Inoculating an Infodemic: An Ecological Approach to Understanding Engagement With COVID-19 Online Information

As the global COVID-19 pandemic has been concurrently labelled an “infodemic,” researchers have sought to improve how the general public engages with information that is relevant, timely, and accurate. In this study, we provide an overview of the reasons why people engage and disengage with COVID-19 information. We use context-rich semi-structured interviews which invited participants to discuss online COVID-19-related content they encountered. This qualitative approach allows us to uncover subtle but important details of influences that drive online engagement. Participants both engaged and disengaged with content for individual and social reasons, with seven themes emerging connected to their engagement including actions in response to information, reasoning for engagement, content, motivating concerns, frequency of engagement with information, site of exposure, and given reason for not engaging. Many of these themes intersected and informed each other. Our findings suggest that researchers and public health communicators should approach engagement as an ecology of intersecting influences, both human and algorithmic, which change over time. This information could be potentially helpful to public health communicators who are trying to engage the public with the best information to keep them safe during the pandemic

The health belief model: How public health can address the misinformation crisis beyond COVID-19

Objectives: This paper proposes an intervention into health misinformation that relies upon the health belief model as a means to bridge the risks associated with health misinformation and the impact on individual health, beyond the current recommendations for fact checking and information literacy. Study design: This is a short theoretical paper. Methods: N/A. Results: N/A. Conclusions: Misinformation researchers and public health practitioners and communicators can benefit using the infrastructures afforded by public health offices to mobilize the health belief model as a site for misinformation education

Hereditary spastic paraplegia in Greece: characterisation of a previously unexplored population using next-generation sequencing

Hereditary Spastic Paraplegia (HSP) is a syndrome characterised by lower limb spasticity, occurring alone or in association with other neurological manifestations, such as cognitive impairment, seizures, ataxia or neuropathy. HSP occurs worldwide, with different populations having different frequencies of causative genes. The Greek population has not yet been characterised. The purpose of this study was to describe the clinical presentation and molecular epidemiology of the largest cohort of HSP in Greece, comprising 54 patients from 40 families. We used a targeted next-generation sequencing (NGS) approach to genetically assess a proband from each family. We made a genetic diagnosis in >50% of cases and identified 11 novel variants. Variants in SPAST and KIF5A were the most common causes of autosomal dominant HSP, whereas SPG11 and CYP7B1 were the most common cause of autosomal recessive HSP. We identified a novel variant in SPG11, which led to disease with later onset and may be unique to the Greek population and report the first nonsense mutation in KIF5A. Interestingly, the frequency of HSP mutations in the Greek population, which is relatively isolated, was very similar to other European populations. We confirm that NGS approaches are an efficient diagnostic tool and should be employed early in the assessment of HSP patients

Space Launch System Booster Separation Supersonic Powered Testing with Surface and Off-Body Measurements

A wind tunnel test was run in the NASA Langley Unitary Plan Wind Tunnel simulating the separation of the two solid rocket boosters (SRB) from the core stage of the NASA Space Launch System (SLS). The test was run on a 0.9% scale model of the SLS Block 1B Cargo (27005) configuration and the SLS Block 1B Crew (28005) configuration at a Mach of 4.0. High pressure air was used to simulate plumes from the booster separation motors located at the nose and aft skirt of the two boosters. Force and moment data were taken on both SRBs and on the core stage. Schlieren still photos and video were recorded throughout testing. A set of points were acquired using Cross-correlation Doppler Global Velocimetry (CCDGV) readings to get 3 component velocity measurements between the core and the left-hand SRB. The CCDGV laser was utilized to record flow visualization in the same location, between the core and the left-hand SRB. Pressure Sensitive Paint data were taken on a separate set of runs. Computational Fluid Dynamics (CFD) runs were computed on a subset of the wind tunnel data points for comparison. A combination of the force/moment, CCDGV and Pressure Sensitive Paint (PSP) data (as well as schlieren images) at the CFD-specified test conditions will be used te the CFD simulations that will be used to build an SLS booster separation database flight conditions

Update on leukodystrophies and developing trials

Leukodystrophies are a heterogeneous group of rare genetic disorders primarily affecting the white matter of the central nervous system. These conditions can present a diagnostic challenge, requiring a comprehensive approach that combines clinical evaluation, neuroimaging, metabolic testing, and genetic testing. While MRI is the main tool for diagnosis, advances in molecular diagnostics, particularly whole-exome sequencing, have significantly improved the diagnostic yield. Timely and accurate diagnosis is crucial to guide symptomatic treatment and assess eligibility to participate in clinical trials. Despite no specific cure being available for most leukodystrophies, gene therapy is emerging as a potential treatment avenue, rapidly advancing the therapeutic prospects in leukodystrophies. This review will explore diagnostic and therapeutic strategies for leukodystrophies, with particular emphasis on new trials

TDP-43 pathology in a patient carrying G2019S LRRK2 mutation and a novel p.Q124E MAPT.

