The Influence of HIV-1 Subtype C LTR Genotype on Latency Potential

The persistence of latent viral reservoirs, that are insensitive to antiretroviral therapy (ART), remains the greatest barrier to HIV-1 eradication. The role that viral factors play in HIV-1 latency establishment and maintenance is poorly understood, and characterisation of these factors is imperative for the development of curative strategies or interventions that could lead to HIV-1 remission in infected individuals. Subtype level genotypic variation within regulatory elements of the HIV-1 promoter, the long terminal repeat (LTR), has been shown to influence latency establishment in in vitro models. We investigated the influence of inter-participant subtype C LTR genotypic variation on the establishment of latency in a dual reporter HIV-1 plasmid model and evaluated potential correlates of this latency potential. Long terminal repeats from 11 ART-naïve, acutely subtype-C infected women in the CAPRISA 004 cohort from Durban, South Africa were cloned into an HIV-1-expressing vector (pRGH) used to generate pseudovirions following HEK293T transfection. Pseudoviruses harboured a gag-eGFP gene under the control of the participant LTR, allowing measurement of active replication, and an mCherry gene under the control of a constitutive CMV promoter allowing measurement of viral integration. Latency potential was expressed as the ratio of mCherry only (latent) to eGFP and mCherry (active replication), as measured by flow cytometry after infection of Jurkat E6-1 and CEM.NKR CCR5+ cell lines before and after T cell activation with PMA/Ionomycin. A panel of LTRs cloned into a pGL4.10 luciferase expression vector were used to measure basal LTR expression and Tat-induced LTR expression. All LTR sequences were classified as subtype C, with an average inter-participant pairwise DNA distance of 7.6%. The median basal LTR activity was approximately two times higher than that of the BaL isolate (interquartile range: 1.38-2.14), and Tatinduced activity approximately nine times higher than that of BaL (interquartile range: 6.16-10.33). We observed consistently greater proportions of latently infected cells than actively infected cells. In Jurkat E6-1 cells, the median latent:active infection ratio was 1.97 (range 0.86-2.83; three experiments). Latency was reversible in a proportion of cells as the median latent:active infection ratio decreased to 0.55 (range 0.46-0.78). The latent:active ratio was unchanged, post-stimulation, in CEM.NKR CCR5+ cells and was therefore found not to be a suitable cell-line for the model. Latency potential did not correlate with basal or Tat-induced activity (Spearman correlation tests, basal p=0.25, r=-0.38, Tat-induced p=0.42, r=-0.27). The DNA distance in characterised functional sites from consensus did not correlate with latency potential (Spearman correlation test p=0.67, r=0.14). Our data suggest that HIV-1 LTRs have intrinsic properties which influence latency potential and the proportion of latently infected cells early post-infection. However, since differences were independent of basal and Tat-induced LTR activity, other factors such as regulatory element interaction and the efficiency of recruitment of molecules responsible for establishing latency, such as histone modifiers, may play a role

Dental implant retaining screws: the effect of using gold or titanium on preload

MDent, Faculty of Health Sciences, University of the WitwatersrandPURPOSE The purpose of this in vitro investigation was to determine the effect of using either gold or titanium retaining screws on preload in the dental implant body-abutment complex. This preload is of vital importance for the long term success of the dental implant complex. Inadequate preload results in either loosening or fracture of the retaining screw, and is the most commonly occurring mechanical complication in implant supported/retained prostheses. Similar complications occur when excessive preload is applied to the retaining screws. These complications can result in unscheduled visits with costly and time consuming repairs for the clinician and patient. Routine maintenance protocols for implant supported prostheses range from biannually to five year visits to the dentist. Maintenance visits involve removal of the prosthesis facilitating cleaning of both the implant and prosthesis and inspection of retaining screws . This study sought to gain insight into changes in preload generation after repeated torque application to gold and titanium screws and to observe whether gold or titanium generated better preload. A maintenance protocol would be suggested if any observable pattern was noted. MATERIALS AND METHODS The test setup consisted of an implant body, a cylindrical transmucosal abutment and the retaining screws (gold or titanium). The implant body was anchored using a load cell. Transmucosal abutments were attached to the implant body using either a gold or titanium v retaining screw. A torque gauge was used to apply torque of 20Ncm, 32Ncm and 40Ncm to the retaining screws. This was undertaken to investigate the effect of gold or titanium on preload generated. The effect of applying torque beyond manufacturers recommended 32Ncm was carried out to see if greater preloads could be achieved. All components were from the Southern Implant system. RESULTS Gold retaining screws were found to achieve consistently higher preload values than titanium retaining screws. Preload values were not significantly different from the first to the tenth torque cycle. Titanium screws showed more consistent preload values, albeit lower than those of gold retaining screws. However due to possible galling of the internal thread of the implant body by titanium screws, gold screws remain the retaining screw of choice. Maintenance protocols suggest replacing retaining screws every 20 years. After ten torque cycles were applied to each screw there was an insignificant change in preload generated in both titanium and gold screws. This study was therefore inconclusive with regards to maintenance protocols. CONCLUSION Within the limitations of this study, gold retaining screws generated better preload than titanium. Torque application beyond manufacturers’ recommendations resulted in a more stable implant complex. Further investigation into repeated torque application to retaining screws is required, to determine ideal maintenance protocols

