Medical Specialties Commons^™

Self-Correcting Method For Highly Effective Office-Based Helicobacter Pylori Therapy Using Cumulative Test Of Cure Data, Maria Pina Dore, Ruben Hernaez, David Y Graham

Faculty, Staff and Students Publications

Background and aim: Helicobacter pylori infections have become resistant to many previously highly effective antimicrobial regimens resulting in clarithromycin, metronidazole, or fluoroquinolone-containing therapies becoming unsuccessful. Pretreatment susceptibility testing is only widely available in the United States but is still rarely done. Here, we propose a framework to monitor H. pylori eradication in small clinical settings by routinely assessing the effectiveness of therapy.

Methods: Because of the small sample size in individual practice's, we assume an acceptable cure rate of ≥80% (preferred cure rate ≥85%) in adherent patients, with a dichotomous outcome (cured vs. failed) and consecutive patient enrollment. To obtain …

Management Of Depression/Anxiety In Patients With Chronic Liver Disease, Mauro Garcia-Altieri, Keila Carrera-Mejias, Ruben Hernaez

Faculty, Staff and Students Publications

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Phenotypic And Functional Assessment Of Two Novel Kcnq2 Gain-Of-Function Variants Y141n And G239s And Effects Of Amitriptyline Treatment, Allan Bayat, Stefano Iavarone, Francesco Miceli, Anne V Jakobsen, Katrine M Johannesen, Marina Nikanorova, Rafal Ploski, Krystyna Szymanska, Robert Flamini, Edward C Cooper, Sarah Weckhuysen, Maurizio Taglialatela, Rikke S Møller

Faculty, Staff and Students Publications

While loss-of-function (LoF) variants in KCNQ2 are associated with a spectrum of neonatal-onset epilepsies, gain-of-function (GoF) variants cause a more complex phenotype that precludes neonatal-onset epilepsy. In the present work, the clinical features of three patients carrying a de novo KCNQ2 Y141N (n = 1) or G239S variant (n = 2) respectively, are described. All three patients had a mild global developmental delay, with prominent language deficits, and strong activation of interictal epileptic activity during sleep. Epileptic seizures were not reported. The absence of neonatal seizures suggested a GoF effect and prompted functional testing of the variants. In vitro whole-cell …

Bi-Allelic Variants In Cep295 Cause Seckel-Like Syndrome Presenting With Primary Microcephaly, Developmental Delay, Intellectual Disability, Short Stature, Craniofacial And Digital Abnormalities, Niu Li, Yufei Xu, Hongzhu Chen, Jingqi Lin, Lama Alabdi, Mir Reza Bekheirnia, Guoqiang Li, Yoel Gofin, Nasim Bekheirnia, Eissa Faqeih, Lina Chen, Guoying Chang, Jie Tang, Ruen Yao, Tingting Yu, Xiumin Wang, Wei Fu, Qihua Fu, Yiping Shen, Fowzan S Alkuraya, Keren Machol, Jian Wang

Faculty, Staff and Students Publications

BACKGROUND: Pathogenic variants in the centrosome protein (CEP) family have been implicated in primary microcephaly, Seckel syndrome, and classical ciliopathies. However, most CEP genes remain unlinked to specific Mendelian genetic diseases in humans. We sought to explore the roles of CEP295 in human pathology.

METHODS: Whole-exome sequencing was performed to screen for pathogenic variants in patients with severe microcephaly. Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying pathomechanisms, including centriole/centrosome development, cell cycle and proliferation changes, and ciliogenesis. Complementary experiments using CEP295 mRNA were performed to determine the pathogenicity of the identified missense variant. …

Research Considerations For Prospective Studies Of Patients With Coma And Disorders Of Consciousness, Lorenzo Tinti, Thomas Lawson, Erika Molteni, Daniel Kondziella, Verena Rass, Tarek Sharshar, Yelena G Bodien, Joseph T Giacino, Stephan A Mayer, Moshgan Amiri, Susanne Muehlschlegel, Chethan P Venkatasubba Rao, Paul M Vespa, David K Menon, Giuseppe Citerio, Raimund Helbok, Molly Mcnett

