Immune System Diseases Commons^™

The Mechanisms Of Mitochondrial Dysfunction In T Cell Aging During Chronic Viral Infection, Madison B. Schank

Electronic Theses and Dissertations

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections induce a myriad of disturbances to CD4 T cell functions, including mitochondrial compromise, excessive inflammation, increased telomeric DNA damage and attrition, cellular exhaustion and senescence, and accelerated aging. In this dissertation, the mechanisms underlying metabolic failure, accelerated aging, and cellular dysfunctions were evaluated in CD4 T cells from healthy subjects (HS) treated with a telomere-targeting drug (KML001) or HCV-infected individuals or people living with HIV (PLHIV) compared to HS. We observed that KML001-induced telomere injury resulted in mitochondrial swelling and decreased mitochondrial membrane potential, cellular respiration, mitochondrial DNA (mtDNA) copy …

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

Immunity To Poliovirus In Afghanistan: A Household Sampling Method For Serological Assessment Based On Geographical Information Systems, Amalia Mendes, Ari Whiteman, Benjamin Nygren, Brian Kaplan, Imtiaz Hussain, Sajid Bashir Soofi, Maureen Martinez, Noha H. Farag

Department of Paediatrics and Child Health

Afghanistan continues to experience challenges affecting polio eradication. Mass polio vaccination campaigns, which aim to protect children under the age of 5, are a key eradication strategy. To date, the polio program in Afghanistan has only employed facility-based seroprevalence surveys, which can be subject to sampling bias. We describe the feasibility in implementing a cross-sectional household poliovirus seroprevalence survey based on geographical information systems (GIS) in three districts. Digital maps with randomly selected predetermined starting points were provided to teams, with a total target of 1,632 households. Teams were instructed to navigate to predetermined starting points and enrol the closest …

Factors Associated With Loss Of Motivation And Hesitation To Work Amongst Frontline Health Care Providers During The Covid-19 Pandemic: A Cross-Sectional Survey From A Developing Country, Mehreen Malik, Syeda Tayyaba Rehan, Farheen Malik, Jawad Ahmed, Chaudhary Abdul Fatir, Hassan Ul Hussain, Asiyah Aman, Muhammad Junaid Tahir

Department of Anaesthesia

Background: The COVID-19 took over the world in 2020 and a lockdown has been imposed seeing its fast spread. Frontline health care workers (HCWs) were reported frequently with a lack of motivation, hesitancy and unwillingness to perform their duties during this pandemic. This cross-sectional survey aims to evaluate the factors associated with lack of motivation and increased hesitancy among the frontline HCWs to perform their duties during COVID-19 pandemic.
Materials and methods: A total of 239 HCWs were included in this web-based cross-sectional study, who have worked during the COVID-19 pandemic. The anonymous online questionnaire was sent to all faculty, …

Omicron Spike Function And Neutralizing Activity Elicited By A Comprehensive Panel Of Vaccines, John E. Bowen, Amin Addetia, Ha V Dang, Cameron Stewart, Jack T. Brown, William K. Sharkey, Kaitlin R. Sprouse, Kumail Ahmed, Asefa Shariq Ansari, Najeeha Talat Iqbal

Department of Paediatrics and Child Health

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern comprises several sublineages, with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1 and with BA.4 and BA.5 increasing in prevalence worldwide. We show that the large number of Omicron sublineage spike mutations leads to enhanced angiotensin-converting enzyme 2 (ACE2) binding, reduced fusogenicity, and severe dampening of plasma neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus. Administration of a homologous or heterologous booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1, BA.2, BA.2.12.1, BA.4, and …

Covad Survey 2 Long-Term Outcomes: Unmet Need And Protocol, Zoha Zahid Fazal, Parikshit Sen, Mrudula Joshi, Naveen Ravichandran, James B. Lilleker, Vishwesh Agarwal, Sinan Kardes, Minchul Kim, Jessica Day, Ashima Makol

Medical College Documents

Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term …

Nanotherapeutics And Hiv: Four Decades Of Infection Canvass The Quest For Drug Development Using Nanomedical Technologies, Bhupender S. Chhikara, Nirpendra Singh, Poonam, Parveen Bazard, Rajender S. Varma, Keykavous Parang

Pharmacy Faculty Articles and Research

We have seen four decades of human struggle to cure or eradicate HIV infection since the first clinical detection of HIV infection. Various developed drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, integrase inhibitors, microbicides, and others have known restrictions, such as side effects and resistance development when used alone, and hidden reservoir of the virus, which have opened the gates for the involvement of nanomedicine associated systems, particularly for latent sites of HIV infection. The nanotechnological vehicles, such as liposomes, dendrimers, metal nanoparticles, polymeric nanocapsules/particles, surfactants, and targeted vehicles have become part …

Acquired Hemophilia A: A Possibly Fatal Complication Of Sars-Cov-2 Infection, Hasan Fareed Siddiqui, Taymmia Ejaz, Aisha Fareed Siddiqui, Fahd Niaz Shaikh

Department of Medicine

No abstract provided.

