Substrate Trapping in Polyketide Synthase Thioesterase Domains: Structural Basis for Macrolactone Formation.

Emerging antibiotic resistance requires continual improvement in the arsenal of antimicrobial drugs, especially the critical macrolide antibiotics. Formation of the macrolactone scaffold of these polyketide natural products is catalyzed by a modular polyketide synthase (PKS) thioesterase (TE). The TE accepts a linear polyketide substrate from the termina PKS acyl carrier protein to generate an acyl-enzyme adduct that is resolved by attack of a substrate hydroxyl group to form the macrolactone. Our limited mechanistic understanding of TE selectivity for a substrate nucleophile and/or water has hampered development of TEs as biocatalysts that accommodate a variety of natural and non-natural substrates. To understand how TEs direct the substrate nucleophile for macrolactone formation, acyl-enzyme intermediates were trapped as stable amides by substituting the natural serine OH with an amino group. Incorporation of the unnatural amino acid, 1,3-diaminopropionic acid (DAP), was tested with five PKS TEs. DAP-modified TEs (TE DAP ) from the pikromycin and erythromycin pathways were purified and tested with six full-length polyketide intermediates from three pathways. The erythromycin TE had permissive substrate selectivity, whereas the pikromycin TE was selective for its native hexaketide and heptaketide substrates. In a crystal structure of a native substrate trapped in pikromycin TE DAP , the linear heptaketide was curled in the active site with the nucleophilic hydroxyl group positioned 4 Å from the amide-enzyme linkage. The curled heptaketide displayed remarkable shape complementarity with the TE acyl cavity. The strikingly different shapes of acyl cavities in TEs of known structure, including those reported here for juvenimicin, tylosin and fluvirucin biosynthesis, provide new insights to facilitate TE engineering and optimization.

Formerly used defense sites on Unalaska Island, Alaska: Mapping a legacy of environmental pollution.

Unalaska Island, Alaska, served as a US military base during World War II. The military installed bases on Unalaska and nearby islands, many of which were built adjacent to Unangan communities. The military used toxic compounds in its operations and left a legacy of pollution that may pose health risks to residents and local wildlife. The goals of this study were to identify hotspots of contamination remaining at Unalaska formerly used defense (FUD) sites, evaluate the risk posed by arsenic, and examine "no US Department of Defense action indicated" (NDAI) status determinations for FUD sites near communities. We compiled soil chemistry data from remediation reports prepared by the US Army Corps of Engineers at 18 FUD sites on and near Unalaska. Nine had past and/or active remediation projects and on-site sampling data. Eight sites did not have sampling data and were characterized as NDAI. One site was listed as closed. For the nine sites with sampling data, we compiled data for 22 contaminants of concern (COC) and compared concentrations to soil cleanup levels for human health (18 AAC 75.341). We mapped contaminant concentrations exceeding these levels to identify hotspots of contamination. We found that concentrations of some of the 22 COC exceeded Alaska cleanup levels despite remediation efforts, including diesel range organics, arsenic, and lead. The highest COC concentrations were at the FUD site adjacent to the City of Unalaska. A quantitative risk assessment for arsenic found that the risk of exposure through drinking water is low. We highlight concerns with NDAI designations and current remedial practices at remote FUD sites located adjacent to communities. Our data suggest the need for further remediation and monitoring efforts on Unalaska for certain contaminants and research to examine potential threats to human and animal health associated with these sites. Integr Environ Assess Manag 2024;00:1-12. © 2024 SETAC.

Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA.

