Role of obesity and gestational diabetes mellitus status on the expression of kisspeptin, inflammatory markers and other endocrine signals, and their correlation with foetal outcomes and placental structure

Background: Maternal obesity and gestational diabetes mellitus (GDM) are associated with short and long-term health risks for the mother and child. The placenta produces hormones, including steroids and cytokines, that influence maternal glucose control. Current literature links kisspeptins with glucose-stimulated insulin secretion, and low plasma kisspeptin concentrations have been associated with GDM and markers of insulin resistance. In addition, maternal obesity is characterized by low-grade inflammation and insulin resistance. However, little is known about the effect of maternal obesity and GDM and their interaction on placental kisspeptin and inflammatory marker (TNFα, IL-6) expression, the relationship between placental and circulatory kisspeptin and inflammatory markers with placental villous morphology and maternal and neonatal parameters. There is also a paucity of data on the effect of maternal obesity and GDM on other endocrine signals (leptin, placental lactogen family members), growth factors (IGF2, VEGF), and steroidogenic hormone enzyme gene expression in the placenta. Aim: This work aimed to examine the effect of maternal obesity and/or GDM on molecular expression (placental, maternal and cord serum) of kisspeptin and inflammatory markers (TNFα, IL-6) and placental morphology, and how these effects relate to maternal and neonatal clinical parameters. Additionally, the work aimed to investigate the effect of maternal obesity and/or GDM on leptin, placental lactogen family members, growth factors, and steroidogenic hormone enzymes gene expression in the placenta. Methods: This study included 4 groups of South African pregnant women: Non-GDM, Non-obese (n=14); Non-GDM, Obese (n=19); GDM, Non-obese (n=15); GDM-Obese (n=23). At delivery, the women's placental tissue was fixed and processed for immunohistochemistry and histological assessment as well as snap-frozen for RT-qPCR and Western Blot analysis. Maternal and cord blood were also collected for the measurement of placenta-derived factors by ELISA. Data were compared by two-way ANOVA with Bonferroni multiple comparisons tests. Results: Maternal obesity and GDM had no effect on placental kisspeptin gene and protein expression, immunostaining or circulatory levels. There was a significant negative correlation between placental kisspeptin gene expression and volume of villous syncytiotrophoblasts and theoretical diffusion capacity in non-obese women irrespective of their GDM status. There was a significant inverse correlation between plasma kisspeptin protein and BMI and maternal systolic blood pressure in GDM women regardless of obesity. Cord serum kisspeptin concentration correlated negatively with BMI. Maternal obesity reduced placental Leptin and KISS1R gene expression in the absence of GDM. Overall, placental TNFα protein abundance by immunostaining was significantly higher in women with obesity irrespective of GDM status. TNFα staining of terminal villi syncytiotrophoblast was increased in women with obesity, while IL-6 staining of terminal villi stroma and foetal vessels was reduced in obese women, significantly so in GDM women. There was a positive correlation between the expression of placental TNFα gene and IL6 protein and maternal diastolic blood pressure in obese non-GDM and GDM women, respectively. In obese non-GDM women, maternal serum TNFα and IL-6 concentrations correlated negatively with placenta weight, foetoplacental ratio and volume of intervillous space, and theoretical and specific diffusion capacity, respectively. Women with obesity showed fewer terminal villi with fewer syncytiotrophoblast, foetal vessels and stroma dependent on GDM diagnosis while GDM influenced intervillous space volume by increasing it in obese groups. Maternal obesity also affected the surface areas for maternal-foetal exchange; the surface area of maternal blood space and foetal capillary were reduced in women with obesity regardless of GDM status. Again, the physiological diffusion gradients for oxygen transfer at the maternal-foetal interface were significantly reduced by maternal obesity. Conclusion: This study shows neither maternal obesity nor GDM influences kisspeptin levels, although maternal obesity in the absence of GDM seems to downregulate KISS1R, which may impact the kisspeptin-KISS1R signalling pathway. GDM rather than obesity may have a greater effect on TNF-α mediated maternal circulatory and placental inflammation. This study suggests that placental inflammation and insulin resistance may have a relationship with hypertension. In obese women alone, maternal inflammatory cytokines seem to be associated with altered placental structure and function. Indeed, maternal obesity was shown to compromise placental maturation and decrease the surface area and diffusion capacity required for maternal-foetal nutrient and oxygen exchange. These observations are likely to contribute novel insights into the interplay between metabolic dysfunction, obesity, and inflammation in the pathophysiology of GDM and placental dysfunction

