Racial Disparities in Surgical Management For Early-Stage Laryngeal Squamous Cell Carcinoma and Recurrent Dysplasia.

Objective: The aim of this study is to evaluate the association between race and the treatment of laryngeal dysplasia and early-stage laryngeal squamous cell carcinoma (LSCC). Study design: Retrospective Cohort Study. Setting: Large multispecialty academic medical center. Methods: Patients were treated for laryngeal dysplasia or LSCC between September 2019 and September 2022. A retrospective chart review was conducted to collect demographic and clinical information. Two-sample t tests, chi-square tests, and linear regression models were used to compare characteristics (α = 0.05). Analyses were performed in STATA 17. Results: Sixty-five patients were identified that underwent potassium titanyl phosphate (KTP) transoral laser microsurgery for management of early-stage LSCC (n = 29) or dysplasia (n = 36). The cohort consisted of 23 Black and 42 White patients. No significant difference was found in age, alcohol or tobacco use, rate of adjuvant radiotherapy, stage of disease, nor insurance status between the 2 groups. White patients underwent more procedures to address initial disease and subsequent recurrent dysplasia on average than Black patients (2.52 vs 1.52, P = .02). This remained true after adjusting for demographic and clinical characteristics and insurance status in a linear regression model. While Black patients were more likely to be lost to follow-up than White patients (30.4% vs 9.5%, P = .03), the average number of procedures between the groups still differed significantly (2.63 vs 1.56, P = .04) when controlling for those lost to follow-up. Conclusion: The findings presented here highlight potential inequities that exist for racial minorities at early stages of treatment and in addressing premalignant conditions, which may contribute to the known downstream disparities in laryngeal cancer outcomes.

Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials.

Chronic low-degree inflammation is a hallmark of atherosclerotic cardiovascular (CV) disease. To assess the effect of lipid-lowering therapies on C-reactive protein (CRP), a biomarker of inflammation, we conducted a meta-analysis according to the PRISMA guidelines. Databases were searched from inception to July 2023. Inclusion criteria were: (i) randomized controlled trials (RCTs) in human, Phase II, III, or IV; (ii) English language; (iii) comparing the effect of lipid-lowering drugs vs. placebo; (iv) reporting the effects on CRP levels; (v) with intervention duration of more than 3 weeks; (vi) and sample size (for both intervention and control group) over than 100 subjects. The between-group (treatment-placebo) CRP absolute mean differences and 95% confidence intervals were calculated for each drug class separately. A total of 171 668 subjects from 53 RCTs were included. CRP levels (mg/L) were significantly decreased by statins [-0.65 (-0.87 to -0.43), bempedoic acid; -0.43 (-0.67 to -0.20), ezetimibe; -0.28 (-0.48 to -0.08)], and omega-3 fatty acids [omega3FAs, -0.27 (-0.52 to -0.01)]. CRP was reduced by -0.40 (-1.17 to 0.38) with fibrates, although not statistically significant. A slight increase of CRP concentration was observed for proprotein convertase subtilisin/kexin type 9 inhibitors [0.11 (0.07-0.14)] and cholesteryl-ester transfer protein inhibitors [0.10 (0.00-0.21)], the latter being not statistically significant. Meta-regression analysis did not show a significant correlation between changes in CRP and LDL cholesterol (LDL-C) or triglycerides. Statins, bempedoic acid, ezetimibe, and omega3FAs significantly reduce serum CRP concentration, independently of LDL-C reductions. The impact of this anti-inflammatory effect in terms of CV prevention needs further investigation.

Supplementation with antioxidant micronutrients in pregnant women with obesity: a randomized controlled trial.

