Lipid profile and reproductive performance of female offspring of SWISS mouse females supplemented with resveratrol or canjiqueira (Byrsonima cydoniifolia A Juss) during gestation.

This study aimed to resveratrol supplementation (at 5 or 10 mg/kg) and a hydroethanolic extract of canjiqueira fruits (150 mg/kg) on female SWISS mice. Total cholesterol, high-density lipoprotein (HDL), triglyceride levels, gestation rates, and embryonic implantation rates in their female Offspring was evaluated. In conclusion, the consumption of canjiqueira fruit extract altered the lipid profile of their female offspring, and did not impact their reproductive performance. Supplementing female SWISS mice with 10 mg/kg of resveratrol increased total cholesterol, triglycerides, and HDL levels, thereby enhancing the reproductive efficiency of their offspring.

1,4-Diaryl-1,2,3-triazole neolignan-celecoxib hybrids inhibit experimental arthritis induced by zymosan.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes cartilage damage. Anti-inflammatories are widely used in the management of RA, but they can have side effects such as gastrointestinal and/or cardiovascular disorders. Studies published by our group showed that the synthesis of hybrid triazole analogs neolignan-celecoxib containing the substituent groups sulfonamide (L15) or carboxylic acid (L18) exhibited anti-inflammatory activity in an acute model of inflammation, inhibited expression of P-selectin related to platelet activation and did not induce gastric ulcer, minimizing the related side effects. In continuation, the present study evaluated the anti-inflammatory effects of these analogs in an experimental model of arthritis and on the functions of one of the important cells in this process, macrophages. Mechanical hyperalgesia, joint edema, leukocyte recruitment to the joint and damage to cartilage in experimental arthritis and cytotoxicity, spread of disease, phagocytic activity and nitric oxide (NO) and hydrogen peroxide production by macrophages were evaluated. Pre-treatment with L15 and L18 reduced mechanical hyperalgesia, joint edema and the influx of leukocytes into the joint cavity after different periods of the stimulus. The histological evaluation of the joint showed that L15 and L18 reduced cartilage damage and there was no formation of rheumatoid pannus. Furthermore, L15 and L18 were non-cytotoxic. The analogs inhibited the spreading, the production of NO and hydrogen peroxide. L15 decreased the phagocytosis. Therefore, L15 and L18 may be potential therapeutic prototypes to treat chronic inflammatory diseases such as RA.

Fine particulate matter damages and value added in the US economy.

Emissions of most pollutants that result in fine particulate matter (PM2.5) formation have been decreasing in the United States. However, this trend has not been uniform across all sectors or regions of the economy. We use integrated assessment models (IAMs) to compute marginal damages for PM2.5-related emissions for each county in the contiguous United States and match location-specific emissions with these marginal damages to compute economy-wide gross external damage (GED) due to premature mortality. We note 4 key findings: First, economy-wide, GED has decreased by more than 20% from 2008 to 2014. Second, while much of the air pollution policies have focused to date on the electricity sector, damages from farms are now larger than those from utilities. Indeed, farms have become the largest contributor to air pollution damages from PM2.5-related emissions. Third, 4 sectors, comprising less than 20% of the national gross domestic product (GDP), are responsible for ∼75% of GED attributable to economic activities. Fourth, uncertainty in GED estimates tends to be high for sectors with predominantly ground-level emissions because these emissions are usually estimated and not measured. These findings suggest that policymakers should target further emissions reductions from such sectors, particularly in transportation and agriculture.

Expert assessments of the cost and expected future performance of proton exchange membrane fuel cells for vehicles.

