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Photosynthesis is initiated when the sun’s light induces electron transfer from chlorophyll to plastoquinone, a para-quinone. While photosynthesis occurs in the intact chloroplasts of living plants, similar photochemical reactions between dietary chlorophyll metabolites and quinones are likely and may affect health outcomes. Herein, we continue our studies of the direct photoreduction of para-quinones and ortho-quinones that were generated by the photo-oxidation of catechols. Chlorophyll metabolites, including pheophorbide A, chlorin e6, and pyropheophorbide A, as well as methylene blue were employed as photosensitizers. We detected hydrogen peroxide using horseradish peroxidase following the photo-oxidation of the catechol dopamine, even in the presence of EDTA, a tertiary amine electron donor. Under ambient oxygen, hydrogen peroxide was also detected after the photoreduction of several para-quinones, including 2,3-dimethoxy-5-methyl-p-benzoquinone (CoQ0), methoxy-benzoquinone, and methyl-benzoquinone. The combinations of methylene blue and EDTA or pheophorbide A and triethanolamine as the electron donor in 20% dimethylformamide were optimized for photoreduction of the para-quinones. Chlorin e6 and pyropheophorbide A were less effective for the photoreduction of CoQ0 but were equivalent to pheophorbide A for generating hydrogen peroxide in photo-oxidation reactions with photosensitizers, oxygen, and triethanolamine. We employed dinitrophenylhydrazine to generate intensely colored adducts of methoxy-benzoquinone, methyl-benzoquinone, and 1,4-benzoquinone.

ABSTRACT The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic caused the biggest public health crises in recent history. Many expect future coronavirus introductions into the human population. Hence, it is essential to understand the basic biology of these viruses. In natural infection, the SARS-CoV-2 Spike (S) glycoprotein is co-expressed with all other viral proteins, which modify cellular compartments to maximize virion assembly. By comparison, most of S is degraded when the protein is expressed in isolation, as in current molecular vaccines. To probe the maturation pathway of S, we redirected its maturation by fusing S to the tetraspanin protein CD81. CD81 is a defining constituent of extracellular vesicles (EVs) or exosomes. EVs are generated in large numbers by all cells, extruded into blood and lymph, and transfer cargo between cells and systemically (estimated 1012 EVs per mL plasma). EVs, like platelets, can be transfused between unrelated donors. When fusing the proline-stabilized form of strain Delta S into the flexible, large extracellular loop of CD81 rather than being degraded in the lysosome, S was extruded into EVs. CD81-S fusion containing EVs were produced in large numbers and could be isolated to high purity. Purified CD81::S EVs bound ACE2, and S displayed on individual EV was observed by cryogenic electron microscopy (EM). The CD81::S-fusion EVs were non-toxic and elicited an anti-S trimer and anti-RBD antibody response in mice. This report shows a design path to maximize viral glycoprotein assembly and release without relying on the co-expression of potentially pathogenic nonstructural viral proteins.IMPORTANCEThe severe acute respiratory syndrome coronavirus 2 pandemic caused the biggest public health crises in recent history. To understand the maturation pathway of S, we fused S to the tetraspanin protein CD81. The resulting molecule is secreted in extracellular vesicles and induces antibodies in mice. This may be a general design path for viral glycoprotein vaccines.

Aim: Whether changes in oxygen metabolism, as measured by oxygen consumption (VO2), carbon dioxide production (VCO2) and the respiratory exchange ratio (RER), are associated with survival after cardiac arrest is poorly understood. In this prospective observational study, we investigated the association between VO2, VCO2, and RER in the initial 12 and 24 h after return of spontaneous circulation (ROSC) and survival to hospital discharge. Methods: Adults with ROSC after cardiac arrest, admitted to the intensive care unit, requiring mechanical ventilation and treated with targeted temperature management were included. VO2 and VCO2 were measured continuously for 24 h after ROSC, using a noninvasive anesthesia monitor. Area under the curve for VO2, VCO2 & RER was calculated using all available values over 12 and 24 h after ROSC. Using logistic regression, we evaluated the relationship between these metabolic variables and survival to hospital discharge. Analyses were adjusted for temperature, vasopressors, and neuromuscular blockade. Results: Sixty four patients were included. Mean age was 64 ± 16 years, and 59% were women. There was no significant association between the area under the curve of VO2 or VCO2 and survival. A higher RER in the initial 12 h was associated with better survival (aOR = 3.97, 95% CI [1.01,15.6], p = 0.048). Survival was lower in those with median RER

Abstract Background Mental health service providers are increasingly interested in patient perspectives. We examined rates and predictors of patient-reported satisfaction and perceived helpfulness in a cross-national general population survey of adults with 12-month DSM-IV disorders who saw a provider for help with their mental health. Methods Data were obtained from epidemiological surveys in the World Mental Health Survey Initiative. Respondents were asked about satisfaction with treatments received from up to 11 different types of providers (very satisfied, satisfied, neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied) and helpfulness of the provider (a lot, some, a little, not at all). We modelled predictors of satisfaction and helpfulness using a dataset of patient-provider observations (n = 5,248). Results Most treatment was provided by general medical providers (37.4%), psychiatrists (18.4%) and psychologists (12.7%). Most patients were satisfied or very satisfied (65.9-87.5%, across provider) and helped a lot or some (64.4-90.3%). Spiritual advisors and healers were most often rated satisfactory and helpful. Social workers in human services settings were rated lowest on both dimensions. Patients also reported comparatively low satisfaction with general medical doctors and psychiatrists/psychologists and found general medical doctors less helpful than other providers. Men and students reported lower levels of satisfaction than women and nonstudents. Respondents with high education reported higher satisfaction and helpfulness than those with lower education. Type of mental disorder was unrelated to satisfaction but in some cases (depression, bipolar spectrum disorder, social phobia) was associated with low perceived helpfulness. Insurance was unrelated to either satisfaction or perceived helpfulness but in some cases was associated with elevated perceived helpfulness for a given level of satisfaction. Conclusions Satisfaction with and perceived helpfulness of treatment varied as a function of type of provider, service setting, mental status, and socio-demographic variables. Invariably, caution is needed in combining data from multiple countries where there are cultural and service delivery variations. Even so, our findings underscore the utility of patient perspectives in treatment evaluation and may also be relevant in efforts to match patients to treatments.

Abstract Soils contribute 15%–75% of total atmospheric nitrogen oxide (NOx) emissions in agricultural regions during the growing season. However, the impacts of cropland fertilizer management on spatially heterogeneous, temporally episodic NOx emission patterns are highly uncertain. We examine the effects of liquid slurry dairy manure application practices on soil NOx emissions in rainfed, corn‐soybean rotations during spring 2016 and 2017. Daily soil NOx emissions and weekly soil inorganic N measurements were performed in a randomized split–split plot design for 1–4 weeks following manure applications. NOx emissions and soil N with shallow‐disk injection and chisel‐disk manure incorporation methods were compared with unincorporated broadcast practices. Injected manure and chisel‐disk incorporation exhibited two–four times larger mean NOx emissions than those with unincorporated broadcast manure. Larger soil NOx emissions with manure incorporation practices were driven by the predominance of nitrification in these treatments with evidence of soil nitrate production. Soil NOx emission differences between treatments were detectable across order of magnitude changes in daily NOx emissions during two growing seasons. Larger soil NOx emissions associated with manure incorporation practices compared with unincorporated broadcast practices occur alongside larger N2O and smaller NH3 emissions, highlighting important air quality and climate impact tradeoffs for cropland manure fertilizer management choices.

