Residue and dietary intake risk assessment of lufenuron and chlorfenapyr and its corresponding metabolite in cabbage under field conditions.

A simple, low-cost, and highly sensitive method using a modified QuECHERS procedure based on a liquid chromatography-tandem mass spectrometer (LC-MS/MS) was established to simultaneously quantify lufenuron and chlorfenapyr and the corresponding metabolite tralopyril in cabbage for the first time. On the basis of this method, terminal residue and dietary risk of lufenuron and chlorfenapyr in cabbage were investigated. The recoveries of lufenuron, chlorfenapyr, and tralopyril ranged from 88 to 110%, with relative standard deviation of less than 12.4%. The field trial results showed that at the pre-harvest interval (PHI) of 21 days, the terminal residues of lufenuron, chlorfenapyr, and tralopyril in the supervised trials were not higher than 0.02 mg/kg, and the highest detected residue levels of lufenuron, chlorfenapyr, and tralopyril were 0.047, 0.055, and <0.02 mg·kg-1 at 14-day pre-harvest respectively, which were lower than the maximum residue limits (MRLs) for cabbage established in China. For the dietary risk assessment, the national estimated daily intakes (NEDIs) as proportion of acceptable daily intakes (ADIs) were 80.4% and 29.9% for chlorfenapyr and lufenuron respectively indicating an acceptable dietary risk to Chinese population.

Validation of Luminex immunological and competitive Luminex immunological assays for clinical immunogenicity assessment of a 14-valent recombinant human papillomavirus vaccine.

A novel virus-like particle (VLP)-based multivalent recombinant human papillomavirus (HPV) vaccine was developed and evaluated in human, including 14 HPV-type specific VLP antigens (HPV6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59). The pseudovirus-based neutralizing assay (PBNA) method is widely used for immunogenicity assessment of HPV vaccine in clinical trials. However, as many as 14 antigen-specific antibody levels need be determined, PBNA is, for many reasons, challenging and time-consuming. In this study, we developed a Luminex immunological assay (LIA) and a competitive Luminex immunological assay (cLIA). These methods increase the throughput, reproducibility and precision, as well as reduce the complexity. All assay parameters showed good characteristics in the validation of both methods, benefiting from highly purified and structurally correct VLPs, high specific antibodies, standard VLP-microspheres and PE-mAbs conjugating process, adequate assay development and stable system. Validation data support the use of both methods for immunogenicity assessment in clinical trials. LIA showed higher sensitivity than cLIA, and due to limited epitopes of mAb, cLIA detected lower antibody responses, and therefore, fewer antibodies. This work not only supports clinical trials of 14-valent HPV vaccines more efficiently and reliably, but also provides a set of validation strategies and usable standards for general vaccine immunogenicity testing.

Assessment of Adaptation Status of Reintroduced Equus Przewalskii Based on Comparative Analysis of Fecal Bacteria with Those of Captive E. Przewalskii, Domestic Horse and Mongolian Wild Ass.

Intestinal microbiota play an important role in the survival of the host. However, no study to date has elucidated the adjustment of intestinal microbiota of the host during rewilding. Thus, this study aims to describe the intestinal bacterial community of reintroduced Przewalski's horse (RPH) after being released into their original habitat for approximately 20 years in comparison with that of captive Przewalski's horse (CPH), sympatric domestic horse (DH) and Mongolian wild ass (MWA) by sequencing the 16S rRNA gene. The results showed that the prevalent bacterial communities were different among CPHs, RPHs, DHs and MWAs at the family level. NMDS and ANOSIM analysis showed that the pattern of bacterial community composition in captive equines was distinct from that in the wild groups. It is shown that some bacteria had significant differences among different taxa (p < 0.001), such as Firmicutes, Bacteroidetes, Armatimonadetes, Clostrida, Bacteroidia, Clostridiales, Bacteroidales, Rikenellaceae and Bacteroidales_UCG-001. These bacteria were associated with the transition from in captive to in the wild (CPH and RPH), which reflected the change of environmental conditions. Meanwhile, Proteobacteria, Clostridia, Bacilli, Negativicutes, Gammaproteobacteria, Clostridiales, Bacillales, Selenomonadales, Pseudomonadales and Planococcaceae were the changed groups among RPHs, MWAs and DHs, which are related to feeding habits and diseases. Our results clearly showed the differences between intestinal microbiota in reintroduced animals and wild animals and led us to understand the survival state of reintroduced animals in the wild.

Noninvasive assessment of cardiac changes in patients with coronavirus disease-19 (COVID-19) by bedside ultrasound.