Despite decades of development, proton exchange membrane fuel cells (PEMFCs) still lack wide market acceptance in vehicles. To understand the expected trajectories of PEMFC attributes that influence adoption, we conducted an expert elicitation assessment of the current and expected future cost and performance of automotive PEMFCs. We elicited 39 experts' assessments of PEMFC system cost, stack durability, and stack power density under a hypothetical, large-scale production scenario. Experts assessed the median 2017 automotive cost to be $75/kW, stack durability to be 4,000 hours, and stack power density to be 2.5 kW/L. However, experts ranged widely in their assessments. Experts' 2017 best cost assessments ranged from $40 to $500/kW, durability assessments ranged from 1,200 to 12,000 hours, and power density assessments ranged from 0.5 to 4 kW/L. Most respondents expected the 2020 cost to fall short of the 2020 target of the US Department of Energy (DOE). However, most respondents anticipated that the DOE's ultimate target of $30/kW would be met by 2050 and a power density of 3 kW/L would be achieved by 2035. Fifteen experts thought that the DOE's ultimate durability target of 8,000 hours would be met by 2050. In general, experts identified high Pt group metal loading as the most significant barrier to reducing cost. Recommended research and development (R&D) funding was allocated to "catalysts and electrodes," followed in decreasing amount by "fuel cell performance and durability," "membranes and electrolytes," and "testing and technical assessment." Our results could be used to inform public and private R&D decisions and technology roadmaps.

E-Learning Impact on Veterinary Medical Student's Mental Health during the COVID-19 Pandemic.

Veterinary medical students are known to have significant levels of mental illness. The COVID-19 pandemic and the shift to online learning have brought increased psychological stress. We used a web-based survey to ask 415 veterinary medical students from Portugal about the impact of the pandemic and online learning on their anxiety levels. Results were analyzed using logistic regressions and Spearman's correlation. Results indicated that 15.4% had no symptoms of anxiety, 39.5% experienced mild anxiety, 21.4% had moderate anxiety, and 23.6% experienced severe anxiety. Having difficulty sleeping, the stress associated with confinement, and family conflicts were risk factors for anxiety, while being male was found to be protective. Most veterinary medical students (77%) were satisfied with online learning. The university's adaptation to online teaching and time spent participating in online classes were significantly associated with anxiety. Due to the known fragility of veterinary medical students' mental health, this group should be monitored and supported closely during life-disrupting events such as public health emergencies.

Effects of Air Emission Externalities on Optimal Ridesourcing Fleet Electrification and Operations.

Ridesourcing services from transportation network companies, like Uber and Lyft, serve the fastest growing share of U.S. passenger travel demand.1 Ridesourcing vehicles' high use intensity is economically attractive for electric vehicles, which typically have lower operating costs and higher capital costs than conventional vehicles. We optimize fleet composition (mix of conventional vehicles (CVs), hybrid electric vehicles (HEVs), and battery electric vehicles (BEVs)) and operations to satisfy demand at minimum cost and compare findings across a wide range of present-day and future scenarios for three cities. In nearly all cases, the optimal fleet includes a mix of technologies, HEVs and BEVs make up the majority of distance traveled, and CVs are used primarily for periods of peak demand (if at all). When life cycle air pollution and greenhouse gas emission externalities are internalized via a Pigovian tax, fleet electrification increases and externalities decrease, suggesting a role for policy. Externality reductions vary from 10% in New York (where externality costs for both gasoline and electricity consumption are relatively high and a Pigovian tax induces a partial shift to BEVs), to 22% in Los Angeles (where high gasoline and low electric grid externalities lead a Pigovian tax to induce a near-complete shift to BEVs).

Commercial foods for infants under the age of 36 months: an assessment of the availability and nutrient profile of ultra-processed foods.

OBJECTIVE: Considering the negative impact of the consumption of ultra-processed foods on health, the current study assessed the availability and nutritional profile of commercial ultra-processed foods for infants in Natal, Brazil. DESIGN: A cross-sectional exploratory study. SETTING: Foods targeted at children under the age of 36 months sold in retail establishments located in high- and low-income areas of the one capital city of Brazil. PARTICIPANTS: 1645 food products consisting of ninety-five different types of food were available. The foods were assessed according to the NOVA classification: minimally processed, processed and ultra-processed. The nutritional content per 100 g was assessed according to processing classification. RESULTS: Half of foods founded were breast milk substitutes and cereal foods (31·6 and 26·3 %, respectively). The foods were predominantly ultra-processed (79 %) and only 4·2 % were minimally processed, with similar proportions of ultra-processed foods being found in both high- and low-income areas. After excluding breast milk substitutes and follow-up formulas, all cereals, food supplements and some of the fruit or vegetable purees were ultra-processed, higher in energy density, fat, carbohydrate and protein and low in fibre (P < 0·05). CONCLUSIONS: The findings reveal that ultra-processed foods for infants are widely available in Brazil, reaffirming the need to strengthen the regulation of foods for infants and young children by introducing complementary measures designed to promote the production and marketing of foods manufactured using lower levels of processing.

