Quantification of quaternary ammonium compounds by liquid chromatography-mass spectrometry: Minimizing losses from the field to the laboratory.

Quaternary Ammonium Compounds (QACs) are widely used in household, medical and industrial settings. As a consequence, they are ubiquitously found in the environment. Although significant efforts have been put into the development of sensitive and reproducible analytical methods, much less effort has been dedicated to the monitoring of QACs upon sample storage and sample preparation. Here we studied the effect of storage, concentration, and extraction procedures on the concentrations of QACs in samples. Thirteen QACs selected amongst benzalkonium compounds (BACs), dialkyldimethylammonium compounds (DADMACs) and alkyltrimethylammonium compounds (ATMACs) were quantified in aqueous and solid samples using LC-MS/MS. Most QACs adsorbed on container walls could be recovered using a short washing step with MeOH containing 2 % v/v formic acid. Concentrations of QACs from aqueous solutions using solid phase extraction (SPE) with Strata-X cartridges and elution with acidified MeOH utilized to wash the emptied containers gave highly satisfactory recoveries (101-111 %). Good recoveries (89-116 %) were also obtained when extracting a spiked organic-rich synthetic soil using accelerated solvent extraction (ASE) with acidified MeOH at low solid/solvent ratio (0.4 g/20 mL). Applying the recommended methodologies to real samples collected from a Canadian wastewater treatment plant (WWTP) gave QAC concentrations in the ranges of 0.01-30 µg/L, < 1.2 µg/L, and 0.05-27 mg/kg for the influent, effluent and biosolids samples, respectively.

Evaluation of perennial Glycine species for response to Meloidogyne incognita, Rotylenchulus reniformis, and Pratylenchus penetrans.

Root-knot (Meloidogyne incognita (Kofoid & White) Chitwood), reniform (Rotylenchulus reniformis Lindford & Oliveira), and lesion nematodes (Pratylenchus penetrans (Cobb) Filipjev & Schuurmans Stekhoven) are plant-parasitic nematodes that feed on soybean (Glycine max (L.) Merr.) roots, limiting seed production. The availability of resistance in soybeans to these nematodes is limited. However, new sources of resistance can be discovered in wild relatives of agronomic crops. Perennial Glycine species, wild relatives to soybean, are a source of valuable genetic resources with the potential to improve disease resistance in soybean. To determine if these perennials have resistance against nematodes, 18 accessions of 10 perennial Glycine species were evaluated for their response to M. incognita and R. reniformis, and eight accessions of six perennial Glycine species were evaluated for their response to P. penetrans. Pot experiments were conducted for M. incognita and R. reniformis in a growth chamber and in vitro experiments were conducted for P. penetrans. We found both shared and distinct interactions along the resistance-susceptible continuum in response to the three plant-parasitic nematode species. Ten and 15 accessions were classified as resistant to M. incognita based on eggs per gram of root and gall index, respectively. Among them, G. tomentella plant introductions (PIs) 446983 and 339655 had a significantly lower gall index than the resistant soybean check cv. Forrest. Of three R. reniformis resistant accessions identified in this study, G. tomentella PI 441001 showed significantly greater resistance to R. reniformis than the resistant check cv. Forrest based on nematodes per gram of root. In contrast, no resistance to P. penetrans was recorded in any perennial Glycine species.

Mutually exclusive dendritic arbors in C. elegans neurons share a common architecture and convergent molecular cues.

