Combinatorial Approach to Find Nanoparticle Assemblies with Maximum Surface-Enhanced Raman Scattering.

Plasmonic nanoparticles exhibit unique properties that distinguish them from other nanomaterials, including vibrant visible colors, the generation of local electric fields, the production of hot charge carriers, and localized heat emission. These properties are particularly enhanced in the narrow nanogaps formed between nanostructures. Therefore, creating nanogaps in a controlled fashion is the key to achieving a fundamental understanding of plasmonic phenomena originating from the nanogaps and developing advanced nanomaterials with enhanced performance for diverse applications. One of the most effective approaches to creating nanogaps is to assemble individual nanoparticles into a clustered structure. In this study, we present a fast, facile, and highly efficient method for preparing core@satellite (CS) nanoassembly structures using gold nanoparticles of various shapes and sizes, including nanospheres, nanocubes (AuNCs), nanorods, and nanotriangular prisms. The sequential assembly of these building blocks on glass substrates allows us to obtain CS nanostructures with a 100% yield within 4 h. Using 9 different building blocks, we successfully produce 16 distinct CS nanoassemblies and systematically investigate the combinations to search for the highest Raman enhancement. We find that the surface-enhanced Raman scattering (SERS) intensity of AuNC@AuNC CS nanoassemblies is 2 orders of magnitude larger than that of other CS nanoassemblies. Theoretical analyses reveal that the intensity and distribution of the electric field induced in the nanogaps by plasmon excitation, as well as the number of molecules in the interfacial region, collectively contribute to the unprecedentedly large SERS enhancement observed for AuNC@AuNC. This study not only presents a novel assembly method that can be extended to produce many other nanoassemblies but also identifies a highly promising SERS material for sensing and diagnostics through a systematic search process.

A qualitative study of people who use methamphetamine during the early COVID-19 pandemic to inform future ED harm reduction strategies.

BACKGROUND: Morbidity and mortality rates related to methamphetamine are on the rise. Simultaneously, social-distancing guidelines were issued in March 2020 to decrease transmission of COVID-19. The aim of this study was to explore concerns regarding methamphetamine use during the COVID-19 pandemic and subsequent harm reduction strategies with patients who use methamphetamine to inform emergency department (ED)-based harm reduction approaches. METHODS: A mixed-methods study of adults residing in Washington with high-risk methamphetamine use and a recent ED visit from April-September 2020 was performed. Participants completed a survey and a semi-structured interview on perceptions and experiences of COVID-19. Descriptive statistics were used for survey responses. Interview transcripts were analyzed and guided by modified grounded theory using an iterative approach to refine the guide and codebook. Interviews were independently coded by 2 investigators and discussed until consensus. RESULTS: Twenty-five participants completed the survey; 20 participants were interviewed (45% recently used heroin, 40% unstably housed). Thirty-five percent was worried about COVID-19 infection. Three themes emerged from the interviews: (1) increase in meth use, (2) interplay of meth obtention and COVID-19, and (3) interactions with healthcare and social services. CONCLUSIONS: People who use methamphetamine noted an increase in use along with the social distancing guidelines put in place for COVID-19 and employed a variety of harm reduction profiles when obtaining methamphetamine. Also, the pandemic brought difficulties in accessing care and amplified mistrust in healthcare instructions and public health messages. Based on these qualitative interviews, further work should consider aligning methamphetamine and COVID-19 harm reduction messages and working with trusted community resources to improve harm reduction strategies for methamphetamine use and COVID-19. IRB: Informed Consent by the University of Washington Human Subjects Division (approval number, STUDY00009277).

Identification of Vietnamese Flea Species and Their Associated Microorganisms Using Morphological, Molecular, and Protein Profiling.