The Impact Of The Covid-19 Pandemic On Patients With Chronic Liver Disease: Results From The Global Liver Registry, Zobair M. Younossi, Yusuf Yilmaz, Mohamed El-Kassas, Ajay Duseja, Saeed Hamid, Gamal Esmat, Nahum Méndez-Sánchez, Wah Kheong Chan, Ashwani K. Singal, Brian Lam

Department of Medicine

Patients with preexisting chronic liver disease (CLD) may experience a substantial burden from both coronavirus 2019 (COVID-19) infection and pandemic-related life disruption. We assessed the impact of the COVID-19 pandemic on patients with CLD. Patients enrolled in our Global Liver Registry were invited to complete a COVID-19 survey. As of June 2021, 2500 patients (mean age ± SD, 49 ± 13 years; 53% men) from seven countries completed the survey. Of all survey completers, 9.3% had COVID-19. Of these patients, 19% were hospitalized, 13% needed oxygen support, but none required mechanical ventilation. Of all patients including those not infected with …

Diagnostic Accuracy Of Various Immunochromatographic Tests For Ns1 Antigen And Igm Antibodies Detection In Acute Dengue Virus Infection, Mughees Haider, Saira Yousaf, Asifa Zaib, Azza Sarfraz, Zouina Sarfraz, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Introduction: Rapid diagnostic tests (RDTs) were evaluated, in this paper, for their utility as a reliable test, using resource-constrained studies. In most studies, NS1 antigen and immunoglobulin M (IgM)-based immunochromatographic tests (ICTs) were considered for acute phase detection. We aimed to evaluate the diagnostic accuracy of NS1, IgM, and NS1/IgM-based ICTs to detect acute dengue virus (DENV) infection in dengue-endemic regions.
Methods: Studies were electronically identified using the following databases: MEDLINE, Embase, Cochrane Library, Web of Science, and CINAHL Plus. Keywords including dengue, rapid diagnostic test, immunochromatography, sensitivity, specificity, and diagnosis were applied across databases. In total, 15 studies were …

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several …

Disparities In Adult Critical Care Resources Across Pakistan: Findings From A National Survey And Assessment Using A Novel Scoring System, Mustafa Ali Khan, Hamna Shahbaz, Ali Aahil Noorali, Anam Noor Ehsan, Mareeha Zaki, Fahham Asghar, Mohammed Moizul Hassan, Haroon Muhammad Arshad, Muhammad Sohaib, Adil H. Haider

Medical College Documents

Background: In response to the COVID-19 pandemic, concerted efforts were made by provincial and federal governments to invest in critical care infrastructure and medical equipment to bridge the gap of resource-limitation in intensive care units (ICUs) across Pakistan. An initial step in creating a plan toward strengthening Pakistan's baseline critical care capacity was to carry out a needs-assessment within the country to assess gaps and devise strategies for improving the quality of critical care facilities.
Methods: To assess the baseline critical care capacity of Pakistan, we conducted a series of cross-sectional surveys of hospitals providing COVID-19 care across the country. …

A Case Of Adult Multisystem Inflammatory Syndrome Following Covid-19 Vaccine, Meghan Brown, Nika Zorko Garbajs, Simon Zec, Hisham Mushtaq, Anwar Khedr, Abbas Bashir Jama, Ibtisam Rauf, Mikael Mir, Aishwarya Reddy Korsapati, Shikha Jain, Thoyaja Koritala, Ramesh Adhikari, Amos Lal, Ognjen Gajic, Juan Pablo Domecq, Sarah Goksoy, Brian Bartlett, Amit Sharma, Nitesh Kumar Jain, Syed Anjum Khan

