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Open Access Publications from the University of California
Cover page of Monotherapy vs Combination Therapy for the Management of Alzheimer’s Disease

Monotherapy vs Combination Therapy for the Management of Alzheimer’s Disease

(2021)

Alzheimer’s disease is a neurological condition resulting from the death of neural cells that causes a deprivation in cognitive functionality, communication, and motor skills in patients. The condition has an inordinate impact on older populations, with 90% of all cases affecting those 65 years or older1. As the most common type of dementia, comprising approximately 70% of all dementia cases, Alzheimer’s disease affects about 5 million people in the United States. The rate of the condition’s extent among the population is increasing exponentially, with the number of people enduring Alzheimer’s estimated to triple by 2060 in the United States.1

Due to the widespread impact of Alzheimer’s, developing treatments that govern the symptoms of the condition is an immense priority for researchers all over the globe. In the spirit of the venture to aid patients suffering from Alzheimer’s disease, also known as AD, researchers have in recent years been testing several monotherapies, as well as the combination of these drugs to examine the most viable treatment plan for Alzheimer’s for several stages, ranging from mild to moderate to severe AD. Monotherapies are selective agents with a single therapeutic action that may or may not have other less-significant side effects. Combination therapies encompass multimodal agents including drug cocktails and multifunctional molecules that combine multiple mechanisms of therapeutic action which may have a wider range of side effects.  This paper will explore the effects of combining monotherapies and the efficacy of several drugs on Alzheimer’s patients by examining the FDA approved drugs- donepezil, memantine, the combination of donepezil and memantine, rivastigmine, rasagiline, and ladostigil.

Cover page of Effects of SARS-CoV-2 B1.1.7 Spike Mutations on Vaccine Efficacy

Effects of SARS-CoV-2 B1.1.7 Spike Mutations on Vaccine Efficacy

(2021)

This is a literature review on the effects of spike mutations in the B1.1.7 SARS-CoV-2 variant and its effect on vaccine efficacy. This paper has organized the pertinent literature on the researched effects of vaccine efficacy and explores a number of mutations in the spike protein. The search was conducted on PubMed and the criteria for inclusion was based on relevance to specifically mutations in the B1.1.7 variant, being a primary source, conducted after January of 2021, and its reproducibility and pertinence to the research topic. There are 16 fully extracted studies discussed in the results, with a brief overview of the conducted experiment in relation to the papers’ conclusions. The strengths of this paper are distilling the molecular methods of these individual papers and being able to compare and contrast diverse experiments on the same mutations. However, due to the diversity of experiments discussed in this paper, the landscape of SARS-CoV-2 mutations and vaccine efficacy are difficult to distill. The discussed papers were evaluated on the possible threats of the mutations and the comparable effect of known mutations. This is an important step for evaluating transmissibility and virulence. This literature review further shows the need to have a standard set of experiments that can be used to evaluate the effect of mutations in SARS-CoV-2 variants and its effect on vaccine efficacy in order to make

Cover page of Maternal Mortality Rates and their Correlation to Food Deserts

Maternal Mortality Rates and their Correlation to Food Deserts

(2021)

Maternal mortality is defined as the number of deaths related to complications during or after childbirth. Food deserts are defined as regions that have limited access to affordable and healthy food options. This study utilized R to analyze data from the United States Department of Agriculture Economic Research Service’s Food Access Research Atlas and maternal mortality rates from the UCSF paper “Maternal Morbidity and Outcomes Including Mortality, California 2001-2006.” to search for an association between the two variables. The research atlas maps areas in Northern California with low access to grocery stores, as well as provides information on food access throughout the United States using census tracts. The independent variable in this study is food access and the dependent variable is maternal mortality. After analyzing the data collected using R, correlation graphs were created and intercepts and R values were identified. This information was used to further understand the relationship between food access and maternal mortality. For this study, we focused our scope on the Bay Area counties of Alameda, Contra Costa, Marin, San Francisco, Santa Clara, Solano, and Sonoma, which are located in Northern California.

