Conveying campus sexual misconduct policy information to college and university students: Results from a 7-campus study.

OBJECTIVE: To examine the efficacy of different methods (ie, in-class policy reading; in-class policy reading and discussion; no reading or discussion) to deliver campus sexual misconduct policy information to students on 7 campuses. PARTICIPANTS: A total of 1,195 participants at 7 colleges and universities participated in the study from August to October 2014. Participants were randomly assigned at the class level and completed pretest and posttest surveys assessing knowledge of campus policy and resources and confidence to seek help for sexual assault. RESULTS: Students exposed to a larger dosage of material (in-class policy reading plus discussion) showed greater positive changes in attitudes and knowledge than students who did not receive information or were only read the policy. However, on some indices, students who were only read the policy showed positive outcomes compared with students receiving no intervention. CONCLUSION: Colleges and universities must use engaging methods to disseminate campus sexual misconduct policies to students.

Transition-state-guided drug design for treatment of parasitic neglected tropical diseases.

Many of the deadliest neglected tropical diseases are caused by protozoan and helminthic parasites. These organisms have evolved several enzymes to exploit their host's metabolic resources and evade immune responses. Because these essential proteins are absent in humans, they are targets for antiparasitic drug development. Despite decades of investigation, no therapy has been successful in the eradication of these diseases, so new approaches are desired. Chemically stable analogues of the transition states of enzymatic reactions are often potent inhibitors, and several examples of clinically effective compounds are known for other diseases. The design of transition-state analogues is aided by structural models of the transition state, which are obtained by complementing experimental measurement of kinetic isotope effects with theoretical calculations. Such transition-state-guided inhibitor design has been demonstrated for human, bovine, malarial, and trypanosomal enzymes of the purine salvage pathway, including purine nucleoside phosphorylase, nucleoside hydrolases, and adenosine deaminase. Cysteine proteases, trans-sialidase, 1-deoxy-d-xylulose-5-phosphate reductoisomerase, and trypanothione synthetase are presented as additional candidates for application of transition-state analysis with the goal of identifying new leads for the treatment of parasitic neglected tropical diseases.

Flow and image cytometry in thymic neoplasia: correlation with clinical outcome.

OBJECTIVE: To compare nuclear DNA by flow (FCM) and image cytometry (ICM) in thymic neoplasms and to relate results to clinical outcome. STUDY DESIGN: DNA ploidy of 44 thymomas and 6 thymic carcinomas was studied by FCM and ICM of single nuclear suspensions from paraffin blocks. RESULTS: By FCM, 33 thymomas (75%) and one thymic carcinoma (17%) were diploid; 6 thymomas (14%) and 4 thymic carcinomas (67%) were aneuploid. By ICM, 36 thymomas (82%) were diploid; 7 thymomas (16%) and 6 thymic carcinomas (100%) were aneuploid. Mean follow-up in 44 cases was 46.2 months (range, 1-162). Ten patients with persistent/recurrent disease included four with thymic carcinoma, who died of the disease (two aneuploid by both techniques, two aneuploid by ICM with unsatisfactory/diploid FCM). Four had invasive thymoma and recurrence after 13-150 months (two diploid and two aneuploid by both methods), one had diploidy and noninvasive thymoma that recurred at 92 months, and one had an epithelial thymoma that recurred at 144 months (aneuploid by FCM, diploid by ICM). CONCLUSION: The results obtained in this preliminary, retrospective study show a high concordance between FCM and ICM; aneuploidy correlated with poor outcome by both methodologies. While these findings are encouraging, larger numbers of cases will be needed to define the role of FCM and ICM in predicting outcome in thymic tumors.

Neonatal resuscitation in the isolated setting.

This review attempts a practical guide to unscheduled resuscitation of the newborn in the isolated setting, where high-risk cases have been screened for, identified and referred for delivery in the tertiary care. Regarding airway management in this emergency, there is for the most part consensus in Australia, but this is less so for cardiovascular aspects. Material from the 'Advanced Paediatric Life Support' course, which offers definitive instruction in necessary techniques, has been used as a framework, with added material based on the Australian experience. Internationally, specific aspects of resuscitation are under review.

