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Variation in reproductive success is the basis of evolution and allows species to respond to the environment, but only when it is based on fixed individual variation that is heritable. Several recent studies suggest that observed variation in reproduction is due to chance, not inherent individual differences. Our aim was to quantify inherent versus neutral variation in fitness of northern elephant seal ( Mirounga angustirostris (Gill, 1866)) females, including both quality and quantity of their offspring. Using 44 years of observations at Año Nuevo in California, we assembled lifetime pup production of 1065 individual females and mass at weaning for 2120 of their pups. Females varied significantly in mean lifetime mass of their pups, with 28% of the variance due to fixed individual differences among mothers. Variation was repeatable over 6 years of a mother’s lifetime and heritable ( h = 0.48). Moreover, pup mass at weaning was associated with future lifetime fitness, since larger pups had a higher chance of surviving to breed. Larger pups, however, did not produce more offspring once breeding, and lifetime pup production was not heritable. Traits related to offspring quality in elephant seals were inherently different among females, but variation in pup production was neutral.

Effective policies for adaptation to climate change require understanding how impacts are related to exposures and vulnerability, the dimensions of the climate system that will change most and where human impacts will be most draconian, and the institutions best suited to respond. Here, we propose a simple method for more credibly pairing empirical statistical damage estimates derived from recent weather and outcome observations with projected future climate changes and proposed responses. We first analyze agricultural production and loan repayment data from Brazil to understand vulnerability to historical variation in the more predictable components of temperature and rainfall (trend and seasonality) as well as to shocks (both local and over larger spatial scales). This decomposed weather variation over the past two decades explains over 50% of the yield variation in major Brazilian crops and, critically, can be constructed in the same way for future climate projections. Combining our estimates with bias-corrected downscaled climate simulations for Brazil, we find increased variation in yields and revenues (including more bad years and worse outcomes) and higher agricultural loan default at midcentury. Results in this context point to two particularly acute dimensions of vulnerability: Intensified seasonality and local idiosyncratic shocks both contribute to worsening outcomes, along with a reduced capacity for spatially correlated (covariate) shocks to ameliorate these effects through prices. These findings suggest that resilience strategies should focus on institutions such as water storage, financial services, and reinsurance.

Populations and species are threatened by human pressure, but their fate is variable. Some depleted populations, such as that of the northern elephant seal (Mirounga angustirostris), recover rapidly even when the surviving population was small. The northern elephant seal was hunted extensively and taken by collectors between the early 1800s and 1892, suffering an extreme population bottleneck as a consequence. Recovery was rapid and now there are over 200,000 individuals. We sequenced 260 modern and 8 historical northern elephant seal nuclear genomes to assess the impact of the population bottleneck on individual northern elephant seals and to better understand their recovery. Here we show that inbreeding, an increase in the frequency of alleles compromised by lost function, and allele frequency distortion, reduced the fitness of breeding males and females, as well as the performance of adult females on foraging migrations. We provide a detailed investigation of the impact of a severe bottleneck on fitness at the genomic level and report on the role of specific gene systems.

BackgroundHydrogen sulfide is a highly toxic, flammable, and colorless gas. Hydrogen sulfide has been identified as a potential terrorist chemical threat agent in mass-casualty events. Our previous studies showed that cobinamide, a vitamin B12 analog, effectively reverses the toxicity from hydrogen sulfide poisoning. In this study, we investigate the effectiveness of intratracheally administered cobinamide in treating a lethal dose hydrogen sulfide gas inhalation and compare its performance to saline control administration.MethodsA total of 53 pathogen-free New Zealand White rabbits were used for this study. Four groups were compared: (i) received no saline solution or drug intratracheally (n = 15), (ii) slow drip saline intratracheally (n = 15), (iii) fast drip saline intratracheally (n = 15), and (iv) slow drip cobinamide intratracheally (n = 8). Blood pressure was continuously monitored, and deoxy- and oxyhemoglobin concentration changes were monitored in real-time in vivo using continuous wave near-infrared spectroscopy.ResultsThe mean (± standard deviation) weight for all animals (n = 53) was 3.87 ± 0.10 kg. The survival rates of the slow cobinamide and the fast saline groups were 75 percent and 60 percent, respectively, while the survival rates in the slow saline and control groups were 26.7 percent and 20 percent, respectively. A log-rank (Mantel-Cox) test showed that survival in fast saline and slow cobinamide groups were significantly greater than those of no saline control and slow saline groups (P

Punica granatum L., commonly known as the pomegranate, is an abundant source of polyphenols, including hydrolyzable ellagitannins, ellagic acid, anthocyanins, and other bioactive phytochemicals shown to be effective in defending against oxidative stress, and has immunomodulatory activities. Ellagitannins, and their hydrolyzed product ellagic acid, interact with the gut microbiota to yield secondary metabolites known as urolithins that may have health benefits. The objective of this study was to determine the effects of supplementation with a standardized punicalagin-enriched pomegranate extract, Pomella® (250 mg), on the gut microbiome, circulating short-chain fatty acids, and gut microbial-derived ellagitannin metabolite urolithins. A randomized, double-blind, placebo-controlled study was conducted over 4 weeks on healthy volunteers aged 25-55 years. Subjects were randomly assigned to receive either an oral supplement containing 75 mg of punicalagin or an oral placebo. Stool sample collection and venipuncture were performed to analyze the gut microbiome, SCFAs, and urolithin. There was no significant change in the gut microbial diversity in both cohorts after 4 weeks of intervention, but there was a significantly increased relative abundance of Coprococcus eutectus, Roseburia faecis, Roseburia inullnivorans, Ruminococcus bicirculans, Ruminococcus calidus, and Faecalibacterium prausnitzii. Pomegranate extract (PE) supplementation led to the augmentation of circulating propionate levels (p = 0.02) and an increasing trend for acetate levels (p = 0.12). The pomegranate extract (PE) supplementation group had an increased level of circulating urolithins compared to the placebo group (6.6% vs. 1.1%, p = 0.13). PE supplementation correlated with shifts in the gut microbiome and with higher circulating levels of propionate and acetate. Further studies should explore the implications in larger cohorts and over a longer duration.

