PAHs as environmental pollutants and their neurotoxic effects.

Polycyclic aromatic hydrocarbons (PAHs), which are widely present in incompletely combusted air particulate matter <2.5 µm (PM2.5), tobacco and other organic materials, can enter the human body through various routes and are a class of environmental pollutants with neurotoxic effects. PAHs exposure can lead to abnormal development of the nervous system and neurobehavioral abnormalities in animals, including adverse effects on the nervous system of children and adults, such as a reduced learning ability, intellectual decline, and neural tube defects. After PAHs enter cells of the nervous system, they eventually lead to nervous system damage through mechanisms such as oxidative stress, DNA methylation and demethylation, and mitochondrial autophagy, potentially leading to a series of nervous system diseases, such as Alzheimer's disease. Therefore, preventing and treating neurological diseases caused by PAHs exposure are particularly important. From the perspective of the in vitro and in vivo effects of PAHs exposure, as well as its effects on human neurodevelopment, this paper reviews the toxic mechanisms of action of PAHs and the corresponding prevention and treatment methods to provide a relevant theoretical basis for preventing the neurotoxicity caused by PAHs, thereby reducing the incidence of diseases related to the nervous system and protecting human health.

Effect of Food, Crushing of Tablets, and Antacid Coadministration on Maribavir Pharmacokinetics in Healthy Adult Participants: Results From 2 Phase 1, Open-Label, Randomized, Crossover Studies.

The effect of food composition, tablet crushing, and antacid coadministration on maribavir pharmacokinetics was assessed in 2 Phase 1 studies in healthy adults. In the first, a single maribavir 400-mg dose was administered under fasting conditions, with a low-fat/low-calorie or a high-fat/high-calorie meal. In the second, a single maribavir 100-mg dose was administered under fasting conditions, as a crushed tablet, or as a whole tablet alone or with an antacid. The 90% confidence intervals of the geometric mean ratios were within 80%-125% for area under the concentration-time curve (AUC), but not for maximum plasma concentration (Cmax) for low-fat/low-calorie and high-fat/high-calorie meals versus fasting or for whole tablet with antacid versus whole tablet alone. The 90% confidence intervals of the geometric mean ratios for AUC and Cmax were within 80%-125% for crushed versus whole tablet. Maribavir median time to Cmax value in plasma under fed conditions was delayed versus fasting conditions, but there was no statistical difference for crushed versus whole tablet or with versus without antacid. As the antiviral efficacy of maribavir is driven by AUC but not Cmax, findings suggest that maribavir can be administered with food or antacids or as a crushed tablet.

Dynamic changes of DNA methylation induced by benzo(a)pyrene in cancer.

Benzo(a)pyrene (BaP), the earliest and most significant carcinogen among polycyclic aromatic hydrocarbons (PAHs), has been found in foods, tobacco smoke, and automobiles exhaust, etc. Exposure to BaP induced DNA damage directly, or oxidative stress-related damage, resulting in cell apoptosis and carcinogenesis in human respiratory system, digestive system, reproductive system, etc. Moreover, BaP triggered genome-wide epigenetic alterations by methylation, which might cause disturbances in regulation of gene expression, and thereby induced cancer. It has been proved that BaP reduced genome-wide DNA methylation, and activated proto-oncogene by hypomethylation in the promoter region, but silenced tumor suppressor genes by promoter hypermethylation, resulting in cancer initiation and progression. Here we summarized the changes in DNA methylation in BaP exposure, and revealed the methylation of DNA plays a role in cancer development.

Laboratory investigation on added-value application of the COVID-19 disposable mask in hot mix asphalt (HMA).

