A novel homozygous mutation in LSS gene possibly causes hypotrichosis simplex in two siblings of a Tibetan family from the western Sichuan province of China

Aim: Hypotrichosis simplex (MIM 146520) is a rare form of monogenic hereditary alopecia. Several genes have been identified as being associated with the disease, including LPAR6, LIPH, and DSG4. LSS encoding lanosterol synthase (LSS) has been shown to cause hypotrichosis simplex, but the related mechanisms have not been elucidated to date. This study aims to find mutations in LSS from a Chinese family, among which a 21-year-old male patient and his 9-year-old sister were affected by hypotrichosis simplex.Methods: Dermoscopy and histological analysis were used to examine patients’ scalps, while exome sequencing was used to find the mutations in LSS.Results: The hair loss was only detected on the scalp of the proband and his sister, while other ectodermal structures were normal with no systemic abnormalities. Further, the exome sequencing identified a new homozygous mutation NM_002340.6 (LSS_v001):c.812T>C (p.(Ile271Thr)) in the LSS gene of the proband, which was also found in his sister. In addition, a heterozygous mutation of LSS was found in their asymptomatic parents. Finally, the possible protein structure of the mutational LSS was predicted.Conclusion: The hypotrichosis simplex reported here could be an autosomal recessive disease in this family. The mutation on LSS might reduce the enzyme activity of LSS, thus leading to the disease

The Effects of Warfarin on the Pharmacokinetics of Senkyunolide I in a Rat Model of Biliary Drainage After Administration of Chuanxiong

The aim of this study was to elucidate the effects of warfarin on senkyunolide I in a rat model of biliary drainage after oral administration Chuanxiong extract based on pharmacokinetics. Thirty-two rats were randomly divided into four groups: CN, healthy rats after a single administration of Chuanxiong; CO, rats with biliary drainage after a single administration of Chuanxiong; WCN, healthy rats after the administration of Chuanxiong and warfarin; WCO, rats with biliary drainage after the administration of Chuanxiong and warfarin. A series of blood samples were collected at different time points before and after oral administration. An ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method for quantification of the main components of Chuanxiong and methyclothiazide (internal standard) have been established. The validated method was successfully applied to a comparative pharmacokinetics study. After calculated by the DAS 2.1.1 software, the pharmacokinetics parameters of senkyunolide I showed a significant difference between the CN and CO groups, the AUC0−t, and Cmax of CO group increased by 5.45, 4.02 folds, respectively. There was a significant difference between the WCO and WCN groups, the Tmax of WCO group prolonged 67%; compared to the CN group, the AUC0−t, and Cmax of WCN group raised 4.84, 3.49 folds, respectively; the Tmax and Cmax between the CO and WCO groups also showed a significant difference. The drug warfarin significantly affected the senkyunolide I disposition, which partly due to its enterohepatic circulation process in rat plasma after oral administration of Chuanxiong. The present study highlights an urgent evidence for drug-herb interactions

Observation of Fungi, Bacteria, and Parasites in Clinical Skin Samples Using Scanning Electron Microscopy

This chapter highlights the description of the clinical manifestation and its pathogen and the host tissue damage observed under the Scanning Electron Microscope, which helps the clinician to understand the pathogen’s superstructure, the change of host subcell structure, and the laboratory workers to understand the clinical characteristics of pathogen-induced human skin lesions, to establish a two-way learning exchange database with vivid image

Genomewide linkage scan in a multigeneration Caucasian pedigree identifies a novel locus for keratoconus on chromosome 5q14.3-q21.1

Purpose: Keratoconus is a corneal dystrophy with an incidence of 1 in 2000 and a leading cause for cornea transplantation in Western developed countries. Both clinical observations and segregation analyses suggest a major role for genes in its pathogenesis. It is genetically heterogenous, most commonly sporadic, but inherited patterns with recessive or dominant modes have also been reported. We studied a four-generation autosomaldominant pedigree to identify disease loci for keratoconus. Methods: A two-stage genome-wide scan was applied to 27 family members. First linkage analysis was performed with 343 microsatellite markers along the 22 autosomal chromosomes at Ϸ10 cM density. This was followed by fine mapping at Ϸ2 cM density, in regions suggestive of linkage. Multipoint linkage analysis was performed using GeneHunter2. Results: Evidence of suggestive linkage from the initial scan was observed at the 82 to 112 cM region of chromosome 5q14.1-q21.3 with a maximum lod score (LOD) of 3.48 (penetrance ϭ 0.5). Fine mapping by testing an additional 11 microsatellite markers at 1 to 3 cM intervals revealed a narrower and higher peak (99 -119 cM) with LOD 3.53. By analysis of the recombination of haplotypes, the putative locus of keratoconus was further narrowed to a 6 cM region (8

Artemisia pollen allergy in China : Component-resolved diagnosis reveals allergic asthma patients have significant multiple allergen sensitization

