Research Articles (Urology)

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The use of in vitro bioassays and chemical screening to assess the impact of a minimally processed vegetable facility on wastewater quality
(Frontiers Media, 2024-09) Aneck-Hahn, Natalie Hildegard; Van Zijl, Magdalena Catherina; Quinn, Laura; Swiegelaar, Caitlin; Nhlapo, N.S. (Nontete Suzan); De Bruin, Willeke; Korsten, Lise; natalie.aneck-hahn@up.ac.za
Fruit- and vegetable-processing facilities may contaminate wastewater via contaminants found in the produce and disinfecting chemicals used. These contaminants may include agrochemicals, pesticides, and disinfectants such as chlorine and quaternary ammonium compounds (QACs). Some compounds may exhibit harmful endocrine-disrupting activity. This study investigated the impact of a minimally processed vegetable facility on wastewater quality via in vitro bioassays and chemical screening. Estrogen activity was assessed via a yeast estrogen screen (YES), and (anti-)androgenic and glucocorticoid activities were evaluated via an MDA-kb2 reporter gene assay. The samples were screened via gas and liquid chromatography–tandem mass spectrometry (GC-MS/MS and LC-MS/MS) to identify target compounds, and GC coupled with time-of-flight mass spectrometry (GC-TOFMS) was used for non-targeted screening. Sample complexity and chemical profiles were assessed using GC-TOFMS. Estrogenic activity was detected in 16 samples (n = 24) with an upper limit of 595 ± 37 ng/L estradiol equivalents (EEqs). The final wastewater before discharge had an EEq of 0.23 ng/L, which is within the ecological effect-based trigger value range for the estrogenic activity of wastewater (0.2–0.4 ng/L EEq). Androgenic activity was detected in one sample with a dihydrotestosterone equivalent (DHTEq) value of 10 ± 2.7 ng/L. No antiandrogenic activity was detected. The GC-MS/MS and LCMS/MS results indicated the presence of multiple pesticides, nonylphenols, triclocarban, and triclosan. Many of these compounds exhibit estrogenic activity, which may explain the positive YES assay findings. These findings showed that wastewater from the facility contained detergents, disinfectants, and pesticides and displayed hormonal activity. Food-processing facilities release large volumes of wastewater, which may affect the quality of the water eventually being discharged into the environment. We recommend expanding conventional water quality monitoring efforts to include additional factors like endocrine activity and disinfectant byproducts.
The impact of pharmacotherapy on sexual function in female patients being treated for idiopathic overactive bladder : a systematic review
(BMC, 2024-05) Evans, Christopher Neal Bruce; Badenhorst, Anja; Van Wijk, Frans Jacob
BACKGROUND: Overactive bladder (OAB) is a condition defined by urgency with or without incontinence which disproportionately affects female patients and has a negative impact on sexual enjoyment and avoidance behaviour. Pharmacotherapy can be considered one of the main options for treating OAB. This research set out to determine the impact of pharmacotherapy on sexual function in females with OAB. METHODS: This research used the robust methodology of a systematic review. The clinical question was formulated using the PICO (population, intervention, control, and outcomes) format to include females being treated with pharmacotherapy (anticholinergics or beta-3 adrenergic agonists) for idiopathic OAB with the use of a validated questionnaire assessing self-reported sexual function at baseline and post-treatment. The review incorporated the MEDLINE, PubMed and EMBASE databases. The AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) appraisal tool was used to guide the review process. Two reviewers worked independently in screening abstracts, deciding on the inclusion of full-texts, data extraction and risk of bias assessment. RESULTS: In female patients with OAB, pharmacotherapy does seem to offer at least partial improvement in self reported sexual function outcomes after 12 weeks of therapy. Still, the value of this finding is limited by an overall poor quality of evidence. Patients with a higher degree of bother at baseline stand to benefit the most from treatment when an improvement within this health-related quality of life domain is sought. CONCLUSION: This research should form the basis for a well-conducted randomized controlled study to accurately assess sexual function improvements in females being treated with pharmacotherapy for OAB.