BACKGROUND/OBJECTIVE: Obesity increases maternal morbidity and adversely affects child health. Maternal inflammation may play a role in adverse outcomes. The objective of this study was to determine whether providing a higher dose of antioxidant micronutrients to pregnant women with obesity would raise concentrations of key antioxidant vitamins and impact inflammation and oxidative stress during pregnancy. SUBJECTS/METHODS: This was a double-blind, randomized controlled trial. We recruited pregnant women with a body mass index (BMI) ≥ 30 kg/m2 at their initial prenatal visit ( < 13 weeks gestation) and collected blood and urine samples at baseline, 24-28 weeks, and 32-36 weeks to measure micronutrient concentrations (vitamin C, E, B6 and folate), markers of inflammation (C-reactive protein, interleukin-6, 8, and 1ß) and oxidative stress (8-epi-PGF2α and malondialdehyde). We collected maternal and infant health data from enrollment to delivery as secondary outcomes. We enrolled 128 participants (64 in each arm), and 98 (49 in each arm) completed follow-up through delivery. INTERVENTION: Both groups received a standard prenatal vitamin containing the recommended daily allowance of micronutrients in pregnancy. In addition, the intervention group received a supplement with 90 mg vitamin C, 30 αTU vitamin E, 18 mg vitamin B6, and 800 µg folic acid, and the control group received a placebo. RESULTS: The intervention group had higher vit B6 (log transformed (ln), ß 24-28 weeks: 0.76 nmol/L (95% CI: 0.40, 1.12); ß 32-36 weeks: 0.52 nmol/L (95% CI: 0.17, 0.88)) than the control group. Vitamins C, E, erythrocyte RBC folate concentrations did not differ by randomization group. The intervention did not impact biomarkers of inflammation or oxidative stress. There were no differences in maternal or neonatal clinical outcomes by randomization group. CONCLUSIONS: Higher concentrations of antioxidant vitamins during pregnancy increased specific micronutrients and did not impact maternal inflammation and oxidative stress, which may be related to dosing or type of supplementation provided. CLINICAL TRIAL REGISTRATION: Clinical Trial Identification Number: NCT02802566; URL of the Registration Site: www. CLINICALTRIALS: gov .

Effects of a liquefied petroleum gas stove intervention on stillbirth, congenital anomalies and neonatal mortality: A multi-country household air pollution intervention network trial.

Household air pollution (HAP) from cooking with solid fuels used during pregnancy has been associated with adverse pregnancy outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial that assessed the impact of a liquefied petroleum gas (LPG) stove and fuel intervention on health in Guatemala, India, Peru, and Rwanda. Here we investigated the effects of the LPG stove and fuel intervention on stillbirth, congenital anomalies and neonatal mortality and characterized exposure-response relationships between personal exposures to fine particulate matter (PM2.5), black carbon (BC) and carbon monoxide (CO) and these outcomes. Pregnant women (18 to <35 years of age; gestation confirmed by ultrasound at 9 to <20 weeks) were randomly assigned to intervention or control arms. We monitored these fetal and neonatal outcomes and personal exposure to PM2.5, BC and CO three times during pregnancy, we conducted intention-to-treat (ITT) and exposure-response (E-R) analyses to determine if the HAPIN intervention and corresponding HAP exposure was associated with the risk of fetal/neonatal outcomes. A total of 3200 women (mean age 25.4 ± 4.4 years, mean gestational age at randomization 15.4 ± 3.1 weeks) were included in this analysis. Relative risks for stillbirth, congenital anomaly and neonatal mortality were 0.99 (0.60, 1.66), 0.92 (95 % CI 0.52, 1.61), and 0.99 (0.54, 1.85), respectively, among women in the intervention arm compared to controls in an ITT analysis. Higher mean personal exposures to PM2.5, CO and BC during pregnancy were associated with a higher, but statistically non-significant, incidence of adverse outcomes. The LPG stove and fuel intervention did not reduce the risk of these outcomes nor did we find evidence supporting an association between personal exposures to HAP and stillbirth, congenital anomalies and neonatal mortality.

Effects of Cooking with Liquefied Petroleum Gas or Biomass on Stunting in Infants.

BACKGROUND: Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown. METHODS: We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks' gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length of each infant was measured at 12 months of age, and personal exposures to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm) were monitored starting at pregnancy and continuing until the infants were 1 year of age. The primary outcome for which data are presented in the current report - stunting (defined as a length-for-age z score that was more than two standard deviations below the median of a growth standard) at 12 months of age - was one of four primary outcomes of the trial. Intention-to-treat analyses were performed to estimate the relative risk of stunting. RESULTS: Adherence to the intervention was high, and the intervention resulted in lower prenatal and postnatal 24-hour personal exposures to fine particulate matter than the control (mean prenatal exposure, 35.0 µg per cubic meter vs. 103.3 µg per cubic meter; mean postnatal exposure, 37.9 µg per cubic meter vs. 109.2 µg per cubic meter). Among 3061 live births, 1171 (76.2%) of the 1536 infants born to women in the intervention group and 1186 (77.8%) of the 1525 infants born to women in the control group had a valid length measurement at 12 months of age. Stunting occurred in 321 of the 1171 infants included in the analysis (27.4%) of the infants born to women in the intervention group and in 299 of the 1186 infants included in the analysis (25.2%) of those born to women in the control group (relative risk, 1.10; 98.75% confidence interval, 0.94 to 1.29; P = 0.12). CONCLUSIONS: An intervention strategy starting in pregnancy and aimed at mitigating household air pollution by replacing biomass fuel with LPG for cooking did not reduce the risk of stunting in infants. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Liquefied Petroleum Gas or Biomass Cooking and Severe Infant Pneumonia.

