scholarly journals Comparative Transcriptional Analysis of Patient Responders Versus Non-Responders to Glucocorticoid Treatment for Bronchopulmonary Dysplasia

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A80-A80
Author(s):  
Victoria J Shi ◽  
Suban Burale ◽  
Tamorah Lewis ◽  
Neerupma Silswal ◽  
Paula Monaghan-Nichols

Abstract Bronchopulmonary Dysplasia (BPD) is a common heterogeneous lung disease that can result from preterm birth at less than 28-weeks gestation, prenatal and postnatal inflammatory insults, ventilator associated lung injury, and oxygen-related injury. Synthetic glucocorticoids (sGCs) are commonly used pre- and postnatally to treat inflammation and improve lung physiology. Clinical responses to sGC therapy for BPD vary in patients. We hypothesize that genetic background differences in transcriptional response to sGC therapy dictate the efficacy in infants with BPD. Identifying pathways and genes that mediate these differences will allow prospective determination of which infants would respond to sGC treatment. 26 preterm infants that received sGC treatment for BPD were identified. Respiratory Severity Score (RSS), an indication of BPD severity, was measured at diagnosis, 4 days, and 7 days post-sGC treatment. Patients were stratified into Responders versus Non-Responders by improvement in respiratory function after treatment. Changes in RSS were used to discriminate Responders (R >3 decrease in RSS) to treatment from Non-Responders (NR <3 decrease). 13 Responders and 13 Non-Responders were selected. They included 7 females and 19 males with an average gestational age of 24.3 weeks, and were 46% Caucasian, 31% African American, 19% Hispanic, and 4% other. 100µL of blood was collected before and after seven days of a dexamethasone treatment course. To examine differences in transcription response between Responders (n = 13) and Non-Responders (n= 13), RNA was isolated and analyzed using the Clariom S Human Transcriptome Affymetrix array. 21,500 expressed genes were profiled. Results: were imported into the Transcriptome Analysis Console (TAC) software, and genes with a significant difference (fold change >1.48 or < -1.48 and p-value <0.05) in Responders and Non-Responders were identified. Of those, 133 genes were upregulated and 74 downregulated. Ingenuity Pathway Analysis (IPA) was used to identify signaling pathways and disease processes that were uniquely altered in Responders versus Non-Responders. Non-Responders showed significant activation of neuroinflammatory signaling pathways, degranulation pathways, and lymphocyte activation disease pathways. Target genes in the top dysregulated pathways were evaluated using quantitative Polymerase Chain Reaction (qPCR). Expression changes in Matrix Metalloproteinase-25, Interleukin-12 Receptor beta, and Microsomal Glutathione Transferase-1, key mediators of inflammation, were validated in independent studies using qPCR. While response to systemic glucocorticoids in neonates with BPD is variable, these studies identified pathways that are altered in Responders versus Non-Responders and are a step towards developing pre-screening tools to stratify infants for response to sGC BPD therapy.

2019 ◽  
Vol 48 (2) ◽  
pp. 1-6
Author(s):  
Dulal Chandra Das ◽  
Sheikh Mohammad Noor E Alam ◽  
Ripon Das ◽  
Masuda Mohsena ◽  
Mamun Al Mahtab

Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by excessive triglyceride- accumulation in hepatocytes. NAFLD has a multifactorial etiology and a combination of environmental, genetic and metabolic factors play a role in the development of advanced disease. NAFLD consists of a wide spectrum of conditions, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which can progress to cirrhosis and hepatocellular carcinoma (HCC). Despite the high prevalence and severity of hepatic illness, NAFLD remains under diagnosed, because of few symptoms, lack of accurate laboratory markers. The accurate diagnosis of NASH remains dependent on specific histological parameters in liver biopsy. Although liver biopsy remains the ‘gold standard’, there are practical limitations, including costs and risks. There is an increasing requirement for simple, less invasive, highly accurate and affordable screening tools. Alanine aminotransferase (ALT) has been proposed as a noninvasive and available marker for assessment of NASH. A hospital based observational study was carried out for a period of two years in the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Data were analyzed by SPSS version 16. Statistical inference were done by estimating distribution, Chi-square test and student’s t-test respectively. Fifty (50) patients were analysed.Twenty five were NASH and twenty five were simple steatosis. ALT in NASH group  were 97.0±51.5IU/L and insimple steatosis group were 55.5±28.6 IU/L. In NASH group 64%  of raised ALT had NASH . In Non-NASH group 16% of raised ALT had no NASH.There was significant difference in the NAFLD activity score for diagnosing NASH between elevated and normal ALT( P  value 0.001). Bangladesh Med J. 2019 May; 48 (2): 1-6


