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Tissue Engineering of cartilage has been hampered by the inability of engineered tissue to express native levels of type II collagen in vitro. Inadequate levels of type II collagen are, in part, due to a failure to recapitulate the physiological environment in culture. In this study, we engineered primary rabbit chondrocytes to express a secreted reporter, Gaussia Luciferase, driven by the type II collagen promoter, and applied a Design of Experiments approach to assess chondrogenic differentiation in micronutrient-supplemented medium. Using a Response Surface Model, 240 combinations of micronutrients absent in standard chondrogenic differentiation medium, were screened and assessed for type II collagen promoter-driven Gaussia luciferase expression. While the target of this study was to establish a combination of all micronutrients, alpha-linolenic acid, copper, cobalt, chromium, manganese, molybdenum, vitamins A, E, D and B7 were all found to have a significant effect on type II collagen promoter activity. Five conditions containing all micronutrients predicted to produce the greatest luciferase expression were selected for further study. Validation of these conditions in 3D aggregates identified an optimal condition for type II collagen promoter activity. Engineered cartilage grown in this condition, showed a 170% increase in type II collagen expression (Day 22 Luminescence) and in Young’s tensile modulus compared to engineered cartilage in basal media alone.Collagen cross-linking analysis confirmed formation of type II-type II collagen and type II-type IX collagen cross-linked heteropolymeric fibrils, characteristic of mature native cartilage. Combining a Design of Experiments approach and secreted reporter cells in 3D aggregate culture enabled a high-throughput platform that can be used to identify more optimal physiological culture parameters for chondrogenesis.

The surface zone of articular cartilage is the first area impacted by cartilage defects, commonly resulting in osteoarthritis. Chondrocytes in the surface zone of articular cartilage synthesize and secrete lubricin, a proteoglycan that functions as a lubricant protecting the deeper layers from shear stress. Notably, 3D bioprinting is a tissue engineering technique that uses cells encapsulated in biomaterials to fabricate 3D constructs. Gelatin methacrylate (GelMA) is a frequently used biomaterial for 3D bioprinting cartilage. Oxidized methacrylated alginate (OMA) is a chemically modified alginate designed for its tunable degradation rate and mechanical properties. To determine an optimal combination of GelMA and OMA for lubricin expression, we used our novel high-throughput human articular chondrocyte reporter system. Primary human chondrocytes were transduced with PRG4 (lubricin) promoter-driven Gaussia luciferase, allowing for temporal assessment of lubricin expression. A lubricin expression-driven Design of Experiment screen and subsequent validation identified 14% GelMA/2% OMA for further study. Therefore, DoE optimized 14% GelMA/2% OMA, 14% GelMA control, and 16% GelMA (total solid content control) were 3D bioprinted. The combination of lubricin protein expression and shape retention over the 22 days in culture, successfully determined the 14% GelMA/2%OMA to be the optimal formulation for lubricin secretion. This strategy allows for rapid analysis of the role(s) of biomaterial composition, stiffness or other cell manipulations on lubricin expression by chondrocytes, which may improve therapeutic strategies for cartilage regeneration.

Abstract Background Artemisinin-based combination therapy (ACT) was deployed in 2005 as an alternative to chloroquine and is considered the most efficacious treatment currently available for uncomplicated falciparum malaria. While widespread artemisinin resistance has not been reported to date in Africa, recent studies have reported partial resistance in Rwanda. The purpose of this study is to provide a current systematic review and meta-analysis on ACT at Mali study sites, where falciparum malaria is highly endemic. Methods A systematic review of the literature maintained in the bibliographic databases accessible through the PubMed, ScienceDirect and Web of Science search engines was performed to identify research studies on ACT occurring at Mali study sites. Selected studies included trials occurring at Mali study sites with reported polymerase chain reaction (PCR)-corrected adequate clinical and parasite response rates (ACPRcs) at 28 days. Data were stratified by treatment arm (artemether–lumefantrine (AL), the first-line treatment for falciparum malaria in Mali and non-AL arms) and analysed using random-effects, meta-analysis approaches. Results A total of 11 studies met the inclusion criteria, and a risk of bias assessment carried out by two independent reviewers determined low risk of bias among all assessed criteria. The ACPRc for the first-line AL at Mali sites was 99.0% (95% CI (98.3%, 99.8%)), while the ACPRc among non-AL treatment arms was 98.9% (95% CI (98.3%, 99.5%)). The difference in ACPRcs between non-AL treatment arms and AL treatment arms was not statistically significant (p = .752), suggesting that there are potential treatment alternatives beyond the first-line of AL in Mali. Conclusions ACT remains highly efficacious in treating uncomplicated falciparum malaria in Mali. Country-specific meta-analyses on ACT are needed on an ongoing basis for monitoring and evaluating drug efficacy patterns to guide local malaria treatment policies, particularly in the wake of observed artemisinin resistance in Southeast Asia and partial resistance in Rwanda.

