Revisiting the utility of identifying nuclear grooves as unique nuclear changes by an object detector model.

BACKGROUND: Among other structures, nuclear grooves are vastly found in papillary thyroid carcinoma (PTC). Considering that the application of artificial intelligence in thyroid cytology has potential for diagnostic routine, our goal was to develop a new supervised convolutional neural network capable of identifying nuclear grooves in Diff-Quik stained whole-slide images (WSI) obtained from thyroid fineneedle aspiration. METHODS: We selected 22 Diff-Quik stained cytological slides with cytological diagnosis of PTC and concordant histological diagnosis. Each of the slides was scanned, forming a WSI. Images that contained the region of interest were obtained, followed by pre-formatting, annotation of the nuclear grooves and data augmentation techniques. The final dataset was divided into training and validation groups in a 7:3 ratio. RESULTS: This is the first artificial intelligence model based on object detection applied to nuclear structures in thyroid cytopathology. A total of 7,255 images were obtained from 22 WSI, totaling 7,242 annotated nuclear grooves. The best model was obtained after it was submitted 15 times with the train dataset (14th epoch), with 67% true positives, 49.8% for sensitivity and 43.1% for predictive positive value. CONCLUSIONS: The model was able to develop a structure predictor rule, indicating that the application of an artificial intelligence model based on object detection in the identification of nuclear grooves is feasible. Associated with a reduction in interobserver variability and in time per slide, this demonstrates that nuclear evaluation constitutes one of the possibilities for refining the diagnosis through computational models.

Joint family consultations for psychiatric inpatients with severe eating disorders transitioning to adulthood: psychoanalytic design of a therapeutic setting.

While family work is acknowledged as relevant in the care of eating disorders (EDs), not much literature has explored it in the period of transition from adolescence to young adulthood (16-18 to 30 y.o.). Yet this period is of significant importance in the prognosis and evolution of EDs; but its particular stakes require specific therapeutic settings-especially for inpatient EDs. In this paper, we start from the paradoxical observation that some families refuse this type of work in its usual form, with a family-dedicated therapist, and require to only exchange with the psychiatrist in charge of the treatment plan. We use a psychosomatic-informed psychoanalytic approach to shed light on this refusal as a latent denial of the contribution of family dynamics to the current symptom, and an unconscious tendency to stick to a dependency-laden family scheme. We then explain the conception of a specifically dedicated therapeutic setting, designed to address this specific type of resistance, offered to families as a therapeutic compromise designed to give them a specific position in the care of their child. In our joint therapeutic consultations, family dynamics are addressed on the basis of exchanges regarding treatment and in particular feeding. While such exchanges start from medical considerations, the therapeutic couple (psychiatrist-psychologist) uses them to address the parent and patient expectations underlying the symptom. We propose to call this act "inscription"; it enables a separation from the underlying dependency-oriented family scheme, while stressing the importance to care for associated parental anxieties.

Preclinical Assessment of Mesenchymal-Stem-Cell-Based Therapies in Spinocerebellar Ataxia Type 3.

The low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies for neurodegenerative diseases, including spinocerebellar ataxias. Spinocerebellar ataxia type 3 (SCA3)-or Machado-Joseph disease (MJD)-is the most common dominant ataxia, being mainly characterized by motor deficits; however, SCA3/MJD has a complex and heterogeneous pathophysiology, involving many CNS brain regions, contributing to the lack of effective therapies. Mesenchymal stem cells (MSCs) have been proposed as a potential therapeutic tool for CNS disorders. Beyond their differentiation potential, MSCs secrete a broad range of neuroregulatory factors that can promote relevant neuroprotective and immunomodulatory actions in different pathophysiological contexts. The objective of this work was to study the effects of (1) human MSC transplantation and (2) human MSC secretome (CM) administration on disease progression in vivo, using the CMVMJD135 mouse model of SCA3/MJD. Our results showed that a single CM administration was more beneficial than MSC transplantation-particularly in the cerebellum and basal ganglia-while no motor improvement was observed when these cell-based therapeutic approaches were applied in the spinal cord. However, the effects observed were mild and transient, suggesting that continuous or repeated administration would be needed, which should be further tested.

A Cell Culture Model for Studying the Role of Neuron-Glia Interactions in Ischemia.

Ischemic stroke is a clinical condition characterized by hypoperfusion of brain tissue, leading to oxygen and glucose deprivation, and the consequent neuronal loss. Numerous evidence suggests that the interaction between glial and neuronal cells exert beneficial effects after an ischemic event. Therefore, to explore potential protective mechanisms, it is important to develop models that allow studying neuron-glia interactions in an ischemic environment. Herein we present a simple approach to isolate astrocytes and neurons from the rat embryonic cortex, and that by using specific culture media, allows the establishment of neuron- or astrocyte-enriched cultures or neuron-glia cultures with high yield and reproducibility. To study the crosstalk between astrocytes and neurons, we propose an approach based on a co-culture system in which neurons cultured in coverslips are maintained in contact with a monolayer of astrocytes plated in multiwell plates. The two cultures are maintained apart by small paraffin spheres. This approach allows the independent manipulation and the application of specific treatments to each cell type, which represents an advantage in many studies. To simulate what occurs during an ischemic stroke, the cultures are subjected to an oxygen and glucose deprivation protocol. This protocol represents a useful tool to study the role of neuron-glia interactions in ischemic stroke.

Histamine: a new immunomodulatory player in the neuron-glia crosstalk.

Histamine is an amine acting as a major peripheral inflammatory mediator. In the brain, histamine was initially viewed as a neurotransmitter, but new evidences support its involvement in the modulation of innate immune responses. Recently, we showed that histamine modulates microglial migration and cytokine release. Its pleiotropic actions, ranging from neurotransmission to inflammation, highlight histamine as a key player in a vast array of brain physiologic activities and also in the pathogenesis of several neurodegenerative diseases. Herein, we emphasize the role of histamine as a modulator of brain immune reactions, either by acting on invading peripheral immune cells and/or on resident microglial cells. We also unveil the putative involvement of histamine in the microglial-neuronal communication. We first show that histamine modulates the release of inflammatory mediators, namely nitric oxide, by microglia cells. Consequently, the microglia secretome released upon histamine stimulation fosters dopaminergic neuronal death. These data may reveal important new pharmacological applications on the use histamine and antihistamines, particularly in the context of Parkinson's disease.