BACKGROUND: Exposure to household air pollution is a risk factor for severe pneumonia. The effect of replacing biomass cookstoves with liquefied petroleum gas (LPG) cookstoves on the incidence of severe infant pneumonia is uncertain. METHODS: We conducted a randomized, controlled trial involving pregnant women 18 to 34 years of age and between 9 to less than 20 weeks' gestation in India, Guatemala, Peru, and Rwanda from May 2018 through September 2021. The women were assigned to cook with unvented LPG stoves and fuel (intervention group) or to continue cooking with biomass fuel (control group). In each trial group, we monitored adherence to the use of the assigned cookstove and measured 24-hour personal exposure to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm [PM2.5]) in the women and their offspring. The trial had four primary outcomes; the primary outcome for which data are presented in the current report was severe pneumonia in the first year of life, as identified through facility surveillance or on verbal autopsy. RESULTS: Among 3200 pregnant women who had undergone randomization, 3195 remained eligible and gave birth to 3061 infants (1536 in the intervention group and 1525 in the control group). High uptake of the intervention led to a reduction in personal exposure to PM2.5 among the children, with a median exposure of 24.2 µg per cubic meter (interquartile range, 17.8 to 36.4) in the intervention group and 66.0 µg per cubic meter (interquartile range, 35.2 to 132.0) in the control group. A total of 175 episodes of severe pneumonia were identified during the first year of life, with an incidence of 5.67 cases per 100 child-years (95% confidence interval [CI], 4.55 to 7.07) in the intervention group and 6.06 cases per 100 child-years (95% CI, 4.81 to 7.62) in the control group (incidence rate ratio, 0.96; 98.75% CI, 0.64 to 1.44; P = 0.81). No severe adverse events were reported to be associated with the intervention, as determined by the trial investigators. CONCLUSIONS: The incidence of severe pneumonia among infants did not differ significantly between those whose mothers were assigned to cook with LPG stoves and fuel and those whose mothers were assigned to continue cooking with biomass stoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Nationwide Use and Outcome of Surgery for Locally Advanced Pancreatic Cancer Following Induction Chemotherapy.

BACKGROUND: Several international high-volume centers have reported good outcomes after resection of locally advanced pancreatic cancer (LAPC) following chemo(radio)therapy, but it is unclear how this translates to nationwide clinical practice and outcome. This study aims to assess the nationwide use and outcome of resection of LAPC following induction chemo(radio)therapy. PATIENTS AND METHODS: A multicenter retrospective study including all patients who underwent resection for LAPC following chemo(radio)therapy in all 16 Dutch pancreatic surgery centers (2014-2020), registered in the mandatory Dutch Pancreatic Cancer Audit. LAPC is defined as arterial involvement > 90° and/or portomesenteric venous > 270° involvement or occlusion. RESULTS: Overall, 142 patients underwent resection for LAPC, of whom 34.5% met the 2022 National Comprehensive Cancer Network criteria. FOLFIRINOX was the most commonly (93.7%) used chemotherapy [median 5 cycles (IQR 4-8)]. Venous and arterial resections were performed in 51.4% and 14.8% of patients. Most resections (73.9%) were performed in high-volume centers (i.e., ≥ 60 pancreatoduodenectomies/year). Overall median volume of LAPC resections/center was 4 (IQR 1-7). In-hospital/30-day major morbidity was 37.3% and 90-day mortality was 4.2%. Median OS from diagnosis was 26 months (95% CI 23-28) and 5-year OS 18%. Surgery in high-volume centers [HR = 0.542 (95% CI 0.318-0.923)], ypN1-2 [HR = 3.141 (95% CI 1.886-5.234)], and major morbidity [HR = 2.031 (95% CI 1.272-3.244)] were associated with OS. CONCLUSIONS: Resection of LAPC following chemo(radio)therapy is infrequently performed in the Netherlands, albeit with acceptable morbidity, mortality, and OS. Given these findings, a structured nationwide approach involving international centers of excellence would be needed to improve selection of patients with LAPC for surgical resection following induction therapy.