Microbial respiration is a critical component of the marine carbon cycle, determining the proportion of fixed carbon that is subject to remineralization as opposed to being available for export to the ocean depths. Despite its importance, methodological constraints have led to an inadequate understanding of this process, especially in low-activity oligotrophic and mesopelagic regions. Here, we quantify respiration rates as low as 0.2 µmol O2 L-1 d-1 in contrasting ocean productivity provinces using oxygen optode sensors to identify size-fractionated respiration trends. In the low productivity region of the North Pacific Ocean at Station Papa, surface whole water microbial respiration was relatively stable at 1.2 µmol O2 L-1 d-1. Below the surface, there was a decoupling between respiration and bacterial production that coincided with increased phytodetritus and small phytoplankton. Size-fractionated analysis revealed that cells

Abstract Repeat vaccination with egg-based influenza vaccines could preferentially boost antibodies targeting the egg-adapted epitopes and reduce immunogenicity to circulating viruses. In this randomized trial (Clinicaltrials.gov: NCT03722589), sera pre- and post-vaccination with quadrivalent inactivated egg-based (IIV4), cell culture-based (ccIIV4), and recombinant (RIV4) influenza vaccines were collected from healthcare personnel (18-64 years) in 2018−19 (N = 723) and 2019−20 (N = 684) influenza seasons. We performed an exploratory analysis. Vaccine egg-adapted changes had the most impact on A(H3N2) immunogenicity. In year 1, RIV4 induced higher neutralizing and total HA head binding antibodies to cell- A(H3N2) virus than ccIIV4 and IIV4. In year 2, among the 7 repeat vaccination arms (IIV4-IIV4, IIV4-ccIIV4, IIV4-RIV4, RIV4-ccIIV4, RIV4-RIV4, ccIIV4-ccIIV4 and ccIIV4-RIV4), repeat vaccination with either RIV4 or ccIIV4 further improved antibody responses to circulating viruses with decreased neutralizing antibody egg/cell ratio. RIV4 also had higher post-vaccination A(H1N1)pdm09 and A(H3N2) HA stalk antibodies in year 1, but there was no significant difference in HA stalk antibody fold rise among vaccine groups in either year 1 or year 2. Multiple seasons of non-egg-based vaccination may be needed to redirect antibody responses from immune memory to egg-adapted epitopes and re-focus the immune responses towards epitopes on the circulating viruses to improve vaccine effectiveness.

Abstract Background In children with cerebral malaria (CM) admission blood lactate has previously guided intravenous fluid therapy and been validated as a prognostic biomarker associated with death. The usefulness of post-admission measurements of blood lactate in children with CM is less clear. The strength of association between blood lactate and neurological sequelae in CM survivors, as well as the optimal duration of post-admission measurements of blood lactate to identify children at higher risk of adverse outcomes is unknown. Methods A retrospective cohort study of 1674 Malawian children with CM hospitalized from 2000 to 2018 who had blood lactate measurements every 6 h for the first 24 h after admission was performed. The strength of association between admission lactate or values measured at any time point in the first 24 h post-admission and outcomes (mortality and neurological morbidity in survivors) was estimated. The duration of time after admission that lactate remained a valid prognostic biomarker was assessed. Results When lactate is analysed as a continuous variable, children with CM who have higher values at admission have a 1.05-fold higher odds (95% CI 0.99–1.11) of death compared to those with lower lactate values. Children with higher blood lactate at 6 h have 1.16-fold higher odds (95% CI 1.09–1.23) of death, compared to those with lower values. If lactate levels are dichotomized into hyperlactataemic (lactate > 5.0 mmol/L) or not, the strength of association between admission lactate and mortality increases (OR = 2.49, 95% CI 1.47–4.22). Blood lactate levels obtained after 18 h post-admission are not associated with outcomes. Similarly, the change in lactate concentrations through time during the first 24 h of hospital admission is not associated with outcomes. Blood lactate during hospitalization is not associated with adverse neurologic outcomes in CM survivors. Conclusions In children with CM, blood lactate is associated with death but not neurologic morbidity in survivors. To comprehensively estimate prognosis, blood lactate in children with CM should be assessed at admission and for 18 h afterwards.

Abstract Background Current measures of reproductive health care quality, such as rates of “unintended” pregnancies, neglect to incorporate patients’ desires and center their reproductive autonomy. This study explores patients’ perspectives on and receptivity to alternative metrics for measuring quality of such care. Methods An online research recruitment firm identified eligible participants living in New York, ages 18–45, self-identifying as women, and having visited a primary care provider in the last year. We conducted five virtual focus groups and eight in-depth interviews with participants (N = 30) in 2021. Semi-structured guides queried on ideal clinic interactions when preventing or attempting pregnancy and their perspectives on how to measure the quality of such encounters, including receptivity to using our definition of reproductive autonomy to develop one such metric: “whether the patient got the reproductive health service or counseling that they wanted to get, while having all the information about and access to their options, and not feeling forced into anything.” We employed an inductive thematic analysis. Results Participants wanted care that was non-judgmental, respectful, and responsive to their needs and preferences. For pregnancy prevention, many preferred unbiased information about contraceptive options to help make their own decisions. For pregnancy, many desired comprehensive information and more provider support. There was considerable support for using reproductive autonomy to measure quality of care. Conclusions Patients had distinct desires in their preferred approach to discussions about preventing versus attempting pregnancy. Quality of reproductive health care should be measured from the patient’s perspective. Given participants’ demonstrated support, future research is needed to develop and test a new metric that assesses patients’ perceptions of reproductive autonomy during clinical encounters.

ABSTRACTThe continental shelf of the Western Antarctic Peninsula (WAP) is a highly variable system characterized by strong cross-shelf gradients, rapid regional change, and large blooms of phytoplankton, notably diatoms. Rapid environmental changes coincide with shifts in plankton community composition and productivity, food web dynamics, and biogeochemistry. Despite the progress in identifying important environmental factors influencing plankton community composition in the WAP, the molecular basis for their survival in this oceanic region, as well as variations in species abundance, metabolism, and distribution, remains largely unresolved. Across a gradient of physicochemical parameters, we analyzed the metabolic profiles of phytoplankton as assessed through metatranscriptomic sequencing. Distinct phytoplankton communities and metabolisms closely mirrored the strong gradients in oceanographic parameters that existed from coastal to offshore regions. Diatoms were abundant in coastal, southern regions, where colder and fresher waters were conducive to a bloom of the centric diatom, Actinocyclus. Members of this genus invested heavily in growth and energy production; carbohydrate, amino acid, and nucleotide biosynthesis pathways; and coping with oxidative stress, resulting in uniquely expressed metabolic profiles compared to other diatoms. We observed strong molecular evidence for iron limitation in shelf and slope regions of the WAP, where diatoms in these regions employed iron-starvation induced proteins, a geranylgeranyl reductase, aquaporins, and urease, among other strategies, while limiting the use of iron-containing proteins. The metatranscriptomic survey performed here reveals functional differences in diatom communities and provides further insight into the environmental factors influencing the growth of diatoms and their predicted response to changes in ocean conditions.IMPORTANCEIn the Southern Ocean, phytoplankton must cope with harsh environmental conditions such as low light and growth-limiting concentrations of the micronutrient iron. Using metratranscriptomics, we assessed the influence of oceanographic variables on the diversity of the phytoplankton community composition and on the metabolic strategies of diatoms along the Western Antarctic Peninsula, a region undergoing rapid climate change. We found that cross-shelf differences in oceanographic parameters such as temperature and variable nutrient concentrations account for most of the differences in phytoplankton community composition and metabolism. We opportunistically characterized the metabolic underpinnings of a large bloom of the centric diatom Actinocyclus in coastal waters of the WAP. Our results indicate that physicochemical differences from onshore to offshore are stronger than between southern and northern regions of the WAP; however, these trends could change in the future, resulting in poleward shifts in functional differences in diatom communities and phytoplankton blooms.

