Research Articles (Physiology)

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A new dawn : vitalising translational oncology research in Africa with the help of advanced cell culture models
(Elsevier, 2025-06) Klima, Stefanie; Hurrell, Tracey; Goolam, Mubeen; Gouws, Chrisna; Engelbrecht, Anna-Mart; Kaur, Mandeep; Van den Bout, Iman; iman.vandenbout@up.ac.za
The advent of in vitro models such as induced pluripotent stem cells (iPSC) and patient derived (disease) organoids is supporting the development of population and patient specific model systems reflecting human physiology and disease. However, there remains a significant underrepresentation of non-European, especially African model systems. The development of such models should be enthusiastically embraced by Sub-Saharan African countries (SSAC) and middle-income countries (LIMC) to direct their own research focused on the improvement of health of their own populations at a sustainable cost within their respective funding environments. Great care needs to be taken to develop national frameworks to direct, sustainably fund and support such efforts in a way that maximises the output of such models for the investment required. Here, we highlight how advanced culture models can play a role in vitalising local healthcare research by focusing on locally relevant health care questions using appropriate cell culture models. We also provide a potential national platform example that could maximise such output at the lowest cost. This framework presents an opportunity for SSAC and LMIC to base their healthcare research on locally relevant models to ensure that developed health care initiatives and interventions are best suited for the populations they serve and thus represent a reset in global health care research at large. HIGHLIGHTS • Advanced cell culture models herald a unique opportunity for African oncology research. • Rationalizing model development at a national level will achieve amplified advances. • A national framework to optimize African models is proposed.
Countermovement jump kinetic impairments in elite athletes before and after ACL injury : force-time waveform versus discrete kinetic analysis
(Wiley, 2025-05) De Franca, Cassidy; Jordan, Matthew J.; Botha, Tanita; Bayne, Helen
Pre-injury and post-injury countermovement jump (CMJ) force-time data were obtained for elite athletes 6 months after anterior cruciate ligament surgery (ACLR). Jump kinetics were analysed using a traditional phase-specific approach, and force-time data of the CMJ waveform were analysed using statistical parametric mapping (SPM). Elite athletes (n = 10; female n = 6, age = 22.0 ± 3.5 years, mass = 75.9 ± 11.5 kg) performed CMJ testing before (T0) and after ACLR (T1; 24 ± 3 weeks post-surgery). Differences in discrete and continuous metrics were analysed for (1) within-limb differences between T1 and T0 and (2) between-limb differences at T1 and T0. Lower involved limb propulsive impulse (T1: 6.4 ± 1.6 N∙s/kg; T0: 7.7 ± 1.4 N∙s/kg, p = 0.002) and peak force (T1: 6.4 ± 1.6 N/kg; T0: 7.7 ± 1.4 N/kg, p = 0.002) were found after ACLR compared to baseline. After ACLR (T1), lower involved limb propulsive impulse was found compared to the uninvolved limb (involved: 1.26 ± 0.54 N∙s/kg; uninvolved: 1.58 ± 0.56 N∙s/kg, p = 0.007). SPM analysis revealed specific within-limb force loss, notably reduced involved limb propulsion force at T1 compared to pre-injury at T0 (p < 0.001) between 92% and 99% of the CMJ (end of propulsion) and between 36% and 37% of the CMJ (i.e., late unweighting to braking phase transition). SPM analysis revealed within-limb CMJ force loss that was not seen with the discrete analysis, highlighting the complementary value of SPM waveform analysis alongside discrete analysis to identify neuromuscular impairments in stretch-shortening-cycle function in elite athletes after ACLR.