Background: Patients with coronavirus disease-19 (COVID-19) are susceptible to cardiac complications, and cardiac ultrasound is the preferred noninvasive method for clinical cardiac structure and function assessment. Methods: We performed a retrospective study of 34 patients with COVID-19 and analyzed their clinical data, biochemistry test results [creatine kinase-MB (CK-MB), cardiac troponin I (cTnI) and C-reactive protein (CRP)], and parameters of cardiac ultrasound [left atrium (LA), left ventricular end-diastolic dimensions (LVDD), right atrium (RA), right ventricle (RV), main pulmonary artery (MPA), left ventricular ejection fraction (LVEF), tricuspid valve (TV), pulmonic valve (PV) and pulmonary artery systolic pressure (PASP)]. We classified the patients based on their clinical symptoms (mild, moderate, severe, and critical groups), and compared the parameters. CK-MB and cardiac ultrasound parameters are presented as mean ± standard deviation and compared using the one-way ANOVA. CTnI is presented as counts (percentages) and compared using the χ2 test, CRP is presented as [M (P25, P75)] [median (interquartile range)] and compared using nonparametric tests (Kruskal-Wallis test). Results: As the disease progressed, the parameters of both biochemical blood tests and cardiac ultrasound changed regularly, manifested as enlargement of the LA, LVDD, RA, RV, and MPA and increased PASP, CRP, CK-MB, and cTnI. Of these parameters, CRP, LA, LVDD, MPA, and PASP of the severe group were more notably elevated than in the mild and moderate groups (P<0.05). The critical group more showed markedly increased CK-MB, cTnI, and RA than the other groups (P<0.05), and CRP, LA, LVDD, RV, MPA, and PASP rose more sharply than in the mild and moderate groups (P<0.05). Conclusions: As COVID-19 progressed, patients developed an enlarged heart with expanded pulmonary arteries and elevated PASP. Bedside ultrasound can be used as a noninvasive assessment of these changes and for guidance of clinical treatment.

The Association of Residence Permits on Utilization of Health Care Services by Migrant Workers in China.

Due to the limitations in the verifiability of individual identity, migrant workers have encountered some obstacles in access to public health care services. Residence permits issued by the Chinese government are a solution to address the health care access inequality faced by migrant workers. In principle, migrant workers with residence permits have similar rights as urban locals. However, the validity of residence permits is still controversial. This study aimed to examine the impact of residence permits on public health care services. Data were taken from the China Migrants Dynamic Survey (CMDS). Our results showed that the utilization of health care services of migrant workers with residence permits was significantly better than others. However, although statistically significant, the substantive significance is modest. In addition, megacities had significant negative moderating effects between residence permits and health care services utilization. Our research results emphasized that reforms of the household registration system, taking the residence permit system as a breakthrough, cannot wholly address the health care access inequality in China. For developing countries with uneven regional development, the health care access inequality faced by migrant workers is a structural issue.

The effects of a multi-disciplinary team on sleep quality assessment in mild-to-moderate Alzheimer's disease patients with sleep disorders.

BACKGROUND AND AIMS: Sleep disturbances are a severe problem among patients with Alzheimer's disease (AD). By evaluating sleep quality in mild-to-moderate AD patients, this study aimed to assess the effects of multi-disciplinary team (MDT) in reducing the incidence of adverse reactions of AD patients. The reduction in the incidence of adverse reactions to predict multi-disciplinary team (MDT) treatment effects. METHODS AND RESULTS: This study included 60 mild-to-moderate AD patients with sleep problems when hospitalized in Huzhou Third Municipal Hospital. The patients were randomly distributed into two groups, routine and MDT treatments. The cognitive functions, sleep conditions, and psycho-behavioral symptoms were compared between both the groups. Cognitive function declined significantly between pretherapy and follow-up in the routine treatment group (MMSE: t = -7.961, P < 0.001; MoCA: t = -4.672, P < 0.001). There was a significant decline in drowsiness in the MDT group compared to that in the routine treatment group (χ2 = 4.320, P = 0.038). Sleep quality improved significantly during the follow-up in the MDT treatment group (t = 6.098, P < 0.001). The results of the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) among family caregivers (FCGs) demonstrated that MDT treatment could alleviate caregivers' depression (t = -2.867, P = 0.042), and routine treatment can worsen their anxiety (t = 3.258, P = 0.003). CONCLUSION: The MDT treatment method as an effective and meaningful therapy can help mitigate the suffering of patients with AD and FCGs.

Effect of socioeconomic status on the healthcare-seeking behavior of migrant workers in China.

