Vascular study of decellularized porcine long bones: Characterization of a tissue engineering model.

INTRODUCTION: Massive bone allografts enable the reconstruction of critical bone defects in numerous conditions (e.g. tumoral, infection or trauma). Unfortunately, their biological integration remains insufficient and the reconstruction may suffer from several postoperative complications. Perfusion-decellularization emerges as a tissue engineering potential solution to enhance osseointegration. Therefore, an intrinsic vascular study of this novel tissue engineering tool becomes essential to understand its efficacy and applicability. MATERIAL AND METHODS: 32 porcine long bones (humeri and femurs) were used to assess the quality of their vascular network prior and after undergoing a perfusion-decellularization protocol. 12 paired bones were used to assess the vascular matrix prior (N = 6) and after our protocol (N = 6) by immunohistochemistry. Collagen IV, Von Willebrand factor and CD31 were targeted then quantified. The medullary macroscopic vascular network was evaluated with 12 bones: 6 were decellularized and the other 6 were, as control, not treated. All 12 underwent a contrast-agent injection through the nutrient artery prior an angio CT-scan acquisition. The images were processed and the length of medullary vessels filled with contrast agent were measured on angiographic cT images obtained in control and decellularized bones by 4 independent observers to evaluate the vascular network preservation. The microscopic cortical vascular network was evaluated on 8 bones: 4 control and 4 decellularized. After injection of gelatinous fluorochrome mixture (calcein green), non-decalcified fluoroscopic microscopy was performed in order to assess the perfusion quality of cortical vascular lacunae. RESULTS: The continuity of the microscopic vascular network was assessed with Collagen IV immunohistochemistry (p-value = 0.805) while the decellularization quality was observed through CD31 and Von Willebrand factor immunohistochemistry (p-values <0.001). The macroscopic vascular network was severely impaired after perfusion-decellularization; nutrient arteries were still patent but the amount of medullary vascular channels measured was significantly higher in the control group compared to the decellularized group (p-value <0.001). On average, the observers show good agreement on these results, except in the decellularized group where more inter-observer discrepancies were observed. The microscopic vascular network was observed with green fluoroscopic signal in almost every canals and lacunae of the bone cortices, in three different bone locations (proximal metaphysis, diaphysis and distal metaphysis). CONCLUSION: Despite the aggressiveness of the decellularization protocol on medullary vessels, total porcine long bones decellularized by perfusion retain an acellular cortical microvascular network. By injection through the intact nutrient arteries, this latter vascular network can still be used as a total bone infusion access for bone tissue engineering in order to enhance massive bone allografts prior implantation.

[ADI-R and ADOS and the differential diagnosis of autism spectrum disorders: Interests, limits and openings]. / L'ADI-R et l'ADOS face au diagnostic différentiel des troubles du spectre autistique : intérêts, limites et ouvertures.

