Structural basis of Qng1-mediated salvage of the micronutrient queuine from queuosine-5'-monophosphate as the biological substrate.

Eukaryotic life benefits from-and ofttimes critically relies upon-the de novo biosynthesis and supply of vitamins and micronutrients from bacteria. The micronutrient queuosine (Q), derived from diet and/or the gut microbiome, is used as a source of the nucleobase queuine, which once incorporated into the anticodon of tRNA contributes to translational efficiency and accuracy. Here, we report high-resolution, substrate-bound crystal structures of the Sphaerobacter thermophilus queuine salvage protein Qng1 (formerly DUF2419) and of its human ortholog QNG1 (C9orf64), which together with biochemical and genetic evidence demonstrate its function as the hydrolase releasing queuine from queuosine-5'-monophosphate as the biological substrate. We also show that QNG1 is highly expressed in the liver, with implications for Q salvage and recycling. The essential role of this family of hydrolases in supplying queuine in eukaryotes places it at the nexus of numerous (patho)physiological processes associated with queuine deficiency, including altered metabolism, proliferation, differentiation and cancer progression.

CoDesign of a digital intervention for parents with bipolar disorder informed by integrated knowledge translation principles.

OBJECTIVES: To provide detailed information on the codesign of a digital intervention to support parents with bipolar disorder (BD) who have young children. Each step of this process is reported, as well as a detailed description of the final version of the intervention in line with the TIDieR framework. METHODS: Clinical experience and lived experience experts participated in online workshops, meetings, and remote feedback requests, informed by Integrated Knowledge Translation (IKT) principles. The IKT research group responded to each phase of recommendations from the knowledge users. RESULTS: Five clinical experience experts and six lived experience experts engaged with the codesign process. Their recommendations for principles, content, look, and feel, and functionality of the digital intervention were structured over five iterative phases. This led to a final implemented design that was identified by the clinical and lived experience experts (referred to together as the knowledge users group) as genuinely reflecting their input. CONCLUSIONS: The IKT principles offer an accessible structure for engaging with clinical and lived experience experts throughout a codesign process, in this case for a digital intervention for parents with BD. The resulting intervention is described in detail for transparency to aid further evaluation and development and to help other teams planning codesign approaches to intervention development.

Development, validation and application of an LC-MS/MS method quantifying free forms of the micronutrients queuine and queuosine in human plasma using a surrogate matrix approach.

Queuosine (Q) is a hypermodified 7-deaza-guanosine nucleoside exclusively synthesized by bacteria. This micronutrient and its respective nucleobase form queuine (q) are salvaged by humans either from gut microflora or digested food. Depletion of Q-tRNA in human or mouse cells causes protein misfolding that triggers endoplasmic reticular stress and the activation of the unfolded protein responses. In vivo, this reduces the neuronal architecture of the mouse brain affecting learning and memory. Herein, a sensitive method for quantifying free q and Q in human blood was developed, optimised and validated. After evaluating q/Q extraction efficiency in several different solid-phase sorbents, Bond Elut PBA (phenylboronic acid) cartridges were found to have the highest extraction recovery for q (82%) and Q (71%) from pooled human plasma. PBS with 4% BSA was used as surrogate matrix for method development and validation. An LC-MS/MS method was validated across the concentration range of 0.0003-1 µM for both q and Q, showing excellent linearity (r2 = 0.997 (q) and r2 = 0.998 (Q)), limit of quantification (0.0003 µM), accuracy (100.39-125.71%) and precision (CV% < 15.68%). In a sampling of healthy volunteers (n = 44), there was no significant difference in q levels between male (n = 14; mean = 0.0068 µM) and female (n = 30; mean = 0.0080 µM) participants (p = 0.50). Q was not detected in human plasma. This validated method can now be used to further substantiate the role of q/Q in nutrition, physiology and pathology.

Methods for Evaluating Tibial Accelerations and Spatiotemporal Gait Parameters during Unsupervised Outdoor Movement.

