This technical report serves to provide the evidence base for the American Academy of Pediatrics’ policy statements “Clinical Practice Policy to Protect Children From Tobacco, Nicotine, and Tobacco Smoke” and “Public Policy to Protect Children From Tobacco, Nicotine, and Tobacco Smoke.” Tobacco use and involuntary exposure are major preventable causes of morbidity and premature mortality in adults and children. Tobacco dependence almost always starts in childhood or adolescence. Electronic nicotine delivery systems are rapidly gaining popularity among youth, and their significant harms are being documented. In utero tobacco smoke exposure, in addition to increasing the risk of preterm birth, low birth weight, stillbirth, placental abruption, and sudden infant death, has been found to increase the risk of obesity and neurodevelopmental disorders. Actions by pediatricians can help to reduce children’s risk of developing tobacco dependence and reduce children’s involuntary tobacco smoke exposure. Public policy actions to protect children from tobacco are essential to reduce the toll that the tobacco epidemic takes on our children.

Numerous problems exist with the current thinking of RNA as the first genetic material. No plausible prebiotic processes have yet been demonstrated to produce the nucleosides or nucleotides or for efficient two-way nonenzymatic replication. Peptide nucleic acid (PNA) is a promising precursor to RNA, consisting of N-(2-aminoethyl)glycine (AEG) and the adenine, uracil, guanine, and cytosine-N-acetic acids. However, PNA has not yet been demonstrated to be prebiotic. We show here that AEG is produced directly in electric discharge reactions from CH4, N2, NH3, and H2O. Electric discharges also produce ethylenediamine, as do NH4CN polymerizations. AEG is produced from the robust Strecker synthesis with ethylenediamine. The NH4CN polymerization in the presence of glycine leads to the adenine and guanine-N 9 -acetic acids, and the cytosine and uracil-N 1 -acetic acids are produced in high yield from the reaction of cyanoacetaldehyde with hydantoic acid, rather than urea. Preliminary experiments suggest that AEG may polymerize rapidly at 100°C to give the polypeptide backbone of PNA. The ease of synthesis of the components of PNA and possibility of polymerization of AEG reinforce the possibility that PNA may have been the first genetic material.prebiotic synthesis ͉ first genetic material ͉ pre-RNA world ͉ RNA world ͉ chemical evolution T he discovery of the catalytic activity of RNA (1, 2) brought the concept of an RNA world (3-7) into wide acceptance. However, the instability of ribose and other sugars (8), the great difficulty of prebiotic synthesis of the glycosidic bonds of the necessary nucleotides (9, 10), and the inability to achieve twoway non-enzymatic template polymerizations (11, 12) have raised serious questions about whether RNA could have been the first genetic material (13), although there are dissenting opinions (6,14). A pre-RNA world in which the backbone of the first genetic material would have been different from the ribose phosphate seems more likely, but the nature of this backbone is unknown. One proposal offers peptide nucleic acids (PNA) as a possible precursor to RNA (15) because PNA binds DNA and forms double and triple helical structures that are related to the Watson-Crick helix (16-18).The backbone of PNA is a polymer of N-(2-aminoethyl)glycine (AEG), which is sometimes referred to as ethylenediamine monoacetic acid. It is interesting to note that Westheimer listed AEG as one of a number of possible backbones to replace ribose phosphate (19). This was four years before the invention of peptide nucleic acids. The bases are attached to the backbone by a base-substituted acetyl unit, as shown in Fig. 1. The simplicity of the components of PNA suggests that prebiotic syntheses might be feasible. We therefore examined a number of prebiotic syntheses, including electric discharges and NH 4 CN polymerizations for ethylenediamine (ED) and AEG, as well as the adenine and guanine-N 9 -acetic acids and the cytosine and uracil-N 1 -acetic acids. We show here that the components of PNA are synthesized u...

In vitro selection of Zn(2+)-dependent RNA-cleaving DNAzymes with activity at 90 degrees C has yielded a diverse spool of selected sequences. The RNA cleavage efficiency was found in all cases to be specific for Zn(2+) over Pb(2+), Ca(2+), Cd(2+), Co(2+), Hg(2+), and Mg(2+). The Zn(2+)-dependent activity assay of the most active sequence showed that the DNAzyme possesses an apparent Zn(2+)-binding dissociation constant of 234 muM and that its activity increases with increasing temperatures from 50-90 degrees C. A fit of the Arrhenius plot data gave E(a) = 15.3 kcal mol(-1). Surprisingly, the selected Zn(2+)-dependent DNAzymes showed only a modest (approximately 3-fold) activity enhancement over the background rate of cleavage of random sequences containing a single embedded ribonucleotide within an otherwise DNA oligonucleotide. The result is attributable to the ability of DNA to sustain cleavage activity at high temperature with minimal secondary structure when Zn(2+) is present. Since this effect is highly specific for Zn(2+), this metal ion may play a special role in molecular evolution of nucleic acids at high temperature.

Tobacco dependence starts in childhood. Tobacco exposure of children is common and causes illness and premature death in children and adults, with adverse effects starting in the womb. There is no safe level of tobacco smoke exposure. Pediatricians should screen for use of tobacco and other nicotine delivery devices and provide anticipatory guidance to prevent smoking initiation and reduce tobacco smoke exposure. Pediatricians need to be aware of the different nicotine delivery systems marketed and available. Parents and caregivers are important sources of children’s tobacco smoke exposure. Because tobacco dependence is a severe addiction, to protect children’s health, caregiver tobacco dependence treatment should be offered or referral for treatment should be provided (such as referral to the national smoker’s quitline at 1-800-QUIT-NOW). If the source of tobacco exposure cannot be eliminated, counseling about reducing exposure to children should be provided. Health care delivery systems should facilitate the effective prevention, identification, and treatment of tobacco dependence in children and adolescents, their parents, and other caregivers. Health care facilities should protect children from tobacco smoke exposure and tobacco promotion. Tobacco dependence prevention and treatment should be part of medical education, with knowledge assessed as part of board certification examinations.

The efficient prebiotic synthesis of cytosine from urea and cyanoacetaldehyde (CA) has recently been claimed to be invalid on the basis of possible side reactions of the starting materials and the inapplicability of prebiotic syntheses using drying beach conditions. We therefore have investigated the synthesis of cytosine and uracil from urea and cyanoacetaldehyde at 100 degrees C under dry-down conditions, and in solution at 4 degrees C and -20 degrees C. We find that cytosine is produced from the low temperature experiments more efficiently than calculated from the Arrhenius extrapolation from higher temperatures, i.e., 60-120 degrees C. In addition, we find that CA dimer is as efficient as the monomer in cytosine synthesis. We also studied whether evaporating very dilute solutions of nonvolatile organic compounds will concentrate according to theory. Solutions as dilute as 10(-4) M concentrate from pure water approximately according to theory. Similar solutions in 0.5 M NaCl have less than theoretical concentrations due to absorption, but concentrations near dryness were very high.