Medical Sciences Commons^™

Novel Role For St6gal1 Sialyltransferase As A Tumor Driver In Pancreatic Ductal Adenocarcinoma, Nikita Umakant Bhalerao

All ETDs from UAB

ST6Gal1 sialyltransferase adds negatively charged sialic acid in an α2,6 linkage to N-glycans on glycoproteins bound for the cell surface/secretion thus altering receptor structure, function and downstream signaling pathways. ST6Gal1 is upregulated in multiple cancers, including pancreatic, and imparts cancer stem cell-like phenotype. Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a survival rate of ~10%. Acinar to ductal metaplasia (ADM), the tumor initiation stage of PDAC, occurs in response to insults like pancreatitis, when acinar cells dedifferentiate and form ductal-like cells with stem and ductal gene upregulation. These cells, on acquiring mutations such as in KRAS gene, can …

Regulatory Elements Of Polyphosphate Biosynthesis, Marvin Qortez Bowlin

All ETDs from UAB

Polyphosphate (polyP) is an ancient, conserved, inorganic biomolecule. Biological systems have adapted many functions for this high-energy molecule, ranging from immune regulation in mammals to gene regulation in prokaryotes. Of particular interest is its use in bacterial stress responses. Bacteria use polyP to resist hazardous environmental elements like toxic molecules or nutrient starvation. In many bacterial species, polyP is synthesized by polyphosphate kinases (PPKs). PPK – discovered in Escherica coli (E. coli) – hydrolyzes adenosine-5’-triphosphate (ATP) to synthesize polyP. Species that use PPK develop multiple pathogenic defects when PPK activity is impaired, including, among others, antibiotic susceptibility. There is no …

Role Of Proteoglycan Forms Of The Type Iii Tgf-Β Receptor/Betaglycan In Tgf-Β Signaling In Ovarian Cancer Models, Alex Kwon-Bowers Choi

All ETDs from UAB

Proteoglycans (PG) are defined as proteins with one or more covalently bound polysaccharides called glycosaminoglycan chains (GAG). PGs can either be present on the cell surface or in the extracellular matrix to mediate cellular homeostasis in normal physiology as well as exert profound roles in diseases such as cancer. PGs can interact with a host of proteins such as growth factors through their core protein and/or their GAG chains, serving as an accessory receptor to mediate signaling by binding to the ligands and altering ligand-signaling receptor binding, defined as a co-receptor function. Developmentally and in pathologies like cancer, TGF-β signaling …

Challenges And Opportunities In Glioblastoma And Immunovirotherapy With Oncolytic Herpes Simplex Virus Type 1, Dagoberto Estevez-Ordonez

All ETDs from UAB

This dissertation covers data from published and pre-published studies exploring challenges and opportunities in the treatment of malignant glioma with emphasis in glioblastoma and oncolytic immunovirotherapy with an oncolytic herpes simplex virus type 1 (HSV-1) designed to induce expression of IL-12, M002 (murine IL-12) and M032 (human IL-12).It starts with the report of a study that uncovered important racial and socioeconomic disparities experienced by patients with glioblastoma treated in Alabama. Notable results also include the unexpected finding of increased survival in African American patients with glioblastoma even after controlling for factors associated with survival and socioeconomic disparities. The implications of …

Impact Of Exercise On Antioxidative-Stress Induced Endoplasmic Reticulum Dysfunction And Cardiac Remodelling, Arun Jyothidasan

All ETDs from UAB

The gain of function of nuclear factor erythroid 2 like 2 (Nrf2), in the absence of oxidative stress (or toxic insults), its pathophysiology arising from the endoplasmic reticulum and exercise intervention to mitigate the pathology are the focal point of this dissertation. Nrf2, when constitutively expressed, has been previously associated with cardiomyopathy. Chapter II investigated the hypothesis that cardiac-specific expression of Nrf2 (mNrf2-TG) would establish a pro-reductive state and trigger adaptive cardiac remodeling by enhancing the basal antioxidant defense. Through RNA profiling and imaging techniques, the study underscored that while acute preconditioning might prove advantageous against oxidative stress, prolonged pro-reductive …

