Investigating the Prevalence of Reactive Online Searching in the COVID-19 Pandemic: Infoveillance Study.

BACKGROUND: The ongoing pandemic has placed an unprecedented strain on global society, health care, governments, and mass media. Public dissemination of government policies, medical interventions, and misinformation has been remarkably rapid and largely unregulated during the COVID-19 pandemic, resulting in increased misinterpretations, miscommunication, and public panic. Being the first full-scale global pandemic of the digital age, COVID-19 has presented novel challenges pertinent to government advice, the spread of news and misinformation, and the trade-off between the accessibility of science and the premature public use of unproven medical interventions. OBJECTIVE: This study aims to assess the use of internet search terms relating to COVID-19 information and misinformation during the global pandemic, identify which were most used in six affected countries, investigate any temporal trends and the likely propagators of key search terms, and determine any correlation between the per capita cases and deaths with the adoption of these search terms in each of the six countries. METHODS: This study uses relative search volume data extracted from Google Trends for search terms linked to the COVID-19 pandemic alongside per capita case and mortality data extracted from the European Open Data Portal to identify the temporal dynamics of the spread of news and misinformation during the global pandemic in six affected countries (Australia, Germany, Italy, Spain, the United Kingdom, and the United States). A correlation analysis was carried out to ascertain any correlation between the temporal trends of search term use and the rise of per capita mortality and disease cases. RESULTS: Of the selected search terms, most were searched immediately following promotion by governments, public figures, or viral circulation of information, but also in relation to the publication of scientific resources, which were sometimes misinterpreted before further dissemination. Strong correlations were identified between the volume of these COVID-19-related search terms (overall mean Spearman rho 0.753, SD 0.158), and per capita mortality (mean per capita deaths Spearman rho 0.690, SD 0.168) and cases (mean per capita cases Spearman rho 0.800, SD 0.112). CONCLUSIONS: These findings illustrate the increased rate and volume of the public consumption of novel information during a global health care crisis. The positive correlation between mortality and online searching, particularly in countries with lower COVID-19 testing rates, may demonstrate the imperative to safeguard official communications and dispel misinformation in these countries. Online news, government briefings, and social media provide a powerful tool for the dissemination of important information to the public during pandemics, but their misuse and the presentation of misrepresented medical information should be monitored, minimized, and addressed to safeguard public safety. Ultimately, governments, public health authorities, and scientists have a moral imperative to safeguard the truth and maintain an accessible discourse with the public to limit fear.

Gene editing improves endoplasmic reticulum-mitochondrial contacts and unfolded protein response in Friedreich's ataxia iPSC-derived neurons.

Friedreich ataxia (FRDA) is a multisystemic, autosomal recessive disorder caused by homozygous GAA expansion mutation in the first intron of frataxin (FXN) gene. FXN is a mitochondrial protein critical for iron-sulfur cluster biosynthesis and deficiency impairs mitochondrial electron transport chain functions and iron homeostasis within the organelle. Currently, there is no effective treatment for FRDA. We have previously demonstrated that single infusion of wild-type hematopoietic stem and progenitor cells (HSPCs) resulted in prevention of neurologic and cardiac complications of FRDA in YG8R mice, and rescue was mediated by FXN transfer from tissue engrafted, HSPC-derived microglia/macrophages to diseased neurons/myocytes. For a future clinical translation, we developed an autologous stem cell transplantation approach using CRISPR/Cas9 for the excision of the GAA repeats in FRDA patients' CD34+ HSPCs; this strategy leading to increased FXN expression and improved mitochondrial functions. The aim of the current study is to validate the efficiency and safety of our gene editing approach in a disease-relevant model. We generated a cohort of FRDA patient-derived iPSCs and isogenic lines that were gene edited with our CRISPR/Cas9 approach. iPSC derived FRDA neurons displayed characteristic apoptotic and mitochondrial phenotype of the disease, such as non-homogenous microtubule staining in neurites, increased caspase-3 expression, mitochondrial superoxide levels, mitochondrial fragmentation, and partial degradation of the cristae compared to healthy controls. These defects were fully prevented in the gene edited neurons. RNASeq analysis of FRDA and gene edited neurons demonstrated striking improvement in gene clusters associated with endoplasmic reticulum (ER) stress in the isogenic lines. Gene edited neurons demonstrated improved ER-calcium release, normalization of ER stress response gene, XBP-1, and significantly increased ER-mitochondrial contacts that are critical for functional homeostasis of both organelles, as compared to FRDA neurons. Ultrastructural analysis for these contact sites displayed severe ER structural damage in FRDA neurons, that was undetected in gene edited neurons. Taken together, these results represent a novel finding for disease pathogenesis showing dramatic ER structural damage in FRDA, validate the efficacy profile of our FXN gene editing approach in a disease relevant model, and support our approach as an effective strategy for therapeutic intervention for Friedreich's ataxia.