Faculty, Staff and Students Publications

Disorders of consciousness are neurological conditions characterized by impaired arousal and awareness of self and environment. Behavioural responses are absent or are present but fluctuate. Disorders of consciousness are commonly encountered as a consequence of both acute and chronic brain injuries, yet reliable epidemiological estimates would require inclusive, operational definitions of the concept, as well as wider knowledge dissemination among involved professionals. Whereas several manifestations have been described, including coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state, a comprehensive neurobiological definition for disorders of consciousness is still lacking. The scientific literature is primarily observational, and studies-specific aetiologies lead to …

Identification Of Constrained Sequence Elements Across 239 Primate Genomes, Lukas F K Kuderna, Jacob C Ulirsch, Sabrina Rashid, Mohamed Ameen, Laksshman Sundaram, Glenn Hickey, Anthony J Cox, Hong Gao, Arvind Kumar, Francois Aguet, Matthew J Christmas, Hiram Clawson, Maximilian Haeussler, Mareike C Janiak, Martin Kuhlwilm, Joseph D Orkin, Thomas Bataillon, Shivakumara Manu, Alejandro Valenzuela, Juraj Bergman, Marjolaine Rouselle, Felipe Ennes Silva, Lidia Agueda, Julie Blanc, Marta Gut, Dorien De Vries, Ian Goodhead, R Alan Harris, Muthuswamy Raveendran, Axel Jensen, Idriss S Chuma, Julie E Horvath, Christina Hvilsom, David Juan, Peter Frandsen, Joshua G Schraiber, Fabiano R De Melo, Fabrício Bertuol, Hazel Byrne, Iracilda Sampaio, Izeni Farias, João Valsecchi, Malu Messias, Maria N F Da Silva, Mihir Trivedi, Rogerio Rossi, Tomas Hrbek, Nicole Andriaholinirina, Clément J Rabarivola, Alphonse Zaramody, Clifford J Jolly, Jane Phillips-Conroy, Gregory Wilkerson, Christian Abee, Joe H Simmons, Eduardo Fernandez-Duque, Sree Kanthaswamy, Fekadu Shiferaw, Dongdong Wu, Long Zhou, Yong Shao, Guojie Zhang, Julius D Keyyu, Sascha Knauf, Minh D Le, Esther Lizano, Stefan Merker, Arcadi Navarro, Tilo Nadler, Chiea Chuen Khor, Jessica Lee, Patrick Tan, Weng Khong Lim, Andrew C Kitchener, Dietmar Zinner, Ivo Gut, Amanda D Melin, Katerina Guschanski, Mikkel Heide Schierup, Robin M D Beck, Ioannis Karakikes, Kevin C Wang, Govindhaswamy Umapathy, Christian Roos, Jean P Boubli, Adam Siepel, Anshul Kundaje, Benedict Paten, Kerstin Lindblad-Toh, Jeffrey Rogers, Tomas Marques Bonet, Kyle Kai-How Farh

Faculty, Staff and Students Publications

Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3–9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of …

Improved Sequence Mapping Using A Complete Reference Genome And Lift-Over, Nae-Chyun Chen, Luis F Paulin, Fritz J Sedlazeck, Sergey Koren, Adam M Phillippy, Ben Langmead

Faculty, Staff and Students Publications

Complete, telomere-to-telomere genome assemblies promise improved analyses and the discovery of new variants, but many essential genomic resources remain associated with older reference genomes. Thus, there is a need to translate genomic features and read alignments between references. Here we describe a new method called levioSAM2 that accounts for reference changes and performs fast and accurate lift-over between assemblies using a whole-genome map. In addition to enabling the use of multiple references, we demonstrate that aligning reads to a high-quality reference (e.g. T2T-CHM13) and lifting to an older reference (e.g. GRCh38) actually improves the accuracy of the resulting variant calls …