Stress-induced changes to the dendritic architecture of neurons have been demonstrated in numerous mammalian and invertebrate systems. Remodeling of dendrites varies tremendously among neuron types. During the stress-induced dauer stage of Caenorhabditis elegans, the IL2 neurons arborize to cover the anterior body wall. In contrast, the FLP neurons arborize to cover an identical receptive field during reproductive development. Using time-course imaging, we show that branching between these two neuron types is highly coordinated. Furthermore, we find that the IL2 and FLP arbors have a similar dendritic architecture and use an identical downstream effector complex to control branching; however, regulation of this complex differs between stress-induced IL2 branching and FLP branching during reproductive development. We demonstrate that the unfolded protein response (UPR) sensor IRE-1, required for localization of the complex in FLP branching, is dispensable for IL2 branching at standard cultivation temperatures. Exposure of ire-1 mutants to elevated temperatures results in defective IL2 branching, thereby demonstrating a previously unknown genotype by environment interaction within the UPR. We find that the FOXO homolog, DAF-16, is required cell-autonomously to control arborization during stress-induced arborization. Likewise, several aspects of the dauer formation pathway are necessary for the neuron to remodel, including the phosphatase PTEN/DAF-18 and Cytochrome P450/DAF-9. Finally, we find that the TOR associated protein, RAPTOR/DAF-15 regulates mutually exclusive branching of the IL2 and FLP dendrites. DAF-15 promotes IL2 branching during dauer and inhibits precocious FLP growth. Together, our results shed light on molecular processes that regulate stress-mediated remodeling of dendrites across neuron classes.

An Extract from Shrimp Processing By-Products Protects SH-SY5Y Cells from Neurotoxicity Induced by Aß25-35.

Increased evidence suggests that marine unsaturated fatty acids (FAs) can protect neurons from amyloid-ß (Aß)-induced neurodegeneration. Nuclear magnetic resonance (NMR), high performance liquid chromatography (HPLC) and gas chromatography (GC) assays showed that the acetone extract 4-2A obtained from shrimp Pandalus borealis industry processing wastes contained 67.19% monounsaturated FAs and 16.84% polyunsaturated FAs. The present study evaluated the anti-oxidative and anti-inflammatory effects of 4-2A in Aß25-35-insulted differentiated SH-SY5Y cells. Cell viability and cytotoxicity were measured by using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Quantitative PCR and Western blotting were used to study the expression of neurotrophins, pro-inflammatory cytokines and apoptosis-related genes. Administration of 20 µM Aß25-35 significantly reduced SH-SY5Y cell viability, the expression of nerve growth factor (NGF) and its tyrosine kinase TrkA receptor, as well as the level of glutathione, while increased reactive oxygen species (ROS), nitric oxide, tumor necrosis factor (TNF)-α, brain derived neurotrophic factor (BDNF) and its TrkB receptor. Aß25-35 also increased the Bax/Bcl-2 ratio and Caspase-3 expression. Treatment with 4-2A significantly attenuated the Aß25-35-induced changes in cell viability, ROS, GSH, NGF, TrkA, TNF-α, the Bax/Bcl-2 ratio and Caspase-3, except for nitric oxide, BDNF and TrKB. In conclusion, 4-2A effectively protected SH-SY5Y cells against Aß-induced neuronal apoptosis/death by suppressing inflammation and oxidative stress and up-regulating NGF and TrKA expression.

Rapid Learning of Adverse Medical Event Disclosure and Apology.

INTRODUCTION: Despite published recommended best practices for full disclosure and apology to patients and families after adverse medical events, actual practice can be inadequate. The use of "cognitive aids" to help practitioners manage complex critical events has been successful in a variety of fields and healthcare. We wished to extend this concept to disclosure and apology events. The aim of this study was to test if a brief opportunity to review a best practice guideline for disclosure and apology would improve communication performance. METHODS: Thirty pairs of experienced obstetricians and labor nurses participated in a 3-part exercise with mixed-realism simulation. The first part used a standardized actor patient to meet the obstetrical team. The second part used a high-fidelity simulation leading to an adverse medical event (retained sponge), and the third part used standardized actors, patient, and husband, who systematically move through stages of grief response. The participants were randomized into 2 groups, one was provided with a cognitive aid in the form of a best practice guideline for disclosure and apology and the other was only given time to plan. Four blinded raters working in pairs scored subjects on a 7-point scale using a previously developed assessment instrument modified for this study. RESULTS: Pooled ratings of the disclosure and apology discussion for the intervention group (n = 167, mean = 4.9, SD = 0.92) were higher than those from the control group (n = 167, mean = 4.3, SD = 1.21) (P < 0.0001). One specific element was rated higher for the intervention group than the control group; posture toward the patient (n = 27, mean = 5.1, SD = 0.82 versus n = 28, mean = 4.3, SD = 1.33) (P = 0.020). The elements of dealing with anger, dealing with depression, dealing with denial, bargaining, and acceptance were not different. CONCLUSIONS: Experienced practitioners performed better in a simulated disclosure and apology conversation after reviewing a cognitive aid in the form of a best practice guideline than a control group that was only given time to prepare.

