Coagulation factors and natural anticoagulants as surrogate markers of preeclampsia and its subtypes: A case-control study in a Ghanaian population

Preeclampsia (PE) is associated with endothelial injury and hemostatic abnormalities. However, the diagnostic role of coagulation parameters and natural anticoagulants in predicting PE has not been explored in Ghana. This study assessed plasma levels of these factors as surrogate markers of PE and its subtypes. This case-control study included 90 women with PE (cases) and 90 normotensive pregnant women (controls). Blood samples were drawn for the estimation of complete blood count and coagulation tests. The prothrombin time (PT), activated partial thromboplastin time (APTT), and the calculation of the international normalized ratio (INR) were determined by an ACL elite coagulometer while the levels of protein C (PC), protein S (PS), antithrombin III (ATIII), and D-dimers were also measured using the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) method. All statistical analyses were performed using the R Language for Statistical Computing. Results showed significantly (p \u3c .05) shortened APTT (28.25 s) and higher D-dimer levels (1219.00 ng/mL) among PE women, as well as low levels of PC (1.02 g/mL), PS (6.58 g/mL), and ATIII (3.99 ng/mL). No significant difference was found in terms of PT and INR. From the receiver operating characteristic analysis, PC, PS, and ATIII could significantly predict PE and its subtypes at certain cutoffs with high accuracies (area under the curve [AUC] ≥ 0.70). Most women with PE are in a hypercoagulable state with lower natural anticoagulants. PC, PS, and ATIII are good predictive and diagnostic markers of PE and its subtypes (early-onset PE [EO-PE] and late-onset PE [LO-PE]) and should be explored in future studies

Proximate, intermediate, and distal predictors of under-five mortality in Chad: analysis of the 2014–15 Chad demographic and health survey data

Ahinkorah BO, Seidu A-A, Budu E, et al. Proximate, intermediate, and distal predictors of under-five mortality in Chad: analysis of the 2014–15 Chad demographic and health survey data. BMC Public Health. 2020;20(1):1-12.Abstract Background Under-five mortality in Chad reached a minimum value of 119 deaths per 1000 live births in 2018, compared with a maximum of 250 in 1972. Despite this decline in the  mortality trend, for every six children in Chad, one dies before the age of five. This study, therefore, investigated the proximate, intermediate, and distal determinants of under-five mortality in Chad. Methods We used data from the 2014–15 Chad's Demographic and Health Survey. Data of 7782 children below 5 years were used for the study. Both descriptive and multivariable hierarchical logistic regression analyses were performed. Statistical significance was declared at p &lt; 0.05. Results Under-five mortality was found to be 130 deaths per 1000 live births in Chad, with variations across the various population sub-groups. For distal predictors, the likelihood of death was higher in children born in the FChari Baguirmi region (AOR = 3.83, 95% CI: 1.81–8.14). Children whose mothers belonged to the Baguirmi/Barma ethnic group (AOR = 8.04, 95% CI: 1.75–36.99) were more likely to die before the age of five. On the contrary, the likelihood of under-five mortality was low among children born in rural areas (AOR = 0.73, 95% CI: 0.55–0.97). With the intermediate predictors, the likelihood of under-five deaths was higher among children whose mothers had no formal education (AOR = 1.72, 95% CI: 1.06–2.77). Regarding the proximate predictors, the odds of under-five deaths was higher among male children (AOR = 1.03, 95% CI: 1.05–1.63) and first rank children (AOR = 1.58, 95% CI: 1.13–2.21). Conclusion The study found that the determinants of under-five mortality in Chad are region of residence, place of residence, ethnicity, education, sex of child, and birth rank. These findings show that both socio-economic and proximate factors explain the disparities in under-five mortality in Chad. The identification of these factors can be pivotal towards the design of evidence-based interventions intended to improve child survival. Therefore, improving maternal education while refocusing and re-packaging existing strategies to target selected sub-regional populations with high under-five mortality is urgently required. </jats:sec

Empirical linkages between female genital mutilation and multiple sexual partnership: evidence from the 2018 Mali and 2013 Sierra Leone Demographic and Health Surveys

