A review on the impacts of COVID-19 on the auditory system: Implications for public health promotion research

Background: Currently, there are few studies on the relationship between COVID-19 and the auditory system. In the current study, a review of the studies conducted in the fields of etiopathology, clinical manifestations, research, and treatment of hearing loss caused byCOVID-19 was conducted, which can be used as a baseline for future studies. Methods: We utilized the research approach suggested by Arksey and O’Malley to carry out this scoping review. Search was conducted in Farsi and English with a focus on the onset of hearing loss in patients with COVID-19 through Medline and PubMed, and Google Scholar search engine. Studies included were those involving adult patients diagnosed with COVID-19 who experienced hearing loss, ear pain, ear discharge, and otitis media. Studies were eligible for inclusion if there was a description of the otologic dysfunction, specifically onset, duration, or clinical outcomes. Results: Among 90 studies identified, 35 studies were included in the review process. Our findings suggest several possible mechanisms for sudden sensorineural hearing loss (SSNHL) in COVID-19 patients, and COVID-19 infection could have deleterious effects on the inner ear, specifically on the hair cells of the cochlea despite patients being asymptomatic and early identification of SSNHL in COVID-19patients can save the hearing and also patient. Conclusion: Hearing loss in COVID-19 infection has not received much attention by health care professionals. Sensorineural hearing loss (SNHL), tinnitus, and/or vertigo have been shown to occur during and following COVID-19 infection. Due to lack of research studies, and the inconsistency and even contradictory of the findings, it remains questionable whether COVID-19 contributes to the high incidence of hearing loss. The proper understanding of the mechanisms behind hearing loss in COVID-19 infections needs further research. However, it seems likely that SNHL could be included among the manifestations of those-called "long COVID" syndrome

Ontology-based methods for disease similarity estimation and drug repositioning

Title from PDF of title page, viewed on October 2, 2012Dissertation advisor: Deendayal DinakarpandianVitaIncludes bibliographic references (p. 174-181)Thesis (Ph.D.)--School of Computing and Engineering and Dept. of Mathematics and Statistics. University of Missouri--Kansas City, 2012Human genome sequencing and new biological data generation techniques have provided an opportunity to uncover mechanisms in human disease. Using gene-disease data, recent research has increasingly shown that many seemingly dissimilar diseases have similar/common molecular mechanisms. Understanding similarity between diseases aids in early disease diagnosis and development of new drugs. The growing collection of gene-function and gene-disease data has instituted a need for formal knowledge representation in order to extract information. Ontologies have been successfully applied to represent such knowledge, and data mining techniques have been applied on them to extract information. Informatics methods can be used with ontologies to find similarity between diseases which can yield insight into how they are caused. This can lead to therapies which can actually cure diseases rather than merely treating symptoms. Estimating disease similarity solely on the basis of shared genes can be misleading as variable combinations of genes may be associated with similar diseases, especially for complex diseases. This deficiency can be potentially overcome by looking for common or similar biological processes rather than only explicit gene matches between diseases. The use of semantic similarity between biological processes to estimate disease similarity could enhance the identification and characterization of disease similarity besides indentifying novel biological processes involved in the diseases. Also, if diseases have similar molecular mechanisms, then drugs that are currently being used could potentially be used against diseases beyond their original indication. This can greatly benefit patients with diseases that do not have adequate therapies especially people with rare diseases. This can also drastically reduce healthcare costs as development of new drugs is far more expensive than re-using existing ones. In this research we present functions to measure similarity between terms in an ontology, and between entities annotated with terms drawn from the ontology, based on both co-occurrence and information content. The new similarity measure is shown to outperform existing methods using biological pathways. The similarity measure is then used to estimate similarity among diseases using the biological processes involved in them and is evaluated using a manually curated and external datasets with known disease similarities. Further, we use ontologies to encode diseases, drugs and biological processes and demonstrate a method that uses a network-based algorithm to combine biological data about diseases with drug information to find new uses for existing drugs. The effectiveness of the method is demonstrated by comparing the predicted new disease-drug pairs with existing drug-related clinical trials.Introduction and motivation -- Ontologies in biomedical domain -- Methods to compute ontological similarity -- Proposed approach for ontological term similarity -- Augmentation of vocabulary and annotation in ontologies -- Estimation of disease similarity -- Use of ontologies for drug repositioning -- Future directions-perspective from pharmaceutical industry -- Appendix 1. Table for the ontological similarity scores -- Appendix 2. Test set of 200 records for evaluating mapping of disease text to Disease Ontology -- Appendix 3. Curated set of disease similarities used as the benchmark set -- Appendix 4. F-scores for different combinations of Score-Pvalues and GO-Process-Pvalues for PSB estimates of disease similarity -- Appendix 5. Test set formed from opinions of medical residents http://rxinformatics.umn.edu/SemanticRelatednessResources.html -- Appendix 6. Drug repositioning candidate