Cover page of Monotherapy vs Combination Therapy for the Management of Alzheimer’s Disease

Monotherapy vs Combination Therapy for the Management of Alzheimer’s Disease

(2021)

Alzheimer’s disease is a neurological condition resulting from the death of neural cells that causes a deprivation in cognitive functionality, communication, and motor skills in patients. The condition has an inordinate impact on older populations, with 90% of all cases affecting those 65 years or older. As the most common type of dementia, comprising approximately 70% of all dementia cases, Alzheimer’s disease affects about 5 million people in the United States. The rate of the condition’s extent among the population is increasing exponentially, with the number of people enduring Alzheimer’s estimated to triple by 2060 in the United States.

Due to the widespread impact of Alzheimer’s, developing treatments that govern the symptoms of the condition is an immense priority for researchers all over the globe. In the spirit of the venture to aid patients suffering from Alzheimer’s disease, also known as AD, researchers have in recent years been testing several monotherapies, as well as the combination of these drugs to examine the most viable treatment plan for Alzheimer’s for several stages, ranging from mild to moderate to severe AD. Monotherapies are selective agents with a single therapeutic action that may or may not have other less-significant side effects. Combination therapies encompass multimodal agents including drug cocktails and multifunctional molecules that combine multiple mechanisms of therapeutic action which may have a wider range of side effects. This paper will explore the effects of combining monotherapies and the efficacy of several drugs on Alzheimer’s patients by examining donepezil, memantine, the combination of donepezil and memantine, rivastigmine, rasagiline, and ladostigil.

Cover page of The Effect of Enteric Biochemical Modifications and Imbalances on the Progression of Parkinson’s Disease

The Effect of Enteric Biochemical Modifications and Imbalances on the Progression of Parkinson’s Disease

(2021)

This paper analyzes various biochemical differences observed between patients afflicted with Parkinson’s Disease and those without the diagnosis. Such disparities explored in this work include the accumulation of alpha-synuclein in the form of Lewy Bodies along with significant changes in the bacterial populations of Akkermansia, Streptococcaceae, Prevotella, and Lactococcus. Specifically, these distinct markers are examined in the context of the enteric system as a means of synthesizing connections between nuanced changes within the gut and the progression of PD. Essentially, this study supports an alternative attempt of better understanding the disease beyond a sole, isolated focus on the brain and central nervous system. Further confounding variables that have been linked to PD are also examined in a similar context; for instance for the variable age, it was indeed found that one of the potential reasons why age is a risk factor for PD can be tied back to the gut through an analysis into calprotectin. Ultimately, from a broad standpoint, the significance of this paper lies in the connections and pathways tying the aforementioned markers associated with PD to the gut, which are laid out in extensive detail. In turn, based on the findings of this paper, there is potential for driving future research relating to the origin and treatment of the disease, through possibly looking at systematic changes occurring within microbiomes as a promising starting point in addition to the extensive research on the brain already being carried out.

Cover page of Current Limitations and Future Outlook of Nanomedicine Efficacy and Treatment of HIV/Aids

Current Limitations and Future Outlook of Nanomedicine Efficacy and Treatment of HIV/Aids

(2021)

Although the development of antiretroviral treatment has been successful in mitigating and suppressing HIV/AIDS infections globally, it has not changed the fact that 1.7 million new infections have occurred in 2019.The objective of the literature review is to determine the current treatments for HIV and their shortcomings, future approaches using nanotechnology, and the current related health disparities which may be mitigated by advances in this field.  Both globally and in the United States, the main demographic of HIV/AIDs victims are from disadvantaged communities that lack access to treatment and prevention education. Despite the use of antiretroviral treatment reaching global access and its successful efforts, there are still many challenges with the containment of the virus since the treatment does not effectively suppress the virus. Future approaches using nanotechnology are quite varied in the types of particles used but are mainly used to increase delivery efficiency and show promising results in the pre-clinical and clinical stage. There is significant evidence that nanotechnology can increase the efficacy of drugs targeting HIV and several implications that these improved drugs can help mitigate some health disparities on the national and global level.

