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2.
J Synchrotron Radiat ; 27(Pt 5): 1218-1226, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32876596

RESUMEN

In order to push the spatial resolution limits to the nanoscale, synchrotron-based soft X-ray microscopy (XRM) experiments require higher radiation doses to be delivered to materials. Nevertheless, the associated radiation damage impacts on the integrity of delicate biological samples. Herein, the extent of soft X-ray radiation damage in popular thin freeze-dried brain tissue samples mounted onto Si3N4 membranes, as highlighted by Fourier transform infrared microscopy (FTIR), is reported. The freeze-dried tissue samples were found to be affected by general degradation of the vibrational architecture, though these effects were weaker than those observed in paraffin-embedded and hydrated systems reported in the literature. In addition, weak, reversible and specific features of the tissue-Si3N4 interaction could be identified for the first time upon routine soft X-ray exposures, further highlighting the complex interplay between the biological sample, its preparation protocol and X-ray probe.


Asunto(s)
Liofilización , Lóbulo Frontal/efectos de la radiación , Espectroscopía Infrarroja por Transformada de Fourier , Sincrotrones , Animales , Técnicas In Vitro , Dosis de Radiación , Ratas , Manejo de Especímenes , Rayos X
3.
J Clean Prod ; 236: 117535, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31680729

RESUMEN

Pursuing a responsible and sustainable development, the United Nations urged to decouple economic growth from environmental impacts. Several European Union (EU) policies have been implemented towards such goal. Although multiple authors have evaluated the decoupling of the economic growth from the resource use or environmental concerns, the environmental assessment mostly focused on pressures rather than impacts, and used single indicators assumed to be a proxy of the overall effects on the environment. Furthermore, no studies were found using a process-based life cycle approach to quantify the environmental impacts of consumption. To solve such research gap, this paper assesses the decoupling in the EU focusing on potential environmental impacts, complementing a production-based approach with two options for accounting for the impacts of consumption. The aim of this paper is to evaluate the decoupling of the economic growth (in terms of Gross Domestic Product) from the environmental impacts due to EU-28 consumption, assessed by means of life cycle assessment (LCA). The decoupling is then assessed in impact terms rather than limited to pressures by using the Environmental Footprint (EF2017) indicators, which allows assessing 16 different impacts. The Consumption Footprint indicator quantified the environmental impacts of EU apparent consumption, including the territorial impacts (Domestic Footprint) and the embodied impacts in both imports and exports (Trade Footprint). The inventory of pressures for the trade component is compiled either with a bottom-up approach (process-based LCA of representative traded goods) or a top-down approach (input-output-based LCA). Methodological aspects influencing the decoupling assessment and the resulting outputs are presented and discussed. According to the results, the environmental impacts of EU-28 consumption showed decoupling during the last decades (2005-2014), between relative to absolute decoupling depending on the inventory modeling approach taken. Some countries showed higher decoupling levels than others displaying a heterogeneous map of EU-28 decoupling, which was led by acidification, particulate matter, land use and eutrophication impacts. Notwithstanding current limitations, the assessment of decoupling using consumption-based environmental indicators is very promising for supporting policy-making towards addressing the actual impacts driven by the EU production and consumption system.

4.
J Clean Prod ; 227: 378-391, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31379419

RESUMEN

Food security and biodiversity conservation are closely interconnected challenges to be addressed to achieve a sustainable food system on a global scale. Due to the complex nature of food production and consumption system, quantifying the impacts of food supply chains on biodiversity is challenging. Life cycle assessment (LCA) allows for systematically addressing environmental impacts along supply chains, representing a reference methodology that can be applied for assessing food systems. In the present study, 32 representative food products of consumption in the European Union (EU) were selected and their environmental impacts calculated through a process-based LCA. The potential contribution of EU food consumption to the current biodiversity decline has been evaluated adopting both midpoint and endpoint indicators. A comparison of the impact drivers was performed. Meat products, the underpinning land use for agricultural purposes, and climate change represent the main hotspots of impacts on biodiversity. Notwithstanding several drivers of biodiversity loss can be accounted for with LCA, the evidence of the increasing biodiversity decline on both a European and a global scale indicates that the assessment system should be further expanded, especially for what concerns refining impact categories such as ecotoxicity, and including resource overexploitation, and impact due to invasive species. This study illustrates: how far the current LCA based impact assessment framework may help to address the drivers of biodiversity loss; which are the main uncertainties associated to results stemming from the application of different endpoint methods; which aspects need to be elaborated further to ensure a comprehensive assessment of biodiversity impacts due to food production and consumption.

