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- ItemOpen AccessA 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia(2014) Blom, Dirk J; Hala, Tomas; Bolognese, Michael; Lillestol, Michael J; Toth, Phillip D; Burgess, Lesley; Ceska, Richard; Roth, Eli; Koren, Michael J; Ballantyne, Christie M; Monsalvo, Maria Laura; Tsirtsonis, Kate; Kim, Jae B; Scott, Rob; Wasserman, Scott M; Stein, Evan ABACKGROUND Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/ kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab. METHODS We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52. RESULTS Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain. CONCLUSIONS At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks.
- ItemOpen AccessA biregional survey and review of first-line treatment failure and second-line paediatric antiretroviral access and use in Asia and southern Africa(2011)BackgroundTo better understand the need for paediatric second-line antiretroviral therapy (ART), an ART management survey and a cross-sectional analysis of second-line ART use were conducted in the TREAT Asia Paediatric HIV Observational Database and the IeDEA Southern Africa (International Epidemiologic Databases to Evaluate AIDS) regional cohorts.MethodsSurveys were conducted in April 2009. Analysis data from the Asia cohort were collected in March 2009 from 12 centres in Cambodia, India, Indonesia, Malaysia, and Thailand. Data from the IeDEA Southern Africa cohort were finalized in February 2008 from 10 centres in Malawi, Mozambique, South Africa and Zimbabwe.ResultsSurvey responses reflected inter-regional variations in drug access and national guidelines. A total of 1301 children in the TREAT Asia and 4561 children in the IeDEA Southern Africa cohorts met inclusion criteria for the cross-sectional analysis.Ten percent of Asian and 3.3% of African children were on second-line ART at the time of data transfer. Median age (interquartile range) in months at second-line initiation was 120 (78-145) months in the Asian cohort and 66 (29-112) months in the southern African cohort. Regimens varied, and the then current World Health Organization-recommended nucleoside reverse transcriptase combination of abacavir and didanosine was used in less than 5% of children in each region.ConclusionsIn order to provide life-long ART for children, better use of current first-line regimens and broader access to heat-stable, paediatric second-line and salvage formulations are needed. There will be limited benefit to earlier diagnosis of treatment failure unless providers and patients have access to appropriate drugs for children to switch to.
- ItemOpen AccessA comparison of physician emigration from Africa to the United States of America between 2005 and 2015(2017) Duvivier, Robbert J; Burch, Vanessa C; Boulet, John RBACKGROUND: Migration of health professionals has been a cause for global concern, in particular migration from African countries with a high disease burden and already fragile health systems. An estimated one fifth of African-born physicians are working in high-income countries. Lack of good data makes it difficult to determine what constitutes "African" physicians, as most studies do not distinguish between their country of citizenship and country of training. Thus, the real extent of migration from African countries to the United States (US) remains unclear. This paper quantifies where African migrant physicians come from, where they were educated, and how these trends have changed over time. METHODS: We combined data from the Educational Commission for Foreign Medical Graduates with the 2005 and 2015 American Medical Association Physician Masterfiles. Using a repeated cross-sectional study design, we reviewed the available data, including medical school attended, country of medical school, and citizenship when entering medical school. RESULTS: The outflow of African-educated physicians to the US has increased over the past 10 years, from 10 684 in 2005 to 13 584 in 2015 (27.1% increase). This represents 5.9% of all international medical graduates in the US workforce in 2015. The number of African-educated physicians who graduated from medical schools in sub-Saharan countries was 2014 in 2005 and 8150 in 2015 (304.6% increase). We found four distinct categorizations of African-trained physicians migrating to the US: (1) citizens from an African country who attended medical school in their own country (86.2%, n = 11,697); (2) citizens from an African country who attended medical school in another African country (2.3%, n = 317); (3) US citizens who attended medical school in an African country (4.0%, n = 537); (4) citizens from a country outside Africa, and other than the United States, who attended medical school in an African country (7.5%, n = 1013). Overall, six schools in Africa provided half of all African-educated physicians. CONCLUSIONS: The number of African-educated physicians in the US has increased over the past 10 years. We have distinguished four migration patterns, based on citizenship and country of medical school. The majority of African graduates come to the US from relatively few countries, and from a limited number of medical schools. A proportion are not citizens of the country where they attended medical school, highlighting the internationalization of medical education.
