To date, an accurate understanding of the dynamics between the fibre's inherent geometric, mechanical and biological characteristics is deficient, affecting the reliability and robustness of hair data. There is also insufficient scientific clarity on the behaviour of curly hair, as most of the conclusions have been drawn from studies focusing on straight fibres. This research project aimed at gaining a more accurate understanding of the interrelationships between fibre curliness, strength and chemical bonding. In the current understanding of hair mechanics, curly fibres are considered to have a lower tensile strength than straight fibres. Furthermore, the current understanding of hair fibres does not associate hydrogen bonding with fibre shape. During experimentation, inadvertent observations suggested that current tensile methods ignore an important component of hair strength in curly fibres, and that hydrogen bonding supports fibre curliness. Intensive scrutiny of these observations led to fundamental contributions to the understanding of curly hair. Research tools included tensile, geometric, image, (FTIR) spectroscopic assessments, regression modelling and multivariate statistical analysis. Through this research, the role of hydrogen bonding in fibre curliness has been established. A theory is presented about extraordinary hydrogen bonds and the existence of hydrogen bond networks across the fibre matrix of curly hair. The theory has been substantiated experimentally via FTIR and weight measurements. The research also established the importance of the preelastic tensile region for curly fibres. It was clearly demonstrated that tensile strength of hair fibres is not only dependent on Young's modulus, but also on the fibre's inherent viscoelasticity, which appears to be important in curly fibres but becomes negligible with loss of curl. A model, developed from experimental observations and insights from similar biological fibres, is also presented. The model gives insights into ultrastructural changes at the early onset of fibre elongation. It also demonstrates the association between viscoelasticity and hydrogen bond networks. Taking this into consideration, a constitutive equation, developed to determine hair fibre strength accurately, is also presented in this work. This work does not replace current fibre curvature theories, but provides additional insights into hair shape, and therefore presents a fundamental contribution to curvature in human hair. It also highlights the shortcomings of current instrumentation methods that contribute to inaccurate conclusions regarding the strength of curly fibres.

Complex Regional Pain Syndrome (CRSP) is a neuropathic disorder that has proven to be particularly difficult to treat based on the wide array of symptoms experienced by patients and the ambiguity surrounding their origin. The vast majority of treatment options today deal with the management of pain symptoms experienced by patients as a result of neuroinflammation. Physical therapy is an instrumental aspect of the treatment plan; however the need for more effective pharmacological interventions is paramount. This study reviews a large volume of current and fundamental literature covering the plethora of treatment options currently used for CRPS. Data from double blind clinical trials as well as observational clinical results were gathered in hopes of illuminating the efficacy of each treatment. The goal was to assess current and future treatment options and determine what interventions are optimal for the management of CRPS. Furthermore, this review highlights some of the limitations of the current treatment options, in addition to providing a synopsis of CRPS as it is understood today. This paper paints a picture of where we have been in the treatment of CRPS, what is working, what is not working, and where we might go in the future.

Colorectal Cancer (CRC) is one of the most prevalent cancers among men and women in the world. Its presence is increasingly being felt in people who east a western diet. A sedentary life, lack of physical activity, and excessive consumption of red meat are some of the major risk factors associated with the disease. Furthermore, increasing correlations are demonstrating that diabetic and obese patients are at a higher risk of developing colorectal cancer. Of increasing interest is the presence of growth factors present in these individuals. One such growth factor, which is being crucially studied for the purposes of treatment and prevention, is insulin-like growth factor-1 (IGF-1.) IGF-1 is part of the IGF axis, an endocrine axis, composed of IGF-1 receptor (IGF-1R), numerous IGF binding proteins (IGFBPs), and insulin. Many studies have highlighted the high levels of IGF-1 in the blood of patients with CRC. However, currently IGF-1 is only regarded as a biomarker for CRC. The role that a dysregulated IGF axis plays in the development and progression of CRC is largely unknown. This review of the current literature has underlined major risk factors of colorectal cancers which are able to exert their unwanted effect through their impact on the IGF axis. These factors include obesity, diabetes, radiotherapy, and oxidative stress. The understanding of the dysregulation of IGF axis’ pathways in colorectal cancer is crucial for the development of new treatment options for the disease in the future. In this paper the known mechanisms through which IGF-1s binding to IGF-1R causes unnecessary cellular proliferation in colorectal cancer patients is discussed. IGF-1R is a dimer with a tyrosine kinase domain on the intracellular side. Ligand binding to this receptor causes autophosphrylation and the activation of the Phosphoinositide 3-kinase/Protein Kinase B/Wnt (PI3K/Akt/Wnt) pathway. The PI3K/Akt/Wnt pathway is known to cause cellular proliferation and, in excess, metastasis. The potential for the IGF axis to cause metastasis will also be discussed in more direct terms. Levels of IGF-1R and IGF-1 are positively correlated with different stages of metastasis. Furthermore, in vitro and in vivo studies have demonstrated that IGF-1 has the ability to increase lymphatic vessel density. The potential for changes in the treatment of patients with colorectal cancer and prevention of the disease in those who are at risk of it is also discussed. Currently the main therapies through which the IGF axis is targeted are chemotherapy and immunotherapy. However, these therapies can cause a lot of damage to the body as they are not specific to the cancer cells. A new theory known as the cancer stem cell theory is readily being used to design treatment options for the future. According to this theory, cancer stem cells are present in small amounts in everyone and are responsible for the relapse of cancer after radiation or chemotherapy. These cells are increasingly being targeted for drug design as they provide specificity which would, hypothetically, not produce as many side effects. Another mechanism, which provides specificity and is gaining popularity in treating CRC, involves the use of microRNAs. microRNAs are small RNAs which can bind to mRNAs of major genes and prevent their translation. miRNAs which suppress the genes of the IGF axis can be administered to the patient to specifically address the problem. Numerous such miRNAs have been discovered and their roles were discussed in further detail. Lastly, the ability of some bioactive compounds to perturb the IGF axis in CRC is also discussed. These compounds are mainly found in some of the fruits and vegetables, and spices like curcumin. Vitamin D is another dietary compound which has the potential to prevent CRC in the susceptible population. However the extent to which small amounts of these compounds can prevent CRC is largely indeterminate and there is a need to conduct studies on the compounds’ dosing regimen. The review of the literature on colorectal cancer has discussed some of the latest strategies in tackling the disease as well as providing mechanistic insights into IGF axis’ dysregulation in CRC.

