Osteoporosis is a skeletal disorder characterized by decreased BMD and the increased prospect of fracture. These fractures can have a detrimental impact on an individual’s standard of living and are sometimes fatal. Increased bone resorption by osteoclasts relative to the bone formation by osteoblasts triggers osteoporosis. Osteoporosis predominantly affects post-menopausal white and Asian women. BMD is used to diagnose this disease and determine fracture risks; however, osteoporosis often goes unreported and untreated. The purpose of this study was to correlate biochemical assays of bone growth with each subject's cells' gene expression grown in culture. Bone samples were taken from each subject undergoing hip replacement surgery. Each subject’s bone cells were grown in culture then assayed for ALP and hydroxyproline. ALP and hydroxyproline were used as proxies of the osteogenic potential of the cultured cells. The assayed ALP for each subject was compared to COL1A1 RNA gene expression. Further, the hydroxyproline assay results were compared to DMP1 RNA gene expression. The results of this study did not signal a measurable association between any of these metrics. The genetic mechanisms of osteoporosis remain unclear, and advanced research to elucidate how cells’ behavior in culture is related to the underlying nature of the person’s BMD could result in better data to treat and prevent this disease.

INTRODUCTION: Inflammatory Bowel Disease (IBD) is a multifactorial chronic relapsing condition thought to be caused by an interplay between a patient’s genetics, immune system, and susceptibility to environmental factors. Oxidative Stress (OS) is one pathogenic mechanism driving the inflammation and tissue damage observed in patients with IBD. OS in IBD is mediated by an overwhelming abundance of reactive oxygen and nitrogen species (RONS) generated by activated immune cells, including neutrophils and macrophages, that have been recruited to the intestinal mucosa. The relative abundance of RONS is assessed using technology capable of directly measuring the ambient oxidative-reductive potential (ORP) in tissue or a fluid sample. ORP values can provide new approaches that link disease pathogenesis with treatment. ORP assessment may prove to be a sensitive, inexpensive, and non-invasive biological marker in the diagnosis and interval assessment of patients with IBD. OBJECTIVES: The goal of this study was to assess the relationship between disease activity and oxidative-reductive potential (ORP) in the stool and urine of patients with and without IBD. METHODS: Patients admitted to Boston Children’s Hospital (Boston, MA) were recruited and consented to participate in this study. Stool and urine samples were collected, and the ORP (mV) was measured using the Arrowdox, PCE, and Redoxsys devices. Samples were collected between the period of November 2018 and March 2021. RESULTS: The data demonstrate that measuring the ORP of stool supernatants may be a useful biomarker for assessing disease activity in patients with IBD. The several phases of this study include addressing (1) the accuracy, reliability, and validity of ORP measurements in stool and urine (2) establishing methods that provide consistent intra- and inter-device readings. These findings ultimately led to the measurement of stool supernatant & pellet using the Arrowdox and Redoxsys platforms. Data collected demonstrate a relationship between ORP (mV) measurements of stool supernatants and increased disease activity in patients with IBD. CONCLUSION: The measurement of ORP in the stool of patients with and without IBD may be a reliable tool for indicating clinical disease status. Stool supernatant ORP readings appear to provide the most consistent intra- and inter-device readings. The future of developing this technology study will focus on amplifying patient recruitment to more definitively assess the relationship between stool ORP measurement and disease activity in patients with and without IBD. Urine ORP values may not reflect disease activity in patients with IBD. However, further studies that focus on how urine ORP changes over time and under certain conditions (2°C, 20°C, and -80°C) are necessary. A more thorough understanding of the impact of diet, gut aerobic and anaerobic bacterial makeup, and hematochezia prevalence on redox status is also needed to control for potentially confounding variables. The ability to reliably measure redox measurements will support clinical trials assessing candidate antioxidant therapies.

Severe malnutrition may adversely affect digestive function, and result in the difficulties frequently encountered when attempting to re-feef such patients. To investigate the effects of undernutrition, and subsequent re-feeding, on digestive function in human patients, severely malnourished patients were studies before, and after a period of intensive nutritional support.

