Sustained neural activity to gaze and emotion perception in dynamic social scenes

To understand social interactions, we must decode dynamic social cues from seen faces. Here, we used magnetoencephalography (MEG) to study the neural responses underlying the perception of emotional expressions and gaze direction changes as depicted in an interaction between two agents. Subjects viewed displays of paired faces that first established a social scenario of gazing at each other (mutual attention) or gazing laterally together (deviated group attention) and then dynamically displayed either an angry or happy facial expression. The initial gaze change elicited a significantly larger M170 under the deviated than the mutual attention scenario. At around 400 ms after the dynamic emotion onset, responses at posterior MEG sensors differentiated between emotions, and between 1000 and 2200 ms, left posterior sensors were additionally modulated by social scenario. Moreover, activity on right anterior sensors showed both an early and prolonged interaction between emotion and social scenario. These results suggest that activity in right anterior sensors reflects an early integration of emotion and social attention, while posterior activity first differentiated between emotions only, supporting the view of a dual route for emotion processing. Altogether, our data demonstrate that both transient and sustained neurophysiological responses underlie social processing when observing interactions between others.     

In vivo assessment of skin electroporation using square wave pulses.

The application of short-duration high-voltage pulses to the skin has been shown to enhance transdermal drug delivery by several orders of magnitude and to transiently permeabilize cells in tissue. Both exponentially decaying (ED) pulses and square wave (SW) pulses have been applied. The latter have also been used for electrochemotherapy. To date, their effect on skin integrity has not been analyzed. The scope of this work was (i) to investigate the effect induced by SW pulses on the stratum corneum and the skin, (ii) to evaluate the safety issue associated with electroporation, (iii) to contribute to the understanding of drug transport. Biophysical techniques (transepidermal water loss, chromametry, impedance and laser Doppler velocimetry or imaging measurement) and histological methods were combined to provide a global picture of the effects. Ten SW pulses applied to the skin induced a mild impairment of the skin barrier function and a dramatic decrease in skin resistance. These changes were reversible. A transient decrease (<5 min) in blood flow was observed. Neither inflammation, nor necroses were observed. These studies confirm the tolerance of the skin to square wave pulses in vivo.     

Regenerative therapy with mesenchymal stem cells at the site of malignant primary bone tumour resection: what are the risks of early or late local recurrence?

Purpose

There is concern that regenerative cell-based therapies at the site of malignant primary bone tumours could result in increased risk of local tumour recurrence. We therefore investigated the long-term risks for site-specific recurrences in patients who had received an autologous bone marrow derived mesenchymal stem cell suspension to improve healing at the host-to-allograft bone junction of the reconstruction after bone tumour resection.

Methods

A total of 92 patients were treated from 1993 to 2003 with bone marrow-derived mesenchymal stem cells after bone tumour resection. Patients were monitored for cancer incidence from the date of first operation (1993) until death, or until 31 December 2013. The mean follow-up time was 15.4 years (range ten to 20 years). The average number of MSCs returned to the patient was 234,000 MSCs?±?215,000. The primary outcome was to evaluate the risk of tumorigenesis recurrence at the cell therapy treatment sites with radiographs and/or MRIs. The relative risk of cancer recurrence was expressed as the ratio of observed and expected number of cases according to three different control populations.

Results

Thirteen recurrences were found at the treatment sites among the 92 patients. The expected number of recurrences based on incidence in the three cohort populations was between 15 and 20 for the same cancer, age and sex distribution. The standardized incidence ratio (equal to observed cancers divided by expected cancers) for the entire follow-up period and for all recurrences was between 0.65 and 0.86 (95 % CI 0.60–1.20).

Conclusion

This study found no increased cancer local recurrence risk in patients after application of autologous cell-based therapy using bone marrow-derived mesenchymal stem cells at the treatment site after an average follow-up period of 15.4 years, ranging from ten to 20 years.     

Neural representations of ethologically relevant hand/mouth synergies in the human precentral gyrus

