The A-ring reduction of 11-ketotestosterone is efficiently catalysed by AKR1D1 and SRD5A2 but not SRD5A1

Testosterone and its 5α-reduced form, 5α-dihydrotestosterone, were previously thought to represent the only active androgens in humans. However, recent studies have shown that the potent androgen, 11-ketotestosterone, derived from the adrenal androgen precursor, 11β-hydroxyandrostenedione, may in fact serve as the primary androgen in healthy women. Yet, despite recent renewed interest in these steroids, their downstream metabolism has remained undetermined. We therefore set out to investigate the metabolism of 11-ketotestosterone by characterising the 5α- or 5β-reduction commitment step. We show that inactivation of 11-ketotestosterone is predominantly driven by AKR1D1, which efficiently catalyses the 5β-reduction of 11-ketotestosterone, committing it to a metabolic pathway that terminates in 11-ketoetiocholanolone. We demonstrate that 5α-reduction of 11-ketotestosterone is catalysed by SRD5A2, but not SRD5A1, and terminates in 11-ketoandrosterone, but is only responsible for a minority of 11-ketotestosterone inactivation. However, as 11-ketoetiocholanolone is also generated by the metabolism of the glucocorticoid cortisone, 11-ketoandrosterone should be considered a more specific urinary marker of 11-ketotestosterone production

Early non-psychotic deviant behaviour as an endophenotypic marker in bipolar disorder, schizo-affective disorder and schizophrenia

Objective: To determine and compare the incidence of early non-psychotic deviant behaviour (i.e. under the age of ten) in Afrikaner patients with bipolar disorder, schizo-affective disorder and schizophrenia. Methods: Patients with bipolar disorder, schizo-affective disorder and schizophrenia were interviewed using a structured questionnaire probing for early deviant childhood behaviour starting before the age of 10 years. Information from close family members was also obtained where possible. Seven areas of possible deviance were probed into: social dysfunction, unprovoked aggression, extreme anxiety, chronic sadness, extreme odd behaviours, attention impairment and learning difficulties. Demographic data included: age, marital status, gender, and years of formal education. The following clinical features were also recorded: age of onset of illness and suicide attempts. Results: A total of 74 patients diagnosed with bipolar disorder, 43 patients diagnosed with schizo-affective disorder and 80 patients diagnosed with schizophrenia were interviewed. Early deviant behaviour was statistically more prevalent in schizophrenia (65%) and schizo-affective disorder (60,5%), than in the bipolar group (21,6%). Deviant childhood behaviour was grouped into 3 clusters: social functioning impairment cluster (social isolation, aggression, extreme odd behavior), mood/anxiety cluster (extreme fears, chronic sadness) and a cognitive impairment cluster (attention impairment, learning disability). Bipolar patients showed significantly less social functioning and cognitive impairment compared to patients with schizo-affective disorder and schizophrenia. Conclusion: Our findings suggest that early deviant behaviour may be a possible endophenotypic marker in schizophrenia and schizoaffective disorder. Keywords: early non-psychotic deviant behaviour, endophenotype, bipolar disorder, schizo-affective disorder, schizophrenia South African Psychiatry Review Vol. 8(4) 2005: 153-15

Knee movement patterns of injured and uninjured adolescent basketball players when landing from a jump: A case-control study