Ahinkorah BO, Hagan Jr. JE, Seidu A-A, et al. Empirical linkages between female genital mutilation and multiple sexual partnership: evidence from the 2018 Mali and 2013 Sierra Leone Demographic and Health Surveys. Journal of biosocial science. 2021:1-16.Female genital mutilation (FGM) is very pervasive in Africa, with significant regional variations in the prevalence of this traditional practice. This study examined the linkages between FGM and multiple sexual partnership in Mali and Sierra Leone - two African countries with a high prevalence of FGM. Data were from the 2018 Mali and 2013 Sierra Leone Demographic and Health Surveys, and the study sample comprised 4750 women from Mali and 16,614 from Sierra Leone. Multilevel logistic regression was used for the data analysis, with reported adjusted odds ratios (aOR) and associated 95% confidence intervals. In Mali, women who had not undergone FGM were less likely to have multiple sexual partners (aOR=0.60, CI=0.38-0.96) compared with those who had undergone FGM. In Sierra Leone, women who had undergone FGM (aOR=1.15, CI=1.02-1.30) were more likely to have multiple sexual partners compared with those who had not undergone FGM. Age, level of education, wealth quintile, sex of household head, community socioeconomic status, mass media exposure, and community literacy level were found to be associated with the likelihood of multiple sexual partnership among women in Mali and Sierra Leone. Comprehensive, age-group-based risk-reduction strategies, such as abstinence education and decision-making skills (assertiveness) training, are needed to reduce girls' and young women's engagement in multiple sexual partnerships. Policy interventions, such as anti-FGM legislation and initiatives like the 'Schooling for the Female Child' initiative aimed at reducing social inequality among girls and women, might help decrease FGM and the likelihood of health-compromising behaviours like multiple sexual partnership

Maternal healthcare utilization and full immunization coverage among 12-23 months children in Benin: a cross sectional study using population-based data.

Budu E, Seidu A-A, Agbaglo E, et al. Maternal healthcare utilization and full immunization coverage among 12-23 months children in Benin: a cross sectional study using population-based data. Archives of public health = Archives belges de sante publique. 2021;79(1):1-12.BACKGROUND: Maternal and child health are important issues for global health policy, and the past three decades have seen a significant progress in maternal and child healthcare worldwide. Immunization isa critical, efficient, and cost-effective public health intervention for newborns. However, studies on these health-promoting indicators in low-income and middle-income countries, especially in sub-Sahara Africaare sparse.We investigated theassociation between maternal healthcare utilization and completevaccination in the Republic of Benin.; METHODS: We analysed data from the 2018 Benin Demographic and Health Survey (BDHS). Specifically, the children's recode file was used for the study. The outcome variable used was complete vaccination. Number ofantenatal care visits, assistance during delivery, and postnatal check-up visits were the key explanatory variables. Bivariate and multilevel logistic regression analyseswere carried out. The results were presented as unadjusted odds ratios (uOR) and adjusted odds ratios (aOR), with their corresponding 95% confidence intervals(CIs) signifying their level of precision. Statistical significance was declared at p<0.05.; RESULTS: The prevalence of full immunization coveragein Benin was 85.4%. The likelihood of full immunization was lower among children whose mothers had no antenatal care visits, compared to those whose mothers had 1-3 visits [aOR=0.11, 95% CI: 0.08-0.15], those who got assistance from Traditional Birth Attendants/other during delivery, compared to those who had assistance from Skilled Birth Attendants/health professionals [aOR=0.55, 95% CI: 0.40-0.77], and mothers who had no postnatal care check-up visit, compared to those who had postnatal care check-up <24h after delivery [aOR=0.49, 95% CI: 0.36-0.67]. With the covariates, religion, partner's level of education, parity, wealth quintile, and place of residence also showed significant associations with full immunization.; CONCLUSION: The study has demonstrated strong association between full immunization and antenatal care, skilled attendance at birth, and postnatal care check-up visit. We found that full immunization decreases among women with no antenatal care visits, those who receive assistance from Traditional Birth Attendants during delivery, and those who do not go for postnatal care visits. To help achieve full immunization, it is prudent that the government of Benin collaborates with international organisations such as WHO and UNICEF to provide education to pregnant women on the importance of immunization after delivery. Such education can be embedded in the antenatal care, delivery and postnatal care services offered to pregnant women during pregnancy, delivery, and after delivery

PEA15 impairs cell migration and correlates with clinical features predicting good prognosis in neuroblastoma