The blood brain barrier (BBB) plays a crucial role in maintaining brain homeostasis by selectively preventing the entry of substances from the peripheral blood into the central nervous system (CNS). Comprised of endothelial cells, pericytes, and astrocytes, this highly regulated barrier encompasses the majority of the brain’s vasculature. In addition to its protective function, the BBB also engages in significant crosstalk with perivascular macrophages (MΦ) and microglia, the resident MΦ of the brain. These interactions play a pivotal role in modulating the activation state of cells comprising the BBB, as well as MΦs and microglia, themselves. Alterations in systemic metabolic and inflammatory states can promote endothelial cell dysfunction, reducing the integrity of the BBB and potentially allowing peripheral blood factors to leak into the CNS compartment. This may mediate activation of perivascular MΦs, microglia, and astrocytes, and initiate further immune responses within the brain parenchyma, suggesting neuroinflammation can be triggered by signaling from the periphery, without primary injury or disease originating within the CNS. The intricate interplay between the periphery and the CNS through the BBB highlights the importance of understanding the role of microglia in mediating responses to systemic challenges. Despite recent advancements, our understanding of the interactions between microglia and the BBB is still in its early stages, leaving a significant gap in knowledge. However, emerging research is shedding light on the involvement of microglia at the BBB in various conditions, including systemic infections, diabetes, and ischemic stroke. This review aims to provide a comprehensive overview of the current research investigating the intricate relationship between microglia and the BBB in health and disease. By exploring these connections, we hope to advance our understanding of the role of brain immune responses to systemic challenges and their impact on CNS health and pathology. Uncovering these interactions may hold promise for the development of novel therapeutic strategies for neurological conditions that involve immune and vascular mechanisms.

Aims and method Recently, the Health of the Nation Outcome Scales 65+ (HoNOS65+) were revised. Twenty-five experts from Australia and New Zealand completed an anonymous web-based survey about the content validity of the revised measure, the HoNOS Older Adults (HoNOS OA). Results All 12 HoNOS OA scales were rated by most (≥75%) experts as ‘important’ or ‘very important’ for determining overall clinical severity among older adults. Ratings of sensitivity to change, comprehensibility and comprehensiveness were more variable, but mostly positive. Experts’ comments provided possible explanations. For example, some experts suggested modifying or expanding the glossary examples for some scales (e.g. those measuring problems with relationships and problems with activities of daily living) to be more older adult-specific. Clinical implications Experts agreed that the HoNOS OA measures important constructs. Training may need to orient experienced raters to the rationale for some revisions. Further psychometric testing of the HoNOS OA is recommended.

We assessed the impact of metagenomic next-generation sequencing (mNGS) on patient care using previously established criteria. Among 37 patients receiving mNGS testing, 16% showed results that had a positive clinical impact. While mNGS results may offer valuable supplementary information, results should be interpreted within the broader clinical context and evaluation.

Oxygen stable isotopes (i.e., 16O, 17O, 18O) of nitrite (NO2−) are useful for investigating chemical processes and sources contributing to this important environmental contaminant and nutrient. However, it remains difficult to quantify the oxygen isotope compositions of NO2− due to the lack of internationally recognized NO2− reference materials with a well-known Δ(17O) value. Here we have adopted a combination of methodologies to develop a technique for measuring Δ(17O) of NO2− by reducing nitrate (NO3−) materials with internationally recognized Δ(17O) values to NO2− using activated cadmium catalyzed by chloride in a basic solution while conserving Δ(17O). The NO3− reference materials reduced to NO2− and sample NO2− unknowns are converted to N2O using sodium azide/acetic acid reagent and decomposed to O2 by passing through a heated gold tube and introduced into a continuous flow isotope ratio mass spectrometer for analysis at m/z 32, 33, and 34 for Δ(17O) quantification.The adapted method involves the following main points: • NO3− reference materials with internationally recognized oxygen isotope composition are reduced to NO2− under high pH conditions that conserve Δ(17O) values. • The NO3− reference materials reduced to NO2− and sample NO2− with unknown Δ(17O) values are reduced to N2O using chemical methods involving sodium azide/acetic acid. • The product N2O is extracted, purified, decomposed to O2, and analyzed for its isotope composition using a continuous flow isotope ratio mass spectrometer for Δ(17O) quantification. The Δ(17O) of NO2− samples are calibrated with respect to the NO3− reference materials with known Δ(17O) values.

Abstract Background Posttraumatic stress disorder (PTSD) is associated with significant morbidity, but efficacious pharmacotherapy and psychotherapy are available. Data from the World Mental Health Surveys were used to investigate extent and predictors of treatment coverage for PTSD in high-income countries (HICs) as well as in low- and middle-income countries (LMICs). Methods Seventeen surveys were conducted across 15 countries (9 HICs, 6 LMICs) by the World Health Organization (WHO) World Mental Health Surveys. Of 35,012 respondents, 914 met DSM-IV criteria for 12-month PTSD. Components of treatment coverage analyzed were: (a) any mental health service utilization; (b) adequate pharmacotherapy; (c) adequate psychotherapy; and (d) effective treatment coverage. Regression models investigated predictors of treatment coverage. Results 12-month PTSD prevalence in trauma exposed individuals was 1.49 (S.E., 0.08). A total of 43.0% (S.E., 2.2) received any mental health services, with fewer receiving adequate pharmacotherapy (13.5%), adequate psychotherapy (17.2%), or effective treatment coverage (14.4%), and with all components of treatment coverage lower in LMICs than HICs. In a multivariable model having insurance (OR = 2.31, 95 CI 1.17, 4.57) and severity of symptoms (OR = .35, 95% CI 0.18, 0.70) were predictive of effective treatment coverage. Conclusion There is a clear need to improve pharmacotherapy and psychotherapy coverage for PTSD, particularly in those with mild symptoms, and especially in LMICs. Universal health care insurance can be expected to increase effective treatment coverage and therefore improve outcomes.

In a cohort of essential workers in the United States previously infected with SARS-CoV-2, risk factors for reinfection included being unvaccinated, infrequent mask use, time since first infection, and being non-Hispanic Black. Protecting workers from reinfection requires a multipronged approach including up-to-date vaccination, mask use as recommended, and reduction in underlying health disparities.

Background: Health-related quality of life (HRQOL) is a critical issue for patients undergoing surgery for congenital heart disease (CHD) but has never been assessed in a low-income country. We conducted a cross-sectional mixed methods study with age-matched healthy siblings serving as controls at the Uganda Heart Institute. Methods: One-hundred fifteen CHD pediatric and young adult patients and sibling control participants were recruited. Health-related quality of life was assessed using the Pediatric Quality of Life Inventory Version 4.0 in participants ages 5–17 and 36-Item Short Form Survey for young adults aged 18–25. A subset of 27 participants completed face-to-face interviews to supplement quantitative findings. Results: Eighty-six pediatric (age 5–17) sibling and parent pairs completed Peds QOL surveys, and 29 young adult (age 18–25) sibling pairs completed SF-36 surveys. One third of patients had surgery in Uganda. Ventricular septal defects and tetralogy of Fallot were the most common diagnoses. Health-related quality of life scores in patients were lower across all domains compared to control participants in children. Reductions in physical and emotional domains of HRQOL were also statistically significant for young adults. Variables associated with lower HRQOL score on multivariate analysis in pediatric patients were younger age in the physical and emotional domains, greater number of surgeries in the physical domain and surgery outside Uganda in the school domain. The only predictor of lower HRQOL score in young adults was surgery outside Uganda in the social domain. Qualitative interviews identified a number of themes that correlated with survey results including abandonment by family, isolation from peers and community, financial hardship and social stigmatization. Conclusion: Health-related quality of life was lower in Ugandan patients after CHD surgery than siblings. Younger patients and those who had surgery outside of Uganda had lower HRQOL. These data have important implications for patients undergoing CHD surgery in LMIC and have potential to inform interventions.

