Genetic counseling experiences at the University of Cape Town during COVID-19.

Soon after the first COVID-19 case was reported in December 2019 in Wuhan, China, South Africa announced a national lockdown in an attempt to curb the spread of the disease. Under national lockdown, businesses were closed, learning institutions moved to emergency remote teaching (ERT), and hospitals reduced their patient loads. De-escalation of clinical services at Groote Schuur and Red Cross War Memorial Children's Hospitals affected Genetic Counseling Services and resulted in a decrease in in-person and an increase in telecounseling sessions. ERT, offered by the University of Cape Town, affected the teaching of Genetic Counseling students, and other methods of training had to be found to compensate for the lack of patient contact. In this paper, we present our Genetic Counseling team's experiences of learning and clinical services during the COVID-19 pandemic in South Africa. The team met online as a group in November 2020 to discuss their experiences. The discussion was recorded and transcribed, and topics that arose during the discussion were identified. The pandemic and the accompanying lock down, which forced trainees to move back home, resulted in great uncertainty. The trainees found ERT on an online platform, including simulated cases, very helpful, but they lost the confidence to work with real patients. Telecounseling became the predominant form of service delivery and was experienced as positive when video sessions were possible. The telephone service for advanced maternal age counseling was problematic due to unreliable networks. The biggest loss for the GCs was the feeling of disconnection from peers, supervisors, and patients. The experiences highlighted positive and negative aspects as well as specific challenges faced in South Africa. Lessons learnt from the COVID-19 pandemic will be used in future to improve training of GCs and to enhance service delivery.

Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans.

The Southern African Human Genome Programme is a national initiative that aspires to unlock the unique genetic character of southern African populations for a better understanding of human genetic diversity. In this pilot study the Southern African Human Genome Programme characterizes the genomes of 24 individuals (8 Coloured and 16 black southeastern Bantu-speakers) using deep whole-genome sequencing. A total of ~16 million unique variants are identified. Despite the shallow time depth since divergence between the two main southeastern Bantu-speaking groups (Nguni and Sotho-Tswana), principal component analysis and structure analysis reveal significant (p < 10-6) differentiation, and FST analysis identifies regions with high divergence. The Coloured individuals show evidence of varying proportions of admixture with Khoesan, Bantu-speakers, Europeans, and populations from the Indian sub-continent. Whole-genome sequencing data reveal extensive genomic diversity, increasing our understanding of the complex and region-specific history of African populations and highlighting its potential impact on biomedical research and genetic susceptibility to disease.

Antiangiogenic VEGF165b expression in human breast MCF-7 and MCF-10A cells exposed to reverse transcriptase and protease inhibitors / Expresión de VEGF165b antiangiogénico en células MCF-7 y MCF-10A de mama humana expuesto a inhibidores de la transcriptasa inversa y la proteasa

The combined antiretroviral therapy (cART), a multidrug combination regimen, usually consisting Nucleoside Reverse Transcriptase Inhibitors, non- Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors has altered the morbidity pattern affecting HIV-infected individuals to include non-AIDS-defining malignancies (nADMs). The speculation is rife; does cART induce or promote the progression of nADMs such as breast cancer? This study was therefore designed to investigate of the effects of some antiretroviral drugs (at clinically relevant concentrations) on the expression of anti-angiogenic gene; VEGF165b in two human breast cell lines; MCF-7 and MCF-10A by Real Time qPCR and immuno-fluorescence. All of the antiretroviral drugs and combinations tested produced patterns of slight up or downregulation of VEGF165b mRNA expression but the alterations did not attain statistical significance. They also did not alter VEGF165bprotein localisation in both cell lines. The findings reported here suggest that antiretroviral drugs probably do not influence the angiogenic pathway in the development of breast cancer in patients under the combined antiretroviral regimen.

El tratamiento antirretroviral combinado (TARc), un régimen de combinación de múltiples fármacos, consistiendo generalmente en inhibidores nucleósidos de la transcriptasa reversa, inhibidores no-nucleósidos de la transcriptasa reversa e inhibodres de proteasa que alteran el patrón de mortalidad que afecta a infectados por el VIH incluyendo neoplasias definidas como no HIV (nADMs). La especulación es moneda corriente; TARc induce o promueve la progresión de nADMs como cáncer de mama? Por lo tanto, este estudio se diseñó para investigar los efectos de algunos de los fármacos antirretrovirales (en concentraciones clínicamente relevantes) sobre la expresión del gen anti-angiogénico; VEGF165b en dos líneas celulares de mama humana; MCF-7 y MCF-10A por PCR tiempo real e inmunofluorescencia. Todos los fármacos antirretrovirales y las combinaciones probadas pueden regular en forma ligera hacia arriba o hacia abajo la expresión de ARNm producidos por VEGF165b pero las alteraciones no fueron estadísticamente significativos. Además, no se alteran los niveles de proteína VEGF165b, para la localización en ambas líneas celulares. Los resultados aquí presentados sugieren que los medicamentos antirretrovirales probablemente no influyen en la vía angiogénica en el desarrollo del cáncer de mama en pacientes bajo el régimen antirretroviral combinado.

A high resolution SEM study of the effects of RU486, used as a postcoital contraceptive, on the rat uterus during early pregnancy.

During the window of receptivity, a narrow range of time under the control of the ovarian hormones progesterone and oestrogen, when a blastocyst can attach to the uterine surface, the plasma membrane of the uterine epithelial cells undergoes a remarkable change in structure, known as 'the plasma membrane transformation' of early pregnancy. RU486, the controversial abortion drug (Mifegyne), acts as a progesterone receptor antagonist, resulting in transcriptionally inactive progesterone receptors. In view of this, a change in the well-documented sequences of the plasma membrane transformation is postulated. This study therefore aims to investigate the effects of RU486 on this sequence of events in the implantation and non-implantation sites of the rat uterus. In both RU486 treated and control animals, on days 4.5, 5.5 and 6.5 of pregnancy, scanning electron microscopy revealed a distinct pattern of folding of the uterine surface in non-implantation sites. In contrast, folding was not observed within the implantation sites. These results indicate that surface alterations are probably not under the control of progesterone signalling. The lack of folding at the implantation sites possibly ensures maximum close contact between the blastocyst and the maternal tissue thus promoting implantation. During early pregnancy, specifically on day 5.5, the microvilli of the uterine epithelial cells in the treated animals were more dense than those in the untreated animals. Such microvilli are characteristic of the uterine epithelial cells of a uterus under-stimulated by hormones. Flattening of the apical cell borders usually seen at the time of blastocyst attachment and implantation was not observed following RU486 treatment. Large apical protrusions were observed in the RU486 treated animals only, possibly linked in some way to apoptosis. The antiprogestin properties of RU486 may further elucidate the progesterone effects associated with early pregnancy.