ERK and RSK2 drive proliferation and invasion of many cancers. Phosphoprotein enriched in astrocytes 15 (PEA15) binds ERK and RSK2 and high PEA15 levels can impair ERK- and RSK2-dependent transcription. PEA15 expression also inversely correlates with cell motility and invasiveness. We therefore tested PEA15 effects on neuroblastoma cells in vitro. We further analyzed PEA15 expression in the context of clinical and genetic features of neuroblastoma in tumor samples to determine its correlation with disease progression. Affymetrix microarray analysis was performed using 24 different neuroblastoma cell lines. Cell lines expressing low to intermediate levels of PEA15 were chosen for in vitro functional studies. The cell line results were verified by Affymetrix analysis of three different neuroblastic tumor types (total of 110 samples) PEA15 overexpression inhibited neuroblastoma migration in vitro. We verified that inhibition of motility required PEA15 interaction with its binding partners ERK and RSK2. Additionally, synthetic inhibitors of RSK2 suppressed integrin-dependent migration. PEA15 expression correlates with clinical parameters and a 25% increase in patient survival rate. The highest PEA15 levels were found in low stage, more differentiated and less metastatic neuroblastic tumors, and correlated with lack of MYCN amplification. PEA15 blocks neuroblastoma migration through inhibition of ERK/RSK2 signaling. PEA15 expression levels correlate with favorable clinical features suggesting that PEA15 limits metastatic progression of neuroblastoma. Thus, PEA15 and its partners ERK and RSK2 are potential targets for the development of new therapeutics to impede progression of minimal residual disease in patients with high-risk neuroblastom

Syrbactin Structural Analog TIR-199 Blocks Proteasome Activity And Induces Tumor Cell Death.

Multiple myeloma (MM) is an aggressive hematopoietic cancer of plasma cells. The recent emergence of three effective FDA-approved proteasome-inhibiting drugs, bortezomib (Velcade), carfilzomib (Kyprolis), and ixazomib (Ninlaro) confirms that proteasome inhibitors are therapeutically useful against neoplastic disease, in particular refractory MM and mantle cell lymphoma. This study describes the synthesis, computational affinity assessment, and preclinical evaluation of TIR-199, a natural product-derived syrbactin structural analog. Molecular modeling and simulation suggested TIR-199 covalently binds each of the three catalytic subunits (β1, β2 and β5) and revealed key interaction sites. In vitro and cell culture-based proteasome activity measurements confirmed that TIR-199 inhibits the proteasome in a dose-dependent manner and induces tumor cell death in multiple myeloma and neuroblastoma cells as well as other cancer types in the NCI-60 cell panel. It is particularly effective against kidney cancer cell lines, with more than 250-fold higher anti-tumor activities than observed with the natural product syringolin A (SylA). In vivo studies in mice revealed a maximum tolerated dose (MTD) of TIR-199 at 25 mg/kg. The anti-tumor activity of TIR-199 was confirmed in hollow fiber assays in mice. Adverse drug reaction screens in a kidney panel revealed no off-targets of concern. This is the first study to examine the efficacy of a syrbactin in animals. Taken together, the results suggest that TIR-199 is a potent new proteasome inhibitor with promise for further development into a clinical drug for the treatment of multiple myeloma and other forms of cancer

Syrbactin Structural Analog TIR-199 Blocks Proteasome Activity And Induces Tumor Cell Death.

Multiple myeloma (MM) is an aggressive hematopoietic cancer of plasma cells. The recent emergence of three effective FDA-approved proteasome-inhibiting drugs, bortezomib (Velcade), carfilzomib (Kyprolis), and ixazomib (Ninlaro) confirms that proteasome inhibitors are therapeutically useful against neoplastic disease, in particular refractory MM and mantle cell lymphoma. This study describes the synthesis, computational affinity assessment, and preclinical evaluation of TIR-199, a natural product-derived syrbactin structural analog. Molecular modeling and simulation suggested TIR-199 covalently binds each of the three catalytic subunits (β1, β2 and β5) and revealed key interaction sites. In vitro and cell culture-based proteasome activity measurements confirmed that TIR-199 inhibits the proteasome in a dose-dependent manner and induces tumor cell death in multiple myeloma and neuroblastoma cells as well as other cancer types in the NCI-60 cell panel. It is particularly effective against kidney cancer cell lines, with more than 250-fold higher anti-tumor activities than observed with the natural product syringolin A (SylA). In vivo studies in mice revealed a maximum tolerated dose (MTD) of TIR-199 at 25 mg/kg. The anti-tumor activity of TIR-199 was confirmed in hollow fiber assays in mice. Adverse drug reaction screens in a kidney panel revealed no off-targets of concern. This is the first study to examine the efficacy of a syrbactin in animals. Taken together, the results suggest that TIR-199 is a potent new proteasome inhibitor with promise for further development into a clinical drug for the treatment of multiple myeloma and other forms of cancer

