The fate and toxicity of Raman-active silica-gold nanoparticles in mice

Raman spectroscopy is an optical imaging method that is based on the Raman effect, the inelastic scattering of a photon when energy is absorbed from light by a surface. Although Raman spectroscopy is widely used for chemical and molecular analysis, its clinical application has been hindered by the inherently weak nature of the Raman effect. Raman-silica-gold-nanoparticles (R-Si-Au-NPs) overcome this limitation by producing larger Raman signals through surface-enhanced Raman scattering. Because we are developing these particles for use as targeted molecular imaging agents, we examined the acute toxicity and biodistribution of core polyethylene glycol (PEG)-ylated R-Si-Au-NPs after different routes of administration in mice. After intravenous administration, PEG-R-Si-Au-NPs were removed from the circulation by macrophages in the liver and spleen (that is, the reticuloendothelial system). At 24 hours, PEG-R-Si-Au-NPs elicited a mild inflammatory response and an increase in oxidative stress in the liver, which subsided by 2 weeks after administration. No evidence of significant toxicity was observed by measuring clinical, histological, biochemical, or cardiovascular parameters for 2 weeks. Because we are designing targeted PEG-R-Si-Au-NPs (for example, PEG-R-Si-Au-NPs labeled with an affibody that binds specifically to the epidermal growth factor receptor) to detect colorectal cancer after administration into the bowel lumen, we tested the toxicity of the core nanoparticle after administration per rectum. We observed no significant bowel or systemic toxicity, and no PEG-R-Si-Au-NPs were detected systemically. Although additional studies are required to investigate the long-term effects of PEG-R-Si-Au-NPs and their toxicity when carrying the targeting moiety, the results presented here support the idea that PEG-R-Si-Au-NPs can be safely used in living subjects, especially when administered rectally.     

Prevalence and correlates of probable adolescent mental health problems reported by parents in Vietnam

Purpose

The purpose of the present study was to estimate the prevalence of probable mental health problems in an epidemiologic study of Vietnamese adolescents. A secondary aim was to examine the correlates of probable mental health caseness.

Methods

Interviewers visited 1,914 households that were randomly selected to participate in a multi-agency study of mental health in select provinces of Vietnam. Semi-structured interviews assessed adolescent mental health problems using the Strengths and Difficulties Questionnaire (SDQ) parent informant version, and additionally the interviewers collected information on demographic variables (age, gender, ethnic group, religious affiliation, social capital). The final sample included data on 1,368 adolescents (aged 11?C18?years).

Results

The average score on the total problem composite of the SDQ scale was 6.66 (SD?=?4.89), and 9.1% of the sample was considered a case (n?=?124). Bivariate analyses were conducted to determine which demographic variables were related to the SDQ case/non-case score. All variables except gender were significant in bivariate analyses, and therefore were entered into a logistic regression. Results indicated that age, religion, and wealth remained significant predictors of probable caseness.

Conclusions

Overall, prevalence estimates of mental health problems generated by the SDQ were consistent with those reported in the US and other Western and non-Western samples. Results of the current study suggest some concordance of risk and protective factors between Western and Vietnamese youth (i.e., age and SES).     

AEDs availability and professional practices in delivery outlets in a city center in southern Vietnam

In developing countries, from 80 to 90% of the people with active epilepsy do not have access to treatment. A multitude of factors such as nonavailability of antiepileptic drugs (AEDs) contributes to the treatment gap in epilepsy. Our study carried out in 2003 in southern Vietnam showed that 57% of pharmacies had AEDs. A majority of these pharmacies were located in specific areas like market area or hospital area. The pharmacist in charge was present in only 24% of the pharmacies. The different kinds of AEDs available were carbamazepine (94%), phenytoin (61%), valproate (56%) and diazepam (16%). The maximum stock of a drug was two box. The availability of AEDs in southern Vietnam can be regarded as sufficient but does not allow an adequate treatment for a long time. An effort must be made to sensitize professional health workers to decrease the treatment gap in epilepsy.     