Evaluation of computer-based medical histories taken by patients at home.

The authors developed a computer-based general medical history to be taken by patients in their homes over the internet before their first visit with their primary care doctor, and asked six doctors and their participating patients to assess this history and its effect on their subsequent visit. Forty patients began the history; 32 completed the history and post-history assessment questionnaire and were for the most part positive in their assessment; and 23 continued on to complete their post-visit assessment questionnaire and were for the most part positive about the helpfulness of the history and its summary at the time of their visit with the doctor. The doctors in turn strongly favored the immediate, routine use of two modules of the history--the family and social histories--for all their new patients. The doctors suggested further that the summaries of the other modules of the history be revised and shortened to make it easier for them to focus on clinical issues in the order of their preference.

Electronic problem-solving treatment: description and pilot study of an interactive media treatment for depression.

BACKGROUND: Computer-automated depression interventions rely heavily on users reading text to receive the intervention. However, text-delivered interventions place a burden on persons with depression and convey only verbal content. OBJECTIVE: The primary aim of this project was to develop a computer-automated treatment for depression that is delivered via interactive media technology. By using branching video and audio, the program simulates the experience of being in therapy with a master clinician who provides six sessions of problem-solving therapy. A secondary objective was to conduct a pilot study of the program's usability, acceptability, and credibility, and to obtain an initial estimate of its efficacy. METHODS: The program was produced in a professional multimedia production facility and incorporates video, audio, graphics, animation, and text. Failure analyses of patient data are conducted across sessions and across problems to identify ways to help the user improve his or her problem solving. A pilot study was conducted with persons who had minor depression. An experimental group (n = 7) used the program while a waitlist control group (n = 7) was provided with no treatment for 6 weeks. RESULTS: All of the experimental group participants completed the trial, whereas 1 from the control was lost to follow-up. Experimental group participants rated the program high on usability, acceptability, and credibility. The study was not powered to detect clinical improvement, although these pilot data are encouraging. CONCLUSIONS: Although the study was not powered to detect treatment effects, participants did find the program highly usable, acceptable, and credible. This suggests that the highly interactive and immersive nature of the program is beneficial. Further clinical trials are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00906581; http://clinicaltrials.gov/ct2/show/NCT00906581 (Archived by WebCite at http://www.webcitation.org/6A5Ni5HUp).

Workplace telecommunications technology to identify mental health disorders and facilitate self-help or professional referrals.

PURPOSE: Test the feasibility and impact of an automated workplace mental health assessment and intervention. DESIGN: Efficacy was evaluated in a randomized control trial comparing employees who received screening and intervention with those who received only screening. SETTING: Workplace. SUBJECTS: 463 volunteers from Boston Medical Center, Boston University, and EMC and other employed adults, among whom 164 were randomized to the intervention (N  =  87) and control (N  =  77) groups. INTERVENTION: The system administers a panel of telephonic assessment instruments followed by tailored information, education, and referrals. MEASURES: The Work Limitation Questionnaire, the Medical Outcomes Questionnaire Short Form-12, the Patient Health Questionnaire-9, question 10 from the Patient Health Questionnaire to measure functional impairment, and the Perceived Stress Scale-4 and questions written by study psychiatrists to measure emotional distress and social support respectively. The WHO-Five Well-being Index was administered to measure overall well-being. ANALYSIS: Independent sample t-tests and χ(2) tests as well as mean change were used to compare the data. RESULTS: No significant differences on 16 of the 20 comparisons at 3- and 6-month time points. The intervention group showed a significant improvement in depression (p ≤ .05) at 3 months and on two Work Limitation Questionnaire subscales, the Mental-Interpersonal Scale (p ≤ .05) and the Time and Scheduling Scale (p ≤ .05), at 3 and 6 months respectively with a suggestive improvement in mental health at 6 months (p ≤ .10). CONCLUSIONS: This is a potentially fruitful area for research with important implications for workplace behavioral interventions.

Test-retest reliability in a computer-based medical history.