Background: Post-traumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. Available pharmacotherapies are limited, take weeks to show modest benefit and remain ineffective for up to 40% of patients. Methylone is currently in clinical development for the treatment of PTSD. Preclinical studies show rapid, robust and long-lasting antidepressant-like and anxiolytic effects. The mechanism of action underlying these effects is not yet fully understood. This study investigated the downstream gene expression changes and signaling pathways affected by methylone in key brain areas linked to PTSD and MDD. It also sought to determine whether neuroplasticity-related genes were involved. We compared effects of methylone with MDMA to explore similarities and differences in their brain effects because MDMA-assisted psychotherapy has recently shown benefit in clinical trials for PTSD and methylone is a structural analog of MDMA. Methods: Monoamine binding, uptake and release studies were performed and a high-throughput-screen evaluated agonist/antagonist activities at 168 GPCRs in vitro. We used RNA sequencing (RNA-seq) to probe drug-induced gene expression changes in the amygdala and frontal cortex, two brain areas responsible for emotional learning that are affected by PTSD and MDD. Rats were treated with methylone or MDMA (both 10 mg/kg, IP), and their responses were compared with controls. We performed functional enrichment analysis to identify which pathways were regulated by methylone and/or MDMA. We confirmed changes in gene expression using immunohistochemistry. Results: Methylone, a monoamine uptake inhibitor and releaser, demonstrated no off-target effects at 168 GPCRs, unlike MDMA, which showed activity at 5HT2A and 5HT2C receptors. RNA-seq results revealed significant regulation of myelin-related genes in the amygdala, confirmed by immunohistochemistry. In the frontal cortex, methylone significantly upregulated genes implicated in neuroplasticity. Conclusion: Results suggest that (1) methylone is a rapid-acting neuroplastogen that affects key brain substrates for PTSD and MDD and that (2) methylone appears to exhibit higher specificity and fewer off-target effects than MDMA. Together, these results are consistent with the reported clinical experiences of methylone and MDMA and bolster the potential use of methylone in the treatment of PTSD and, potentially, other neuropsychiatric disorders.

Subjective and physiological reactivity to emotional stressors in somatic symptom disorder.

OBJECTIVE: We examined whether autonomic flexibility to experimentally presented stressors is reduced in somatic symptom disorder (SSD) as this would point to reduced vagal control as a proposed indicator of emotion regulation deficits. METHOD: In this experimental study, the influence of health-related and social stressors on subjective and physiological reactivity was investigated in 29 subjects with SSD without any medical condition SSD(mc-), 33 subjects with SSD with medical condition SSD(mc+) and 32 healthy controls at the age from 18 to 70 years. Self-report and physiological variables were measured before and after/during stressor exposure, using state ratings of symptom intensity, disability, tension and mood, heart rate (HR), and heart rate variability (HRV). RESULTS: Overall, the tension increased and the mood worsened after exposure to stressors compared to pre-exposure. Compared to HC, the two SSD groups showed higher symptom intensity, disability, tension and worse mood. The SSD(mc-) group revealed higher HR than HC (p = .012, d = -0.77). Compared to pre-exposure, symptom impairment increased after social stressor exposure in SSD(mc-) (p < .001, d = 1.36). HRV-root mean square of successive differences (RMSSD) only decreased in HC during exposure (p = .003, d = -1.09), not in the SSD groups. The two SSD groups did not differ in their reactivity to stressors. CONCLUSION: HRV in SSD, seems to respond less flexibly to stressors, potentially reflecting overall physiological disturbance through reduced parasympathetic influence on HR. Stress reactivity in SSD(mc-) and SSD(mc+) do not seem to differ.

Increasing multi-hazard climate risk and financial and health impacts on northern homeowners.

Currently, more than half of the world's human population lives in urban areas, which are increasingly affected by climate hazards. Little is known about how multi-hazard environments affect people, especially those living in urban areas in northern latitudes. This study surveyed homeowners in Anchorage and Fairbanks, USA, Alaska's largest urban centers, to measure individual risk perceptions, mitigation response, and damages related to wildfire, surface ice hazards, and permafrost thaw. Up to one third of residents reported being affected by all three hazards, with surface ice hazards being the most widely distributed, related to an estimated $25 million in annual damages. Behavioral risk response, policy recommendations for rapidly changing urban environments, and the challenges to local governments in mitigation efforts are discussed.

Annual Recurrence of the Critically Endangered Bowmouth Guitarfish (Rhina ancylostomus) in Djibouti Waters.