5.
Gynecol Obstet Fertil Senol ; 47(9): 662-671, 2019 09.
Artículo en Francés | MEDLINE | ID: mdl-31200110

RESUMEN

OBJECTIVES: To study the psychic self-representations and experiences of menstrual blood in women and their impact on the choice of a contraceptive method, with or without amenorrhea. METHODS: Qualitative study based on semi-structured interviews with French women over age 18, under contraception. RESULTS: Twenty-three interviews were conducted with women of various ages and socio-economic classes. Three themes have been studied: the menarche experience, the representation and experience of menstrual blood, and the representation and experience of amenorrhea induced by contraception. Menarche has been a negative experience for most of them, and menarche is known to influence menstrual self-representation. About menstrual bleeding, two profiles of women could be described. Those with a positive self-representation of menstrual blood considered it necessary for the purification of their bodies as well as for procreation and were reluctant to the idea of amenorrhea induced by their contraception. Those with a negative representation of menstrual blood considered it as a source of physical and mental suffering and accepted the idea of having amenorrhea induced by their contraception, amenorrhea being considered as a treatment or a release. CONCLUSION: The choice of a contraception with or without a induced-amenorrhea seems to be specific to every woman and depends on there self-psychic representation of menstrual blood, independently from their socio-economic class. The results of this study highlighted the effect of women's psychic representations and experience of menstrual blood on their contraceptive choice.


Asunto(s)
Anticoncepción/métodos , Anticoncepción/psicología , Menstruación/psicología , Adolescente , Adulto , Amenorrea/etiología , Amenorrea/psicología , Sangre , Conducta de Elección , Femenino , Francia , Humanos , Menarquia/psicología , Persona de Mediana Edad
6.
Sci Adv ; 5(5): eaav7610, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31058223

RESUMEN

Interference of matter waves is at the heart of quantum physics and has been observed for a wide range of particles from electrons to complex molecules. Here, we demonstrate matter wave interference of single positrons using a period-magnifying Talbot-Lau interferometer based on material diffraction gratings. The system produced high-contrast periodic fringes, which were detected by means of nuclear emulsions capable of determining the impact point of each individual positron with submicrometric resolution. The measured energy dependence of fringe contrast in the range of 8 to 16 keV proves the quantum-mechanical origin of the periodic pattern and excludes classical projective effects, providing the first observation to date of antimatter wave interference. Future applications of this interferometric technique include the measurement of the gravitational acceleration of neutral antimatter systems exploiting the inertial sensing capabilities of Talbot-Lau interference.

9.
Nucleus ; 9(1): 380-391, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29929425

RESUMEN

Cardiac laminopathies, associated with mutations in the LMNA gene, encompass a wide spectrum of clinical manifestations, involving electrical and mechanical alterations of cardiomyocytes. Thus, dilated cardiomyopathy, bradyarrhythmias and atrial or ventricular tachyarrhythmias may occur in a number of combined phenotypes. Nowadays, some attempt has been made to identify clinical predictors for the most life-threatening complications of LMNA-associated heart disease, i.e. sudden cardiac death and end-stage heart failure. The goal of this manuscript is to combine the most recent evidences in an updated review to show the state-of-the-art of such a complex disease group. This is supposed to be the starting point to collect more data and design new ad hoc studies to identify clinically useful predictors to stratify risk in mutation carriers, including probands and their asymptomatic relatives.


