The emerging role of cancer nanotechnology in the panorama of sarcoma

In the field of nanomedicine a multitude of nanovectors have been developed for cancer application. In this regard, a less exploited target is represented by connective tissue. Sarcoma lesions encompass a wide range of rare entities of mesenchymal origin affecting connective tissues. The extraordinary diversity and rarity of these mesenchymal tumors is reflected in their classification, grading and management which are still challenging. Although they include more than 70 histologic subtypes, the first line-treatment for advanced and metastatic sarcoma has remained unchanged in the last fifty years, excluding specific histotypes in which targeted therapy has emerged. The role of chemotherapy has not been completely elucidated and the outcomes are still very limited. At the beginning of the century, nano-sized particles clinically approved for other solid lesions were tested in these neoplasms but the results were anecdotal and the clinical benefit was not substantial. Recently, a new nanosystem formulation NBTXR3 for the treatment of sarcoma has landed in a phase 2-3 trial. The preliminary results are encouraging and could open new avenues for research in nanotechnology. This review provides an update on the recent advancements in the field of nanomedicine for sarcoma. In this regard, preclinical evidence especially focusing on the development of smart materials and drug delivery systems will be summarized. Moreover, the sarcoma patient management exploiting nanotechnology products will be summed up. Finally, an overlook on future perspectives will be provided

Virtual Surgical Planning, 3D-Printing and Customized Bone Allograft for Acute Correction of Severe Genu Varum in Children

Complex deformities of lower limbs are frequent in children with genetic or metabolic skeletal disorders. Early correction is frequently required, but it is technically difficult and burdened by complications and recurrence. Herein, we described the case of a 7-year-old girl affected by severe bilateral genu varum due to spondyloepiphyseal dysplasia. The patient was treated by patient-specific osteotomies and customized structural wedge allograft using Virtual Surgical Planning (VSP) and 3D-printed patient-specific instrumentation (PSI). The entire process was performed through an in-hospital 3D-printing Point-of-Care (POC). VSP and 3D-printing applied to pediatric orthopedic surgery may allow personalization of corrective osteotomies and customization of structural allografts by using low-cost in-hospital POC. However, optimal and definitive alignment is rarely achieved in such severe deformities in growing skeleton through a single operation

310 A new proposal for the clinical classification of vulvar lichen sclerosus: an observational prospective study

Introduction/Background Vulvar Lichen Sclerosus (VLS) is a chronic inflammatory disorder which commonly affects the female anogenital epithelium, leading to scarring, anatomical distortions, impaired sexual function, decreased quality of life and increased vulvar cancer risk. An agreement to measure VLS severity in a standard way is yet to be defined and, to our knowledge, no standardized clinical classification of anatomical modifications in VLS has been validated. The purpose of this study was to prepare a clinical classification for VLS aimed at defining the morphological patterns of this condition, while stratifying them into grades. The classification is intended to provide a homogeneous and reproducible description of the different features of this disease. It also serves as an important tool for the evaluation of the course of the disease over time, response to treatment, and for comparison of clinical studies. Methodology A board of seven specialists with expertise in vulvar pathology were asked to outline the anatomical criteria for the definition of VLS severity (phimosis of the clitoris, resorption of the labia minora, involvement of the inter-labial sulcus, and narrowing of the vulvar introitus), identifying five grades to be used to build-up of a score model. The classification was validated by 13 physicians upon pictures of 137 consecutive patients. Each physician individually assigned a grade to each case, according to the abovementioned criteria. Inter-rater agreement among evaluators was analysed by means of ICC (Intraclass Correlation Coefficient). Intra-observer reproducibility and inter-observer concordance in vivo were analysed by means of Kappa index. Results This study provides a new classification of VLS, based on defined anatomical criteria and graded into mutually exclusive progressive classes (table 1). The ICC analysis showed a substantial agreement in the attribution of the grade of VLS among the 137 cases, ICC=0,89 (0.87–0.91), both in the expert and in the non-expert group (ICC=0.92 and 0.87 respectively). An 'almost perfect' agreement was achieved for intra-observer reproducibility and among physicians in vivo (Kappa 0.93). Conclusion Our classification showed a high accuracy in defining morphological modifications in VLS. It is easy to use, reproducible, and can be applied by different health care providers in daily clinical practice and in all clinical settings. Disclosure Nothing to disclose

