Conformational stability in dinucleoside phosphate crystals. Semiempirical potential energy calculations for uridylyl-3'-5'-adenosine monophosphate (UpA) and guanylyl-3',5'-cytidine monophosphate (GpC)

Classical potential energy calculations were performed for the dinucleoside phosphates UpA and GpC. Two widely accessible low-energy regions of conformation space were found for the w', w pair. That of lowest energy contains conformations similar to helical RNA, with w' and w in the vicinity of 300° and 280°, respectively. All five experimental observations of crystalline GpC, two of ApU, and the helical fragment of ApApA fall in this range. The second lowest region has w' and w at about 20° and 80°, respectively, which is in the general region of one experimentally observed crystalline conformer of UpA, and the nonhelical region of ApApA. It is concluded that GpC and ApU, which were crystallized as either sodium or calcium salts, are shielded from each other in the crystal by the water of hydration and are therefore free to adopt their predicted in vacuo minimum energy helical conformations. By contrast, crystalline UpA had only 1/2 water per molecule, and was forced into higher energy conformations in order to maximize intermolecular hydrogen bonding

Posttraumatic Stress Disorder after Hurricane Sandy among Persons Exposed to the 9/11 Disaster.

BACKGROUND: Traumatic exposure during a hurricane is associated with adverse mental health conditions post-event. The World Trade Center Health Registry provided a sampling pool for a rapid survey of persons directly affected by Hurricane Sandy in the New York City (NYC) metropolitan area in late October 2012. This study evaluated the relationship between Sandy experiences and Sandy-related posttraumatic stress disorder (PTSD) among individuals previously exposed to the September 11, 2001 (9/11) disaster. METHODS: A total of 4,558 surveys were completed from April 10-November 7, 2013. After exclusions for missing data, the final sample included 2,214 (53.5%) respondents from FEMA-defined inundation zones and 1,923 (46.5%) from non-inundation zones. Sandy exposures included witnessing terrible events, Sandy-related injury, fearing for own life or safety of others, evacuation, living in a home that was flooded or damaged, property loss, and financial loss. Sandy-related PTSD was defined as a score of ≥44 on a Sandy-specific PTSD Checklist. RESULTS: PTSD prevalence was higher in the inundation zones (11.3%) and lower in the non-inundation zones (4.4%). The highest prevalence of Sandy-related PTSD was among individuals in the inundation zone who sustained an injury (31.2%), reported a history of 9/11-related PTSD (28.8%), or had low social support prior to the event (28.6%). In the inundation zones, significantly elevated adjusted odds of Sandy-related PTSD were observed among persons with a prior history of 9/11-related PTSD, low social support, and those who experienced a greater number of Sandy traumatic events. CONCLUSIONS: Sandy-related stress symptoms indicative of PTSD affected a significant proportion of persons who lived in flooded areas of the NYC metropolitan area. Prior 9/11-related PTSD increased the likelihood of Sandy-related PTSD, while social support was protective. Public health preparation for events similar to Sandy should incorporate outreach and linkages to care for persons with prior disaster-related trauma

Ignoring Puff Counts: Another Shortcoming of the Federal Trade Commission Cigarette Testing Programme

OBJECTIVES; To examine reasons behind the failure of the Federal Trade Commission (FTC) to preserve puff count information from standard cigarette testing and to elucidate the importance of puff count to overall tar yields.METHODS; We reviewed industry documents on origins of the FTC test and data sets provided by the Tobacco Institute Testing Laboratory to the tobacco industry and FTC for reporting purposes.RESULTS; The majority of the tobacco industry argued for "dual reporting" of tar yields-both per cigarette and per puff. Despite a request from the Tobacco Institute in 1967 that puff count information be preserved, documents and recent communications with the FTC indicate that puff number data have not been maintained by the government. In contrast, for the cigarette industry, puff count data are a fundamental and routine part of testing and important to cigarette design. A sample of puff counts for cigarettes tested in 1996 (n = 471) shows that on average 100 mm cigarettes have 18% more puffs taken on them than do 85 mm cigarettes in standard tests (7.66 vs 9.03; p<0.01). The 10th percentile puff count is 6.8 and the 90th percentile is 8.8 for king size; the 10th percentile puff count is 8.2 and the 90th percentile is 10.0 for 100 mm cigarettes, indicating that puff counts can vary substantially among brands.CONCLUSIONS; The FTC has failed to seek or preserve puff count information that the industry finds important. Any standard test of tar and nicotine yields should at minimum preserve puff count information