Brain-death in rats increases neutrophil extracellular trap formation in donor organs
(Frontiers Media, 2025-04) Van Zyl, Maryna; Armstrong Junior, Roberto; Ottens, Petra; Van Goor, Harry; Van Rooy, Mia-Jeanne; Lisman, Ton; Leuvenink, Henri G.D.; Hillebrands, Jan-Luuk
During brain-death, increased numbers of neutrophils are recruited to organs as part of the inflammatory response. In the organ microenvironment, the recruited neutrophils may release neutrophil extracellular traps (NETs) through interaction with various pro-inflammatory stimuli, contributing to brain-death-induced endothelial activation, microthrombus formation and ultimately a decline in organ quality. To investigate whether NETs form in organs from brain-dead donors; kidneys, hearts, livers, and plasma samples were collected from brain-dead or sham-operated rats. The presence of NET-specific components, neutrophils and macrophages were analyzed through immunofluorescent microscopy. Endothelial activation and platelet infiltration were analyzed through immunohistochemistry and qRT-PCR analysis. Plasma free thiol levels were used to evaluate systemic oxidative stress. Increased neutrophils, NETs and NET/neutrophil ratios were observed in kidneys, hearts and livers of brain-dead rats compared to sham-operated rats. Numbers of NETs positively correlated with the extent of endothelial cell activation. Brain-dead animals also had increased kidney and liver macrophages, increased infiltrated platelets in the liver, and elevated systemic oxidative stress, compared to sham-operated animals. Our findings established the presence of NETs in organs from a brain-dead donor model and suggest that NETs, alongside increased inflammation and a redox imbalance, might prime organs for microvascular endothelial dysfunction and increased injury during brain-death.
Relationships between coordination, strength and performance during initial sprint acceleration
(Routledge, 2025) Donaldson, Byron John; Bezodis, Neil; Bayne, Helen
Despite strong logical and theoretical links, no studies have directly examined the relationship between physical qualities and coordination during sprint acceleration. The aim of this study was to assess the associations between initial acceleration coordination and lower body strength and explore potential interactions between strength and coordination in relation to acceleration performance. Sagittal plane kinematics and velocity-time profiles were obtained for highly trained to world class male sprinters (100 m PB: 9.95–11.17 s). Thigh–thigh and shank–foot coordination was determined for the first four steps using vector coding, and external kinetic parameters derived from a mono-exponential fit to velocity-time profiles. Lower body strength was measured with isometric squat (ISqT), countermovement jump (CMJ), repeated hop (HJ) and Nordic hamstring tests. Large to very large correlations (ρ = 0.59–0.82) existed between ISqT, CMJ, HJ tests and specific coordination features in both step 1 and steps 2–4, and exploratory regression analyses suggested the potential for higher or lower magnitudes of a given strength capacity to modify the relationships between coordination features and acceleration performance. These findings support an individualised approach to technique in sprint training, and consideration of the influence of strength qualities on the adoption and effectiveness of particular movement patterns.
Pharmacological potential of Portulacaria afra : a review on bioactive compounds, pharmacological uses and therapeutic prospects
(Elsevier, 2024-12) Mhosva, Yvonne; Nkomozepi, Pilani; Nalla, Shahed; Nyakudya, Trevor Tapiwa
There has been a notable increase in the use of ethnomedicines in developing nations, primarily due to their low cost, widespread availability, and the belief that they are safer alternatives to conventional medicines. Portulacaria afra (P. afra), a medicinal plant native to South Africa, has been traditionally used in treating diseases such as diabetes, diarrhoea, fever, hypertension, and various skin and blood disorders. This review examines the pharmaceutical potential of P. afra, focusing on its bioactive compounds, pharmacological uses, and therapeutic potential. Various approaches were used to gather relevant data, including searches through databases such as Google Scholar, PubMed, and ScienceDirect. In vitro studies have demonstrated multiple biological activities, including antioxidant, anti-inflammatory, anti-diabetic, anti-bacterial, and cytotoxic effects. Phytochemical analysis has identified groups of compounds in P. afra, such as flavonoids, phenolic acids, alkaloids, saponins, tannins, and glycosides. Bioactive compounds such as lupeol and piperidine have also been identified recently. However, a major limitation is that these pharmacological findings are confined to in vitro studies, with little or no significant in vivo studies to validate these effects. Hence, further research is essential to assess the pharmacological activities in vivo, clinical efficacy, safety of P. afra, and the therapeutic mechanism(s) to understand its folkloric use as a possible candidate in modern therapeutics.
