The development of the brain depends on an individual's nature (genes) and nurture (environments). This interaction between genetic predispositions and environmental events during brain development drives the maturation of functional brain circuits such as sensory, motor, emotional, and complex cognitive pathways. Adverse environmental conditions such as early life stress can interfere with the functional development of emotional and cognitive brain systems and thereby increase the risk of developing psychiatric disorders later in life. In order to develop more efficient and individualized protective and therapeutic interventions, it is essential to understand how environmental stressors during infancy affect cellular and molecular mechanisms involved in brain maturation. Animal models of early life stress have been able to reveal brain structural and metabolic changes in prefrontolimbic circuits, which are time, brain region, neuron, and sex specific. By focusing on animal models of separation stress during infancy, this review highlights epigenetic and cytoarchitectural modifications which are assumed to mediate lasting changes of brain function and behavior.

Keywords:
Maternal stress separation, Epigenetics, Synaptic structural plasticity, Psychiatric disorders
1.
Dekaban AS: Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights. Ann Neurol 1978;4:345-356.
2.
Knickmeyer RC, Gouttard S, Kang C, Evans D, Wilber K, Smith JK, Hamer RM, Lin W, Gerig G, Gilmore JH: A structural MRI study of human brain development from birth to 2 years. J Neurosci 2008;28:12176-12182.
3.
Bhardwaj RD, Curtis MA, Spalding KL, Buchholz BA, Fink D, Björk-Eriksson T, Nordborg C, Gage FH, Druid H, Eriksson PS, Frisén J: Neocortical neurogenesis in humans is restricted to development. Proc Natl Acad Sci USA 2006;103:12564-12568.
4.
Kostovic I, Rakic P: Cytology and time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol 1980;9:219-242.
5.
Shankle WR, Rafii MS, Landing BH, Fallon JH: Approximate doubling of numbers of neurons in postnatal human cerebral cortex and in 35 specific cytoarchitectural areas from birth to 72 months. Pediatr Dev Pathol 1999;2:244-259.
6.
Weickert CS, Webster MJ, Colvin SM, Herman MM, Hyde TM, Weinberger DR, Kleinman JE: Localization of epidermal growth factor receptors and putative neuroblasts in human subependymal zone. J Comp Neurol 2000;423:359-372.
7.
Andersen SL: Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci Biobehav Rev 2003;27:3-18.
8.
Bourgeois JP: Synaptogenesis, heterochrony and epigenesis in the mammalian neocortex. Acta Paediatr Suppl 1997;422:27-33.
9.
Huttenlocher PR, Dabholkar AS: Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 1997;387:167-178.
10.
Landing BH, Shankle WR, Hara J, Brannock J, Fallon JH: The development of structure and function in the postnatal human cerebral cortex from birth to 72 months: changes in thickness of layers II and III co-relate to the onset of new age-specific behaviors. Pediatr Pathol Mol Med 2002;21:321-342.
11.
Lund JS, Lewis DA: Local circuit neurons of developing and mature macaque prefrontal cortex: Golgi and immunocytochemical characteristics. J Comp Neurol 1993;328:282-312.
12.
Mrzljak L, Uylings HB, Van Eden CG, Judás M: Neuronal development in human prefrontal cortex in prenatal and postnatal stages. Prog Brain Res 1990;85:185-222.
13.
Supèr H, Soriano E, Uylings HB: The functions of the preplate in development and evolution of the neocortex and hippocampus. Brain Res Brain Res Rev 1998;27:40-64.
14.
Zecevic N, Bourgeois JP, Rakic P: Changes in synaptic density in motor cortex of rhesus monkey during fetal and postnatal life. Brain Res Dev Brain Res 1989;50:11-32.
15.
Berardi N, Pizzorusso T, Maffei L: Critical periods during sensory development. Curr Opin Neurobiol 2000;10:138-145.
16.
Ehrlich I, Malinow R: Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity. J Neurosci 2004;24:916-927.
