Case Report: Down-staging locally advanced head and neck cancer in an HIV infected patient in a limited resource setting

No Abstrac

Cell cycle-dependent and independent mating blocks ensure fungal zygote survival and ploidy maintenance.

To ensure genome stability, sexually reproducing organisms require that mating brings together exactly 2 haploid gametes and that meiosis occurs only in diploid zygotes. In the fission yeast Schizosaccharomyces pombe, fertilization triggers the Mei3-Pat1-Mei2 signaling cascade, which represses subsequent mating and initiates meiosis. Here, we establish a degron system to specifically degrade proteins postfusion and demonstrate that mating blocks not only safeguard zygote ploidy but also prevent lysis caused by aberrant fusion attempts. Using long-term imaging and flow-cytometry approaches, we identify previously unrecognized and independent roles for Mei3 and Mei2 in zygotes. We show that Mei3 promotes premeiotic S-phase independently of Mei2 and that cell cycle progression is both necessary and sufficient to reduce zygotic mating behaviors. Mei2 not only imposes the meiotic program and promotes the meiotic cycle, but also blocks mating behaviors independently of Mei3 and cell cycle progression. Thus, we find that fungi preserve zygote ploidy and survival by at least 2 mechanisms where the zygotic fate imposed by Mei2 and the cell cycle reentry triggered by Mei3 synergize to prevent zygotic mating

Maternal near miss and maternal death in the Pretoria Academic Complex, South Africa: A population-based study

Background. In order to reduce maternal mortality in South Africa (SA), it is important to understand the process of obstetric care, identify weaknesses within the system, and implement interventions for improving care.Objective. To determine the spectrum of maternal morbidity and mortality in the Pretoria Academic Complex (PAC), SA.Methods. A descriptive population-based study that included all women delivering in the PAC. The World Health Organization definition, criteria and indicators of near miss and maternal death were used to identify women with severe complications in pregnancy.Results. Between 1 August 2013 and 31 July 2014, there were 26 614 deliveries in the PAC. The institutional maternal mortality ratio was 71.4/100 000 live births. The HIV infection rate was 19.9%, and 2.7% of women had unknown HIV status. Of the women, 1 120 (4.2%) developed potentially life-threatening conditions and 136 (0.5%) life-threatening conditions. The mortality index was 14.0% overall, 30.0% for non-pregnancy-related infections, 2.0% for obstetric haemorrhage and 13.6% for hypertension. Of the women with life-threatening conditions, 39.3% were referred from the primary level of care. Vascular, uterine and coagulation dysfunctions were the most frequent organ dysfunctions in women with life-threatening conditions. The perinatal mortality rate was 26.9/1 000 births overall, 23.1/1 000 for women with non-life-threatening conditions, and 198.0/1 000 for women with life-threatening conditions.Conclusion. About one in 20 pregnant women in the PAC had a potentially life-threatening condition; 39.3% of women presented to a primary level facility as an acute emergency and had to be transferred for tertiary care. All healthcare professionals involved in maternity care must have knowledge and skills that equip them to manage obstetric emergencies. Review of the basic antenatal care protocol may be necessary

Outbreak of Rift Valley fever affecting veterinarians and farmers in South Africa, 2008

Background. During 2008, Rift Valley fever (RVF) virus re-emerged in South Africa as focal outbreaks in several provinces. Aims. To investigate an outbreak affecting cattle farmers and farm workers, and the staff and students of a veterinary school, assess the prevalence of infection during the outbreak, document the clinical presentation of cases, and identify potential risk factors. Methods. We conducted a cross-sectional serological survey of exposed veterinarians and farmers, who were examined to determine the presence of current or recent illness. Blood specimens were collected for virus isolation, nucleic acid detection and serology. A subset was interviewed using a standardised questionnaire to obtain data on recent exposures and risk factors for infection. Results. Of 53 participants potentially exposed to infected domestic ruminants, 15% had evidence of recent infection and 4% evidence of past exposure to the RVF virus. The prevalence of acute infection was 21% in veterinarians compared with 9% in farmers and farm workers. After a mean incubation period of 4.3 days, the most frequent symptoms experienced included myalgia (100%), headache (88%) and malaise (75%). No asymptomatic cases were identified. Transmission by direct contact with infected animals was the major risk factor in these professional groups. Performing animal autopsies was significantly associated with acute infection (risk ratio 16.3, 95% confidence interval 2.3 - 114.2). Conclusions. Increased risks associated with veterinary practices highlight a need for the use of personal protective equipment, and identify veterinarians as a primary target group for future vaccination

Rights of the fetus : voice of the unborn baby and constitutional court decision

No abstract available.http://www.sajbl.org.zaam2023Obstetrics and Gynaecolog

The role of the C8 proton of ATP in the regulation of phosphoryl transfer within kinases and synthetases

<p>Abstract</p> <p>Background</p> <p>The kinome comprises functionally diverse enzymes, with the current classification indicating very little about the extent of conserved regulatory mechanisms associated with phosphoryl transfer. The apparent <it>K</it>_mof the kinases ranges from less than 0.4 μM to in excess of 1000 μM for ATP. It is not known how this diverse range of enzymes mechanistically achieves the regulation of catalysis via an affinity range for ATP varying by three-orders of magnitude.</p> <p>Results</p> <p>We have demonstrated a previously undiscovered mechanism in kinase and synthetase enzymes where the overall rate of reaction is regulated via the C8-H of ATP. Using ATP deuterated at the C8 position (C8D-ATP) as a molecular probe it was shown that the C8-H plays a direct role in the regulation of the overall rate of reaction in a range of kinase and synthetase enzymes. Using comparative studies on the effect of the concentration of ATP and C8D-ATP on the activity of the enzymes we demonstrated that not only did C8D-ATP give a kinetic isotope effect (KIE) but the KIE's obtained are clearly not secondary KIE effects as the magnitude of the KIE in all cases was at least 2 fold and in most cases in excess of 7 fold.</p> <p>Conclusions</p> <p>Kinase and synthetase enzymes utilise C8D-ATP in preference to non-deuterated ATP. The KIE obtained at low ATP concentrations is clearly a primary KIE demonstrating strong evidence that the bond to the isotopically substituted hydrogen is being broken. The effect of the ATP concentration profile on the KIE was used to develop a model whereby the C8H of ATP plays a role in the overall regulation of phosphoryl transfer. This role of the C8H of ATP in the regulation of substrate binding appears to have been conserved in all kinase and synthetase enzymes as one of the mechanisms associated with binding of ATP. The induction of the C8H to be labile by active site residues coordinated to the ATP purine ring may play a significant role in explaining the broad range of <it>K</it>_massociated with kinase enzymes.</p

Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer.

Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC) and it is amenable to local treatments, with intravesical (IVES) Bacillus-Calmette-Guerin (BCG) immunotherapy being routinely used after transurethral resection of the lesion. However, this treatment is associated with significant side-effects and treatment failures, highlighting the necessity of novel strategies. One potent approach is the suicide-gene mediated therapy/prodrug combination, provided tumor-specificity can be ensured and anti-tumor immune responses induced. Using the mouse syngeneic orthotopic MB49-bladder tumor model, here we show that IVES human papillomavirus non-replicative pseudovirions (PsV) can pseudoinfect tumors with a ten-fold higher efficacy than normal bladders. In addition, PsV carrying the suicide-gene herpes-simplex virus thymidine kinase (PsV-TK) combined to Ganciclovir (GCV) led to immunogenic cell-death of tumor cells in vitro and to MB49-specific CD8 T-cells in vivo. This was associated with reduction in bladder-tumor growth and increased mice survival. Altogether, our data show that IVES PsV-TK/GCV may be a promising alternative or combinatory treatment for NMIBC

Acceptable care? Illness constructions, healthworlds, and accessible chronic treatment in South Africa

Achieving equitable access to health care is an important policy goal, with access influenced by affordability, availability, and acceptability of specific services. We explore patient narratives from a 5-year program of research on health care access to examine relationships between social constructions of illness and the acceptability of health services in the context of tuberculosis treatment and antiretroviral therapy in South Africa. Acceptability of services seems particularly important to the meanings patients attach to illness and care, whereas—conversely—these constructions appear to influence what constitutes acceptability and hence affect access to care. We highlight the underestimated role of individually, socially, and politically constructed healthworlds; traditional and biomedical beliefs; and social support networks. Suggested policy implications for improving acceptability and hence overall health care access include abandoning patronizing approaches to care and refocusing from treating “disease” to responding to “illness” by acknowledging and incorporating patients’ healthworlds in patient–provider interactions

Challenges in recruiting children to a multidrug-resistant TB prevention trial

BACKGROUND: Recruitment to randomised clinical trials can be challenging and slow recruitment has serious consequences. This study aimed to summarise and reflect on the challenges in enrolling young children to a multidrug-resistant TB (MDR-TB) prevention trial in South Africa. METHODS: Recruitment to the Tuberculosis Child Multidrug-resistant Preventive Therapy Trial (TB-CHAMP) was tracked using an electronic recruiting platform, which was used to generate a recruiting flow diagram. Structured personnel questionnaires, meeting minutes and workshop notes were thematically analysed to elucidate barriers and solutions. RESULT: Of 3,682 (85.3%) adult rifampicin (RIF) resistant index cases with pre-screening outcomes, 1597 (43.4%) reported having no children under 5 years in the household and 562 (15.3%) were RIF-monoresistant. More than nine index cases were pre-screened for each child enrolled. Numerous barriers to recruitment were identified. Thorough recruitment planning, customised tracking data systems, a dedicated recruiting team with strong leadership, adequate resources to recruit across large geographic areas, and excellent relationships with routine TB services emerged as key factors to ensure successful recruitment. CONCLUSION: Recruitment of children into MDR-TB prevention trials can be difficult. Several MDR-TB prevention trials are underway, and lessons learnt from TB-CHAMP will be relevant to these and other TB prevention studies

Delays in HIV-1 infant polymerase chain reaction testing may leave children without confirmed diagnoses in the Western Cape province, South Africa

CITATION: Mahlakwane, K. L. et al. 2022. African Journal of Laboratory Medicine, 11(1):1485, doi:10.4102/ajlm.v11i1.1485.The original publication is available at https://ajlmonline.orgBackground: Early diagnosis and confirmation of HIV infection in newborns is crucial for expedited initiation of antiretroviral therapy. Confirmatory testing must be done for all children with a reactive HIV PCR result. There is no comprehensive data on confirmatory testing and HIV PCR test request rejections at National Health Laboratory Service laboratories in South Africa. Objective: This study assessed the metrics of routine infant HIV PCR testing at the Tygerberg Hospital Virology Laboratory, Cape Town, Western Cape, South Africa, including the proportion of rejected test requests, turn-around time (TAT), and rate of confirmatory testing. Methods: We retrospectively reviewed laboratory-based data on all HIV PCR tests performed on children ≤ 24 months old (n = 43 346) and data on rejected HIV PCR requests (n = 1479) at the Tygerberg virology laboratory over two years (2017–2019). Data from sample collection to release of results were analysed to assess the TAT and follow-up patterns. Results: The proportion of rejected HIV PCR requests was 3.3%; 83.9% of these were rejected for various pre-analytical reasons. Most of the test results (89.2%) met the required 96-h TAT. Of the reactive initial test results, 53.5% had a follow-up sample tested, of which 93.1% were positive. Of the initial indeterminate results, 74.7% were negative on follow-up testing. Conclusion: A high proportion of HIV PCR requests were rejected for pre-analytical reasons. The high number of initial reactive tests without evidence of follow-up suggests that a shorter TAT is required to allow confirmatory testing before children are discharged.https://ajlmonline.org/index.php/ajlm/article/view/1485Publisher's versio