Reduced specificity of autobiographical memory and aging: Do the executive and feature binding functions of working memory have a role?

Autobiographical memory (AM) is built up from various kinds of knowledge, from general to specific, via generative processes. Aging seems to particularly affect the episodic autobiographical information while preserving information that is more semantic. However, the mechanism of this deficit has not yet been thoroughly tested in relation to working memory. This study is designed to investigate, in a group of 100 subjects, the relationships between age, accessibility to different levels of AM specificity, and two main components of working memory: the central executive and the episodic buffer. We used a new task composed of four embedded verbal autobiographical fluencies (VAF) - from low to highest specificity levels - exploring lifetime periods, general events, specific events, and details, plus tasks exploring free recall of episodic AM and updating, shifting, inhibition, and feature binding in working memory. The results demonstrate that age-related difficulties increase with level of specificity of autobiographical knowledge, i.e., from semantic to episodic aspects. Moreover, regression analyses mainly show that increase in age-related deficit with level of specificity of AM is largely mediated by performance on executive functions (updating and inhibition) and to a lesser extent feature binding in working memory. The results confirm in episodic AM the executive/working memory aging hypothesis, and for the first time highlight the role of episodic buffer in associating the various different details of specific events that elicit the conscious recollection.     

Extensive biliary intraepithelial neoplasia (BilIN) and multifocal early intrahepatic cholangiocarcinoma in non-biliary cirrhosis

Biliary intraepithelial neoplasia (BilIN), a preneoplastic condition that may precede invasive intrahepatic cholangiocarcinoma (ICC), has been compared to pancreatic intraepithelial neoplasia (PanIN), a precursor lesion of pancreatic carcinoma. Biliary tract carcinoma development and progression is associated with several gene alterations, but BilIN lesions have yet to be studied in detail by molecular techniques. We describe a case of extensive intrahepatic biliary dysplasia, with lesions ranging from BilIN-1 to BilIN-3 lesions, and multifocal microscopic ICC in hepatitis C virus (HCV)- and alcohol-related cirrhosis. The small ICC foci had remained undetected prior to transplantation. Fluorescence in situ hybridization (FISH) analysis was performed on three foci of BilIN-3 lesions and on three microinvasive ICC foci with a combination of three FISH probes directed against genes frequently altered in pancreatic and biliary tract carcinomas. FISH analysis revealed a CDKNA2 heterozygous deletion in one BilIN-3 focus, and in one non-contiguous ICC focus, although the deletion was just above the chosen threshold. No deletions were detected in the genomic regions encoding TP53 and SMAD4. This report documents for the first time the development of multifocal ICC in the setting of extensive biliary dysplasia in a patient with three risk factors, HCV infection, alcohol abuse, and cirrhosis, and suggests heterogeneous carcinogenesis in ICC and possible involvement of the CDKNA2 gene.     

A very rapid and simple assay based on trogocytosis to detect and measure specific T and B cell reactivity by flow cytometry

Detection, quantification, separation and characterization of T and B cells reactive to specific antigens are important tasks in both basic and clinical immunology. Here, we describe an approach allowing the performance of all four tasks on a functional basis by flow cytometry. The assay is based on the property of lymphocytes to capture membrane components from the cells they interact with, in a process we call trogocytosis. Working with CD8+ CTL and target cells labeled with membrane markers, we describe the conditions allowing reactive lymphocytes to be detected rapidly and inexpensively within mixed populations. Accordingly, we used this method to monitor the CTL response triggered in mice after vaccination. In addition, we documented the applicability of this method to the detection of antigen-specific CD4+ T and B cells. While our method is, for the time being, not as sensitive as staining of CTL with MHC class I multimers, it allows the simultaneous quantitative identification of reactive CD8+, CD4+ and B cells. Altogether, our method offers a simple and general alternative to other methods previously described to detect and quantify lymphocyte reactivity, and it can also be used in combination with those.     