Abstract Background Joint degeneration and large or complex bone defects are a significant source of morbidity and diminished quality of life worldwide. There is an unmet need for a functional implant with near‐native biomechanical properties. The potential for their generation using 3D bioprinting (3DBP)‐based tissue engineering methods was assessed. We systematically reviewed the current state of 3DBP in orthoregeneration. Methods This review was performed using PubMed and Web of Science. Primary research articles reporting 3DBP of cartilage, bone, vasculature, and their osteochondral and vascular bone composites were considered. Full text English articles were analyzed. Results Over 1300 studies were retrieved, after removing duplicates, 1046 studies remained. After inclusion and exclusion criteria were applied, 114 articles were analyzed fully. Bioink material types and combinations were tallied. Cell types and testing methods were also analyzed. Nearly all papers determined the effect of 3DBP on cell survival. Bioink material physical characterization using gelation and rheology, and construct biomechanics were performed. In vitro testing methods assessed biochemistry, markers of extracellular matrix production and/or cell differentiation into respective lineages. In vivo proof‐of‐concept studies included full‐thickness bone and joint defects as well as subcutaneous implantation in rodents followed by histological and µCT analyses to demonstrate implant growth and integration into surrounding native tissues. Conclusions Despite its relative infancy, 3DBP is making an impact in joint and bone engineering. Several groups have demonstrated preclinical efficacy of mechanically robust constructs which integrate into articular joint defects in small animals. However, notable obstacles remain. Notably, researchers encountered pitfalls in scaling up constructs and establishing implant function and viability in long term animal models. Further, to translate from the laboratory to the clinic, standardized quality control metrics such as construct stiffness and graft integration metrics should be established with investigator consensus. While there is much work to be done, 3DBP implants have great potential to treat degenerative joint diseases and provide benefit to patients globally.

Hepatitis B virus (HBV) causes a potentially life-threatening liver infection that frequently results in life-long chronic infection. HBV is responsible for 887,000 deaths each year, most resulting from chronic liver diseases and hepatocellular carcinoma. Presently, there are 250 million chronic HBV carriers worldwide who are at a high risk for developing cirrhosis and hepatocellular carcinoma (HCC). HCC is the most common type of liver cancer with a strong association with HBV infection. HBV transmission through blood transfusions and perinatal transfer from infected mother to child have been common routes of infection. In the present study, we describe the development of a synthetic DNA plasmid encoding an anti-HBV human monoclonal antibody specific for the common “a determinant region” of HBsAg of hepatitis B virus and demonstrate the ability of this platform at directing in vivo antibody expression. In vivo delivery of this DNA encoded monoclonal antibody (DMAb) plasmid in mice resulted in expression of human IgG over a period of one month following a single injection. Serum antibody was found to recognize the relevant conformational epitope from plasma purified native HBsAg as well as bound HBV in HepG2.2.15 cells. The serum DMAb efficiently neutralized HBV and prevented infection of HepaRG cells in vitro. Additional study of these HBV-DMAb as a possible therapy or immunoprophylaxis for HBV infection is warranted.