BACKGROUND: A common knee injury mechanism sustained during basketball is landing badly from a jump. Landing is a complex task and requires good coordination, dynamic muscle control and flexibility. For adolescents whose coordination and motor control has not fully matured, landing badly from a jump can present a significant risk for injury. There is currently limited biomechanical information regarding the lower limb kinetics of adolescents when jumping, specifically regarding jump kinematics comparing injured with uninjured adolescents. This study reports on an investigation of biomechanical differences in landing patterns of uninjured and injured adolescent basketball players. METHODS: A matched case-control study design was employed. Twenty-two basketball players aged 14–16 years participated in the study: eleven previously knee-injured and eleven uninjured players matched with cases for age, gender, weight, height and years of play, and playing for the same club. Six high-speed, three-dimensional Vicon 370 cameras (120 Hz), Vicon biomechanical software and SAS Version 8 software were employed to analyse landing patterns when subjects performed a "jump shot". Linear correlations determined functional relationships between the biomechanical performance of lower limb joints, and paired t-tests determined differences between the normalised peak biomechanical parameters. RESULTS: The average peak vertical ground reaction forces between the cases and controls were similar. The average peak ground reaction forces between the cases and controls were moderately correlated (r = -0.47). The control (uninjured) players had significantly greater hip and knee flexion angles and significantly greater eccentric activity on landing than the uninjured cases (p < 0.01). CONCLUSION: The findings of the study indicate that players with a history of knee injuries had biomechanically compromised landing techniques when compared with uninjured players matched for gender, age and club. Descriptions (norms) of expected levels of knee control, proprioceptive acuity and eccentric strength relative to landing from a jump, at different ages and physical developmental stages, would assist clinicians and coaches to identify players with inappropriate knee performance comparable to their age or developmental stage

Postmortem lung biopsies from four patients with COVID-19 at a tertiary hospital in Cape Town, South Africa

CITATION: Bruce-Brand, C. et al. 2020. Postmortem lung biopsies from four patients with COVID-19 at a tertiary hospital in Cape Town, South Africa. South African Medical Journal, 110(12):1195-1200, doi:10.7196/SAMJ.2020.v110i12.15290.The original publication is available at http://www.samj.org.zaPublication of this article was funded by the Stellenbosch University Open Access FundBackground. An outbreak of a novel coronavirus in China in late 2019 has resulted in a global pandemic. The virus (SARS-CoV-2) causes a severe acute respiratory syndrome and had been responsible for >14 000 deaths in South Africa (SA) at the time of writing, 30 August 2020. Autopsies in our setting have not been prioritised owing to the infective risks for staff, resulting in a lack of information on the histopathology of the disease in the SA setting. Postmortem biopsies are relatively quick and easy to perform and reduce the infective risk posed by full autopsies. Objectives. To determine whether postmortem biopsies of lung tissue could be used to determine cause of death in lieu of full autopsies in patients dying from COVID-19. Methods. We performed postmortem biopsies of lung tissue on 4 patients with SARS-CoV-2 confirmed by reverse transcriptase polymerase chain reaction who died in the Tygerberg Hospital (Cape Town, SA) intensive care unit (ICU) in June - July 2020, in order to determine their cause of death. The biopsies were performed in the ICU with the necessary personal protective equipment within 2 hours after death. Clinical information was obtained from the hospital records and the histopathology was reviewed by two consultant histopathologists. Microbiology and electron microscopy were also performed on this tissue. Results. All 4 patients were aged >50 years and had multiple comorbidities. Pulmonary pathology was present in only 3 cases, and the findings were surprisingly heterogeneous. One case demonstrated several findings including diffuse alveolar damage, extensive fibrin thrombi in pulmonary arteries with pulmonary infarction, organising pneumonia and bronchopneumonia. Other findings included type 2 pneumocyte hyperplasia, intra-alveolar macrophages and squamous metaplasia. An organising pneumonia was present in 2 other cases, although these findings were not deemed to be severe enough to be the cause of death. Fibrin thrombi were present in pulmonary arteries of 3 cases. One case showed no significant acute pulmonary pathology. The cause of death could only be determined in 1 case. Conclusions. The pulmonary findings we observed are in keeping with those described in the international literature. However, the pathology was surprisingly heterogeneous between cases, and was only deemed severe enough to be the cause of death in 1 of 4 cases. While lung-targeted, standardised postmortem biopsies may be safe, easy to perform and provide useful insights into the disease, they are not suitable to replace full autopsies in determining cause of death.http://www.samj.org.za/index.php/samj/article/view/13116Publisher's versio

High HIV prevalence in an early cohort of hospital admissions with COVID-19 in Cape Town, South Africa