The Critical Period Of Long-Term Plasticity In Adult-Born Granule Cells Is Mediated By T-Type Calcium Channels, William Michael Kennedy

All ETDs from UAB

Neurogenesis occurs in the dentate gyrus of adult rodents leading to a heterogeneous population of dentate granule cells (GCs) in the granule cell layer. Adult-born granule cells (abGCs) exhibit a transient period of elevated synaptic plasticity that contributes to their role in dentate gyrus function. Various mechanisms have been proposed to underlie the critical period of plasticity, including minimal GABAergic synaptic inhibition, robust NMDAR2B currents, and high intrinsic excitability conferred by T-type Ca2+ channels. In this collection of work, we investigate the critical period for long-term potentiation (LTP) in 4–6-week-old abGCs. We conclude that GABAergic inhibition regulates LTP in 4-week-old …

Characterizing The Role Of Mapk Phosphatases In Age-Dependent Macrophage Dysfucntion And Increased Suceptiblity To Pneumonia In A Tnf-Dependent Manner, Katherine Lauren Kruckow

All ETDs from UAB

Lower respiratory infections are the primary cause of infectious death among the elderly. One reason for this is ‘inflamm-aging,’ a chronic low-grade inflammatory state that develops with advanced age. Pertinently, our group has shown increases in TNF levels to be responsible for age-dependent macrophage dysfunction (ADMD) and, in turn, enhanced susceptibility to Streptococcus pneumoniae, the leading cause of community-acquired pneumonia. The underlying molecular mechanisms responsible, however, remain unclear. Following adoptive transfer of alveolar macrophages (AM) from aged (18+ months) or young (3-6 month) mice into young mice, followed by infection with S. pneumoniae, we found that aged AM were sufficient …

Time-Restricted Feeding Attenuates Obesity-Induced Muscle Dysfunction Through Energy Metabolism And Microbiota Modulation, Christopher Livelo

All ETDs from UAB

Obesity is a global epidemic that affects countless numbers of people caused by genetic and environmental factors including circadian disruption, which poses significant health risks to skeletal muscle physiology and other tissues. While a feeding fasting intervention known as time-restricted feeding (TRF) has been shown to mitigate obesity-related muscle dysfunction, the underlying mechanisms remain a subject of investigation. In this study, we delve into potential mechanisms underlying TRF's protective effects on muscle physiology in the context of diet- and genetic-induced obesity using Drosophila models. Our findings reveal that TRF triggers the upregulation of key genes involved in glycine production (Sardh …

Time-Restricted Feeding Modulates Dgat2 Expression In Cardiac And Skeletal Muscle, Yiming Guo Livelo

All ETDs from UAB

Circadian disruption caused by aging, genetic, environmental, and lifestyle factors can lead to compromised cardiac and skeletal muscle function and potentially accelerate the progression of metabolic diseases. Time-restricted feeding/eating (TRF/TRE, referred to as TRF hereafter), a dietary intervention that confines food intake within a consistent window of the day, has pleiotropic benefits from flies and mice to humans. However, the effectiveness of TRF on heart and muscle in the context of various metabolic challenges such as circadian disruption and obesity is largely unknown. Current insights into the mechanisms of TRF are primarily based on multi-omics approaches, particularly transcriptomes; however, limited …

Molecular Imaging To Evaluate Tumor Heterogeneity And Guide Treatment Of Breast Cancer, Yun Lu

All ETDs from UAB

Molecular imaging plays an important role in predicting and evaluating treatment response and revealing the underlying biological mechanisms in the cancer field. Especially, PET imaging serves as a valuable tool for comprehending the tumor microenvironment (TME), allowing us to track tumor metabolism, proliferation, receptor expression, and immune infiltration. In this comprehensive study, three distinct aspects of cancer research were explored using molecular imaging techniques.The first study aimed to evaluate the accuracy of the fluorescence ubiquitination cell cycle indicator (FUCCI) system with fluorescence in vivo imaging compared to 3'-Deoxy-3'-[18F]fluorothymidine ([18F]-FLT) positron emission tomography (PET)/computed tomography (CT) in assessing cancer cell proliferation. …

