Changes in Glial Fibrillary Acidic Protein-Immunoreactive Astrocytes in the Prefrontal Cortex of the Male Rat following Chronic Khat Use.

Background: Long-term khat consumption is associated with significant neurocognitive changes, which have been elucidated in behavioral studies. With current research showing the centrality of astrocytes and other glial cells in neuronal signaling, there is possibility that these cells are also affected by chronic khat use. There is little literature on the structural changes in the prefrontal cortex neuronal and astrocytic cytoarchitecture and morphometry in chronic khat users. Objective: The objective of this study was to describe the changes in astrocyte morphometry and structure in rats after long-term use of khat (miraa). Materials and Methods: Adult male Wistar rats, aged 2-3 months, weighing 200-300 g were randomized into four groups of 10 each (control, Group 1, Group 2, and Group 3) to correspond with those used as controls and those that received 500 mg/kg, 1000 mg/kg, and 2000 mg/kg body weight khat extracts, respectively. Fresh khat leaves were purchased from Maua market in Meru, and crude extract was prepared using lyophilization. The control rats were fed on normal diet, while the experimental groups were fed on normal diet and khat extracts using oral gavage for 6 weeks. The animals were sacrificed and their brains were removed. We performed immunohistochemical visualization of astrocytes using glial fibrillary acidic protein. Photomicrographs of the stained sections were transferred to ImageJ Fiji software to study the astrocyte density and astrocytic processes. We used Kruskal-Wallis test to correlate the four animal groups in terms of astrocyte densities. Results: We observed an increase in the average number of astrocytes with increasing doses of khat compared to controls, with those in Group 3 (2000 mg/kg) having an exuberant reactive astrocytosis. Further, escalating khat doses resulted in increased glial fibrillary acidic protein immunoreactivity in the nuclei and astrocytic processes, gliotic changes, and increased complexity of astrocytic processes. Conclusion: Chronic khat use, especially at high doses, results in reactive astrocytosis and astrogliosis, which may be part of the mechanisms involved in the cognitive changes associated with its use.

Reversible effect of castration induced hypogonadism on the morphology of the left coronary arteries in adult male rabbits.

Hypogonadism is associated with an increased risk of coronary artery disease. This study sought to describe the histomorphology of the left coronary arteries of the adult male rabbit following orchiectomy and subsequent testosterone administration. We included 20 adult male rabbits, divided into a baseline group (n=2), an interventional group subjected to castration only (n=6), an intervention group subjected to castration followed by testosterone injection (n=6), and a control group (n=6). Key variables under investigation were serum testosterone levels, the intima-media thickness of coronary arteries, smooth muscle cell density, and adventitial collagen fiber density. The mean coronary arteries' intimal medial thickness was significantly higher in the castrated group than in controls (0.488 mm and 0.388 mm, respectively), while the testosterone-injected group had a mean of 0.440 mm. Mean smooth muscle cell density was significantly lower in the castrated rabbits vs. controls (26.96% and 47.80%, respectively), this observation being reversed with testosterone injection (47.53%). Mean adventitial collagen fiber density was significantly higher in the castrated group than in controls (66.6% and 36.1%, respectively), with a marginal difference after testosterone injection (65.2%). This study demonstrates that castration-induced hypogonadism causes morphological changes in the coronary arteries that are partly reversible using testosterone injections. These findings provide a morphological basis for understanding the role of testosterone in coronary arteries.

Placental characteristics and neonatal weights among women with malaria-preeclampsia comorbidity and healthy pregnancies.

BACKGROUND: Malaria and preeclampsia are leading causes of maternal morbidity and mortality in sub-Saharan Africa. They contribute significantly to poor perinatal outcomes like low neonatal weight by causing considerable placental morphological changes that impair placental function. Previous studies have described the effects of either condition on the placental structure but the structure of the placenta in malaria-preeclampsia comorbidity is largely understudied despite its high burden. This study aimed to compare the placental characteristics and neonatal weights among women with malaria-preeclampsia comorbidity versus those with healthy pregnancies. METHODOLOGY: We conducted a retrospective cohort study among 24 women with malaria-preeclampsia comorbidity and 24 women with healthy pregnancies at a County Hospital in Western Kenya. Neonatal weights, gross and histo-morphometric placental characteristics were compared among the two groups. RESULTS: There was a significant reduction in neonatal weights (P<0.001), placental weights (P = 0.028), cord length (P<0.001), and cord diameter (P<0.001) among women with malaria-preeclampsia comorbidity compared to those with healthy pregnancies. There was also a significant reduction in villous maturity (P = 0.016) and villous volume density (P = 0.012) with increased villous vascularity (P<0.007) among women with malaria-preeclampsia comorbidity compared to those with healthy pregnancies. CONCLUSION: Placental villous maturity and villous volume density are significantly reduced in patients with malaria-preeclampsia comorbidity with a compensatory increase in villous vascularity. This leads to impaired placental function that contributes to lower neonatal weights.

