Learning and vulnerability to phonological and semantic interference in normal aging: an experimental study.

ABSTRACTThis study compares semantic and phonological interference vulnerability across the full range of learning processes. Method: 43 controls aged 61-88 underwent a neuropsychological examination, French adaptation of the LASSI-L, and an experimental phonological test, the TIP-A. Paired sample t-tests, factorial ANOVA and hierarchical regressions were conducted, psychometric properties were calculated. Results: TIP-A efficiently generated phonological interference between concurrent word lists and was associated with short-term memory, unlike LASSI-L. On LASSI-L, proactive interference was higher than retroactive interference; the opposite pattern was found on TIP-A. Memory performance was better explained by age in the semantic than in the phonological task. Age was not associated with interference vulnerability. Intrusions and false recognition were associated with cognitive functioning regardless of age, particularly in the semantic context. Conclusion: To our knowledge, this is the first study to assess phonological and semantic interference using homologous concurrent word list tasks, and not a working memory build-up or DRM paradigm. The pattern obtained illustrates the weak initial memory trace in a phonological context and results are discussed according to depth-of-processing and dual-process theories. Similar paradigms could be studied among various pathologies for a better understanding of generalised interference vulnerability vs. specific semantic or phonological impairment.

Combination of PI3K and MEK inhibitors yields durable remission in PDX models of PIK3CA-mutated metaplastic breast cancers.

BACKGROUND: Metaplastic breast cancer (MBC) is a rare form of breast cancer characterized by an aggressive clinical presentation, with a poor response to standard chemotherapy. MBCs are typically triple-negative breast cancers (TNBCs), frequently with alterations to genes of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. The objective of this study was to determine the response to PI3K and MAPK pathway inhibitors in patient-derived xenografts (PDXs) of MBCs with targetable alterations. METHODS: We compared survival between triple-negative MBCs and other histological subtypes, in a clinical cohort of 323 TNBC patients. PDX models were established from primary breast tumors classified as MBC. PI3K-AKT-mTOR and RTK-MAPK pathway alterations were detected by targeted next-generation sequencing (NGS) and analyses of copy number alterations. Activation of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways was analyzed with reverse-phase protein arrays (RPPA). PDXs carrying an activating mutation of PIK3CA and genomic changes to the RTK-MAPK signaling pathways were treated with a combination consisting of a PI3K inhibitor and a MEK inhibitor. RESULTS: In our clinical cohort, the patients with MBC had a worse prognosis than those with other histological subtypes. We established nine metaplastic TNBC PDXs. Three had a pathogenic mutation of PIK3CA and additional alterations to genes associated with RTK-MAPK signaling. The MBC PDXs expressed typical EMT and stem cell genes and were of the mesenchymal or mesenchymal stem-like TNBC subtypes. On histological analysis, MBC PDXs presented squamous or chondroid differentiation. RPPA analysis showed activation of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. In vivo, the combination of PI3K and MAPK inhibitors displayed marked antitumor activity in PDXs carrying genomic alterations of PIK3CA, AKT1, BRAF, and FGFR4. CONCLUSION: The treatment of metaplastic breast cancer PDXs by activation of the PI3K-AKT-mTOR and RTK-MAPK pathways at the genomic and protein levels with a combination of PI3K and MEK inhibitors resulted in tumor regression in mutated models and may therefore be of interest for therapeutic purposes.

An Examination of Semantic Impairment in Amnestic MCI and AD: What Can We Learn From Verbal Fluency?

INTRODUCTION: The Verbal Fluency Test (VF) is commonly used in neuropsychology. Some studies have demonstrated a marked impairment of semantic VF compared to phonemic VF in Alzheimer's disease (AD). Since amnestic Mild Cognitive Impairment (aMCI) is associated with increased risk of conversion to incident AD, it is relevant to examine whether a similar impairment is observed in this population. The objective of the present empirical study is to compare VF performance of aMCI patients to those of AD and elderly controls matched one-to-one for age and education. METHOD: Ninety-six participants divided into three equal groups (N = 32: AD, aMCI and Controls) were included in this study. Participants in each group were, on average, 76 years of age and had 13 years of education. A repeated measures ANOVA with the Group (AD, aMCI, NC) as between-subject factor and the Fluency condition ("P" and "animals") as within-subject factor was performed. T-tests and simple ANOVAs were also conducted to examine the interaction. RESULTS: There was a significant interaction between the groups and the verbal fluency condition. In AD, significantly fewer words were produced in both conditions. In contrast, participants with aMCI demonstrated a pattern similar to controls in the phonemic condition, but generated significantly fewer words in the semantic condition. CONCLUSION: These results indicate a semantic memory impairment in aMCI revealed by a simple, commonly-used neuropsychological test. Future studies are needed to investigate if semantic fluency deficits can help predict future conversion to AD.

