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Investigation Of Heterosynaptic Long-Term Potentiation Of Non-Nociceptive Synapses, Synaptically Relevant Kinase Discovery, And Virtual Screening For A Pkmz Inhibitor In Hirudo Verbana", Avery Franzen Jan 2025

Investigation Of Heterosynaptic Long-Term Potentiation Of Non-Nociceptive Synapses, Synaptically Relevant Kinase Discovery, And Virtual Screening For A Pkmz Inhibitor In Hirudo Verbana", Avery Franzen

Dissertations and Theses

There is a considerable lack in efficacy for current chronic pain treatments. One therapy that has gained attention are cannabinoid-based medications. However, preclinical and clinical trials do not produce anti-nociceptive results consistently and occasionally produce pro-nociceptive results. Understanding this ambiguity between anti-nociceptive and pro-nociceptive effects is vital to cannabinoids’ future utilization. One symptom of chronic pain conditions is allodynia in which pain is perceived following non-painful stimuli. This may be due to non-nociceptive afferents activating nociceptive circuitry in an abnormal manner. Using the medicinal leech, Hirudo verbana, we have begun to elucidate mechanisms by which endocannabinoids strengthen non-nociceptive afferent synapses. …


Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu Jan 2025

Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing …


Lymphoma Chronicles: Insights From A Distinct Hodgkin's Lymphoma Case Report, Srirangam Shankaralingam, Vibha Nagaragatta Jan 2025

Lymphoma Chronicles: Insights From A Distinct Hodgkin's Lymphoma Case Report, Srirangam Shankaralingam, Vibha Nagaragatta

Digital Journal of Clinical Medicine

Hodgkin lymphoma (HL) is a kind of lymphatic malignancy distinguished by the presence of Reed-Sternberg cells. It often manifests as painless lymphadenopathy and systemic symptoms (B symptoms and can affect a variety of lymphoid tissues. The causes of HL are complicated and include genetic predisposition, environmental conditions and viral infections, particularly the Epstein-Barr virus (EBV). The diagnosis is primarily based on histological evaluation of lymph node samples, with immunophenotyping assisting classification. Herein, we report a case of classical Hodgkin’s lymphoma (HL) in an otherwise healthy 31-year-old male who had a mass per abdomen for a year and recently noticed a …


Pregnancy-Related Delusional Beliefs In Midlife And Late-Life Women: A Case Series, Dyuksha Arora, Ashita Adarsh, Kishor M. Manohar Rao, Anand R, Soumya Rajshekar Patil, Akshatha Cj Jan 2025

Pregnancy-Related Delusional Beliefs In Midlife And Late-Life Women: A Case Series, Dyuksha Arora, Ashita Adarsh, Kishor M. Manohar Rao, Anand R, Soumya Rajshekar Patil, Akshatha Cj

Digital Journal of Clinical Medicine

Pseudocyesis and delusional pregnancy represent rare but clinically significant presentations across psychiatric practice. While pseudocyesis involves a false belief of pregnancy accompanied by physical manifestations, delusion of pregnancy refers to a fixed belief of being pregnant despite clear contrary evidence. Both conditions pose considerable challenges as they involve close consultation and liaison between Obstetrics & Gynaecology and Psychiatry. There are a few studies from tertiary care general hospitals in India. Here we report two case series.

Case 1: A 43-year-old married woman from a rural background with an 8-year history of recurrent depressive disorder and dysthymia, presented with 3 months …


One Airway, One Disease In Pregnancy: A Prospective Observational Study On The Correlation Between Upper And Lower Airway Inflammation In Pregnant Women, Durga K, Yuvarajan S Jan 2025

One Airway, One Disease In Pregnancy: A Prospective Observational Study On The Correlation Between Upper And Lower Airway Inflammation In Pregnant Women, Durga K, Yuvarajan S

Digital Journal of Clinical Medicine

Background: The well-established "One Airway, One Disease" concept recognizes the deep physiological and pathological connections between conditions affecting both the upper and lower respiratory tracts, most notably allergic rhinitis and asthma. During pregnancy, a woman's body undergoes significant immunological, hormonal, and physiological changes, which can profoundly influence and modulate existing or emerging airway inflammation.

Objective: This prospective observational study was designed with the primary objective of meticulously evaluating the correlation between upper and lower airway inflammation in pregnant women. We aimed to achieve this by assessing a range of clinical symptoms, objective functional parameters, and specific inflammatory markers.