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Sepideh Abdollahi ◽  
Pantea Izadi ◽  
Shahla Noori Ardebili ◽  
Samaneh Chegeni ◽  
Mir Saead Yekaninejad

Background: Endometriosis is one of the common gynecological diseases and can lead to pelvic pain, dysmenorrhea, dyspareunia, and infertility in women. Thus, accurate and early diagnosis is a pivotal issue and an essential need for managing this disorder. At the present, the gold standard diagnostic method for endometriosis is laparoscopic surgery that is an invasive method and can lead to delay in diagnosis. Thus, there is an immediate necessity to search for non-invasive diagnostic biomarkers, such as blood-based ones. Objectives: Matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor-A (VEGF-A) have essential roles in the pathogenesis of endometriosis. Therefore, in this study, we evaluated the plasma mRNA levels of MMP-9 and VEGF-A, as potential non-invasive diagnostic biomarkers for endometriosis. Methods: This study included 48 women (24 cases and 24 controls) who underwent laparoscopy for suspected endometriosis. Preoperative plasma samples were collected, and after RNA extraction, the levels of MMP-9 and VEGF-A mRNAs were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: Plasma MMP-9 mRNA level was statistically higher in endometriosis patients compared with the control group (P value = 0.01). However, plasma VEGF-A mRNA level did not show a significant difference between the two groups (P value =0.5). Conclusions: It seems that the plasma level of MMP-9 mRNA in endometriosis patients is significantly higher than in non-endometriosis women. This finding can provide new insights regarding this mRNA’s applicability as a non-invasive diagnostic biomarker for discovering new cases of endometriosis (newly diagnosed). According to our results, despite the suggested role of VEGF-A in endometriosis pathogenesis, it seems that the plasma level of VEGF-A mRNA does not have the potential to be used as a non-invasive diagnostic biomarker.


2020 ◽  
Vol 16 (4) ◽  
pp. 222-229
Author(s):  
Surakchhya Gautam ◽  
Sangita Thapa ◽  
Anju Khapung

ABSTRACT Background Serum uric acid (UA) is associated with many health conditions, including renal, cardiovascular and metabolic disorders. Diagnosis and monitoring often require painful invasive procedures which will add undue stress to the patients. The aim of this study was to correlate salivary and serum UA, so that, salivary sampling will help to bypass these measures and evaluate the condition of both healthy and the diseased. Methods This hospital based descriptive cross sectional study was conducted in 100 participants between age groups 21 to 82 years. Demographic data including height, weight and blood pressure were recorded. Serum and salivary samples were collected and UA level in both type of samples were estimated and correlation statistics was carried out. Results Total participants are categorized in three groups, 20-40, 41-60 and more than 60 years, among which maximum participants 43% are between 41-60 years of age. Average of body mass index (BMI) was found to be 24.46, where 50% were within normal range. Mean serum and salivary UA(mg/dl) was 4.15 and 1.90 respectively, exhibiting moderate positive correlation. They were correlated with significant “p-value” according to gender, age groups and disease conditions. Paired t- test was done between the measured and calculated salivary UA and no statistically significant difference in mean of these two values was obtained. Conclusions Salivary and serum UA are associated in our study so salivary UA can be used as a biomarker. Salivary UA was found to be more gender specific and specific among adults. Salivary UA can also be used as a screening tools for young and adult population.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3988-3988
Author(s):  
Vincenzo Fontana ◽  
J.Y. Wenche ◽  
Lawrence Horstman ◽  
Pamela Dudkiewicz ◽  
Joaquim Jimenez ◽  
...  