The bowmouth guitarfish (Rhina ancylostomus) is among the most endangered of marine vertebrates, and evidence of severe declines and localized extinctions has been reported. Yet its life history and ecology suffer from a lack of scientific attention due to the scarcity and unpredictable movements of the species. By collecting opportunistic records from 2015 to 2023 during diving activities, this study describes for the first time the occurrence of a predictable aggregation of R. ancylostomus in the Gulf of Tadjoura (Djibouti). These data provide a key record of this species in the area, whose presence is strongly associated with sandy seabeds and corals at approximately 35 m depth. Based on the opportunistic sightings of R. ancylostomus during diving activity, Ras Eiro and Ras Korali appear to be the currently known core habitats for this species and may serve as breeding or feeding grounds. Overall, our data show that the Gulf of Tadjoura is a globally important conservation hotspot, and therefore its protection should be prioritized.

Phyllosphere microbial diversity and specific taxa mediate within-cultivar resistance to Phytophthora palmivora in cacao.

The oomycete pathogen Phytophthora palmivora, which causes black pod rot (BPR) on cacao (Theobroma cacao L.), is responsible for devastating yield losses worldwide. Genetic variation in resistance to Phytophthora spp. is well documented among cacao cultivars, but variation has also been observed in the incidence of BPR even among trees of the same cultivar. In light of evidence that the naturally occurring phyllosphere microbiome can influence foliar disease resistance in other host-pathogen systems, it was hypothesized that differences in the phyllosphere microbiome between two field accessions of the cultivar Gainesville II 164 could be responsible for their contrasting resistance to P. palmivora. Bacterial alpha diversity was higher but fungal alpha diversity was lower in the more resistant accession MITC-331, and the accessions harbored phyllosphere microbiomes with distinct community compositions. Six bacterial and 82 fungal amplicon sequence variants (ASVs) differed in relative abundance between MITC-333 and MITC-331, including bacterial putative biocontrol agents and a high proportion of fungal pathogens, and nine fungal ASVs were correlated with increased lesion development. The roles of contrasting light availability and host mineral nutrition, particularly potassium, are also discussed. Results of this preliminary study can be used to guide research into microbiome-informed integrated pest management strategies effective against Phytophthora spp. in cacao. IMPORTANCE Up to 40% of the world's cacao is lost each year to diseases, the most devastating of which is black pod rot, caused by Phytophthora palmivora. Though disease resistance is often attributed to cacao genotypes (i.e., disease-resistant rootstocks), this study highlights the role of the microbiome in contributing to differences in resistance even among accessions of the same cacao cultivar. Future studies of plant-pathogen interactions may need to account for variation in the host microbiome, and optimizing the cacao phyllosphere microbiome could be a promising new direction for P. palmivora resistance research.

Mercury Concentrations in Whale Shark (Rhincodon typus) Embryo Muscle Tissue.

Mercury (Hg) is known to be maternally transferred during embryonic development in sharks; however, Hg concentrations in embryos of filter feeding shark species have not previously been reported. This study measured the total Hg (THg) concentration in muscle tissue of 27 embryos taken from a pregnant whale shark (Rhincodon typus) landed in Taiwan in 1995 and the mean THg concentration compared to the mean muscle THg concentration in embryos from other shark species. The mean (± standard deviation) THg concentration in whale shark embryos was 0.0762 ± 0.0163 µg/g dry weight (0.0224 ± 0.0054 µg/g wet weight). There was no relationship between muscle THg concentration and body length and no significant difference in THg concentration between male and female embryos (p > 0.05). Whale shark embryos have the lowest reported muscle THg concentrations compared to literature values for muscle THg concentrations for embryos from other shark species.

Discovery of IACS-52825, a Potent and Selective DLK Inhibitor for Treatment of Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major unmet medical need with limited treatment options. Despite different mechanisms of action, diverse chemotherapeutics can cause CIPN through a converged pathway─an active axon degeneration program that engages the dual leucine zipper kinase (DLK). DLK is a neuronally enriched kinase upstream in the MAPK-JNK cascade, and while it is dormant under physiological conditions, DLK mediates a core mechanism for neuronal injury response under stress conditions, making it an attractive target for treatment of neuronal injury and neurodegenerative diseases. We have developed potent, selective, brain penetrant DLK inhibitors with excellent PK and activity in mouse models of CIPN. Lead compound IACS-52825 (22) showed strongly effective reversal of mechanical allodynia in a mouse model of CIPN and was advanced into preclinical development.