Asunto(s)
Cardiopatías/genética , Cardiopatías/fisiopatología , Lamina Tipo A/genética , Enfermedades Musculoesqueléticas/genética , Enfermedades Musculoesqueléticas/fisiopatología , Cardiopatías/metabolismo , Humanos , Lamina Tipo A/metabolismo , Enfermedades Musculoesqueléticas/metabolismo
10.
Skeletal Radiol ; 47(1): 131-136, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28889228

RESUMEN

Calcific tendinopathy of the rotator cuff is a common cause of shoulder pain. Inflammation of the rotator cuff tendons may be complicated by adjacent bone erosion and subsequent migration of calcific deposits within the bone resulting in marrow inflammation. Bone marrow involvement is not readily visible using X-ray and ultrasound (US) and further testing is necessary. Magnetic resonance imaging (MRI) is a highly sensitive technique that can detect a focal bone T1 and T2-weighted hypointensity with bone marrow edema-like signal and cortical erosion. These findings can mislead the radiologist by suggesting an infectious or neoplastic lesion, often requiring further evaluation with computed tomography (CT) and biopsy. We report two cases of patients with shoulder pain in which different radiological approaches were used with pathological confirmation in one of them. In the first case, MRI revealed significant bone involvement in the head of the humerus and cortical erosion of the greater tuberosity. A CT examination and a biopsy was necessary for a final diagnosis of inflammatory bone reaction from intraosseous migration of tendinous calcifications. In the second case, similar MRI findings prompted re-evaluation of imaging to make a diagnosis of intraosseous migration of tendinous calcifications, obviating the need to perform CT and biopsy. We illustrate MRI signs of this complication that we think would allow to narrow the differential diagnosis potentially avoiding biopsy and additional CT examinations.


Asunto(s)
Calcinosis/diagnóstico por imagen , Manguito de los Rotadores/diagnóstico por imagen , Tendinopatía/diagnóstico por imagen , Adulto , Calcinosis/patología , Calcinosis/terapia , Tratamiento Conservador , Medios de Contraste , Diagnóstico Diferencial , Femenino , Humanos , Biopsia Guiada por Imagen , Imagen por Resonancia Magnética , Manguito de los Rotadores/patología , Tendinopatía/patología , Tendinopatía/terapia , Tomografía Computarizada por Rayos X , Ultrasonografía
11.
Chem Soc Rev ; 45(23): 6520-6545, 2016 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-27722570

RESUMEN

Molecular self-assembly has enabled the fabrication of biologically inspired, advanced nanostructures as lipid-based nanovesicles (L-NVs). The oldest L-NVs, liposomes, have been widely proposed as potential candidates for drug delivery, diagnostic and/or theranostic applications and some liposome-based drug products have already stepped from the lab-bench to the market. This success is attributed to their ability to encapsulate both hydrophobic and/or hydrophilic molecules, efficiently carry and protect them within the body and finally deliver them at the target site. These positive features are also coupled with high biocompatibility. However, liposomes still present some unsolved drawbacks, such as poor colloidal stability, short shelf-life, restricted and expensive conditions of preparation because of the inherent nature of their fundamental constituents (phospholipids). The new tools available in the self-assembly of controlled molecules have significantly advanced the field of L-NV design and synthesis, and non-liposomal L-NVs have been recently developed; this new generation of nanovesicles can represent a paradigm shift in nanomedicine: they may complement liposomes, showing their advantages and overcoming most of their drawbacks. Clearly, being still young, their rocky way to the clinic first and then to the market has just started and it is still long, but they have all the potentialities to reach their objective target. The purpose of this review is to first present the large plethora of L-NVs available, focusing on this new generation of non-liposomal L-NVs and showing their similarities and differences with respect to their ancestors (liposomes). Since the overspread of a nanomaterial to the market is also strongly dependent on the availability of technological-scale preparation methods, we will also extensively review the current approaches exploited for L-NV production. The most cutting-edge approaches based on compressed fluid (CF) technologies will be highlighted here since they show the potential to represent a game-change in the production of L-NVs, favouring their step from the bench to the market. Finally, we will briefly discuss L-NV applications in nanomedicine, looking also for their future perspectives.