- ItemOpen AccessA comparison of the conditional inference survival forest model to random survival forests based on a simulation study as well as on two applications with time-to-event data(2017) Nasejje, Justine B; Mwambi, Henry; Sabur, Natasha F; Lesosky, MaiaAbstract Background Random survival forest (RSF) models have been identified as alternative methods to the Cox proportional hazards model in analysing time-to-event data. These methods, however, have been criticised for the bias that results from favouring covariates with many split-points and hence conditional inference forests for time-to-event data have been suggested. Conditional inference forests (CIF) are known to correct the bias in RSF models by separating the procedure for the best covariate to split on from that of the best split point search for the selected covariate. Methods In this study, we compare the random survival forest model to the conditional inference model (CIF) using twenty-two simulated time-to-event datasets. We also analysed two real time-to-event datasets. The first dataset is based on the survival of children under-five years of age in Uganda and it consists of categorical covariates with most of them having more than two levels (many split-points). The second dataset is based on the survival of patients with extremely drug resistant tuberculosis (XDR TB) which consists of mainly categorical covariates with two levels (few split-points). Results The study findings indicate that the conditional inference forest model is superior to random survival forest models in analysing time-to-event data that consists of covariates with many split-points based on the values of the bootstrap cross-validated estimates for integrated Brier scores. However, conditional inference forests perform comparably similar to random survival forests models in analysing time-to-event data consisting of covariates with fewer split-points. Conclusion Although survival forests are promising methods in analysing time-to-event data, it is important to identify the best forest model for analysis based on the nature of covariates of the dataset in question.
- ItemOpen AccessA decade of tobacco control: The South African case of politics, health policy, health promotion and behaviour change(2013) Reddy, Priscilla; James, Shamagonam; Sewpaul, Ronel; Yach, Derek; Resnicow, Ken; Sifunda, Sibusiso; Mthembu, Zanele; Mbewu, AnthonyBACKGROUND: The South African (SA) government has implemented comprehensive tobacco control measures in line with the requirements of the Framework Convention on Tobacco Control. The effect of these measures on smoking prevalence and smoking-related attitudes, particularly among young people, is largely unknown. OBJECTIVE: To describe the impact of a comprehensive health promotion approach to tobacco control amongst SA school learners. METHODS: Four successive cross-sectional Global Youth Tobacco Surveys (GYTSs) were conducted in 1999, 2002, 2008 and 2011 among nationally representative samples of SA grades 8 - 10 school learners. We assessed the prevalence of current smoking (having smoked a cigarette on ≥1 day in the 30 days preceding the survey) and smoking-related attitudes and behaviours. RESULTS: Over the 12-year survey period current smoking among learners declined from 23.0% (1999) to 16.9% (2011) - a 26.5% reduction. Reductions in smoking prevalence were less pronounced amongst girls and amongst black learners. We observed an increase in smoking prevalence amongst learners between 2008 and 2011. Smoking-related attitudes and behaviours showed favourable changes over the survey period. CONCLUSION: These surveys demonstrate that the comprehensive and inter-sectorial tobacco control health promotion strategies implemented in SA have led to a gradual reduction in cigarette use amongst school learners. Of concern, however, are the smaller reductions in smoking prevalence amongst girls and black learners and an increase in smoking prevalence from 2008 to 2011. Additional efforts, especially for girls, are needed to ensure continued reduction in smoking prevalence amongst SA youth.