Arginase is a complex and unique enzyme that plays diverse roles in health and disease. By metabolizing arginine, it can shape the outcome of innate and adaptive immune responses. The immunomodulatory capabilities of arginase could potentially be applied for local immunosuppression or induction of immune tolerance. With the use of an enhanced DNA delivery approach, we designed and studied a DNA-encoded secretable arginase enzyme as a tool for immune modulation and evaluated its immunomodulatory function in vivo. Strong immunosuppression of cluster of differentiation 4 (CD4) and CD8 T cells, as well as macrophages and dendritic cells, was observed in vitro in the presence of an arginase-rich supernatant. To further evaluate the efficacy of DNA-encoded arginase on in vivo immunosuppression against an antigen, a cancer antigen vaccine model was used in the presence or absence of DNA-encoded arginase. Significant in vivo immunosuppression was observed in the presence of DNA-encoded arginase. The efficacy of this DNA-encoded arginase delivery was examined in a local, imiquimod-induced, psoriasis-like, skin-inflammation model. Pretreatment of animals with the synthetic DNA-encoded arginase led to significant decreases in skin acanthosis, proinflammatory cytokines, and costimulatory molecules in extracted macrophages and dendritic cells. These results draw attention to the potential of direct in vivo-delivered arginase to function as an immunomodulatory agent for treatment of local inflammation or autoimmune diseases.

There is currently no licensed SARS-CoV-2 vaccine. Here, the authors generate an optimized DNA vaccine candidate encoding the SARS-CoV-2 spike antigen, demonstrating induction of specific T cells and neutralizing antibody responses in mice and guinea pigs. These initial results support further development of this vaccine candidate.

Orientation: The consultancy industry globally has witnessed a paradigm shift over the past few years in terms of its nature, employee turnover and attraction and retention of talent. These changes have posed a challenge because the industry struggles to attain commitment from their employees. Research purpose: To explore strategies to retain talent whilst ensuring performance in a consulting firm based in the south of Johannesburg, Gauteng province, South Africa. Motivation for the study: Currently there is limited research on strategies to retain talent and enhance employee performance within the consultancy industry in South Africa. Exploring the experiences and views of consultants can assist consulting firms to develop effective retention strategies to retain talent whilst enhancing employee performance. Research design, approach and method: A qualitative research method was adopted in this study. Semi-structured interviews were used to gather data. Thematic analysis was employed to identify patterns of meaning across the data set. Data coding was conducted on the themes that were identified. Different categories and subcategories were identified and analysed to determine themes and findings. Data collected were analysed and interpreted for meaningful conclusions. A non-probability sampling procedure was employed using purposive sampling. The sample included men and women, between 25 and 60 years of age, with a minimum of 5 years’ experience as consultants in the consultancy industry in Gauteng. Main findings: The findings show the following strategies to retain consultants in the consulting industry: (1) rewards, (2) work–life balance, (3) performance management system, (4) improved training and development, (5) employee recognition and (6) career progression opportunities. Practical/managerial implications: The findings of this study can be used by human capital managers to develop reward systems that will enhance employee performance and retain consultants. Contribution/value-add: This study provided important practical guidelines that could be used by consulting firms to develop and implement retention strategy valued by consultants.

Unwanted uptake in the liver and limited accumulation in target organs is a major obstacle to targeted drug delivery. Here, the authors report on the hitchhiking of nanocarriers on red blood cells and the targeted upstream delivery to different target organs in mice, pigs and ex vivo human lungs.

Hookworms infect more people than HIV and malaria combined, predominantly in third world countries. Treatment of infection with chemotherapy can have limited efficacy and re-infections after treatment are common. Heavy infection often leads to debilitating diseases. All these factors suggest an urgent need for development of vaccine. In an attempt to develop a vaccine targeting the major human hookworm, Necator americanus, a B-cell peptide epitope was chosen from the apical enzyme in the hemoglobin digestion cascade, the aspartic protease Na-APR-1. The A(291)Y alpha helical epitope is known to induce neutralizing antibodies that inhibit the enzymatic activity of Na-APR-1, thus reducing the capacity for hookworms to digest hemoglobin and obtain nutrients. A(291)Y was engineered such that it was flanked on both termini by a coil-promoting sequence to maintain native conformation, and subsequently incorporated into a Lipid Core Peptide (LCP) self-adjuvanting system. While A(291)Y alone or the chimeric epitope with or without Freund's adjuvants induced negligible IgG responses, the LCP construct incorporating the chimeric peptide induced a strong IgG response in mice. Antibodies produced were able to bind to and completely inhibit the enzymatic activity of Na-APR-1. The results presented show that the new chimeric LCP construct can induce effective enzyme-neutralising antibodies in mice, without the help of any additional toxic adjuvants. This approach offers promise for the development of vaccines against helminth parasites of humans and their livestock and companion animals.