The outbreak of the COVID-19 pandemic has stimulated the demand for disposable masks to an unprecedented level, which also poses a significant risk to the natural environment from the improper treatment or disposal of waste masks. To lower such an environmental risk and maximize the added value of the waste masks, this paper proposed to recycle the waste mask fiber (MF) in combination with the waste cooking oil (WCO) for hot mix asphalt (HMA) application. A series of MF + WCO modified asphalt binders were first designed and fabricated. Their performance properties were then systematically measured. The physical-rheological test results showed that the incorporation of MF can significantly improve the high-temperature rutting resistance performance of asphalt binder. However, it may also lower the asphalt's low-temperature anti-cracking performance. The addition of WCO was found to compensate for this low-temperature performance loss effectively, and the MF5% + WCO3% was identified as the best combination. The Fourier transform infrared (FTIR) spectroscopy test results revealed that the asphalt modified by the MF + WCO involved only a physical modification. The performance test results indicated that the high-temperature permanent deformation resistance and low-temperature anti-cracking of MF5% + WCO3% modified HMA was greatly enhanced, while its moisture stability was slightly reduced but still met the specification requirement. The environmental benefit assessments proved that recycling the waste masks for asphalt paving can provide an enormous added value to pavement engineering in terms of carbon emission reduction and land resource saving.

Endothelial cell-derived exosomal circHIPK3 promotes the proliferation of vascular smooth muscle cells induced by high glucose via the miR-106a-5p/Foxo1/Vcam1 pathway.

The abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development and progression of diabetic vascular complications. In high-glucose (HG) conditions, endothelial cells (ECs) act as the first barrier to damaging stimuli and trigger a multi-response, including EC and VSMC crosstalk. However, the crosstalk pathways between ECs and VSMCs under HG conditions remain unclear. This study aimed to explore the roles and underlying mechanism of exosomes derived from ECs in the crosstalk between ECs and VSMCs. Our results showed that mouse aortic endothelial cell (MAEC)-secreted exosomes could promote the proliferation and inhibit the apoptosis of VSMCs induced by HG. Furthermore, we isolated the exosomes secreted by MAECs and found that exosomes derived from MAECs that were exposed to HG could transfer circHIPK3, which is enriched in MAEC-derived exosomes, to VSMCs. Exosomal circHIPK3 promoted the proliferation and inhibited the apoptosis of VSMCs. circHIPK3 sponged miR-106a-5p to relieve its repression of forkhead box O1 (Foxo1) expression. The increased expression of Foxo1 acted as a transcription factor to promote Vcam1 expression, thus facilitating the uptake of MAEC-derived exosomes by VSMCs. The results of this study suggested that exosomal circHIPK3 derived from MAECs promotes the proliferation of VSMCs induced by HG via the miR-106a-5p/Foxo1/Vcam1 pathway.

Effect of surgical versus medical therapy on estimated cardiovascular event risk among adolescents with type 2 diabetes and severe obesity.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of mortality in type 2 diabetes (T2D). Better interventions are needed to mitigate the high lifetime risk for CVD in youth T2D. OBJECTIVE: To compare 30-year risk for CVD events in 2 cohorts of adolescents with T2D and severe obesity undergoing medical or surgical treatment of T2D. SETTING: Longitudinal multicenter studies at University hospitals. METHODS: A secondary analysis of data collected from the participants with T2D enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS, n = 30) and participants of similar age and racial distribution from the Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY, n = 63) studies was performed. Teen-LABS participants underwent metabolic bariatric surgery (MBS). TODAY participants were randomized to metformin alone or in combination with rosiglitazone or intensive lifestyle intervention, with insulin therapy given for glycemic progression. A 30-year CVD event score developed by the Framingham Heart Study was the primary outcome, assessed at baseline (preoperatively for Teen-LABS), 1 year, and 5 years of follow-up. RESULTS: Participants with T2D from Teen-LABS (n = 30; mean ± SD age = 16.9 ± 1.3 yr; 70% female; 60% white; body mass index (BMI) = 54.4 ± 9.5 kg/m2) and TODAY (n = 63; 15.3 ± 1.3 yr; 56% female; 71% white; BMI 40.5 ± 4.9 kg/m2) were compared. The likelihood of CVD events was higher in Teen-LABS versus TODAY at baseline (17.66 [1.59] versus 12.11 [.79]%, adjusted P = .002). One year after MBS, event risk was significantly lower in Teen-LABS versus TODAY (6.79 [1.33] versus 13.64 [0.96]%, adjusted P < .0001), and sustained at 5 years follow-up (adjusted P < .0001). CONCLUSION: Despite higher pretreatment risk for CVD events, treatment with MBS resulted in a reduction in estimated CVD event risks, whereas medical therapy associated with an increase in risk among adolescents with T2D and severe obesity.