Background: Artemisia pollen allergy is a major cause of asthma in Northern China. Possible associations between IgE responses to Artemisia allergen components and clinical phenotypes have not yet been evaluated. This study was to establish sensitization patterns of four Artemisia allergens and possible associations with demographic characteristics and clinical phenotypes in three areas of China. Methods: Two hundred and forty patients allergic to Artemisia pollen were examined, 178 from Shanxi and 30 from Shandong Provinces in Northern China, and 32 from Yunnan Province in Southwestern China. Allergic asthma, rhinitis, conjunctivitis, and eczema symptoms were diagnosed. All patients sera were tested by ImmunoCAP with mugwort pollen extract and the natural components nArt v 1, nArt ar 2, nArt v 3, and nArt an 7. Results: The frequency of sensitization and the IgE levels of the four components in Artemisia allergic patients from Southwestern China were significantly lower than in those from the North. Art v 1 and Art an 7 were the most frequently recognized allergens (84% and 87%, respectively), followed by Art v 3 (66%) and Art ar 2 (48%). Patients from Northern China were more likely to have allergic asthma (50%) than patients from Southwestern China (3%), and being sensitized to more than two allergens increased the risk of allergic asthma, in which cosensitization to three major allergens Art v 1, Art v 3, and Art an 7 is prominent. Conclusions: Componentresolved diagnosis of Chinese Artemisia pollenallergic patients helps assess the potential risk of mugwortassociated allergic asthma.(VLID)329956

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Turbulent flow over a rough backward-facing step

This work characterizes the impacts of the realistic roughness due to deposition of foreign materials on the turbulent flows at surface transition from elevated rough-wall to smooth-wall. High resolution PIV measurements were performed in the streamwise-wall-normal (x–y) planes at two different spanwise positions in both smooth and rough backward-facing step flows. The experiment conditions were set at a Reynolds number of 3450 based on the free stream velocity U∞ and the mean step height h, expansion ratio of 1.01, and the ratio of incoming boundary layer thickness to the step height, δ/h, of 8. The mean flow structures are observed to be modified by the roughness and they illustrate three-dimensional features in rough backward-facing step flows. The mean reattachment length Xr is significantly reduced by the roughness at one PIV measurement position while is slightly increased by the different roughness topography at the other measurement position. The mean velocity profiles at the reattachment point indicate that the studied roughness weakens the perturbation of the step to the incoming turbulent flow. Comparisons of Reynolds normal and shear stresses, productions of normal stresses, quadrant analysis of the instantaneous shear-stress contributing events, and mean spanwise vorticity reveal that the turbulence in the separated shear layer is reduced by the studied roughness. The results also indicate an earlier separation of the turbulent boundary layer over the current rough step, probably due to the adverse pressure gradient produced by the roughness topography even before the step

Discrimination in Singapore job advertisements.

Singapore is a culturally rich society. At first glance, diverse racial and nationality groups in this city state seem harmonious. On closer examination, we realise that job market discrimination exists. While there have been many comments and debates about discrimination in the job market, few studies have been done to probe deeper into whether there is an existence of discrimination in Singapore labour market. The aim of this paper is to look at employers’ hiring patterns in advertisements which could imply discrimination. The job-advertisement methodology was chosen because employers in Singapore are not strictly governed by anti-discrimination legislation, Instead, they are only required to adhere to the non-mandatory Tripartite Guidelines, whose basic purpose is to ensure non-discriminatory job advertisements. Thus, employers are not encouraged to specify for certain requirements like gender, race or age. Without such legislations, the Tripartite Guidelines allow employers to ask for certain things such as photographs, language proficiency or state preferences for Singaporean nationality. Given such freely usage of requirements in job advertisements, the adoption of the job-advertisement approach in this study will enable us to detect discrimination at the initial stage of the hiring process. Job advertisements from an online job portal were collected over a span of one week as our sample. In the first model, we assessed the association between specification for both Mandarin and photograph in job advertisements. The intuition behind the first model is that when employers ask for Mandarin, it may be due to business needs where employees are required to liaise with Chinese clientele, or it may simply be employers’ desire to recruit Chinese candidates. In the latter case, there should be evidence that employers are more likely to ask for photograph when they ask for Mandarin to filter out non-Chinese candidates. Our results prove that there is relationship between Mandarin and photograph specification in job advertisements even after taking into account confounders. In the second model, we looked at which job industries have less preference for Singaporeans. The rationale behind this model is to determine whether the non-specification for Singaporeans in the job advertisements is due to the shortage of local labour or lack of foreign talents, or simply because employers do not favour Singaporeans.Bachelor of Art

Impact of Stress-Dependent Matrix and Fracture Properties on Shale Gas Production

Unconventional shale gas production is often characterized by a short period of high production followed by a rapid decline in the production rate. Given the high costs of hydraulic fracturing and horizontal drilling, it is critical to identify the mechanisms behind the production loss. The existing shale gas production models often assume constant matrix permeability. However, laboratory observations show that matrix permeability can decrease significantly with increasing effective stress, which highlights the necessity of considering the stress-dependent properties of shale matrix in production analysis. Moreover, the compaction of pore space will also increase the matrix permeability by enhancing the gas-slippage effect. In this paper, a matrix permeability model which couples the effect of pore volume compaction and non-Darcy slip flow is derived. Numerical simulations are conducted to understand the role of matrix permeability evolution during production. Changes of fractures’ permeability and contact area during depletion process are also taken into account. The results indicate that the loss of fracture permeability has a greater impact at the early stage of the depletion process, while matrix permeability evolution is more important for the long-term production