Fleas are obligatory blood-sucking ectoparasites of medical and veterinary importance. The identification of fleas and associated flea-borne microorganisms, therefore, plays an important role in controlling and managing these vectors. Recently, Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) has been reported as an innovative and effective approach to the identification of arthropods, including fleas. This study aims to use this technology to identify ethanol-preserved fleas collected in Vietnam and to use molecular biology to search for microorganisms associated with these fleas. A total of 502 fleas were collected from wild and domestic animals in four provinces in Vietnam. Morphological identification led to the recognition of five flea species, namely Xenopsylla cheopis, Xenopsylla astia, Pulex irritans, Ctenocephalides canis, and Ctenocephalides felis. The cephalothoraxes of 300 individual, randomly selected fleas were tested using MALDI-TOF MS and molecular analysis for the identification and detection of microorganisms. A total of 257/300 (85.7%) of the obtained spectra from the cephalothoraxes of each species were of good enough quality to be used for our analyses. Our laboratory MALDI-TOF MS reference database was upgraded with spectra achieved from five randomly selected fleas for every species of Ctenocephalides canis and Ctenocephalides felis. The remaining spectra were then queried against the upgraded MALDI-TOF MS database, which showed 100% correspondence between morphology and MALDI-TOF MS identification for two flea species (Ctenocephalides canis and Ctenocephalides felis). The MS spectra of the remaining species (three P. irritans, five X. astia, and two X. cheopis) were visually generated low-intensity MS profiles with high background noise that could not be used to update our database. Bartonella and Wolbachia spp. were detected in 300 fleas from Vietnam using PCR and sequencing with primers derived from the gltA gene for Bartonella and the 16S rRNA gene for Wolbachia, including 3 Bartonella clarridgeiae (1%), 3 Bartonella rochalimae (1%), 1 Bartonella coopersplainsensis (0.3%), and 174 Wolbachia spp. endosymbionts (58%).

"That Line Just Kept Moving": Motivations and Experiences of People Who Use Methamphetamine.

INTRODUCTION: Methamphetamine use is on the rise with increasing emergency department (ED) visits, behavioral health crises, and deaths associated with use and overdose. Emergency clinicians describe methamphetamine use as a significant problem with high resource utilization and violence against staff, but little is known about the patient's perspective. In this study our objective was to identify the motivations for initiation and continued methamphetamine use among people who use methamphetamine and their experiences in the ED to guide future ED-based approaches. METHODS: This was a qualitative study of adults residing in the state of Washington in 2020, who used methamphetamine in the prior 30 days, met criteria for moderate- to high-risk use, reported recently receiving care in the ED, and had phone access. Twenty individuals were recruited to complete a brief survey and semi-structured interview, which was recorded and transcribed prior to being coded. Modified grounded theory guided the analysis, and the interview guide and codebook were iteratively refined. Three investigators coded the interviews until consensus was reached. Data was collected until thematic saturation. RESULTS: Participants described a shifting line that separates the positive attributes from the negative consequences of using methamphetamine. Many initially used methamphetamine to enhance social interactions, combat boredom, and escape difficult circumstances by numbing the senses. However, continued use regularly led to isolation, ED visits for the medical and psychological sequelae of methamphetamine use, and engagement in increasingly risky behaviors. Because of their overwhelmingly frustrating experiences in the past, interviewees anticipated difficult interactions with healthcare clinicians, leading to combativeness in the ED, avoidance of the ED at all costs, and downstream medical complications. Participants desired a non-judgmental conversation and linkage to outpatient social resources and addiction treatment. CONCLUSION: Methamphetamine use can lead patients to seek care in the ED, where they often feel stigmatized and are provided little assistance. Emergency clinicians should acknowledge addiction as a chronic condition, address acute medical and psychiatric symptoms adequately, and provide positive connections to addiction and medical resources. Future work should incorporate the perspectives of people who use methamphetamine into ED-based programs and interventions.

Mosquitoes and Mosquito-Borne Diseases in Vietnam.

Mosquito-borne diseases pose a significant threat to humans in almost every part of the world. Key factors such as global warming, climatic conditions, rapid urbanisation, frequent human relocation, and widespread deforestation significantly increase the number of mosquitoes and mosquito-borne diseases in Vietnam, and elsewhere around the world. In southeast Asia, and notably in Vietnam, national mosquito control programmes contribute to reducing the risk of mosquito-borne disease transmission, however, malaria and dengue remain a threat to public health. The aim of our review is to provide a complete checklist of all Vietnamese mosquitoes that have been recognised, as well as an overview of mosquito-borne diseases in Vietnam. A total of 281 mosquito species of 42 subgenera and 22 genera exist in Vietnam. Of those, Anopheles, Aedes, and Culex are found to be potential vectors for mosquito-borne diseases. Major mosquito-borne diseases in high-incidence areas of Vietnam include malaria, dengue, and Japanese encephalitis. This review may be useful to entomological researchers for future surveys of Vietnamese mosquitoes and to decision-makers responsible for vector control tactics.

MALDI-TOF mass spectrometry identification of mosquitoes collected in Vietnam.