Assessment of neuropathic pain management knowledge, attitudes, and practices among urology trainees and consultants in prostate cancer care : a survey-based study
(Springer, 2024-04) Sinkila, Ongeziwe; Matjomane, N.; Cronje, Tanita; Mathabe, Kgomotso
BACKGROUND: Effective neuropathic pain management is crucial in improving the quality of life for patients with prostate cancer. There is an abundance of research about cancer pain and guidelines that have been developed by World Health Organization including the analgesia stepladder, yet patients with cancer pain are still sub optimally analgesed. This is due to a variety of both patient and physician factors which include: lack of knowledge on the use of adjuvant medication, fear of addiction and poor characterization of the type of pain. This study intended to assess the knowledge, attitudes, and practices of urology trainees and consultants in the the context of neuropathic pain in prostatecancer care. METHODS: The study involved 91 urologists, comprising of junior registrars, medical officers and experienced specialists who are members of the South African Urological Association (SAUA). Data was collected through a 25-question web-based survey. The survey covered: demographic information, knowledge, attitudes, and practices related to cancer pain management. RESULTS: The study revealed that a significant proportion of urologists assessed neuropathic pain reactively, with only 8% of respondents being familiar with screening scales. Approximately, one-third preferred referrals, and 74% expressed confidence in self-treatment. Concerns regarding opioid prescription were observed in 40.4% of respondents. Furthermore, the usage of adjuvant medications was limited, with only 35% proficiently combining analgesia and adjuvants. Notably, 65% continued to escalate analgesic monotherapy. CONCLUSION: Effective neuropathic pain management in prostate cancer care necessitates a multidisciplinary approach, comprehensive assessment and expertise in adjuvant medication usage. The discrepancies observed among urologists are likely due to variations in experience levels. The study identifies knowledge gaps and suboptimal practices in neuropathic pain management among urologists. Addressing these issues through education, awareness, and interdisciplinary collaboration is imperative to enhance patient outcomes and improve the quality of life for individuals with prostate cancer. This study underscores the need for improved education and interdisciplinary collaboration among urologists in managing neuropathic pain among prostate cancer patients. Enhancing these aspects is essential to achieve better patient outcomes and overall quality of life.
Quality and safety of South African hand sanitisers during the COVID-19 pandemic
(Taylor and Francis, 2024) De Bruin, Willeke; Van Zijl, Magdalena Catherina; Aneck-Hahn, Natalie H.; Korsten, Lise; lise.korsten@up.ac.za
Health agencies recommend using hand sanitisers as protection against the coronavirus. Thus far, the emphasis on hand sanitiser studies is limited to an analysis of disinfectant content only. This study aims to provide an extended analysis of 60 off-the-shelf alcohol-based hand sanitisers by using gas chromatography to report on alcohol content and the presence of impurities, a recombinant yeast estrogen screen to assess estrogenic activity, and an investigation into labelling compliance with the South African National Standard. Fifty hand sanitisers had an alcohol content of ≥60% v/v alcohol; however, most contained skin irritants and substances that could harm human and environmental health. Estrogenic activity was detected in 29 hand sanitisers and none of the products complied with all the labelling requirements. Since off-the-shelf hand sanitisers in South Africa are not regulated and monitored, evidence-based public awareness programmes on hand sanitiser quality and safety should become a priority.
In silico bioinformatics analysis on the role of long non-coding RNAs as drivers and gatekeepers of androgen-independent prostate cancer using LNCaP and PC-3 cells
(MDPI, 2023-09-01) Mbeje, Mandisa; Kandhavelu, Jeyalakshmi; Penny, Clement; Kgoebane-Maseko, Minah; Dlamini, Zodwa; Marima, Rahaba; zodwa.dlamini@up.ac.za
Prostate cancer (PCa) is the leading cancer in men globally. The association between PCa and long non-coding RNAs (lncRNAs) has been reported. Aberrantly expressed lncRNAs have been documented in each of the cancer “hallmarks”. Androgen signaling plays an important role in PCa progression. This study aimed to profile the aberrantly expressed lncRNAs in androgen-dependent (LNCaP) PCa compared to androgen-independent (PC-3) PCa cells. This was achieved by using a 384-well plate of PCa lncRNA gene panel. Differential expression of 2 up or downregulation was determined using the CFX Maestro software v2.1. LncSEA and DIANA-miRPath were used to identify the enriched pathways. Telomerase RNA component (TERC) lncRNA was illustrated to participate in various tumourigenic classes by in silico bioinformatics analysis and was thus selected for validation using RT-qPCR. Further bioinformatics analysis revealed the involvement of differentially expressed lncRNAs in oncogenic pathways. Some lncRNAs undergo hypermethylation, others are encapsulated by exosomes, while others interact with several microRNAs (miRNAs), favouring tumourigenic pathways. Notably, TERC lncRNA was shown to interact with tumour-suppressor miRNAs hsamiR- 4429 and hsa-miR-320b. This interaction in turn activates TGF- -signaling and ECM-receptor interaction pathways, favouring the progression of PCa. Understanding lncRNAs as competitive endogenous RNA molecules and their interactions with miRNAs may aid in the identification of novel prognostic PCa biomarkers and therapeutic targets.