A common pitfall of many conventional heat therapy methods is the propensity to lose heat over time and the need for reheating and reapplication. Pain-relieving digital heating devices are now available that can be held in place on the body via adhesive or magnet and provide pulsed heat. However, the safety of such devices among different ages and skin types must be established. We conducted a prospective, open-label study to assess the effect of three consecutive thirty-minute treatment cycles on skin parameters and pain. Effects on mood and anxiety were secondarily assessed. 22 adult participants (20 female, 2 male; mean 58 ± 17.63 years) were recruited. The participants attended one visit with heating device intervention and a follow-up visit after 7-10 days. A 97% significant increase in transepidermal water loss was observed immediately following intervention (p = 8.04487 × 10-7), although significance was not sustained at follow-up. There was an increase along the red/green axis at 13/14 treatment locations immediately following treatment, although only four locations remained significantly increased at follow-up. Pain non-significantly decreased immediately following treatment (p = 0.057). A 38.6% decrease in subjective anxiety was observed immediately after treatment (p = 0.0139), and scores remained non-significantly reduced at follow-up (19.3% reduction from baseline; p = 0.1397). The heating devices elicit temporary changes to the skin, although the lack of significance at follow-up suggests that the devices can be safely used without long-term changes in skin color or barrier status.

Introduction: It is estimated that at least 1 million children are living with a congenital heart defect (CHD) in the U.S. Most of these patients are born with some degree of right ventricular outflow tract (RVOT) abnormalities that at some point require pulmonary valve replacement to mitigate the detrimental effects of pulmonary valve regurgitation (PVR) on the right ventricle (RV). Due to their size, available solutions, e.g., the Melody™ valve (Medtronic Inc., Minneapolis, MN) cannot be implanted in small children under 20 Kg. Those must wait until they grow to a suitable weight to receive the valve, which may lead to RV dysfunction. Hypothesis: To mitiagte the detrminental effects to the RV, the IRIS™ valve is implantable at 12 mm with a 12-Fr delivery catheter. As the valve annulus grows, the valve would be balloon expanded up to 20 mm. Methods: The IRIS™ valve has been designed according to origami concepts such that its three leaflets would retain a fully-coapted form as it is expanded to a larger size. Here we report our methods and results of implantation in 9-17Kg Yucatan pigs. Results: The IRIS™ valve is made of thin porcine pericardial leaflets sewn into a laser-cut stainless-steel stent. The stented valve is covered with an ePTFE skirt to mitigate paravalvular leak. The IRIS™ valve is fully crimped over a 12-Fr delivery catheter for transfemoral implantation. We have successfully implanted the valve at the native pulmonary valve position with minimal regurgitation in three pigs ranging from 9 to 17kg with varying pulmonary annulus sizes. Conclusions: The IRIS™ transcatheter pulmonary valve has been successfully developed according to proprietary origami concepts. Using the 12Fr delivery catheter, the smallest delivery profile reported, we successfully implanted the IRIS™ valve within the pulmonary annulus of mini pigs with encouraging results.

Abstract The purpose of this study is to examine the effect of early incomplete follow-up on overall survival among stage I lung cancer patients. Patients with clinical stage I lung cancer at our institution between 2007 and 2016 were identified (N = 1111). Exclusions included

Fuzzy Time Series (Fts) models are experiencing an increase in popularity due to their effectiveness in forecasting and modelling diverse and intricate time series data sets. Essentially these models use membership functions and fuzzy logic relation functions to produce predicted outputs through a defuzzification process. In this study, we suggested using a Second Order Type-1 fts (S-O T-1 F-T-S) forecasting model for the analysis of time series data sets. The suggested method was compared to the state-of-theart First Order Type 1 Fts method. The suggested approach demonstrated superior performance compared to the First Order Type 1 Fts method when applied to household consumption data from the Magene Regency in Indonesia, as measured by absolute percentage error rate (APER).

The United States government has indicated a desire to advance environmental justice through climate policy. As fossil fuel combustion produces both conventional pollutants and greenhouse gas (GHG) emissions, climate mitigation strategies may provide an opportunity to address historical inequities in air pollution exposure. To test the impact of climate policy implementation choices on air quality equity, we develop a broad range of GHG reduction scenarios that are each consistent with the US Paris Accord target and model the resulting air pollution changes. Using idealized decision criteria, we show that least cost and income-based emission reductions can exacerbate air pollution disparities for communities of color. With a suite of randomized experiments that facilitates exploration of a wider climate policy decision space, we show that disparities largely persist despite declines in average pollution exposure, but that reducing transportation emissions has the most potential to reduce racial inequities.

