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Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill 2022 Technological University of the Shannon: Midlands Midwest

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE_J: Science Undergraduate Research Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …


Intercellular Communication Via Gap Junctions Influences Cell Survival During Hypoxia, Lauren E. Harmon, David L. Geenen 2022 Grand Valley State University

Intercellular Communication Via Gap Junctions Influences Cell Survival During Hypoxia, Lauren E. Harmon, David L. Geenen

Student Summer Scholars Manuscripts

Stem cell therapy can be beneficial following myocardial infarction. However, when murine bone marrow-derived mesenchymal stem cells (mBM-MSCs) are injected into the ischemic area, a large percentage of these cells undergo apoptosis resulting in decreased therapeutic benefits. We hypothesize that the loss of these mBM-MSCs is regulated by intercellular channels or gap junctions (GJs) that provide apoptotic signals passed between ischemic cardiomyocytes and mBM-MSCs. Our research aims to attenuate these GJs by suppressing Connexin-43 (Cx43) expression, the predominant channel-forming protein. We will accomplish this by transiently transfecting a Cx43 siRNA into mBM-MSCs. Our data demonstrate that intracellular fluorescent dyes and …


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 …


Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter 2022 Jacksonville State University

Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter

Theses

Ewing sarcoma (ES) is an aggressive pediatric bone cancer with low five-year survival rates, particularly with recurrent disease because ES often becomes resistant to chemotherapy in these recurrences. Cannabidiol (CBD) has been identified as a potentially promising therapeutic for patients with ES. In other cancer types, CBD has demonstrated effects on two major proteins that contribute to chemotherapy resistance. The first, Poly (ADP-ribose) Polymerase I (PARP1), is a DNA damage repair enzyme that is overexpressed in recurrent ES. Though chemotherapy induces DNA damage in these cancer cells, the high levels of PARP1 facilitate repair of the DNA, allowing the mutated …


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

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, …


Burden, Clinical Characteristics, Risk Factors, And Seasonality Of Adenovirus 40/41 Diarrhea In Children In Eight Low-Resource Settings, Godfrey Guga, Sarah Elwood, Caroline Kimathi, Gagandeep Kang, Margaret N. Kosek, Aldo A M Lima, Pascal O. Bessong, Amidou Samie, Najeeha Talat Iqbal, Zulfiqar Ahmed Bhutta 2022 Haydom Global Health Research Centre, Haydom

Burden, Clinical Characteristics, Risk Factors, And Seasonality Of Adenovirus 40/41 Diarrhea In Children In Eight Low-Resource Settings, Godfrey Guga, Sarah Elwood, Caroline Kimathi, Gagandeep Kang, Margaret N. Kosek, Aldo A M Lima, Pascal O. Bessong, Amidou Samie, Najeeha Talat Iqbal, Zulfiqar Ahmed Bhutta

Department of Biological & Biomedical Sciences

Background: The application of molecular diagnostics has identified enteric group adenovirus serotypes 40 and 41 as important causes of diarrhea in children. However, many aspects of the epidemiology of adenovirus 40/41 diarrhea have not been described.
Methods: We used data from the 8-site Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project birth cohort study to describe site- and age-specific incidence, risk factors, clinical characteristics, and seasonality.
Results: The incidence of adenovirus 40/41 diarrhea was substantially higher by quantitative polymerase chain reaction than enzyme immunoassay and peaked at ∼30 episodes …


The Role Of Nuclear Focal Adhesion Kinase In Tumor And The Tumor Microenvironment, Yelitza Angelica Rodriguez-Rodriguez 2022 University of South Alabama

The Role Of Nuclear Focal Adhesion Kinase In Tumor And The Tumor Microenvironment, Yelitza Angelica Rodriguez-Rodriguez

Theses and Dissertations

Focal adhesion kinase (FAK) is a ubiquitous expressed protein tyrosine kinase. In growing cells, FAK localizes to the plasma membrane where it interacts with several components of the focal adhesion complex and coordinates integrin signaling. Early studies using genetic mouse models revealed that deletion or catalytic inactivation of FAK resulted in early embryonic lethality with vascular, cell proliferation, and cell survival defects. As a result, FAK was coined as a vital mediator of cell migration, proliferation, and cell survival and multiple small molecule FAK inhibitors (FAK-I) had been designed to inactivate FAK catalytic functions in multiple pathologies, particularly in cancer. …