Association of traumatic brain injury and Alzheimer disease onset: A systematic review.

BACKGROUND: Inconsistencies regarding the risk of developing Alzheimer disease after traumatic brain injury (TBI) remain in the literature. Indeed, why AD develops in certain TBI patients while others are unaffected is still unclear. OBJECTIVE: The aim of this study was to performed a systematic review to investigate whether certain variables related to TBI, such as TBI severity, loss of consciousness (LOC) and post-traumatic amnesia (PTA), are predictors of risk of AD in adults. METHODS: From 841 citations retrieved from MEDLINE via PubMed, EMBASE, PSYINFO and Cochrane Library databases, 18 studies were eligible for the review. RESULTS: The review revealed that about 55.5% of TBI patients may show deteriorated condition, from acute post-TBI cognitive deficits to then meeting diagnostic criteria for AD, but whether TBI is a risk factor for AD remains elusive. CONCLUSIONS: Failure to establish such a link may be related to methodological problems in the studies. To shed light on this dilemma, future studies should use a prospective design, define the types and severities of TBI and use standardized AD and TBI diagnostic criteria. Ultimately, an AD prediction model, based on several variables, would be useful for clinicians detecting TBI patients at risk of AD.

Naming unique entities in the semantic variant of primary progressive aphasia and Alzheimer's disease: Towards a better understanding of the semantic impairment.

While the semantic variant of primary progressive aphasia (svPPA) is characterized by a predominant semantic memory impairment, episodic memory impairments are the clinical hallmark of Alzheimer's disease (AD). However, AD patients also present with semantic deficits, which are more severe for semantically unique entities (e.g. a famous person) than for common concepts (e.g. a beaver). Previous studies in these patient populations have largely focused on famous-person naming. Therefore, we aimed to evaluate if these impairments also extend to other semantically unique entities such as famous places and famous logos. In this study, 13 AD patients, 9 svPPA patients, and 12 cognitively unimpaired elderly subjects (CTRL) were tested with a picture-naming test of non-unique entities (Boston Naming Test) and three experimental tests of semantically unique entities assessing naming of famous persons, places, and logos. Both clinical groups were overall more impaired at naming semantically unique entities than non-unique entities. Naming impairments in AD and svPPA extended to the other types of semantically unique entities, since a CTRL>AD>svPPA pattern was found on the performance of all naming tests. Naming famous places and famous persons appeared to be most impaired in svPPA, and both specific and general semantic knowledge for these entities were affected in these patients. Although AD patients were most significantly impaired on famous-person naming, only their specific semantic knowledge was impaired, while general knowledge was preserved. Post-hoc neuroimaging analyses also showed that famous-person naming impairments in AD correlated with atrophy in the temporo-parietal junction, a region functionally associated with lexical access. In line with previous studies, svPPA patients' impairment in both naming and semantic knowledge suggest a more profound semantic impairment, while naming impairments in AD may arise to a greater extent from impaired lexical access, even though semantic impairment for specific knowledge is also present. These results highlight the critical importance of developing and using a variety of semantically-unique-entity naming tests in neuropsychological assessments of patients with neurodegenerative diseases, which may unveil different patterns of lexical-semantic deficits.

Relying on procedural memory to enhance independence in daily living activities: Smartphone use in a case of semantic dementia.

Relying on procedural memory is a promising approach for interventions that address the cognitive difficulties found in semantic dementia. The aim of this study was to determine if procedural memory could be used to optimise learning of relevant smartphone functions in MH, a 55-year-old man with semantic dementia. The impact of learning to use specific smartphone applications, which display concepts and their semantic characteristics, on relearning useful significant concepts, was also explored in MH. This patient, who showed no deficits in procedural learning on a serial reaction time paradigm, was able to learn manipulations related to 15 smartphone functions although, because of his deficit in word comprehension, he generally needed verbal cues to clarify which functions he was asked to perform. Six months after the end of the intervention, he was still using 8 of the 15 functions regularly. However, repeated exposure to concepts through the use of two applications did not improve naming or retrieval of semantic attributes. This study showed the potential of relying on procedural memory to optimise learning of new technologies in the ecological rehabilitation of semantic dementia.

