Association between longer hospitalization and development of de novo donor specific antibodies in simultaneous liver–kidney transplant recipients

© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Background:De novo Donor Specific Antibodies (DSA) are considered as a risk factor for the kidney allograft outcomes in recipients after simultaneous liver–kidney transplantation (SLKT). We hypothesized that length of hospital stay (LOS) might be associated with de novo DSA development of due to the increased likelihood of receiving blood transfusions with reduced immunosuppressive regimens. Methods: This study is a single-center, retrospective cohort study consisting of 85 recipients who underwent SLKT from 2009 to 2018 in our hospital. We divided the patients into two groups according to LOS [long hospital stay (L) group (LOS \u3e14 days) and short hospital stay (S) group (LOS ≤14 days)]. Propensity score (PS) has been created using logistic regression to predict LOS greater than median of 14 days. The association between the presence of de novo DSA and LOS was assessed by logistic regression models adjusted for PS. Results: The mean age at transplantation of the entire cohort was 55.5 ± 10.1 years. Sixty percent of the recipients were male and Caucasian. Median LOS in (L) group was three-fold longer than (S) group [L: median 30 days (IQR: 21–52), S: median 8.5 days (IQR: 7–11)]. Eight patients developed de novo DSA after SLKT (9.4%), all of them were in (L) group. Longer LOS was significantly associated with higher risk of development of de novo DSA in unadjusted (OR+ each 5 days: 1.09, 95% CI:1.02–1.16) and PS adjusted (OR+ each 5 days: 1.11, 95% CI:1.02–1.21) analysis. Conclusion: Longer hospitalization is significantly associated with the development of de novo DSA in SLKT

Vulnerability of primitive human placental trophoblast to Zika virus

Infection of pregnant women by Asian lineage strains of Zika virus (ZIKV) has been linked to brain abnormalities in their infants, yet it is uncertain when during pregnancy the human conceptus is most vulnerable to the virus. We have examined two models to study susceptibility of human placental trophoblast to ZIKV: cytotrophoblast and syncytiotrophoblast derived from placental villi at term and colonies of trophoblast differentiated from embryonic stem cells (ESC). The latter appear to be analogous to the primitive placenta formed during implantation. The cells from term placentas, which resist infection, do not express genes encoding most attachment factors implicated in ZIKV entry but do express many genes associated with antiviral defense. By contrast, the ESC-derived trophoblasts possess a wide range of attachment factors for ZIKV entry and lack components of a robust antiviral response system. These cells, particularly areas of syncytiotrophoblast within the colonies, quickly become infected, produce infectious virus and undergo lysis within 48 h after exposure to low titers (multiplicity of infection > 0.07) of an African lineage strain (MR766 Uganda: ZIKVU) considered to be benign with regards to effects on fetal development. Unexpectedly, lytic effects required significantly higher titers of the presumed more virulent FSS13025 Cambodia (ZIKVC). Our data suggest that the developing fetus might be most vulnerable to ZIKV early in the first trimester before a protective zone of mature villous trophoblast has been established. Additionally, MR766 is highly trophic toward primitive trophoblast, which may put the early conceptus of an infected mother at high risk for destruction

Rift Valley Fever Phlebovirus Reassortment Study in Sheep

Rift Valley fever (RVF) in ungulates and humans is caused by a mosquito-borne RVF phlebovirus (RVFV). Live attenuated vaccines are used in livestock (sheep and cattle) to control RVF in endemic regions during outbreaks. The ability of two or more different RVFV strains to reassort when co-infecting a host cell is a significant veterinary and public health concern due to the potential emergence of newly reassorted viruses, since reassortment of RVFVs has been documented in nature and in experimental infection studies. Due to the very limited information regarding the frequency and dynamics of RVFV reassortment, we evaluated the efficiency of RVFV reassortment in sheep, a natural host for this zoonotic pathogen. Co-infection experiments were performed, first in vitro in sheep-derived cells, and subsequently in vivo in sheep. Two RVFV co-infection groups were evaluated: group I consisted of co-infection with two wild-type (WT) RVFV strains, Kenya 128B-15 (Ken06) and Saudi Arabia SA01-1322 (SA01), while group II consisted of co-infection with the live attenuated virus (LAV) vaccine strain MP-12 and a WT strain, Ken06. In the in vitro experiments, the virus supernatants were collected 24 h post-infection. In the in vivo experiments, clinical signs were monitored, and blood and tissues were collected at various time points up to nine days post-challenge for analyses. Cell culture supernatants and samples from sheep were processed, and plaque-isolated viruses were genotyped to determine reassortment frequency. Our results show that RVFV reassortment is more efficient in co-infected sheep-derived cells compared to co-infected sheep. In vitro, the reassortment frequencies reached 37.9% for the group I co-infected cells and 25.4% for the group II co-infected cells. In contrast, we detected just 1.7% reassortant viruses from group I sheep co-infected with the two WT strains, while no reassortants were detected from group II sheep co-infected with the WT and LAV strains. The results indicate that RVFV reassortment occurs at a lower frequency in vivo in sheep when compared to in vitro conditions in sheep-derived cells. Further studies are needed to better understand the implications of RVFV reassortment in relation to virulence and transmission dynamics in the host and the vector. The knowledge learned from these studies on reassortment is important for understanding the dynamics of RVFV evolution