Evaluation and optimization of the syndromic management of female genital tract infections in Nairobi, Kenya.

BACKGROUND: Genital tract infections pose a public health concern. In many low-middle-income countries, symptom-based algorithms guide treatment decisions. Advantages notwithstanding, this strategy has important limitations. We aimed to determine the infections causing lower genital tract symptoms in women, evaluated the Kenyan syndromic treatment algorithm for vaginal discharge, and proposed an improved algorithm. METHODS: This cross-sectional study included symptomatic non-pregnant adult women presenting with lower genital tract symptoms at seven outpatient health facilities in Nairobi. Clinical, socio-demographic information and vaginal swabs microbiological tests were obtained. Multivariate logistic regression analyses were performed to find predictive factors for the genital infections and used to develop an alternative vaginal discharge treatment algorithm (using 60% of the dataset). The other 40% of data was used to assess the performance of each algorithm compared to laboratory diagnosis. RESULTS: Of 813 women, 66% had an infection (vulvovaginal candidiasis 40%, bacterial vaginosis 17%, Neisseria gonorrhoea 14%, multiple infections 23%); 56% of women reported ≥ 3 lower genital tract symptoms episodes in the preceding 12 months. Vulvovaginal itch predicted vulvovaginal candidiasis (odds ratio (OR) 2.20, 95% CI 1.40-3.46); foul-smelling vaginal discharge predicted bacterial vaginosis (OR 3.63, 95% CI 2.17-6.07), and sexually transmitted infection (Neisseria gonorrhoea, Trichomonas vaginalis, Chlamydia trachomatis, Mycoplasma genitalium) (OR 1.64, 95% CI 1.06-2.55). Additionally, lower abdominal pain (OR 1.73, 95% CI 1.07-2.79) predicted sexually transmitted infection. Inappropriate treatment was 117% and 75% by the current and alternative algorithms respectively. Treatment specificity for bacterial vaginosis/Trichomonas vaginalis was 27% and 82% by the current and alternative algorithms, respectively. Performance by other parameters was poor to moderate and comparable between the two algorithms. CONCLUSION: Single and multiple genital infections are common among women presenting with lower genital tract symptoms at outpatient clinics in Nairobi. The conventional vaginal discharge treatment algorithm performed poorly, while the alternative algorithm achieved only modest improvement. For optimal care of vaginal discharge syndrome, we recommend the inclusion of point-of-care diagnostics in the flowcharts.

Coronavirus disease 2019 and the placenta: A literature review.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been implicated in the clinical pathology of multiple organs and organ systems. Due to the novelty of the disease, there is a need to review emerging literature to understand the profile of SARS-CoV-2 in the placenta. This review sought to evaluate the literature on the mediators, mechanism of entry, pathogenesis, detection, and pathology of SARS-CoV-2 in the placenta. Systematic literature searches found 96 eligible studies. Our review revealed that SARS-CoV-2 canonical mediators, angiotensin-converting enzyme-2 (ACE2), and transmembrane serine protease-2 (TMPRSS2) are variably expressed in various placenta compartments, including the villous cytotrophoblasts, syncytiotrophoblasts (STBs), and extravillous trophoblasts (EVTs) throughout pregnancy. Placental SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs), including basigin (BSG/CD147), dipeptidyl peptidase-4 (DPP4/CD26), cathepsin B/L (CTL B/L), furin, interferon-induced transmembrane protein (IFITM1-3), and lymphocyte antigen 6E (LY6E) may increase or reduce the permissiveness of the placenta to SARS-CoV-2. EVTs express genes that code for proteins that may drive viral pathogenesis in the placenta. Viral RNA, proteins, and particles were detected primarily in the STBs by in situ hybridization, immunohistochemistry, electron microscopy, and polymerase chain reaction. Placental pathology in SARS-CoV-2-infected placentas included maternal and fetal vascular malperfusion and a generally nonspecific inflammatory-immune response. The localization of SARS-CoV-2 receptors, proteases, and genes involved in coding proteins that drive viral pathogenesis in the placenta predisposes the placenta to SARS-CoV-2 infection variably in all pregnancy trimesters, with antecedent placental pathology. There is a need for further studies to explicate the mechanism of entry and pathogenesis of SARS-CoV-2 in the placenta.