Complex motor responses are often thought to result from the combination of elemental movements represented at different neural sites. However, in monkeys, evidence indicates that some behaviors with critical ethological value, such as self-feeding, are represented as motor primitives in the precentral gyrus (PrG). In humans, such primitives have not yet been described. This could reflect well-known interspecies differences in the organization of sensorimotor regions (including PrG) or the difficulty of identifying complex neural representations in peroperative settings. To settle this alternative, we focused on the neural bases of hand/mouth synergies, a prominent example of human behavior with high ethological value. By recording motor- and somatosensory-evoked potentials in the PrG of patients undergoing brain surgery (2–60 y), we show that two complex nested neural representations can mediate hand/mouth actions within this structure: (i) a motor representation, resembling self-feeding, where electrical stimulation causes the closing hand to approach the opening mouth, and (ii) a motor–sensory representation, likely associated with perioral exploration, where cross-signal integration is accomplished at a cortical site that generates hand/arm actions while receiving mouth sensory inputs. The first finding extends to humans’ previous observations in monkeys. The second provides evidence that complex neural representations also exist for perioral exploration, a finely tuned skill requiring the combination of motor and sensory signals within a common control loop. These representations likely underlie the ability of human children and newborns to accurately produce coordinated hand/mouth movements, in an otherwise general context of motor immaturity.Since Penfield’s original work, it is commonly assumed that complex motor responses are produced by combining elemental movements that are independently represented at different neural sites (1). However, the generality of this model was recently challenged in nonhuman primates, where reaching, grasping, defensive, and hand/mouth movements have been found to be represented as complex motor primitives in independent circumscribed territories of the precentral gyrus (PrG) (2–4). To account for this observation, it was suggested that complex motor primitives have emerged during primate evolution to optimize the production of ethologically relevant behaviors (4). However, to date, direct evidence is lacking that such integrated representations of ethologically relevant movements also exist in humans. This may have two different origins.First, it could be that complex ethologically relevant representations exist in human PrG but have not yet been described, due to the difficulty of identifying neural representations associated with the expression of elaborate sensorimotor behaviors in peroperative contexts. With respect to this point, Penfield and other researchers have clearly reported complex multijoint motor responses following cortical stimulation (5–8), including concurrent movements of the hand and mouth (9). Nevertheless, these movements were not investigated systematically in several subjects, described in detail, or related to the existence of integrated neural representations for ethologically relevant behaviors. An obstacle to the investigation of these representations could have been the tendency to stop the stimulation following movement onset. This was explicitly acknowledged by Penfield in the following terms: “the stimulating electrode has frequently been removed at the first evidence of response, and thus the opportunity of producing more of the elaborate synergic responses may have been missed” (6).At a second level, it could be that the PrG does not contain functional representations of complex ethologically relevant behaviors in humans. This possibility is consistent with the existence of substantial dissimilarities in sensorimotor organization between human and nonhuman primates (10, 11). Interestingly, these dissimilarities are well documented for the precentral region mediating ethological synergies in monkeys. In this species, electrical stimulation in the rostral part of PrG evokes coordinated hand-to-mouth movements (12). These movements are part of the behavioral repertoire of the primate newborns (13), which is consistent with the observation that the rostral (phylogenetically oldest) part of PrG lacks cortico-motoneural cells and generates movements by recruiting the integrative mechanisms of the spinal cord through descending projections that are mature at birth (14). However, in human infants, the difficulty of evoking motor responses through electrical stimulation of the rostral PrG does not seem consistent with the existence of early mature descending projections (15, 16). Also, in adults, transcranial magnetic stimulation studies have suggested, in apparent contrast with monkey data, that late-maturing cortico-motoneural cells are present in the human rostral PrG (17, 18).The main aim of this study was to determine whether integrated neural representations of complex actions can be found in the human PrG. We investigated this possibility by studying the neural bases of hand/mouth synergies, a salient example of early and elaborate human behavior with high ethological value (19–21). To this end, motor and somatosensory mapping were combined in children and adult patients undergoing brain surgeries.     

C3 nephritic factor associated with C3 glomerulopathy in children

Background

C3 glomerulopathy (C3G) is characterized by predominant C3 deposits in glomeruli and dysregulation of the alternative pathway of complement. Half of C3G patients have a C3 nephritic factor (C3NeF). C3G incorporated entities with a range of features on microscopy including dense deposit diseases (DDD) and C3 glomerulonephritis (C3GN). The aim of this work was to study children cases of C3G associated with C3NeF.

Methods

We reviewed 18 cases of C3G with a childhood onset associated with C3NeF without identified mutations in CFH, CFI, and MCP genes.

Results

Clinical histories started with recurrent hematuria for seven patients, nephrotic syndrome for four, acute post-infectious glomerulonephritis for three and acute renal failure for four. Twelve patients had a low C3 at first investigation. Kidney biopsy showed ten C3GN and eight DDD. Twenty-three percent of the patients tested presented elevated sC5b9. Seven patients relapsed 3 to 6 years after the onset. At the end of follow-up, two patients were under dialysis, 11 had a persistent proteinuria, five had none; four patients did not follow any treatment. Steroids were first used in 80 % of cases.

Conclusions

C3NeF associated C3G has a heterogeneous presentation and outcome. Anti-proteinuric agents may control the disease during follow-up, even after nephrotic syndrome at the onset. The efficiency of immunosuppressive therapy remains questionable.     

Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis

Purpose  

The endothelial protein C receptor (EPCR) negatively regulates the coagulopathy and inflammatory response in sepsis. Mechanisms controlling the expression of cell-bound and circulating soluble EPCR (sEPCR) are still unclear. Moreover, the clinical impact of EPCR shedding and its potential value to predict sepsis progression and outcome remain to be established.     

Metabolic syndrome and low high-density lipoprotein cholesterol are associated with adverse pathological features in patients with prostate cancer treated by radical prostatectomy

Background

Previous studies have suggested a link between metabolic syndrome (MetS) and prostate cancer (PCa). In the present study, we aimed to assess the association between MetS and markers of PCa aggressiveness on radical prostatectomy (RP).