Monitoring SARS-CoV-2 Using Infoveillance, National Reporting Data, and Wastewater in Wales, United Kingdom: Mixed Methods Study.

BACKGROUND: The COVID-19 pandemic necessitated rapid real-time surveillance of epidemiological data to advise governments and the public, but the accuracy of these data depends on myriad auxiliary assumptions, not least accurate reporting of cases by the public. Wastewater monitoring has emerged internationally as an accurate and objective means for assessing disease prevalence with reduced latency and less dependence on public vigilance, reliability, and engagement. How public interest aligns with COVID-19 personal testing data and wastewater monitoring is, however, very poorly characterized. OBJECTIVE: This study aims to assess the associations between internet search volume data relevant to COVID-19, public health care statistics, and national-scale wastewater monitoring of SARS-CoV-2 across South Wales, United Kingdom, over time to investigate how interest in the pandemic may reflect the prevalence of SARS-CoV-2, as detected by national testing and wastewater monitoring, and how these data could be used to predict case numbers. METHODS: Relative search volume data from Google Trends for search terms linked to the COVID-19 pandemic were extracted and compared against government-reported COVID-19 statistics and quantitative reverse transcription polymerase chain reaction (RT-qPCR) SARS-CoV-2 data generated from wastewater in South Wales, United Kingdom, using multivariate linear models, correlation analysis, and predictions from linear models. RESULTS: Wastewater monitoring, most infoveillance terms, and nationally reported cases significantly correlated, but these relationships changed over time. Wastewater surveillance data and some infoveillance search terms generated predictions of case numbers that correlated with reported case numbers, but the accuracy of these predictions was inconsistent and many of the relationships changed over time. CONCLUSIONS: Wastewater monitoring presents a valuable means for assessing population-level prevalence of SARS-CoV-2 and could be integrated with other data types such as infoveillance for increasingly accurate inference of virus prevalence. The importance of such monitoring is increasingly clear as a means of objectively assessing the prevalence of SARS-CoV-2 to circumvent the dynamic interest and participation of the public. Increased accessibility of wastewater monitoring data to the public, as is the case for other national data, may enhance public engagement with these forms of monitoring.

MEDI: Macronutrient Extraction and Determination from invertebrates, a rapid, cheap and streamlined protocol.

Macronutrients, comprising carbohydrates, proteins and lipids, underpin many ecological processes, but their quantification in ecological studies is often inaccurate and laborious, requiring large investments of time and bulk samples, which make individual-level studies impossible. This study presents Macronutrient Extraction and Determination from Invertebrates (MEDI), a protocol for the direct, rapid and relatively low-cost determination of macronutrient content from single small macroinvertebrates.Macronutrients were extracted by a sequential process of soaking in 1:12 chloroform:methanol solution to remove lipid and then solubilising tissue in 0.1 M NaOH. Proteins, carbohydrates and lipids were determined by colorimetric assays from the same individual specimens.The limits of detection of MEDI with the equipment and conditions used were 0.067, 0.065 and 0.006 mg/ml for proteins, carbohydrates and lipids respectively. Adjusting the volume of reagents used for extraction and determination can broaden the range of concentrations that can be detected. MEDI successfully identified taxonomic differences in macronutrient content between five insect species.Macronutrient Extraction and Determination from Invertebrates can directly and rapidly determine macronutrient content in tiny (dry mass ~3 mg) and much larger individual invertebrates. Using MEDI, the total macronutrient content of over 50 macroinvertebrates can be determined within around 3 days of collection at a cost of ~$1.35 per sample.

Detrimental effect of zwitterionic buffers on lysosomal homeostasis in cell lines and iPSC-derived neurons.

Good's buffers are commonly used for cell culture and, although developed to have minimal to no biological impact, they cause alterations in cellular processes such as autophagy and lysosomal enzyme activity. Using Chinese hamster ovary cells and induced pluripotent stem cell-derived neurons, this study explores the effect of zwitterionic buffers, specifically HEPES, on lysosomal volume and Ca2+ levels. Certain zwitterionic buffers lead to lysosomal expansion and reduced lysosomal Ca2+. Care should be taken when selecting buffers for growth media to avoid detrimental impacts on lysosomal function.