The effect of possible mediators on the association between chewing khat during pregnancy and fetal growth and newborn size at birth in Eastern Ethiopia.

INTRODUCTION: Restriction in the growth of the fetus is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Documented existing scientific evidence have shown the effects of maternal drugs use, alcohol drinking, tobacco smoking, cocaine use and heroin use on fetal growth restriction. However, data is lacking on the effects of khat chewing during pregnancy on fetal growth status and newborn size at birth. Therefore, the aim of the present study was to measure the effect of chewing khat during pregnancy on fetal growth and size at birth in eastern Ethiopia. METHOD: A cohort study was conducted in selected health institutions in eastern Ethiopia. All pregnant women fulfilled the eligibility criteria in the selected health institutions was the source population. The calculated sample size of exposed and unexposed groups included in the study, in total, was 344. Data collection was performed prospectively by interviewers administered questionnaires, and anthropometric, clinical and ultrasound measurements. Data was analyzed using SPSS version 27 and STATA version 16 software. The survival analysis (cox proportional hazards model) and generalized linear model (GLM) for the binomial family analysis were performed to estimate the crude and adjusted relative risk and attributable risk (AR) with corresponding 95% CI of chewing khat on fetal growth restriction. The mediation effect has been examined through Generalized Structural Equation Modeling (GSEM) analysis using the Stata 'gsem' command. Statistically significant association was declared at p-value less than 5%. RESULTS: In the present study, the incidence of fetal growth restriction (FGR) among the study cohorts was 95 (29.7%); of this, 81 (85.3%) were among khat chewer cohorts. The relative risk of fetal growth restriction among khat chewer cohort mothers was significantly higher (aRR = 4.32; 95%CI 2.62-7.12). Moreover, the incidence of small for gestational age at birth among the present study cohorts was 100 (31.3%); 84 (84%) were from khat chewer cohorts' deliveries. More importantly, in the present study, 98.95% of the ultrasound-identified fetuses with FGR were found to be SGA at birth. Hence, in the current study, FGR was highly associated with SGA at birth. In additional analysis, the regression coefficient of khat chewing during pregnancy on fetal growth restriction has been decreased in size from path o, ß = 0.43, p < 0.001 to path o', ß = 0.32, p < 0.001, after adjusting for gestational hypertension and maternal anemia. CONCLUSION: In sum, the present study showed khat chewing during pregnancy is not simply affected the mothers, but it also affected the unborn fetuses. Therefore, the health workers as well as the local community and religious leaders should give high emphasis on provision of health education regarding the damage of chewing khat by pregnant mothers, with especial focus of the effects on their fetuses.

A retrospective review on the histopathological pattern of childhood malignant solid tumors in Ethiopia.

In low- and middle-income countries (LMICs), malignancies remain underreported due to lack of quality data. This study outlines the histopathological pattern of pediatric solid malignancies in children aged 0-15 years at the largest referral hospital in Ethiopia. A total of 432 solid malignancies were evaluated. The most common malignancies were lymphoma (21.8%), retinoblastoma (19.4%), and Wilms tumor (13.9%). Burkitt lymphoma accounted for 2.1%, despite being the most reported pediatric malignancy in sub-Saharan Africa in published literature. Definitive diagnosis could not be made in 7% of cases, related to the lack of confirmatory testing. The study highlights the need for improvement in diagnostic capabilities in LMICs.

Intrinsic subtypes in Ethiopian breast cancer patient.