Covalent Histone Modification by an Electrophilic Derivative of the Anti-HIV Drug Nevirapine.

Nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor widely used in combined antiretroviral therapy and to prevent mother-to-child transmission of the human immunodeficiency virus type 1, is associated with several adverse side effects. Using 12-mesyloxy-nevirapine, a model electrophile of the reactive metabolites derived from the NVP Phase I metabolite, 12-hydroxy-NVP, we demonstrate that the nucleophilic core and C-terminal residues of histones are targets for covalent adduct formation. We identified multiple NVP-modification sites at lysine (e.g., H2BK47, H4K32), histidine (e.g., H2BH110, H4H76), and serine (e.g., H2BS33) residues of the four histones using a mass spectrometry-based bottom-up proteomic analysis. In particular, H2BK47, H2BH110, H2AH83, and H4H76 were found to be potential hot spots for NVP incorporation. Notably, a remarkable selectivity to the imidazole ring of histidine was observed, with modification by NVP detected in three out of the 11 histidine residues of histones. This suggests that NVP-modified histidine residues of histones are prospective markers of the drug's bioactivation and/or toxicity. Importantly, NVP-derived modifications were identified at sites known to determine chromatin structure (e.g., H4H76) or that can undergo multiple types of post-translational modifications (e.g., H2BK47, H4H76). These results open new insights into the molecular mechanisms of drug-induced adverse reactions.

The King's Sliding Hindfoot Osteotomy for the Treatment of Talus Body Defects-Results of a New Technique in Tibiotalocalcaneal Arthrodesis.

Bone loss after avascular necrosis of the talus secondary to acute traumatic or chronic pathologies often requires surgical reconstruction. This study reports the early results of a sliding oblique hindfoot osteotomy for salvage procedures combined with tibiotalar arthrodesis to achieve a well-aligned, painless, plantigrade foot. All patients presenting to our institution with severe talus body defects requiring corrective surgery between January 2016 and August 2020 were included. An oblique osteotomy of the diseased talus was performed to correct anterior talus subluxation and prevent excessive loss of height at the tibiotalar apposition and to correct varus-valgus deformity. A retrograde hindfoot nail was used for intramedullary tibiotalocalcaneal arthrodesis. Patients were prospectively followed. Primary outcomes included assessment of mobility and union at 6 months. Secondary outcomes included 30-day postoperative complications, patient satisfaction and change in American Orthopaedic Foot & Ankle Society (AOFAS) score at 1-year postoperation. Nine patients underwent this procedure with a mean follow-up of 18 months (4-36 months). Average age was 66 (58-81) years. Mean body mass index was 33.7 (22-38) kg/m2. All patients went on to fusion and were ambulating at 6 months (n = 8). At 1 year, the mean improvement in AOFAS was 28.9 points (p < .05) (n = 7) and all patients were satisfied with the outcome of their treatment. This technique represents an alternative to conventional hindfoot salvage techniques showing predictable outcomes in complex hindfoot deformity with talar body collapse and anterior subluxation. Further quantitative studies are needed to define if this technique minimizes limb shortening/limb-length discrepancies when compared to traditional horizontal cuts.

Climate and Health Benefits of Rapid Coal-to-Gas Fuel Switching in the U.S. Power Sector Offset Methane Leakage and Production Cost Increases.

In this paper, we ask whether rapidly displacing coal electricity generation with underutilized, existing natural gas capacity has net societal benefits or net costs when considering climate change, economics, and air pollution. We use a power plant dispatch model to quantify the effects of dispatching because of a tax on carbon or because of a tax on carbon, methane leakage, and air pollution. We explicitly model exhaust stack CO2 emissions, production costs, health damages caused by criteria air pollutants, and methane leakage from the natural gas infrastructure. We show that (1) the optimal coal-to-gas redispatch displaces 62-77% of coal energy, leaving some coal online, (2) the health benefits of redispatch are larger in magnitude than the climate benefits, (3) reducing methane leakage rates from 2.3 to 2.0% increases the net climate benefits of redispatch by $1.1B-$1.4B, (4) although internalizing methane leakage, climate damages, and health damages in the power plant dispatch maximizes the net benefits of redispatch, 75-87% of these benefits can be achieved using a carbon tax mechanism alone, and (5) when choosing an optimal carbon tax, focusing on climate at the exclusion of health-and vice-versa-provides less net benefit than looking at both issues jointly.