Emotional intelligence and effective team functioning of MBA syndicate groups at the NMMU business school

A common issue in leadership development is the high flyers who reach a position where their lack of “soft” skills hampers their performance and proves a barrier to their continued progression to higher levels of responsibility (Newell, 2002: 288). Business Schools offering Masters in Business Administration (MBA) programmes assist in developing managers with not just managerial competence but also with “soft” skills. By delivering educated business managers, these managers through their intellectual skills and community sensitive values, will lead future transformational processes. It is useful and interesting to consider how important emotional intelligence is for effective performance at work. A considerable body of research suggests that an employee’s ability to perceive, identify, and manage emotion provides the basis for the kinds of social and emotional competencies that are important for success in almost any position. Furthermore, as the pace of change increases and the world of work make ever-greater demands on an employee’s cognitive, emotional, and physical resources, this particular set of abilities will become increasingly important (Cherniss, 2000). The primary objective of this study is to determine the perceptions of the Masters in Business Administration (MBA), B-Tech in Business Administration (BBA), Advanced Business Programme (ABP) programmes and the Business School Alumni to determine the overall emotional intelligence profile of students as well as the effective team functions of the syndicate groups. Based on the main findings of the survey, it was concluded that emotional intelligence is an important factor for the NMMU Business School, MBA Unit students. The skills attained through the course work will not only improve team effectiveness in the syndicate group functioning but also enhance their performance in the business environment. The MBA team learning experiences enhances workplace learning as the ability to work in a team and ability to think and act independently are highly desired skills and competencies for success in the workplace

Contractile Effects of Radiofrequency Energized Helium Plasma on the Fibrous Septal Network

Body contouring with liposuction has evolved significantly from the early approach of simply debulking excess fatty tissue, to affecting the mechanical properties of different tissue types and layers. Operative paradigms have been expanded to apply energy-based technologies intraoperatively to provide more uniform aspiration, selective fatty tissue emulsification in soft and fibrous body areas, minimize trauma to nerves and vessels, expose the fibrous septal network, reduce operator fatigue and help deliver smooth shapes with less discomfort and bruising. Advanced refinements with the delivery of monopolar and bipolar radiofrequency energy for soft tissue heating have been shown to reduce the residual soft tissue laxity that often follows voluminous fat removal. The Renuvion® (Apyx™ Medical, Clearwater, FL) radiofrequency powered helium plasma technology introduces an emerging concept in which the delivery of subdermal thermal energy preferentially coagulates the fascia and fibrous septal network through a conductive helium plasma stream seeking the path of least resistance, which in turn results in collagen contraction and tissue shrinkage that permits re-draping of the skin and enhanced definition. The physics and mechanics of Renuvion® subdermal soft tissue coagulation will be presented, along with clinical applications that have provided the authors more contouring finesse and has augmented liposuction outcomes

Deciding on prosthodontic treatment in children with inherited dental abnormalities : should psychological or dental well-being take precedence?

