One size fits ball: Macrocyclic hosts for fullerenes with micromolar affinity

Date du colloque : 25/03/2012International audienc

Cost analysis of the management of brain metastases in patients with advanced ALK+ NSCLC: alectinib versus crizotinib

Aim: To estimate management cost of NSCLC ALK+ patients with and without brain metastasis (BM), and to compare annual costs in patients treated with alectinib or crizotinib. Methods: Management cost/year (euro 2018) in patients with and without BM was estimated with disaggregated resource consumption provided by local oncologists, including medical visits, hospitalizations, diagnostic/laboratory tests, imaging techniques and surgical procedures. The comparison of costs/year with alectinib and crizotinib, considered the cumulative 12-month incidence of BM in ALEX trial (9.4 and 41.4%, respectively). Results: Management cost was euro6173.42/patient-year without BM and euro21,637.50/patient-year with BM. With alectinib, average cost/patient was lower than crizotinib (euro4948.51/patient-year). Conclusion: Prevention of BM with alectinib may result in reductions of cost/year in the management of advanced ALK+ NSCLC

Macrocyclic Hosts for Fullerenes: Extreme Changes in Binding Abilities with Small Structural Variations

Exploiting the shape and electronic complementarity of C60 and C70 with π-extended derivatives of tetrathiafulvalene (exTTF), we have very recently reported a macrocyclic receptor featuring two exTTF recognizing units which forms 1:1 complexes with C60 with log Ka = 6.5 ± 0.5 in chlorobenzene at 298 K. This represents one of the highest binding constants toward C60 reported to date and a world-record for all-organic receptors. Here, we describe our efforts to fine-tune our macrocyclic bis-exTTF hosts to bind C60 and/or C70, through structural variations. On the basis of preliminary molecular modeling, we have explored p-xylene, m-xylene, and 2,6-dimethylnaphthalene as aromatic spacers between the two exTTF fragments and three alkene-terminated chains of different length to achieve macrocycles of different size through ring closing metathesis. Owing to the structural simplicity of our design, all nine receptors could be accessed in a synthetically straightforward manner. A thorough investigation of the binding abilities of these nine receptors toward C60 and C70 has been carried out by means of UV−vis titrations. We have found that relatively small variations in the structure of the host lead to very significant changes in affinity toward the fullerene, and in some cases even in the stoichiometry of the associates. Our results highlight the peculiarities of fullerenes as guests in molecular recognition. The extreme stability of these associates in solution and the unique combination of electronic and geometrical reciprocity of exTTF and fullerenes are the main features of this new family of macrocyclic hosts for fullerenes

Macrocyclic Hosts for Fullerenes: the New Collection

Date du colloque : 07/2011</p

Automatic speech analysis to early detect functional cognitive decline in elderly population

This study aimed at evaluating whether people with a normal cognitive function can be discriminated from subjects with a mild impairment of cognitive function based on a set of acoustic features derived from spontaneous speech. Voice recordings from 90 Italian subjects (age &gt;65 years; group 1: 47 subjects with MMSE&gt;26; group 2: 43 subjects with 20≤ MMSE ≤26) were collected. Voice samples were processed using a MATLAB-based custom software to derive a broad set of known acoustic features. Linear mixed model analyses were performed to select the features able to significantly distinguish between groups. The selected features (% of unvoiced segments, duration of unvoiced segments, % of voice breaks, speech rate, and duration of syllables), alone or in addition to age and years of education, were used to build a learning-based classifier. The leave-one-out cross validation was used for testing and the classifier accuracy was computed. When the voice features were used alone, an overall classification accuracy of 0.73 was achieved. When age and years of education were additionally used, the overall accuracy increased up to 0.80. These performances were lower than the accuracy of 0.86 found in a recent study. However, in that study the classification was based on several tasks, including more cognitive demanding tasks. Our results are encouraging because acoustic features, derived for the first time only from an ecologic continuous speech task, were able to discriminate people with a normal cognitive function from people with a mild cognitive decline. This study poses the basis for the development of a mobile application performing automatic voice analysis on-the-fly during phone calls, which might potentially support the detection of early signs of functional cognitive decline

Tau Oligomer–Containing Synapse Elimination by Microglia and Astrocytes in Alzheimer Disease

