Surgical Repositioning of the Premaxilla: Incidence, Indications and Growth Study About a 189 Bilateral Cleft Lip ± Palate Population.

OBJECTIVE: We aimed to evaluate the rate of patient requiring Surgical Repositioning of the Premaxilla in a population carrying BCL ± P, retrieve age and operative indication. Our secondary objective was to present further facial growth characteristics. SETTINGS: This was a retrospective, single-center cohort study conducted in Nantes University Hospital, Oral and Maxillofacial Surgery department, tertiary cleft center. PATIENTS: Patients with BCL ± P born between 1980 and 2019 treated at Nantes University Hospital were included. MAIN OUTCOME MEASURE: Our primary outcome measure was the rate of patient requiring SRP. RESULTS: Over the whole period, 189 patients with BCL ± P were identified. Three patients (1,58%) underwent SRP. Patients who underwent SRP all had BCLP. SRP was performed during their primary dentition period. The indication for surgical repositioning was always premaxilla vertical overgrowth with an overbite over 10 mm. Facial growth features in the three patients were mostly comparable with a population carrying BCLP who had no premaxillary surgery. CONCLUSION: Our results showed a low incidence of SRP. No SRP was necessary during early infancy (ie, before lip repair) or during adulthood. Surgical repositioning of the premaxilla is beneficial for patient with orthodontically uncorrectable vertical premaxillary excess, even more since facial development compared with other patients with BCLP appears comparable.

Sensitivity of the Montreal Cognitive Assessment in screening for cognitive impairment in patients with newly diagnosed high-grade glioma.

INTRODUCTION: Cognitive impairment is frequent in patients with high-grade glioma and requires cognitive follow-up. Cognitive screening tools such as the Montreal Cognitive Assessment (MoCA) have been used to assess cognition in these patients. Here we assessed the sensitivity of the MoCA in screening for cognitive impairment in a cohort of 156 patients with newly-diagnosed high-grade glioma, after surgery and before radiochemotherapy. METHODS: We assessed cognitive performance with the MoCA and a neuropsychological battery. Cognitive scores were analyzed in terms of a previously validated framework designed to control false positives and data for 1003 control participants from the GRECOGVASC study. After comparison of performance on the tests, we used stepwise logistic regression to produce a cognitive summary score from the neuropsychological battery. Then we analyzed sensitivity and specificity of the MoCA with receiver operator characteristic (ROC) curve analysis. RESULTS: Both raw and adjusted MoCA scores showed only moderate sensitivity. The area under the ROC curve was 0.759 (95% CI 0.703-0.815) for the raw score and 0.788 (95% CI 0.734-0.842) for the adjusted score. Optimal discrimination was obtained with a raw score ≤ 25 (sensitivity: 0.526; specificity: 0.832; positive predictive value: 0.2; negative predictive value: 0.96) and an adjusted score - 0.603 (sensitivity: 0.716; specificity: 0.768; positive predictive value: 0.24; negative predictive value: 0.96). CONCLUSION: The moderate sensitivity of MoCA indicates that it is not a suitable screening tool for detecting cognitive impairment in patients with newly-diagnosed high-grade glioma.

Combined Proteomic and Metabolomic Profiling of the Arabidopsis thaliana vps29 Mutant Reveals Pleiotropic Functions of the Retromer in Seed Development.

The retromer is a multiprotein complex conserved from yeast to humans, which is involved in intracellular protein trafficking and protein recycling. Selection of cargo proteins transported by the retromer depends on the core retromer subunit composed of the three vacuolar protein sorting (VPS) proteins, namely VPS26, VPS29, and VPS35. To gain a better knowledge of the importance of the plant retromer in protein sorting, we carried out a comparative proteomic and metabolomic analysis of Arabidopsis thaliana seeds from the wild-type and the null-retromer mutant vps29. Here, we report that the retromer mutant displays major alterations in the maturation of seed storage proteins and synthesis of lipid reserves, which are accompanied by severely impaired seed vigor and longevity. We also show that the lack of retromer components is counterbalanced by an increase in proteins involved in intracellular trafficking, notably members of the Ras-related proteins in brain (RAB) family proteins. Our study suggests that loss of the retromer stimulates energy metabolism, affects many metabolic pathways, including that of cell wall biogenesis, and triggers an osmotic stress response, underlining the importance of retromer function in seed biology.

New insights in radiation-induced leukoencephalopathy: a prospective cross-sectional study.

