LENS: A New Pulsed Neutron Source for Research and Education

A new pulsed neutron source is under construction at the Indiana University Cyclotron Facility (IUCF). Neutrons are produced via (p,n) reactions by a low-energy proton beam incident on a thin beryllium target. The source is tightly coupled to a cold methane moderator held at a temperature of 20 K or below. The resulting time-averaged cold neutron flux is expected to be comparable to that of the Intense Pulsed Neutron Source (IPNS) facility at Argonne National Laboratory. The initial experimental suite will include instrumentation for small angle neutron scattering (SANS), moderator studies, radiography, and zero-field spin-echo SANS.     

Women's satisfaction with medical abortion with RU486

The combination of RU486 (mifepristone) and prostaglandin analogues has been used for medical abortion in several European centres. We surveyed 41 Australian women who successfully used this method of abortion in a World Health Organization-sponsored trial. Overall, the women were satisfied with the method and found the associated pain level acceptable.     

Evaluation of head injury in a pediatric emergency department: pretrauma and posttrauma system

OBJECTIVE: To determine if trauma center protocols affect the number of tests and consultations performed and the length of time spent in the emergency department or hospital. DESIGN: A retrospective review and comparison of treatment for children with isolated head injury admitted to the emergency department before trauma center designation (group 1, 1985), and 5 years after implementation of trauma center protocols (group 2, 1991). SETTING: Urban children's hospital, level I trauma center. RESULTS: One hundred sixty-five children met the enrollment criteria in 1985 and 162 met the criteria in 1991. Falls were the predominant mechanism of injury (55%) for both years. For patients with moderate injury (Glasgow Coma Scale score, 9-12) or severe injury (Glasgow Coma Scale score, <9), there was no difference in radiographic or laboratory evaluation. For patients with minimal head injury (Glasgow Coma Scale score, 15, no loss of consciousness, amnesia, seizure, focal neurologic findings, or persistent symptoms) and minor head injury (Glasgow Coma Scale score, >12, and loss of consciousness or amnesia), more radiologic and laboratory studies were done in 1991 that showed no clinically significant abnormalities. Patients with minimal head injury in group 2 were 14 times more likely to have cranial computed tomographic scans performed (95% confidence interval [CI], 3.4-67); 11 times more likely to have cervical spine radiographs (95% CI, 2.2-76.6); and 23 times more likely to have hepatic enzymes obtained (95% CI, 3-491). These differences persisted when analyzed by both the age of the patient and mechanism of injury. CONCLUSIONS: Application of trauma system protocols to isolated head injury patient evaluation results in increased use of laboratory and radiologic services. These practices have the potential to increase the cost of medical care without significantly improving outcome.     

Prevalence and severity of substance use disorders and onset of psychosis in first-admission psychotic patients

BACKGROUND: Past studies have found inconsistent evidence that substance use disorders are related to earlier onset of schizophrenia or more severe symptoms. This study examines prevalence and severity of current substance use disorders and onset of psychotic illness in a multi-facility sample. METHODS: Data are from the Suffolk County Mental Health Project, an epidemiological study of first admission psychosis. The SCID and instruments measuring symptomatology, personality and background characteristics were administered. Respondents were stratified into three groups: (a) no life-time substance diagnosis; (b) in remission or reporting current mild use at admission; and (c) current moderate-severe substance abuse at admission. RESULTS: Using the SCID severity rating, 17.4% of males and 6.2% of the females had moderate or severe current substance abuse, while 41.5% of males and 68.2% of females had no lifetime substance diagnosis. In almost all cases categorized as moderate-severe, the substance diagnosis predated onset of psychosis. Females categorized as moderate-severe have an earlier age of onset of psychosis than did females in the other groups. There were only slight differences in symptom severity among the groups but more marked antisocial behaviour in the moderate-severe group. Variables discriminating the moderate-severe from non-abuse groups were BPRS thought disturbance, adult anti-social behaviour and current cigarette smoking for males and adult anti-social behaviour and child-teen antisocial behaviour for females. CONCLUSIONS: Severity of substance abuse does not appear to be a pivotal correlate of the early features of psychotic illness.     

Preclinical evaluation of anticancer drugs: a model remaining a model!