Thirty-Year Risk of Cardiovascular Disease Events in Adolescents with Severe Obesity.

OBJECTIVE: Quantifying risk for cardiovascular disease (CVD) events among adolescents is difficult owing to the long latent period between risk factor development and disease outcomes. This study examined the 30-year CVD event risk among adolescents with severe obesity treated with and without metabolic and bariatric surgery (MBS), compared with youths with moderate obesity, overweight, or normal weight. METHODS: Cross-sectional and longitudinal comparisons of five frequency-matched (age and diabetes status) groups were performed: normal weight (n = 247), overweight (n = 54), obesity (n = 131), severe obesity without MBS (n = 302), and severe obesity undergoing MBS (n = 215). A 30-year CVD event score developed by the Framingham Heart Study was the primary outcome. Data are mean (SD) with differences between time points for MBS examined using linear mixed models. RESULTS: Preoperatively, the likelihood of CVD events was higher among adolescents undergoing MBS (7.9% [6.7%]) compared with adolescents with severe obesity not referred for MBS (5.5% [4.0%]), obesity (3.9% [3.0%]), overweight (3.1% [2.4%]), and normal weight (1.8% [0.8%]; all P < 0.001). At 1 year after MBS, event risk was significantly reduced (7.9% [6.7%] to 4.0% [3.4%], P < 0.0001) and was sustained for up to 5 years after MBS (P < 0.0001, all years vs. baseline). CONCLUSIONS: Adolescents with severe obesity are at elevated risk for future CVD events. Following MBS, the predicted risk of CVD events was substantially and sustainably reduced.

Effect of Surgical Versus Medical Therapy on Diabetic Kidney Disease Over 5 Years in Severely Obese Adolescents With Type 2 Diabetes.

OBJECTIVE: To compare diabetic kidney disease (DKD) rates over 5 years of follow-up in two cohorts of severely obese adolescents with type 2 diabetes (T2D) undergoing medical or surgical treatment for T2D. RESEARCH DESIGN AND METHODS: A secondary analysis was performed of data collected from obese participants of similar age and racial distribution enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) and the Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY) studies. Teen-LABS participants underwent metabolic bariatric surgery (MBS). TODAY participants were randomized to metformin alone or in combination with rosiglitazone or intensive lifestyle intervention, with insulin therapy given for glycemic progression. Glycemic control, BMI, estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), and prevalence of hyperfiltration (eGFR ≥135 mL/min/1.73 m2) and elevated UAE (≥30 mg/g) were assessed annually. RESULTS: Participants with T2D from Teen-LABS (n = 30, mean ± SD age, 16.9 ± 1.3 years; 70% female; 60% white; BMI 54.4 ± 9.5 kg/m2) and TODAY (n = 63, age 15.3 ± 1.3 years; 56% female; 71% white; BMI 40.5 ± 4.9 kg/m2) were compared. During 5 years of follow-up, hyperfiltration decreased from 21% to 18% in Teen-LABS and increased from 7% to 48% in TODAY. Elevated UAE decreased from 27% to 5% in Teen-LABS and increased from 21% to 43% in TODAY. Adjusting for baseline age, sex, BMI, and HbA1c, TODAY participants had a greater odds of hyperfiltration (odds ratio 15.7 [95% CI 2.6, 94.3]) and elevated UAE (27.3 [4.9, 149.9]) at 5 years of follow-up. CONCLUSIONS: Compared with MBS, medical treatment of obese youth with T2D was associated with a higher odds of DKD over 5 years.