Comparative Study of Maximum Power Point Tracking with a Modified DC DC Converter

Maximum power points are used to find the voltages and currents at which a photovoltaic (PV) panel should operate to obtain maximum power. In order to deliver highest power, an efficient DC DC converter and a reliable tracking algorithm are used. There is also the need to continuously find the maximum power under any environmental conditions at all times. This research is intended to study a comparative performance of maximum power point (MPP) which is presented under uniform irradiance condition. The algorithm employed is an improved cuckoo search algorithm and the DC-DC Converter( switched mode power supply) has been modified by including a synchronous rectifier connected to a load, the performance of the system is validated using MATLAB/Simulink and practical implementation for this work. A comparison of the MATLAB Simulation with the practical implementation of MPP is presented using maximum power and percentage tracking efficiency as performance metric. From the MATLAB results obtained, maximum extracted power is 26.81W and the hardware implementation gives a maximum power of 28.71W. Tracking efficiency improves by 6.62%. The results show the practical MPP gives a better maximum power, which consequently improves the Photovoltaic systems efficiency and conversely mitigates the power consumption and the cost of the system than the simulation result obtained in MATLAB

The Nexus between Unsustainable Mining, Livelihood and Environmental Degradation: A Case of Tin and Columbite Mining on Jos Plateau Nigeria

Tin and columbite have been extensively mined on the Jos plateau since the time of the colonial era. Tin and columbite mining were characterized by many unsustainable practices that adversely impacts on the environment. The study examines the nexus between the unsustainable practices associated with the mining activities, the livelihood opportunities it provided to the residents and the environmental degradation that results from the mining activities in the study area. The study is based on field visit to some of the active and abandoned mine sites and reclaimed mine sites. During the fieldwork, observation and measurement were made and recorded. Interviews of some artisanal miners, mine supervisors and staff of mineral processing company were made and the data collected analyzed using content analysis method. The findings of the study reveals that tin and columbite mining activities degrade the land thereby reducing land needed for farming and building of residential houses. Despite the risk associated with it, tin mining provide a lucrative source of livelihood to many natives in the area. The laborers were paid between ₦50,000 to ₦100,000 daily according to some of the people interviewed. Although this depends on the amount of tin extracted, the earning of ₦50,000 daily is more than the national minimum wage of N33,000 per month. Despite the risk associated with mine openings, effort to reclaim the abandoned mine has been very slow. Based on the findings, the study recommends the need for surface mining control and reclamation Act, abandoned mine reclamation fund and the need to tie ecological fund to specific projects that promote ecological restoration, conservation and preservation

Evaluating South African Weather Service information on Idai tropical cyclone and KwaZulu-Natal flood events

Severe weather events associated with strong winds and flooding can cause fatalities, injuries and damage to property. Detailed and accurate weather forecasts that are issued and communicated timeously, and actioned upon, can reduce the impact of these events. The responsibility to provide such forecasts usually lies with government departments or state-owned entities; in South Africa that responsibility lies with the South African Weather Service (SAWS). SAWS is also a regional specialised meteorological centre and therefore provides weather information to meteorological services within the Southern African Development Community (SADC). We evaluated SAWS weather information using near real-time observations and models on the nowcasting to short-range forecasting timescales during two extreme events. These are the Idai tropical cyclone in March 2019 which impacted Mozambique, Zimbabwe and Malawi resulting in over 1000 deaths, and the floods over the KwaZulu-Natal (KZN) province in April 2019 that caused over 70 deaths. Our results show that weather models gave an indication of these systems in advance, with warnings issued at least 2 days in advance in the case of Idai and 1 day in advance for the KZN floods. Nowcasting systems were also in place for detailed warnings to be provided as events progressed. Shortcomings in model simulations were shown, in particular on locating the KZN flood event properly and over/-underestimation of the event. The impacts experienced during the two events indicate that more needs to be done to increase weather awareness, and build disaster risk management systems, including disaster preparedness and risk reduction.Significance: This paper is relevant for all South Africans and the SADC region at large because it provides information on: the weather forecasting processes followed at the South African Weather Service, available early warning products in South Africa and for the SADC region made possible through the public purse, the performance of nowcasting and modelling systems in the case of predicting two extreme weather events that had adverse impacts on southern African society, and the dissemination of warnings of future extreme weather events

Evaluating South African weather service information on Idai tropical cyclone and KwaZulu- Natal flood events

Severe weather events associated with strong winds and flooding can cause fatalities, injuries and damage to property. Detailed and accurate weather forecasts that are issued and communicated timeously, and actioned upon, can reduce the impact of these events. The responsibility to provide such forecasts usually lies with government departments or state-owned entities; in South Africa that responsibility lies with the South African Weather Service (SAWS). SAWS is also a regional specialised meteorological centre and therefore provides weather information to meteorological services within the Southern African Development Community (SADC). We evaluated SAWS weather information using near real-time observations and models on the nowcasting to short-range forecasting timescales during two extreme events. These are the Idai tropical cyclone in March 2019 which impacted Mozambique, Zimbabwe and Malawi resulting in over 1000 deaths, and the floods over the KwaZulu-Natal (KZN) province in April 2019 that caused over 70 deaths. Our results show that weather models gave an indication of these systems in advance, with warnings issued at least 2 days in advance in the case of Idai and 1 day in advance for the KZN floods. Nowcasting systems were also in place for detailed warnings to be provided as events progressed. Shortcomings in model simulations were shown, in particular on locating the KZN flood event properly and over/underestimation of the event. The impacts experienced during the two events indicate that more needs to be done to increase weather awareness, and build disaster risk management systems, including disaster preparedness and risk reduction. Significance: This paper is relevant for all South Africans and the SADC region at large because it provides information on: • the weather forecasting processes followed at the South African Weather Service, • available early warning products in South Africa and for the SADC region made possible through the public purse, • the performance of nowcasting and modelling systems in the case of predicting two extreme weather events that had adverse impacts on southern African society, and • the dissemination of warnings of future extreme weather events.The Climate Research for Development (CR4D) Postdoctoral Fellowship CR4D-19-11 implemented by the African Academy of Sciences (AAS) in partnership with the United Kingdom’s Department for International Development (DfID) Weather and Climate Information Services for Africa (WISER) programme and the African Climate Policy Center (ACPC) of the United Nations Economic Commission for Africa (UNECA).http://www.sajs.co.zaam2022Geography, Geoinformatics and Meteorolog

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Hypergonadotropic hypogonadism in Nigerian men with type 2 diabetes mellitus

Background. Studies have reported a higher preva-lence of hypogonadism in men with type 2 diabetes mellitus (T2DM) than non-diabetic men. The pattern of hypogonadism in men with T2DM using gonado-tropin-releasing hormone (GnRH) stimulation test in Sub-Saharan Africa is unknown. Objective. This study was conducted to determine the prevalence and pattern of hypogonadism in Nigerian men with T2DM. Methods. A cross-sectional study involving 358 men with T2DM and 179 non-diabetic men as controls. Androgen Deficiency in the Ageing Male (ADAM) questionnaire was administered. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) both at 0 hours and 4 hours after subcutaneous buserelin injec-tion, fasting total testosterone (TT), fasting plasma glucose and glycated haemoglobin were measured. Ninety-nine men with T2DM selected by randomiza-tion using a computer underwent GnRH stimulation test, with subcutaneous injection of 100 micrograms of buserelin.Results. The mean TT of T2DM men was significantly lower compared to the controls (8.79 ± 3.35 nmol/L vs 15.41 ± 3.79 nmol/L, p < 0.001). The prevalence of hypogonadism in T2DM men was 80.4%, comprising 38.5% of severe hypogonadism and 41.9% mild hypogonadism. The mean LH and FSH levels were significantly higher in T2DM men than the controls (9.62 ± 6.82 IU/L vs 8.24 ± 5.91 IU/L, p = 0.022 and 8.50 ± 8.17 IU/L vs 5.17 ± 3.89 IU/L, p < 0.001 respectively). There was a statistically significant exaggerated response in mean (±SD) LH and FSH levels at 4 hours after buserelin in-jection compared to the 0-hour levels (58.58 ± 40.72 IU/L vs 8.38 ± 6.10 IU/L, p < 0.001 and 23.03 ± 18.02 IU/L vs 8.41 ± 7.45 IU/L, p < 0.001 respectively) in men with T2DM who had GnRH stimulation tests.Conclusion. This study shows that the prevalence of hypogonadism in men with T2DM is significantly higher than in non-diabetic men with mild hypogonadism accounting for most cases. Hypergonadotropic hypo-gonadism occurs more frequently in men with T2DM in Nigeria.