BackgroundThe COVID-19 pandemic required clinicians to care for a disease with evolving characteristics while also adhering to care changes (e.g., physical distancing practices) that might lead to diagnostic errors (DEs).ObjectiveTo determine the frequency of DEs and their causes among patients hospitalized under investigation (PUI) for COVID-19.DesignRetrospective cohort.SettingEight medical centers affiliated with the Hospital Medicine ReEngineering Network (HOMERuN).Target populationAdults hospitalized under investigation (PUI) for COVID-19 infection between February and July 2020.MeasurementsWe randomly selected up to 8 cases per site per month for review, with each case reviewed by two clinicians to determine whether a DE (defined as a missed or delayed diagnosis) occurred, and whether any diagnostic process faults took place. We used bivariable statistics to compare patients with and without DE and multivariable models to determine which process faults or patient factors were associated with DEs.ResultsTwo hundred and fifty-seven patient charts underwent review, of which 36 (14%) had a diagnostic error. Patients with and without DE were statistically similar in terms of socioeconomic factors, comorbidities, risk factors for COVID-19, and COVID-19 test turnaround time and eventual positivity. Most common diagnostic process faults contributing to DE were problems with clinical assessment, testing choices, history taking, and physical examination (all p

Extension programming can be effective at delivering nutrition education to food pantry clients. This study aimed to understand the perceptions of food pantry personnel towards nutrition education. A mixed methods survey was administered to food pantry personnel (n=53). Most (62.3%) reported their food pantry was church-affiliated, and few (22.6%) reported any Extension collaboration. Qualitative themes included perceptions that nutrition education was resource intensive, clients were not interested in nutrition education, and differing attitudes towards nutrition education. When working with food pantries, Extension should educate personnel about the importance of nutrition education, offer resources, and facilitate programming.

Tropical dry forests are highly threatened at a global scale. Long-term monitoring of remaining stands is needed to assess forest health, efficacy of management practices, and potential impacts of climate change. Using a multi-seasonal Landsat time series, we examined Normalized Difference Vegetation Index (NDVI) patterns in native dry forest, non-native vegetation types, and dry forest restoration sites from 1999 to 2022 in the Hawaiian Islands. We calculated trends in median NDVI and robust coefficient of variation of NDVI for dry and wet seasons, and used Breaks for Additive Seasonal and Trend analysis to detect trend departures. To assess the impact of regional drying trends, NDVI trends were compared to the seasonal long-term precipitation anomaly and cumulative precipitation anomaly. We found that native dry forest was less green than non-native forest, particularly during the dry season, and that median NDVI increased in both native and non-native dry forests over the study period despite negative precipitation anomaly trends. This result differs from coarser-scale studies in Hawaii, but is supported by trends in other dry forest regions. Greening was also observed in restoration study sites, especially larger sites where native species establishment and recruitment has been reported. Non-native grassland NDVI exhibited a strong positive link to precipitation anomalies, suggesting that drier climate scenarios may exacerbate the invasive grass-wildfire cycle that threatens native dry forest. These results demonstrate that Landsat time series may be used to detect seasonal variation in dry forest plots and to support restoration site monitoring in a highly fragmented ecosystem.

Current American Thoracic Society (ATS) standards promote the use of race and ethnicity-specific reference equations for pulmonary function test (PFT) interpretation. There is rising concern that the use of race and ethnicity in PFT interpretation contributes to a false view of fixed differences between races and may mask the effects of differential exposures. This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation. The ATS convened a diverse group of clinicians and investigators for a workshop in 2021 to evaluate the use of race and ethnicity in PFT interpretation. Review of evidence published since then that challenges current practice and continued discussion concluded with a recommendation to replace race and ethnicity-specific equations with race-neutral average reference equations, which must be accompanied with a broader re-evaluation of how PFTs are used to make clinical, employment, and insurance decisions. There was also a call to engage key stakeholders not represented in this workshop and a statement of caution regarding the uncertain effects and potential harms of this change. Other recommendations include continued research and education to understand the impact of the change, to improve the evidence for the use of PFTs in general, and to identify modifiable risk factors for reduced pulmonary function.

Abstract Background Semiparametric survival analysis such as the Cox proportional hazards (CPH) regression model is commonly employed in endometrial cancer (EC) study. Although this method does not need to know the baseline hazard function, it cannot estimate event time ratio (ETR) which measures relative increase or decrease in survival time. To estimate ETR, the Weibull parametric model needs to be applied. The objective of this study is to develop and evaluate the Weibull parametric model for EC patients’ survival analysis. Methods Training (n = 411) and testing (n = 80) datasets from EC patients were retrospectively collected to investigate this problem. To determine the optimal CPH model from the training dataset, a bi-level model selection with minimax concave penalty was applied to select clinical and radiomic features which were obtained from T2-weighted MRI images. After the CPH model was built, model diagnostic was carried out to evaluate the proportional hazard assumption with Schoenfeld test. Survival data were fitted into a Weibull model and hazard ratio (HR) and ETR were calculated from the model. Brier score and time-dependent area under the receiver operating characteristic curve (AUC) were compared between CPH and Weibull models. Goodness of the fit was measured with Kolmogorov-Smirnov (KS) statistic. Results Although the proportional hazard assumption holds for fitting EC survival data, the linearity of the model assumption is suspicious as there are trends in the age and cancer grade predictors. The result also showed that there was a significant relation between the EC survival data and the Weibull distribution. Finally, it showed that Weibull model has a larger AUC value than CPH model in general, and it also has smaller Brier score value for EC survival prediction using both training and testing datasets, suggesting that it is more accurate to use the Weibull model for EC survival analysis. Conclusions The Weibull parametric model for EC survival analysis allows simultaneous characterization of the treatment effect in terms of the hazard ratio and the event time ratio (ETR), which is likely to be better understood. This method can be extended to study progression free survival and disease specific survival. Trial registration ClinicalTrials.gov NCT03543215, https://clinicaltrials.gov/ , date of registration: 30th June 2017.