Pilot Study: Short Term Impact of Radiation Therapy on Bone Mineral Density and Bone Metabolism.

Despite the risk of complications, high dose radiation therapy is increasingly utilized in the management of selected bone malignancies. In this study, we investigate the impact of moderate to high dose radiation (over 50 Gy) on bone metabolism and structure. Between 2015 and 2018, patients with a primary malignant bone tumor of the sacrum that were either treated with high dose definitive radiation only or a combination of moderate to high dose radiation and surgery were prospectively enrolled at a single institution. Quantitative CTs were performed before and after radiation to determine changes in volumetric bone mineral density (BMD) of the irradiated and non-irradiated spine. Bone histomorphometry was performed on biopsies of the irradiated sacrum and the non-irradiated iliac crest of surgical patients using a quadruple tetracycline labeling protocol. In total, 9 patients were enrolled. Two patients received radiation only (median dose 78.3 Gy) and 7 patients received a combination of preoperative radiation (median dose 50.4 Gy), followed by surgery. Volumetric BMD of the non-irradiated lumbar spine did not change significantly after radiation, while the BMD of the irradiated sacrum did (pre-radiation median: 108.0 mg/cm3 (IQR 91.8-167.1); post-radiation median: 75.3 mg/cm3 (IQR 57.1-110.2); p = 0.010). The cancellous bone of the non-irradiated iliac crest had a stable bone formation rate, while the irradiated sacrum showed a significant decrease in bone formation rate [pre-radiation median: 0.005 mm3/mm2/year (IQR 0.003-0.009), post-radiation median: 0.001 mm3/mm2/year (IQR 0.001-0.001); p = 0.043]. Similar effects were seen in the cancellous and endocortical envelopes. This pilot study shows a decrease of volumetric BMD and bone formation rate after high-dose radiation therapy. Further studies with larger cohorts and other endpoints are needed to get more insight into the effect of radiation on bone. Level of evidence: IV.

Fidelity and adherence to a liquefied petroleum gas stove and fuel intervention: The multi-country Household Air Pollution Intervention Network (HAPIN) trial.

BACKGROUND: Reducing household air pollution (HAP) to levels associated with health benefits requires nearly exclusive use of clean cooking fuels and abandonment of traditional biomass fuels. METHODS: The Household Air Pollution Intervention Network (HAPIN) trial randomized 3,195 pregnant women in Guatemala, India, Peru, and Rwanda to receive a liquefied petroleum gas (LPG) stove intervention (n = 1,590), with controls expected to continue cooking with biomass fuels (n = 1,605). We assessed fidelity to intervention implementation and participant adherence to the intervention starting in pregnancy through the infant's first birthday using fuel delivery and repair records, surveys, observations, and temperature-logging stove use monitors (SUMs). RESULTS: Fidelity and adherence to the HAPIN intervention were high. Median time required to refill LPG cylinders was 1 day (interquartile range 0-2). Although 26% (n = 410) of intervention participants reported running out of LPG at some point, the number of times was low (median: 1 day [Q1, Q3: 1, 2]) and mostly limited to the first four months of the COVID-19 pandemic. Most repairs were completed on the same day as problems were reported. Traditional stove use was observed in only 3% of observation visits, and 89% of these observations were followed up with behavioral reinforcement. According to SUMs data, intervention households used their traditional stove a median of 0.4% of all monitored days, and 81% used the traditional stove < 1 day per month. Traditional stove use was slightly higher post-COVID-19 (detected on a median [Q1, Q3] of 0.0% [0.0%, 3.4%] of days) than pre-COVID-19 (0.0% [0.0%, 1.6%] of days). There was no significant difference in intervention adherence pre- and post-birth. CONCLUSION: Free stoves and an unlimited supply of LPG fuel delivered to participating homes combined with timely repairs, behavioral messaging, and comprehensive stove use monitoring contributed to high intervention fidelity and near-exclusive LPG use within the HAPIN trial.

Integrating mindfulness and the expressive arts for meaning making in cancer care: A grounded theory of the processes, facilitators, and challenges.