Indispensable Role Of Immunophenotyping In Diagnosing Leukemic Phase Of Blastic Plasmacytoid Dendritic Cell Neoplasm Without Cutaneous Manifestation, Hareem Alam, Nabiha Saeed, Anila Rashid 2022 Aga Khan University

Indispensable Role Of Immunophenotyping In Diagnosing Leukemic Phase Of Blastic Plasmacytoid Dendritic Cell Neoplasm Without Cutaneous Manifestation, Hareem Alam, Nabiha Saeed, Anila Rashid

Department of Pathology and Laboratory Medicine

Blastic plasmacytoid dendritic cell neoplasm usually presents as skin lesions. Diagnostic error occurs when it primarily presents in leukemic phase without skin involvement. Triad of CD4, CD56 and CD123 immunophenotype expression is essential to avoid misdiagnosis of this rare hematological malignancy. Here we describe a patient who presented in overt leukemic phase of BPDCN highlighting diagnostic challenges encountered that resulted in delayed diagnosis and poor outcome


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


Variations In Antibody Response To Aspergillus Fumigatus Inhalation In Mice, Andrea Wells 2022 Minnesota State University Moorhead

Variations In Antibody Response To Aspergillus Fumigatus Inhalation In Mice, Andrea Wells

Student Academic Conference

Studies have configured immunological responses to Aspergillus fumigatus in mice, leading to advanced understandings. However, the comparisons of the immune responses between juvenile (younger than 6 weeks) male and female C57BL/6J mice after A. fumigatus exposure, remains uninvestigated. In this study, we intranasally inoculated 3 week old male and female mice with Aspergillus fumigatus spores dilution of 2 106spores per 40 l. They were exposed to the allergen once a week for 8 consecutive weeks and euthanized on day 28 post the last inoculation. As compared to our last report, we increased the sample size for each group in this …


Paratesticular Solitary Fibrous Tumour Mimicking Cellular Angiofibroma: An Unusual Morphology And Rare Site, Madiha Bilal Qureshi, Muhammad Usman, Qurratulain Chundriger, Nasir uddin 2022 Aga Khan University

Paratesticular Solitary Fibrous Tumour Mimicking Cellular Angiofibroma: An Unusual Morphology And Rare Site, Madiha Bilal Qureshi, Muhammad Usman, Qurratulain Chundriger, Nasir Uddin

Department of Pathology and Laboratory Medicine

Solitary fibrous tumour (SFT) is a ubiquitous benign mesenchymal tumour of fibroblastic origin, which occurs most often in middle-aged adults. It usually presents as lung mass originating from pleura, but extrapleural occurrence is also common. Tumour is characterised by hypo- and hyper-cellular areas of spindle-shaped cells, arranged in haphazard manner with dispersed staghorn-shaped vessels. Surgical excision is the curative treatment. SFTs of the primary testicular or paratesticular region are extremely rare, but they exhibit histologic findings similar to SFTs originating at other body sites. Here, we report the case of a paratesticular SFT in a 37-year male, who presented with …


A Streptococcus Pneumoniae Lineage Usually Associated With Pneumococcal Conjugate Vaccine (Pcv) Serotypes Is The Most Common Cause Of Serotype 35b Invasive Disease In South Africa, Following Routine Use Of Pcv, Kedibone M. Ndlangisa, Mignon du Plessis, Stephani Lo, Linda de Gouveia, Chrispin Chaguza, Martin Antonio, Brenda Kwambana-Adams, Jennifer Cornick, Dean B. Everett, Sadia Shakoor 2022 National Institute for Communicable Diseases

A Streptococcus Pneumoniae Lineage Usually Associated With Pneumococcal Conjugate Vaccine (Pcv) Serotypes Is The Most Common Cause Of Serotype 35b Invasive Disease In South Africa, Following Routine Use Of Pcv, Kedibone M. Ndlangisa, Mignon Du Plessis, Stephani Lo, Linda De Gouveia, Chrispin Chaguza, Martin Antonio, Brenda Kwambana-Adams, Jennifer Cornick, Dean B. Everett, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Pneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emergence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction. We also compared 35B isolates belonging to a predominant 35B lineage in South Africa (GPSC5), with isolates belonging to the same lineage in other parts of the world. Serotype 35B isolates that caused invasive pneumococcal disease in South Africa in …


High Cd44 Immunoexpression Correlates With Poor Overall Survival: Assessing The Role Of Cancer Stem Cell Markers In Oral Squamous Cell Carcinoma Patients From The High-Risk Population Of Pakistan, Yumna Mirza, Syed Adnan Ali, Hasnain Ahmed Farooqui, Hammad A. Kayani, Romana Idress, Mohammad Sohail Awan 2022 Aga Khan University