12.
Memory ; 24(3): 295-305, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-25651475

RESUMEN

Some studies have reported a low rate of false recognition (FR) in individuals with autism spectrum disorder (ASD) relative to non-autistic comparison participants (CPs). This finding, however, has not always been replicated and the source of the discrepancy remains unknown. We hypothesised that poor episodic memory functions may account for this finding. We used an adapted version of the Deese, Roediger and McDermott paradigm which presents lists of words, pictures or word-picture pairs to obtain measures of performance which reflect episodic [hits and false alarms (FAs)] and semantic (FR) memory functions. Results showed a decreased rate of FR in ASD individuals with lists of words which rose above the rate seen in non-autistic CPs with lists of word-picture pairs. This increased rate of FR in ASD was accompanied by a parallel increase in hits and a decrease in FA which reached a similar level in the two groups. Poor episodic memory functions may prevent individuals with ASD from acquiring item information which in turn precludes the formation of semantic links between items. This could render them less prone to FR.


Asunto(s)
Trastorno del Espectro Autista/psicología , Memoria Episódica , Reconocimiento en Psicología/fisiología , Represión Psicológica , Adolescente , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Adulto Joven
13.
Environ Sci Pollut Res Int ; 22(24): 19786-92, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26282437

RESUMEN

In this study, monthly variations in biomass of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) were analysed over a 1-year period by fluorescence in situ hybridization (FISH) at the full-scale Fusina WWTP. The nitrification capacity of the plant was also monitored using periodic respirometric batch tests and by an automated on-line titrimetric instrument (TITrimetric Automated ANalyser). The percentage of nitrifying bacteria in the plant was the highest in summer and was in the range of 10-15 % of the active biomass. The maximum nitrosation rate varied in the range 2.0-4.0 mg NH4 g(-1) VSS h(-1) (0.048-0.096 kg TKN kg(-1) VSS day(-1)): values obtained by laboratory measurements and the on-line instrument were similar and significantly correlated. The activity measurements provided a valuable tool for estimating the maximum total Kjeldahl nitrogen (TKN) loading possible at the plant and provided an early warning of whether the TKN was approaching its limiting value. The FISH analysis permitted determination of the nitrifying biomass present. The main operational parameter affecting both the population dynamics and the maximum nitrosation activity was mixed liquor volatile suspended solids (MLVSS) concentration and was negatively correlated with ammonia-oxidizing bacteria (AOB) (p = 0.029) and (NOB) (p = 0.01) abundances and positively correlated with maximum nitrosation rates (p = 0.035). Increases in concentrations led to decreases in nitrifying bacteria abundance, but their nitrosation activity was higher. These results demonstrate the importance of MLVSS concentration as key factor in the development and activity of nitrifying communities in wastewater treatment plants (WWTPs). Operational data on VSS and sludge volume index (SVI) values are also presented on 11-year basis observations.


Asunto(s)
Betaproteobacteria/crecimiento & desarrollo , Nitritos/análisis , Nitrobacter/crecimiento & desarrollo , Aguas del Alcantarillado/microbiología , Aguas Residuales/microbiología , Purificación del Agua/métodos , Betaproteobacteria/genética , Biomasa , Hibridación Fluorescente in Situ , Italia , Nitrificación , Nitritos/metabolismo , Nitrobacter/genética , Planctomycetales/genética , Planctomycetales/crecimiento & desarrollo , Estaciones del Año , Verrucomicrobia/genética , Verrucomicrobia/crecimiento & desarrollo
14.
Q J Exp Psychol (Hove) ; 68(1): 75-82, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25017768