Inference Of Phylogenetic Trees Directly From Raw Sequencing Reads Using Read2tree, David Dylus, Adrian Altenhoff, Sina Majidian, Fritz J Sedlazeck, Christophe Dessimoz

Faculty, Staff and Students Publications

Current methods for inference of phylogenetic trees require running complex pipelines at substantial computational and labor costs, with additional constraints in sequencing coverage, assembly and annotation quality, especially for large datasets. To overcome these challenges, we present Read2Tree, which directly processes raw sequencing reads into groups of corresponding genes and bypasses traditional steps in phylogeny inference, such as genome assembly, annotation and all-versus-all sequence comparisons, while retaining accuracy. In a benchmark encompassing a broad variety of datasets, Read2Tree is 10-100 times faster than assembly-based approaches and in most cases more accurate-the exception being when sequencing coverage is high and reference …

Idppub: Illuminating The Dark Phosphoproteome Through Pubmed Mining, Sara R Savage, Yaoyun Zhang, Eric J Jaehnig, Yuxing Liao, Zhiao Shi, Huy Anh Pham, Hua Xu, Bing Zhang

Faculty, Staff and Students Publications

Global phosphoproteomics experiments quantify tens of thousands of phosphorylation sites. However, data interpretation is hampered by our limited knowledge on functions, biological contexts, or precipitating enzymes of the phosphosites. This study establishes a repository of phosphosites with associated evidence in biomedical abstracts, using deep learning-based natural language processing techniques. Our model for illuminating the dark phosphoproteome through PubMed mining (IDPpub) was generated by fine-tuning BioBERT, a deep learning tool for biomedical text mining. Trained using sentences containing protein substrates and phosphorylation site positions from 3000 abstracts, the IDPpub model was then used to extract phosphorylation sites from all MEDLINE abstracts. …

Neuronal Ablation Of Ghsr Mitigates Diet-Induced Depression And Memory Impairment Via Ampk-Autophagy Signaling-Mediated Inflammation, Hongying Wang, Zheng Shen, Chia-Shan Wu, Pengfei Ji, Ji Yeon Noh, Cédric G Geoffroy, Sunja Kim, David Threadgill, Jianrong Li, Yu Zhou, Xiaoqiu Xiao, Hui Zheng, Yuxiang Sun

Faculty, Staff and Students Publications

Obesity is associated with chronic inflammation in the central nervous system (CNS), and neuroinflammation has been shown to have detrimental effects on mood and cognition. The growth hormone secretagogue receptor (GHSR), the biologically relevant receptor of the orexigenic hormone ghrelin, is primarily expressed in the brain. Our previous study showed that neuronal GHSR deletion prevents high-fat diet-induced obesity (DIO). Here, we investigated the effect of neuronal GHSR deletion on emotional and cognitive functions in DIO. The neuron-specific GHSR-deficient mice exhibited reduced depression and improved spatial memory compared to littermate controls under DIO. We further examined the cortex and hippocampus, the …

Proton Pump Inhibitors: Rational Use And Use-Reduction - The Windsor Workshop, Peter Kahrilas, Foteini Anastasiou, Albert J Bredenoord, Hashem B El Serag, Joachim Labenz, Juan Mendive, Edoardo V Savarino, Daniel Sifrim, Mihaela Udrescu, Rena Yadlapati, A Pali Hungin

Faculty, Staff and Students Publications

BACKGROUND: Despite deprescribing initiatives to curb overutilization of proton pump inhibitors (PPIs), achieving meaningful reductions in PPI use is proving a challenge.

SUMMARY: An international group of primary care doctors and gastroenterologists examined the literature surrounding PPI use and use-reduction to clarify: (i) what constitutes rational PPI prescribing; (ii) when and in whom PPI use-reduction should be attempted; and (iii) what strategies to use when attempting PPI use-reduction.