Abstract INTRODUCTION: Lymphoproliferative diseases embrace a variety of disorders including chronic lymphocytic leukemia (CLL), lymphomas and multiple myeloma (MM). The incidence of thrombosis varies in these disorders. C-MP are microvesicles released upon activation or apoptosis from endothelial cells (EMP), platelets (PMP), leukocytes (LMP) and red cells (RMP), and are believed to play a role as mediators of inflammation, hemostasis and thrombosis. METHODS: Forty-two patients with lymphoproliferative diseases were enrolled (24M/ 18F; mean age 67.5yr). These included 18 CLL (11M/7F; mean 69.2yr), 11 lymphomas (7M/4F; mean 65.3yr) and 13 MM (6M/7F; mean 67.1yr). History of thrombosis during the course of the lymphoproliferative disease was obtained. C-MP were measured by flow cytometry. LMP were identified by anti-CD45, PMP by anti-CD41, RMP by anti-glycophorin and EMP by CD31+ / CD41−. C-MP were compared between the three groups, and between patients with thrombosis (TB) and without (NTB). RESULTS: (1) History of thrombosis was most prevalent in MM (29%), followed by lymphomas (18%) and none of the CLL. (2) When C-MP were compared among CLL vs. lymphomas, and CLL vs. MM groups, mean levels of EMP, PMP showed no significant differences. However, RMP were higher in lymphomas than CLL (1193 vs. 746, p=0.03), and were markedly higher in MM than CLL (1623 vs. 746, p=0.009). LMP were also higher in CLL vs. MM (1,495 vs. 1,086, p = 0.02). No significant difference was seen in MP when comparing CLL vs. MM. Table 1. Data on patients and C-MP CLL Lymphoma MM p value p value CLL vs. Lymph CLL vs. MM No pts 18 11 13 Age 69.2 65.3 67.1 Sex (M/F) 11/7 7/4 6/7 Thrombosis 0/0 0/2 (18%) 0/4 (29%) n. s. 0.04 C-MP:     EMP 349 340 442 n. s. n. s.     PMP 8,688 8,691 8,079 n. s. n. s.     LMP 1,495 1,270 1,086 n. s. 0.02     RMP 746 1,193 1,623 0.03 0.009 (3) When c omparing C-MP between TB vs. NTB groups, RMP were nearly 3-fold higher in TB (mean values 2423 vs. 900; p<0.0001). EMP were also significantly higher in TB but less markedly (568 vs. 344; p= 0.008). There was no significant difference of PMP or LMP, between these 2 groups (p>0.05). Table 2. Comparison of C-MP in TB vs. NTB TB NTB p value No pts 6 36 C-MP: EMP 568 344 0.008 PMP 11,253 8,042 n. s. LMP 1,151 1,315 n. s. RMP 2,423 900 <0.0001 CONCLUSIONS: History of thrombosis was most prevalent in MM, followed by lymphomas, least in CLL. Our data from this limited patient population is consistent with the literature. PMP and EMP were similar in CLL, lymphomas and MM. However, RMP were higher in lymphomas and MM. Conversely, LMP were higher in CLL than in MM probably due to higher white count. Levels of RMP and EMP were associated strongly with thrombosis, being higher in TB. RMP are enriched in procoagulant phospholipids. We reported elevated RMP as a risk factor for thrombosis in myeloproliferative disorders [Fontana et al, ASH Abst #1483, 2006] and prevent bleeding in thrombocytopenia [Fontana et al, ASH Abst #1087, 2006]. These findings suggest that RMP play a role in the pathogenesis of thrombosis in lympho- and myelo-prolifertive disorders. However, the mechanism of their generation and the exact nature of their likely role remains to be elucidated.


Author(s):  
Zainab H El-Dahshan ◽  
Mohammed M El-Naggar ◽  
Om Ali Y El-Khawaga ◽  
Ahmed El-Waseef ◽  
 Sherin Abd El-Aziz ◽  
...  

Background and aim for the work: Bone marrow failure (BMF) is the inability of the bone marrow to produce an adequate number of peripheral blood cells. BMF included inherited and acquired conditions. The telomerase complex maintains telomere length (TL) in embryonic cells and in few adult cell types such as germ cells, stem cells, T lymphocytes, and monocytes. All the other adult cells, including blood cells, show a progressive reduction in telomere length, which correlates with the age and rate of cell proliferation. Our study aims to evaluate the utility of Real-Time Quantitative-Polymerase Chain Reaction (RQ-PCR) in measuring the relative telomere length and to investigate its correlation with the clinicopathological data of the Egyptian BMF patients. Materials and methods: The study included 3 groups: a group of inherited BMF (25 patients), a group of acquired BMF (10 patients) and a third healthy control group (15 cases). The relative telomere length (RTL) is evaluated for them using RQ-PCR. Results: We have found a significant difference in RTL between all BMF patients and healthy controls (P value= 0.001), there was a significant difference in RTL between inherited BMF patients and its age-matched controls (P value=0.009), also a significant difference between acquired BMF patients and its age-matched controls (P value= 0.034). However, there was no significant difference between inherited and acquired BMF patients (P value= 0.479). On the other hand, we find an association between RTL and lymphocyte count (P value= 0.032) in inherited BMF patients. While another association observed with RTL and red blood cell count (RBCs) in acquired BMF patients (P value= 0.048). There was no significant correlation with RTL and the overall survival or prognosis of those patients. Conclusion: We conclude that the telomere lengths are significantly altered in Egyptian BMF patients, either whether inherited or acquired compared to the control group, with some hematological changes.


