An investigation into the perception of academic staff on talent retention in higher education institutions.

Masters Degree. University of KwaZulu-Natal, Durban.Among the findings of the institutional audits performed by the HEQC (January 2012), institutions experienced serious challenges in retaining competent academic staff (HEQC Report, 2012, p.34). The aim is to explore the motivation and hygiene needs that influence staff retention at tertiary institutions; and to determine the perceptions of staff regarding staff retention practices in tertiary institutions. This study uses quantitative research methodology. Academic staff is the target population for this study with a sample of 78 participants. The highest percentage of 85.8 per cent (n=67) indicates that academic staff are still available for another employer who may want to hire them, and they could leave anytime. The majority of employees, 87.3 per cent (n=62) are unhappy with developmental opportunities in the universities. Additionally, those unhappy with training opportunities and unhappy with the job itself include 80.3 per cent (n=57). The majority of the respondents, 44.8 per cent (n=35) have a negative perception towards staff retention. After analysis has been made, it shows that good retention could ensue, but only through taking the respondents’ views into consideration, when the institutions develop their retention policy, and talent management strategies. The supervisor is the main factor in an employee’s decision to stay or leave. He/she should be a trust-builder, a good communicator, talent developer and a good coach. The research revealed that one of the bedrock aspects of the institution, namely working conditions, seems not to be conducive for better performance and this affects other strategies in the long run, and the work system causes many employees to fail to perform, and as a result, they feel demotivated and want to leave the institution. Promotion and compensation have also shown to be other factors that need to be overhauled in order to keep employees from leaving the institution. Finally, it should be clear to the employees what constitutes success in the institution. Employees should be valued and recognised for the work they are contributing, and recognition is the key for high performance and effective work management

Characterization of the interaction between rat pyruvate dehydrogenase kinase 4 and adp

The primary role of pyruvate dehydrogenase kinase (PDK) is to regulate the activity of pyruvate dehydrogenase complex (PDC) with respect to the metabolic clearance of glucose via a phosphorylation mechanism. Therefore, inhibition of PDK is predicted to be important in the treatment of diabetes. ADP binds to the active site of PDK; and has been shown to inhibit PDK activity. This research work was aimed at studying one of the isoforms of PDK, specifically the rodent form, PDK4 (rPDK4) and further elucidating the binding properties of ADP to rPDK4. The hypothetical structure of rPDK4 was modelled based on the coordinates of the published rPDK2 structure. The overall structural topology of rPDK2 appears to be preserved in rPDK4. Further, the ADP binding site between rPDK2 and rPDK4 was conserved at both the primary and tertiary level, and this suggested the mechanism of ADP binding to rPDK2 would be similar to that of rPDK4. A histidine tagged-rPDK4 protein was expressed and purified using affinity and gel filtration chromatography. It was determined to be a homodimer (97 kDa) comprising two identical subunits. The rPDK4 protein was further identified to be rPDK4 using Western blot analysis as it reacted positively with an anti-rPDK4 monoclonal antibody. The purified rPDK4 protein contained kinase activity since it was able to undergo autophosphorylation and subsequently phosphorylate a peptide that contained the E1a subunit sites that are known to be phosphorylated by PDKs. The structure of rPDK4 protein was also characterised using circular dichroism and fluorescence spectroscopy.The spectroscopic data of rPDK4 was consistent with published data on the structure of rPDK4. The binding of ADP and ATP was studied using fluorescence quenching as both these ligands quench the intrinsic tryptophan fluorescence of rPDK4. The dissociation constant (Kd) values for ADP and ATP were determined to be 37 and 17.4 μM, respectively. The moderate affinity binding of ATP will greatly favour the exchange of ADP for a molecule of ATP to prevent PDK inhibition by ADP

The N-subdomain of the thioredoxin fold of glutathione transferase is stabilised by topologically conserved leucine residue