Renal papillary necrosis (RPN) in an African population : disease patterns, relevant pathways, and management
(MDPI, 2023-01) Gaudji, Guy Roger; Bida, M.; Conradie, Marius; Damane, Botle Precious; Bester, Megan; megan.bester@up.ac.za
Renal papillary necrosis (RPN) is characterized by coagulative necrosis of the renal medullary pyramids and papillae. Multiple conditions and toxins are associated with RPN. Several RPN risk factors, or POSTCARDS, have been identified, with most patients presenting with RPN having at least two contributing risk factors. Currently, there is no specific test to diagnose and confirm RPN; however, several imaging tools can be used to diagnose the condition. RPN is currently underdiagnosed in African populations, often with fatal outcomes. In African clinical settings, there is a lack of consensus on how to define and describe RPN in terms of kidney anatomy, pathology, endourology, epidemiology, the identification of African-specific risk factors, the contribution of oxidative stress, and lastly an algorithm for managing the condition. Several risk factors are unique to African populations including population-specific genetic factors, iatrogenic factors, viral infections, antimicrobial therapy, schistosomiasis, substance abuse, and hypertension (GIVASSH). Oxidative stress is central to both GIVASSH and POSTCARDS-associated risk factors. In this review, we present information specific to African populations that can be used to establish an updated consensual definition and practical grading system for radiologists, urologists, nephrologists, nuclear physicians, and pathologists in African clinical settings.
Standards in semen examination : publishing reproducible and reliable data based on high-quality methodology
(Oxford University Press, 2022-10) Bjorndahl, Lars; Barratt, Christopher L.R.; Mortimer, David; Agarwal, Ashok; Aitken, Robert J.; Alvarez, Juan G.; Aneck-Hahn, Natalie Hildegard; Arver, Stefan; Baldi, Elisabetta; Bassas, Lluis; Boitrelle, Florence; Bornman, Maria S. (Riana); Carrell, Douglas T.; Castilla, Jose A.; Cerezo Parra; Parra, Gerardo Cerezo; Check, Jerome H.; Cuasnicu, Patricia S.; Darney, Sally Perreault; De Jager, Christiaan; De Jonge, Christopher J.; Drevet, Joel R.; Drobnis, Erma Z.; Du Plessis, Stefan S.; Eisenberg, Michael L.; Esteves, Sandro C.; Evgeni, Evangelini A.; Ferlin, Alberto; Garrido, Nicolas; Giwercman, Aleksander; Goovaerts, Ilse G.F.; Haugen, Trine B.; Henkel, Ralf; Henningsohn, Lars; Hofmann, Marie-Claude; Hotaling, James M.; Jedrzejczak, Piotr; Jouannet, Pierre; Jorgensen, Niels; Kirkman Brown, Jackson C.; Krausz, Csilla; Kurpisz, Maciej; Kvist, Ulrik; Lamb, Dolores J.; Levine, Hagai; Loveland, Kate L.; McLachlan, Robert, I.; Mahran, Ali; Maree, Liana; Da Silva, Sarah Martins; Mbizvo, Michael T.; Meinhardt, Andreas; Menkveld, Roelof; Mortimer, Sharon T.; Moskovtsev, Sergey; Muller, Charles H.; Jose Munuce, Maria; Muratori, Monica; Niederberger, Craig; O'Flaherty, Cristian; Oliva, Rafael; Ombelet, Willem; Pacey, Allan A.; Palladino, Michael A.; Ramasamy, Ranjith; Ramos, Liliana; Rives, Nathalie; Roldan, Eduardo Rs; Rothmann, Susan; Sakkas, Denny; Salonia, Andrea; Sanchez-Pozo, Maria Cristina; Sapiro, Rosanna; Schlatt, Stefan; Schlegel, Peter N.; Schuppe, Hans-Christian; Shah, Rupin; Skakkebaek, Niels E.; Teerds, Katja; Toskin, Igor; Tournaye, Herman; Turek, Paul J.; Van der Horst, Gerhard; Vazquez-Levin, Monica; Wang, Christina; Wetzels, Alex; Zeginiadou, Theodosia; Zini, Armand
Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.