PURPOSE: There is a growing interest in mindfulness-based expressive arts interventions in oncology, to help patients process their experiences, learn how to live with cancer, and ameliorate psychological distress. Our research purpose was to explore how patients with cancer experience a mindfulness-based expressive arts group intervention, and to articulate individual and contextual factors influencing their experiences. METHODS: We conducted a constructivist grounded theory study and recruited 32 participants who experienced a 10-week mindfulness-based expressive arts group intervention at a tertiary cancer center in mid-Western Canada. We gathered socio-demographic data and descriptions of their experiences through semi-structured interviews. Participants brought art they had created to facilitate art elicitation. Socio-demographic data were analyzed with descriptive statistics and all other data with grounded theory methods. RESULTS: Our findings revealed how entering the group and meaning making processes through mindfulness enabled participants to let go of their ruminations and calm their minds so they could fully engage in arts activities. Participants found inspiration for their artistic expressions in mindfulness meditation which allowed them to express themselves in new ways. Although this work was challenging, combining mindfulness and the arts created a unique healing space in which individual work was nested within group processes. There were notable personal factors and perspectives that influenced participants' experiences, as well as factors related to the group design and facilitator. CONCLUSIONS: Our findings provide insight into how and when this intervention was meaningful for patients, and have important implications to guide ongoing intervention development, implementation, and evaluation.

Effects of a LPG stove and fuel intervention on adverse maternal outcomes: A multi-country randomized controlled trial conducted by the Household Air Pollution Intervention Network (HAPIN).

Household air pollution from solid cooking fuel use during gestation has been associated with adverse pregnancy and birth outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial of free liquefied petroleum gas (LPG) stoves and fuel in Guatemala, Peru, India, and Rwanda. A primary outcome of the main trial was to report the effects of the intervention on infant birth weight. Here we evaluate the effects of a LPG stove and fuel intervention during pregnancy on spontaneous abortion, postpartum hemorrhage, hypertensive disorders of pregnancy, and maternal mortality compared to women who continued to use solid cooking fuels. Pregnant women (18-34 years of age; gestation confirmed by ultrasound at 9-19 weeks) were randomly assigned to an intervention (n = 1593) or control (n = 1607) arm. Intention-to-treat analyses compared outcomes between the two arms using log-binomial models. Among the 3195 pregnant women in the study, there were 10 spontaneous abortions (7 intervention, 3 control), 93 hypertensive disorders of pregnancy (47 intervention, 46 control), 11 post postpartum hemorrhage (5 intervention, 6 control) and 4 maternal deaths (3 intervention, 1 control). Compared to the control arm, the relative risk of spontaneous abortion among women randomized to the intervention was 2.32 (95% confidence interval (CI): 0.60, 8.96), hypertensive disorders of pregnancy 1.02 (95% CI: 0.68, 1.52), postpartum hemorrhage 0.83 (95% CI: 0.25, 2.71) and 2.98 (95% CI: 0.31, 28.66) for maternal mortality. In this study, we found that adverse maternal outcomes did not differ based on randomized stove type across four country research sites.

Chronic SIRT1 supplementation in diabetic mice improves endothelial function by suppressing oxidative stress.

AIMS: Enhancing SIRT1 activity exerts beneficial cardiovascular effects. In diabetes, plasma SIRT1 levels are reduced. We aimed to investigate the therapeutic potential of chronic recombinant murine SIRT1 (rmSIRT1) supplementation to alleviate endothelial and vascular dysfunction in diabetic mice (db/db). METHODS AND RESULTS: Left internal mammary arteries obtained from patients undergoing coronary artery bypass grafting with or without a diagnosis of diabetes were assayed for SIRT1 protein levels. Twelve-week-old male db/db mice and db/+ controls were treated with vehicle or rmSIRT1 intraperitoneally for 4 weeks, after which carotid artery pulse wave velocity (PWV) and energy expenditure/activity were assessed by ultrasound and metabolic cages, respectively. Aorta, carotid, and mesenteric arteries were isolated to determine endothelial and vascular function using the myograph system.Arteries obtained from diabetic patients had significantly lower levels of SIRT1 relative to non-diabetics. In line, aortic SIRT1 levels were reduced in db/db mice compared to db/+ mice, while rmSIRT1 supplementation restored SIRT1 levels. Mice receiving rmSIRT1 supplementation displayed increased physical activity and improved vascular compliance as reflected by reduced PWV and attenuated collagen deposition. Aorta of rmSIRT1-treated mice exhibited increased endothelial nitric oxide (eNOS) activity, while endothelium-dependent contractions of their carotid arteries were significantly decreased, with mesenteric resistance arteries showing preserved hyperpolarization. Ex vivo incubation with reactive oxygen species (ROS) scavenger Tiron and NADPH oxidase inhibitor apocynin revealed that rmSIRT1 leads to preserved vascular function by suppressing NADPH oxidase (NOX)-related ROS synthesis. Chronic rmSIRT1 treatment resulted in reduced expression of both NOX1 and NOX4, in line with a reduction in aortic protein carbonylation and plasma nitrotyrosine levels. CONCLUSIONS: In diabetic conditions, arterial SIRT1 levels are significantly reduced. Chronic rmSIRT1 supplementation improves endothelial function and vascular compliance by enhancing eNOS activity and suppressing NOX-related oxidative stress. Thus, SIRT1 supplementation may represent novel therapeutic strategy to prevent diabetic vascular disease.

