Recent Update on the Molecular Mechanisms of Gonadal Steroids Action in Adipose Tissue

The gonadal steroids, including androgens, estrogens and progestogens, are involved in the control of body fat distribution in humans. Nevertheless, not only the size and localization of the fat depots depend on the sex steroids levels, but they can also highly affect the functioning of adipose tissue. Namely, the gonadocorticoids can directly influence insulin signaling, lipid metabolism, fatty acid uptake and adipokine production. They may also alter energy balance and glucose homeostasis in adipocytes in an indirect way, e.g., by changing the expression level of aquaglyceroporins. This work presents the recent advances in understanding the molecular mechanism of how the gonadal steroids influence the functioning of adipose tissue leading to a set of detrimental metabolic consequences. Special attention is given here to highlighting the sexual dimorphism of adipocyte functioning in terms of health and disease. Particularly, we discuss the molecular background of metabolic disturbances occurring in consequence of hormonal imbalance which is characteristic of some common endocrinopathies such as the polycystic ovary syndrome. From this perspective, we highlight the potential drug targets and the active substances which can be used in personalized sex-specific management of metabolic diseases, in accord with the patient’s hormonal status.     

Antisense Oligonucleotide-Based Rescue of Aberrant Splicing Defects Caused by 15 Pathogenic Variants in ABCA4

The discovery of novel intronic variants in the ABCA4 locus has contributed significantly to solving the missing heritability in Stargardt disease (STGD1). The increasing number of variants affecting pre-mRNA splicing makes ABCA4 a suitable candidate for antisense oligonucleotide (AON)-based splicing modulation therapies. In this study, AON-based splicing modulation was assessed for 15 recently described intronic variants (three near-exon and 12 deep-intronic variants). In total, 26 AONs were designed and tested in vitro using a midigene-based splice system. Overall, partial or complete splicing correction was observed for two variants causing exon elongation and all variants causing pseudoexon inclusion. Together, our results confirm the high potential of AONs for the development of future RNA therapies to correct splicing defects causing STGD1.     

Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology

Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies. Methods of targeted delivery of toxins to cancer cells, different drug carriers based on nanosized materials (liposomes, nanoparticles, polymers), the most promising designed light-activated toxins, as well as mechanisms of the cytotoxic action of the main natural toxins used in modern experimental oncology, are discussed in this review. The prospects of the combined therapy of tumors based on multimodal nanostructures are also discussed.     

Polymorphisms in EGFR Gene Predict Clinical Outcome in Unresectable Non-Small Cell Lung Cancer Treated with Radiotherapy and Platinum-Based Chemoradiotherapy

For non-small cell lung cancer (NSCLC), radiotherapy (RT) and platinum-based chemotherapy (CHT) are among the main treatment options. On the other hand, radioresistance and cytotoxic drug resistance are common causes of failure. The epidermal growth factor receptor (EGFR) plays an important role in radioresponse and therapy resistance. We hypothesized that single nucleotide polymorphisms (SNPs) in the EGFR gene might affect individual sensitivity to these treatments, and thus, therapy outcome and prognosis. The association between functional EGFR SNPs and overall (OS), locoregional recurrence-free (LFRS), and metastasis-free (MFS) survival was examined in 436 patients with unresectable NSCLC receiving RT and platinum-based CHTRT. In a multivariate analysis, the rs712830 CC homozygotes showed reduced OS in the whole group (p = 0.039) and in the curative treatment subset (p = 0.047). The rs712829 TT genotype was strongly associated with decreased LRFS (p = 0.006), and the T-C haplotype was a risk factor for locoregional recurrence in our patients (p = 0.003). The rs2227983 GG alone and in combination with rs712829 T was an indicator of unfavorable LRFS (p = 0.028 and 0.002, respectively). Moreover, significant independent effects of these SNPs on OS, LRFS, and MFS were observed. Our results demonstrate that inherited EGFR gene variants may predict clinical outcomes in NSCLC treated with DNA damage-inducing therapy.     

pHEMA: An Overview for Biomedical Applications

Poly(2-hydroxyethyl methacrylate) (pHEMA) as a biomaterial with excellent biocompatibility and cytocompatibility elicits a minimal immunological response from host tissue making it desirable for different biomedical applications. This article seeks to provide an in-depth overview of the properties and biomedical applications of pHEMA for bone tissue regeneration, wound healing, cancer therapy (stimuli and non-stimuli responsive systems), and ophthalmic applications (contact lenses and ocular drug delivery). As this polymer has been widely applied in ophthalmic applications, a specific consideration has been devoted to this field. Pure pHEMA does not possess antimicrobial properties and the site where the biomedical device is employed may be susceptible to microbial infections. Therefore, antimicrobial strategies such as the use of silver nanoparticles, antibiotics, and antimicrobial agents can be utilized to protect against infections. Therefore, the antimicrobial strategies besides the drug delivery applications of pHEMA were covered. With continuous research and advancement in science and technology, the outlook of pHEMA is promising as it will most certainly be utilized in more biomedical applications in the near future. The aim of this review was to bring together state-of-the-art research on pHEMA and their applications.     