Children diagnosed with presymptomatic type 1 diabetes through public health screening have milder diabetes at clinical manifestation.

AIMS/HYPOTHESIS: We aimed to determine whether disease severity was reduced at onset of clinical (stage 3) type 1 diabetes in children previously diagnosed with presymptomatic type 1 diabetes in a population-based screening programme for islet autoantibodies. METHODS: Clinical data obtained at diagnosis of stage 3 type 1 diabetes were evaluated in 128 children previously diagnosed with presymptomatic early-stage type 1 diabetes between 2015 and 2022 in the Fr1da study and compared with data from 736 children diagnosed with incident type 1 diabetes between 2009 and 2018 at a similar age in the DiMelli study without prior screening. RESULTS: At the diagnosis of stage 3 type 1 diabetes, children with a prior early-stage diagnosis had lower median HbA1c (51 mmol/mol vs 91 mmol/mol [6.8% vs 10.5%], p<0.001), lower median fasting glucose (5.3 mmol/l vs 7.2 mmol/l, p<0.05) and higher median fasting C-peptide (0.21 nmol/l vs 0.10 nmol/l, p<0.001) compared with children without previous early-stage diagnosis. Fewer participants with prior early-stage diagnosis had ketonuria (22.2% vs 78.4%, p<0.001) or required insulin treatment (72.3% vs 98.1%, p<0.05) and only 2.5% presented with diabetic ketoacidosis at diagnosis of stage 3 type 1 diabetes. Outcomes in children with a prior early-stage diagnosis were not associated with a family history of type 1 diabetes or diagnosis during the COVID-19 pandemic. A milder clinical presentation was observed in children who participated in education and monitoring after early-stage diagnosis. CONCLUSIONS/INTERPRETATION: Diagnosis of presymptomatic type 1 diabetes in children followed by education and monitoring improved clinical presentation at the onset of stage 3 type 1 diabetes.

Appearance-related concerns in individuals with pathological skin picking-a comparison with individuals with dermatological conditions and skin-healthy controls.

Introduction: Pathological skin picking (PSP) is an excessive behavior which characterizes Skin Picking Disorder. Individuals repeatedly pick their skin and cause skin lesions, but are unable to control the behavior, which can cause severe distress. Visible self-inflicted skin lesions can additionally affect individuals with PSP due to emerging appearance-related concerns. However, these concerns and their role in PSP have hardly been studied, especially not in comparison with individuals with dermatological conditions and skin-healthy controls. Methods: The present cross-sectional study (n = 453, 83.9% female, 15.9% male, 0.2% diverse) aimed at analyzing appearance-related concerns and mental health outcomes between four groups: Individuals with PSP and dermatological conditions (SP/DC; n = 83), PSP without dermatological conditions (SP; n = 56), dermatological conditions without PSP (DC; n = 176) and skin-healthy controls (SH, n = 138). We compared questionnaire data on dysmorphic concerns, appearance-based rejection sensitivity, and body dysmorphic symptoms, as well as PSP-symptoms and mental health outcomes (depression, anxiety, and self-esteem) between groups. Results: The analyses showed a significant multivariate group effect in the appearance-related variables, F(6, 896) = 19.92, Wilks' Λ = 0.78, p < 0.001, and mental health outcomes, F(6, 896) = 16.24, Wilks' Λ = 0.81, p < 0.001. The SP/DC group had the strongest appearance-related concerns and mental health impairments, followed by the SP group, the DC group and the SH group. The SP/DC group and SP group only differed significantly with regard to dysmorphic concerns, but not in other variables. The DC group was less affected but still showed higher dysmorphic concerns and mental health impairments than skin-healthy controls. In contrast to the PSP groups, the other two groups did not exceed clinically relevant cut-off scores. Discussion: The present study shows that individuals with PSP exhibit strong appearance-related concerns, regardless of the presence or absence of underlying or comorbid dermatological conditions. These findings shed new light on the importance of appearance-related concerns in Skin Picking Disorder and the role of PSP as a potentially overlooked risk factor in dermatological patients. Therefore, appearance-related concerns should be explicitly addressed in dermatological and psychotherapeutic settings. Future studies should also include longitudinal and experimental analyses to more clearly classify the role of appearance-related concerns in the etiology of PSP and Skin Picking Disorder.

