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1.
Rev Esp Quimioter ; 36(5): 526-530, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37365797

ABSTRACT

OBJECTIVE: Letermovir (LMV) is used for prophylaxis of cytomegalovirus (CMV) reactivation and end-organ disease in adult CMV-seropositive allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). In turn, sirolimus (SLM) which displays in vitro anti-CMV activity, is frequently employed for prophylaxis of Graft vs. Host disease in allo-HSCT. Here, we aimed at assessing whether LMV and SLM used in combination may act synergistically in vitro on inhibiting CMV replication. METHODS: The antiviral activity of LMV and SLM alone or in combination was evaluated by a checkerboard assay, using ARPE-19 cells infected with CMV strain BADrUL131-Y. LMV and SLM were used at concentrations ranging from 24 nM to 0.38 nM and 16 nM to 0.06 nM, respectively. RESULTS: The mean EC50 for LMV and SLM was 2.44 nM (95% CI, 1.66-3.60) and 1.40 nM (95% CI, 0.41-4.74), respective. LMV and SLM interaction yielded mainly additive effects over the range of concentrations tested. CONCLUSIONS: The additive nature of the combination of LMV and SLM against CMV may have relevant clinical implications in management of CMV infection in allo-HSCT recipients undergoing prophylaxis with LMV.


Subject(s)
Cytomegalovirus Infections , Hematopoietic Stem Cell Transplantation , Adult , Humans , Cytomegalovirus , Sirolimus/pharmacology , Sirolimus/therapeutic use , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/prevention & control , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use
2.
Int Endod J ; 53(8): 1131-1139, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32294253

ABSTRACT

AIM: To evaluate the effect of the addition of surfactants to sodium hypochlorite (NaOCl) on the removal of accumulated hard tissue debris (AHTD), before and after final irrigation with 17% EDTA, from mesial canals of mandibular molars through microcomputed tomographic (micro-CT) analysis. METHODOLOGY: Thirty moderately curved mandibular mesial roots with Vertucci type II canal configuration were selected and scanned in a micro-CT device at an isotropic resolution of 22.9 µm. The specimens were assigned to three groups (n = 10) with respect to the root length, degree of curvature of the mesial root, volume and 3D anatomy of the root canals according to the irrigating solution used during root canal preparation: 2.5% NaOCl and 0.1% Benzalkonium Chloride, 2.5% NaOCl and 0.1% Tween 80 and 2.5% NaOCl without additives. The root canals were instrumented up to Reciproc R25 instrument. Then, the specimens were scanned again after canal preparation and after final irrigation with 17% EDTA, and the registered data sets were examined to evaluate the percentage of AHTD. For comparison between the different groups before and after using 17% EDTA, the Kruskal-Wallis test was used with a significance level of 5%. For comparison between the same groups before and after using 17% EDTA, the Wilcoxon test was used with a significance level of 5%. RESULTS: None of the irrigant solutions tested was able to completely eliminate hard tissue debris from mesial canals of mandibular molars. There were no significant differences in the percentage of AHTD amongst the different irrigation solutions (P > 0.05). Final irrigation with 17% EDTA significantly reduced the percentage of AHTD (P < 0.05), without differences amongst the groups (P > 0.05). CONCLUSIONS: The addition of surfactants to NaOCl did not affect the removal of AHTD from mesial canals of extracted mandibular molars. Final irrigation with 17% EDTA significantly improved AHTD removal.


Subject(s)
Root Canal Irrigants , Sodium Hypochlorite , Dental Pulp Cavity , Edetic Acid , Root Canal Preparation , Surface-Active Agents , Therapeutic Irrigation
4.
Case Rep Hematol ; 2017: 3724017, 2017.
Article in English | MEDLINE | ID: mdl-29163992

ABSTRACT

BACKGROUND: Aggressive natural killer cell leukemia (ANKL) is extremely rare and habitually manifests as a systemic disease with multiorgan failure that rapidly evolves to death. The neoplastic natural killer (NK) cells usually harbor the Epstein-Barr virus (EBV) with a latent viral infection pattern type II; they often have a cytoplasmic CD3ε+ and surface CD3-, CD2+, and CD56+ immunophenotype, and they show complex genetic abnormalities affecting multiple tumor suppressor genes and oncogenes. We present a rare case of CD56-negative ANKL and review the clinical and laboratorial criteria for the diagnosis, as well as the available therapies. CASE PRESENTATION: A European 36-year-old male presented with acute onset fever, pallor, weakness, and jaundice. He had hepatosplenomegaly, severe pancytopenia, hepatic cytolysis, and very high serum lactic dehydrogenase levels. The bone marrow studies resulted in the diagnosis of an EBV-positive, CD56-negative ANKL. The patient failed to respond to gemcitabine and cisplatin-based polychemotherapy, dying three months later with leukemic meningitis and multiple cranial nerves palsies. CONCLUSIONS: The diagnosis of ANKL is difficult and requires both clinical suspicion and an extensive laboratorial approach. Absence of CD56 expression on the neoplastic NK cells may impose difficulties in the diagnosis, which requires morphological, immunophenotypic, histopathological, immunohistochemical, cytogenetic, and molecular studies.