The purpose of this paper is to introduce a method of measuring spatiotemporal gait patterns, tibial accelerations, and heart rate that are matched with high resolution geographical terrain features using publicly available data. These methods were demonstrated using data from 218 Marines, who completed loaded outdoor ruck hikes between 5-20 km over varying terrain. Each participant was instrumented with two inertial measurement units (IMUs) and a GPS watch. Custom code synchronized accelerometer and positional data without a priori sensor synchronization, calibrated orientation of the IMUs in the tibial reference frame, detected and separated only periods of walking or running, and computed acceleration and spatiotemporal outcomes. GPS positional data were georeferenced with geographic information system (GIS) maps to extract terrain features such as slope, altitude, and surface conditions. This paper reveals the ease at which similar data can be gathered among relatively large groups of people with minimal setup and automated data processing. The methods described here can be adapted to other populations and similar ground-based activities such as skiing or trail running.

Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19.

While evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The median infectious dose, assessed by seroconversion, was 52 TCID50 (95% CI: 23-363 TCID50), and was significantly lower than the median dose for fever (256 TCID50, 95% CI: 102-603 TCID50), resulting in a group of animals that developed an immune response post-exposure but did not develop fever or other clinical signs of infection. In a subset of these animals, virus was detected in nasopharyngeal and/or oropharyngeal swabs, suggesting that infected animals without signs of disease are able to shed virus and may be infectious, which is consistent with reports of asymptomatic spread in human cases of COVID-19. These results suggest that differences in exposure dose may be a factor influencing disease presentation in humans, and reinforce the importance of public health measures that limit exposure dose, such as social distancing, masking, and increased ventilation. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, and, ultimately, mitigation strategies. Additionally, these data will be useful to inform dose selection in future studies examining the efficacy of therapeutics and vaccines against inhalational COVID-19, and as a baseline in healthy, young adult animals for assessment of the importance of other factors, such as age, comorbidities, and viral variant, on the infectious dose and disease presentation.

Non-targeted LC-MS/MS metabolomic profiling of human plasma uncovers a novel Mediterranean diet biomarker panel.

INTRODUCTION: Consumption of a Mediterranean diet (MD) has established health benefits, and the identification of novel biomarkers could enable objective monitoring of dietary pattern adherence. OBJECTIVES: The present investigation performed untargeted metabolomics on blood plasma from a controlled study of MD adherence, to identify novel blood-based metabolite biomarkers associated with the MD pattern, and to build a logistic regression model that could be used to characterise MD adherence. METHODS: A hundred and thirty-five plasma samples from n = 58 patients collected at different time points were available. Using a 14-point scale MD Score (MDS) subjects were divided into 'high' or 'low' MDS adherence groups and liquid chromatography-mass spectrometry (LC-MS/MS) was applied for analysis. RESULTS: The strongest association with MDS was pectenotoxin 2 seco acid (r = 0.53; ROC = 0.78), a non-toxic marine xenobiotic metabolite. Several lipids were useful biomarkers including eicosapentaenoic acid, the structurally related lysophospholipid (20:5(5Z,8Z,11Z,14Z,17Z)/0:0), a phosphatidylcholine (P-18:1(9Z)/16:0) and also xi-8-hydroxyhexadecanedioic acid. Two metabolites negatively correlated with MDS, these were the monoacylglycerides (0:0/16:1(9Z)/0:0) and (0:0/20:3(5Z,8Z,11Z)/0:0). By stepwise elimination we selected a panel of 3 highly discriminatory metabolites and developed a linear regression model which identified 'high MDS' individuals with high sensitivity and specificity [AUC (95% CI) 0.83 (0.76-0.97)]. CONCLUSION: Our study highlights the utility of metabolomics as an approach for developing novel panels of dietary biomarkers. Quantitative profiling of these metabolites is required to validate their utility for evaluating dietary adherence.

Debulking SARS-CoV-2 in saliva using angiotensin converting enzyme 2 in chewing gum to decrease oral virus transmission and infection.