BACKGROUND: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a tool that has revolutionised clinical microbiology and has recently been described as an innovative and effective approach to arthropod identification. METHODS: In this study, mosquitoes were captured in Vietnam using four different methods (human landing catch, CDC light traps, BG-Sentinel traps, animal-baited net traps). A total of 4215 mosquitoes were captured and morphologically identified as belonging to three genera: Aedes, Anopheles and Culex. We randomly selected 1253 mosquitoes, including 662 specimens of 14 Anopheles species, 200 specimens of two Aedes species and 391 morphologically unidentified Culex specimens, for molecular and MALDI-TOF MS analysis. The DNA from 98 mosquitoes (69 Anopheles specimens, 23 Culex specimens and six Aedes sp. specimens) was subjected to molecular analysis, either to confirm our morphological identification or the MALDI-TOF MS results, as well as to identify the Culex species that were morphologically identified at the genus level and to resolve the discrepancies between the morphological identification and the MALDI-TOF MS identification. RESULTS: High-quality MS spectra were obtained for 1058 of the 1253 specimens (84%), including 192/200 for Aedes, 589/662 for Anopheles and 277/391 for Culex. The blind test showed that 986/997 (99%) of the specimens were correctly identified by MALDI-TOF MS, with log score values ranging from 1.708 to 2.843. Eleven specimens of Culex could not be identified based on morphological features, MALDI-TOF MS or molecular analysis. CONCLUSIONS: This study enabled us to identify several species of mosquitoes from Vietnam using MALDI-TOF MS, and to enrich our database of MALDI-TOF MS reference spectra.

The Emergency Department Longitudinal Integrated Care (ED-LINC) intervention targeting opioid use disorder: A pilot randomized clinical trial.

INTRODUCTION: Opioid use disorder (OUD) and related comorbid conditions are highly prevalent among patients presenting to emergency department (ED) settings. Research has developed few comprehensive disease management strategies for at-risk patients presenting to the ED that both decrease illicit opioid use and improve initiation and retention in medication treatment for OUD (MOUD). METHODS: The research team conducted a pilot pragmatic clinical trial that randomized 40 patients presenting to a single ED to a collaborative care intervention (n = 20) versus usual care control (n = 20) conditions. Interviewers blinded to patient intervention and control group status followed-up with participants at 1, 3, and 6 months after presentation to the ED. The 3-month Emergency Department Longitudinal Integrated Care (ED-LINC) collaborative care intervention for patients at risk for OUD included: 1) a Brief Negotiated Interview at bedside, 2) overdose education and facilitation of MOUD, 3) longitudinal proactive care management, 4) utilization of the statewide health information exchange platform for 24/7 tracking of recurrent ED utilization, and 5) weekly caseload supervision that incorporated measurement-based care treatment assessment with stepped-up care for patients with recalcitrant symptoms. RESULTS: Overall, the ED-LINC intervention was feasibly delivered and acceptable to patients. The pilot study achieved >80% follow-up rates at 1, 3, and 6 months. In adjusted longitudinal mixed model regression analyses, no statistically significant differences existed in days of opioid use over the past 30 days for ED-LINC intervention patients when compared to patients receiving usual care (incidence-rate ratio (IRR) 1.50, 95% CI 0.54-4.16). The unadjusted mean number of days of illicit opioid use decreased at the 1-month and 3-month follow-up time points for both groups. ED-LINC intervention patients had increased rates of MOUD initiation compared to control patients (50% versus 30%); intervention versus control comparisons did not achieve statistical significance, although power to detect significant differences in the pilot was limited. CONCLUSIONS: The ED-LINC intervention for patients with OUD can be feasibly implemented and warrants testing in larger scale, adequately powered randomized pragmatic clinical trial investigations. CLINICALTRIALS: gov NCT03699085.

Morphological, molecular and MALDI-TOF MS identification of ticks and tick-associated pathogens in Vietnam.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been reported as a promising and reliable tool for arthropod identification, including the identification of alcohol-preserved ticks based on extracted leg protein spectra. In this study, the legs of 361 ticks collected in Vietnam, including 251 Rhiphicephalus sanguineus s.l, 99 Rhipicephalus (Boophilus) microplus, two Amblyomma varanensis, seven Dermacentor auratus, one Dermacentor compactus and one Amblyomma sp. were submitted for MALDI-TOF MS analyses. Spectral analysis showed intra-species reproducibility and inter-species specificity and the spectra of 329 (91%) specimens were of excellent quality. The blind test of 310 spectra remaining after updating the database with 19 spectra revealed that all were correctly identified with log score values (LSV) ranging from 1.7 to 2.396 with a mean of 1.982 ± 0.142 and a median of 1.971. The DNA of several microorganisms including Anaplasma platys, Anaplasma phagocytophilum, Anaplasma marginale, Ehrlichia rustica, Babesia vogeli, Theileria sinensis, and Theileria orientalis were detected in 25 ticks. Co-infection by A. phagocytophilum and T. sinensis was found in one Rh. (B) microplus.