Introduction Comorbidities in systemic lupus erythematosus (SLE) impact negatively on health-related quality of life (HRQoL) and life expectancy. We investigated the frequency and spectrum of comorbidities in privately insured South Africans with SLE. Methods The data of SLE patients based on International Classification of Diseases, Tenth Revision (ICD-10) codes and insured with Discovery Health Medical Scheme (DHMS), South Africa, aged ≥16 years at diagnosis and with ≥6 months of follow-up were reviewed. Demographics, comorbidities listed in the Charlson comorbidity index (CCI), other common comorbidities, intercurrent illnesses, and drug therapy were documented. Results Of the 520 patients coded as SLE, 207 met the inclusion criteria. Most were females (90.8%), with a median (interquartile range {IQR}) age and follow-up duration of 39 (30.3-53.0) and 6.1 (3.7-8.1) years, respectively. All patients had at least one comorbidity; the most frequent CCI comorbidities were pulmonary disease (30.9%), congestive heart failure (CHF, 15%), and renal disease (14.0%). Other common comorbidities were hypertension (53.1%) and mood and anxiety disorders (46.9%). Urinary tract infections (UTIs, 37.7%) and pneumonia (33.8%) were common intercurrent illnesses. The independent predictors of CHF were renal disease (odds ratio {OR}=855), dyslipidemia (OR=15.3), and male gender (OR=43.0); the independent predictors of hypertension were age at diagnosis (OR=1.03), type 2 diabetes (OR=4.45), and renal disease (OR=4.34); and the independent predictors of mood and anxiety disorders were female gender (OR=3.98), stroke (OR=3.18), UTI (OR=2.39), and chloroquine use (OR=1.94). Conclusion In this study of privately insured South Africans with SLE, comorbidities were common, and all patients had at least one comorbidity. Hypertension, infections, and mood and anxiety disorders were the leading comorbidities overall, and pulmonary disease was the most common CCI comorbidity. There is an obvious need to formally study the burden of mental health disorders in South African SLE patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ngandu Ntumba et al.)

Management of ANCA-associated vasculitis (AAV) during the COVID-19 pandemic poses unique therapeutic challenges. An online survey was conducted to understand physician's choices for treating AAV during the COVID-19 pandemic. Web-based survey featuring nineteen questions was circulated amongst physicians across various specialties. The responses regarding immunosuppressive therapy for remission induction and maintenance, COVID-19 testing, and preventive measures were recorded. A total of 304 responses were recorded. Most of the respondents were from India (83.9%) and comprised rheumatologists (66%) in practice for ≥ 5 years (71%). Though a majority preferred Rituximab or intravenous cyclophosphamide (CYC) as a remission induction agent, a significant proportion opted for oral CYC and mycophenolate mofetil (MMF) also. Only one-third wanted to test for COVID-19 before initiating immunosuppressive therapy in patients with organ/life-threatening manifestations. Rituximab was the most favored maintenance therapy (47%), followed by azathioprine, MMF, and methotrexate. The results of this focused survey of managing AAV patients depict the real-world dilemmas and physicians' choices in this setting., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Systemic lupus erythematosus has a predilection for women of childbearing age. Globally a shortage of rheumatologists exists resulting in general physicians and obstetricians treating systemic lupus erythematosus in pregnancy., Methods: We conducted a survey amongst medical and obstetric registrars in South Africa to assess their subjective and objective competence in managing pregnant women with systemic lupus erythematosus., Results: The pass rate for the objective section was 70.8% with no statistically significant difference in the pass rate between medical and obstetric registrars. Participants felt unprepared to manage pregnant women with systemic lupus erythematosus, with a mean overall score of 3.4 out of 7 for the subjective section, based on four Likert scale type questions., Conclusion: Trainees are not able to accurately assess their own levels of competence in order to identify their learning needs. Due to the shortage of rheumatologists and lack of obstetric physicians in South Africa, general physicians and obstetricians must be equipped to provide adequate care to pregnant women with systemic lupus erythematosus., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Objectives: To develop recommendations for the management of rheumatic and musculoskeletal diseases (RMDs) during the COVID-19 pandemic., Method: A task force comprising of 25 rheumatologists from the 5 regions of the continent was formed and operated through a hub-and-spoke model with a central working committee (CWC) and 4 subgroups. The subgroups championed separate scopes of the clinical questions and formulated preliminary statements of recommendations which were processed centrally in the CWC. The CWC and each subgroup met by several virtual meetings, and two rounds of voting were conducted on the drafted statements of recommendations. Votes were online-delivered and recommendations were pruned down according to predefined criteria. Each statement was rated between 1 and 9 with 1-3, 4-6 and 7-9 representing disagreement, uncertainty and agreement, respectively. The levels of agreement on the statements were stratified as low, moderate or high according to the spread of votes. A statement was retired if it had a mean vote below 7 or a 'low' level of agreement., Results: A total of 126 initial statements of recommendations were drafted, and these were reduced to 22 after the two rounds of voting., Conclusions: The preliminary statements of recommendations will serve to guide the clinical practice of rheumatology across Africa amidst the changing practices and uncertainties in the current era of COVID-19. It is recognized that further updates to the recommendations will be needed as more evidence emerges. Key Points • AFLAR has developed preliminary recommendations for the management of RMDs in the face of the COVID-19 pandemic. • COVID-19 is an unprecedented experience which has brought new concerns regarding the use of some disease-modifying anti-rheumatic drugs (DMARDs), and these recommendations seek to provide guidelines to the African rheumatologists. • Hydroxychloroquine shortage has become rampart across Africa as the drug is being used as prophylaxis against COVID-19 and this may necessitate a review of treatment plan for some patients with RMDs. • Breastfeeding should continue for as long as possible if a woman is positive for SARS-CoV-2 as there is currently no evidence that the infection can be transmitted through breast milk., (© 2020. The Author(s).)