5.
Biotechnol Bioeng ; 113(1): 150-62, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26134455

ABSTRACT

Many mammalian cell lines used in the manufacturing of biopharmaceuticals exhibit high glycolytic flux predominantly channeled to the production of lactate. The accumulation of lactate in culture reduces cell viability and may also decrease product quality. In this work, we engineered a HEK 293 derived cell line producing a recombinant gene therapy retroviral vector, by down-regulating hypoxia inducible factor 1 (HIF1) and pyruvate dehydrogenase kinase (PDK). Specific productivity of infectious viral titers could be increased more than 20-fold for single gene knock-down (HIF1 or PDK) and more than 30-fold under combined down-regulation. Lactate production was reduced up to 4-fold. However, the reduction in lactate production, alone, was not sufficient to enhance the titer: high-titer clones also showed significant enrollment of metabolic routes not related to lactate production. Transcriptome analysis indicated activation of biological amines metabolism, detoxification routes, including glutathione metabolism, pentose phosphate pathway, glycogen biosynthesis and amino acid catabolism. The latter were validated by enzyme activity assays and metabolite profiling, respectively. High-titer clones also presented substantially increased transcript levels of the viral genes expression cassettes. The results herein presented demonstrate the impact of HIF1 and PDK down-regulation on the production performance of a mammalian cell line, reporting one of the highest fold-increase in specific productivity of infectious virus titers achieved by metabolic engineering. They additionally highlight the contribution of secondary pathways, beyond those related to lactate production, that can be also explored to pursue improved metabolic status favoring a high-producing phenotype.


Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis , Lactic Acid/metabolism , Protein Serine-Threonine Kinases/biosynthesis , Retroviridae/growth & development , Viral Load , Virus Cultivation/methods , Cell Line , Down-Regulation , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Protein Serine-Threonine Kinases/genetics , Pyruvate Dehydrogenase Acetyl-Transferring Kinase
6.
Gene Ther ; 22(9): 685-95, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25938191

ABSTRACT

This article describes a novel method merging the cloning of viral vector producer cells with vector titer screening, allowing for screening 200-500 clones in 2 weeks. It makes use of a GFP separated into two fragments, S10 and S11 (Split GFP), fluorescing only upon transcomplementation. Producer cells carrying a S11 viral transgene are cloned in 96-well plates and co-cultured with target cells stably expressing S10. During the period of clone expansion, S11 viruses infect S10 target cells reconstituting the GFP signal. Transcomplemented fluorescence data provide direct estimation of the clone's productivity and can be analyzed in terms of density distribution, offering valuable information on the average productivity of the cell population and allowing the identification of high-producing clones. The method was validated by establishing a retrovirus producer from a nude cell line, in <3 months, inserting three vector constructs without clone selection or screening in between. Clones producing up to 10(8) infectious particles per ml were obtained, delivering optimal ratios of infectious-to-total particles (1 to 5). The method was additionally used to evaluate the production performance of HEK 293 and HEK 293T cell lines demonstrating that the latter sustains increased titers. Finally, it was used to study genetic manipulation of glutathione metabolism in retrovirus production showing that changing cell metabolism steers higher vector expression with titer increases of more than one order of magnitude.This method is a valuable tool not only for cell line development but also for genetic manipulation of viral vector and/or producer cells contributing to advancing the field of viral gene therapy.


Subject(s)
Cloning, Molecular/methods , Genetic Testing/methods , Retroviridae/metabolism , Cell Line , Genetic Therapy/methods , Genetic Vectors , Humans , Retroviridae/genetics , Transduction, Genetic
7.
Arq. bras. med. vet. zootec ; 67(2): 535-546, Mar-Apr/2015. tab
Article in English | LILACS, VETINDEX | ID: lil-747057

ABSTRACT

The aim of this work was to evaluate the effects of adding different levels of glycerin in the feeding on the lipid profile and cholesterol of the meat of finishing pigs. The experiment was arranged in a completely randomized design (CRD) with factorial 5x2, being five levels of glycerin in the diet and two genders. Sixty (60) swine of the Topigs genetics (30 barrows and 30 gilts) were used; they presented initial average weight of 79.3+4.0kg and were finished with the weight of 106.2+4.5kg. The levels of glycerin utilized were 0, 50, 100, 150 and 200g/kg in the natural matter. The analyses of lipid and cholesterol profile were conducted in the muscles longissimus dorsi (loin) andsemimembranosus (ham) on the left side of the carcasses. Interaction occurred between the levels of crude glycerin in the diet and the sexual category for the profile of fatty acids and cholesterol. On the loin the meat of the barrows presented higher means of C16:0, C16:1, C20:3ω3, C18:1ω9c, Total of saturated (SFA) and monounsaturated (MUFA) fatty acids. On the ham, increased means were found for the fatty acids C18:1ω9c, MUFA, activity of ∆9-desaturaseC18 and ElongaseC16-18 in barrows. The sows' meat presented higher proportions of polyunsaturated fatty acids and of the series ω6 for both the cuts. The amount of cholesterol in the sows' meat presented increase according to the level of glycerin in the meat. The barrows' meat presented indices of atherogenicity greater than the gilts. The levels of glycerin altered the lipid profile and cholesterol content according to the sexual category, promoting a distinct effect on the loin and ham.(AU)