Leucine-rich repeat kinase 2 (LRRK2) mutation is the most common cause of genetic-related parkinsonism and is usually associated with Lewy body pathology; however, tau, α-synuclein, and ubiquitin pathologies have also been reported. We report the case of a patient carrying the LRRK2 G2019S mutation and a novel heterozygous variant c.370C>G, p.Q124E in exon 4 of the microtubule-associated protein tau (MAPT). The patient developed parkinsonism with good levodopa response in her 70s. Neuropathological analysis revealed nigral degeneration and Alzheimer-type tau pathology without Lewy bodies. Immunohistochemical staining using phospho-TDP-43 antibodies identified occasional TDP-43 pathology in the hippocampus, temporal neocortex, striatum, and substantia nigra. However, TDP-43 pathology was not identified in another 4 archival LRRK2 G2019S cases with Lewy body pathology available in the Queen Square Brain Bank. Among other published cases of patients carrying LRRK2 G2019S mutation, only 3 were reportedly evaluated for TDP-43 pathology, and the results were negative. The role of the MAPT variant in the clinical and pathological manifestation in LRRK2 cases remains to be determined

Generation of TWO G51D SNCA missense mutation iPSC lines (CRICKi011-A, CRICKi012-A) from two individuals at risk of Parkinson's disease

Mutations or multiplications of the SNCA (Synuclein Alpha) gene cause rare autosomal dominant Parkinson's disease (PD). The SNCA G51D missense mutation is associated with a synucleinopathy that shares PD and multiple system atrophy (MSA) characteristics. We generated induced pluripotent stem cell (iPSC) lines from two individuals with SNCA G51D missense mutations at risk of PD. Dermal fibroblasts were reprogrammed to pluripotency using a non-integrating mRNA-based protocol. The resulting human iPSCs displayed normal morphology, expressed markers associated with pluripotency, and differentiated into the three germ layers. The iPSC lines could facilitate disease-modelling and therapy development studies for synucleinopathies

Tay-Sachs Disease: Two Novel Rare HEXA Mutations from Pakistan and Morocco

Background: Tay-Sachs disease (TSD) is a rare autosomalrecessive genetic disorder characterized by progressive destruction of nerve cells in the brain and spinal cord. It is caused by genetic variations in the HEXA gene leading to a deficiency of β hexosaminidase A (HEXA) isoenzyme activity. This study aimed to identify causative gene variants in 3 unrelated consanguineous families presented with TSD from Pakistan and Morocco. / Methods: Detailed clinical investigations were carried out on probands in 3 unrelated consanguineous families of Pakistani and Moroccan origin. Targeted gene sequencing and Whole Exome Sequencing (WES) were performed for variant identification. Candidate variants were checked for co-segregation with the phenotype using Sanger sequencing. Public databases including ExAC, GnomAD, dbSNP and the 1,000 Genome Project were searched to determine frequencies of the alleles. Conservation of the missense variants was ensured by aligning orthologous protein sequences from diverse vertebrate species. / Results: We report on 3 children presented with Tay-Sachs Disease. The β hexosaminidaseA enzyme activity was reduced in the Pakistani patient in one of the pedigrees. Genetic testing revealed 2 novel homozygous variants (p.Asp386Alafs*13 and p.Trp266Gly) in the gene HEXA in Pakistani and Moroccan patients respectively.The third family of Pakistani origin revealed a previously reported variant (p.Tyr427Ilefs*5) in HEXA. p.Tyr427Ilefs*5 is the most commonly occurring pathogenic variationin Ashkenazi but was not reported in Pakistani population. / Conclusion: Our study further expands the ethnic and mutational spectrum of Tay-Sachs disease emphasizing the usefulness of WES as a powerful diagnostic tool where enzymatic activity is not performed for Tay-Sachs disease. The study recommends targeted screening for these mutations (p.Tyr427Ilefs5) for cost effective testing of TSD patients. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families

De novo mutation in SLC25A22 gene: expansion of the clinical and electroencephalographic phenotype

The SLC25A22 (Solute Carrier Family 25, Member 22) gene encodes for a mitochondrial glutamate/H+ symporter and is involved in the mitochondrial transport of metabolites across the mitochondrial membrane. We hereby report a 12-year-old girl presenting with early-onset epileptic encephalopathy, hypotonia, and global developmental delay. Whole exome sequencing identified a novel homozygous missense mutation in SLC25A22 gene (c.97A>G; p.Lys33Glu), as the likely cause of the disease. The phenotype of our patient and EEG recordings do not completely overlap with the phenotypes previously described, leading to a new and more complex form of disease associated with SLC25A22 variants, characterized by dyskinetic movements and oculogyric crisis