RESUMEN

Despite the growing interest in the ability of foreseeing (episodic future thinking), it is still unclear how healthy people construct possible future scenarios. We suggest that different future thoughts require different processes of scene construction. Thirty-five participants were asked to imagine desirable and less desirable future events. Imagining desirable events increased the ease of scene construction, the frequency of life scripts, the number of internal details, and the clarity of sensorial and spatial temporal information. The initial description of general personal knowledge lasted longer in undesirable than in desirable anticipations. Finally, participants were more prone to explicitly indicate autobiographical memory as the main source of their simulations of undesirable episodes, whereas they equally related the simulations of desirable events to autobiographical events or semantic knowledge. These findings show that desirable and undesirable scenarios call for different mechanisms of scene construction. The present study emphasizes that future thinking cannot be considered as a monolithic entity.


Asunto(s)
Imaginación , Memoria Episódica , Motivación/fisiología , Pensamiento/fisiología , Adolescente , Ansiedad/psicología , Femenino , Humanos , Modelos Lineales , Masculino , Pruebas Neuropsicológicas , Estimulación Luminosa , Escalas de Valoración Psiquiátrica , Factores de Tiempo , Adulto Joven
15.
Br J Surg ; 101(11): 1460-7, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25139143

RESUMEN

BACKGROUND: Complete mesocolic excision with central vascular ligation (CME) produces an optimal colonic cancer specimen. The ability of expert laparoscopic surgeons to produce equivalent specimens is unknown. METHODS: Fresh specimen photographs and clinicopathological data from patients undergoing laparoscopically assisted CME at St Mark's Hospital, Harrow, were submitted for independent pathological review. Surgery was performed by a mixture of consultant specialists and trainees under consultant specialist supervision, between February 2010 and July 2011. The planes of surgery were graded and tissue morphometry was performed using standard methods. The results were compared with published data from open CME and non-CME surgery. RESULTS: In total, 69 patients were identified, and in 96 per cent resection was performed completely or partially by surgical trainees. Laparoscopic CME produced a similar specimen to open CME. The laparoscopic mesocolic plane resection rate was similar to that for open surgery (90 versus 88 per cent). The distance between the bowel wall and site of vascular division was similar for laparoscopic and open right-sided CME (92 versus 95 mm respectively). The corresponding values for left-sided CME were also similar (103 versus 107 mm). Compared with values from two non-CME series, laparoscopic CME had a higher mesocolic plane rate (90 versus 40 and 48 per cent), and resected more tissue between the bowel wall and the vascular division (right-sided: 92 versus 72 and 76 mm; left-sided: 103 versus 85 and 70 mm). The lymph node yield remained low following laparoscopic CME compared with open CME (median 18 versus 32; P < 0·001) and identical to that of non-CME surgery (median 18). CONCLUSION: Laparoscopic CME can be performed to the same standard as open surgery by supervised trainees. However, this did not increase the lymph node yield.


Asunto(s)
Colectomía/normas , Neoplasias del Colon/cirugía , Laparoscopía/normas , Escisión del Ganglio Linfático/normas , Anciano , Anciano de 80 o más Años , Colectomía/métodos , Neoplasias del Colon/patología , Cirugía Colorrectal/educación , Femenino , Humanos , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Masculino , Persona de Mediana Edad , Clasificación del Tumor/normas , Fotograbar , Manejo de Especímenes
16.
J Gastrointest Surg ; 17(11): 1960-5, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24002754