O objetivo deste trabalho foi avaliar os efeitos do fornecimento de diferentes níveis de glicerina na alimentação sobre o perfil lipídico e colesterol da carne de suínos em terminação. O delineamento experimental foi organizado inteiramente ao acaso (DIC), com fatorial 5x2, sendo: cinco níveis de glicerina na dieta e dois sexos. Foram utilizados 60 suínos da genética Topigs (30 machos castrados e 30 fêmeas), apresentando peso médio inicial de 79,3+4,0kg, e foram terminados com peso de 106,2+4,5kg. Os níveis de glicerina utilizados foram de 0, 50, 100, 150 e 200g/kg na matéria natural. As análises de perfil lipídico e de colesterol foram realizadas nos músculos longissimus dorsi (lombo) e semimembranosus (pernil) do lado esquerdo das carcaças. Ocorreu interação entre os níveis de glicerina bruta na dieta e a categoria sexual para o perfil de ácidos graxos e colesterol. A carne dos machos castrados apresentou no lombo maiores médias de C16:0, C16:1, C20:3ω3, C18:1ω9c, Total de ácidos graxos Saturados (SFA) e Monoinsaturados (MUFA). No pernil, maiores médias foram verificadas para os ácidos graxos C18:1ω9c, MUFA, atividade da ∆9-desaturaseC18 e ElongaseC16-C18 em machos castrados. A carne das fêmeas suínas apresentou maiores proporções de ácidos graxos poli-insaturados e da série ω6 para ambos os cortes. A quantidade de colesterol na carne das fêmeas suínas apresentou aumento em função do nível de glicerina na dieta. A carne dos machos castrados apresentou maiores índices de aterogenicidade que das fêmeas. Os níveis de glicerina alteraram o perfil lipídico e teor de colesterol em função da categoria sexual, promovendo efeito diferenciado no lombo e pernil.(AU)


Subject(s)
Animals , Swine , Cholesterol , Glycerol/administration & dosage , Lipids , Animal Feed , Meat/analysis
8.
Biomed Res Int ; 2015: 256340, 2015.
Article in English | MEDLINE | ID: mdl-25685775

ABSTRACT

The aim of this research was to analyze temporal auditory processing and phonological awareness in school-age children with benign childhood epilepsy with centrotemporal spikes (BECTS). Patient group (GI) consisted of 13 children diagnosed with BECTS. Control group (GII) consisted of 17 healthy children. After neurological and peripheral audiological assessment, children underwent a behavioral auditory evaluation and phonological awareness assessment. The procedures applied were: Gaps-in-Noise test (GIN), Duration Pattern test, and Phonological Awareness test (PCF). Results were compared between the groups and a correlation analysis was performed between temporal tasks and phonological awareness performance. GII performed significantly better than the children with BECTS (GI) in both GIN and Duration Pattern test (P < 0.001). GI performed significantly worse in all of the 4 categories of phonological awareness assessed: syllabic (P = 0.001), phonemic (P = 0.006), rhyme (P = 0.015) and alliteration (P = 0.010). Statistical analysis showed a significant positive correlation between the phonological awareness assessment and Duration Pattern test (P < 0.001). From the analysis of the results, it was concluded that children with BECTS may have difficulties in temporal resolution, temporal ordering, and phonological awareness skills. A correlation was observed between auditory temporal processing and phonological awareness in the suited sample.


Subject(s)
Auditory Perception , Awareness , Epilepsy, Rolandic/physiopathology , Adolescent , Child , Cross-Sectional Studies , Female , Humans , Male , Prospective Studies
9.
Persoonia ; 35: 242-63, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26823635