In recent years, China has made great efforts to resolve the health inequality caused by household registration restrictions, and the unequal allotment of health services faced by migrant workers has been effectively alleviated. However, inequality in health services may exist not only between migrant workers and local citizens but also among migrant workers. Thus, the unbalanced utilization of health services among migrant workers deserves attention. Using data from the 2017 China Migrants Dynamic Survey (CMDS), we examined the relationship between socioeconomic status (SES) and healthcare-seeking behavior through multivariate regression analysis. Then, from the perspective of SES, this study divided migrant workers into different groups to explore the characteristics of healthcare-seeking behavior in different groups. The results showed that SES had a significant relationship with healthcare-seeking behavior. Those with high SES were more likely to use high-quality health services. By subdividing the category of migrant workers, we found that the utilization of health services among migrant workers was unbalanced. Education and income had significant gradients in multiple measures of healthcare-seeking behavior, while occupation had no significant difference in the behavior. Migrant workers with higher income and education were more likely to use high-quality health services. Especially for migrant workers who had high incomes (above 15,000 CNY) or whose educational backgrounds were graduate level or above, their utilization of health resources was significantly higher than that of other groups. When designing particular policies to improve the healthcare-seeking behavior of different SES migrant workers, we should pay attention to the low-education groups and low-income groups. Policymakers can reduce the current health inequality of migrant workers by strengthening health education and increasing medical subsidies to achieve health equality among migrant workers and between migrant workers and local citizens.

A new framework to address challenges in quantitative benefit-risk assessment for medical products.

In recent years, there has been a proliferation of regulatory and industry-wide initiatives on structured benefit-risk (BR) assessment. Examples of structured BR frameworks include the PrOACT-URL (Problem formulation, Objectives, Alternatives, Consequences, Trade-Offs, Uncertainties, Risk Attitude and Linked Decisions) from European Medicines Agency Work Package 3, multiple U.S. Food and Drug Administration guidance documents on benefit-risk assessment for medical devices, and U.S. Food and Drug Administration implementation plans for benefit-risk assessment in drug regulatory decision-making. In June 2016, the ICH Expert Working Group finalized the Common Technical Document (CTD) Section 2.5.6 on Benefit-Risk Evaluations. As a result of these efforts, the uptake and utilization of structured benefit-risk (BR) assessments has been increasing. However, the aforementioned BR frameworks are mostly qualitative in nature, and the utility of quantitative BR approaches has not been systemically explored, creating uncertainty about settings in which quantitative BR assessment (qBRA) could be optimally applied. In this paper, we will provide an overview of the current qBRA methods, discuss challenges of qBRA, and describe a structural qBRA framework. The performance of the described qBRA framework will be evaluated by simulations based on a case study.

Homogeneity assessment for pivotal medical device clinical studies.

A question that routinely arises in medical device clinical studies is the homogeneity across demographic subgroups, geographical regions, or investigational sites of the enrolled patients in terms of treatment effects or outcome variables. The main objective of this paper is to discuss statistical concepts and methods for the assessment of such homogeneity and to provide the practitioner a statistical framework and points to consider in conducting homogeneity assessment. Demographic subgroups, geographical regions, and investigational sites are discussed separately as each has its unique issues. Specific considerations are also given to randomized controlled trials, non-randomized comparative studies, and single-arm studies. We point out that judicious use of statistical methods, in conjunction with sound clinical judgment, is essential in handling the issue of homogeneity of treatment effect in medical device clinical studies.

[Pollution Characteristics and Health Risk Assessment of VOCs in Areas Surrounding a Petrochemical Park in Shanghai].

To investigate the pollution characteristics of volatile organic compounds (VOCs) in the vicinity of a petrochemical park, the composition and concentration of VOCs was successively monitored by application of a gas chromatography-flame ionization detector in the residential area surrounding a petrochemical park in Shanghai in October 2017. Moreover, the maximum incremental reactive method was employed to estimate the O3-formation potential contributed by VOCs, and health risks were assessed. Results showed that during the observation period, TVOCs concentrations ranged from 16.4 µg·m-3 to 1947.8 µg·m-3 with an average concentration of 40.7 µg·m-3, whereas the average proportions of alkanes, alkene/alkynes, and aromatic hydrocarbons were 66.2%, 25.9%, and 7.9%, respectively. The diurnal variation of total VOCs concentration showed a monomodal change, with a peak concentration of 127.9 µg·m-3 at 07:00, whereas the TVOCs had an average ozone formation potential (OFP) of 249.7 µg·m-3. Analysis of OFP indicated that trans-2-butene and ethylene were the most important species in ozone production with accountabilities for total OFP of 153.4 µg·m-3. Propylene, trans-2-butene, and ethylene were the key active species. Furthermore, health risk assessments revealed that no significant health risks had been caused by hexane, benzene, toluene, ethylbenzene, o-xylene, and m-xylene.