Commentary on the published position statement regarding the pathogenesis of fetal basal gangliathalamic hypoxic-ischaemic injury
(South African Medical Association, 2024-01) Anthony, J.; Smith, J.; Murray, L.; Kirsten, G.F.; Gericke, George Sebastian; Kara, Y.; Davies, V.; Pearce, D.; Van Toorn, R.; Lippert, M.M.; Lotz, J.W.; Andronikou, S.; Alheit, B.; Van Wyk, L.; Ebrahim, A.S.; Schifrin, B.S.
No abstract available.
The impact of selected regimens of chronic HIV-antiretroviral treatment on glycemic control markers and correlates : a systematic review and meta-analysis protocol
(Wiley, 2025-01) Gamede, Mlindeli; Sosibo, Mbulelo Aubrey; Gumede, Nontobeko Myllet; Luvuno, Mluleki; mlindeli.gamede@up.ac.za
BACKGROUND AND AIM : Diabetes mellitus is one of the leading causes of morbidity and mortality among non-communicable diseases worldwide. The etiology of diabetes can be mainly attributed to factors such as genetic susceptibility, unhealthy diets, and chronic medications. Chronic medications such as HIV-antiretrovirals (ARVs) have been previously associated with the risks of developing metabolic complications. Hence, this protocol outlines the process for conducting a systematic review to investigate the association between chronic ARV treatment and the onset of metabolic syndrome complications. METHODOLOGY AND ANALYSIS : The studies included in the systematic review are selected according to the inclusion and exclusion criteria. These studies are searched using search engines or databases such as PUBMED, GOOGLE SCHOLAR, MEDLINE, ScienceDirect, and EMBASE DATABASE. The articles that remained after full article screening will be assessed for bias using the Downs and Black checklist, and the data will be extracted. Additionally, heterogeneity tests will be conducted using both Χ2 and I2 tests, meta-analysis will be conducted using the Review Manager version 5.4 software (RevMan), and data will be presented in forest plots. Grading of Recommendations Assessment, Development, and Evaluation approach (GRADE) will be used to assess the strength of evidence in eligible reports. DISSEMINATION AND REGISTRATION : The findings intend to give an insight into the ARVs as a risk factor for metabolic diseases and further elaborate on the regimen that possesses a high risk between the first and second regimens. This protocol has been registered on PROSPERO Database #CRD42024521322.
Care and compassion in healthcare provision
(South African Dental Association, 2024-09) Sykes, Leanne M.; Bester, Janette; leanne.sykes@up.ac.za
The quality of patient care forms the basis of all doctor-patient relationships. However, it requires more than mere provision of what is necessary to maintain or restore their health, and should encompass an emotional connection, and a desire to help them. Care covers a wide range of activities and is often seen as the technical and procedural aspects of medicine, while compassion revolves around the relational aspects of patient care. It requires clinicians to be able to express empathy and understanding, share their patients' feelings, be available, communicate, try to provide support and encouragement, and treat them with respect and dignity. This paper discusses care and compassion and explores issues such as whether a person can be taught to care and/ or show compassion; if too much compassion could cloud a practitioner's judgement; if it's possible to deliver good care without being compassionate; and whether a person who has never experienced compassion can develop this ability. Care and compassion are essential components of effective medical practice, and need to be integrated into healthcare. Clinicians should adopt a patient-centred approach that prioritises the patient's values, needs and preferences during their decision-making process. At the same time, they must cultivate emotional intelligence, and identify when they need mental, emotional or physical support.
