anorexia

Summary

Summary: The lack or loss of APPETITE accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder ANOREXIA NERVOSA.

Top Publications

  1. Dev R, Del Fabbro E, Schwartz G, Hui D, Palla S, Gutierrez N, et al. Preliminary report: vitamin D deficiency in advanced cancer patients with symptoms of fatigue or anorexia. Oncologist. 2011;16:1637-41 pubmed publisher
    ..We investigated the prevalence of low serum vitamin D levels in cancer patients with fatigue or poor appetite and their association with symptom burden and other correctable endocrine abnormalities...
  2. Ohata H, Shibasaki T. Involvement of CRF2 receptor in the brain regions in restraint-induced anorexia. Neuroreport. 2011;22:494-8 pubmed publisher
    ..that corticotropin-releasing factor (CRF) receptor subtypes, CRF1 and CRF2, are involved in stress-induced anorexia. To clarify in which brain regions the CRF receptor is involved in mediating stress-induced anorexia, we examined ..
  3. Just N, Gruetter R. Detection of neuronal activity and metabolism in a model of dehydration-induced anorexia in rats at 14.1 T using manganese-enhanced MRI and 1H MRS. NMR Biomed. 2011;24:1326-36 pubmed publisher
    In this study, hypothalamic activation was performed by dehydration-induced anorexia (DIA) and overnight food suppression (OFS) in female rats...
  4. Muliawati Y, Haroen H, Rotty L. Cancer anorexia - cachexia syndrome. Acta Med Indones. 2012;44:154-62 pubmed
    Cancer anorexia-cachexia syndrome (CACS) is a devastating and debilitating aspect at any stage of malignancy. It presents primarily as anorexia, weight loss and muscle wasting secondary to inadequate oral intake and metabolic changes...
  5. Klenotich S, Seiglie M, McMurray M, Roitman J, le Grange D, Dugad P, et al. Olanzapine, but not fluoxetine, treatment increases survival in activity-based anorexia in mice. Neuropsychopharmacology. 2012;37:1620-31 pubmed publisher
    b>Anorexia nervosa (AN) is an eating disorder characterized by extreme hypophagia, hyperactivity, and fear of weight gain. No approved pharmacological treatments exist for AN despite high mortality rates...
  6. Verhagen L, Luijendijk M, de Groot J, van Dommelen L, Klimstra A, Adan R, et al. Anticipation of meals during restricted feeding increases activity in the hypothalamus in rats. Eur J Neurosci. 2011;34:1485-91 pubmed publisher
    ..DMH) and lateral hypothalamus] in the early development of FAA in rats exposed to the activity-based anorexia (ABA) model...
  7. Soenen S, Chapman I. Body weight, anorexia, and undernutrition in older people. J Am Med Dir Assoc. 2013;14:642-8 pubmed publisher
    ..weight loss in older people may be a result of protein-energy malnutrition, cachexia, the physiological anorexia of aging, or a combination of these...
  8. Rivera H, Santollo J, Nikonova L, Eckel L. Estradiol increases the anorexia associated with increased 5-HT(2C) receptor activation in ovariectomized rats. Physiol Behav. 2012;105:188-94 pubmed publisher
    ..anorexigenic effect prompted us to investigate whether a regimen of acute estradiol treatment increases the anorexia associated with increased 5-HT(2C) receptor activation in ovariectomized (OVX) rats...
  9. Asp M, Tian M, Kliewer K, Belury M. Rosiglitazone delayed weight loss and anorexia while attenuating adipose depletion in mice with cancer cachexia. Cancer Biol Ther. 2011;12:957-65 pubmed publisher
    ..These changes predict for modest improvement in adipose, but no improvement in muscle strength in late-stage cachexia...

More Information

Publications62

  1. Laviano A, Seelaender M, Sanchez Lara K, Gioulbasanis I, Molfino A, Rossi Fanelli F. Beyond anorexia -cachexia. Nutrition and modulation of cancer patients' metabolism: supplementary, complementary or alternative anti-neoplastic therapy?. Eur J Pharmacol. 2011;668 Suppl 1:S87-90 pubmed publisher
    b>Anorexia and muscle wasting are frequently observed in cancer patients and influence their clinical outcome...
