Therapeutic vaccination halts disease progression in BALB-neuT mice: the amplitude of elicited immune response is predictive of vaccine efficacy

The aim of this study was to evaluate the efficacy of genetic vaccination with rat ErbB2 antigen in a therapeutic setting for the BALB-neuT mouse model of mammary carcinoma and to establish immunological correlates with vaccine efficacy. To define an early therapeutic setting we performed imaging studies of mouse mammary glands with a high-frequency ultrasound system that allowed the diagnosis of tumor lesions before they become palpable, starting from week 13 after mouse births. An intensive immunization protocol of vaccination was implemented at this stage, consisting of four weekly DNA injections with electroporation followed by two injections of adenovirus carrying the codon usage-optimized cDNA encoding the extracellular-transmembrane domain of rat ErbB2. Immunological parameters were monitored in each individual mouse by analyzing peripheral blood leukocytes. The appearance of the first palpable tumor in vaccinated mice was delayed and there was a statistically significant time gap before additional masses developed, indicating disease stabilization. As a result of the immunization, antibodies and CD8(+) T cells to rat ErbB2 were detected and the amplitude of elicited responses correlated with the efficacy of vaccination. Moreover, the vaccination regimen specifically halted the rise in circulating myeloid suppressor cells (MSCs). All three parameters, that is, CD8(+) T cells, antibodies to rat ErbB2, and circulating MSCs, measured at the end of vaccination could be used as predictive biomarkers for future tumor development. This study emphasizes the potential of genetic vaccines for the therapeutic treatment of malignancies and suggests possible predictive biomarkers to be further validated in the clinic for the follow-up of vaccinated cancer patients.     

Complementary information from multi-exponential T2 relaxation and diffusion tensor imaging reveals differences between multiple sclerosis lesions

While conventional magnetic resonance imaging (MRI) has long been used to study multiple sclerosis (MS), more sensitive and specific approaches to studying both MS lesions and normal appearing white matter (NAWM) are needed to gain a better understanding of the pathogenesis of the disease. Two MRI techniques thought to offer insight regarding myelin and axonal integrity are T(2) relaxation and diffusion tensor imaging (DTI). In this study, metrics obtained from T(2) relaxation (specifically myelin water content (MWC) and long-T(2) fraction) and DTI experiments (in particular the fractional anisotropy, mean diffusivity , parallel diffusivity lambda(||), and perpendicular diffusivity lambda(perpendicular)) were compared for 19 MS patients within both lesion and contralateral NAWM with the goal of better understanding how each of the measures are affected by pathology. In particular, it was successfully determined that the detection of a long-T(2) signal within an MS lesion is indicative of a different underlying pathology than is present in lesions without long-T(2) signal. All of the diffusion metrics were significantly different in lesions with a long-T(2) signal than in those without. While no significant correlations were found between MWC and , lambda(||) or lambda(perpendicular) in NAWM (R(2)=0.02-0.04, p>0.07), and only weak correlations were found in lesions without long-T(2) signal (R(2)=0.05-0.14, p<0.04), strong correlations were observed in lesions exhibiting long-T(2) signal (R(2)=0.54-0.61, p<0.0001).     

An fMRI study measuring analgesia enhanced by religion as a belief system

Although religious belief is often claimed to help with physical ailments including pain, it is unclear what psychological and neural mechanisms underlie the influence of religious belief on pain. By analogy to other top-down processes of pain modulation we hypothesized that religious belief helps believers reinterpret the emotional significance of pain, leading to emotional detachment from it. Recent findings on emotion regulation support a role for the right ventrolateral prefrontal cortex (VLPFC), a region also important for driving top-down pain inhibitory circuits. Using functional magnetic resonance imaging in practicing Catholics and avowed atheists and agnostics during painful stimulation, here we show the existence of a context-dependent form of analgesia that was triggered by the presentation of an image with a religious content but not by the presentation of a non-religious image. As confirmed by behavioral data, contemplation of the religious image enabled the religious group to detach themselves from the experience of pain. Critically, this context-dependent modulation of pain specifically engaged the right VLPFC, whereas group-specific preferential liking of one of the pictures was associated with activation in the ventral midbrain. We suggest that religious belief might provide a framework that allows individuals to engage known pain-regulatory brain processes.     

Seeking refuge from the storm

I didn't think I had much to offer my home health care patient, but I unexpectedly met some of her needs that snowy day.     

Is the modified Tardieu scale in semi‐standing position better associated with knee extension and hamstring activity in terminal swing than the supine Tardieu?

The aim of this study was to investigate whether the modified Tardieu scale (MTS) in a semi-standing position, used for the assessment of hamstrings spasticity, was better associated with knee extension and hamstrings activity in terminal swing than the MTS in a supine position in children with cerebral palsy (CP). Seven children diagnosed with spastic CP (Gross Motor Function Classification System Levels I-II) and seven healthy comparison children participated in the study. An instrumented MTS in supine and semi-standing position and an instrumented gait assessment were conducted. Results showed that spasticity-related outcomes of the semi-standing MTS do not show better associations with terminal swing characteristics of gait than the same outcomes of the supine MTS in children with spastic CP. Only the passive restricted knee angle from the supine MTS was strongly associated with the maximum knee extension during gait (r(s)=0.99; p <0.001), suggesting that hamstrings length is more important for terminal swing behaviour than hamstrings spasticity.