Methods: We …


Resilience And Reality: Exploring The Lived Experiences Of People Living With Hiv In Texas During The Covid-19 Pandemic – A Qualitative Study., Ahmed F. Alanazi Jan 2025

Resilience And Reality: Exploring The Lived Experiences Of People Living With Hiv In Texas During The Covid-19 Pandemic – A Qualitative Study., Ahmed F. Alanazi

Social Work Dissertations - Archive

This study investigated the lived experiences of individuals living with HIV (PLWH) in the Dallas-Fort Worth (DFW) area of Texas during the COVID-19 pandemic, using an Interpretative Phenomenological Analysis (IPA) framework. The research examined the intersection of health, social dynamics, and psychological resilience among PLWH, who faced compounded vulnerabilities due to systemic inequities and the dual public health crises of HIV and COVID-19. Through semi-structured interviews with ten participants from diverse backgrounds, the study captured the profound impacts of disrupted healthcare systems, heightened stigma, and social isolation on this marginalized population. The findings reveal that the pandemic exacerbated existing inequities …


The Physiological Effects Of Anabolic Steroids On The Human Body, Aedan Kerr Jan 2025

The Physiological Effects Of Anabolic Steroids On The Human Body, Aedan Kerr

Undergraduate Honors Theses

Anabolic-androgenic steroids (AAS) are synthetic derivatives of testosterone used both medically and illicitly for their muscle-building and performance-enhancing properties. While clinically prescribed for conditions like hypogonadism, osteoporosis, and muscle-wasting diseases, AAS are frequently abused by athletes and recreational lifters seeking rapid physical gains. AAS increase muscle protein synthesis via androgen receptor-mediated gene transcription, but they also predispose users to tendon ruptures and various organ functions. AAS abuse is strongly associated with a host of side effects including gynecomastia, male-pattern hair loss, infertility, hepatotoxicity, erythrocytosis, dyslipidemia, insulin resistance, and hypogonadism. Cardiovascular complications such as left ventricular hypertrophy, cardiomyopathy, and myocardial infarctions …


Dean's Update, January 2025, Neil W. Schluger Jan 2025

Dean's Update, January 2025, Neil W. Schluger

SOM Dean's Research Newsletter

No abstract provided.


Comparative Analysis Of Gut Microbiota In Post-Mortem Chronic Alcoholics Versus Minimal To No Alcohol Users In The Thai Population, Laiba Pervez Jan 2025

Comparative Analysis Of Gut Microbiota In Post-Mortem Chronic Alcoholics Versus Minimal To No Alcohol Users In The Thai Population, Laiba Pervez

Chulalongkorn University Theses and Dissertations (Chula ETD)

Chronic alcohol consumption induces long-term disruption of the gut microbiota, contributing to inflammation, metabolic imbalance, and impaired intestinal integrity. This study investigated 24 postmortem gut microbiota samples from the Thai population, including 12 chronic alcoholic and 12 non-alcoholic cadavers, focusing on cecal and fecal samples to identify site-specific microbial signatures of alcohol-associated dysbiosis. Following DNA extraction, the V3–V4 regions of the 16S rRNA gene were sequenced on the Illumina MiSeq platform. Data were processed in QIIME for OTU clustering and taxonomic profiling. Alpha (Shannon, Chao1, ACE) and beta (Bray–Curtis) diversity were analyzed with PERMANOVA (p< 0.05) while LEfSe, cladogram, and STAMP analyses identified differentially abundant taxa.. At the phylum level, alcoholic cecal samples (AC) showed a decrease in Firmicutes (59.07%) and increases in Proteobacteria (5.54%), Fusobacteria (8.48%), and Actinobacteria (2.78%) compared with controls (NAC). The rise in Actinobacteria was statistically significant. The class Bacilli was also elevated, reflecting a more oxygenated and inflammatory intestinal environment. At the genus level, Paeniclostridium was enriched in alcoholics, while the butyrate-producing Coprococcus was reduced, suggesting impaired SCFA metabolism and gut barrier function. In fecal samples (AF vs NAF), phylum-level differences were minimal, although Clostridium sensu stricto 1 was notably higher in alcoholics, consistent with inflammation-associated dysbiosis. When comparing gut regions, distinct spatial heterogeneity was observed. Within the alcoholic group, Firmicutes were more abundant in cecum, while Actinobacteria were lower compared to feces. Among controls, Actinobacteria and Bacteroidetes were enriched in feces, whereas Firmicutes predominated in the cecum. Alpha diversity analysis using ACE and Chao1 indices showed significant differences between cecal and fecal samples of the control group. Overall, postmortem gut microbiota retained distinct alcoholassociated signatures, with the cecum preserving clearer microbial patterns than feces. These findings highlight the cecum’s potential as a reliable site for detecting alcohol-related dysbiosis in forensics.


