Assessment of toxic mechanisms and mode of action to three different levels of species for 14 antibiotics based on interspecies correlation, excess toxicity, and QSAR.

Antibiotics have received much attention owing to their ecotoxicity toward nontarget aquatic creatures. However, the mode of action (MOA) of toxicity against nontarget organisms is unclear in some aquatic organisms. In this study, the comparison of toxicities through interspecies correlations, excess toxicity calculated from toxicity ratio, and quantitative structure-activity relationship (QSAR) was carried out to investigate the MOAs for 14 antibiotics among Daphnia magna, Vibrio fischeri, and Pseudokirchneriella subcapitata. The results showed that interspecies toxicity correlations were very poor between any two of the three species for the 14 antibiotics. The toxicity ratio revealed that most antibiotics exhibited excess toxicity to algae and Daphnia magna but not to V. fischeri, demonstrating that some antibiotics share the same MOA, but some antibiotics share different MOAs among the three different levels of species. P. subcapitata was the most sensitive species, and V. fischeri was the least sensitive species. This is because of the differences in the biouptake and interactions of antibiotics with the target receptors between the three different trophic levels of the species. Molecular docking simulations suggested that the toxicity of antibiotics depends highly on their interactions with target receptors through hydrogen bonds, electrostatic or polar interactions, π bond interactions, and van der Waals forces. QSAR models demonstrated that hydrogen bonding and electrophilicity/nucleophilicity play key roles in the interaction of antibiotics with different receptors in the three species. The toxic mechanisms of antibiotics are attributed to the interactions between electrophilic antibiotics and biological nucleophiles, and hydrogen-bond interactions. These results are valuable for understanding the toxic mechanisms and MOA of the three different levels of species.

[Assessment of cognitive function of the elderly by serum metabolites of brain-gut axis].

Objective: To investigate the feasibility of assessing cognitive function of the elderly by serum metabolites of brain-gut axis. Methods: Convenience sampling was used to select 100 and 60 participants from the healthy population cohort and microecological balance cohort of the longevity population in Guangxi, to constitute subset of healthy population and longevity population, respectively. A questionnaire was used to investigate the demographic characteristics of the subjects, 2-5 ml of fasting venous blood was collected from the subjects, and the serum untargeted metabolomics was determined by liquid chromatography tandem mass spectrometry. The biomarkers related to the brain-gut axis were collected through literature retrieval, and the results were intersected with the untargeted metabolites and annotated. Spearman correlation analysis was used to screen serum metabolites of brain-gut axis associated with aging, and multiple linear regression method was used to construct biological age model. The mini mental status examination was used to evaluate the cognitive function of longevity population subsets. The differences of biological age and chronological age of longevity population subsets with different cognitive function were compared. Results: The M (Q1, Q3) of subset of healthy population and longevity population were 64 (38, 72) and 97 (95, 99) years old, respectively, and there were 50 (50.0%) and 44 (73.3%) females, respectively. Nine serum metabolites of brain-gut axis were obtained by initial screening, which were propionic acid, glutamic acid, γ-aminobutyric acid (GABA), lactic acid, 5-hydroxytryptamine (5-HT), tryptophan, trimethylamine oxide, dopamine and canine urea. Spearman correlation analysis showed that glutamic acid and dopamine were positively correlated with aging (r values were 0.208 and 0.524, respectively, all P values<0.05), and tryptophan, 5-HT and GABA were negatively correlated with aging (r values were -0.308, -0.533 and -0.213, respectively, all P values<0.05). The biological age model was constructed as: y=49.81-1.18×10-5× GABA-1.82×10-4×5-HT+1.99×10-3×dopamine+1.65×10-6×glutamic acid -2.04×10-6×tryptophan+2.36×gender, where y was the biological age (years), the items on the right were the intercept item, the relative concentration of each metabolite, and gender (male=1, female=2). The coefficient of determination of model was 0.50 (P<0.001). The M (Q1, Q3) of the chronological age of the subset of longevity population with poor, moderate and good cognitive function were 97 (94, 100), 97 (93, 101) and 96 (94, 101) years old, respectively, and there was no statistical significance in pairwise comparison (all P values>0.05). The M (Q1, Q3) of the biological age of the subjects with better cognitive function was 51 (38, 54) years old, which was lower than that of the subjects with poor cognitive function [57 (47, 61)] (P=0.040). Conclusion: The biological age model can be constructed based on serum metabolites of brain-gut axis and used to evaluate the cognitive function of the elderly.