Abstract Background Ovarian cancer is the most lethal and endometrial cancer the most common gynaecological cancer in the UK, yet neither have a screening program in place to facilitate early disease detection. The aim is to evaluate whether online search data can be used to differentiate between individuals with malignant and benign gynaecological diagnoses. Methods This is a prospective cohort study evaluating online search data in symptomatic individuals (Google user) referred from primary care (GP) with a suspected cancer to a London Hospital (UK) between December 2020 and June 2022. Informed written consent was obtained and online search data was extracted via Google takeout and anonymised. A health filter was applied to extract health-related terms for 24 months prior to GP referral. A predictive model (outcome: malignancy) was developed using (1) search queries (terms model) and (2) categorised search queries (categories model). Area under the ROC curve (AUC) was used to evaluate model performance. 844 women were approached, 652 were eligible to participate and 392 were recruited. Of those recruited, 108 did not complete enrollment, 12 withdrew and 37 were excluded as they did not track Google searches or had an empty search history, leaving a cohort of 235. Results The cohort had a median age of 53 years old (range 20–81) and a malignancy rate of 26.0%. There was a difference in online search data between those with a benign and malignant diagnosis, noted as early as 360 days in advance of GP referral, when search queries were used directly, but only 60 days in advance, when queries were divided into health categories. A model using online search data from patients (n = 153) who performed health-related search and corrected for sample size, achieved its highest sample-corrected AUC of 0.82, 60 days prior to GP referral. Conclusions Online search data appears to be different between individuals with malignant and benign gynaecological conditions, with a signal observed in advance of GP referral date. Online search data needs to be evaluated in a larger dataset to determine its value as an early disease detection tool and whether its use leads to improved clinical outcomes.

Probiotic supplementation has been shown to modulate the gut-skin axis. The goal of this study was to investigate whether oral spore-based probiotic ingestion modulates the gut microbiome, plasma short-chain fatty acids (SCFAs), and skin biophysical properties. This was a single-blinded, 8-week study (NCT03605108) in which 25 participants, 7 with noncystic acne, were assigned to take placebo capsules for the first 4 weeks, followed by 4 weeks of probiotic supplementation. Blood and stool collection, facial photography, sebum production, transepidermal water loss (TEWL), skin hydration measurements, and acne assessments were performed at baseline, 4, and 8 weeks. Probiotic supplementation resulted in a decreasing trend for the facial sebum excretion rate and increased TEWL overall. Subanalysis of the participants with acne showed improvement in total, noninflammatory, and inflammatory lesion counts, along with improvements in markers of gut permeability. The gut microbiome of the nonacne population had an increase in the relative abundance of Akkermansia, while the subpopulation of those with acne had an increase in the relative abundance of Lachnospiraceae and Ruminococcus gnavus. Probiotic supplementation augmented the circulating acetate/propionate ratio. There is preliminary evidence for the use of spore-based probiotic supplementation to shift the gut microbiome and augment short-chain fatty acids in those with and without acne. Further spore-based supplementation studies in those with noncystic acne are warranted.

Acne vulgaris is a common inflammatory condition that can be associated with profound psychosocial impacts. Conventional treatment includes topical retinoids, benzoyl peroxide, and antimicrobials, and some may cause irritation and skin dryness. In this 8-week open-label study, we examined the effects of a botanical skin care regimen (Codex Labs Shaant Balancing regimen) on mild to moderate facial and truncal acne. Twenty-four male and female subjects between the ages of 12 and 45 years were assessed for eligibility, 20 were enrolled, and 15 completed all study visits. Facial and truncal acne lesion counts, skin hydration, sebum excretion rate, and mood were assessed at baseline, week 4, and week 8. Total facial lesion counts (inflammatory and non-inflammatory lesions) decreased by 20.5% at week 4 (p = 0.06) and by 25.2% at week 8 (p < 0.05). Inflammatory lesion counts on the trunk were found to decrease at week 8 relative to baseline by 48% (p < 0.05). Forehead sebum excretion rate decreased by 40% at week 4 (p = 0.07) and 22% at week 8 (p = 0.08), and cheek skin hydration increased by 27.6% at week 4 (p = 0.14) and 65% at week 8 (p = 0.10). Participants also experienced significant improvement in components of a positive effect, such as feeling "strong" and "inspired", and a decrease in negative effects, such as feeling "irritable." Overall, the botanical skin care regimen was found to be well-tolerated. Our study suggests that a botanical skin care regimen may reduce facial and truncal acne lesion counts, increase skin hydration, reduce sebum production, and augment positive effects and moods in those with mild to moderate facial and truncal acne.