Potentiation Of Gelonin Cytotoxicity By Pulsed Electric Fields, Olga N. Pakhomova, Eleni Zivla, Giedre Silkuniene, Mantas Silkunas, Andrei G. Pakhomov Jan 2025

Potentiation Of Gelonin Cytotoxicity By Pulsed Electric Fields, Olga N. Pakhomova, Eleni Zivla, Giedre Silkuniene, Mantas Silkunas, Andrei G. Pakhomov

Bioelectrics Publications

Gelonin is a ribosome-inactivating protein with extreme intracellular toxicity but poor permeation into cells. Targeted disruption of cell membranes to facilitate gelonin entry is explored for cancer and tissue ablation. We demonstrate a hundreds- to thousands-fold enhancement of gelonin cytotoxicity by pulsed electric fields in the T24, U-87, and CT26 cell lines. The effective gelonin concentration to kill 50% of cells (EC₅₀) after electroporation ranged from <1 nM to about 100 nM. For intact cells, the EC₅₀ was unattainable even at the highest gelonin concentration of 1000 nM, which reduced cell survival by only 5–15%. For isoeffective electroporation treatments using 300 ns, 9 µs, and 100 µs pulses, longer pulses were more efficient at lowering gelonin EC₅₀. Increasing the electric field strength of 8, 100 µs pulses from 0.65 to 1.25 kV/cm reduced gelonin EC₅₀ from 128 nM to 0.72 nM. Conversely, the presence of 100 nM gelonin enabled a more than 20-fold reduction in the number of pulses required for equivalent cell killing. Pulsed electric field-mediated delivery of gelonin shows promise for hyperplasia ablation at concentrations sufficiently low to minimize or avoid systemic toxicity.


Optimizing Decision-Making In A Cerebral Palsy Model Using Reinforcement Learning, Richard Ampah Jan 2025

Optimizing Decision-Making In A Cerebral Palsy Model Using Reinforcement Learning, Richard Ampah

Pitzer Senior Theses

This study presents an original interdisciplinary investigation into how reinforcement learning (RL) can model motor and cognitive defects and potentially improve motor and cognitive functions in individuals with cerebral palsy (CP), a non-progressive neurological disorder that impairs movement and adaptability. Integrating computational neuroscience and machine learning, the research applies policy gradient methods and Markov Decision Processes (MDPs) to simulate adaptive learning in agents with and without CP-related constraints.

The central aim is to compare the cumulative rewards of optimal policies, derived from value iteration, and human-like learning policies using the REINFORCE algorithm, both with and without the Bellman baseline. The …


Targeting Cancer-Associated Fibroblast-Driven Lif/Lifr Axis Improves The Therapeutic Efficacy Of Gemcitabine And Nab-Paclitaxel In Pancreatic Cancer, Rakesh Bhatia, Imran Khan, Xiaoqi Li, Shailendra Gautam, Parthasarathy Seshacharyulu, Zahraa Wajih Alsafwani, Namita Bhyravbhatla, Moorthy P. Ponnusamy, Maneesh Jain, Mokenge Malafa, Santhamma Bindu, Ahmed Gulzar, Hareesh Nair, Surinder K. Batra, Sushil Kumar Jan 2025

Targeting Cancer-Associated Fibroblast-Driven Lif/Lifr Axis Improves The Therapeutic Efficacy Of Gemcitabine And Nab-Paclitaxel In Pancreatic Cancer, Rakesh Bhatia, Imran Khan, Xiaoqi Li, Shailendra Gautam, Parthasarathy Seshacharyulu, Zahraa Wajih Alsafwani, Namita Bhyravbhatla, Moorthy P. Ponnusamy, Maneesh Jain, Mokenge Malafa, Santhamma Bindu, Ahmed Gulzar, Hareesh Nair, Surinder K. Batra, Sushil Kumar

Journal Articles: Biochemistry & Molecular Biology

Pancreatic ductal adenocarcinoma (PDAC) is inherently therapy resistant due to cancer cell-stroma crosstalk across several signaling pathways. Among these, the LIF/LIFR axis has been implicated in cancer cell and cancer-associated fibroblast (CAF) crosstalk. We evaluated the efficacy of EC359, a competitive inhibitor of LIFR, in combination with gemcitabine. EC359 reduced tumor burden by 90% compared to controls and by 55% compared to gemcitabine alone in cancer cell and CAFs co-implannation model. The RNA-seq analysis revealed a significant alteration in extracellular matrix components, stemness, microtubule assembly, and immune response, suggesting simultaneous targeting of cancer cell-intrinsic and stroma-mediated mechanisms by EC359. In …