RESUMEN

INTRODUCTION: Surgery is the mainstay of treatment of anal fistulas. Low fistulas are often laid open, but higher fistulas present a more difficult problem. Patient choice centres on a compromise between risk of recurrence and risk of impairment of continence. We aimed to determine the efficacy and safety of fistulotomy at a tertiary referral centre, in particular the additional risk of impairment of continence following fistulotomy of the often recurrent, multiply-operated patients seen. METHODS: Patients undergoing surgery under the senior author (RKSP) for an anal fistula during the study period (2005-2006) were identified, and a thorough review of the patients' clinical records was undertaken. Demographic, fistula anatomy, treatment and follow-up data were obtained. RESULTS: Eighty-four patients underwent either fistulotomy (50), insertion of permanent loose (drainage) seton (28) or EUA with or without drainage of abscess. Mean length of follow up was 11 months (SD 14.22). In the fistulotomy group, we found an overall success rate of 93 %. Secondary extensions were associated with failure to achieve cure (P = 0.008). Nine patients (20 %) suffered deterioration in continence after surgery. A longer time to referral was associated with impaired final continence. In the group referred from a surgeon in secondary care, 91 % of patients were cured, and continence impairment (mostly minor) rose from 32 % at referral to 40 % after surgery. CONCLUSIONS: We have shown that it is safe and reasonable to offer fistulotomy to appropriate patients despite previous surgery and within the tertiary setting. By so doing, a very high rate of healing can be achieved in patients who have previously failed. The additional risk of impairment of continence is around one in five, and in the majority will represent only minor incontinence.


Asunto(s)
Incontinencia Fecal/etiología , Complicaciones Posoperatorias , Fístula Rectal/cirugía , Adolescente , Adulto , Anciano , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Masculino , Persona de Mediana Edad , Fístula Rectal/patología , Recurrencia , Derivación y Consulta , Medición de Riesgo , Centros de Atención Terciaria , Factores de Tiempo , Adulto Joven
17.
Br J Surg ; 100(3): 330-8, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23300071

RESUMEN

BACKGROUND: Percutaneous, transcutaneous and sham transcutaneous posterior tibial nerve stimulation was compared in a prospective blinded randomized placebo-controlled trial. METHODS: Patients who had failed conservative treatment for faecal incontinence were randomized to one of three groups: group 1, percutaneous; group 2, transcutaneous; group 3, sham transcutaneous. Patients in groups 1 and 2 received 30-min sessions of posterior tibial nerve stimulation twice weekly for 6 weeks. In group 3, transcutaneous electrodes were placed in position but no stimulation was delivered. Symptoms were measured at baseline and after 6 weeks using a bowel habit diary and St Mark's continence score. Response to treatment was defined as a reduction of at least 50 per cent in weekly episodes of faecal incontinence compared with baseline. RESULTS: Thirty patients (28 women) were enrolled. Nine of 11 patients in group 1, five of 11 in group 2 and one of eight in group 3 had a reduction of at least 50 per cent in weekly episodes of faecal incontinence at the end of the 6-week study phase (P = 0·035). Patients undergoing percutaneous nerve stimulation had a greater reduction in the number of incontinence episodes and were able to defer defaecation for a longer interval than those undergoing transcutaneous and sham stimulation. These improvements were maintained over a 6-month follow-up period. CONCLUSION: Posterior tibial nerve stimulation has short-term benefits in treating faecal incontinence. Percutaneous therapy appears to have superior efficacy to stimulation applied by the transcutaneous route. REGISTRATION NUMBER: NCT00530933 (http://www.clinicaltrials.gov).


Asunto(s)
Incontinencia Fecal/terapia , Nervio Tibial , Estimulación Eléctrica Transcutánea del Nervio/métodos , Canal Anal/fisiología , Análisis de Varianza , Incontinencia Fecal/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Presión , Estudios Prospectivos , Calidad de Vida , Recto/fisiología , Método Simple Ciego , Estimulación Eléctrica Transcutánea del Nervio/efectos adversos , Resultado del Tratamiento
18.
Phys Rev Lett ; 110(20): 203202, 2013 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-25167405

RESUMEN

We perform a theoretical and experimental study of a system of two ultracold atoms with tunable interaction in an elongated trapping potential. We show that the coupling of center-of-mass and relative motion due to an anharmonicity of the trapping potential leads to a coherent coupling of a state of an unbound atom pair and a molecule with a center of mass excitation. By performing the experiment with exactly two particles we exclude three-body losses and can therefore directly observe coherent molecule formation. We find quantitative agreement between our theory of inelastic confinement-induced resonances and the experimental results. This shows that the effects of center-of-mass to relative-motion coupling can have a significant impact on the physics of quantum systems near center-of-mass to relative-motion coupling resonances.