  2. Moss C, Dhillo W, Frost G, Hickson M. Gastrointestinal hormones: the regulation of appetite and the anorexia of ageing. J Hum Nutr Diet. 2012;25:3-15 pubmed publisher
    Loss of appetite is frequently observed during ageing, termed the 'anorexia of ageing'. Ageing is associated with the inability to appropriately increase food intake after under-eating in the short- and long-term...
  3. Flannery B, Wu W, Pestka J. Characterization of deoxynivalenol-induced anorexia using mouse bioassay. Food Chem Toxicol. 2011;49:1863-9 pubmed publisher
    ..DON dose-dependently induced anorexia within 2 h of exposure when administered either by intraperitoneal (ip.) injection or by oral gavage...
  4. Robert F, Mills J, Agenor A, Wang D, Dimarco S, Cencic R, et al. Targeting protein synthesis in a Myc/mTOR-driven model of anorexia-cachexia syndrome delays its onset and prolongs survival. Cancer Res. 2012;72:747-56 pubmed publisher
    b>Anorexia-cachexia syndrome (ACS) is a major determinant of cancer-related death that causes progressive body weight loss due to depletion of skeletal muscle mass and body fat...
  5. Fung E, Tsung L, Dale R. Aquaporin-4 autoantibody: a neurogenic cause of anorexia and weight loss. Dev Med Child Neurol. 2012;54:45-7 pubmed publisher
    ..We describe a 14-year-old female with positive aquaporin-4 antibody whose clinical course was dominated by severe anorexia with associated weight loss (from 68-41kg; body mass index 25.2-15.6)...
  6. Fudim M, Wagman G, Altschul R, Yucel E, Bloom M, Vittorio T. Pathophysiology and treatment options for cardiac anorexia. Curr Heart Fail Rep. 2011;8:147-53 pubmed publisher
    The anorexia-cachexia syndrome (ACS) occurs in many chronic illnesses, such as cancer, AIDS, and chronic obstructive pulmonary disease in addition to chronic congestive heart failure (CHF)...
  7. Landi F, Liperoti R, Lattanzio F, Russo A, Tosato M, Barillaro C, et al. Effects of anorexia on mortality among older adults receiving home care: an observation study. J Nutr Health Aging. 2012;16:79-83 pubmed
    We describe the prevalence of secondary anorexia in a population of older people living in community and receiving home care. In addition, we examined the relationship between secondary anorexia and mortality.
  8. Chasen M, Hirschman S, Bhargava R. Phase II study of the novel peptide-nucleic acid OHR118 in the management of cancer-related anorexia/cachexia. J Am Med Dir Assoc. 2011;12:62-7 pubmed publisher
    OHR118 represents a new class of immunomodulatory and cytoprotective drugs in managing anorexia cachexia. Previously in patients with advanced HIV-AIDS, increases in appetite, strength, and alertness were noted...
  9. Fujitsuka N, Asakawa A, Uezono Y, Minami K, Yamaguchi T, Niijima A, et al. Potentiation of ghrelin signaling attenuates cancer anorexia-cachexia and prolongs survival. Transl Psychiatry. 2011;1:e23 pubmed publisher
    Cancer anorexia-cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients...
  10. Bennani Baiti N, Walsh D. Animal models of the cancer anorexia-cachexia syndrome. Support Care Cancer. 2011;19:1451-63 pubmed publisher
    ..Animal models expand our understanding of its mechanisms. A review of cancer cachexia and anorexia animal models will help investigators make an informed choice of the study model.
  11. Flannery B, Clark E, Pestka J. Anorexia induction by the trichothecene deoxynivalenol (vomitoxin) is mediated by the release of the gut satiety hormone peptide YY. Toxicol Sci. 2012;130:289-97 pubmed publisher
    ..Although this growth impairment is believed to result from anorexia, the initiating mechanisms for appetite suppression remain unknown...
