Formation of S-Cl phosphorothioate adduct radicals in dsDNA S-oligomers: hole transfer to guanine vs disulfide anion radical formation.

In phosphorothioate-containing dsDNA oligomers (S-oligomers), one of the two nonbridging oxygen atoms in the phosphate moiety of the sugar-phosphate backbone is replaced by sulfur. In this work, electron spin resonance (ESR) studies of one-electron oxidation of several S-oligomers by Cl2(•-) at low temperatures are performed. Electrophilic addition of Cl2(•-) to phosphorothioate with elimination of Cl(-) leads to the formation of a two-center three-electron σ(2)σ*(1)-bonded adduct radical (-P-S-̇Cl). In AT S-oligomers with multiple phosphorothioates, i.e., d[ATATAsTsAsT]2, -P-S-̇Cl reacts with a neighboring phosphorothioate to form the σ(2)σ*(1)-bonded disulfide anion radical ([-P-S-̇S-P-](-)). With AT S-oligomers with a single phosphorothioate, i.e., d[ATTTAsAAT]2, reduced levels of conversion of -P-S-̇Cl to [-P-S-̇S-P-](-) are found. For guanine-containing S-oligomers containing one phosphorothioate, -P-S-̇Cl results in one-electron oxidation of guanine base but not of A, C, or T, thereby leading to selective hole transfer to G. The redox potential of -P-S-̇Cl is thus higher than that of G but is lower than those of A, C, and T. Spectral assignments to -P-S-̇Cl and [-P-S-̇S-P-](-) are based on reaction of Cl2(•-) with the model compound diisopropyl phosphorothioate. The results found for d[TGCGsCsGCGCA]2 suggest that [-P-S-̇S-P-](-) undergoes electron transfer to the one-electron-oxidized G, healing the base but producing a cyclic disulfide-bonded backbone with a substantial bond strength (50 kcal/mol). Formation of -P-S-̇Cl and its conversion to [-P-S-̇S-P-](-) are found to be unaffected by O2, and this is supported by the theoretically calculated electron affinities and reduction potentials of [-P-S-S-P-] and O2.

Physicians' use of the personal digital assistant (PDA) in clinical decision making.

PURPOSE: This study examined how frequently attending physicians and physicians in training used personal digital assistants (PDAs) for patient care and explored physicians' perceptions of the impact of PDA use on several areas of clinical decision making. SETTING/SUBJECTS: The 108 participants included 59 attending physicians and 49 physicians in training from teaching hospitals in Tennessee, Florida, Alabama, Kentucky, and Pennsylvania. METHODOLOGY: Respondents completed a questionnaire designed to explore PDA use in a clinical setting. RESULTS: Eighty-seven percent of the respondents reported PDA use for patient encounters. Fifty-five percent of respondents reported frequent use, and 32% reported occasional use of a PDA for patient care. Of the frequent PDA users, 85% said PDA use had influenced their overall clinical decision making and 73% mentioned treatment alterations specifically. Approximately 60% of the participants reporting occasional PDA use indicated that the PDA had influenced their overall clinical decision making, while 54% specifically mentioned a change to their patient's treatment plan. DISCUSSION/CONCLUSION: Attending physicians and physicians in training who used a PDA during patient encounters perceived that even occasional PDA use had an impact on their clinical decision making and treatment choices. Health sciences librarians are perfectly positioned to provide PDA training and assistance not only to physicians who are frequent PDA users, but also to those who are occasional users.

Reactions of 5-methylcytosine cation radicals in DNA and model systems: thermal deprotonation from the 5-methyl group vs. excited state deprotonation from sugar.

PURPOSE: To study the formation and subsequent reactions of the 5-methyl-2'-deoxycytidine cation radical (5-Me-2'-dC•(+)) in nucleosides and DNA-oligomers and compare to one-electron oxidized thymidine. MATERIALS AND METHODS: Employing electron spin resonance (ESR), cation radical formation and its reactions were investigated in 5-Me-2'-dC, thymidine (Thd) and their derivatives, in fully double-stranded (ds) d[GC*GC*GC*GC*](2) and in the 5-Me-C/A mismatched, d[GGAC*AAGC:CCTAATCG], where C* = 5-Me-C. RESULTS: We report 5-Me-2'-dC•(+) production by one-electron oxidation of 5-Me-2'-dC by Cl(2)•- via annealing in the dark at 155 K. Progressive annealing of 5-Me-2'-dC•(+) at 155 K produces the allylic radical (C-CH(2)•). However, photoexcitation of 5-Me-2'-dC•(+) by 405 nm laser or by photoflood lamp leads to only C3'• formation. Photoexcitation of N3-deprotonated thyminyl radical in Thd and its 5'-nucleotides leads to C3'• formation but not in 3'-TMP which resulted in the allylic radical (U-CH(2)•) and C5'• production. For excited 5-Me-2',3'-ddC•(+), absence of the 3'-OH group does not prevent C3'• formation. For d[GC*GC*GC*GC*](2) and d[GGAC*AAGC:CCTAATCG], intra-base paired proton transferred form of G cation radical (G(N1-H)•: C(+ H(+))) is found with no observable 5-Me-2'-dC•(+) formation. Photoexcitation of (G(N1-H)•:C(+ H(+))) in d[GC*GC*GC*GC*](2) produced only C1'• and not the expected photoproducts from 5-Me-2'-dC•(+). However, photoexcitation of (G(N1-H)•:C(+ H(+))) in d[GGAC*AAGC:CCTAATCG] led to C5'• and C1'• formation. CONCLUSIONS: C-CH(2)• formation from 5-Me-2'-dC•(+) occurs via ground state deprotonation from C5-methyl group on the base. In the excited 5-Me-2'-dC•(+) and 5-Me-2',3'-ddC•(+), spin and charge localization at C3' followed by deprotonation leads to C3'• formation. Thus, deprotonation from C3' in the excited cation radical is kinetically controlled and sugar C-H bond energies are not the only controlling factors in these deprotonations.

Blogging and the health care manager.

The use of blogs in the workplace has emerged as a communication tool that can rapidly and simultaneously connect managers with their employees, customers, their peers, and other key stakeholders. Nowhere is this connection more critical than in health care, especially because of the uncertainty surrounding health care reform and the need for managers to have access to timely and authentic information. However, most health care managers have been slow to join the blogging bandwagon. This article examines the phenomenon of blogging and offers a list of blogs that every health care manager should read and why. This article also presents a simplified step-by-step process to set up a blog.