Years of running, chronic diseases, and allergies are associated with gradual onset Achilles tendon injuries in 61,252 running race entrants
(Wiley, 2024-11) Young, Jonah Dylan; Wood, Paola Silvia; Schwellnus, Martin Peter; Jordaan, Esme; Swanevelder, Sonja
BACKGROUND : Gradual-onset Achilles tendon injuries (GoATIs) in runners are common. Data show that chronic diseases are associated with GoATI. OBJECTIVE : To determine risk factors associated with a history of GoATIs among long-distance runners (21.1 and 56 km) entering a mass community-based running event. METHODS : Online pre-race medical screening questionnaire data from 76,654 consenting Two Ocean Marathon race entrants (71.8% entrants) were collected prospectively over 4 years (2012-2015); this cross-sectional study is a retrospective analysis of these data. A total of 617 entrants (0.8%) reported a GoATI in the last 12 months; 60,635 entrants reported no history of any running injury (controls). Categories of factors associated with GoATI were explored (univariate and multiple regression analyses): demographics (age group, sex, race, distance), training/racing history, and history of allergy, history of chronic disease, and Composite Chronic Disease Score. Prevalence and prevalence ratios (PRs; 95% CI) are reported. RESULTS : Factors associated with a higher prevalence of a history of GoATI (univariate analysis vs. controls) were older age (>31 years) (p < .001), male sex (PR = 1.76; p < .001), and longer race distance (56 km vs. 21.1 km) (PR = 2.06; p < .001). Independent factors associated with a history of GoATI (multiple regression) were increased years of recreational running (PR = 1.17 for every 5-year increase, p < .001), higher Composite Chronic Disease Score (PR = 2.07 for every 2-unit increase, p < .001), and allergy history (PR = 1.98 p < .001). CONCLUSION : Novel independent factors associated with a history of GoATI in distance runners were increased years of recreational running, chronic disease history, and allergy history. Runners at risk for GoATI could be targeted for injury prevention interventions. Future studies should focus on establishing a causal relationship.
Association between recorded physical activity and cancer progression or mortality in individuals diagnosed with cancer in South Africa
(BMJ Publishing, 2025-05) Mabena, Ntokozo; Rugbeer, Nivash; Lehmann, Sandra; Torres, Georgia; Patel, Deepak; Mabunda, Mosima; Greyling, Mike; Thornton, Jane S.; Choi, Yun-Hee; Stranges, Saverio; Patricios, Jon S.
OBJECTIVES : This study aimed to determine the association between progression and mortality in individuals with stage 1 cancer and their recorded physical activity before the diagnosis of the cancer. METHODS : We included 28 248 members with stage 1 cancers enrolled in an oncology programme in South Africa. Physical activity was recorded using fitness devices, logged gym sessions and participation in organised fitness events. Levels of physical activity over the 12 months before cancer diagnosis were categorised as no physical activity, low physical activity (an average of <60 min/week) and moderate to high physical activity (≥60 min/week). Measured outcomes were time to progression, time to death and all cause mortality. RESULTS : Physically active members showed lower rates of cancer progression and lower rates of death from all causes. The HR for progression to higher stages or death was 0.84 (95% CI 0.79 to 0.89), comparing low activity with no physical activity, and 0.73 (95% CI 0.70 to 0.77), comparing medium to high physical activity with no physical activity. The HR for all cause mortality was 0.67 (95% CI 0.61 to 0.74), comparing low physical activity with no activity, and 0.53 (95% CI 0.50 to 0.58), comparing medium to high physical activity with no physical activity. CONCUSIONS : Individuals engaging in any level of recorded physical activity showed a reduced risk of cancer progression or mortality than those not physically active. There was a further reduction among individuals with moderate to high levels of physical activity compared with those with lower levels.
