Maleic anhydride-modified chicken ovalbumin as an effective and inexpensive anti-HIV microbicide candidate for prevention of HIV sexual transmission

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown that 3-hydroxyphthalic anhydride (HP)-modified bovine milk protein, β-lactoglobulin (β-LG), is a promising microbicide candidate. However, concerns regarding the potential risk of prion contamination in bovine products and carcinogenic potential of phthalate derivatives were raised. Here we sought to replace bovine protein with an animal protein of non-bovine origin and substitute HP with another anhydride for the development of anti-HIV microbicide for preventing HIV sexual transmission.</p> <p>Results</p> <p>Maleic anhydride (ML), succinic anhydride (SU) and HP at different conditions and variable pH values were used for modification of proteins. All the anhydrate-modified globulin-like proteins showed potent anti-HIV activity, which is correlated with the percentage of modified lysine and arginine residues in the modified protein. We selected maleic anhydride-modified ovalbumin (ML-OVA) for further study because OVA is easier to obtain than β-LG, and ML is safer than HP. Furthermore, ML-OVA exhibited broad antiviral activities against HIV-1, HIV-2, SHIV and SIV. This modified protein has no or low <it>in vitro </it>cytotoxicity to human T cells and vaginal epithelial cells. It is resistant to trypsin hydrolysis, possibly because the lysine and arginine residues in OVA are modified by ML. Mechanism studies suggest that ML-OVA inhibits HIV-1 entry by targeting gp120 on HIV-1 virions and also the CD4 receptor on the host cells.</p> <p>Conclusion</p> <p>ML-OVA is a potent HIV fusion/entry inhibitor with the potential to be developed as an effective, safe and inexpensive anti-HIV microbicide.</p

Relationship between occupational stress and job burnout among rural-to-urban migrant workers in Dongguan, China: a cross-sectional study

Objectives: In China, there have been an increasing number of migrant workers from rural to urban areas, and migrant workers have the highest incidence of occupational diseases. However, few studies have examined the impact of occupational stress on job burnout in these migrant workers. This study aimed to investigate the relationship between occupational stress and job burnout among migrant workers. Design: This study used a cross-sectional survey. Setting: This investigation was conducted in Dongguan city, Guangdong Province, China. Participants: 3806 migrant workers, aged 18–60 years, were randomly selected using multistage sampling procedures. Primary and secondary outcome measures: Multistage sampling procedures were used to examine demographic characteristics, behaviour customs and jobrelated data. Hierarchical linear regression and logistic regression models were constructed to explore the relationship between occupational stress and burnout. Results: Demographics, behaviour customs and jobrelated characteristics significantly affected on burnout. After adjusting for the control variable, a high level of emotional exhaustion was associated with high role overload, high role insufficiency, high role boundary, high physical environment, high psychological strain, high physical strain, low role ambiguity, low responsibility and low vocational strain. A high level of depersonalisation was associated with high role overload, high role ambiguity, high role boundary, high interpersonal strain, high recreation, low physical environment and low social support. A low level of personal accomplishment was associated with high role boundary, high role insufficiency, low responsibility, low social support, low physical environment, low self-care and low interpersonal strain. Compared to the personal resources, the job strain and personal strain were more likely to explain the burnout of rural-to-urban migrant workers in our study. Conclusions: The migrant workers have increased job burnouts in relation to occupational stress. Relieving occupational stress and maintaining an appropriate quantity and quality of work could be important measures for preventing job burnout among these workers

Microwave-assisted aqueous two-phase extraction of alkaloids from Radix Sophorae Tonkinensis with ethanol/Na2HPO4 system: process optimization, composition identification and quantification analysis