Breast cancer is the most common type of cancer among women in the United States. Cancer diagnosis and treatment usually induce significant amount of psychological stress on patients, and breast cancer patients are especially susceptible to cancer-related distress. Chronic stress activates the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenomedullary (SAM) axis, whose prolonged activation initiates physiological events harmful to the immune system and negatively influence cancer progression and recurrence. Therefore, it is important to identify and introduce effective cancer-related stress management programs and incorporate them into the standard cancer care routine besides conventional therapy. Mindfulness-based stress reduction (MBSR) is an 8-week stress reduction program that has deep roots in ancient Buddhist practice and is used widely in clinics around the world nowadays. Is has been demonstrated to be effective in relieving stress and promoting well-being in a variety of populations, both clinical and nonclinical. And now it has started to be adapted into a complementary breast cancer therapy. However, much of MBSR’s mechanism is still unknown, and no definite proof exists to show its efficacy in improving the negative psychological and physiological side effects of breast cancer treatment. This thesis summarizes and evaluates the current evidence of MBSR’s effectiveness in relieving psychological and physiological stress symptoms among breast cancer patients and survivors.

Shigella flexneri causes millions of diarrheal infections and hundreds of thousands of deaths each year, mostly in children in developing countries. Shigella uniquely evolved to adapt and utilize host variables to its advantage despite the harsh gastrointestinal environment. Our previous research has demonstrated that Shigella resists the bactericidal nature of bile salts, found mostly in the small intestine, and utilizes the compound as a signal to regulate virulence for subsequent colonic infection. The ospC1 and ospD3 genes, which are encoded on the virulence plasmid and known to affect neutrophil migration and interleukin-8 (IL-8) secretion during infection, are upregulated in the presence of bile salts. The goal of this study was to examine the effects of bile salts pre-exposure on subsequent colonic cell infection and IL-8 secretion. We first confirmed the expression of ospC1 and ospD3 was induced in bile salts. Next, overnight colonic HT-29 epithelial cell infections and IL-8 secretion analyses were performed using wild-type bacteria, a virulence-plasmid cured strain (BS103) as a negative infection control, and mutants ΔospC1, ΔospD3, and ΔospC1+ΔospD3. Single mutants retained wild-type levels of infection; but surprisingly, the double mutant ΔospC1+ΔospD3 had less bacterial recovery after infection that was exacerbated following bile salts pre-exposure. For IL-8 secretion in the absence of bile salts, ΔospD3 had significantly higher levels, indicating the OspD3 protein suppresses IL-8 secretion. However, following bile salts pre-exposure, ΔospC1 displayed higher IL-8 secretion, suggesting the OspC1 protein is more important to suppress IL-8 secretion. Future analyses will continue to explore these findings and evaluate subsequent effects on neutrophil migration. Our data provide support that Shigella exposure to appropriate in vivo-like conditions is essential to understand infection dynamics in the colonic epithelium. / 2021-10-02

Amyotrophic Lateral Sclerosis (ALS), which is also referred to as Charcot disease or Lou Gehrig’s disease, is a fatal and incurable neuromuscular disorder that affects motor neurons. Developing a long-term hiPSC-derived motor neuron culture system helps analyze and visualize age-related phenomenon that would not be apparent in typical shorter-term culture systems. Ren-VM Cells were used prior to hiPSCs to demonstrate that protein localization and mislocalization associated with ALS can be analyzed. A novel hiPSC-derived motor neuron maintenance protocol was developed to generate ideal conditions for imaging and analyzing protein localization and mislocalization. Ultimately, a novel replating protocol was developed, which generates hiPSC-derived motor neuronal cultures that are mature and can be analyzed effectively. / 2021-10-07T00:00:00Z