  12. Penna F, Minero V, Costamagna D, Bonelli G, Baccino F, Costelli P. Anti-cytokine strategies for the treatment of cancer-related anorexia and cachexia. Expert Opin Biol Ther. 2010;10:1241-50 pubmed publisher
    ..Among the general mechanisms proposed to account for cachexia, anorexia and altered homeostasis of hormones and cytokines appear to play a major role.
  13. Nicolini A, Ferrari P, Masoni M, Fini M, Pagani S, Giampietro O, et al. Malnutrition, anorexia and cachexia in cancer patients: A mini-review on pathogenesis and treatment. Biomed Pharmacother. 2013;67:807-17 pubmed publisher
    Malnutrition, anorexia and cachexia are a common finding in cancer patients. They become more evident with tumor growth and spread. However, the mechanisms by which they are sustained often arise early in the history of cancer...
  14. Kinzig K, Hargrave S. Adolescent activity-based anorexia increases anxiety-like behavior in adulthood. Physiol Behav. 2010;101:269-76 pubmed publisher
    Activity-based anorexia is a paradigm that induces increased physical activity, reduced food intake, and heightened activity of the hypothalamic-pituitary-adrenal axis in adult rats...
  15. Yom Tov E, Fernandez Luque L, Weber I, Crain S. Pro-anorexia and pro-recovery photo sharing: a tale of two warring tribes. J Med Internet Res. 2012;14:e151 pubmed publisher
    There is widespread use of the Internet to promote anorexia as a lifestyle choice. Pro-anorexia content can be harmful for people affected or at risk of having anorexia...
  16. Landi F, Lattanzio F, Dell Aquila G, Eusebi P, Gasperini B, Liperoti R, et al. Prevalence and potentially reversible factors associated with anorexia among older nursing home residents: results from the ULISSE project. J Am Med Dir Assoc. 2013;14:119-24 pubmed publisher
    The principal aims of the present study were to explore the prevalence of anorexia and the factors correlated to anorexia in a large population of older people living in nursing home...
  17. Steinglass J, Figner B, Berkowitz S, Simpson H, Weber E, Walsh B. Increased capacity to delay reward in anorexia nervosa. J Int Neuropsychol Soc. 2012;18:773-80 pubmed publisher
    Individuals with anorexia nervosa (AN) are often characterized as possessing excessive self-control and are unusual in their ability to reduce or avoid the consumption of palatable foods...
  18. Cheng K, Li Y, Cheng J. The use of herbal medicine in cancer-related anorexia/ cachexia treatment around the world. Curr Pharm Des. 2012;18:4819-26 pubmed
    ..However, randomized effectiveness of herbal medicines shall be further identified in controlled clinical trials involving cancer patients with cachexia. ..
  19. Ruud J, Nilsson A, Engström Ruud L, Wang W, Nilsberth C, Iresjö B, et al. Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1. Brain Behav Immun. 2013;29:124-35 pubmed publisher
    ..and evidence indicates that PGs also are important for the reduced food intake and body weight loss, the anorexia-cachexia syndrome, in malignant cancer...
  20. Zhu X, Krasnow S, Roth Carter Q, Levasseur P, Braun T, Grossberg A, et al. Hypothalamic signaling in anorexia induced by indispensable amino acid deficiency. Am J Physiol Endocrinol Metab. 2012;303:E1446-58 pubmed publisher
    Animals exhibit a rapid and sustained anorexia when fed a diet that is deficient in a single indispensable amino acid (IAA). The chemosensor for IAA deficiency resides within the anterior piriform cortex (APC)...
  21. Maccio A, Madeddu C, Mantovani G. Current pharmacotherapy options for cancer anorexia and cachexia. Expert Opin Pharmacother. 2012;13:2453-72 pubmed publisher
    b>Anorexia and cachexia syndrome represents a complex clinical picture that occurs in the late stage of several chronic inflammatory diseases, including cancer...
  22. Donini L, Dominguez L, Barbagallo M, Savina C, Castellaneta E, Cucinotta D, et al. Senile anorexia in different geriatric settings in Italy. J Nutr Health Aging. 2011;15:775-81 pubmed
    b>Anorexia is the most frequent modification of eating habits in old age, which may lead to malnutrition and consequent morbidity and mortality in older adults...