ABSTRACT

The aim of this study was to assess potential candidate gene regions and corresponding universal primer pairs as secondary DNA barcodes for the fungal kingdom, additional to ITS rDNA as primary barcode. Amplification efficiencies of 14 (partially) universal primer pairs targeting eight genetic markers were tested across > 1 500 species (1 931 strains or specimens) and the outcomes of almost twenty thousand (19 577) polymerase chain reactions were evaluated. We tested several well-known primer pairs that amplify: i) sections of the nuclear ribosomal RNA gene large subunit (D1-D2 domains of 26/28S); ii) the complete internal transcribed spacer region (ITS1/2); iii) partial ß -tubulin II (TUB2); iv) γ-actin (ACT); v) translation elongation factor 1-α (TEF1α); and vi) the second largest subunit of RNA-polymerase II (partial RPB2, section 5-6). Their PCR efficiencies were compared with novel candidate primers corresponding to: i) the fungal-specific translation elongation factor 3 (TEF3); ii) a small ribosomal protein necessary for t-RNA docking; iii) the 60S L10 (L1) RP; iv) DNA topoisomerase I (TOPI); v) phosphoglycerate kinase (PGK); vi) hypothetical protein LNS2; and vii) alternative sections of TEF1α. Results showed that several gene sections are accessible to universal primers (or primers universal for phyla) yielding a single PCR-product. Barcode gap and multi-dimensional scaling analyses revealed that some of the tested candidate markers have universal properties providing adequate infra- and inter-specific variation that make them attractive barcodes for species identification. Among these gene sections, a novel high fidelity primer pair for TEF1α, already widely used as a phylogenetic marker in mycology, has potential as a supplementary DNA barcode with superior resolution to ITS. Both TOPI and PGK show promise for the Ascomycota, while TOPI and LNS2 are attractive for the Pucciniomycotina, for which universal primers for ribosomal subunits often fail.

10.
Gene Ther ; 22(1): 40-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25338917

ABSTRACT

Helper-dependent adenovirus vectors (HDVs) are safe and efficient tools for gene transfer with high cloning capacity. However, the multiple amplification steps needed to produce HDVs hamper a robust production process and in turn the availability of high-quality vectors. To understand the factors behind the low productivity, we analyzed the progression of HDV life cycle. Canine adenovirus (Ad) type 2 vectors, holding attractive features to overcome immunogenic concerns and treat neurobiological disorders, were the focus of this work. When compared with E1-deleted (ΔE1) vectors, we found a faster helper genome replication during HDV production. This was consistent with an upregulation of the Ad polymerase and pre-terminal protein and led to higher and earlier expression of structural proteins. Although genome packaging occurred similarly to ΔE1 vectors, more immature capsids were obtained during HDV production, which led to a ~4-fold increase in physical-to-infectious particles ratio. The higher viral protein content in HDV-producing cells was also consistent with an increased activation of autophagy and cell death, in which earlier cell death compromised volumetric productivity. The increased empty capsids and earlier cell death found in HDV production may partially contribute to the lower vector infectivity. However, an HDV-specific factor responsible for a defective maturation process should be also involved to fully explain the low infectious titers. This study showed how a deregulated Ad cycle progression affected cell line homeostasis and HDV propagation, highlighting the impact of vector genome design on virus-cell interaction.


Subject(s)
Adenoviruses, Canine/genetics , Virus Replication , Adenoviruses, Canine/physiology , Animals , Autophagy , Cell Survival , DNA Replication , Dogs , Genetic Therapy , Genetic Vectors , Genome, Viral , Madin Darby Canine Kidney Cells , Transduction, Genetic
11.
Neurología (Barc., Ed. impr.) ; 28(8): 477-487, oct. 2013. ilus, graf
Article in Spanish | IBECS | ID: ibc-116297

ABSTRACT

Introducción: Estamos asistiendo a un cambio en el paradigma del diagnóstico de la enfermedad de Alzheimer (EA), de modo que tiende a realizarse en fases más precoces de la evolución, incluso antes de la aparición del síndrome completo de demencia. En nuestro entorno no se conoce en qué situación clínica se está realizando el diagnóstico de la EA. Por ese motivo, se ha llevado a cabo este estudio, para describir el estadio evolutivo de los pacientes con EA en el momento del diagnóstico. Métodos: Estudio multicéntrico, observacional y transversal. Se incluyeron pacientes que cumplían criterios NINCDS-ARDRA de EA probable, atendidos en consultas de Atención Especializada en España. Se recogieron los datos sobre los tiempos asistenciales y de evolución de la EA según el MMSE, el cuestionario NPI y la escala CDR. Resultados: Participaron 437 especialistas de todas las Comunidades Autónomas, que incluyeron un total de 1.707 pacientes, de los cuales 1.694 fueron incluidos en el análisis. La puntuación media del MMSE fue de 17,6±4,8 (IC 95%: 17,4-17,9). El 64% de los pacientes presentaban deterioro cognitivo moderado (MMSE entre 10 y 20) y el 6% grave (MMSE < 10). El tiempo medio desde los primeros síntomas hasta la primera consulta a Atención Primaria fue de 10,9±17,2 meses (IC 95%: 9,9-11,8), y hasta el diagnóstico de la EA fue de 28,4±21,3 meses. Conclusiones: Los resultados del EACE ponen de manifiesto que en nuestro entorno la mayor parte de los pacientes con EA acuden a Atención especializada en un estado evolutivo moderado (AU)


