Digital Commons Network^™

Phase Iib, Randomized, Double-Blind Trial Of Gc4419 Versus Placebo To Reduce Severe Oral Mucositis Due To Concurrent Radiotherapy And Cisplatin For Head And Neck Cancer., Carryn M Anderson, Christopher M Lee, Deborah P Saunders, Amarinthia Curtis, Neal Dunlap, Chaitali Nangia, Arielle S Lee, Sharon M Gordon, Philip Kovoor, Roberto Arevalo-Araujo, Voichita Bar-Ad, Abhinand Peddada, Kyle Colvett, Douglas Miller, Anshu K Jain, James Wheeler, Dukagjin Blakaj, Marcelo Bonomi, Sanjiv S Agarwala, Madhur Garg, Francis Worden, Jon Holmlund, Jeffrey M Brill, Matt Downs, Stephen T Sonis, Sanford Katz, John M Buatti

Articles, Abstracts, and Reports

PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM).

PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly …

Epigenetic Hypomethylation And Upregulation Of Gd3s In Triple Negative Breast Cancer., Wan Li, Xiangjin Zheng, Liwen Ren, Weiqi Fu, Jinyi Liu, Jun Xv, Shiwei Liu, Jinhua Wang, Guanhua Du

Articles, Abstracts, and Reports

Background: Breast cancer remains a major health problem in the world. Triple-negative breast cancer (TNBC) is an aggressive subtype with very poor prognosis. Up to now, the mechanism behind TNBC's activity is still unclear and no candidate drug target has been identified. Thus, it is of critical importance to elucidate the pathways in TNBC and identify the relevant biomarkers. Recent studies showed that ganglioside D3 synthase (GD3s) played a very important role in development of cancers. However, the physiological functions and associated pathways of GD3s in TNBC are still unclear.

Methods:

Results:

Conclusions: In summary, these results suggest that GD3s …

Outcome In Patients With Myasthenia Gravis Managed With Or Without Thymectomy, Safia Bano, Muhammad Athar Javed, Waqas Arshad

Pakistan Journal of Neurological Sciences (PJNS)

Myasthenia gravis is a chronic acquired autoimmune disorder in which autoantibodies are produced against acetylcholine receptors present on neuromuscular junction. It results in neuromuscular transmission blockage hence muscle weakness occurs. Thymus gland is considered as having crucial role in development of these antibodies. Screening patients for thymoma and removal of the thymus gland with surgery has an important aspect in management of disease.

Association Between Gastroduodenal Ulcer And Age Of Diagnosis Of Head And Neck, Gastroduodenal And Pancreatic Cancer, Rukevwe Madusor

Capstone Experience: Master of Public Health

Background: Cancer is the second leading cause of death in the United States and remains a major public health problem worldwide. Epidemiological studies have demonstrated that insulin like growth factor-1 (IGF-1) is linked to ulcers and most cancers. Although studies have investigated the role of IGF1 in ulcer healing and cancer pathogenesis, the link between ulcer and cancer remains unclear. Hence, we assessed the relationship between ulcers and cancers.

Methods: This study consists of a sample of 180 cancer patients obtain by convenience sampling who were seen at Nebraska Medicine and were enrolled in the integrated cancer repository for cancer …

Phase Iib, Randomized, Double-Blind Trial Of Gc4419 Versus Placebo To Reduce Severe Oral Mucositis Due To Concurrent Radiotherapy And Cisplatin For Head And Neck Cancer., Carryn M. Anderson, Christopher M Lee, Deborah P. Saunders, Amarinthia Curtis, Neal Dunlap, Chaitali Nangia, Arielle S. Lee, Sharon M. Gordon, Philip Kovoor, Roberto Arevalo-Araujo, Voichita Bar-Ad, Abhinand Peddada, Kyle Colvett, Douglas Miller, Anshu K. Jain, James Wheeler, Dukagjin Blakaj, Marcelo Bonomi, Sanjiv S. Agarwala, Madhur Garg, Francis Worden, Jon Holmlund, Jeffrey M. Brill, Matt Downs, Stephen T. Sonis, Sanford Katz, John M. Buatti

Department of Radiation Oncology Faculty Papers

PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM).

PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly …

A Phase 1 Study Of Intravenous Busulfan As A Conditioning Regimen For Multiple Myeloma, Sabarinath V. Radhakrishnan, Michael Boyer, Catherine M. Sherwin, Maurizio Zangari, Guido Tricot

Pediatrics Faculty Publications

The efficacy of melphalan (MEL) 140 mg/m 2 pre-transplant conditioning versus MEL 200 mg/m 2 for the elderly is still debated. We hypothesized that single-agent intravenous busulfan (BU) would show significant anti-myeloma efficacy and be better tolerated by elderly patients. A prospective 3+3 dose escalation study enrolled symptomatic multiple myeloma (MM) patients 65 years or older with SWOG performance 0–2 for treatment with intravenous BU pre-transplant at different administration levels. The primary objective was to determine the maximum tolerated dose (MTD) of BU that could be safely given over the least number of days. All patients, except one, received maintenance …

Pediatric Acute Lymphoblastic Leukemia: A Review, Luke Geierman

Honors Projects

Acute Lymphoblastic Leukemia (ALL) is the most commonly diagnosed pediatric cancer and the most frequent cancer-induced cause of death among young people. Despite this fact, tremendous progress in treating the disease has been made in the last 50 years. This systematic literature review examines the incidence of the disease as well as the importance of risk stratification in treatment planning. The role of genetics in ALL risk stratification, specifically hypodiploidy and hyperdiploidy, is also considered. Finally, current treatment protocols, treatment failure, and the future of research and treatments are all each examined.

Msto1 Mutations Cause Mtdna Depletion, Manifesting As Muscular Dystrophy With Cerebellar Involvement., S Donkervoort, R Sabouny, P Yun, L Gauquelin, K R Chao, Y Hu, I Al Khatib, A Töpf, P Mohassel, B B Cummings, R Kaur, D Saade, S A Moore, L B Waddell, M A Farrar, J K Goodrich, P Uapinyoying, S H S Chan, A Javed, M E Leach, P Karachunski, J Dalton, L Medne, A Harper, C Thompson, Isabelle Thiffault, S Specht, R E Lamont, Carol J. Saunders, H Racher, F P Bernier, D Mowat, N Witting, J Vissing, R Hanson, Keith A. Coffman, Meagan K. Hainlen, J S Parboosingh, A Carnevale, G Yoon, R E Schnur, Care4rare Canada Consortium, K M Boycott, J K Mah, V Straub, A Reghan Foley, A M Innes, C G Bönnemann, T E Shutt

Manuscripts, Articles, Book Chapters and Other Papers

MSTO1 encodes a cytosolic mitochondrial fusion protein, misato homolog 1 or MSTO1. While the full genotype-phenotype spectrum remains to be explored, pathogenic variants in MSTO1 have recently been reported in a small number of patients presenting with a phenotype of cerebellar ataxia, congenital muscle involvement with histologic findings ranging from myopathic to dystrophic and pigmentary retinopathy. The proposed underlying pathogenic mechanism of MSTO1-related disease is suggestive of impaired mitochondrial fusion secondary to a loss of function of MSTO1. Disorders of mitochondrial fusion and fission have been shown to also lead to mitochondrial DNA (mtDNA) depletion, linking them to the mtDNA …

A Cross-Sectional Analysis Of Factors Associated With Detection Of Oncogenic Human Papillomavirus In Human Immunodeficiency Virus-Infected And Uninfected Kenyan Women, Aaron Ermel, P. Tonui, M. Titus, Y. Tong, N. Wong, J. Ong’Echa, Kapten Muthoka, Stephen Kiptoo, A. Moormann, Elkanah Omenge

Obstetrics and Gynaecology, East Africa

Background: Cervical cancer is caused by oncogenic human papillomaviruses (HPV) and is one of the most common malignancies in women living in sub-Saharan Africa. Women infected with the human immunodeficiency virus (HIV) have a higher incidence of cervical cancer, but the full impact on HPV detection is not well understood, and associations of biological and behavioral factors with oncogenic HPV detection have not been fully examined. Therefore, a study was initiated to investigate factors that are associated with oncogenic HPV detection in Kenyan women.

Methods: Women without cervical dysplasia were enrolled in a longitudinal study. Data from enrollment are presented …

Culture Bound Syndromes In Pakistan: Implications And Strategic Vision For Health Management, Lamae Zulfiqar, Nazish Idrees, Muhammad Rafiq

Pakistan Journal of Neurological Sciences (PJNS)

Understanding the culture a person belongs to is crucial as it forms the beliefs, values, perspectives, worries and hopes. It can then be used to assess the problems a person goes through and devise a treatment plan with a focus on belief system of a person. Culture bound syndromes are common in every society but are usually overlooked or given less consideration by professionals. These syndromes are belief systems associated with various diseases and disorders and can be very helpful in treatment, if understood in the perspective of a particular person as every syndrome is perceived differently by an individual …

Mental Health Of University Male Students Viewing Internet Pornography: A Qualitative Study, Komal Razzaq, Muhammad Rafiq

Pakistan Journal of Neurological Sciences (PJNS)

This research was carried out to explore psychosocial and mental health issues of adults viewing pornography on the internet. Study Design: For this purpose, a qualitative research design was used. Method: In- depth interviews were conducted with twenty five university male students to explore the psychosocial issues in cases of internet pornography. After gathering the data from participants, a software, NVivo11 Plus was used for data management and analysis. This was also used for labelling and themes and categories generation. Results: After data analysis, main three categories generated on psychosocial issues associated with viewing internet pornography which were psychological issues, …

Development And Validation Of Juvenile Criminal Thinking Styles’ Inventory, Fatima Sana, Muhammad Rafiq

Pakistan Journal of Neurological Sciences (PJNS)

The current research explored the styles of criminal thinking among juvenile delinquents in Pakistani cultural context. Initially, 40 juvenile delinquents were interviewed individually to generate an item pool of 34 distinct thought statements. After excluding repetitive items a list of 19 items was piloted on 30 juvenile delinquents as a self-report measure of 5-point rating scale (Juvenile Criminal Thinking Styles’ Inventory). Finally, a sample of 211 juvenile delinquents were given the final list of 19 items, Measure of Criminal Social Identity (Boduszek, Adamson, Shevlin, & Hyland, 2012; Shagufta, 2015), and a demographic form. Principal Component factor analysis determined a three …

Role Of Arginine And/Or Taurine In Protection Against Gentamicin-Induced Nephrotoxicity In Male And Female Rats, Amal H. Emara, Wafaa M. Ismaeil

Journal of Medicine in Scientific Research

Background As a highly effective antibiotic, gentamicin is used in the treatment of serious and life-threatening gram-negative infections. L-arginine (2-amino-5-guanidino-pentanoic acid) has a protective role on renal failure that induced by gentamicin administration and it may decrease the tubular reabsorption of another cationic substance, gentamicin due to its cationic structure. The aim of this study is to determine the influence of gender on nephroprotective effects of L-arginine (Arg) and/or taurine (Tau) on gentamicin (G) induced nephrotoxicity. Methods Adult Sprague-Dawley albino rats of both sexes (150-200 g, 48 male and 48 female), were bred from the animal unit of National Nutrition …

One-Year Angiographic Results Of Left Anterior Descending Bypass Using Internal Mammary Artery: A Series Of 48 Consecutive Patients, Ahmed S. Mahlab

Journal of Medicine in Scientific Research

The left internal mammary artery (LIMA) has been used as a conduit for coronary artery revascularization since 1968. Here we are reporting A total of 48 consecutive patients were operated upon using double mammary arteries. All of them received a mammary graft to the left anterior descending artery (LAD). All 48 of them were controlled angiographically at 1 year postoperative to ensure satisfactory well-functioning grafts.

Worldwide Network For Blood And Marrow Transplantation Recommendations For Establishing A Hematopoietic Stem Cell Transplantation Program In Countries With Limited Resources, Part Ii: Clinical, Technical, And Socioeconomic Considerations, Mahmoud Aljurf, Daniel Weisdorf, Shahrukh Hashmi, Amr Nassar, Eliane Gluckman, Mohamad Mohty, Doug Rizzo, Marcelo Pasquini, Mehdi Hamadani, Salman Adil

Department of Pathology and Laboratory Medicine

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The …

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

Dissertations and Theses (Open Access)

Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal …

From Lepidoptera To Uveal Melanoma: Finding My Career In Ocular Oncology., Jerry A Shields

Wills Eye Hospital Papers

No abstract provided.

Prognostication Of Uveal Melanoma Is Simple And Highly Predictive Using The Cancer Genome Atlas (Tcga) Classification: A Review., Carol L. Shields, Lauren A. Dalvin, Pornpattana Vichitvejpaisal, Mehdi Mazloumi, Arupa Ganguly, Jerry A. Shields

Wills Eye Hospital Papers

Purpose: The cancer genome atlas (TCGA) is a comprehensive project supported by the National Cancer Institute (NCI) in the United States to explore molecular alterations in cancer, including uveal melanoma (UM). This led to TCGA classification for UM. In this report, we review the American Joint Committee on Cancer (AJCC) classification and TCGA classification for UM from the NCI's Center for Cancer Genomics (NCI CCG) (based on enucleation specimens [n = 80 eyes]) and from Wills Eye Hospital (WEH) (based on fine needle aspiration biopsy [FNAB] specimens [n = 658 eyes]). We then compare accuracy and predictability of AJCC versus …

Extract And Active Principal Of The Neotropical Vine Souroubea Sympetala Gilg. Block Fear Memory Reconsolidation, Anthony Murkar, Hristian Cayer, Jon James, Tony Durst, John T. Arnason, Pablos E. Sanchez-Vindas, M. Otarola Rojas, Zul Merali

Brain and Mind Institute

Background: Souroubea sympetala Gilg. is a neotropical vine native to Central America, investigated as part of a targeted study of the plant family Marcgraviaceae. Our previous research showed that extract of S. sympetala leaf and small branch extract had anxiolytic effects in animals and acts as an agonist for the GABAA receptor at the benzodiazepine binding site. To date, the potential effects of S. sympetala and its constituents on reconsolidation have not been assessed. Reconsolidation, the process by which formed memories are rendered labile and susceptible to change, may offer a window of opportunity for pharmacological manipulation of learned fear. …

The Identification Of Long Non-Coding Rna Zfas1 Through An Exploratory Rna-Sequencing Analysis And Its Association With Epithelial-To-Mesenchymal Transition In Colon Cancer Adenocarcinoma., Stephen J. O'Brien

Electronic Theses and Dissertations

Colorectal adenocarcinoma is the fourth most common cancer diagnosed worldwide and is a significant cause of morbidity and mortality. This dissertation performed an exploratory RNA-sequencing analysis comparing gene expression between colon adenocarcinoma tissue and paired normal colon epithelium. After identification of a number of lncRNAs that were increased in expression in colon adenocarcinoma compared to normal colon epithelium, we aimed to validate the expression and investigate their function in vitro. Specifically, we focused on the lncRNA ZFAS1 and its association with epithelial-to-mesenchymal transition. These studies found the following: 1. Seven candidate lncRNAs were identified from the exploratory RNA-sequencing analysis to …

Acne Severity And Sleep Quality In Adults., Kory P Schrom, Sayeeda Ahsanuddin, Michelle Baechtold, Raghav Tripathi, Amy Ramser, Elma Baron

Ambulatory and Primary Care Articles

Poor sleep quality is extremely prevalent, with about one third of adults in the USA obtaining less than the recommended amount of sleep. In addition, poor sleep quality has been linked to an increased risk of many conditions, including diabetes, hypertension, psychiatric conditions, and overall all-cause mortality. Research has shown that sleep disturbance does impact skin disease, although many details of this relationship are still unclear. The goal of this study is to determine if there is a relationship between acne severity and sleep quality in adults. Forty subjects with acne were recruited from dermatology clinics in Cleveland, OH, to …

Phase Iii Randomized Trial Of Chemotherapy With Or Without Bevacizumab In Patients With Recurrent Or Metastatic Head And Neck Cancer., Athanassios Argiris, Shuli Li, Panayiotis Savvides, James P. Ohr, Jill Gilbert, Marshall A. Levine, Arnab Chakravarti, Missak Haigentz, Nabil F. Saba, Chukwuemeka V. Ikpeazu, Charles J. Schneider, Harlan A. Pinto, Arlene A. Forastiere, Barbara Burtness

Department of Medical Oncology Faculty Papers

PURPOSE: We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

PATIENTS AND METHODS: Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved.

