Ambiguous Genitalia Due to 3β-Hydroxysteroid Dehydrogenase Type 2 Deficiency: Clinical, Genetic, and Functional Characterization of Two Novel Variants.

3β-Hydroxysteroid dehydrogenase 2 deficiency (3βHSD2D) is a rare form of congenital adrenal hyperplasia (CAH) with variable clinical presentation. We describe a 46, XY child with ambiguous genitalia and CAH without apparent adrenal insufficiency due to 2 novel heterozygous variants in the gene (c.779C > T/p.

First ABO-Incompatible Pediatric Kidney Transplant in South Africa-A Case Report.

Background: Blood group incompatibility previously represented an obstacle to living related donor (LRD) options; desensitization modalities have expanded LRD options. ABO-incompatible kidney transplants have been successful in adults and pediatric liver transplants, but to date not yet in pediatric kidney transplants in South Africa.

Case Report: Patient X is a 5 year old male with end-stage kidney failure due to Posterior Urethral Valves, requiring peritoneal dialysis pre-transplant.

Initial empirical antibiotic therapy in kidney transplant recipients with pyelonephritis: A global survey of current practice and opinions across 19 countries on six continents.

Background: Despite the burden of pyelonephritis after kidney transplantation, there is no consensus on initial empirical antibiotic management.

Methods: We surveyed clinicians throughout the world on their practice and opinions about the initial empirical therapy of post-transplant pyelonephritis, using clinical vignettes. A panel of experts from 19 countries on six continents designed this survey, and invited 2145 clinicians to participate.

A tale of two kidneys, and the case for machine perfusion in South Africa.

Extended-criteria donors (ECDs) are seen as a means of addressing the shortfall in solid-organ availability for transplant. However, the use of ECD kidneys is associated with a greater risk of primary non-function compared with standard-criteria donor kidneys, and a higher discard rate has been described internationally. There seems to be a lack of consensus in the consideration of ECD kidneys for transplant, with reliance often placed on the subjective assessment of individual clinicians.

Kidney transplant utilising donors after circulatory death: The first report from the African continent.

Background: At Groote Schuur Hospital in Cape Town, South Africa, the number of deceased organ donors has declined over the past 2 decades, necessitating a more liberal approach to donor selection. In 2007, measures to expand the deceased kidney donor pool were implemented, including an HIV positive-to-positive transplant programme and the utilisation of extended-criteria donors as well as donors after circulatory death (DCDs).

Objectives: To report on our institutional experience with DCD kidney transplants and to encourage this approach among other African centres to improve access to transplantation.

The state of paediatric deceased-organ donation at a South African tertiary public- sector hospital: A 14-year analysis.

Background: Solid-organ transplantation (SOT) has been proven to be a highly effective and life-saving treatment modality for adults and children suffering from end-stage organ failure. However, high paediatric waiting-list mortality has been reported, and children may suffer irreversible physical and deleterious psychological effects if not transplanted timeously.

Objectives: To identify in-hospital barriers to organ donation and gain a better understanding of the paediatric donor landscape.

Clinical course, management and outcomes of COVID-19 in HIV-infected renal transplant recipients: A case series.

Background: HIV-infected kidney transplant recipients with COVID-19 are at increased risk of acute illness and death owing to their underlying comorbidities and chronic immunosuppression.

Objectives: To describe the incidence, clinical presentation and course of COVID-19, vaccination status, and SARS-CoV-2 antibody positivity rate among HIV-infected-to-HIV-infected kidney transplant recipients in South Africa (SA).

Methods: This retrospective study reports on rates of SARS-CoV-2 infection, COVID-19 and mortality among SA HIV-infected kidney transplant recipients who received organs from HIV-infected donors (HIV positive to HIV positive), before and after vaccination.

Circulating adrenal and gonadal steroid hormones heterogeneity in active young males and the contribution of 11-oxy androgens.

The classical androgens, testosterone and dihydrotestosterone, together with dehydroepiandrosterone, the precusrsor to all androgens, are generally included in diagnostic steroid evaluations of androgen excess and deficiency disorders and monitored in androgen replacement and androgen suppressive therapies. The C11-oxy androgens also contribute to androgen excess disorders and are still often excluded from clinical and research-based steroids analysis. The contribution of the C11-oxy androgens to the androgen pool has not been considered in androgen deficiency.

Frameworks describing the transition to open labour employment for persons with mild and moderate intellectual disability: a scoping review protocol.

Introduction: Persons with mild and moderate intellectual disability (MMID) have the right to participate in all aspects of society and be afforded equal opportunities to realise their full potential. However, it is a challenge for persons with MMID to find and maintain employment due to many different barriers. Currently, there is no contextually relevant framework in South Africa that considers the unique employment support needs and accommodation of persons with MMID, which can guide and inform the transition to employment interventions, strategies and national policy directives.

FDXR variants cause adrenal insufficiency and atypical sexual development.

Genetic defects affecting steroid biosynthesis cause cortisol deficiency and differences of sex development; among these defects are recessive mutations in the steroidogenic enzymes CYP11A1 and CYP11B, whose function is supported by reducing equivalents donated by ferredoxin reductase (FDXR) and ferredoxin. So far, mutations in the mitochondrial flavoprotein FDXR have been associated with a progressive neuropathic mitochondriopathy named FDXR-related mitochondriopathy (FRM), but cortisol insufficiency has not been documented. However, patients with FRM often experience worsening or demise following stress associated with infections.

Multiple androgen pathways contribute to the steroid signature of adrenarche.