Empowering medicine residents to order labs mindfully to improve patient-centered care.

BACKGROUND: Unnecessary laboratory testing of hospitalized patients is prevalent. OBJECTIVE: We conducted a study focused on "mindful ordering" to decrease unnecessary laboratory ordering within an Internal Medicine residency program. DESIGNS, SETTINGS AND PARTICIPANTS: We collected survey data on resident/faculty perceptions of laboratory ordering as well as order information from the electronic medical record (EMR). INTERVENTION: Interventions focused on resident-identified barriers such as knowledge, EMR, habit and faculty expectations. Interventions were cumulative and included resident/faculty education and EMR optimization. MAIN OUTCOMES AND MEASURES: We assessed basic and complete metabolic panels (BMP, CMP) and complete blood counts with and without differential (CBC w/diff, w/o diff). Primary outcomes included: total labs ordered per week, lab and frequency, and resident perception of ordering practices. Secondary outcomes included: length-of stay (LOS) and venipuncture utilization. RESULTS: Survey data demonstrated increased resident perception of both mindful ordering and team discussion. Total labs ordered per week decreased 20% in the first year (1944 to 1500 labs/week). Residents' use of the "one-time draw" option increased; use of "daily" frequency decreased. Trends showed an increase in BMP relative to CMP, and an increase in CBC w/o diff relative to CBC w/diff. These changes were sustained through 127 weeks. There was an approximately 10% decrease in monthly average of patients undergoing venipuncture each day (86.7% to 74.2%). The shifts in laboratory ordering in conjunction with increased discussion about labs suggest a sustained change in resident lab ordering behavior. This study shows the impact of focusing interventions on resident-identified barriers to mindful ordering to create a sustained decrease laboratory orders.

Global gateways as telecoupled human and natural systems: The emerging case of the Bering Strait.

Numerous narrow marine passages around the world serve as essential gateways for the transportation of goods, the movement of people, and the migration of fish and wildlife. These global gateways facilitate human-nature interactions across distant regions. The socioeconomic and environmental interactions among distant coupled human and natural systems affect the sustainability of global gateways in complex ways. However, the assessment and analysis of global gateways are scattered and fragmented. To fill this knowledge gap, we frame global gateways as telecoupled human and natural systems using an emerging global gateway, the Bering Strait, as a demonstration. We examine how three telecoupling processes (tourism, vessel traffic, and natural resource development) impact and are impacted by the coupled human and natural system of the Bering Strait Region. Given that global gateways share many similarities, our analysis of the Bering Strait Region provides a foundation for the assessment of other telecoupled global gateways.

Cancer Education for High School Students in the Northwest Arctic Increases Knowledge and Inspires Intent to Share Information and Reduce Cancer Risk.

Culturally appropriate cancer education is an opportunity to reduce health inequities in cancer. This manuscript describes the outcomes of piloting cancer education for youth in the Northwest Arctic region of Alaska. The project began due to community concerns, was focused through sharing circles conducted in the region, and was guided by a community advisory board. The project was based on the principles of Community Based Participatory Action Research (CBPAR), honored Indigenous Ways of Knowing, and was grounded in Empowerment Theory. In response to community requests, eleven cancer education lessons were developed for young people in the Northwest Arctic. Several lessons were piloted in spring 2022. Each participant was invited to complete a pre-lesson and a post-lesson survey. A total of 113 surveys were completed from five different lessons: 66 pre-lesson surveys and 47 post-lesson surveys. Respondents' mean cancer knowledge scores were significantly higher after the Cancer Basics lesson. On 98% of post-lesson surveys, respondents said they planned to share cancer education messages such as staying tobacco-free and increasing physical activity with others, including their family, friends, and community members. On 93% of the post-lesson surveys, respondents indicated they planned to make changes to reduce their own personal cancer risk, including by staying tobacco-free, eating healthier, and increasing physical activity. "Cancer is serious, and something we should start talking about".