To advance a novel concept of debulking virus in the oral cavity, the primary site of viral replication, virus-trapping proteins CTB-ACE2 were expressed in chloroplasts and clinical-grade plant material was developed to meet FDA requirements. Chewing gum (2 g) containing plant cells expressed CTB-ACE2 up to 17.2 mg ACE2/g dry weight (11.7% leaf protein), have physical characteristics and taste/flavor like conventional gums, and no protein was lost during gum compression. CTB-ACE2 gum efficiently (>95%) inhibited entry of lentivirus spike or VSV-spike pseudovirus into Vero/CHO cells when quantified by luciferase or red fluorescence. Incubation of CTB-ACE2 microparticles reduced SARS-CoV-2 virus count in COVID-19 swab/saliva samples by >95% when evaluated by microbubbles (femtomolar concentration) or qPCR, demonstrating both virus trapping and blocking of cellular entry. COVID-19 saliva samples showed low or undetectable ACE2 activity when compared with healthy individuals (2,582 versus 50,126 ΔRFU; 27 versus 225 enzyme units), confirming greater susceptibility of infected patients for viral entry. CTB-ACE2 activity was completely inhibited by pre-incubation with SARS-CoV-2 receptor-binding domain, offering an explanation for reduced saliva ACE2 activity among COVID-19 patients. Chewing gum with virus-trapping proteins offers a general affordable strategy to protect patients from most oral virus re-infections through debulking or minimizing transmission to others.

Dynamic queuosine changes in tRNA couple nutrient levels to codon choice in Trypanosoma brucei.

Every type of nucleic acid in cells undergoes programmed chemical post-transcriptional modification. Generally, modification enzymes use substrates derived from intracellular metabolism, one exception is queuine (q)/queuosine (Q), which eukaryotes obtain from their environment; made by bacteria and ultimately taken into eukaryotic cells via currently unknown transport systems. Here, we use a combination of molecular, cell biology and biophysical approaches to show that in Trypanosoma brucei tRNA Q levels change dynamically in response to concentration variations of a sub-set of amino acids in the growth media. Most significant were variations in tyrosine, which at low levels lead to increased Q content for all the natural tRNAs substrates of tRNA-guanine transglycosylase (TGT). Such increase results from longer nuclear dwell time aided by retrograde transport following cytoplasmic splicing. In turn high tyrosine levels lead to rapid decrease in Q content. Importantly, the dynamic changes in Q content of tRNAs have negligible effects on global translation or growth rate but, at least, in the case of tRNATyr it affected codon choice. These observations have implications for the occurrence of other tunable modifications important for 'normal' growth, while connecting the intracellular localization of modification enzymes, metabolites and tRNAs to codon selection and implicitly translational output.

Paraneoplastic pemphigus associated with Castleman disease: A multicenter case series.

INTRODUCTION: Paraneoplastic pemphigus (PNP) is a rare, often fatal, autoimmune blistering disease of the skin and mucous membranes. In children, PNP is frequently associated with Castleman disease (CD). This series describes five cases of PNP associated with CD. METHODS: Data were collected retrospectively from the medical records of patients with a diagnosis of PNP and CD from January 2013 to June 2022. Patients ≤22 years old with clinical and immunopathologic evidence of PNP were included; CD was diagnosed histopathologically. RESULTS: Two children, two adolescents, and one young adult (two males, three females) were included. The average age at disease presentation was 11.8 years (range: 7-22 years). Oral (n = 5) and anogenital (n = 3) mucositis were common. Four patients had "unicentric" CD (UCD); one patient had "multicentric" CD (MCD). Castleman tumors were in the retroperitoneum (n = 4) or axilla (n = 1). One patient had myasthenia gravis without thymoma. Three patients had bronchiolitis obliterans (BO). Three patients had complete resection of their CD; two had partial resection. Three patients remain alive with a median follow-up of 13 months (range: 12 months to 13 years); two are clinically stable with resolution of mucocutaneous lesions; one has persistent BO requiring ongoing ventilatory support. Patients who remain alive had UCD with complete resection; all deceased patients had partial resection and BO. CONCLUSION: Most patients had UCD, and the retroperitoneum was the most common location. Patients with MCD, incomplete resection, and BO died; patients with UCD and complete resection remain alive, even in the setting of BO. Consideration of PNP is critical when pediatric patients present with mucositis as PNP may be clinically indistinguishable from more common causes of mucositis.

