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and introduction: The HIV/AIDS pandemic has irrevocably changed the face of healthcare delivery and research. This is especially true in South Africa with its estimated 5.26 million HIV-infected people. It was not until the significant up scaling of the anti-retroviral therapy roll-out that the HIV-incidence rate in South Africa started declining substantially from an estimated 1.32% in 2005 to an estimated 0.85% in 2013. Cytopaenias are common in HIV-infected individuals. Their risk of developing anaemia ranges from 60 to 95% during the course of the disease. The impact of HIV/AIDS on blood utilisation in the country is largely unknown. With this study we aimed to address the lack of knowledge regarding the blood requirements of the HIV-positive population and how the changing epidemic may affect future blood utilisation, by establishing what proportion of blood issued to medical and surgical patients admitted to a large referral hospital in the Eastern Cape Province of South Africa, was issued to HIV-positive patients Methods We conducted a retrospective cross-sectional study analysing the prevalence of HIV among patients receiving blood and blood products. Baseline demographic data was collected on all patients admitted during a three-month period with additional clinical data collected on patients who received a blood transfusion. Ethics approval was obtained from the UFS and the South African National Blood Service (SANBS). Approval to complete the study was obtained from the senior management of the Hospital and the local blood service offices. Following a short pilot study during which the various systems were tested, data collection commenced on 7 January 2013 and was completed on 6 April 2013. Results A total of 3438 patient admissions were included in the study with equal distribution between male and female patients. Patients tended to be younger with almost 75% of patients younger than 60. Almost 8% of patients were transfused. HIV status was poorly recorded. Only 25% of patients had a HIV test result on file. The reported HIV prevalence was 14%. The median LOS was 7 days and in-patient mortality 8%. During 330 transfusion episodes, 267 patients received 609 units of RBC, i.e. 1.24 transfusion episodes per patient. Except for 6 units, all units issued were recorded as transfused, translating to a transfused ratio of 1.00:0.99. Being HIV-positive, surgical admissions, having been admitted to ICU, extended LOS and death at discharge were independently association with having received a transfusion. Mean pre- and post-transfusion Hb levels were significantly lower in HIV-positive patients and these patients were less likely to have had a correctly completed consent form on record, but were more likely to have had their anaemia investigated. Discussion The complex HIV-testing at this facility hampered the analysis of the data and raises serious public health questions. Despite this, it is clear that HIV significantly impacts blood utilisation at this facility. HIV-prevalence among all admissions was found to be ~ 14%, as compared to the almost 20% among the recipients of blood. Similarly 26% of the transfusion episodes involved HIV positive patients. However, only 16% of the units issued were issued to HIV-positive patients. The data suggests that HIV-status significantly influenced doctorsâ transfusion practices. HIV-positive patients had significantly lower pre- and post-transfusion Hb levels suggesting lower transfusion triggers and targets for HIV-positive patients. These patients were also less likely to have had correctly completed consent forms; only a third of HIV-positive patients had correctly completed forms on record. Conclusion HIV contributes significantly to the blood utilisation at a tertiary hospital in the Eastern Cape and would appear to influence cliniciansâ transfusion practice. The exact nature of the interaction between HIV and transfusion requires further investigation.

Physical growth

Inaug.-Diss.--Universität Erlangen-Nürnberg, Nürnberg. / Vita.

Thesis--Universität Erlangen-Nürnberg. / At head of title: Aus dem Seminar für Geschichte der Medizin der Universität Erlangen-Nürnberg. Vita. Includes index.

Point-of-care detection of urine lipoarabinomannan (LAM) is a low-cost rapid TB diagnostic for use in HIV co-infected patients. However, its sensitivity in these patients is suboptimal. Strategies to improve its performance is a need. The hypothesis was that early morning urine (EMU), rather than random urine sampling, would improve LAM's sensitivity. Methods Recruitment process conducted between June 2012 and February 2014 for HIV-infected patients from four hospitals in Cape Town, South Africa presenting with possible TB (all patients initiated on TB treatment). Fresh random and early morning urine (EMU) samples (~10-30 ml) collected in sterile containers. Following the manufacturer's instructions, an Alere Determine® TB Lateral flow assay performed on each sample, using both grade 1 and 2 cut-points. A single sputum Xpert MTB/RIF and/or liquid TB culture was a reference standard. Those designated probable TB patients were sputum Xpert MTB/RIF and/ TB culture negative, but started on TB treatment.

