Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

Discovery and Validation of a Volatile Signature of Eosinophilic Airway Inflammation in Asthma.

RATIONALE: Volatile organic compounds (VOCs) in asthmatic breath may be associated with sputum eosinophilia. We developed a volatile biomarker-signature to predict sputum eosinophilia in asthma. METHODS: VOCs emitted into the space above sputum samples (headspace) from severe asthmatics (n=36) were collected onto sorbent tubes and analysed using thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Elastic net regression identified stable VOCs associated with sputum eosinophilia ≥3% and generated a volatile biomarker signature. This VOC signature was validated in breath samples from: (I) acute asthmatics according to blood eosinophilia ≥0.3x109cells/L or sputum eosinophilia of ≥ 3% in the UK EMBER consortium (n=65) and U-BIOPRED-IMI consortium (n=42). Breath samples were collected onto sorbent tubes (EMBER) or Tedlar bags (U-BIOPRED) and analysed by gas-chromatography-mass spectrometry (GC×GC-MS -EMBER or GC-MS -U-BIOPRED). MAIN RESULTS: The in vitro headspace identified 19 VOCs associated with sputum eosinophilia and the derived VOC signature yielded good diagnostic accuracy for sputum eosinophilia ≥ 3% in headspace (AUROC (95% CI) 0.90(0.80-0.99), p<0.0001), correlated inversely with sputum eosinophil % (rs= -0.71, p<0.0001) and outperformed FeNO (AUROC (95% CI) 0.61(0.35-0.86). Analysis of exhaled breath in replication cohorts yielded a VOC signature AUROC (95% CI) for acute asthma exacerbations of 0.89(0.76-1.0) (EMBER cohort) with sputum eosinophilia and 0.90(0.75-1.0) in U-BIOPRED - again outperforming FeNO in U-BIOPRED 0.62 (0.33-0.90). CONCLUSIONS: We have discovered and provided early-stage clinical validation of a volatile biomarker signature associated with eosinophilic airway inflammation. Further work is needed to translate our discovery using point of care clinical sensors.

Identification of allergens from Aspergillus fumigatus-Potential association with lung damage in asthma.

BACKGROUND: Component-resolved diagnosis allows detection of IgE sensitization having the advantage of reproducibility and standardization compared to crude extracts. The main disadvantage of the traditional allergen identification methods, 1- or 2-dimensional western blotting and screening of expression cDNA libraries with patients' IgEs, is that the native structure of the protein is not necessarily maintained. METHODS: We used a novel immunoprecipitation technique in combination with mass spectrometry to identify new allergens of Aspergillus fumigatus. Magnetic Dynabeads coupled with anti-human IgE antibodies were used to purify human serum IgE and subsequently allergens from A. fumigatus protein extract. RESULTS: Of the 184 proteins detected by subsequent mass peptide fingerprinting, a subset of 13 were recombinantly expressed and purified. In a panel of 52 A. fumigatus-sensitized people with asthma, 23 non-fungal-sensitized asthmatics and 18 healthy individuals, only the former showed an IgE reaction by immunoblotting and/or ELISA. We discovered 11 proteins not yet described as A. fumigatus allergens, with fructose-bisphosphate aldolase class II (FBA2) (33%), NAD-dependent malate dehydrogenase (31%) and Cu/Zn superoxide dismutase (27%) being the most prevalent. With respect to these three allergens, native versus denatured protein assays indicated a better recognition of the native proteins. Seven of 11 allergens fulfilled the WHO/IUIS criteria and were accepted as new A. fumigatus allergens. CONCLUSION: In conclusion, we introduce a straightforward method of allergen identification from complex allergenic sources such as A. fumigatus by immunoprecipitation combined with mass spectrometry, which has the advantage over traditional methods of identifying allergens by maintaining the structure of the proteins.

The effects of inhaled corticosteroids on healthy airways.

