The House-Drawing Test: Using a projective test in assessment to differentiate normal from pathological ageing

This article proposes to show how the use of the drawing of the home can help differentiate two older populations, with or without cognitive impairment as part of research to identify early signs of Alzheimer's disease. The projective test of the house is complementary to the cognitive assessment. Two groups of older adults are compared: an experimental group with 24 people aged 67 with cognitive impairment and a control group with 36 people aged 71.5 years with normal cognitive aging. Analysis of the house drawings revealed significant differences in the realization of the drawings between the control group (CG) and the experimental group (EG). The characteristics of the drawings of elderly people with cognitive impairment show more difficult access to imagination and a feeling of insecurity as of the first memory impairment. This article puts the body at the center of psychoanalytic work and explores the relationship between the psychic and bodily dimensions of elderly subjects using a projective spatiography test. This projective tool allowed us to collect information on the psychic functioning of the elderly

275: Percutaneous insertion of a Melody valve in tricuspid position: technical aspects

Backgroundpercutaneous transcatheter heart valve replacement of aortic or pulmonary valve is established. Transcatheter atrioventricular valve replacement is been described. We report our experience focusing on the technical aspects.Methodswe retrospectively review the files of patients who received a transcatheter valve in tricuspid position between 2008 and 2012.ResultsFour patients were found. 3 had a heterograft (conduit of 14-mm, Sorin 33 et Edwards Perimount 33) and one had a connection between the RA and the RV infundibulum without a valve. Two patients had tricuspid regurgitation as a primary lesion, one had stenotic valve and the last one a mixted lesion. All successfully received a Melody valve from a femoral access. In patients with stenotic lesion, a predilatation using a high pressure balloon was performed before valve implant. In patients with regurgitation, the landing zone was calibrated using a low pressure balloon. These patients were presented to create a landing zone of adequate diameter. Melody valves were inserted using a 22-mm balloon catheter in 3 and a 24-mm in one. All but one were post-dilated. There was no significant regurgitation. The mean gradient across the tricuspid valve felt from 12 to 4.6-mmHg. One patient needed an epicardic pacemaker because of AV block following balloon dilatation. One patient required inotropic support and ventilation following the procedure but recovered after few days.ConclusionTranscatheter tricuspid valve insertion is feasible in patients with surgical hetero or homografts after a careful selection. The mechanism of dysfunction must be known. In case of stenosis or mixted lesions, the only question is to know if the stenosis could be relief. In case of regurgitation, it is very important to know the features of surgical substrats and to calibrate the tricuspid orifice. Finally, patients with inappropriate landing zone should be presented prior to valve insertion

Catheter ablation of atrial tachyarrhythmias in patients with atrioventricular septal defect

AIMS: The incidence of atrial tachyarrhythmias is high in patients with atrioventricular septal defect (AVSD). No specific data on catheter ablation have been reported so far in this population. We aimed to describe the main mechanisms of atrial tachyarrhythmias in patients with AVSD and to analyse outcomes after catheter ablation. METHODS AND RESULTS: This observational multi-centric cohort study enrolled all patients with AVSD referred for catheter ablation of an atrial tachyarrhythmia at six tertiary centres from 2004 to 2022. The mechanisms of the different tachyarrhythmias targeted were described and outcomes were analysed. Overall, 56 patients (38.1 ± 17.4 years, 55.4% females) were included. A total of 87 atrial tachyarrhythmias were targeted (mean number of 1.6 per patient). Regarding main circuits involved, a cavo-annular isthmus-dependent intra-atrial re-entrant tachycardia (IART) was observed in 41 (73.2%) patients and an IART involving the right lateral atriotomy in 10 (17.9%) patients. Other tachyarrhythmias with heterogeneous circuits were observed in 13 (23.2%) patients including 11 left-sided and 4 right-sided tachyarrhythmias. Overall, an acute success was achieved in 54 (96.4%) patients, and no complication was reported. During a mean follow-up of 2.8 ± 3.8 years, 22 (39.3%) patients had at least one recurrence. Freedom from atrial tachyarrhythmia recurrences was 77.5% at 1 year. Among 15 (26.8%) patients who underwent repeated ablation procedures, heterogeneous circuits including bi-atrial and left-sided tachyarrhythmias were more frequent. CONCLUSION: In patients with AVSD, most circuits involve the cavo-annular isthmus, but complex mechanisms are frequently encountered in patients with repeated procedures. The acute success rate is excellent, although recurrences remain common during follow-up.</p

Ville et campagne de Fréjus romaine

En 2006, une fouille d’archéologie préventive, désignée sous le nom de « Villa Romana », a été réalisée dans le quartier de Villeneuve à Fréjus. Durant l’Antiquité il s’agit d’une zone périurbaine située entre la ville de Forum Iulii et le débouché de l’Argens. Connu depuis longtemps en raison de la présence d’un édifice thermal toujours en élévation, le quartier a été fouillé à plusieurs occasions et est interprété comme étant l’emplacement du camp de la flotte, établi après la bataille d’Actium. Celui-ci se transforme progressivement durant le Ier siècle apr. J.-C. en quartier suburbain au fur et à mesure que se développe Forum Iulii. Le secteur fouillé se situe dans la partie sud du camp, bordée par la mer durant les premiers temps de l’Antiquité. La fouille a permis de révéler la présence d’une plage aménagée. Les terrains ont ensuite été rapidement gagnés sur la mer, en raison d’une avancée rapide du littoral, que des études récentes ont permis de bien connaitre à Fréjus. Des jardins y sont alors aménagés. A partir du IIe siècle, cet espace est transformé en zone agricole, et constitue l’illustration de l’exploitation de la campagne aux portes de Fréjus, et cela, jusqu’à la fin de l’Antiquité. S’ensuit une longue période d’abandon de plusieurs siècles, avant que l’espace ne soit à nouveau voué à l’agriculture et ce jusqu’à l’orée des années soixante. Depuis, le développement de la ville actuelle de Fréjus a de nouveau transformé ce quartier en zone urbaine. Cet ouvrage, publié quelques années seulement après la fouille, présente l’ensemble des études archéologiques et paléoenvironnementales, réalisées à l’occasion de cette opération, largement pluridisciplinaire. Elles fournissent un contexte environnemental nouveau pour ce quartier antique et permettent de redéfinir un paysage à partir d’analyses bioarchéologiques et paléoécologiques récentes. L’étude de l’ensemble des mobiliers archéologiques est également présentée, en suivant la chronologie et l’évolution de ce quartier à travers l’Antiquité et l’époque moderne

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors