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H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam 2023 LSU Health Sciences Center - New Orleans

H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …


Frequency Of Von Willebrand Disease And Its Types: Data From A Tertiary Care Hospital Of Karachi, Pakistan, Jyoti Mohan Lal, Anila Rashid, Natasha Ali 2023 Aga Khan University

Frequency Of Von Willebrand Disease And Its Types: Data From A Tertiary Care Hospital Of Karachi, Pakistan, Jyoti Mohan Lal, Anila Rashid, Natasha Ali

Department of Pathology and Laboratory Medicine

Introduction: von Willebrand disease is the most common inherited bleeding disorder. It is classified into 3 main types, type I and III are quantitative defects whereas type II is qualitative defect which is further sub-classified in to II-A, II-B, II-M, II-N. The aim of the present study is to see frequency and types of von Willebrand disease in a tertiary care hospital of Karachi, Pakistan.
Materials and methods: This retrospective cross-sectional study was conducted in the section of Hematology and Transfusion Medicine, Department of Pathology and Laboratory Medicine, the Aga Khan University hospital, Karachi, from May 2020 to April 2021 …


Magnetic Resonance Imaging-Derived Microvascular Perfusion Modeling To Assess Peripheral Artery Disease, Olga A. Gimnich, Tatiana Belousova, Christina M. Short, Addison A. Taylor, Vijay Nambi, Joel D. Morrisett, Christie M. Ballantyne, Jean Bismuth, Dipan J. Shah, Gerd Brunner 2023 Penn State Health Milton S. Hershey Medical Center

Magnetic Resonance Imaging-Derived Microvascular Perfusion Modeling To Assess Peripheral Artery Disease, Olga A. Gimnich, Tatiana Belousova, Christina M. Short, Addison A. Taylor, Vijay Nambi, Joel D. Morrisett, Christie M. Ballantyne, Jean Bismuth, Dipan J. Shah, Gerd Brunner

School of Medicine Faculty Publications

BACKGROUND: Computational fluid dynamics has shown good agreement with contrast-enhanced magnetic resonance imaging measurements in cardiovascular disease applications. We have developed a biomechanical model of microvascular perfusion using contrast-enhanced magnetic resonance imaging signal intensities derived from skeletal calf muscles to study peripheral artery disease (PAD). METHODS AND RESULTS: The computational microvascular model was used to study skeletal calf muscle perfusion in 56 in-dividuals (36 patients with PAD, 20 matched controls). The recruited participants underwent contrast-enhanced magnetic resonance imaging and ankle-brachial index testing at rest and after 6-minute treadmill walking. We have determined associations of microvascular model parameters including the transfer …


Relationship Of Abdominal Circumference And Trunk Length With Spinal Anesthesia Block Height In Geriatric Patients Undergoing Transurethral Resection Of Prostate, Muhammad Yahya, Aliya Ahmed, Iayla Fatima, Muhammad Nasir 2023 South West Acute Hospital, United Kingdom

Relationship Of Abdominal Circumference And Trunk Length With Spinal Anesthesia Block Height In Geriatric Patients Undergoing Transurethral Resection Of Prostate, Muhammad Yahya, Aliya Ahmed, Iayla Fatima, Muhammad Nasir

Department of Anaesthesia

Introduction: Spinal anesthesia is commonly used for various surgical procedures. Prediction of spinal anesthesia block height is always a challenging task for anesthetists. Higher than desired levels of spinal anesthesia blocks are associated with serious side effects, while inadequate block height does not provide satisfactory surgical anesthesia. In this study, we observed the relationship between the ratio of trunk length (TL) and square of the abdominal circumference (AC2) and spinal anesthesia sensory block height in geriatric patients undergoing transurethral resection of the prostate (TURP).
Material & Methods: This is a cross-sectional study conducted at the Aga Khan University …


Testicular Choriocarcinoma With Small Bowel Metastasis And Active Gastrointestinal Bleeding, Asad Saulat Fatimi, Khizer Masroor Anns, Faheemullah Khan, Wasim Ahmed Memon, Junaid Iqbal, Muhammad Aman, Izaz Ahmad, Sahar Fatima 2023 Aga Khan University

Testicular Choriocarcinoma With Small Bowel Metastasis And Active Gastrointestinal Bleeding, Asad Saulat Fatimi, Khizer Masroor Anns, Faheemullah Khan, Wasim Ahmed Memon, Junaid Iqbal, Muhammad Aman, Izaz Ahmad, Sahar Fatima

Medical College Documents

Testicular choriocarcinomas make up less than 1% of all germ-cell tumors and are highly malignant, attributable to hematogenous spread. While the most common sites of metastasis are the lungs and liver, metastatic spread to the gastrointestinal tract is rare wherein patients may present with GI distress or even an upper GI bleed. In this report, we present a case of known testicular choriocarcinoma in a 40-year-old male who presented to the emergency room with severe anemia and a suspected upper GI bleed.


Integrating Shear Flow And Trypsin Treatment To Assess Cell Adhesion Strength, Antra Patel, Bhavana Bhavanam, Trevor Keenan, Venkat Maruthamuthu 2023 Old Dominion University

Integrating Shear Flow And Trypsin Treatment To Assess Cell Adhesion Strength, Antra Patel, Bhavana Bhavanam, Trevor Keenan, Venkat Maruthamuthu

Mechanical & Aerospace Engineering Faculty Publications

Cell adhesion is of fundamental importance in cell and tissue organization and for designing cell-laden constructs for tissue engineering. Prior methods to assess cell adhesion strength for strongly adherent cells using hydrodynamic shear flow either involved the use of specialized flow devices to generate high shear stress or used simpler implementations like larger height parallel plate chambers that enable multihour cell culture but generate low wall shear stress and are, hence, more applicable for weakly adherent cells. Here, we propose a shear flow assay for adhesion strength assessment of strongly adherent cells that employs off-the-shelf parallel plate chambers for shear …


TCf21 Marks Visceral Adipose Mesenchymal Progenitors And Functions As A Rate-Limiting Factor During Visceral Adipose Tissue Development, Qianglin Liu, Chaoyang Li, Buhao Deng, Peidong Gao, Leshan Wang, Yuxia Li, Mohammad Shiri, Fozi Alkaifi, Junxing Zhao, Jacqueline M. Stephens, Constantine A. Simintiras, Joseph Francis, Jiangwen Sun, Xing Fu 2023 Old Dominion University

TCf21 Marks Visceral Adipose Mesenchymal Progenitors And Functions As A Rate-Limiting Factor During Visceral Adipose Tissue Development, Qianglin Liu, Chaoyang Li, Buhao Deng, Peidong Gao, Leshan Wang, Yuxia Li, Mohammad Shiri, Fozi Alkaifi, Junxing Zhao, Jacqueline M. Stephens, Constantine A. Simintiras, Joseph Francis, Jiangwen Sun, Xing Fu

Computer Science Faculty Publications

Distinct locations of different white adipose depots suggest anatomy-specific developmental regulation, a relatively understudied concept. Here, we report a population of Tcf21 lineage cells (Tcf21 LCs) present exclusively in visceral adipose tissue (VAT) that dynamically contributes to VAT development and expansion. During development, the Tcf21 lineage gives rise to adipocytes. In adult mice, Tcf21 LCs transform into a fibrotic or quiescent state. Multiomics analyses show consistent gene expression and chromatin accessibility changes in Tcf21 LC, based on which we constructed a gene-regulatory network governing Tcf21 LC activities. Furthermore, …


A Single-Cell Atlas Of Bovine Skeletal Muscle Reveals Mechanisms Regulating Intramuscular Adipogenesis And Fibrogenesis, Leshan Wang, Peidong Gao, Chaoyag Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth McMillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu 2023 Louisiana State University

A Single-Cell Atlas Of Bovine Skeletal Muscle Reveals Mechanisms Regulating Intramuscular Adipogenesis And Fibrogenesis, Leshan Wang, Peidong Gao, Chaoyag Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth Mcmillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu

Computer Science Faculty Publications

Background: Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.