Sensitivity of the Indo-Pacific coral Acropora millepora to aromatic hydrocarbons.

The risks posed by petroleum spills to coral reefs are poorly understood and quantifying acute toxicity thresholds for aromatic hydrocarbons to reef-building corals is required to assess their sensitivity relative to other taxa. In this study, we exposed Acropora millepora to toluene, naphthalene and 1-methylnaphthalene (1-MN) in a flow-through system and assessed survivorship and sublethal responses including growth, colour and the photosynthetic performance of symbionts. Median 50% lethal concentrations (LC50s) decreased over the 7-d exposure period, reaching asymptotic values of 22,921, 5,268, 1167 µg L-1 for toluene, naphthalene and 1-MN, respectively. Corresponding toxicokinetic parameters (εLC50) defining the time progression of toxicity were 0.830, 0.692, and 0.256 d-1, respectively. Latent effects after an additional 7-d recovery in uncontaminated seawater were not observed. Effect concentrations (EC50s) for 50% growth inhibition were 1.9- to 3.6-fold lower than the LC50s for each aromatic hydrocarbon. There were no observed effects of aromatic hydrocarbon exposure on colour score (a proxy for bleaching) or photosynthetic efficiency. Acute and chronic critical target lipid body burdens (CTLBBs) of 70.3 ± 16.3 and 13.6 ± 18.4 µmol g-1 octanol (± standard error) were calculated for survival and growth inhibition based on 7-d LC50 and EC10 values, respectively. These species-specific constants indicate adult A. millepora is more sensitive than other corals reported so far but is of average sensitivity in comparison with other aquatic taxa in the target lipid model database. These results advance our understanding of acute hazards of petroleum contaminants to key habitat-building tropical coral reef species.

Omega-3 Fatty Acids and Heart Rhythm, Rate, and Variability in Atrial Fibrillation.

Background Previous randomized control trials showed mixed results concerning the effect of omega-3 fatty acids (n-3 FAs) on atrial fibrillation (AF). The associations of n-3 FA blood levels with heart rhythm in patients with established AF are unknown. The goal of this study was to assess the associations of total and individual n-3 FA blood levels with AF type (paroxysmal versus nonparoxysmal), heart rate (HR), and HR variability in patients with AF. Methods and Results Total n-3 FAs, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and alpha-linolenic acid blood levels were determined in 1969 patients with known AF from the SWISS-AF (Swiss Atrial Fibrillation cohort). Individual and total n-3 FAs were correlated with type of AF, HR, and HR variability using standard logistic and linear regression, adjusted for potential confounders. Only a mild association with nonparoxysmal AF was found with total n-3 FA (odds ratio [OR], 0.97 [95% CI, 0.89-1.05]) and docosahexaenoic acid (OR, 0.93 [95% CI, 0.82-1.06]), whereas other individual n-3 FAs showed no association with nonparoxysmal AF. Higher total n-3 FAs (estimate 0.99 [95% CI, 0.98-1.00]) and higher docosahexaenoic acid (0.99 [95% CI, 0.97-1.00]) tended to be associated with slower HR in multivariate analysis. Docosapentaenoic acid was associated with a lower HR variability triangular index (0.94 [95% CI, 0.89-0.99]). Conclusions We found no strong evidence for an association of n-3 FA blood levels with AF type, but higher total n-3 FA levels and docosahexaenoic acid might correlate with lower HR, and docosapentaenoic acid with a lower HR variability triangular index.

Radiation Resilient Two-Dimensional Electronics.