PURPOSE: The recent development of multi-gene assays for gene expression profiling has contributed significantly to the understanding of the clinically and biologically heterogeneous breast cancer (BC) disease. PAM50 is one of these assays used to stratify BC patients and individualize treatment. The present study was conducted to characterize PAM50-based intrinsic subtypes among Ethiopian BC patients. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tissues were collected from 334 BC patients who attended five different Ethiopian health facilities. All samples were assessed using the PAM50 algorithm for intrinsic subtyping. RESULTS: The tumor samples were classified into PAM50 intrinsic subtypes as follows: 104 samples (31.1%) were luminal A, 91 samples (27.2%) were luminal B, 62 samples (18.6%) were HER2-enriched and 77 samples (23.1%) were basal-like. The intrinsic subtypes were found to be associated with clinical and histopathological parameters such as steroid hormone receptor status, HER2 status, Ki-67 proliferation index and tumor differentiation, but not with age, tumor size or histological type. An immunohistochemistry-based classification of tumors (IHC groups) was found to correlate with intrinsic subtypes. CONCLUSION: The distribution of the intrinsic subtypes confirms previous immunohistochemistry-based studies from Ethiopia showing potentially endocrine-sensitive tumors in more than half of the patients. Health workers in primary or secondary level health care facilities can be trained to offer endocrine therapy to improve breast cancer care. Additionally, the findings indicate that PAM50-based classification offers a robust method for the molecular classification of tumors in the Ethiopian context.

Endometrial tuberculosis among patients undergoing endometrial biopsy at Tikur Anbesa specialized hospital, Addis Ababa, Ethiopia.

BACKGROUND: Female genital tuberculosis (FGTB) is known to cause severe tubal disease leading to infertility and its incidence closely parallels with the overall prevalence of tuberculosis (TB) in a community. Its magnitude is underreported because diagnosis is difficult and requires invasive techniques. In this study we determined the prevalence of endometrial tuberculosis and characterized isolates among women who underwent endometrial biopsy for evaluation of various conditions at a Tikur Anbessa Specialized Hospital (TAHS), Addis Ababa, Ethiopia. METHODS: A cross sectional study was conducted on 152 consecutive gynecologic patients who underwent endometrial biopsy for different gynecologic diseases. Endometrial tissue taken for routine histopathology examination was shared after informed consent was obtained from the patient and subjected to polymerase chain reaction (PCR) and culture for Mycobacterium tuberculosis (Mtb). RESULTS: The prevalence of endometrial TB in this study by IS1081PCR was 4.6% (7/152) while culture proven endometrial TB was 2.6% (4/152). However, histological examination identified only 2/152 (1.3%) endometrial tuberculosis. While all culture proven TB samples were also PCR positive for Mtb, only one histologic proven endometrial TB was culture and PCR positive. All of the four isolates by culture were M. tuberculosis. CONCLUSION: This study has shown that the magnitude of endometrial TB is fairly high in gynecologic patients visiting outpatient departments for various complaints and PCR detects more cases than culture or Histopathology.

Tuberculosis of the cervix mimicking cervical cancer.

Tuberculosis of the cervix is a rare disease and accounts for 0.1-0.65% of all cases of tuberculosis. We present an unusual case of a 57 years old female who presented with chief complaints of Serosaguineous vaginal discharge of one year duration and irregular firm cervix with contact bleeding and was clinically diagnosed to have cervical cancer. Histopathology revealed typical findings of cervical tuberculosis. Cervical tuberculosis should be considered as a differential diagnosis of cervical malignancy. The clinical presentation and diagnosis of cervical tuberculosis is reviewed.

The impact of chewing khat during pregnancy on selected pregnancy outcomes in eastern Ethiopia: A cohort study with a generalized structural equation modeling analysis approach.

