Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

X-linked juvenile retinoschisis (XLRS), linked to mutations in the RS1 gene, is a degenerative retinopathy with a retinal splitting phenotype. We generated human induced pluripotent stem cells (hiPSCs) from patients to study XLRS in a 3D retinal organoid in vitro differentiation system. This model recapitulates key features of XLRS including retinal splitting, defective retinoschisin production, outer-segment defects, abnormal paxillin turnover, and impaired ER-Golgi transportation. RS1 mutation also affects the development of photoreceptor sensory cilia and results in altered expression of other retinopathy-associated genes. CRISPR/Cas9 correction of the disease-associated C625T mutation normalizes the splitting phenotype, outer-segment defects, paxillin dynamics, ciliary marker expression, and transcriptome profiles. Likewise, mutating RS1 in control hiPSCs produces the disease-associated phenotypes. Finally, we show that the C625T mutation can be repaired precisely and efficiently using a base-editing approach. Taken together, our data establish 3D organoids as a valid disease model

Magnetic Particle-Based Hybrid Platforms for Bioanalytical Sensors

Biomagnetic nano and microparticles platforms have attracted considerable interest in the field of biological sensors due to their interesting physico-chemical properties, high specific surface area, good mechanical stability and opportunities for generating magneto-switchable devices. This review discusses recent advances in the development and characterization of active biomagnetic nanoassemblies, their interaction with biological molecules and their use in bioanalytical sensors

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Measuring the health-related Sustainable Development Goals in 188 countries : a baseline analysis from the Global Burden of Disease Study 2015

Background In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015). Methods We applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices. Findings In 2015, the median health-related SDG index was 59.3 (95% uncertainty interval 56.8-61.8) and varied widely by country, ranging from 85.5 (84.2-86.5) in Iceland to 20.4 (15.4-24.9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r(2) = 0.88) and the MDG index (r(2) = 0.2), whereas the non-MDG index had a weaker relation with SDI (r(2) = 0.79). Between 2000 and 2015, the health-related SDG index improved by a median of 7.9 (IQR 5.0-10.4), and gains on the MDG index (a median change of 10.0 [6.7-13.1]) exceeded that of the non-MDG index (a median change of 5.5 [2.1-8.9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened. Interpretation GBD provides an independent, comparable avenue for monitoring progress towards the health-related SDGs. Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be sufficient. Although considerable progress on the health-related MDG indicators has been made, these gains will need to be sustained and, in many cases, accelerated to achieve the ambitious SDG targets. The minimal improvement in or worsening of health-related indicators beyond the MDGs highlight the need for additional resources to effectively address the expanded scope of the health-related SDGs.Peer reviewe

Effect of kidsolone on isolated rat′s tracheal smooth muscle

Purpose: Prednisolone (Kidsolone) is an anti-inflammatory drug that is mainly used for patients with chronic obstructive airway diseases (COAD), such as asthma and chronic obstructive pulmonary diseases (COPD). The objective of this study was to determine the effects of Kidsolone on the trachea of rats in vitro. Materials and Methods: We tested the effectiveness of Kidsolone on isolated rat trachea submersed in Krebs solution in a muscle bath. Changes in tracheal contractility in response to the application of parasympathetic mimetic agents were measured. The following assessments of Kidsolone were performed: (1) Effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10-6 M methacholine; (3) effect of the drug on electrically-induced tracheal smooth muscle contractions. Result: Our results demonstrated that no significant effects were induced by the addition of 10-8-10-5 M Kidsolone on tracheal tension after methacholine treatment, indicating that Kidsolone had no anti-cholinergic effect. It alone had a minimal effect on the basal tension of the trachea as the concentration increased. Furthermore, Kidsolone did not affect electrical field stimulation-induced spike contraction, which represent the Kidsolone could not antagonize the parasympathetic innervation responsible for trachea smooth muscle contraction. Conclusion: The immediate effect of Kidsolone on COAD may be indirectly. Therefore, sorely use of inhalation Kidsolone without β2-agonist in treating acute asthma or COPD attack may be more suboptimal than co-administration of them

The Effect of Inspiration and Phonation on Vocal Fold Length

The detection of metric dimensions of laryngeal structures yielded valuable information for both clinical and research purposes. The aim of this paper was to evaluate the absolute dimensions of true vocal fold length (TVFL) during inspiration and phonation with a stroboscope coupling with laser equipment. Forty graduate student subjects including 20 males and 20 females were examined. The measurements were made during inspiration and phonation at a fixed fundamental frequency within each participant. The maximal TVFL was got from the inspiration and the minimal from the phonation. Results showed that the mean values of male inspiration and phonation TVFL were 12.81 + 2.97 mm and 10.92 + 4.40 mm respectively. While in female, they were 11.27 + 2.71 mm and 7.16 + 2.65 mm respectively. There was statistically significant between inspiration and phonation TVFL in the female group. In female, TVFL at phonation was significantly shortened than in male. We concluded stroboscope coupling with laser projection marking module could be used to assess physiological variation of TVFL. This technique enabled the detection of absolute spatial laryngeal dimensions, which was useful in providing valuable information in diagnostics and interpretation of voice disorders