Background: Current efforts to integrate reproductive health care into primary care in the United States involve assessing pregnancy intentions and reproductive goals, which are often not meaningful or attainable for some. Alternatively, we designed a reproductive health services-based screening question: ?Can I help you with any reproductive health services today, such as preventing pregnancy or planning a healthy pregnancy?? In this study, we describe women's interpretations of this question as part of a larger study, exploring perspectives on reproductive health care quality in primary care. Materials and Methods: We utilized a third-party research firm to recruit New York women of reproductive age (18?45), who visited a primary care provider in the past year. We conducted five focus groups and eight interviews (N?=?30). Semistructured guides queried participants on interpretations of the screening question and preferences for raising reproductive health concerns during a primary care visit. We employed inductive thematic analysis. Results: Participants interpreted the question as offering contraception or pregnancy counseling and care, although younger participants also understood it as offering sexual and reproductive health services broadly. Participants also connected the question with discussions about their ability to conceive. Some participants described experiences with provider assumptions and implicit bias. Tensions emerged around accepting primary care as a setting for reproductive health due to a perceived lack of specialized training. Conclusions: Participants interpreted the screening question as intended, indicating face validity. Primary care settings should increase patients' awareness of reproductive health service availability, such as by routinely introducing a services-based screening question.

The rapid rollout of vaccines against COVID-19 as a key mitigation strategy to end the global pandemic might be informed by lessons learned from rubella vaccine implementation in response to the global rubella epidemic of 1963–1965. That rubella epidemic led to the development of a rubella vaccine that has been introduced in all but 21 countries worldwide and has led to elimination of rubella in 93 countries. Although widespread introduction and use of rubella vaccines was slower than that for COVID-19 vaccines, the process can provide valuable insights for the continued battle against COVID-19. Experiences from the rubella disease control program highlight the critical and evolving elements of a vaccination program, including clearly delineated goals and strategies, regular data-driven revisions to the program based on disease and vaccine safety surveillance, and evaluations to identify the vaccine most capable of achieving disease control targets.

Abstract Background The post-partum period is a risk factor for tuberculosis (TB), possibly including the period after miscarriage as illustrated here. This case demonstrates how non-specific symptoms can hide widely disseminated TB. Case presentation A healthy 26-year-old female with a history of recent miscarriage presented to the emergency department with non-specific symptoms of headache, abdominal pain, and sub-acute fevers. She had immigrated to the United States from the Marshall Islands 9 years prior. Two months prior to presentation she had a miscarriage at 18 weeks of pregnancy. On admission, transvaginal ultrasound revealed retained products of conception and abdominal computed tomography revealed findings consistent with tubo-ovarian abscesses and peritonitis. The obstetrics and gynecology service performed dilation and curettage (D&C) to remove retained products of conception. Acid-fast bacilli cultures from cerebrospinal fluid as well as specimens from D&C and intra-abdominal abscesses subsequently all grew TB. She was diagnosed with TB meningitis, peritonitis, endometritis, and tubo-ovarian abscesses. Her treatment course was complicated by a paradoxical response resulting in a spinal tuberculoma causing lower extremity weakness. The tuberculoma was treated with surgical decompression as well as continuation of treatment with anti-tubercular chemotherapy and steroids. Conclusion Disseminated and extrapulmonary TB can present with non-specific symptoms. Recognition of risk factors for TB is critical for prompt diagnostic evaluation and treatment of this deadly disease. A paradoxical reaction needs to be taken into consideration when any new neurological symptoms occur during TB treatment.

Abstract Snow nitrate is vulnerable to photolytic loss that causes isotopic alteration, and thus its isotopes can potentially track the extent of snow nitrate photolysis and its impacts in environments where loss is significant. Large increases in δ15N‐NO3− below the snow surface have been attributed to photolysis and this behavior is generally consistent amongst theoretical as well as lab and field studies. Oxygen isotope ratios are thought to be influenced by photolysis as well as secondary condensed‐phase chemistry, but the competing effects have yet to be reconciled. Here we use a model that simulates nitrate burial, photolytic fractionation, and re‐oxidation in snow to quantitatively assess these processes with the aim of developing a consistent framework for interpreting the photolytic effects of the complete nitrate isotopic composition (δ15N, δ18O, and Δ17O). This study reveals that isotopic effects of nitrate photolysis and aqueous‐phase re‐oxidation chemistry are important sources of uncertainties in modeling δ18O‐NO3−.

ABSTRACT Purifying extracellular vesicles (EVs) has been challenging because EVs are heterogeneous in cargo yet share similar sizes and densities. Most surface marker‐based affinity separation methods are limited to research or diagnostic scales. We report that heparin chromatography can separate purified EVs into two distinct subpopulations as ascertained by MS/MS: a non‐heparin‐binding (NHB) fraction that contains classical EV markers such as tetraspanins and a heparin‐binding (HB) fraction enriched in fibronectins and histones. Both fractions were similarly fusogenic but induced different transcriptional responses in endothelial cells. While EVs that were purified by conventional, non‐affinity methods alone induced ERK1/2 phosphorylation and Ki67, the NHB fraction did not. This result suggests heparin chromatography as an additional novel fractionation step that is inherently scalable, does not lead to loss of material, and separates inflammatory and pyrogenic EVs from unreactive EVs, which will improve clinical applications.

Abstract Background Most individuals with major depressive disorder (MDD) receive either no care or inadequate care. The aims of this study is to investigate potential determinants of effective treatment coverage. Methods In order to examine obstacles to providing or receiving care, the type of care received, and the quality and use of that care in a representative sample of individuals with MDD, we analyzed data from 17 WHO World Mental Health Surveys conducted in 15 countries (9 high-income and 6 low/middle-income). Of 35,012 respondents, 3341 had 12-month MDD. We explored the association of socio-economic and demographic characteristics, insurance, and severity with effective treatment coverage and its components, including type of treatment, adequacy of treatment, dose, and adherence. Results High level of education (OR = 1.63; 1.19, 2.24), private insurance (OR = 1.62; 1.06, 2.48), and age (30–59yrs; OR = 1.58; 1.21, 2.07) predicted effective treatment coverage for depression in a multivariable logistic regression model. Exploratory bivariate models further indicate that education may follow a dose—response relation; that people with severe depression are more likely to receive any services, but less likely to receive adequate services; and that in low and middle-income countries, private insurance (the only significant predictor) increased the likelihood of receiving effective treatment coverage four times. Conclusions In the regression models, specific social determinants predicted effective coverage for major depression. Knowing the factors that determine who does and does not receive treatment contributes to improve our understanding of unmet needs and our ability to develop targeted interventions.

Abstract Background As the COVID-19 pandemic evolves, more information is needed on its long-term impacts on health-related quality of life (HRQoL) and social determinants of health (SDoH). The aim of the study was to assess HRQoL and SDoH among a predominantly Latino population of COVID-19 survivors and to compare effects in Latinos versus non-Latinos. Methods This cross-sectional study consisted of a survey (in English and Spanish) of COVID-19 survivors from December 2020 to July 2021. The study assessed sociodemographic data, clinical characteristics, and SDoH, consisting of 10 COVID-19—related concerns. The PROMIS-29 + 2 (PROPr) measure, which captures 8 HRQoL domains and a preference-based health utility, was used to assess HRQoL. Bivariate analyses included chi-square tests and t-tests. Generalized linear models were conducted for multivariable analyses. Results Of 230 respondents (6.3% response rate), the mean [SD] age was 43.1 [14.3] years; 83.0% were Latino; the mean [SD] time since diagnosis was 8.1 [3.2] months; and 12.6% had a history of hospitalization with COVID-19. HRQoL scores were slightly worse than population norms on all domains, especially anxiety; the mean [SD] PROPr health utility was 0.36 [0.25]. Domain scores were similar by ethnicity except for cognitive function—abilities, where scores were lower in Latinos. Multivariable analyses revealed that: (1) financial concerns were associated with worse health utility, as well as worse scores on all 8 PROMIS domains; (2) interpersonal conflict was associated with worse health utility and worse scores on 6 of the 8 PROMIS domains (anxiety, depression, fatigue, sleep disturbance, social function, and pain interference); and (3) Latino ethnicity was only associated with 1 PROMIS domain (cognitive function—abilities) after controlling for covariates. Conclusion COVID-19 infection is associated with HRQoL decrements long after the acute infection, and financial concerns and interpersonal conflict are particularly associated with worse HRQoL.