Terminalia chebula (TC) is a medicinal plant that exhibits antioxidant, anti-inflammatory, and antibacterial properties and that is widely used in Ayurveda and herbal formulations. However, the skin effects of TC as an oral supplement have not been studied. The objective of this study is to determine if oral TC fruit extract supplementation can modulate the skin's sebum production and reduce the appearance of wrinkles. A prospective double-blind placebo-controlled study was conducted on healthy females aged 25-65. Subjects were supplemented with an oral placebo or Terminalia chebula (250 mg capsule, Synastol TC) capsules twice daily for eight weeks. A facial image collection and analysis system was used to assess the facial appearance of wrinkle severity. Standardized, non-invasive tools were used to measure facial moisture, sebum production, transepidermal water loss, melanin index and erythema index. For those who had a baseline sebum excretion rate >80 ug/cm2, TC supplementation produced a significant decrease in forehead sebum excretion rate compared to the placebo at four weeks (-17 decrease vs. 20% increase, p = 0.07) and at eight weeks (-33% decrease vs. 29% increase, p < 0.01). Cheek erythema decreased by 2.2% at eight weeks, while the placebo treatment increased cheek erythema by 1.5% (p < 0.05). Facial wrinkles decreased by 4.3% in the TC group and increased by 3.9% in the placebo group after eight weeks of supplementation (p < 0.05). TC supplementation reduces facial sebum and improves the appearance of wrinkles. Future studies should consider evaluating oral TC as adjuvant therapy for acne vulgaris.

Terminalia chebula (TC) is an Ayurvedic herb containing polyphenolic compounds that interact with gut microbiota to modulate bioactivity. To examine how TC supplementation modulates the gut microbiome and associated metabolic pathways, a double-blind, randomized, placebo-controlled study that screened 58 and enrolled 43 females aged 25–55 with a BMI of 25–35 kg/m2 and HbA1C between 5.5–7. Subjects were randomized to standardized preparation of TC (250 mg, Synastol® TC) capsules or oral placebo twice daily for 8 weeks. Stool sample collections and venipuncture were performed. Α-diversity of the gut microbiome increased in the TC group at week 8 versus placebo (p

BackgroundPhysicians and patient-facing caregivers have increasingly used mobile health (mHealth) technologies in the past several years, accelerating during the COVID-19 pandemic. However, barriers and feedback surrounding adoption remain relatively understudied and varied across health systems, particularly in rural areas. ObjectiveThis study aims to identify provider adoption, attitudes, and barriers toward mHealth in a large, multisite, rural US health care system. We investigated (1) mHealth apps that providers use for their own benefit and (2) mHealth apps that a provider uses in conjunction with a patient. MethodsWe surveyed all patient-seeing providers within the Marshfield Clinic Health System with a brief, 16-item, web-based survey assessing attitudes toward mHealth, adoption of these technologies, and perceived barriers faced by providers, their peers, and the institution. Survey results were summarized via descriptive statistics, with log-binomial regression and accompanying pairwise analyses, using Kruskal-Wallis and Jonckheere-Terpstra tests for significance, respectively. Respondents were grouped by reported clinical role and specialty. ResultsWe received a 38% (n/N=916/2410) response rate, with 60.7% (n=556) of those sufficiently complete for analyses. Roughly 54.1% (n=301) of respondents reported mHealth use, primarily around decision-making and supplemental information, with use differing based on provider role and years of experience. Self-reported barriers to using mHealth included a lack of knowledge and time to study mHealth technologies. Providers also reported concerns about patients’ internet access and the complexity of mHealth apps to adequately use mHealth technologies. Providers believed the health system’s barriers were largely privacy, confidentiality, and legal review concerns. ConclusionsThese findings echo similar studies in other health systems, surrounding providers’ lack of time and concerns over privacy and confidentiality of patient data. Providers emphasized concerns over the complexity of these technologies for their patients and concerns over patients’ internet access to fully use mHealth in their delivery of care.

Introduction Physicians can be unaware that many US adults have intermediate or lower health literacy. Avoiding medical jargon in patient communication can improve poor outcomes associated with lower health literacy, but physicians may struggle to do so as health literacy education is neither standardized nor universal at US allopathic medical schools. As with other skills-based proficiencies in medical education, repeat exposure and active learning help build competency. Medical students developed the Patient Communication Challenge (PCC), an adaptation of the Hasbro game Taboo, to facilitate practice of patient-centered communication skills among medical trainees. Methods Hour-long workshops were held for groups of preclinical medical students. Students watched a communication exemplar video, played the PCC game, and completed a postworkshop survey. To play, two teams competed to earn points by identifying medical concepts as explained by a teammate who described the term without using medical jargon. Results Evaluations indicated that the game was enjoyable and reinforced didactic concepts through active learning, with self-reported participant satisfaction and competency gain. Overall, 59% of participants (53 of 90) completed postworkshop surveys; 91% (48 of 53) agreed they felt more proficient in avoiding jargon, 94% (50 of 53) would recommend the workshop to a classmate, and 100% (53 of 53) would play again. Discussion The PCC can help early medical trainees develop health communication skills through gamification with utilization of adult learning principles and adequate frequency for skill retention. Future applications include longitudinal assessment and expanding to later stages of medical training and other health professions.

