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OBJECTIVE: Traditional naming tests are unsuitable to assess naming impairment in diverse populations, given the influence of culture, language, and education on naming performance. Our goal was therefore to develop and validate a new test to assess naming impairment in diverse populations: the Naming Assessment in Multicultural Europe (NAME). METHOD: We carried out a multistage pilot study. First, we generated a list of 149 potentially suitable items - e.g. from published cross-linguistic word lists and other naming tests - and selected those with a homogeneous age of acquisition and word frequency across languages. We selected three to four colored photographs for each of the 73 remaining items; 194 controls selected the most suitable photographs. Thirteen items were removed after a pilot study in 15 diverse healthy controls. The final 60-item test was validated in 39 controls and 137 diverse memory clinic patients with subjective cognitive impairment, neurological/neurodegenerative disease or psychiatric disorders in the Netherlands and Turkey (mean age: 67, SD: 11). Patients were from 15 different countries; the majority completed primary education or less (53%). RESULTS: The NAME showed excellent reliability (Spearman-Brown coefficient: 0.95; Kuder-Richardson coefficient: 0.94) and robust correlations with other language tests (ρ = .35-.73). Patients with AD/mixed dementia obtained lower scores on most (48/60) NAME items, with an area under the curve of 0.88. NAME scores were correlated with age and education, but not with acculturation or sex. CONCLUSIONS: The NAME is a promising tool to assess naming impairment in culturally, educationally, and linguistically diverse individuals.
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Doenças Neurodegenerativas , Humanos , Idoso , Reprodutibilidade dos Testes , Projetos Piloto , Testes Neuropsicológicos , Europa (Continente)RESUMO
Abstract Although richness and distribution of woody species in the Cerrado physiognomies have been extensively studied, the shifts of woody species from savanna physiognomies to dry forests have not yet been addressed. Here, we investigate the effect of soil physical-chemical traits on the woody species turnover between adjacent cerrado stricto sensu and dry forest physiognomies. Woody species were surveyed, and soil and topographic variables measured, in 30 10×40 m plots systematically distributed, with 15 plots in each physiognomy. We found a spatially structured distribution of woody species, and differences of soil traits between cerrado stricto sensu and dry forest areas, mainly related to the aluminum saturation, base saturation, and available phosphorus. Aluminum saturation increased toward the savanna area, while base saturation increased toward the dry forest. Most woody species predominated in one physiognomy, such as Callisthene major in the cerrado stricto sensu and Anadenanthera colubrina in the dry forest. Only 20% of the species were widely distributed across both physiognomies or, not often, restricted to the intermediary values of the soil gradient. General results indicate that contrasting soil traits between cerrado stricto sensu and dry forest produce a strongly spatially organized and sharp transition in terms of species distribution between these physiognomies.
Resumo Embora a distribuição e a riqueza em espécies arbóreas nas fitofisionomias do Cerrado venham sendo bastante estudadas, a transição entre savanas e florestas deciduais ainda não foi abordada. Investigamos o efeito de características físico-químicas do solo sobre a distribuição de espécies arbóreas em região de contato entre cerrado sentido restrito e floresta estacional decidual (FED). As espécies arbóreas foram amostradas sistematicamente, e variáveis de topografia e características do solo foram medidas em 30 parcelas de 10×40 m, sendo 15 parcelas em cada fisionomia. A distribuição das espécies arbóreas foi espacialmente estruturada, e as características do solo diferiram entre as áreas de cerrado sentido restrito e FED, principalmente relacionadas à saturação de alumínio, saturação de bases e teores de fósforo. A saturação de alumínio aumentou em direção ao cerrado sentido restrito, enquanto a saturação de bases aumentou em direção à FED. A maioria das espécies arbóreas predominou em uma das fisionomias, como Callisthene major em cerrado sentido restrito e Anadenanthera colubrina em FED. Apenas 20% das espécies foram amplamente distribuídas em ambas as fisionomias ou, em poucos casos, restritas aos valores intermediários do gradiente de solo. Os resultados indicam um forte contraste de características do solo entre o cerrado sentido restrito e a FED, assim como uma transição acentuada e espacialmente organizada quanto à distribuição de espécies arbóreas.