Journal of Community Hospital Internal Medicine Perspectives

Multisystem inflammatory syndrome is a life-threatening condition associated with elevated inflammatory markers and multiple organ injury. A diagnosis of exclusion, it has been reported after severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2) in children and adults; recently it has been described in some post-COVID-19 vaccinated individuals. The prognosis with supportive care and immunomodulatory therapy is good, although some individuals may require treatment in the intensive care unit (ICU). Here we report a case of a 58-year-old man who developed multi-organ failure after receiving the second dose of the Moderna mRNA-1273 COVID-19 vaccine. He required critical organ support in the …

Use Of Long-Acting Injectable Cabotegravir And Rilpivirine As An Alternative For Treatment In Hiv Positive Patients, Aravindh Nirmalan

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

Mantsios A, Murray M, Karver TS, et al. Efficacy and Freedom: Patient Experiences with the Transition from Daily Oral to Long-Acting Injectable Antiretroviral Therapy to Treat HIV in the Context of Phase 3 Trials. AIDS Behav. 2020;24(12):3473-3481. https://doi.org/10.1007/s10461-020-02918-x

for a young adult patient struggling with adherence.

Ameliorative Effects Of Minor Cannabinoids Over Hiv-1 Tat-Mediated Visceral Pain, Charlie Worth

Honors Theses

As the total number of people living with HIV continues to rise across the world, an effective HIV treatment is still sought after. While modern-day advanced therapies exist for mitigating much of the negative effects of HIV, the virus remains evasive and problematic in the central nervous system. Thus, even with treatment, many people living with HIV continue to suffer from a plethora of symptoms. However, a large proportion of HIV-positive patients claim to feel a reduction in those persevering symptoms after cannabis usage. This anecdotal evidence has sparked interest in the efficacy of cannabis constituents for HIV therapy. This …

Telemedicine For Rheumatology Patients In Covid-19 Pandemic: Perspectives Of Patients, Muhammad Mehmood Riaz, Saad Bin Zafar Mahmood, Noreen Nasir

Section of Internal Medicine

Telemedicine use for patients with autoimmune rheumatic conditions during the pandemic mandates better characterization. We conducted a telephonic survey on patients who consulted rheumatologists remotely to determine their attitudes toward telemedicine. The study was conducted at Aga Khan University Hospital, a tertiary care hospital in Pakistan which is a lower-middle-income country. Descriptive analyses were performed. Fifty patients visited tele-rheumatology clinic, 35 (70.0%) were female with a mean (SD) age of 47.6 (18.1) years. Majority (27, 54.0%) learned about telemedicine from hospital website and outpatient clinic desk or helpline. Lack of examination was the biggest concern with teleconsultation (18, 22.2%). Most …

The Response To Covid-19 Among Drug Retail Outlets In Indonesia: A Cross-Sectional Survey Of Knowledge, Attitudes, And Practices, Yusuf Ari Mashuri, Luh Putu Lila Wulandari, Mishal Khan, Astri Ferdiana, Ari Probandari, Tri Wibawa, Neha Batura, Marco Liverani, Richard Day, Stephen Jan

Community Health Sciences

Background: Pharmacists have been at the frontline of the COVID-19 response in Indonesia, providing medicines, advice, and referral services often in areas with limited healthcare access. This study aimed to explore their knowledge, attitudes, and practices during the pandemic, so that we can be better prepared for future emergencies.
Methods: A cross-sectional online survey of community pharmacists and pharmacy technicians in Indonesia was conducted between July and August 2020. The dataset was analysed descriptively, and logistic regression was used to explore willingness to participate in COVID-19 interventions.
Findings: 4716 respondents participated in the survey. Two-thirds (66·7%) reported knowing only "a …

Use Of Steroids In Covid-19 Patients: What Is Known?, Syed Muhammad Mustahsan, Marzia Tahir, Emaduddin Siddiqui

Department of Emergency Medicine

COVID-19 pandemic has exaggerated the role of steroids in the standard of care despite minimum direct evidence of their efficacy in COVID-19 patients and their well-known adverse effects. The literature abounds on the side effects of steroids affecting different organ systems of the body. COVID-19 patients, who are on long-term steroids, are more susceptible to their adverse effects. We, herein, briefly review the potential uses and the adverse effects of steroids on different organ systems of the body. Key Words: Steroids, COVID-19, Adverse effects.