AI and precision oncology in clinical cancer genomics : from prevention to targeted cancer therapies-an outcomes based patient care
(Elsevier, 2022) Dlamini, Zodwa; Skepu, Amanda; Kim, Namkug; Mkhabele, Mahlori; Khanyile, Richard; Molefi, Thulo; Mbatha, Sikhumbuzo; Setlai, Botle; Mulaudzi, Thanyani Victor; Mabongo, Mzubanzi; Bida, Nndweleni Meshack; Kgoebane-Maseko, Minah; Mathabe, Kgomotso; Lockhat, Zarina I.; Kgokolo, C.M.; Chauke-Malinga, Nkhensani; Ramagaga, Serwalo; Hull, Rodney; zodwa.dlamini@up.ac.za
Precision medicine is the personalization of medicine to suit a specific group of people or even an individual patient, based on genetic or molecular profiling. This can be done using genomic, transcriptomic, epigenomic or proteomic information. Personalized medicine holds great promise, especially in cancer therapy and control, where precision oncology would allow medical practitioners to use this information to optimize the treatment of a patient. Personalized oncology for groups of individuals would also allow for the use of population group specific diagnostic or prognostic biomarkers. Additionally, this information can be used to track the progress of the disease or monitor the response of the patient to treatment. This can be used to establish the molecular basis for drug resistance and allow the targeting of the genes or pathways responsible for drug resistance. Personalized medicine requires the use of large data sets, which must be processed and analysed in order to identify the particular molecular patterns that can inform the decisions required for personalized care. However, the analysis of these large data sets is difficult and time consuming. This is further compounded by the increasing size of these datasets due to technologies such as next generation sequencing (NGS). These difficulties can be met through the use of artificial intelligence (AI) and machine learning (ML). These computational tools use specific neural networks, learning methods, decision making tools and algorithms to construct and improve on models for the analysis of different types of large data sets. These tools can also be used to answer specific questions. Artificial intelligence can also be used to predict the effects of genetic changes on protein structure and therefore function. This review will discuss the current state of the application of AI to omics data, specifically genomic data, and how this is applied to the development of personalized or precision medicine on the treatment of cancer.
Influence of the microbiome metagenomics and epigenomics on gastric cancer
(MDPI, 2022-11) Mathebela, Precious; Damane, Botle Precious; Mulaudzi, Thanyani Victor; Mkhize-Khwitshana, Zilungile Lynette; Gaudji, Guy Roger; Dlamini, Zodwa; precious.setlai@up.ac.za
Gastric cancer (GC) is one of the major causes of cancer deaths worldwide. The disease is seldomly detected early and this limits treatment options. Because of its heterogeneous and complex nature, the disease remains poorly understood. The literature supports the contribution of the gut microbiome in the carcinogenesis and chemoresistance of GC. Drug resistance is the major challenge in GC therapy, occurring as a result of rewired metabolism. Metabolic rewiring stems from recurring genetic and epigenetic factors affecting cell development. The gut microbiome consists of pathogens such as H. pylori, which can foster both epigenetic alterations and mutagenesis on the host genome. Most of the bacteria implicated in GC development are Gram-negative, which makes it challenging to eradicate the disease. Gram-negative bacterium co-infections with viruses such as EBV are known as risk factors for GC. In this review, we discuss the role of microbiome-induced GC carcinogenesis. The disease risk factors associated with the presence of microorganisms and microbial dysbiosis are also discussed. In doing so, we aim to emphasize the critical role of the microbiome on cancer pathological phenotypes, and how microbiomics could serve as a potential breakthrough in determining effective GC therapeutic targets. Additionally, consideration of microbial dysbiosis in the GC classification system might aid in diagnosis and treatment decision-making, taking the specific pathogen/s involved into account.