Author(s):  
Weni F. Nazulis ◽  
Delmi Sulastri ◽  
Yuniar Lestari

Background: Life expectancy was one indicator of human development index in the health sector, one of which was affected by the telomere shortening process. There were many factors that cause shortening of telomere, including an imbalance of carbohydrate consumption then oxidative stress. The study aimed to examine the association between carbohydrate and carbohydrate simplex (sucrose) consumption with telomere length based on plasma malondialdehyde in Minangkabau male.Methods: The study was cross-sectional with 97 samples from male civil servant, Minangkabau ethnic, 40-50 years old in Padang City. Carbohydrate and sucrose consumptions were obtained through semiquantitative food frequency questionnaire, plasma malondialdehyde examination with thiobarbituric acid test and telomere length measured by quantitative polymerase chain reaction using O'Challagan and Fenech method.Results: The result showed mean of telomere length was 550.43±188.47 bp; mean of carbohydrate consumption 1280.97±433.57 kcal or 48.80±16.52%; mean of sucrose consumption 179.40±126.61 kcal or 6.83±4.82% and mean plasma malondialdehyde 66.91±13.93 nmol/ml. The association of carbohydrate consumption with telomere length based on plasma malondialdehyde was obtained p-value = 0.714, 0.908 and 0.903. The relationship of sucrose consumption with telomere length based on malondialdehyde was obtained p-value=0,667 and 1,000. Differences in mean telomere length in various categories of carbohydrate and sucrose consumption obtained p-value = 0.547 and 0.559.Conclusions: There was no significant association between carbohydrate and carbohydrate simplex (sucrose) consumption with telomere length based on plasma malondialdehyde of Minangkabau male; and no significant difference in telomere length in different categories of carbohydrate consumption and different sucrose consumption.


2019 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Dini Kesuma

Synthesis of the 4-chlorobenzoylthiourea compound was carried out by acylating thiourea with 4-chlorobenzoyl chloride. The 4-chlorobenzoylthiourea compound  will increase the lipophilic and the electronic properties other than the lead compounds of benzoylthiourea in order to, by expectation, raise the central nervous system depressant as well. The lipophilic would affect the ability of the compounds in penetrating biological membranes, which is highly dependent on the solubility of the drug within lipid/water. Log P is the most common method used in determining the parameter value. This experiment was to mix two dissolvents (octanol and water) which are immissible. The both levels of the compounds were carefully observed by a spectrophotometer UV-Vis. From the test, the result of log P value of the 4-chlorobenzoylthiourea compound was 2.32, while the theoretical log P value of the compounds, by using the π Hansch-Fujita method is 1.62 and the f Rekker-Mannhold method is 2.225. Consequently, the result of the test shows that there is a significant difference between the progress experiment and both theoretical log P methods. Moreover, in the test of the central nervous system depressant through the potentiation test to thiopental using mice indicates that the 4-chlorobenzoylthiourea compound have potentiation effects to thiopental compared to the lead compounds of benzoylthiourea.


Author(s):  
Eliyas Sulaiman Mohandas ◽  
Nik Mastura Nik Ismail Azlan ◽  
Salwa Othman ◽  
Muhammad Aizat Azhari

This study aims to investigate whether the use of six selected short stories throughout the duration of a 14-week course could enhance students’ reading comprehension achievement at the end of the semester. Out of the six short stories read, three were chosen as in-class assignments known as ‘Personal Reading Logs’ (hereafter, PRLs). One group of semester two Diploma students taking a reading skills course was selected through a convenience sampling method. A pre-test was conducted by having the students answer a past semester reading quiz of which the results would then be compared to their post-test (final reading exam) results. A paired samples t-test revealed no significant difference in the reading scores of the pre-test and the post-test, t (17) = -.265, p > .05. Since the p-value was bigger than 0.05, this indicated that the mean reading score of the post-test (M = 50.556) was not significantly higher than the mean reading score of the pre-test (M = 49.722). Therefore, the null hypothesis which stated that there was no difference in the mean score of the pre-test and post-test was retained. Overall, the result refuted the findings of other studies promoting the effectiveness of using short stories to enhance L2 reading comprehension achievement.