Cumulative exposure to low-density lipoprotein cholesterol (LDL-C) is a key driver of atherosclerotic cardiovascular disease (ASCVD) risk. An armamentarium of therapies to achieve robust and sustained reduction in LDL-C can reduce ASCVD risk. The gold standard for LDL-C assessment is ultracentrifugation but in routine clinical practice LDL-C is usually calculated and the most accurate calculation is the Martin/Hopkins equation. For primary prevention, consideration of estimated ASCVD risk frames decision making regarding use of statins and other therapies, and tools such as risk enhancing factors and coronary artery calcium enable tailoring of risk assessment and decision making. In patients with diabetes, lipid lowering therapy is recommended in most patients to reduce ASCVD risk with an opportunity to tailor therapy based on other risk factors. Patients with primary hypercholesterolemia and familial hypercholesterolemia (FH) with baseline LDL-C greater than or equal to 190 mg/dL are at elevated risk, and LDL-C lowering with high-intensity statin therapy is often combined with non-statin therapies to prevent ASCVD. Secondary prevention of ASCVD, including in patients with prior myocardial infarction or stroke, requires intensive lipid lowering therapy and lifestyle modification approaches. There is no established LDL-C level below which benefit ceases or safety concerns arise. When further LDL-C lowering is required beyond lifestyle modifications and statin therapy, additional medications include oral ezetimibe and bempedoic acid, or injectables such as PCSK9 monoclonal antibodies or siRNA therapy. A novel agent that acts independently of hepatic LDL receptors is evinacumab, which is approved for patients with homozygous FH. Other emerging agents are targeted at Lp(a) and CETP. In light of the expanding lipid treatment landscape, this manuscript reviews the importance of early, intensive, and sustained LDL-C-lowering for primary and secondary prevention of ASCVD.

The magnitude and distribution of physical and societal impacts from long-lived greenhouse gases are insensitive to the emission source location; the same is not true for major coemitted short-lived pollutants such as aerosols. Here, we combine novel global climate model simulations with established response functions to show that a given aerosol emission from different regions produces divergent air quality and climate changes and associated human system impacts, both locally and globally. The marginal global damages to infant mortality, crop productivity, and economic growth from aerosol emissions and their climate effects differ by more than an order of magnitude depending on source region, with certain regions creating global external climate changes and impacts much larger than those felt locally. The complex distributions of aerosol-driven societal impacts emerge from geographically distinct and region-specific aerosol-climate interactions, estimation of which is enabled by the full Earth System Modeling Framework used here.

Maritime forests are coastal ecosystems that stabilize coastlines, recharge aquifers, and provide protection against storm surges. The range of these forests has been decreasing due to threats such as urban expansion, clearing for agriculture, climate change, and an influx of native but competitive loblolly pine (Pinus taeda L.) from pine plantations. To restore maritime forests, southern live oak (Quercus virginiana Mill.) should be established as the dominant canopy species; however, knowledge of how to grow live oak in a restoration setting is limited. We planted southern live oak seedlings into a clearcut experimental site that was formerly a loblolly pine plantation. Our goal was to test how planting density (1, 2, or 3 m), mulch, and fertilization at planting impacted the initial growth of seedlings over the course of four growing seasons. The application of fertilizer had an initial positive effect on seedling diameter (36%) after the first growing season. The application of mulch increased seedling height in years 2 through 4 (25.6% to 22.7%), diameter in years 3 and 4 (20.9% to 19.3%), and crown width in year four (8.5%). Planting density had no consistent effect over the first four years. These results demonstrate the potential benefits of incorporating fertilizer and mulch into restoration prescriptions to promote seedling field establishment. Planting density should continue to be monitored through canopy closure for potential effects of plant facilitation. Integrating silvicultural treatments such as planting density, soil amendments, and vegetation control may inform cost-effective management recommendations for maritime forest restoration.

Nitrogen oxides (NOx) are among the most widely emitted pollutants in the world, yet their impacts on agriculture remain poorly known. NOx can directly damage crop cells and indirectly affect growth by promoting ozone (O3) and aerosol formation. We use satellite measures of both crop greenness and NOx during 2018-2020 to evaluate crop impacts for five major agricultural regions. We find consistent negative associations between NO2 and greenness across regions and seasons. These effects are strongest in conditions where O3 formation is NOx limited but remain significant even in locations where this pathway is muted, suggesting a role for direct NOx damage. Using simple counterfactuals and leveraging published relationships between greenness and growth, we estimate that reducing NOx levels to the current fifth percentile in each region would raise yields by ~25% for winter crops in China, ~15% for summer crops in China, and up to 10% in other regions.

Summary: Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Funding: Wellcome Trust.

ContextMethyl mercaptan (CH3SH) is a colorless, toxic gas with potential for occupational exposure and used as a weapon of mass destruction. Inhalation at high concentrations can result in dyspnea, hypoventilation, seizures, and death. No specific methyl mercaptan antidote exists, highlighting a critical need for such an agent. Here, we investigated the mechanism of CH3SH toxicity, and rescue from CH3SH poisoning by the vitamin B12 analog cobinamide, in mammalian cells. We also developed lethal CH3SH inhalation models in mice and rabbits, and tested the efficacy of intramuscular injection of cobinamide as a CH3SH antidote.ResultsWe found that cobinamide binds to CH3SH (Kd = 84 µM), and improved growth of cells exposed to CH3SH. CH3SH reduced cellular oxygen consumption and intracellular ATP content and activated the stress protein c-Jun N-terminal kinase (JNK); cobinamide reversed these changes. A single intramuscular injection of cobinamide (20 mg/kg) rescued 6 of 6 mice exposed to a lethal dose of CH3SH gas, while all six saline-treated mice died (p = 0.0013). In rabbits exposed to CH3SH gas, 11 of 12 animals (92%) treated with two intramuscular injections of cobinamide (50 mg/kg each) survived, while only 2 of 12 animals (17%) treated with saline survived (p = 0.001).ConclusionWe conclude that cobinamide could potentially serve as a CH3SH antidote.