The role of effect-based methods to address water quality monitoring in South Africa : a developing country’s struggle
(Springer, 2022-12) Kruger, Annika; Pieters, Rialet; Horn, Suranie; Van Zijl, Catherina; Aneck-Hahn, Natalie Hildegard
Water is an important resource, and it is a worldwide struggle to provide water of good quality to the whole population. Despite good governing laws and guidelines set in place to help protect the water resources and ensure it is of good quality for various consumers, the water quality in South Africa is worsening due to lack of management. The deteriorating infrastructure is becoming progressively worse, due to corruption and insufficient funds. The ever-increasing number of toxicants, as well as the identification of emerging chemicals of concern, are also challenges South Africa is facing. Chemical analysis cannot determine the total biological effect of a mixture of chemical compounds, but this shortcoming can be addressed by adding effect-based methods (EBMs) to water quality monitoring programmes. In this paper, the current status of water quality monitoring in South Africa is discussed, as well as the capacity of the country to add EBMs to its water quality monitoring programmes to protect and improve human and animal life.
Role of precision oncology in type II endometrial and prostate cancers in the African population : global cancer genomics disparities
(MDPI, 2022-01-06) Marima, Rahaba; Hull, Rodney; Mbeje, Mandisa Pearl; Molefi, Thulo; Mathabe, Kgomotso; Elbagory, Abdulrahman M.; Demetriou, Demetra Danielle; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
Precision oncology can be defined as molecular profiling of tumors to identify targetable alterations. Emerging research reports the high mortality rates associated with type II endometrial cancer in black women and with prostate cancer in men of African ancestry. The lack of adequate genetic reference information from the African genome is one of the major obstacles in exploring the benefits of precision oncology in the African context. Whilst external factors such as the geography, environment, health-care access and socio-economic status may contribute greatly towards the disparities observed in type II endometrial and prostate cancers in black populations compared to Caucasians, the contribution of African ancestry to the contribution of genetics to the etiology of these cancers cannot be ignored. Non-coding RNAs (ncRNAs) continue to emerge as important regulators of gene expression and the key molecular pathways involved in tumorigenesis. Particular attention is focused on activated/repressed genes and associated pathways, while the redundant pathways (pathways that have the same outcome or activate the same downstream effectors) are often ignored. However, comprehensive evidence to understand the relationship between type II endometrial cancer, prostate cancer and African ancestry remains poorly understood. The sub-Saharan African (SSA) region has both the highest incidence and mortality of both type II endometrial and prostate cancers. Understanding how the entire transcriptomic landscape of these two reproductive cancers is regulated by ncRNAs in an African cohort may help elucidate the relationship between race and pathological disparities of these two diseases. This review focuses on global disparities in medicine, PCa and ECa. The role of precision oncology in PCa and ECa in the African population will also be discussed.
Immune checkpoints, inhibitors and radionuclides in prostate cancer : promising combinatorial therapy approach
(MDPI Publishing, 2021-04-15) Kgatle, Mankgopo; Boshomane, Tebatso M.G.; Lawal, Ismaheel Opeyemi; Mokoala, Kgomotso M.G.; Mokgoro, Neo P.; Lourens, Nico; Kairemo, Kalevo; Zeevaart, Jan Rijn; Vorster, Mariza; Sathekge, Mike Machaba; mike.sathekge@up.ac.za
Emerging research demonstrates that co-inhibitory immune checkpoints (ICs) remain the most promising immunotherapy targets in various malignancies. Nonetheless, ICIs have offered insignificant clinical benefits in the treatment of advanced prostate cancer (PCa) especially when they are used as monotherapies. Current existing PCa treatment initially offers an improved clinical outcome and overall survival (OS), however, after a while the treatment becomes resistant leading to aggressive and uncontrolled disease associated with increased mortality and morbidity. Concurrent combination of the ICIs with radionuclides therapy that has rapidly emerged as safe and effective targeted approach for treating PCa patients may shift the paradigm of PCa treatment. Here, we provide an overview of the contextual contribution of old and new emerging inhibitory ICs in PCa, preclinical and clinical studies supporting the use of these ICs in treating PCa patients. Furthermore, we will also describe the potential of using a combinatory approach of ICIs and radionuclides therapy in treating PCa patients to enhance efficacy, durable cancer control and OS. The inhibitory ICs considered in this review are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD1), V-domain immunoglobulin suppressor of T cell activation (VISTA), indoleamine 2,3-dioxygenase (IDO), T cell Immunoglobulin Domain and Mucin Domain 3 (TIM-3), lymphocyteactivation gene 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), B7 homolog 3 (B7-H3) and B7-H4.