Optimizing Emissions Reductions from the U.S. Power Sector for Climate and Health Benefits.

Improved air quality and human health are often discussed as "co-benefits" of mitigating climate change, yet they are rarely considered when designing or implementing climate policies. We analyze the implications of integrating health and climate when determining the best locations for replacing power plants with new wind, solar, or natural gas to meet a CO2 reduction target in the United States. We employ a capacity expansion model with integrated assessment of climate and health damages, comparing portfolios optimized for benefits to climate alone or both health and climate. The model estimates county-level health damages and accounts for uncertainty by using a range of air quality models (AP3, EASIUR, and InMAP) and concentration-response functions (American Cancer Society and Harvard Six Cities). We find that reducing CO2 by 30% yields $21-68 billion in annual health benefits, with an additional $9-36 billion possible when co-optimizing for climate and health benefits. Additional benefits accrue from prioritizing emissions reductions in counties with high population exposure. Total health benefits equal or exceed climate benefits across a wide range of modeling assumptions. Our results demonstrate the value of considering health in climate policy design and the need for interstate cooperation to achieve additional health benefits equitably.

Spatially resolved air-water emissions tradeoffs improve regulatory impact analyses for electricity generation.

Coal-fired power plants (CFPPs) generate air, water, and solids emissions that impose substantial human health, environmental, and climate change (HEC) damages. This work demonstrates the importance of accounting for cross-media emissions tradeoffs, plant and regional emissions factors, and spatially variation in the marginal damages of air emissions when performing regulatory impact analyses for electric power generation. As a case study, we assess the benefits and costs of treating wet flue gas desulfurization (FGD) wastewater at US CFPPs using the two best available treatment technology options specified in the 2015 Effluent Limitation Guidelines (ELGs). We perform a life-cycle inventory of electricity and chemical inputs to FGD wastewater treatment processes and quantify the marginal HEC damages of associated air emissions. We combine these spatially resolved damage estimates with Environmental Protection Agency estimates of water quality benefits, fuel-switching benefits, and regulatory compliance costs. We estimate that the ELGs will impose average net costs of $3.01 per cubic meter for chemical precipitation and biological wastewater treatment and $11.26 per cubic meter for zero-liquid discharge wastewater treatment (expected cost-benefit ratios of 1.8 and 1.7, respectively), with damages concentrated in regions containing a high fraction of coal generation or a large chemical manufacturing industry. Findings of net cost for FGD wastewater treatment are robust to uncertainty in auxiliary power source, location of chemical manufacturing, and binding air emissions limits in noncompliant regions, among other variables. Future regulatory design will minimize compliance costs and HEC tradeoffs by regulating air, water, and solids emissions simultaneously and performing regulatory assessments that account for spatial variation in emissions impacts.

Null Effects of Game Violence, Game Difficulty, and 2D:4D Digit Ratio on Aggressive Behavior.

Researchers have suggested that acute exposure to violent video games is a cause of aggressive behavior. We tested this hypothesis by using violent and nonviolent games that were closely matched, collecting a large sample, and using a single outcome. We randomly assigned 275 male undergraduates to play a first-person-shooter game modified to be either violent or less violent and hard or easy. After completing the game-play session, participants were provoked by a confederate and given an opportunity to behave aggressively. Neither game violence nor game difficulty predicted aggressive behavior. Incidentally, we found that 2D:4D digit ratio, thought to index prenatal testosterone exposure, did not predict aggressive behavior. Results do not support acute violent-game exposure and low 2D:4D ratio as causes of aggressive behavior.

Performance of SLEDAI-2K to detect a clinically meaningful change in SLE disease activity: a 36-month prospective cohort study of 334 patients.