Galectin-1, -3, -7 expressions in congenital and acquired pediatric cholesteatomas compared to external auditory canal skin

Objectives

There is a classical distinction based on clinical criteria between acquired and congenital cholesteatomas. To determine if these two types of lesions show different immunohistochemical features, we have studied the expression patterns of three distinctive galectins (animal lectins implied especially in cellular proliferation and apoptosis) in both types of cholesteatomas and compared it to their expression patterns in external auditory canal skin.

Methods

Our study is based on nine acquired and eight congenital cholesteatomas, obtained from children during ear surgery. Six specimens of normal adult auditory meatal skin served as control. Specimens were analyzed by immunohistochemistry using monoclonal antibodies with galectin-1 and galectin-3, and a polyclonal antibody with galectin-7.

Results

We did not observe any differences in the galectin distribution pattern between congenital and acquired pediatric cholesteatomas. Compared to the control group, cholesteatomas present some particular features. There was no expression of galectin-1 and a lower expression of galectin-3 in the epithelium. Furthermore, we observed a preferentially nuclear distribution of galectin-7 in cholesteatomas, whereas it is essentially cytoplasmic in the control group.

Conclusion

The data reported in this study suggest, on the basis of a lesser marked galectin-3 in cholesteatomas epithelium compared with an external auditory canal skin, that an immature keratinocytes population is at the origin of these lesions and that galectin-3 and galectin-7 play a part in the capacity as apoptosis modulators. Our study does not establish a difference in the galectin expressions of congenital and acquired cholesteatomas, but it constitutes however an additional argument in favor of the "undifferentiated" origin of keratinocytes in cholesteatomas.     

Bisphosphonate sequestering agents. Synthesis and preliminary evaluation for in vitro and in vivo uranium(VI) chelation

A library of bisphosphonate-based ligands was prepared using solution-phase parallel synthesis and tested for its uranium-binding properties. With the help of a screening method, based on a chromophoric complex displacement procedure, 23 dipodal and tripodal chelates bearing bisphosphonate chelating functions were found to display very high affinity for the uranyl ion and were selected for evaluation of their in vivo uranyl-removal efficacy. Among them, 11 ligands induced a huge modification of the uranyl biodistribution by deviating the metal from kidney and bones to liver. Among the other ligands, the most potent was the dipodal bisphosphonate 3C which reduced the retention of uranyl and increased its excretion by around 10% of the injected metal.     

Représentations de la Seconde Guerre mondiale dans le cinéma japonais (de Kon Ichikawa)