பழங்குடியினர் துணைத் திட்டம் (TSP), தமிழ்நாட்டின் கடலோர நீர்நிலைகளில் மீன் வளர்ப்பு நடைமுறைகள் பற்றிய - பயிற்சி கையேடு (10-12 அக்டோபர் 2022).

பழங்குடியினர் துணைத் திட்டம் (TSP), தமிழ்நாட்டின் கடலோர நீர்நிலைகளில் மீன் வளர்ப்பு நடைமுறைகள் பற்றிய - பயிற்சி கையேடு (10-12 அக்டோபர் 2022). Hands on training manual for mariculture practices in coastal waters of Tamil Nadu (TSP

ஆதிதிராவிடர் துணைத் திட்டம் (SCSP), தமிழ்நாட்டின் கடலோர நீர்நிலைகளில் மீன் வளர்ப்பு நடைமுறைகள் பற்றிய - பயிற்சி கையேடு (13-15 டிசம்பர் 2022)

ஆதிதிராவிடர் துணைத் திட்டம் (SCSP), தமிழ்நாட்டின் கடலோர நீர்நிலைகளில் மீன் வளர்ப்பு நடைமுறைகள் பற்றிய - பயிற்சி கையேடு (13-15 டிசம்பர் 2022) Hands on training manual for mariculture practices in coastal waters of Tamil Nadu (SCSP

THE ANALYSIS OF PUNCTUATION USE IN UNPUNCTUATED PASSAGES: A DISCOURSE-GRAPHOLOGY PERSPECTIVE

Diski Eginda Rismianti. 14111310149. The Analysis of Punctuation Use in Unpunctuated Passages: A Discourse-Graphology Perspective. Punctuation is the basic element in writing which is important to clarify meaning. Without punctuation or ignoring the rule of punctuation in a passage, the writing will be ambiguous. The writing course in IAIN Syekh Nurjati Cirebon is studied by English Student in 5 levels. Based the phenomenon, this research aims to find out the students’ error in the use of punctuation and how does the use relate to the meaning of restrictive and nonrestrictive elements. The analyses process in this research is constructed based on the theory from Marcella Frank. This research used qualitative method in analyzing data where the data contains the two original passages which is taken from the book of academic writing and the three participants’ work which are got by examining the passages as a main data source to be analyzed in this research. Those passages are changed be unpunctuated passages then examined to the 3 EFL learner which comes from the high score, medium score, and low score of writing. The result of this analysis shows that there are fifteen punctuation marks which are used in the two passages; they are capitalization, periods, commas, semicolons, colons, quotation marks, parentheses, apostrophes, hyphen, en dashes, ellipses, percent, underscore, at sign, and citation. FP has highest number of error in Capitalization with 100%. SP has big problem in commas exactly in the nineteenth rule with 90% and TP are wrong in parentheses. For restrictive and nonrestrictive elements, restrictive elements has higher number than nonrestrictive elements, except is in appositive. The numbers of the elements are same with the three participants. The differences come from the number of appositive which passages has higher number of nonrestrictive appositive than restrictive appositives. The results show that punctuation in unpunctuated passages used the rule from APA (American Psychological Association). The effects of the use of punctuation are in the number of sentences and clauses, types of phrases, and restrictive and nonrestrictive elements. For the students’ error, there are some sentences in FP and TP which only contain phrase. Key words: Punctuation Marks, Restrictive and Nonrestrictive Clause, Restrictive and Nonrestrictive Phrase, Restrictive and Nonrestrictive Appositives

The Pharmacogenomics of Bipolar Disorder study (PGBD): Identification of genes for lithium response in a prospective sample