BACKGROUND: Radiation-induced leukoencephalopathy (RIL) is the most threatening delayed complication of cerebral radiotherapy (RT) and remains roughly defined by cognitive dysfunction associated with diffuse FLAIR MRI white matter hyperintensities after brain irradiation. We documented clinical, neuropsychological, and radiological aspects of RI in order to refine diagnostic criteria. METHODS: Patients referred to our center for deterioration in cognitive complaint at least 6 months after completing a focal or whole brain RT underwent a systematic cross-sectional assessment including clinical examination, neuropsychological tests, and a standardized MRI protocol. Patients with progressive tumor were excluded. RESULTS: Forty patients were prospectively enrolled. Of these, 26 had received a focal RT, median dose of 53 Gy (range 50 to 60), and 14 had received a whole brain RT, median dose of 30 Gy. Cognitive complaints, gait apraxia, and urinary troubles were reported in 100, 67, and 38% of cases, respectively. On neuropsychological examination, patients displayed a global and severe cognitive decline through a subcortical frontal mode. The cognitive changes observed were not hippocampic, but related to executive dysfunction. On MRI, 68% of the patients had extensive FLAIR hyperintensities with anterior predominance, 87% had brain atrophy, and 21% had intraparenchymal cysts. T2*-weighted MRI showed small asignal areas in 53% of the patients. These abnormalities are evocative of cerebral small vessel disease. Fractional anisotropy in the corpus callosum correlated with the cognitive evaluation. No differentiation in terms of cognitive and MRI features could be made between patients treated with focal brain RT (glioma) and patients treated with WBRT (for brain metastases or PCNSL). CONCLUSIONS: RIL can be defined by clinical symptoms (subcortical frontal decline, gait apraxia, urinary incontinence) and MRI criteria (cortico-subcortical atrophy, spread FLAIR HI, T2* asignals). This condition mimics a diffuse progressive cerebral small vessel disease triggered by RT, independent of RT protocol.

Seizure response to perampanel in drug-resistant epilepsy with gliomas: early observations.

Drug-resistant epilepsy (DRE) occurs commonly in gliomas, possibly due to a shared mechanism of AMPA-activation involving both seizure activity and tumor growth. We tested the AMPA-receptor blocker perampanel (PER) in patients with DRE in low- and high-grade gliomas. Seizure response was defined as 50% drop in seizure frequency or as seizure-freedom. Cognitive function was examined by computerized test on cognitive speed (CTCS), which is sensitive to the type of cognitive dysfunction associated with epilepsy and use of anticonvulsants. Treatment policy included reduction of dose or discontinuation of one or more concurrent AEDs, once a seizure-free response was observed. Twelve patients were included patients, median age 41 years, 9 men versus 3 women and 6 months median duration of follow-up. An objective seizure response (75%) was observed in 9 (75%) out of 12 patients: 50%-seizure response in 3, seizure-freedom in 6, which is plainly more than seen with other types of DRE. Side-effects occurred in six patients. Cognitive function as examined by CTCS improved in six out of eight associated withlowering of concurrent AEDs. The final median dose of PER was 8 mg (varying between 2 and 12 mg). These results of an objective seizure response in 9 (75%) out of 12 patients treated by PER in DRE may be interpreted as a surrogate-marker of tumor response secondary to AMPA blockade, advancing confirmation by MR imaging. These results warrant further study of PER on tumor activity in gliomas.

Cognitive outcome after radiotherapy in brain tumor.

PURPOSE OF REVIEW: Survival of brain tumor patients has increased with improvements in cancer treatments. However, treatments like radiotherapy can be neurotoxic and thus new end-points in clinical trials, as well as in individual management, have appeared. This article reviews the cognitive outcomes after radiotherapy in brain tumor patients, focusing on radiation-induced impairments, and then discusses actual cognitive assessment limitations. RECENT FINDINGS: Although physiopathology of radiation-induced cognitive impairments remains elusive, a general course can be described as acute, early-delayed, and late-delayed effects corresponding to different processes. The last is of high interest because the related impairments are irreversible. In this context, a cognitive assessment should be performed as often as possible, but actual tools are unfortunately not developed. Nevertheless, with respect to neuro-oncologic specificities, new cognitive tools could be developed to overcome these limitations. SUMMARY: Improvements in neuropsychologic assessment for brain tumor patients are urgently needed. A dynamic vision of radiation-induced cognitive impairments appears inevitable and should lead to a change in actual considerations about neurotoxicity follow-up.

EpiBrainRad: an epidemiologic study of the neurotoxicity induced by radiotherapy in high grade glioma patients.