  23. Ruud J, Wilhelms D, Nilsson A, Eskilsson A, Tang Y, Ströhle P, et al. Inflammation- and tumor-induced anorexia and weight loss require MyD88 in hematopoietic/myeloid cells but not in brain endothelial or neural cells. FASEB J. 2013;27:1973-80 pubmed publisher
    ..Here we addressed the question of determining in which cells the MyD88 signaling that results in anorexia development occurs by using chimeric mice and animals with cell-specific deletions...
  24. Sadakane C, Muto S, Nakagawa K, Ohnishi S, Saegusa Y, Nahata M, et al. 10-Gingerol, a component of rikkunshito, improves cisplatin-induced anorexia by inhibiting acylated ghrelin degradation. Biochem Biophys Res Commun. 2011;412:506-11 pubmed publisher
    ..RKT), a Japanese traditional medicine, has been shown to stimulate food intake in rats with cisplatin-induced anorexia; however, the underlying mechanisms remain unknown...
  25. Kalson N, Hext F, Davies A, Chan C, Wright A, Imray C. Do changes in gastro-intestinal blood flow explain high-altitude anorexia?. Eur J Clin Invest. 2010;40:735-41 pubmed publisher
    ..Therefore, blood flow in the superior mesenteric artery (SMA) and hepatic portal vein (HPV) was examined at sea level (SL) and after ascent to 4392 m (HA)...
  26. Tagay S, Düllmann S, Schlegl S, Nater Mewes R, Repic N, Hampke C, et al. [Effects of inpatient treatment on eating disorder symptoms, health-related quality of life and personal resources in anorexia and bulimia nervosa]. Psychother Psychosom Med Psychol. 2011;61:319-27 pubmed publisher
    The aim of the present prospective-naturalistic study was the evaluation of psychosomatic inpatient treatment for anorexia nervosa (AN) and bulimia nervosa (BN)...
  27. Bennani Baiti N, Walsh D. What is cancer anorexia-cachexia syndrome? A historical perspective. J R Coll Physicians Edinb. 2009;39:257-62 pubmed
    Cancer anorexia-cachexia syndrome (CACS) is a lethal but poorly defined involuntary wasting disorder. Loss of skeletal muscle and fat distinguishes it from starvation...
  28. Fearon K, Strasser F, Anker S, Bosaeus I, Bruera E, Fainsinger R, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12:489-95 pubmed publisher
    ..Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment...
  29. Adan R, Hillebrand J, Danner U, Cardona Cano S, Kas M, Verhagen L. Neurobiology driving hyperactivity in activity-based anorexia. Curr Top Behav Neurosci. 2011;6:229-50 pubmed publisher
    Hyperactivity in anorexia nervosa is difficult to control and negatively impacts outcome. Hyperactivity is a key driving force to starvation in an animal model named activity-based anorexia (ABA)...
  30. Hattori T, Yakabi K, Takeda H. Cisplatin-induced anorexia and ghrelin. Vitam Horm. 2013;92:301-17 pubmed publisher
    ..The mechanism of action for anorexia, which continues during or after treatment, is, however, still unclear...
  31. Hinney A, Scherag S, Hebebrand J. Genetic findings in anorexia and bulimia nervosa. Prog Mol Biol Transl Sci. 2010;94:241-70 pubmed publisher
    b>Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders associated with disordered eating behavior...
  32. Madeddu C, Dessì M, Panzone F, Serpe R, Antoni G, Cau M, et al. Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib ± megestrol acetate for patients with cancer-related anorexia/cachexia syndrome. Clin Nutr. 2012;31:176-82 pubmed publisher
    ..e. antioxidants) with carnitine + celecoxib ± megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total ..
  33. Martone A, Onder G, Vetrano D, Ortolani E, Tosato M, Marzetti E, et al. Anorexia of aging: a modifiable risk factor for frailty. Nutrients. 2013;5:4126-33 pubmed publisher
    b>Anorexia of aging, defined as a loss of appetite and/or reduced food intake, affects a significant number of elderly people and is far more prevalent among frail individuals...