Indicators for Assessing the Quality of Refractive Error Care.

SIGNIFICANCE: Quality refractive error care is essential for reducing vision impairment. Quality indicators and standardized approaches for assessing the quality of refractive error care need to be established. PURPOSE: This study aimed to develop a set of indicators for assessing the quality of refractive error care and test their applicability in a real-world setting using unannounced standardized patients (USPs). METHODS: Patient outcomes and three quality of refractive error care (Q.REC) indicators (1, optimally prescribed spectacles; 2, adequately prescribed spectacles; 3, vector dioptric distance) were developed using existing literature, refraction training standards, and consulting educators. Twenty-one USPs with various refractive errors were trained to visit optical stores across Vietnam to have a refraction, observe techniques, and order spectacles. Spectacles were assessed against each Q.REC indicator and tested for associations with vision and comfort. RESULTS: Overall, 44.1% (184/417) of spectacles provided good vision and comfort. Of the spectacles that met Q.REC indicators 1 and 2, 62.5 and 54.9%, respectively, provided both good vision and comfort. Optimally prescribed spectacles (indicator 1) were significantly more likely to provide good vision and comfort independently compared with spectacles that did not meet any indicator (good vision: 94.6 vs. 85.0%, P = .01; comfortable: 66.1 vs. 36.3%, P < .01). Adequately prescribed spectacles (indicator 2) were more likely to provide good comfort compared with spectacles not meeting any indicator (57.7 vs. 36.3%, P < .01); however, vision outcomes were not significantly different (85.9 vs. 85.0%, P = .90). Good vision was associated with a lower mean vector dioptric distance (P < .01) but not with comfort (P = .52). CONCLUSIONS: The optimally prescribed spectacles indicator is a promising approach for assessing the quality of refractive error care without additional assessments of vision and comfort. Using USPs is a practical approach and could be used as a standardized method for evaluating the quality of refractive error care.

Plasmon-driven protodeboronation reactions in nanogaps.

Boronic acids are the key compounds in Suzuki coupling reactions and in the detection of monosaccharides. The C-B bond cleavage deboronation is an important side reaction that lowers the Suzuki coupling reaction yield and even disables saccharide detection. Here, we report that protodeboronation occurs for 4-mercaptophenylboronic acid (MPBA) within narrow nanogaps between gold nanoparticles (AuNPs) and planar gold substrates. The irradiation of such nanoparticle-on-mirror (NPoM) systems at 785 nm drives the protodeboronation reaction to form benzenethiol (BT). Wavelength-dependence experiments, combined with dark-field single-particle scattering spectroscopy, reveal that excitation of the bonding dipole plasmon mode of the NPoM leads to the best efficiency. Among the excited plasmon decay pathways, the generation of hot charge carriers induces the protodeboronation of MPBA. The possibility of plasmonic thermal reactions is ruled out because external heating of the substrates does not cause the reaction to take place. A comparison of the reaction yield under ambient, Ar, and oxygen gas conditions reveals that hot charge carriers directly transfer to MPBA, which subsequently produces BT, but the presence of oxygen promotes the reaction by opening another hot-electron transfer channel. The protodeboronation reaction of MPBA is an important addition to the catalog of plasmon-driven chemical reactions, not only because the reaction is relevant to organic and analytical chemistry but also because it deepens our understanding of the hot carrier dynamics at the interface between plasmonic nanoparticles and molecules.

Identification of processes that mediate the impact of workplace violence on emergency department healthcare workers in the USA: results from a qualitative study.