Includes abstract. / Includes bibliographical references. / A Disintegrin And Metalloproteinase 10 (ADAM10) is a cell surface molecule that activates proteins such as: adhesion molecules, cytokines, and growth factors. ADAM10 has been associated with the proliferation and metastasis of cancers including, breast, lung, and colon. While ADAM10 has been investigated in these cancers, very little is known of its role in cervical and oesophageal cancer. The aim of this study was to investigate the endogenous expression of ADAM10 in cervical and oesophageal patient material and representative cell lines.

Severe malnutrition may adversely affect digestive function, and result in the difficulties frequently encountered when attempting to re-feef such patients. To investigate the effects of undernutrition, and subsequent re-feeding, on digestive function in human patients, severely malnourished patients were studies before, and after a period of intensive nutritional support.

Background Delirium is associated with increased mortality and hospital length of stay. Limited data are available from HIV-infected acute hospital admissions in developing countries. We conducted a prospective study of delirium amongst acute medical admissions in South Africa - a developing country with universal ART access and high burdens of TB and noncommunicable disease. Methods Three cohorts of adult acute medical admissions to Groote Schuur and Victoria Hospitals, Cape Town, South Africa were evaluated for prevalent delirium within 24 hours of admission. Reference delirium testing was performed by either consultant physicians or neuropsychologists, using the Confusion Assessment Method (CAM). Findings The study included 1182 acute medical admissions; with 318 (26·9%) HIV-infected Median(IQR) age and CD4 count was 35(30-43) years and 132(61-256) cells/mm3 respectively, with 140/318(44%) using ART on admission. Delirium prevalence was 17·6%(95% CI 13·7-22·1%) amongst HIV-infected patients and was an independent risk factor for inpatient mortality. In multivariable logistic regression, factors associated with delirium were age ≥55 years(AOR 6·95[2·03-23·67], p=0·002) and urea ≥15(AOR 4·83[1·7- 13·44], p=0·003), while ART use reduced risk (p=0·014). Low CD4 count, unsuppressed viral load, and active TB were not predictors of delirium; nor were other traditional risk factors such as non-opportunistic, acute infections or polypharmacy. Interpretation Delirium is common and predicts poor outcome in HIV-infected acute medical admissions in endemic settings despite increased ART use. Older HIV-infected patients with renal dysfunction are at high risk for inpatient delirium while those using ART on admission are protected.

Appropriate use of laboratory investigations is increasingly important in resource-constrained environments. We receive the anti-neutrophil cytoplasmic antibody (ANCA) testing practices in a tertiary hospital in South Africa.

BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune disease with autoantibodies leading to a localized inflammation reaction in the joints. An important type of antibody involved in RA include antibodies against citrullinated peptides/proteins. Citrullination is a normal cellular process, however, RA is marked by a state of pathologic hypercitrullination. Specific risk factors, such as genetic predisposition, gender, and smoking, have been identified as contributing to the development of RA, but the mechanism behind how autoantibodies lead to RA pathology, what leads to pathological hypercitrullination and the generation of anti-citrullinated protein antibodies (ACPA) is insufficiently understood. It has been established that RA patients have antibodies to human endogenous retroviruses (HERVs), and more specifically, to the HERV-K family of such viruses. HERV-Ks are ancient retroviruses that have been integrated into the human genome and rendered inactive due to the accumulation of mutations. However, the presence of HERV-K antibodies suggests that there may be the capability to restore viral transcription in certain cases. If HERV-K was to be expressed, it would elicit the same immune reaction that exogenous viruses do, however, since it is a part of the human genome, this would effectively be an autoimmune reaction. OBJECTIVE: This thesis aims to explore the RA immune response to HERV-K, with a focus on neutrophils. Further, the relationship between HERV-K immunity and pathological hypercitrullination will also be explored. METHODS: Our studies utilized protein/antibody detection techniques to quantitate specific proteins/antibodies in sera and leukocytes isolated from RA patients. These techniques included enzyme-linked immunosorbent assay (ELISA), flow cytometry, and western blot analysis. Antibodies against HERV-K envelope (Env), an important viral protein, and citrullinated-Env (citEnv) were affinity-purified from patient sera to be used in these experiments. Results: Our experiments first replicated a result that has been previously established in the literature: RA patients produce antibodies against HERV-K. More specifically, we found that RA patient’s Env antibodies almost exclusively recognize the surface portion of the protein. Our data also presents the finding that patient antibodies are more reactive to citEnv than they are to unmodified Env, and that citEnv is expressed on patient neutrophils. Lastly, we found that some patient neutrophils are associated with the membrane attack complex of complement. CONCLUSION: The fact that RA patient’s neutrophils express citEnv suggests a link between HERV-K and the pathological hypercitrullination that’s a hallmark of RA. Additionally, the association of the membrane attack complex (MAC) with patient neutrophils suggests a potential mechanism of how this may occur: neutrophils express Env (following the re-initiation of HERV-K transcription), which then undergo citrullination and get recognized by ACPA, stimulating an immune response. This leads to complement activation and eventually MAC-induced neutrophil lysis. In doing so, neutrophils, which are enriched in citrullinating enzymes, can spill such enzymes into the extracellular space, leading to further citrullination and ACPA development. Further studies need to be done to confirm these data, as well as to fill gaps in knowledge regarding the novel hypothesis that HERV-K expression in RA patients may play a role in hypercitrullination and the disease’s pathogenesis.