Elucidating the mechanism behind and investigating the efficacy of Traditional Chinese Medicine and Traditional Tibetan Medicine in combination with standard therapeutics in hepatocellular carcinoma and cholangiocarcinoma in vitro.

In this study, we investigated compounds of plant and mushroom origin belonging to Traditional Chinese Medicine (TCM) and to Traditional Tibetan Medicine (TTM): a sandy beige mushroom Trametes robiniophila Murr, commonly known as Huaier/TCM as well as Ershiwuwei Songshi Wan and Qiwei Honghua Shusheng Wan, which both belong to TTM. We aimed to study the efficacy of TTM and TCM in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) in vitro. TCM and TTM were tested either as a monotherapy, or in combination with standard therapeutics: sorafenib for HCC treatment and gemcitabine for CCA. We also discovered a protective mechanism behind the most successful therapeutic combinations. The results demonstrated that TCM and TTM inhibited the proliferation of cancer cells in a time- and dose-dependent manner. The results were compared to classical chemotherapeutics currently used in the clinic: sorafenib for HCC and gemcitabine for CCA. In HCC settings, a combination of Huaier (16 mg/ml) with half of the human plasma concentration of sorafenib, Qiwei Honghua Shusheng Wan (1 mg/ml) monotherapy as well as its combination with half or even a quarter dose of the human plasma concentration of sorafenib represented the most efficient treatments, inhibiting the growth of HCC cells more effectively than the standard therapy. The inhibitory mechanism relied on a strong induction of apoptosis. In CCA settings, Ershiwuwei Songshi Wan and Qiwei Honghua Shusheng Wan as monotherapies or in combination with very low doses of gemcitabine inhibited the growth of CCA cells more efficiently than the standard therapy. Importantly, Ershiwuwei Songshi Wan at the 8 and 16 mg/ml concentrations and Qiwei Honghua Shusheng Wan at the 4 mg/ml concentration were efficacious with gemcitabine applied at massively reduced concentrations. The protective mechanism in CCA relied on a strong induction of early and late apoptosis. Cellular senescence and necroptosis were not associated with protection against HCC/CCA. Combination therapy with TCM or TTM allowed for a dose reduction of standard chemotherapeutics. This is especially important as both chemotherapeutic drugs show strong side effects in patients. The reduction of chemotherapeutics and the synergistic effect observed while applying them in combination with TCM and TTM has strong perspectives for the clinic and patients suffering from HCC and CCA.

Contemporary evolution rivals the effects of rhizobium presence on community and ecosystem properties in experimental mesocosms.

Because genotypes within a species commonly differ in traits that influence other species, whole communities, or even ecosystem functions, evolutionary change within one key species may affect the community and ecosystem processes. Here we use experimental mesocosms to test how the evolution of reduced cooperation in rhizobium mutualists in response to 20 years of nitrogen fertilization compares to the effects of rhizobium presence on soil nitrogen availability and plant community composition and diversity. The evolution of reduced rhizobium cooperation caused reductions in soil nitrogen, biological nitrogen fixation, and leaf nitrogen concentrations that were as strong as, or even stronger than, experimental rhizobium inoculation (presence/absence) treatments. Effects of both rhizobium evolution and rhizobium inoculation on legume dominance, plant community composition, and plant species diversity were often smaller in magnitude, but suggest that rhizobium evolution can alter the relative abundance of plant functional groups. Our findings indicate that the consequences of rapid microbial evolution for ecosystems and communities can rival the effects resulting from the presence or abundance of keystone mutualists.

Chemoenzymatic synthesis of fluorinated polyketides.

Modification of polyketides with fluorine offers a promising approach to develop new pharmaceuticals. While synthetic chemical methods for site-selective incorporation of fluorine in complex molecules have improved in recent years, approaches for the biosynthetic incorporation of fluorine in natural compounds are still rare. Here, we report a strategy to introduce fluorine into complex polyketides during biosynthesis. We exchanged the native acyltransferase domain of a polyketide synthase, which acts as the gatekeeper for the selection of extender units, with an evolutionarily related but substrate tolerant domain from metazoan type I fatty acid synthase. The resulting polyketide-synthase/fatty-acid-synthase hybrid can utilize fluoromalonyl coenzyme A and fluoromethylmalonyl coenzyme A for polyketide chain extension, introducing fluorine or fluoro-methyl units in polyketide scaffolds. We demonstrate the feasibility of our approach in the chemoenzymatic synthesis of fluorinated 12- and 14-membered macrolactones and fluorinated derivatives of the macrolide antibiotics YC-17 and methymycin.

