Janus-faced liposomes enhance antimicrobial innate immune response in Mycobacterium tuberculosis infection

We have generated unique asymmetric liposomes with phosphatidylserine (PS) distributed at the outer membrane surface to resemble apoptotic bodies and phosphatidic acid (PA) at the inner layer as a strategy to enhance innate antimycobacterial activity in phagocytes while limiting the inflammatory response. Results show that these apoptotic body-like liposomes carrying PA (ABL/PA) (i) are more efficiently internalized by human macrophages than by nonprofessional phagocytes, (ii) induce cytosolic Ca(2+) influx, (iii) promote Ca(2+)-dependent maturation of phagolysosomes containing Mycobacterium tuberculosis (MTB), (iv) induce Ca(2+)-dependent reactive oxygen species (ROS) production, (v) inhibit intracellular mycobacterial growth in differentiated THP-1 cells as well as in type-1 and -2 human macrophages, and (vi) down-regulate tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β, IL-18, and IL-23 and up-regulate transforming growth factor (TGF)-β without altering IL-10, IL-27, and IL-6 mRNA expression. Also, ABL/PA promoted intracellular killing of M. tuberculosis in bronchoalveolar lavage cells from patients with active pulmonary tuberculosis. Furthermore, the treatment of MTB-infected mice with ABL/PA, in combination or not with isoniazid (INH), dramatically reduced lung and, to a lesser extent, liver and spleen mycobacterial loads, with a concomitant 10-fold reduction of serum TNF-α, IL-1β, and IFN-γ compared with that in untreated mice. Altogether, these results suggest that apoptotic body-like liposomes may be used as a Janus-faced immunotherapeutic platform to deliver polar secondary lipid messengers, such as PA, into phagocytes to improve and recover phagolysosome biogenesis and pathogen killing while limiting the inflammatory response.     

Maxillary Sinus Augmentation Using Prehydrated Corticocancellous Porcine Bone: Hystomorphometric Evaluation after 6 Months

Background: Insufficient alveolar bone height often prevents the placement of standard dental implants in the posterior part of edentulous maxilla. In order to increase adequately the vertical dimension of the reabsorbed alveolar process, a sinus lift procedure is often necessary. The aim of this study was to evaluate histologic results of a prehydrated corticocancellous porcine bone used in maxillary sinus augmentation. Methods: Patients (age 18–70 years) with a residual bone height requiring a maxillary sinus augmentation procedure to place dental implants were eligible for this study. All patients were treated with the same surgical technique consisting of sinus floor augmentation via a lateral approach. The space obtained by elevation of the mucosa wall was grafted with prehydrated and collagenated corticocancellous porcine bone. Biopsies were harvested 6 months after the augmentation procedures. Results: Twenty‐four patients were enrolled. The mean percentage of new formed bone was 43.9 ± 18.6% (range 7.5–100%), whereas the mean percentage of residual graft material was 14.2 ± 13.6% (range 0–41.9%). The new bone/residual graft material ratio in the maxillary sinuses was 3.1. The mean soft tissues percentage was 41.8 ± 22.7% (range 0–92.5%). Conclusion: The present study suggested that porcine bone showed excellent osteoconductive properties and could be used successfully for sinus augmentation. Moreover, the porcine bone showed a high percentage of reabsorption after 6 months; this might be because of the presence of collagen and the porosity of the graft material.     

Left anterior descending coronary artery pseudoaneurysm compressing the main pulmonary artery in a patient with Behçet's disease

Behçet's disease is a systemic inflammatory vascular disorder that may affect the cardiovascular system. Left anterior descending (LAD) artery aneurysm is a rare but potentially fatal complication of Behçet's disease. An accurate diagnosis of this clinical entity requires multimodal imaging (computerized tomography, angiography, and echocardiography) and is essential to guide appropriate therapeutic management. We report the case of a 22‐year‐old female with LAD pseudoaneurysm who underwent surgical repair with transesophageal echocardiography guidance. We describe the importance of the use of an alternative view to define the origin and location of this unusual pathology. (Echocardiography 2012;29:E91‐E93)     

A practical definition of minor stroke

It is generally assumed that minor stroke (MS) is an ischemic stroke with a short-term, good functional outcome. However, no clear definition of MS exists. Modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS) are still the most accredited standards, but scores and timing of the assessment are not homogeneous. As suggested by a qualified sample of Italian neurologists, the index parameter chosen in our analysis was mRS at the time of hospital discharge. The database of the SIRIO study (a large observational study of 2,573 patients with stroke admitted in Italian hospitals in 2005) was used to identify an mRS threshold to define MS. Reference was made to outcome markers such as rate of discharge to home, 1-year disability and 1-year mortality. The rate of discharge progressively decreased with increase in mRS, while the rates of 1-year mortality and disability progressively increased. Our proposal is one of defining a stroke “minor” when the rate of discharge to home is above the SIRIO database overall value and the 1-year mortality and disability is below the respective overall values. This definition is consistent with a score ≤2 on the mRS.     

MRI Predicts Efficacy of Constraint-Induced Movement Therapy in Children With Brain Injury

Using resting state (RS) functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), we identified the predictors of clinical improvement following constraint-induced movement therapy (CIMT) in pediatric patients with chronic hemiplegia.From 14 children with congenital or acquired brain injury and 10 sex- and age-matched healthy controls, brain dual-echo, DTI and RS fMRI sequences were acquired before CIMT. The Quality of Upper Extremities Skills Test and the Gross Motor Function Measure (GMFM) were administered at baseline, at the end of CIMT (10 weeks), and after 6 months. Mean diffusivity and fractional anisotropy (FA) were measured in the lesion responsible for the clinical symptomatology, the affected and unaffected corticospinal tract (CST), motor transcallosal fibers, and uncinate fasciculus (as an internal control). Independent component analysis was used to identify the sensorimotor RS network. The ability of baseline MRI variables to predict clinical changes over time was assessed using multivariate linear models. At baseline, patients had increased mean diffusivity in the symptomatic lesion and decreased FA in the symptomatic lesion, affected corticospinal tract, and motor transcallosal fibers. A reduced RS functional connectivity was found in the bilateral cerebellum, left precentral gyrus, and right secondary sensorimotor cortex. At follow up, Quality of Upper Extremities Skills Test and GMFM scales improved significantly. Baseline average lesion FA predicted clinical improvement at week 10, and baseline functional connectivity of the right secondary sensorimotor cortex and cerebellum predicted GMFM improvement at month 6. DTI and RS fMRI offer promising and objective markers to predict clinical outcomes following CIMT in pediatric patients with congenital or acquired hemiplegia.     

Attentional shifts between audition and vision in Autism Spectrum Disorders

Previous evidence on neurotypical adults shows that the presentation of a stimulus allocates the attention to its modality, resulting in faster responses to a subsequent target presented in the same (vs. different) modality. People with Autism Spectrum Disorders (ASDs) often fail to detect a (visual or auditory) target in a stream of stimuli after shifting attention between modalities, possibly because they do not fully switch their attention from one modality to the other. In this study, the performance of a group of high-functioning patients with ASDs and a group of neurotypical controls was compared. Participants were asked to detect a target, auditory or visual, which was preceded, at different temporal intervals (i.e., 150, 600, 1000 ms), by an uninformative cue, either in the same or a different modality. In controls, when the target was visual, the cue modality did not affect performance. Unlike, when the target was auditory, a visual cue produced longer reaction times as compared to when it was auditory. In the ASD group, irrespectively of the modality of the cue, a slowing-down of responses to the target was observed at increasing temporal intervals. The discrepancy of performance is consistent with the ‘over-focused’ theory of sensory processing.