KEY MESSAGES: Before starting a PPI for reflux-like symptoms, patients should be educated on potential causes and alternative approaches including dietary and lifestyle modification, weight loss, and relaxation strategies. When commencing a …

Gsk-3Β As A Potential Coordinator Of Anabolic And Catabolic Pathways In Hepatitis C Virus Insulin Resistance, Gokul C Das, F Blaine Hollinger

Faculty, Staff and Students Publications

INTRODUCTION: Chronic hepatitis C infection can result in insulin resistance (IR). We have previously shown that it occurs through the interaction of pathways for glucose homeostasis, insulin signaling, and autophagy. But it is not known how soon the pathways are activated and how IR is related to the signals generated by catabolic and anabolic conditions occurring in infected cells. We have extended our studies to a cell culture system mimicking acute infection and to downstream pathways involving energy-sensor AMPK and nutrient-sensor mTOR that are active in catabolic and anabolic processes within the infected cells.

METHODS: Huh7 liver cells in culture …

Trends In Cardiovascular Disease-Related Mortality In Texas, Muhammad Shariq Usman, Adeena Jamil, Zainali Chunawala, Mahboob Alam, Vijay Nambi, Layla A Abushamat, Arunima Misra, Salim S Virani, Christie M Ballantyne, George E Taffet, Khurram Nasir, Sachin Goel, Sadeer Al-Kindi, Javed Butler, Abdul Mannan Khan Minhas

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular disease (CVD) is associated with high mortality in the United States, but the burden of CVD mortality is unevenly distributed between demographic and geographic subgroups, with poor characterization of state-specific trends. In this study, the disparities in CVD-related mortality trends in Texas and the United States from 1999 to 2019 were assessed.

METHODS: Trends in CVD-related mortality were evaluated through analysis of the Multiple Causes of Death Files from the National Center for Health Statistics. Crude and age-adjusted mortality rates (AAMRs) per 100,000 population with associated annual percentage changes were determined. Joinpoint regression was used to assess trends …

A Multi-Institutional Natural Language Processing Pipeline To Extract Performance Status From Electronic Health Records, Arash Maghsoudi, Yvonne H Sada, Sara Nowakowski, Danielle Guffey, Huili Zhu, Sudha R Yarlagadda, Ang Li, Javad Razjouyan

Faculty, Staff and Students Publications

PURPOSE: Performance status (PS), an essential indicator of patients' functional abilities, is often documented in clinical notes of patients with cancer. The use of natural language processing (NLP) in extracting PS from electronic medical records (EMRs) has shown promise in enhancing clinical decision-making, patient monitoring, and research studies. We designed and validated a multi-institute NLP pipeline to automatically extract performance status from free-text patient notes.

PATIENTS AND METHODS: We collected data from 19,481 patients in Harris Health System (HHS) and 333,862 patients from veteran affair's corporate data warehouse (VA-CDW) and randomly selected 400 patients from each data source to train …

A Case Report Navigating Cvid And Sarcoidosis Overlaps In Pediatric Nephritis, Amanda Salih, Amanda Brown, Amanda Grimes, Sana Hasan, Manuel Silva-Carmona, Leyat Tal, Joud Hajjar

Faculty, Staff and Students Publications

Common variable immunodeficiency (CVID) can be complicated by granulomatous disease, often granulomatous lymphocytic interstitial lung disease (GLILD). Granulomatous interstitial nephritis represents an atypical presentation in pediatrics. Our patient is a previously healthy 13-year-old white male with a recent diagnosis of CVID. He presented with a rash and laboratory findings included pancytopenia (white blood cells 2.6 cells × 103/μl, hemoglobin 11.8 g/dl, platelets 60 × 103/μl), hypercalcemia (14.9 mg/dl), elevated Vit D 1,25 OH level (>200 pg/ml), hyperuricemia (8.8 mg/dl), and acute kidney injury (AKI) (serum creatinine 1.1 mg/dl; baseline 0.64 mg/dl). A broad infectious workup was unremarkable. The rash …

Β2-Glycoprotein I Promotes The Clearance Of Circulating Mitochondria, Swapan Kumar Dasgupta, Jahnavi Gollamudi, Stefanie Rivera, Ross A Poche, Rolando E Rumbaut, Perumal Thiagarajan

