Rapid,Label-Free Screening of Diverse Biotransformations by Flow-Injection Mass Spectrometry

Mass spectrometry-based high-throughput screening methods combine the advantages of photometric or fluorometric assays and analytical chromatography, as they are reasonably fast (throughput ≥1 sample/min) and broadly applicable, with no need for labelled substrates or products. However, the established MS-based screening approaches require specialised and expensive hardware, which limits their broad use throughout the research community. We show that a more common instrumental platform, a single-quadrupole HPLC-MS, can be used to rapidly analyse diverse biotransformations by flow-injection mass spectrometry (FIA-MS), that is, by automated infusion of samples to the ESI-MS detector without prior chromatographic separation. Common organic buffers can be employed as internal standard for quantification, and the method provides readily validated activity and selectivity information with an analytical run time of one minute per sample. We report four application examples that cover a broad range of analyte structures and concentrations (0.1–50 mM before dilution) and diverse biocatalyst preparations (crude cell lysates and whole microbial cells). Our results establish FIA-MS as a versatile and reliable alternative to more traditional methods for screening enzymatic reactions.     

The role of perceived vulnerability in adjustment to lower extremity amputation: A preliminary investigation.

Objective: To examine the role of feelings of vulnerability in postamputation adjustment problems such as depression and diminished quality of life. Participants: Eighty-four patients with a lower extremity amputation. Setting: Five affiliated prosthetic clinics in Chicago. Main Measures: The Center for Epidemiologic Studies Depression Scale (CES-D), a 3-item quality-of-life measure, and a 2-item vulnerability measure. Participants' prosthetists completed a single-item rating of perceived adjustment. Results: Vulnerability accounted for significant portions of the variance in CES-D scores, quality-of-life ratings, and prosthetists' adjustment ratings. Conclusion: Feelings of vulnerability significantly affect adjustment in persons with amputations, and this impact is not limited to a single domain. Clinicians should assess feelings of vulnerability, the degree to which such feelings are realistic, and any past experiences with victimization. These issues need to be addressed with both individual counseling and community interventions aimed at reducing victimization of individuals with disabilities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inspiration produced by bilateral electromagnetic, cervical phrenicnerve stimulation in man

Eddy-current stimulation of both phrenic nerves at the base of the neck in human subjects was carried out to provide inspiration resulting from tetanic diaphragm contraction. The inspired volume obtained was in excess of spontaneous tidal volume.     

Vascular dementia: a contemporary review of epidemiology, diagnosis, prevention, and treatment

The past decade has seen a renewed interest in vascular dementia. Key epidemiologic studies have examined the prevalence, incidence, course and risk factors of vascular dementia. New classification systems have been developed to improve the reliability of the diagnosis, and there have been advances in diagnostic methodology, such as neuroimaging and neuropsychological assessment. New treatments for vascular dementia are being developed to protect the brain from cerebral ischemia and to limit progression of cognitive impairment. Diagnostic criteria for vascular dementia remain to be validated by carefully designed, systematic, clinicopathologic study. Once such criteria are validated, meaningful study of subgroups of vascular dementia can be explored. Until the relationship between vascular dementia and Alzheimer's disease is better defined, the nosology for vascular dementia may be defined best as dementia associated with stroke.     

Simulation of human respiration in fMRI with a mechanical model

Obtaining functional magnetic resonance images of the brain is a challenging measurement process having a low characteristic signal-to-noise ratio. Images contain various forms of noise, including those induced by physiologic processes. One of the prevalent disturbances is hypothesized to result from susceptibility fluctuations caused by abdominal volume changes during respiration. To test this hypothesis and characterize the contribution of respiration noise to both magnitude and phase images, a mechanical model of a respiring human was constructed. The model was tested by comparing data from the model with that of a resting human. Power spectrum analyses show that the model induces both phase and magnitude disturbances similar to those in the human. The disturbances are directly related to the frequency of the respiration, with the noise most prevalent in the phase images. Though magnitude image noise is hard to identify in the human, the manikin demonstrates the presence of this disturbance. The construction of the manikin rules out motion as the primary source of the observed fluctuations and variation of the electrical properties of the manikin also indicates that signal fluctuations are not primarily due to eddy currents. Therefore, the changes are most probably induced by bulk susceptibility changes correlating with respiration.     