The authors developed a computer-based medical history for patients to take in their homes via the internet. The history consists of 232 'primary' questions asked of all patients, together with more than 6000 questions, explanations, and suggestions that are available for presentation as determined by a patient's responses. The purpose of this research was to measure the test-retest reliability of the 215 primary questions that have preformatted, mutually exclusive responses of 'Yes,' 'No,' 'Uncertain (Don't know, Maybe),' 'Don't understand,' and 'I'd rather not answer.' From randomly selected patients of doctors affiliated with Beth Israel Deaconess Medical Center in Boston, 48 patients took the history twice with intervals between sessions ranging from 1 to 35 days (mean 7 days; median 5 days). High levels of test-retest reliability were found for most of the questions, but as a result of this study the authors revised five questions. They recommend that structured medical history questions that will be asked of many patients be measured for test-retest reliability before they are put into widespread clinical practice.

A roadmap to computer-based psychotherapy in the United States.

Computers can be used to deliver self-guided interventions and to provide access to live therapists at remote locations. These treatment modalities could help overcome barriers to treatment, including cost, availability of therapists, logistics of scheduling and traveling to appointments, stigma, and lack of therapist training in evidence-based treatments (EBTs). EBTs could be delivered at any time in any place to individuals who might otherwise not have access to them, improving public mental health across the United States. In order to fully exploit the opportunities to use computers for mental health care delivery, however, advances need to be made in four domains: (1) research, (2) training, (3) policy, and (4) industry. This article discusses specific challenges (and some possible solutions) to implementing computer-based distance therapy and self-guided treatments in the United States. It lays out both a roadmap and, in each of the four domains, the milestones that need to be met to reach the goal of making EBTs for behavioral health problems available to all Americans.

Terrorism, trauma, and mass casualty triage: how might we solve the latest mind-body problem?

The global war on terrorism has led to increased concern about the ability of the U.S. healthcare system to respond to casualties from a chemical, biological, or radiological agent attack. Relatively little attention, however, has focused on the potential, in the immediate aftermath of such an attack, for large numbers of casualties presenting to triage points with acute health anxiety and idiopathic physical symptoms. This sort of "mass idiopathic illness" is not a certain outcome of chemical, biological, or radiological attack. However, in the event that this phenomenon occurs, it could result in surges in demand for medical evaluations that may disrupt triage systems and endanger lives. Conversely, if continuous primary care is not available for such patients after initial triage, many may suffer with unrecognized physical and emotional injuries and illness. This report is the result of an expert planning initiative seeking to facilitate triage protocols that will address the possibility of mass idiopathic illness and bolster healthcare system surge capacity. The report reviews key triage assumptions and gaps in knowledge and offers a four-stage triage model for further discussion and research. Optimal triage approaches offer flexibility and should be based on empirical studies, critical incident modeling, lessons from simulation exercises, and case studies. In addition to staging, the proposed triage and longitudinal care model relies on early recognition of symptoms, development of a registry, and use of non-physician care management to facilitate later longitudinal followup and collaboration between primary care and psychiatry for the significant minority of patients who develop persistent idiopathic symptoms associated with reduced functional status.

Design and development of a mental health assessment and intervention system.

Mental health disorders are the leading cause of disability and functional impairment in the United States (1 in 5). The negative effect of mental health disorders is felt both in the personal and public lives of the affected individuals, particularly in the workplace where it adversely impacts productivity. Only a small fraction of the affected people in the work force seeks help. The cost to employers and the economy of these untreated individuals is staggering. Some employers have tried to address employees' emotional well-being by establishing Employee Assistance Programs. Yet, even these programs do not sufficiently address existing barriers to the detection and treatment of mental health disorders in the workplace. This paper describes the design of an automated workplace program that uses an Interactive, computer-assisted telephonic system (Interactive Voice Response or IVR) to assess workers for a variety of mental health disorders and subsequently refers untreated and inadequately treated workers to appropriate treatment settings.

Psychosomatic medicine and biodefense preparedness--a new role for the American Psychosomatic Society.