Associating serum testosterone levels with African ancestral prostate cancer health disparities
(Nature Research, 2025-04) Lebelo, Maphuti Tebogo; Mmekwa, Naledi; Louw, Melanie; Jaratlerdsiri, Weerachai; Mutambirwa, Shingai B.A.; Loda, Massimo; Hayes, Vanessa M.; Bornman, Maria S. (Riana); riana.bornman@up.ac.za
Serum testosterone levels decrease in the aging male, while the risk for prostate cancer (PCa) increases concomitantly. Higher levels in younger men have been linked with racially driven PCa disparities, with African men disproportionately impacted. In turn, higher levels of serum lipids have been associated with aggressive disease, while racial disparity between serum testosterone, cholesterol and cancer mortality has been suggested. Having previously reported a 2.1-fold increased age-adjusted risk for aggressive PCa in Black South African over Black American men, we determined the serum testosterone and associated lipid levels in 250 Black South African men either with or without clinicopathologically diagnosed disease. Observing no associations with serum lipid levels, Black South Africans presented with testosterone levels between 1.24 (< 60 years) and 1.3-fold (≥ 60 years) greater than Black Americans. Notably, a rapid drop in total-, bioavailable- and free testosterone levels in men 65 years or older was significantly associated with PCa risk (P = 0.0057, 0.009 and 0.005, respectively), while irrespective of age, further associated with advanced disease (P = 0.004, 0.0012 and 0.0036, respectively). These preliminary data provide insights into the potential role of androgens in driving PCa health disparities, with important consequence for tailoring treatment for Black men.
Objective classification of countermovement jump force-time curve modality : within athlete-consistency and associations with jump performance
(Routledge, 2024) Bayne, Helen; Cockcroft, John; Robyn, Aneurin; Louw, Quinette; helen.bayne@up.ac.za
Force-time curves produced during a countermovement jump (CMJ) have traditionally been classified by visual observation as either unimodal (one concentric phase peak) or bimodal (two peaks). The association between CMJ modality and jump performance remains unclear and future studies may benefit from standardising and expanding modality classification. This study described a numerical method based on the timing and relative magnitude of concentric force-time curve prominences. Adult male elite rugby union players (n = 214) performed six CMJs on a force-instrumented treadmill and an algorithm using turning-point logic was applied to categorise jumps and define modality sub-groups. A sensitivity analysis demonstrated that the minimum prominence threshold (MPT) affected categorisation, as the proportion of bimodal jumps decreased with each 1% increase in MPT. Within-athlete consistency was also affected; between 43% and 63% of participants were consistently categorised as bimodal or unimodal depending on the selected MPT. Modified reactive strength index (RSImod), but not jump height or take-off momentum, was greater in unimodal jumps. Take-off momentum and RSImod were greater in subcategories where maximum force occurred early in the concentric phase. Future research should implement objective classification methods to enhance transparency and comparability and consider subcategories to investigate CMJ force production strategies.
Multi-target inhibitor CUDC-101 impairs DNA damage repair and enhances radiation response in triple-negative breast cell line
(MDPI, 2024-11-01) Seane, Elsie Neo; Nair, Shankari; Vandevoorde, Charlot; Bisio, Alessandra; Joubert, Anna Margaretha; annie.joubert@up.ac.za
BACKGROUND : Since the discovery that Histone deacetylase inhibitors (HDCAi) could enhance radiation response, a number of HDACi, mainly pan-HDAC inhibitors, have been studied either as monotherapy or in combination with X-ray irradiation or chemotherapeutic drugs in the management of breast cancer. However, studies on the combination of HDACi and proton radiation remain limited. CUDC-101 is a multitarget inhibitor of Histone deacetylases (HDACs), epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER-2). In this paper, the effectiveness of CUDC-101 in enhancing radiation response to both proton and X-ray irradiation was studied. METHODS : MCF-7, MDA-MB-231, and MCF-10A cell lines were pre-treated with CUDC- 101 and exposed to 148 MeV protons, and X-rays were used as reference radiation. Colony survival, γ-H2AX foci, apoptosis, and cell cycle analysis assays were performed. RESULTS : γ-H2AX foci assays showed increased sensitivity to CUDC-101 in the MDA-MB-231 cell line compared to the MCF-7 cell line. In both cell lines, induction of apoptosis was enhanced in CUDC-101 pre-treated cells compared to radiation (protons or X-rays) alone. Increased apoptosis was also noted in CUDC-101 pre-treated cells in the MCF-10A cell line. Cell cycle analysis showed increased G2/M arrest by CUDC-101 mono-treatment as well as combination of CUDC-101 and X-ray irradiation in the MDA-MB-231 cell line. CONCLUSIONS : CUDC-101 effectively enhances response to both proton and X-ray irradiation, in the triple-negative MDA-MB-231 cell line. This enhancement was most notable when CUDC-101 was combined with proton irradiation. This study highlights that CUDC-101 holds potential in the management of triple-negative breast cancer as monotherapy or in combination with protons or X-ray irradiation.