BackgroundThe objective of this 3-arm randomized controlled trial was to evaluate the efficacy of computerized cognitive training (CCT) in improving primary outcomes of delayed-recall memory and serum brain-derived neurotrophic factor (BDNF) levels; and the secondary outcomes were working memory, instrumental activities of daily living (IADLs) and health-related quality of life (HRQL) in patients with heart failure (HF).Methods and resultsPatients (n = 256) were randomly assigned to 8 weeks of CCT using BrainHQ, computerized crossword puzzles active control intervention, and usual care. All patients received weekly nurse-enhancement interventions. Data were collected at enrollment and baseline visits and at 10 weeks and 4 and 8 months. In mixed effects models, there were no statistically significant group or group-by-time differences in outcomes. There were statistically significant differences over time in all outcomes in all groups. Patients improved over time on measures of delayed-recall memory, working memory, IADLs, and HRQL and had decreased serum BDNF.ConclusionsCCT did not improve outcomes compared with the active control intervention and usual care. Nurse-enhancement interventions may have led to improved outcomes over time. Future studies are needed to test nurse-enhancement interventions in combination with other cognitive interventions to improve memory in persons with HF.

Abstract Epidemiological studies have reported a strong association between circulating Klotho and physical function; however, the cohorts were comprised of older adults with multiple comorbidities. Herein, we examined the relationship between Klotho and physical function in a community-based cohort of healthy adults. In this cross-sectional study, serum Klotho was measured in 80 adults who visited the Musculoskeletal Function, Imaging, and Tissue Resource Core of the Indiana Center for Musculoskeletal Health. Participants (n = 20, 10 [50%] men per group) were chosen into four age groups: 20–34, 35–49, 50–64, and ≥ 65 years, and were further grouped based on performance (low vs. high) on grip strength and chair stand tests. Klotho levels were lower in the ≥ 65 years group (703.0 [189.3] pg/mL; p = 0.022) and the 50–64 years group (722.6 [190.5] pg/mL; p = 0.045) compared to 20–34 years (916.1 [284.8] pg/mL). No differences were observed in Klotho between the low and high performers. The ≥ 65 years group walked a shorter distance during the 6-min walk test (6MWT) compared to 20–34 years (p = 0.005). Klotho was correlated with age (p

(1) Background: The pomegranate fruit (Punica granatum L.) has been widely used in traditional medicine and has increasingly gained popularity among consumers in order to manage different facets of health. The objective of this study was to evaluate the effects of the fruit extract of P. granatum L. on different parameters of skin health. (2) Methods: A prospective, double-blind placebo-controlled study was conducted on both healthy males and females aged 25−55 years. Subjects were supplemented with a standardized punicalagin enriched oral pomegranate extract [Pomella® (Verdure Science, Noblesville, IN, USA), PE group] or a placebo (control group) daily for four weeks. Changes in wrinkle severity, facial biophysical properties, skin microbiome, and the gut microbiome were assessed. (3) Results: The PE group had significant reductions in wrinkle severity (p < 0.01) and a decreasing trend in the forehead sebum excretion rate (p = 0.14). The participants in the PE group with a higher relative abundance of Eggerthellaceae in the gut had a decrease in their facial TEWL (p < 0.05) and wrinkle severity (p = 0.058). PE supplementation led to an increase in the Staphylococcus epidermidis species and the Bacillus genus on the skin. (4) Conclusions: Overall, the study demonstrated improvements in several biophysical properties, wrinkles, and shifts in the skin microbiome with oral PE supplementation in healthy subjects.

External and internal stressors have been found to adversely affect skin health and overall wellness. There is growing interest in the use of anti-inflammatory and antioxidant plant-derived ingredients, such as ashwagandha, saffron, l-theanine, and tocopherol, to mitigate the impact of these stressors. In this study, we evaluate the effectiveness of oral and topical products (InnerCalm and SuperCalm, respectively) that contain naturally derived ingredients on skin redness, skin pigmentation, sleep, and mood in healthy females with Fitzpatrick skin type 1−4 and self-perceived sensitive skin. Subjects were randomized to an oral (oral group), a topical (topical group), or a combination of both the oral and topical interventions (combined group). Standardized photography-based image analysis was used to assess skin redness and pigment. Self-assessments of mood and sleep were measured with the abbreviated profile of mood states (POMS) questionnaire, and the Pittsburgh sleep-quality index (PSQI), respectively. Assessments were made at the baseline, 1-week, 4-weeks, and 8-weeks of the intervention. The average facial redness decreased in the topical group at 8-weeks (p < 0.001) and in the combined group at 4-weeks (p < 0.05) and 8-weeks (p < 0.001), relative to the baseline. The average facial pigmentation decreased in the oral (p < 0.05) and combined (p < 0.05) cohorts at 8-weeks, relative to the baseline. The oral group exhibited an improvement in sleep quality at 1-week relative to the baseline (p < 0.05) and at 8-weeks relative to the baseline (p < 0.05). Finally, the combined group demonstrated improvement in fatigue (p < 0.01) and confusion (p < 0.05) at 8-weeks relative to the baseline, though total mood disturbance increased in all 3 groups over the course of the study. Measured outcomes relating to mood may be confounded with the timing of the study, which ran during the COVID pandemic. Overall, we demonstrate the role of oral and topical herbs and of nutraceuticals for skin health and wellness. Further research will be needed to elucidate synergistic effects in oral and topical combination regimens.