Context: Adrenarche is a normal developmental event in mid-childhood characterized by increasing adrenal androgen secretion. The role of the classic androgen pathway has been well described in adrenarche, but the role of newer active androgens and additional androgen pathways is less clear.

Objective: To study the contribution of novel androgens and related steroid biosynthesis pathways to the development of adrenarche, and to identify additional steroid biomarkers of adrenarche.

Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450.

Endocrine-disrupting chemicals (EDCs) may impact the development of prostate cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 which are involved in the production of androgens or estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women.

Adrenal Abcg1 Controls Cholesterol Flux and Steroidogenesis.

Cholesterol is the precursor of all steroids, but how cholesterol flux is controlled in steroidogenic tissues is poorly understood. The cholesterol exporter ABCG1 is an essential component of the reverse cholesterol pathway and its global inactivation results in neutral lipid redistribution to tissue macrophages. The function of ABCG1 in steroidogenic tissues, however, has not been explored.

No extra-adrenal aldosterone production in various human cell lines.

Extra-adrenal de novo aldosterone (Aldo) production has been described inconsistently. Systematic data based upon state-of-the-art technology including validated controls are sparse. We hypothesized that aldosterone synthase (CYP11B2) expression and de novo Aldo production are absent in nonadrenal human cell lines, either immortalized cell lines or commercially available primary cell lines, including peripheral blood mononuclear cells (PBMCs) of individuals without and with primary hyperaldosteronism (PA).

Investigating the biosynthesis and metabolism of 11β-hydroxyandrostenedione.

The "rediscovery" 11β-hydroxyandrostenedione (11OHA4) placed the spotlight on this unique adrenal-derived hormone with researchers and clinicians once again focusing on the steroid's presence in endocrine pathology. Little was known about the steroid other than its chemical characterisation and that a mitochondrial cytochrome P450 enzyme catalysed the 11β-hydroxylation of 11OHA4. The fact that neither the biosynthesis nor metabolism of 11OHA4 had been fully characterised presented an ideal opportunity to investigate the metabolic pathways.

Exploring the Potential of Sulfur Moieties in Compounds Inhibiting Steroidogenesis.

This study reports on the synthesis and evaluation of novel compounds replacing the nitrogen-containing heterocyclic ring on the chemical backbone structure of cytochrome P450 17α-hydroxylase/12,20-lyase (CYP17A1) inhibitors with a phenyl bearing a sulfur-based substituent. Initial screening revealed compounds with marked inhibition of CYP17A1 activity. The selectivity of compounds was thereafter determined against cytochrome P450 21-hydroxylase, cytochrome P450 3A4, and cytochrome P450 oxidoreductase.

The serum steroid signature of PCOS hints at the involvement of novel pathways for excess androgen biosynthesis.

Context: Polycystic ovary syndrome (PCOS) is defined by androgen excess and ovarian dysfunction in the absence of a specific physiological diagnosis. The best clinical marker of androgen excess is hirsutism, while the best biochemical parameter is still a matter of debate. Current consensus guidelines recommend, among other hormones, serum free testosterone as an important serum parameter to measure androgen excess.

The state of kidney replacement therapy in Eastern Cape Province, South Africa: A call to action.

Background: South Africa (SA) is one of the most financially unequal countries in the world. This situation is highlighted by disparate access to healthcare, particularly provision of kidney replacement therapy (KRT). Unlike the private sector, public sector access to KRT is highly rationed, and patient selection is based on suitability for transplantation and capacity.

Transplant Unit, Division of General Surgery, Department of Surgery, Faculty of Health Sciences, University of Cape Town, South Africa.

Organ and tissue donation depends on non-transplant clinicians to identify and timeously refer potential donors and to counsel families compassionately about the prognosis at end of life. Organ donation referral is often felt to be beyond the capacity of district-level hospital services. In this case series, we report on four referrals from a geographically remote, public sector district-level hospital, and review the identification, referral and consent process of potential donors after brain death, and also donors after circulatory death.

Development and function of the fetal adrenal.

The adrenal cortex undergoes multiple structural and functional rearrangements to satisfy the systemic needs for steroids during fetal life, postnatal development, and adulthood. A fully functional adrenal cortex relies on the proper subdivision in regions or 'zones' with distinct but interconnected functions, which evolve from the early embryonic stages to adulthood, and rely on a fine-tuned gene network. In particular, the steroidogenic activity of the fetal adrenal is instrumental in maintaining normal fetal development and growth.

The use of brachiobasilic arteriovenous fistulae for haemodialysis: a single-centre descriptive study.

Aim: The main aim of the study was to report on our local experience with the use of brachiobasilic arteriovenous fistulae (BBAVF) and to encourage wider local acceptance of the procedure in accordance with international guidelines. The primary aim was to report on access patency. The secondary aims were to report on functional outcomes and complications.

Basics of androgen synthesis and action.

Androgens are essential sex steroid hormones for both sexes. Testosterone (T) is the predominant androgen in males, while in adult females, T concentrations are about 15-fold lower and androgen precursors are converted to estrogens. T is produced primarily in testicular Leydig cells in men, while in women precursors are biosynthesised in the adrenal cortex and ovaries and converted into T in the periphery.

Organ transplantation during the COVID-19 pandemic - impact on deceased organ donor referrals and consent rates in the Western Cape, South Africa.

Background: The impact of the COVID-19 pandemic on transplantation is multifactorial. This study reports on its influence on deceased donation for transplantation in the Western Cape.

Methods: The volume of referrals and those who were consented for organ donation in the province in the pre-pandemic period of May 2017 to February 2020 were compared to those of the initial pandemic period (March through December 2020).