The effects of low intensity focused ultrasonic stimulation on dorsal root ganglion neurons and Schwann cells in vitro

Satisfactory treatment of peripheral nerve injury (PNI) faces difficulties owing to the intrinsic biological barriers in larger injuries and invasive surgical interventions. Injury gaps >3 cm have low chances of full motor and sensory recovery, and the unmet need for PNI repair techniques which increase the likelihood of functional recovery while limiting invasiveness motivate this work. Building upon prior work in ultrasound stimulation (US) of dorsal root ganglion (DRG) neurons, the effects of US on DRG neuron and Schwann cell (SC) cocultures were investigated to uncover the role of SCs in mediating the neuronal response to US in vitro. Acoustic intensity‐dependent alteration in selected neuromorphometrics of DRG neurons in coculture with SCs was observed in total outgrowth, primary neurites, and length compared to previously reported DRG monoculture in a calcium‐independent manner. SC viability and proliferation were not impacted by US. Conditioned medium studies suggest secreted factors from SCs subjected to US impact DRG neuron morphology. These findings advance the current understanding of mechanisms by which these cell types respond to US, which may lead to new noninvasive US therapies for treating PNI.     

Microfluidic System for Facilitated Quantification of Nanoparticle Accumulation to Cells Under Laminar Flow

The identification of novel, synthetic targeting ligands to endothelial receptors has led to the rapid development of targeted nanoparticles for drug, gene and imaging probe delivery. Central to development and optimization are effective models for assessing particle binding in vitro. Here, we developed a simple and cost effective method to quantitatively assess nanoparticle accumulation under physiologically-relevant laminar flow. We designed reversibly vacuum-sealed PDMS microfluidic chambers compatible with 35?mm petri dishes, which deliver uniform or gradient shear stress. These chambers have sufficient surface area for facile cell collection for particle accumulation quantitation through FACS. We tested this model by synthesizing and flowing liposomes coated with APN (K _D?~?300???M) and VCAM-1-targeting (K _D?~?30???M) peptides over HUVEC. Particle binding significantly increased with ligand concentration (up to 6?mol%) and decreased with excess PEG. While the accumulation of particles with the lower affinity ligand decreased with shear, accumulation of those with the higher affinity ligand was highest in a low shear environment (2.4?dyne/cm²), as compared with greater shear or the absence of shear. We describe here a robust flow chamber model that is applied to optimize the properties of 100?nm liposomes targeted to inflamed endothelium.     

Mild cognitive impairment in patients with Parkinson's disease is associated with increased cortical degeneration

Mild cognitive impairment (MCI) can occur early in the course of Parkinson's disease (PD), and its presence increases the risk of developing dementia. Determining the cortical changes associated with MCI in PD, thus, may be useful in predicting the future development of dementia. To address this objective, 37 patients with PD, divided into 2 groups according to the presence or absence MCI (18 with and 19 without) and 16 matched controls, underwent anatomic magnetic resonance imaging. Corticometry analyses were performed to measure the changes in cortical thickness and surface area as well as their correlation with disease duration. Compared with healthy controls, the PD‐MCI group exhibited increased atrophy and changes of local surface area in the bilateral occipital, left temporal, and frontal cortices; whereas the PD non‐MCI group exhibited only unilateral thinning and decreased surface area in the occipital lobe and in the frontal cortex. In addition, a comparison between the PD‐MCI and PD non‐MCI groups revealed increased local surface area in the occipital lobe, temporal lobe, and postcentral gyrus for the cognitively impaired patients. It is noteworthy that, in the PD‐MCI group, cortical thickness had a significant negative correlation with disease duration in the precentral, supramarginal, occipital, and superior temporal cortices; whereas, in the PD non‐MCI group, such a correlation was absent. The findings from this study reveal that, at the same stage of PD evolution, the presence of MCI is associated with a higher level of cortical changes, suggesting that cortical degeneration is increased in patients with PD because of the presence of MCI. © 2013 International Parkinson and Movement Disorder Society     

Same day injections of Tc-99m methoxy isobutyl isonitrile (hexamibi) for myocardial tomographic imaging: Comparison between rest-stress and stress-rest injection sequences

It has been shown that both rest and stress ^99mTc-hexamibi myocardial perfusion imaging can be performed on the same day using two different doses injected within few hours (the first one at rest followed by a second at stress). In order to evaluate and compare 2 sequences (rest-stress and stress-rest) of ^99mTc-hexamibi injections performed the same day, 18 patients with either abnormal ²⁰¹Tl myocardial scan or abnormal coronary angiography were studied with 2 ^99mTc-hexamibi injections protocols. The rest-stress study was performed as follows: 7 mCi ^99mTc-hexamibi was injected at rest. Single photon emission computed tomography (SPECT) was performed 60 min later. Immediately after the rest study, patients were injected at peak stress with 25 mCi ^99mTc-hexamibi. Tomographic imaging was repeated 1 h later. Patients were submitted to the stress-rest protocol within 3 days. Tomographic imaging was done 1 h after a 7 mCi injection at stress. This study was followed by an injection of 25 mCi ^99mTc-hexamibi at rest, a tomographic study was performed 60 min later. Myocardial sections were reconstructed in horizontal long, vertical long, and short axes. Data analysis also included polar map representation. A total of 324 segments were interpreted blind by 3 observers, there was an agreement in 283/324 (87.3%) segments between the 2 protocols. However, 24 segments (7.4%) judged ischemic on rest-stress were called scars on stress-rest. In three patients, myocardial segments were judged normal on the rest image of the rest-stress protocol while they were found abnormal (false positive images) on the stress-rest sequence. Stress images from both protocols were judged similar in 17 patients. In conclusion, when using a short time interval (less than 2 h) between two ^99mTc-hexamibi injections, it is preferable to do a rest-stress sequence since the rest image performed initially represents a true rest study, which is not necessarily the case with the stress-rest sequence.     