Introduction: Preovulatory follicle response to the luteinizing hormone (LH) surge leads to metabolic, molecular, and functional changes in the oocyte and somatic follicular cells from the onset of estrus to ovulation. Follicular fluid contains metabolites, miRNAs, proteins, and hormones that are byproducts of follicular metabolism and support cellular processes of oocyte, cumulus, and granulosa constituents. Numerous studies have highlighted the importance of follicular fluid composition to support fertility, but critical gaps exist toward understanding dynamic modifications in the follicular fluid metabolome from estrous onset to ovulation. The hypothesis was that abundance of follicular fluid metabolites is dependent on follicle progression post LH surge and variability in follicular fluid metabolome profiles indicate key processes required for preparation of the follicle and oocyte for optimal fertility. The objective was to generate preovulatory follicular fluid metabolome profiles and discern differences in the metabolome of preovulatory follicular fluid samples collected at onset of estrus, 11 h post estrous onset, and 18 h post estrous onset.Methods: Estrus was synchronized in non-lactating Jersey cows (n=40) and follicular fluid was collected immediately after the first observed standing mount (hr 0) or at approximately h 11 or 18 after the first standing mount. Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry was performed on preovulatory follicular fluid samples (n = 9 collected at hr 0, 9 at h 11, and 10 at h 18) and a multiple linear model was performed to determine if time post estrous onset impacted metabolite abundance.Results: Metabolites influenced by time post estrous onset were tested for enrichment in KEGG pathways. Ninety metabolites were identified in follicular fluid samples. Twenty metabolites differed in abundance among timepoints post estrous onset (p ≤ 0.05). Pathways corresponding to amino acid and energy metabolism were enriched with metabolites impacted by time post estrous onset (FDR ≤ 0.10).Discussion: Results from the current study indicate early response to the LH surge to increase bioavailability of amino acids and metabolites used by the cumulus and granulosa cells for energy production and shuttled into the oocyte to support meiotic maturation. Such metabolites may later be used by the ovulatory follicle for protein production.

Abstract Geosciences remain one of the least diverse fields. Efforts to diversify the discipline need to address the role of hostile and exclusionary work and learning environments. A workplace climate survey distributed to five professional organizations illustrates varied experiences of earth and space scientists over a 12‐month period (pre‐COVID). A majority experienced positive interactions in the workplace. However, scientists of color, women and non‐binary individuals, scientists with disabilities, and lesbian, gay, bisexual, queer, pansexual, and asexual (LGBQPA+) scientists more frequently experienced negative interactions, including interpersonal mistreatment, discriminatory language, and sexual harassment. Geoscientists of color were more likely to experience devaluation of their work than white scientists. More than half of women and non‐binary respondents, as well as those who identify as LGBQPA+ experienced identity‐based discriminatory remarks. Disabled geoscientists were more likely to hear negative identity‐based language than those who did not disclose a disability. Overall, 14% of all respondents experienced sexual harassment in the previous year. Rates were greatest for historically excluded groups: non‐binary (51%), LGBQPA+ (33%), disabled (26%), women (20%), and geoscientists of color (17%). A majority of geoscientists reported avoiding their colleagues and almost a third considered leaving their institution or a career change. Historically excluded groups were more likely to report opting out of professional activities with potential career consequences. To address continued exclusion and low retention in the earth and space sciences, recruitment is not enough. We need to create environments that ensure opportunities for all to thrive.

COVID-19 can result in neurological manifestations and animal models could provide insights into the mechanisms. Here, the authors describe neuroinflammation, microhemorrhages and brain hypoxia in SARS-CoV-2 infected non-human primates, including in animals that don’t develop severe respiratory disease.

Abstract Background Mental healthcare is delivered across service sectors that differ in level of specialization and intervention modalities typically offered. Little is known about the perceived helpfulness of the combinations of service sectors that patients use. Methods Respondents 18 + years with 12-month DSM-IV mental or substance use disorders who saw a provider for mental health problems in the year before interview were identified from WHO World Mental Health surveys in 17 countries. Based upon the types of providers seen, patients were grouped into nine mutually exclusive single-sector or multi-sector ‘treatment profiles’. Perceived helpfulness was defined as the patient’s maximum rating of being helped (‘a lot’, ‘some’, ‘a little’ or ‘not at all’) of any type of provider seen in the profile. Logistic regression analysis was used to examine the joint associations of sociodemographics, disorder types, and treatment profiles with being helped ‘a lot’. Results Across all surveys combined, 29.4% (S.E. 0.6) of respondents with a 12-month disorder saw a provider in the past year (N = 3221). Of these patients, 58.2% (S.E. 1.0) reported being helped ‘a lot’. Odds of being helped ‘a lot’ were significantly higher (odds ratios [ORs] = 1.50–1.89) among the 12.9% of patients who used specialized multi-sector profiles involving both psychiatrists and other mental health specialists, compared to other patients, despite their high comorbidities. Lower odds of being helped ‘a lot’ were found among patients who were seen only in the general medical, psychiatrist, or other mental health specialty sectors (ORs = 0.46–0.71). Female gender and older age were associated with increased odds of being helped ‘a lot’. In models stratified by country income group, having 3 or more disorders (high-income countries only) and state-funded health insurance (low/middle-income countries only) were associated with increased odds of being helped ‘a lot’. Conclusions Patients who received specialized, multi-sector care were more likely than other patients to report being helped ‘a lot’. This result is consistent with previous research suggesting that persistence in help-seeking is associated with receiving helpful treatment. Given the nonrandom sorting of patients by types of providers seen and persistence in help-seeking, we cannot discount that selection bias may play some role in this pattern.

Abstract Background Treatment guidelines for generalized anxiety disorder (GAD) are based on a relatively small number of randomized controlled trials and do not consider patient-centered perceptions of treatment helpfulness. We investigated the prevalence and predictors of patient-reported treatment helpfulness for DSM-5 GAD and its two main treatment pathways: encounter-level treatment helpfulness and persistence in help-seeking after prior unhelpful treatment. Methods Data came from community epidemiologic surveys in 23 countries in the WHO World Mental Health surveys. DSM-5 GAD was assessed with the fully structured WHO Composite International Diagnostic Interview Version 3.0. Respondents with a history of GAD were asked whether they ever received treatment and, if so, whether they ever considered this treatment helpful. Number of professionals seen before obtaining helpful treatment was also assessed. Parallel survival models estimated probability and predictors of a given treatment being perceived as helpful and of persisting in help-seeking after prior unhelpful treatment. Results The overall prevalence rate of GAD was 4.5%, with lower prevalence in low/middle-income countries (2.8%) than high-income countries (5.3%); 34.6% of respondents with lifetime GAD reported ever obtaining treatment for their GAD, with lower proportions in low/middle-income countries (19.2%) than high-income countries (38.4%); 3) 70% of those who received treatment perceived the treatment to be helpful, with prevalence comparable in low/middle-income countries and high-income countries. Survival analysis suggested that virtually all patients would have obtained helpful treatment if they had persisted in help-seeking with up to 10 professionals. However, we estimated that only 29.7% of patients would have persisted that long. Obtaining helpful treatment at the person-level was associated with treatment type, comorbid panic/agoraphobia, and childhood adversities, but most of these predictors were important because they predicted persistence rather than encounter-level treatment helpfulness. Conclusions The majority of individuals with GAD do not receive treatment. Most of those who receive treatment regard it as helpful, but receiving helpful treatment typically requires persistence in help-seeking. Future research should focus on ensuring that helpfulness is included as part of the evaluation. Clinicians need to emphasize the importance of persistence to patients beginning treatment.