Includes bibliographical references.

Introduction: There is a high incidence of patient presentation at our hospital following train accidents. The literature describing the pattern of injuries and management following these accidents is sparse. In addition, the literature looking specifically at orthopaedic injuries and their management is lacking. The aim of this study was to investigate the demographics of patients sustaining traumatic injuries following train accidents and to specifically analyse injury patterns and management of orthopaedic injuries. Furthermore, the mortality rates and the effectiveness of advanced surgical care have also been evaluated and the outcomes of newer limb salvage techniques compared to amputation, which has been widely used in the past. Methods This is a retrospective observational study of patients presenting to a Level I Trauma Centre in Cape Town, South Africa. Prospectively collected data from January 2013 to July 2019 was reviewed retrospectively. All patients presenting with injury mechanism ‘train casualty' or ‘train-' were included in the study. Data was collected by one individual using a set proforma to ensure consistency. Patient folders were reviewed to ascertain specific details including mechanism of injury, types of injury and surgical intervention. Results Two hundred and twenty-two patients were identified through the trauma registers as presenting as train casualties to the Groote Schuur Hospital (GSH) trauma department; 48 patients were excluded, leaving a total of 174 patients included in the study; 92 of these were orthopaedic referrals. The average age was 32 years and males accounted for 87% of the patients. Fifty-four patients were involved in violence, 38 were accidental falls and 15 had been jumping on or off a train. Eight patients (4.6%) in total died in the trauma unit. Most accidents occurred between the hours of 20:00 h and 05:00 h. Of the orthopaedic referrals, males accounted for 89% of patients and the average age was 33 years. Fortynine percent of patients sustained upper limb injuries and 49% sustained lower limb injuries. Spinal injuries were found in 27% of patients and pelvic injuries in 5%. Revised trauma score was calculable for 65 patients, with a mean score of 7.5. Each orthopaedic patient had on average injuries to 1.74 body parts. Thirty-five patients sustained open fractures (38%). Non- operative management was undertaken in 32% of patients. Operative management took place in 68% of patients. A total of 61 patients had surgery for orthopaedic injuries. Each patient underwent on average 2.38 operations. There were 145 theatre encounters for 172 procedures. There were 19 amputation procedures for 12 patients; 10 of these patients had sustained traumatic amputations. There were 10 postoperative complications in total. Conclusion The findings of this retrospective descriptive study provide an insight into train accident victims and their orthopaedic injuries and management with a large sample size. As could be predicted from previous studies, the victims of these accidents are young males from poor socioeconomic areas. The victims who make it to hospital have a good chance of survival and even limb salvage. However, in this day and age, more needs to be done in terms of controlling and preventing railway violence. Similarly, increased health and safety measures need to be implemented in order to minimise accidental injuries on the railways in Cape Town. Further research into the long-term outcomes of these patients and their surgeries would provide further evidence into the role for limb salvage procedures.