Outcomes of hyperglycaemia in pregnancy in Africa: Systematic review study protocol

Introduction The prevalence of diabetes mellitus globally has increased considerably over the past decades with a resultant increase in the incidence of diabetes-complicated pregnancies. Hyperglycaemia in pregnancy is the most common metabolic complication encountered during pregnancy and is associated with adverse maternal and fetal outcomes. This systematic review aims to examine maternal, fetal, neonatal, childhood and long-term maternal outcomes of hyperglycaemia in pregnancy in Africa. Methods and analysis A systematic review of all studies that investigated hyperglycaemia in pregnancy outcomes, carried out in Africa from 1998 to 2019. A comprehensive search of all published articles indexed in PubMed-MEDLINE, Cochrane Library, Scopus, CINAHL (EBSCOhost), Embase and Web of Science databases will be performed. Studies will be screened for eligibility by title, abstract and full text in duplicate by two independent reviewers. For data where meta-analysis is not possible, narrative analysis will be carried out using themes from data. For data where meta-analysis is possible, random effects meta-analysis will be conducted. This systematic review will be reported according to the Meta-analyses of Observational Studies in Epidemiology. Ethics and dissemination Ethical approval is not required for this study considering this is a systematic review protocol that uses only published data. The findings of this study will be disseminated through peer-reviewed publications and conference presentations. PROSPERO registration number CRD42020184573

Obesity and gestational diabetes independently and collectively induce specific effects on placental structure, inflammation and endocrine function in a cohort of South African women.

Maternal obesity and gestational diabetes mellitus (GDM) are associated with insulin resistance and health risks for mother and offspring. Obesity is also characterized by low-grade inflammation, which in turn, impacts insulin sensitivity. The placenta secretes inflammatory cytokines and hormones that influence maternal glucose and insulin handling. However, little is known about the effect of maternal obesity, GDM and their interaction, on placental morphology, hormones and inflammatory cytokines. In a South African cohort of non-obese and obese pregnant women with and without GDM, this study examined placental morphology using stereology, placental hormone and cytokine expression using real-time PCR, western blotting and immunohistochemistry, and circulating TNFα and IL-6 concentrations using ELISA. Placental expression of endocrine and growth factor genes was not altered by obesity or GDM. However, LEPTIN gene expression was diminished, syncytiotrophoblast TNFα immunostaining elevated and stromal and fetal vessel IL-6 staining reduced in the placenta of obese women in a manner that was partly influenced by GDM status. Placental TNFα protein abundance and maternal circulating TNFα concentrations were reduced in GDM. Both maternal obesity and, to a lesser extent, GDM were accompanied by specific changes in placental morphometry. Maternal blood pressure and weight gain and infant ponderal index were also modified by obesity and/or GDM. Thus, obesity and GDM have specific impacts on placental morphology and endocrine and inflammatory states that may relate to pregnancy outcomes. These findings may contribute to developing placenta-targeted treatments that improve mother and offspring outcomes, which is particularly relevant given increasing rates of obesity and GDM worldwide. KEY POINTS: Rates of maternal obesity and gestational diabetes (GDM) are increasing worldwide, including in low-middle income countries (LMIC). Despite this, much of the work in the field is conducted in higher-income countries. In a well-characterised cohort of South African women, this study shows that obesity and GDM have specific impacts on placental structure, hormone production and inflammatory profile. Moreover, such placental changes were associated with pregnancy and neonatal outcomes in women who were obese and/or with GDM. The identification of specific changes in the placenta may help in the design of diagnostic and therapeutic approaches to improve pregnancy and neonatal outcomes with particular significant benefit in LMICs