Methods: Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate …


Glucocentric Drugs In Cardiovascular Disease Protection And Heart Failure, Khawaja M. Talha, Gregg C. Fonarow, Salim S. Virani, Javed Butler 2022 University of Mississippi Medical Center, United States

Glucocentric Drugs In Cardiovascular Disease Protection And Heart Failure, Khawaja M. Talha, Gregg C. Fonarow, Salim S. Virani, Javed Butler

Office of the Provost

Evidence for cardiovascular outcomes with older-generation antihyperglycemic drugs in the management of type 2 diabetes is based on aggregated data from prior randomized controlled trials and observational studies that were not focused on prespecified cardiovascular end points. Newer antihyperglycemic medications have undergone a rigorous evaluation of cardiovascular outcomes through randomized controlled trials since the US Food and Drug Administration imposed a mandatory requirement for all glucose-lowering drugs in 2008. The three classes of drugs that have been most extensively studied are dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, the latter two reporting significant …


Anticancer Effect Of Illicium Verum (Star Anise Fruit) Against Human Breast Cancer Mcf-7 Cell Line, Asra Khan Pahore, Shagufta Khan, Nasim Karim 2022 Altamash Institute of Dental Medicine, Pakistan

Anticancer Effect Of Illicium Verum (Star Anise Fruit) Against Human Breast Cancer Mcf-7 Cell Line, Asra Khan Pahore, Shagufta Khan, Nasim Karim

Department of Biological & Biomedical Sciences

Objective: To investigate the anticancer effect of Illicium verum against human breast cancer MCF-7 cell line.
Methods: An experimental study was conducted in Multidisciplinary and Tissue Culture Laboratory, Aga Khan University in collaboration with Pharmacology Department of Bahria University Medical and Dental College, Karachi, Pakistan from January 2021 to June 2021. MCF-7 cells of Luminal-A breast cancer were seeded in 96-well plate and treated with I.verum methanol extract. After incubation, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) dye was used for cell viability and cell proliferation assays to determine the number of dead and viable cells, and the absorbance was measured using an enzyme-linked …


Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir uddin 2022 Hopp Children's Cancer Center Heidelberg, Germany

Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin

Department of Pathology and Laboratory Medicine

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal …


Temporal Trends In Lipoprotein(A) Concentrations: The Atherosclerosis Risk In Communities Study, Matthew R. Deshotels, Caroline Sun, Vijay Nambi, Salim S. Virani, Kunihiro Matsushita, Bing Yu, Christie . M. Ballantyne, Ron C. Hoogeveen 2022 Baylor College of Medicine, United States

Temporal Trends In Lipoprotein(A) Concentrations: The Atherosclerosis Risk In Communities Study, Matthew R. Deshotels, Caroline Sun, Vijay Nambi, Salim S. Virani, Kunihiro Matsushita, Bing Yu, Christie . M. Ballantyne, Ron C. Hoogeveen

Office of the Provost

Background: Plasma lipoprotein(a) (Lp[a]) concentrations are primarily determined by genetic factors and are believed to remain stable throughout life. However, data are scarce on longitudinal trends in Lp(a) concentrations over time. Therefore, it is unclear whether measurement of Lp(a) once in a person's life is sufficient for cardiovascular risk assessment in all adults.
Methods and Results: Lp(a) concentrations, specifically apolipoprotein(a) concentrations, were measured at visits 4 and 5, ≈15 years apart, in 4734 adult participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age at visits 4 and 5, 60.7±5.1 and 75.5±5.2 years, respectively). Participants were categorized by baseline …


Chronic Diarrhea: A Rare Presentation Of Hodgkin's Lymphoma, Saira Furqan, Sajjad Ali Khan, Dania Ali, Kaleemullah Badini 2022 Aga Khan University

Chronic Diarrhea: A Rare Presentation Of Hodgkin's Lymphoma, Saira Furqan, Sajjad Ali Khan, Dania Ali, Kaleemullah Badini

Section of Diabetes, Endocrinology and Metabolism

Hodgkin's Lymphoma is a cancer affecting the lymphatic system. There are two subtypes of Hodgkin's Lymphoma: Nodular lymphocyte predominant (NLPHL) and classical Hodgkin's Lymphoma which has further four types. It has a bimodal distribution and is more common among males. The most common presentation is painless swelling in the neck, armpit or groin region. Associated Symptoms include night sweats, unintentional weight loss, fever, persistent cough or dyspnea. Involvement of the gastrointestinal tract is a rare occurrence. Diagnosis is based on hematological, radiological and histochemical studies. Here we report a rare presentation of a 47-year-old male who presented with symptoms of …