The most common risk factors for chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC) include chronic alcohol abuse and infection with hepatitis B (HBV) or hepatitis C (HCV) virus. Growing evidence from human studies and experimental models suggests that pre-degenerative and premalignant abnormalities include disturbances in intracellular signaling and ongoing injury with oxidative stress, inflammation, and lipotoxicity. The major signal transduction pathways affected in both degenerative and neoplastic disease states in liver include: insulin/IGF, Wnt/β-catenin, and others.

There is a pressing need for modeling of the symbiotic and at times dysbiotic relationship established between bacterial microbiomes and human mucosal surfaces. In particular clinical studies have indicated that the complex vaginal microbiome (VMB) contributes to the protection against sexually-transmitted pathogens including the life-threatening human immunodeficiency virus (HIV-1). The human microbiome project has substantially increased our understanding of the complex bacterial communities in the vagina however, as is the case for most microbiomes, very few of the community member species have been successfully cultivated in the laboratory limiting the types of studies that can be completed. A genetically controlled ex vivo model system is critically needed to study the complex interactions and associated molecular dialog. We present the first vaginal mucosal culture model that supports colonization by both healthy and dysbiotic VMB from vaginal swabs collected from routine gynecological patients. The immortalized vaginal epithelial cells used in the model and VMB cryopreservation methods provide the opportunity to reproducibly create replicates for lab-based evaluations of this important mucosal/bacterial community interface. The culture system also contains HIV-1 susceptible cells allowing us to study the impact of representative microbiomes on replication. Our results show that our culture system supports stable and reproducible colonization by VMB representing distinct community state types and that the selected representatives have significantly different effects on the replication of HIV-1. Further, we show the utility of the system to predict unwanted alterations in efficacy or bacterial community profiles following topical application of a front line antiretroviral.

Mycobacterium chimaera, a nontuberculous mycobacterium, is a member of the Mycobacterium avium complex (MAC). This microorganism has recently gained significant notoriety for its association with outbreaks in patients exposed to contaminated heater –cooler devices used during open heart surgeries. We report a case of Mycobacterium chimaera pulmonary infection in a healthcare worker who presented with cough, low grade fever and weight loss with evidence of a lung mass that was initially thought to be a tumor on CT scan imaging. The patient underwent partial left lung lobectomy and pathology revealed necrotizing granulomas with acid fast bacilli and a culture grew M. chimaera. The patient received combination antimycobacterial therapy according to susceptibility results for twelve months with complete resolution of his symptoms and radiographic findings. Infection Control investigation could not find a source of infection in the hospital where he worked during the last ten years. However, the patient rotated in different hospitals before coming to work at this facility and assisted in surgeries in several operating rooms where the heater-cooler devices in question were used.

Myocardial infarction (MI), characterized by ischemia-induced cardiomyocyte apoptosis, is the leading cause of mortality worldwide. NR4A2, a member of the NR4A orphan nucleus receptor family, is upregulated in mouse hearts with MI injury. Furthermore, NR4A2 knockdown aggravates heart injury as evidenced by enlarged hearts and increased apoptosis. To elucidate the underlying mechanisms of NR4A2-regulated apoptosis, we used H9c2 cardiomyocytes deprived of serum and neonatal rat cardiomyocytes (NRCMs) exposed to hypoxia to mimic ischemic conditions in vivo. As NR4A2 knockdown aggravates cardiomyocyte apoptosis, while NR4A2 overexpression ameliorates it, NR4A2 upregulation was considered an adaptive response to ischemia-induced cardiomyocyte apoptosis. By detecting changes in LC3 and using autophagy detection tools including Bafilomycin A1, 3MA and rapamycin, we found that NR4A2 knockdown promoted apoptosis through blocking autophagic flux. This apoptotic response was phenocopied by downregulation of NR4A2 after autophagic flux was impaired by Bafilomycin A1. Further study showed that NR4A2 binds to p53 directly and decreases its levels when it inhibits apoptosis; thus, p53/Bax is the downstream effector of NR4A2-mediated apoptosis, as previously reported. Changes in p53/Bax that were regulated by NR4A2 were also detected in injured hearts with NR4A2 knockdown. In addition, miR-212-3p is the upstream regulator of NR4A2, and it could downregulate the expression of NR4A2, as well as p53/Bax. The mechanism underlying the role of NR4A2 in apoptosis and autophagy was elucidated, and NR4A2 may be a therapeutic drug target for heart failure.