Behavioral and developmental toxicity assessment of the strobilurin fungicide fenamidone in zebrafish embryos/larvae (Danio rerio).

Strobilurin fungicides are among the most widely used in the world and have characteristics that include high water solubility and toxicity to aquatic organisms. While several studies report on mechanisms of toxicity of strobilurins in fish, there are no data on the sub-lethal toxicity of fish to the fungicide fenamidone. To address this gap, survival and hatch rate, deformities, mitochondrial bioenergetics, expression of oxidative stress and apoptotic genes, and behavior (locomotor activity and anxiolytic-related behaviors) were assessed in zebrafish embryos and larvae following exposure to fenamidone. Fenamidone negatively affected development of zebrafish embryos, causing a delay of hatching time at concentrations of 2.5 and 5 µM. Fenamidone caused morphological deformities in zebrafish, including pericardial edema, yolk sac edema, tail deformities, and spinal curvature. Exposure to 1.5 µM fenamidone reduced surface area of swim bladder in larvae at 6 dpf. Fenamidone significantly reduced oxygen consumption rates of embryos; 5 µM fenamidone decreased basal respiration (~85%), oligomycin induced ATP-linked respiration (~70%), FCCP-induced maximal respiration (~75%) and non-mitochondrial respiration (~90%) compared to controls. Sod2 mRNA levels were decreased by fenamidone in larval fish. Locomotor activity was significantly decreased in zebrafish larvae following exposure to 2 µM fenamidone but there was no evidence for anxiolytic nor anxiety-related behaviors (exposures of 100 nM up to 1.5 µM). This study addresses a data gap for potential risks associated with fenamidone exposure in developing fish.

Use of dynamic contrast-enhanced MRI for the early assessment of outcome of CyberKnife stereotactic radiosurgery for patients with spinal metastases.

AIM: To explore the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for evaluating early outcomes of CyberKnife radiosurgery for spinal metastases. MATERIALS AND METHODS: Patients with spinal metastases who were treated with CyberKnife radiosurgery from July 2018 to December 2020 were enrolled. Conventional MRI and DCE-MRI were performed before treatment and at 3 months after treatment. Patients showing disease progression were defined as the progressive disease (PD) group and those showing complete response, partial response, and stable disease were defined as the non-PD group. The haemodynamic parameters (volume transfer constant [Ktrans], rate constant [Kep], and extravascular space [Ve]) before and after treatment between the groups were analysed. Area under the curve (AUC) values were calculated. RESULTS: A total of 27 patients with 39 independent spinal lesions were included. The median follow-up time was 18.6 months (6.2-36.4 months). There were 27 lesions in the non-PD group and 12 lesions in the PD group. Post-treatment Kep, ΔKtrans and ΔKep in the non-PD group (0.959/min, - 32.6% and -41.1%, respectively) were significantly lower than the corresponding values in PD group (1.429/min, 20.4% and -6%; p<0.05). Post-treatment Ve and ΔVe (0.223 and 27.8%, respectively) in the non-PD group were significantly higher than that of the PD group (0.165 and -13.5%, p<0.05). ΔKtrans showed the highest diagnostic efficiency, with an AUC of 0.821. CONCLUSIONS: DCE-MRI parameters change significantly at an early stage after CyberKnife stereotactic radiosurgery for spinal metastases. DCE-MRI may be of value in determining the early treatment response.

Attitudes Toward Living Organ Donation and Willingness to Be a Living Organ Donor Among Chinese Citizens in 3 Cities.

OBJECTIVE: The level of awareness of living organ donation demonstrated by citizens may affect the rate of organ transplantation in their area of residence. The objective of this study was to assess the attitudes toward living organ donation and willingness to be a living organ donor among Chinese citizens. METHODS: The study population consisted of 2250 citizens in Beijing, Shanghai, and Wuhan. Data were collected using a questionnaire developed by the researchers based on the existing literature and expert opinions. The questionnaire included questions designed to assess demographics, attitudes, and willingness. The data were analyzed using SPSS 22.0 software. RESULTS: Overall, 2198 citizens completed the questionnaire, of whom 845 (38.4%) supported living organ donation; however, only 213 (9.6%) participants were supportive of their family members donating living organs. A total of 424 (19.3%) citizens were willing to be living organ donors. Of the respondents, 1173 (53.4%) were neutral toward living organ donation and 1463 (66.6%) were undecided about their willingness to donate. In addition, willingness was positively correlated with age, education level, income, marital status, and having descendants (P < .05). Those who had relatives or friends who had undergone organ transplantation were significantly more likely to be donors than those who did not (P < .05). CONCLUSIONS: The results of our study suggest that Chinese citizens lack an understanding of living organ transplantation, indicating that more work needs to be done to inform the public about organ transplantation in China.