A rapid method for simultaneous extraction and separation of multiple alkaloids from Radix Sophorae Tonkinensis (RST) was developed by microwave-assisted aqueous two-phase extraction (MAATPE) using the aqueous two-phase extraction system (ATPS) of ethanol/Na2HPO4 as the extraction solvent. The effects of key factors on extraction yield were investigated by utilizing single-factor experiment coupled to response surface methodology (RSM). The regression model by RSM was significant (p < 0.0001) and adequate for prediction of process efficacy, the optimized conditions were successfully validated by the parallel experiments with the yield very close to the predicted value. The optimum conditions were summarized as follows: the phase ratio of 2.60 for the ATPS, the particle size of 100 mesh, the liquid-to-material ratio of 75:1, the extraction temperature of 90 °C and the extraction time of 5 min, respectively. In MAATPE process, alkaloids were extracted preferentially from RST in the top phase with a higher yield and shorter extraction time than those of heating reflux extraction (HRE) and ultrasonic-assisted extraction (UAE). Nine alkaloids extracted were identified and quantified by high-resolution ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometry (UPLC-Q-Orbitrap/MS) and HPLC with UV detection. The contents of matrine, sophocarpine, oxymatrin, sophoranol, oxysophocarpine, 5α-hydroxysophocarpine, sophoridine, cytisine and N-methylcytisine in RST were quantified in range of 0.493–10.284 mg/g with recoveries of 90.26–106.3% and RSD’s of 0.8–2.1%, respectively. Moreover, the MAATPE mechanism was explored using the different extraction systems in combination of scanning electron microscopy (SEM) morphological studies. Significant differences in extraction yield and cell rupture exhibited that the addition of the salt in the ethanol-water mixture not only improved the thermal and demixing effects, but also accelerated the mass transfer and biphasic extraction processes. MAATPE integrated the advantages of microwave-assisted extraction (MAE) and aqueous two-phase extraction (ATPE) was proved as a green, efficient and promising alternative to extraction of alkaloids from RST

White Matter Heritability Using Diffusion Tensor Imaging in Neonatal Brains

Understanding genetic and environmental effects on white matter development in the first years of life is of great interest, as it provides insights into the etiology of neurodevelopmental disorders. In this study, the genetic and environmental effects on white matter were estimated using data from 173 neonatal twin subjects. Diffusion tensor imaging scans were acquired around 40 days after birth and were non-rigidly registered to a group-specific atlas and parcellated into 98 ROIs. A model of additive genetic, and common and specific environmental variance components was used to estimate overall and regional genetic and environmental contributions to diffusion parameters of fractional anisotropy, radial diffusivity, and axial diffusivity. Correlations between the regional heritability values and diffusion parameters were also examined. Results indicate that individual differences in overall white matter microstructure, represented by the average diffusion parameters over the whole brain, are heritable, and estimates are higher than found in studies in adults. Estimates of genetic and environmental variance components vary considerably across different white matter regions. Significant positive correlations between radial diffusivity heritability and radial diffusivity values are consistent with regional genetic variation being modulated by maturation status in the neonatal brain: the more mature the region is, the less genetic variation it shows. Common environmental effects are present in a few regions that tend to be characterized by low radial diffusivity. Results from the joint diffusion parameter analysis suggest that multivariate modeling approaches might be promising to better estimate maturation status and its relationship with genetic and environmental effects

Automatic Recognition of Laryngoscopic Images Using a Deep-Learning Technique

Objectives/Hypothesis: To develop a deep-learning–based computer-aided diagnosis system for distinguishing laryngeal neoplasms (benign, precancerous lesions, and cancer) and improve the clinician-based accuracy of diagnostic assessments of laryngoscopy findings. Study Design: Retrospective study. Methods: A total of 24,667 laryngoscopy images (normal, vocal nodule, polyps, leukoplakia and malignancy) were collected to develop and test a convolutional neural network (CNN)-based classifier. A comparison between the proposed CNN-based classifier and the clinical visual assessments (CVAs) by 12 otolaryngologists was conducted. Results: In the independent testing dataset, an overall accuracy of 96.24% was achieved; for leukoplakia, benign, malignancy, normal, and vocal nodule, the sensitivity and specificity were 92.8% vs. 98.9%, 97% vs. 99.7%, 89% vs. 99.3%, 99.0% vs. 99.4%, and 97.2% vs. 99.1%, respectively. Furthermore, when compared with CVAs on the randomly selected test dataset, the CNN-based classifier outperformed physicians for most laryngeal conditions, with striking improvements in the ability to distinguish nodules (98% vs. 45%, P <.001), polyps (91% vs. 86%, P <.001), leukoplakia (91% vs. 65%, P <.001), and malignancy (90% vs. 54%, P <.001). Conclusions: The CNN-based classifier can provide a valuable reference for the diagnosis of laryngeal neoplasms during laryngoscopy, especially for distinguishing benign, precancerous, and cancer lesions. Level of Evidence: NA Laryngoscope, 130:E686–E693, 2020

Correction: Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios.

An important detail was omitted in the Method of the original Article, I.E, The CARS and other evaluations were conducted 'blind' to condition (Bumetanide or no treatment) by experienced clinicians. This has now been updated in the HTML and PDF versions of this Article