Cd151+ T Cell Frequencies As An Immunological Clock That Identifies Premature Immunological Aging In People With Hiv, Mildred Perez

All ETDs from UAB

Antiretroviral therapy (ART) has greatly improved the life expectancy of People With HIV (PWH), but despite ART, PWH show signs of chronic immune hyperactivation (CIH), which results in the development of early-onset comorbidities, such as metabolic syndrome, diabetes, cardiovascular complications, neurodegenerative impairment, and can-cer. The underlying causes of CIH are, at best, incompletely understood, with suggested roles of microbial translocation, viral coinfections, T cell imbalances, and persistent HIV replication. Given that the CD4+ T cell population is most affected during acute HIV infec-tion, it is surprising that no T cell populations have been identified as drivers of CIH. Herein, we …

Exercise-Driven Epigenetic And Transcriptomic Changes In An Experimental Model Of Temporal Lobe Epilepsy, Silvienne C. Sint Jago

All ETDs from UAB

Temporal lobe epilepsy (TLE) is a neurological disease marked by recurring unprovoked seizures originating from temporal lobe structures and is frequently associated with cognitive deficits. Exercise holds promise as a therapeutic approach to alleviate seizures and cognitive impairments in TLE. However, the exact cellular and molecular mechanisms by which exercise influences pathways related to seizure activity and cognition in the context of TLE still need to be understood. Neuronal network formation relies on the regulation of gene expression, which can lead to either an increase or a decrease in the production of essential proteins involved in neuronal signaling. Genes are …

The Influence Of Proximity On Patient Outcomes For Differently Structured Ambulatory Surgery Centers, Wendy Michelle Smith

All ETDs from UAB

THE INFLUENCE OF PROXIMITY ON PATIENT OUTCOMES FOR DIFFERENTLY STRUCTURED AMBULATORY SURGERY CENTERSWENDY SMITH HEALTH SERVICES ADMINISTRATION ABSTRACT This study examines the complication rates and patient-reported outcome measures (PROMs) for total hip and knee replacement surgeries conducted in one of two differently structured ambulatory surgical centers (ASCs) with varying interprofessional surgical teams. There is an ongoing shift from in-hospital total joint replacement surgeries to ASCs. Additionally, there is specialization occurring within ASCs. In this study, we compare single specialty ASCs designed to perform solely TJR surgeries with one orthopedic group and interprofessional team, with multi-specialty ASCs that perform an array …

Neuropeptide Y Overexpression In The Presence Of P23h Rhodopsin Mutation, Jean Sun

All ETDs from UAB

Neuropeptide Y (NPY), a 36-amino acid peptide, has been found to be the most abundant neuropeptide in the central nervous system, and it is widespread across mammalian species. NPY plays a dual role as a neurotransmitter and neuromodulator in the nervous system. NPY functions as a multifaceted neuromodulator through binding NPY receptors (NPYRs). NYP interacts with NPYRs and regulates various activities, such as cell growth, neurogenesis, neuroprotection, mitochondrial behaviors, food intake, anxiety, and addiction formation. In terms of NPY’s neuroprotective potential, NPY inhibits neuronal death signaling, thus preventing apoptosis, and displays anti-inflammatory and anti-oxidative effects. Additionally, it influences metabolism by …

Select Lipid Signaling. Derived From T-Cells Is An Important Contributor To Type 1 Diabetes Development, Tayleur White