High-throughput assessment of oxidative respiration in fish embryos: Advancing adverse outcome pathways for mitochondrial dysfunction.

Mitochondrial dysfunction is a prevalent molecular event that can result in multiple adverse outcomes. Recently, a novel high throughput method to assess metabolic capacity in fish embryos following exposure to chemicals has been adapted for environmental toxicology. Assessments of oxygen consumption rates using the Seahorse XF(e) 24/96 Extracellular Flux Analyzer (Agilent Technologies) can be used to garner insight into toxicant effects at early stages of development. Here we synthesize the current state of the science using high throughput metabolic profiling in zebrafish embryos, and present considerations for those wishing to adopt high throughput methods for mitochondrial bioenergetics into their research. Chemicals that have been investigated in zebrafish using this metabolic platform include herbicides (e.g. paraquat, diquat), industrial compounds (e.g. benzo-[a]-pyrene, tributyltin), natural products (e.g. quercetin), and anti-bacterial chemicals (i.e. triclosan). Some of these chemicals inhibit mitochondrial endpoints in the µM-mM range, and reduce basal respiration, maximum respiration, and spare capacity. We present a theoretical framework for how one can use mitochondrial performance data in zebrafish to categorize chemicals of concern and prioritize mitochondrial toxicants. Noteworthy is that our studies demonstrate that there can be considerable variation in basal respiration of untreated zebrafish embryos due to clutch-specific effects as well as individual variability, and basal oxygen consumption rates (OCR) can vary on average between 100 and 300 pmol/min/embryo. We also compare OCR between chorionated and dechorionated embryos, as both models are employed to test chemicals. After 24 h, dechorionated embryos remain responsive to mitochondrial toxicants, although they show a blunted response to the uncoupling agent carbonylcyanide-4-trifluoromethoxyphenylhydrazone (FCCP); dechorionated embryos are therefore a viable option for investigations into mitochondrial bioenergetics. We present an adverse outcome pathway framework that incorporates endpoints related to mitochondrial bioenergetics. High throughput bioenergetics assays conducted using whole embryos are expected to support adverse outcome pathways for mitochondrial dysfunction.

Quantitative assessment of the relationship between radiant heat exposure and protective performance of multilayer thermal protective clothing during dry and wet conditions.

The beneficial effect of clothing on a person is important to the criteria for people exposure to radiant heat flux from fires. The thermal protective performance of multilayer thermal protective clothing exposed to low heat fluxes during dry and wet conditions was studied using two designed bench-scale test apparatus. The protective clothing with four fabric layers (outer shell, moisture barrier, thermal linear and inner layer) was exposed to six levels of thermal radiation (1, 2, 3, 5, 7 and 10kW/m(2)). Two kinds of the moisture barrier (PTFE and GoreTex) with different vapor permeability were compared. The outside and inside surface temperatures of each fabric layer were measured. The fitting analysis was used to quantitatively assess the relationship between the temperature of each layer during thermal exposure and the level of external heat flux. It is indicated that there is a linear correlation between the temperature of each layer and the radiant level. Therefore, a predicted equation is developed to calculate the thermal insulation of the multilayer clothing from the external heat flux. It can also provide some useful information on the beneficial effects of clothing for the exposure criteria of radiant heat flux from fire.

Assessment of trans fatty acids content in popular Western-style products in China.

To date, the published information on trans fatty acids (TFAs) in food products in China remains scarce and of questionable accuracy. Systematic approaches to educate the consumers and to ensure proper labeling of TFAs are among the many urgent challenges the regulatory agencies in this rapidly growing country have to face. In the present study, 97 most popular, national brand food products on the Chinese market, including 6 cheeses, 10 chocolates, 10 crisps, chips, and fries, 10 ice creams, 15 margarines, 10 pies and cakes, 8 sauces and dressings, 19 wafers and biscuits, and 9 Chinese-style snacks, were assayed to profile their fat content and fatty acid composition, particularly the TFAs. The highest level of TFAs, up to 30.9% of total fatty acids, were found in pies. The average TFAs contents in different product categories, ranging from high to low, were: pie and cake (12.07%), cheese (6.95%), margarine (5.09%), wafer and biscuit (4.35%), ice cream (2.67%), sauce and dressing (2.65%), crisps, chips, and fries (2.15%), chocolate (1.44%), and Chinese-style snacks (0.83%). One hundred percent of cheese contained TFAs, so did pie and cake, followed by crisps, chips, and fries (90%), sauce and dressing (88%), ice cream and margarine (80%), chocolate (60%), wafer and biscuit (53%), then Chinese-style snacks (33%). Profiling of key TFAs constituents could yield information characteristic to the types of partially hydrogenated oils employed, which is a critical step towards product reformulation in order to reduce or eliminate TFAs in the products.