Children with inherited dental anomalies have many complex problems that may interfere with their physical, mental and psychological well-being.1,2 The anomalies generally present early in life as isolated conditions, or associated with other defects, and may require immediate as well as prolonged multidisciplinary management.2 The spectrum of defects is diverse, as is the range of deformities that can manifest in the head and neck region.1 Common to all is their potential to have “profound negative consequences for the individual and their families, ranging from aesthetic concerns that impact on their self-esteem, to masticatory difficulties, tooth sensitivity, financial burdens, and protracted dental treatment.”http://www.sada.co.zaam2019Prosthodontic

The Changes of Skin Temperature on Hands and Feet During and after T3 Sympathicotomy for Palmar Hyperhidrosis

Unilateral thoracic sympathectomy in patients with palmar hyperhidrosis causes a skin temperature drop in the contralateral hand. A cross-inhibitory effect by the post-ganglionic neurons innervating hands is postulated as a mechanism of contralateral vasoconstriction. The purpose of our study was to evaluate whether this cross-inhibitory effect also occurs in the feet. Twenty patients scheduled for thoracoscopic sympathicotomy due to palmar hyperhidosis were studied. Right T3 sympathicotomy was performed first, followed by left T3 sympathicotomy. The thenar skin temperatures of both hands and feet were continuously monitored using a thermometer and recorded before induction of anesthesia, during the operation, 4 hr after and 1 week later. Following right T3 sympathicotomy, the skin temperature of the ipsilateral hand gradually increased, however the skin temperature of the contralateral hand gradually decreased. Immediately after bilateral sympathicotomy, the skin temperature differences between hands and feet increased, but these differences decreased 1 week later. Our results show that cross-inhibitory control may exist in feet as well as in the contralateral hand. Thus, the release of cross-inhibitory control following T3 sympathicotomy results in vasoconstriction and decrease of skin temperature on the contralateral hand and feet. One week later, however, the temperature balance on hands and feet recovers

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner

The Johnson and Johnson Ad26.COV2.S single-dose vaccine represents an attractive option for coronavirus disease 2019 (COVID-19) vaccination in countries with limited resources. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naive with those either infected with the ancestral D614G virus or infected in the second wave when Beta predominated. Prior infection significantly boosts spike-binding antibodies, antibody-dependent cellular cytotoxicity, and neutralizing antibodies against D614G, Beta, and Delta; however, neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses are induced after vaccination, regardless of prior infection. T cell recognition of variants is largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination after infection could result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern

The timing of HIV-1 infection of cells that persist on therapy is not strongly influenced by replication competency or cellular tropism of the provirus

People with HIV-1 (PWH) on antiretroviral therapy (ART) can maintain undetectable virus levels, but a small pool of infected cells persists. This pool is largely comprised of defective proviruses that may produce HIV-1 proteins but are incapable of making infectious virus, with only a fraction (~10%) of these cells harboring intact viral genomes, some of which produce infectious virus following ex vivo stimulation (i.e. inducible intact proviruses). A majority of the inducible proviruses that persist on ART are formed near the time of therapy initiation. Here we compared proviral DNA (assessed here as 3’ half genomes amplified from total cellular DNA) and inducible replication competent viruses in the pool of infected cells that persists during ART to determine if the original infection of these cells occurred at comparable times prior to therapy initiation. Overall, the average percent of proviruses that formed late (i.e. around the time of ART initiation, 60%) did not differ from the average percent of replication competent inducible viruses that formed late (69%), and this was also true for proviral DNA that was hypermutated (57%). Further, there was no evidence that entry into the long-lived infected cell pool was impeded by the ability to use the CXCR4 coreceptor, nor was the formation of long-lived infected cells enhanced during primary infection, when viral loads are exceptionally high. We observed that infection of cells that transitioned to be long-lived was enhanced among people with a lower nadir CD4+ T cell count. Together these data suggest that the timing of infection of cells that become long-lived is impacted more by biological processes associated with immunodeficiency before ART than the replication competency and/ or cellular tropism of the infecting virus or the intactness of the provirus. Further research is needed to determine the mechanistic link between immunodeficiency and the timing of infected cells transitioning to the long-lived pool, particularly whether this is due to differences in infected cell clearance, turnover rates and/or homeostatic proliferation before and after ART