A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 2012The thioredoxin-like (Trx-like) fold is preserved in various protein families with diverse functions despite their low sequence identity. Glutathione transferases (GSTs) are characterised by a conserved N-terminal domain with a thioredoxin–like βαβαββα secondary structure topology and an all alpha-helical domain. GSTs are the principal phase II enzymes involved in protecting cellular macromolecules from a wide variety of reactive electrophilic compounds. It catalyses the conjugation of reduced glutathione (GSH) to an electrophilic substrate to form a hydrophilic and non-toxic compound. The binding site for GSH (G-site) is located in the N-terminal domain of GSTs. The sequence identity within members of the Trx-like superfamily is low; however, the members of this family fold into a conserved βαβαββα topology. It, therefore, seems reasonable that there are topologically conserved residues within this fold whose main role is to drive folding and/or maintain the structural integrity of the Trx-like fold. Structural alignments of the N-subdomain (βαβ motif) of the GST family shows that Leu7 in β1 and Leu23 in α1 are topologically conserved residues. The Leu7 side chain is involved in the packing of α1β1α2 and α3, whilst Leu23 is mainly involved in van der Waals interactions with residues in α1 and the loop region connecting α1 and β2. Taking into account the types of interaction that both Leu7 and Leu23 are involved in, as well their location in close proximity to the G-site, it was postulated that both these residues may play a role in the structure, function and stability of the GST family of proteins. Leu7 and Leu23 are not directly involved in the binding of GSH but they could be important in maintaining the G-site in a functional conformation via correct packing of the Nsubdomain. The homodimeric human class Alpha of GST (hGSTA1-1) was used as the representative of the GST family to test this hypothesis. The bulky side chains of Leu7 and Leu23 were replaced with a less bulky alanine residue to prevent altering the hydrophobicity of the βαβ motif. The effect of the mutation on the structure, function and stability of hGSTA1-1 was, therefore, studied in comparison with the wild-type using spectroscopic tools, X-ray crystallography, functional assays and conformational stability studies. The impact of the mutations on the structure of the enzyme was determined using spectroscopic tools and X-ray crystallography. The X-ray structures of the L7A and L23A mutants were resolved at 1.79 Å and 2.2 Å, respectively. Analysis of both X-ray structures shows that the mutation did not significantly perturb the global structure of the protein, which correlates with far-UV CD and intrinsic fluorescence spectroscopic data. In addition, structural alignments using the C-alpha gave root mean square deviation (r.m.s.d) values of 0.63 Å (L7A) and 0.67 Å (L23A) between the wild-type and mutant structures. However, both the L7A and L23A structures showed the presence of a cavity within the local environment of each mutation. The functional properties of the mutants were also similar to those of the wild-type as determined by specific activity and 8-anilino-1-naphthalene sulfonate (ANS)-binding, indicating that Leu7 and Leu23 are not involved in the function of hGSTA1- 1. The conformational stability of L7A and L23A proteins was probed using thermal-induced unfolding, pulse proteolysis and urea-induced equilibrium unfolding studies. The thermal stability of L7A and L23A hGSTA1-1 was reduced in comparison to the wild-type protein. This was consistent with proteolytic susceptibility of L7A and L23A proteins which indicates that both mutants are more prone to thermolysin digestion when compared to wild-type hGSTA1-1. This also correlates with urea-induced equilibrium studies. The ΔG(H2O) value (23.88 kcal.mol-1) for the wild-type protein was reduced to 12.6 and 10.49 kcal.mol-1 in L7A and L23A hGSTA1-l, respectively. Furthermore, the m-values obtained for the L7A and L23A proteins were 1.46 and 1.06 kcal.mol-1.M-1 urea, respectively; these were much lower than that obtained for the wild-type protein (4.06 kcal.mol-1.M-1 urea). The low m-values obtained for the mutant proteins indicated that the cooperativity of hGSTA1-1 unfolding was significantly diminished in both mutations. The results obtained in this study indicate that the topologically conserved Leu7 and Leu23 in the N-subdomain of hGSTA1-1 play a crucial role in maintaining the structural stability of the thioredoxin-like domain and are not involved in the function of the enzyme