Development of an antibody cocktail for treatment of Sudan virus infection.

Antibody-based therapies are a promising treatment option for managing ebolavirus infections. Several Ebola virus (EBOV)-specific and, more recently, pan-ebolavirus antibody cocktails have been described. Here, we report the development and assessment of a Sudan virus (SUDV)-specific antibody cocktail. We produced a panel of SUDV glycoprotein (GP)-specific human chimeric monoclonal antibodies (mAbs) using both plant and mammalian expression systems and completed head-to-head in vitro and in vivo evaluations. Neutralizing activity, competitive binding groups, and epitope specificity of SUDV mAbs were defined before assessing protective efficacy of individual mAbs using a mouse model of SUDV infection. Of the mAbs tested, GP base-binding mAbs were more potent neutralizers and more protective than glycan cap- or mucin-like domain-binding mAbs. No significant difference was observed between plant and mammalian mAbs in any of our in vitro or in vivo evaluations. Based on in vitro and rodent testing, a combination of two SUDV-specific mAbs, one base binding (16F6) and one glycan cap binding (X10H2), was down-selected for assessment in a macaque model of SUDV infection. This cocktail, RIID F6-H2, provided protection from SUDV infection in rhesus macaques when administered at 50 mg/kg on days 4 and 6 postinfection. RIID F6-H2 is an effective postexposure SUDV therapy and provides a potential treatment option for managing human SUDV infection.

Cell wall protein variation, break-induced replication, and subtelomere dynamics in Candida glabrata.

Candida glabrata is an opportunistic pathogen of humans, responsible for up to 30% of disseminated candidiasis. Adherence of C. glabrata to host cells is mediated by adhesin-like proteins (ALPs), about half of which are encoded in the subtelomeres. We performed a de novo assembly of two C. glabrata strains, BG2 and BG3993, using long single-molecule real-time (SMRT) reads, and constructed high-quality telomere-to-telomere assemblies of all 13 chromosomes to assess differences between C. glabrata strains. We documented variation between strains, and in agreement with earlier studies, found high (~0.5%-1%) frequencies of SNVs across the genome, including within subtelomeric regions. We documented changes in ALP gene structure and complement: there are large length differences in ALP genes in different strains, resulting from copy number variation in tandem repeats. We compared strains to characterize chromosome rearrangement events including within the poorly characterized subtelomeric regions. We show that rearrangements within the subtelomere regions all affect ALP-encoding genes, and 14/16 involve just the most terminal ALP gene. We present evidence that these rearrangements are mediated by break-induced replication. This study highlights the constrained nature of subtelomeric changes impacting ALP gene complement and subtelomere structure.

An ELISA-based antigenicity test of rabies recombinant glycoprotein cannot predict its protective potency in vivo.