BACKGROUND: The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined. OBJECTIVES: To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease-related genes and disease-related alterations in ICS responsiveness. METHODS: Randomized open-label bronchoscopy study of high-dose ICS therapy in 30 healthy adult volunteers randomized 2:1 to (i) fluticasone propionate 500 mcg bd daily or (ii) no treatment, for 4 weeks. Laboratory staff were blinded to allocation. Biopsies and brushings were analysed by immunohistochemistry, bulk RNA sequencing, DNA methylation array and metagenomics. RESULTS: ICS induced small between-group differences in blood and lamina propria eosinophil numbers, but not in other immunopathological features, blood neutrophils, FeNO, FEV1, microbiome or DNA methylation. ICS treatment upregulated 72 genes in brushings and 53 genes in biopsies, and downregulated 82 genes in brushings and 416 genes in biopsies. The most downregulated genes in both tissues were canonical markers of type-2 inflammation (FCER1A, CPA3, IL33, CLEC10A, SERPINB10 and CCR5), T cell-mediated adaptive immunity (TARP, TRBC1, TRBC2, PTPN22, TRAC, CD2, CD8A, HLA-DQB2, CD96, PTPN7), B-cell immunity (CD20, immunoglobulin heavy and light chains) and innate immunity, including CD48, Hobit, RANTES, Langerin and GFI1. An IL-17-dependent gene signature was not upregulated by ICS. CONCLUSIONS: In healthy airways, 4-week ICS exposure reduces gene expression related to both innate and adaptive immunity, and reduces markers of type-2 inflammation. This implies that homeostasis in health involves tonic type-2 signalling in the airway mucosa, which is exquisitely sensitive to ICS.

Mechanisms, mitigation, and management of urinary toxicity from prostate radiotherapy.

Urinary toxicity is common following pelvic radiotherapy and can have a substantial negative effect on survivorship. Due to its prevalence and the increasing number of related clinical trials, localised prostate cancer radiotherapy is a useful illustrative tool to explore urinary toxicity. A good understanding of the interplay between anatomy, radiation-sensitive cell populations, and treatment sequencing is necessary for optimal outcomes. Emerging evidence suggests that the prostatic urethra is a radiation-sensitive structure, not only for stricture development, but also chronic irritative symptoms. Tools now exist not only to identify the urethra, but also to direct radiation dose away from the urethra, with early data suggesting that this reduces moderate-to-severe late urinary toxicity. Coupled with new evidence supporting dominant nodule microboosting and ultrahypofractionation as emerging standards of care, urethral sparing radiotherapy is a powerful tool against radiation induced urinary toxicity while also maximising disease control.

Addressing Missing Data in GC × GC Metabolomics: Identifying Missingness Type and Evaluating the Impact of Imputation Methods on Experimental Replication.

Missing data is a significant issue in metabolomics that is often neglected when conducting data preprocessing, particularly when it comes to imputation. This can have serious implications for downstream statistical analyses and lead to misleading or uninterpretable inferences. In this study, we aim to identify the primary types of missingness that affect untargeted metabolomics data and compare strategies for imputation using two real-world comprehensive two-dimensional gas chromatography (GC × GC) data sets. We also present these goals in the context of experimental replication whereby imputation is conducted in a within-replicate-based fashion─the first description and evaluation of this strategy─and introduce an R package MetabImpute to carry out these analyses. Our results conclude that, in these two GC × GC data sets, missingness was most likely of the missing at-random (MAR) and missing not-at-random (MNAR) types as opposed to missing completely at-random (MCAR). Gibbs sampler imputation and Random Forest gave the best results when imputing MAR and MNAR compared against single-value imputation (zero, minimum, mean, median, and half-minimum) and other more sophisticated approaches (Bayesian principal component analysis and quantile regression imputation for left-censored data). When samples are replicated, within-replicate imputation approaches led to an increase in the reproducibility of peak quantification compared to imputation that ignores replication, suggesting that imputing with respect to replication may preserve potentially important features in downstream analyses for biomarker discovery.

Parallel decay of vision genes in subterranean water beetles.

In the framework of neutral theory of molecular evolution, genes specific to the development and function of eyes in subterranean animals living in permanent darkness are expected to evolve by relaxed selection, ultimately becoming pseudogenes. However, definitive empirical evidence for the role of neutral processes in the loss of vision over evolutionary time remains controversial. In previous studies, we characterized an assemblage of independently-evolved water beetle (Dytiscidae) species from a subterranean archipelago in Western Australia, where parallel vision and eye loss have occurred. Using a combination of transcriptomics and exon capture, we present evidence of parallel coding sequence decay, resulting from the accumulation of frameshift mutations and premature stop codons, in eight phototransduction genes (arrestins, opsins, ninaC and transient receptor potential channel genes) in 32 subterranean species in contrast to surface species, where these genes have open reading frames. Our results provide strong evidence to support neutral evolutionary processes as a major contributing factor to the loss of phototransduction genes in subterranean animals, with the ultimate fate being the irreversible loss of a light detection system.

A proof of concept for continuous, non-invasive, free-living vital signs monitoring to predict readmission following an acute exacerbation of COPD: a prospective cohort study.

BACKGROUND: The use of vital signs monitoring in the early recognition of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) post-hospital discharge is limited. This study investigated whether continuous vital signs monitoring could predict an AECOPD and readmission. METHODS: 35 people were recruited at discharge following hospitalisation for an AECOPD. Participants were asked to wear an Equivital LifeMonitor during waking hours for 6 weeks and to complete the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a 14-item symptom diary, daily. The Equivital LifeMonitor recorded respiratory rate (RR), heart rate (HR), skin temperature (ST) and physical activity (PA) every 15-s. An AECOPD was classified as mild (by EXACT score), moderate (prescribed oral steroids/antibiotics) or severe (hospitalisation). RESULTS: Over the 6-week period, 31 participants provided vital signs and symptom data and 14 participants experienced an exacerbation, of which, 11 had sufficient data to predict an AECOPD. HR and PA were associated with EXACT score (p < 0.001). Three days prior to an exacerbation, RR increased by mean ± SD 2.0 ± 0.2 breaths/min for seven out of 11 exacerbations and HR increased by 8.1 ± 0.7 bpm for nine of these 11 exacerbations. CONCLUSIONS: Increased heart rate and reduced physical activity were associated with worsening symptoms. Even with high-resolution data, the variation in vital signs data remains a challenge for predicting AECOPDs. Respiratory rate and heart rate should be further explored as potential predictors of an impending AECOPD. TRIAL REGISTRATION: ISRCTN registry; ISRCTN12855961. Registered 07 November 2018-Retrospectively registered, https://www.isrctn.com/ISRCTN12855961.

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.

BACKGROUND: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms. METHODS: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators. RESULTS: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. CONCLUSIONS: Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.

Per- and Poly-Fluoroalkyl Substances in Runoff and Leaching from AFFF-Contaminated Soils: a Rainfall Simulation Study.

The mobilization and transport of per- and poly-fluoroalkyl substances (PFASs) via surface runoff (runoff) from aqueous film-forming foam (AFFF)-contaminated soils during rainfall, flooding, or irrigation has not been thoroughly evaluated, and the effectiveness of carbonaceous sorbents in limiting PFASs in runoff is similarly unquantified. Here, laboratory-scale rainfall simulations evaluate PFAS losses in runoff and in leaching to groundwater (leachate) from AFFF-contaminated soils varying in texture, PFAS composition and concentration, and remediation treatment. Leaching dominated PFAS losses in soils with a concentration of ∑PFAS = 0.2-2 mg/kg. However, with higher soil PFAS concentrations (∑PFAS = 31 mg/kg), leachate volumes were negligible and runoff dominated losses. The concentration and variety of PFASs were far greater in leachates regardless of the initial concentrations in soil. Losses of PFASs were dependent on the C-chain length for leachates and more on the initial concentration in soil for runoff. Suspended materials did not meaningfully contribute to runoff losses. While concentrations of most PFASs declined significantly after the first rainfall event, desorption and transport in both runoff and leachates persisted over several rainfall events. Finally, results showed that sorption to AC mostly occurred during, not prior to, rainfall events and that 1% w/w AC substantially reduced losses in runoff and leachates from all soils.

Large-scale group genetic counseling: Evaluation of a novel service delivery model in a Canadian hereditary cancer clinic.

Increasing demand for genetic services has led to the development of streamlined genetic counseling (GC) models. We piloted large-scale group pre-test GC with up to 50 patients per group and compared this to a traditional one-on-one approach. Patients referred to the British Columbia (BC) Cancer Hereditary Cancer Program were eligible if they had: (a) family history meeting our program's referral criteria; (b) no relevant personal history of cancer; (c) no prior genetic testing in the family; and (d) no living testable relative in BC. Patient-reported outcome measures included: (a) Genetic Counselling Outcome Scale (GCOS) prior to pre-test GC (T1) and at 4 weeks post-test GC (T2); (b) Satisfaction Survey after pre-test GC; and (c) the Multidimensional Impact of Cancer Risk Assessment (MICRA) for patients undergoing testing (4 weeks after post-test GC). In total, 391 patients underwent GC, 184 by group and 207 by one-on-one appointments. Between May 2018 and May 2019, 6 pre-test group sessions were conducted (median number of patients per group = 28; range 15-48). 8% of patients (n = 32) declined large group GC due to personal preference for one-on-one GC. There were no statistically significant differences in MICRA and GCOS survey results when comparing the pre-test large group versus traditional pre-test one-on-one models (based on 3 MICRA subscales: p = 0.063, p = 0.612, p = 0.842; and GCOS p = 0.169). Overall, the large group pre-test counseling approach was more time-efficient with 15-48 patient group sessions conducted over a mean duration of 80 min as compared to 42 min per patient with the traditional one-on-one GC model. Large-scale group GC was feasible and acceptable to patients and represents a novel streamlined model for GC to enable timely access to cancer genetic services.

Characteristics of COVID-19 in Homeless Shelters : A Community-Based Surveillance Study.

BACKGROUND: Homeless shelters are a high-risk setting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission because of crowding and shared hygiene facilities. OBJECTIVE: To investigate SARS-CoV-2 case counts across several adult and family homeless shelters in a major metropolitan area. DESIGN: Cross-sectional, community-based surveillance study. (ClinicalTrials.gov: NCT04141917). SETTING: 14 homeless shelters in King County, Washington. PARTICIPANTS: A total of 1434 study encounters were done in shelter residents and staff, regardless of symptoms. INTERVENTION: 2 strategies were used for SARS-CoV-2 testing: routine surveillance and contact tracing ("surge testing") events. MEASUREMENTS: The primary outcome measure was test positivity rate of SARS-CoV-2 infection at shelters, determined by dividing the number of positive cases by the total number of participant encounters, regardless of symptoms. Sociodemographic, clinical, and virologic variables were assessed as correlates of viral positivity. RESULTS: Among 1434 encounters, 29 (2% [95% CI, 1.4% to 2.9%]) cases of SARS-CoV-2 infection were detected across 5 shelters. Most (n = 21 [72.4%]) were detected during surge testing events rather than routine surveillance, and most (n = 21 [72.4% {CI, 52.8% to 87.3%}]) were asymptomatic at the time of sample collection. Persons who were positive for SARS-CoV-2 were more frequently aged 60 years or older than those without SARS-CoV-2 (44.8% vs. 15.9%). Eighty-six percent of persons with positive test results slept in a communal space rather than in a private or shared room. LIMITATION: Selection bias due to voluntary participation and a relatively small case count. CONCLUSION: Active surveillance and surge testing were used to detect multiple cases of asymptomatic and symptomatic SARS-CoV-2 infection in homeless shelters. The findings suggest an unmet need for routine viral testing outside of clinical settings for homeless populations. PRIMARY FUNDING SOURCE: Gates Ventures.

Optimal LiDAR Data Resolution Analysis for Object Classification.

When classifying objects in 3D LiDAR data, it is important to use efficient collection methods and processing algorithms. This paper considers the resolution needed to classify 3D objects accurately and discusses how this resolution is accomplished for the RedTail RTL-450 LiDAR System. We employ VoxNet, a convolutional neural network, to classify the 3D data and test the accuracy using different data resolution levels. The results show that for our data set, if the neural network is trained using higher resolution data, then the accuracy of the classification is above 97%, even for the very sparse testing set (10% of original test data set point density). When the training is done on lower resolution data sets, the classification accuracy remains good but drops off at around 3% of the original test data set point density. These results have implications for determining flight altitude and speed for an unmanned aerial vehicle (UAV) to achieve high accuracy classification. The findings point to the value of high-resolution point clouds for both the training of the convolutional neural network and in data collected from a LiDAR sensor.

Tinnitus Does Not Interfere with Auditory and Speech Perception.

Tinnitus is a sound heard by 15% of the general population in the absence of any external sound. Because external sounds can sometimes mask tinnitus, tinnitus is assumed to affect the perception of external sounds, leading to hypotheses such as "tinnitus filling in the temporal gap" in animal models and "tinnitus inducing hearing difficulty" in human subjects. Here we compared performance in temporal, spectral, intensive, masking and speech-in-noise perception tasks between 45 human listeners with chronic tinnitus (18 females and 27 males with a range of ages and degrees of hearing loss) and 27 young, normal-hearing listeners without tinnitus (11 females and 16 males). After controlling for age, hearing loss, and stimulus variables, we discovered that, contradictory to the widely held assumption, tinnitus does not interfere with the perception of external sounds in 32 of the 36 measures. We interpret the present result to reflect a bottom-up pathway for the external sound and a separate top-down pathway for tinnitus. We propose that these two perceptual pathways can be independently modulated by attention, which leads to the asymmetrical interaction between external and internal sounds, and several other puzzling tinnitus phenomena such as discrepancy in loudness between tinnitus rating and matching. The present results suggest not only a need for new theories involving attention and central noise in animal tinnitus models but also a shift in focus from treating tinnitus to managing its comorbid conditions when addressing complaints about hearing difficulty in individuals with tinnitus.SIGNIFICANCE STATEMENT Tinnitus, or ringing in the ears, is a neurologic disorder that affects 15% of the general population. Here we discovered an asymmetrical relationship between tinnitus and external sounds: although external sounds have been widely used to cover up tinnitus, tinnitus does not impair, and sometimes even improves, the perception of external sounds. This counterintuitive discovery contradicts the general belief held by scientists, clinicians, and even individuals with tinnitus themselves, who often report hearing difficulty, especially in noise. We attribute the counterintuitive discovery to two independent pathways: the bottom-up perception of external sounds and the top-down perception of tinnitus. Clinically, the present work suggests a shift in focus from treating tinnitus itself to treating its comorbid conditions and secondary effects.

Incidence of Medically Attended Acute Respiratory Illnesses Due to Respiratory Viruses Across the Life Course During the 2018/19 Influenza Season.

BACKGROUND: Although multiple respiratory viruses circulate in humans, few studies have compared the incidence of different viruses across the life course. We estimated the incidence of outpatient illness due to 12 different viruses during November 2018 through April 2019 in a fully enumerated population. METHODS: We conducted active surveillance for ambulatory care visits for acute respiratory illness (ARI) among members of Kaiser Permanente Washington (KPWA). Enrolled patients provided respiratory swab specimens which were tested for 12 respiratory viruses using reverse transcription polymerase chain reaction (RT-PCR). We estimated the cumulative incidence of infection due to each virus overall and by age group. RESULTS: The KPWA population under surveillance included 202 562 individuals, of whom 2767 (1.4%) were enrolled in the study. Influenza A(H3N2) was the most commonly detected virus, with an overall incidence of 21 medically attended illnesses per 1000 population; the next most common viruses were influenza A(H1N1) (18 per 1000), coronaviruses (13 per 1000), respiratory syncytial virus (RSV, 13 per 1000), and rhinovirus (9 per 1000). RSV was the most common cause of medically attended ARI among children aged 1-4 years; coronaviruses were the most common among adults aged ≥65 years. CONCLUSIONS: Consistent with other studies focused on single viruses, we found that influenza and RSV were major causes of acute respiratory illness in persons of all ages. In comparison, coronaviruses and rhinovirus were also important pathogens. Prior to the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronaviruses were the second-most common cause of medically attended ARI during the 2018/19 influenza season.

Longitudinal changes to quadriceps thickness demonstrate acute sarcopenia following admission to hospital for an exacerbation of chronic respiratory disease.

Acute admission to hospital for an exacerbation of chronic respiratory disease (CRD) may impair skeletal muscle mass and function. We measured quadriceps thickness (Qthick), as a surrogate marker of muscle mass, at hospital admission, discharge, 6 weeks and 3 months in 55 patients with CRD. Qthick fell by 8.3% during the period of hospitalisation, which was sustained at 6 weeks, and only partially recovered at 3 months. Sustained loss was most marked in patients readmitted during the follow-up period. Acute reduction in quadriceps muscle mass occurs during hospitalisation, with prolonged and variable recovery, which is prevented with subsequent hospital readmission.

COVID-19 pandemic-related changes in wellness behavior among older Americans.

BACKGROUND: COVID-19 has taken its toll on citizens in all 50 states of the United States. The United States (U.S.) leads the world with 30,291,863 confirmed reported cases and 549,664 deaths as of March 29, 2021 compared to globally confirmed cases at 127,442,926 and 2,787,915 deaths as of March 29, 2021. The U.S. federal government primarily left the response to the virus to individual states, and each implemented varying measures designed to protect health of citizens and the state's economic well-being. Unintended consequences of the virus and measures to stop its spread may include decreased physical activity and exercise, shifting access and consumption of food, and lower quality-of-life. Therefore, our primary goal was to quantify the impact of COVID-19 on health and well-being by measuring changes in physical activity, mental health-quality of life, food security and nutrition in adults ages 40 and older. We believed shifts in health behaviors would be more prevalent in minorities, less educated, lower socio-economic status, older adults, and those with underlying health conditions, so a secondary goal was to determine the impact of COVID-19 on these sub-populations. METHODS: We conducted an online survey with 9969 adults 40 years and older between 9 August and 15 September 2020 in urban areas across the four U.S. census regions. The survey included questions about demographic variables, pre-existing health conditions, physical activity, access to food, quality-of-life, and nutritional food status and asked participants to respond with information from pre-pandemic and pandemic conditions. We used paired-sample t-tests to detect changes in variables after the start of the pandemic and Cohen's d to determine effect sizes. RESULTS: Our main findings showed a decrease in physical activity since the onset of COVID-19 for minorities and non-minorities. Food security also slightly increased for minorities during the pandemic, but we found no other changes in food security, quality-of-life indicators, or nutritional status of those who responded to this survey. CONCLUSIONS: It is concerning that physical activity declined. Such activity helps maintain physical and mental health, and it is also an important time to socialize for many older adults. In many ways, our data indicate that the older adult population in U.S. cities may be more resilient than expected during the pandemic. However, the pandemic could have negative impacts that we did not detect, either due to the survey instrument or the timing of our survey, so the health and well-being of older adults should continue to be monitored in order to mitigate potential negative impacts.

Input-Output Functions in Human Heads Obtained With Cochlear Implant and Transcranial Electric Stimulation.

OBJECTIVES: Electric stimulation is used to treat a number of neurologic disorders such as epilepsy and depression. However, delivering the required current to far-field neural targets is often ineffective because of current spread through low-impedance pathways. Here, the specific aims are to develop an empirical measure for current passing through the human head and to optimize stimulation strategies for targeting deeper structures, including the auditory nerve, by utilizing the cochlear implant (CI). MATERIALS AND METHODS: Outward input/output (I/O) functions were obtained by CI stimulation and recording scalp potentials in five CI subjects. Conversely, inward I/O functions were obtained by noninvasive transcranial electric stimulation (tES) and recording intracochlear potentials using the onboard recording capability of the CI. RESULTS: I/O measures indicate substantial current spread, with a maximum of 2.2% gain recorded at the inner ear target during tES (mastoid-to-mastoid electrode configuration). Similarly, CI stimulation produced a maximum of 1.1% gain at the scalp electrode nearest the CI return electrode. Gain varied with electrode montage according to a point source model that accounted for distances between the stimulating and recording electrodes. Within the same electrode montages, current gain patterns varied across subjects suggesting the importance of tissue properties, geometry, and electrode positioning. CONCLUSION: These results provide a novel objective measure of electric stimulation in the human head, which can help to optimize stimulation parameters that improve neural excitation of deep structures by reducing the influence of current spread. CONFLICT OF INTEREST: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The airway fungal microbiome in asthma.

BACKGROUND: Fungal involvement in asthma is associated with severe disease. The full spectrum of fungal species in asthma is not well described and is derived largely from insensitive culture techniques. OBJECTIVES: To use high-throughput sequencing to describe the airway mycobiota in asthmatics with and without fungal sensitization and healthy controls; to compare samples representing different airway compartments; to determine whether the mycobiota was influenced by the fungal composition of outdoor air; and to compare findings with clinically relevant outcomes. METHODS: We amplified the internal transcribed spacer region 2 of the nuclear ribosomal operon to identify the fungal species present. Ninety-seven subjects were recruited and provided sputum (83 asthmatics; 14 healthy subjects), with 29 also undergoing a bronchoscopy. A subset of airway samples were compared with matched outdoor air and mouthwash samples. RESULTS: Two hundred and six taxa at the species level were identified in sputum, most at low relative abundance. Aspergillus fumigatus, Candida albicans and Mycosphaerella tassiana had the highest relative abundances and were the most prevalent species across all subjects. The airway mycobiota consisted of a complex community with high diversity between individuals. Notable shifts in the balance of fungi detected in the lung were associated with asthma status, asthma duration and biomarkers of inflammation. Aspergillus tubingensis, a member of the Aspergillus niger species complex, was most prevalent from bronchoscopic protected brush samples and significantly associated with a low sputum neutrophilia. Cryptococcus pseudolongus, from the Cryptococcus humicola species complex, was more abundant from bronchoscopy samples than sputum, and differentially more abundant in asthma than health. CONCLUSIONS AND CLINICAL RELEVANCE: The airway mycobiota was dominated by a relatively small number of species, but was distinct from the oropharyngeal mycobiota and air samples. Members of the A. niger and C. humicola species complexes may play unexpected roles in the pathogenesis of asthma.

Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma.

BACKGROUND: Whether the clinical or pathophysiologic significance of the "treatable trait" high blood eosinophil count in COPD is the same as for asthma remains controversial. We sought to determine the relationship between the blood eosinophil count, clinical characteristics and gene expression from bronchial brushings in COPD and asthma. METHODS: Subjects were recruited into a COPD (emphysema versus airway disease [EvA]) or asthma cohort (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes, U-BIOPRED). We determined gene expression using RNAseq in EvA (n = 283) and Affymetrix microarrays in U-BIOPRED (n = 85). We ran linear regression analysis of the bronchial brushings transcriptional signal versus blood eosinophil counts as well as differential expression using a blood eosinophil > 200 cells/µL as a cut-off. The false discovery rate was controlled at 1% (with continuous values) and 5% (with dichotomized values). RESULTS: There were no differences in age, gender, lung function, exercise capacity and quantitative computed tomography between eosinophilic versus noneosinophilic COPD cases. Total serum IgE was increased in eosinophilic asthma and COPD. In EvA, there were 12 genes with a statistically significant positive association with the linear blood eosinophil count, whereas in U-BIOPRED, 1197 genes showed significant associations (266 positive and 931 negative). The transcriptome showed little overlap between genes and pathways associated with blood eosinophil counts in asthma versus COPD. Only CST1 was common to eosinophilic asthma and COPD and was replicated in independent cohorts. CONCLUSION: Despite shared "treatable traits" between asthma and COPD, the molecular mechanisms underlying these clinical entities are predominately different.