Parkinson’s disease is an idiopathic movement disorder that occurs as a result of the gradual loss of dopaminergic neurons in the substantia nigra. This progressive deterioration causes Parkinson’s disease patients to experience motor symptoms, such as tremor & bradykinesia, and non-motor symptoms, such as sleep disorders, depression, and anxiety. Though research has been conducted for over fifty years, scientists have not been able to isolate the disease’s primary causes nor find a cure. The gold standard treatment for Parkinson’s disease is the drug carbidopa-levodopa. It alleviates the motor symptoms by acting as a supplement to the declining dopamine levels. Unfortunately, as the disease progresses, the efficacy of levodopa begins to fade, making the accompanying side effects, namely dyskinesia and motor fluctuations, unbearable. Exercise has been found to act as an adjunct therapy to standard Parkinson’s disease treatment, ameliorating both motor and non-motor symptoms, as well as slowing progression of the disease, without the pharmacological side effects. Therefore, clinicians have begun recommending physical activity as part of patients’ treatment plans, even to those at the most advanced levels of disease progression. Unfortunately, though they know exercise will help, many patients choose to remain sedentary due to lack of motivation, and depression, among numerous other barriers. Forced, assisted exercise has been shown to provide the most benefit for patients, helping them to maintain an improvement in symptoms for weeks after physical activity is performed. This paper concludes that exercise needs to be made a prescribed and mandatory part of treatment, in the form of an individualized plan which takes into account each patient’s unique symptoms and abilities. In so doing, patients can overcome their barriers, improve their quality of life, and maintain their ability to perform activities of daily living for as long as possible.

Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome of multiple etiologies that leads to widespread alveolar inflammation, hyaline membrane formation and noncompliant lungs. ARDS remains underdiagnosed and undertreated with a high mortality rate in high and low income countries. There are limited treatment options for ARDS, including protective lung ventilation, fluid management, prone positioning and ECMO, which may not be used for a patient if they are not diagnosed correctly with ARDS. ARDS is underdiagnosed in low income countries due to the lack of resources, and the resulting lack of access to invasive tools used in the current gold standard diagnostic criteria for ARDS, the Berlin Criteria. To address this issue, Riviello and colleagues introduced the Kigali criteria, that diagnose ARDS using noninvasive tools which are available in low income nations. Vercesi and colleagues examined the Kigali criteria in ICU patients in the Netherlands and found a strong specificity when using stricter Lung Ultrasound criteria. The purpose of this study is to validate the utilization of the Kigali criteria in the early diagnosis of ARDS, with the use of echocardiography, physical exam findings, strict lung ultrasound criteria, and SpO2/FiO2 in screening patients on arrival to Emergency Departments and repeatedly during admission to 7 hospitals in the Boston area.

Breast cancer is the most common cancer in women. While advances have been made in its detection and treatment, breast cancer is still responsible for significant mortality annually. One aspect of treatment that needs to be considered is the type of operation a woman should undergo. Studies have shown that fewer women are choosing breast conserving surgery even though the survival rate is equivalent compared to bilateral mastectomy. One component that can help guide this decision and establish those that would benefit from contralateral risk reducing mastectomy is genetic testing. Many studies have found that high penetrance mutations influence the type of operation women undergo. There have, however, been no studies investigating whether undergoing genetic testing and not carrying a high penetrance mutation influences one’s surgical decision. This proposed study is a one-year prospective cohort study that aims to determine if undergoing genetic testing and not carrying a high penetrance mutation increases a woman’s likelihood of choosing contralateral risk reducing mastectomy. This study will help understand how women use genetic counseling and testing information to guide their surgical decision. In addition, this study will examine if future studies are needed to improve breast cancer treatment counseling to decrease unnecessary surgery, surgical complications and decrease cost.

Non-communicable diseases are on the rise throughout Uganda and the management of four chronic disease states -- hypertension, diabetes, breast cancer, and prostate cancer -- have shown to be inadequate. This gap in chronic disease care leaves room for an educational intervention in the training of medical professionals and the implementation of a novel workforce. Similar to the model seen in the United States, this research aims to create a cohort of physician assistant students at the Makerere University College of Health Sciences in Kampala, Uganda. Physician assistants in the United States provide medical care in many ways, including primary care where chronic diseases can be managed. The cohort of physician assistant students in this study will be trained alongside their medical student counterparts, however, their curriculum will focus on the management of chronic disease. This will be accomplished through shortening and restructuring the didactic and clinical medical school curriculum such that a greater focus is on the management of chronic conditions. Physician assistant and medical students in this study will be assessed for both knowledge and clinical skills gained over the course of their training regarding the management of the four chronic disease states noted above. Knowledge of chronic disease states will be tested with the administration of pre- and post- examinations at the orientation of their medical training and after their completion, respectively. Further, all students will be assessed for their views and will self-evaluate their skills regarding interprofessional collaboration at the orientation of their medical training and after their completion. This study aims to demonstrate how a novel workforce of trained clinicians, known as physician assistants, can display competency in the management of chronic conditions as means to aid a growing healthcare concern throughout Uganda. A secondary outcome being examined in this study is how training these future clinicians together with medical students will improve their views on interprofessional collaboration as means to provide optimal care to patients and enhanced interconnectedness between clinicians in Uganda.