The potency of human and veterinary rabies vaccines is measured based on the National Institute of Health (NIH) potency test that is laborious, time-consuming, variable, and requires sacrifice of large numbers of mice. ELISA-based methods quantifying rabies glycoprotein (rGP) are being developed as potential alternatives to the NIH potency test for release of rabies vaccines. The aim of the current study was focused on the evaluation of in vitro- and in vivo-based assays in order to assess their concurrence for adequate and reliable assessment of immunogenicity and protective potency of a plant-derived recombinant rGP. The recombinant rGP of strain ERA.KK was engineered, expressed and purified from Nicotiana benthamiana plants. The recombinant rGP excluded the transmembrane and intracytoplasmic domains. It was purified by chromatography (≥90%) from the plant biomass, characterized, and mainly presented as high molecular weight forms, most likely soluble aggregates, of the rGP ectodomain. It was well-recognized and quantified by an ELISA, which utilizes two mouse monoclonal antibodies, D1-25 and 1112-1, and which should only recognize the native trimeric form of the rGP. However, in mice, the recombinant rGP did not induce the production of anti-rabies virus neutralizing antibodies and did not confer protection after intracerebral viral challenge. Similar immunogenicity was observed in guinea pigs and rabbits. Our results demonstrate that use of the ELISA method described here is not predictive of performance in vivo. These data highlight the critical need to develop in vitro potency assays that reliably define the antigen content that can induce a protective response.

Efficacy of pediatric dermatology Extension for Community Healthcare Outcomes (ECHO) sessions on augmenting primary care providers' confidence and abilities.

Due to the shortage of pediatric dermatologists and the abundance of skin disorders presenting in childhood, general pediatricians shoulder the management of many pediatric dermatologic disorders and would benefit from additional dermatology-specific training. To address this educational gap, general pediatricians were enrolled in a pediatric dermatology-specific Project Extension for Community Healthcare Outcomes (ECHO) program and surveyed to assess the efficacy of the program in increasing providers' ability and confidence in managing pediatric dermatologic conditions. Providers unanimously reported increased confidence and abilities in assessment and management of pediatric dermatologic conditions. Pediatric dermatology Project ECHO demonstrated high efficacy in improving general practitioners' comfort and knowledge on dermatology-specific topics and may be used as an education model for enhancing primary care providers' knowledge and management of common disorders.

1,2,3,4,6-Penta-O-galloyl-d-glucose Interrupts the Early Adipocyte Lifecycle and Attenuates Adiposity and Hepatic Steatosis in Mice with Diet-Induced Obesity.

Phytochemicals that interrupt adipocyte lifecycle can provide anti-obesity effects. 1,2,3,4,6-penta-O-galloyl-d-glucose (PGG) is a tannin with two isomers that occurs widely in plants and exhibits various pharmacological activities. The aim of the investigation is to comprehensively examine effects of PGG isomer(s) on adipocyte lifecycle and diet-induced obesity. Human mesenchymal stem cells (hMSC), 3T3-L1 fibroblasts, and H4IIE hepatoma cells were used to determine the effects of PGG isomers on cell viability and adipogenesis. Mice with diet-induced obesity were generated from male C57/BL6 mice fed with a 45% high fat diet. Oral administration of ß-PGG (0.1 and 5 mg/kg) lasted for 14 weeks. Viability was reduced by repeated PGG treatment in hMSC, preadipocytes, and cells under differentiation. PGG mainly induces apoptosis, and this effect is independent of its insulin mimetic action. In vivo, administration of ß-PGG attenuated shortening of the colon, hyperlipidaemia, fat cells and islet hypertrophy in DIO mice. Hepatic steatosis and related gene expression were improved along with glucose intolerance. Increased serum adiponectin, leptin, and glucagon-like peptide-1 levels were also observed. In conclusion, repeated PGG treatment interrupts the adipocyte lifecycle. PGG administration reduces adiposity and fatty liver development in DIO mice, and therefore, PGG could aid in clinical management of obesity.

Dipeptidyl peptidase-4 (DPP-4) inhibitory activity and glucagon-like peptide (GLP-1) secretion in arsenically safe pigmented red rice (Oryza sativa L.) and its product.