Association of Race and Neighborhood Disadvantage with Patient Engagement in a Home-Based COVID-19 Remote Monitoring Program.

BACKGROUND: COVID-positive outpatients may benefit from remote monitoring, but such a program often relies on smartphone apps. This may introduce racial and socio-economic barriers to participation. Offering multiple methods for participation may address these barriers. OBJECTIVES: (1) To examine associations of race and neighborhood disadvantage with patient retention in a monitoring program offering two participation methods. (2) To measure the association of the program with emergency department visits and hospital admissions. DESIGN: Retrospective propensity-matched cohort study. PARTICIPANTS: COVID-positive outpatients at a single university-affiliated healthcare system and propensity-matched controls. INTERVENTIONS: A home monitoring program providing daily symptom tracking via patient portal app or telephone calls. MAIN MEASURES: Among program enrollees, retention (until 14 days, symptom resolution, or hospital admission) by race and neighborhood disadvantage, with stratification by program arm. In enrollees versus matched controls, emergency department utilization and hospital admission within 30 days. KEY RESULTS: There were 7592 enrolled patients and 9710 matched controls. Black enrollees chose the telephone arm more frequently than White enrollees (68% versus 44%, p = 0.009), as did those from more versus less disadvantaged neighborhoods (59% versus 43%, p = 0.02). Retention was similar in Black enrollees and White enrollees (63% versus 62%, p = 0.76) and in more versus less disadvantaged neighborhoods (63% versus 62%, p = 0.44). When stratified by program arm, Black enrollees had lower retention than White enrollees in the app arm (49% versus 55%, p = 0.01), but not in the telephone arm (69% versus 71%, p = 0.12). Compared to controls, enrollees more frequently visited the emergency department (HR 1.71 [95% CI 1.56-1.87]) and were admitted to the hospital (HR 1.16 [95% CI 1.02-1.31]). CONCLUSIONS: In a COVID-19 remote patient monitoring program, Black enrollees preferentially selected, and had higher retention in, telephone- over app-based monitoring. As a result, overall retention was similar between races. Remote monitoring programs with multiple modes may reduce barriers to participation.

Chewing gum reduces visually induced motion sickness.

Visually induced motion sickness (VIMS) is a common side-effect of exposure to virtual reality (VR). Its unpleasant symptoms may limit the acceptance of VR technologies for training or clinical purposes. Mechanical stimulation of the mastoid and diverting attention to pleasant stimuli-like odors or music have been found to ameliorate VIMS. Chewing gum combines both in an easy-to-administer fashion and should thus be an effective countermeasure against VIMS. Our study investigated whether gustatory-motor stimulation by chewing gum leads to a reduction of VIMS symptoms. 77 subjects were assigned to three experimental groups (control, peppermint gum, and ginger gum) and completed a 15-min virtual helicopter flight, using a VR head-mounted display. Before and after VR exposure, we assessed VIMS with the Simulator Sickness Questionnaire (SSQ), and during the virtual flight once every minute with the Fast Motion Sickness Scale (FMS). Chewing gum (peppermint gum: M = 2.44, SD = 2.67; ginger gum: M = 2.57, SD = 3.30) reduced the peak FMS scores by 2.05 (SE = 0.76) points as compared with the control group (M = 4.56, SD = 3.52), p < 0.01, d = 0.65. Additionally, taste ratings correlated slightly negatively with both the SSQ and the peak FMS scores, suggesting that pleasant taste of the chewing gum is associated with less VIMS. Thus, chewing gum may be useful as an affordable, accepted, and easy-to-access way to mitigate VIMS in numerous applications like education or training. Possible mechanisms behind the effect are discussed.