INTRODUCTION: Little is known about the fetal and pregnancy effects of khat chewing during pregnancy. The aim of the current study was to determine the impact of chewing khat during pregnancy on selected pregnancy outcomes in Ethiopia, 2022: A Cohort Study with a Generalized Structural Equation Modeling Analysis Approach. METHODS: An institution-based prospective cohort study was employed in selected hospitals in eastern Ethiopia. Pregnant women who visited the selected hospitals in the study area during the study period that fulfilled the eligibility criteria were included until a sample size (344) was fulfilled. The main outcomes studied in the present study were preterm birth and low birth weight. Data were collected through anthropometric and clinical measurements, and interviewers administered questionnaires. The survival analysis and generalized linear model analysis were performed to estimate the crude and adjusted relative risk and attributable risk. The Generalized Structural Equation Modeling (GSEM) analysis was performed using the Statistical software for data science (Stata) 'GSEM' command to examine the mediation effect. RESULTS: The risk of occurrence of preterm birth was significantly higher among khat chewers [adjusted relative risk (aRR) = 2.19; 95%CI 1.21-3.96]. In further analysis after adjusting for gestational hypertension and cesarean delivery, the regression coefficient of khat chewing during pregnancy on preterm birth has been decreased in size from path n, ß = 0.37, p<0.001 to path n', ß = 0.15, p<0.005. The risk of occurrence of low birth weight among khat chewers was significantly higher (aRR = 4.17; 95%CI 2.11-8.25). In further analysis after adjusting for gestational hypertension, cesarean delivery, preterm birth and maternal anemia, the regression coefficient of khat chewing during pregnancy on low birth weight has been decreased in size from path q, ß = 0.4, p<0.001 to path q', ß = 0.2, p<0.001. CONCLUSION: Overall, the present study revealed that khat chewing is not only a worry of the current population but also a public health concern of the generation affecting unborn fetuses.

Magnitude and associated factors of chewing khat during pregnancy in Eastern Ethiopia, 2022: a mixed method cross-sectional study.

Introduction: khat (Catha edulis Forsk), is an evergreen flowering tree or shrub widely produced and consumed in East Africa and the Arabian Peninsula. In Ethiopia, it is largely produced, freely marketed and consumed by almost all segments of the population. This is more pronounced in the Eastern part of the country. However, there exists little scientific information on the level and associated factors of khat use among pregnant women in Ethiopia, despite a few available evidences indicated its adverse effect on pregnancy outcomes. Moreover, the perceived reasons for chewing khat during pregnancy were not yet explored qualitatively to triangulate the quantitative findings. Hence, the aim of the present study was to determine the magnitude and associated factors of chewing khat during pregnancy in Eastern Ethiopia, 2022, in a Mixed Method study approach. Methods: an institution-based cross-sectional study was conducted from August 1st to 14th, 2022 using both quantitative and qualitative methods. Two hundred forty-two pregnant mothers on Antenatal care (ANC) were included in the study. Moreover, 18 purposively selected pregnant mothers on ANC were also considered for qualitative data. Analysis of quantitative data was performed on Statistical Package for the Social Sciences (SPSS) version 27 and thematic framework analysis was performed for qualitative data. Univariable and multivariable logistic regression analysis was performed to identify variables which are significantly associated with khat chewing during pregnancy and to estimate the variable's crude and adjusted odds' ratio with corresponding 95% CI. The statistically significant association was declared at p-value of less than 5. Results: the overall magnitude of chewing khat during pregnancy in the present study was 27.4% (95% CI: 22.2-33.0). Variables which significantly associated with chewing khat during pregnancy in this study were being >26 years [adjusted odds' ratio (AOR)=2.81 95% CI: 1.19-6.59], being a rural resident (AOR=2.82 95% CI: 1.19-6.69), being illiterate (AOR=4.31 95% CI: 1.02-18.20), participants having chewer husbands (AOR=3.51 95% CI: 1.33-9.24) and respondents having other chewer family members (AOR=3.05 95% CI: 1.19-7.77). In addition, the perceived reasons for chewing khat explored through in-depth interviews were for socialization, to obey tradition, to be happy with friends, husbands and families, to be free from tensioned situations, to be effective in performing daily activities, and due to lack of knowledge of its harm. Conclusion: in the present study, a relatively higher proportion of mothers chewed khat during their current pregnancy. Being older age, living in rural areas, being illiterate, having khat chewer husbands and other family members were statistically significant variables associated with khat chewing during pregnancy. Moreover, pregnant mothers are practicing chewing of khat in the current study area due to deep-rooted sociocultural issues. Hence, creation of awareness on possible harm of chewing khat during pregnancy especially for those found to be at significantly increased risk of consumption in this study is highly recommended during their antenatal care visits. In addition, creation of awareness out of health institutions, at household and community level, is highly recommended, probably using community volunteers (health development armies) in the present study area. At last, we highly also recommend the local government and religious leaders to work on how to stop the chewing practice especially during pregnancy. For example, the local government and religious leaders can work on averting consideration of chewing by the community as culturally accepted practices.