Biodefense preparations in the United States have focused mostly on improving biosurveillance and hospital surge capacity in the event of an outbreak or a weapons of mass destruction (WMD) event. However, what if an invisible bioweapon or dirty bomb was released in a major population center, or if avian flu took hold with sustained human to human transmission? Suddenly, we need to combine efforts from psychosomatic medicine and general medicine with public health practice to triage nonexposed patients with somatic symptoms from those with medical sequelae resulting from hazardous exposures. This would better enable the limited acute care resources to be directed to those most in need of urgent medical care. Furthermore, psychosomatic medicine experts are potentially important players in biodefense planning related to risk communication and health education strategies in a WMD scenario or outbreak in which individuals must make informed choices about their need for immediate medical attention.

Deviation from the mobile proton model in amino-modified peptides: implications for multiple reaction monitoring analysis of peptides.

The study of peptide fragmentation is important to the understanding of chemical processes occurring in the gas phase and the more practical concern of peptide identification for proteomic analysis. Using the mobile proton model as a framework, we explore the effect of amino-group modifications on peptide fragmentation. Three aldehydes are used to transform the peptides' primary amino groups into either a dimethylamino or a heterocyclic structure (five- or six-membered). The observed fragmentation patterns deviate strongly from those observed for the analogous underivatised peptides. In particular, the a1 ion is the base peak in most tandem mass spectra of the derivatised peptides. The a1 ion intensity depends strongly on the N-terminal amino acid, with tyrosine and phenylalanine having the strongest enhancement. Despite the change in fragmentation patterns of the derivatised peptides, they still provide high-quality tandem mass spectra that, in many cases, are more amenable to database searching than the spectra of underivatised peptides. In addition, the reliable presence of the a1 ion facilitates rapid quantitative measurements using the multiple reaction monitoring approach.

The effect of a telephone counseling intervention on self-rated health of cardiac patients.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of a telephone-based intervention on psychological distress among patients with cardiac illness. METHODS: We recruited hospitalized patients surviving an acute coronary syndrome with scores on the Hospital and Anxiety Depression Scale (HADS) indicating mild to severe depression and/or anxiety at 1 month postdischarge. Recruited patients were randomized into either an intervention or control group. Intervention patients received up to six 30-minute telephone-counseling sessions focused on identifying cardiac-related fears. Control patients received usual care. For both groups, we collected patients' responses to the HADS and to the Global Improvement (CGI-I) subscale of the Clinical Global Impressions (CGI) Scale at baseline and at 2, 3, and 6 months postbaseline using Interactive Voice Recognition (IVR) technologies. We used mixed-effects analysis to estimate patients' changes in CGI-I measures over the three time points of data collection postbaseline. RESULTS: We enrolled 100 patients, and complete CGI-I measures were collected for 79 study patients. The mean age was 60 years (standard deviation = 10), and 67% of the patients were male. A mixed-effects analysis confirmed that patients in the intervention group had significantly greater improvements in self-rated health (SRH) between baseline and month 3 than the control group (p = .01). Between month 3 and month 6, no significant differences in SRH improvements were observed between the control and intervention groups. CONCLUSIONS: Study patients reported greater SRH improvement resulting from the telephone-based intervention compared with control subjects. Future research should include additional outcome measures to determine the effect of changes in SRH on patients with comorbid physical and emotional disorders.

Using the Hospital Anxiety and Depression Scale to screen for depression in cardiac patients.