OBJECTIVE: The objective of this paper is to evaluate the performance of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) in detecting clinically meaningful changes in SLE disease activity. METHODS: A longitudinal cohort study was conducted of 334 SLE patients during a 36-month follow-up. At each outpatient visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI-2K. Correlations between PGA and SLEDAI-2K were assessed. A clinically meaningful change in SLE disease activity was defined as a ΔPGA ≥ 0.3 points from baseline. Performance of SLEDAI-2K in detecting a clinically meaningful worsening or improvement was tested using receiver operating characteristic (ROC) analysis. RESULTS: Adjusted mean PGA and SLEDAI-2K scores presented a high correlation (rho = 0.824, p < 0.0005). In ROC analysis, a SLEDAI-2K variation presented an area under the curve (AUC) of 0.697 (95% confidence interval (CI) (0.628-0.766), p < 0.0005) to detect a clinically meaningful improvement, with a sensitivity of 28.8% for a SLEDAI-2K ≥ 4 reduction. The AUC to detect a clinically meaningful worsening was 0.877 (95% CI (0.822-0.932), p < 0.0005), with a sensitivity of 35.3%. CONCLUSIONS: SLEDAI-2K has a limited ability to detect clinically meaningful changes in SLE disease activity, failing to identify almost two-thirds of cases judged as having a clinically meaningful improvement or worsening. There is a need for more sensitive SLE disease activity measures in clinical practice and research.

Reduced-Order Dispatch Model for Simulating Marginal Emissions Factors for the United States Power Sector.

This study develops a reduced-order power plant dispatch model and uses it to simulate marginal emissions factors (MEFs) for the 2014-2017 United States (U.S.) electric grid at the North American Electric Reliability Corporation (NERC) regional level. MEFs help quantify the health, environmental, and climate change impacts caused by changes in marginal net electricity consumption, which could result, for example, from new technologies or policies. This study develops the model, validates it against historical data, and compares its simulated MEFs against historically derived regression-based MEFs. Our method accurately reproduces CO2, SO2, and NOx emissions for multiple U.S. NERC regions and years and enables us to analyze future scenarios that are absent from the historical data. Though historically derived regression-based MEFs are generally more accurate, our simulated MEFs provide a more nuanced picture of how clusters of low- or high-emitting power plants of similar production cost create large swings in MEFs throughout the day. Policymakers could use these dynamic MEFs to target demand-reduction strategies at high-emissions portions of the power plant merit order.

Trace Element Mass Flow Rates from U.S. Coal Fired Power Plants.

Trace elements (TEs) exit coal-fired power plants (CFPPs) via solid, liquid, and gaseous waste streams. Estimating the TE concentrations of these waste streams is essential to selecting pollution controls and estimating emission reduction benefits. This work introduces a generalizable mass balance model for estimating TE mass flow rates in CFPP waste streams and evaluates model accuracy for the U.S. coal fleet given current data constraints. We stochastically estimate, using a bootstrapping approach, the 2015 plant-level mass flow rates of Hg, Se, As, and Cl to solid, liquid, and gas phase waste streams by combining publicly available data for combusted coal TE concentrations with estimates of TE partitioning within installed air pollution control processes. When compared with measured and reported data on TE mass flow rates, this model generally overestimates masses by 30-50%, with larger errors for Hg. The partitioning estimates are consistent for Se, As, and Cl removal from flue gas, but tend to underestimate Hg removal. While our model is suitable for first-order estimates of TE mass flows, future work to improve model performance should focus on collecting and using new data on TE concentrations in the coal blend, where data quality is the weakest.

Fine Particulate Air Pollution from Electricity Generation in the US: Health Impacts by Race, Income, and Geography.

Electricity generation is a large contributor to fine particulate matter (PM2.5) air pollution. However, the demographic distribution of the resulting exposure is largely unknown. We estimate exposures to and health impacts of PM2.5 from electricity generation in the US, for each of the seven Regional Transmission Organizations (RTOs), for each US state, by income and by race. We find that average exposures are the highest for blacks, followed by non-Latino whites. Exposures for remaining groups (e.g., Asians, Native Americans, Latinos) are somewhat lower. Disparities by race/ethnicity are observed for each income category, indicating that the racial/ethnic differences hold even after accounting for differences in income. Levels of disparity differ by state and RTO. Exposures are higher for lower-income than for higher-income, but disparities are larger by race than by income. Geographically, we observe large differences between where electricity is generated and where people experience the resulting PM2.5 health consequences; some states are net exporters of health impacts, other are net importers. For 36 US states, most of the health impacts are attributable to emissions in other states. Most of the total impacts are attributable to coal rather than other fuels.