Gutka Consumption And Dietary Partialities Explaining Anemia In Women Of A Coastal Slum Of Karachi, Pakistan: A Mixed-Method Study, Ameer Muhammad, Sarah Saleem, Daniyaal Ahmad, Eleze Tariq, Yasir Shafiq 2022 VITAL Pakistan Trust, Pakistan

Gutka Consumption And Dietary Partialities Explaining Anemia In Women Of A Coastal Slum Of Karachi, Pakistan: A Mixed-Method Study, Ameer Muhammad, Sarah Saleem, Daniyaal Ahmad, Eleze Tariq, Yasir Shafiq

Community Health Sciences

Background: Limited literature is available on the dietary pattern and its consequences on health of women living in coastal slums of Karachi, Pakistan.
Material and methods: The study employed a mixed-method approach where concurrent quantitative and qualitative assessments were carried out. An analytical cross-sectional survey was conducted to collect information on demographic, household, obstetrics characteristics, and dietary pattern of married women of reproductive age (MWRA). Blood samples were collected to identify the hemoglobin level to determine anemia. For the qualitative component, focus group discussions were carried out with women and in-depth interviews with shopkeepers to understand the availability of food …


Immunohistochemical Detection And Prognostic Significance Of P53, Epidermal Growth Factor Receptor, Murine Double Minute 2, And Isocitrate Dehydrogenase 1 In Glioblastoma Multiforme Patients Of Pakistan, Syed Muhammad Adnan Ali, Muhammad Shahzad Shamim, Syed Ather Enam, Zubair Ahmad, Yumna Adnan, Hasnain Ahmed Farooqui 2022 Aga Khan University

Immunohistochemical Detection And Prognostic Significance Of P53, Epidermal Growth Factor Receptor, Murine Double Minute 2, And Isocitrate Dehydrogenase 1 In Glioblastoma Multiforme Patients Of Pakistan, Syed Muhammad Adnan Ali, Muhammad Shahzad Shamim, Syed Ather Enam, Zubair Ahmad, Yumna Adnan, Hasnain Ahmed Farooqui

Department of Surgery Docs

Introduction: Glioblastoma multiforme (GBM) is one of the deadliest cranial tumors occurring in adults. Various biomarkers have been tested for their significance in diagnosis, prognosis, and treatment of GBM. Some well-studied markers in GBM are Isocitrate dehydrogenase 1 (IDH1), Murine double minute 2 (MDM2), Epidermal Growth Factor Receptor (EGFR), and p53. The aim of this study was to investigate the protein expression of these markers in GBM patients of Pakistan.
Methods: A total of 102 surgically resected formalin-fixed paraffin-embedded specimens from patients diagnosed and treated at Aga Khan University Hospital were included in this study. Immunohistochemistry (IHC) for IDH1, MDM2, …


Association Between The Baseline Gene Expression Profile In Periapical Granuloma And Periapical Wound Healing After Surgical Endodontic Treatment, Muhammad Adeel Ahmed, Fizza Nazim, Khalid Ahmed, Muhammad Furqan Bari, Abdulaziz Abdulwahed, Ahmed A. AlMokhatieb, Yaseen Alalvi, Tariq Abduljabbar, Muhammad Nouman Mughal, Syed Hani Abidi 2022 King Faisal University, Saudi Arabia

Association Between The Baseline Gene Expression Profile In Periapical Granuloma And Periapical Wound Healing After Surgical Endodontic Treatment, Muhammad Adeel Ahmed, Fizza Nazim, Khalid Ahmed, Muhammad Furqan Bari, Abdulaziz Abdulwahed, Ahmed A. Almokhatieb, Yaseen Alalvi, Tariq Abduljabbar, Muhammad Nouman Mughal, Syed Hani Abidi