RESULTS: The study randomly assigned 403 patients. …

Efficient And Robust Nk-Cell Transduction With Baboon Envelope Pseudotyped Lentivector., Aurelien B L Colamartino, William Lemieux, Panojot Bifsha, Simon Nicoletti, Nitin Chakravarti, Joaquín Sanz, Hugo Roméro, Silvia Selleri, Kathie Béland, Mélanie Guiot, Camille Tremblay-Laganière, Renée Dicaire, Luis Barreiro, Dean A Lee, Els Verhoeyen, Elie Haddad

Department of Medical Oncology Faculty Papers

NK-cell resistance to transduction is a major technical hurdle for developing NK-cell immunotherapy. By using Baboon envelope pseudotyped lentiviral vectors (BaEV-LVs) encoding eGFP, we obtained a transduction rate of 23.0 ± 6.6% (mean ± SD) in freshly-isolated human NK-cells (FI-NK) and 83.4 ± 10.1% (mean ± SD) in NK-cells obtained from the NK-cell Activation and Expansion System (NKAES), with a sustained transgene expression for at least 21 days. BaEV-LVs outperformed Vesicular Stomatitis Virus type-G (VSV-G)-, RD114- and Measles Virus (MV)- pseudotyped LVs (p < 0.0001). mRNA expression of both BaEV receptors, ASCT1 and ASCT2, was detected in FI-NK and NKAES, with higher expression in NKAES. Transduction with BaEV-LVs encoding for CAR-CD22 resulted in robust CAR-expression on 38.3 ± 23.8% (mean ± SD) of NKAES cells, leading to specific killing of NK-resistant pre-B-ALL-RS4;11 cell line. Using a larger vector encoding a dual CD19/CD22-CAR, we were able to transduce and re-expand dual-CAR-expressing NKAES, even with lower viral titer. These dual-CAR-NK efficiently killed both CD19KO- and CD22KO-RS4;11 cells. Our results suggest that BaEV-LVs may efficiently enable NK-cell biological studies and translation of NK-cell-based immunotherapy to the clinic.

Identification Of The Kaposi's Sarcoma-Associated Herpesvirus (Kshv) Surface Glycoprotein Targets Of Human Kshv-Specific Neutralizing Antibody Responses, Yasaman Mortazavi

School of Biological Sciences: Dissertations, Theses, and Student Research

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is the etiological agent of Kaposi’s sarcoma (KS), and is also associated with two B cell malignancies, primary effusion lymphoma and multicentric Castleman's disease. The distribution of KSHV varies globally with high prevalence in some areas of sub-Saharan Africa (SSA), where seroprevalence can be as high as 80%. It is estimated that nearly 44,000 new cases of KS emerge annually globally, with the highest incidents occurring in Africa, where KSHV is endemic. Currently, there is no prophylactic vaccine against KSHV, and efforts to develop prophylactic vaccines have been limited. …

Structural Basis Of Amino Acid Surveillance By Higher-Order Trna-Mrna Interactions, Shuang Li, Zhaoming Su, Jean Lehmann, Vassiliki Stamatopoulou, Nikoleta Giarimoglou, Frances E Henderson, Lixin Fan, Grigore D Pintilie, Kaiming Zhang, Muyuan Chen, Steven J Ludtke, Yun-Xing Wang, Constantinos Stathopoulos, Wah Chiu, Jinwei Zhang

Faculty, Staff and Students Publications

Amino acid availability in Gram-positive bacteria is monitored by T-box riboswitches. T-boxes directly bind tRNAs, assess their aminoacylation state, and regulate the transcription or translation of downstream genes to maintain nutritional homeostasis. Here, we report cocrystal and cryo-EM structures of Geobacillus kaustophilus and Bacillus subtilis T-box-tRNA complexes, detailing their multivalent, exquisitely selective interactions. The T-box forms a U-shaped molecular vise that clamps the tRNA, captures its 3' end using an elaborate 'discriminator' structure, and interrogates its aminoacylation state using a steric filter fashioned from a wobble base pair. In the absence of aminoacylation, T-boxes clutch tRNAs and form a continuously …

Bipolar Fresh Osteochondral Allograft Transplantation And Joint Reconstruction For Patellar And Trochlear Cartilage Defects, Omid Jalali, Zachary Vredenburgh, John Prodromo, Neilen Benvegnu, George Frederick Rick Hatch