Inhibition of DPP-4 and stimulation of GLP-1 secretion are therapeutic strategies for controlling glycaemia in type 2 diabetes. The present study assessed the DPP-4 inhibitory activity and GLP-1 secretory action of pigmented and non-pigmented rice (Oryza sativa L.), along with an extruded food product. Cereal-based extruded food products, with or without passion fruit powder, were prepared from red rice using a twin extruder. Optimal extrusion conditions were determined using a CCD of response surface methodology resulting in optimal conditions to be 97.5 °C, a screw speed of 250 rpm, feed moisture of 25.2% and addition of 11.25% passion fruit powder. Samples were sequentially extracted in n-hexane, ethanol (50%) and water. Ethanol/water (50:50) extracts of rice bran significantly inhibited DPP-4 activity by 70.48 ± 1.06%, comparing favourably with RR (42.55 ± 0.84%), PRR (35.91 ± 1.27%) and PA (29.14 ± 1.23%). DPP-4 inhibitory activity was retained in both extruded products albeit at reduced levels. GLP-1 secretion was stimulated mostly by extruded products extracted with n-hexane or ethanol which upregulated basal secretion by 6.1-fold and 4.2-fold, respectively. ICP-MS results showed that extruded food items have a lower arsenic content. In conclusion, there are potential opportunities for the nutraceuticals and functional food products using pigmented red rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05444-x.

De novo genome assembly of Candida glabrata reveals cell wall protein complement and structure of dispersed tandem repeat arrays.

Candida glabratais an opportunistic pathogen in humans, responsible for approximately 20% of disseminated candidiasis. Candida glabrata's ability to adhere to host tissue is mediated by GPI-anchored cell wall proteins (GPI-CWPs); the corresponding genes contain long tandem repeat regions. These repeat regions resulted in assembly errors in the reference genome. Here, we performed a de novo assembly of the C. glabrata type strain CBS138 using long single-molecule real-time reads, with short read sequences (Illumina) for refinement, and constructed telomere-to-telomere assemblies of all 13 chromosomes. Our assembly has excellent agreement overall with the current reference genome, but we made substantial corrections within tandem repeat regions. Specifically, we removed 62 genes of which 45 were scrambled due to misassembly in the reference. We annotated 31 novel ORFs of which 24 ORFs are GPI-CWPs. In addition, we corrected the tandem repeat structure of an additional 21 genes. Our corrections to the genome were substantial, with the length of new genes and tandem repeat corrections amounting to approximately 3.8% of the ORFeome length. As most corrections were within the coding regions of GPI-CWP genes, our genome assembly establishes a high-quality reference set of genes and repeat structures for the functional analysis of these cell surface proteins.

Multi-layer longitudinally specular optics for distributing diffuse light.

Multi-layer optical thin films can reflect light to guide it along a hollow tube that they internally line. However, reflecting broadband white light for a range of angles requires many precise thin optical layers, which can be too expensive for large-scale applications such as architectural illumination. Here, we present an alternative configuration that requires only one readily achievable aspect of precision-having a substantially constant cross section, perpendicular to the planned longitudinal propagation direction. This aspect conserves a light ray's longitudinal directional component, while the ray's path in the perpendicular direction can be macroscopically chaotic, much like the diffuse reflection characteristic arising from many non-absorbing pigment particles. This macroscopic characteristic is described here as "longitudinally specular" and "transversely diffuse." This new design overcomes two problems that are found with current prism light guides (PLGs), which are a class of hollow light guides that also have a constant cross section. The PLG has two problems: (1) it requires structured surfaces having near-perfect linear prisms that are much larger than the wavelength of light, wasting optical material and increasing absorption; (2) it only works well with light that has been partially collimated, which limits étendue and requires expensive, inefficient input optics. In this paper, a new, to the best of our knowledge, approach, labeled a "multi-layer prism light guide," simultaneously addresses both problems. Although the new structure is more complex than a conventional PLG, it may be simpler to manufacture. One potential application is for guiding sunlight into buildings for illumination purposes, without requiring complex sun-tracking solar collection optics.

Simulated Sunlight Rapidly Inactivates SARS-CoV-2 on Surfaces.