Introduction: We evaluated knowledge, attitudes, and practices (KAP) related to influenza and influenza vaccination among pregnant women in three selected countries. Methods: During 2017, pregnant women seeking antenatal care at hospitals at participating sites were enrolled. We described characteristics and responses to KAP questions. We also evaluated predictors associated with influenza vaccination during pregnancy at sites with substantial influenza vaccine uptake by multivariable logistic regression. Results: Overall, 4,648 pregnant women completed the survey. There were substantial differences among the three survey populations; only 8% of the women in Nagpur had heard of influenza, compared to 90% in Lima and 96% in Bangkok (p-value

BackgroundAssessing the real-world effectiveness of COVID-19 vaccines and understanding the incidence and severity of SARS-CoV-2 illness in children are essential to inform policy and guide health care professionals in advising parents and caregivers of children who test positive for SARS-CoV-2. ObjectiveThis report describes the objectives and methods for conducting the Pediatric Research Observing Trends and Exposures in COVID-19 Timelines (PROTECT) study. PROTECT is a longitudinal prospective pediatric cohort study designed to estimate SARS-CoV-2 incidence and COVID-19 vaccine effectiveness (VE) against infection among children aged 6 months to 17 years, as well as differences in SARS-CoV-2 infection and vaccine response between children and adolescents. MethodsThe PROTECT multisite network was initiated in July 2021, which aims to enroll approximately 2305 children across four US locations and collect data over a 2-year surveillance period. The enrollment target was based on prospective power calculations and accounts for expected attrition and nonresponse. Study sites recruit parents and legal guardians of age-eligible children participating in the existing Arizona Healthcare, Emergency Response, and Other Essential Workers Surveillance (HEROES)-Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) network as well as from surrounding communities. Child demographics, medical history, COVID-19 exposure, vaccination history, and parents/legal guardians’ knowledge and attitudes about COVID-19 are collected at baseline and throughout the study. Mid-turbinate nasal specimens are self-collected or collected by parents/legal guardians weekly, regardless of symptoms, for SARS-CoV-2 and influenza testing via reverse transcription-polymerase chain reaction (RT-PCR) assay, and the presence of COVID-like illness (CLI) is reported. Children who test positive for SARS-CoV-2 or influenza, or report CLI are monitored weekly by online surveys to report exposure and medical utilization until no longer ill. Children, with permission of their parents/legal guardians, may elect to contribute blood at enrollment, following SARS-CoV-2 infection, following COVID-19 vaccination, and at the end of the study period. PROTECT uses electronic medical record (EMR) linkages where available, and verifies COVID-19 and influenza vaccinations through EMR or state vaccine registries. ResultsData collection began in July 2021 and is expected to continue through the spring of 2023. As of April 13, 2022, 2371 children are enrolled in PROTECT. Enrollment is ongoing at all study sites. ConclusionsAs COVID-19 vaccine products are authorized for use in pediatric populations, PROTECT study data will provide real-world estimates of VE in preventing infection. In addition, this prospective cohort provides a unique opportunity to further understand SARS-CoV-2 incidence, clinical course, and key knowledge gaps that may inform public health. International Registered Report Identifier (IRRID)RR1-10.2196/37929

ABSTRACT Respiratory specimen collection materials shortages hampers severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. We compared specimen alternatives and evaluated SARS-CoV-2 RNA stability under simulated shipping conditions. We compared concordance of RT-PCR detection of SARS-CoV-2 from flocked midturbinate swabs (MTS) in viral transport media (VTM), foam MTS without VTM, and saliva. Specimens were collected between August 2020 and April 2021 from three prospective cohorts. We compared RT-PCR cycle quantification (Cq) for Spike (S), Nucleocapsid (N), and the Open Reading Frame 1ab (ORF) genes for flocked MTS and saliva specimens tested before and after exposure to a range of storage temperatures (4–30°C) and times (2, 3, and 7 days). Of 1,900 illnesses with ≥2 specimen types tested, 335 (18%) had SARS-CoV-2 detected in ≥1 specimen; 304 (91%) were concordant across specimen types. Among illnesses with SARS-CoV-2 detection, 97% (95% confidence interval [CI]: 94–98%) were positive on flocked MTS, 99% (95% CI: 97–100%) on saliva, and 89% (95% CI: 84–93%) on foam MTS. SARS-CoV-2 RNA was detected in flocked MTS and saliva stored up to 30°C for 7 days. All specimen types provided highly concordant SARS-CoV-2 results. These findings support a range of viable options for specimen types, collection, and transport methods that may facilitate SARS-CoV-2 testing during supply and personnel shortages. IMPORTANCE Findings from this analysis indicate that (1) self-collection of flocked and foam MTS and saliva samples is feasible in both adults and children, (2) foam MTS with VTM and saliva are both viable and reasonable alternatives to traditional flocked MTS in VTM for SARS-CoV-2 detection, and (3) these sample types may be stored and transported at ambient temperatures for up to 7 days without compromising sample quality. These findings support methods of sample collection for SARS-CoV-2 detection that may facilitate widespread community testing in the setting of supply and personnel shortages during the current pandemic.

Abstract Background Psychological interventions (PIs) are good practice treatment for both subthreshold and diagnosed mental disorders. Australia has implemented major reforms to expand the provision of subsidised psychological services for individuals with a diagnosed mental disorder. But there are gaps in knowledge about demand for PIs (i.e., use of and perceived need for PIs) across the population. This study uses nationally representative survey data from the 2007 Australian National Survey of Mental Health and Wellbeing to analyse demand for PIs. It also provides a method for analysing survey data to estimate demand for PIs when new survey data becomes available, along with suggestions to inform future survey development. Methods Nationally representative community survey respondents (n = 8841, 16–85 years) indicated their perceived need for nine types of help for mental health problems in the past 12 months, including three PIs (cognitive behavioural therapy, psychotherapy, and counselling), and whether these needs were unmet, partially met, or fully met. Types of help were grouped as: PIs only; PIs plus other; and other only. Chi-square analyses were used to examine the association between type of intervention, sociodemographic and clinical factors, and type of professional consulted; multinomial logistic regression models were used to examine predictors of type of intervention(s) received. Results 7.9% (95%CI: 7.2–8.6) received PIs. Receipt of PIs was positively associated with higher education and consulting a mental health specialist. Twice as many respondents received PIs plus medication as compared to PIs only (4.2% vs. 2.0%). Almost half (45.4, 95%CI 36.5–54.6) incurred out-of-pocket costs for treatment. The most common reason for partially met need for PIs was cost (24.8, 95%CI 17.2–34.3); for unmet need, it was preference for self-management (33.9, 95%CI 21.2–49.5). Perceived unmet need for PIs only (3.1, 95%CI 2.1–4.6) or PIs plus other interventions (5.2, 95%CI 3.9–6.9%) was lower than for other interventions only (22.8, 95%CI 18.7–27.6). Conclusions Continued reforms in Australia means that on-going monitoring of demand for PIs, using nationally representative data, is required. This study provides a baseline for comparison of the long-term effects of these reforms; this comparison may be undertaken using data from the third iteration of Australia’s NSMHWB, due for completion in 2021–22.