Introduction: The diagnostic paradigm of Alzheimer disease (AD) is changing; there is a trend toward diagnosing the disease in its early stages, even before the complete syndrome of dementia is apparent. The clinical stage at which AD is usually diagnosed in our area is unknown. Therefore, the purpose of this study is to describe the clinical stages of AD patients at time of diagnosis. Methods: Multicentre, observational and cross-sectional study. Patients with probable AD according to NINCDS-ARDRA criteria, attended in specialist clinics in Spain, were included in the study. We recorded the symptom onset to evaluation and symptom onset to diagnosis intervals and clinical status of AD (based on MMSE, NPI questionnaire, and CDR scale). Results: Participants in this study included 437 specialists representing all of Spain’s autonomous communities and a total of 1,707 patients, of whom 1,694 were included in the analysis. Mean MMSE score was 17.6±4.8 (95% CI: 17.4-17.9). Moderate cognitive impairment (MMSE between 10 and 20) was detected in 64% of the patients, and severe cognitive impairment (MMSE<10) in 6%. The mean interval between symptom onset and the initial primary care visit was 10.9±17.2 months (95% CI: 9.9-11.8), and the interval between symptom onset and diagnosis with AD was 28.4±21.3 months. Conclusions: Results from the EACE show that most AD patients in our are area have reached a moderate clinical stage by the time they are evaluated in a specialist clinic (AU)


Subject(s)
Humans , Alzheimer Disease/epidemiology , Cognition Disorders/epidemiology , Disease Progression , Cross-Sectional Studies
12.
J Anim Sci ; 91(4): 1775-83, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23345561

ABSTRACT

The effects of rumen digesta volume and pH on VFA absorption and its relation to rumen wall morphology were evaluated. Nine rumen cannulated cows formed 3 groups based on desired variation in rumen morphology: The High group was formed by Holsteins yielding 25.9 kg milk/d and fed on a high-grain total mixed ration (TMR); the Medium group by Holstein-Zebu crossbreds yielding 12.3 kg milk/d and fed on corn silage, tropical pasture, and a commercial concentrate; and the Dry group by nonlactating grazing Jerseys fed exclusively on tropical pasture. Within each group, a sequence of 3 ruminal conditions was induced on each cow in 3 × 3 Latin Squares, with 7-d periods: high digesta volume and high pH (HVHP), low volume and high pH (LVHP), and low volume and low pH (LVLP). Rumen mucosa was biopsied on the first day of Period 1. Ruminal morphometric variables evaluated were mitotic index, absorptive surface and papillae number per square centimeter of wall, area per papillae, papillae area as a percentage of absorptive surface, and epithelium, keratinized layer, and nonkeratinized layer thickness. There was marked variation in rumen morphology among the groups of cows. Grazing Jerseys had decreased rumen wall absorptive surface area and basal cells mitotic index, and increased thickness of the epithelium and of the keratin layer compared with cows receiving concentrates. Mean rumen pH throughout the 4 h sampling period was: 6.78 for HVHP, 7.08 for LVHP, and 5.90 for LVLP (P < 0.01). The capacity of the rumen wall to absorb VFA was estimated by the Valerate/CrEDTA technique. The fractional exponential decay rate for the ratio of valeric acid to Cr (k Val/Cr) was determined by rumen digesta sampling at 20-min intervals during 4 h, after the mixing of markers and the return of the evacuated ruminal content. The k Val/Cr values for treatments HVHP, LVHP, and LVLP were, respectively: 19.6, 23.9, and 35.0 %/h (SEM = 2.01; P = 0.21 for contrast HVHP vs. LVHP and P < 0.01 for contrast LVHP vs. LVLP). The k Val/Cr was faster under low pH, but decreasing digesta volume under high pH did not elicit such a response. The correlation between the absorptive surface area per square centimeter of rumen wall and the mean of the 3 k Val/Cr values of each cow was 0.90 (P < 0.01). Cows capable of maintaining a less-acidic rumen environment had greater inflow of water into the digestive cavity, had a more developed rumen mucosa, and were more efficient VFA absorbers.


Subject(s)
Fatty Acids, Volatile/metabolism , Rumen/anatomy & histology , Absorption , Animal Feed , Animal Nutritional Physiological Phenomena/physiology , Animals , Cattle , Diet/veterinary , Female , Gastrointestinal Contents/chemistry , Hydrogen-Ion Concentration , Organ Size/physiology , Rumen/physiology
13.
Neurologia ; 28(8): 477-87, 2013 Oct.
Article in Spanish | MEDLINE | ID: mdl-23246220

ABSTRACT

INTRODUCTION: The diagnostic paradigm of Alzheimer disease (AD) is changing; there is a trend toward diagnosing the disease in its early stages, even before the complete syndrome of dementia is apparent. The clinical stage at which AD is usually diagnosed in our area is unknown. Therefore, the purpose of this study is to describe the clinical stages of AD patients at time of diagnosis. METHODS: Multicentre, observational and cross-sectional study. Patients with probable AD according to NINCDS-ARDRA criteria, attended in specialist clinics in Spain, were included in the study. We recorded the symptom onset to evaluation and symptom onset to diagnosis intervals and clinical status of AD (based on MMSE, NPI questionnaire, and CDR scale). RESULTS: Participants in this study included 437 specialists representing all of Spain's autonomous communities and a total of 1,707 patients, of whom 1,694 were included in the analysis. Mean MMSE score was 17.6±4.8 (95% CI:17.4-17.9). Moderate cognitive impairment (MMSE between 10 and 20) was detected in 64% of the patients, and severe cognitive impairment (MMSE<10) in 6%. The mean interval between symptom onset and the initial primary care visit was 10.9±17.2 months (95% CI:9.9-11.8), and the interval between symptom onset and diagnosis with AD was 28.4±21.3 months. CONCLUSIONS: Results from the EACE show that most AD patients in our area have reached a moderate clinical stage by the time they are evaluated in a specialist clinic.


