Dependence of sonoporation efficiency on microbubble size: An in vitro monodisperse microbubble study.

Sonoporation is the process where intracellular drug delivery is facilitated by ultrasound-driven microbubble oscillations. Several mechanisms have been proposed to relate microbubble dynamics to sonoporation including shear and normal stress. The present work aims to gain insight into the role of microbubble size on sonoporation and thereby into the relevant mechanism(s) of sonoporation. To this end, we measured the sonoporation efficiency while varying microbubble size using monodisperse microbubble suspensions. Sonoporation experiments were performed in vitro on cell monolayers using a single ultrasound pulse with a fixed frequency of 1 MHz while the acoustic pressure amplitude and pulse length were varied at 250, 500, and 750 kPa, and 10, 100, and 1000 cycles, respectively. Sonoporation efficiency was quantified using flow cytometry by measuring the FITC-dextran (4 kDa and 2 MDa) fluorescence intensity in 10,000 cells per experiment to average out inherent variations in the bioresponse. Using ultra-high-speed imaging at 10 million frames per second, we demonstrate that the bubble oscillation amplitude is nearly independent of the equilibrium bubble radius at acoustic pressure amplitudes that induce sonoporation (≥ 500 kPa). However, we show that sonoporation efficiency is strongly dependent on the equilibrium bubble size and that under all explored driving conditions most efficiently induced by bubbles with a radius of 4.7 µm. Polydisperse microbubbles with a typical ultrasound contrast agent size distribution perform almost an order of magnitude lower in terms of sonoporation efficiency than the 4.7-µm bubbles. We elucidate that for our system shear stress is highly unlikely the mechanism of action. By contrast, we show that sonoporation efficiency correlates well with an estimate of the bubble-induced normal stress.

Personal Problems Questionnaire (PPQ): Normative Data and Utility in Assessing Acquired Neurological Impairment.

OBJECTIVE: The Personal Problems Questionnaire (PPQ) is a measure designed to assess acquired cognitive, emotional, and physical complaints. The present study sought to develop a normative database to allow clinicians and researchers to assess self-reported complaints among people with disabilities, and evaluate the response consistency and validity of their self-report. METHOD: 404 community-dwelling participants (n 200 males, 204 females) completed the PPQ, as well as an acquired brain injury (ABI) group (n 59), mainly following stroke and traumatic brain injuries, and seen for clinical (i.e., non-forensic) evaluations. Multiple regression analyses were conducted to derive norms from the healthy community sample taking into account age, gender, and educational level. RESULTS: Normative T scores and cut-off points for the Clinical and Validity scales were derived, respectively, and used to assess the responses of the ABI group. The results indicated that the ABI group showed good response consistency and elevated scores on the Clinical scales, indicating that the PPQ is likely to be useful in detecting acquired disabilities. On the other hand, scores on the Validity scales were not elevated, indicating that the measures were unaffected by the ABI participants' cognitive difficulties. CONCLUSIONS: The PPQ provides a comprehensive assessment of complaints and response validity and the present study provides further data to assist with its use and interpretation.

Cognitive dysfunction in patients hospitalized with acute exacerbation of COPD.

BACKGROUND: Cognitive impairment is one of the least well-studied COPD comorbidities. It is known to occur in hypoxemic patients, but its presence during acute exacerbation is not established. OBJECTIVES: The purpose of this study was to assess neuropsychological performance in patients with COPD who were awaiting discharge from hospital following acute exacerbation and recovery and to compare them with stable outpatients with COPD and with healthy control subjects. METHODS: We recruited 110 participants to the study: 30 inpatients with COPD who were awaiting discharge following an exacerbation, 50 outpatients with stable COPD, and 30 control subjects. Neuropsychological tests measured episodic memory, executive function, visuospatial function, working memory, processing speed, and an estimate of premorbid abilities. Follow-up cognitive assessments for patients who were stable and those with COPD exacerbation were completed at 3 months. RESULTS: Patients with COPD exacerbation were significantly worse (P<.05) than stable patients over a range of measures of cognitive function, independent of hypoxemia, disease severity, cerebrovascular risk, or pack-years smoked. Of the patients with COPD exacerbation, up to 57% were in the impaired range and 20% were considered to have suffered a pathologic loss in processing speed. Impaired cognition was associated with worse St. George's Respiratory Questionnaire score (r=-0.40-0.62, P≤.02) and longer length of stay (r=0.42, P=.02). There was no improvement in any aspect of cognition at recovery 3 months later. CONCLUSIONS: In patients hospitalized with an acute COPD exacerbation, impaired cognitive function is associated with worse health status and longer hospital length of stay. A significant proportion of patients are discharged home with unrecognized mild to severe cognitive impairment, which may not improve with recovery.

Brain structure and function in chronic obstructive pulmonary disease: a multimodal cranial magnetic resonance imaging study.