Determination of McGowan volumes for ions and correlation with van der Waals volumes.

The McGowan volume has been widely used for the analysis of physicochemical and biochemical properties in chemistry and drug industry. Because McGowan volumes are not available for ions, its application is limited to only neutral compounds. Pauling radii of metallic ions have been collected and studied to obtain McGowan volumes for ions. Regression analysis was carried out between Pauling radii (R(p)) and McGowan radii (R(x)) for a wide range of compounds. It was found that Pauling radii and McGowan radii derived from McGowan volumes by using a volume-radius formula are linearly related (R(x) = 1.115R(p) + 0.0623, r(2) = 0.995). This equation is then used to calculate McGowan volumes for various ions and charged groups. McGowan volumes have been calculated for inorganic, organic, and organometallic compounds and correlated with van der Waals volumes. Results show that McGowan volumes (V(x)) are entirely equivalent to computer-calculated van der Waals volumes.

Clinical trials in Alzheimer's disease. Calculating Alzheimer's Disease Assessment Scale-cognitive subsection with the data from the consortium to establish a registry for Alzheimer's disease.

The database of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is a seminal work in the field of cognitive dysfunction and Alzheimer's disease. This 24-center study of 1,094 patients with Alzheimer's disease who received no treatment for their cognitive dysfunction and 463 normal control subjects is rich in neurobehavioral data and contains extensive imaging and neuropathologic findings. However, the Alzheimer's Disease Assessment Scale (ADAS) was not administered as part of the CERAD study, which limits the study's applicability to modern drug trials, in which the ADAS-cognitive subsection (ADAS-cog) is a popular end point. The purpose of this investigation was to develop a derived ADAS-cog score from the neurobehavioral data obtained from subjects during their evaluation in the CERAD study. Two calculated ADAS-cog scores were developed. The first was based on clinically mapping the items on the ADAS-cog to assessments that were performed in the CERAD study. The second was based on rescaling the Mini-Mental Status Exam (MMSE), using published results correlating the ADAS-cog to the MMSE. Standard characteristics of both calculated ADAS-cog scores were calculated and compared with each other and with the literature. Both calculated ADAS-cog scores performed comparably to published characteristics of the ADAS-cog. The clinically based calculated ADAS-cog outperformed the rescaled MMSE. Using the CERAD database, it is now possible to model the progression of an untreated (placebo) population of patients with Alzheimer's disease and correlate it to a study using ADAS-cog.

Demographic differences in body composition of Navy and Marine Corps personnel: findings from the perception of wellness and readiness assessment.

With the recent increase in women's representation in the military, baseline physical measurement data are needed to help set appropriate accession and retention standards and to design useful prevention and intervention programs in the areas of physical fitness and health. This study incorporated several body composition indices to obtain anthropometric data for a representative sample of 1,292 active duty Navy and Marine Corps women and men. It also assessed the extent to which personnel met weight-for-height and body fat standards. The prevalence of overweight was considerably lower among Marine Corps women compared with Navy women and was slightly less for Marine Corps men compared with their Navy counterparts. Between one-fifth and one-third of military personnel exceeded Navy/Marine Corps weight-for-height standards. Navy women tended to meet weight standards more often than Navy men. Fewer Marine Corps women than men were overweight, but more exceeded their weight-for-height standards.

The mental health status of women in the Navy and Marine Corps: preliminary findings from the Perceptions of Wellness and Readiness Assessment.

The 1995 Perceptions of Wellness and Readiness Assessment was designed to provide baseline health and risk-factor information on the physical and mental health status of women in the U.S. Navy and Marine Corps and to make comparisons both within military subpopulations and with civilian populations. A population-based, multi-stage, cluster sample of 782 active duty Navy and Marine Corps women and men were administered a structured computerized telephone interview to make Diagnostic and Statistical Manual-III-R psychiatric diagnoses. Estimates were 40 and 21% for overall lifetime and 1-year prevalence of psychiatric disorders, respectively. Women had about five times the risk of experiencing post-traumatic stress disorder than men and about twice the risk of a major depressive episode. Of all personnel meeting diagnostic criteria for an active mental disorder, only 19% sought mental health care in the last year. Women generally sought treatment more readily than men.