Faculty, Staff and Students Publications

β2-glycoprotein I (β2-Gp1) is a cardiolipin-binding plasma glycoprotein. It is evolutionarily conserved from invertebrates, and cardiolipin-bound β2-Gp1 is a major target of antiphospholipid antibodies seen in autoimmune disorders. Cardiolipin is almost exclusively present in mitochondria, and mitochondria are present in circulating blood. We show that β2-Gp1 binds to cell-free mitochondria (CFM) in the circulation and promotes its phagocytosis by macrophages at physiological plasma concentrations. Exogenous CFM had a short circulation time of less than 10 minutes in mice. Following infusion of CFM, β2-Gp1-deficient mice had significantly higher levels of transfused mitochondria at 5 minutes (9.9 ± 6.4 pg/ml versus 4.0 …

Ibrutinib-Associated Cutaneous Mucormycosis Due To An Apophysomyces Species: Report Of A Case And Review Of The Literature, Trung Minh Nguyen, Eva Amenta, Lynne Chapman, Sarvari Yellapragada, Bhuvaneswari Krishnan, Jonathan Lim, Richard J Hamill

Faculty, Staff and Students Publications

The use of ibrutinib, a Bruton tyrosine kinase inhibitor, has been associated with invasive fungal infections (IFIs). We describe a case of Apophysomyces infection associated with long-term use of ibrutinib for the treatment of chronic lymphocytic leukemia as well as perform a literature review of Mucormycosis infections in patients on ibrutinib. Our review found that the onset of IFI can occur within months to years of starting tyrosine kinase inhibitors. These reports provide a more complete picture of the risk of IFI while patients are on ibrutinib. Our case also demonstrates the utility of molecular techniques in the diagnosis of …

The Great Masquerade: Not All Coronary Artery Stenosis Are Created Equal, Prasanti A Kotta, Ajit K Koduri, Jeffrey Berman, Veronica V Rosen, Waleed T Kayani

Faculty, Staff and Students Publications

We present the case of a 60-year-old male, with active smoking and cocaine use disorder, who reported progressive chest pain. Various anatomical and functional cardiac imaging, performed to further evaluate chest pain etiology, revealed changing severity and distribution of left main artery (LMA) stenosis, raising suspicion for vasospasm. Intracoronary nitroglycerin relieved the vasospasm, with resolution of the LMA pseudostenosis. A diagnosis of vasospastic angina (VA) led to starting appropriate medical therapy with lifestyle modification counselling. This case highlights VA, a frequently underdiagnosed etiology of angina pectoris. We discuss when to suspect VA, its appropriate work-up, and management.

Risk Factors, Incidence, And Outcomes Associated With Clinically Significant Airway Ischemia, Gloria Li, Zejian Liu, Marcelo Salan-Gomez, Emma Keeney, Ethan D'Silva, Babith Mankidy, Andres Leon, Aladdein Mattar, Abdusallam Elsennousi, Jennalee Coster, Anupam Kumar, Bruno Rodrigues, Meng Li, Alexis Shafii, Puneet Garcha, Gabriel Loor

Faculty, Staff and Students Publications

Airway complications following lung transplantation remain an important cause of morbidity and mortality. We aimed to identify the incidence, risk factors and outcomes associated with clinically significant airway ischemia (CSAI) in our center. We reviewed 217 lung transplants (386 airway anastomoses) performed at our institution between February 2016 and December 2020. Airway images were graded using the 2018 ISHLT grading guidelines modified slightly for retrospective analysis. Airways were considered to have CSAI if they developed ischemia severity >B2, stenosis >50%, and/or any degree of dehiscence within 6-months of transplant. Regression analyses were used to evaluate outcomes and risk factors for …

Cardiac Tamponade Secondary To Esophagopericardial Fistula, Caitlin T Perez-Stable, Lauren T Callaghan, Christopher K Wong, Jorge M Escobar, Mahboob Alam

Faculty, Staff and Students Publications

Esophagopericardial fistulas are an extremely rare structural defect that may arise from malignant or iatrogenic etiologies. This article reports the case of a patient with cardiac tamponade secondary to hydropneumopericardium from esophagopericardial fistula. Given the high morbidity and mortality of this condition, this article describes challenges in diagnosis and clinical decision-making to improve early identification and interdisciplinary management.

