Paracrine cellular senescence exacerbates biliary injury and impairs regeneration

Senescence has been suggested as causing biliary cholangiopathies but how this is regulated is unclear. Here, the authors generate a mouse model of biliary senescence by deleting Mdm2 in bile ducts and show that inhibiting TGFβ limits senescence-dependent aggravation of cholangiopathies

How does split announcement affect stock liquidity? Evidence from Bursa Malaysia

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This study examines the impact of stock splits on stock liquidity in Bursa Malaysia from 2004–2018. The study uses event study methodology and investigates liquidity changes, the role of liquidity, and the relationship between abnormal returns and liquidity as well. We found a significant liquidity improvement on the splits announcement, announcement of book closing date and split execution date (Ex-date), while it declined after the split Ex-date. The findings also indicate that firms with a low-level liquidity prior to split announcements experienced an increase in liquidity after Ex-date. Using panel data analysis, we find that the fixed effect model is more appropriate than the pooled OLS, and the abnormal announcement returns are driven by stock liquidity

Genetic risk factors in patients with deep venous thrombosis, a retrospective case control study on Iranian population

Background: Venous thromboembolism (VTE) could be manifested as deep venous thrombosis (DVT) or pulmonary embolism (PE). DVT is usually the more common manifestation and is usually formation of a thrombus in the deep veins of lower extremities. DVT could occur without known underlying cause (idiopathic thrombosis) which could be a consequence of an inherited underlying risk factor or could be a consequence of provoking events, such as trauma, surgery or acute illness (provoked thrombosis). Our aim in this study was to assess the impact of some previously reported genetic risk factors including, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, plasminogen activator inhibitor-1(PAI-1) 4G/5G, prothrombin 20210 and FV Leiden on occurrence of DVT in a population of Iranian patients. Methods: This long-term study was conducted on 182 patients with DVT and also 250 age and sex matched healthy subjects as control group. The diagnosis of DVT was based on patient's history, clinical findings, D-dimer test, and confirmed by Doppler ultrasonography. After confirmation of DVT, both groups were assessed for the five mentioned mutations. The relationship between mutations and predisposition to DVT was calculated by using logistic regression and expressed as an OR with a 95 confidence interval (CI). Results: Our results revealed that FV Leiden (OR 6.7; 95 CI = 2.2 to 20.3; P = 0.001), MTHFR C677T (OR 6.0; 95 CI = 2.2 to 16.4; P < 0.001), MTHFR A1298C (OR 8.3; 95 CI = 4.4 to 15.8; P < 0.001), and PAI-1 4G/5G (OR 3.8; 95 CI = 2.1 to 7.2; P < 0.001) mutations were all significantly associated with an increased risk of DVT. Prothrombin 20210 was found in none of the patients and controls. Conclusion: Our findings suggest that genetic risk factors have a contributory role on occurrence of DVT. © 2015 Hosseini et al

The Founder Effect? -FXIII Deficiency in Southeast Iran: A Molecular Study Report

Background: Congenital factor XIII (FXIII) deficiency is an extremely rare bleeding disorder (RBD) with different clinical coagulation disorders and great impacts on the perioperative patient outcome. Its prevalence in Southeast Iran is approximately 4,000 times higher than the worldwide prevalence, with Trp187Arg (c.559T&gt; C as the only causative mutation of FXIIID there. We investigated the founder effect of rs1742924, rs4960181, rs3778360 and rs4142290 using haplotype analysis to define the genetic phenomenon in this geographic region. Materials and Methods: In a case-control study, 10 patients with FXIIID and 10 healthy individuals were assessed. Initially, Trp187Arg (c.559T&gt; C) mutation was assessed in all study populations using a PCR-RFLP technique, then haplotype analysis was performed by assessing rs1742924, rs4960181, rs3778360 and rs4142290 polymorphisms. Data were analyzed using a two-proportion z-test. Results: All patients were homozygote for Trp187Arg (c.559T&gt;C), and this mutation was not observed in any form of homozygote or heterozygote in the control group. Polymorphisms in rs1742924, rs4960181, and rs377836 were homozygote (TT, GG, GG, respectively) and T, G, and G alleles distribution in cases and controls with significant difference (P&lt;0.001, P&lt;0.001, and P=0.01 respectively). Rs4142290 polymorphism showed no significant difference between patients and controls (P=0.3). Two types of haplotypes were observed in the case group, and haplotype number 1* was observed among 90% of them, while not observed in the control group. Conclusion: It seems that founder effectors of haplotype number *1 have more antiquity versus other haplotypes, and probably founder effect is responsible for this high prevalence of FXIIID in the southeast of Iran

Prenatal diagnosis in rare bleeding disorders�An unresolved issue?