Old and new challenges in Parkinson's disease therapeutics

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored.Portuguese Foundation for Science and Technology (FCT) for the PhD fellowship attributed to A.O. Pires (Reference: SFRH/BD/33900/2009) and the IF development grant to A.J. Salgado (Reference: IF/00111/2013). Project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). Funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038info:eu-repo/semantics/publishedVersio

In vivo assessment of non-dopaminergic systems in Parkinson’s disease with Positron Emission Tomography

Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons. Non-dopaminergic neurotransmission is also impaired. Intraneuronal Lewy bodies, the pathological hallmark of PD, have been observed in serotoninergic, noradrenergic, and cholinergic neurons. Dysfunction of these systems could play a role in the occurrence of non-motor symptoms including fatigue. However, the extent of non-dopaminergic degeneration in PD, rates of its progression, and its contribution to the development of non-motor symptoms is unclear. First, I used 18F-dopa Positron Emission Tomography (PET), a marker of monoaminergic terminal function, to assess the involvement of dopaminergic, noradrenergic, and serotoninergic pathways in PD and in parkin-linked parkinsonism, a genetic form of PD. I found that parkin patients and PD patients have distinct patterns of monoaminergic involvement, with more widespread dysfunction in PD. In a second study, I used serial 18F-dopa PET to assess longitudinal changes in tracer uptake in brain monoaminergic structures over a 3-year period in a group of PD patients. I also assessed the relationship between striatal function decline and dysfunction in extra-striatal areas in the same patients. I found that the degeneration in extrastriatal monoaminergic structures in PD occurs independently from nigrostriatal degeneration and at a slower rate. Brain compensatory mechanisms disappear within the first years of disease. I then used 18F-dopa and 11C-DASB PET to investigate whether fatigue in PD is associated with dysfunction of dopaminergic/serotoninergic innervation. I found that PD patients with fatigue show severe loss of serotoninergic innervation in basal ganglia and limbic areas. Finally, I assessed the relationship between 18F-dopa uptake and measurements of serotonin transporter availability by 11C-DASB PET within brain serotoninergic structures and I provided evidence for the hypothesis that 18F-dopa PET can be used to evaluate the distribution and the function of serotoninergic systems in the brain of PD patients

