preceded and followed by general remarks. Each small group session consisted of one senior mentor, a junior/early career faculty moderator, and three to four junior/early career mentees. All participants completed an exit survey to evaluate perceived benefit of this event. RESULTS: We recruited 103 mentees, 26 moderators, and 26 mentors for the event. Mentees were primarily at the resident training level or above (17% students). 56% of registered mentees, 100% of moderators and 96% of mentors attended the event for a total of 110 participants. Due to mentee attrition, each room contained 2-3 mentees. 90% of respondents felt the session met their goals very well or extremely well. Further, 99% felt this session was at least comparable to in-person networking at conferences and 60% felt this session was better than in-person networking. INTERPRETATION: Virtual networking sessions between junior and senior academic neurologists are feasible and are at least comparable to, if not better than, in-person conference networking. Future events should consider nuanced mechanisms of matching mentors and mentees, inclusion of ad hoc small groups to foster organic networking, and measures to safeguard against mentee attrition. Future studies should evaluate the long-term benefits of this event to determine if virtual networking should be utilized moving forward

Evaluation of Interleukin 8 gene polymorphism for predicting inflammation in Indian chronic kidney disease and peritoneal dialysis patients

Background and aim: Previous studies have observed the association between inflammation and chronic kidney disease (CKD). The role played by Interleukin 8 (IL8) gene polymorphism has not been studied yet. Hence, the present study has been designed as the first attempt to identify the possible associations between polymorphism of the IL-8 gene and patients with diabetic CKD and on continuous ambulatory peritoneal dialysis (CAPD).Materials and methods: A total of 150 participants were selected from a private nephrology outpatient clinic. The subjects were divided into three groups: healthy individuals without any renal complications (group 1, control, n=50), patients with diabetic chronic kidney disease of stages 3 and 4 (group 2, n= 50) and CAPD (group 3, n= 50). Blood deoxyribo nucleic acid (DNA) isolated from the members of the study group, was confirmed by agarose gel electrophoresis and primers specific for IL8 gene were designed, using primer3 software tool.Results: Restriction digestion of the amplicons with Escherichia coli restriction enzyme I (EcoRI) ended up in 203 base pairs (bp) band in control and 108 bp band in all diabetic and non-diabeticCKD. This indicated the presence of polymorphismin +781 Cytosine/Thymine (C/T) of IL-8 gene in diabetic CKD and CAPD patients. Statistical analysis of the distribution of frequencies of alleles C and T by chi square test confirmed the presence of polymorphismat+781C/T of IL-8 gene in patient groups compared to control.Conclusion: The polymorphismin+781C/T of IL-8 gene studied in this work suggests its possible role as an inflammatory marker for both chronic kidney disease and CAPD.Keywords: IL-8 gene polymorphism; CKD; CAPD; +781 C/

A supramolecular strategy for ratiometric luminescence sensing of nitroaromatic explosives in water

In the present work we have demonstrated a supramolecular approach for ratiometric luminescence sensing of nitroaromatic explosive compounds (NAEs) by employing a red luminescent Eu(III) complex and a green luminescent Pt(II) complex with in a Triton X-100 surfactant based micellar host in water. The Eu-complex gets entrapped inside micellar core whereas the Pt-C2 remains grafted on the surface of the spherical micelles due to their structural amendments and thus facilitates preferential interaction of Pt-C2 with NAE molecules mainly through p-p interaction. The presence of explosive traces quenches the green emission (508-545 nm) of Pt-complex whereas the red emission (614 nm) of Eu-complex remains unaffected. The strategy demonstrates first report of two independent luminophore based ratiometric sensing in water using a micellar host

Whole-genome sequencing expands diagnostic utility and improves clinical management in paediatric medicine