17.
Huttenlocher PR, De Courten C, Garey LJ, Van der Loos H: Synaptogenesis in human visual cortex - evidence for synapse elimination during normal development. Neurosci Lett 1982;33:247-252.
18.
Takahashi T, Svoboda K, Malinow R: Experience strengthening transmission by driving AMPA receptors into synapses. Science 2003;299:1585-1588.
19.
Morishita H, Hensch TK: Critical period revisited: impact on vision. Curr Opin Neurobiol 2008;18:101-107.
20.
Bock J, Wainstock T, Braun K, Segal M: Stress in utero: prenatal programming of brain plasticity and cognition. Biol Psychiatry 2015;78:315-326.
21.
Bock J, Rether K, Gröger N, Xie L, Braun K: Perinatal programming of emotional brain circuits: an integrative view from systems to molecules. Front Neurosci 2014;8:11.
22.
Guedeney A, Guedeney N, Tereno S, Dugravier R, Greacen T, Welniarz B, Saias T, Tubach F: Infant rhythms versus parental time: promoting parent-infant synchrony. J Physiol Paris 2011;105:195-200.
23.
Kober H, Barrett LF, Joseph J, Bliss-Moreau E, Lindquist K, Wager TD: Functional grouping and cortical-subcortical interactions in emotion: a meta-analysis of neuroimaging studies. Neuroimage 2008;42:998-1031.
24.
Swain JE: The human parental brain: in vivo neuroimaging. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:1242-1254.
25.
Grossmann K, Grossmann KE, Kindler H, Zimmermann P: A wider view of attachment and exploration: the influence of mothers and fathers on the development of psychological security from infancy to young adulthood; in Cassidy J, Shaver PR (eds): Handbook of Attachment: Theory, Research, and Clinical Applications, ed 2. New York, Guilford Press, 2008, pp 857-879.
26.
Ranson KE, Urichuk LJ: The effect of parent-child attachment relationships on child biopsychosocial outcomes: a review. Early Child Dev Care 2008;178:129-152.
27.
Thompson RA: Early attachment and later development: familiar questions, new answers; in Cassidy J, Shaver PR (eds): Handbook of Attachment: Theory, Research, and Clinical Applications, ed 2. New York, Guilford Press, 2008, pp 348-365.
28.
Bowlby J: Attachment and loss: retrospect and prospect. Am J Orthopsychiatry 1982;52:664-678.
29.
Waters E, Cummings EM: A secure base from which to explore close relationships. Child Dev 2000;71:164-172.
30.
Anand KJ, Scalzo FM: Can adverse neonatal experiences alter brain development and subsequent behavior? Biol Neonate 2000;77:69-82.
31.
Maunder RG, Hunter JJ: Attachment and psychosomatic medicine: developmental contributions to stress and disease. Psychosom Med 2001;63:556-567.
32.
Bowlby J: Attachment and Loss. Attachment. London, Hogarth Press, 1969, vol 1.
33.
Bowlby J: Attachment and Loss. Separation: Anxiety and Anger. London, Basic Books, 1973, vol 2.
34.
Green J, Goldwyn R: Annotation: attachment disorganisation and psychopathology: new findings in attachment research and their potential implications for developmental psychopathology in childhood. J Child Psychol Psychiatry 2002;43:835-846.
35.
Boris NW, Fueyo M, Zeanah CH: The clinical assessment of attachment in children under five. J Am Acad Child Adolesc Psychiatry 1997;36:291-293.
36.
Carlson EA: A prospective longitudinal study of attachment disorganization/disorientation. Child Dev 1998;69:1107-1128.
37.
Lyons-Ruth K, Alpern L, Repacholi B: Disorganized infant attachment classification and maternal psychosocial problems as predictors of hostile-aggressive behavior in the preschool classroom. Child Dev 1993;64:572-585.
38.