Racial Health Disparities Among Pregnant Women Of Color In New York City: Biological And Systemic Impacts, Kaylin Peña Jan 2025

Racial Health Disparities Among Pregnant Women Of Color In New York City: Biological And Systemic Impacts, Kaylin Peña

Pitzer Senior Theses

Racial Health Disparities Among Pregnant Women of Color in New York City: Biological and Systemic Impacts

Abstract

This thesis aims to explore how racial health disparities, underrepresentation in gynecology, and socioeconomic barriers contribute to adverse pregnancy outcomes among women of color in New York City. Through an interdisciplinary approach that combines resources from medical anthropology and human biology, this research will examine the biological implications of chronic stress, specifically HPA axis dysregulation, and its role in maternal health outcomes. With the idea of intersectionality, as conceptualized by Kimberlé Crenshaw, the study analyzes the various effects of systemic inequities and social …


Serum Metabolome Profiling In Patients With Mild Cognitive Impairment Reveals Sex Differences In Lipid Metabolism, Rocio Diaz Escarcega, Vijay Kumar M J, Vasilia E Kyriakopoulos, Guadalupe J Ortiz, Aaron M Gusdon, Huihui Fan, Pedram Peesh, Maria P Blasco Conesa, Gabriela Delevati Colpo, Hilda W Ahnstedt, Lucy Couture, Stella H Kim, Miriam Hinojosa, Christine M Farrell, Sean P Marrelli, Akihiko Urayama, Bhanu P Ganesh, Paul E Schulz, Louise D Mccullough, Andrey S Tsvetkov Jan 2025

Serum Metabolome Profiling In Patients With Mild Cognitive Impairment Reveals Sex Differences In Lipid Metabolism, Rocio Diaz Escarcega, Vijay Kumar M J, Vasilia E Kyriakopoulos, Guadalupe J Ortiz, Aaron M Gusdon, Huihui Fan, Pedram Peesh, Maria P Blasco Conesa, Gabriela Delevati Colpo, Hilda W Ahnstedt, Lucy Couture, Stella H Kim, Miriam Hinojosa, Christine M Farrell, Sean P Marrelli, Akihiko Urayama, Bhanu P Ganesh, Paul E Schulz, Louise D Mccullough, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Alzheimer's disease (AD) affects more women than men. Although women live longer than men, it is not longevity alone, but other factors, including metabolic changes, that contribute to the higher risk of AD in women. Metabolic pathways have been implicated in AD progression, but studies to date examined targeted pathways, leaving many metabolites unmeasured. Sex is often a neglected biological variable, and most metabolomic studies were not designed to investigate sex differences in metabolomic profiles. Here, we performed untargeted metabolomic profiling of sera from male and female patients with mild cognitive impairment (MCI), a common precursor to AD, and matched …


Sex Differences In Brain Iron Deposition And Microglial Ferritin In Alzheimer’S Disease, Syed Mushfiqur Rahman, Chunfeng Tan, Akiyoshi Kakita, Jose Felix Moruno-Manchon Jan 2025

Sex Differences In Brain Iron Deposition And Microglial Ferritin In Alzheimer’S Disease, Syed Mushfiqur Rahman, Chunfeng Tan, Akiyoshi Kakita, Jose Felix Moruno-Manchon

Faculty, Staff and Student Publications

Objective

Iron is the most abundant metal in the human brain, and plays a crucial role in many biological processes. However, disruptions in brain iron metabolism can lead to iron buildup, which occurs with aging and is linked to several brain disorders, including Alzheimer's disease. Microglia, the brain's resident immune cells, have the highest capacity to store iron, which is stored intracellularly within ferritin complexes. Importantly, women are at a higher risk of developing Alzheimer's disease and experience faster disease progression compared to men.