The standard of care for first-Tier clinical investigation of the aetiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy-number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion-deletions (indels) and single-nucleotide variant (SNV) mutations. Whole-genome sequencing (WGS) has the potential to capture all classes of genetic variation in one experiment; however, the diagnostic yield for mutation detection of WGS compared to CMA, and other tests, needs to be established. In a prospective study we utilised WGS and comprehensive medical annotation to assess 100 patients referred to a paediatric genetics service and compared the diagnostic yield versus standard genetic testing. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a fourfold increase in diagnostic rate over CMA (8%; P value = 1.42E - 05) alone and more than twofold increase in CMA plus targeted gene sequencing (13%; P value = 0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harbouring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counselling. Clinical implementation of WGS as a primary test will provide a higher diagnostic yield than conventional genetic testing and potentially reduce the time required to reach a genetic diagnosis

A supramolecular strategy for ratiometric luminescence sensing of nitroaromatic explosives in water

1814-1821In the present work we have demonstrated a supramolecular approach for ratiometric luminescence sensing of nitroaromatic explosive compounds (NAEs) by employing a red luminescent Eu(III) complex and a green luminescent Pt(II) complex with in a Triton X-100 surfactant based micellar host in water. The Eu-complex gets entrapped inside micellar core whereas the Pt-C2 remains grafted on the surface of the spherical micelles due to their structural amendments and thus facilitates preferential interaction of Pt-C2 with NAE molecules mainly through π-π interaction. The presence of explosive traces quenches the green emission (508-545 nm) of Pt-complex whereas the red emission (614 nm) of Eu-complex remains unaffected. The strategy demonstrates first report of two independent luminophore based ratiometric sensing in water using a micellar host

Analysis of five deep-sequenced trio-genomes of the Peninsular Malaysia Orang Asli and North Borneo populations

BackgroundRecent advances in genomic technologies have facilitated genome-wide investigation of human genetic variations. However, most efforts have focused on the major populations, yet trio genomes of indigenous populations from Southeast Asia have been under-investigated.ResultsWe analyzed the whole-genome deep sequencing data (30x) of five native trios from Peninsular Malaysia and North Borneo, and characterized the genomic variants, including single nucleotide variants (SNVs), small insertions and deletions (indels) and copy number variants (CNVs). We discovered approximately 6.9 million SNVs, 1.2 million indels, and 9000 CNVs in the 15 samples, of which 2.7% SNVs, 2.3% indels and 22% CNVs were novel, implying the insufficient coverage of population diversity in existing databases. We identified a higher proportion of novel variants in the Orang Asli (OA) samples, i.e., the indigenous people from Peninsular Malaysia, than that of the North Bornean (NB) samples, likely due to more complex demographic history and long-time isolation of the OA groups. We used the pedigree information to identify de novo variants and estimated the autosomal mutation rates to be 0.81x10(-8) - 1.33x10(-8), 1.0x10(-9) - 2.9x10(-9), and 0.001 per site per generation for SNVs, indels, and CNVs, respectively. The trio-genomes also allowed for haplotype phasing with high accuracy, which serves as references to the future genomic studies of OA and NB populations. In addition, high-frequency inherited CNVs specific to OA or NB were identified. One example is a 50-kb duplication in DEFA1B detected only in the Negrito trios, implying plausible effects on host defense against the exposure of diverse microbial in tropical rainforest environment of these hunter-gatherers. The CNVs shared between OA and NB groups were much fewer than those specific to each group. Nevertheless, we identified a 142-kb duplication in AMY1A in all the 15 samples, and this gene is associated with the high-starch diet. Moreover, novel insertions shared with archaic hominids were identified in our samples.ConclusionOur study presents a full catalogue of the genome variants of the native Malaysian populations, which is a complement of the genome diversity in Southeast Asians. It implies specific population history of the native inhabitants, and demonstrated the necessity of more genome sequencing efforts on the multi-ethnic native groups of Malaysia and Southeast Asia

De Novo and Rare Inherited Copy-Number Variations in the Hemiplegic Form of Cerebral Palsy

PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs