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Alessandro Fiocchi,1 R Sharon Chinthrajah,2 Ignacio J Ansotegui,3 Panida Sriaroon,4 S Shahzad Mustafa,5 Pranil Raut,6 Briana Cameron,6 Sachin Gupta,1 David M Fleischer7 1Bambino Gesù Childrens’ Hospital IRCCS, Rome, Italy; 2Stanford University, Stanford, CA, USA; 3Hospital Quironsalud Bizkaia, Bilbao, Spain; 4University of South Florida, Tampa, FL, USA; 5Rochester Regional Health & University of Rochester, Rochester, NY, USA; 6Genentech Inc., South San Francisco, CA, USA; 7Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USACorrespondence: David M Fleischer, Section Head, Allergy & Immunology, University of Colorado School of Medicine and Children’s Hospital Colorado, 13123 East 16th Avenue, B518, Aurora, CO, 80045, USA, Tel +1-720-777-4393, Email David.Fleischer@childrenscolorado.orgBackground: The intrinsic link between food allergy and asthma is well-established, and comorbidity can exacerbate both conditions. Omalizumab, an anti-immunoglobulin E (IgE) antibody, has the biological plausibility to manage both conditions, but only a few small studies have assessed omalizumab in patients with comorbid asthma and food allergy.Patients and Methods: We conducted a post hoc analysis of placebo-controlled, randomized clinical trials (IA05 in children and 008/009 in adolescents/adults) and real-world observational studies (EXCELS and PROSPERO). For each study, patients with asthma were stratified by whether they had physician-reported food allergy, as per baseline characteristics data.Results: For patients with comorbid food allergy, there was evidence for increased atopy at baseline (numerically higher total IgE levels and atopic comorbidities). The collective body of evidence found that omalizumab consistently improved general and asthma-specific patient-centered outcomes (food allergy-specific outcomes were not available). For patients with asthma, omalizumab improved healthcare resource use (emergency room visits, hospitalizations, unscheduled doctor visits), quality of life (asthma-specific Asthma Quality of Life Questionnaire), productivity (missed work/school days and the Work Productivity and Activity Impairment: Asthma), and asthma outcomes (asthma exacerbations and Asthma Control Test score) regardless of comorbid food allergy.Conclusion: There was no loss of omalizumab efficacy even though patients with both asthma and food allergy appeared to be generally more atopic. Omalizumab may be a viable management option for patients with these comorbidities.Clinical trial registration: NCT00079937; NCT01922037; NCT00252135.Plain Language Summary: Food allergy and asthma are linked and if you have both conditions then you can feel worse. There is a treatment available, called omalizumab, that helps people with asthma and helps people with food allergy, but it’s not clear if it can help people with both conditions. Here, we look at whether omalizumab can help people with bad to very bad asthma (also called moderate to severe asthma) who also have food allergy. We found that omalizumab improved many aspects of a person’s life, including whether they visited the emergency room, were admitted to hospital, their quality of life, whether they missed school or work, and whether their asthma improved. These improvements occurred in all people with moderate to severe asthma, whether they had food allergy or did not have food allergy. This suggests that omalizumab can help people with both conditions.Keywords: asthma, food allergy, food hypersensitivity, healthcare resource use, omalizumab, productivity, quality of life

Abstract The AS04-adjuvanted human papillomavirus (HPV)16/18 vaccine, an L1-based vaccine, provides strong vaccine efficacy (VE) against vaccine-targeted type infections, and partial cross-protection to phylogenetically-related types, which may be affected by variant-level heterogeneity. We compared VE against incident HPV31, 33, 35, and 45 detections between lineages and SNPs in the L1 region among 2846 HPV-vaccinated and 5465 HPV-unvaccinated women through 11-years of follow-up in the Costa Rica HPV Vaccine Trial. VE was lower against HPV31-lineage-B (VE=60.7%;95%CI = 23.4%,82.8%) compared to HPV31-lineage-A (VE=94.3%;95%CI = 83.7%,100.0%) (VE-ratio = 0.64;95%CI = 0.25,0.90). Differential VE was observed at several lineage-associated HPV31-L1-SNPs, including a nonsynonymous substitution at position 6372 on the FG-loop, an important neutralization domain. For HPV35, the only SNP-level difference was at position 5939 on the DE-loop, with significant VE against nucleotide-G (VE=65.0%;95%CI = 28.0,87.8) but not for more the common nucleotide-A (VE=7.4%;95%CI = −34.1,36.7). Because of the known heterogeneity in precancer/cancer risk across cross-protected HPV genotype variants by race and region, our results of differential variant-level AS04-adjuvanted HPV16/18 vaccine efficacy has global health implications.

Background: Bithermal caloric irrigation, video head impulse test (vHIT), and rotational testing are commonly used to assess peripheral vestibular function, but the relative clinical utility of each test in differentiating patients with peripheral vestibulopathy is debated. Objectives: To determine whether (1) the combination of two or more vestibular tests enhances diagnostic utility over a single test; (2) abnormal test results on vestibular tests correlate with one another. Methods: Retrospective analysis of data collected from multidisciplinary vestibular clinics at two academic medical centers from 2016 to 2022. Results: 150 patients (54.10 ± 15.09 years, 88 females) were included. No individual test was significantly better at predicting the presence of peripheral vestibular damage (p > 0.05). vHIT test results improved significantly when combined with either the caloric test (p = 0.007) or rotary chair test (p = 0.039). Caloric and rotational testing had high sensitivity (74.65% and 76.06%, respectively) and specificity (83.54% and 78.48%, respectively). vHIT demonstrated excellent specificity (89.87%) but poor sensitivity (47.89%). Caloric, vHIT, and rotary chair tests results did not correlate with one another (p > 0.05). Conclusions: Vestibular function tests have comparable diagnostic utility, yet each offers unique advantages. Caloric and rotational testing may be best suited for screening peripheral damage and vHIT may function ideally as a confirmatory test.

ABSTRACT: The benefit of ovarian superstimulation using exogenous FSH before ovum pick-up (OPU) and in vitro embryo production (IVEP) has been the subject of conflicting results. The objective of the present study, therefore, was to evaluate the effect of use and dose of porcine FSH (p-FSH) before OPU/IVEP on ovarian response and embryo production in pregnant heifers. Pregnant Holstein heifers (n = 48) were randomly assigned to receive 0, 160, or 300 mg NIH-FSH-P1 in a crossover design. Ovum pick-up was performed at 49, 63, and 77 d of gestation with a 14 d “washout” between OPU sessions. Follicle ablation was performed on D 0 (p.m.) and p-FSH treatments, consisting of 4 decreasing dose injections administered 12 h apart, were initiated 36 h after follicle ablation (d 2 a.m.). Heifers underwent OPU on D 5 (a.m.), 40 h after the last p-FSH treatment, and cumulus oocyte complexes (COC) were subjected to IVEP procedures. Differences between treatment groups were evaluated using generalized linear mixed models. There were quadratic effects of treatment on both number and percentage of small (10 mm) follicles. Number and percentage of medium follicles increased with increasing p-FSH dosages, although the magnitude of the change was greater between 0 and 160 mg, than between 160 and 300 mg of p-FSH. Total number of follicles, number of COC recovered and number of viable COC increased linearly with increasing p-FSH dose. Conversely, there was no evidence for an effect of p-FSH dose on COC recovery percentage nor the percentage of viable COC. Cleavage percentage, number of cleaved oocytes, blastocyst percentage, and number of blastocysts increased linearly with increasing p-FSH dose. In conclusion, use of p-FSH before OPU resulted in greater superstimulatory response and oocyte competence which in turn increased IVEP. Furthermore, these effects were dose dependent such that use of a greater dose of p-FSH up to 300 mg progressively increased embryo yield.

We investigate the contribution of host galaxies to the overall dispersion measures (DMs) for fast radio bursts (FRBs) using the Feedback in Realistic Environments (FIRE-2) cosmological zoom-in simulation suite. We calculate DMs from every star particle in the simulated L * galaxies by ray-tracing through their multiphase interstellar medium, summing the line-of-sight free thermal electron column for all gas elements within ±20 kpc of the galactic midplane. At z = 0, we find average (median) host-galaxy DMs of 74 (43) and 210 (94) pc cm ^−3 for older (≳10 Myr) and younger (≲10 Myr) stellar populations, respectively. Inclination raises the median DM measured for older populations (≳10 Myr) in the simulations by a factor of ∼2 but generally does not affect the younger stars deeply embedded in H ii regions except in extreme edge-on cases (inclination ≳85°). In kinematically disturbed snapshots ( z = 1 in FIRE), the average (median) host-galaxy DMs are higher: 80 (107) and 266 (795) pc cm ^−3 for older (≳10 Myr) and younger (≲10 Myr) stellar populations, respectively. FIRE galaxies tend to have higher DM values than cosmological simulations such as IllustrisTNG, with larger tails in their distributions to high DMs. As a result, FRB host galaxies may be closer (lower redshift) than previously inferred. Furthermore, constraining host-galaxy DM distributions may help significantly constrain FRB progenitor models.

Abstract The use of in vivo spectroscopy to detect plant stress in its early stages has the potential to enhance food safety and reduce the need for plant protection products. However, differentiating between various stress types before symptoms appear remains poorly studied. In this study, we investigated the potential of Vis–NIR spectroscopy to differentiate between stress types in apple trees (Malus x domestica Borkh.) exposed to apple scab, waterlogging, and herbicides in a greenhouse. Using a spectroradiometer, we collected spectral signatures of leaves still attached to the tree and utilized machine learning techniques to develop predictive models for detecting stress presence and classifying stress type as early as 1–5 days after exposure. Our findings suggest that changes in spectral reflectance at multiple regions accurately differentiate various types of plant stress on apple trees. Our models were highly accurate (accuracies between 0.94 and 1) when detecting the general presence of stress at an early stage. The wavelengths important for classification relate to photosynthesis via pigment functioning (684 nm) and leaf water (~ 1800–1900 nm), which may be associated with altered gas exchange as a short-term stress response. Overall, our study demonstrates the potential of spectral technology and machine learning for early diagnosis of plant stress, which could lead to reduced environmental burden through optimizing resource utilization in agriculture.

Abstract The actual interaction between signaling species in cellular processes is often more important than their expression levels. Förster resonance energy transfer (FRET) is a popular tool for studying molecular interactions, since it is highly sensitive to proximity in the range of 2–10 nm. Spectral spillover-corrected quantitative (3-cube) FRET is a cost effective and versatile approach, which can be applied in flow cytometry and various modalities of fluorescence microscopy, but may be hampered by varying levels of autofluorescence. Here, we have implemented pixel-by-pixel autofluorescence correction in microscopy FRET measurements, exploiting cell-free calibration standards void of autofluorescence that allow the correct determination of all spectral spillover factors. We also present an ImageJ/Fiji plugin for interactive analysis of single images as well as automatic creation of quantitative FRET efficiency maps from large image sets. For validation, we used bead and cell based FRET models covering a range of signal to autofluorescence ratios and FRET efficiencies and compared the approach with conventional average autofluorescence/background correction. Pixel-by-pixel autofluorescence correction proved to be superior in the accuracy of results, particularly for samples with spatially varying autofluorescence and low fluorescence to autofluorescence ratios, the latter often being the case for physiological expression levels.

We present CloudFlex , an open-source tool for predicting absorption-line signatures of cool gas in galaxy halos with small-scale structure. Motivated by analyses of ∼10 ^4 K material in hydrodynamical simulations of turbulent, multiphase media, we model cool gas structures as complexes of cloudlets sampled from a power-law distribution of mass $\propto {m}_{\mathrm{cl}}^{-\alpha }$ with velocities drawn from a turbulent velocity field. The user may specify α , the lower limit of the cloudlet mass distribution ( ${m}_{\mathrm{cl},\min }$ ), and several other parameters that set the mass, size, and velocity distribution of the complex. This permits investigation of the relation between these parameters and absorption-line observables. As a proof-of-concept, we calculate the Mg ii λ 2796 absorption induced by the cloudlets in background quasi-stellar object (QSO) spectra. We demonstrate that, at fixed metallicity, the covering fraction of sight lines with equivalent widths W _2796 < 0.3 Å increases significantly with decreasing ${m}_{\mathrm{cl},\min }$ , cloudlet number density ( n _cl ), and complex size. We then use this framework to predict the halo-scale W _2796 distribution around ∼ L ^* galaxies. We show that the observed incidences of W _2796 > 0.3 Å sight lines with impact parameters 10 kpc < R _⊥ < 50 kpc in projected QSO–galaxy studies are consistent with our model over much of parameter space. However, they are underpredicted by models with ${m}_{\mathrm{cl},\min }\geqslant 100{M}_{\odot }$ and n _cl ≥ 0.03 cm ^−3 , in keeping with a picture in which the inner cool circumgalactic medium (CGM) is dominated by numerous low-mass cloudlets ( m _cl ≲ 100 M _⊙ ) with a volume filling factor ≲1%. When used to model absorption-line data sets built from multi-sight line and/or spatially extended background probes, CloudFlex enables detailed constraints on the size and velocity distributions of structures comprising the photoionized CGM.

A California stalagmite records vegetation shifts and increased fire activity during the 8.2 kyr event. These changes occur alongside oscillations between wet and dry extremes suggesting tight coupling between climate whiplash and fire activity.

Abstract Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene–environment (G × E) interactions and may provide information on the underlying biological pathway. We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based G × E approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case–control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4839 genes with available genetically predicted expression. We pooled results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. We used a false discovery rate of 0.2 to identify genes with suggestive evidence of an interaction. We found suggestive evidence of interaction with folate intake on CRC risk for genes including glutathione S-Transferase Alpha 1 (GSTA1; p = 4.3E−4), Tonsuko Like, DNA Repair Protein (TONSL; p = 4.3E−4), and Aspartylglucosaminidase (AGA: p = 4.5E−4). We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk. Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein.

BackgroundThe prevalence of substance use in people with HIV (PWH) in the United States is higher than in the general population and is an important driver of HIV-related outcomes. We sought to assess if previously identified genetic associations that contribute to substance use are also observed in a population of PWH.MethodsWe performed genome-wide association studies (GWAS) of alcohol, smoking, and cannabis use phenotypes in a multi-ancestry population of 7,542 PWH from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). We conducted multi-ancestry GWAS for individuals of African (n = 3,748), Admixed American (n = 1,334), and European (n = 2,460) ancestry. Phenotype data were self-reported and collected using patient reported outcomes (PROs) and three questions from AUDIT-C, an alcohol screening tool. We analyzed nine phenotypes: 1) frequency of alcohol consumption, 2) typical number of drinks on a day when drinking alcohol, 3) frequency of five or more alcoholic drinks in a 30-day period, 4) smoking initiation, 5) smoking cessation, 6) cigarettes per day, 7) cannabis use initiation, 8) cannabis use cessation, 9) frequency of cannabis use during the previous 30 days. For each phenotype we considered a) variants previously identified as associated with a substance use trait and b) novel associations.ResultsWe observed evidence for effects of previously reported single nucleotide polymorphisms (SNPs) related to alcohol (rs1229984, p = 0.001), tobacco (rs11783093, p = 2.22E-4), and cannabis use (rs2875907, p = 0.005). We also report two novel loci (19p13.2, p = 1.3E-8; and 20p11.21, p = 2.1E-8) associated with cannabis use cessation.ConclusionsOur analyses contribute to understanding the genetic bases of substance use in a population with relatively higher rates of use compared to the general population.

Background: An alternative to population-based genetic testing, automated cascade genetic testing facilitated by sharing of family health history, has been conceptualized as a more efficient and cost-effective approach to identify hereditary genetic conditions. However, existing software and applications programming interfaces (API) for the practical implementation of this approach in health care settings have not been described.Methods: We reviewed API available for facilitating cascade genetic testing in electronic health records (EHRs). We emphasize any information regarding informed consent as provided for each tool. Using semi-structured key informant interviews, we investigated uptake of and barriers to integrating automated family cascade genetic testing into the EHR.Results: We summarized the functionalities of six tools related to utilizing family health history to facilitate cascade genetic testing. No tools were explicitly capable of facilitating family cascade genetic testing, but few enterprise EHRs supported family health history linkage. We conducted five key informant interviews with four main considerations that emerged including: 1) incentives for interoperability, 2) HIPAA and regulations, 3) mobile-app and alternatives to EHR deployment, 4) fundamental changes to conceptualizing EHRs.Discussion: Despite the capabilities of existing technology, limited bioinformatic support has been developed to automate processes needed for family cascade genetic testing and the main barriers for implementation are nontechnical, including an understanding of regulations, consent, and workflow. As the trade-off between cost and efficiency for population-based and family cascade genetic testing shifts, the additional tools necessary for their implementation should be considered.

Abstract Background Anti-citrullinated protein antibodies (ACPA) are central to rheumatoid arthritis (RA) pathogenesis and may develop at inflamed mucosa. We investigated whether asthma, a disease of airway mucosal inflammation, was associated with elevated ACPA before RA diagnosis. Methods We performed a nested case-control study among women in two prospective cohorts, the Nurses’ Health Study (NHS; 1976–2014) and NHSII (1989–2015). Blood was obtained on a subset (NHS: 1989–1990; NHSII: 1996–1999). Cases met 1987 ACR or 2010 ACR/EULAR RA criteria by medical record review and were classified as seropositive (ACPA+ or rheumatoid factor positivity) or seronegative by clinical laboratory testing at diagnosis. We identified RA cases with blood drawn before the date of RA diagnosis (index date), matching each to three controls by age, cohort, year, time from blood draw to index date, and menopause. Pre-RA ACPA elevation for cases was defined as >99th percentile of the control distribution on a research assay composed of autoantibodies targeting citrullinated protein epitopes or positivity on the second-generation commercial assay for cyclic citrullinated peptide. Asthma status and covariates were obtained through biennial questionnaires before blood draw. Conditional logistic regression estimated ORs and 95%CIs for RA by pre-RA ACPA and clinical serostatus, adjusted for matching factors, smoking pack-years, passive smoking, and body mass index (BMI). Results We identified 284 incident RA cases and 849 matched controls; mean age at the index date was 61.2 years (SD 10.1). Blood was drawn 9.7 years (mean; SD 5.8) before the index date. We identified 96 (33.8%) RA cases with elevated pre-RA ACPA. At blood draw, 17.7% of pre-RA ACPA+ cases and 6.3% of matched controls (p = 0.0008) reported clinician-diagnosed asthma. After adjusting for matching factors, smoking pack-years, passive smoking, and BMI, asthma was significantly associated with pre-RA ACPA+ RA (OR 3.57, 95%CI 1.58,8.04). Asthma was not associated with overall RA (OR 1.45, 95%CI 0.91,2.31), but was significantly associated with seropositive RA (OR 1.79, 95%CI 1.01,3.18). Conclusions Asthma was strongly associated with ACPA elevation in blood drawn prior to RA diagnosis, independent of smoking. Chronic mucosal airway inflammation may contribute to ACPA development and RA pathogenesis.

OBJECTIVES:. To assess if genetic predictors for C-reactive protein and risk of venous thromboembolism are associated with severe outcomes among individuals who tested positive for severe acute respiratory syndrome coronavirus 2. DESIGN:. Retrospective cohort study. SETTING:. U.K. Biobank. PATIENTS OR SUBJECTS:. U.K. Biobank participants with European ancestry who were recorded to have a positive polymerase chain reaction test result for severe acute respiratory syndrome coronavirus 2 between March 16, 2020, and August 14, 2020. INTERVENTIONS:. Not applicable. MEASUREMENTS AND MAIN RESULTS:. We constructed separate genetic risk scores for C-reactive protein and venous thromboembolism consisting of 56 and 37 genetic variants that have been significantly associated with venous thromboembolism and C-reactive protein, respectively. Among 1,126 individuals who were diagnosed with coronavirus disease 2019, 48% had a coronavirus disease 2019–related hospitalization, 16% received critical care support, 10% had critical respiratory support, and 21% died from coronavirus disease 2019. Genetic predisposition to high C-reactive protein concentrations was marginally associated with a lower risk of death from coronavirus disease 2019 (odds ratio, 0.85; 95% CI, 0.73–1.00; p = 0.05). No other associations were significant. CONCLUSIONS:. Our results do not support associations between polygenic risk for elevated blood C-reactive protein concentrations or venous thromboembolism and severe coronavirus disease 2019 health outcomes. Thus, considering genetic predisposition associated with C-reactive protein concentrations or venous thromboembolism risk is not meaningful for predicting severe coronavirus disease 2019 health outcomes.

Abstract Efforts for tissue engineering vascular grafts focuses on the tunica media and intima, although the tunica adventitia serves as the primary structural support for blood vessels. In surgery, during endarterectomies, surgeons can strip the vessel, leaving the adventitia as the main strength layer to close the vessel. Here, we adapted our recently developed technique of forming vascular tissue rings then stacking the rings into a tubular structure, to accommodate human fibroblasts to create adventitia vessels in 8 days. Collagen production and fibril cross-linking was augmented with TGF-β and ascorbic acid, significantly increasing tensile strength to 57.8 ± 3.07 kPa (p = 0.008). Collagen type I gel was added to the base fibrin hydrogel to further increase strength. Groups were: Fibrin only; 0.7 mg/ml COL; 1.7 mg/ml COL; and 2.2 mg/ml COL. The 0.7 mg/ml collagen rings resulted in the highest tensile strength at 77.0 ± 18.1 kPa (p = 0.015). Culture periods of 1–2 weeks resulted in an increase in extracellular matrix deposition and significantly higher failure strength but not ultimate tensile strength. Histological analysis showed the 0.7 mg/ml COL group had significantly more, mature collagen. Thus, a hydrogel of 0.7 mg/ml collagen in fibrin was ideal for creating and strengthening engineered adventitia vessels.

Patients with Parkinson’s disease (PD) are at increased risk of aspiration pneumonia, their primary cause of death. Their oral microbiota differs from healthy controls, exacerbating this risk. Our goal was to explore if poor oral health, poor oral hygiene, and dysphagia status affect the oral microbiota composition of these patients. In this cross-sectional case-control study, the oral microbiota from hard and soft tissues of patients with PD (n = 30) and age-, gender-, and education-matched healthy controls (n = 30) was compared using 16S rRNA gene sequencing for bacterial identification. Study participants completed dietary, oral hygiene, drooling, and dysphagia questionnaires, and an oral health screening. Significant differences in soft tissue beta-diversity (p < 0.005) were found, and a higher abundance of opportunistic oral pathogens was detected in patients with PD. Factors that significantly influenced soft tissue beta-diversity and microbiota composition include dysphagia, drooling (both p < 0.05), and salivary pH (p < 0.005). Thus, patients with PD show significant differences in their oral microbiota compared to the controls, which may be due, in part, to dysphagia, drooling, and salivary pH. Understanding factors that alter their oral microbiota could lead to the development of diagnostic and treatment strategies that improve the quality of life and survivability of these patients.

The mechanisms underlying the transition from acute to chronic pain remain unclear. Here, we sought to characterize the transcriptome associated with chronic low back pain as well as the transcriptome of the transition from acute to chronic low back pain. For the analysis, we compared the whole blood transcriptome of: (a) patients at the onset of low back pain who no longer had pain within 6 weeks after onset (acute) with patients who developed chronic low back pain at 6 months (chronic T5); and, (b) patients at the onset of low back pain (chronic T1) who developed chronic pain at 6 months with healthy pain-free (normal) controls. The majority of differentially expressed genes were protein coding. We illustrate a unique chronic low back pain transcriptome characterized by significant enrichment for known pain genes, extracellular matrix genes, and genes from the extended major histocompatibility complex (MHC) genomic locus. The transcriptome of the transition from acute to chronic low back pain was characterized by significant upregulation of antigen presentation pathway (MHC class I and II) genes and downregulation of mitochondrial genes associated with oxidative phosphorylation, suggesting a unique genomic signature of vulnerability to low back pain chronicity.

Measurements of molecular chlorine (Cl2), nitryl chloride (ClNO2), and dinitrogen pentoxide (N2O5) were taken as part of the DISCOVER-AQ Texas 2013 campaign with a High Resolution Time-of-Flight Chemical Ionization Mass Spectrometer (HR-ToF-CIMS) using iodide (I-) as a reagent ion. ClNO2 concentrations exceeding 50 ppt were regularly detected with peak concentrations typically occurring between 7:00 a.m. and 10:00 am. Hourly averaged Cl2 concentrations peaked daily between 3:00 p.m. and 4:00 p.m., with a 29-day average of 0.9 ± 0.3 (1σ) ppt. A day-time Cl2 source of up to 35 ppt∙h−1 is required to explain these observations, corresponding to a maximum chlorine radical (Cl•) production rate of 70 ppt∙h−1. Modeling of the Cl2 source suggests that it can enhance daily maximum O3 and RO2• concentrations by 8%–10% and 28%–50%, respectively. Modeling of observed ClNO2 assuming a well-mixed nocturnal boundary layer indicates O3 and RO2• enhancements of up to 2.1% and 38%, respectively, with a maximum impact in the early morning. These enhancements affect the formation of secondary organic aerosol and compliance with air quality standards for ozone and particulate matter.

Introduction Patients with Parkinson's disease (PD) suffer progressive neurodegeneration and experience motor and nonmotor symptoms. Oropharyngeal dysfunctions are increasingly recognized as nonmotor PD symptoms that negatively impact a patient's quality of life. This module was primarily created to update dental health professionals and educate dental students on the oral health needs of patients with PD, with an emphasis on interprofessional collaboration and evidence-based dentistry. The module may also benefit other health professionals from different disciplines working with patients with PD. Methods The module was developed to be delivered in one 55-minute large-group session followed by a short assessment and case study discussion. Associated materials include PowerPoint slides with transcript, a narrated video version of the PowerPoint lecture, a quiz, and the case study. Thirty-four first-year dental students were invited to watch the narrated presentation, complete a pre-/postsurvey, and take the quiz. Results All participants agreed dental schools should provide education regarding oral health in patients with neurological disorders, as only 29% of them had previously taken a related class. After watching the presentation, students reported that most of the information was new content and that the difficulty level met their expectations. All students reported that the lecture increased their interest in interprofessional collaboration. In a quiz taken immediately after the presentation, the class average grade was 82.7, with 94% of the class passing the quiz with a grade of 70 or more. Discussion Educating dental professionals regarding care of patients with PD must emphasize interprofessional collaborations among health care providers.

Hydrogen bonding is a key molecular interaction in biological processes, drug delivery, and catalysis. This report describes a high throughput UV-Vis spectroscopic method to measure hydrogen bonding capacity using a pyrazinone sensor. This colormetric sensor reversibly binds to a hydrogen bond donor, resulting in a blue shift as additional equivalents of donor are added. Titration with excess equivalents of donor is used to determine the binding coefficient, ln(Keq ). Over 100 titrations were performed for a variety of biologically relevant compounds. This data enabled development a multiple linear regression model that is capable of predicting 95 % of ln(Keq ) values within 1 unit, allowing for the estimation of hydrogen bonding affinity from a single measurement. To show the effectiveness of the single point measurements, hydrogen bond strengths were obtained for a set of carboxylic acid bioisosteres. The values from the single point measurements were validated with full titrations.