Assessment of rat and mouse RGC apoptosis imaging in vivo with different scanning laser ophthalmoscopes

PURPOSE: We have recently described a novel way of imaging apoptosing retinal ganglion cells in vivo in the rat. This study investigated if this technique could be used in the mouse, and whether the Heidelberg Retina Angiograph II (HRAII) was appropriate. METHODS: Retinal ganglion cell (RGC) death was induced by intravitreal injections in rat and mouse eyes using staurosporine. Fluorescent-labeled apoptosing cells were detected by imaging with both the HRAII and a prototype Zeiss confocal scanning laser ophthalmoscope (cSLO). Averaged in vivo images were analyzed and results compared with histologic analysis. RESULTS: Fluorescent points (FPs) used as a measure of RGC apoptosis in vivo were detected in the mouse eye but only with the HRAII and not the Zeiss cSLO. The HRAII was able to detect 62% more FPs in rat than the Zeiss cSLO. Both cSLOs showed peak FP counts at the 5- to 10-microm range in rat and mouse. Maximal FP counts were detected in the superior and superior temporal regions in the rat, with no obvious pattern of distribution in the mouse. The HRAII was found to have more FP correspondence with histologically identified apoptosing RGCs. CONCLUSIONS: To our knowledge, this is the first demonstration of visualized apoptosing RGC in vivo in a mouse. The improved image quality achieved with the HRAII compared with the Zeiss cSLO was validated by histology. This together with its enhanced maneuverability and the fact that it is already commercially available make the HRAII a potential tool for the early detection and diagnosis of glaucomatous disease in patients.     

Canadian Outcomes Study in Dementia: study methods and patient characteristics.

OBJECTIVE: To describe the methods and patient characteristics of the Canadian Outcomes Study in Dementia (COSID). METHODS: COSID is a 3-year prospective study of dementia patients living in the community at the time of study registration. We assessed patients' cognition, behaviour, and functioning every 6 months, using the Modified Mini-Mental State Examination (3MS), the Neuropsychiatric Inventory (NPI), and the Functional Autonomy Measurement System (SMAF), respectively. We assessed caregivers, using the Zarit Burden Interview (ZBI). Additional information included the Global Deterioration Scale (GDS), patients' driving status, and clinical information including family history, dementia type, concomitant medications, and comorbid conditions. From the patient or caregiver, we collected details of inpatient and outpatient resources used by the patient and (or) caregiver. RESULTS: We enrolled 766 patients from 31 Canadian sites. Overall mean age was 76.8 years, and mean age of onset was 73.1 years. Of the total patients, 98% were white, 54% were women, and 84% were diagnosed with Alzheimer's disease. Mean baseline 3MS was 66.5, NPI was 9.5, and SMAF was 18.30. Of these patients, 48% reported a GDS score of 3 (that is, moderate), 16% reported a GDS score of 4 (that is, moderately severe), and the remaining 36% reported a GDS score of 1 or 2 (that is, mild or very mild). At baseline, 83% of patients received cholinesterase inhibitors, 46% received nonsteroidal antiinflammatory drugs, 39% received vitamin E, and 25% received antidepressants. Adult day care and home help were the largest cost factors in this population, with mean monthly costs of $65 and $64, respectively. We found interesting differences in the resources used among geographic regions and care settings. CONCLUSIONS: COSID is already generating valuable information about treatment patterns, outcomes, and resource use in Canadian patients with dementia. As the data mature, it will be possible to build robust models on treatment effectiveness and costs of care.     

Management of Distal Fibular Fractures With Minimally Invasive Technique: A Systematic Review

Ankle fractures are extremely common, with isolated distal fibular fractures being the most common variant. The current gold standard in treating unstable distal fibular fractures is open reduction internal fixation. However, with potential risk of wound complications, minimally invasive techniques have been introduced. This systematic review was performed to evaluate the clinical and functional outcomes of varying minimally invasive techniques including minimally invasive plate osteosynthesis, intramedullary (IM) nailing, and IM screw fixation. A comprehensive English literature search on PubMed was performed yielding 543 studies. With specific study selection criteria, a total of 13 articles were selected. After studying the reference of each of the 13 studies, an additional 7 articles were included, resulting in a total of 20 studies reviewed. A total of 8 articles reviewed used IM nailing as the fixation of choice with a total of 211 patients. Of the 211 patients, 33 experienced complications. Six articles using minimally invasive plate osteosynthesis were reviewed with a total of 264 patients. Of the 264 patients, 39 experienced complications. IM screw fixation was used in 6 articles reviewed with a total of 219 patients. There were 30 cases of complications from the 132 patients. Additionally, mean American Orthopedic Foot and Ankle Society hindfoot-ankle scores among all fixation types was 88.4 ± 3.40 whereas the mean Olerud and Molander Score among all fixation types was 76.7 ± 16.58. The results of this study indicate that minimally invasive techniques for fixation of distal fibular fractures can provide excellent functional results with low complication rates compared with traditional open reduction internal fixation.