Mechanistic sequence of histone deacetylase inhibitors and radiation treatment : an overview
(MDPI, 2024-05-08) Seane, Elsie Neo; Nair, Shankari; Vandevoorde, Charlot; Joubert, Anna Margaretha; annie.joubert@up.ac.za
Histone deacetylases inhibitors (HDACis) have shown promising therapeutic outcomes in haematological malignancies such as leukaemia, multiple myeloma, and lymphoma, with disappointing results in solid tumours when used as monotherapy. As a result, combination therapies either with radiation or other deoxyribonucleic acid (DNA) damaging agents have been suggested as ideal strategy to improve their efficacy in solid tumours. Numerous in vitro and in vivo studies have demonstrated that HDACis can sensitise malignant cells to both electromagnetic and particle types of radiation by inhibiting DNA damage repair. Although the radiosensitising ability of HDACis has been reported as early as the 1990s, the mechanisms of radiosensitisation are yet to be fully understood. This review brings forth the various protocols used to sequence the administration of radiation and HDACi treatments in the different studies. The possible contribution of these various protocols to the ambiguity that surrounds the mechanisms of radiosensitisation is also highlighted.
PhysioCAFUN : a competency-based curriculum development guideline to strengthen physiology education in Africa
(American Physiological Society, 2025-03) Alagbonsi, Abdullateef Isiaka; Essop, M. Faadiel; El-Wazir, Yasser; Nyakudya, Trevor Tapiwa; Fastone, Goma; Mojiminiyi, Frank; Saeed, Amal; Stienen, Ger J.M.; Balandya, Emmanuel; Raji, Yinusa; Bintou Sarr, Fatou; Samb, Abdoulaye; Ebrahim, Ashabilan; Pohl, Ulrich; Silverthorn, Dee U.
Physiology education in Africa faces challenges due to gaps in curricula across many of its universities, such as divergent content, a lack of standardized competencies, and suitable benchmarking. Here, we describe the development of the Physiology Curriculum for African Universities (PhysioCAFUN), a competency-based curriculum development guideline, as a first step to address such shortcomings. A committee of 15 physiologists from different African regions, Europe, and the United States was constituted to draft the PhysioCAFUN, which was introduced and revised during the joint East African Society of Physiological Sciences (EASPS) and African Association of Physiological Sciences (AAPS) conference held in Tanzania late 2023. The PhysioCAFUN consists of 23 modules. Modules 1–15 cover the organ systems, including principles and concepts of physiology, molecular biology, and cell physiology. Modules 16–23 contain optional content, including environmental physiology, pharmacology, and topics related to skill development. PhysioCAFUN serves as a freely available resource document for African stakeholders regarding the desired undergraduate physiology training and competencies. It will help universities in Africa, and elsewhere to draft a curriculum suitable for their local needs where there is a dearth of physiologists or to benchmark and revise their curricula where physiology programs are already in place. NEW & NOTEWORTHY : We described the development of Physiology Curriculum for African Universities (PhysioCAFUN), a competency-based curriculum development guideline to promote physiology education in Africa. This freely accessible resource document should help African universities where there is a dearth of physiologists and thus aid in drafting a curriculum suitable for their local needs. Likewise, it should assist universities globally where physiology programs are already in place to benchmark and/or revise their curriculum as may be needed.