Emotion and attention regulation in arachnophobic subjects: an fMRI study

Emotions are adaptively useful for our survival, but when they are not appropriate to the situation they can become disadvantageous. Fear has the primary function to motivate escape from dangerous stimuli and to guide selfprotective behaviour, but if it is too strong it can disturb the normal physiological and psychological functioning of individuals. In our everyday life we often have to control our emotions, and we use different automatic and controlled strategies to either up- or down-regulate our reactions. Within the current research we studied individuals who suffer from arachnophobia. This disease is a clear example of how an excessive and unreasonable fear toward a phobic stimulus could have a negative influence on an individual’s life. In the last decades several studies have shown that phobic subjects have a deficit in the recruitment of those brain regions that are linked with both automatic and controlled emotion regulation strategies, but some results are still contradictory and the mechanisms that underlie the control of emotions in phobic subjects remain largely unclear. In order to better understand this topic, we asked arachnophobic and control subjects to down-regulate or keep their emotional reactions, applying both automatic (attentional deployment) and voluntary (reappraisal) control strategies. The manipulation of the automatic strategy consisted in driving subject’s visual attention toward or away from the threatening stimulus, while the voluntary strategy was manipulated asking the subjects to down-regulate their emotions or keep them unaltered during the viewing of spiders. Regarding the manipulation of the automatic control of emotional reaction, we found that this kind of regulation had a greater impact on arachnophobic subjects compared to controls. This was displayed by the activation of the ACC, one important region involved in the automatic control of emotions. As for the controlled regulation of emotional reaction, we didn’t find any significant difference between the two groups in the dorsal prefrontal regions that normally are linked to the controlled regulation of emotions. Moreover, we found that the presentation order of the images gives rise to different neural reactions. In the FS condition (alterting) there was stronger recruitment of the amygdala and the ACC than in the SF condition (relief) for phobic subjects, suggesting that they experienced an increase of anxiety. In the opposite contrast instead, there was stronger recruitment of the precuneus in the SF condition (relief) than in the FS condition (alerting). A better understanding of the neural correlates linked to these deficits of emotion regulation could be useful from a therapeutical point of view, helping phobic subjects to improve the control of their reactions and to manage their fears

Orbitofrontal reality filtering specified: relation to temporal order memory, role of emotion, and development

Orbitofrontal reality filtering (ORFi) is a memory mechanism that allows to sense if a memory pertains to reality or not. A deficit in ORFi is typically associated to amnesia, disorientation and behaviourally spontaneous confabulations. Electrophysiologically, it is characterized by a frontal positivity at 200-400ms. Anatomically, it is associated to an activation of the orbitofrontal cortex, the regions usually damaged in behavioural spontaneous confabulating patients. This thesis used electrophysiological and behavioural data to disentangle some aspects about ORFi that were still unclear. Taken together, our results showed that: 1) ORFi behaviourally and electrophysiologically dissociates from another memory mechanism, that is the ability to recall the temporal context of a memory; 2) ORFi electrophysiologically dissociates from memory's emotionality effects, and it is not modulated by the emotional value of a memory; 3) Children of 7 years old are already capable to perform the task, indicating that at this age ORFi is already functional

Effects of two types of numerical problems on the emotions experienced in adults and in 9-year-old children

