Digital Commons Network^™

Probing Membrane-Associated Cytoskeletal Oligomers Of The Bacterial Divisome By Electron Microscopy And Tomography, Bo Hu, William Margolin

Faculty, Staff and Student Publications

The cell division machinery or "divisome" of many bacteria, including Escherichia coli, contains homologs of tubulin (FtsZ) and actin (FtsA) that interact with each other to promote the synthesis of septal peptidoglycan. FtsA oligomers have an essential role as a track for tethering dynamically treadmilling FtsZ protofilaments to the cytoplasmic membrane. Other bacterial cytoskeletal oligomers such as MreB also assemble on and move along the membrane. Structures of these oligomers on membranes in vitro may mimic their behavior in the cell. Here, we describe a protocol to visualize FtsA oligomeric structures on membranes and their interactions with FtsZ protofilaments using …

Usp22 Overexpression Fails To Augment Tumor Formation In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …

Protection Against Fibrosis By A Bacterial Consortium In Metabolic Dysfunction-Associated Steatohepatitis And The Role Of Amino Acid Metabolism, Suet-Ying Kwan, Kristyn A Gonzales, Mohamed A Jamal, Heather L Stevenson, Lin Tan, Philip L Lorenzi, P Andrew Futreal, Ernest T Hawk, Joseph B Mccormick, Susan P Fisher-Hoch, Robert R Jenq, Laura Beretta

Faculty, Staff and Student Publications

The gut microbiota drives progression to liver fibrosis, the main determinant of mortality in metabolic dysfunction-associated steatohepatitis (MASH). In this study, we aimed to identify bacterial species associated with protection against liver fibrosis in a high-risk population, and test their potential to protect against liver fibrosis in vivo. Based on stool shotgun metagenomic sequencing of 340 subjects from a population cohort disproportionally affected by MASH, we identified bacterial species from the Bacteroidales and Clostridiales orders associated with reduced risk of liver fibrosis. A bacterial consortium was subsequently tested in a mouse model of MASH, which demonstrated protective effects against …

Usp22 Overexpression Fails To Augment Tumor Formation In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …

Interleukin-1beta And Inflammasome Expression In Spinal Cord Following Chronic Constriction Injury In Male And Female Rats, Suzanne M Green-Fulgham, Jayson B Ball, Andrew J Kwilasz, Michael E Harland, Matthew G Frank, Joseph M Dragavon, Peter M Grace, Linda R Watkins

Faculty, Staff and Student Publications

Females represent a majority of chronic pain patients and show greater inflammatory immune responses in human chronic pain patient populations as well as in animal models of neuropathic pain. Recent discoveries in chronic pain research have revealed sex differences in inflammatory signaling, a key component of sensory pathology in chronic neuropathic pain, inviting more research into the nuances of these sex differences. Here we use the chronic constriction injury (CCI) model to explore similarities and differences in expression and production of Inflammatory cytokine IL-1beta in the lumbar spinal cord, as well as its role in chronic pain. We have discovered …

Dissecting The Shared Genetic Architecture Between Alzheimer’S Disease And Frailty: A Cross-Trait Meta-Analyses Of Genome-Wide Association Studies, Nitesh Enduru, Brisa S Fernandes, Zhongming Zhao

Faculty, Staff and Student Publications

Introduction: Frailty is the most common medical condition affecting the aging population, and its prevalence increases in the population aged 65 or more. Frailty is commonly diagnosed using the frailty index (FI) or frailty phenotype (FP) assessments. Observational studies have indicated the association of frailty with Alzheimer's disease (AD). However, the shared genetic and biological mechanism of these comorbidity has not been studied.

Methods: To assess the genetic relationship between AD and frailty, we examined it at single nucleotide polymorphism (SNP), gene, and pathway levels.