All ETDs from UAB

We reported that Ca2+-independent phospholipase A2β (iPLA2) contributes to type 1 diabetes (T1D) development; however, the impact of lipid signaling from T-cells is unknown. To address this, we first administered splenocytes from NOD, NOD.iPLA2+/- (NOD.HET), or NOD.iPLA2-/- (NOD.KO) mice to 4-week-old NOD.scid recipients. As expected, T1D onset was rapid in NOD cell recipients and 100% by 12 weeks. However, onset was delayed by 1-3 weeks in NOD.HET or NOD.KO cell recipients and only 60% became diabetic, suggesting a role for T-cell iPLA2. Next, to establish importance of iPLA2 in CD4 or CD8 cells, purified cells were administered to NOD.scid mice. …

The Role Of Tissue- And Cell-Type-Specific Expression And Regulation In Setbp1-Associated Diseases, Jordan Hailey Whitlock

All ETDs from UAB

SET binding protein 1 (SETBP1) encodes a transcription factor (TF) participating in diverse cellular processes. SETBP1 is an epigenetic hub associated with variants linked to three distinct diseases. Germline variants cause rare pediatric Schinzel Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disorder (SETBP1-HD), featuring multisystemic abnormalities and neurodegeneration or milder brain issues with hypotonia, respectively. On the other hand, somatic variants contribute to hematological malignancies and adult cancer. To understand tissue-specific SETBP1 mechanisms, public RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project were analyzed. SETBP1 and targets were broadly expressed across 31 adult human tissues, revealing three distinct expression patterns: transcription …

Genetic Sequencing Of Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infections In Fully Vaccinated Healthcare Workers, Sara Haddad, John Zurlo, Zi-Xuan Wang, Bonnie Richards, Nitika Badjatia, Dagan Coppock

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Introduction

Since the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several efforts have been made to prevent infection, culminating in the development of highly effective vaccines. However, as genetic variants of the virus have emerged, concerns have arisen regarding potential limitations of available vaccines.

Methods

In this article, we evaluated SARS-CoV-2 breakthrough infections among 520 healthcare workers in a 950-bed hospital from March 1, 2021, to October 31, 2021, and stratified them according to the type of vaccine received. We tested for associations between Alpha and Delta strains of SARS-CoV-2 and clinical characteristics.

Results

During the study period, …

Mechanically Driven In Vivo Osteocyte Ca2+ Signaling: Aging And Pharmacologic Effects, James Padgett

Dissertations and Theses

Bone’s ability to respond and adapt to mechanical loading declines significantly with age which is a major contributor to bone fragility. It is widely accepted that osteocytes are the key cells responsible for orchestrating the development of the “ideal” skeleton. This ability is attributed to osteocyte’s role as the primary mechanosensing cell that is responsible for maintaining the skeleton’s integrity throughout life. Recent work from our laboratory has shed light into how osteocytes respond to mechanical loading in vivo. The breakthrough approaches that enabled these discoveries were development of: (1) the first ever reporter mouse model with a genetically encoded …

Prenatal Ethanol Exposure Impairs Performance On Spatial And Tactile Sequential Discrimination Task In Juvenile Rats, Caleb S. Bailey

Theses and Dissertations--Psychology

Fetal alcohol spectrum disorders (FASDs) are a set of cognitive and behavioral abnormalities that arise in ~5% of children who have been prenatally-exposed to alcohol. Prenatal alcohol exposure (PAE) can cause impairments in learning acquisition, working memory, response inhibition, and attentional-set shifting that result in exaggerated deficits in executive function and impairments in goal-seeking behavior. There are standard procedures used in rodent research to address some components of these deficits, but few procedures are sensitive enough to comprehensively assess such deficits. To address this issue in FASDs research techniques, we developed a procedure that requires prolonged executive function in a …

Ethanol Decreases Expression Of Developing Neurons, But Not Neuronal Viability, In A Cultured Rat Hippocampus, Cassidy Count

Theses and Dissertations--Psychology

As of 2019, alcohol use disorders (AUDs) affect roughly 14.1 million individuals over the age of 18 and cost up to $249 billion in economic burden in the United States. In addition to central nervous system (CNS), those affected by AUDs can present with cognitive and behavioral abnormalities. Specifically, those affected by AUDs experience deficits in memory consolidation and retrieval as well as executive functioning, which may be due to cellular changes within the hippocampus. There are at least two prominent and contended theories which explain the mechanism of functional impairment caused by alcohol: 1) alcohol induces excitotoxic neuronal death …