Canine melanoma diagnosis: RACK1 as a potential biological marker.

Melanoma diagnosis in dogs can be challenging due to the variety of histological appearances of canine melanocytic neoplasms. Markers of malignancy are needed. Receptor for activated C-kinase 1 (RACK1) was found to characterize melanomas in other mammals. We investigated the value of RACK1 detection in the classification of 19 cutaneous and 5 mucosal melanocytic neoplasms in dogs. These tumors were categorized as melanocytomas or benign and melanomas or malignant after evaluation of their morphology, mitotic index, and Ki-67 growth fraction. Using immunofluorescence, we confirmed microphthalmia-associated transcription factor (MITF) as a marker of normal and transformed melanocytic cells in dog tissues. All control (n = 10) and tumoral (n = 24) samples stained positively for MITF (34/34, 100%). Whereas RACK1 was not detected in healthy skin melanocytes, melanocytic lesions were all positive for RACK1 signal (24/24, 100%). RACK1 cytoplasmic staining appeared with 2 distinct distribution patterns: strong, diffuse, and homogeneous or granular and heterogeneous. All melanoma samples (13/13, 100%) stained homogeneously for RACK1. All melanocytomas (11/11, 100%) stained heterogeneously for RACK1. Immunohistochemistry was less consistent than immunofluorescence for all labelings in melanocytic lesions, which were often very pigmented. Thus, the fluorescent RACK1-MITF labeling pattern helped to distinguish melanomas from melanocytomas. Furthermore, RACK1 labeling correlated with 2 of 11 morphological features linked to malignancy: cell and nuclear size. These results suggest that RACK1 may be used as a marker in dog melanomas.

The utilization of red cell concentrates at Kimberley Hospital Complex, Northern Cape Province, South Africa.

This prospective clinical audit of the utilization of red cell concentrates assesses 55 consecutive transfusion episodes in chronically anaemic adult patients. It examines the appropriateness and outcome of the transfusion episodes; over-transfusion and wastage rates, assessment of anaemia, the informed consent process, and if teaching influenced these parameters when compared to an earlier retrospective audit. The audit revealed several strengths and weaknesses relating to our institution's transfusion practices. Training sessions led to clinically and economically important improvements in transfusion decisions, the investigation of anaemia and the obtainment of informed consent prior to transfusions.

Modeling of response to endocrine therapy in a panel of human luminal breast cancer xenografts.

Resistance to endocrine therapy is a major complication of luminal breast cancer and studies of the biological features of hormonal resistance are limited by the lack of adequate preclinical models. The aim of this study is to establish and characterize a panel of primary human luminal breast carcinoma xenografts, and to evaluate their response to endocrine therapies. Four hundred and twenty-three tumor fragments obtained directly from patients have been grafted in the interscapular fatpad of Swiss nude mice. After stable engraftment with estradiol supplementation, xenografted tumors have been validated by conventional pathology and immunohistochemistry examination, and additional molecular studies. In vivo tumor growth and response to different endocrine treatments were evaluated. We have engrafted 423 tumors including 314 ER+ tumors, and 8 new luminal breast cancer xenografts have been obtained (2.5%). Tumor take was much lower for luminal tumors than for non-luminal tumors (2.5 vs. 24.7%, P < 0.0001), and was associated with two independent criteria, i.e., ER status (P < 0.0001) and a high grade tumor (P = 0.05). Histological and immunohistochemical analyses performed on patient's tumors and xenografts showed striking similarities in the tumor morphology as well as in the expression level of ER, PR, and HER2. Response to hormone therapy, evaluated in 6 luminal models, showed different sensitivities, thus exhibiting heterogeneity similar to what is observed in the clinic. We have established a panel of primary human luminal breast cancer xenografts, recapitulating the biological and clinical behaviors of patient tumors, and therefore suitable for further preclinical experiments.