Predicting life-threatening coagulopathy in the massively transfused trauma patient: hypothermia and acidoses revisited.

BACKGROUND: Recalcitrant coagulopathy "the bloody vicious cycle," produces the majority of deaths after torso trauma. A model predicting this life-threatening complication may facilitate clinical decision-making. METHODS: We prospectively analyzed patients > 15 years old who received a massive transfusion (> 10 units of packed red blood cells (PRBC)/24 h) over a 2-year period. Excluding massive head injuries and pre-existing disease, the 58 study patients had a mean age = 35.4 years, Injury Severity Score (ISS) = 30.6, and PRBC = 24.2 units/24 h. RESULTS: Defined as prothrombin time of two times that of normal laboratory controls and partial thromboplastin time as two times that of normal laboratory controls, 27 patients (47%) developed life-threatening coagulopathy. Using a multiple logistic regression model, the four significant risk factors (with odds ratio) were (1) pH < 7.10 (12.3), (2) temperature < 34 degrees C (8.7), (3) ISS > 25 (7.7), and (4) systolic blood pressure < 70 mm Hg (5.8). The conditional probability of developing coagulopathy was ISS > 25 + systolic blood pressure < 70 mm Hg = 39%, ISS > 25 + temperature < 34 degrees C = 49%, ISS > 25 + pH < 7.10 = 49%; with all four risk factors the incidence was 98%. CONCLUSION: Postinjury life-threatening coagulopathy in the seriously injured requiring massive transfusion is predicted by persistent hypothermia and progressive metabolic acidosis.

Loss of an X chromosome in aggressive angiomyxoma of female soft parts: a case report.

Cytogenetic analysis of an aggressive angiomyxoma of the vulvar region of a 16-year-old female revealed loss of one X chromosome (45,X,-X) in eight of 20 metaphase cells analyzed. Fluorescence in situ hybridization (FISH) performed on disaggregated cells from paraffin embedded lesional tissue confirmed loss of an X chromosome in 31% of cells. Cytogenetic analysis performed on peripheral blood showed a normal chromosomal complement (46,XX). Thus, loss of one X chromosome appears to be confined to the neoplasm. This anomaly has not been previously described in aggressive angiomyxoma.

p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis.

Mutations of the p53 tumor suppressor gene have been described in several subtypes of non-Hodgkin's lymphoma, but the incidence of p53 mutations in mantle cell lymphoma (MCL) is unknown. We hypothesized that cases of MCL with a variant or high-grade cytology would have a higher likelihood of p53 mutations than typical MCL. We were also interested in the prognostic significance of p53 mutations in MCL. Therefore, a series of 53 well-characterized cases of MCL with DNA from 62 tissue samples were analyzed by the polymerase chain reaction with denaturing gradient gel electrophoresis for exons 5-8 of p53. Immunoperoxidase studies with the antibody DO-7 to p53 protein were also performed on frozen sections. We found mutations of the p53 gene in 8 of the 53 cases (15%) of MCL. Missense mutations predominated, and 50% of the mutations occurred at known p53 hotspot codons. Of 21 cases with variant cytology (ie, anaplastic or blastic), 6 (28.6%) had p53 mutations as compared with only 2 of 32 cases (6.3%) with typical MCL cytology (P = .05), and p53 mutations preceded the development of variant cytology in 2 patients. Overexpression of p53 protein was observed in 6 of the 8 cases (75%) with p53 mutations and in none of the 45 wild-type cases. The median survival of the cases with mutant p53 was only 1.3 years (all died), whereas the median survival of cases with germline p53 was 5.1 years (P = .023). These results suggest that mutations of p53 may be one mechanism involved in the development of variant forms of MCL and indicate that p53 mutations in MCL predict a poor prognosis.

Lymphomatous polyposis. A neoplasm of either follicular mantle or germinal center cell origin.