Zeanah CH, Boris NW, Larrieu JA: Infant development and developmental risk: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 1997;36:165-178.
39.
Kreppner JM, Rutter M, Beckett C, Castle J, Colvert E, Groothues C, Hawkins A, O'Connor TG, Stevens S, Sonuga-Barke EJ: Normality and impairment following profound early institutional deprivation: a longitudinal follow-up into early adolescence. Dev Psychol 2007;43:931-946.
40.
Field T: Attachment and separation in young children. Annu Rev Psychol 1996;47:541-561.
41.
Frodi A, Bridges L, Grolnick W: Correlates of mastery-related behavior: a short-term longitudinal study of infants in their second year. Child Dev 1985;56:1291-1298.
42.
Bock J, Riedel A, Braun K: Differential changes of metabolic brain activity and interregional functional coupling in prefronto-limbic pathways during different stress conditions: functional imaging in freely behaving rodent pups. Front Cell Neurosci 2012;6:19.
43.
Bock J, Breuer S, Poeggel G, Braun K: Early life stress induces attention deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model. Brain Struct Funct 2016, Epub ahead of print.
44.
Chugani HT, Behen ME, Muzik O, Juhász C, Nagy F, Chugani DC: Local brain functional activity following early deprivation: a study of postinstitutionalized Romanian orphans. Neuroimage 2001;14:1290-1301.
45.
Mehta MA, Golembo NI, Nosarti C, Colvert E, Mota A, Williams SC, Rutter M, Sonuga-Barke EJ: Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: the English and Romanian Adoptees study pilot. J Child Psychol Psychiatry 2009;50:943-951.
46.
Lorenz K: Der Kumpan in der Umwelt des Vogels. J Ornithol 1935;83:289-431.
47.
Wallhäusser E, Scheich H: Auditory imprinting leads to differential 2-deoxyglucose uptake and dendritic spine loss in the chick rostral forebrain. Brain Res 1987;428:29-44.
48.
Bock J, Braun K: Blockade of N-methyl-D-aspartate receptor activation suppresses learning-induced synaptic elimination. Proc Natl Acad Sci USA 1999;96:2485-2490.
49.
Wolff JR, Missler M: Synaptic remodelling and elimination as integral processes of synaptogenesis. APMIS Suppl 1993;40:9-23.
50.
Bock J, Braun K: Differential emotional experience leads to pruning of dendritic spines in the forebrain of domestic chicks. Neural Plast 1998;6:17-27.
51.
Bock J, Braun K: Filial imprinting in domestic chicks is associated with spine pruning in the associative area, dorsocaudal neostriatum. Eur J Neurosci 1999;11:2566-2570.
52.
Bock J, Wolf A, Braun K: Influence of the N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid on auditory filial imprinting in the domestic chick. Neurobiol Learn Mem 1996;65:177-188.
53.
Segal M: Dendritic spines and long-term plasticity. Nat Rev Neurosci 2005;6:277-284.
54.
Helmeke C, Ovtscharoff W, Poeggel G, Braun K: Juvenile emotional experience alters synaptic inputs on pyramidal neurons in the anterior cingulate cortex. Cereb Cortex 2001;11:717-727.
55.
Ovtscharoff W, Braun K: Maternal separation and social isolation modulate the postnatal development of synaptic composition in the infralimbic cortex of Octodon degus. Neuroscience 2001;104:33-40.
56.
Poeggel G, Helmeke C, Abraham A, Schwabe T, Friedrich P, Braun K: Juvenile emotional experience alters synaptic composition in the rodent cortex, hippocampus, and lateral amygdala. Proc Natl Acad Sci USA 2003;100:16137-16142.
57.
Monroy E, Hernández-Torres E, Flores G: Maternal separation disrupts dendritic morphology of neurons in prefrontal cortex, hippocampus, and nucleus accumbens in male rat offspring. J Chem Neuroanat 2010;40:93-101.
58.