Limitations in cloud-based computing have prompted a paradigm shift toward all-in-one "edge" devices capable of independent data sensing, computing, and storage. Advanced defense and space applications stand to benefit immensely from this due to their need for continual operation in areas where maintaining remote oversight is difficult. However, the extreme environments relevant to these applications necessitate rigorous testing of technologies, with a common requirement being hardness to ionizing radiation. Two-dimensional (2D) molybdenum disulfide (MoS2) has been noted to enable the sensing, storage, and logic capabilities necessary for all-in-one edge devices. Despite this, the investigation of ionizing radiation effects in MoS2-based devices remains incomplete. In particular, studies on gamma radiation effects in MoS2 have been largely limited to standalone films, with few device investigations; to the best of our knowledge, no explorations have been made into gamma radiation effects on the sensing and memory capabilities of MoS2-based devices. In this work, we have used a statistical approach to study high-dose (1 Mrad) gamma radiation effects on photosensitive and programmable memtransistors fabricated from large-area monolayer MoS2. Memtransistors were divided into separate groups to ensure accurate extraction of device characteristics pertaining to baseline performance, sensing, and memory before and after irradiation. All-MoS2 logic gates were also assessed to determine the gamma irradiation impact on logic implementation. Our findings show that the multiple functionalities of MoS2 memtransistors are not severely impacted by gamma irradiation even without dedicated shielding/mitigation techniques. We believe that these results serve as a foundation for more application-oriented studies going forward.

Long-term dietary n3 fatty acid prevents aging-related cardiac diastolic and vascular dysfunction.

AIMS: The prevalence of left ventricular (LV) diastolic and vascular dysfunction increases with age, eventually leading to heart failure with preserved ejection fraction (HFpEF). A preventive strategy is an unmet medical need. We and others reported previously on the beneficial effects of omega-3 fatty acid alpha linolenic acid (ALA) on cardiovascular disorders in animal models and translational studies. We now investigate whether long-term dietary ALA could prevent LV diastolic dysfunction and vascular aging in a murine model. METHODS AND RESULTS: Wild-type C57BL/6 J mice were fed a chow or ALA diet for 12 months, starting at 6 months of age. Here, we show that aged (~18 months) mice recapitulate major hallmarks of HFpEF, including LV diastolic dysfunction with preserved ejection fraction, impaired vascular function, cardiac fibrosis, arterial stiffening and inflammation, as well as elevated B-type natriuretic peptide (BNP). Long-term ALA supplementation upregulated the mitochondrial tricarboxylic acid enzyme Idh2 and the antioxidant enzymes SOD1 and Gpx1. It also has been associated with reduced inflammation and ECM remodeling, accompanied by a significant downregulation of fibrosis biomarkers MMP-2 and TGF-ß in both cardiac and vascular tissues obtained from aged mice. Our data exhibited the preventive effects of dietary ALA against LV diastolic dysfunction, impaired vasorelaxation, cardiac fibrosis, inflammation and arterial stiffening in aged mice. CONCLUSIONS: We provide evidence and a simplified mechanistic insight on how long-term ALA supplementation is a successful strategy to prevent the development of age-related diastolic and vascular dysfunction.

Network-Guided Multiomic Mapping of Aortic Valve Calcification.

Despite devastating clinical sequelae of calcific aortic valve disease that range from left ventricular remodeling to arrhythmias, heart failure, and early death, the molecular insights into disease initiation and progression are limited and pharmacotherapies remain unavailable. The pathobiology of calcific aortic valve disease is complex and comprehensive studies are challenging valvular calcification is heterogeneous and occurs preferentially on the aortic surface, along a fibrocalcific spectrum. Here, we review efforts to study (epi-)genomic, transcriptomic, proteomic, and metabolomic aspects of aortic valve calcification in combination with network medicine-/systems biology-based strategies to integrate multilayered omics datasets and prioritize druggable targets for experimental validation studies. Ultimately, such holistic approach efforts may open therapeutic avenues that go beyond invasive and costly valve replacement therapy.

Proton-pump inhibitor use amongst patients with severe hypomagnesemia.