Methods

We used postmortem brain samples from patients with Alzheimer's disease and small vessel disease patients …


In Vitro Evaluation Of Retention Of Double-Crown Prostheses Connecting Natural Teeth And Implants. A Comparative Analysis Of Zirconia, Pekk, And Cobalt Chromium Materials For Primary And Secondary Crowns, Sarah Zaman Sahib Awad, Khloud Ezzat Mourad, Ahmed Sameh Abdelaziz Ismail, Aisha Zakaria Hashem Mostafa Jan 2025

In Vitro Evaluation Of Retention Of Double-Crown Prostheses Connecting Natural Teeth And Implants. A Comparative Analysis Of Zirconia, Pekk, And Cobalt Chromium Materials For Primary And Secondary Crowns, Sarah Zaman Sahib Awad, Khloud Ezzat Mourad, Ahmed Sameh Abdelaziz Ismail, Aisha Zakaria Hashem Mostafa

Mansoura Journal of Dentistry

Purpose Objective: To assess and compare the retention performance of different material combinations—Zirconia, PEKK, and Cobalt-Chromium—over time using insertionremoval tests simulating one year of use. Materials and Methods: Nine mandibular polyurethane models with two canines and two dummy implants (first molar area) were used. Three groups of double-crown prostheses were fabricated, differing in materials used for both primary and secondary crowns: Zirconia, PEKK, and Cobalt-Chromium. All crowns were CAD/CAM-designed. Retention was tested using a Universal Testing Machine, with each overdenture subjected to 1,440 insertionremoval cycles to simulate one year. Final retention forces were measured and analyzed using SPSS v23, with …


Mandibular Chondrosarcoma: A Rare Case Report, Moataz Elhefny, Islam Hamada, Ahmed Khalil Jan 2025

Mandibular Chondrosarcoma: A Rare Case Report, Moataz Elhefny, Islam Hamada, Ahmed Khalil

Mansoura Journal of Dentistry

Purpose: Chondrosarcoma is a malignant tumor of cartilaginous tissue. It is more apparent in the axial skeletal bone but rare in the head and neck region. The biopsy is the definite way to diagnose Chondrosarcoma and surgical dissection is the direct way of management. Case description: A 76 years old male patient diagnosed with Chondrosarcoma in the mandible at the the premolar region after a history of a non-specific sclerosing osteomyeiltis at the same region 7 months ago. It was a low-grade form with good prognosis. Conclusions: Chondrosarcoma is malignant neoplasm of cartilaginous tissue. It is rare in the oral …


Effect Of Different Implant Designs On Primary Stability In Different Substrates, Mohamed Adel Ebrahim, Ahmad Mostafa Hussein, Mohamed Abdelmonem Tawfik, Elsayed Gad Eid Jan 2025

Effect Of Different Implant Designs On Primary Stability In Different Substrates, Mohamed Adel Ebrahim, Ahmad Mostafa Hussein, Mohamed Abdelmonem Tawfik, Elsayed Gad Eid

Mansoura Journal of Dentistry

Objective To clarify whether implant macrodesign has any influence on primary stability. Implant primary stability was evaluated in different substrates (fresh cow ribs and polyurethane artificial bone blocks) using several methods. Materials and Methods A total of 36 titanium dental implants (3.5 mm × 10 mm) and then divided into 3 groups (n=12): implants have trapezoidal thread design, implants have buttress thread design and implants have reverse buttress thread design were inserted in two different substrates (six fresh cow ribs and eighteen polyurethane casts). Immediately after insertion of dental implant, the implant stability was measured using three different methods (insertion …


Fracture Resistance Of Different Lithium Disilicate Restorations After Endodontic Access Cavity Preparation: Effect Of Repair Method, Hebah Agamal Abdulghafor, Essam A. Khedr, Nesma M. Elgohary, Walid A. Al-Zordk Jan 2025

Fracture Resistance Of Different Lithium Disilicate Restorations After Endodontic Access Cavity Preparation: Effect Of Repair Method, Hebah Agamal Abdulghafor, Essam A. Khedr, Nesma M. Elgohary, Walid A. Al-Zordk

Mansoura Journal of Dentistry

Objective: To evaluate the effect of different repair methods on the fracture resistance of lithium disilicate restorations after endodontic access cavity preparation. Materials and Methods: One hundred sixty sound human mandibular first molars were prepared and restored with four types of lithium disilicate–based crowns: IPS e.max CAD, GC Initial LiSi Block, Straumann n!ce, and CEREC Tessera (n = 40 each). Standardized endodontic access cavities were prepared in all specimens, then repaired using one of four techniques: (1) inlay restoration with Monobond Etch&Prime, (2) inlay restoration with IPS Ceramic Etching Gel + Monobond Plus, (3) direct composite with IPS Ceramic Etching …


Regulation Of Human Dna Mismatch Repair, Breanna Knicely Jan 2025

Regulation Of Human Dna Mismatch Repair, Breanna Knicely

Theses and Dissertations--Toxicology and Cancer Biology

The DNA mismatch repair (MMR) pathway identifies and corrects misincorporations that arise during DNA replication. MMR is a pathway that is critical for maintaining genomic stability. Mutations within the MMR pathway, both germline and somatic, lead to the development of cancer. There are a variety of mechanisms that regulate the MMR pathway including protein-protein interactions, DNA damage response, and post-translational modifications. In this study, we aim to dive deeper into each of these mechanisms to obtain novel information regarding the mechanisms and regulation of human DNA MMR. In this study we generated hExo1 constructs mutating Exo1’s interactions with MSH2 and …


