Novel therapeutics regarding paroxysmal night hemoglobinuria
991). The assay was applied to the determination of FB1 contents in spiked corn samples. The average recoveries ranged from 92 to 107%, confirming the practicality of this method. The results obtained by this assay are in good agreement with that of LC-MS/MS method. Graphical abstractSchematic illustration of a bimodal aptasensor based on surface enhanced Raman scattering (SERS) and fluorescence change for the detection of fumonisin B1 (FB1).Bleeding from the small intestine remains a clinically challenging diagnostic and therapeutic problem. It may be minor, requiring only supplemental iron treatment, to patients who have severe overt bleeding that requires multimodal intervention. This article provides an up-to-date review of the state-of-the-art of diagnosis and treatment of small intestinal bleeding.INTRODUCTION X-linked hypophosphatemia (XLH) is a rare, lifelong, progressive disease characterised by renal phosphate wasting and abnormal bone mineralisation. Symptoms begin in early childhood, with the development of rickets and related skeletal deformities and reduced growth, progressing to long-term complications, including pseudofractures and fractures, as well as pain, stiffness and fatigue. The present study was designed to explore the patient experience of pain, stiffness and fatigue and the psychosocial impact of XLH in detail. METHODS A cross-sectional qualitative study was conducted in the United Kingdom (18), Finland (6), France (4), Germany (1) and Luxembourg (1) with XLH patients aged 26 and over. Interview discussion guides were developed in consultation with clinical experts and patient associations. Data were analysed thematically. RESULTS Participants (N = 30) described pain, stiffness and fatigue as frequently experienced symptoms with a significant impact on physical functioning and activities of daily living (ADLs). Some also described the symptoms as impacting their mood/mental health, relationships, social life and leisure activities. Participants described how common symptoms could interact or aggravate other symptoms. Symptoms had often worsened over time, and for many, were associated with concern about the future. GSK-3 beta pathway Most participants were worried or felt guilty about having children with XLH. The findings confirmed and extended the existing model of the burden of XLH. CONCLUSION The present study is the first to provide an in-depth analysis of pain, stiffness and fatigue, their impact and the interrelatedness of these symptoms among adults with XLH. The study also described the psychosocial impact of XLH as a hereditary, lifelong progressive disease.We construct a three-dimensional anatomically accurate multicellular model of a parotid gland acinus to investigate the influence that the topology of its lumen has on primary fluid secretion. Our model consists of seven individual cells, coupled via a common lumen and intercellular signalling. Each cell is equipped with the intracellular calcium ([Formula see text])-signalling model developed by Pages et al, Bull Math Biol 81 1394-1426, 2019. https//doi.org/10.1007/s11538-018-00563-z and the secretion model constructed by Vera-Sigüenza et al., Bull Math Biol 81 699-721, 2019. https//doi.org/10.1007/s11538-018-0534-z. The work presented here is a continuation of these studies. While previous mathematical research has proven invaluable, to the best of our knowledge, a multicellular modelling approach has never been implemented. Studies have hypothesised the need for a multiscale model to understand the primary secretion process, as acinar cells do not operate on an individual basis. Instead, they form racemous clusters that form intricate water and protein delivery networks that join the acini with the gland's ducts-questions regarding the extent to which the acinus topology influences the efficiency of primary fluid secretion to persist. We found that (1) The topology of the acinus has almost no effect on fluid secretion. (2) A multicellular spatial model of secretion is not necessary when modelling fluid flow. Although the inclusion of intercellular signalling introduces vastly more complex dynamics, the total secretory rate remains fundamentally unchanged. (3) To obtain an acinus, or better yet a gland flow rate estimate, one can multiply the output of a well-stirred single-cell model by the total number of cells required.Genome-wide association studies (GWASs) have identified hundreds of single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D) and coronary artery disease (CAD), respectively. Nevertheless, these studies were generally performed for single-trait/disease and failed to assess the pleiotropic role of the identified variants. To identify novel functional loci and the pleiotropic relationship between CAD and T2D, the targeted cFDR analysis on CpG-SNPs was performed by integrating two independent large and multi-centered GWASs with summary statistics of T2D (26,676 cases and 132,532 controls) and CAD (60,801 cases and 123,504 controls). Applying the cFDR significance threshold of 0.05, we observed a pleiotropic enrichment between T2D and CAD by incorporating pleiotropic effects into a conditional analysis framework. We identified 79 novel CpG-SNPs for T2D, 61 novel CpG-SNPs for CAD, and 18 novel pleiotropic loci for both traits. Among these novel CpG-SNPs, 33 of them were annotated as methylation quantitative trait locus (meQTL) in whole blood, and ten of them showed expression QTL (eQTL), meQTL, and metabolic QTL (metaQTL) effects simultaneously. To the best of our knowledge, we performed the first targeted cFDR analysis on CpG-SNPs, and our findings provided novel insights into the shared biological mechanisms and overlapped genetic heritability between T2D and CAD.BACKGROUND Studies among pregnant Asian women with chronic kidney disease (CKD) have not been widely performed; therefore, clinical criteria for these patients have not been well established. METHODS We conducted a retrospective study among pregnant women with CKD who received prenatal care at our institution for 8 consecutive years. Primary outcome was the development of severe adverse events (SAEs). We analyzed correlations between primary outcome and CKD parameters [age, body mass index (BMI), estimated glomerular filtration rate (eGFR), urinary protein-creatinine ratio (UP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and not normal blood pressure (non-NBP)] at the time of referral. Secondary outcomes were low birth weight (LBW), preterm delivery (PreD), and small for gestational age (SGA). We divided into two categories, CKD stage G1, and G2 or higher according to eGFR, and proteinuria negative and proteinuria positive according to UP, respectively. RESULTS We observed 89 pregnancies. SAE was observed in 28 pregnancies.