Post-traumatic Stress Disorder among American Legionnaires in Relation to Combat Experience in Vietnam: Associated and Contributing Factors

The relationship between combat stress, DSM-III-defined post-traumatic stress disorder (PTSD), and a variety of behavioral factors was examined in a large nonclinical population. A total of 2858 randomly selected American Legion members who had served in Southeast Asia completed a questionnaire which elicited information on military service, personal health, and a variety of mental health outcomes. The data confirm the utility of the PTSD diagnosis as a distinct clinical entity. The frequency of PTSD and the extent of symptoms developed varied with the severity of criteria used for determining the extent of traumatic exposure. The PTSD rate ranged from 1.8 to 15.0% of the total sample, depending on whether "exposure" to combat was defined relatively narrowly or broadly. A distinct linear dose-response relationship between combat stress and a quantitative measure of PTSD intensity was observed. The frequency of PTSD diagnosis was not affected by the presence of either physical or mental health problems which predated military service. A strong, stable relationship was found between combat stress and PTSD intensity for cohorts with differing intervals since the experience of combat trauma, which persisted up to 20 years after discharge from the military. The data thus support a broader approach to defining traumatic events which recognizes individual differences in response to combat, as well as the existence of other behavioral outcomes as residual effects of combat. Implications of these findings and the importance of treating veterans with varying presentations of PTSD are discussed

Chronic Physical Health Consequences of Being Injured During the Terrorist Attacks on World Trade Center on September 11, 2001

Few studies have focused on injuries from the World Trade Center disaster on September 11, 2001. Severe injury has health consequences, including an increased mortality risk 10 years after injury and the risk of mental health problems, such as posttraumatic stress disorder (PTSD). The World Trade Center Health Registry identified 14,087 persons with none of a selected group of preexisting chronic conditions before 2002 who were present during and soon after the World Trade Center attacks, 1,980 of whom reported sustaining 1 or more types of injury (e.g., a broken bone or burn). Survey data obtained during 2003−2004 and 2006−2007 were used to assess the odds of reporting a diagnosis of chronic conditions (heart disease, respiratory disease, diabetes, cancer) up to 5–6 years after the attacks. Number of injury types and probable PTSD were significantly associated with having any chronic conditions diagnosed in 2002–2007. Persons with multiple injuries and PTSD had a 3-fold higher risk of heart disease than did those with no injury and no PTSD, and persons with multiple injuries and with no PTSD had a 2-fold higher risk of respiratory diseases. The present study shows that injured persons with or without comorbid PTSD have a higher risk of developing chronic diseases. Clinicians should be aware of the heightened risk of chronic heart and respiratory conditions among injured persons

Evaluation of non-response bias in a cohort study of World Trade Center terrorist attack survivors

Background: Few longitudinal studies of disaster cohorts have assessed both non-response bias in prevalence estimates of health outcomes and in the estimates of associations between health outcomes and disaster exposures. We examined the factors associated with non-response and the possible non-response bias in prevalence estimates and association estimates in a longitudinal study of World Trade Center (WTC) terrorist attack survivors. Methods: In 2003-04, 71,434 enrollees completed the WTC Health Registry wave 1 health survey. This study is limited to 67,670 adults who were eligible for both wave 2 and wave 3 surveys in 2006-07 and 2011-12. We first compared the characteristics between wave 3 participants (wave 3 drop-ins and three-wave participants) and non-participants (wave 3 drop-outs and wave 1 only participants). We then examined potential non-response bias in prevalence estimates and in exposure-outcome association estimates by comparing one-time non-participants (wave 3 drop-ins and drop-outs) at the two follow-up surveys with three-wave participants. Results: Compared to wave 3 participants, non-participants were younger, more likely to be male, non-White, non-self enrolled, non-rescue or recovery worker, have lower household income, and less than post-graduate education. Enrollees' wave 1 health status had little association with their wave 3 participation. None of the disaster exposure measures measured at wave 1 was associated with wave 3 non-participation. Wave 3 drop-outs and drop-ins (those who participated in only one of the two follow-up surveys) reported somewhat poorer health outcomes than the three-wave participants. For example, compared to three-wave participants, wave 3 drop-outs had a 1.4 times higher odds of reporting poor or fair health at wave 2 (95% CI 1.3-1.4). However, the associations between disaster exposures and health outcomes were not different significantly among wave 3 drop-outs/drop-ins as compared to three-wave participants. Conclusion: Our results show that, despite a downward bias in prevalence estimates of health outcomes, attrition from the WTC Health Registry follow-up studies does not lead to serious bias in associations between 9/11 disaster exposures and key health outcomes. These findings provide insight into the impact of non-response on associations between disaster exposures and health outcomes reported in longitudinal studies