[Pulsed Doppler echocardiography assessment of acute hemodynamic effects of nifedipine on pulmonary hypertension in chronic obstructive lung disease].

To observe acute hemodynamic effects of pulmonary hypertension in chronic obstructive lung disease by nifedipine, we studied 16 patients with pulsed doppler ultrasound. Pulsed doppler ultrasonogram was employed to measure hemodynamic parameters before and 45 minutes after nifedipine 20 mg (give po) in 16 patients. Results indicate that PAMP decreased significantly (P less than 0.01) from 5.5 +/- 1.6 to 4.0 +/- 1.5 kPa. We conclude that nifedipine reduces pulmonary artery pressure, at least acutely, in patients with hypoxic pulmonary hypertension.

The feasibility of population migration from arid mountainous areas of Central Gansu to the oasis west of the Yellow River in the province.

PIP: This article on population migration from Central Gansu, China, which is made up of 18 impoverished counties in Dingxi Region, to Hexi in the Yellow River Valley focuses on the basic mechanisms and characteristics of population migration, the effects of migration on adaptability, the return rate, and the socioeconomic and ecological benefits of migration. Analysis is based on logical deduction and empirical evidence. The reasons for migration are poverty and unchecked population growth. Population in Central Gansu doubled (110.1%) between 1952-83, while the population in the province increased 86.67% and in the country 83.52%. Per capita grain allocations in Dingxi and the marginal utility of agricultural production declined. Population pressure led to short supplies of food and fuel and excessive land reclamation, which produced soil erosion, and a downward spiral. Migrants were attracted to Hexi because of favorable farming conditions and a developed economy. Subsidies were used to encourage people to migrate voluntarily. 31,485 people migrated to the Hexi Corridor in 1988. 4450 came from Huining County and 3743 from Dingxi. Most went to Jiuquan (17,490 people), and 7,357 migrated to Zhongye, both areas with good irrigation facilities. 78.33% of the migrants were individually placed and 21.67% were placed as groups in "hanging" villages of 320/village. The inter-regional migration rate was 85.27% between 1983-86 in Jiuquan region, or 14,000 people. Migrants found their living conditions to be greatly improved. Per capita income increased 12.8 times from 497.5 yuan in 1983, while the income of nonmigrants underwent only a 4.45-fold increase. There were also differences in grain allocation. Jiuquan had a low return migration rate of 14.73% between 1983-86. Variations occur from region to region due to excessive economic disparity, incomplete basic facilities, and forced group migration. The annual yield of investment in migration was 19.87%, which makes the investment recoverable in 5 years, and migrants contributed to a reduction of grain resold by the state and a better solution to the grain ration problem. Individual investment could be recovered in 2.6 years. The ecological benefit is that the steep slopes unsuitable for farming could be returned to forest and pasture land. Future efforts will be made to determine the carrying capacity of Hexi and the extent of migration necessary to alleviate poverty in central Gansu.^ieng

Rehabilitation of the patient with chronic back pain. A search for outcome predictors.

This prospective study was initiated 3 years ago to evaluate the outcome and to identify predictors of success or failure in patients admitted to a rehabilitation program for chronic low-back pain. Multiple parameters were evaluated, including psychologic data (MMPI, personal interview, pain drawing, etc.), physical measurements (flexibility, strength and endurance), and demographic data concerning the patient's home and working environment. Information was available on each patient admitted to the program prior to his admission, at completion of the program, 6 weeks following completion of the program and 3 months following completion of the program. A telephone interview was carried out 2 1/2 years following the patient's discharge from the program. Linear regression analysis was used to identify the important independent variables with regard to the dependent variables of relief of back pain, return to work and increased activities at home. Demographic data were of no value as a predictor with the exception of age and returning to work. The patients over the age of 50 returned to work with much less frequency than those less than 50. Psychologic information from the MMPI and similar tests were of no value. The personal preadmission interview of a trained psychologist, however, was a good predictor of an individual's eventual return to work and overall improvement. Worker's Compensation and other litigation was a negative factor in a patient's prognosis. The treatment team's prognosis at the time of discharge from the program was the best overall predictor of a patient's chance of success or failure in the longterm.