A model of mandibular irradiation in the rabbit: preliminary results

Radiotherapy is widely used in the treatment of head and neck cancers. Its major adverse effect is osteoradionecrosis, which can occur during the whole life of the patient, involving the vital prognosis. The aim of the study was to develop a model for irradiation of the rabbit mandible in order to have a better knowledge of radiotherapy-induced bone alterations and thus a better prevention and treatment of osteoradionecrosis. The control group consisted in 7 rabbits and was used to assess anatomical and histological parameters of the rabbit’s mandible. A first group of 14 rabbits was weekly irradiated at doses of 5.5 Gy during 5 weeks, at a total dose of 46.8Gy. Sacrifices were done at 1 week, 4 weeks, 12 weeks and 24 weeks. As histological analysis did not reveal statistical differences with the control group, a second group (3 rabbits) was weekly irradiated at 8.0, 8.5 and 9 Gy during 5 weeks. The first histological results seem to show vascular alterations, bone cells decrease and alterations of bone architecture. The role of intra alveolar collagen sponges, PRF®, ultrasounds and stem cells in bone regeneration after radiotherapy will be further studied. La radiothérapie est une modalité thérapeutique utilisée quasi systématiquement dans le traitement des cancers des voies aérodigestives supérieures. Son principal effet secondaire est l’ostéoradionécrose, qui peut survenir tout au long de la vie du patient et compromettre le pronostic vital. Le but de ce travail est de mettre au point un modèle d’irradiation des maxillaires chez le lapin afin de mieux connaître la pathogénie de l’ostéoradionécrose et proposer une prévention et des traitements plus efficaces. Un groupe contrôle de 7 lapins a permis de connaître l’anatomie et l’histologie de la mandibule de lapin. Un premier groupe de 14 lapins a été irradié à raison d’une séance hebdomadaire de 5.5 Gy pendant 5 semaines, soit un équivalent de dose de 46.8 Gy. Ils ont été sacrifiés à 1, 4, 12 et 24 semaines. L’analyse statistique n’ayant pas montré de différences significatives avec le groupe contrôle, un second groupe de 3 lapins a été irradié à une séance hebdomadaire de 8.0, 8.5 et 98.0 Gy respectivement pendant 5 semaines. Les premiers résultats histologiques montrent une altération vasculaire, la diminution du nombre de cellules osseuses et des modifications de l’architecture osseuse. Le rôle des éponges collagéniques intra alvéolaires, du PRF®, des ultrasons et des cellules souches sera étudié ultérieurement

Ａ病院の師長会における「整体」の研修報告

La radiothérapie (RTE) constitue une thérapeutique majeure dans la prise en charge des cancers ORL. Elle entraîne une altération cellulaire, matricielle et vasculaire des tissus. Au niveau du tissu osseux, cela aboutit à un déséquilibre entre apposition et résorption osseuses, avec pour conséquence un risque d’ostéoradionécrose (ORN)1. Le traitement de l’ORN peut être médical ou chirurgical. Il peut alors comporter des chirurgies lourdes (interruption mandibulaire ), avec des conséquences dramatiques sur les fonctions oro-faciales2. Il apparaît donc nécessaire de développer des techniques préventives et thérapeutiques plus efficaces et moins mutilantes, afin d’améliorer la qualité de vie de ces patients. L’objectif de l’étude est de mettre au point un modèle animal (lapin), permettant de simuler une perte de substance osseuse alvéolaire sur une mandibule irradiée, afin d’évaluer la cicatrisation osseuse après extraction dentaire en territoire irradié, et d’évaluer les effets des ultras sons de faible intensité (LIPUS) dans la prévention ou le traitement de l’ORN. L’étude a été approuvée par le comité d’éthique pour l’expérimentation animale du Centre Léon Bérard (n° d’agrément 69.388.0501). Le modèle animal retenu est le lapin femelle adulte (race New-Zealand White). La première partie de l’étude consiste à confirmer le schéma de radiothérapie. 30 lapins sont inclus ; 10 sont témoins, et 20 sont irradiés selon les modalités suivantes : 8.5 Gy par séance, 5 séances, 1 séance par semaine. A la fin de la radiothérapie, un défaut osseux mandibulaire simulant une extraction dentaire est réalisé. Les animaux sont ensuite sacrifiés à J0, J7, J14, J28, J42. L’évaluation de la reconstruction osseuse au niveau du site d’extraction se fait grâce à des analyses histologiques, la réalisation d’un microscanner et des tests de microdureté. Ensuite, un protocole d’insonification est développé. Après réalisation du défaut osseux chez 12 lapins, 10 mandibules de lapins (2 lapins contrôles) sont insonifiées selon le protocole suivant : fréquence = 1,05MHz, tension = 77mV, 2ms on/8ms off, Intensité acoustique = 300mW/cm. Les sacrifices et l’évaluation de la reconstruction osseuse sont réalisés selon les mêmes modalités que précédemment. Enfin, les LIPUS sont étudiés sur des mandibules de lapins irradiés : 20 lapins sont irradiés puis bénéficient de la création du défaut osseux. 10 recoivent les LIPUS comme précédemment (10 lapins contrôles). Les sacrifices et les analyses histologiques, radiologiques et micro-mécaniques sont réalisés comme précédemment. Une étude de faisabilité est actuellement en cours, afin de déterminer les modalités de création du défaut osseux, et de préciser les paramètres d’évaluation. Différentes études ont montré que les LIPUS stimulaient le tissu osseux en stimulant la différenciation ostéoblastique3. Une utilisation dans le traitement des ORN semble donc envisageable, ce qui permettrait de diminuer les mutilations oro-faciales liées aux chirurgies réalisées actuellement