“If psychiatry had not existed, the movies would have had to invent it. And in a sense they did”, wrote Irving Schneider in the foreword to the excellent book by Krin and Glen Gabbard, Psychiatry and the Cinema. For this session of the Société Médico-Psychologique focusing on Cinema and Psychiatry, opportunistically “delocalized” at the misfit theatre called Le Brady, we wanted to present two masterpieces of the Japanese director Kon Ichikawa. These two powerful war stories, The Burmese Harp and Fires on the Plain illustrate the fascinating dialogue between movies and psychiatry, specifically in this case around war trauma and its consequences. “While Ozu depicted the consequences of war on contemporary 1950 Japan, Ichikawa remained stuck on the last weeks of agony of 1945… Ozu's films begin where those of Ichikawa end”, wrote Serge Kaganski in the Inrocks in 1994, when the Parisian public was able to discover Kon Ichikawa's movies. Of course, we could have chosen to rather “psycho”-analyze Godzilla, this terrible monster awaken from his deep prehistoric sleep by the Bikini atomic explosions and appearing for the first time on Japanese screens in 1954 as a metaphor of the horror of Hiroshima and Nagasaki, and as a subtle criticism of the US presence in Japan, nine years after the end of the war. We should not forget that King Kong against Godzilla (1962) directed by Inoshiro Honda was part of the Brady unconventional program. Kon Ichikawa was discovered by the majority of the Occidental public in 1960, when he received in Cannes the Jury's Prize for his film Kagi (The strange obsession) together with Antonioni for L’Avventura while the Palme d’Or was awarded to Fellini for La Dolce Vita. Kon Ichikawa, Japanese filmmaker (1915–2008) began his career as a cartoonist. Considered as the tenant of a rather commercial school, Ichikawa directed numerous films, more than fifty, not all always well received by the critics. However, we concur with Max Tessier who in his book Images of the Japanese cinema, states “to see several of his films, you realize that there is in some of his movies a true Ichikawa's ‘eye’, mix of black humor and cinematographic entomology” (indeed Ichikawa depicts some of his main characters as helpless insects), and a very recognizable aesthetic, especially in his films in cinemascope. His first films were satirical comedies, scratching the moral conventions of the Japanese cinema. Then came more drama and deep movies, especially three masterpieces, two great war films, The Burmese Harp in 1956, Fires on the Plain in 1959 and Kagi (The strange obsession) presented and awarded at the Cannes festival in 1960. The characters painted by Ichikawa are not the typical “heros” but individuals lost in a quest of an absurd goal, often isolated, like the two soldiers of his two war films, The Burmese Harp and Fires on the Plain. In Les Carabiniers, Jean-Luc Godard reminds us the true nature of war: (in war…) “there is no victory, there are only flags and men falling”. In these two war films, Ichikawa is far from lecturing us, and far from an alleged exaltation of the values of feudal Japan like what was reproached to his first film by the US censorship. Kon Ichikawa personal aesthetic develops on screen an almost clinical vision of the traumatic destinies of two Japanese soldiers, caught in chaos, lost in the middle a disorganized mass of soldiers. Interestingly, we would suggest to watch these two movies in a row, as they are at the same time so similar and so different, like a kind of construct in mirror, the second prolonging the first in a vertiginous horror. They are quite similar in the sense that they are both depicting the destiny of an anti-hero, a Japanese soldier defeated at the end of the Second World War. But they differ totally aesthetically, to the classical academic format of Buddhist meditation of The Burmese Harp, responds the crude cinemascope format of the Fires on the Plain, using the black and white to emphasize the horror, the unspeakable, the unbearable, making in my opinion Fires on the Plain one of the greatest war movies. This cinematographic artwork reflects the true creative qualities of Kon Ichikawa i.e. the Ichikawa's eye… The Burmese Harp is his last work before switching to cinemascope, which was introduced relatively late in Japan, only in 1957. The classic cinematographic format throughout the film instils a slow pace that drives Mizushima the musician soldier in his journey towards Buddhism. Taken prisoner with what remains of his company, Mizushima is sent by his commanding officer, at the request of the British allied forces, to convince a few soldiers isolated in a cave of the futility of their resistance in front of the British guns. Mizushima manages to reach these survivors but they consider him a traitor, honor ordering them to die in battle but not surrender. Mizushima will only be saved from their violence by the British bombs. Only survivor to rise, he finally collapsed under the Burmese sun. This is his first step of his initiatory journey to Buddhism, that has somewhat been announced by Ichikawa portraying the soldier Mizushima with unusual artistic qualities. The second step is the encounter with a monk who will help him to survive and heal. Finally, Mizushima, considered dead by his comrades, becomes a monk to save the souls of his fellow soldiers, and decides to stay in Burma to give burial to all the dead Japanese soldiers whose bodies cover the beaches and woodland of Burma, and thus to cleanse the shame of the war. In contrast to this Buddhist fable, Fires on the Plain also shows defeated Japanese soldiers exiled this time in the Philippines, and again, through an anti-hero, the soldier Tamura, expelled from his unit because of his tuberculosis, but not sick enough to be admitted to the military hospital, and finally isolated in a mass of wandering soldiers with no goal. By adapting one of the masterpieces of the literature of war, the Fires (Nobi) of Shôhei Ooka, Ichikawa subtly uses the cinemascope to depict with absolute darkness the horror, the deprivation, the degradation, and the unspeakable. In Fires on the Plain, rain and mud, light and shadow exhibit an incredible cinematographic beauty, even when the horror is such that it could become gore, especially when Tamura discovers the true nature of monkey meat that his comrades pretend eating, or when the same Tamura witnesses the murder of a tyrannical sergeant by the young soldier forced to kill “monkeys”, murder followed by strange cannibalistic ritual by this young soldier on the body of his commanding officer. We will not make any psychopathological analysis of the two soldiers depicted by Ichikawa, but we recommend you to see The Burmese Harp and Fires on the Plain, to let you choose to be either a psychiatrist or an entomologist to analyze the destinies of Mizushima, the soldier/bonze and Tamura, cannibal against his will. Let's conclude with Samuel Fuller, who served in the First US Infantry Division during World War II, the famous Big Red One (and who actually directed the eponymous film): “War is barbarous, cannibalistic, barbaric as The Burmese Harp and cannibalistic as Fires on the Plain…”     