Pascual R, Zamora-León SP: Effects of neonatal maternal deprivation and postweaning environmental complexity on dendritic morphology of prefrontal pyramidal neurons in the rat. Acta Neurobiol Exp (Wars) 2007;67:471-479.
59.
Andersen SL, Teicher MH: Delayed effects of early stress on hippocampal development. Neuropsychopharmacology 2004;29:1988-1993.
60.
Oomen CA, Soeters H, Audureau N, Vermunt L, van Hasselt FN, Manders EM, Joëls M, Lucassen PJ, Krugers H: Severe early life stress hampers spatial learning and neurogenesis, but improves hippocampal synaptic plasticity and emotional learning under high-stress conditions in adulthood. J Neurosci 2010;30:6635-6645.
61.
Huot RL, Plotsky PM, Lenox RH, McNamara RK: Neonatal maternal separation reduces hippocampal mossy fiber density in adult Long Evans rats. Brain Res 2002;950:52-63.
62.
Lie DC, Song H, Colamarino SA, Ming GL, Gage FH: Neurogenesis in the adult brain: new strategies for central nervous system diseases. Annu Rev Pharmacol Toxicol 2004;44:399-421.
63.
Ming GL, Song H: Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 2005;28:223-250.
64.
Fabricius K, Wörtwein G, Pakkenberg B: The impact of maternal separation on adult mouse behaviour and on the total neuron number in the mouse hippocampus. Brain Struct Funct 2008;212:403-416.
65.
Nair A, Vadodaria KC, Banerjee SB, Benekareddy M, Dias BG, Duman RS, Vaidya VA: Stressor-specific regulation of distinct brain-derived neurotrophic factor transcripts and cyclic AMP response element-binding protein expression in the postnatal and adult rat hippocampus. Neuropsychopharmacology 2007;32:1504-1519.
66.
Hulshof HJ, Novati A, Sgoifo A, Luiten PG, Den Boer JA, Meerlo P: Maternal separation decreases adult hippocampal cell proliferation and impairs cognitive performance but has little effect on stress sensitivity and anxiety in adult Wistar rats. Behav Brain Res 2011;216:552-560.
67.
Mirescu C, Peters JD, Gould E: Early life experience alters response of adult neurogenesis to stress. Nat Neurosci 2004;7:841-846.
68.
Lee HJ, Kim JW, Yim SV, Kim MJ, Kim SA, Kim YJ, Kim CJ, Chung JH: Fluoxetine enhances cell proliferation and prevents apoptosis in dentate gyrus of maternally separated rats. Mol Psychiatry 2001;6:610, 725-728.
69.
Park HJ, Lim S, Lee HS, Lee HJ, Yoo YM, Lee HJ, Kim SA, Yin CS, Seo JC, Chung JH: Acupuncture enhances cell proliferation in dentate gyrus of maternally separated rats. Neurosci Lett 2002;319:153-156.
70.
Joseph R: Environmental influences on neural plasticity, the limbic system, emotional development and attachment: a review. Child Psychiatry Hum Dev 1999;29:189-208.
71.
Lupien SJ, McEwen BS, Gunnar MR, Heim C: Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 2009;10:434-445.
72.
Andersen SL, Teicher MH: Stress, sensitive periods and maturational events in adolescent depression. Trends Neurosci 2008;31:183-191.
73.
Bock J, Gruss M, Becker S, Braun K: Experience-induced changes of dendritic spine densities in the prefrontal and sensory cortex: correlation with developmental time windows. Cereb Cortex 2005;15:802-808.
74.
Gos T, Bock J, Poeggel G, Braun K: Stress-induced synaptic changes in the rat anterior cingulate cortex are dependent on endocrine developmental time windows. Synapse 2008;62:229-232.
75.
Braun K, Champagne FA: Paternal influences on offspring development: behavioural and epigenetic pathways. J Neuroendocrinol 2014;26:697-706.
76.