- ItemOpen AccessA global compilation of dissolved iron measurements: focus on distributions and processes in the Southern Ocean(2012) Tagliabue, A; Mtshali, T; Aumont, O; Bowie, A R; Klunder, M B; Roychoudhury, A N; Swart, SDue to its importance as a limiting nutrient for phytoplankton growth in large regions of the world's oceans, ocean water column observations of concentration of the trace-metal iron (Fe) have increased markedly over recent decades. Here we compile >13 000 global measurements of dissolved Fe (dFe) and make this available to the community. We then conduct a synthesis study focussed on the Southern Ocean, where dFe plays a fundamental role in governing the carbon cycle, using four regions, six basins and five depth intervals as a framework. Our analysis highlights depth-dependent trends in the properties of dFe between different regions and basins. In general, surface dFe is highest in the Atlantic basin and the Antarctic region. While attributing drivers to these patterns is uncertain, inter-basin patterns in surface dFe might be linked to differing degrees of dFe inputs, while variability in biological consumption between regions covaries with the associated surface dFe differences. Opposite to the surface, dFe concentrations at depth are typically higher in the Indian basin and the Subantarctic region. The inter-region trends can be reconciled with similar ligand variability (although only from one cruise), and the inter-basin difference might be explained by differences in hydrothermal inputs suggested by modelling studies (Tagliabue et al., 2010) that await observational confirmation. We find that even in regions where many dFe measurements exist, the processes governing the seasonal evolution of dFe remain enigmatic, suggesting that, aside from broad Subantarctic - Antarctic trends, biological consumption might not be the major driver of dFe variability. This highlights the apparent importance of other processes such as exogenous inputs, physical transport/mixing or dFe recycling processes. Nevertheless, missing measurements during key seasonal transitions make it difficult to better quantify and understand surface water replenishment processes and the seasonal Fe cycle. Finally, we detail the degree of seasonal coverage by region, basin and depth. By synthesising prior measurements, we suggest a role for different processes and highlight key gaps in understanding, which we hope can help structure future research efforts in the Southern Ocean.
- ItemOpen AccessA mother’s choice: a qualitative study of mothers’ health seeking behaviour for their children with acute diarrhoea(2016) Cunnama, Lucy; Honda, AyakoAbstract Background Diarrhoea presents a considerable health risk to young children and is one of the leading causes of infant mortality. Although proven cost-effective interventions exist, South Africa is yet to reach the Sustainable Development Goals set for the elimination of preventable under-five mortality and water-borne diseases. The rural study area in the Eastern Cape of South Africa continues to have a parallel health system comprising traditional and modern healthcare services. It is in this setting that this study aimed to qualitatively examine the beliefs surrounding and perceived quality of healthcare accessed for children’s acute diarrhoea. Methods Purposive sampling was used to select participants for nine focus-group-discussions with mothers of children less than 5 years old and 11 key-informant-interviews with community members and traditional and modern practitioners. The focus-group-discussions and interviews were held to explore the reasons why mothers seek certain types of healthcare for children with diarrhoea. Data was analysed using manual thematic coding methods. Results It was found that seeking healthcare from traditional practitioners is deeply ingrained in the culture of the society. People’s beliefs about the causative agents of diarrhoea are at the heart of seeking care from traditional practitioners, often in order to treat supposed supernatural causes. A combination of care-types is acceptable to the community, but not necessarily to modern practitioners, who are concerned about the inclusion of unknown ingredients and harmful substances in some traditional medicines, which could be toxic to children. These factors highlight the complexity of regulating traditional medicine. Conclusion South African traditional practitioners can be seen as a valuable human resource, especially as they are culturally accepted in their communities. However due to the variability of practices amongst traditional practitioners and some reluctance on the part of modern practitioners regulation and integration may prove complex.
- ItemOpen AccessA new species of Merxmuellera (Arundineae, Poaceae) from South Africa(1991) Barker, N P; Ellis, R PMerxmuellera setacea N.P. Barker from the south-western Cape. South Africa, is formally described. Descriptions of the morphology and leaf anatomy, in transectional and surface view, as observed under the light- and scanning electron microscope are given. Comparisons between this taxon and other southern African arundinoid species are made on the basis of morphological and anatomical observations. While the morphology of M setacea is in keeping with the generic limits of Merxmuellera Conert. the leaf blade anatomy appears to be intermediate between Merxmuellera, Pentameris Beauv. and Pentaschistis (Nees) Spach.
