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tissues to conduct electrical energy that could be strongly infused by total body water change. However, ascites and edema, which are the cardinal symptoms of cirrhosis or severe liver disease, might strongly effect BIA measurements [3]. Moreover, the validity of segmental BIA has been compared with other techniques and discussed in this regard [4,5]. Additionally, data on the validity of segmental BIA are limited as its non-inferiority was compared with dual energy X-ray absorptiometry, which is not an appropriate standard [6,7]. When comparing an instrument with a reference modality that is not an appropriate standard, the degree to which the correlation between instruments is influenced by measurement errors of the reference instrument cannot be correctly defined. As second concern, immunosuppressive treatment provides additional prophylaxis against acute rejection over the first weeks of liver transplantation, but these therapies merely increase post-transplant infection complications [8]. However, the study by Kaido et al. lacks the critical analyses of the effects of immunosuppressive therapy on post-transplantation infectious complications. In other words, the authors could provide some data on the differential effects of different immunosuppressive therapies administered in their patients.

References [1] Kaido T, Mori A, Ogura Y, Ogawa K, Hata K, Yoshizawa A, et al. Pre- and perioperative factors affecting infection after living donor liver transplantation. Nutrition 2012;28:1104–8. [2] Eshraghian A. Metabolic syndrome after liver transplantation: is there a role for infections? Nutrition 2012;28:825–6. [3] Mijnarends DM, Meijers JM, Halfens RJ. Validity and reliability of tools to measure muscle mass, strength, and physical performance in communitydwelling older people: a systematic review. J Am Med Dir Assoc 2013;14: 170–8. [4] Mally K, Trentmann J, Heller M, Dittmar M. Reliability and accuracy of segmental bioelectrical impedance analysis for assessing muscle and fat mass in older Europeans: a comparison with dual-energy X-ray absorptiometry. Eur J Appl Physiol 2011;111:1879–87. [5] Safer U, Tasci I, Binay Safer V, Doruk H. Comment on “Comparison of three BIA muscle indices for sarcopenia screening in old adult”. Eur Geriatr Med; 2013. http://dx.doi.org/10.1016/j.eurger.2013.04 (in press). [6] Ling CH, de Craen AJ, Slagboom PE, Gunn DA, Stokkel MP, Westendorp RG, et al. Accuracy of direct segmental multi-frequency bioimpedance analysis in the assessment of total body and segmental body composition in middle-aged adult population. Clin Nutr 2011;30:610–5. [7] Heymsfield SB. New bioimpedance analysis system: improved phenotyping with whole-body analysis. Eur J Clin Nutr 2004;58:1479–84. [8] Rostaing L, Saliba F, Calmus Y, Dharancy S, Boillot O. Review article: use of induction therapy in liver transplantation. Transplant Rev (Orlando) 2012; 26:246–60.

Umut Safer, M.D. Ilker Tasci Department of Geriatrics Gulhane School of Medicine Ankara, Turkey Vildan Binay Safer, M.D. Department of Physical Medicine and Rehabilitation Ankara Physical Medicine and Rehabilitation Research and Training Hospital, Ankara, Turkey Huseyin Doruk Department of Geriatrics Gulhane School of Medicine Ankara, Turkey http://dx.doi.org/10.1016/j.nut.2013.05.001