การศึกษาลักษณะกลายพันธุ์ของยีนที่ถอดรหัสเป็นโปรตีนในเยื่อหุ้มเซลล์เม็ดเลือดแดงในผู้ป่วยกลุ่มเยื่อหุ้มเซลล์เม็ดเลือดแดงผิดปกติ, จารุวรรณ ปานาราช

Chulalongkorn University Theses and Dissertations (Chula ETD)

โรคกลุ่มเยื่อหุ้มเซลล์เม็ดเลือดแดงผิดปกติเป็นโรคโลหิตจางตั้งแต่กำเนิดเกิดจากการกลายพันธุ์ของยีนที่กำหนดการสร้างโปรตีนไซโทสเกเลตอนซึ่งเป็นโครงสร้างของเยื่อหุ้มเซลล์เม็ดเลือดแดงเพื่อให้เซลล์เม็ดเลือดแดงมีความยืดหยุ่นและรักษารูปร่างได้โดยยีนที่เกี่ยวข้องได้แก่ ANK1, SPTA1, SPTB, EPB42 และ SLC4A1 งานวิจัยนี้ทำการศึกษาการกลายพันธุ์โดยใช้ Whole exome sequence (WES) และตรวจยืนยันผลด้วยเทคนิค Sanger sequencing ซึ่งงานวิจัยนี้พบการกลายพันธุ์ตำแหน่งใหม่ที่เป็นสาเหตุทำให้เกิดโรคเม็ดเลือดแดงป่องพันธุกรรมจำนวน 3 ตำแหน่งและพบการกลายพันธุ์ในผู้ป่วย hereditary pyropoikilocytosis (HPP) 1 ตำแหน่ง การกลายพันธุ์ตำแหน่งใหม่ประกอบด้วยการกลายพันธุ์ในยีน SPTB ตำแหน่ง c.5692C>T และ c.3823delG และในยีน ANK1 c.1994C>A ผลการศึกษาผลของการกลายพันธุ์ในระดับอาร์เอ็นเอพบว่าการกลายพันธุ์ตำแหน่ง c.5692C>T และ c.3823delG ในยีน SPTB และ c.1994C>A ในยีน ANK1 ส่งผลให้เกิด premature stop codon และพบว่าการกลายพันธุ์ตำแหน่ง c.5692C>T และ c.3823delG ในยีน SPTB ส่งผลให้ระดับการแสดงออกของยีนลดลงเมื่อเทียบกับคนปกติซึ่งอาจเกิดจากกระบวนการ nonsense-mediated mRNA degradation ทำให้ mRNA ที่ผิดปกติถูกทำลาย ผลจากการเพาะเลี้ยงเซลล์เม็ดเลือดตัวอ่อนพบว่าผู้ป่วยเม็ดเลือดแดงป่องพันธุกรรมมีอัตราการเพิ่มจำนวนเซลล์เม็ดเลือดแดงตัวอ่อนมากกว่าคนปกติ แต่มีการเจริญเติบโตและพัฒนาช้ากว่าคนปกติ จากการวัดปริมาณไมโครพาติเคิลด้วยเทคนิคโฟลไซโทเมทรีพบว่าในผู้ป่วยกลุ่มเยื่อหุ้มเซลล์เม็ดเลือดแดงผิดปกติมีปริมาณไมโครพาติเคิลที่สูงกว่าคนปกติ องค์ความรู้ที่ได้จากงานวิจัยนี้ทำให้ทราบกลไกการเกิดความผิดที่เกิดจากการกลายพันธุ์ของยีน SPTB และ ANK1 ในเซลล์เม็ดเลือดแดงผู้ป่วยกลุ่มเยื่อหุ้มเซลล์เม็ดเลือดแดงผิดปกติเพิ่มขึ้น