Microbial Remodeling Of Gut Tryptophan Metabolism And Indole-3-Lactate Production Regulate Epithelial Barrier Repair And Viral Suppression In Human And Simian Immunodeficiency Virus Infections, Clarissa Santos Rocha, Katie L. Alexander, Carolina Herrera, Mariana G. Weber, Irina Grishina, Lauren A. Hirao, Dylan J. Kramer, Juan Arredondo, Abigail Mende, Katti R. Crakes, Anne N. Fenton, Maria L. Marco, David A. Mills, John C. Kappes, Lesley E. Smythies, Paul Ziprin, Sumathi Sankaran-Walters, Phillip D. Smith, Satya Dandekar Jan 2025

Microbial Remodeling Of Gut Tryptophan Metabolism And Indole-3-Lactate Production Regulate Epithelial Barrier Repair And Viral Suppression In Human And Simian Immunodeficiency Virus Infections, Clarissa Santos Rocha, Katie L. Alexander, Carolina Herrera, Mariana G. Weber, Irina Grishina, Lauren A. Hirao, Dylan J. Kramer, Juan Arredondo, Abigail Mende, Katti R. Crakes, Anne N. Fenton, Maria L. Marco, David A. Mills, John C. Kappes, Lesley E. Smythies, Paul Ziprin, Sumathi Sankaran-Walters, Phillip D. Smith, Satya Dandekar

Department of Obstetrics & Gynecology Faculty Publications

Gut inflammatory diseases cause microbial dysbiosis. Human immunodeficiency virus-1 (HIV) infection disrupts intestinal integrity, subverts repair/renewal pathways, impairs mucosal immunity and propels microbial dysbiosis. However, microbial metabolic mechanisms driving repair mechanisms in virally inflamed gut are not well understood. We investigated the capability and mechanisms of gut microbes to restore epithelial barriers and mucosal immunity in virally inflamed gut by using a multipronged approach: an in vivo simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV/AIDS, ex vivo HIV-exposed human colorectal explants and primary human intestinal epithelial cells. SIV infection reprogrammed tryptophan (TRP) metabolism, increasing kynurenine catabolite levels that are …


Longitudinal Assessment Of Intravillous Arterioles In Normal Pregnancy Using Superb Microvascular Imaging, R. Horgan, E. Sinkovskaya, G. Saade, E. Kalafat, A. Heeze, A. Abuhamad Jan 2025

Longitudinal Assessment Of Intravillous Arterioles In Normal Pregnancy Using Superb Microvascular Imaging, R. Horgan, E. Sinkovskaya, G. Saade, E. Kalafat, A. Heeze, A. Abuhamad

Department of Obstetrics & Gynecology Faculty Publications

Objective

To use superb microvascular imaging (SMI) to longitudinally evaluate blood flow in intravillous arterioles (IVA) in pregnancy, and to develop reference ranges for IVA pulsatility index (PI) and peak systolic velocity (PSV) from 12 to 38 weeks' gestation.

Methods

The data for this study were obtained from the National Institutes of Health-funded Human Placenta Project. Eligible for inclusion were women aged 18-35 years, with a body mass index of <  30 kg/m², without comorbidities, with a singleton pregnancy conceived spontaneously and a gestational age of ≤ 13 + 6 weeks. Exclusion criteria were maternal or neonatal complications, fetal or umbilical cord anomalies, abnormal placental implantation and delivery <  37 weeks. Each participant underwent eight ultrasound examinations during pregnancy. Using SMI technology, the total number of IVA identified was recorded in a sagittal placental section at the level of cord insertion. The PI and PSV were measured in a total of six IVA (two in the central portion of the placenta, two peripherally towards the uterine fundal portion and two peripherally towards the lower uterine segment). Umbilical artery (UA)-PI was also obtained. Multilevel regression models were used to create reference ranges for IVA-PI and IVA-PSV at 12-38 weeks' gestation.