BACKGROUND: Radiotherapy is one of the most important treatments of primary and metastatic brain tumors. Unfortunately, it can involve moderate to severe complications among which leukoencephalopathy is very frequent and implies cognitive deficits such as memory, attention and executive dysfunctions. However, the incidence of this complication is not well established and the risk factors and process are poorly understood. The main objective of the study is to improve knowledge on radio-induced leukoencephalopathy based on pluridisciplinar approaches combining cognitive, biologic, imagery and dosimetric investigations. METHOD/DESIGN: The EpiBrainRad study is a prospective cohort study including newly diagnosed high grade gliomas patients treated by radiotherapy and concomitant-adjuvant temozolomide chemotherapy. Patients are included between their surgery and first day of radio-chemotherapy, and the follow-up lasts for 3 years after treatment. Cognitive functioning assessments, specific blood biomarkers measures and magnetic resonance imagery are performed at different moment during the follow-up, and a specific dosimetric assessment of organs involved in the beam fields is performed. Firstly, leukoencephalopathy incidence rate will be estimated in this population. Secondly, correlations between cognitive impairments and dosimetry, biomarkers ranges and anomalies on imagery will be analyzed in order to better understand the onset and evolution of cognitive decrement associated with radiotherapy. Furthermore, a new cognitive test, quickly and easily performed, will be studied to determine its sensibility to detect leukoencephalopathy decrement. DISCUSSION: With an original multidisciplinary approach, the EpiBrainRad study aims to improve knowledge on radio-induced leukoencephalopathy in order to improve its early diagnosis and prevention. The main challenge is to preserve quality-of-life after cancer treatments which imply to study the incidence of radiation-induced complications and their associated risk factors. TRIAL REGISTRATION: NCT02544178.

Alveolar bone changes after tooth-borne surgically assisted rapid maxillary expansion: A three-dimensional study.

INTRODUCTION: Surgically assisted rapid maxillary expansion (SARME) with a dental-anchorage appliance can induce dental and skeletal complications adjacent to the teeth supporting the device. The purpose of this study was to quantify the dentoskeletal changes observed after SARME using a tooth-borne device. MATERIALS AND METHODS: Cone beam CT images from 39 patients were compared between the preoperative (T1) and the postoperative period (T2). The mean time to complete the second imaging was 13.8 ± 6.9 months after the SARME. Dental and bone parameters were assessed: the vestibular bone height (BH), the bone thickness (BT), the existence of fenestrations, and the root resorption at the level of first upper premolar (P1) and the first upper molar (M1). The maxillary expansion parameters were also collected. RESULTS: Both vertical and horizontal vestibular bone loss were observed mainly in the first upper molar sectors: The BT decreased from 0.93 ± 0.50 mm to 0.53 ± 0.51 mm (p < 0.0001) and the BH decreased from 1.84 ± 1.05 mm to 0.93 ± 1.02 mm (p < 0.0001) for tooth #16. The bone loss also affected the first upper premolars but in a more limited manner. Significant fenestrations were observed at the apex of the mesio-vestibular root of teeth #16 and #26. We noted significant root resorption affecting the mesio-, disto-vestibular and palatal roots of tooth #16 (mean reductions of 0.32, 0.35, and 0.55 mm, respectively; p < 0.05), and the palatal root of tooth # 26 (loss of 0.58 mm; p = 0.004). The mean bone expansion was 3.76 mm and 1.41 mm at the premolar and molar levels, respectively (p < 0.0001), while a mean 6.24 mm and 4.23 mm inter-cuspid expansion was noted at the P1 and M1 levels (p < 0.0001). CONCLUSION: Our results document the vestibular bone changes and low root resorption, mostly in the molar sectors, associated with SARME using dental-anchorage devices.

Impact of Orthodontic Gap Closure versus Prosthetic Replacement of Missing Maxillary Lateral Incisor on Dental Arch Relationships and Symmetry in 212 Patients with Cleft Palate: Retrospective Study.