Introduction: Although the development of COVID-19 vaccines represents a triumph of modern medicine, studies suggest vaccine hesitancy exists among key populations, including healthcare professionals. In December 2020, a large academic medical center offered COVID-19 vaccination to 3439 students in medicine, nursing, dentistry, and other health professions. With limited vaccine hesitancy research in this population, this study evaluates the prevalence of COVID-19 vaccine hesitancy among healthcare students, including predictors of hesitancy and top concerns with vaccination. Methods: The authors distributed a cross-sectional survey to all healthcare students (n = 3,439) from 12/17/2020 to 12/23/2020. The survey collected age, sex, perceived risk of contracting SARS-CoV-2 without vaccination, perceived impact on health if infected with SARS-CoV-2, vaccine hesitancy, and vaccine concerns. In 2021, logistic regressions identified risk factors associated with hesitancy. Results: The response rate was 30.0% (n = 1030) with median age of 25.0. Of respondents, 19.4% were hesitant to accept COVID-19 vaccination, while 66.6% reported at least one concern with the vaccine. Medical discipline, history of COVID-19 infection, perceived risk of contracting COVID-19, and perceived severity of illness if infected were predictor variables of COVID-19 vaccine hesitancy (p

Abstract Extracellular vesicles (EVs) are secreted from all cell types and are intimately involved in tissue homeostasis. They are being explored as vaccine and gene therapy platforms, as well as potential biomarkers. As their size is below the diffraction limit of light microscopy, direct visualizations have been daunting and single‐particle studies under physiological conditions have been hampered. Here, direct stochastic optical reconstruction microscopy (dSTORM) was employed to visualize EVs in three‐dimensions and to localize molecule clusters such as the tetraspanins CD81 and CD9 on the surface of individual EVs. These studies demonstrate the existence of membrane microdomains on EVs. These were confirmed by Cryo‐EM. Individual particle visualization provided insights into the heterogeneity, structure, and complexity of EVs not previously appreciated

Human societies create and maintain structures in which individuals and groups experience varying degrees of inequity and suffering that may be skeletally and dentally embodied. It is necessary to foreground these social and structural impacts for forensic anthropologists to eschew biologically deterministic interpretations of human variation and overly individualistic interpretations of health and disease. We thus propose a ‘Structural Vulnerability Profile’ (SVP), akin to the Structural Vulnerability Assessment Tool of medical anthropology [1], to be considered along with the traditional ‘biological’ profile estimated by forensic anthropologists. Assembling an SVP would involve examining and assessing skeletal/dental biomarkers indicative of embodied social inequity—the lived experiences of social marginalization that can get ‘under the skin’ to leave hard-tissue traces. Shifting our emphasis from presumably hereditary variation to focus on embodied social marginalization, the SVP will allow forensic anthropologists to sensitively reconstruct the lived experiences of the people we examine.

BackgroundWorkers critical to emergency response and continuity of essential services during the COVID-19 pandemic are at a disproportionally high risk of SARS-CoV-2 infection. Prospective cohort studies are needed for enhancing the understanding of the incidence of symptomatic and asymptomatic SARS-CoV-2 infections, identifying risk factors, assessing clinical outcomes, and determining the effectiveness of vaccination. ObjectiveThe Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) prospective cohort study was designed to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infections, examine the risk factors for infection and clinical spectrum of illness, and assess the effectiveness of vaccination among essential workers. MethodsThe RECOVER multisite network was initiated in August 2020 and aims to enroll 3000 health care personnel (HCP), first responders, and other essential and frontline workers (EFWs) at 6 US locations. Data on participant demographics, medical history, and vaccination history are collected at baseline and throughout the study. Active surveillance for the symptoms of COVID-19–like illness (CLI), access of medical care, and symptom duration is performed by text messages, emails, and direct participant or medical record reports. Participants self-collect a mid-turbinate nasal swab weekly, regardless of symptoms, and 2 additional respiratory specimens at the onset of CLI. Blood is collected upon enrollment, every 3 months, approximately 28 days after a reverse transcription polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 infection, and 14 to 28 days after a dose of any COVID-19 vaccine. From February 2021, household members of RT-PCR–confirmed participants are self-collecting mid-turbinate nasal swabs daily for 10 days. ResultsThe study observation period began in August 2020 and is expected to continue through spring 2022. There are 2623 actively enrolled RECOVER participants, including 280 participants who have been found to be positive for SARS-CoV-2 by RT-PCR. Enrollment is ongoing at 3 of the 6 study sites. ConclusionsData collected through the cohort are expected to provide important public health information for essential workers at high risk for occupational exposure to SARS-CoV-2 and allow early evaluation of COVID-19 vaccine effectiveness. International Registered Report Identifier (IRRID)DERR1-10.2196/31574

Abstract Posterior reversible encephalopathy syndrome (PRES) is acute neurologic symptoms with specific radiologic findings. This unique case shows coexisting PRES with acute liver injury, which could suggest common pathophysiologic process.

Abstract Nitrogen stable isotope composition (δ15N) of nitrate (NO3−) deposition can aid in source apportionment of its precursor emissions, nitrogen oxides (NOx), with implications in mitigation policy to address serious air pollution. However, potential δ15N fractionation during atmospheric NO3− formation may hinder accurate quantification of NOx contributions. Previously, NOx photochemical reactions have been suggested to be the dominant δ15N fractionation process in NO3− formation. Here, we have quantified the potential fractionation effects associated with NOx photochemical reactions based upon δ15N‐NO3− measured in 1 year of daily‐based bulk deposition samples in Shenyang, a megacity with distinct seasonal fossil fuel combustion in northeastern China. The mean δ15N was 0.9 ± 4.0‰ and ranged from −4.9 to 8.3‰, with the lowest and highest values observed during summer and winter, respectively. Calculated NOx photochemical equilibrium fractionation may account for up to 42% of the observed seasonal δ15N change in NO3− deposition. However, the relative NOx source contribution trends, estimated based upon a δ15N Bayesian mixing model, were insensitive to NOx photochemical fractionation considerations. Overall, NOx source partitioning based upon averaged year‐long δ15N of bulk NO3− deposition estimated the following relative trend in NOx emission sources: coal combustion > biomass burning = vehicle emissions ≫ soil emissions. Seasonally, the increase of coal combustion emissions from summer to winter drives the seasonality of δ15N in NO3− deposition, indicating a necessity to control NOx emissions from coal combustion to improve wintertime air quality.

Abstract Background Intentions-oriented approaches to measuring pregnancy do not necessarily align with how people view and approach pregnancy. Our objective was to obtain an in-depth understanding of the notions women and men hold regarding pregnancy. Methods We conducted semi-structured in-depth interviews with 176 heterosexual women and men ages 18–35, in the United States. Data were analyzed using grounded theory methodology. Results Participants described notions of getting pregnant in one of three ways. One group of participants used language that solely described pregnancy as a deliberate process, either premeditated or actively avoided. Another described pregnancy as a predetermined phenomenon, due to fate or something that ‘just happens.’ The third group represented a blending of both notions. Conclusions Our findings underscore the need to shift the current paradigm of deliberate intentions to one that recognizes that pregnancy can also be viewed as predetermined. These findings can be used to improve measurement, health services, and better direct public health resources.

Methylmercury (MeHg) biomagnifies through aquatic food webs resulting in elevated concentrations in fish globally. Stable carbon and nitrogen isotopes are frequently used to determine dietary sources of MeHg and to model its biomagnification. However, given the strong links between MeHg and sulfur cycling, we investigated whether sulfur isotopes (δ34S) would improve our understanding of MeHg concentrations ([MeHg]) in Arctic lacustrine food webs. Delta34S values and total mercury (THg) or MeHg were measured in water, sediments, and biota from six lakes near Resolute Bay, NU, Canada. In two lakes impacted by historical eutrophication, aqueous sulfate δ34S was ∼8‰ more positive than sedimentary δ34S, suggestive of bacterial sulfate reduction in the sediment. In addition, aqueous δ34S showed a significant positive relationship with aqueous [MeHg] across lakes. Within taxa across lakes, [THg] in Arctic char muscle and [MeHg] in their main prey, chironomids, were positively related to their δ34S values across lakes, but inconsistent relationships were found across entire food webs among lakes. Across lakes, nitrogen isotopes were better predictors of biotic [THg] and [MeHg] than δ34S within this dataset. Our results suggest some linkages between Hg and S biogeochemistry in high Arctic lakes, which is an important consideration given anticipated climate-mediated changes in nutrient cycling.

