Commentary to 'surrogate decision making in crisis'

This is an accepted manuscript of an article published by BMJ in Journal of Medical Ethics on 15/03/2021, available online: http://dx.doi.org/10.1136/medethics-2020-107180 The accepted version of the publication may differ from the final published versionIn providing commentary to the case presented by DJC Wilkinson and T Pillay, we describe the uncertainties around complex decision making for the critically ill surrogate baby. We share our dilemma in recognizing that we, not the intended parents hold parental authority for Baby T. Despite this, we argue our case for compassionately including the intended parents in discussions and considering their perspectives in the complex decision making processes for Baby T.Published versio

Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer

Cancer was recently annexed to diabetic complications. Furthermore, recent studies suggest that cancer can increase the risk of diabetes. Consequently, diabetes and cancer share many risk factors, but the cellular and molecular pathways correlating diabetes and colon and rectal cancer (CRC) remain far from understood. In this study, we assess the effect of hyperglycemia on cancer cell aggressiveness in human colon epithelial adenocarcinoma cells in vitro and in an experimental animal model of CRC. Our results show that Nox (NADPH oxidase enzyme) 4-induced reactive oxygen species (ROS) production is deregulated in both diabetes and CRC. This is paralleled by inactivation of the AMPK and activation of the mammalian target of rapamycin (mTOR) C1 signaling pathways, resulting in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) accumulation, induction of DNA damage, and exacerbation of cancer cell aggressiveness, thus contributing to the genomic instability and predisposition to increased tumorigenesis in the diabetic milieu. Pharmacologic activation of AMPK, inhibition of mTORC1, or blockade of Nox4 reduce ROS production, restore the homeostatic signaling of 8-oxoguanine DNA glycosylase/8-oxodG, and lessen the progression of CRC malignancy in a diabetic milieu. Taken together, our results identify the AMPK/mTORC1/Nox4 signaling axis as a molecular switch correlating diabetes and CRC. Modulating this pathway may be a strategic target of therapeutic potential aimed at reversing or slowing the progression of CRC in patients with or without diabetes.-Mroueh, F. M., Noureldein, M., Zeidan, Y. H., Boutary, S., Irani, S. A. M., Eid, S., Haddad, M., Barakat, R., Harb, F., Costantine, J., Kanj, R., Sauleau, E.-A., Ouhtit, A., Azar, S. T., Eid, A. H., Eid, A. A. Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer.Scopu

Placental malaria and its effect on pregnancy outcomes in Sudanese women from Blue Nile State

Abstract Background Malaria infection during pregnancy can result in placental malaria and is associated with adverse pregnancy outcomes particularly among primigravidae. The aim of this study was to assess the prevalence and risk factors for placental malaria and its effect on pregnancy outcomes in Blue Nile state, Sudan. Methods A cross-sectional hospital-based study was conducted consecutively during January 2012–December 2015 in three main hospitals in Blue Nile State, Sudan. At delivery, peripheral and placental blood samples were collected from consenting women. Finger prick blood was used for preparation of peripheral smears and for haemoglobin measurement. Smears were stained with Giemsa and examined microscopically for malaria parasites. Pregnancy outcomes in association to placental malaria were investigated. Results A total of 1149 mothers and their newborns were recruited. The mean (SD) of the age was 23.3 (5.2) years. Detection of malaria parasites was confirmed in 37.8% of the peripheral blood films and 59.3% of the placental films with Plasmodium falciparum as the only species detected. In multivariate analysis, younger age ≤23.2 years old (AOR = 3.2, 95% CI 1.9–5.5; P < 0.001), primiparae (AOR = 3.9, CI 2.1–7.6; P < 0.001), secundiparae (AOR = 2.8, 95% CI 1.5–5.1; P < 0.001, no antenatal care (ANC) visits (AOR = 11.9, 95% CI 7.8–18.1; P < 0.001) and not using bed nets (AOR = 3.5, 95% CI 1.7–6.8; P < 0.001) were risk factors for placental malaria. Education and residence were not associated with placental malaria infection. Placental malaria was significantly associated with maternal anaemia (AOR = 41.6, 95% CI 23.3–74.4; P < 0.001) and low birth weight (LBW) (AOR = 25.2, 95% CI 15.1–41.3; P < 0.001). Conclusion During the study, there was a high prevalence of placental malaria in Blue Nile State-Sudan, as the enhanced control activities were not practiced, leading to adverse pregnancy outcomes, such as maternal anaemia and LBW