Current Immunotherapeutic Treatments in Colon Cancer

The immune system is able to act against cancer cells and consequently these cells have developed a range of responses to evade or suppress the immune systems anticancer responses. The concept of cancer immunotherapy is based on techniques developed to restore or boost the ability of the immune system to recognize and target tumor cells. It is known that colon cancer does initiate an immune response and that this type of cancer initiates pathways and responses to evade or suppress the immune system. This chapter will discuss some of the dominant therapies being developed to treat colon cancer based on the concept of cancer immunotherapy. Cancer vaccines are based on the concept of providing the immune system with antigen targets derived from tumor-specific molecules, while monoclonal antibodies involve the development of antibodies specifically targeting proteins expressed on the surface of tumor cells. Antibody-based immunotherapy has further applications in the use of bispecific antibodies (BsAb), which are synthetic antibodies designed to be able to recognize two different antigens or epitopes and in this way can increase the immunoresponse and limit immune evasion observed in mono-targeted therapy. Immune checkpoint inhibitors target proteins that are responsible for keeping immune responses in check. Tumor cells overexpress these proteins in order to evade the immune response. Blocking these proteins will lead to an increased immune response against these cells. Cytokine-based immunotherapies involve the use of the immune systems’ own molecular messengers that are responsible for a robust immune response, to boost the antitumor response of the immune system. Oncolytic viral therapy is based on the use of viruses that selectively infect and replicate in cancer and associated endothelial cells and subsequently kills these cells. Adoptive immunotherapy involves the use of immune cells from the patient to be cultured and altered in the laboratory and then reintroduced to boost the immune response. This is normally performed with T cells. Immunotherapy may be the next logical step in the development of an effective therapy for colon cancer and other cancers. The combination of these therapies with traditional chemotherapy or radiotherapy has shown promise in cancer treatment

Protocol: Mapping social networks, social influence and sexual health among youth in rural KwaZulu-Natal, the Sixhumene cohort study [version 1; peer review: awaiting peer review]

Background: Sexual behaviour and sexually transmitted infections are strongly affected by social connections, and interventions are often adapted more readily when diffused through social networks. However, evidence on how young people acquire ideas and change behaviour through the influence of important social contacts is not well understood in high-HIV-prevalence settings, with the result that past peer-led HIV-prevention interventions have had limited success. / Methods: We therefore designed a cohort study (named Sixhumene or ‘we are connected’) to follow young people in three rural and small-town communities in uMkhanyakude district, KwaZulu-Natal, South Africa, and the people that these youth identify as important in their lives. We will interview them five times over three years, at each visit collecting information on their socioeconomic, social and sexual health lives, and testing them for HIV and herpes simplex virus 2 (HSV-2). We will use this information to understand how these young people’s sexual health decisions are formed. This will include evaluating how poor sexual health outcomes are correlated across social networks, how youth mimic the attitudes and behaviours of those around them, who is at greatest risk of acquiring HIV and HSV-2, and who might be most influential within communities and thus best able to promote protective interventions. / Discussion: The information gathered through this study will allow us to describe social connection and influence spread through these real-world social networks, and how this leads to sexual health outcomes. Sixhumene will provide vital inputs for mathematical models of communities and spreading processes, as well as inform the development of effective interventions to protect the sexual health of community members through appropriate targeting with optimised messaging requiring fewer resources

Protocol: Mapping social networks, social influence and sexual health among youth in rural KwaZulu-Natal, the Sixhumene cohort study

Background: Sexual behaviour and sexually transmitted infections are strongly affected by social connections, and interventions are often adapted more readily when diffused through social networks. However, evidence on how young people acquire ideas and change behaviour through the influence of important social contacts is not well understood in high-HIV-prevalence settings, with the result that past peer-led HIV-prevention interventions have had limited success. Methods: We therefore designed a cohort study (named Sixhumene or ‘we are connected’) to follow young people in three rural and small-town communities in uMkhanyakude district, KwaZulu-Natal, South Africa, and the people that these youth identify as important in their lives. We will interview them five times over three years, at each visit collecting information on their socioeconomic, social and sexual health lives, and testing them for HIV and herpes simplex virus 2 (HSV-2). We will use this information to understand how these young people’s sexual health decisions are formed. This will include evaluating how poor sexual health outcomes are correlated across social networks, how youth mimic the attitudes and behaviours of those around them, who is at greatest risk of acquiring HIV and HSV-2, and who might be most influential within communities and thus best able to promote protective interventions. Discussion: The information gathered through this study will allow us to describe social connection and influence spread through these real-world social networks, and how this leads to sexual health outcomes. Sixhumene will provide vital inputs for mathematical models of communities and spreading processes, as well as inform the development of effective interventions to protect the sexual health of community members through appropriate targeting with optimised messaging requiring fewer resources.</ns3:p

