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The Ras-related GTP-binding protein D (RRAGD) gene plays a crucial role in cellular processes. Recently, RRAGD variants found in patients have been implicated in a novel disorder with kidney tubulopathy and dilated cardiomyopathy. Currently, the consequences of RRAGD variants at the organismal level are unknown. Therefore, this study investigated the impact of RRAGD variants on cardiac function using a zebrafish embryo model. Furthermore, the potential usage of rapamycin, an mTOR inhibitor, as a therapy was assessed in this model. Zebrafish embryos were injected with RRAGD p.S76L and p.P119R cRNA and the resulting heart phenotypes were studied. Our findings reveal that overexpression of RRAGD mutants resulted in decreased ventricular fractional shortening, ejection fraction, and pericardial swelling. In RRAGD S76L-injected embryos, lower survival and heartbeat were observed, whereas survival was unaffected in RRAGD P119R embryos. These observations were reversible following therapy with the mTOR inhibitor rapamycin. Moreover, no effects on electrolyte homeostasis were observed. Together, these findings indicate a crucial role of RRAGD in cardiac function. In the future, the molecular mechanisms by which RRAGD variants result in cardiac dysfunction and if the effects of rapamycin are specific for RRAGD-dependent cardiomyopathy should be studied in clinical studies. NEW & NOTEWORTHY: The resultant heart-associated phenotypes in the zebrafish embryos of this study serve as a valuable experimental model for this rare cardiomyopathy. Moreover, the potential therapeutic property of rapamycin in cardiac dysfunctions was highlighted, making this study a pivotal step toward prospective clinical applications. [ABSTRACT FROM AUTHOR]

The increase number of natural disasters that struck the world gives damaging impacts to the people and properties. This paper attempts to examine crucial pressing issues and challenges in mitigating flood losses and loss of lives in Malaysia. Only qualitative approach is used to address these pressing issues and challenges of natural disaster. Kelantan is one the states in the east coast of Malaysia that experienced the highest loss of properties and infrastructure in 2014 massive flood. Semi-structured interview was designed and used to collect data from six government agencies in the state of Kelantan. These agencies were, Kelantan State Education Department (KSED), Kelantan State Department of Rescue and Fire Brigade (KDRFB), Kelantan State Health Department (KSHD), Local Authority of Kuala Krai (LAKK), Kelantan State Social and Welfare Department (KSSWD) and Kelantan State Police Contingent (KSPC). The finding of the study revealed that were eight pressing issues and four challenges. The eight pressing issues are flood preparations, lack of rescuers, lack of awareness, communication difficulty, lack of assets for rescue, transportation issues, the absence of food supply, and other constraints. On the other hand, the challenges are lack of provisions, redevelopment, the social and economic situation, and trauma. These pressing issues and challenges need to be seriously addressed by the State and Federal level of Government of Malaysia so that future natural disaster like the 2014 flood can be managed in a much more prepared way or manner.