Introduction: Long-term proton pump inhibitor (PPI) use has been associated with hypomagnesemia. It is unknown how frequently PPI use is implicated in patients with severe hypomagnesemia, and its clinical course or risk factors. Methods: All patients with severe hypomagnesemia from 2013 to 2016 in a tertiary center were assessed for likelihood of PPI-related hypomagnesemia using Naranjo algorithm, and we described the clinical course. The clinical characteristics of each case of PPI-related severe hypomagnesemia was compared with three controls on long-term PPI without hypomagnesemia, to assess for risk factors of developing severe hypomagnesemia. Results: Amongst 53,149 patients with serum magnesium measurements, 360 patients had severe hypomagnesemia (<0.4 mmol/L). 189 of 360 (52.5%) patients had at least possible PPI-related hypomagnesemia (128 possible, 59 probable, two definite). 49 of 189 (24.7%) patients had no other etiology for hypomagnesemia. PPI was stopped in 43 (22.8%) patients. Seventy (37.0%) patients had no indication for long-term PPI use. Hypomagnesemia resolved in most patients after supplementation, but recurrence was higher in patients who continued PPI, 69.7% versus 35.7%, p = 0.009. On multivariate analysis, risk factors for hypomagnesemia were female gender (OR 1.73; 95% CI: 1.17-2.57), diabetes mellitus (OR, 4.62; 95% CI: 3.05-7.00), low BMI (OR, 0.90; 95% CI: 0.86-0.94), high-dose PPI (OR, 1.96; 95% CI: 1.29-2.98), renal impairment (OR, 3.85; 95% CI: 2.58-5.75), and diuretic use (OR, 1.68; 95% CI: 1.09-2.61). Conclusion: In patients with severe hypomagnesemia, clinicians should consider the possibility of PPI-related hypomagnesemia and re-examine the indication for continued PPI use, or consider a lower dose.

Adopting a toxic unit model paradigm in design, analysis and interpretation of oil toxicity testing.

The lack of a conceptual understanding and unifying quantitative framework to guide conduct and interpretation of laboratory oil toxicity tests, has led investigators to divergent conclusions that can confuse stakeholders and impede sound decision-making. While a plethora of oil toxicity studies are available and continue to be published, due to differences in experimental design, results between studies often cannot be compared. Furthermore, much resulting data fails to advance quantitative effect models that are critically needed for oil spill risk and impact assessments. This paper discusses the challenges posed when evaluating oil toxicity test data based on traditional, total concentration-based exposure metrics and offers solutions for improving the state of practice by adopting a unifying toxic unit (TU) model framework. Key advantages of a TU framework is that differences in test oil composition, sensitivity of the test organism/endpoint, and toxicity test design (i.e., type of test) can be taken into quantitative account in predicting aquatic toxicity. This paradigm shift is intended to bridge the utility of laboratory oil toxicity tests with improved assessment of effects in the field. To illustrate these advantages, results from literature studies are reassessed and contrasted with conclusions obtained based on past practice. Using instructive examples, model results are presented to explain how dissolved oil composition and concentrations and resulting TUs vary in WAFs prepared using variable loading or dilution test designs and the important role that unmeasured oil components contribute to predicted oil toxicity. Model results are used to highlight how the TU framework can serve as a valuable aid in designing and interpreting empirical toxicity tests and provide the data required to validate/refine predictive toxicity models. To further promote consistent exposure and hazard assessment of physically and chemically dispersed oil toxicity tests recommendations for advancing the TU framework are presented.

Bridging the lab to field divide: Advancing oil spill biological effects models requires revisiting aquatic toxicity testing.

Oil fate and exposure modeling addresses the complexities of oil composition, weathering, partitioning in the environment, and the distributions and behaviors of aquatic biota to estimate exposure histories, i.e., oil component concentrations and environmental conditions experienced over time. Several approaches with increasing levels of complexity (i.e., aquatic toxicity model tiers, corresponding to varying purposes and applications) have been and continue to be developed to predict adverse effects resulting from these exposures. At Tiers 1 and 2, toxicity-based screening thresholds for assumed representative oil component compositions are used to inform spill response and risk evaluations, requiring limited toxicity data, analytical oil characterizations, and computer resources. Concentration-response relationships are employed in Tier 3 to quantify effects of assumed oil component mixture compositions. Oil spill modeling capabilities presently allow predictions of spatial and temporal compositional changes during exposure, which support mixture-based modeling frameworks. Such approaches rely on summed effects of components using toxic units to enable more realistic analyses (Tier 4). This review provides guidance for toxicological studies to inform the development of, provide input to, and validate Tier 4 aquatic toxicity models for assessing oil spill effects on aquatic biota. Evaluation of organisms' exposure histories using a toxic unit model reflects the current state-of the-science and provides an improved approach for quantifying effects of oil constituents on aquatic organisms. Since the mixture compositions in toxicity tests are not representative of field exposures, modelers rely on studies using single compounds to build toxicity models accounting for the additive effects of dynamic mixture exposures that occur after spills. Single compound toxicity data are needed to quantify the influence of exposure duration and modifying environmental factors (e.g., temperature, light) on observed effects for advancing use of this framework. Well-characterized whole oil bioassay data should be used to validate and refine these models.