Conformation of Guanosine Cytidine 3',5'-Monophosphate (GpC)

A brief communication of preliminary results of solution of dinucleoside phosphate GpC

The crystal and molecular structure of a calcium salt of guanylyl-3',5'-cytidine (GpC)

The calcium salt, Ca(C_19H_24N_8O_I2P)_2.18H_20, of guanylyl-3',5'-cytidine (GpC) has been refined to an R of 8·2 % for 2918 observed reflections (11% for 4237 reflections, including unobserved). The molecule crystallized in space group P2_1 with a=21·224, b=34·207, c=9·327 Å, β=90·527°, Z=4. The asymmetric unit contains four GpC, 36 waters and two Ca^2+ ions, for a total of 198 non-hydrogen atoms. The four GpC occur as two dimers related by a pseudo C-face-centering. Each dimer consists of two crystallographically independent GpC as Watson-Crick base-pairs, and possesses a pseudo twofold axis broken by a Ca^2+ ion and associated solvent. The structure was solved by an unusual series of steps including semi-empirical potential-energy methods, packing analysis, rigid-body refinement, least-squares and difference Fourier techniques, and direct-methods tangent-formula phase refinement. The four GpC have conformational angles in the range of helical RNA, but are not identical. The different crystallographic environments perturb the GpC from exact symmetry and demonstrate the range of the basic helical conformations. All eight bases are anti, sugars are all C(3’) endo, the C(4')-C(5') bond rotations are gauche-gauche, and the ω', ω angle pair about the O-P bonds is gauche—gauche-

Structure of guanylyl-3′,5′-cytidine monophosphate. II. Description of the molecular and crystal structure of the calcium derivative in space group P2₁

The structural features of calcium guanosine-3′,5′-cytidine monophosphate (GpC) have been elucidated by X-ray diffraction analysis. The molecule was crystallized in space group P2₁ with cell constants of a = 21.224 Å, b = 34.207 Å, c = 9.327 Å, and β = 90.527°, Z = 8. The hydration of the crystal is 21% by weight with 72 water molecules in the unit cell. The four GpC molecules in the asymmetric unit occur as two Watson-Crick hydrogen-bonded dimers related by a pseudo-C face centering. Each dimer consists of two independent GpC molecules whose bases are hydrogen bonded to each other in the traditional Watson-Crick fashion. Each dimer possesses a pseudo twofold axis broken by a calcium ion and associated solvent. The four molecules are conformationally similar to helical RNA, but are not identical to it or to each other. Instead, values of conformational angles reflect the intrinsic flexibility of the molecule within the range of basic helical conformations. All eight bases are anti, sugars are all C3′-endo, and the C4′-C5′ bond rotations are gauche-gauche. The R factor is 12.6% for 2918 observed reflections at 1.2-Å resolution

Structure of guanosine-3′,5′-cytidine monophosphate. I. Semi-empirical potential energy calculations and model-building

The conformation and packing scheme for guanosine-3’,5’-cytidine monophosphate, GpC, were computed by minimizing the classical potential energy. The lowest energy conformation of the isolated molecule had dihedral angles in the range of helical RNA’s, and the sugar pucker was C3‘ endo. This was used as the starting conformation in a packing search over orientation space, the dihedral angles being flexible in this step also. The packing search was restricted by constraints from our x-ray data, namely, (1) the dimensions of the monoclinic unit cell and its pseudo-C2 symmetry (the real space group is P21), (2) t,he location of the phosphorous atom, and (3) the orientation of the bases. In addition, a geometric function was devised to impose Watson-Crick base pairing. Thus, a trial structure could be sought without explicit inclusion of intermolecular potentials. An interactive computer graphics system was used for visualizing the calculated structures. The packing searches yielded two lowest energy schemes in which the molecules had the same conformation (similar to double-helical RNA) but different orientations within the unit cell. One of these was refined by standard x-ray methods to a discrepancy index of 14.4% in the C2 pseudocell. This served as the starting structure for the subsequent refinement in the real P21 cell