Background: It is plausible that optimal cardiovascular disease (CVD) risk management differs in patients with rheumatoid arthritis (RA) from low or middle income compared to high income populations. This study aimed at producing evidence-based points to consider for CVD prevention in South African RA patients., Methods: Five rheumatologists, one cardiologist and one epidemiologist with experience in CVD risk management in RA patients, as well as two patient representatives, two health professionals and one radiologist, one rheumatology fellow and 11 rheumatologists that treat RA patients regularly contributed. Systematic literature searches were performed and the level of evidence was determined according to standard guidelines., Results: Eighteen points to consider were formulated. These were grouped into 6 categories that comprised overall CVD risk assessment and management ( n  = 4), and specific interventions aimed at reducing CVD risk including RA control with disease modifying anti-rheumatic drugs, glucocorticoids and non-steroidal anti-inflammatory drugs ( n  = 3), lipid lowering agents ( n  = 8), antihypertensive drugs ( n  = 1), low dose aspirin ( n  = 1) and lifestyle modification ( n  = 1). Each point to consider differs partially or completely from recommendations previously reported for CVD risk management in RA patients from high income populations. Currently recommended CVD risk calculators do not reliably identify South African black RA patients with very high-risk atherosclerosis as represented by carotid artery plaque presence on ultrasound., Conclusions: Our findings indicate that optimal cardiovascular risk management likely differs substantially in RA patients from low or middle income compared to high income populations. There is an urgent need for future multicentre longitudinal studies on CVD risk in black African patients with RA., Competing Interests: Competing interestsMiguel A Gonzalez-Gay received grants/research support from AbbVie, MSD, Janssen and Roche, and had consultation fees/participation in company sponsored speaker’s bureau from AbbVie, Pfizer, Roche, Sanofi, Celgene, Sobi and MSD. Santos Castañeda received grants/research support from MSD, Pfizer and Roche, and had consultation/honorary fees from Amgen, Celgene, Eli-Lilly, Sanofi, Sobi and UCB. Patrick H Dessein received a consultation/honorary fee from Janssen Pharmaceutica. Santos Castañeda is assistant professor of a chair supported by ROCHE at the Autonomous University of Madrid (UAM), Spain. The other co-authors declare that they have no declarations of interest., (© The Author(s) 2020.)