Total hip arthroplasty in osteonecrosis secondary to sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a multisystem disease, and the predominant articular manifestation is osteonecrosis (ON). Total hip arthroplasty (THA) is technically challenging, and the complication rates are high. In this retrospective study, we have analysed the outcome of THA in a cohort of patients with SCD at our institution. MATERIALS AND METHODS: We identified 34 THAs between 1999 and 2016 in 30 patients (mean age 37 years) from our SCD database. Co-morbidities, both sickle and non-sickle-related, were documented. Complications and indications for revision surgery were analysed. RESULTS: An uncemented prosthesis was predominantly used. The mean follow-up was 10.5 years (range 1-18). Six patients had revision surgery (17.6%), 2 (5.8%) for Prosthetic Joint Infection (PJI), and 4 (11.7%) for osteolysis of the acetabular component. CONCLUSION: Our revision rates were comparable to the published literature. Our combined sickle cell clinic and the coordinated multidisciplinary management have been successful in reducing morbidity.

Welfare and pregnancy rate of ewes undergoing transcervical artificial insemination with ketamine subarachnoid anesthesia.

This study aimed to evaluate the impact of subarachnoid anesthesia with ketamine during transcervical artificial insemination (TCAI) on the welfare of ewes and on subsequent pregnancy rates. Ninety Suffolk adult ewes were randomized into three treatment groups: control group (CG), which underwent the TCAI procedure as established by cervical traction (CG; n = 30) and two groups that received subarachnoid anesthesia with ketamine at a dose of either 0.75 mg/kg (KE0.75; n = 30) or 1.5 mg/kg (KE1.5; n = 30) 5 min before the cervical traction procedure. Intrauterine insemination was performed using frozen semen from three males previously analyzed and approved for fertility. The use of subarachnoid anesthesia decreased ewes' vocalizations (P = 0.0001) and abdominal contraction (P = 0.0150) during cervical manipulations. The CG had more groans and vocalizations at the moment of cervix clamping and applicator passage through the cervix (P = 0.001). The cervix traction was facilitated by anesthesia. For the control group, most of the cervical traction was done just up to the middle of the vagina (P = 0.0021). Pregnancy rates increased significantly with anesthesia (P = 0.04) as shown by the rates of 40.0%, 56.7%, and 66.7% for CG, KE1.5, and KE0.75, respectively. The CG showed behaviors associated with absolute immobility, which is suggestive of distress. In brief, the use of ketamine in subarachnoid anesthesia for transcervical artificial insemination in ewes facilitated cervical traction, increased the pregnancy rate, and improved animal welfare.

Multitarget therapy of mycophenolate mofetil and cyclosporine A for induction treatment of refractory lupus nephritis.

Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) is often ineffective. Evidence on rescue induction regimens is scarce. We analyzed efficacy and tolerability of multitarget immunosuppression with MMF and cyclosporine A (CsA) as induction treatment for LN (class III/IV/V) refractory to CYC and/or MMF. We included all six refractory LN patients (class IV = 3, class V = 2, class III = 1) from our 400-patient tertiary Lupus Clinic observed between 2012 and 2015. Four patients had previously received pulse CYC. All six received MMF as first or second induction therapy and CsA was added once failure to reach remission was established. Daily dose of MMF was 2-3 g and CsA was dosed up to 2.6-3.7 mg/kg/day. Mean proteinuria was reduced from 2407 mg/24 hours at the start of the MMF+CsA regimen to 544 mg/day after six months. The mean prednisolone dose was reduced from 17.5 to 6 mg/day after six months of MMF+CsA. Four patients achieved a complete renal response, one patient had a partial renal response and one failed to respond. None of the patients presented with adverse events. These data suggest that adding CsA to MMF can induce complete remission of refractory LN and is well tolerated.