Inquérito sorológico para toxoplasmose e leptospirose em mamíferos selvagens neotropicais do Zoológico de Aracaju, Sergipe / Serological survey of toxoplasmosis and leptospirosis in neotropical wild mammals from Aracaju Zoo, Sergipe, Brazil

Os zoológicos modernos são instituições destinadas à manutenção da fauna selvagem com o objetivo de promover a conservação, pesquisa científica, lazer, recreação e educação ambiental. A ampla variedade de espécies selvagens, vivendo em condições diferentes do seu habitat natural, representa um ambiente propício à disseminação de doenças, muitas delas zoonóticas. Devido à escassez de dados e à relevância dos mamíferos selvagens neste contexto epidemiológico, tanto na toxoplasmose, quanto na leptospirose, foi efetuado o inquérito sorológico para toxoplasmose e leptospirose em mamíferos selvagens neotropicais do Zoológico de Aracaju, Sergipe, Brasil. Para tanto foram colhidas amostras sanguíneas de 32 animais, adultos, de ambos os sexos incluindo: 14 macacos-prego (Cebus libidinosus), quatro macacos-prego-do-peito-amarelo (Cebus xanthosternus), três onças-suçuaranas (Puma concolor), uma onça-pintada (Pantheraonca), uma raposa (Cerdocyon thous), seis guaxinins (Procyon cancrivorus), dois quatis (Nasua nasua) e um papa-mel (Eira barbara). Para a pesquisa de anticorpos anti-Toxoplasma gondii foi utilizado o Teste de Aglutinação Modificada (MAT ³"1:25) e para pesquisa de anticorpos anti-Leptospira spp. foi utilizado o teste de Soroaglutinação Microscópica (ponto de corte ³1:100) com uma coleção de antígenos vivos que incluiu 24 variantes sorológicas de leptospiras patogênicas e duas leptospiras saprófitas. Dentre os 32 mamíferos, 17 (53,1 por cento) apresentaram anticorpos anti-T. gondii e quatro (12,5 por cento) foram positivos para anticorpos anti-Leptospira spp. De acordo com o sexo, 60 por cento (9/15) dos machos e 47,1 por cento (8/17) das fêmeas foram soropositivos para T. gondii e 26,7 por cento (4/15) dos machos apresentaram anticorpos anti-Leptospira spp. Dos mamíferos que apresentaram anticorpos anti-T. gondii, 47 por cento (8/17) nasceram no zoológico, 41,2 por cento (7/17) foram oriundos de outras instituições e dois (11,8 por cento) ...

Modern zoological gardens are institutions to wildlife maintenance, aiming its conservation, the performance of scientific research and leisure, recreation and environ-mental education activities. The variety of wild species living in conditions different from the one found in its natural habitats represents a propitious environment for diseases spread, specially the zoonotic ones. Due to data shortage and wild mammals' epidemio-logical relevance both for toxoplasmosis as for leptospirosis, this study aimed to determine the serological survey of toxoplasmosis and leptospirosis in Neotropical wild mammals, from Zoo of Aracaju, Sergipe, Brazil. Blood samples were collected from 32 wild mammals, adults and from both sexes: 14 wild bearded capuchins (Cebus libidinosus), four golden-bellied capuchins (Cebus xanthosternus), three pumas (Puma concolor), one jaguar (Pantheraonca), one crab-eating fox (Cerdocyon thous), six crab-eating raccoons (Procyon cancrivorus), two South American coatis (Nasua nasua), and one tayra (Eira barbara). Sera were tested to Toxoplasma gondii antibodies by the modified agglutination test (MAT e"1:25), and by the microscopic seroaglutination test (cut-off e"1:100) using 24 serovar of pathogenic leptospiras and two serovar of saprophyte leptospiras. Antibodies to T. gondii were found in 17 of 32 (53.1 percent) wild mammals, and antibodies to Leptospira spp. were found in 4 of 32 (12.5 percent) wild mammals. In relation to gender, 9 of 15 (60 percent) males, and 8 of 17 (47.1 percent) females had antibodies to Toxoplasma gondii, and 4 of 15 (26.7 percent) males had antibodies to Leptospira spp. Considering the origin of the seropositive animals to T. gondii, 8 of 17 (47 percent) were born in the zoo, 7 of 17 (41.2 percent) were from other zoos, and 2 (11.8 percent) were from the wild. Three of 4 (75 percent) mammals seropositive to Leptospira spp. were born in zoo, and 1 of 4 (25 percent) was from the wild. This is ...