OBJECTIVES: Violence towards emergency department healthcare workers is pervasive and directly linked to provider wellness, productivity and job satisfaction. This qualitative study aimed to identify the cognitive and behavioural processes impacted by workplace violence to further understand why workplace violence has a variable impact on individual healthcare workers. DESIGN: Qualitative interview study using a phenomenological approach to initial content analysis and secondary thematic analysis. SETTING: Three different emergency departments. PARTICIPANTS: We recruited 23 emergency department healthcare workers who experienced a workplace violence event to participate in an interview conducted within 24 hours of the event. Participants included nurses (n=9; 39%), medical assistants (n=5; 22%), security guards (n=5; 22%), attending physicians (n=2; 9%), advanced practitioners (n=1; 4%) and social workers (n=1; 4%). RESULTS: Five themes emerged from the data. The first two supported existing reports that workplace violence in healthcare is pervasive and contributes to burn-out in healthcare. Three novel themes emerged from the data related to the objectives of this study: (1) variability in primary cognitive appraisals of workplace violence, (2) variability in secondary cognitive appraisals of workplace violence and (3) reported use of both avoidant and approach coping mechanisms. CONCLUSION: Healthcare workers identified workplace violence as pervasive. Variability in reported cognitive appraisal and coping strategies may partially explain why workplace violence negatively impacts some healthcare workers more than others. These cognitive and behavioural processes could serve as targets for decreasing the negative effect of workplace violence, thereby improving healthcare worker well-being. Further research is needed to develop interventions that mitigate the negative impact of workplace violence.

Emotional suppression in torture survivors: Relationship to posttraumatic stress symptoms and trauma-related negative affect.

While clinical reports suggest that torture survivors may try to suppress their emotions during torture, little is known about the use of emotional suppression following torture. In this study, 82 refugees and asylum-seekers (including 33 torture survivors) completed self-report measures of trait suppression, PTSD symptoms and baseline negative affect before being exposed to images depicting scenes of interpersonal trauma. The use of suppression while viewing the images was indexed and negative affect was measured both immediately after viewing the images and following a five minute rest period. Findings indicated that torture survivors did not show higher rates of trait suppression or state emotional suppression during the experimental session compared to non-torture survivors. However, torture survivors who endorsed state suppression higher levels of distress, and this relationship was especially strong for those with more severe PTSD symptoms. In contrast, there was a negative relationship between state suppression and distress for non-torture survivors with high levels of PTSD symptoms. These findings suggest that, while torture exposure does not lead to greater use of suppression, it does influence the impact of suppression on emotional responses to stimuli.

Preoperative staging of invasive bladder cancer with dynamic gadolinium-enhanced magnetic resonance imaging: results from a prospective study.

OBJECTIVE: To evaluate the accuracy of dynamic gadolinium-enhanced magnetic resonance imaging (DGE-MRI) to detect extravesical bladder cancer (BC) and lymph node-positive disease in patients with invasive BC. MATERIAL AND METHODS: In a prospective single-center study from 2004 to 2009, patients with clinically invasive BC, who were candidates for curative surgery, underwent preoperative DGE-MRI. Radiologic T and N staging was determined by 2 MRI expert radiologists, and the interobserver agreement was calculated. The sensitivity, specificity, positive and negative predictive values, and accuracy of radiologic staging in differentiating lymph node-negative organ-confined vs nonorgan-confined BC and negative vs positive nodal disease was determined and compared with the postoperative pathologic staging as the reference standard method. RESULTS: A total of 122 patients (72 men) with a mean age of 67.8 years were included. Pathologic examination revealed invasive BC in 80/122 (65.5%), including stage pT4 in 15/122 (12.3%), pT3 in 27/122 (22.1%), and pT2 in 38/122 (31.1%), and 27 patients (22.1%) had node-positive disease. The interobserver agreement for T and N staging according to the κ score was 0.44 and 0.49, respectively. The sensitivity, specificity, and accuracy of DGE-MRI in differentiating lymph node-negative organ-confined from nonorgan-confined BC was 87.5%, 47.6%, and 74% and for the detection of positive nodal disease was 40.7%, 91.5%, and 80.3%, respectively. CONCLUSION: We have presented the results of the largest cohort of patients with invasive BC underwent preoperative DGE-MRI. Although DGE-MRI improved T and N staging of invasive BC, it is still not the ideal modality and needs a standardized protocol for interpretation of the imaging findings.

Circadian rhythms of heart rate and locomotion after treatment with low-dose acetylcholinesterase inhibitors.