Autodocking Studies Of Oxygenated Fullerenes As Inhibitors Of The Hiv Protease, Michael Kaminski

All Student Theses and Dissertations

In a previous study, several oxygenated fullerene compounds were produced by ozonation of C60 (Buckminsterfullerene) and were identified by elemental analysis and by SALI (surface analysis by laser ionization). Some of these compounds, especially a batch, SK-5, a mixture of C60O1-8, were shown to inhibit activities of HIV-Protease with IC50 (concentration for 50% inhibition) of 1 mg/mol in the in-vitro studies. The oxygenated fullerenes were shown to have epoxide, ketones, and hydroxyl functionalities. As expected, C60 interacted with ozone with alkene functionality and not as an aromatic compound. It was postulated that C60O had epoxide functionality, as a product of …

Development Of A Pseudotype-Based Neutralization Test For Sars-Cov-2 Antibody Measurement, Kunlanan Charsangbong

Chulalongkorn University Theses and Dissertations (Chula ETD)

The gold standard for measuring anti-SARS-CoV-2 neutralizing antibody is a live-virus neutralization test (VNT). However, VNT is rather complex and must be performed in a biosafety level 3 facility. Therefore, a gene-encoding spike protein of the original SARS-CoV-2 variant was designed to develop a lentivirus-based SARS-CoV-2 pseudotype in this study to replace the live virus, which can be conducted in a biosafety level 2 facility. The 2nd generation lentiviral pseudotype with green fluorescent protein (GFP) and the 3rd generation lentiviral pseudotype with luciferase as a reporter system, respectively, provided a sufficient titer (TCID50/mL) for a neutralization test. However, the 3rd …

Measurement Of Precipitated Calcium Citrate In Urine By Murexide-Based Indicator Displacement Assay And Its Clinical Utility In Calcium Oxalate Urolithiasis, Chaiyadol Tantasith

Chulalongkorn University Theses and Dissertations (Chula ETD)

Urinary stone, mainly composed of calcium oxalate (CaOx), is a longstanding urologic condition with high prevalence and recurrence rates. Dietary habits, specifically increased consumption of high oxalate diet and low intake of citrate-containing foods, lead to hyperoxaluria and hypocitraturia that directly contribute to CaOx stone formation. Measurements of urinary oxalate and citrate are essential to estimate the risk of CaOx stone formation. Currently, high-performance liquid chromatography is used for urinary citrate measurement, but it is complicated and requires well-trained technicians. We hypothesized that instead of directly measuring citrate in urine, measurement of calcium citrate (CalCit) precipitated in urine challenging with …

Development Of Raman Spectroscopy-Integrated Calcium Oxalate Crystallization Index (Rcoci) Test And Its Clinical Validation For Diagnosing Calcium Oxalate Urolithiasis, Kamonchat Boonkam

Chulalongkorn University Theses and Dissertations (Chula ETD)

Urinary stone disease is mostly formed in the kidney and is highly recurrent. The most common type of urinary stones is calcium oxalate (CaOx). The development of urinary screening tests for estimating risk of CaOx stone formation is still challenging. Recently, we developed a urinary test, called indole-reacted calcium oxalate crystallization index (iCOCI) test, that provided a high diagnostic accuracy for CaOx urolithiasis. However, the iCOCI test is time-consuming and highly acidic chemicals are required for quantifying amount of CaOx. In this study, we proposed to develop a new method, called Raman spectroscopy-integrated calcium oxalate crystallization index (rCOCI) test, that …