Background: Bipolar disorder is a serious and common psychiatric disorder characterized by manic and depressive mood switches and a relapsing and remitting course. The cornerstone of clinical management is stabilization and prophylaxis using mood-stabilizing medications to reduce both manic and depressive symptoms. Lithium remains the gold standard of treatment with the strongest data for both efficacy and suicide prevention. However, many patients do not respond to this medication, and clinically there is a great need for tools to aid the clinician in selecting the correct treatment. Large genome wide association studies (GWAS) investigating retrospectively the effect of lithium response are in the pipeline; however, few large prospective studies on genetic predictors to of lithium response have yet been conducted. The purpose of this project is to identify genes that are associated with lithium response in a large prospective cohort of bipolar patients and to better understand the mechanism of action of lithium and the variation in the genome that influences clinical response. Methods/Design: This study is an 11-site prospective non-randomized open trial of lithium designed to ascertain a cohort of 700 subjects with bipolar I disorder who experience protocol-defined relapse prevention as a result of treatment with lithium monotherapy. All patients will be diagnosed using the Diagnostic Interview for Genetic Studies (DIGS) and will then enter a 2-year follow-up period on lithium monotherapy if and when they exhibit a score of 1 (normal, not ill), 2 (minimally ill) or 3 (mildly ill) on the Clinical Global Impressions of Severity Scale for Bipolar Disorder (CGI-S-BP Overall Bipolar Illness) for 4 of the 5 preceding weeks. Lithium will be titrated as clinically appropriate, not to exceed serum levels of 1.2 mEq/L. The sample will be evaluated longitudinally using a wide range of clinical scales, cognitive assessments and laboratory tests. On relapse, patients will be discontinued or crossed-over to treatment with valproic acid (VPA) or treatment as usual (TAU). Relapse is defined as a DSM-IV manic, major depressive or mixed episode or if the treating physician decides a change in medication is clinically necessary. The sample will be genotyped for GWAS. The outcome for lithium response will be analyzed as a time to event, where the event is defined as clinical relapse, using a Cox Proportional Hazards model. Positive single nucleotide polymorphisms (SNPs) from past genetic retrospective studies of lithium response, the Consortium on Lithium Genetics (ConLiGen), will be tested in this prospective study sample; a meta-analysis of these samples will then be performed. Finally, neurons will be derived from pluripotent stem cells from lithium responders and non-responders and tested in vivo for response to lithium by gene expression studies. SNPs in genes identified in these cellular studies will also be tested for association to response. Discussion: Lithium is an extraordinarily important therapeutic drug in the clinical management of patients suffering from bipolar disorder. However, a significant proportion of patients, 30–40 %, fail to respond, and there is currently no method to identify the good lithium responders before initiation of treatment. Converging evidence suggests that genetic factors play a strong role in the variation of response to lithium, but only a few genes have been tested and the samples have largely been retrospective or quite small. The current study will collect an entirely unique sample of 700 patients with bipolar disorder to be stabilized on lithium monotherapy and followed for up to 2 years. This study will produce useful information to improve the understanding of the mechanism of action of lithium and will add to the development of a method to predict individual response to lithium, thereby accelerating recovery and reducing suffering and cost.publishedVersio

Nicotine exposure and transgenerational impact: a prospective study on small regulatory microRNAs

Early developmental stages are highly sensitive to stress and it has been reported that pre-conditioning with tobacco smoking during adolescence predisposes those youngsters to become smokers as adults. However, the molecular mechanisms of nicotine-induced transgenerational consequences are unknown. In this study, we genome-widely investigated the impact of nicotine exposure on small regulatory microRNAs (miRNAs) and its implication on health disorders at a transgenerational aspect. Our results demonstrate that nicotine exposure, even at the low dose, affected the global expression profiles of miRNAs not only in the treated worms (F0 parent generation) but also in two subsequent generations (F1 and F2, children and grandchildren). Some miRNAs were commonly affected by nicotine across two or more generations while others were specific to one. The general miRNA patterns followed a “two-hit� model as a function of nicotine exposure and abstinence. Target prediction and pathway enrichment analyses showed daf-4, daf-1, fos-1, cmk-1, and unc-30 to be potential effectors of nicotine addiction. These genes are involved in physiological states and phenotypes that paralleled previously published nicotine induced behavior. Our study offered new insights and further awareness on the transgenerational effects of nicotine exposed during the vulnerable post-embryonic stages, and identified new biomarkers for nicotine addiction.ECU Open Access Publishing Support Fun