BACKGROUND: Maxillary lateral incisors are frequently missing in patients with cleft lip and/or palate. The aim of this study was to assess how orthodontic gap closure or prosthetic rehabilitation of the missing maxillary lateral incisor affected dental arch relationships and symmetry at the end of treatment. The authors also aimed to determine the effect of the level of oral hygiene on the decision made to manage the missing maxillary lateral incisor gap. METHODS: A descriptive, retrospective cohort study including all patients with cleft lip and/or palate born between 1980 and 1999 and treated at Nantes Cleft Center was performed. Patients presenting unilateral or bilateral missing maxillary lateral incisors were reviewed. Data on management of the missing incisor gap, dental arch relationships, symmetry, and level of oral hygiene were collected. RESULTS: A total of 486 patients with cleft lip and/or palate were reviewed, including 212 patients with unilateral or bilateral missing maxillary lateral incisors. When compared with orthodontic gap closure, prosthetic replacement of the gap was associated with better final dental arch relationships (59.8 percent versus 10.3 percent; p < 0.01) and better dental arch symmetry (88.1 percent versus 44.0 percent; p < 0.01) for patients with unilateral missing incisors but not for patients with bilateral missing incisors. A higher level of oral hygiene was associated with more cases of prosthetic replacement for patients with unilateral missing incisors ( p = 0.03) but had no effect for patients with bilateral missing incisors. CONCLUSION: Prosthetic replacement of the missing maxillary lateral incisor gap provided better functional and aesthetic results for patients with cleft lip and/or palate presenting with unilateral missing maxillary lateral incisor.

Acute metal stress in Populus tremula x P. alba (717-1B4 genotype): leaf and cambial proteome changes induced by cadmium 2+.

The comprehension of metal homeostasis in plants requires the identification of molecular markers linked to stress tolerance. Proteomic changes in leaves and cambial zone of Populus tremula x P. alba (717-1B4 genotype) were analyzed after 61 days of exposure to cadmium (Cd) 360 mg/kg soil dry weight in pot-soil cultures. The treatment led to an acute Cd stress with a reduction of growth and photosynthesis. Cd stress induced changes in the display of 120 spots for leaf tissue and 153 spots for the cambial zone. It involved a reduced photosynthesis, resulting in a profound reorganisation of carbon and carbohydrate metabolisms in both tissues. Cambial cells underwent stress from the Cd actually present inside the tissue but also a deprivation of photosynthates caused by leaf stress. An important tissue specificity of the response was observed, according to the differences in cell structures and functions.

Evaluation of vertical ramus osteotomy for the surgical correction of unilateral mandibular posterior vertical insufficiency: Long-term follow-up results.

PURPOSE: Unilateral posterior vertical insufficiency (PVI) is a growth defect of the mandibular condyle that results in a facial asymmetry. Various surgical procedures can be used to elongate the hypoplastic ramus. The aim of this study was to evaluate long-term aesthetic and architectural outcomes of vertical ramus osteotomy (VRO) in patients with unilateral PVI. MATERIALS AND METHODS: Patients operated on with unilateral VRO were included in this retrospective study. Aesthetic and architectural parameters were evaluated on frontal photographs as well as on frontal and lateral cephalograms preoperatively, postoperatively, at 1-year and at the end of the follow-up. RESULTS: A total of 48 patients were analyzed. The aesthetic assessment revealed significant correction of the chin deviation (CD) and of the lip commissural line tilt after VRO (p1 = 0.0038 and p2 = 0.0067, respectively) with stable results. The architectural analysis revealed significant improvement in the maxillary and mandibular occlusal planes, as well as the chin deviation (p < 0.0001). A tendency to relapse was noted for the mandibular canting and the CD during the follow-up. VRO allowed for a mean mandibular lengthening of 8.39 mm (ranging from 2.5 to 14 mm). CONCLUSION: VRO allows for immediate restoration of the symmetry of the lower third of the face in patients with unilateral PVI. A revisional procedure may be needed due to a tendency for the chin deviation to relapse.

How to assess and manage cognitive impairment induced by treatments of non-central nervous system cancer.

A number of neurotoxicity associated with oncological treatments has been reported in non-central nervous system cancers. An expert group presents the state of the art and a guide to help the choice of appropriated tools to assess patient cognition in studies on oncology and neurobehavior in animal models. In addition, current cognitive rehabilitation programs currently under evaluation are also discussed. Cognitive assessments in oncology depend on the research question, study design, cognitive domains, patients' characteristics, psychometric properties of the tests, and whether the tests are supervised or not by a neuropsychologist. Batteries of electronic tests can be proposed, but several of them are characterized by weak psychometric developments. In order to improve the comprehension on the impact of cancer treatments on cognition, new animal models are in development, and would in the future include non-human primate models. By bringing together the skills and practices of oncologists, neurologists, neuropsychologists, neuroscientists, we propose a series of specific tools and tests that accompany the cognitive management of non-CNS cancer patients.

