Objective The ALSFRS-R is limited by multidimensionality, which originates from the summation of various subscales. This prevents a direct comparison between patients with identical total scores. We aim to evaluate how multidimensionality affects the performance of the ALSFRS-R in clinical trials. Methods We simulated clinical trial data with different treatment effects for the ALSFRS-R total score and its subscales (i.e. bulbar, fine motor, gross motor and respiratory). We considered scenarios where treatment reduced the rate of ALSFRS-R subscale decline either uniformly (i.e. all subscales respond identically to treatment) or non-uniformly (i.e. subscales respond differently to treatment). Two main analytical strategies were compared (1) analyzing only the total score or (2) utilizing a subscale-based test (i.e. alternative strategy). For each analytical strategy, we calculated the empirical power and required sample size. Results Both strategies are valid when there is no treatment benefit and provide adequate control of type 1 error. If all subscales respond identically to treatment, using the total score is the most powerful approach. As the differences in treatment responses between subscales increase, the more the total score becomes affected. For example, to detect a 40% reduction in the bulbar rate of decline with 80% power, the total score requires 1380 patients, whereas this is 336 when using the alternative strategy. Conclusions Ignoring the multidimensional structure of the ALSFRS-R total score could have negative consequences for ALS clinical trials. We propose determining treatment benefit on a subscale level, prior to stating whether a treatment is generally effective.Current research is focused on the development of drug candidates from natural products. Rhein a Traditional Chinese Medicine (TCM) from Polygonaceae (rhubarb) has exhibited antioxidant, anti-inflammatory and anticancer activities, however no work has reported its antiviral potential, thus this study was performed to investigate the antiviral activities of rhein on new castle disease virus (NDV) in vitro.NDV infection of chicken embryo fibroblasts (CEFs) was prepared using 10-day-old specific pathogen free chicken embryos. Cytotoxicity and anti-viral activities of rhein were assessed using the MTT method. The interaction between NDV and cell membrane proteins were also detected using virus overlay protein binding assay (VOPBA). In addition NDV genes expressions in CEFs were measured using real-time fluorescent quantitative (RTFQ) PCR.The results showed that rhein effectively inhibit NDV activities maximal safe concentration of 0.125 mg/ml. This finding indicated that, rhein could be used as future antiviral drug against NDV.In clinical practice, micronized progesterone (MP) is frequently recommended to treat signs and symptoms of skin and hair aging in menopausal women. The aim of this comprehensive review was to evaluate whether topically or systemically applied MP may effectively prevent or slow down signs of skin and hair aging. Three out of six identified studies reported an impact of MP on skin aging markers in menopausal women. Of these, two studies reported a benefit one for topically applied MP, another for systemically applied combined menopausal hormone therapy (MHT) comprising MP as progestogen for endometrial protection. Tolerability and safety of MP were good. However, there was no study investigating the impact of MP on menopausal scalp hair. In conclusion, delay of skin aging comprises lifestyle adjustment, antioxidants, and several esthetic procedures. In menopausal women, MHT displays beneficial effects on skin aging. There is poor quality but promising scientific evidence for MP displaying anti-aging skin effects in menopausal women. However, good quality studies are needed.For many dairy products such as cappuccino-style beverages, the top foam layer determines the overall product quality (e.g. their appearance, texture, mouthfeel and coffee aroma release rate) and the consumer acceptance. Proteins in milk are excellent foaming agents, but the foaming properties of milk are greatly affected by several factors such as the protein content, ratio of caseins to whey proteins, casein micelle size, pH, minerals, proteolysis, presence of low molecular weight compounds (lipids and their hydrolyzed products) and high molecular weight compounds (polysaccharides); milk processing conditions (e.g. homogenization, heat treatment and aging); and foaming method and temperature. These factors either induce changes in the molecular structure, charge and surface activity of the milk proteins; or interfere and/or compete with milk proteins in the formation of highly viscoelastic film to stabilize the foam. Some factors affect the foamability while others determine the foam stability. In this review, functionality of milk proteins in the production and stabilization of liquid foam, under effects of these factors is comprehensively discussed. This will help to control the foaming process of milk on demand for a particular application, which still is difficult and challenging for researchers and the dairy industry.Autologous cells replacement therapy by liver to pancreas transdifferentiation (TD) allows diabetic patients to be also the donors of their own therapeutic tissue. Aim To analyze whether the efficiency of the process is affected by liver donors' heterogeneity with regard to age, gender and the metabolic state. Materials & methods TD of liver cells derived from nondiabetic and diabetic donors at different ages was characterized at molecular and cellular levels, in vitro. Results Neither liver cells proliferation nor the propagated cells TD efficiency directly correlate with the age (3-60 years), gender or the metabolic state of the donors. Conclusion Human liver cells derived from a wide array of ages and metabolic states can be used for autologous cells therapies for diabetics.Aim As an important epigenetic modulator, histone lysine-specific demethylase 1 (LSD1) has been proved to be associated with the progression of renal cell carcinoma (RCC). Discovering novel LSD1 inhibitors offers therapeutic potential for RCC treatment. https://www.selleckchem.com/products/AZD2281(Olaparib).html Methods & Results We identified raloxifene as a novel LSD1 inhibitor (IC50 = 2.08 μM) through small compound library screening. Molecular docking indicated raloxifene might bind LSD1 in the flavin adenine dinucleotide (FAD) binding cavity in a reversible manner. Cell viability and migration assays showed raloxifene could suppress the proliferation and migration of RCC cells bearing overexpressed LSD1. Conclusion Our findings indicated that LSD1 might be a promising therapeutic target for RCC and that raloxifene could serve as a lead compound for further anti-RCC metastasis drug discovery.