Primary Tracheobronchial Amyloidosis Presenting with an Upper Airway Obstruction.

This is a case of localized primary tracheobronchial amyloidosis in a patient who presented with upper airway obstruction. Tracheobronchial amyloidosis is a type of localized bronchopulmonary amyloidosis that is frequently overlooked. It involves the deposition of amyloid protein on the tracheal and bronchial tissue, leading to progressive tracheal stenosis and airway obstruction that can be seen on imaging as a tracheal mass. Because of its significant diagnostic difficulty and therapeutic conundrum, it ought to be considered in the differential diagnosis of upper airway symptoms with an unknown etiology.

Evidence for distinct mechanisms of immune suppression in EBV-positive and EBV-negative Hodgkin lymphoma.

Epstein Barr Virus (EBV) has been recognized for its ability to transform B lymphocytes and for its association with different types of cancers including Hodgkin lymphoma. In addition, EBV may also modulate the microenvironment of HL. In this study, we aimed to investigate the prevalence of EBV among HL cases in Ethiopia and to assess the tissue cellular composition of EBV-related and EBV-unrelated cases. We constructed a tissue microarray (TMA) of 126 consecutive cases of classical HL (CHL) and nodular lymphocyte predominant HL (NLPHL) from a tertiary cancer centre, Tikur Anbessa Hospital, Addis Ababa, Ethiopia, and evaluated a panel of immunohistochemical markers. The quantification of immune cells was performed using HALO 2.3, a platform for image analysis from Indica Lab Inc. A total of 77/126 (61.1%) of HL cases expressed LMP1/EBER. Infiltration of CD8+, T-bet+ and FoxP3+ cells was higher in the microenvironment of EBV-related CHL, with P values of <0.001, <0.001 and <0.016, respectively. In contrast, the expression of PD1 was higher in the microenvironment of EBV-unrelated CHL cases (P < 0.001). Unlike in Western countries, the majority of HL cases in Ethiopia were associated with EBV. As FoxP3+ and PD1-expressing cells are thought to participate in down regulation of the immune response by different mechanisms, this finding highlights the previously unrecognized possibility that distinct immunosuppressive mechanisms may be ongoing within EBV positive and negative HL types. This may have important prognostic and therapeutic implications.

Toxic effect of Syzygium guineense ethanolic extract on female reproduction in rats: An evidence from a 10 week repeated-dose toxicity study.

Introduction: It has been reported that some herbal products affect reproduction. To date, reproductive toxicity of Syzygium guineense has not been investigated although the plant is widely used in treating fertility related problems. Thus, the objective of the current study was to investigate the toxic effects of 70% ethanol extract of S. guineense leaves on the reproductive function and histopathology of reproductive organs in female rats. Methods: Eighty female Wistar albino rats were randomly divided into four groups where each group consisted of 20 rats. Rats in the first three groups were treated with S. guineense extract at doses of 250, 500 and 1000 mg/kg body weight, respectively. The fourth group served as a control group. The rats were treated for ten consecutive weeks. The length of estrous cycle, reproductive indices, pregnancy outcomes, and number of postnatal deaths were recorded. At necropsy, organ weight was measured, gross and histopathological examinations of ovaries, uterus, and vagina were conducted. Results: Treatment of rats, with high dose (1000 mg/kg) of S. guineense, significantly prolonged the duration of estrous cycle and reduced weight of uterus and ovaries as well as the number of total and live birth pups. However, there were no significant changes observed in reproductive indices and gross morphology as well as histopathology of ovaries, uterus, and vagina. Conclusion: Administration of high doses of S. guineense could be toxic to some aspects of the reproductive system of female rats and might also affect reproduction. Therefore, consuming high dose of S. guineense leaves is not recommended.