[Pure progressive amnesia: an amnestic syndrome with preserved independence in daily life]. / L'amnésie pure progressive : un syndrome amnésique avec préservation de l'autonomie.

INTRODUCTION: Pure progressive amnesia, a form of progressive focal cortical atrophy is thought to represent the early stages of a rare form of Alzheimer's disease (AD). This syndrome is characterized by the insidious and slowly progressive breakdown of memory, in the absence of a significant impairment in other cognitive domains or in the realm of behavior. The aims of the present study were to contribute to the characterization of this poorly documented type of amnesia, to compare it with other forms of amnestic syndromes resulting from lesions to the medial temporal lobes and to discuss its potential pathophysiological basis. PATIENTS AND METHOD: We carried out three single case studies in patients presenting with pure progressive amnesia. They all underwent a neuropsychological evaluation that included an extensive assessment of spatial and recognition memory, along with brain magnetic resonance imaging and a cerebral blood flow study. RESULTS: All three patients had a severe deficit in the storage of context-free information, along with a severe visual recognition memory impairment, as previously reported in a case study on a patient with pure progressive amnesia (Cognitive Neuropsychology 23 (2006) 1230-1247). Yet, spatial memory remained well preserved, and patients maintained totally independent in everyday life. In addition, a significant atrophy of the medial temporal structures was found. DISCUSSION: This specific pattern of impairment differs from other types of amnestic syndromes after medial temporal damage and raises the question of lesional topography, as well as possible compensatory phenomena. We suggest that pure progressive amnesia results from selective damage to the ventral subhippocampal route into the hippocampal formation leading to impaired context-free memory. Spatial memory may remain intact because the dorsal parahippocampal route into the hippocampus remains functional. Pure progressive amnesia may contribute to a better understanding of the neural systems involved in declarative memory and provide a better understanding into the nature of the memory impairment that characterizes the initial stages of AD.

Proteomic and phosphoproteomic analysis of cellular responses in medaka fish (Oryzias latipes) following oral gavage with microcystin-LR.

Chronic and subchronic toxicity resulting from exposure to microcystins (MCs) receives increasing attention due to the risk of bioaccumulation of these toxins by aquatic animals, including fish. The mechanisms of action of MCs that target the liver, involve modifications of protein phosphorylation resulting from phosphatases 1 and 2A inhibition. Therefore, studying phosphoprotein modifications by using a specific phosphoprotein stain Pro-Q Diamond in fish liver contaminated with MC-leucine-arginine (MC-LR), the most toxic MC, should help dissecting disturbed signaling and metabolic networks. We have recently used this technology to identify several proteins that are modulated either in expression or phosphorylation in the liver of medaka following short-term exposure to MC-LR by balneation. In the present study, we have decided to use an alternative way of introducing the toxin into fish; that is by gavage (force-feeding). This was first achieved using tritiated MC-LR and allowed us to quantify the quantity of toxin incorporated into fish and to demonstrate that the toxin is mainly accumulated in liver. Afterwards a proteomics study limited to liver cytosolic proteins of contaminated animals showed that several proteins were up or down regulated either in quantity or in phosphorylation or both. Some of them had been previously detected as modified in balneation experiments but new molecules were identified as involved in signal transduction pathways activated by the toxin. In addition, in the conditions used (5 microg toxin/g body weight) anatomopathological studies supported a process of apoptonecrosis established after 24h, which was suggested to proceed by the evolution of some of the proteins after 2h contamination.

Progressive prosopagnosia: clinical and neuroimaging results.

The authors report the longitudinal case study of a patient with the right temporal variant of frontotemporal lobar degeneration. His deficit, initially limited to visuoperceptual disturbances, progressed 2 years later to a severe semantic breakdown. Neuroimaging data indicate that the underlying degenerative process, initially confined to unimodal visual associative cortices, progressed along the ventral pathways to multimodal areas in charge of integrating knowledge from various modalities (the anterior temporal lobes).

[The human perirhinal cortex]. / Le cortex périrhinal chez l'homme.