Previous studies have demonstrated that SARS-CoV-2 is stable on surfaces for extended periods under indoor conditions. In the present study, simulated sunlight rapidly inactivated SARS-CoV-2 suspended in either simulated saliva or culture media and dried on stainless steel coupons. Ninety percent of infectious virus was inactivated every 6.8 minutes in simulated saliva and every 14.3 minutes in culture media when exposed to simulated sunlight representative of the summer solstice at 40°N latitude at sea level on a clear day. Significant inactivation also occurred, albeit at a slower rate, under lower simulated sunlight levels. The present study provides the first evidence that sunlight may rapidly inactivate SARS-CoV-2 on surfaces, suggesting that persistence, and subsequently exposure risk, may vary significantly between indoor and outdoor environments. Additionally, these data indicate that natural sunlight may be effective as a disinfectant for contaminated nonporous materials.

Airborne SARS-CoV-2 Is Rapidly Inactivated by Simulated Sunlight.

Aerosols represent a potential transmission route of COVID-19. This study examined effect of simulated sunlight, relative humidity, and suspension matrix on stability of SARS-CoV-2 in aerosols. Simulated sunlight and matrix significantly affected decay rate of the virus. Relative humidity alone did not affect the decay rate; however, minor interactions between relative humidity and other factors were observed. Mean decay rates (± SD) in simulated saliva, under simulated sunlight levels representative of late winter/early fall and summer were 0.121 ±â€…0.017 min-1 (90% loss, 19 minutes) and 0.306 ±â€…0.097 min-1 (90% loss, 8 minutes), respectively. Mean decay rate without simulated sunlight across all relative humidity levels was 0.008 ±â€…0.011 min-1 (90% loss, 286 minutes). These results suggest that the potential for aerosol transmission of SARS-CoV-2 may be dependent on environmental conditions, particularly sunlight. These data may be useful to inform mitigation strategies to minimize the potential for aerosol transmission.

Assessment of Adaptive Engagement and Support Model for People With Chronic Health Conditions in Online Health Communities: Combined Content Analysis.

BACKGROUND: With the pervasiveness of social media, online health communities (OHCs) are an important tool for facilitating information sharing and support among people with chronic health conditions. Importantly, OHCs offer insight into conversations about the lived experiences of people with particular health conditions. Little is known about the aspects of OHCs that are important to maintain safe and productive conversations that support health. OBJECTIVE: This study aimed to assess the provision of social support and the role of active moderation in OHCs developed in accordance with and managed by an adaptive engagement model. This study also aimed to identify key elements of the model that are central to the development, maintenance, and adaptation of OHCs for people with chronic health conditions. METHODS: This study used combined content analysis, a mixed methods approach, to analyze sampled Facebook post comments from 6 OHCs to understand how key aspects of the adaptive engagement model facilitate different types of social support. OHCs included in this study are for people living with multiple sclerosis, migraine, irritable bowel syndrome, rheumatoid arthritis, lung cancer, and prostate cancer. An exploratory approach was used in the analysis, and initial codes were grouped into thematic categories and then confirmed through thematic network analysis using the Dedoose qualitative analysis software tool. Thematic categories were compared for similarities and differences for each of the 6 OHCs and by topic discussed. RESULTS: Data on the reach and engagement of the Facebook posts and the analysis of the sample of 5881 comments demonstrate that people with chronic health conditions want to engage on the web and find value in supporting and sharing their experiences with others. Most comments made in these Facebook posts were expressions of social support for others living with the same health condition (3405/5881, 57.89%). Among the comments with an element of support, those where community members validated the knowledge or experiences of others were most frequent (1587/3405, 46.61%), followed by the expression of empathy and understanding (1089/3405, 31.98%). Even among posts with more factual content, such as insurance coverage issues, user comments still had frequent expressions of support for others (80/213, 37.5%). CONCLUSIONS: The analysis of this OHC adaptive engagement model in action shows that the foundational elements-social support, engagement, and moderation-can effectively be used to provide a rich and dynamic community experience for individuals with chronic health conditions. Social support is demonstrated in a variety of ways, including sharing information or validating information shared by others, expressions of empathy, and sharing encouraging statements with others.