Human Breast Tissue Microbiota Reveals Unique Microbial Signatures that Correlate with Prognostic Features in Adult Ethiopian Women with Breast Cancer.

Breast cancer (BC) is the leading cause of cancer mortality among women in Ethiopia. Overall, women of African ancestry have the highest death toll due to BC compared to other racial/ethnic groups. The cause of the disparity in mortality is unclear. Recently, studies conducted in the United States and other high-income countries highlighted the role of microbial dysbiosis in BC initiation, tumor growth, and treatment outcome. However, the extent to which inter-individual differences in the makeup of microbiota are associated with clinical and histopathological outcomes in Ethiopian women has not been studied. The goal of our study was to profile the microbiome in breast tumor and normal adjacent to tumor (NAT) tissues of the same donor and to identify associations between microbial composition and abundance and clinicopathological factors in Ethiopian women with BC. We identified 14 microbiota genera in breast tumor tissues that were distinct from NAT tissues, of which Sphingobium, Anaerococcus, Corynebacterium, Delftia, and Enhydrobacter were most significantly decreased in breast tumors compared to NAT tissues. Several microbial genera significantly differed by clinicopathological factors in Ethiopian women with BC. Specifically, the genus Burkholderia more strongly correlated with aggressive triple negative (TNBC) and basal-like breast tumors. The genera Alkanindiges, Anoxybacillus, Leifsonia, and Exiguobacterium most strongly correlated with HER2-E tumors. Luminal A and luminal B tumors also correlated with Anoxybacillus but not as strongly as HER2-E tumors. A relatively higher abundance of the genus Citrobacter most significantly correlated with advanced-stage breast tumors compared to early-stage tumors. This is the first study to report an association between breast microbial dysbiosis and clinicopathological factors in Ethiopian women.

Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa.

The low overall survival rates of patients with breast cancer in sub-Saharan Africa (SSA) are driven by regionally differing tumor biology, advanced tumor stages at diagnosis, and limited access to therapy. However, it is not known whether regional differences in the composition of the tumor microenvironment (TME) exist and affect patients' prognosis. In this international, multicentre cohort study, 1,237 formalin-fixed, paraffin-embedded breast cancer samples, including samples of the "African Breast Cancer-Disparities in Outcomes (ABC-DO) Study," were analyzed. The immune cell phenotypes, their spatial distribution in the TME, and immune escape mechanisms of breast cancer samples from SSA and Germany (n = 117) were investigated using histomorphology, conventional and multiplex IHC, and RNA expression analysis. The data revealed no regional differences in the number of tumor-infiltrating lymphocytes (TIL) in the 1,237 SSA breast cancer samples, while the distribution of TILs in different breast cancer IHC subtypes showed regional diversity, particularly when compared with German samples. Higher TIL densities were associated with better survival in the SSA cohort (n = 400), but regional differences concerning the predictive value of TILs existed. High numbers of CD163+ macrophages and CD3+CD8+ T cells accompanied by reduced cytotoxicity, altered IL10 and IFNγ levels and downregulation of MHC class I components were predominantly detected in breast cancer samples from Western SSA. Features of nonimmunogenic breast cancer phenotypes were associated with reduced patient survival (n = 131). We therefore conclude that regional diversity in the distribution of breast cancer subtypes, TME composition, and immune escape mechanisms should be considered for therapy decisions in SSA and the design of personalized therapies. See related Spotlight by Bergin et al., p. 705.

Heterotopic pregnancy in a young adult: a case report.

Heterotopic gestation, although fairly common with assisted reproductive techniques, is very rare in natural conception. Here we are reporting a case of heterotopic pregnancy in a 27-year-old woman who presented with sign and symptoms of acute abdomen from aborting tubal pregnancy with intrauterine gestation at 7 weeks of amenorrhea.

Prenatal Developmental Toxicity and Histopathological Changes of the Placenta Induced by Syzygium guineense Leaf Extract in Rats.