This study tested the hypothesis that repeated exposure to low levels of sarin, pyridostigmine bromide (PB) or their combination, at doses equivalent to those possibly experienced by veterans of the 1991 Persian Gulf War, could lead to persistent or delayed autonomic effects and thus help to explain the cause of clinical findings in this population. Male Sprague-Dawley rats were treated for 3 weeks with: saline injection (0.5 ml kg(-1), s.c., 3 times weekly) with tap drinking water (control); saline injection with PB (80 mg l(-1) in drinking water); sarin injection (62.5 microg kg(-1), s.c., 0.5 x LD(50), 3 times weekly) with tap drinking water (sarin); or sarin injection with PB in drinking water (sarin + PB). At 2, 4 or 16 weeks post-treatment, heart rate (HR) and locomotor activity (LA) were studied by radiotelemetry. Two weeks posttreatment, HR in drug-treated animals was significantly lower than in controls. A decrease in low-frequency HR power spectrum (PS) was found at 00:00 h and 08:00 h with sarin + PB and at 00:00 h with sarin, while total power was enhanced with sarin + PB at 22:00 h. Minimal effects of drug treatments on HR and HR PS were detected at 4 and 16 weeks post-treatment. No significant differences in LA between control and other groups were found. Since no consistent long-term effects were found in any of the variables studied, these experiments do not support the hypothesis that repeated administration of low doses of PB and the nerve agent sarin can induce persistent or delayed alterations in autonomic function.

Effects of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, on human mast cells bearing wild-type or mutated codon 816 c-kit.

Most adults with systemic mastocytosis (SM) carry an activating mutation in the codon 816 of c-kit. We investigated the activity of the new tyrosine kinase inhibitor AMN107 on c-kit mutated mast cell lines and bone marrow samples from patients with SM and compared it to that of imatinib mesylate, a tyrosine kinase inhibitor effective in some patients with SM. In HMC-1(560) mast cells carrying wild-type codon 816 c-kit, AMN107 was very effective and as potent as imatinib in inhibiting cellular proliferation and inducing apoptosis (P<0.0823). By contrast, in HMC-1(560,816) cells bearing a c-kit mutation in codon 816, neither drug exerted a significant effect (P<0.0015). AMN107 was also as effective as imatinib in inhibiting phosphorylation of c-kit in HMC-1(560) cells. However, AMN107 had little effect on ex vivo survival of bone marrow mast cells with 816 c-kit mutation obtained from patients with SM. Based upon our results, AMN107 and imatinib are equipotent against mast cells with wild-type c-kit and those harboring the juxtamembrane D560G c-kit mutant but have no significant activity over the dose range tested against cells expressing the c-kit D816V mutant tyrosine kinase.

Activity of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, against human FIP1L1-PDGFR-alpha-expressing cells.

Idiopathic hypereosinophilic syndrome (HES) is a myeloproliferative disorder characterized by tissue involvement and organ dysfunction due to abnormal eosinophil proliferation. In a subset of patients, this is caused by the FIP1L1-PDGFR-alpha fusion tyrosine kinase. Cumulative evidence indicates that the Bcr-Abl tyrosine kinase inhibitor imatinib mesylate (Gleevec) is active for the treatment of patients with HES, particularly those expressing the FIP1L1-PDGFR-alpha oncoprotein. The novel tyrosine kinase inhibitor AMN107 was initially developed as a potent Bcr-Abl inhibitor based on the molecular structure of imatinib. We tested the in vitro efficacy of imatinib and AMN107 in the EOL-1 cell line and in cells from a patient with HES harboring the FIP1L1-PDGFR-alpha fusion kinase. AMN107 was as potent as imatinib in inducing apoptosis and inhibiting proliferation of EOL-1 cells, with IC(50) values of 0.54 and 0.20 nM, respectively. In addition, both drugs inhibited the phosphorylation of PDGFR-alpha tyrosine kinase with equivalent efficacy. We conclude that AMN107 and imatinib are active and equipotent against cells expressing the FIP1L1-PDGFR-alpha fusion gene.

Cerebral acetylcholine and choline contents and turnover following low-dose acetylcholinesterase inhibitors treatment in rats.