Subject(s)
Alzheimer Disease/epidemiology , Alzheimer Disease/psychology , Aged , Aged, 80 and over , Alzheimer Disease/therapy , Cross-Sectional Studies , Disease Progression , Female , Humans , Male , Primary Health Care/statistics & numerical data , Psychiatric Status Rating Scales , Socioeconomic Factors , Spain/epidemiology
14.
Enferm. glob ; 11(25): 59-74, ene. 2012.
Article in Spanish | IBECS | ID: ibc-100455

ABSTRACT

Introducción: El dolor forma parte de la condición humana y es inalienable de su existencia. Es entendido como una experiencia universal con inicio precoz en cada individuo y gana heterogeneidad de configuraciones sociales y variabilidad de grados de intensidad. Como experiencia intransmisible, marcará, de diversas formas, la construcción psicológica y social de la persona. En el niño es una experiencia común y perturbadora, muchas veces subestimada y subintervencionada en contextos de salud. Metodología: Con este estudio exploratorio de naturaleza mixta, basado en la teoría de las representaciones sociales, pretendemos dar voz a los niños sometidos a punción venosa. Los objetivos de este trabajo son identificar las representaciones asociadas a la experiencia de punción venosa y evaluar el grado de dolor asociado a esta experiencia, en niños en edad escolar. Se aplicó la asociación libre de palabras con dos cuestiones estímulo: «El dolor me hece pensar en…», «El pinchazo de la aguja me hace sentir…» y la escala numérica de evaluación del dolor, a 43 niños con edades comprendidas entre 6 y 12 años ingresados en un hospital de la Sub-región de Salud de Lisboa. Los datos se analizaron con recurso del software SPAD-T (análisis factorial de correspondencias simples) y SPSS (estadística descrpitiva). Resultados: Los datos obtenidos permiten decir que los niños que participaron en este estudio consideraron que el dolor funciona como factor desencadenante de sufrimiento y está asociado a manifestaciones físicas como el llanto y a sentimentos expresados ante el dolor, como el miedo y la ansiedad. El grado de dolor está asociado a la punción venosa y presenta variabilidad con factores como la edad y las experiencias anteriores. Conclusión: La punción venosa es un procedimiento doloroso y, según los niños que participaron en el estudio, provoca miedo y ansiedad. Sin embargo, muchos evitaron tener comportamientos sugestivos de dolor por vergüenza de ser considerados más flojos o por entender que es un dolor necesario. De ahí el hecho de que algunos niños, asociaran al dolor la valentía que se necesita tener para soportarla (AU)


Introduction: Pain is a part ofhuman nature and is an unalienable part of our existence. It is understood as a universal experience, with an early beginning, in each person, and it gans heterogeneity from social configurations and varying intensity. As an untransferrableexperience, it marks the construction of the psychological and social person in various ways. For children, pain is a common and disturbing experience that is sometimes underestimated in health contexts. Methodology: This exploratory study is of a mixed nature, which was based on the theory of social representations, aims to dentify the representation associated to pain, in school age children submitted to venous puncture and to the degree ofpain associated to venous puncture. Therefore, the free association of words technique was applied using two stimulus questions: «Pain makes me think about…», the needle prick makes me feel…», and the numerical scale of pain evaluation, to forty three children with ages between six and twelve years old, who were hospitalized in Lisbon’s Health Sub-region. The data have been analyzed using SPAD-T (factorial analysis of simple correspondence) and SPSS (descriptive statistics) software. The Results show that for those children pain is a factor which arouses suffering and is associated, by children, to physical manifestations, such as crying and to feelings expressed in the presence of pain, like fear. This procedure provokes fear and anxiety in hospitalized children. The degree of pain associated to venous puncture changes with factors like age and mainly with previous experience. In Conclusion, venipuncture is a painful procedure and according to the children who participated in the study, it causes fear and anxiety. However, many avoided suggestive feelings of pain, because they were ashamed to be considered weaker or deem it a necessary pain; hence the fact that some children associate pain and the need to have the necessary courage to support it (AU)


Subject(s)
Humans , Male , Female , Child , Punctures/nursing , Punctures/psychology , Needlestick Injuries/nursing , Needlestick Injuries/psychology , Pain/nursing , Pain/psychology , Anxiety/nursing , Anxiety/psychology , Anxiety Disorders/nursing , Phobic Disorders/nursing , Factor Analysis, Statistical , Data Collection , Needlestick Injuries/epidemiology
15.
Heredity (Edinb) ; 108(5): 461-8, 2012 May.
Article in English | MEDLINE | ID: mdl-21971178