Results: Overall, 16 genome-wide significant loci (15 unique loci) (p meta-analysis < 5 × 10-8) and 22 genes (21 unique genes) were identified between AD and frailty using cross-trait meta-analysis. The 8 shared loci implicated 11 genes: CLRN1-AS1, CRHR1 …

Polaris: A Phase 2 Trial Of Encorafenib Plus Binimetinib Evaluating High-Dose And Standard-Dose Regimens In Patients With Braf V600-Mutant Melanoma With Brain Metastasis, Alexander M Menzies, Georgina V Long, Amiee Kohn, Hussein Tawbi, Jeffrey Weber, Keith Flaherty, Grant A Mcarthur, Paolo A Ascierto, Yanina Pfluger, Karl Lewis, Katy K Tsai, Omid Hamid, Hans Prenen, Luis Fein, Erjian Wang, Carolin Guenzel, Fan Zhang, Joseph F Kleha, Alessandra Di Pietro, Michael A Davies

Faculty, Staff and Student Publications

Background: POLARIS (phase 2 [ph2]; NCT03911869) evaluated encorafenib (BRAF inhibitor) in combination with binimetinib (MEK1/2 inhibitor) in BRAF/MEK inhibitor-naïve patients with BRAF V600-mutant melanoma with asymptomatic brain metastases.

Methods: The safety lead-in (SLI) assessed tolerability for high-dose encorafenib 300 mg twice daily (BID) plus binimetinib 45 mg BID. If the high dose was tolerable in ph2, patients would be randomized to receive high or standard dose (encorafenib 450 mg once daily [QD] plus binimetinib 45 mg BID). Otherwise, standard dose was evaluated as the recommended ph2 dose (RP2D). Patients who tolerated standard dosing during Cycle 1 could be dose …

Association Of Preoperative Lung Function With Complications After Lobectomy Using Race-Neutral And Race-Specific Normative Equations, Ajay Sheshadri, Ravi Rajaram, Aaron Baugh, Mario Castro, Arlene M Correa, Felipe Soto, Carrie R Daniel, Liang Li, Scott E Evans, Burton F Dickey, Ara A Vaporciyan, David E Ost

Faculty, Staff and Student Publications

Rationale: Pulmonary function testing (PFT) is performed to aid patient selection before surgical resection for non-small cell lung cancer (NSCLC). The interpretation of PFT data relies on normative equations, which vary by race, but the relative strength of association of lung function using race-specific or race-neutral normative equations with postoperative pulmonary complications is unknown. Objectives: To compare the strength of association of lung function, using race-neutral or race-specific equations, with surgical complications after lobectomy for NSCLC.

Methods: We studied 3,311 patients who underwent lobectomy for NSCLC and underwent preoperative PFT from 2001 to 2021. We used Global Lung Function Initiative …

The Prognostic Impact Of Various Circulating Cytokine Levels On Response To Egfr-Tkis Treatment In Advanced Nsclc Patients, Warissara Khuntharuks

Chulalongkorn University Theses and Dissertations (Chula ETD)

Advanced NSCLC patients are routinely treated with EGFR-TKIs but often eventually develop acquired resistance, influenced by circulating cytokines. This study investigated cytokine associations with disease control in EGFR-mutant NSCLC patients (N=123) by analyzing plasma samples at pre-treatment and 6–12 weeks post-treatment using a 27-bioplex cytokine panel, compared with healthy controls (N=30). Patients were classified as durable responders (16.3%) (PFS ≥ 104 weeks) and non-durable responders (83.7%) (PFS<104 weeks). Notably, IL-1Ra, IL2, IL-6, IL-7, IL-12p(70), TNF- alpha, IL-4, IL-5, IL-8, IL-13, Eotaxin, IP-10, MIP-1 alpha, RANTES, Basic FGF, GM-CSF and PDGF-BB were significantly presented with high levels in the patient’s pre-treatment plasma compared to healthy controls (p<0.05). High IL-6 and IL-10 levels were significant in non-durable responders (p = 0.0076 and p = 0.0166, respectively). At second-time points, non-durable responders exhibited significantly lower IL-6 levels (p=0.0019), whereas durable responders showed increased IL-10 (p = 0.0234). High pre-treatment IL-6 correlated with poor PFS (p=0.018), OS (p<0.001), and TTF (p<0.001). Consistently, high IL-10 was also correlated with shorter TTF (p<0.005). IL-6 and IL-10 showed strong diagnostic performance (AUC with 0.755 and 0.738, respectively). These cytokines may serve as prognostic biomarkers for evaluating durable EGFR-TKI responses in NSCLC patients.