Fabrication of Large Single Crystals for Platinum-Based Linear Polymers with Controlled-Release and Photoactuator Performance.

Preparation of large single crystals of linear polymers for X-ray analysis is very challenging. Herein, we employ a coordination-driven self-assembly strategy to secure the appropriate head-to-tail alignment of anthracene moieties, and for the first time obtained large-sized Pt-based linear polymer crystals through a [4+4] cycloaddition of anthracene in a single-crystal to single-crystal fashion. Using X-ray diffraction to determine the polymer crystal structure, we found that both the polymerisation and depolymerisation steps proceed via a stable intermediate. Taking advantage of the temperature-dependent slow depolymerization, the Pt-based linear polymer showed potential as a sustained release anticancer drug platform. Utilizing the reversible contraction effect of unit-cell volume upon irradiation or heating, the stimuli-responsive crystals were hybridized with polyvinylidene fluoride to obtain a "smart material" with outstanding photoactuator performance.

Timing of Advanced Airway Placement after Witnessed Out-of-Hospital Cardiac Arrest.

Background: Advanced airways (endotracheal tubes, supraglottic airways) are frequently placed by Emergency Medical Services (EMS) in patients with out-of-hospital cardiac arrest (OHCA). However, if an airway is to be placed, it is unknown whether this should occur early or late in the sequence of resuscitation events. This study evaluated the association between the timing of airway placement and the minute-to-minute probability of achieving return of spontaneous circulation (ROSC). Methods: This secondary analysis of Resuscitation Outcomes Consortium Prehospital Resuscitation using an Impedance Valve and Early versus Delayed (ROC PRIMED) study data included adult, non-traumatic, witnessed OHCA patients with airway placement by EMS before ROSC. The primary exposure variable was time from EMS arrival to advanced airway placement. The outcome was prehospital ROSC. Since resuscitations occur over time, a Cox proportional hazards model was fit to estimate the probability of ROSC as a function of the airway timing, adjusting for Utstein variables. Results: A total of 7,547 patients were included. Time to airway placement was 0-5 minutes in 12% of the cohort, >5-10 (36%), >10-15 (29%), >15-20 (14%), >20-25 (5%), >25-30 (2%), and >30 (2%). ROSC occurred in 43%. Time to airway had a statistically significant impact on ROSC. A negative association between the time to airway placement and the hazard of ROSC was observed, such that increasing intervals between EMS arrival and airway placement were associated with decreasing probabilities of ROSC, regardless of initial cardiac rhythm. Conclusions: EMS advanced airway placement has a time-dependent association with ROSC. In witnessed OHCA patients receiving advanced airways, early airway placement is associated with increased probability of ROSC.

Photomechanical Organic Crystals as Smart Materials for Advanced Applications.

Photomechanical molecular crystals are receiving much attention due to their efficient conversion of light into mechanical work and advantages including faster response time; higher Young's modulus; and ordered structure, as measured by single-crystal X-ray diffraction. Recently, various photomechanical crystals with different motions (contraction, expansion, bending, fragmentation, hopping, curling, and twisting) are appearing at the forefront of smart materials research. The photomechanical motions of these single crystals during irradiation are triggered by solid-state photochemical reactions and accompanied by phase transformation. This Minireview summarizes recent developments in growing research into photoresponsive molecular crystals. The basic mechanisms of different kinds of photomechanical materials are described in detail; recent advances in photomechanical crystals for promising applications as smart materials are also highlighted.

Speech Situation Checklist-Revised: Investigation With Adults Who Do Not Stutter and Treatment-Seeking Adults Who Stutter.