Age-Associated Gut Dysbiosis, Marked By Loss Of Butyrogenic Potential, Correlates With Altered Plasma Tryptophan Metabolites In Older People Living With Hiv., Smita Ghare, Richa Singhal, Vaughn Bryant, Sabina Gautam, Chanakya Charan Tirumala, Praneet Kumar Srisailam, Andrea Reyes-Vega, Dushan Ghooray, Craig J. Mcclain, Kristi Hoffman, Joseph Petrosino, Kendall Bryant, Varand Govind, Ronald Cohen, Robert L. Cook, Shirish Barve

Faculty and Staff Scholarship

Background:

Imbalance in tryptophan (TRP) metabolism and its neuroactive metabolites, serotonin and kynurenine (KYN), is a known pathogenic mechanism underlying neurocognitive impairment. Gut microbiota plays an important role in TRP metabolism, and the production of these neuroactive molecules affects neurocognitive function. Although both HIV infection and normal aging independently induce gut dysbiosis and influence TRP metabolism, their interactive effects on compositional/functional changes in gut microbiota and consequent alterations in TRP metabolites remain largely undetermined.

Methods:

Older people living with HIV infection (PLWH, aged 50–70 years, n = 22) were enrolled in this cross-sectional pilot study. Metagenomic analysis of fecal microbiome …

Clinical Outcomes Of Immunomodulatory Therapies In The Management Of Covid-19: A Tertiary-Care Experience From Pakistan, Noreen Nasir, Salma Tajuddin, Sarah Khaskheli, Naveera Khan, Hammad Niamatullah, Nosheen Nasir

Section of Internal Medicine

The pharmacological management of COVID-19 has evolved significantly and various immunomodulatory agents have been repurposed. However, the clinical efficacy has been variable and a search for cure for COVID-19 continues. A retrospective cohort study was conducted on 916 patients hospitalized with polymerase chain reaction (PCR)-confirmed COVID-19 between February 2020 and October 2020 at a tertiary care academic medical center in Karachi, Pakistan. The median age was 57 years (interquartile range (IQR) 46–66 years). The most common medications administered were Methylprednisolone (65.83%), Azithromycin (50.66%), and Dexamethasone (46.6%). Majority of the patients (70%) had at least two or more medications used in …

The Role Of Emergency Departments For Antimicrobial Stewardship In Covid-19 Pandemic; The Time Is Now, Madiha Ismail, Nazeer Najeeb Kapadia, Sara Usman

Department of Emergency Medicine

No abstract provided.

Balancing Science And Public Policy In Pakistan's Covid-19 Response, Zulfiqar Ahmed Bhutta, Faisal Sultan, Aamer Ikram, Adil H. Haider, Assad Hafeez, Muhammad Islam

Department of Paediatrics and Child Health

Background: Coronavirus disease 2019 (COVID-19) has affected the world in an unprecedented manner and South Asian countries were among the first to experience imported cases. Pakistan's response to COVID-19 has been under scrutiny for its granularity, reach and impact.
Aims: to evaluate objectively the chronology and depth of the response to COVID-19 in Pakistan.
Methods: We evaluated available national and subnational epidemiological and burden information on COVID-19 cases and deaths in Pakistan, including projection models available to the Government at an early stage of the pandemic.
Results: Pakistan, with a population of 215 million and considerable geographic diversity, experienced case …

Assessment Of Pathogenic Changes In The Gut-Liver Axis In Plwh With Heavy Alcohol Drinking And Gut Dysbiosis Marked By Decreased Butyrogenic Potential., Smita Ghare, Vaughn Bryant, Richa Singhal, Sabina Gautam, Chanakya Charan Tirumala, Andrea Reyes-Vega, Craig J. Mcclain, Ronald Cohen, Varand Govind, Robert L. Cook, Shirish Barve

Faculty and Staff Scholarship

Purpose: People living with HIV infection (PLWH) experience increasing risk for non-AIDS diseases including liver dysfunction and injury. Both HIV-infection and heavy alcohol drinking (HAD) are known to cause gut microbial dysbiosis and systemic inflammation that may potentially contribute to altered Gut-Liver axis. However, the specific pathogenic features associated with combinatorial harmful effects of alcohol and HIV infection on gut-liver interactions are not completely understood. This study evaluate the pathogenic changes in the Gut-Liver axis in PLWH with HAD.

Rebuilding Trust On Routine Immunization In Era Of Covid-19 Fear-Role That Civil Society Organizations Can Play Hands-In-Hand With Immunization Program, Ameer Muhammad, Daniyaal Ahmad, Eleze Tariq, Yasir Shafiq

Medical College Documents

No abstract provided.