การประเมินช่วงค่าอ้างอิงมาตรฐานใหม่ของการนับจำนวนเรติคูโลไซต์สำหรับประชากรไทยผู้ใหญ่สุขภาพดี: การเปรียบเทียบกับวิธีโฟลไซโตเมตรี และการนับด้วยกล้องจุลทรรศน์, หทัยพร อภัยวิวัฒน์

Chulalongkorn University Theses and Dissertations (Chula ETD)

บทนำ: การศึกษานี้ประเมินประสิทธิภาพการตรวจวิเคราะห์ของเครื่องตรวจนับเม็ดเลือดอัตโนมัติ Mindray BC-6200 สำหรับการนับจำนวนเรติคูโลไซต์ โดยมุ่งเน้นไปที่การประเมินความไม่แม่นยํา, การทดสอบการปนเปื้อนระหว่างตัวอย่าง และการทดสอบระยะเวลาคงสภาพของเรติคูโลไซต์ในหลอดทดสอบ ความถูกต้องของการนับจำนวนเรติคูโลไซต์ถูกเปรียบเทียบกับวิธีการนับด้วยกล้องจุลทรรศน์แบบแมนนวลและโฟลไซโตเมตรีซึ่งเป็นวิธีอ้างอิงมาตรฐาน นอกจากนี้ยังมีการหาค่าช่วงอ้างอิงมาตรฐานของจำนวนเรติคูโลไซต์ และพารามิเตอร์อื่น ๆ ที่เกี่ยวข้องสำหรับประชากรไทย วิธีการ: ประชากรไทย ผู้ใหญ่สุขภาพดีทั้งเพศชายและเพศหญิง จำนวนอย่างละ 60 ราย และตัวอย่างเลือดที่เหลือจากการตรวจวิเคราะห์ 182 ตัวอย่างจากผู้ป่วยที่มีภาวะทางพยาธิสภาพต่าง ๆ ถูกนำมาใช้ตรวจนับจำนวนเรติคูโลไซต์ด้วยเครื่องตรวจนับเม็ดเลือดอัตโนมัติ Mindray BC-6200, วิธีการนับด้วยกล้องจุลทรรศน์แบบแมนนวล และโฟลไซโตเมตรี เพื่อหาค่าช่วงอ้างอิงมาตรฐานของจำนวนเรติคูโลไซต์ และประเมินความสัมพันธ์ของค่าเรติคูโลไซต์ระหว่างวิธีการตรวจวิเคราะห์ ผลการทดลอง: การประเมินความไม่แม่นยําในการนับจำนวนเรติคูโลไซต์ในทุกระดับของสารควบคุมคุณภาพ (ค่าสัมประสิทธิ์ความแปรปรวน, %CV) ต่ำกว่า %CV ที่อ้างอิงโดยผู้ผลิต, การทดสอบการปนเปื้อนระหว่างตัวอย่างมีค่าน้อยกว่า 0.01% และการทดสอบระยะเวลาคงสภาพของค่าเรติคูโลไซต์ในหลอดทดสอบนั้นสามารถคงสภาพได้ถึง 24 ชั่วโมง ช่วงค่าอ้างอิงมาตรฐานมีดังนี้: จำนวนเรติคูโลไซต์สัมบูรณ์ (x109/L): 34.88-118.50, อัตราส่วนของเรติคูโลไซต์ตัวอ่อนต่อจำนวนเรติคูโลไซต์ทั้งหมด (IRF, %): 2.71-15.28, ปริมาณฮีโมโกลบินของเซลล์เรติคูโลไซต์ (RHE, pg): 22.84-29.70, การประเมินความสัมพันธ์ระหว่างวิธีการตรวจวิเคราะห์พบว่าการนับจำนวนเรติคูโลไซต์ด้วยเครื่องตรวจนับเม็ดเลือดอัตโนมัติ, วิธีการนับด้วยกล้องจุลทรรศน์แบบแมนนวลและโฟลไซโตเมตรี มีความสัมพันธ์ที่ดีมาก (r > 0.9785, p-value