Abstract. Irrigation has important implications for sustaining global food production by enabling crop water demand to be met even under dry conditions.Added water also cools crop plants through transpiration; irrigation mightthus play an important role in a warmer climate by simultaneously moderating water and high temperature stresses. Here we used satellite-derived evapotranspiration estimates, land surface temperature (LST) measurements, and crop phenological stage information from Nebraska maize to quantify how irrigation relieves both water and temperature stresses. Unlike air temperature metrics, satellite-derived LST revealed a significant irrigation-induced cooling effect, especially during the grain filling period (GFP) of crop growth. This cooling appeared to extend the maize growing season, especially for GFP, likely due to the stronger temperature sensitivity of phenological development during this stage. Our analysis also revealed that irrigation not only reduced water and temperature stress but also weakened the response of yield to these stresses. Specifically, temperature stress was significantly weakened for reproductive processes in irrigated maize. Attribution analysis further suggested that water and high temperature stress alleviation was responsible for 65±10 % and 35±5.3 % of the irrigation yield benefit, respectively. Our study underlines the relative importance of high temperature stress alleviation in yield improvement and the necessity of simulating crop surface temperature to better quantify heat stress effects in crop yield models. Finally, considering the potentially strong interaction between water and heat stress, future research on irrigation benefits should explore the interaction effects between heat and drought alleviation.

BACKGROUND: The greatest burden of chronic respiratory disease is in low- and middle-income countries, with recent population-based studies reporting substantial levels of obstructive and restrictive lung function.OBJECTIVE: To characterise the common chronic respiratory diseases encountered in hospital outpatient clinics in three African countries.METHODS This was a cross-sectional study of consecutive adult patients with chronic respiratory symptoms (>8 weeks) attending hospital outpatient departments in Ethiopia, Kenya and Sudan. Patients were assessed using a respiratory questionnaire, spirometry and chest radiography. The diagnoses of the reviewing clinicians were ascertained.RESULT: A total of 519 patients (209 Kenya, 170 Ethiopia, 140 Sudan) participated; the mean age was 45.2 years (SD 16.2); 53% were women, 83% had never smoked. Reviewing clinicians considered that 36% (95% CI 32-40) of patients had asthma, 25% (95% CI 21-29) had chronic bronchitis, 8% (95% CI 6-11) chronic obstructive pulmonary disease (COPD), 5% (95% CI 4-8) bronchiectasis and 4% (95% CI 3-6) post-TB lung disease. Spirometry consistent with COPD was present in 35% (95% CI 30-39). Restriction was evident in 38% (95% CI 33-43). There was evidence of sub-optimal diagnosis of asthma and COPD.CONCLUSION: In Ethiopia, Kenya and Sudan, asthma, COPD and chronic bronchitis account for the majority of diagnoses in non-TB patients with chronic respiratory symptoms. The suboptimal diagnosis of these conditions will require the widespread use of spirometry.

Our aim was to develop a method for estimating the number of animals using a single site in an asynchronous species, meaning that not all animals are present at once so that no one count captures the entire population. This is a common problem in seasonal breeders, and in northern elephant seals, we have a model for quantifying asynchrony at the Año Nuevo colony. Here we test the model at several additional colonies having many years of observations and demonstrate how it can account for animals not present on any one day. This leads to correction factors that yield total population from any single count throughout a season. At seven colonies in California for which we had many years of counts of northern elephant seals, we found that female arrival date varied < 2 days between years within sites and by < 5 days between sites. As a result, the correction factor for any one day was consistent, and at each colony, multiplying a female count between 26 and 30 Jan by 1.15 yielded an estimate of total population size that minimized error. This provides a method for estimating the female population size at colonies not yet studied. Our method can produce population estimates with minimal expenditure of time and resources and will be applicable to many seasonal species with asynchronous breeding phenology, particularly colonial birds and other pinnipeds. In elephant seals, it will facilitate monitoring the population over its entire range.

BackgroundIn Sub-Saharan Africa cross-sectional studies report a high prevalence of abnormal lung function indicative of chronic respiratory disease. The natural history and health impact of this abnormal lung function in low-and middle-income countries is largely unknown.MethodsA cohort of 1481 adults representative of rural Chikwawa in Malawi were recruited in 2014 and followed-up in 2019. Respiratory symptoms and health-related quality of life (HRQoL) were quantified. Lung function was measured by spirometry.Findings1232 (83%) adults participated; spirometry was available for 1082 (73%). Mean (SD) age 49.5 (17.0) years, 278(23%) had ever smoked, and 724 (59%) were women. Forced expiratory volume in one second (FEV1) declined by 53.4 ml/year (95% CI: 49.0, 57.8) and forced vital capacity (FVC) by 45.2 ml/year (95% CI: 39.2, 50.5) . Chronic airflow obstruction increased from 9.5% (7.6, 11.6%) in 2014 to 17.5% (15.3, 19.9%) in 2019. There was no change in diagnosed asthma or in spirometry consistent with asthma or restriction. Rate of FEV1 decline was not associated with diagnosed Chronic obstructive pulmonary disease (COPD), asthma, or spirometry consistent with asthma, COPD, or restriction. HRQoL was adversely associated with respiratory symptoms (dyspnoea, wheeze, cough), previous tuberculosis, declining FEV1 and spirometry consistent with asthma or restriction. These differences exceeded the minimally important difference.InterpretationIn this cohort, the increasing prevalence of COPD is associated with the high rate of FEV1 decline and lung function deficits present before recruitment. Respiratory symptoms and sub-optimal lung function are independently associated with reduced HRQoL.