A decision support system for Rey-Osterrieth complex figure evaluation

Objective: The Rey Osterrieth complex figure (ROCF) is one of the most used neuropsychological tests for the assessment of mild cognitive impairment (MCI) and dementia. In the copy test, the patient has to draw a replica of a 18-pattern image and the outcome is a score based on the accuracy of the overall drawing. The standard scoring system however have limitations related to its subjective nature and its inability to evaluate other cognitive domains than constructional abilities. Previous works addressed those problems by proposing tablet-based automated evaluation systems. Even promising, such methods are still far away from clinical validation and translation. In this work, we developed a decision support system (DSS) for the evaluation of the ROCF copy test in the common practice using retrospective information from previously performed drawings. The goal of our system was to support the professionals providing a qualitative judgement for each of the 18 patterns, estimating the most probable diagnosis for the patient, and identifying the main signs associated to the obtained diagnosis. Methods: A total of 250 human evaluated ROCF copies were scanned from 57 healthy subjects, 131 individuals with MCI, and 62 individuals with dementia. The images were pre-processed and analysed using both computer vision and deep learning techniques to assign a qualitative label to the 18 patterns. Then, the 18 labels were used as features in 3 binary (healthy VS MCI, healthy VS dementia, MCI VS dementia) and a 3-class classifications with model explanation (SHAP).Results: Very good to excellent performance were obtained in all the diagnosis classification tasks. Indeed, an accuracy of about 85%, 91%, and 83% was obtained in discriminating healthy subjects from MCI, healthy subjects from dementia and MCI from dementia respectively. An accuracy of 73% was achieved in the 3-class classification. The model explanation showed which patterns are responsible for each prediction and how the importance of some patterns changes according to the severity of the cognitive decline. Significance: The proposed DSS enriches the standard evaluation and interpretation of the ROCF copy test. Being trained with retrospective knowledge, the performance of the DSS can be further enhanced by extending the dataset with existing ROCF copies

Stratification of unresponsive patients by an independently validated index of brain complexity.

OBJECTIVE: Validating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness-the Perturbational Complexity Index (PCI)-in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs). METHODS: The benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]). RESULTS: We found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition. INTERPRETATION: Given its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior

TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells

The family of tripartite-motif (TRIM) proteins are involved in diverse cellular processes, but are often characterized by critical protein–protein interactions necessary for their function. TRIM16 is induced in different cancer types, when the cancer cell is forced to proceed down a differentiation pathway. We have identified TRIM16 as a DNA-binding protein with histone acetylase activity, which is required for the retinoic acid receptor β2 transcriptional response in retinoid-treated cancer cells. In this study, we show that overexpressed TRIM16 reduced neuroblastoma cell growth, enhanced retinoid-induced differentiation and reduced tumourigenicity in vivo. TRIM16 was only expressed in the differentiated ganglion cell component of primary human neuroblastoma tumour tissues. TRIM16 bound directly to cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. TRIM16 reduced cell motility and this required downregulation of vimentin. Retinoid treatment and enforced overexpression caused TRIM16 to translocate to the nucleus, and bind to and downregulate nuclear E2F1, required for cell replication. This study, for the first time, demonstrates that TRIM16 acts as a tumour suppressor, affecting neuritic differentiation, cell migration and replication through interactions with cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells

Analysis of gpr101 and aip genes mutations in acromegaly: a multicentric study.

Purpose: This multicentric study aimed to investigate the prevalence of the G protein-coupled receptor 101 (GPR101) p.E308D variant and aryl hydrocarbon receptor interacting protein (AIP) gene mutations in a representative cohort of Italian patients with acromegaly. Methods: 215 patients with GH-secreting pituitary adenomas, referred to 4 Italian referral centres for pituitary diseases have been included. Three cases of gigantism were present. Five cases were classified as FIPA. All the patients have been screened for germline AIP gene mutations and GPR101 gene p.E308D variant. Results: Heterozygous AIP gene variants have been found in 7 patients (3.2%). Five patients carried an AIP mutation (2.3%; 4 females): 3 patients harboured the p.R3O4Q mutation, one had the p.R304* mutation and the last one the IVS3+1G>A mutation. The prevalence of AIP mutations was 3.3% and 2.8% when considering only the patients diagnosed when they were < 30 or < 40 years old, respectively. Furthermore, 2.0% of the patients with a pituitary macroadenoma and 4.2% of patients resistant to somatostatin analogs (SSA) treatment were found to harbour an AIP gene mutation. None of the patients was found to carry the GPR101 p.E308D variant. Conclusion: The prevalence of AIP gene mutations among our sporadic and familial acromegaly cases was similar to that one reported in previous studies, but lower when considering only the cases diagnosed before 40 years of age. The GPR101 p.E308D change is unlikely to have a role in somatotroph adenomas tumorigenesis, since none of our sporadic or familial patients tested positive for this variant

A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia

Notch signalling is a central regulator of differentiation in a variety of organisms and tissue types(1). Its activity is controlled by the multisubunit gamma-secretase (gamma SE) complex(2). Although Notch signalling can play both oncogenic and tumour-suppressor roles in solid tumours, in the haematopoietic system it is exclusively oncogenic, notably in T-cell acute lymphoblastic leukaemia, a disease characterized by Notch1-activating mutations(3). Here we identify novel somatic-inactivating Notch pathway mutations in a fraction of patients with chronic myelomonocytic leukaemia (CMML). Inactivation of Notch signalling in mouse haematopoietic stem cells (HSCs) results in an aberrant accumulation of granulocyte/monocyte progenitors (GMPs), extramedullary haematopoieisis and the induction of CMML-like disease. Transcriptome analysis revealed that Notch signalling regulates an extensive myelomonocytic-specific gene signature, through the direct suppression of gene transcription by the Notch target Hes1. Our studies identify a novel role for Notch signalling during early haematopoietic stem cell differentiation and suggest that the Notch pathway can play both tumour-promoting and -suppressive roles within the same tissue

Cocaine and oral health

In the UK almost one million individuals use cocaine on a regular basis, implying that dentists are likely to encounter individuals that use cocaine. Regular use of this drug may have several orofacial effects, such as perforation of the nasal septum and palate, gingival lesions and erosion of tooth surfaces. In addition, recent use of cocaine increases the risk of a medical emergency during dental treatment, especially when epinephrine-containing local anaesthetics or retraction cords are used. Therefore, dental treatment should be postponed for 6 to 24 hours after the use of cocaine