The Association Of Mirnas As Biomarkers For Severe Liver Dysfunction In Severe Dengue Infection, Napat Pas-Arj

Chulalongkorn University Theses and Dissertations (Chula ETD)

Identification early biomarkers for severe liver dysfunction in severe dengue patients is essential. Currently, there is no any data on circulating miRNAs to predict this important complication, Therefore, this study aimed to explore the role of circulating miRNAs in severe liver dysfunction in dengue infection. On the initial day of admission, serum samples were gathered from patients with dengue infection. These patients were monitored for 14 days post-admission to ascertain their final diagnosis. Following the WHO 2009 criteria, participants were categorized into severe liver dysfunction and non-severe liver dysfunction group. To conduct a transcriptomic analysis of circulating miRNAs used the …

Gene Expression By Nanostring Rna Profiling Of Monocytic Myeloid-Derived Suppressor Cells In Knee Osteoarthritis, Varote Shotelersuk

Chulalongkorn University Theses and Dissertations (Chula ETD)

Osteoarthritis (OA) is a widespread degenerative joint disease marked by cartilage destruction. This study investigates the role of monocytic myeloid-derived suppressor cells (M-MDSCs) in OA, focusing on their gene expression profiles and their relationship with body mass index (BMI) in knee OA patients. Previous research has shown a positive correlation between M-MDSCs and BMI in OA. We explored the role of M-MDSCs derived from the infrapatellar fat pad (IPFP) in OA patients.Using NanoString technology, we examined the transcriptional profile of M-MDSCs from the IPFP of knee OA patients undergoing total knee replacement surgery, categorized into different BMI groups. Flow cytometry …

อาการวัยหมดระดูและความสัมพันธ์กับการสูญเสียผลิตภาพในการทำงานของพยาบาล ณ โรงพยาบาลแห่งหนึ่งในกรุงเทพมหานคร, ภคณาพร จงจิตรไพศาล

Chulalongkorn University Theses and Dissertations (Chula ETD)

การเข้าสู่วัยหมดระดูเป็นสิ่งที่ไม่สามารถหลีกเลี่ยงได้ในชีวิตของเพศหญิง การศึกษานี้มีวัตถุประสงค์ในการศึกษาความสัมพันธ์ของอาการวัยหมดระดูและการสูญเสียผลิตภาพในการทำงาน ความชุกของการประสบอาการวัยหมดระดูในพยาบาลในกรุงเทพมหานครและปัจจัยที่เกี่ยวข้อง การศึกษานี้เป็นการศึกษาภาคตัดขวางเชิงวิเคราะห์ ศึกษาในพยาบาลอายุ 45 ถึง 60 ปีทั้งหมด ณ โรงพยาบาลแห่งหนึ่งในกรุงเทพมหานคร ข้อมูลทั่วไป ข้อมูลสูตินรีเวช ข้อมูลด้านการทำงาน ข้อมูลอาการวัยหมดระดู และข้อมูลการสูญเสียผลิตภาพในการทำงานถูกเก็บในรูปแบบของแบบสอบถาม การวิเคราะห์การถดถอยโลจิสติกและการวิเคราะห์การถดถอยโลจิสติกเชิงพหุถูกใช้เพื่อวิเคราะห์ปัจจัยที่เกี่ยวข้องกับอาการวัยหมดระดู การวิเคราะห์การถดถอยเชิงเส้นและการวิเคราะห์การถดถอยพหุคูณถูกใช้เพื่อวิเคราะห์ความสัมพันธ์ของอาการวัยหมดระดูกับการสูญเสียผลิตภาพในการทำงาน การศึกษานี้มีผู้เข้าร่วมทั้งหมด 182 คน ความชุกของอาการวัยหมดระดูอยู่ที่ 74.2% จำนวนและร้อยละของอาการวัยหมดระดูโดยแบ่งกลุ่มตามความรุนแรง ได้แก่ กลุ่มไม่มีอาการ 47 คน (25.8%) กลุ่มรุนแรงเล็กน้อย 38 คน (20.9%) กลุ่มรุนแรงปานกลาง 65 คน (35.7%) และกลุ่มรุนแรงมาก 32 คน (17.6%) จากการศึกษาพบว่าการมีอาการวัยหมดระดูในระดับรุนแรงมากมีความสัมพันธ์กับร้อยละการมาทำงานแต่ไม่ได้งานและการสูญเสียผลิตภาพในงานโดยรวมอย่างมีนัยสำคัญทางสถิติ โดยมีผลต่างค่าเฉลี่ยและช่วงค่าความเชื่อมั่น 95% อยู่ที่ 20.84 (11.10-30.59) และ 20.49 (10.39-30.58) ตามลำดับ พยาบาลที่มีอาการวัยหมดระดูในระดับรุนแรงควรได้รับการวินิจฉัย รักษา หรือช่วยเหลือในด้านต่างๆ จากทั้งแพทย์เฉพาะทาง หัวหน้าแผนก และเพื่อนร่วมงาน เพื่อป้องกันการสูญเสียผลิตภาพในการทำงาน เพิ่มประสิทธิภาพในการทำงาน ลดการเกษียณอายุงานก่อนเวลา และรักษามาตรฐานการให้บริการของโรงพยาบาลต่อไปในอนาคต