Peripheral nerve stimulation by gradient switching fields in magnetic resonance imaging

A heterogeneous model of the human body and the scalar potential finite difference method are used to compute electric fields induced in tissue by magnetic field exposures. Two types of coils are considered that simulate exposure to gradient switching fields during magnetic resonance imaging (MRI). These coils producing coronal (y axis) and axial (z axis) magnetic fields have previously been used in experiments with humans.The computed fields can, therefore, be directly compared to human response data. The computed electric fields in subcutaneous fat and skin corresponding to peripheral nerve stimulation (PNS) thresholds in humans in simulated MRI experiments range from 3.8 to 5.8 V/m for the fields exceeded in 0.5% of tissue volume (skin and fat of the torso). The threshold depends on coil type and position along the body, and on the anatomy and resolution of the human body model. The computed values are in agreement with previously established thresholds for neural stimulation.     

The development, standardization, and initial validation of the Chicago Multiscale Depression Inventory

Current self-report depression scales may overestimate depression symptoms in medical patients by including items measuring symptoms inherent to many medical conditions. They may therefore reflect a patient's medical rather than psychological state. We present the Chicago Multiscale Depression Inventory (CMDI), a factorially derived self-report depression scale that includes Mood, Evaluative, and Vegetative subscales. The CMDI and its subscales were designed to be used separately or combined; we posit that the nonvegetative CMDI subscales are the most accurate means of examining depression in medical patients. In this study we outline the development, standardization, and initial validation of the CMDI, a multistep process that required a total sample of 1,062 adults. We show the CMDI and each of its subscales to be internally consistent, reliable, and valid. Confirmatory factor analysis supports the CMDI factor structure. Finally, we report standardization scores for each of the CMDI scales, derived from an age-, race- and gender-stratified standardization sample of 420 adults.     

MRI and implanted medical devices: basic interactions with an emphasis on heating

There are three principal magnetic fields in magnetic resonance imaging (MRI) that may interact with medical implants. The static field will induce force and torque on ferromagnetic objects. The pulsed gradients are of audio frequency and the implant may concentrate the induced currents, with a potential for nerve stimulation or electrical inference. The currents induced in the body by the radio frequency (RF) field may also be concentrated by an implant, resulting in potentially dangerous heating of surrounding tissues. This paper presents basic information about MRI interactions with implants with an emphasis on RF-induced heating of leads used for deep brain stimulation (DBS). The temperature rise at the electrodes was measured in vitro as a function of the overall length of a DBS lead at an RF frequency of 64 MHz. The maximal temperature rise occurred for an overall length of 41 cm. The method of moments was used to calculate the current induced in the lead. From the induced currents, the RF power deposition near the electrodes was calculated and the heat equation was used to model the temperature rise. The calculated temperature rises as a function of lead length were in good agreement with the measured values.     

Body image, perceived social stigma, and the prediction of psychosocial adjustment to leg amputation.

Examined whether body image (BI) and perceived social stigma (PSS) are important predictors of psychosocial adjustment (PA) to leg amputation, in 112 clients (aged 21–83 yrs) from 5 prosthetic clinics. Two scales were developed to measure BI disturbances and PSS resulting from amputation. The Center for Epidemiological Studies Depression Scale, a quality of life scale, and prosthesist ratings, were used to measure PA. BI was an independent predictor of all 3 adjustment measures after controlling for effects of age at the time and site of amputation, time since amputation, self-rated health, and perceived social support. PSS made a significant contribution to depression, but was not an independent predictor for the other 2 measures of adjustment. The overall rate of depression was 28%, indicating that this is both a short-, and a long-term adjustment problem following amputation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)