- ItemOpen AccessA Point Mutation in the Juxtamembrane Stalk of Human Angiotensin I-converting Enzyme Invokes the Action of a Distinct Secretase(2001) Alfalah, Marwan; Parkin, Edward T; Jacob, Ralf; Sturrock, Edward D; Mentele, Reinhard; Turner, Anthony J; HOOPER, Nigel M; Naim, Hassan YAngiotensin I-converting enzyme (ACE) is one of a number of integral membrane proteins that is proteolytically shed from the cell surface by a zinc metallosecretase. Mutagenesis of Asn(631) to Gln in the juxtamembrane stalk region of ACE resulted in more efficient secretion of the mutant protein (ACE(NQ)) as determined by pulse-chase analysis. In contrast to the wild-type ACE, the cleavage of ACE(NQ) was not blocked by the metallosecretase inhibitor batimastat but by the serine protease inhibitor, 1,3-dichloroisocoumarin. Incubation of the cells at 15 degrees C revealed that ACE(NQ) was cleaved in the endoplasmic reticulum, and mass spectrometric analysis of the secreted form of the protein indicated that it had been cleaved at the Asn(635)-Ser(636) bond, three residues N-terminal to the normal secretase cleavage site at Arg(638)-Ser(639). These data clearly show that a point mutation in the juxtamembrane region of an integral membrane protein can invoke the action of a mechanistically and spatially distinct secretase. In light of this observation, previous data on the effect of mutations in the juxtamembrane stalk of shed proteins being accommodated by a single secretase having a relaxed specificity need to be re-evaluated.
- ItemOpen AccessA Qualitative study of language barriers between South African health care providers and cross-border migrants(2017) Hunter-Adams, Jo; Rother, Hanna-AndreaAbstract Background Communication with health care providers represents an essential part of access to health care for the over 230 million cross-border migrants around the world. In this article, we explore the complexity of health communication from the perspective of cross-border migrants seeking antenatal care in Cape Town, South Africa in order to highlight the importance of high quality medical interpretation. Methods As part of a broader study of migrant maternal and infant nutrition, we conducted a secondary data analysis of semi-structured in-depth interviews (N = 23) with Congolese (n = 7), Somali (n = 8) and Zimbabwean (n = 8) women living in Cape Town, as well as nine focus group discussions (including men: n = 3 and women: n = 6) were conducted with migrant Somalis, Congolese, and Zimbabweans (N = 48). We first used content analysis to gather all data related to language and communication. We then analysed this data thematically. Results Zimbabwean participants described how the inability to speak the local South African language (IsiXhosa) gave rise to labelling and stereotyping by healthcare staff. Congolese and Somali participants described medical procedures, including tubal ligation, which were performed without consent. Partners often tried to play the role of interpreter, which resulted in loss of income and non-professional medical interpretation. Participants’ highlighted fears over unwanted procedures or being unable to access care. Challenges of communication without a common language (and without professional medical interpretation), rather than outright denial of care by healthcare professionals, mediated these encounters. Conclusion Although there are several factors impeding cross-border migrants’ access to health care, effective communication is a prerequisite for quality care. Free-to-patient professional medical interpretation would not only benefit migrant populations but would benefit the broader community where language and health literacy are barriers to accessing health care. Novel approaches to language access may include technology-enabled professional interpretation.
- ItemOpen AccessA re-evaluation of isotope screening for skeletal metastases in node-negative breast cancer(1996) Gudgeon, CA; Werner, I D; Dent, D MThe International Society for Burns Injuries (ISBI) has published guidelines for the management of multiple or mass burns casualties, and recommends that 'each country has or should have a disaster planning system that addresses its own particular needs.' The need for a national burns disaster plan integrated with national and provincial disaster planning was discussed at the South African Burns Society Congress in 2009, but there was no real involvement in the disaster planning prior to the 2010 World Cup; the country would have been poorly prepared had there been a burns disaster during the event. This article identifies some of the lessons learnt and strategies derived from major burns disasters and burns disaster planning from other regions. Members of the South African Burns Society are undertaking an audit of burns care in South Africa to investigate the feasibility of a national burns disaster plan. This audit (which is still under way) also aims to identify weaknesses of burns care in South Africa and implement improvements where necessary.
- ItemOpen AccessAcceptability, feasibility and impact of routine screening to detect undiagnosed HIV infection in 17 - 24-month-old children in the western sub-district of Cape Town(2012) Levin, Michael; Mathema, Hlengani; Stinson, Kathryn; Jennings, KarenOBJECTIVES: To explore the acceptability and feasibility of routine HIV screening in children at primary healthcare clinics and ascertain the prevalence of previously undiagnosed HIV infection in 17 - 24 month old children accessing curative and routine services. METHODS: A survey was conducted in 4 primary health clinics in the western sub-district of Cape Town. Rapid HIV screening of 17 - 24 month old children was performed for consenting caregiver-child pairs. Data on demographics, child health and antenatal history were collected using questionnaires. RESULTS: During recruitment, 358 children (72%) were tested for HIV infection. Most of the children (95.8%) were accompanied by a parent. The prevalence of reported HIV exposure among children was 21% (107/499). Of these, 3 had previously confirmed HIV infection; 1 was reportedly confirmed by a 6-week HIV test, and the other 2 probably contracted the virus via late post-partum transmission. The overall transmission rate was 3.5% (3/86) and the confirmed proportion of HIV-infected children was 0.8% (3/361). No previously unknown HIV infection was detected. CONCLUSIONS: Programmes to prevent mother-to-child transmission are effective, but at-risk infants who test negative at 6 weeks should be monitored for subsequent seroconversion. Parents of HIV-exposed infants are more likely to permit (re)testing of their infants than those whose offspring are not at risk. Routine HIV testing of children is feasible and acceptable at primary level, but may require additional resources to achieve universal coverage. Routine screening at an earlier age may detect previously undiagnosed HIV infection.
- ItemOpen AccessAction-based flood forecasting for triggering humanitarian action(2016) Coughlan de Perez, Erin; van den Hurk, Bart; van Aalst, Maarten K; Amuron, Irene; Bamanya, Deus; Hauser, Tristan; Jongma, Brenden; Lopez, Ana; Mason, Simon; Mendler de Suarez, Janot; Pappenberger, Florian; Rueth, Alexandra; Stephens, Elisabeth; Suarez, Pablo; Wagemaker, Jurjen; Zsoter, ErvinToo often, credible scientific early warning information of increased disaster risk does not result in humanitarian action. With financial resources tilted heavily towards response after a disaster, disaster managers have limited incentive and ability to process complex scientific data, including uncertainties. These incentives are beginning to change, with the advent of several new Forecast-based Financing systems that provide funding based on a forecast of an extreme event. Given the changing landscape, here we demonstrate a method to select and use appropriate forecasts for specific humanitarian disaster prevention actions, even in a data-scarce location. This action-based forecasting methodology takes into account the parameters of each action, such as action lifetime, when verifying a forecast. Forecasts are linked with action based on an understanding of (1) the magnitude of previous flooding events and (2) the willingness to act "in vain" for specific actions. This is applied in the context of the Uganda Red Cross Society Forecast-based Financing pilot project, with forecasts from the Global Flood Awareness System (GloFAS). Using this method, we define the "danger level" of flooding, and we select the probabilistic forecast triggers that are appropriate for specific actions. Results from this methodology can be applied globally across hazards, and fed into a financing system that ensures that automatic, pre-funded early action will be triggered by forecasts.
- ItemOpen AccessAcute glycaemic effects of co-trimoxazole at prophylactic dose in healthy adults(2016) Kenteu, Bernold; Noubiap, Jean Jacques N; Etoa, Martine Claude; Azabji-Kenfack, Marcel; Dehayem, Mesmin; Sobngwi, EugèneAbstract Background Cases of severe hypoglycaemia were reported in HIV/AIDS patients receiving high dose of the sulfonylurea co-trimoxazole for opportunistic infections. Whether co-trimoxazole at prophylactic dose would induce similar side effects is unknown. We aimed to investigate the acute effects of co-trimoxazole at prophylactic dose on glucose metabolism in healthy adults. Methods We enrolled 20 healthy volunteers (15 males and 5 females) aged 23.0 (SD 2.0) years, with mean BMI of 22.3 (SD 3.6) Kg/m 2 with normal glucose tolerance, hepatic and renal function. We performed a 75-g oral glucose tolerance test (OGTT) with and without concomitant oral co-trimoxazole administered 60 min before the test. Blood glucose response was measured using a capillary test at baseline and at 30, 60, 90, 120 and 180 min following oral glucose load on the two occasions. C-peptide response was also measured. Absolute values of blood glucose and C-peptide with and without co-trimoxazole were compared using the Wilcoxon test. Results During the OGTT without co-trimoxazole (control) vs. the OGTT with co-trimoxazole (test), the glycaemia varied from 4.83 (SD 0.39) mmol/l vs. 4.72 (SD 0.28) mmol/l at T0 (P = 0.667), to 8.00 (SD 1.11) mmol/l vs. 7.44 (SD 0.78) mmol/l at T30 (P = 0.048), 8.00 (SD 1.17) mmol/l vs. 7.67 (SD 1.00) mmol/l at T60 (P = 0.121), 7.33 (SD 0.94) mmol/l vs. 7.11 (SD 0.83) mmol/l at T90 (P = 0.205), 6.78 (SD 1.00) mmol/l vs. 6.67 (SD 1.00) mmol/l at T120 (P = 0.351) and 4.72 (SD 1.39) mmol/l vs. 4.72 (SD 1.56) mmol/l at T180 (P = 0.747). The ratio of area under the glycaemia curve during the control and test investigation was 96.7 %, thus a 3.3 decreased glycaemic response (p = 0.062). A decrease of glycaemia by more than 10 % occurred in 6/20 participants at T30, 7/20 participants at T60 and 1/20 participant at T30 and T60. None of the volunteers experienced co-trimoxazole-induced hypoglycaemia. At the same time, the C-peptide response during the control vs. the test investigation varied from 278.1 (SD 57.5) pmol/l vs. 242.8 (SD 42.5) pmol/l at T0 (P = 0.138), to 1845.6 (SD 423.6) pmol/l vs. 2340.6 (SD 701.3) pmol/l at T60 (P = 0.345) and 1049.8 (SD 503.1) pmol/l vs. 1041.63 (SD 824.21) pmol/l at T180 (P = 0.893). Conclusion Ninety minutes after its administration, co-trimoxazole induced a significant reduction of the early glycaemic response to oral glucose in parallel with a 27-% increase in insulin secretory response. Co-trimoxazole induced within 120 min a more than 10-% blood glucose reduction in 2/3 of participants. However none of the volunteers experienced hypoglycaemia.
- ItemOpen AccessAdipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans(2009) Lindemans, M; Liu, F; Janssen, T; Husson, S J; Mertens, I; Gäde, G; Schoofs, LIn mammals, hypothalamic gonadotropin-releasing hormone (GnRH) is a neuropeptide that stimulates the release of gonadotropins from the anterior pituitary. The existence of a putative functional equivalent of this reproduction axis in protostomian invertebrates has been a matter of debate. In this study, the ligand for the GnRH receptor in the nematode Caenorhabditis elegans (Ce-GnRHR) was found using a bioinformatics approach. The peptide and its precursor are reminiscent of both insect adipokinetic hormones and GnRH-preprohormone precursors from tunicates and higher vertebrates. We cloned the AKH-GnRH-like preprohormone and the Ce-GnRHR and expressed the GPCR in HEK293T cells. The GnRHR was activated by the C. elegans AKH-GnRH-like peptide (EC50 = 150 nM) and by Drosophila AKH and other nematode AKH-GnRHs that we found in EST databases. Analogous to both insect AKH receptor and vertebrate GnRH receptor signaling, Ce-AKH-GnRH activated its receptor through a Gαq protein with Ca2+ as a second messenger. Gene silencing of Ce-GnRHR, Ce-AKH-GnRH, or both resulted in a delay in the egg-laying process, comparable to a delay in puberty in mammals lacking a normal dose of GnRH peptide or with a mutated GnRH precursor or receptor gene. The present data support the view that the AKH-GnRH signaling system probably arose very early in metazoan evolution and that its role in reproduction might have been developed before the divergence of protostomians and deuterostomians.
- ItemOpen AccessAdjuvant chemotherapy for stage I non-seminomatous testicular cancer(1994) Abratt, R P; Pontin, AR; Barnes, RD; Reddi, BVThe International Society for Burns Injuries (ISBI) has published guidelines for the management of multiple or mass burns casualties, and recommends that 'each country has or should have a disaster planning system that addresses its own particular needs.' The need for a national burns disaster plan integrated with national and provincial disaster planning was discussed at the South African Burns Society Congress in 2009, but there was no real involvement in the disaster planning prior to the 2010 World Cup; the country would have been poorly prepared had there been a burns disaster during the event. This article identifies some of the lessons learnt and strategies derived from major burns disasters and burns disaster planning from other regions. Members of the South African Burns Society are undertaking an audit of burns care in South Africa to investigate the feasibility of a national burns disaster plan. This audit (which is still under way) also aims to identify weaknesses of burns care in South Africa and implement improvements where necessary.
- ItemOpen AccessAdolescent and young pregnant women at increased risk of mother-to-child transmission of HIV and poorer maternal and infant health outcomes: A cohort study at public facilities in the Nelson Mandela Bay Metropolitan district, Eastern Cape, South Africa(2014) Fatti, Geoffrey; Shaikh, Najma; Eley, Brian; Jackson, Debra; Grimwood, AshrafBACKGROUND: South Africa (SA) has the highest burden of childhood HIV infection globally, and has high rates of adolescent and youth pregnancy OBJECTIVE: To explore risks associated with pregnancy in young HIV-infected women, we compared mother-to-child transmission (MTCT) of HIV and maternal and infant health outcomes according to maternal age categories METHODS: A cohort of HIV-positive pregnant women and their infants were followed up at three sentinel surveillance facilities in the Nelson Mandela Bay Metropolitan (NMBM) district, Eastern Cape Province, SA. Young women were defined as 24 years as the comparison group RESULTS: Of 956 mothers, 312 (32.6%) were young women; of these, 65 (20.8%) were adolescents. The proportion of young pregnant women increased by 24% between 2009/10 and 2011/12 (from 28.3% to 35.1%). Young women had an increased risk of being unaware of their HIV status when booking (adjusted risk ratio (aRR) 1.37; 95% confidence interval (CI) 1.21 - 1.54), a reduced rate of antenatal antiretroviral therapy (ART) uptake (adjusted hazard ratio 0.46; 95% CI 0.31 - 0.67), reduced early infant HIV diagnosis (aRR 0.94; 95% CI 0.94 - 0.94), and increased MTCT (aRR 3.07; 95% CI 1.18 - 7.96; adjusted for ART use). Of all vertical transmissions, 56% occurred among young women. Additionally, adolescents had increased risks of first presentation during labour (aRR 3.78; 95% CI 1.06 - 13.4); maternal mortality (aRR 35.1; 95% CI 2.89 - 426) and stillbirth (aRR 3.33; 95% CI 1.53 - 7.25 CONCLUSION: An increasing proportion of pregnant HIV-positive women in NMBM were young, and they had increased MTCT and poorer maternal and infant outcomes than older women. Interventions targeting young women are increasingly needed to reduce pregnancy, HIV infection and MTCT and improve maternal and infant outcomes if SA is to attain its Millennium Development Goals
- ItemOpen AccessAdrenaline and amiodarone dosages in resuscitation: Rectifying misinformation(2013) Botha, Martin; Wells, Mike; Dickerson, Roger; Wallis, Lee; Stander, MelanieDespite the recognition of specialists in emergency medicine and the professionalisation of prehospital emergency care, international guidelines and consensus are often ignored, and the lag between guideline publication and translation into clinical practice is protracted. South African literature should reflect the latest evidence to guide resuscitation and safe patient care. This article addresses erroneous details regarding life-saving interventions in the South African Medicines Formulary , 10th edition.
- ItemOpen AccessAn approach to the patient with suspected pericardial disease(2016) Kyriakakis, Charles G; Mayosi, Bongani M; de Vries, Elma; Isaacs, Abdul; Doubell, Anton FDiseases of the pericardium commonly manifest in one of three ways: acute pericarditis, pericardial effusion and constrictive pericarditis. In the developed world, the most common cause of acute pericarditis is viral or idiopathic disease, while in the developing world tuberculous aetiology, particularly in sub-Saharan Africa, is commonplace owing to the high prevalence of HIV. This article provides an approach to the diagnosis, investigation and management of these patients.
- ItemOpen AccessAnalysis of Nonlinear Dispersion of a Pollutant Ejected by an External Source into a Channel Flow(2010) Chinyoka, T; Makinde, O DThis paper focuses on the transient analysis of nonlinear dispersion of a pollutant ejected by an external source into a laminar flow of an incompressible fluid in a channel. The influence of density variation with pollutant concentration is approximated according to the Boussinesq approximation, and the nonlinear governing equations of momentum and pollutant concentration are obtained. The problem is solved numerically using a semi-implicit finite difference method. Solutions are presented in graphical form and given in terms of fluid velocity, pollutant concentration, skin friction, and wall mass transfer rate for various parametric values. The model can be a useful tool for understanding the polluting situations of an improper discharge incident and evaluating the effects of decontaminating measures for the water body.