Potential pharmacologic interventions targeting TLR signaling in placental malaria.

Complications from placental malaria cause poor pregnancy outcomes, including low birthweight, preterm delivery, and stillbirths. Many of these complications are driven by maternal innate proinflammatory responses to the sequestration of Plasmodium falciparum in the placenta. However, recent studies show that, in reaction to maternal innate immune responses that are detrimental to the fetus, the fetus mounts innate immune counter-responses that ameliorate pregnancy outcomes. Such fetal-maternal conflict in placental malaria has potential for pharmacologic modulation for better pregnancy outcomes. Here, we discuss placental malaria pathogenesis, its complications, and the role of innate immunity and fetal-maternal innate immune conflict in placental malaria. Finally, we discuss pharmacologic immunomodulatory strategies and agents with the potential to improve placental malaria outcomes.

Changes in the structure of chorioamniotic membrane in patients with malaria in pregnancy.

INTRODUCTION: Malaria infection in pregnancy has adverse consequences for both fetal and maternal health. There is insufficient data on the effect malaria in pregnancy has on the structure of the chorioamniotic membrane. Our objective was to determine the structure of the chorioamniotic membrane in patients with malaria in pregnancy. METHODS: Specimens of the chorioamniotic membrane from 58 women with malaria in pregnancy and 58 women without malaria in pregnancy were used for this study. Biopsies of the fetal membranes were obtained immediately after delivery and processed for light microscopy. They were stained using H & E. Photomicrographs were taken for morphological analysis and statistical analyses were performed using Statistical Package for Social Sciences (SPSS, Version 23.0, Chicago, Illinois). The independent-sample t-test and odds ratios were used to compare the appropriate values between the two groups at a 95% confidence interval. RESULTS: Photomicrographs of the chorioamniotic membrane showed histological alterations, including a change of amniotic epithelium to columnar and stratified types, epithelial delamination, extensive fibrin deposition, and leukocyte infiltration in women with malaria in pregnancy. Statistical analysis found significant differences in epithelial type (p-value 0.001, ×2 = 17.9), epithelial denudation (p-value <0.001, ×2 = 19.4) and extensive fibrin deposition (p-value of 0.02 and ×2 = 7.5) between the study groups. DISCUSSION: This study has demonstrated histological alterations in the chorioamniotic membrane in association with malaria in pregnancy. Further studies may be conducted to characterize chorioamnionitis in malaria in pregnancy and associations with adverse pregnancy outcomes.

Policy and research frame of the coronavirus disease 2019 (COVID-19) pandemic: reflections on urban informality.

How has the informality of urban slums exposed a gap in policy formulation and research questions in the wake of the coronavirus disease 2019 (COVID-19) pandemic? This paper seeks to identify the appropriate questions and policy frame that would assist future researchers and policymakers on the subject of pandemics in densely populated urban settlements. The authors argue that the nexus between asking the appropriate questions and developing appropriate policy response measures during a pandemic can significantly impact the outcome of the response. The paper examines how the government of Kenya's response to the COVID-19 pandemic reveals a deep-rooted socio-economic and cultural inequality when "blanket" policies are adopted without taking into consideration the unique dynamics characterizing the society. The findings show that the effectiveness of implementing COVID-19 containment policies such as lockdowns, the cession of movement, working from home, distance learning, and social distancing are affected by other factors such as the nature of jobs, one's income levels, where someone lives, cultural beliefs, access to water, sanitation, internet, and medical facilities. This means that a significant number of people within the society experience a double tragedy from the pandemic and impact of government response measures. Yet most of the existing literature has focused on the causes, spread, and impact of the pandemic on health institutions, economies, and public health with little emphasis on the impact on policy measures especially on the vulnerable segments of the society. This paper, therefore, looks at the question of how the various public health intervention strategies disrupt or construct the livelihood of the already complex informal settlement. It provides policymakers and researchers with a number of questions that can frame policy and research during a pandemic with important consideration to urban informality.

