Gender differences in the associations between body mass index, depression, anxiety, and stress among endocrinologists in China.

BACKGROUND: Depression, anxiety, and stress symptoms have been found to be associated with overweight or obesity, but the gender differences in the associations have not been well-examined. Based on a national sample of endocrinologists in China, we examined such associations with a focus on gender differences. METHODS: Data were collected from endocrinologists in China using an online questionnaire, which included demographic data, body weight, and height. Depression, anxiety, and stress symptoms were assessed using the Depression, Anxiety, and Stress Scale-21 (DASS-21). RESULTS: In total, 679 endocrinologists (174 males and 505 females) completed the survey. One-fourth (25.6%) were classified as overweight, with a significant gender difference (48.9% in males vs. 17.6% in females, p < 0.05). Overall, 43.4% of the participants endorsed probable depressive symptoms (54.6% in males and 39.6% in females, p = 0.004), 47.6% for anxiety (51.7% in males vs. 46.1% in females, p = 0.203), and 29.6% for stress symptoms (34.5% in males vs. 27.92% in females, p = 0.102). After controlling for confounders, in the whole group, male gender (aOR = 4.07, 95% CI:2.70-6.14, p < 0.001), depression (aOR = 1.05, 95% CI:1.00-1.10, p = 0.034) and age (aOR = 1.03, 95% CI:1.00-1.05, p = 0.018) were positively associated with overweight. In males, depression (aOR = 1.14, 95% CI:1.05-1.25, p = 0.002), administration position (aOR = 4.36, 95% CI:1.69-11.24, p = 0.002), and night shifts/month (aOR = 1.26, 95% CI:1.06-1.49, p = 0.008) were positively associated with overweight, while anxiety (aOR = 0.90, 95% CI:0.82-0.98, p = 0.020) was negatively associated with overweight. In females, only age (aOR = 1.04, 95% CI:1.01-1.07, p = 0.014) was significantly associated with overweight status, while depression and anxiety were not associated with overweight. Stress symptoms were not associated with overweight in either gender. CONCLUSIONS: One-fourth of endocrinologists in China are overweight, with a rate in males nearly triple the one in females. Depression and anxiety are significantly associated with overweight in males but not females. This suggests possible differences in the mechanism. Our findings also highlight the need to screen depression and overweight in male physicians and the importance of developing gender-specific interventions.

Application of a high-resolution in vitro human MDR1-MDCK assay and in vivo studies in preclinical species to improve prediction of CNS drug penetration.

P-glycoprotein (P-gp, MDR1) is expressed at the blood-brain barrier (BBB) and restricts penetration of its substrates into the central nervous system (CNS). In vitro MDR1 assays are frequently used to predict the in vivo relevance of MDR1-mediated efflux at the BBB. It has been well established that drug candidates with high MDR1 efflux ratios (ERs) display poor CNS penetration. Following a comparison of MDR1 transporter function between the MDR1-MDCKI cell line from National Institutes of Health (NIH) and our internal MDR1-MDCKII cell line, the former was found to provide better predictions of in vivo brain penetration than our in-house MDR1-MDCKII cell line. In particular, the NIH MDR1 assay has an improved sensitivity to differentiate the compounds with ERs of <3 in our internal cell line and is able to reduce the risk of false negatives. A better correlation between NIH MDR1 ERs and brain penetration in rat and non-human primate (NHP) was demonstrated. Additionally, a comparison of brain penetration time course of MDR1 substrates and an MDR1 non-substrate in NHP demonstrated that MDR1 interaction can delay the time to equilibrium of drug concentration in the brain with plasma. It is recommended to select highly permeable compounds without MDR1 interaction for rapid brain penetration to produce the maximal pharmacological effect in the CNS with a quicker onset.

The Study of Enteromorpha-Based Reinforcing-Type Flame Retardant on Flame Retardancy and Smoke Suppression of EPDM.

Enteromorpha, as a waste from marine pollution, brings great pressure to environmental governance every year, especially for China. Under the premise of a shortage of industrial materials, taking appropriate measures can turn waste into wealth, which will benefit us a lot. In this work, a bio-based reinforcing-type flame retardant based on Enteromorpha is designed. The designed Enteromorpha-based flame retardant system (AEG) mainly focuses on the reinforcing and flame retardant effects on ethylene-propylene-diene tripolymer (EPDM). For the AEG system, ammonium polyphosphate (APP) serves as both the acid source and the gas source; the simple hybrid material (GN) produced by loading graphene (GE) and Enteromorpha (EN) using tannic acid (TA) as a regulator serves as an acid source and a carbonizing source. The results show that when 40 phr AEG is added, the LOI of EPDM/AEG40 reaches 32.5% and the UL-94 reaches the V-0 level. The PHRR and THR values of EPDM/AEG40 are 325.9 kW/m2 and 117.6 MJ/m2, respectively, with decrements of 67.3% and 29.7%, respectively, compared with the results of neat EPDM composite. Especially, the TSP and TSR values of EPDM/AEG40 are reduced from 15.2 m2 of neat EPDM to 9.9 m2 with a decrement of 34.9% and reduced from 1715.2 m2/m2 of neat EPDM to 1124.5 m2/m2 with a decrement of 34.4%, indicating that AEG is effective in flame retardancy and smoke suppression. Meanwhile, the tensile strength and tear strength of EPDM/AEG composites are much higher than neat EPDM, therefore, with the future development of innovate reinforcing-type flame-retardant Enteromorpha, the application of Enteromorpha in the polymer flame-retardant field will surely usher in bright development.