A Comparative Study Of Portal Versus Peripheral Circulating Tumor Cells In Patients With Stage I-Iii Pancreatic Cancer, Thaninee Prasoppokakorn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Portal venous circulating tumor cells (CTCs) detection may better reflect vascular metastasis and predict micro-metastasis risk in pancreatic ductal adenocarcinoma (PDAC) than peripheral blood. We hypothesize that portal CTCs could better represent micro-metastasis and predict survival in PDAC patients. Methods: We conducted a single-center, prospective interventional cohort study of patients with stage I-III PDAC between January 2020 and September 2021, with followed up until February 2024. Portal venous blood was obtained via endoscopic ultrasound (EUS)-guided sampling, and peripheral blood was collected on the same day. CTCs were detected using EpCAM and mucin1 antibodies and reported as cells/8mL of blood. …

Sugar Composition Of Thai Desserts And Gut Microbiome Profiles In Healthy Volunteers: A Randomized Controlled Trial, Sayamon Senaprom

Chulalongkorn University Theses and Dissertations (Chula ETD)

The glycemic index (GI) measures the blood glucose-raising potential of carbohydrate-rich foods and is associated with obesity and insulin resistance. In addition, an imbalanced gut microbiota has been linked to elevated postprandial blood glucose levels. However, the relationship between consuming Thai desserts predominantly composed of carbohydrates and gut microbiome profiles remains unclear. This study aimed to evaluate the effects of consuming various Thai desserts with different GI values on the gut microbiomes of healthy volunteers. This open-label, parallel randomized clinical trial involved 30 healthy individuals aged 18 to 45 years. Participants were randomly assigned to one of three groups: Phetchaburi’s …

Development Of 3d Cell Culture Model For Graves’ Ophthalmopathy, Rajit Chompoowong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Orbital tissue fibrosis and remodeling contribute to the development of exophthalmos, a hallmark symptom of Graves’ ophthalmopathy (GO). The central pathogenesis to this process are orbital fibroblasts (GOF), which express autoantigen, thyroid-stimulating hormone receptor (TSHR). However, there are limitations in preclinical models for studying the pathogenesis and drug discovery of GO, which poses challenges for developing effective treatment options. This study aimed to identify markers of GOF, explore epigenetic alteration, and develop a scaffold-free 3D cell culture model for GO. The novel results from immunohistochemical analysis showed that vimentin was uniquely expressed in GO but absent in control samples. Additionally, …

Belzutifan, Hif-2Α Inhibitor, And Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-Of-Function Mutation, Kok Hoe Chan, Ningjing Li, Ran Lador, Mark Amsbaugh, Anneliese Gonzalez, Putao Cen