How urban 'informality' can inform response to COVID-19: a research agenda for the future.

In the era of increasingly defined ontological insecurity and uncertainty driven by the ravages of COVID-19, urban informal settlement has emerged as a source of resilience. Indeed, the effects of a pandemic transcends its epidemiological characteristics to political economy and societal resilience. If resilience is the capacity of a system to adapt successfully to significant challenges that threaten the function or development of the human society, then ontological insecurity is about the lack of such capacity. Drawing on Keith Hartian's understanding of 'informality' of spaces, this policy brief attempts to identify and frame a research agenda for the future. The agenda would assist future researchers and policymakers provide responses that appropriately recognize groups and actors that define the urban informal space.

Association between utilization and quality of antenatal care with stillbirths in four tertiary hospitals in a low-income urban setting.

INTRODUCTION: About 2.6 million stillbirths per year occur globally with 98% occurring in low- and middle-income countries including Kenya, where an estimated 35 000 stillbirths occur annually. Most studies have focused on the direct causes of stillbirth. The aim of this study was to determine the association between antenatal care utilization and quality with stillbirth in a Kenyan set up. This information is key when planning strategies to reduce the stillbirth burden. MATERIAL AND METHODS: This was a case-control study in four urban tertiary hospitals carried out between August 2018 and April 2019. A total of 214 women with stillbirths (cases) and 428 with livebirths (controls) between 28 and 42 weeks were enrolled. Information was obtained through interviews and data abstracted from medical records. Antenatal care utilization was assessed by the proportions of women not attending antenatal care; booking first antenatal care visit in first trimester and not making the requisite four antenatal care visits. Quality of antenatal care was assessed using individual surrogate indicators (antenatal profile testing, weight/blood pressure/urinalysis testing in each antenatal visit, utilization of early obstetric ultrasound, completeness of antenatal records) and a codified indicator made up of seven parameters (attending antenatal care, booking first antenatal care in the first trimester, making four or more antenatal visits, having all antenatal profile tests, having a complete antenatal record, having blood pressure and weight measured at all visits). The association between antenatal care utilization and quality with stillbirth was assessed using univariate and multivariate analysis using logistic regression. Statistical significance was defined as a two-tailed P value ≤ .05. RESULTS: Women with stillbirth were likely to have a parity ≥4 (19.6% vs 12.6%, P = .02), have an obstetric complication (36% vs 8.6%, P = .001) and have a medical disorder (5.6% vs 1.6%, P = .01). The odds of a stillbirth were four times higher among those who did not attend antenatal care ( odds ratio [OR] 4.1, 95% confidence interval [CI] 1.6-10, P < .003). Compared with four antenatal care visits, those who had one or two visits had higher odds of a stillbirth: OR 2.96 (95% CI 1.4-6.1), P = .003, and OR 2.9 (95% CI 1.7-5), P = .003, respectively. As per the individual surrogate indicators, the likelihood of a stillbirth was lower in women who received good quality antenatal care: Hemoglobin testing (OR 0.6, 95% CI 0.4-0.8, P = .03), blood group test (OR 0.4, 95% CI 0.2-0.6, P < .001), HIV test (OR 0.3, 95% CI 0.2-0.5, P = .001), venereal disease research laboratory test (OR 0.2, 95% CI 0.1-0.4, P = .001), weight measurement (OR 0.7, 95% CI 0.5-1.0, P = .047). As per the composite indicator, the quality of antenatal care was poor across the board and there was no association between this surrogate indicator and stillbirth. CONCLUSIONS: Lack of antenatal care, attending fewer than four antenatal visits and poor quality antenatal care as measured by surrogate indicators were significantly associated with stillbirth. In addition, women with low education level, obstetric complications, multiparity and medical complications had a significantly higher likelihood of stillbirth. Improving the utilization of four or more antenatal visits and the quality of antenatal care can reduce the risk of stillbirth.