Results

A total of 90 women fulfilled the study criteria. IVA-PI decreased throughout pregnancy from a mean ± SD of 1.04 ± 0.23 in the first trimester (at 12-13 weeks) …


Parenteral Nutritional Support In Surgical Patients: Expert Consensus Statements Regarding Intravenous Lipid Emulsions Containing Omega-3 Fatty Acids., Robert G Martindale, David C Evans, Dan Waitzberg, Malissa Warren, Manpreet S Mundi, Stanislaw Klek, Paul E Wischmeyer, Martin D Rosenthal Jan 2025

Parenteral Nutritional Support In Surgical Patients: Expert Consensus Statements Regarding Intravenous Lipid Emulsions Containing Omega-3 Fatty Acids., Robert G Martindale, David C Evans, Dan Waitzberg, Malissa Warren, Manpreet S Mundi, Stanislaw Klek, Paul E Wischmeyer, Martin D Rosenthal

Surgery Articles

OBJECTIVES: The International Lipids in Parenteral Nutrition (PN) Summit was convened to offer practical guidance and expert consensus opinion regarding the use of intravenous lipid emulsions (ILEs) in various clinical settings. Herein, we briefly review aspects from this summit that are of particular importance for surgical/hospitalized patients.

METHODS: Summit participants identified and discussed new evidence, data, and analyses, that potentially influence the benefits and risks of ILEs in PN or their use in clinical practice. The summit meeting consisted of expert presentations that assessed recent clinical data and best practice, followed by periodic panel discussions to formulate consensus statements. Consensus …


Heritability And Shared Environmental Effects Of Brain Diseases In 12,040 Extended Families, Janna I R Dijkstra, Marc Hulsman, Lisa Waterink, Henne Holstege, Charlotte E Teunissen, Wouter F L Christiaansen, Bryan A De Jong, Peter Kochunov, Brian Donohue, Marissa D Zwan, Anouk Den Braber, Lisa Vermunt, Sven J Van Der Lee Jan 2025

Heritability And Shared Environmental Effects Of Brain Diseases In 12,040 Extended Families, Janna I R Dijkstra, Marc Hulsman, Lisa Waterink, Henne Holstege, Charlotte E Teunissen, Wouter F L Christiaansen, Bryan A De Jong, Peter Kochunov, Brian Donohue, Marissa D Zwan, Anouk Den Braber, Lisa Vermunt, Sven J Van Der Lee

Faculty, Staff and Student Publications

Brain diseases have complex patterns of genetic and environmental risk factors, and better understanding of these risks is required for more effective prevention strategies. Participants of the Dutch Brain Research Registry provided detailed information on family structure and occurrence of brain diseases. A total of 12,040 participants (73% female, aged 64.9 ± 11 years) provided information on 101,379 family members (53% female, aged 62 ± 25 years). We estimated heritability (h2) of the nine most common brain diseases using polygenic modeling in SOLAR and assessed variations in h2 through bootstrapping; Alzheimer’s disease (AD) (h2 = …


Cost-Effective Hierarchical Cobalt Nanostructured Laser-Induced Graphene For Enhanced Uric Acid Detection, Anju Joshi, Gymama Slaughter Jan 2025

Cost-Effective Hierarchical Cobalt Nanostructured Laser-Induced Graphene For Enhanced Uric Acid Detection, Anju Joshi, Gymama Slaughter

Center for Bioelectronics Publications

This study presents an innovative, cost-effective strategy to develop a flexible, enzyme-free biosensor for the sensitive detection of uric acid (UA). Utilizing electrochemically modified cobalt nanostructured on laser-induced graphene electrodes (CoNCs/LIG), this approach surpasses traditional noble metal-based electrocatalysts in sensitivity and affordability. The one-step electrochemical modification method is efficient and straightforward, enabling the uniform deposition of hierarchical flower-like cobalt nanostructures. These structures synergistically enhance the performance of the LIG, resulting in a broad detection range of 5 to 700 µM with a sensitivity of 6.75 µA µM-¹ cm-² and a low detection limit of 3.66 µM for UA. …


Endoneurial Immune Interplay In Peripheral Nerve Repair: Insights And Implications For Future Therapeutic Interventions, Alina Sprenger-Svačina, Martin K R Svačina, Husniye G Otlu, Tong Gao, Kazim A Sheikh, Gang Zhang Jan 2025

Endoneurial Immune Interplay In Peripheral Nerve Repair: Insights And Implications For Future Therapeutic Interventions, Alina Sprenger-Svačina, Martin K R Svačina, Husniye G Otlu, Tong Gao, Kazim A Sheikh, Gang Zhang