Faculty, Staff and Student Publications

The Von-Hippel-Lindau (VHL) gene, acting as a tumor suppressor, plays a crucial role in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). Approximately 90% of individuals with advanced ccRCC exhibit somatic mutations in the VHL gene. Belzutifan, orally administered small-molecule inhibitor of hypoxia-induced factor-2α, has demonstrated promising efficacy in solid tumors associated with germline loss-of-function mutations in VHL, including ccRCC. However, its impact on cases with somatic or sporadic VHL mutations remains unclear. Here, we present 2 cases where belzutifan monotherapy was employed in patients with advanced ccRCC and somatic loss-of-function mutations in VHL. Both patients exhibited a swift …

Does An Early, Balanced Resuscitation Strategy Reduce The Incidence Of Hypofibrinogenemia In Hemorrhagic Shock?, David T Lubkin, Krislynn M Mueck, Gabrielle E Hatton, Jason B Brill, Mariela Sandoval, Jessica C Cardenas, Charles E Wade, Bryan A Cotton

Faculty, Staff and Student Publications

OBJECTIVES: Some centers have recommended including concentrated fibrinogen replacement in massive transfusion protocols (MTPs). Given our center's policy of aggressive early balanced resuscitation (1:1:1), beginning prehospital, we hypothesized that our rates of hypofibrinogenemia may be lower than those previously reported.

METHODS: In this retrospective cohort study, patients presenting to our trauma center November 2017 to April 2021 were reviewed. Patients were defined as hypofibrinogenemic (HYPOFIB) if admission fibrinogen

RESULTS: Of 29 782 patients, 6618 level 1 activations, and 1948 patients receiving emergency release blood,

CONCLUSIONS: Low rates of hypofibrinogenemia were found in our center which treats hemorrhage with early, balanced …

Preparation Of Uniformly Oriented Inverted Inner (Cytoplasmic) Membrane Vesicles From Gram-Negative Bacterial Cells, Mikhail Bogdanov

Faculty, Staff and Student Publications

The complex double-membrane organization of the envelope in Gram-negative bacteria places unique biosynthetic and topological constraints that can affect translocation of lipids and proteins synthesized on cytoplasm facing leaflet of cytoplasmic (inner) membrane (IM), across IM and between IM and outer membrane (OM). Uniformly oriented inside-out (ISO) vesicles became functional requisite for many biochemical reconstitution functional assays, vectorial proteomics, and vectorial lipidomics. Due to these demands, it is necessary to develop simple and reliable approaches for preparation of uniformly oriented IM membrane vesicles and validation of their sidedness. The uniformly ISO oriented membrane vesicles which have the cytoplasmic face of …

Exploring Uniform, Dual, And Dynamic Topologies Of Membrane Proteins By Substituted Cysteine Accessibility Method (Scam™), Mikhail Bogdanov

Faculty, Staff and Student Publications

A described simple and advanced protocol for Substituted Cysteine Accessibility Method as applied to transmembrane (TM) orientation (SCAM™) permits a topology analysis of proteins in their native state and can be universally adapted to any membrane system to either systematically map an uniform or identify and quantify the degree of mixed topology or establish transmembrane assembly dynamics from relatively static experimental data such as endpoint topologies of membrane proteins. In this approach, noncritical individual amino acids that are thought to reside in the putative extracellular or intracellular loops of a membrane protein are replaced one at the time by cysteine …

Impact Of Maternal Depressive Symptoms On Offspring Executive Functions: A Systematic Review, Júlia De Souza Rodrigues, María Pastor-Valero, Lucas R Trambaiolli, Ana Beatriz Bozzini, Alicia Matijasevich

Faculty, Staff and Student Publications

OBJECTIVE: To conduct a thorough examination of the current understanding of the effect of maternal depression exposure on the executive functions (EFs) of offspring.

METHODS: Following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement, a comprehensive search for peer-reviewed cohort studies was performed on the MEDLINE (via PubMed), ScienceDirect, LILACS, PsycINFO, and SciELO databases. Study quality was assessed using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The evidence was evaluated using the Grading of Recommendation, Assessment, Development, and Evaluation framework.