Importance: Factors associated with synapse loss beyond amyloid-β plaques and neurofibrillary tangles may more closely correlate with the emergence of cognitive deficits in Alzheimer disease (AD) and be relevant for early therapeutic intervention. // Objective: To investigate whether accumulation of tau oligomers in synapses is associated with excessive synapse elimination by microglia or astrocytes and with cognitive outcomes (dementia vs no dementia [hereinafter termed resilient]) of individuals with equal burdens of AD neuropathologic changes at autopsy. // Design, Setting, and Participants: This cross-sectional postmortem study included 40 human brains from the Massachusetts Alzheimer Disease Research Center Brain Bank with Braak III to IV stages of tau pathology but divergent antemortem cognition (dementia vs resilient) and cognitively normal controls with negligible AD neuropathologic changes. The visual cortex, a region without tau tangle deposition at Braak III to IV stages, was assessed after expansion microscopy to analyze spatial relationships of synapses with microglia and astrocytes. Participants were matched for age, sex, and apolipoprotein E status. Evidence of Lewy bodies, TDP-43 aggregates, or other lesions different from AD neuropathology were exclusion criteria. Tissue was collected from July 1998 to November 2020, and analyses were conducted from February 1, 2022, through May 31, 2023. // Main Outcomes and Measures: Amyloid-β plaques, tau neuropil thread burden, synapse density, tau oligomers in synapses, and internalization of tau oligomer–tagged synapses by microglia and astrocytes were quantitated. Analyses were performed using 1-way analysis of variance for parametric variables and the Kruskal-Wallis test for nonparametric variables; between-group differences were evaluated with Holm-Šídák tests. // Results: Of 40 included participants (mean [SD] age at death, 88 [8] years; 21 [52%] male), 19 had early-stage dementia with Braak stages III to IV, 13 had resilient brains with similar Braak stages III to IV, and 8 had no dementia (Braak stages 0-II). Brains with dementia but not resilient brains had substantial loss of presynaptic (43%), postsynaptic (33%), and colocalized mature synaptic elements (38%) compared with controls and significantly higher percentages of mature synapses internalized by IBA1-positive microglia (mean [SD], 13.3% [3.9%] in dementia vs 2.6% [1.9%] in resilient vs 0.9% [0.5%] in control; P < .001) and by GFAP-positive astrocytes (mean [SD], 17.2% [10.9%] in dementia vs 3.7% [4.0%] in resilient vs 2.7% [1.8%] in control; P = .001). In brains with dementia but not in resilient brains, tau oligomers more often colocalized with synapses, and the proportions of tau oligomer–containing synapses inside microglia (mean [SD] for presynapses, mean [SD], 7.4% [1.8%] in dementia vs 5.1% [1.9%] resilient vs 3.7% [0.8%] control; P = .006; and for postsynapses 11.6% [3.6%] dementia vs 6.8% [1.3%] resilient vs 7.4% [2.5%] control; P = .001) and astrocytes (mean [SD] for presynapses, 7.0% [2.1%] dementia vs 4.3% [2.2%] resilient vs 4.0% [0.7%] control; P = .001; and for postsynapses, 7.9% [2.2%] dementia vs 5.3% [1.8%] resilient vs 3.0% [1.5%] control; P < .001) were significantly increased compared with controls. Those changes in brains with dementia occurred in the absence of tau tangle deposition in visual cortex. // Conclusion and Relevance: The findings from this cross-sectional study suggest that microglia and astrocytes may excessively engulf synapses in brains of individuals with dementia and that the abnormal presence of tau oligomers in synapses may serve as signals for increased glial-mediated synapse elimination and early loss of brain function in AD

Vigilancia de Parálisis Flácida Aguda. España, 2011

Desde que en el año 2002 Europa recibiera la certificación de Región Libre de Polio, no han cesado los esfuerzos para mejorar las coberturas de vacunación y evitar que se relaje la vigilancia de la Parálisis Flácida Aguda (PFA). El importante brote de polio que se registró en Tayikistán en el año 2010 puso de manifiesto la necesidad real de alerta ante la importación de poliovirus. Todo apunta, no obstante, a que el éxito para conseguir el objetivo de erradicación de la polio, no sólo radica en las cuestiones técnicas, sino también en el compromiso veraz de todas las partes involucradas. A nivel mundial, el número de casos de polio ha descendido en un 99%, pasando de 350.000 casos notificados en más de 150 países en 1988 a 650 casos declarados en 2011. En la actualidad sólo algunas zonas de tres países (Afganistán, Nigeria y Pakistán) se consideran endémicas de polio, lo que supone que la polio está geográficamente más confinada que nunca. En España, desde el año 1996 las coberturas de vacunación frente a polio son superiores al 90% en todas las regiones; en 2011 la cobertura nacional para la serie primaria con vacuna de polio fue 97,1% (rango 92,6% - 100%). En 2011 el sistema de vigilancia de la PFA ha mantenido los estándares de calidad en cuanto a la investigación epidemiológica y al estudio en el laboratorio de los casos notificados, sin embargo la sensibilidad en la identificación de casos está por debajo de la esperada

Efeito do pH na atividade de lacase e na descoloração de corantes industriais por extrato enzimático de Panus lecomtei.

O objetivo deste trabalho foi investigar o efeito da variação do pH na atividade de lacase e na descoloração de corantesindustriais por um extrato enzimático do fungo de podridão branca Panus lecomteicultivado em meio líquido

Vigilancia del Sarampión, Rubéola y Síndrome de Rubéola Congénita. España 2011

Entre 2010 y 2012 España, igual que otros países europeos, ha sufrido una onda epidémica de sarampión; se han registrado las mayores incidencias desde que se implantó el Plan Nacional de Eliminación de Sarampión: 0,66 casos/100.000 habitantes en 2010, 7,45/100.000 habitantes en 2011 y 2,54/100.00 habitantes en 2012. En 2011 se notificaron 3.518 casos confirmados de sarampión; los niños < 4 años y los adultos jóvenes (20-29 años) han sido los más afectados; la mayoría de los casos (96 %) estaban sin vacunar o mal vacunados. Grupos de niños mal vacunados y profesionales sanitarios sin inmunizar han tenido mucha importancia en la generación y difusión de los brotes. Los países de la Región Europea de la Organización Mundial de la Salud (OMS), están inmersos en la última fase del proceso con el objetivo de interrumpir la circulación del sarampión y de la rubéola endémicos en la región en 2015. El avance hacia la eliminación se conseguirá si se mantiene la calidad del sistema de vigilancia y se mantienen altas coberturas de vacunación (> 95 %) con dos dosis de vacuna triple vírica en todos los niveles geográficos y grupos de población; establecer recordatorios sistemáticos para las dosis del calendario de vacunación infantil y asegurar que los profesionales sanitarios se vacunen son intervenciones eficaces para evitar que un caso importado origine un brote cuando el sarampión y la rubéola están próximos a la eliminación