Severe hematopoietic stem cell inflammation compromises chronic granulomatous disease gene therapy

X-linked chronic granulomatous disease (CGD) is associated with defective phagocytosis, life-threatening infections, and inflammatory complications. We performed a clinical trial of lentivirus-based gene therapy in four patients (NCT02757911). Two patients show stable engraftment and clinical benefits, whereas the other two have progressively lost gene-corrected cells. Single-cell transcriptomic analysis reveals a significantly lower frequency of hematopoietic stem cells (HSCs) in CGD patients, especially in the two patients with defective engraftment. These two present a profound change in HSC status, a high interferon score, and elevated myeloid progenitor frequency. We use elastic-net logistic regression to identify a set of 51 interferon genes and transcription factors that predict the failure of HSC engraftment. In one patient, an aberrant HSC state with elevated CEBPβ expression drives HSC exhaustion, as demonstrated by low repopulation in a xenotransplantation model. Targeted treatments to protect HSCs, coupled to targeted gene expression screening, might improve clinical outcomes in CGD

System-level determinants of immunization coverage disparities among health districts in Burkina Faso: a multiple case study

<p>Abstract</p> <p>Background</p> <p>Despite rapid and tangible progress in vaccine coverage and in premature mortality rates registered in sub-Saharan Africa, inequities to access remain firmly entrenched, large pockets of low vaccination coverage persist, and coverage often varies considerably across regions, districts, and health facilities' areas of responsibility. This paper focuses on system-related factors that can explain disparities in immunization coverage among districts in Burkina Faso.</p> <p>Methods</p> <p>A multiple-case study was conducted of six districts representative of different immunization trends and overall performance. A participative process that involved local experts and key actors led to a focus on key factors that could possibly determine the efficiency and efficacy of district vaccination services: occurrence of disease outbreaks and immunization days, overall district management performance, resources available for vaccination services, and institutional elements. The methodology, geared toward reconstructing the evolution of vaccine services performance from 2000 to 2006, is based on data from documents and from individual and group interviews in each of the six health districts. The process of interpreting results brought together the field personnel and the research team.</p> <p>Results</p> <p>The districts that perform best are those that assemble a set of favourable conditions. However, the leadership of the district medical officer (DMO) appears to be the main conduit and the rallying point for these conditions. Typically, strong leadership that is recognized by the field teams ensures smooth operation of the vaccination services, promotes the emergence of new initiatives and offers some protection against risks related to outbreaks of epidemics or supplementary activities that can hinder routine functioning. The same is true for the ability of nurse managers and their teams to cope with new situations (epidemics, shortages of certain stocks).</p> <p>Conclusion</p> <p>The discourse on factors that determine the performance or breakdown of local health care systems in lower and middle income countries remains largely concentrated on technocratic and financial considerations, targeting institutional reforms, availability of resources, or accessibility of health services. The leadership role of those responsible for the district, and more broadly, of those we label "the human factor", in the performance of local health care systems is mentioned only marginally. This study shows that strong and committed leadership promotes an effective mobilization of teams and creates the conditions for good performance in districts, even when they have only limited access to supports provided by external partners.</p> <p>Abstract in French</p> <p>See the full article online for a translation of this abstract in French.</p

Glial Fibrillary Acidic Protein Autoimmunity: A French Cohort Study

Background and ObjectivesTo report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies.MethodsWe retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers.ResultsWe identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies.DiscussionGFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome

Preface

This is the final version. Available from CEUR Workshop Proceedings via the URL in this record.

A reassessment of the Hypoglossum group (Delesseriaceae, Rhodophyta), with a critique of its genera

A reassessment of the Hypoglossum group (Delesseriaceae, Rhodophyta), with a critique of its genera. Eight genera are assigned to the Hypoglossum Kützing, Phitymophora J. Agardh, Pseudobranchioglossum Bodard, and Zellera Martens. The circumscription of the group is emended to include forms with network-forming ( Zellera ) an dspirally twisted ( Duckerella ) thalli. The definition of the group is lalso modified to include members (e.g. some species of Hypoglossum ) in which tetrasporangia are produced by primary cells as in the Caloglossa group. Exogenous branching, a distinguishing feature of the closely related Caloglossa group, never occurs in the Hypoglossum group.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47938/1/10152_2006_Article_BF02365624.pd