Abstract Background Providing unpaid support to family and friends with disabling health conditions can limit a carer’s capacity to participate in employment. The emotional support needs and unpredictability of caring for people with mental illness may be particularly demanding. While previous research suggests variable employment rates across carers for different conditions, there are limited data on mental health carers specifically. Methods This study analysed employment patterns for working-age, co-resident carers of adults with mental illness in an Australian cross-sectional household survey, the 2015 Survey of Disability, Ageing and Carers. Results Significantly more mental health carers were not employed (42.3%, 95% CI: 36.6–48.1) compared to non-carers (24.0%, 95% CI: 23.5–24.6). Employed mental health carers were more likely to work fewer than 16 h per week (carers: 17.2%, 95% CI: 12.8–22.8, vs. non-carers: 11.7%, 95% CI: 11.3–12.1) and in lower skilled occupations (carers: 22.6, 95% CI: 17.5–28.7, vs. non-carers: 15.7, 95% CI: 15.1–16.2). Among the sub-group of primary mental health carers, 25.8% (95% CI: 15.6–39.5) had reduced their working hours to care and a further 26.4% (95% CI: 17.2–38.2) stopped working altogether. In corresponding comparisons between mental health carers and carers for people with other cognitive/behavioural conditions, and physical conditions with or without secondary mental illness, there were no differences except that mental health carers were more likely to be working in a lower skilled occupation than other cognitive/behavioural condition carers (14.8% of the latter, 95% CI 10.1–21.2). Multivariate logistic regression analyses revealed that female mental health carers were less likely to be employed if they were aged 35–54, had no post-secondary education, had a disability, or cared for someone with severe activity limitations. For male mental health carers, having a disability or caring for someone with severe limitations or who did not receive paid assistance were significantly associated with not being employed. Conclusions These results highlight the employment disadvantage experienced by mental health carers compared to non-carers, and similarities in employment patterns across carers for different conditions. Improving the availability of paid support services for people with mental illness may be an important target to assist carers to maintain their own employment.

ContextStandard pregnancy intentions measures do not always align with how people approach pregnancy. Studies that have investigated beyond a binary framework found that those with "ambivalent" feelings towards pregnancy are less likely to use contraception consistently, but the reasons for this are unclear. We sought to gain a nuanced understanding of pregnancy desires, and how perceptions about pregnancy are associated with contraceptive use.MethodsWe used non-probability quota sampling based on sex, age, and geographic region for a web-based survey of heterosexual men and women, aged 21-44 years, who could become pregnant/impregnate and were not currently pregnant (n = 1,477; 51% female). The survey was created using unique items informed by recent literature. Bivariate and multivariable analyses explored relationships between various perceptions about pregnancy with pregnancy desires categorized as: wanting a pregnancy, not wanting a pregnancy, and not trying but would be okay with a pregnancy. We conducted a sub-group analysis of those who were not trying but would be okay with a pregnancy (n = 460), using descriptive statistics to examine how consistent contraceptive use was associated with emotions and beliefs about avoiding pregnancy.ResultsAfter adjustment, those who felt that pregnancy may not always be avoidable, but instead determined by fate/higher power, or a natural process that happens when it is meant to, were significantly more likely (aOR: 1.83, 95% CI: 1.05-3.36; aOR: 2.21, 95% CI: 1.29-3.76, respectively) to report not trying but being okay with pregnancy, whereas those with negative feelings about a pregnancy were less likely to feel okay about a pregnancy (aOR: 0.11, 95% CI: 0.08-0.15), versus not wanting a pregnancy. In the sub-group analysis, those who felt pregnancy was determined by fate/higher power or a natural process were more likely to report not using contraception consistently (70%, 68%, respectively).ConclusionsThose who state they are not trying but would be okay with pregnancy may not use contraception consistently because of beliefs that pregnancy is predetermined. Our findings support less categorical and more multidimensional approaches to measuring fertility intentions, with important implications for reproductive health service provision.

The stable isotopes of nitrogen in nitrate archived in polar ice have been interpreted as reflecting a shift in reactive nitrogen sources or changes in atmospheric chemical reactivity. Here, we present a novel concentration and isotopic record of nitrate (δ15N-NO3−) from a central Tibetan Plateau ice core over the last ~200 years. We find that nitrate concentration increased from 6.0 ± 2.3 μeq/L (mean ± 1σ) in the preindustrial period (prior to 1900s) to 7.3 ± 2.7 μeq/L in post-1950. Over the same time period, the δ15N-NO3− decreased from 8.7 ± 3.7‰ to 4.2 ± 3.1‰, with much larger interannual variation in δ15N-NO3− during the preindustrial period. We present a useful framework for quantifying the sensitivity of the isotopic composition of atmospheric nitrate to changes in both sources and chemistry (gas and aerosol phase). After 1950, nitrogen deposition is primarily driven by fertilizer use, leading to significant increases in concentration and decreases in δ15N-NO3−. The large interannual variability of ice core δ15N-NO3− in the preindustrial reflects natural processes, namely the El Niño Southern Oscillation (ENSO) and dust events. Our results highlight a new connection between the nitrogen cycle and ENSO, and the overprinting of natural climate signals by recent anthropogenic increases in reactive nitrogen release. Keywords: Ice core, Nitrogen stable isotope, Agriculture NOx emissions, Climate variability

BackgroundChoice of initial antiretroviral therapy regimen may help children with HIV maintain optimal, continuous therapy. We assessed treatment-naïve children for differences in time to treatment disruption across randomly-assigned protease inhibitor versus non-nucleoside reverse transcriptase inhibitor-based initial antiretroviral therapy.MethodsWe performed a secondary analysis of a multicenter phase 2/3, randomized, open-label trial in Europe, North and South America from 2002 to 2009. Children aged 31 days to ResultsThe modified intention-to-treat analysis included 263 participants. Seventy-two percent (n = 190) of participants experienced at least one treatment disruption during study. At 4 years, treatment disruption probabilities were 70% (protease inhibitor) vs. 63% (non-nucleoside reverse transcriptase inhibitor). The unadjusted hazard ratio (HR) for treatment disruptions comparing protease inhibitor vs. non-nucleoside reverse transcriptase inhibitor-based regimens was 1.19, 95% confidence interval [CI] 0.88-1.61 (adjusted HR 1.24, 95% CI 0.91-1.68). By study end, treatment disruption probabilities converged (protease inhibitor 81%, non-nucleoside reverse transcriptase inhibitor 84%) with unadjusted HR 1.11, 95% CI 0.84-1.48 (adjusted HR 1.13, 95% CI 0.84-1.50). Reported reasons for treatment disruptions suggested that participants on protease inhibitors experienced greater tolerability problems.ConclusionsChildren had similar time to treatment disruption for initial protease inhibitor and non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy, despite greater reported tolerability problems with protease inhibitor regimens. Initial pediatric antiretroviral therapy with either a protease inhibitor or non-nucleoside reverse transcriptase inhibitor may be acceptable for maintaining optimal, continuous therapy.

Abstract Carbon accumulation in tropical secondary forests may be limited in part by nitrogen (N) availability, but changes in N during tropical forest succession have rarely been quantified. We explored N cycle dynamics across a chronosequence of secondary tropical forests in the Mata Atlântica of Bahia, Brazil in order to understand how quickly the N cycle recuperates. We hypothesized that N fixation would decline over the course of succession as N availability and N gaseous losses increased. We measured N fixation, KCl-extractable N, net mineralization and nitrification, resin-strip sorbed N, gaseous N emissions and the soil δ15N in stands that were 20, 35, 50, and > 50 years old. Contrary to our initial hypothesis, we found no significant differences between stand ages in any measured variable. Our findings suggest that secondary forests in this region of the Atlantic forest reached pre-disturbance N cycling dynamics after just 20 years of succession. This result contrasts with previous study in the Amazon, where the N cycle recovered slowly after abandonment from pasture reaching pre-disturbance N cycling levels after ~50 years of succession. Our results suggest the pace of the N cycle, and perhaps tropical secondary forest, recovery, may vary regionally.