Intracranial haemorrhage (ICH) is the most dreadful complication, and the main cause of death among patients with rare bleeding disorders (RBD) and prenatal diagnosis (PND) is a preventative lifesaving program. A total of 39 PNDs were reported in the literature through a search on PubMed, EMBASE, SCOPUS and Web of Science databases, most often for congenital factor (F) XIII and FVII deficiencies and rarely in FX, FV deficiencies and afibrinogenemia. The main cause to request a PND is ICH and related morbidity and mortality. Different molecular methods including direct sequencing and linkage analysis as well as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for a specific mutation are the most common used methods for PND, while factor assay and combination of molecular and factor assay also were used. In this research, 7 severely affected foetuses were identified during PND including 3 foetuses with FXIII deficiency, 3 with FVII deficiency and 1 with FX deficiency. Out of these 7 cases, intrauterine ICH occurred in 1 case with FXIII deficiency, 1 was electively aborted and 1 case with severe FVII deficiency received intrauterine factor transfusion. Postdelivery ICH was reported for 1 patient with severe FVII deficiency within the first month of life. All other pregnancies were uneventful. © 2018 John Wiley & Sons Lt

Genome-wide mapping of cystitis due to Streptococcus agalactiae and Escherichia coli in mice identifies a unique bladder transcriptome that signifies pathogen-specific antimicrobial defense against urinary tract infection

The most common causes of urinary tract infections (UTIs) are Gram-negative pathogens such as Escherichia coli; however, Gram-positive organisms, including Streptococcus agalactiae, or group B streptococcus (GBS), also cause UTI. In GBS infection, UTI progresses to cystitis once the bacteria colonize the bladder, but the host responses triggered in the bladder immediately following infection are largely unknown. Here, we used genome-wide expression profiling to map the bladder transcriptome of GBS UTI in mice infected transurethrally with uropathogenic GBS that was cultured from a 35-year-old women with cystitis. RNA from bladders was applied to Affymetrix Gene-1.0ST microarrays; quantitative reverse transcriptase PCR (qRT-PCR) was used to analyze selected gene responses identified in array data sets. A surprisingly small significant-gene list of 172 genes was identified at 24 h; this compared to 2,507 genes identified in a side-by-side comparison with uropathogenic E. coli (UPEC). No genes exhibited significantly altered expression at 2 h in GBS-infected mice according to arrays despite high bladder bacterial loads at this early time point. The absence of a marked early host response to GBS juxtaposed with broad-based bladder responses activated by UPEC at 2 h. Bioinformatics analyses, including integrative system-level network mapping, revealed multiple activated biological pathways in the GBS bladder transcriptome that regulate leukocyte activation, inflammation, apoptosis, and cytokine-chemokine biosynthesis. These findings define a novel, minimalistic type of bladder host response triggered by GBS UTI, which comprises collective antimicrobial pathways that differ dramatically from those activated by UPEC. Overall, this study emphasizes the unique nature of bladder immune activation mechanisms triggered by distinct uropathogens

Evaluating the effect of remote ischemic preconditioning on kidney ischemia-reperfusion injury

Background: Acute kidney injury is a high-risk complication in a variety of clinical situations mostly due to ischemia-reperfusion (IR) injuries. The novel idea of remote ischemic preconditioning (rIPC) was proposed to prevent serious ischemia sequels. To address the controversy of previous reports, the current study was performed to assess the effect of rIPC on kidney IR injury. Materials and Methods: Male BALB/c mice were exposed to either rIPC or sham intervention, 24 h before kidney IR. In two independent sets of experiments, rIPC was accomplished by inducing three cycles of 5 min ischemia with 5 min reperfusion intervals through the ligation of the left external iliac artery or infrarenal abdominal aorta. Kidney IR injury was performed by left renal pedicle occlusion for 35 min and simultaneous right nephrectomy. After 48 h, mice were sacrificed for the assessment of kidney function and structure. Results: According to the serum urea and creatinine, as well as histopathological measures, none of the exploited rIPC procedures could significantly protect against kidney IR injury. Conclusion: Based on our findings and the divergent results of previous animal and human studies, it can be concluded that the renoprotective effects of rIPC are minimal, if any, and are not robustly detectable

Laboratory Diagnosis of Factor XIII Deficiency in Developing Countries: An Iranian Experience

Factor XIII (FXIII) deficiency is an extremely rare bleeding disorder with an approximately 12-times higher than the rest of the world. The International Society for Thrombosis and Hemostasis (ISTH) suggested a standard algorithm for precise diagnosis and classification of FXIII deficiency (FXIIID). However, due to lack of investment in proper equipment and procedures in Iran, almost no part of this algorithm can be used to diagnose Iranian patients. Thus, this study proposes a guideline for accurate molecular and laboratory diagnosis of FXIIID based on the available tools. Because this study suggests a simple and reliable algorithm for early diagnosis, it can therefore, reduce the rates of morbidity and mortality of FXIIID patients with this condition. © 2016 American Society for Clinical Pathology, 2016. All rights reserved