Author(s):  
Hilman Syarif

Introduction: Student Centered Learning (SCL) is an effective method to develop student's soft skills and hard skills which are very important to support their successful carrier later. This research was conducted to identify the differences of developed soft skills between students who learn with PBL method and lecturing method. Methods: Descriptive comparative method was used in this study. The samples consisted of 15 students who learned with PBL method and 15 students who learned with lecturing method. The sample for this research was selected by random sampling method. Results: The result showed that the average of student's soft skills score in PBL method was 122.63, while student's soft skills score in lecturing method was 116.27. Discussion & Conclusion: There was significant difference of student's soft skills in PBL method and lecturing method (p value = 0.038; α = 0.05). This study recommends nursing program management, faculty of medicine at the University of Syiah Kuala keeps PBL method running and develops other methods which facilitate hard skills and soft skills are development. Keywords: nursing students, soft skill, PBL


2018 ◽  
Vol 1 (2) ◽  
pp. 114
Author(s):  
Wahdaniah Wahdaniah ◽  
Sri Tumpuk

Abstract: Routine blood examination is the earliest blood test or screening test to determine the diagnosis of an abnormality. Blood easily froze if it is outside the body and can be prevented by the addition of anticoagulants, one of which Ethylene Diamine Tetra Acetate (EDTA). Currently available vacuum tubes containing EDTA anticoagulants in the form of K2EDTA and K3EDTA. K3EDTA is usually a salt that has better stability than other EDTA salts because it shows a pH approaching a blood pH of about 6.4. The purpose of this research is to know the difference of erythrocyte index results include MCH, MCV and MCHC using K3EDTA anticoagulant with K2EDTA. This research is a cross sectional design. This study used venous blood samples mixed with K2EDTA anticoagulant and venous blood mixed with K3EDTA anticoagulants, each of 30 samples. Data were collected and analyzed using paired different test. Based on data analysis that has been done on MCH examination, p value <0,05 then there is a significant difference between samples with K3EDTA anticoagulant with K2EDTA to erythrocyte index value. Then on the examination of MCV and MCHC obtained p value <0.05 then there is no significant difference between samples with K3EDTA anticoagulant with K2EDTA to erythrocyte index value.Abstrak: Pemeriksaan darah rutin merupakan pemeriksaan darah yang paling awal atau screening test untuk mengetahui diagnosis suatu kelainan. Darah mudah membeku jika berada diluar tubuh dan bisa dicegah dengan penambahan antikoagulan, salah satunya Ethylene Diamine Tetra Acetate (EDTA). Dewasa ini telah tersedia tabung vakum yang sudah berisi antikoagulan EDTA dalam bentuk  K2EDTA dan  K3EDTA. K3EDTA  biasanya berupa garam yang mempunyai stabilitas yang lebih baik dari garam EDTA yang lain karena menunjukkan pH yang mendekati pH darah yaitu sekitar 6,4. Tujuan dari penelitian ini adalah untuk mengetahui perbedaan hasil indeks eritrosit meliputi MCH, MCV dan MCHC menggunakan antikoagulan K3EDTA dengan K2EDTA. Penelitian ini merupakan penelitian dengan desain cross sectional. Penelitian ini menggunakan sampel darah vena yang dicampur dengan antikoagulan K2EDTA dan darah vena yang dicampur dengan antikoagulan K3EDTA, masing-masing sebanyak 30 sampel. Data dikumpulkan dan dianalisis menggunakan uji beda berpasangan. Berdasarkan analisis data yang telah dilakukan pada pemeriksaan MCH didapatkan nilai p < 0,05 maka ada perbedaan yang signifikan antara sampel dengan antikoagulan K3EDTA dengan K2EDTA terhadap nilai indeks eritrosit. Kemudian pada pemeriksaan MCV dan MCHC didapatkan nilai p < 0,05 maka tidak ada perbedaan yang signifikan antara sampel dengan antikoagulan K3EDTA dengan K2EDTA terhadap nilai indeks eritrosit.


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