Many of the traditional herbal products are served to the consumer without proper efficacy and safety investigations. A laboratory-based experimental study was employed to investigate the toxic effects of Syzygium guineense leaf extract on the fetal development and histopathology of the placenta in rats. Fifty pregnant Wistar albino rats were randomly allocated into five groups, each consisting of 10 rats. S. guineense leaf extract, at doses of 250, 500, and 1000 mg/kg of body weight, was respectively administered to groups I-III rats. Groups four and five were control and ad libitum control, respectively. The number of resorptions, implantation sites, and live or dead fetuses was counted. The weight and crown-rump length of the fetuses were measured. The histopathological investigation of the placenta was conducted. Administration of 70% ethanol extract of S. guineense leaves reduced weight gain and food intake of pregnant rats at p value <0.05. The crown-rump length of the near-term rat fetus was significantly reduced in rats treated with 1000 mg/kg body weight of S. guineense extract (p value <0.05). The plant extract did not affect the number of implantations, fetal resorptions, live births, and stillbirths. The weight of the fetuses and the placentae also decreased dose-dependently. Decidual cystic degeneration was the most prevalent histopathological change observed in a rat's placenta treated with 1000 mg/kg body weight of S. guineense extract. Consumption of S. guineense leaves, especially at a high dose, may affect fetal development. Therefore, liberal use of S. guineense leaves during pregnancy should be avoided.

Sub-chronic toxicity of ethanol leaf extract of Syzygium guineense on the biochemical parameters and histopathology of liver and kidney in the rats.

BACKGROUND: Syzygium guineense Wall. leaf is being used as a traditional medicine against hypertension and diabetes mellitus. Unlike its efficacy, the safety profile of this plant upon long-term administration has not been investigated yet. Therefore, this study investigated the sub-chronic toxicity of S. guineense leaves in rats. METHODS: Wistar albino rats, 10/sex/group were randomly assigned into four groups. Group I-III respectively received 250, 500, and 1000 mg/kg of body weight of 70 % ethanol extract ofS. guineense leaves for 90 consecutive days. Group IV (control) received distilled water. Throughout the experiment, clinical observations were carried out, food intake and weight of the rats also were measured. Finally, different biochemical parameters, organ weight, and histopathology of liver and kidneys were evaluated. RESULTS: Administration of 70 % ethanol extract ofS. guineense leaves decreased food intake and body weight gain of the test animals. Rats treated with 1000 mg/kg of S. guineense extract showed significantly increased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. Serum urea levels also increased in female rats treated with 500 and 1000 mg/kg body weight of S. guineense. Moreover, the blood glucose level of rats treated with 1000 mg/kg body weight was significantly decreased compared to the control group. However, the histology of the liver and kidneys were not significantly altered by any of the doses administered. CONCLUSION: Administration ofS. guineense in rats at a dose of 1000 mg/kg body weight affected the food consumption, weight gain, and serum levels of liver and kidney enzymes suggesting that S. guineense intake at high doses may be toxic. Therefore, liberal consumption of S. guineense leaves should be taken curiously and cautiously.

Teratogenic Effect of High Dose of Syzygium guineense (Myrtaceae) Leaves on Wistar Albino Rat Embryos and Fetuses.

Syzygium guineense is an important medicinal plant effective against hypertension, diabetes mellitus, and cancer but with no evidence of its teratogenicity. This study was planned to investigate the teratogenic potential of S. guineense leaves on rat embryos and fetuses. Five groups of Wistar albino rats, each consisting of ten pregnant rats, were used as experimental animals. Groups I-III rats were treated with 250, 500, and 1000 mg/kg of hydroethanolic extract of S. guineense leaves, and groups IV and V were control and ad libitum control, respectively. Rats were treated during day 6-12 of gestation. Embryos and fetuses were retrieved at day 12 and day 20 of gestation, respectively. The embryos were assessed for developmental delays and growth retardation. The fetuses were examined for gross external, skeletal, and visceral anomalies. In 12-day old rat embryos, crown-rump length, number of somites, and morphological scores were significantly reduced by the treatment of 1000 mg/kg of the extract. The external morphological and visceral examinations of rat fetuses did not reveal any detectable structural malformations in the cranial, nasal, oral cavities, and visceral organs. The ossification centers of fetal skull, vertebrae, hyoid, forelimb, and hindlimb bones were not significantly varied across all groups. However, even if not statistically significant, high-dose treated rat fetuses had a reduced number of ossification centers in the sternum, caudal vertebrae, metatarsal, metacarpal, and phalanges. Treatment with the hydroethanolic extract of S. guineense leaves produced no significant skeletal and soft tissue malformations. The plant extract did not produce significant teratogenic effects on rat embryos/fetuses up to 500 mg/kg doses but retarded the growth of embryos at high dose (1000 mg/kg) as evidenced by decreased crown-rump length, number of somites, and morphological scores. Therefore, it is not advisable to take large doses of the plant during pregnancy.