INTRODUCTION: Current developments in international public health are leading qualified authorities to release clinical practice guidelines for Autism Spectrum Disorders (ASD) assessment and diagnosis. Such documents incorporate procedures that rely on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) which are considered to be the "gold standard" assessment measures in the evaluation of ASD. Although these tools do prove their effectiveness in the evaluation of autistic symptomatology, they nevertheless stumble whenever the situation becomes more complex and reveal differential diagnostic issues in infantile and adult autism cases. This differential diagnostic issue remains significant in the clinical practice of daily life and has strong implications for the course of therapeutic treatment. OBJECTIVES: Our objective is to underline and nuance the metrological qualities of the ADI-R and the ADOS in the differential diagnosis of autistic disorders by presenting a synthesis of recent studies, thus supporting the interest of maintaining an open debate on diagnostic practices. METHODS: Our selective review of the recent literature focuses on studies that confront the ADI-R and the ADOS - used either independently or in a combination - with various differential issues in adulthood and childhood autism in order to highlight their qualities and limits. RESULTS: The ADI-R is a semi-structured interview applied by trained examiners and applied to relatives and/or caregivers who collect developmental information about the patient's first years of life on a variety of behaviors and skills. It is therefore relatively dependent on the availability and personal bias of the interviewed third parties. Metric features highlighted by the reviewed studies straightforwardly reveal a certain effectiveness of the tool and a good discrimination of childhood disorders. At the same time, the tool's discriminatory capacity seems insufficient when applied to toddlers, very young children, and adults alike. The latter seems particularly true when it comes to differentiating between autistic and schizophrenic spectrum disorders. The ADOS is a semi-structured standardized observation assessment tool that has experienced several successive developments, such as optimizations concerning the sensitivity of its cutoffs. Many works have contributed to building such a tool with reliable and solid metric qualities which nevertheless retain important biases such as the subjectivity of the caregiver or the evaluator during the scoring process. For assessments of autistic children the tool still has a good diagnostic validity but seems to retain cases of incorrect diagnosis of ASD (false positives). In other words, disorders or developmental disabilities of some children and adolescents could not be distinguished from ASD when relying on this test alone. The ADOS Module 4, designed for the diagnosis of adolescents and adults with fluent speech, has undergone less updating. This revisited algorithm has metrological qualities useful for clinicians and remains one of the few available tools for this population. Unfortunately, its diagnostic accuracy is lower when applied to women, the elderly, people with personality disorders or higher intellectual abilities, or for the discrimination between ASD and schizophrenia. Overall, scores from these two instruments bring strong evidence of their usefulness in the diagnostic process of ASD, provided that they are used with caution and a critical clinical perspective, and only as a secondary technical support. Their use in combination is effective since they are complementary and compensate for each other's limitations. However, their globalized hegemony as "gold-standard" tools constitutes a setback insofar as it constrains the diagnosis of ASD to a set of stereotyped items. The latter in turn sets a normative model of autism that excludes other phenotypic forms, especially in the case of women and the elderly. Finally, the discrimination between autism and psychosis for children seems to remain an insoluble task even for the ADI-R/ADOS combination. CONCLUSIONS: The problematics of differential diagnosis remain critical for clinical approaches to autism. Therefore, formalizations of the diagnostic procedures must be able to remain open-minded and accompanied by a creative clinical approach, especially in the case of complex situations that are not soluble by means of conventional diagnostic tools. One possibility may lie in the deepening of the phenomenological approach to autism as an attempt to model the subjective phenomena of autistic subjects and thus operationalize elements that serve the diagnostic process. In the same way, a psychodynamic epistemology could help clinicians to go beyond the consideration of observable behaviors and scores, introducing a psychoanalytic point of view that interfaces objective behaviors with the individual's dynamic intrapsychic functioning. This project could be articulated with projective methodologies - notably the Rorschach test - which respects the needs for standardization and quantification of conventionally used diagnostic tools.

[African histoplamosis. A report of three pediatric cases]. / Trois cas pédiatriques d'histoplasmose africaine à Brazzaville.

Histoplasmosis duboisii (Histoplasma capsulatum var duboisii) is uncommon disease especially in children. It is observed in Africa where the incidence is unknown. The authors report a series of three pediatric cases. The report concerned 2 girls and one boy who were 3, 9 and 4 year-old, respectively. Symptoms evolved for more than two months in each case. At admission, we found fever and poor general condition. Observed lesions were lymphnodes localisation disseminated (cases 1 and 2), subcutaneous (cold abscess) and cutaneous simulating molluscum contagiosum (case 2), osteoarticular (cases 2 and 3), abdominal including peritoneal and hepatosplenic (case 1). In all cases, a mild leukocytosis was found and an accelerated erythrocyte sedimentation rate (ESR) greater than 70mm. The HIV serology was negative. The treatment consisted of itraconazole in 2 cases and ketoconazole in one case. The evolution was insidious, leading to the discharge against medical advice. The death occurred at home in all cases. CONCLUSION: Histoplasmosis duboisii can realize two main clinical presentations (localized or disseminated), affecting the skin, lymph nodes, bones, sometimes the intra-abdominal organs. HIV serology is not always positive in disseminated forms. The evolution is unpredictable and capricious under antifungal treatment. The disease should be well explained to prevent a possible discharge against medical advice, often pejorative.

Polar interface phonons in ionic toroidal systems.

We use the dielectric continuum model to obtain the polar (Fuchs-Kliewer like) interface vibration modes of toroids made of ionic materials either embedded in a different material or in vacuum, with applications to nanotoroids specially in mind. We report the frequencies of these modes and describe the electric potential they produce. We establish the quantum-mechanical Hamiltonian appropriate for their interaction with electric charges. This Hamiltonian can be used to describe the effect of this interaction on different types of charged particles either inside or outside the torus.