Cognitive impairment and morphological changes after radiation therapy in brain tumors: A review.

Life expectancy of patients treated for brain tumors has lengthened due to the therapeutic improvements. Cognitive impairment has been described following brain radiotherapy, but the mechanisms leading to this adverse event remain mostly unknown. Technical evolutions aim at enhancing the therapeutic ratio. Sparing of the healthy tissues has been improved using various approaches; however, few dose constraints have been established regarding brain structures associated with cognitive functions. The aims of this literature review are to report the main brain areas involved in cognitive adverse effects induced by radiotherapy as described in literature, to better understand brain radiosensitivity and to describe potential future improvements.

Episodic Memory Impairments in Primary Brain Tumor Patients.

OBJECTIVE: Cognitive investigations in brain tumor patients have mostly explored episodic memory without differentiating between encoding, storage, and retrieval deficits. The aim of this study is to offer insight into the memory sub-processes affected in primary brain tumor patients and propose an appropriate assessment method. METHOD: We retrospectively reviewed the clinical and memory assessments of 158 patients with primary brain tumors who had presented to our departments with cognitive complaints and were investigated using the Free and Cued Selective Reminding Test. RESULTS: Retrieval was the process of episodic memory most frequently affected, with deficits in this domain detected in 92% of patients with episodic memory impairments. Storage and encoding deficits were less prevalent, with impairments, respectively, detected in 41% and 23% of memory-impaired patients. The pattern of episodic memory impairment was similar across different tumor histologies and treatment modalities. CONCLUSION: Although all processes of episodic memory were found to be impaired, retrieval was by far the most widely affected function. A thorough assessment of all three components of episodic memory should be part of the regular neuropsychological evaluation in patients with primary brain tumors.

Chemotherapy-related cognitive impairment or « chemobrain ¼: concept and state of art.

Cognitive complaints are frequent in patients who received chemotherapy for a non-CNS cancer. These observations have been described as « chemobrain ¼. However, studies results are contradictory concerning the implication of chemotherapy in the onset of cognitive defects. Moreover, other factors as mood, anxiety and fatigue are often associated in this population and could be confounding. This article present principal results of research in human experiencing chemobrain, concerning clinical presentation, neuropsychological examination, imaging techniques and treatment possibilities. Physiopathological hypothesis are presented. The implication of hormonotherapy is also discussed.

Screening for changes in leaf and cambial proteome of Populus tremula × P. alba under different heat constraints.

Young poplar plants were exposed to different heat regimes, a rapid heat constraint at 42°C (heat shock HS) alone or preceded by a stepwise increase in temperature (heat gradient HG). Proteomics analyses were carried out on both leaf and cambial tissues. The responses of both tissues were compared and linked to morphological and physiological observations. Both heat treatments negatively affected the photosynthetic rate while increasing the stomatal conductance. In the leaf, the HS impacted some photosynthetic proteins, and particularly induced an increase in abundance of proteins of the oxygen evolving complexes. On the other hand, the HG reduced carbohydrate metabolism and induced mainly an increase in germin-like proteins. In the cambial zone, the HS caused a decrease in sucrose synthase content and in enzymes related to protein synthesis. The main effect of HG was the accumulation of thaumatin-like proteins as well as an increase in the abundance of proteins involved in carbohydrate metabolism. Further, both tissues underwent changes in the content of heat shock proteins, but more importantly, of peroxiredoxins. The results show more sustainable changes in leaf and cambial proteomes in response to HS compared to HG.

Poplar under drought: comparison of leaf and cambial proteomic responses.

The forest ecosystem is of particular importance from an economic and ecological perspective. However, the stress physiology of trees, perennial and woody plants, is far from being fully understood. For that purpose, poplar plants were exposed to drought; the plants exhibited commonly reported drought stress traits in the different plant tissues. Leafy rooted cuttings of poplar were investigated through a proteomic approach in order to compare the water constraint response of two plant tissues, namely leaf and cambium. Sampling was realized during the drought period at 2 time points with increased drought intensity and 7 days after rewatering. Our data show that there is a difference in the moment of response to the water constraint between the two tissues, cambium being affected later than leaves. In leaves, drought induced a decrease in rubisco content, and an increase in the abundance of light harvesting complex proteins as well as changes in membrane-related proteins. In the cambial tissue, the salient proteome pattern change was the decrease of multiple proteins identified as bark storage proteins. After rewatering, almost all changes in cambial proteome disappeared whereas a significant number of leaf proteins appeared to be differentially regulated only during the recovery from drought.