RESULTS: Thirty-three cohort studies from different countries, …

Endoscopic Innovations In Diagnosis And Management Of Pancreatic Cancer: A Narrative Review And Future Directions, Prateek Suresh Harne, Vaishali Harne, Curtis Wray, Nirav Thosani

Faculty, Staff and Student Publications

Pancreatic cancer serves as the third leading cause of cancer-associated morbidity and mortality in the United States, with a 5-year survival rate of only 12% with an expected increase in incidence and mortality in the coming years. Pancreatic ductal adenocarcinomas constitute most pancreatic malignancies. Certain genetic syndromes, including Lynch syndrome, hereditary breast and ovarian cancer syndrome, hereditary pancreatitis, familial adenomatous polyposis, Peutz-Jeghers syndrome, familial pancreatic cancer mutation, and ataxia telangiectasia, confer a significantly higher risk. Screening for pancreatic malignancies currently targets patients with germline mutations or those with significant family history. Screening the general population is not currently viable owing …

Mental Health Prevention And Treatment Programs For Infants Experiencing Homelessness: A Systematic Review, Megan M Hare, Taylor D Landis, Melissa Hernandez, Paulo A Graziano

Faculty, Staff and Student Publications

Experiencing homelessness in infancy has been linked to negative physical and mental health outcomes. Parental well-being and the parent-infant relationship can also be negatively impacted by experiencing homelessness. While numerous parent-based infant mental health programs have been identified by a recent review, the goal of this study was to further determine the extent to which these existing programs were developed and/or examined with at-risk populations such as families experiencing homelessness. Out of 60 programs identified by Hare et al., in press, only three had been implemented specifically in shelter settings with infants 0-12 months (Parent-Infant Psychotherapy, New Beginnings, and My …

Severe Degranulation Of Mesenteric Mast Cells In An Experimental Rat Mammary Tumor Model, Senem Yavaş, Özkan Yavaş, Semi̇ha Ersoy, Gürsel Sönmez

Turkish Journal of Medical Sciences

Background/aim: Breast cancers are one of the most common cancers in women and are responsible for many deaths worldwide. Mast cells are inflammatory cells. Their role in cancers is controversial, and there is limited data on systemic mast cell activation in cancer cases. This study aimed to evaluate systemic mast cell activation in an experimentally induced rat model of breast cancer. Materials and methods: Sprague Dawley female rats were divided into control (n=6) and mammary tumor (n=12) groups. In the tumor group, 20 mg 12-dimethylbenz[a]anthracene (DMBA) dissolved in 1 ml cottonseed oil was administered intragastrically by gavage, and the rats …

The Role Of Circadian Rhythm Proteins Rev-Erb Α/ And Β In The Development Of Neuronal Injury After Taumatic Brain Injury, Mahmud Pençe, Enes Dogan, Hali̇l Koç, Ci̇gdem Bayraktaroglu, Serdar Altunay, Zeynep Balçikanli, Ertugrul Kiliç, Mustafa Beker

Turkish Journal of Medical Sciences

Background/Aim:Circadian rhythm proteins (CRP) play critical roles in both physiological and pathophysiological conditions, including neurodegenerative disorders. As member of CRP, the nuclear receptors REV-ERBα/β regulates circadian rhythm particularly by inhibiting Bmal1 protein and involved in the neuroinflammation- and cell death processes. However, their roles in the development of neuronal injury after traumatic brain injury (TBI) were largely unexplored, which were investigated in the present study.Materials and Methods: For the induction of TBI, animals were submitted to the cryogenic model of TBI, which is a commonly used animal model and shares essential similarities with cerebral ischemia in terms of pathophysiological cascades. …

In Silico Study Of Bioactive Compounds Derived From Indonesian Marine Invertebrates As Novel Antituberculosis Agent, Ayu Masyita, Eri̇s Septiana, Asep Bayu, Bustanussalam Bustanussalam, Jonathan A. Panggabean, Fi̇rdayani̇ Firdayani, Tuti̇k Murniasih

Turkish Journal of Medical Sciences

Background/aim: Tuberculosis has still become the most deadly disease globally. The problem of finding an effective therapeutic is one of the obstacles in the treatment of patients. Marine invertebrates were a treasure since they produced many active compounds. Following up on this issue, screening active compounds is very important. This study will explain the result of anti-tuberculosis screening of compounds derived from marine invertebrates using in silico and confirmed to the in vitro-data.Materials and methods: Three-dimensional (3D) structures of pantothenate kinase (MtPanK type 1, PDB ID: 4BFT), Mycobacterium tuberculosis InhA (MtInhA, PDB ID: 2X23), protein kinase B (PDB ID: 5U94), …