  34. Jáuregui Garrido B, Bolaños Ríos P, Santiago Fernández M, Jauregui Lobera I. Lipid profile and cardiovascular risk in anorexia nervosa; the effect of nutritional treatment. Nutr Hosp. 2012;27:908-13 pubmed publisher
    The aim of this study was to explore the lipid profile in patients with anorexia nervosa (AN), and the changes with refeeding.
  35. Pardo M, Roca Rivada A, Al Massadi O, Seoane L, Camiña J, Casanueva F. Peripheral leptin and ghrelin receptors are regulated in a tissue-specific manner in activity-based anorexia. Peptides. 2010;31:1912-9 pubmed publisher
    ..to investigate the effect of long-term exposure to low leptin and high ghrelin levels, inherent to activity-based anorexia (ABA), on peripheral metabolism-implicated tissues such as muscle and fat depots...
  36. Molfino A, Laviano A, Rossi Fanelli F. Contribution of anorexia to tissue wasting in cachexia. Curr Opin Support Palliat Care. 2010;4:249-53 pubmed publisher
    b>Anorexia is a severe debilitating symptom characterizing the clinical course of several chronic diseases. It negatively impacts on patient outcome by contributing to weight loss, lean body mass catabolism and adipose tissue wasting...
  37. Hopkinson J. The emotional aspects of cancer anorexia. Curr Opin Support Palliat Care. 2010;4:254-8 pubmed publisher
    To discuss the psychosocial support of people affected by cancer anorexia, drawing on recent publications.
  38. Wu Q, Palmiter R. GABAergic signaling by AgRP neurons prevents anorexia via a melanocortin-independent mechanism. Eur J Pharmacol. 2011;660:21-7 pubmed publisher
    ..We also describe a compensatory mechanism that is gradually engaged after ablation of AgRP neurons that allows mice to continue eating without them...
  39. Aoki C, Sabaliauskas N, Chowdhury T, Min J, Colacino A, Laurino K, et al. Adolescent female rats exhibiting activity-based anorexia express elevated levels of GABA(A) receptor ?4 and ? subunits at the plasma membrane of hippocampal CA1 spines. Synapse. 2012;66:391-407 pubmed publisher
    Activity-based anorexia (ABA) is an animal model for anorexia nervosa that has revealed genetic links to anxiety traits and neurochemical characteristics within the hypothalamus...
  40. Verty A, Evetts M, Crouch G, McGregor I, Stefanidis A, Oldfield B. The cannabinoid receptor agonist THC attenuates weight loss in a rodent model of activity-based anorexia. Neuropsychopharmacology. 2011;36:1349-58 pubmed publisher
    b>Anorexia nervosa (AN) is characterized by anhedonia whereby patients experience little pleasure or reward in many aspects of their lives. Reward pathways and the endocannabionid system have been implicated in the mediation of food intake...
  41. Mogami S, Suzuki H, Fukuhara S, Matsuzaki J, Kangawa K, Hibi T. Reduced ghrelin production induced anorexia after rat gastric ischemia and reperfusion. Am J Physiol Gastrointest Liver Physiol. 2012;302:G359-64 pubmed publisher
    ..These data show that gastric I/R evoked anorexia with decreased plasma ghrelin levels and ghrelin production, which appears to be attributable to the I/R-induced ..
  42. Ruiz Garcia V, Lopez Briz E, Carbonell Sanchis R, Gonzálvez Perales J, Bort Marti S. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2013;:CD004310 pubmed publisher
    ..a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'...
  43. Syed Abdul S, Fernandez Luque L, Jian W, Li Y, Crain S, Hsu M, et al. Misleading health-related information promoted through video-based social media: anorexia on YouTube. J Med Internet Res. 2013;15:e30 pubmed publisher
    ..There are thousands of YouTube videos promoting misleading information about anorexia (eg, anorexia as a healthy lifestyle).