Faculty, Staff and Student Publications

The mechanisms underlying axonal injury and repair in peripheral nerves, whether due to traumatic damage or autoimmune neuropathies, are complex and not yet fully understood. Recent research indicates that an orchestrated interplay between damaged neurons, Schwann cells, and especially endoneurial immune cells such as macrophages or T cells is crucial to achieve satisfactory nerve recovery. Following axonal injury, degenerating axons and reactive Schwann cells release chemoattractants and cytokines that recruit immune cells into the endoneurium. Among them, macrophages play a pivotal role by clearing axonal and myelin debris and subsequently creating a pro-regenerative microenvironment that supports axonal outgrowth. There is …


From Misinformation To Policy Solutions: Teaching Herd Immunity And Vaccine Hesitancy Through Real-World Case Studies Of Measles Outbreaks, Laurieann Klockow Jan 2025

From Misinformation To Policy Solutions: Teaching Herd Immunity And Vaccine Hesitancy Through Real-World Case Studies Of Measles Outbreaks, Laurieann Klockow

Biomedical Sciences Faculty Research and Publications

Vaccine hesitancy threatens herd immunity, contributing to the resurgence of measles outbreaks. This lesson engages upper-level biomedical science students in analyzing the complex interplay between vaccination rates, herd immunity and vaccine exemption policies through examination of the 2019 New York measles outbreak that threatened the United States’ measles elimination status. Students critically evaluate anti-vaccine misinformation, analyze epidemiological data and develop evidence-based policy recommendations to increase vaccination rates. The lesson combines team-based learning with authentic assessment through vaccine policy development, moving beyond knowledge acquisition and content to building scientific literacy and evidence-based reasoning skills essential for scientifically literate citizens and future …


Effects Of Perinatal Exposure To Lipopolysaccharide And Acetaminophen On Learning In Adult Long-Evans Rats, Lucy A. Sivils Jan 2025

Effects Of Perinatal Exposure To Lipopolysaccharide And Acetaminophen On Learning In Adult Long-Evans Rats, Lucy A. Sivils

College of Graduate Studies: Theses & Dissertations

The present study investigated the individual and combined effects of elevated perinatal inflammation, oxidative stress caused by acetaminophen (APAP) exposure, or elevated inflammation and oxidative stress on adult learning behaviors in Long-Evans rats. While prior studies have examined these factors independently, the combined effects of inflammation and oxidative stress via APAP exposure during early development on learning-related behaviors remain unexplored. The present research aimed to address this gap by the analysis of potential long-term neurodevelopmental consequences of lipopolysaccharide (LPS)-induced inflammation and APAP-induced oxidative stress. LPS, APAP, or LPS + APAP was administered during the perinatal period: postnatal days (PD) 9, …


The Role Of Horizontal Gene Transfer In Antibiotic Resistance Amidst Prevalent Community And Healthcare-Associated Mrsa Rates, Gabrielle Nascimento Jan 2025

The Role Of Horizontal Gene Transfer In Antibiotic Resistance Amidst Prevalent Community And Healthcare-Associated Mrsa Rates, Gabrielle Nascimento

Honors College Theses

In recent decades, cases of community-acquired MRSA (CA-MRSA) and healthcare-associated MRSA (HA-MRSA) have been on the rise. The ability of antibiotic resistance to transfer between microorganisms greatly expands its threat to the effective treatment and containment of bacterial infections. The mecA gene is found on a mobile cassette within the Staphylococcal cell and encodes for PBP2a, an alternate version of penicillin-binding protein (PBP) with less binding affinity for β-lactam antibiotics, increasing resistance to the effects of antibiotics. The goal of this research is to investigate the horizontal transfer of the mecA gene between various Staphylococcus species as well as to …


Evaluation Of Leptospirosis Vaccine Efficacy After Modifications Of N-Linked Glycosylation In Liga Mrna Vaccines., Rampapat Phaetthayanan Jan 2025

Evaluation Of Leptospirosis Vaccine Efficacy After Modifications Of N-Linked Glycosylation In Liga Mrna Vaccines., Rampapat Phaetthayanan

Chulalongkorn University Theses and Dissertations (Chula ETD)

Leptospirosis, caused by pathogenic Leptospira species, is a widespread zoonotic disease, particularly prevalent in developing countries in tropical areas. Commercially available bacterins have several limitations. A previous study developed a messenger RNA (mRNA) vaccine encoding the carboxy-terminal domain 7-13 of LigA (LigAc) that was expressed with glycosylation in mammalian cells and elicited high humoral immune response in a hamster model but failed to provide protection against lethal challenge. To improve the protective efficacy, this study aimed to develop LigAc-mRNA vaccines with minimal glycosylation. Three mRNA constructs were developed based on two strategies: modifying the potential N-glycosylation sites (from asparagine to …