Clinician’s guide to perineal and obstetric anal sphincter injury
(In House Publications, 2020-07) Paterson, Frances; Retief, Francois; Swart, Paul; Abdool, Zeelha; zeelha.abdool@up.ac.za
Perineal trauma is a common consequence of vaginal childbirth. This may be spontaneous or an iatrogenic event following an episiotomy, or a combination of the two. One UK study states that up to 85% of women experience some form of perineal damage during labour. Many of these are minor lacerations, but up to 70% may require suturing. Obstetric anal sphincter injuries (OASIS) are severe perineal lacerations involving part or all of the anal sphincter complex. Improved knowledge and education in the identification and management of OASIS are essential in view of the substantial acute and chronic morbidity associated with such trauma.
Many voices in a choir: tumor-induced neurogenesis and neuronal driven alternative splicing sound like suspects in tumor growth and dissemination
(MDPI, 2021-05) Dlamini, Zodwa; Mathabe, Kgomotso; Padayachy, Llewellyn; Marima, Rahaba; Evangelou, George; Syrigos, Konstantinos N.; Bianchi, Arianna; Lolas, Georgios; Hull, Rodney; zodwa.dlamini@up.ac.za
During development, as tissues expand and grow, they require circulatory, lymphatic, and nervous system expansion for proper function and support. Similarly, as tumors arise and develop, they also require the expansion of these systems to support them. While the contribution of blood and lymphatic systems to the development and progression of cancer is well known and is targeted with anticancer drugs, the contribution of the nervous system is less well studied and understood. Recent studies have shown that the interaction between neurons and a tumor are bilateral and promote metastasis on one hand, and the formation of new nerve structures (neoneurogenesis) on the other. Substances such as neurotransmitters and neurotrophins being the main actors in such interplay, it seems reasonable to expect that alternative splicing and the different populations of protein isoforms can affect tumor-derived neurogenesis. Here, we report the different, documented ways in which neurons contribute to the development and progression of cancer and investigate what is currently known regarding cancer-neuronal interaction in several specific cancer types. Furthermore, we discuss the incidence of alternative splicing that have been identified as playing a role in tumor-induced neoneurogenesis, cancer development and progression. Several examples of changes in alternative splicing that give rise to different isoforms in nerve tissue that support cancer progression, growth and development have also been investigated. Finally, we discuss the potential of our knowledge in alternative splicing to improve tumor diagnosis and treatment.
Prostate cancer racial, socioeconomic, geographic disparities : targeting the genomic landscape and splicing events in search for diagnostic, prognostic and therapeutic targets
(e-Century Publishing, 2021-04) Marima, Rahaba; Hull, Rodney; Mathabe, Kgomotso; Setlai, Botle Precious; Batra, Jyotsna; Sartor, Oliver; Mehrotra, Ravi; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
Prostate cancer (PCa) is one of the leading causes of deaths in men globally. This is a heterogeneous and complex disease that urgently warrants further insight into its pathology. Developed countries have thus far the highest PCa incidence rates, with comparatively low mortality rates. Even though PCa in the Asian population seems to have high incidence and mortality rates, the African countries are emerging as the focal center for this disease. It has also been reported that the Sub-Saharan (SSA) countries have both the highest incidence and mortality rates. To date, few studies have reported the link between PCa and African populations. Adequate evidence is still missing to fully comprehend this relationship. While it has been brought to attention that racial, geographical and socioeconomic status are contributing factors, men of African descent across the globe, irrespective of their geographical position have higher PCa incidence and mortality rates compared to their white counterparts. To date, hormone therapy is the mainstay treatment of PCa, while the dysregulation of androgen receptor (AR) signaling is a hallmark of PCa. One of the emerging problems with this therapeutic approach is resistance to antiandrogens, and that AR splice isoforms implicated in the progression of PCa lack the therapeutic ligand-binding domain (LBD) target. AR splice variants targeted therapy is emerging and in clinical trials. Leveraging PCa transcriptomics is key towards PCa precision medicine. The aim of this review is to outline the PCa epidemiology globally and in Africa, PCa associated risk factors, discuss AR signaling and PCa mechanisms, the role of dysregulated splicing in PCa as novel prognostic indicators and therapeutic targets.