Toxic Effect of Khat in Rat Embryos and Fetuses.

Khat (Catha edulis Forsk) is a plant consumed by many people in Eastern Africa, including Ethiopia, and Southern Arabia to be stimulated. There are several human and animal studies on khat that provide information about its toxic effects. However, the potential toxic effects of khat on embryos and fetuses have not been elucidated. The aim of the present study was to investigate the embryotoxic and fetotoxic effects of khat exposure during the earliest period of gestation in rats. Pregnant Wistar albino rats were treated with khat extract at 250, 500, and 750 mg/kg doses from day 6 through day 12 of gestation. The treatment was delivered by gavage. Embryos and fetuses were recovered on gestational day 12 or day 20, respectively, and were quantitatively and qualitatively assessed for developmental anomalies. Placentae from the treatment and control groups were investigated for histopathological effects. Results of the present study showed that khat exposure during pregnancy had dose-dependent toxic effects in rat embryos and fetuses. Prenatal growth retardation such as reduced fetal weight and crown-rump length was observed in near-term fetuses, especially, in animals treated with the highest dose of khat (p < 0.05). Growth retardation and developmental anomalies were also observed in day 12 embryos of khat-treated rats. Maternal weight gain of the khat-treated group was also significantly lower than the control group. Cytolysis, decidual hypoplasia, and atrophy were observed in the placenta of the khat-treated rats. Findings of the present study revealed, for the first time, that exposure of pregnant rat to crude extract of khat causes embryotoxic and fetotoxic effects.

Minimally Invasive Tissue Sampling in Preterm Deaths: A Validation Study.

Uncertainty about the causes of neonatal deaths impedes achieving global health targets to reduce mortality. Complete diagnostic autopsy (CDA) is the gold standard to determine cause of death. However, it is often difficult to perform in high-burden, low-income settings. Validations of more feasible methods to determine cause of death are needed. This prospective, multi-center study in Ethiopia assessed the validity of the minimally invasive tissue sampling (MITS) approach to contribute to causes of death in preterm neonates compared to CDA. The MITS and CDA of 105 cases were reviewed. The MITS sampling success for lungs and liver was 100% and 84%, respectively. The kidney and brain had sampling successes of 58% each. MITS showed good agreement with CDA for the diagnosis of hyaline membrane disease (kappa = 0.78), and moderate to substantial agreement for pneumonia and pulmonary hemorrhage (kappa = 0.59 and 0.68, respectively). Even though CDA is the gold standard in identifying the cause of death, we believe that the MITS method can be a useful alternative method in supporting determination of cause of death in low-resource settings.

Major causes of death in preterm infants in selected hospitals in Ethiopia (SIP): a prospective, cross-sectional, observational study.