Exploring the genetic contribution to idiopathic Parkinson disease

Background: Parkinson disease (PD) is a major cause of death and disability and has a devastating global socioeconomic impact. It affects 1-2% of the population above the age of 65 and its prevalence increases as the population ages. Several biological processes have been implicated in Parkinson disease, including mitochondrial dysfunction, aberrant protein clearance, and neuroinflammation. To which degree these processes are cause, effect or bystander to disease initiation and progression, remains however largely unknown. Having limited understanding of the mechanisms underlying the pathogenesis and pathophysiology of Parkinson disease, we are unable to develop disease-modifying therapies and patients face a future of progressive disability and premature death. There is a clear hereditary component to idiopathic PD, established through both twin studies and genome-wide association studies. However, only a minor fraction of the total estimated heritability can be explained by known associated genetic variability. It has been hypothesized that the cumulative effects of rare, low-impact mutations spread across genes and biological pathways could explain some of this “missing heritability”. Aims: The aim of this work was to explore the genetic contribution to idiopathic PD, focusing on the cumulative effects of rare mutations. Materials and methods: The main study population utilized in all four papers was the ParkWest cohort, a Norwegian population-based cohort of incident PD. In paper I, ParkWest provided both cases and controls, including clinical longitudinal data up to and including 7 years after baseline. All ParkWest cases were whole-exome sequenced and combined with previously sequenced control samples to form the genetic cohort utilized in papers II-IV. Additionally, a whole-exome sequencing cohort from the Parkinson Progression Markers Initiative was used in papers II-IV. Finally, a publicly available chip-genotyped dataset (NeuroX) from the International Parkinson’s Disease Genomics Consortium was used as a replication cohort in paper IV. In paper I, we characterized the familial aggregation of Parkinson disease in the ParkWest cohort and explored the effect of family history on disease progression. Subsequently, we used genetic data from multiple cohorts to assess the impact of rare, protein-altering mutations in mitochondrial biological pathways (paper III) and in genes previously linked to PD (paper II and IV). Results and conclusions: We show that, while familial aggregation is present in our Norwegian cohort, this has a slightly lower effect size compared to previous studies. Through regression analysis we also show that having a family history of PD among first degree relatives is associated with a slightly milder phenotype, which may be due to genetic variability. In paper II, we attempted to replicate the results of a recently published study reporting an association between genetic variation in the TRAP1 gene and Parkinson disease. Our analyses did not replicate this association in our Norwegian cohort. Moreover, using stricter quality control parameters abolished the association in the same dataset used in the original study. Our results do not support the proposed role of TRAP1 in idiopathic PD. In paper III, we sought to investigate the role of rare, amino acid changing variation in molecular pathways related to mitochondrial function. Using the sequence kernel association (SKAT) test, we detected a statistically significant enrichment in the pathway of mitochondrial DNA maintenance. Impaired mitochondrial DNA homeostasis has previously been shown to be present in PD neurons, and our results indicate that this dysfunction could be partly mediated by inherited genetic mutations. In paper IV, we performed a targeted single gene and gene-set association study on genes that had previously been implicated in PD through genome-wide association studies. We identified 303 genes of interest, but did not find statistically significant associations, either in the single gene or gene-set analyses. Our results do not therefore support a major role for rare variant enrichment in genes tagged by GWAS, but cannot rule out effects with small effect sizes.Doktorgradsavhandlin

Emerging Perspectives on Gene Therapy Delivery for Neurodegenerative and Neuromuscular Disorders.

Neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD) and Parkinson's Disease (PD), are a group of heterogeneous diseases that mainly affect central nervous system (CNS) functions. A subset of NDDs exhibit CNS dysfunction and muscle degeneration, as observed in Gangliosidosis 1 (GM1) and late stages of PD. Neuromuscular disorders (NMDs) are a group of diseases in which patients show primary progressive muscle weaknesses, including Duchenne Muscular Dystrophy (DMD), Pompe disease, and Spinal Muscular Atrophy (SMA). NDDs and NMDs typically have a genetic component, which affects the physiological functioning of critical cellular processes, leading to pathogenesis. Currently, there is no cure or efficient treatment for most of these diseases. More than 200 clinical trials have been completed or are currently underway in order to establish safety, tolerability, and efficacy of promising gene therapy approaches. Thus, gene therapy-based therapeutics, including viral or non-viral delivery, are very appealing for the treatment of NDDs and NMDs. In particular, adeno-associated viral vectors (AAV) are an attractive option for gene therapy for NDDs and NMDs. However, limitations have been identified after systemic delivery, including the suboptimal capacity of these therapies to traverse the blood-brain barrier (BBB), degradation of the particles during the delivery, high reactivity of the patient's immune system during the treatment, and the potential need for redosing. To circumvent these limitations, several preclinical and clinical studies have suggested intrathecal (IT) delivery to target the CNS and peripheral organs via cerebrospinal fluid (CSF). CSF administration can vastly improve the delivery of small molecules and drugs to the brain and spinal cord as compared to systemic delivery. Here, we review AAV biology and vector design elements, different therapeutic routes of administration, and highlight CSF delivery as an attractive route of administration. We discuss the different aspects of neuromuscular and neurodegenerative diseases, such as pathogenesis, the landscape of mutations, and the biological processes associated with the disease. We also describe the hallmarks of NDDs and NMDs as well as discuss current therapeutic approaches and clinical progress in viral and non-viral gene therapy and enzyme replacement strategies for those diseases

2005 Annual Research Symposium Abstract Book

2005 annual volume of abstracts for science research projects conducted by students at Trinity College

2018 Touro College & University System Faculty Publications

This is the 2018 edition of the Faculty Publications Book of the Touro College & University System. It includes all eligible 2018 publication citations of faculty within the Touro College & University System, including New York Medical College (NYMC). It was produced as a joint effort of the Touro College Libraries and the Health Sciences Library at NYMC.https://touroscholar.touro.edu/facpubs/1008/thumbnail.jp