Department of Biological & Biomedical Sciences

In this study, we have investigated the association between the baseline gene expression profile in periapical granuloma and periapical wound healing after surgical endodontic treatment. Twenty-seven patients aged between 15 and 57 years underwent periapical surgery. The retrieved periapical tissue sample was used for mRNA expression analysis of COL1A1, VTN, ITGA5, IL-4, TNF, ANGPT, VEGFA, and CTGF. All patients were recalled after 6 and 12 months for periapical healing evaluation. Healing was then correlated with baseline gene expression. Healing was observed in 15 patients at the end of 6 months, which increased to 21 patients after 12 months. Six patients …


Reporting Of Mycetoma Cases From Skin And Soft Tissue Biopsies Over A Period Of Ten Years: A Single Center Report And Literature Review From Pakistan, Mohammad Zeeshan, Saira Fatima, Joveria Farooqi, Kauser Jabeen, Arsalan Ahmed, Afreen Haq, Muhammad Omer Arif, Afia Zafar 2022 Aga Khan University

Reporting Of Mycetoma Cases From Skin And Soft Tissue Biopsies Over A Period Of Ten Years: A Single Center Report And Literature Review From Pakistan, Mohammad Zeeshan, Saira Fatima, Joveria Farooqi, Kauser Jabeen, Arsalan Ahmed, Afreen Haq, Muhammad Omer Arif, Afia Zafar

Department of Pathology and Laboratory Medicine

Background: Mycetoma is an important neglected tropical disease associated with debilitation, disfigurement and death if not diagnosed and treated adequately. In Pakistan, mycetoma cases have frequently been diagnosed in histopathology and microbiology laboratories. However, there is scarcity of published data from this country. Therefore, the objectives of this study were to evaluate the frequency and type of mycetoma reported in skin and soft tissue biopsies from a single center over 10 years and review of published literature from Pakistan.
Method: This descriptive observational retrospective study was conducted at the Aga Khan University Hospital laboratory, Karachi, Pakistan. Laboratory data from 2009-2018 …


Alternative Fixation Of Venous Valves For Bioprosthetic Applications, Makenzie Kapales 2022 University of Arkansas, Fayetteville

Alternative Fixation Of Venous Valves For Bioprosthetic Applications, Makenzie Kapales

Biomedical Engineering Undergraduate Honors Theses

Venous valve failure allows for the retrograde, or backward, flow of blood into the lower extremities, which leads to Chronic Venous Insufficiency (CVI). CVI infringes upon quality of life through ulceration and can result in death due to Deep Vein Thrombosis (DVT), or blood clots, causing pulmonary embolism. A successful treatment of CVI restores valve function and prevents retrograde blood flow; however, current bioprosthetic venous valves exhibit low patency and high calcification. To improve upon bioprosthetic venous valves and CVI treatment, the University of Arkansas’s Cardiovascular Biomechanics Lab conducts studies with the purpose of comparing the properties and performance of …


Medial Edge Chondrification Of The Vocal Folds Of E. Pustulosus And Its Function In Sexual Selection, Helena Soon Czochanski 2022 University of the Pacific

Medial Edge Chondrification Of The Vocal Folds Of E. Pustulosus And Its Function In Sexual Selection, Helena Soon Czochanski

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.


Lenalidomide Induced Secondary Acute Lymphoblastic Leukemia In A Multiple Myeloma Patient: A Case-Report, Saqib Raza Khan, Muhammad Tariq, Sidra Malik Fayyaz, Salman Muhammad Soomar, Munira Moosajee 2022 Aga Khan University

Lenalidomide Induced Secondary Acute Lymphoblastic Leukemia In A Multiple Myeloma Patient: A Case-Report, Saqib Raza Khan, Muhammad Tariq, Sidra Malik Fayyaz, Salman Muhammad Soomar, Munira Moosajee

Section of Haematology/Oncology

Lenalidomide mechanism of action has been shown to modulate the different components of the immune system. A 68-year-old lady presented to us with severe backache and was then diagnosed with MM. Lenalidomide started as per protocol along with dexamethasone. Later, she presented with complaints of generalized weakness and her workup showed significant blast cells with Pan-B-cell markers consistent with secondary B-ALL. The reported incidence of secondary Acute Lymphocytic Leukemia is 2.3%. The development of more aggressive neoplasm in a patient with prior malignancy dictates a poor outcome and hence such patients should be enrolled in a clinical trial whenever available


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