Veterinary growth promoters in cattle feedlot runoff : estrogenic activity and potential effects on the rat male reproductive system
(Springer, 2020-04) Patrick, Sean Mark; Aneck-Hahn, Natalie Hildegard; Van Wyk, Susan; Van Zijl, Magdalena Catherina; Huma, Mampedi; De Jager, Christiaan; tiaan.dejager@up.ac.za
The contribution of veterinary growth promoters (VGP) to the environmental burden of endocrine-disrupting chemicals (EDCs) is largely unknown. At cattle feedlots, the excrement of cattle may contain VGPs, which can contaminate aquatic systems and pose reproductive health risks. The study identifies VGPs used at cattle feedlots in South Africa and confirms associated estrogenic activity in feedlot runoff water. Using a rat model, we investigate the potential reproductive health effects and thyroid function of an environmentally relevant mixture of VGPs. Collected water samples had low levels of selected VGPs, and estrogenic activity was detected in the T47D-KBluc bioassay. Rats exposed to VGP had significant adverse effects on male reproductive health, including shortened anogenital distance, lowered sperm counts, disorganized seminiferous tubules, and thyroid parameters. In conclusion, VGP can contribute to complex environmental EDC mixtures and may adversely affect the reproductive and thyroid health of both humans and wildlife. The varied topography of individual cattle feedlots will govern the rate and extent of effluent runoff, thus continuous monitoring of VGPs in aquatic systems surrounding cattle feedlots is necessary.
Endocrine-disrupting activity of the fungicide mancozeb used in the Vhembe District of South Africa
(NISC (Pty) Ltd and Informa UK Limited (trading as Taylor & Francis Group), 2021) Seshoka, M.F.; Van Zijl, Magdalena Catherina; Aneck-Hahn, Natalie Hildegard; Barnhoorn, I.E.J.
Many chemicals released into the environment are believed to disrupt normal endocrine functions in humans and animals. A major group of endocrine disrupting chemicals (EDCs) that could be responsible for reproductive defects are those that mimic natural oestrogens, known as xenoestrogens. A number of in vivo and in vitro screening strategies are being developed to identify and classify xenoestrogens, in order to determine whether they pose a health risk to humans and animals. Oestrogens and androgens mediate their activity via intracellular receptors, directly in muscular tissue, as well as indirectly via stimulation of growth hormones from the pituitary glands and other growth factors from liver plus several other organs. Mancozeb is a metal ethylenebisdithiocarbamate (EBDC) fungicide used to protect many fruits and vegetables and field crops against pathogenic fungal. The T47D-KBluc, GH3.TRE-Luc and MDA-kb2 reporter gene assays were used to determine the possible endocrine disrupting activity/potential of mancozeb. No activity was detected in any of the assays and no mancozeb was detected in any of the dams either. Oestrogenic activity was detected in Albasini Dam, Nandoni Dam and Xikundu weir, but all values were below 0.7 ng l−1 trigger value for oestrogenic activity in drinking water.
A qualitative exploration of South African men’s perceived effects of androgen deprivation therapy (ADT) as a treatment for advanced prostate cancer
(Taylor and Francis, 2020) Gray, Peter B.; Meintjes, F.; Moshokwa, Evelyn; Mathabe, Kgomotso
OBJECTIVE : We undertake qualitative research with men treated in a Pretoria, South Africa Oncology clinic to address men’s self-reported experiences on androgen deprivation therapy (ADT). METHODS : Analyses rely upon 22 men’s responses to open-ended questions during interviews. These men were 63–78 years of age, and almost all married (three widowed), had children and were no longer engaged in paid work. RESULTS : In addressing questions about the anticipated and experienced positive and broader side effects of ADT, men referred to its treatment for prostate cancer, with several generally specifying health or life. Patients also referred to a variety of more specific effects such as pain, nausea, difficulties urinating, gaining weight, low energy and sleep disruptions that appeared to reflect a mixture of influences of prostate cancer, ADT and oncological treatment. In addressing a question about the effects of ADT on romantic/sex life, 16 of 19 married men referred to deleterious impacts on their sex lives. With respect to perceived family, work or broader social life impacts, some men noted others’ worries and social support. CONCLUSION : Findings are situated within discussions of existing research on ADT largely from North American or European samples, and broader views of testosterone and male social behavior.