The Combination Effect Of Lapatinib And Palbociclib In Endocrine-Resistant Breast Cancer Cells, Kantasorn Horpratraporn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Hormonal therapy is necessary in hormone receptor-positive breast cancer patients. It is used in both early and advanced-stage patients. Unfortunately, many patients developed endocrine resistance later on after the treatment was initiated and this could progress the disease. Endocrine resistance results from many mechanisms, including HER2 signaling pathway. These resistant breast cancer cells exhibit more HER2 signaling proteins such as AKT and ERK, compared to wild-type hormone receptor-positive breast cancer cells. Palbociclib is a CDK4/6 inhibitor and is indicated in patients who developed tamoxifen resistance. Lapatinib is a dual tyrosine kinase inhibitor- HER1 and HER2 and is used in HER2-overexpressed …

Epigenetic Regulation Of Leucine Rich Repeat Containing G Protein Coupled Receptor 5 (Lgr5) In Corneal Endothelial Cells, Kulsiri Prakanrattana

Chulalongkorn University Theses and Dissertations (Chula ETD)

Human corneal endothelial cells (hCECs) are vital for maintaining corneal transparency. However, their limited capacity for proliferation can result in vision loss, requiring corneal transplantation. The Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) plays a critical role in maintaining various fetal and adult stem cell types by promoting the Wnt/β-catenin signaling. Although LGR5 is present in corneal endothelial progenitors, its expression decreases as these cells mature, coinciding with the loss of replicative properties. In this study, we explore strategies to reactivate LGR5 expression in cultured hCECs through epigenetic modulation. We found low levels of DNA methylation and hydroxymethylation at LGR5 …

Crispr-Cas12a-Based Detection And Differentiation Of Mycobacterium Spp., Peeraphan Compiro

Chulalongkorn University Theses and Dissertations (Chula ETD)

Mycobacterium species cause several vital human diseases, including tuberculosis (TB) and non-tuberculous mycobacterial (NTM) infections. TB is a chronic infectious disease caused by the Mycobacterium tuberculosis complex (MTBC). Additionally, non-tuberculous mycobacteria infections are caused by major NTM species, including Mycobacterium abscessus, Mycobacterium avium, Mycobacterium fortuitum, Mycobacterium kansasii, Mycobacterium gordonae, and Mycobacterium intracelulare, are medically necessary. Both groups of infections can lead to outbreaks in immunocompromised individuals and AIDS patients. It is crucial to differentiate between these two groups of mycobacterial infections, as they require distinct treatment approaches. However, initial diagnosis poses limitations in terms of time and diagnostic tools. Therefore, …

Functional Studies Of P.N258k And P.G279d Variants In The Kcnq2 Gene, Suphalak Chokvithaya

Chulalongkorn University Theses and Dissertations (Chula ETD)

Mutations in the KCNQ2 gene encoding for voltage-gated K channel subunits underlying the neuronal M-current, have been associated with infantile-onset epileptic disorders. The clinical spectrum ranges from self-limited neonatal seizures to epileptic encephalopathy and delayed development. Although gain- and loss-of-function mutations of KCNQ2 leads to indistinguishable phenotypes, different therapeutic approaches are required. To better understand genotype-phenotype correlation, more reports of patients and their mutations with elucidated molecular mechanism are needed. Here, we report nine unrelated patients with KCNQ2-related epilepsy carrying de novo heterozygous KCNQ2 p.N258K or p.G279D identified via Trio exome sequencing that has never been previously reported. To investigates …

The Effect Of Water Temperature And Carbohydrate Drink On Intestinal Epithelial Injury, Endotoxemia, Splanchnic Perfusion, And Core Temperature, During Running In The Heat, Warot Rangsimahariwong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Prolonged exercise can result in splanchnic hypoperfusion and elevated core body temperature (Tcore), which can contribute to gastrointestinal injury and endotoxemia. The effects of fluid temperature and carbohydrate consumption during exercise on these variables are less clear. Objectives: The study aimed to determine the effects of the temperature of water and carbohydrate drinks on intestinal epithelial injury, endotoxemia, splanchnic perfusion, and Tcore during 60-minute of moderate-intensity running. Methods: Ten participants completed four 60-minute running trials at 70% VO2max with different types of hydration: no water (NW), ambient temperature water (ATW), cold water (CW), and cold carbohydrate water (CW+CHO). Doppler …