  44. Diakowska D, Krzystek Korpacka M, Markocka Maczka K, Diakowski W, Matusiewicz M, Grabowski K. Circulating leptin and inflammatory response in esophageal cancer, esophageal cancer-related cachexia-anorexia syndrome (CAS) and non-malignant CAS of the alimentary tract. Cytokine. 2010;51:132-7 pubmed publisher
    We investigated the association between esophageal cancer and cachexia-anorexia syndrome (CAS) of the alimentary tract and leptin, an adipocytokine crucial for body weight regulation, a modulator of inflammatory/immune response, ..
  45. Landi F, Liperoti R, Russo A, Giovannini S, Tosato M, Barillaro C, et al. Association of anorexia with sarcopenia in a community-dwelling elderly population: results from the ilSIRENTE study. Eur J Nutr. 2013;52:1261-8 pubmed publisher
    There is increasing evidence that anorexia of aging can cause physical and mental impairment. The aim of the present study was to evaluate the relationship between anorexia and sarcopenia in elderly persons aged 80 years or older.
  46. Lindfors C, Nilsson I, Garcia Roves P, Zuberi A, Karimi M, Donahue L, et al. Hypothalamic mitochondrial dysfunction associated with anorexia in the anx/anx mouse. Proc Natl Acad Sci U S A. 2011;108:18108-13 pubmed publisher
    ..We therefore hypothesized that the anorexia and degenerative phenotypes in the anx/anx mouse could be related to defects in the OXPHOS...
  47. Girardet C, Bonnet M, Jdir R, Sadoud M, Thirion S, Tardivel C, et al. The food-contaminant deoxynivalenol modifies eating by targeting anorexigenic neurocircuitry. PLoS ONE. 2011;6:e26134 pubmed publisher
    ..regulation of appetite relies on complex neurocircuitry which disturbance may alter energy balance and result in anorexia or obesity...
  48. Saegusa Y, Takeda H, Muto S, Nakagawa K, Ohnishi S, Sadakane C, et al. Decreased plasma ghrelin contributes to anorexia following novelty stress. Am J Physiol Endocrinol Metab. 2011;301:E685-96 pubmed publisher
    We hypothesized that anorexia induced by novelty stress caused by exposure to a novel environment may be due to activation of corticotropin-releasing factor (CRF) and subsequently mediated by decreasing peripheral ghrelin concentration ..
  49. Xu Y, Jones J, Lauzon D, Anderson J, Balthasar N, Heisler L, et al. A serotonin and melanocortin circuit mediates D-fenfluramine anorexia. J Neurosci. 2010;30:14630-4 pubmed publisher
    ..we found that global deletion of 5-HT 2C receptors (5-HT(2C)Rs) significantly attenuated D-Fen-induced anorexia. These anorexigenic effects were restored in mice with 5-HT(2C)Rs expressed only in pro-opiomelanocortin (POMC) ..
  50. Harrison A, Tchanturia K, Treasure J. Attentional bias, emotion recognition, and emotion regulation in anorexia: state or trait?. Biol Psychiatry. 2010;68:755-61 pubmed publisher
    b>Anorexia nervosa (AN) is associated with difficulties in emotion recognition and regulation and with attentional biases to social affective stimuli...
  51. Hevrøy E, Waagbø R, Torstensen B, Takle H, Stubhaug I, Jørgensen S, et al. Ghrelin is involved in voluntary anorexia in Atlantic salmon raised at elevated sea temperatures. Gen Comp Endocrinol. 2012;175:118-34 pubmed publisher
    ..Y, and anorexigenic factors at transcriptional levels in the hypothalamus, which over time lead to a voluntary anorexia development in adult salmon held at 19 °C...
  52. Donini L, Poggiogalle E, Piredda M, Pinto A, Barbagallo M, Cucinotta D, et al. Anorexia and eating patterns in the elderly. PLoS ONE. 2013;8:e63539 pubmed publisher
    To evaluate the change in eating habits occurring in community-dwelling and institutionalized elderly subjects with senile anorexia.
  53. Yakabi K, Sadakane C, Noguchi M, Ohno S, Ro S, Chinen K, et al. Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia. Endocrinology. 2010;151:3773-82 pubmed publisher
    ..cancer treatment, the undesirable gastrointestinal side effects associated with it, such as nausea, vomiting, and anorexia, markedly decrease patients' quality of life...