Diagnostic accuracy of 18F-FDG PET/CT for assessing response to radiofrequency ablation treatment in lung metastases: a multicentre prospective study

Purpose

To assess diagnostic accuracy of ¹⁸F-FDG PET/CT at 3 months for the detection of local recurrence after radiofrequency ablation (RFA) of lung metastases.

Methods

The PET/CT scan at 3 months was compared with a baseline PET/CT scan from a maximum of 2 months before RFA, with the reference standard as recurrence diagnosed by CT during a 12-month follow-up. Local recurrence was diagnosed on the PET/CT scan if lesional uptake was greater than the mediastinal background. Maximum standardized uptake values (SUVmax) were recorded. ROC curve analysis for SUVmax was performed. Overall survival (OS) and time to local relapse were computed from the date of RFA using the Kaplan-Meier method (www.clinicaltrials.gov: NCT 00382252).

Results

Between 2005 and 2009, 89 patients (mean age 65 years) underwent RFA for 115 lung metastases (mean size 16.2 ± 6.9 mm). The median SUVmax before RFA was 5.8?±?4. PET/CT at 3 months and the reference standard were available in 77 patients and 100 lesions. Accuracy was 66.00 % (95 % CI 55.85–75.18 %), sensitivity 90.91 % (95 % CI 58.72–99.77 %), specificity 62.92 % (95 % CI 52.03–72.93 %), PPV 23.26 % (95 % CI 11.76–38.63 %), and NPV 98.25 % (95 % CI 90.61–99.96 %). One-year OS was 94.2 % (95 % CI 86.6–97.5 %) and the probability of being free of local recurrence 1 year after RFA was 84.6 % (95 % CI 75.0–90.8 %).

Conclusion

The specificity of PET/CT at 3 months is low because of persistent inflammation, especially when the lesion is close to the pleura. This technique is useful for its negative predictive value, but positive findings need to be confirmed by histology before new treatment is planned.     

Caroli disease, bilateral diffuse cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas: a ciliopathy caused by a homozygous NPHP3 mutation

We report the rare association of Caroli disease (intrahepatic bile duct ectasia associated with congenital hepatic fibrosis), bilateral cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas in a female child. She presented with end-stage renal disease at the age of 1 month, followed by a rapidly progressing hepatic fibrosis and dilatation of the intrahepatic bile ducts, leading to secondary biliary cirrhosis and portal hypertension. Combined liver–kidney transplantation was performed at the age of 4 years, with excellent outcome. DNA analysis showed a NPHP3 (coding nephrocystin-3) homozygote mutation, confirming that this malformation complex is a ciliopathy. Conclusion: This rare association required an exceptional therapeutic approach: combined simultaneous orthotopic liver and kidney transplantation in a situs inversus recipient. The long-term follow-up was excellent with a very good evolution of the renal and hepatic grafts and normalization of growth and weight. This malformation complex has an autosomal recessive inheritance with a 25% recurrence risk in each pregnancy.