Optimised electronic patient records to improve clinical monitoring of HIV-positive patients in rural South Africa (MONART trial): study protocol for a cluster-randomised trial

Background There is poor viral load monitoring (VLM) and inadequate management of virological failure in HIV-positive individuals on antiretroviral therapy in rural KwaZulu-Natal, South Africa. This could be contributing to increasing HIV drug resistance in the setting. This study aims to investigate the clinical and process impediments in VLM within the health system and to evaluate a quality improvement package (QIP) to address the identified gaps. The QIP comprises (i) a designated viral load champion responsible for administrative management and triaging of viral load results (ii) technological enhancement of the routine clinic-based Three Interlinked Electronic Register (TIER.Net) to facilitate daily automatic import of viral load results from the National Health Service Laboratory to TIER.Net (iii) development of a dashboard system to support VLM. Methods/design The study will evaluate the effectiveness of the QIP compared to current care for improving VLM and virological suppression using an effectiveness implementation hybrid type 3 design. This will use a cluster-randomised design with the primary healthcare clinics as the unit of randomisation with ten clinics randomised in a 1:1 ratio to either the intervention or control arm. We will enrol 150 HIV-positive individuals who had been on ART for ≥ 12 months from each of the ten clinics (750 in 5 intervention clinics vs. 750 in 5 control clinics) and follow them up for a period of 12 months. The primary outcome is the proportion of all patients who have a viral load (VL) measurement and are virally suppressed (composite outcome) after 12 months of follow up. Secondary outcomes during follow up include proportion of all patients with at least one documented VL in TIER.Net, proportion with VL ≥ 50 copies/mL, proportion with VL ≥ 1000 copies/mL (virological failure) and subsequent switch to second-line ART. Discussion We aim to provide evidence that a staff-centred quality improvement package, designated viral load monitoring champion, and augmentation of TIER.Net with a dashboard system will improve viral load monitoring and lead to improved virological suppression. Trial registration: This trial is registered on ClinicalTrials.gov on 8 Oct 2021. Identifier: NCT05071573; https://clinicaltrials.gov/ct2/show/NCT05071573?term=NCT05071573&draw=2&rank=

Isisekelo Sempilo study protocol for the effectiveness of HIV prevention embedded in sexual health with or without peer navigator support (Thetha Nami) to reduce prevalence of transmissible HIV amongst adolescents and young adults in rural KwaZulu-Natal: a 2 × 2 factorial randomised controlled trial

BACKGROUND: Antiretroviral therapy (ART) through universal test and treat (UTT) and HIV pre-exposure prophylaxis (PrEP) substantially reduces HIV-related mortality, morbidity and incidence. Effective individual-level prevention modalities have not translated into population-level impact in southern Africa due to sub-optimal coverage among adolescents and youth who are hard to engage. We aim to investigate the feasibility, acceptability, and preliminary population level effectiveness of HIV prevention services with or without peer support to reduce prevalence of transmissible HIV amongst adolescents and young adults in KwaZulu-Natal. METHODS: We are conducting a 2 × 2 factorial trial among young men and women aged 16-29 years, randomly selected from the Africa Health Research Institute demographic surveillance area. Participants are randomly allocated to one of four intervention combinations: 1) Standard of Care (SOC): nurse-led services for HIV testing plus ART if positive or PrEP for those eligible and negative; 2) Sexual and Reproductive Health (SRH): Baseline self-collected vaginal and urine samples with study-organized clinic appointments for results, treatment and delivery of HIV testing, ART and PrEP integrated with SRH services; 3) Peer-support: Study referral of participants to a peer navigator to assess their health, social and educational needs and provide risk-informed HIV prevention, including facilitating clinic attendance; or 4) SRH + peer-support. The primary outcomes for effectiveness are: (1) the proportion of individuals with infectious HIV at 12 months and (2) uptake of risk-informed comprehensive HIV prevention services within 60 days of enrolment. At 12 months, all participants will be contacted at home and the study team will collect a dried blood spot for HIV ELISA and HIV viral load testing. DISCUSSION: This trial will enable us to understand the relative importance of SRH and peer support in creating demand for effective and risk informed biomedical HIV prevention and preliminary data on their effectiveness on reducing the prevalence of transmissible HIV amongst all adolescents and youth. TRIAL REGISTRATION: Trial Registry: clincialtrials.gov. CLINICALTRIALS: gov Identifier NCT04532307 . Registered: March 2020