Champagne FA, Curley JP: Epigenetic mechanisms mediating the long-term effects of maternal care on development. Neurosci Biobehav Rev 2009;33:593-600.
77.
Fagiolini M, Jensen CL, Champagne FA: Epigenetic influences on brain development and plasticity. Curr Opin Neurobiol 2009;19:207-212.
78.
Hoffmann A, Spengler D: The lasting legacy of social stress on the epigenome of the hypothalamic-pituitary-adrenal axis. Epigenomics 2012;4:431-444.
79.
Kundakovic M, Lim S, Gudsnuk K, Champagne FA: Sex-specific and strain-dependent effects of early life adversity on behavioral and epigenetic outcomes. Front Psychiatry 2013;4:78.
80.
Lutz PE, Turecki G: DNA methylation and childhood maltreatment: from animal models to human studies. Neuroscience 2014;264:142-156.
81.
Mueller BR, Bale TL: Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci 2008;28:9055-9065.
82.
Szyf M: DNA methylation, behavior and early life adversity. J Genet Genomics 2013;40:331-338.
83.
Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, Huebert DJ, McMahon S, Karlsson EK, Kulbokas EJ 3rd, Gingeras TR, Schreiber SL, Lander ES: Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 2005;120:169-181.
84.
Berger SL: The complex language of chromatin regulation during transcription. Nature 2007;447:407-412.
85.
Kouzarides T: Chromatin modifications and their function. Cell 2007;128:693-705.
86.
Ruthenburg AJ, Allis CD, Wysocka J: Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Mol Cell 2007;25:15-30.
87.
Taverna SD, Ueberheide BM, Liu Y, Tackett AJ, Diaz RL, Shabanowitz J, Chait BT, Hunt DF, Allis CD: Long-distance combinatorial linkage between methylation and acetylation on histone H3 N termini. Proc Natl Acad Sci USA 2007;104:2086-2091.
88.
Shahbazian MD, Grunstein M: Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem 2007;76:75-100.
89.
Hake SB, Allis CD: Histone H3 variants and their potential role in indexing mammalian genomes: the ‘H3 barcode hypothesis'. Proc Natl Acad Sci USA 2006;103:6428-6435.
90.
Szyf M: Implications of a life-long dynamic epigenome. Epigenomics 2009;1:9-12.
91.
Meaney MJ: Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 2001;24:1161-1192.
92.
Szyf M: Nongenetic inheritance and transgenerational epigenetics. Trends Mol Med 2015;21:134-144.
93.
Kember RL, Dempster EL, Lee TH, Schalkwyk LC, Mill J, Fernandes C: Maternal separation is associated with strain-specific responses to stress and epigenetic alterations to Nr3c1, Avp, and Nr4a1 in mouse. Brain Behav 2012;2:455-467.
94.
Murgatroyd C, Patchev AV, Wu Y, Micale V, Bockmühl Y, Fischer D, Holsboer F, Wotjak CT, Almeida OF, Spengler D: Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci 2009;12:1559-1566.
95.
Levine A, Worrell TR, Zimnisky R, Schmauss C: Early life stress triggers sustained changes in histone deacetylase expression and histone H4 modifications that alter responsiveness to adolescent antidepressant treatment. Neurobiol Dis 2012;45:488-498.
96.
Xie L, Korkmaz KS, Braun K, Bock J: Early life stress-induced histone acetylations correlate with activation of the synaptic plasticity genes Arc and Egr1 in the mouse hippocampus. J Neurochem 2013;125:457-464.
97.
Rodenas-Ruano A, Chávez AE, Cossio MJ, Castillo PE, Zukin RS: REST-dependent epigenetic remodeling promotes the developmental switch in synaptic NMDA receptors. Nat Neurosci 2012;15:1382-1390.
98.
Chen Y, Baram TZ: Toward understanding how early-life stress reprograms cognitive and emotional brain networks. Neuropsychopharmacology 2016;41:197-206.