Malnutrition in the 21st century To the Editor: Malnutrition is critical for the physiologic function of different systems in organisms, among them the central nervous system and bone marrow, tissues that are extremely important for maintaining life. As a classification, malnutrition may be taken as a subacute, acute, and chronic state of undernutrition in which a number sequence of changeable qualities of nutrition and inflammatory reactions lead to abnormalities in body composition and aberrant function [1,2]. Acute malnutrition arises as a consequence of a sudden period of food shortage and is associated with loss of body fat and wasting of skeletal muscle. Chronic malnutrition refers to a long period of hunger through an insufficient supply of both macronutrients and certain micronutrients and has major long-term negative effects on brain development and function, including mental skills and activity, physical movement and coordination, and the acquisition of skills needed to socially interact [2]. A number of circumstances other than social position may lead to malnutrition. These involve eating disorders, elderly individuals, and patients with chronic diseases with or without long-term hospitalization [3,4]. In the hospitalization phase of different diseases, the odds of being malnourished were increased significantly, although it was impossible to ascertain whether clinical care practices or lack thereof contributed its development [3]. In 2010, the Food and Agriculture Organization of the United Nations reported [5] that approximately 925 million people worldwide were malnourished in developing and developed countries. These numbers are contributing to a worldwide health dilemma. Malnutrition is not restricted to an aging population, but is an important concern, especially in the developmental period. The causes of malnutrition in childhood range from poor maternal diet, intrauterine growth retardation secondary to placental insufficiency, short breastfeeding, late introduction of complementary foods, inadequate quantity and quality of complementary foods, impairment of nutrient digestion, and absorption by severe and chronic diseases [6]. Nevertheless, undernutrition makes a major contribution to the global disease burden, accounting for more than one-third of child deaths worldwide [7] and a mild degree of malnutrition doubles the risk for mortality from infectious diseases [1]. Malnutrition compromises child immunity such that episodes of illness tend to last longer and be more severe, and interacts with infection in a negative vicious cycle, each worsening the effect of the other [1]. Malnutrition is implicated in a variety of childhood diseases, some of which arise soon after birth or as the child progresses into adulthood. There is considerable evidence that nutritional insults in children are strongly associated with impaired physical growth, anemia [8], and altered immunologic function [1], as well as impaired psychomotor and mental development because of negative effects on brain development and function [2]. Undernourished children are more likely to be short in adulthood; present reducing productivity; give birth to smaller infants; and achieve lower educational levels and economic status, resulting in lower physical capacity and energy for work as an adult, with associated economic costs [2]. Chronic undernutrition during the age of rapid development, in so-called “critical periods of development” influence children’s metabolism, inhibit physiological patterns of growth and development, and exerts a lifelong effect on human health [2]. Long-term consequences of malnutrition show an increased risk for chronic cardiovascular diseases, kidney damage, and diabetes in later life [1,2]. Moreover, early

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childhood stunting is now recognized as a risk factor for obesity, hyperinsulinemia, and insulin resistance, which is called metabolic syndrome, and is characterized by a combination of abdominal obesity, hyperglycemia, hypertension, high blood triglycerides, and reduced high-density lipoprotein cholesterol. In adulthood, metabolic syndrome increases an individual’s risk for atherosclerotic vascular disease and is associated with a substantially higher risk for major vascular events, causing high mortality rates. Multiple diseases arise from nutritional deficits in nutrition. However, little is known about the molecular diseases that are characteristic of poor nutrition and how these deficits can be immediately corrected or stopped to avoid or ameliorate these disorders and to provide these individuals with a chance at life. Malnutrition has diverse roles in many functional processes during health and diseases, including but not limited to enzyme catalysis, protein stabilization, energy production, and oxygen delivery. The importance of good nutrition results from the numerous roles that it has, such as stabilization of transcription factors and proteins [9]. In fact, the first clinical consequences of malnutrition are bone marrow changes manifested as anemia and leukopenia [8], which are associated with modification of the immune system and predispose individuals to increased susceptibility to infections [1]. The biological roles of general nutrition are widely investigated and reviewed in the literature, with a large focus on the connection to neurologic conditions such as neurodegenerative diseases mainly associated with aging [3,4]. Among the percentage of neurodegenerative patients who were identified as malnourished, the most likely explanation was a prolonged period of inadequate dietary intake during inpatient hospitalization, highlighting the importance of closely monitoring the sufficiency of nutritional intake during neurodegenerative diseases [3]. Although the pathologic symptoms of malnutrition are in most cases well understood, the exact key mechanisms often are unknown. Two pools of cells are found in bone marrow: hematopoietic stem cells and hematopoietic progenitor cells, These cells possess the ability to produce all blood cell lines in proper quantities for homeostasis. This is reached by the rigorous cell cycle regulation by external factors within bone marrow and internal factors at the cell level [10]. One study [11] highlights what we know about the influence of malnutrition on bone marrow changes, which are very important especially in relation to hospitalized patients. Malnourished experimental animals showed nutritional, hormonal, and hematologic abnormalities. The researchers concluded that malnutrition affecting hematopoietic progenitor cells could be important in some clinical treatments, especially in bone marrow transplantation, in which the bone marrow microenvironment integrity could be critical to the cell engraftment. The study’s [11] finding could be extremely relevant if we consider that hematopoietic stem cells and hematopoietic progenitor cells are the key steps that regulate the hematopoiesis; from their self-renewal, differentiation and proliferation course, blood homeostasis is kept under physiological requirements. The researchers presented the animal model to determine how the molecular mechanisms of malnutrition suppress cell cycle progression of hematopoietic progenitor cells via cyclin D1 downregulation, which we hope will aid in our understanding of the role of malnutrition in