PURPOSE: The aim of this study was to evaluate the usefulness of the Speech Situation Checklist for adults who stutter (SSC) in differentiating people who stutter (PWS) from speakers with no stutter based on self-reports of anxiety and speech disruption in communicative settings. The SSC's psychometric properties were examined, norms were established, and suggestions for treatment were formulated. METHOD: The SSC was administered to 88 PWS seeking treatment and 209 speakers with no stutter between the ages of 18 and 62. The SSC consists of 2 sections investigating negative emotional reaction and speech disruption in 38 speech situations that are identical in both sections. RESULTS: The SSC-Emotional Reaction and SSC-Speech Disruption data show that these self-report tests differentiate PWS from speakers with no stutter to a statistically significant extent and have great discriminative value. The tests have good internal reliability, content, and construct validity. Age and gender do not affect the scores of the PWS. CONCLUSIONS: The SSC-Emotional Reaction and SSC-Speech Disruption seem to be powerful measures to investigate negative emotion and speech breakdown in an array of speech situations. The item scores give direction to treatment by suggesting speech situations that need a clinician's attention in terms of generalization and carry-over of within-clinic therapeutic gains into in vivo settings.

Identifying the readiness of patients in implementing telemedicine in northern Louisiana for an oncology practice.

This study identified the readiness factors that may create challenges in the use of telemedicine among patients in northern Louisiana with cancer. To identify these readiness factors, the team of investigators developed 19 survey questions that were provided to the patients or to their caregivers. The team collected responses from 147 respondents from rural and urban residential backgrounds. These responses were used to identify the individuals' readiness for utilising telemedicine through factor analysis, Cronbach's alpha reliability test, analysis of variance and ordinary least squares regression. The analysis results indicated that the favourable factor (positive readiness item) had a mean value of 3.47, whereas the unfavourable factor (negative readiness item) had a mean value of 2.76. Cronbach's alpha reliability test provided an alpha value of 0.79. Overall, our study indicated a positive attitude towards the use of telemedicine in northern Louisiana.

Estimating the Net Career Income of a Geriatrician and a Nurse Practitioner: Still Want to Be a Doctor?

OBJECTIVES: With a continual shortage of geriatricians, adult-gerontology primary care nurse practitioners have assumed a greater role in the delivery of outpatient care for older adults. Given the long duration of physician training, the high cost of medical school, and the lower salaries compared with subspecialists, the financial advantage of a career as a geriatrician as opposed to a nurse practitioner is uncertain. This study compares the estimated career earnings of a geriatrician and an adult-gerontology primary care nurse practitioner. METHODS: We used a synthetic model of estimated net earnings during a 43-year career span for a 22-year old person embarking on a career as a geriatrician versus a career as an adult-gerontology primary care nurse practitioner. We estimated annual net income and net retirement savings using different annual compound rates and calculated the financial impact of forgiving medical student loans, shortening the duration of physician training, and reinstituting the practice pathway for geriatric medicine certification. RESULTS: Career net incomes for the geriatrician did not match the nurse practitioner until almost age 40. At 65 years of age, the difference between the geriatrician and nurse practitioner was 30.6%. A higher annual compound rate was associated with an even smaller percentage difference. Combining all three health policy interventions lowered the break-even age to 28 and more than doubled the difference in career earnings. CONCLUSIONS: Small estimated differences in net career earnings exist between geriatricians and adult-gerontology primary care nurse practitioners. Health policy interventions had a dramatic positive effect on geriatricians' lifetime net earnings in calculated estimates.

Copper-catalyzed alkyne-aryne and alkyne-alkene-aryne coupling reactions.

The efficient copper-catalyzed two-component coupling reaction of alkynes with arynes and the three-component coupling reaction of alkynes with allylic chlorides and arynes have been developed. Copper acetylide was postulated as a transient intermediate for the initiation of the coupling reactions.

Synthesis of indolo[1,2-f]phenanthridines from palladium-catalyzed reactions of arynes.

A novel convenient approach for the construction of indolo[1,2-f]phenanthridine was developed from the reaction of arynes with 1-(2-bromophenyl)-1H-indole in the presence of palladium catalyst.