The perirhinal cortex is a structure that lies within the medial temporal lobe. In the present paper, we review current knowledge of the anatomical boundaries and functional correlates of this structure. In the past decade, numerous animal studies have attempted to understand the contribution of the perirhinal cortex to memory. Taken together, they suggest that the perirhinal cortex is crucially involved in recognition memory. This function appears to be independent from those assumed to be subserved by the hippocampus. In humans, data are scarce but tend to corroborate results found in the animal literature. The perirhinal cortex appears to support context-free (non-episodic) knowledge, such as general knowledge about the world and "item-specific" memories. Models of declarative memory that take into account the specific contribution of the perirhinal cortex are discussed, along with their potential application to early cortical neurodegenerative disorders.

Evaluation of visual recognition memory in MCI patients.

BACKGROUND: Neurofibrillary tangles seen early in Alzheimer disease (AD) initially appear in a subregion of the perirhinal cortex. In the monkey, damage to the perirhinal cortex impairs performance on visual recognition memory tasks. The authors evaluated impairment of visual recognition memory as a potential early diagnostic marker of AD. METHODS: The authors developed a visual delayed matching-to-sample task (DMS48) designed to assess visual recognition memory in humans. Twenty-three patients fulfilling the criteria of amnestic mild cognitive impairment (MCI) (mean Mini-Mental State Examination [MMSE]: 26.6, SD = 1.6) were recruited. All underwent a full neuropsychological evaluation, which included the Free and Cued Selective Reminding (FCSR) test. Their performance was compared with that of 10 patients with mild AD, 20 patients with moderate AD, 20 patients with Parkinson disease (PD), and 40 age-matched controls. RESULTS: Control subjects and patients with PD performed close to ceiling. Patients with mild AD had very low scores, while patients with moderate AD answered at random. MCI patients obtained scores that were between those of control subjects and patients with mild AD (78%, SD = 16%). MCI patients who failed on the DMS48 had lower scores on free recall (p < 0.05) and received less benefit from cueing (p < 0.01) on the FCSR than the other MCI, suggesting a profile of genuine memory impairment related to medial temporal lobe lesions. CONCLUSION: The DMS48, a test of visual recognition memory, is impaired early in the course of patients with MCI. Further studies are necessary to determine whether the evaluation of visual recognition memory may contribute to the identification of patients with AD.

Reduced activity of the NPR-A kinase triggers dephosphorylation and homologous desensitization of the receptor.

NPR-A, the receptor for the atrial natriuretic peptide (ANP), is a 130-kDa protein presenting an extracellular ANP-binding domain, a single transmembrane domain, an intracellular regulatory kinase homology domain (KHD), and a guanylyl cyclase catalytic domain. Upon stimulation, NPR-A receptors are activated to produce cyclic guanosine monophosphate (cGMP) and are subsequently desensitized through dephosphorylation of residues at their KHD. We used wild-type rat (r) NPR-A (WT) and a disulfide-bridged mutant (C423S) expressed in human embryonic kidney (HEK) 293 cells to study receptor phosphorylation. We have previously characterized the C423S receptor as constitutively active and desensitized. At basal state, 32P incorporation in the rNPR-A(C423S) covalent dimer is about 24 times less efficient than incorporation in the WT rNPR-A. When membranes from WT and rNPR-A(C423S) are incubated with [35S]ATPgammaS, the mutant dimer receptor displays 3.5% of the thiophosphate incorporation found for WT rNPR-A. Since the rNPR-A(C423S) dimer is already extensively dephosphorylated, we then used the WT rNPR-A to study dephosphorylation. As previously documented, adding ANP globally induces time-dependent dephosphorylation of the receptor. However, in pulse-chase experiments with the WT rNPR-A, adding ANP during the chase does not lead to a significant effect on receptor dephosphorylation. On the other hand, thiophosphorylation of the WT rNPR-A previously desensitized with ANP is reduced to 8.3% of the incorporation for untreated receptor, similar to results found with the rNPR-A(C423S) at basal state. These results demonstrate that ANP-induced rNPR-A desensitization is modulated by a significant reduction in the activity or affinity of the rNPR-A kinase that contributes to the low phosphorylation level after induction. Moreover, we further document a close relationship between tight dimerization, dephosphorylation, and desensitization.

The role of nasals in reading: a normative study in French.