Removal of pharmaceutical' estrogenic activity of sequencing batch reactor effluents assessed in the T47D-KBluc report
(Elsevier, 2019-06) Kasonga, Teddy Kabeya; Coetzee, Martie A.A.; Van Zijl, Magdalena Catherina; Momba, Maggy Ndombo Benteke
Various water treatment processes may be ineffective to remove pharmaceutical compounds (PhCs) and their by-products, leading to endocrine-disruptive activity that might be detrimental to wildlife and human health. This study investigated the degradation of carbamazepine (CBZ), diclofenac (DCF), ibuprofen (IBP), and their intermediates, as well as estrogenic activity that is not effectively removed by conventional methods. A consortium of isolated South African indigenous fungi A. niger, M. circinelloides, T. polyzona, T. longibrachiatum and R. microsporus, was used in a sequencing batch reactor (SBR) to remove PhCs, their intermediates and strongly reduce their estrogenic activity. The fungal ligninolytic enzymatic activity was determined for laccase (Lac), manganese peroxidase (MnP) and lignin peroxidase (LiP) using a spectrophotometric method. The biodegradation of PhCs and their intermediates was monitored by SPE-UPLC/MS. The in vitro estrogenic activity was assessed in the T47D-KBluc reporter gene assay. Lac, MnP and LiP production appeared to be biomass growth dependent. During a lag phase of growth, a constant biomass of about 122.04 mg/100 mL was recorded with average enzymatic activity around 63.62 U/L for Lac, 151.91 U/L for MnP and 42.12 U/L for LiP. The exponential growth phase from day 7 to day 17, was characterised by a biomass increase of 124.46 units, and an increase in enzymatic activity of 9.91 units for Lac, 99.03 units for MnP and 44.24 units for LiP. These enzymes played an important synergistic role in PhCs degradation in the cytochrome P450 system. A decrease of 13.89%, 29.7% and 16.15% in PhC concentrations was observed for CBZ, DCF and IBP, respectively, and their intermediates were identified within 4 h of incubation. The removal efficiency achieved after 24 h in the SBR was about 89.77%, 95.8% and 91.41% for CBZ, DCF and IBP, respectively. The estradiol equivalent (EEq) values of 1.71 ± 0.30 ng/L and 2.69 ± 0.17 ng/L were recorded at the start-up time and after 4 h, respectively. The presence of intermediates was found to induce estrogenic activity. The EEq values after 24 h incubation was found to be below the LoQ and below the LoD of the assay. None of the samples exhibited any anti-estrogenic activity. The fungal consortium inoculum was found to induce toxicity at a 0.4× concentration, as observed under a microscope. This study revealed that the use of the fungal consortium can remove the estrogenic activity of pharmaceutical metabolites, which appeared to be the most significant contributors to the endocrine-disrupting activity of the wastewater treatment plant effluents.
Data on UPLC/MS method validation for the biodegradation of pharmaceuticals and intermediates by a fungal consortium and on T47DK-Bluc reporter gene assay to assess the reduction of their estrogenic activity
(Elsevier, 2019-08) Kasonga, Teddy Kabeya; Coetzee, Martie A.A.; Van Zijl, Magdalena Catherina; Momba, Maggy Ndombo Benteke
In term of pharmaceutical and their intermediate compounds analysis, UPLC/MS method is a valuable equipment to achieve better confirmation on their biodegradation by fungi. The T47DKBluc reporter gene assay is an appropriate tool to investigate to removal of estrogenic and antiestrogenic activities of pharmaceuticals and their metabolites from a synthetic wastewater. A consortium of isolated South African indigenous fungi Aspergillus niger, Mucor circinelloides, Trichoderma longibrachiatum, Trametes polyzona and Rhizopus microspores was found to perform a removal of pharmaceuticals and their metabolites and to reduce their estrogenic activity below the limit of detection in a sequencing batch reactor. Here are presented data regarding the phenolic compounds list and the method validation for UPLC/MS analysis used for selected pharmaceutical compounds namely carbamazepine, diclofenac, ibuprofen and their metabolites, as well as the T47DKBluc bioassay using as positive control, the agonist E2 for estrogenic activity and the antagonist ICI 182,780 for antiestrogenic activity. For better understanding of the data presented in this paper, please see the research paper “Removal of pharmaceutical’ estrogenic activity of sequencing batch reactor effluents assessed in the T47DK-Bluc reporter gene assay” [1].

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