19.
Blood Cells Mol Dis ; 49(3-4): 140-6, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22664374

RESUMEN

Dyskeratosis congenita (DC) is a rare inherited bone-marrow failure syndrome with high clinical heterogeneity. Cells derived from DC patients present short telomeres at early ages, as a result of mutations in genes encoding components of the telomerase complex (DKC1, TERC, TERT, NHP2 and NOP10), or the shelterin complex (TINF2). However, mutations have been identified only in around 50% of the cases, indicating that other genes could be involved in the development of this disease. Indeed, mutations in TCBA1 or chromosome segment C16orf57 have been described recently. We have used HRM technology to perform genetic analysis in the above mentioned genes, in Spanish patients showing both, some clinical features of DC and short telomeres. The mutations have been identified by PCR amplification of DC genes followed by high resolution melting (HRM) and direct DNA sequencing analysis. We have identified seven new families with DC, three with X-linked DC and four with autosomal dominant DC, in which we have found two novel mutations in DKC1 (p.His68Arg and p.Lys390del) and four novel mutations in TERT gene (p.Pro530Leu, p.Arg698Trp, p.Arg971His and p.Arg698Gln). The results show that the use of HRM analysis enables a rapid and inexpensive identification of mutations in dyskeratosis congenita associated genes.


Asunto(s)
Proteínas de Ciclo Celular/genética , Disqueratosis Congénita/genética , Proteínas Nucleares/genética , Análisis de Secuencia de ADN/métodos , Telomerasa/genética , Adolescente , Adulto , Médula Ósea/metabolismo , Médula Ósea/patología , Niño , Preescolar , Disqueratosis Congénita/diagnóstico , Disqueratosis Congénita/patología , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Mutación , Desnaturalización de Ácido Nucleico , Reacción en Cadena de la Polimerasa , Telómero/patología , Población Blanca
20.
Neurology ; 78(13): 969-75, 2012 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-22377806

RESUMEN

OBJECTIVE: To assess the correlation between cognitive impairment and overall vs regional CNS damage, quantified using conventional and diffusion tensor (DT) MRI tractography in multiple sclerosis (MS). METHODS: Brain dual-echo, T1-weighted, and DT MRI data were acquired from 82 patients with MS. DT tractography was used to produce maps of white matter (WM) tracts involved in cognition. The sensory thalamocortical projections and optic radiations were studied as "control" WM tracts. The contribution of global brain damage (T2 lesion volume, normalized brain volume, gray matter [GM] volume, WM volume, DT MRI measures of normal-appearing WM and GM damage) and damage to selected WM tracts to overall cognitive impairment and to impairment at individual neuropsychological tests was assessed using a random forest (RF) analysis. RESULTS: Thirty-three patients had cognitive impairment. The majority of MRI measures differed significantly between cognitively impaired and cognitively preserved (CP) patients. Significant correlations were found between performance in the majority of neuropsychological tests and global or regional brain damage (r ranging from -0.60 to 0.57). The RF analysis showed a high performance in classifying cognitively impaired vs CP patients, with a classification (C)-index = 76.8, as well as in classifying patients' impairment in individual neuropsychological tests (C-index between 75.6% and 86.6%). Measures of lesional damage in cognitive-related tracts, rather than measures of normal-appearing WM damage in the same tracts or global brain/WM/GM damage, resulted in the highest classification accuracy. CONCLUSIONS: Lesions in strategic brain WM tracts contribute to cognitive impairment in MS through a multisystem disconnection syndrome.


Asunto(s)
Encéfalo/patología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Imagen de Difusión Tensora , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/epidemiología , Adulto , Trastornos del Conocimiento/psicología , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/psicología , Pruebas Neuropsicológicas , Síndrome , Adulto Joven
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