Prevalence and predictors of premarital sexual intercourse among young women in sub-Saharan Africa

Budu E, Seidu A-A, Armah-Ansah EK, et al. Prevalence and predictors of premarital sexual intercourse among young women in sub-Saharan Africa. Reproductive Health. 2023;20(1):1-11.INTRODUCTION: Premarital sexual intercourse (PSI) without adequate information and/or appropriate application of the relevant knowledge about sex before marriage, potentially has adverse effects on the sexual and reproductive health outcomes of vulnerable young women in sub-Saharan Africa (SSA). This study sought to examine the prevalence and predictors of PSI among young womenaged 15-24 in SSA.; METHODS: Nationally representative cross-sectional data from 29 countries in SSA were extracted for the study. A weighted sample size of 87,924 never marriedyoung women was used to estimate the prevalence of PSI in each country. A multilevel binary logistic regression modelling approach was used to examine the predictors of PSI at p<0.05.; RESULTS: The prevalence of PSI among young women in SSA was 39.4%. Young women aged 20-24 (aOR=4.49, 95% CI=4.34, 4.65) and those who had secondary/higher educational level (aOR=1.63, 95% CI=1.54, 1.72) were more likely to engage in PSI compared to those aged 15-19 and those with no formal education. However, young women who belonged to the Islamic religion (aOR=0.66, 95% CI=0.56, 0.78); those whowere working (aOR=0.75, 95% CI=0.73, 0.78); belonged to the richest wealth index (aOR=0.55, 95% CI=0.52, 0.58); were not exposed to radio at all (aOR=0.90, 95% CI=0.81, 0.99); were not exposed to television at all (aOR=0.50, 95% CI=0.46, 0.53); resided in rural areas (aOR=0.73, 95% CI=0.70, 0.76); and those who were living in the East African sub-region (aOR=0.32, 95% CI=0.29, 0.35) were less likely to engage in PSI compared to those who were traditionalist, unemployed, belonged to the poorest wealth index, exposed to radio frequently, exposed to television frequently, resided in urban areas, and lived in the Southern Africa sub-region, respectively.; CONCLUSION: Sub-regional variations in the prevalence of PSI exist amidst multiple risk factors among young women in SSA. Concerted efforts are required to empower young women financially, including education on sexual and reproductive health behaviors such as the detrimental effects of sexual experimentation and encouraging abstinence and/or condom use through regular youth-risk communication advocacy. © 2023. The Author(s)

Syrbactin Structural Analog TIR-199 Blocks Proteasome Activity and Induces Tumor Cell Death

Multiple myeloma is an aggressive hematopoietic cancer of plasma cells. The recent emergence of three effective FDA-approved proteasome-inhibiting drugs, bortezomib (Velcade®), carfilzomib (Kyprolis®), and ixazomib (Ninlaro®), confirms that proteasome inhibitors are therapeutically useful against neoplastic disease, in particular refractory multiple myeloma and mantle cell lymphoma. This study describes the synthesis, computational affinity assessment, and preclinical evaluation of TIR-199, a natural product-derived syrbactin structural analog. Molecular modeling and simulation suggested that TIR-199 covalently binds each of the three catalytic subunits (β1, β2, and β5) and revealed key interaction sites. In vitro and cell culture-based proteasome activity measurements confirmed that TIR-199 inhibits the proteasome in a dose-dependent manner and induces tumor cell death in multiple myeloma and neuroblastoma cells as well as other cancer types in the NCI-60 cell panel. It is particularly effective against kidney tumor cell lines, with >250-fold higher anti-tumor activities than observed with the natural product syringolin A. In vivo studies in mice revealed a maximum tolerated dose of TIR-199 at 25 mg/kg. The anti-tumor activity of TIR-199 was confirmed in hollow fiber assays in mice. Adverse drug reaction screens in a kidney panel revealed no off-targets of concern. This is the first study to examine the efficacy of a syrbactin in animals. Taken together, the results suggest that TIR-199 is a potent new proteasome inhibitor with promise for further development into a clinical drug for the treatment of multiple myeloma and other forms of cancer