Activities of MSCs Derived from Transgenic Mice Seeded on ADM Scaffolds in Wound Healing and Assessment by Advanced Optical Techniques.

BACKGROUND/AIMS: Bone marrow Mesenchymal stem cells (MSCs) are promising for promoting cutaneous wound healing through reinforcing cellular processes. We evaluated the effect of GFP-tagged MSCs transplantation on skin regeneration in excisional wounds in mice. METHODS: MSCs from GFP-labeled transgenic mice were co-cultured with acellular dermal matrix (ADM) scaffolds, and MSC-ADM scaffolds were transplanted into surgical skin wounds of BALB/c mice. After implantation, the survival and behavior of MSCs were examined by second harmonic generation and two-photon excitation fluorescence imaging, western blotting and DNA amplification and sequencing. RESULTS: GFP-tagged MSCs were retained inside the regenerating skin until day 14 post-transplantation. Alpha-smooth muscle actin (α-SMA) and vimentin (VIM) were detected at 3, 5, 7, and 14 days post-transplantation by immunofluorescence double labeling. Although the GFP+/α-SMA+- and GFP+/VIM+-cell numbers decreased gradually with healing time, α-SMA+- and VIM+-cell numbers significantly increased, most of them were endogenous functional cells which were related to angiogenesis and collagen fiber structural remodeling. CONCLUSION: Therefore, in the initial stage of wound healing, transplanted MSCs differentiated into functional cells and played paracrine roles to recruit more endogenous cells for tissue remodeling. With the disappearance of exogenous cells, endogenous cells were responsible for the latter stage of cutaneous wound healing.

A combined experimental and computational study of novel nanocage-based metal-organic frameworks for drug delivery.

Three new metal organic frameworks (MOFs) with chemical formulae [(CH3)2NH2] [Sm3(L1)2(HCOO)2(DMF)2(H2O)]·2DMF·18H2O (1), [Cu2(L2)(H2O)2]·2.22DMA (2) and [Zn2(L1)(DMA)]·1.75DMA were synthesized and structurally characterized. 1 and 2 show a classical NbO-like topology and have two types of interconnected cages. 3 exhibits an uncommon zzz topology and has two types of interconnected cages. These MOFs can adsorb large amounts of the drug 5-fluorouracil (5-FU) and release it in a progressive way. 5-FU was incorporated into desolvated 1, 2 and 3 with loadings of 0.40, 0.42, and 0.45 g g(-1), respectively. The drug release rates were 72%, 96% and 79% of the drug after 96 hours in 1, 120 hours in 2 and 96 hours in 3, respectively. Grand Canonical Monte Carlo (GCMC) simulations were performed to investigate the molecular interactions during 5-FU adsorption to the three novel materials. The GCMC simulations reproduced the experimental trend with respect to the drug loading capacity of each material. They also provided a structural description of drug packing within the frameworks, helping to explain the load capacity and controlled release characteristics of the materials. 5-FU binding preferences to 1, 2 and 3 reflect the diversity in pore types, chemistry and sizes. The calculated drug load is more related to the molecular properties of accessible volume Vacc than to the pore size.

Decision analysis of retrievable inferior vena cava filters in patients without pulmonary embolism.

BACKGROUND: Retrievable filters are increasingly implanted for prophylaxis in patients without pulmonary embolism (PE) but who may be at transient risk. These devices are often not removed after the risk of PE has diminished. This study employs decision analysis to weigh the risks and benefits of retrievable filter use as a function of the filter's time in situ. METHODS: Medical literature on patients with inferior vena cava (IVC) filters and a transient risk of PE were reviewed. Weights reflecting relative severity were assigned to each adverse event. The risk score was defined as weight × occurrence rate and combines the frequency and severity for each type of adverse event. The value function in the decision model combines the following risks: (1) risk in situ; (2) risk of removal, and (3) relative risk without filters. A decreasing net risk score represents a net expected benefit, and an increasing net risk score indicates the expected harm outweighs the expected benefit. RESULTS: The net risk score reaches its minimum between day 29 and 54 postimplantation. This is consistent with an increasing net risk associated with continued use of retrievable IVC filters in patients with transient, reversible risk of PE. The results were insensitive to reasonable variations in the assessed weights and adverse event occurrence rates. CONCLUSIONS: For patients with retrievable IVC filters in whom the transient risk of PE has passed, quantitative decision analysis suggests the benefit/risk profile begins to favor filter removal between 29 and 54 days after implantation.