Faculty, Staff and Students Publications

Patellar instability is a debilitating condition, and trauma due to the dislocations may severely damage the articular cartilage of the patellofemoral joint. The lack of healing capacity of cartilage makes treatment of such lesions challenging. In young patients, preservation of native bone and cartilage is a priority, and therefore arthroplasty procedures should be avoided even in relatively larger lesions. Fresh osteochondral allografting has been described for these difficult and complex cases, with recent studies showing promising results. In this surgical technique, we describe the use of bipolar osteochondral allografts of the patella and trochlea and patellofemoral joint reconstruction for large …

Burnout, Job Dissatisfaction, And Mental Health Outcomes Among Medical Students And Health Care Professionals At A Tertiary Care Hospital In Pakistan: Protocol For A Multi-Center Cross-Sectional Study, Syed Hamza Mufarrih, Aeman Naseer, Nada Qaisar Qureshi, Zohaib Anwar, Nida Zahid, Riaz Hussain Lakdawala, Shahryar Noordin

Department of Biological & Biomedical Sciences

Burnout, a state of vital exhaustion, has frequently been related to work-related stress and job dissatisfaction. Given the emotionally and physically challenging nature of their work, high rates of burnout have been reported among health care professionals. This may put them at a higher risk for of suffering from adverse mental health outcomes, including depression, anxiety and stress. In our study, we aim to assess the prevalence i of and associations among burnout and job dissatisfaction and adverse mental health outcomes in a developing country, where the challenges faced by the health care system are unique. Facilities are over-burdened and …

Immune-Mediated Colitis From Dual Checkpoint Inhibitors., Nishanth Thalambedu, Yasir Khan, Qian Zhang, Shristi Khanal, Ammar Ashfaq

Abington Jefferson Health Papers

Melanoma is a deadly disease with immunotherapy treatment options that emerged in the last few years and have changed the disease outcome. However, it is associated with immune-related toxic effects despite improving survival. We present the case of a 53-year-old woman who had two weeks of diarrhea after she was treated with dual immunotherapy agents for her advanced melanoma. The final workup revealed pancolitis, possibly due to immunotherapy adverse effects. Initial conservative treatment, unfortunately, did not lead to a clinical improvement until a steroid was introduced. We are reporting this case to alert our fellow physicians about the immune-mediated toxicities …

New Insights Into The Lactate Shuttle: Role Of Mct4 In The Modulation Of The Exercise Capacity., Sara Bisetto, Megan C Wright, Romana A Nowak, Angelo C Lepore, Tejvir S Khurana, Emanuele Loro, Nancy J Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Lactate produced by muscle during high-intensity activity is an important end product of glycolysis that supports whole body metabolism. The lactate shuttle model suggested that lactate produced by glycolytic muscle fibers is utilized by oxidative fibers. MCT4 is a proton coupled monocarboxylate transporter preferentially expressed in glycolytic muscle fibers and facilitates the lactate efflux. Here we investigated the exercise capacity of mice with disrupted lactate shuttle due to global deletion of MCT4 (MCT4−/−) or muscle-specific deletion of the accessory protein Basigin (iMSBsg−/−). Although MCT4−/− and iMSBsg−/− mice have normal muscle morphology and contractility, only MCT4−/− mice exhibit an exercise intolerant …

Pediatric Brainstem Gliomas: An Institutional Experience, Altaf Ali Laghari, Mirza Zain Baig, Muhammad Ehsan Bari, Aneela Darbar, Naureen Mushtaq, Umme E Hani Abdullah, Daniya Aziz Khan

Section of Neurosurgery

Objective: The aim of this study was to analyze the clinical profiles and outcomes of pediatric brainstem gliomas treated at our institute.
Methodology: We reviewed the files of 18 pediatric age group patients diagnosed with brainstem glioma at our institution. The following variables were recorded: age, sex, duration of symptoms, date of diagnosis, main clinical symptoms, Karnofsky performance status score, magnetic resonance imaging findings, histopathology findings, details of the treatment given, disease progression, and date of mortality/last follow-up. This data were then transferred to SPSS version 23 which was used for further analysis.
Results: The mean age of our cohort …