Synergistic Fire Hazard Effect of a Multifunctional Flame Retardant in Building Insulation Expandable Polystyrene through a Simple Surface-Coating Method.

This work reports a strategy based on γ-aminopropyltriethoxysilane (KH550) and graphene oxide (GO)-functionalized 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) to fabricate P-N-Si integrated flame retardant [KDOPO-modified GO (DGO)] through mild Mannich and Silanization reactions to overcome the challenge of single gas-phase fire retardancy of DOPO. DGO-based phenolic epoxy resin (DGO/PER) is manufactured and coated on the surface of expandable polystyrene (EPS) foam plates to achieve fire safety, which is used as the thermally insulating external wall in buildings and constructions. The DGO/PER paintcoat imparts high fire safety to the EPS foam plate, exhibiting a high limiting oxygen index value of 29%, and a UL-94 V-0 classification is achieved with only 300 µm of layer thickness compared with the DOPO/PER paintcoat. Meanwhile, all combustion parameters such as peak heat release rate, heat release rate, total heat release, smoke release rate, total smoke rate, and ignition time present excellent promotions for EPS@DGO compared with EPS@DOPO. These dramatically reduced fire hazards are mainly attributed to the synergistic effects of DGO. Meanwhile, the DGO/PER flame-retardant paintcoat cannot deteriorate the thermal insulation performance of the EPS foam plate.

In utero and postnatal VX-770 administration rescues multiorgan disease in a ferret model of cystic fibrosis.

Cystic fibrosis (CF) is a multiorgan disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). In patients with CF, abnormalities initiate in several organs before birth. However, the long-term impact of these in utero pathologies on disease pathophysiology is unclear. To address this issue, we generated ferrets harboring a VX-770 (ivacaftor)-responsive CFTR G551D mutation. In utero VX-770 administration provided partial protection from developmental pathologies in the pancreas, intestine, and male reproductive tract. Homozygous CFTR G551D/G551D animals showed the greatest VX-770-mediated protection from these pathologies. Sustained postnatal VX-770 administration led to improved pancreatic exocrine function, glucose tolerance, growth and survival, and to reduced mucus accumulation and bacterial infections in the lung. VX-770 withdrawal at any age reestablished disease, with the most rapid onset of morbidity occurring when withdrawal was initiated during the first 2 weeks after birth. The results suggest that CFTR is important for establishing organ function early in life. Moreover, this ferret model provides proof of concept for in utero pharmacologic correction of genetic disease and offers opportunities for understanding CF pathogenesis and improving treatment.

Pharmacokinetic and Drug-Drug Interaction Profiles of the Combination of Tezacaftor/Ivacaftor.

Drug-drug interaction (DDI) studies are described for tezacaftor/ivacaftor, a new cystic fibrosis transmembrane conductance regulator modulator therapy for the treatment of cystic fibrosis. Three phase I DDI studies were conducted in healthy subjects to characterize the DDI profile of tezacaftor/ivacaftor with cytochrome P450 (CYP)3A substrates, CYP3A inhibitors, and a permeability glycoprotein (P-gp) substrate. The effects of steady-state tezacaftor/ivacaftor on the pharmacokinetics (PKs) of digoxin (a P-gp substrate), midazolam, and ethinyl estradiol/norethindrone (CYP3A substrates) were evaluated. Effects of strong (itraconazole) and moderate (ciprofloxacin) CYP3A inhibitors on tezacaftor/ivacaftor PKs were also determined. Tezacaftor/ivacaftor increased digoxin area under the curve (AUC) by 30% but did not affect midazolam, ethinyl estradiol, or norethindrone exposures. Itraconazole increased the AUC of tezacaftor 4-fold and ivacaftor 15.6-fold. Ciprofloxacin had no significant effect on tezacaftor or ivacaftor exposure. Coadministration of tezacaftor/ivacaftor may increase exposure of sensitive P-gp substrates. Tezacaftor/ivacaftor is unlikely to impact exposure of drugs metabolized by CYP3A, including hormonal contraceptives. Strong CYP3A inhibitors significantly increase the exposures of tezacaftor and ivacaftor.

Lubrication and plasticization behavior of large-size micro-spherical structured SiO2 for natural rubber.

In many rubber dynamic applications such as tires and seals, imparting excellent flex fatigue properties and processing behavior are of prime importance. Research in this direction has been done based on a judicious choice of polymer type or a blend thereof and the compounding ingredients. In this study, the effect of micro-spherical SiO2 on the flex fatigue properties and processing behavior of natural rubber (NR) is studied. Two different particle sizes of spherical SiO2 (N90, average diameter: 200 nm and N98, average diameter: 120 nm) were used to optimize the flex fatigue properties and processing behavior, and the mechanism is investigated. In this blend, 5 phr loading of N90 was effective in imparting the best overall combination of properties. This work was aimed at providing some theoretical basis and application basis for the use of micro-spherical SiO2 in the rubber industry.