Lymphomatous polyposis (LP) is generally thought to be an expression of non-Hodgkin's lymphoma (NHL) of follicular mantle cell (MC) origin. We report nine patients with LP from more than 3,500 cases of NHL studied by the Nebraska Lymphoma Study Group. Our patients differed from those reported previously in that LP represented a follicular center cell (FCC) NHL in two of the nine cases, with the remainder consisting of MC NHL. Three patients developed LP during a relapse of previously diagnosed and treated extraintestinal MC NHL (parotid gland, tonsil, and inguinal lymph node, respectively), whereas the other six patients presented with primary LP. In seven of the nine LP cases, a large mass predominated among a myriad of small polyps. The FCC cases were confined to the small intestine, whereas the MC cases were either pan-intestinal or colonic on their localization. Two MC cases studied by Southern blotting exhibited rearrangement of the bcl-1 locus. Bcl-2 rearrangement was not detected in any of the nine cases when studied by either a polymerase chain reaction-based assay (seven cases) or by Southern blotting (two cases). To date, four patients (three MC, one FCC) have experienced recurrent NHL in gastrointestinal sites. With follow-up ranging from 13 to 147 months, the entire group had a median survival of 41 months (primary MC LP:13, 13, 41, and 77 months; primary FCC LP:45 and 147 months; secondary MC LP:17, 41 and 76 months), and only one patient has died. We conclude that LP is a rare manifestation of NHL of either follicular MC or germinal center cell origin.

Chilling-Induced Heat Evolution in Plants.

Increases in respiration, particularly via the alternative pathway, are observed in response to chilling. These increases result in increased heat evolution. We have measured increases in heat evolution in response to chilling in a number of plant species using a microcalorimeter. After 8 h of exposure to 8[deg]C, heat evolution in a variety of chilling-sensitive species increased 47 to 98%. No increase in heat evolution was seen with the extremely chilling-sensitive ornamental Episcia cupreata Hook. Heat evolution increased only 7 to 22% in the chilling-resistant species. Increases in heat evolution were observed when plants were chilled in constant light or in the dark, but not when plants were chilled at high humidity. Increased capacity to produce respiratory heat after exposure to chilling temperatures may contribute to the cold-acclimation process.

Splenic infection simulating lymphoma: an unusual presentation of disseminated Pneumocystis carinii infection.

This report of disseminated pneumocystosis in an HIV-infected patient describes an unusual presentation consisting of splenic disease mimicking lymphoma, absence of typical roentgenographic signs of pulmonary or disseminated pneumocystis, and absence of use of aerosolized pentamidine. Because of these factors, a diagnosis of disseminated pneumocystosis was not considered. Our case in combination with other recent reports emphasizes the need to consider disseminated pneumocystosis in HIV-infected patients, even if they have no obvious pulmonary disease and have not received aerosolized pentamidine therapy. Timely recognition of this lethal infection is important for initiation of potentially curative therapy.

The effect of Aviation Officer Candidate's School on aerobic and anaerobic fitness.

The purpose of this study was to determine the effect of Aviation Officer's Candidate School (AOCS) on the aerobic and anaerobic fitness of the candidates. Thirty candidates were tested prior to and post-AOCS. Anaerobic measures included vertical jump and seated shot-put throw. A 1.5-mile run was used as an aerobic measure. Timed push-ups and sit-ups were used as overall strength and endurance measures. Body fat was assessed by OPNAV 6110.1 standards. Statistically significant increases were achieved in all areas, except for body fat and push-ups, which produced no significant changes.

Placement of alkyl substituents on the C-7 piperazine ring of fluoroquinolones: dramatic differential effects on mammalian topoisomerase II and DNA gyrase.

Several substituted analogs of 7-(cis-3,5-dimethylpiperazinyl)-6,8-difluoro-5-amino-1-cyclopropyl quinolone were prepared and tested in a DNA cleavage assay with calf thymus topoisomerase II. Positioning of the methyl groups on the C-7 piperazine ring influenced potency against the mammalian enzyme; the cis-3,5-dimethyl configuration did not stimulate cleavage at drug concentrations less than or equal to 2,000 microM, while the trans configuration was active at drug levels as low as 36 microM. Removal of the cis-methyl groups produced a compound that was only sixfold less potent than the antitumor agent etoposide in stimulating enzyme-mediated DNA cleavage. The cis- and trans-methyl substitutions on the piperazine that conferred potency against the mammalian type II enzyme had little effect on bacterial DNA gyrase cleavage activity, suggesting that an asymmetric barrier exists with the mammalian enzyme which influences productive quinolone interaction, favoring the less bulky trans-3,5-dimethylpiperazine substituent at C-7.