High Cd44 Immunoexpression Correlates With Poor Overall Survival: Assessing The Role Of Cancer Stem Cell Markers In Oral Squamous Cell Carcinoma Patients From The High-Risk Population Of Pakistan, Yumna Mirza, Syed Adnan Ali, Hasnain Ahmed Farooqui, Hammad A. Kayani, Romana Idress, Mohammad Sohail Awan

Department of Surgery

Oral squamous cell carcinoma (OSCC) is a top-ranked cancer in the Pakistani population, and patient survival has remained unchanged at ∼50% for several decades. Recent advances have claimed that a subset of tumour cells, called cancer stem cells (CSCs), are responsible for tumour progression, treatment resistance, and metastasis, which leads to a poor prognosis. This study investigated the impact of CSC markers expression on overall survival (OS) and disease-free survival (DFS) of OSCC patients. Materials and Methods. Immunohistochemistry was used to evaluate CD44, CD133, L1CAM, and SOX2 expression in a well-characterized cohort of 100 Pakistani patients with primary treatment …


Covid-19 In Cns And Pns: Basic And Clinical Focus On The Mechanisms Of Infection And New Tools For The Therapeutic Approach, Jorge Matias-Guiu, Jordi A. Matias-Guiu, Carmen Garrido, Genaro Pimienta, Patricio F. Reyes, Abdul Mannan Baig, Ulises Gomez-Pinedo 2022 Institute of Neurosciences

Covid-19 In Cns And Pns: Basic And Clinical Focus On The Mechanisms Of Infection And New Tools For The Therapeutic Approach, Jorge Matias-Guiu, Jordi A. Matias-Guiu, Carmen Garrido, Genaro Pimienta, Patricio F. Reyes, Abdul Mannan Baig, Ulises Gomez-Pinedo

Department of Biological & Biomedical Sciences

No abstract provided.


What Stops Us From Eating: A Qualitative Investigation Of Dietary Barriers During Pregnancy In Punjab, Pakistan, Muhammad Asim, Zarak Hussain Ahmed, Amy R. Nichols, Rachel Rickman, Elena Neiterman, Anita Mahmood, Elizabeth M. Widen 2022 Aga Khan University

What Stops Us From Eating: A Qualitative Investigation Of Dietary Barriers During Pregnancy In Punjab, Pakistan, Muhammad Asim, Zarak Hussain Ahmed, Amy R. Nichols, Rachel Rickman, Elena Neiterman, Anita Mahmood, Elizabeth M. Widen

Community Health Sciences

Objective: Adequate dietary intake during pregnancy is vital for the health and nutritional status of both mother and fetus. The nutritional status of reproductive age women in Pakistan is poor, with 14 % being underweight (BMI < 18·5) and 42 % experiencing Fe deficiency anaemia. This may stem from beliefs, practices and other barriers influencing dietary intake. This qualitative study seeks to determine which factors impact dietary intake during pregnancy in rural Punjab.
Design: In-depth interviews and focus group discussions were conducted and then analysed using thematic analysis.
Setting: Three purposively selected rural districts (Sahiwal, Okara and Pakpatan) with the highest prevalence of maternal and child malnutrition in the province of Punjab, Pakistan.
Participants: Mothers with children under age two (n 29) and healthcare providers with at least 5 years of experience working in the district (n …


Perspective On Newborn Screening (Nbs): Evidence Sharing On Conditions To Be Included In Nbs In Pakistan, Hafsa Majid, Lena Jafri, Sibtain Ahmed, Khadija Humayun, Salman Kirmani, Natasha Bahadur Ali, Bushra Moiz, Aysha Habib, Bushra Afroze 2022 Aga Khan University

Perspective On Newborn Screening (Nbs): Evidence Sharing On Conditions To Be Included In Nbs In Pakistan, Hafsa Majid, Lena Jafri, Sibtain Ahmed, Khadija Humayun, Salman Kirmani, Natasha Bahadur Ali, Bushra Moiz, Aysha Habib, Bushra Afroze

Department of Pathology and Laboratory Medicine

Newborn screening aims at detecting treatable disorders early so that the treatment can be initiated to prevent mortality and morbidity. Such programmes are well established in most developed countries, and all newborns are screened for selected metabolic, endocrine and other disorders based on disease epidemiology, testing and treatment availability, efficiency and cost-effectiveness. Even in developing countries, such screening programmes are initiated using heel prick capillary blood collected on filter paper. The current narrative review was planned to provide a perspective with evidence in favour of starting newborn screening for different disorders. The programme project should be initiated nationwide, taking one …