Background. South Africa (SA) has a high prevalence of HIV and tuberculosis. Cape Town was the SA metropole most affected in the early stages of the COVID-19 pandemic. Early observational data from Africa may provide valuable insight into what can be expected as the pandemic expands across the continent.Objectives. To describe the prevalence, clinical features, comorbidities and outcome of an early cohort of HIV-positive and HIV-negative patients admitted with COVID-19.Methods. This was a descriptive observational study of an early cohort of adults with COVID-19 pneumonia admitted from 25 March to 11 May 2020.Results. Of 116 patients (mean age 48 years, 61% female) admitted, 24 were HIV-positive (21%). The most common symptoms reported were cough (n=88; 73%), shortness of breath (n=78; 69%), fever (n=67; 59%), myalgia (n=29; 25%) and chest pain (n=22; 20%). The most common comorbidities were hypertension (n=46; 41%), diabetes mellitus (n=43; 38%), obesity (n=32; 28%) and HIV (n=24; 21%). Mortality was associated with older age (mean (standard deviation) 55 (12) years v. 46 (14) years; p&lt;0.01); the presence of hypertension or hypertension along with diabetes and/or obesity; lower partial pressure of arterial oxygen to fraction of inspired oxygen ratio; and higher urea level, white cell count, neutrophil count, and C-reactive protein, lactate dehydrogenase and ferritin levels, and high neutrophil to lymphocyte ratio. The overall survival rate for all hospital admissions was 86/116 (73%). In this early cohort, survival was similar in patients with HIV (n=18; 75%) compared with those without HIV (n=67; 75%) (p=1). Of the 74 patients admitted to the wards, 63 (85%) survived, whereas 22 of 42 (52%) admitted to the intensive care unit survived.Conclusions. Patients with HIV infection represented a large proportion of all COVID-19 admissions. The presentation and outcome of patients with HIV did not differ significantly from those of patients without HIV

Preconditioning of mesenchymal stromal cells with low-intensity ultrasound: influence on chondrogenesis and directed SOX9 signaling pathways

Background: Continuous low-intensity ultrasound (cLIUS) facilitates the chondrogenic differentiation of human mesenchymal stromal cells (MSCs) in the absence of exogenously added transforming growth factor-beta (TGFβ) by upregulating the expression of transcription factor SOX9, a master regulator of chondrogenesis. The present study evaluated the molecular events associated with the signaling pathways impacting SOX9 gene and protein expression under cLIUS. Methods: Human bone marrow-derived MSCs were exposed to cLIUS stimulation at 14 kPa (5 MHz, 2.5 Vpp) for 5 min. The gene and protein expression of SOX9 was evaluated. The specificity of SOX9 upregulation under cLIUS was determined by treating the MSCs with small molecule inhibitors of select signaling molecules, followed by cLIUS treatment. Signaling events regulating SOX9 expression under cLIUS were analyzed by gene expression, immunofluorescence staining, and western blotting. Results: cLIUS upregulated the gene expression of SOX9 and enhanced the nuclear localization of SOX9 protein when compared to non-cLIUS-stimulated control. cLIUS was noted to enhance the phosphorylation of the signaling molecule ERK1/2. Inhibition of MEK/ERK1/2 by PD98059 resulted in the effective abrogation of cLIUS-induced SOX9 expression, indicating that cLIUS-induced SOX9 upregulation was dependent on the phosphorylation of ERK1/2. Inhibition of integrin and TRPV4, the upstream cell-surface effectors of ERK1/2, did not inhibit the phosphorylation of ERK1/2 and therefore did not abrogate cLIUS-induced SOX9 expression, thereby suggesting the involvement of other mechanoreceptors. Consequently, the effect of cLIUS on the actin cytoskeleton, a mechanosensitive receptor regulating SOX9, was evaluated. Diffused and disrupted actin fibers observed in MSCs under cLIUS closely resembled actin disruption by treatment with cytoskeletal drug Y27632, which is known to increase the gene expression of SOX9. The upregulation of SOX9 under cLIUS was, therefore, related to cLIUS-induced actin reorganization. SOX9 upregulation induced by actin reorganization was also found to be dependent on the phosphorylation of ERK1/2. Conclusions: Collectively, preconditioning of MSCs by cLIUS resulted in the nuclear localization of SOX9, phosphorylation of ERK1/2 and disruption of actin filaments, and the expression of SOX9 was dependent on the phosphorylation of ERK1/2 under cLIUS