Drug features that contribute to the activity of quinolones against mammalian topoisomerase II and cultured cells: correlation between enhancement of enzyme-mediated DNA cleavage in vitro and cytotoxic potential.

CP-115,953 [6,8-difluoro-7-(4'-hydroxyphenyl)-1-cyclopropyl-4- quinolone-3-carboxylic acid] is a novel quinolone that is highly active against topoisomerase II in vitro and in mammalian cells in culture (M. J. Robinson, B. A. Martin, T. D. Gootz, P. R. McGuirk, M. Moynihan, J. A. Sutcliffe, and N. Osheroff, J. Biol. Chem. 266:14585-14592, 1991). However, the features of the drug that contribute to its activity towards mammalian systems have not been characterized. Therefore, CP-115,953 and a series of related quinolones were examined for their activity against calf thymus topoisomerase II and cultured mammalian cells. CP-115,953 stimulated DNA cleavage mediated by the type II enzyme with a potency that was approximately 600-fold greater than that of the antimicrobial quinolone ciprofloxacin and approximately 50-fold greater than that of the antineoplastic drug etoposide. As determined by the ability to enhance enzyme-mediated DNA cleavage, quinolone activity towards calf thymus topoisomerase II was enhanced by the presence of a cyclopropyl group at the N-1 ring position and by the presence of a fluorine at C-8. Furthermore, the 4'-hydroxyphenyl substituent at the C-7 position was critical for the potency of CP-115,953 towards the mammalian type II enzyme. In this regard, the aromatic nature of the C-7 ring as well as the presence and the position of the 4'-hydroxyl group contributed greatly to drug activity. Finally, the cytotoxicity of quinolones in the CP-115,953 series towards mammalian cells paralleled the in vitro stimulation of DNA cleavage by topoisomerase II rather than the inhibition of enzyme-catalyzed DNA relaxation. This correlation strongly suggests that these quinolones promote cell death by converting topoisomerase II to a cellular poison.

Biologic properties of eugenol and zinc oxide-eugenol. A clinically oriented review.

Eugenol-containing dental materials are frequently used in clinical dentistry. When zinc oxide-eugenol (ZOE) is applied to a dentinal cavity, small quantities of eugenol diffuse through the dentin to the pulp. Low concentrations of eugenol exert anti-inflammatory and local anesthetic effects on the dental pulp. Thus use of ZOE temporary filling may facilitate pulpal healing; on the other hand, high eugenol concentrations are cytotoxic. Direct application of eugenol to pulp tissue may result in extensive tissue damage. The ability of ZOE-based endodontic sealers to influence periapical tissue healing is considered in view of eugenol's anti-inflammatory and toxic properties.

Effects of CO2 laser irradiation on pulpal blood flow.

CO2 laser may be beneficially applied to teeth in preventive and restorative dentistry, but its physiopathologic effects on the dental pulp have not been reported. To address the dynamic pulpal changes induced by CO2 laser the purpose of this study was to examine such changes in pulpal microcirculation. The enamel surfaces of 4 cat canines were irradiated by CO2 laser beam, delivered by either a handpiece or microslad with a focal spot diameter of 0.21mm and 0.33mm, respectively. Exposure powers of 2.6-20 W were used for durations of 0.05-0.2 sec, resulting in energy density range of 304-1440 J/cm2. Non-invasive measurement of pulpal blood flow (PBF) by a laser Doppler flowmeter was maintained continuously before and following CO2 laser irradiation. CO2 laser irradiation resulted in an immediate increase in PBF, which subsided after 2-3 min. Large pulps responded with a significantly higher PBF increase than small pulps. These results confirm that CO2 laser irradiation of the tooth surface has a thermal effect on the pulp, which is moderated by the insulating capability of dentin. It appears that the associated thermal damage is not extensive when laser exposure parameters are such as used herein.