BACKGROUND: Neonatal deaths now account for 47% of all deaths in children younger than 5 years globally. More than a third of newborn deaths are due to preterm birth complications, which is the leading cause of death. Understanding the causes and factors contributing to neonatal deaths is needed to identify interventions that will reduce mortality. We aimed to establish the major causes of preterm mortality in preterm infants in the first 28 days of life in Ethiopia. METHODS: We did a prospective, cross-sectional, observational study in five hospitals in Ethiopia. Study participants were preterm infants born in the study hospitals at younger than 37 gestational weeks. Infants whose gestational age could not be reliably estimated and those born as a result of induced abortion were excluded from the study. Data were collected on maternal and obstetric history, clinical maternal and neonatal conditions, and laboratory investigations. For neonates who died of those enrolled, consent was requested from parents for post-mortem examinations (both complete diagnostic autopsy and minimally invasive tissue sampling). An independent panel of experts established the primary and contributory causes of preterm mortality with available data. FINDINGS: Between July 1, 2016, to May 31, 2018, 4919 preterm infants were enrolled in the study and 3852 were admitted to neonatal intensive care units. By 28 days of post-natal age, 1109 (29%) of those admitted to the neonatal intensive care unit died. Complete diagnostic autopsy was done in 441 (40%) and minimally invasive tissue sampling in 126 (11%) of the neonatal intensive care unit deaths. The main primary causes of death in the 1109 infants were established as respiratory distress syndrome (502 [45%]); sepsis, pneumonia and meningitis (combined as neonatal infections; 331 [30%]), and asphyxia (151 [14%]). Hypothermia was the most common contributory cause of preterm mortality (770 [69%]). The highest mortality occurred in infants younger than 28 weeks of gestation (89 [86%] of 104), followed by infants aged 28-31 weeks (512 [54%] of 952), 32-34 weeks (349 [18%] of 1975), and 35-36 weeks (159 [8%] of 1888). INTERPRETATION: Three conditions accounted for 89% of all deaths among preterm infants in Ethiopia. Scale-up interventions are needed to prevent or treat these conditions. Further research is required to develop effective and affordable interventions to prevent and treat the major causes of preterm death. FUNDING: Bill & Melinda Gates Foundation.

Toxicological evaluation of methanol leaves extract of Vernonia bipontini Vatke in blood, liver and kidney tissues of mice.

BACKGROUND: Various medicinal plants have been studied using modern scientific approaches. These plants have a variety of properties and various biological components that can be used to treat various diseases. However, harmful effects of plants are common clinical occurrence. OBJECTIVE: This study was designed to investigate toxicological assessment of acute and chronic methanol leaf extract of Vernonia bipontini Vatke (V.bipontini V) on blood, liver and kidney tissues of mice. METHODS: Lethal dose (LD) at which 50% of experimental mice died and long term toxicity of methanolic leaf extract of V. bipontini V were determined. Some hematological and biochemical parameters were evaluated. Then, liver and kidney tissues of each animal were taken and processed for light microscopy. RESULTS: Almost all mice treated with 800mg/kg methanol leaf extract of V. bipontini V showed swellings on the left part of abdominal region related to location of spleen, mild diarrhea and enlargement of spleen. The LD50 of the methanol leaf extract of V. bipontini V was 2130.6±1.5mg/kg. Treatment with 800mg/kg body weight of methanol leaf extract significantly decreased body, liver and kidney weights, red blood cells (RBC), haemoglobin (Hgb), mean cell haemoglobin (Mch), Mchc, platelet and significantly increased serum aspartate transferance (AST), vatanine tranferance(ALT) and alkaline phosphate (ALP) levels while 400mg/kg dose had no effect on these parameters. The reduced organ weights did not correlate with loss of body weight at 800mg/kg of methanol leaf extract of the plant. Light microscope observations of liver tissue of mice treated with 800mg/kg of the methanol leaf extract revealed dilated sinusoids, nuclear enlargement, lots of bi-nucleation of hepatocytes, peripheral cramped chromatin, shrinkages (single cell death) of hepatocytes, fragmentation of hepatocytes while no histopathological changes were observed in liver and kidney of mice treated at 400mg/kg. Kidney tissue sections of mice did not show significant histopathological changes at 400mg/kg. However, at 800mg/kg kidney sections showed increased cellularity of glomerulus, urinary space obliteration and enlarged macula densa. CONCLUSION: This study suggests that the methanol leaf extract may have been phytotoxic to liver that resulted in a rise in serum AST, ALT and ALP levels.