Leaky Gut And Inflammatory Biomarkers In A Medication Overuse Headache Model In Male Rats, Doğa Vuralli, Hale Gök Dağidir, Elif Abbasoğlu Topa, Hayrunnisa Bolay Belen

Turkish Journal of Medical Sciences

Medication overuse is common among chronic migraine patients and nonsteroidal antiinflammatory drugs (NSAIDs)are the most frequently overused drugs. The pathophysiological mechanisms underlying medication overuse headache (MOH) are notcompletely understood. Intestinal hyperpermeability and leaky gut are reported in patients using NSAIDs. The aim of the study is toinvestigate the role of leaky gut and inflammation in an MOH model MOH model in male rats.Methods: The study was conducted in male Sprague Dawley rats. There were two experimental groups. The first group was the chronicNSAID group in which the rats received mefenamic acid (n = 8) for four weeks intraperitoneally (ip) and …

Effects Of Glutamine And Omega-3 Fatty Acids On Intestinal Neomucosa Formation On Colon Serosa In Rats, Mehmet Köstek, Uygar Demi̇r, Ramazan Uçak, Burak Yasin Avci, Aydın Ünal, Osman Bilgin Gülçi̇çek, Ozan Çalişkan, Bülent Çi̇tgez, Erdinç Seri̇n, Sıtkı Gürkan Yetki̇n, Mehmet Mi̇hmanli, Mehmet Uludağ

Turkish Journal of Medical Sciences

Intestinal neomucosa formation is a technique defined for the treatment of short bowel syndrome. This study evaluates the effect of glutamine and omega-3 fatty acids on the growth of intestinal neomucosa on the colonic serosal surface has been evaluated.Materials and methods: Thirty-two adult male Sprague-Dawley rats were randomly divided into 4 groups: sham, control, glutamine, and omega-3. Laparotomy was performed on all groups. For rats other than the sham group, a 1-cm full-thickness incision was made 4 cm proximal to the ileocecal valve, and colonic serosal surface was sutured as a serosal patch over these openings. By using the oral …

Effect Of Humic Acid On Oxidative Stress And Neuroprotection In Traumatic Spinal Cord Injury: An Experimental Study, Burak Kinali, Nail Özdemi̇r, Ali Karadağ, Özge Kaya Korkmaz, Ayşe Gülden Di̇ni̇z, Fatma Demet Arslan

Turkish Journal of Medical Sciences

Traumatic spinal cord injury (TSCI) is an important health problem, especially in developing countries withadditional socioeconomic loss. Humic acid (HA) usually has antioxidant, antiinflammatory, blood circulating, and antiviral effects.Hence, it was aimed herein to show the effect of HA on neuroprotection in a TSCI model.Materials and method: A TSCI model was used, in which 24 Wistar albino rats were divided into 4 groups: control group: subjectedto only laminectomy; sham group: subjected to laminectomy + TSCI; HA 5 mg/kg group: subjected to laminectomy + TSCI +intraperitoneal (IP) injection of 5 mg/kg of HA; and HA 10 mg/kg group: subjected to laminectomy …

Tracking The Footsteps Of Burkholderia Mallei: Determination Of The Molecular Differences And Potential Resistance Genes, Dilek Dülger, Seda Eki̇ci̇, Mehmet Demi̇rci̇, Akın Yi̇ği̇n, Orkun Babacan

Turkish Journal of Medical Sciences

Chemical biological radiological nuclear threats are at an important point in the agenda of world health today, as theycan cause mass deaths. B. mallei attracts attention as a potential biological warfare agent due to its features such as multidrug resistance,a rapid transmission mechanism via aerosol, the absence of a complete treatment protocol for the infection it causes, and the absence ofan approved vaccine for protection against the bacteria. B. mallei suspect samples must be studied by experienced personnel in biosafetylevel III laboratories. B mallei is a difficult and troublesome pathogen to diagnose and many unknowns about B. mallei today. Therefore,the …