Effects of quinolone derivatives on eukaryotic topoisomerase II. A novel mechanism for enhancement of enzyme-mediated DNA cleavage.

The effects of two novel quinolone derivatives, CP-67,804 and CP-115,953 (the 1-ethyl and 1-cyclopropyl derivatives of 6,8-difluoro-7-(4-hydroxyphenyl)-4-quinolone-3-carboxylic acid, respectively), on the enzymatic activities of Drosophila melanogaster topoisomerase II were examined. Both drugs enhanced the enzyme's pre- and post-strand passage DNA cleavage activities. CP-67,804 was nearly as potent an enhancer as etoposide, while CP-115,953 was approximately 2 times more potent than this topoisomerase II-targeted antineoplastic drug. In contrast to etoposide, which stabilizes enzyme-DNA cleavage complexes primarily by inhibiting topoisomerase II-mediated DNA religation, neither quinolone impaired the enzyme's ability to religate cleaved DNA. To further assess the characteristics of these unusual quinolone derivatives, the cytotoxic effects of CP-67,804 and CP-115,953 toward wild-type Chinese hamster ovary cells and VpmR-5 cells (an epipodophyllotoxin-resistant Chinese hamster ovary line) were examined. Both quinolones were cytotoxic to the wild-type cells. CP-115,953 was the more potent agent and displayed a level of cytotoxicity similar to that of etoposide. Finally, the VpmR-5 line showed cross-resistance to CP-67,804 (approximately 3.7-fold) and CP-115,953 (approximately 1.3-fold). Although quinolone cross-resistance was less pronounced than observed for etoposide (approximately 12-fold), it indicates that topoisomerase II is a physiological target for CP-67,804 and CP-115,953 in mammalian cells. These findings strongly suggest that these quinolone derivatives represent a novel class of topoisomerase II-targeted drugs which have potential as antineoplastic agents.

Influence of alcohols, temperature, and region on the mobility of lipids in neuronal membrane.

Fluorescence recovery after photobleaching was used to examine lipid diffusibility in different regions of Aplysia neurons. Differences in diffusion of 1-acyl-2-(6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4- yl)]aminohexanoyl)phosphatidylcholine (NBD-C6-PC) in the cell body, axon hillock, and axon were not apparent. Lipid diffusibility during temperature variations and exposure to alcohols was also examined by photobleaching techniques. For these studies, all measurements were made on the cell body. Alcohols were found to be selective in their effects upon the diffusibility of lipid probes. Neither ethanol nor butanol affected the diffusibility of NBD-PC. However, at the same concentrations, both of these alcohols caused a significant increase in the diffusion coefficient (D) for rhodamine-phosphatidylethanolamine (Rho-PE). The diffusion coefficient for NBD-PC in the cell body plasma membrane did not increase with warming, between 4 degrees C and 25 degrees C. The fraction of lipid probe free to diffuse (per cent recovery; %R) however, increased as temperature increased, within this range. The nonconventional relationship between temperature and D was even more pronounced for Rho-PE. As temperature increased, D became smaller for this probe, concurrent with an increase in %R. These results suggest that immobile viscous lipid is recruited into a mobile fraction as temperature increases, resulting in the maintenance of constant diffusibility. The effects of temperature on D and %R, and the selective effects of alcohols on lipid diffusibility suggest that the membrane is heterogeneously organized, on a submicroscopic scale, into domains. The implications of this organization for nerve function and responses of nervous systems to temperature and anesthetics are discussed.

Assessing the educational needs of post-myocardial infarction patients.

Nurses involved in cardiac rehabilitation have a responsibility and an opportunity to promote positive changes in lifestyle through patient education programs. Assessing patients' needs and setting goals with the patient are essential for attainment of the maximum benefit from the educational program. The problem of dwindling resources and pressures to control health care costs have complicated the delivery of this care in some institutions. The educational strategy chosen by the nurse will depend on the resources available. Nevertheless, whichever strategy is chosen, the nurse, by virtue of his or her role in the health care delivery system and specialized knowledge, can still significantly impact on the successful goal attainment of goals for increasing numbers of post-myocardial infarction patients.