Lymphoma With Tuberculous Granulomas, Jyoti Mohan Lal, Anila Rashid 2022 Aga Khan University

Lymphoma With Tuberculous Granulomas, Jyoti Mohan Lal, Anila Rashid

Department of Pathology and Laboratory Medicine

Chronic granulomatous inflammation is a common finding in lymphoproliferative disorders (LPDs), but it is important to exclude coexisting mycobacterium tuberculosis (MTB) especially in patients from areas of high endemicity. This case emphasizes the relevance of performing MTB culture on bone marrow exhibiting LPD and concomitant granulomas


Diagnostic Accuracy Of Axillary Nodal Ultrasound After Neoadjuvant Chemotherapy In Node-Positive Breast Cancer Patients: A Validation Study, Syeda Sakina Abidi, Lubna Mushtaque Vohra, Asad Ali Kerawala, Imrana Masroor, Muhammad Umair Tahseen 2022 Aga Khan University

Diagnostic Accuracy Of Axillary Nodal Ultrasound After Neoadjuvant Chemotherapy In Node-Positive Breast Cancer Patients: A Validation Study, Syeda Sakina Abidi, Lubna Mushtaque Vohra, Asad Ali Kerawala, Imrana Masroor, Muhammad Umair Tahseen

Section of General Surgery

Objective: To determine the accuracy and false negative rate of axillary ultrasound compared to sentinel node biopsy.
Methods: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, from February 1 to March 31, 2021, and comprised data of breast cancer patients who had undergone neo-adjuvant chemotherapy followed by axillary lymph node dissection or axillary disease diagnosed using lymph node biopsy or sentinel lymph node biopsy between January 1, 2016, and December 30, 2020. After receiving neoadjuvant chemotherapy, axillary ultrasound findings were compared with histopathology of lymph nodes. Data was analysed using SPSS 22.
Results: Of the 155 …


Pulmonary Adenoid Cystic Carcinoma Presenting Late With Intrapericardial Extension: Case Report, Manzar Abbas, Usama Qamar, Syeda Maria Ahmad Zaidi, Faiqa Binte Aamir, Ali Aahil Noorali, Haseeb Ur Rahman, Saulat Hasnain Fatimi 2022 Aga Khan University

Pulmonary Adenoid Cystic Carcinoma Presenting Late With Intrapericardial Extension: Case Report, Manzar Abbas, Usama Qamar, Syeda Maria Ahmad Zaidi, Faiqa Binte Aamir, Ali Aahil Noorali, Haseeb Ur Rahman, Saulat Hasnain Fatimi

Medical College Documents

Adenoid cystic carcinoma, also known as cylindroma, is one of the rare and unexplored clinical presentations of lung cancer, for which existing knowledge is scarce. This case report discusses a presentation of this tumor in the right lung, which subsequently extended to the left atrium through the right superior pulmonary vein. The extension of this rare tumor into the left atrium makes this case both uniquely distinctive and clinically relevant. The management strategy opted for this case was a right posterolateral thoracotomy and right pneumonectomy with partial resection of the left atrium. The desired outcome of this report is to …


In Vitro And In Vivo Correlation Of Skin And Cellular Responses To Nucleic Acid Delivery, M. Bosnjak, K. Znidar, A. Sales Conniff, T. Jesenko, B. Markelc, Nina Semenova, J. Tur, K. Kohena, S. Kranjc Brezar, L. Heller, M. Cemazar 2022 Old Dominion University

In Vitro And In Vivo Correlation Of Skin And Cellular Responses To Nucleic Acid Delivery, M. Bosnjak, K. Znidar, A. Sales Conniff, T. Jesenko, B. Markelc, Nina Semenova, J. Tur, K. Kohena, S. Kranjc Brezar, L. Heller, M. Cemazar

Bioelectrics Publications

Skin, the largest organ in the body, provides a passive physical barrier against infection and contains elements of the innate and adaptive immune systems. Skin consists of various cells, including keratinocytes, fibroblasts, endothelial cells and immune cells. This diversity of cell types could be important to gene therapies because DNA transfection could elicit different responses in different cell types. Previously, we observed the upregulation and activation of cytosolic DNA sensing pathways in several non-tumor and tumor cell types as well in tumors after the electroporation (electrotransfer) of plasmid DNA (pDNA). Based on this research and the innate immunogenicity of …


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