It is widely acknowledged that emotions and cognition are closely related, and that negative emotions are detrimental on school achievement, especially on mathematical performance. On the other hand, positive emotions have a positive impact on motivation and cognitive abilities underlying the learning processes. Nevertheless, studies about the effects of experienced emotions on problem solving, a specific type of mathematical activity, are sparse. The present research focuses on experienced epistemic and achievement emotions after the resolution of two types of numerical word problems: the application problems , that requires the use of a specific and expected algorithm to be solved and are regularly proposed at school; and the non-application problems , which cannot be solved directly but using different solving strategies. This type of numerical word problems appears less frequently in French school curricula. In experiment 1, 105 adults (M = 24.4 years), of which the majority was university students, were involved in an online experiment with APs and NAPs problems and were asked to rate their experienced emotions after the resolution of the problems. In experiment 2, 65 children aged 9-year-old were asked to individually solve APs and NAPs problems with age-appropriate difficulty and then rate their associated emotions. The adults’ sample reported higher epistemic and achievement positive emotions towards APs compared to NAPs. In both adults and children NAPs were more associated to surprise than APs. In children anxiety was more experienced after resolution of NAPs than APs. Results suggest the importance of varying the types of problems proposed in school curricula so that children become accustomed to using different solving strategies. This approach could be useful in decreasing negative emotions toward mathematics such as anxiety, which begins to settle as early as elementary school. </p

No Influence of Positive Emotion on Orbitofrontal Reality Filtering: Relevance for Confabulation

Orbitofrontal reality filtering (ORFi) is a mechanism that allows us to keep thought and behavior in phase with reality. Its failure induces reality confusion with confabulation and disorientation. Confabulations have been claimed to have a positive emotional bias, suggesting that they emanate from a tendency to embellish the situation of a handicap. Here we tested the influence of positive emotion on ORFi in healthy subjects using a paradigm validated in reality confusing patients and with a known electrophysiological signature, a frontal positivity at 200-300 ms after memory evocation. Subjects made two continuous recognition tasks ("two runs"), composed of the same set of neutral and positive pictures, but arranged in different order. In both runs, participants had to indicate picture repetitions within, and only within, the ongoing run. The first run measures learning and recognition. The second run, where all items are familiar, requires ORFi to avoid false positive responses. High-density evoked potentials were recorded from 19 healthy subjects during completion of the task. Performance was more accurate and faster on neutral than positive pictures in both runs and for all conditions. Evoked potential correlates of emotion and reality filtering occurred at 260-350 ms but dissociated in terms of amplitude and topography. In both runs, positive stimuli evoked a more negative frontal potential than neutral ones. In the second run, the frontal positivity characteristic of reality filtering was separately, and to the same degree, expressed for positive and neutral stimuli. We conclude that ORFi, the ability to place oneself correctly in time and space, is not influenced by emotional positivity of the processed material

An electrophysiological dissociation between orbitofrontal reality filtering and context source monitoring

Memory influences behavior in multiple ways. One important aspect is to remember in what precise context in the past a piece of information was acquired (context source monitoring). Another important aspect is to sense whether an upcoming thought, composed of fragments of memories, refers to present reality and can be acted upon (orbitofrontal reality filtering). Whether these memory control processes share common underlying mechanisms is unknown. Failures of both have been held accountable for false memories, including confabulation. Electrophysiological and imaging studies suggest a dissociation but used very different paradigms. In this study, we juxtaposed the requirements of context source monitoring and reality filtering within a unique continuous recognition task, which healthy participants performed while high-resolution evoked potentials were recorded. The mechanisms dissociated both behaviorally and electrophysiologically: Reality filtering induced a frontal positivity, absence of a specific electrocortical configuration, and posterior medial orbitofrontal activity at 200-300 msec. Context source monitoring had no electrophysiological expression in this early period. It was slower and less accurate than reality filtering and induced a prolonged positive potential over frontal leads starting at 400 msec. The study demonstrates a hitherto unrecognized separation between orbitofrontal reality filtering and source monitoring. Whereas deficient orbitofrontal reality filtering is associated with reality confusion in thinking, the behavioral correlates of deficient source monitoring should be verified with controlled experimental exploration