Cover page of Analysis of Potential Antibody Dependent Enhancement (ADE) in SARS-CoV-2 infections

Analysis of Potential Antibody Dependent Enhancement (ADE) in SARS-CoV-2 infections

(2021)

Antibody Dependent Enhancement (ADE) is a phenomenon in which viral particles bind to virus-specific antibodies, enhancing their uptake by host cells and resulting in increased viral replication and infection. First discovered while studying dengue virus (DENV) in primates, ADE can be explained by two general mechanisms, depending on the type of virus involved. In DENV infection, ADE manifests as largely different reactivity upon secondary infection with a cross-reactive serotype and this information provides a large implication to the authorization of DENGVAXIA vaccine use. Looking into the need of vaccines considering the current SARS-CoV-2 pandemic, authors are providing a review of current knowledge correlating SARS-CoV-2 and ADE phenomenon. Using SARS-CoV-1 as a model, we can hypothesize the possible ADE pathway in SAR- CoV-2. The S protein binds to the ACE2 receptor on the host cell and triggers different immune responses depending on the titer of antibodies present. Despite in vitro studies suggesting some cross-reactivity of some antibodies generated in response to other coronaviruses to SARS-CoV-2, ADE does not appear to be a major concern in vivo. Similarly with vaccines, although there may be variation in efficacy to respective strains of SARS-CoV-2 there does not appear to be serious concern for ADE due to vaccination.

Cover page of The Exploration of CRISPR within Infectious and Genetic Disease Research, Diagnoses, and Treatments

The Exploration of CRISPR within Infectious and Genetic Disease Research, Diagnoses, and Treatments

(2021)

Prokaryotes, such as bacteria, have evolved defense mechanisms that protect them from foreign bodies invading and harming them.1 One of these mechanisms is the clustered regularly interspaced short palindromic repeats (CRISPR), alongside their accompanying CRISPR-associated (Cas) proteins.1 This system functions as an immune response that protects prokaryotes from viruses (and other harmful bodies) by detecting foreign genetic material invading them and disabling their functionality and ability to spread.2 Understanding the underlying mechanism of this immune response allowed scientists around the world to develop CRISPR and adapt it to various uses in gene editing, agriculture, and most recently, diagnosis of infectious and noninfectious diseases.2  The discovery of CRISPR as a biomedical disease detection tool has revolutionized modern day medicine and its accessibility. 

Infectious diseases are those that are caused by microorganisms and easily passed from one human to another. Currently, CRISPR--specifically the Cas13 protein system--is being utilized for disease detection and diagnosis through the detection and cleavage of specific ssRNA molecules. SHERLOCK, Specific High-sensitivity Enzymatic Reporter unLOCKing, is a specific breed of CRISPR Cas13a disease detection technology that has been deployed in West African countries to combat infectious disease such as Lassa Fever-- a disease caused by the zoonotic virus Lassa mammarenavirus that originates from the Mastomys natalensis rodent group.5 SHERLOCK’s ability to succeed in the detection and diagnosis of Lassa fever in West African countries that lack proper infrastructure relies on SHERLOCK’s accessibility and efficiency. Cas13a’s specificity and sensitivity in the detection of viral nucleic acids caters to the fact that Lassa Fever has high genetic diversity and requires highly sensitive tools to detect the disease.8 

Moreover, genetic diseases are those caused by an error in the DNA of a person. The three main types include monogenic, complex, and chromosomal; the treatment and causes of the diseases are different for each type.17 There are still many obstacles when it comes to curing genetic diseases, yet scientists are using powerful tools such as CRISPR to help those who suffer from these diseases.18 The CRISPR Cas9 enzyme is one powerful system that can be used to disrupt, delete, or insert genes to help edit any errors in the genome and treat genetic diseases.23 It is comprised of the CRISPR-associated (Cas) enzyme and the guide RNA (gRNA), which work together to act as a scissor for the DNA.19 Adrenoleukodystrophy (ALD) is an X-linked genetic disease that is primarily due to a mutation within the ABCD1 gene. Currently, the Cas9 system provides a disease model in order to study the pathogenesis of ALD and target (and repair) the mutation causing this genetic disease.