Ideologies implicated in IT innovation in government: a critical discourse analysis of Mexico’s international trade administration

We develop a perspective of IT innovation in the public sector as a process that involves three complementary areas of ideology and concomitant dispute: first, the widespread view of e-government as a transformative force that leads to major improvements of public sector functions for the benefit of society at large; second, ideologies concerning the substantive policies enacted by public sector organizations; and third, ideology regarding public sector modernization. Our research examines how the objectives of IT projects and their actual effects in government are influenced by such ideologies and contestations that surround them. We develop our theoretical contribution with a critical discourse analysis that traces the ideological underpinnings of two consecutive IT projects for the administration of international trade in Mexico. This analysis associates the objectives of the IT projects with the emergence and ensuing contestation in Mexican politics of two ideologies: the first ideology concerns free international trade as imperative for economic development; the second ideology concerns public sector modernization that sought to overcome historically formed dysfunctionalities of public administration bureaucracies by adopting management practices from the private sector. The analysis then identifies the effects of the ideologically shaped IT projects on two key values of public administration: efficiency and legality. The insights of this research on the role of ideology in IT innovation complement organizational perspectives of e-government; socio-cognitive perspectives that focus on ideas and meaning, such as technology frames and organizing visions; and perspectives that focus on politics in IT innovation

A profile of hospital-admitted paediatric burns patients in South Africa

<p>Abstract</p> <p>Background</p> <p>Injuries and deaths from burns are a serious, yet preventable health problem globally. This paper describes burns in a cohort of children admitted to the Red Cross Children's Hospital, in Cape Town, South Africa.</p> <p>This six month retrospective case note review looked at a sample of consecutively admitted patients from the 1 ^stApril 2007 to the 30 ^thSeptember 2007. Information was collected using a project-specific data capture sheet. Descriptive statistics (percentages, medians, means and standard deviations) were calculated, and data was compared between age groups. Spearman's correlation co-efficient was employed to look at the association between the total body surface area and the length of stay in hospital.</p> <p>Findings</p> <p>During the study period, 294 children were admitted (f= 115 (39.1%), m= 179 (60.9%)). Hot liquids caused 83.0% of the burns and 36.0% of these occurred in children aged two years or younger. Children over the age of five were equally susceptible to hot liquid burns, but the mechanism differed from that which caused burns in the younger child.</p> <p>Conclusion</p> <p>In South Africa, most hospitalised burnt children came from informal settlements where home safety is a low priority. Black babies and toddlers are most at risk for sustaining severe burns when their environment is disorganized with respect to safety. Burns injuries can be prevented by improving the home environment and socio-economic living conditions through the health, social welfare, education and housing departments.</p

The Development of a Code for Australian Psychologists

Section 35(1)(c) of the Health Practitioner Regulation National Law Act (200929. Health Practitioner Regulation National Law Act of 2009. (Queensland). View all references) requires the newly formed Psychology Board of Australia (PsyBA) “to develop or approve standards, codes and guidelines.” In 2010 the PsyBA decided to initially adopt the Australian Psychological Society\u27s (APS) Code of Ethics (200711. Australian Psychological Society . 2007 . Code of ethics , Melbourne, , Australia : Author . View all references) and develop a new code in the future with the involvement of key stakeholders without deciding what the nature of this code will be. The PsyBA now has to decide exactly how it will proceed in future. My aim in this article is to examine the options available to the PsyBA by exploring the definition and function of codes; presenting a history of the APS Code; and considering approaches that had been followed in Europe, Israel, New Zealand, and South Africa