Validation of a task demand measure for predicting mental workloads of physical therapists

The purpose of this study is to validate an analytical method in assessing demanded mental workloads for physical therapists, and to discuss its possible ergonomics implications on the design of healthcare working systems in which physical therapists are considered as the users. A task analysis was first used to understand the operation steps of three identified physical therapies. Then, the McCracken–Aldrich technique was applied to assign ratings of mental workload demanded for performing each step of the therapies. Finally, the assigned ratings were validated by the analysis of correlation with the answers of the NASA-TLX questionnaire collected from seventeen physical therapists in the rehabilitation center of a university-affiliated hospital. Results showed that the proposed McCracken–Aldrich technique was suitable as an analysis tool for predicting metal workloads of physical therapists. Some possible implications about the information provision and user interface design for reducing therapists' mental workloads on current therapy operations were discussed.Relevance to industryResults of this paper are expected to contribute the research and development in healthcare industry on its system design and workflow analysis.     

Brain mass estimation by head circumference and body mass methods in neonatal glycaemic modelling and control

Introduction

Hyperglycaemia is a common complication of stress and prematurity in extremely low-birth-weight infants. Model-based insulin therapy protocols have the ability to safely improve glycaemic control for this group. Estimating non-insulin-mediated brain glucose uptake by the central nervous system in these models is typically done using population-based body weight models, which may not be ideal.

Method

A head circumference-based model that separately treats small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) infants is compared to a body weight model in a retrospective analysis of 48 patients with a median birth weight of 750 g and median gestational age of 25 weeks. Estimated brain mass, model-based insulin sensitivity (S_I) profiles, and projected glycaemic control outcomes are investigated. SGA infants (5) are also analyzed as a separate cohort.

Results

Across the entire cohort, estimated brain mass deviated by a median 10% between models, with a per-patient median difference in S_I of 3.5%. For the SGA group, brain mass deviation was 42%, and per-patient S_I deviation 13.7%. In virtual trials, 87–93% of recommended insulin rates were equal or slightly reduced (Δ < 0.16 mU/h) under the head circumference method, while glycaemic control outcomes showed little change.

Conclusion

The results suggest that body weight methods are not as accurate as head circumference methods. Head circumference-based estimates may offer improved modelling accuracy and a small reduction in insulin administration, particularly for SGA infants.     

考虑出行方向的广州出租车时空可达性研究

出行方向是可达性研究中的一个关键要素, 因此, 提出一种考虑出行方向的出租车时空可达性分析方法。根据出租车经验路径分方向构建经验等级路网, 采用基于分层路网的Dijkstra算法计算得到各OD对之间的行程时间, 作为可达性评价指标, 并采用网格法和反距离加权插值法绘制得到广州市中心商业区等时线及其渲染图, 分方向、分时段对其时空可达性进行分析。结果证明了不同出行方向下, 特别是处于高峰时段, 可达性有较大的不同。     

基于CUDA的AES并行算法优化

为提升高级加密标准(AES)的加密性能,利用显卡的通用计算能力,在统一计算设备架构(CUDA)平台上实现AES的128位、192位和256位3个版本的GPU并行算法,并提出优化的AES并行算法。在考虑块内线程数量、共享存储器容量和总块数的基础上,根据分块最优值的经验数据指导AES算法在GPU上的最优分块。实验结果表明,与未优化的AES并行算法相比,该算法的3个版本在Nvidia Geforce G210显卡上的加密速度分别提高5.28%,14.55%和12.53%,而在Nvidia Geforce GTX460显卡上的加密速度分别提高12.48%,15.40%和15.84%,且能更好地对SSL数据进行加密。     

电子书包支持的体验学习活动设计与应用研究

旨在研究电子书包支持的体验学习的活动模型和应用效果。首先通过理论分析提出了电子书包支持的体验学习活动模型,并设计了《校园植物知多少》等3个教学专题,之后在某小学进行了试点实验研究。研究结果表明,电子书包支持的体验学习模型确实有助于提高学生的认知体验、行为体验和情感体验的参与度。