Simian Varicella Virus Antibody Response In Recombinant Svv-Siv Immunized Primates, Kiser Horne

Honors Theses

Since its emergence in the early 1980’s HIV has killed approximately 32 million people, and continues to kill over half a million people every year. Significant research into potential vaccines and cures for HIV has been ongoing for decades but has been largely unsuccessful. One of the more promising technologies that is being investigated to develop an HIV vaccine is recombinant vaccine technology. The study presented in this thesis aims to use simian varicella virus (SVV) and simian immunodeficiency virus (SIV) to act as a model for recombinant vaccine development. If a recombinant SVV-SIV vaccine can be proven safe and …

Environmentally Marginalized Populations: The "Perfect Storm" For Infectious Disease Pandemics, Including Covid-19, Gabriella Y. Meltzer, Oyemwenosa Avenbuan, Christina Awada, Oluwakemi B. Oyetade, Tricia Blackman, Simona Kwon Drph, Mph, Esther Erdei Phd, Judith T. Zelikoff Phd

Journal of Health Disparities Research and Practice

COVID-19 has exacted a severe toll on the United States population’s physical and mental health and its effects have been felt most severely among people of color and low socioeconomic status. Using illustrative case studies, this commentary argues that in addition to COVID-19 health disparities created by psychosocial stressors such as the inability to socially distance and access quality healthcare, environmental justice communities have the additional burden of disproportionate exposure to toxic contaminants that contribute to their higher risk of COVID-19. Environmental contaminants including heavy metals and persistent organic pollutants found contaminating their nearby environments can alter the immune response, …

United States Nursing Homes And Health Equity During The Covid-19 Pandemic, Carla Cooper

College of Graduate Studies: Theses & Dissertations

Objective: The COVID-19 pandemic disproportionately affected older populations, with nursing homes impacted early on by the disease. The contribution of race/ethnicity of nursing home residents and facility characteristics on COVID-19 were unknown. The Donabedian model framework was used to study the relationship between the racial/ethnic characteristics of nursing home residents and COVID-19 outcomes and to examine if this relationship was moderated by the racial/ethnic composition of the county of nursing home location.

Method: Cross-sectional research design merging data from five publicly available sources. Laboratory confirmed COVID-19 cases and deaths were compared by the racial composition of the county and nursing …

High Rates Of Misdiagnosis Of Pediatric Acute-Onset Neuropsychiatric Syndrome And How To Reduce Them, Aliya Centner

Honors Undergraduate Theses

Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is a clinical diagnosis characterized by sudden onset of obsessive compulsive disorder and is considered a type of Autoimmune Encephalitis. Pediatric Autoimmune Neuropsychiatric Disorder associated with Streptococcal Infection (PANDAS) is a subset of PANS characterized by a similar presentation but specifically results from infection by Group A β-hemolytic streptococcus. Early and accurate diagnosis is essential, as PANS can become a chronic condition. PANS and PANDAS are frequently misdiagnosed. There are a variety of differential diagnoses. The intent of this thesis is to evaluate differences in symptoms between PANDAS patients and those with a differential diagnosis …

Identification And Characterization Of Epitope Specific Immune Responses In Humans And Mice, David Henson

Theses and Dissertations--Pharmacy

Cardiovascular disease (CVD) is a major cause of morbidity and mortality around the world causing approximately 14% of total disease burden. A major factor in the progression to major CVD within patients is immune activation, which led to the study of various immune products as potential biomarkers for the prediction of cardiovascular events, including antigen-specific antibodies and immune complexes. One focus of this biomarker research is IgG autoantibodies targeting apolipoprotein A-I (ApoA-I), and several studies of these antibodies have found an association with increased CVD events. Based on the encouraging results from these studies and previous research which has identified …

The Intellectual Property Of Covid-19, Ana Santos Rutschman

All Faculty Scholarship

The response to COVID-19 is indissolubly tied to intellectual property. In an increasingly globalized world in which infectious disease pathogens travel faster and wider than before, the development of vaccines, treatments and other forms of medical technology has become an integral part of public health preparedness and response frameworks. The development of these technologies, and to a certain extent the allocation and distribution of resulting outputs, is informed by intellectual property regimes. These regimes influence the commitment of R&D resources, shape scientific collaborations and, in some cases, may condition the widespread availability of emerging technologies. As seen throughout this chapter, …