Male Sprague-Dawley rats were treated for 3 weeks with (1) regular tap drinking water plus subcutaneous (s.c.) saline (0.5 ml/kg) injections three times/week, (2) pyridostigmine bromide (PB) in drinking water (80 mg/L) plus s.c. saline injections three times/week, (3) regular tap drinking water plus s.c. sarin (0.5 x LD(50)) injections three times/week, or (4) PB in drinking water plus s.c. sarin injections three times/week. Repeated doses of sarin, in the presence or absence of PB, were devoid of acute toxicity during the three-week treatment period. Two, 4, and 16 weeks post-treatment, animals were given an intravenous pulse injection of choline labeled with 4 deuterium atoms (D4Ch) followed, after 1 min, by microwave fixation of the brain in vivo. Tissue levels of endogenous acetylcholine (D0ACh), endogenous choline (D0Ch), D4Ch, and ACh synthesized from D4Ch (D4ACh) were measured by gas-chromatography mass-spectrometry in hippocampus, infundibulum, mesencephalon, neocortex, piriform cortex, and striatum. Ch uptake from blood and ACh turnover were estimated from D4Ch and D4ACh concentrations in brain tissue, respectively. Statistically significant differences among brain regions were found for D0Ch, D4Ch, D0ACh and D4ACh at 2, 4 and 16 weeks post-treatment. However, differences in the values of these parameters between control and drug treatments were found only for D0ACh and D0Ch at 2 and 4 weeks, but not at 16 weeks post-treatment. In conclusion, the results from these experiments do not support a delayed or persistent alteration in cholinergic function after exposure to low doses of PB and/or sarin.

Low-dose cholinesterase inhibitors do not induce delayed effects on cerebral blood flow and metabolism.

The acetylcholinesterase (AChE) inhibitors sarin and pyridostigmine bromide (PB) have been proposed as causes of neurobehavioral dysfunction in Persian Gulf War veterans. To test possible delayed effects of these agents, we exposed rats to low (subsymptomatic) levels of sarin (0.5 LD50 s.c. 3 times weekly) and/or PB (80 mg/L in drinking water) for 3 weeks. Controls received saline s.c. and tap water. At 2, 4 and 16 weeks after exposure, regional cerebral blood flow (rCBF) and glucose utilization (rCGU) were measured in conscious animals with the Iodo-14C-antipyrine and 14C-2 deoxyglucose methods, respectively. Two weeks after exposure, PB+sarin caused significant rCBF elevations, but no changes in rCGU, in neocortex, with lesser effects on allocortex. Four weeks after exposure, the same general pattern was found with sarin. Only a few changes were found at 16 weeks post-treatment. The predominant effects of sarin or PB+sarin on rCBF at earlier times after treatment are consistent with the well known direct cerebral vascular effect of cholinergic agonists. The lack of changes in rCBF and rCGU observed at 16 weeks after treatment does not support the hypothesis that repeat exposure to low-dose cholinesterase inhibitors can generate permanent alterations in cerebral activity.

Patient encounter time intervals in the evaluation of emergency department patients requiring abdominopelvic CT: oral contrast versus no contrast.

The aim of the study was to assess various time intervals during patient encounters involving unenhanced (NECT) versus oral-contrast-enhanced (CECT) abdominopelvic (A/P) CT performed in the emergency department (ED) on adult patients presenting with acute abdominal pain. Computerized patient order entry and administrative data as well as scans themselves were retrospectively evaluated at a high-volume (107,000 visits per annum) regional medical center urban ED for a period of 30 consecutive days. All adult patients who had CT of abdomen and pelvis for abdominal pain during the 30 days of the study period were included. Data collected included demographic information, time of registration, time of first encounter in the ED, time of CT order, clinical indication for scan, time of scan, time of disposition (i.e., discharge or admit), and final disposition. Patients were excluded if they were less than 16 years old, pregnant, or met criteria for major trauma and evaluation in the trauma suite. Patients were also excluded from analysis if they received more than one scan on the same day (3 patients). Of 183 patients, 102 underwent NECT and 81 CECT. Some of the patients who underwent NECT had urinary colic. Among patients who did not have urinary colic there is a statistically significant difference in the median time intervals between: (1) patient arrival in the ED and evaluation by a physician (NECT 57 min, CECT 84 min, P<0.001); (2) patient exam by the physician and the time the A/P CT was ordered (NECT 35 min, CECT 63 min, P<0.01); (3) receipt of the CT order and the time of the scan (NECT 104 min, CECT 172 min, P<0.001); and (4) time of arrival in ED and disposition (NECT 358 min, CECT 599 min, P<0.001). There are significant time interval differences between CECT and NECT during patient encounters involving adults presenting with abdominal pain to the ED. The differences are greater than the amount of time allotted for opacification of small bowel (90 min). Baseline data such as these may prove useful in assessing the efficacy of scan techniques and improving resource utilization.