Number of symptoms during the acute phase of SARS-CoV-2 infection in athletes is associated with multiorgan involvement : AWARE III
(Lippincott Williams and Wilkins, 2025) Snyders, Carolette; Dyer, Marlise; Jordaan, Esme; Scholtz, Leonie; Du Plessis, Andre; Mpe, Martin; Kaulback, Kelly; Schwellnus, Martin Peter; carolette.cloete@semli.co.za
OBJECTIVE : Acute respiratory infections (ARinf), including SARS-CoV-2 infection, can affect multiple organ systems that may influence return to sport (RTS) in athletes. Factors associated with multiorgan involvement in athletes with ARinf are lacking. The aim of this study was to explore whether factors such as demographics, sport participation, history of comorbidities/allergies, and number of acute symptoms are associated with multiorgan involvement in athletes with recent SARS-CoV-2 infection. DESIGN : Prospective cohort study with cross-sectional analysis. SETTING : Institutional clinical research facilities. PARTICIPANTS : Ninety-five athletes (18–60 years) underwent a comprehensive medical assessment 10 to 28 days after SARS-CoV-2 infection. INDEPENDANT FACTORS : Demographics, sport participation, history of comorbidities/allergies, and the number of acute symptoms (in 3 subgroups:1 = ≤5, 2 = 6-9, or 3 ≥ 10). MAIN OUTCOME MEASURES : Number of organs involved in athletes with recent SARS-CoV-2 infection. RESULTS : The number of organ systems involved was not associated with demographics (age, sex), sport participation (level and type), or history of comorbidities and allergies. However, the number of organ systems involved was significantly higher in athletes with 6 to 9 symptoms (subgroup 2) compared with those with ≤5 symptoms (subgroup 1) and this was more pronounced when comparing athletes with ≥10 symptoms (subgroup 3) with those with ≤5 symptoms (subgroup 1) (P < 0.0001). CONCLUSIONS : Total number of acute symptoms of SARS-CoV-2 infection is related to number of organ systems involved, which is a measure of disease severity, and could therefore influence RTS decision making. Future studies should explore whether this observation holds for athletes with ARinf caused by other pathogens.
COVID-19-induced diabetes mellitus : comprehensive cellular and molecular mechanistic insights
(MDPI, 2024-06) Nhau, Praise T.; Gamede, Mlindeli; Sibiya, Ntethelelo
Despite evidence demonstrating the risks of developing diabetes mellitus because of SARSCoV-2, there is, however, insufficient scientific data available to elucidate the relationship between diabetes mellitus and COVID-19. Research indicates that SARS-CoV-2 infection is associated with persistent damage to organ systems due to the systemic inflammatory response. Since COVID-19 is known to induce these conditions, further investigation is necessary to fully understand its longterm effects on human health. Consequently, it is essential to consider the effect of the COVID-19 pandemic when predicting the prevalence of diabetes mellitus in the future, especially since the incidence of diabetes mellitus was already on the rise before the pandemic. Additional research is required to fully comprehend the impact of SARS-CoV-2 infection on glucose tolerance and insulin sensitivity. Therefore, this article delves deeper into the current literature and links the perceived relationship between SARS-CoV-2 and diabetes. In addition, the article highlights the necessity for further research to fully grasp the mechanisms that SARS-CoV-2 utilises to induce new-onset diabetes. Where understanding and consensus are reached, therapeutic interventions to prevent the onset of diabetes could be proposed. Lastly, we propose advocating for the regular screening of diabetes and pre-diabetes, particularly for the high-risk population with a history of COVID-19 infection.
Evaluation of [68Ga]Ga-DOTA-AeK as a potential imaging tool for PET imaging of cell wall synthesis in bacterial infections
(MDPI, 2024-09) Koatale, Palesa Caroline; Welling, Mick M.; Mdanda, Sipho; Mdlophane, Amanda; Takyi-Williams, John; Durandt, Chrisna; Van den Bout, Iman; Cleeren, Frederik; Sathekge, Mike Machaba; Ebenhan, Thomas; thomas.ebenhan@up.ac.za
Please read abstract in article.