Prevalence of Curable Sexually Transmitted Infections in a Population-Representative Sample of Young Adults in a High HIV Incidence Area in South Africa

BACKGROUND: Recent population-representative estimates of sexually transmitted infection (STI) prevalence in high HIV burden areas in southern Africa are limited. We estimated the prevalence and associated factors of 3 STIs among adolescents and young adults (AYA) in rural South Africa. METHODS: Between March 2020 and May 2021, a population-representative sample of AYA aged 16 to 29 years were randomly selected from a Health and Demographic Surveillance Site in rural KwaZulu-Natal, South Africa, for a 2 × 2 factorial randomized controlled trial. Participants in 2 intervention arms were offered baseline testing for gonorrhea, chlamydia, and trichomoniasis using GeneXpert. Prevalence estimates were weighted for participation bias, and logistic regression models were used to assess factors associated with STIs. RESULTS: Of 2323 eligible AYA, 1743 (75%) enrolled in the trial. Among 863 eligible for STI testing, 814 (94%) provided specimens (median age of 21.8 years, 52% female, and 71% residing in rural areas). Population-weighted prevalence estimates were 5.0% (95% confidence interval [CI], 4.2%-5.8%) for gonorrhea, 17.9% (16.5%-19.3%) for chlamydia, 5.4% (4.6%-6.3%) for trichomoniasis, and 23.7% (22.2%-25.3%) for any STI. In multivariable models, female sex (adjusted odds ratio [aOR], 2.24; 95% CI, 1.48-3.09) and urban/periurban (vs. rural) residence (aOR, 1.48; 95% CI, 1.02-2.15) were associated with STIs; recent migration was associated with lower odds of STI (aOR, 0.37; 95% CI, 0.15-0.89). Among those with an STI, 53 (31.0%) were treated within 7 days; median time to treatment was 11 days (interquartile range, 6-77 days). CONCLUSIONS: We identified a high prevalence of curable STIs among AYA in rural South Africa. Improved access to STI testing to enable etiologic diagnosis and rapid treatment is needed

Protocol: Leveraging a demographic and health surveillance system for Covid-19 Surveillance in rural KwaZulu-Natal

A coordinated system of disease surveillance will be critical to effectively control the coronavirus disease 2019 (Covid-19) pandemic. Such systems enable rapid detection and mapping of epidemics and inform allocation of scarce prevention and intervention resources. Although many lower- and middle-income settings lack infrastructure for optimal disease surveillance, health and demographic surveillance systems (HDSS) provide a unique opportunity for epidemic monitoring. This protocol describes a surveillance program at the Africa Health Research Institute�s Population Intervention Platform site in northern KwaZulu-Natal. The program leverages a longstanding HDSS in a rural, resource-limited setting with very high prevalence of HIV and tuberculosis to perform Covid-19 surveillance. Our primary aims include: describing the epidemiology of the Covid-19 epidemic in rural KwaZulu-Natal; determining the impact of the Covid-19 outbreak and non-pharmaceutical control interventions (NPI) on behaviour and wellbeing; determining the impact of HIV and tuberculosis on Covid-19 susceptibility; and using collected data to support the local public-sector health response. The program involves telephone-based interviews with over 20,000 households every four months, plus a sub-study calling 750 households every two weeks. Each call asks a household representative how the epidemic and NPI are affecting the household and conducts a Covid-19 risk screen for all resident members. Any individuals screening positive are invited to a clinical screen, potential test and referral to necessary care � conducted in-person near their home following careful risk minimization procedures. In this protocol we report the details of our cohort design, questionnaires, data and reporting structures, and standard operating procedures in hopes that our project can inform similar efforts elsewhere.</ns4:p