Genetic dependence of cochlear cells and structures injured by noise

The acute and permanent effects of a single damaging noise exposure were compared in CBA/J, C57BL/6 (B6), and closely related strains of mice. Two hours of broadband noise (4-45 kHz) at 110 dB SPL led to temporary reduction in the endocochlear potential (EP) of CBA/J and CBA/CaJ (CBA) mice and acute cellular changes in cochlear stria vascularis and spiral ligament. For the same exposure, B6 mice showed no EP reduction and little of the pathology seen in CBA. Eight weeks after exposure, all mice showed a normal EP, but only CBA mice showed injury and cell loss in cochlear lateral wall, despite the fact that B6 sustained larger permanent threshold shifts. Examination of noise injury in B6 congenics carrying alternate alleles of genes encoding otocadherin (Cdh23), agouti protein, and tyrosinase (albinism) indicated that none of these loci can account for the strain differences observed. Examination of CBA x B6 F1 mice and N2 backcross mice to B6 further indicated that susceptibility to noise-related EP reduction and associated cell pathology are inherited in an autosomal dominant manner, and are established by one or a few large effect quantitative trait loci. Findings support a common genetic basis for an entire constellation of noise-related cochlear pathologies in cochlear lateral wall and spiral limbus. Even within species, cellular targets of acute and permanent cochlear noise injury may vary with genetic makeup.     

Pain,fatigue, function and participation among long-term manual wheelchair users partnered with a mobility service dog

Purpose: To assess the effects of a mobility service dog (MSD) on pain, fatigue, wheelchair-related functional tasks, participation and satisfaction among manual wheelchair users over a nine-month period.

Method: A longitudinal study with repeated assessment times before and three, six and nine months after intervention was achieved. Intervention consisted in partnering each participant with a MSD. The setting is a well-established provincial service dog training school and participants homes. A convenience sample of 24 long-term manual wheelchair users with a spinal cord injury was involved. Outcome measures were: Wheelchair User’s Shoulder Pain Index (WUSPI), Rate of Perceived Exertion (RPE), vitality scale from the SF-36, grip strength, Wheelchair Skills Test (WST), Canadian Occupational Performance Measure (COPM), Reintegration to Normal Living Index (RNLI), Life Space Assessment, Psychosocial Impact of Assistive Devices Scale (PIADS) and Quebec User Evaluation of Satisfaction with assistive Technology (QUEST 2.0).

Results: Shoulder and wrist pain as well as fatigue decreased significantly over time with the use of a MSD as evidenced by scores from WUSPI, RPE and SF-36 (feeling less worn out). Manual wheelchair propulsion skills (steep slopes, soft surfaces and thresholds) improved significantly over time as confirmed by the WST. Participation increased significantly over time as revealed by the COPM (for five occupations) and the RNLI (for five items). Satisfaction with the MSD was high over time (QUEST: nine items) and with a high positive psychosocial impact (PIADS: 10 items).

Conclusion: MSD represents a valuable mobility assistive technology option for manual wheelchair users.

• IMPLICATIONS FOR REHABILITATION

• For manual wheelchair users partenered with mobility service dog ??Shoulder pain and fatigue significantly decreased and continued to decrease between the third and sixth month and the ninth month.

• ??Performance with propelling the wheelchair up steep slopes increased from 41 to 88% and on soft surfaces increased from 53 to 100% after 3 months, respectively.

• ??Occupational performance satisfaction was significantly increased for mobility in relation with the transfers, navigating in a natural environment and picking up objects.

• ??High satisfaction towards psychosocial competency, psychosocial adequacy and self-esteem were reported at months three, six and nine.

     

The prevalence and correlates of nonaffective psychosis in the National Comorbidity Survey Replication (NCS-R).

BACKGROUND: To estimate the prevalence and correlates of clinician-diagnosed DSM-IV nonaffective psychosis (NAP) in a national household survey. METHODS: Data came from the United States National Comorbidity Survey Replication (NCS-R). A screen for NAP was followed by blinded sub-sample clinical reappraisal interviews. Logistic regression was used to impute clinical diagnoses to respondents who were not re-interviewed. The method of Multiple Imputation (MI) was used to estimate prevalence and correlates. RESULTS: Clinician-diagnosed NAP was well predicted by the screen (area under the curve [AUC] = .80). The MI prevalence estimate of NAP (standard error in parentheses) is 5.0 (2.6) per 1000 population lifetime and 3.0 (2.2) per 1000 past 12 months. The vast majority (79.4%) of lifetime and 12-month (63.7%) cases met criteria for other DSM-IV hierarchy-free disorders. Fifty-eight percent of 12-month cases were in treatment, most in the mental health specialty sector. CONCLUSIONS: The screen for NAP in the NCS-R greatly improved on previous epidemiological surveys in reducing false positives, but coding of open-ended screening scale responses was still needed to achieve accurate prediction. The lower prevalence estimate than in total-population incidence studies raises concerns that systematic nonresponse bias causes downward bias in survey prevalence estimates of NAP.