Identification of small-molecule antagonists targeting the growth hormone releasing hormone receptor (GHRHR)
(American Chemical Society, 2024-08-29) Matsoukas, Minos-Timotheos; Radomsky, Tarryn; Panagiotopoulos, Vasilis; Du Preez, Robin; Papadourakis, Michail; Tsianakas, Konstantinos; Millar, Robert P.; Anderson, Ross Calley; Spyroulias, Georgios A.; Newton, Claire L.
The growth hormone-releasing hormone receptor (GHRHR) belongs to Class B1 of G protein-coupled receptors (GPCRs). Class B1 GPCR peptides such, as growth hormone-releasing hormone (GHRH), have been proposed to bind in a twostep model, where first the C-terminal region of the peptide interacts with the extracellular domain of the receptor and, subsequently, the N-terminus interacts with the seven transmembrane domain of the receptor, resulting in activation. The GHRHR has recently been highlighted as a promising drug target toward several types of cancer and has been shown to be overexpressed in prostate, breast, pancreatic, and ovarian cancer. Indeed, peptide GHRHR antagonists have displayed promising results in many cancer models. However, no nonpeptide GHRHR-targeting compounds have yet been identified. We have utilized several computational tools to target GHRHR and identify potential small-molecule compounds directed at this receptor. These compounds were validated in vitro using a cyclic adenosine monophosphate (cAMP) ELISA to measure activity at the GHRHR. In vitro results suggest that several of the novel small-molecule compounds could inhibit GHRH-induced cAMP accumulation. Preliminary analysis of the specificity/ selectivity of one of the most effective hit compounds indicated that the effect seen was via inhibition of the GHRHR. We therefore report the first nonpeptide antagonists of GHRHR and propose a structural basis for inhibition induced by the compounds, which may assist in the future design of lead GHRHR compounds for treating disorders attributed to dysregulated/aberrant GHRHR signaling.
Obstructive sleep apnea screening protocol and safety measures : advancing treatment quality and reducing medical emergency team activation in patients with atrial fibrillation, respiratory diseases, and frailty
(American Academy of Sleep Medicine, 2024-05) Otto, Monique
Despite ongoing research, the association of in-hospital medical emergency team activation (META) among patients with atrial fibrillation (AF) who are at risk for obstructive sleep apnea (OSA) is unclear. Using sleep questionnaires and other forms of screeners have become useful tools for such patients, but their sensitivity and specificity, application in various diseases and risk factors, and therefore, overall usefulness, require further study.1,2 For instance, a study by El-Sayed2 showed that the sensitivity of the Berlin, STOP (Snoring, Tiredness, Observed apnea, high blood Pressure), and STOP-BANG (Snoring, Tiredness, Observed apnea, high blood Pressure, BMI, Age, Neck circumference, Gender) questionnaires was high when screening for OSA; however, the low specificity of these questionnaires resulted in increased false positives and failure of exclusion of individuals at low risk.2 Undiagnosed and untreated OSA is associated with increased in-hospital morbidity and serves as a risk factor for cardiac complications, including hypertension, diabetes, and dyslipidemia, and diseases such as coronary artery disease and AF.1,3 In addition, pathophysiologic pathways related to OSA, such as alterations in intrathoracic pressure, intermittent hypoxemia, and autonomic nervous system fluctuations, may lead to atrial structural and electrical remodeling, resulting in predisposition to AF.4 Chen et al5 reported that the apnea-hypopnea and desaturation indices cannot fully represent the severity of OSA in patients with stroke. Instead, the mean desaturation value during nocturnal hypoxia must be used. Nocturnal hypoxia due to OSA was shown to be an independent predictor of AF in patients with subacute ischemic stroke, and it was concluded that the use of an overnight pulse oximeter to assess nocturnal hypoxia and to predict paroxysmal AF in patients with cryptogenic stroke requires further evaluation, illustrating the importance of reliable screening methods for OSA and its risk factors.1

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