Implementation Of An Evidence-Based Bundle To Educate Nurses In The Care Of Adult Post-Transplant Diabetes Mellitus Patients, Christine Slaughter

DNP Projects

Background: After solid organ transplantation, between 10-40% of patients develop post-transplant diabetes mellitus (PTDM) due to the immunosuppression regimen, infection, stress response and pain. Hyperglycemia events are common and managing glycemic targets is critical to decrease the likelihood of graft failure and mortality.

Purpose: To determine the impact of an evidenced-based bundle education strategy on the perceived confidence/knowledge of nurses and on their documentation compliance in the care of adult solid organ post-transplant diabetes mellitus patients.

Methods: A single group, pretest-posttest design was implemented to evaluate the effectiveness of the electronic educational program on the nurses perceived confidence/knowledge regarding glycemic …

Utilizing The Stop-Bang Questionnaire To Assess Risk Of Obstructive Sleep Apnea In Hospitalized Patients With Heart Failure To Facilitate Sleep Medicine Referrals Upon Discharge, Chelsea Mitchell

DNP Projects

Background: Obstructive sleep apnea (OSA) is the most common sleep-breathing disorder. Undiagnosed OSA is highly prevalent in the population, especially in those with heart failure. OSA and heart failure combined create a negative feedback loop that can lead to poor clinical outcomes. Unfortunately, many cardiac patients are never screened for OSA.

Purpose: The purpose of this project is to improve screening rates for OSA via the STOP-Bang questionnaire and establish an efficient and effective process for referrals to sleep medicine for heart failure patients screening high-risk.

Methods: The design was a quality improvement project with pre- and post-testing and a …

Improving Knowledge, Confidence, And Competency Among Icu Nurses Concerning The Benefits Of Using The Uk Ventilator Separation Protocol, Brittany Monroe

DNP Projects

Background: The trauma intensive care unit (ICU) at University of Kentucky (UK) Healthcare uses a ventilator separation protocol which provides specific guidelines on the successful weaning of patients from mechanical ventilation. However, many of the nurses are not aware of this protocol as formal education is not included in their orientation or training. This lack of knowledge can lead to risks such as increased patient morbidity, mortality, ICU length of stay, and healthcare-related costs. Research shows that using structured mechanical ventilator weaning tools in the ICU can shorten the duration of mechanical ventilation, which in turn, lowers these associated risks. …

The Impact Of Lung Cancer Screening Education On Knowledge And Screening Rates In A Kentucky Cancer Survivorship Clinic, Alexandra Isler

DNP Projects

Background: Lung cancer is a significant problem in Kentucky, which ranks fourth in the nation in adults who currently smoke. Early detection, through lung cancer screening, can prevent untimely deaths. Several barriers to screening exist including lack of knowledge and awareness among patients regarding lung cancer screening. By increasing knowledge, at risk patients can take the necessary steps to decrease incidence of late stage diagnoses.

Purpose: The purpose of this project was to evaluate patients’ knowledge of lung cancer screening and referral and screening rates before and after one-on-one patient education.

Methods: This was a quality improvement project that used …

The Effect Of An Educational Intervention On Early Mobility Compliance In Oncology Nurses, Jonathan A. Hacker

DNP Projects

Background: Geriatric adult patients admitted into acute care hospital settings are at risk of functional decline in their capacity for activities of daily living and independent ambulation. Many of these patients fail to achieve pre-hospitalization levels of function and continue to decline, requiring additional support and care after discharge. Current literature supports early mobilization and ambulation during hospitalization. However, ambulation and patient mobilization has been shown to be the most missed item of nursing care. There is a gap in literature and patient outcome data regarding the impact of early mobilization on medical-surgical patient populations.