disease development and in attaining possible therapeutics in the future. References [1] Penny ME. Protein-energy malnutrition: pathophysiology, clinical consequences and treatment. In: Walker WA, Watkins J, Duggan C, editors. Nutrition in pediatrics. 4th ed. Hamilton, Ontario: BC Decker, Inc; 2008. p. 127–41. [2] Victora CG, Adair L, Fall C, Hallal PC, Martorell R, Richter L, Sachdev HS. Maternal and child undernutrition: consequences for adult health and human capital. Lancet 2008;371:340–57. [3] Foley NC, Martin RE, Salter KL, Teasell RW. A review of the relationship between dysphagia and malnutrition following stroke. J Rehabil Med 2009;41: 707–13. [4] U1amek-Kozio1 M, Bogucka-Kocka A, Kocki J, Pluta R. Good and bad sites of diet in Parkinson’s disease. Nutrition 2013;29:474–5. [5] Food and Agriculture Organization of the United Nations (FAO) 2010. The state of food insecurity in the world. Addressing food insecurity in protracted crises. Available: http://www.fao.org/docrep/013/i1683e/i1683e00. htm. Accessed 23 August 2012. [6] Sawaya AL, Martins PA, Baccin Martins VJ, et al. Malnutrition, long-term health and the effect of nutritional recovery. In: Kalhan SC, Prentice AM,  Nutr Inst Workshop Ser Pediatr Program, Nestec Yajnik CS, editors. Nestle Ltd. Basel, Switzerland: Vevey/S. Karger AG; 2009. p. 95–108. [7] Picot J, Hartwell D, Harris P, Mendes D, Clegg AJ, Takeda A. The effectiveness of interventions to treat severe acute malnutrition in young children: a systematic review. Health Technol Assess 2012;16:1–316. [8] Fock RA, Blatt SL, Beutler B, Pereira J, Tsujita M, de Barros FE, et al. Study of lymphocyte subpopulations in bone marrow in a model of protein-energy malnutrition. Nutrition 2010;26:1021–8. [9] Fock RA, Rogero MM, Vinolo MA, Curi R, Borges MC, Borelli P. Effects of protein energy malnutrition on NF-kappaB signaling in murine peritoneal macrophages. Inflammation 2010;33:101–9.  E. Cell cycle regulation in hematopoietic [10] Pietras EM, Warr MR, Passegue stem cells. J Cell Biol 2011;195:709–20. [11] Nakajima K, Crisma AR, Batista da Silva G, Rogero MM, Fock RA, Borelli, P. Malnutrition suppresses cell cycle progression of hematopoietic progenitor cells in mice via cyclin D1 downregulation. Nutrition 2013 (in press).

 ska, M.D., Ph.D. Wanda Furmaga-Jab1on Department of Neonate and Infant Pathology Medical University of Lublin Lublin, Poland Marzena U1amek-Kozio1, M.D. Laboratory of Ischemic and Neurodegenerative Brain Research Mossakowski Medical Research Centre Polish Academy of Sciences Warsaw, Poland Judyta Brzozowska, M.S. Department of Clinical Psychology Medical University of Lublin Lublin, Poland Agata Tarkowska, M.D., Ph.D. Department of Neonate and Infant Pathology Medical University of Lublin Lublin, Poland Ryszard Pluta, M.D., Ph.D. Laboratory of Ischemic and Neurodegenerative Brain Research Mossakowski Medical Research Centre Polish Academy of Sciences Warsaw, Poland E-mail addresses: [email protected], [email protected] (R. Pluta) http://dx.doi.org/10.1016/j.nut.2013.06.003

Malnutrition in the 21st century.

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