Dual-route models of reading assume that reading can be done in two ways. A most common lexical route, on the one hand, allows regular and irregular words to be read while a second sublexical route allows nonwords and novel words to be read. A graphemic processing stage in sublexical reading is assumed to assemble the individual letters of a word or a nonword into multiletter graphemes prior to grapheme-phoneme conversion. The purpose of this study was to determine whether vowel/nasal clusters required as much time to be processed asvowel/vowel and consonant/consonant clusters in sublexical nonword reading in French. Results indicate that nonwords that contain vowel/nasal clusters are read significantly faster than nonwords comprising vowel/vowel and consonant/consonant clusters. Furthermore, nonwords that contain single-letter graphemes are read significantly faster than nonwords comprising vowel/nasal clusters and nonwords comprising vowel/vowel and consonant/consonant clusters. These results taken as a whole support the idea that nasals act as diacritic marks rather than being processed by means of a graphemic parsing procedure.

Grapheme-phoneme processing of single words.

Often used in cognitive studies measuring reaction times and in functional imaging studies, the subtraction paradigm is based on the comparison of performance on tasks presupposed to refer to different cognitive levels of processing. Within the framework of the study of phonological processing of words, manipulating the grapheme-phoneme transparency of stimuli can represent a means of counteracting the methodological drawbacks inherent to the subtraction paradigm. Thus, the purpose of this study was to determine the effect of the level of difficulty of grapheme-phoneme matching on the processing of transparent and nontransparent words. Grapheme-phoneme matching was carried out both on the final syllable of words and on sublexical segments within the word. The results indicate that processing is faster for the transparent than for the nontransparent stimuli. This task will now have to be reintroduced in brain imaging studies aiming to look at different levels of difficulty for grapheme-phoneme matching.

The role of sublexical graphemic processing in reading.

Dual-route models of reading postulate the existence of two separate mechanisms: The lexical route allows words to be recognized in their holistic form, and the sublexical route proceeds by converting the written sublexical entities of a word or a nonword into their corresponding phonological equivalents. Sublexical reading is assumed to require three stages of processing: graphemic parsing, graphophonemic conversion, and phoneme blending. This study provides evidence in favor of the existence of a graphemic parsing process which occurs prior to grapheme-phoneme conversion. A group of normal subjects read nonwords which contained multiletter graphemes significantly more slowly than graphemically simple nonwords. These results, best interpretable in the context of a recent dual-route model of reading, confirm previous data obtained in pathology which suggest the functional independence of this cognitive procedure.

Femorodistal bypass using cryopreserved venous allografts for limb salvage.

Critical ischemia due to extensive femoropopliteal occlusive disease often leads to amputation in patients in whom an autologous vein is unavailable for reconstruction. The purpose of this nonrandomized prospective study is to evaluate the usefulness of cryopreserved venous allografts (CPVA) as an arterial substitute in these cases. Between October 1990 and March 1993, long bypass to a tibial or a foot artery using a CPVA was performed in 25 consecutive patients with ulcerations or gangrene. There were 19 women and six men with a mean age of 72 years (range: 51-90). The indication for allograft reconstruction was absence (17 cases) or unsuitability (eight cases) of an autologous vein graft. Greater saphenous vein allografts were harvested from multiple organ donors and frozen at -80 degrees C with 12% dimethylsulfoxide (DMSO). Sixteen patients had undergone one or more previous unsuccessful limb salvage attempts. The plantar arch was absent or incomplete in 16 patients (64%). Patients were followed up prospectively for a mean of 21 months (range: 3-32). One patient died early (32 days) and three patients died late with patent bypasses. Cumulative survival rate was 77% at 1 year and 72% at 2 years. Cumulative secondary patency rate (Kaplan-Meier) was 88% at 1 months, 72% at 6 months, and 52% at 1 year. The cumulative limb salvage rate was 78% at 2 years. When an autologous vein is unavailable, long bypass using a CPVA is a simple, quick, minimally traumatic, economical, and effective method to achieve limb salvage in patients with severe distal arterial occlusive disease. However, CPVA causes immunoreaction and there is a risk of proximal postanastomotic stenosis. Doppler ultrasound surveillance of a subcutaneous graft allows accurate assessment and repair of the abnormalities with no increase in mortality or morbidity.