Two criteria are firstly used in the selection of new anticancer agents:--originality of the mechanism of action and significant experimental antitumor activity in an in vivo animal model. Murine tumors grafted in syngenic mice and human tumor xenografts implanted in nude mice are old models which continue to be widely used. Such models are useful but have the tendency to select many false positives (compounds active in mice but inactive in patients). This discrepancy can be explained by differences due to biological materials and also to the methodologies used in laboratories and clinic. Such models will certainly continue to play a major role in the future but they will have to be used in conditions more relevant for clinical extrapolation. Transgenic mice developing in situ tumors constitute new innovative models for in vivo evaluation of anticancer agents. Finally, a putative new class of antitumor agents emerges with the signal transduction modulators: such compounds have antitumor and toxicological properties very different from those of conventional chemotherapeutic agents. If the first representatives prove to be useful in clinic, rules for toxicology, preclinical and clinical evaluation will have to be changed.     

Trauma exposure and posttraumatic stress disorder in psychosis: Findings from a first-admission cohort.

This study examined the lifetime prevalence of trauma exposure and posttraumatic stress disorder (PTSD) and their demographic, diagnostic, and trauma-related correlates in a clinical cohort of 426 patients with a first psychiatric admission for psychosis. The prevalence of trauma exposure was 68.5%. Female gender and substance abuse were risk factors for trauma exposure. The prevalence of PTSD was 14.3% in the full sample and 26.5% in those with trauma exposure. PTSD was less prevalent in patients with bipolar disorder and schizophrenia and was twice as common in women. Other significant risk factors were younger age and trauma exposure that was repeated and ongoing or that involved childhood victimization. The findings highlight the importance of systematically ascertaining trauma histories in patients with psychotic disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dual topoisomerase I and II inhibition by intoplicine (RP-60475), a new antitumor agent in early clinical trials

The mechanisms of action of intoplicine (RP-60475), a 7H-benzo[e]pyrido[4,3-b]indole derivative that is presently in early clinical trials, have been investigated. Intoplicine induced both topoisomerase I- and II-mediated DNA strand breaks, using purified topoisomerases. The topoisomerase cleavage site patterns induced by intoplicine were unique, relative to those of camptothecin, 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA), and other known topoisomerase inhibitors. Both topoisomerase I- and II-induced DNA breaks decreased at drug concentrations higher than 1 microM, which is consistent with the DNA-intercalating activity of intoplicine. DNA damage was investigated in KB cells in culture by using alkaline elution. Intoplicine induced single-strand breaks (SSB) in a bell-shaped manner with respect to drug concentration (maximum frequency at 1 microM approximately 220 rad-equivalents). SSB formation was fast, whereas reversal after drug removal was slow. Similar bell-shaped curves were obtained for DNA double-strand breaks (DSB) and DNA-protein cross-links. SSB and DNA-protein cross-link frequencies were approximately equal, and no protein-free breaks were detectable, indicating the protein concealment of the breaks, as expected for topoisomerase inhibition. Comparison of SSB and DSB frequencies indicated that intoplicine produced a significant amount of SSB not related to DSB, which is consistent with concomitant inhibition of both DNA topoisomerases I and II in cells. Data derived from resistant cell lines indicated that multidrug-resistant cells were cross-resistant to intoplicine but that m-AMSA- and camptothecin-resistant cells were sensitive to intoplicine. Hence, intoplicine might circumvent topoisomerase I-mediated and topoisomerase II-mediated resistance by poisoning both enzymes simultaneously.     

Functionalization of Carbon Nanoparticles Modulates Inflammatory Cell Recruitment and NLRP3 Inflammasome Activation

The inflammatory effects of carbon nanoparticles (NPs) are highly disputed. Here it is demonstrated that endotoxin‐free preparations of raw carbon nanotubes (CNTs) are very limited in their capacity to promote inflammatory responses in vitro, as well as in vivo. Upon purification and selective oxidation of raw CNTs, a higher dispersibility is achieved in physiological solutions, but this process also enhances their inflammatory activity. In synergy with toll‐like receptor (TLR) ligands, CNTs promote NLRP3 inflammasome activation and it is shown for the first time that this property extends to spherical carbon nano‐onions (CNOs) of 6 nm in size. In contrast, the benzoic acid functionalization of purified CNTs and CNOs leads to significantly attenuated inflammatory properties. This is evidenced by a reduced secretion of the inflammatory cytokine IL‐1β, and a pronounced decrease in the recruitment of neutrophils and monocytes following injection into mice. Collectively, these results reveal that the inflammatory properties of carbon NPs are highly dependent on their physicochemical characteristics and crucially, that chemical surface functionalization allows significant moderation of these properties.