ABSTRACT

Transposable elements (TEs), by their capacity of moving and inducing mutations in the genome, are considered important drivers of species evolution. The successful invasions of TEs in genomes, despite their mutational properties, are an apparent paradox. TEs' transposition is usually strongly regulated to low value, but in some cases these elements can also show high transposition rates, which has been associated sometimes to changes in environmental conditions. It is evident that factors susceptible to induce transpositions in natural populations contribute to TE perpetuation. Different factors were proposed as causative agents of TE mobilization in a wide range of organisms: biotic and abiotic stresses, inter- and intraspecific crosses and populational factors. However, there is no clear evidence of the factors capable of inducing TE mobilization in Drosophila, and data on laboratory stocks show contradictory results. The aim of this review is to have an update critical revision about mechanisms promoting transposition of TEs in Drosophila, and to provide to the readers a global vision of the dynamics of these genomic elements in the Drosophila genome.


Subject(s)
DNA Transposable Elements , Drosophila melanogaster/genetics , Genome, Insect , Animals , Biological Evolution , Mutation
16.
Biotechnol Bioeng ; 108(11): 2623-33, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21656710

ABSTRACT

Retroviral-derived biopharmaceuticals (RV) target numerous therapeutic applications, from gene therapy to virus-like particle (rVLP)-based vaccines. During particle formation, beside the pseudotyped envelope proteins, RV can incorporate proteins derived from the virus producer cells (VPC). This may be detrimental by reducing the amounts of the pseudotyped envelope and/or by incorporating protein capable of inducing immune responses when non-human VPC are used. Manipulating the repertoire of VPC proteins integrated onto the vector structure is an underexplored territory and should provide valuable insights on potential targets to improve vector pharmacokinetic and pharmacodynamic properties. In this work, human HEK 293 cells producing retrovirus-like particles (rVLPs) and infectious RV vectors were used to prove the concept of customizing RV composition by manipulating cellular protein content. The tetraspanin CD81 was chosen since it is significantly incorporated in the RV membrane, conferring to the vector significant immunogenicity when used in mice. RNA interference-mediated by shRNA lentiviral vector transduction was efficiently used to silence CD81 expression (up to 99%) and the rVLPs produced by knocked-down cells lack CD81. Silenced clones were analyzed for cell proliferation, morphological changes, susceptibility to oxidative stress conditions, and rVLP productivities. The results showed that the down-regulation of VPC proteins requires close monitoring for possible side effects on cellular production performance. Yet, they confirm that it is possible to change the composition of host-derived immunogens in RV by altering cellular protein content with no detriment for vector productivity and titers. This constitutes an important manipulation tool in vaccinology--by exploiting the potential adjuvant effect of VPC proteins or using them as fusion agents to other proteins of interest to be exposed on the vector membrane--and in gene therapy, by reducing the immunogenicity of RV-based vector and enhancing in vivo half-life. Such tools can also be applied to lentiviral or other enveloped viral vectors.


Subject(s)
Biological Products/chemistry , Down-Regulation , Genetic Vectors , Retroviridae/chemistry , Retroviridae/genetics , Tetraspanin 28/analysis , Animals , Biological Products/administration & dosage , Biological Products/isolation & purification , Cell Line , Gene Knockdown Techniques/methods , Gene Silencing , Humans , Mice , Retroviridae/growth & development , Retroviridae/isolation & purification
17.
Eur J Neurol ; 18(2): 279-285, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20597968

ABSTRACT

BACKGROUND AND PURPOSE: The centres dedicated to dementia throughout Europe use different neuropsychological tests in clinical practice. The European Federation of Neurological Societies task force on neuropsychological tests produced this survey on neuropsychological tests currently being used in different European countries to gather knowledge on the practice of dementia centres and to promote the harmonization of such instruments and future multicentre collaborations. METHODS: National representatives of 34 countries received a questionnaire and 25 (73.5%) sent it back. RESULTS: A few instruments, Mini-Mental State Examination (MMSE), Trail Making Test (TMT), Verbal Fluency and Clock Drawing Test, were available in all countries. Wechsler Adult Intelligence Scales and MMSE were reported to be valid, respectively, in 20 (80%) and 19 (76%) countries, whereas Verbal Fluency and Stroop Test are valid in 18 (72%) of them. Of the 25 countries, 17 have validation norms for Clock Drawing Test and TMT (68%), and Neuropsychiatric Inventory, Alzheimer's Disease Assessment Scale - Cognitive Subscale, Rey Complex Figure Test, Digit Symbol and Beck Depression Inventory were standardized in 16 countries (64%). The remaining tests were validated, at most, in about half of them. Not all countries certificate neuropsychology. CONCLUSIONS: Despite the substantial differences in the tools used by the EFNS countries for most domains surveyed by the questionnaire, there is at least one neuropsychological instrument used by about 80% of the countries. There is clearly the need for a broader consensus in the use of neuropsychological tests for dementia diagnosis.


