Introduction: Fetal programming by different insults results in low birth weight and reduction in nephron number increasing the risk for adult development of cardiovascular and renal diseases. Maternal smoking is an important modifiable adverse fetal exposure worldwide and leads to a decrease in the offspring's birth weight. Thus far, the specific adverse fetal smoking exposures and mechanisms underlying these associations on renal development and functional disorder are unclear. Methods: The present study investigates, in adult male rats, the effect of smoking exposure (Sk) in uteri on blood pressure (BP) by an indirect tail-cuff method using an electrosphygmomanometer, and its association with nephron structure by stereological estimation, immunohistochemical and histological techniques, in parallel with kidney function creatinine and lithium clearance. Results: The current study showed in a 16-week old Sk offspring enhanced arterial blood pressure associated with, reduced urinary sodium excretion and higher TGF-β1 glomerular expression. Sk glomeruli also presented an upregulated collagen and fibronectin deposition intrinsically related to fibrotic process as compared to age-matched control group. Conclusion: Here, we demonstrate that fetal-programmed Sk offspring present pronounced glomerular TGF-β1 and fibrotic marker expression that may, subsequently, promote a glomerular epithelial-mesenchymal transition activated process in an Sk offspring. Although the precise mechanism responsible for the subsequently renal morphological and functional response in Sk offspring is incompletely known, the current data suggest that changes in renal function are conducive to excess sodium tubule reabsorption that is associated with enhanced TGF-β1, fibronectin and collagen deposition, intrinsically related to fibrotic process, might potentiate the programming of adult hypertension.
Defining Gray Zone Challenges Gray zone security challenges, existing short of a formal state of war, present novel complications for U.S. policy and interests in the 21st century. We have well-developed vocabularies, doctrines and mental models to describe war and peace, but the numerous gray zone challenges in between defy easy categorization. For purposes of this paper, gray zone challenges are defined as competitive interactions among and within state and non-state actors that fall between the traditional war and peace duality. They are characterized by ambiguity about the nature of the conflict, opacity of the parties involved, or uncertainty about the relevant policy and legal frameworks. Gray zone challenges can be understood as a pooling of diverse conflicts exhibiting common characteristics. Notably, combining these challenges does not imply a single solution, since each situation contains unique actors and aspects. Overall, gray zone challenges rise above normal, everyday peacetime geo-political competition and are aggressive, perspective-dependent, and ambiguous. As the world's leading superpower and de facto guarantor ofthe current world order, American national security interests span the globe and intersect with numerous circumstances fitting the definition of gray zone challenges. However, many of these challenges exist independent of U.S. agency or action and do not merit American involvement (e.g. civil conflicts in Africa). Accordingly, this paper acknowledges and briefly discusses the larger construct of gray zone challenges across the world, but it focuses on the United States' national security interests and those gray zone challenges such as Russian actions in eastern Ukraine and Daesh (ISIS) that are relevant to America today. Gray Zone Challenges-The new and old normal The U.S. government can improve its ability to operate effectively in the gray zone between war and peace by reshaping its intellectual, organizational and institutional models. America's conventional military dominance and status as a global power guarantee continual challenges and incentivize competitors to oppose the United States in ways designed to nullify our military advantage. The U.S. already possesses the right mix of tools to prevail in the gray zone, but it must think, organize, and act differently. Gray zone challenges are not new. Monikers such as irregular warfare, low-intensity conflict, asymmetric warfare, Military Operations Other Than War (MOOTW), and Small Wars have all been employed to describe this phenomenon in the past. President Kennedy was speaking about the gray zone during his 1962 address to West Point's graduating class when he said: This is another type of war, new in its intensity, ancient in its origin-war by guerrillas, subversives, insurgents, assassins, war by ambush instead of by combat; by infiltration, instead of aggression, seeking victory by eroding and exhausting the enemy instead of engaging him. 1
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