RATIONALE: Brain pathology is a poorly understood systemic manifestation of chronic obstructive pulmonary disease (COPD). Imaging techniques using magnetic resonance (MR) diffusion tensor imaging (DTI) and resting state functional MR imaging (rfMRI) provide measures of white matter microstructure and gray functional activation, respectively. OBJECTIVES: We hypothesized that patients with COPD would have reduced white matter integrity and that functional communication between gray matter resting-state networks would be significantly different to control subjects. In addition, we tested whether observed differences related to disease severity, cerebrovascular comorbidity, and cognitive dysfunction. METHODS: DTI and rfMRI were acquired in stable nonhypoxemic patients with COPD (n = 25) and compared with age-matched control subjects (n = 25). Demographic, disease severity, stroke risk, and neuropsychologic assessments were made. MEASUREMENTS AND MAIN RESULTS: Patients with COPD (mean age, 68; FEV(1) 53 ± 21% predicted) had widespread reduction in white matter integrity (46% of white matter tracts; P < 0.01). Six of the seven resting-state networks showed increased functional gray matter activation in COPD (P < 0.01). Differences in DTI, but not rfMRI, remained significant after controlling for stroke risk and smoking (P < 0.05). White matter integrity and gray matter activation seemed to account for difference in cognitive performance between patients with COPD and control subjects. CONCLUSIONS: In stable nonhypoxemic COPD there is reduced white matter integrity throughout the brain and widespread disturbance in functional activation of gray matter, which may contribute to cognitive dysfunction. White matter microstructural integrity but not gray matter functional activation is independent of smoking and cerebrovascular comorbidity. The mechanisms remain unclear, but may include cerebral small vessel disease caused by COPD.

The 12-month effects of early motivational interviewing after acute stroke: a randomized controlled trial.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether motivational interviewing (MI), a patient-centered counseling technique, can benefit patients' mood and mortality poststroke. METHODS: This was a single-center, open, randomized, controlled trial. The setting was a hospital with a stroke unit. Four hundred eleven consecutive patients on the stroke register were >18 years old, not known to be moving out-of-area postdischarge, not receiving psychiatric or clinical psychology intervention, and were without severe cognitive or communication problems preventing participation in interviews. All patients received usual stroke care. Patients in the intervention group also received 4 individual, weekly sessions of MI. The primary outcome was the proportion of patients with normal mood measured by the 28-item General Health Questionnaire (normal <5; low ≥5) using a mailed questionnaire at 12 months poststroke. RESULTS: At 12-month follow-up (including imputed data), 37.7% patients in the control group and 48.0% patients in the intervention group had normal mood. Twenty-five (12.8%) of 195 patients in the control group and 13 (6.5%) of 199 patients in the intervention group had died. A significant benefit of motivational interviewing over usual stroke care was found for mood (P=0.020; OR, 1.66; 95% CI, 1.08 to 2.55) and mortality (P=0.035; OR, 2.14; 95% CI, 1.06 to 4.38). CONCLUSIONS: Results suggest that motivational interviewing improves patients' mood and reduces mortality 12 months poststroke. CLINICAL TRIAL REGISTRATION: URL: www.controlled-trials.com. Unique identifier: ISRCTN54465472.

Evaluation of a single-item screening tool for depression after stroke: a cohort study.

OBJECTIVES: To determine the accuracy and utility of a single-item screening tool for depression (the Yale, taken from the Yale-Brown Obsessive Compulsive Scale) in patients who have recently had a stroke. DESIGN: Comparison of a clinical classification of depression with a screening tool in a defined cohort. SETTING: A large teaching hospital in Liverpool, UK. SUBJECTS: One hundred and twenty-two consecutive people admitted with an acute stroke who did not have severe cognitive or communication problems, and who were still in hospital in the second week post stroke. MAIN MEASURES: Classification of depression using the Montgomery-Asberg Depression Rating Scale was compared with the Yale, a single-item screening tool. RESULTS: When comparing the classification of depression according to the Montgomery-Asberg Depression Rating Scale and the response to the Yale we found that at week 2 the Yale had a sensitivity of 86% (57/66), a specificity of 84% (46/55), a positive predictive value of 86% (57/66) and a negative predictive value of 84% (46/55), with an overall efficiency of 85% (103/121); prevalence of depression was 54% (according to the Montgomery-Asberg Depression Rating Scale). At month 3 the Yale had a sensitivity of 95% (52/55), a specificity of 89% (32/36), a positive predictive value of 93% (52/56) and a negative predictive value of 91% (32/35), with an overall efficiency of 92% (84/91); prevalence of depression was 60%. CONCLUSIONS: The Yale, which only requires a 'yes' or 'no' answer to a single question, may prove a useful screening tool in identifying possible depression in people with stroke both two weeks and three months post stroke.

Motivational interviewing early after acute stroke: a randomized, controlled trial.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether motivational interviewing, a patient-centered counseling technique, can benefit patients' mood 3 months after stroke. METHODS: A single-center, open, randomized, controlled trial was conducted at a single hospital with a stroke unit. Subjects consisted of 411 consecutive patients on the stroke register who were over 18 years of age and who did not have severe cognitive and communication problems that would prevent them from taking part in an interview; were not known to be moving out of the area after discharge; and were not already receiving psychiatric or clinical psychology intervention. All patients received usual stroke care. Patients in the intervention group received 4 individual, weekly sessions of motivational interviewing with a trained therapist in addition to usual stroke care. The primary outcome was the proportion of patients with normal mood at 3 months poststroke measured by the 28-item General Health Questionnaire (normal, <5; low > or=5) using a mailed questionnaire. RESULTS: Eighty-one of 207 (39.1%) patients in the control group and 100 of 204 (49.0%) patients in the intervention group had normal mood at follow up. A significant benefit of motivational interviewing over usual stroke care (OR: 1.60, 95% CI: 1.04 to 2.46, P=0.03) was found. CONCLUSIONS: Our results suggest motivational interviewing leads to an improvement in patients' mood 3 months after stroke.