OBJECTIVE: There is an increasing interest in trying to identify patients with chronic physical illness who would benefit from interventions to decrease psychological distress. The Hospital Anxiety and Depression Scale (HADS) is one measure that can be effectively used to identify patients struggling with anxiety and/or depression in addition to comorbid medical illness such as cardiac disease. The aim of this study is to determine if the HADS correctly identified patients with depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [determined using the Primary Care Evaluation of Mental Disorders (PRIME-MD), a gold-standard diagnostic tool], as depressed and to determine which items on the HADS most strongly predicted the PRIME-MD major depression diagnosis among cardiac patients. METHOD: Patient data were obtained from a randomized controlled trial of treatment for psychological distress in patients surviving recent myocardial infarction or life-threatening ischemic heart disease. The HADS was used to evaluate depression and/or anxiety among patients hospitalized for heart disease, and the PRIME-MD was used to diagnose major depressive disorder (MDD) in these patients. We used receiver-operating characteristic (ROC) curves and logistic regression to analyze patient responses to both of these measures. RESULTS: Among the 79 study patients, the area under the ROC curve (AUC) for the HADS depression subscale was 0.81 with an S.E. of 0.05, and the AUC was 0.70 for the HADS anxiety subscale with an S.E. of 0.06. Using a cutoff of 7 on each HADS subscale to determine PRIME-MD diagnosis of MDD, the sensitivity and specificity were 81% and 54%, respectively, for the depression subscale and 81% and 40%, respectively, for the anxiety subscale. In addition, a few individual HADS items predicted PRIME-MD diagnosis of MDD, namely, concentration and positive anticipation (depression items) and relaxed and worry (anxiety items), each of which were strongly correlated with PRIME-MD diagnosis of MDD. Finally, items positive anticipation and relaxed provided reasonable approximations to the results found from the HADS depression subscale measure, which performed better than the HADS anxiety subscale in predicting PRIME-MD diagnosis of depression. CONCLUSIONS: Using the HADS to detect mental disorders in primary care populations can save valuable physician time, and perhaps ensure that patients are treated for their mental distress as well as medical disease.

Improving psychologic adjustment to chronic illness in cardiac patients. The role of depression and anxiety.

BACKGROUND: Poor mood adjustment to chronic medical illness is often accompanied by decrements in function. OBJECTIVE: To evaluate the effectiveness of a telephone-based intervention for psychologic distress and functional impairment in cardiac illness. DESIGN: Randomized, controlled trial. METHODS: We recruited survivors of acute coronary syndromes using the Hospital and Anxiety Depression Scale (HADS) with scores indicative of mood disturbances at 1-month postdischarge. Recruited patients were randomized to experimental or control status. Intervention patients received 6 30-minute telephone counseling sessions to identify and address illness-related fears and concerns. Control patients received usual care. Patients' responses to the HADS and the Workplace Social Adjustment Scale (WSAS) were collected at baseline, 2, 3, and 6 months using interactive voice recognition technology. At baseline, the PRIME-MD was used to establish diagnosis of depression. We used mixed effects regression to study changes in outcomes. RESULTS: We enrolled 100 patients. Mean age was 60; 67% of the patients were male. Findings confirmed that the intervention group had a 27% improvement in depression symptoms (P=.05), 27% in anxiety (P=.02), and a 38% improvement in home limitations (P=.04) compared with controls. Symptom improvement tracked those for WSAS measures of home function (P=.04) but not workplace function. CONCLUSIONS: The intervention had a moderate effect on patient's emotional and functional outcomes that were observed during a critical period in patients' lives. Patient convenience, ease of delivery, and the effectiveness of the intervention suggest that the counseling can help patients adjust to chronic illness.

Psychosocial determinants of relapse in ulcerative colitis: a longitudinal study.

OBJECTIVES: To determine the association between psychosocial characteristics and time to relapse in patients with inactive ulcerative colitis. METHODS: Sixty patients with clinically and endoscopically inactive ulcerative colitis were followed for 1 yr, or less if they relapsed. Demographic, psychosocial, and clinical data were obtained. Stressful life events (Psychiatric Epidemiology Research Interview Life Events Scale), psychological distress (Symptom Checklist-90R), and perceived stress (Perceived Stress Scale) were recorded monthly by self-report. Multivariate time-dependent Cox regression was used to identify the independent determinants of earlier time to clinical relapse. RESULTS: The patients' mean age was 39 yr (SD = 9.4), 37 (62%) were female, and 22 (37%) relapsed during the 1-yr follow-up. Univariate Cox regression indicated a weak association between number of stressful events in the preceding month and time to relapse (p = 0.09). This association strengthened in multivariate analysis (p = 0.02, hazard ratio = 1.26 per event, 95% CI = 1.04-1.53) after adjustment for significant covariates. CONCLUSIONS: After controlling for demographic and clinical variables, more recent stressful events were associated with earlier time to relapse. These findings, which support a biopsychosocial model of disease, might help clinicians identify patients who might benefit from more intensive maintenance medical therapy and behavioral medicine interventions to reduce stress and improve coping.