99.
Singh-Taylor A, Korosi A, Molet J, Gunn BG, Baram TZ: Synaptic rewiring of stress-sensitive neurons by early-life experience: a mechanism for resilience? Neurobiol Stress 2015;1:109-115.
100.
Karsten CA, Baram TZ: How does a neuron ‘know' to modulate its epigenetic machinery in response to early-life environment/experience? Front Psychiatry 2013;4:89.
101.
Moriceau S, Roth TL, Sullivan RM: Rodent model of infant attachment learning and stress. Dev Psychobiol 2010;52:651-660.
102.
Roth TL: Epigenetic mechanisms in the development of behavior: advances, challenges, and future promises of a new field. Dev Psychopathol 2013;25:1279-1291.
103.
Daskalakis NP, Bagot RC, Parker KJ, Vinkers CH, De Kloet ER: The three-hit concept of vulnerability and resilience: toward understanding adaptation to early-life adversity outcome. Psychoneuroendocrinology 2013;38:1858-1873.
104.
Schmidt MV: Animal models for depression and the mismatch hypothesis of disease. Psychoneuroendocrinology 2011;36:330-338.
105.
Nederhof E, Schmidt MV: Mismatch or cumulative stress: toward an integrated hypothesis of programming effects. Physiol Behav 2012;106:691-700.
106.
Krugers HJ, Oomen CA, Gumbs M, Li M, Velzing EH, Joels M, Lucassen PJ: Maternal deprivation and dendritic complexity in the basolateral amygdala. Neuropharmacology 2012;62:534-537.
107.
Leventopoulos M, Rüedi-Bettschen D, Knuesel I, Feldon J, Pryce CR, Opacka-Juffry J: Long-term effects of early life deprivation on brain glia in Fischer rats. Brain Res 2007;1142:119-126.
108.
Oomen CA, Girardi CE, Cahyadi R, Verbeek EC, Krugers H, Joëls M, Lucassen PJ: Opposite effects of early maternal deprivation on neurogenesis in male versus female rats. PLoS One 2009;4:e3675.
109.
Navailles S, Hof PR, Schmauss C: Antidepressant drug-induced stimulation of mouse hippocampal neurogenesis is age-dependent and altered by early life stress. J Comp Neurol 2008;509:372-381.
110.
Spinelli S, Chefer S, Suomi SJ, Higley JD, Barr CS, Stein E: Early-life stress induces long-term morphologic changes in primate brain. Arch Gen Psychiatry 2009;66:658-665.
111.
Helmeke C, Ovtscharoff W, Poeggel G, Braun K: Imbalance of immunohistochemically characterized interneuron populations in the adolescent and adult rodent medial prefrontal cortex after repeated exposure to neonatal separation stress. Neuroscience 2008;152:18-28.
112.
Braun K, Lange E, Metzger M, Poeggel G: Maternal separation followed by early social deprivation affects the development of monoaminergic fiber systems in the medial prefrontal cortex of Octodon degus. Neuroscience 2000;95:309-318.
113.
Kunzler J, Braun K, Bock J: Early life stress and sex-specific sensitivity of the catecholaminergic systems in prefrontal and limbic regions of Octodon degus. Brain Struct Funct 2015;220:861-868.
114.
Desarnaud F, Jakovcevski M, Morellini F, Schachner M: Stress downregulates hippocampal expression of the adhesion molecules NCAM and CHL1 in mice by mechanisms independent of DNA methylation of their promoters. Cell Adh Migr 2008;2: 38-44.
115.
Daniels WM, Fairbairn LR, Van Tilburg G, McEvoy CR, Zigmond MJ, Russell VA, Stein DJ: Maternal separation alters nerve growth factor and corticosterone levels but not the DNA methylation status of the exon 17 glucocorticoid receptor promoter region. Metab Brain Dis 2009;24:615-627.
© 2016 S. Karger AG, Basel
2016
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.