Purpose: The purpose of this …

Evaluation Of Nutritional Guidance From Providers For Patients With Type 2 Diabetes In A Primary Care Setting, Whitney Rice

DNP Projects

Background: Adherence to diet is a challenging part of managing type 2 diabetes mellitus (T2DM). Guidelines recommend including a registered dietician and/or a diabetes educator. While this is the gold standard, there are barriers to implementation in primary care. The Starting the Conversation (STC) diet recall tool can aid primary care providers (PCPs) in providing brief nutrition counseling for patients with T2DM. Purpose: To evaluate the perceptions and practices of PCPs regarding dietary education and documentation for patients with T2DM after provider education and initiation of the STC tool. Methods: This was a quality improvement project using a quasi-experimental pretest …

An Educational Intervention To Improve Neonatal Icu Nurses’ Breastfeeding Support Knowledge, Self-Efficacy, And Breastfeeding Rates At Discharge, Sarah Money

DNP Projects

Background: The benefits of breastfeeding for both mother and baby are known. It is recommended that all infants be exclusively breastfed until six months (Meek & Noble, 2022; North et al., 2021). Despite this, breastfeeding rates remain low, especially in medically fragile infants requiring care in the neonatal intensive care unit (NICU) (Rollins et al., 2016). Receipt of evidence-based breastfeeding support by healthcare providers has been shown to improve breastfeeding success; however, many healthcare providers report not being comfortable or knowledgeable enough to offer support consistently (Mulcahy et al., 2022; Rollins et al., 2016).

Purpose: This study aims …

Klebsiella Pneumoniae Carbapenemase Variant 44 Acquires Ceftazidime-Avibactam Resistance By Altering The Conformation Of Active-Site Loops, Zhizeng Sun, Hanfeng Lin, Liya Hu, Neetu Neetu, Banumathi Sankaran, Jin Wang, B V Venkataram Prasad, Timothy Palzkill

Faculty, Staff and Students Publications

Klebsiella pneumoniae carbapenemase 2 (KPC-2) is an important source of drug resistance as it can hydrolyze and inactivate virtually all β-lactam antibiotics. KPC-2 is potently inhibited by avibactam via formation of a reversible carbamyl linkage of the inhibitor with the catalytic serine of the enzyme. However, the use of avibactam in combination with ceftazidime (CAZ-AVI) has led to the emergence of CAZ-AVI-resistant variants of KPC-2 in clinical settings. One such variant, KPC-44, bears a 15 amino acid duplication in one of the active-site loops (270-loop). Here, we show that the KPC-44 variant exhibits higher catalytic efficiency in hydrolyzing ceftazidime, lower …

A Prdm16-Driven Signal Regulates Body Composition In Testosterone-Treated Hypogonadal Men, Siresha Bathina, Georgia Colleluori, Dennis T Villareal, Lina Aguirre, Rui Chen, Reina Armamento-Villareal

Faculty, Staff and Students Publications

BACKGROUND: Testosterone (T) therapy increases lean mass and reduces total body and truncal fat mass in hypogonadal men. However, the underlying molecular mechanisms for the reciprocal changes in fat and lean mass in humans are not entirely clear.

METHODS: Secondary analysis of specimens obtained from a single-arm, open-label clinical trial on pharmacogenetics of response to T therapy in men with late-onset hypogonadism, conducted between 2011 and 2016 involving 105 men (40-74 years old), who were given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subcutaneous fat (SCF), peripheral blood mononuclear cells (PBMC) and serum were obtained from …

A Comprehensive Meta-Analysis Of Tissue Resident Memory T Cells And Their Roles In Shaping Immune Microenvironment And Patient Prognosis In Non-Small Cell Lung Cancer, Aidan Shen, Aliesha Garrett, Cheng-Chi Chao, Dongliang Liu, Chao Cheng, Zhaohui Wang, Chen Qian, Yangzhi Zhu, Junhua Mai, Chongming Jiang

Faculty, Staff and Students Publications

Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. …