Subject(s)
Dementia/diagnosis , Neuropsychological Tests/statistics & numerical data , Neuropsychological Tests/standards , Europe , Humans , Surveys and Questionnaires
18.
J Nutr Health Aging ; 14(8): 703-9, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20922349

ABSTRACT

Patients with MCI may present minor impairments in activities of daily living (ADL). The main objective of this work was to evaluate the ability of two versions of the Alzheimer's Disease Cooperative Study/Activities of Daily Living scale adapted for MCI patients (ADCS/MCI/ADL18 and ADCS/MCI/ADL24) to distinguish patients with MCI from healthy control subjects. Participants were 60 years or older and community dwelling: 31 control subjects, 30 aMCI patients and 33 AD patients. A protocol of neuropsychological tests, global evaluation scales, functional scales, and depressive symptoms assessment was used. Activities of balancing the cheque book, using a telephone, going shopping, taking medication regularly, finding objects, talking about current events, watching television, initiating complex activities, keeping appointments or meetings, reading, getting around outside the home and driving a car were impaired in aMCI patients. The ADCS/MCI/ADL24 scale was better than the ADCS/MCI/ADL18 scale in distinguishing aMCI patients from healthy controls (sensitivity=0.87, specificity=0.87, ROC c=0.887, cut-off point=52/53). The detection of initial functional changes with appropriate scales may contribute to the early diagnosis of MCI and the development of targeted interventions to improve everyday function or prolong independence.


Subject(s)
Cognition Disorders/diagnosis , Cognition Disorders/physiopathology , Neuropsychological Tests , Activities of Daily Living , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/physiopathology , Diagnosis, Differential , Early Diagnosis , Female , Humans , Male , Memory Disorders/diagnosis , Memory Disorders/physiopathology , Middle Aged , Sensitivity and Specificity , Severity of Illness Index
19.
Clin Neurophysiol ; 121(10): 1740-3, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20674483

ABSTRACT

OBJECTIVE: The aim of this study was to analyze neurophysiologic aspects of rolandic discharges. METHODS: We reviewed 45 electroencephalograms of patients divided into two groups: those with benign childhood epilepsy with centrotemporal spikes (BCECTS) and symptomatic partial epilepsy (SPE), following ILAE criteria (1989). The EEG data analyzed were: horizontal dipole discharges, double spike phenomenon, the extension of epileptiform discharges and background activity. RESULTS: There was a predominance of horizontal dipole between patients with BCECTS compared with patients with SPE; however, this difference was not statistically significant. There was also no statistically significant difference between the two groups when the double spike phenomenon and the extension of discharges beyond the rolandic area were considered. The slower background activity in the SPE group was the only variable with statistical significance. CONCLUSIONS: This study revealed similarities between rolandic discharges of two different epilepsy groups. The only reliable parameter to differentiate the groups was the background activity. SIGNIFICANCE: Our findings suggest that most EEG rolandic features are not pathognomonic of BCECTS, as they are related to the area of the discharges and not to the epileptic syndrome itself.


Subject(s)
Brain/physiopathology , Electroencephalography , Epilepsy, Rolandic/pathology , Adolescent , Child , Child, Preschool , Electroencephalography/classification , Epilepsy, Rolandic/physiopathology , Female , Humans , Magnetic Resonance Imaging/methods , Male , Numerical Analysis, Computer-Assisted , Retrospective Studies
20.
Eur J Neurol ; 17(5): 692-5, 2010 May.
Article in English | MEDLINE | ID: mdl-20050900

ABSTRACT

BACKGROUND: Cognitive tests are known to be influenced by language, culture and education. In addition, there may be an impact of 'epoch' in cognition, because there is secular increase in scores of IQ tests in children. If we assume this is a long lasting process, then it should persist later in life. METHODS: To test this hypothesis, we compared the performance of two cohorts of individuals (>or=50 years of age), evaluated 20 years apart using the Mini-Mental State Examination (MMSE). RESULTS: Study population included 135 participants in 1988 and 411 in 2008. MMSE scores were higher in 2008 than in 1988 for literacy x age-matched subgroups, the difference being significant for participants with lower literacy. Score variance was explained by literacy (beta = 0.479, t = 14.598, P = 0.00), epoch (beta = 0.34, t = 10.33, P = 0.00) and age (beta = -0.142, t = -4.184, P = 0.00). CONCLUSION: The present results are in accordance with a lifelong secular improvement in cognitive performance. The operational cut-off values may change with time, which may have clinical impact in the diagnosis of disorders like mild cognitive impairment or dementia.


Subject(s)
Cognition Disorders/diagnosis , Dementia/diagnosis , Neuropsychological Tests/standards , Aged , Aging/psychology , Cognition/physiology , Cognition Disorders/classification , Cognition Disorders/psychology , Cohort Studies , Culture , Dementia/classification , Dementia/psychology , Disability Evaluation , Female , Humans , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results
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