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Solo , Pradaria , Árvores , Brasil , FlorestasRESUMO
Abstract Although richness and distribution of woody species in the Cerrado physiognomies have been extensively studied, the shifts of woody species from savanna physiognomies to dry forests have not yet been addressed. Here, we investigate the effect of soil physical-chemical traits on the woody species turnover between adjacent cerrado stricto sensu and dry forest physiognomies. Woody species were surveyed, and soil and topographic variables measured, in 30 10×40 m plots systematically distributed, with 15 plots in each physiognomy. We found a spatially structured distribution of woody species, and differences of soil traits between cerrado stricto sensu and dry forest areas, mainly related to the aluminum saturation, base saturation, and available phosphorus. Aluminum saturation increased toward the savanna area, while base saturation increased toward the dry forest. Most woody species predominated in one physiognomy, such as Callisthene major in the cerrado stricto sensu and Anadenanthera colubrina in the dry forest. Only 20% of the species were widely distributed across both physiognomies or, not often, restricted to the intermediary values of the soil gradient. General results indicate that contrasting soil traits between cerrado stricto sensu and dry forest produce a strongly spatially organized and sharp transition in terms of species distribution between these physiognomies.
Resumo Embora a distribuição e a riqueza em espécies arbóreas nas fitofisionomias do Cerrado venham sendo bastante estudadas, a transição entre savanas e florestas deciduais ainda não foi abordada. Investigamos o efeito de características físico-químicas do solo sobre a distribuição de espécies arbóreas em região de contato entre cerrado sentido restrito e floresta estacional decidual (FED). As espécies arbóreas foram amostradas sistematicamente, e variáveis de topografia e características do solo foram medidas em 30 parcelas de 10×40 m, sendo 15 parcelas em cada fisionomia. A distribuição das espécies arbóreas foi espacialmente estruturada, e as características do solo diferiram entre as áreas de cerrado sentido restrito e FED, principalmente relacionadas à saturação de alumínio, saturação de bases e teores de fósforo. A saturação de alumínio aumentou em direção ao cerrado sentido restrito, enquanto a saturação de bases aumentou em direção à FED. A maioria das espécies arbóreas predominou em uma das fisionomias, como Callisthene major em cerrado sentido restrito e Anadenanthera colubrina em FED. Apenas 20% das espécies foram amplamente distribuídas em ambas as fisionomias ou, em poucos casos, restritas aos valores intermediários do gradiente de solo. Os resultados indicam um forte contraste de características do solo entre o cerrado sentido restrito e a FED, assim como uma transição acentuada e espacialmente organizada quanto à distribuição de espécies arbóreas.
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Frontotemporal dementia (FTD) is an early-onset neurodegenerative disorder with a heterogeneous clinical presentation. Verbal fluency is regularly used as a sensitive measure of language ability, semantic memory, and executive functioning, but qualitative changes in verbal fluency in FTD are currently overlooked. This retrospective study examined qualitative, linguistic features of verbal fluency in 137 patients with behavioral variant (bv)FTD (n = 50), or primary progressive aphasia (PPA) [25 non-fluent variant (nfvPPA), 27 semantic variant (svPPA), and 34 logopenic variant (lvPPA)] and 25 control participants. Between-group differences in clustering, switching, lexical frequency (LF), age of acquisition (AoA), neighborhood density (ND), and word length (WL) were examined in the category and letter fluency with analysis of variance adjusted for age, sex, and the total number of words. Associations with other cognitive functions were explored with linear regression analysis. The results showed that the verbal fluency performance of patients with svPPA could be distinguished from controls and other patient groups by fewer and smaller clusters, more switches, higher LF, and lower AoA (all p < 0.05). Patients with lvPPA specifically produced words with higher ND than the other patient groups (p < 0.05). Patients with bvFTD produced longer words than the PPA groups (p < 0.05). Clustering, switching, LF, AoA, and ND-but not WL-were differentially predicted by measures of language, memory, and executive functioning (range standardized regression coefficient 0.25-0.41). In addition to the total number of words, qualitative linguistic features differ between subtypes of FTD. These features provide additional information on lexical processing and semantic memory that may aid the differential diagnosis of FTD.
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The Social Norms Questionnaire-Dutch version (SNQ-NL) measures the ability to understand and identify social boundaries. We examined the psychometric characteristics of the SNQ-NL and its ability to differentiate between patients with behavioral variant frontotemporal dementia (bvFTD; n = 23), Alzheimer's dementia (AD; n = 26), chronic psychiatric disorders (n = 27), and control participants (n = 92). Between-group differences in the Total score, Break errors, and Overadhere errors were examined and associations with demographic variables and other cognitive functions were explored. Results showed that the SNQ-NL Total Score and Break errors differed between patients with AD and bvFTD, but not between patients with bvFTD and psychiatric disorders. Modest correlations with age, sex, and education were observed. The SNQ-NL Total score and Break errors correlated significantly with emotion recognition and verbal fluency but not with processing speed or mental flexibility. In conclusion, the SNQ-NL has sufficient construct validity and can be used to investigate knowledge of social norms in clinical populations.
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Doença de Alzheimer , Demência Frontotemporal , Doença de Alzheimer/diagnóstico , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/psicologia , Humanos , Testes Neuropsicológicos , Normas Sociais , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To investigate the differential ability of the "Test Relaties Abstracte Concepten" (TRACE), a Dutch test for abstract semantic knowledge, in frontotemporal dementia (FTD). METHODS: The TRACE was administered in patients with behavioral variant FTD (bvFTD; n = 16), nonfluent variant (nfvPPA; n = 10), logopenic variant (lvPPA; n = 10), and semantic variant primary progressive aphasia (svPPA; n = 9), and controls (n = 59). We examined group differences, performed correlational analyses with other neuropsychological tests and investigated discriminative ability. We compared the TRACE with a semantic association test for concrete stimuli (SAT). RESULTS: All patient groups, except nfvPPA, performed worse on the TRACE than controls (p < .01). svPPA patients performed worse than the other patient groups (p < .05). The TRACE discriminated well between patient groups, except nfvPPA, versus controls (all p < .01) and between svPPA versus other patient groups with high sensitivity (75-100%) and specificity (86%-92%). In bvFTD and nfvPPA the TRACE correlated with language tests (ρ > 0.6), whereas in svPPA the concrete task correlated (ρ ≥ 0.75) with language tests. Patients with bvFTD, nfvPPA and lvPPA performed lower on the TRACE than the SAT (p < .05), whereas patients with svPPA were equally impaired on both tasks (p = .2). DISCUSSION: We demonstrated impaired abstract semantic knowledge in patients with bvFTD, lvPPA, and svPPA, but not nfvPPA, with svPPA patients performing worse than the other subtypes. The TRACE was a good classifier between each patient group versus controls and between svPPA versus other patient groups. This highlights the value of incorporating semantic tests with abstract stimuli into standard neuropsychological assessment for early differential diagnosis of FTD subtypes.
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Afasia Primária Progressiva , Demência Frontotemporal , Humanos , Idioma , Testes Neuropsicológicos , SemânticaRESUMO
The COVID-19 pandemic has introduced a myriad of challenges to the social life and care of people with Parkinson's disease (PD), which could potentially worsen mental health problems. We used baseline data of the PRIME-NL study (N = 844) to examine whether the association between COVID-19 stressors and mental health is disproportionately large in specific subgroups of people with PD and to explore effects of hypothetical reductions in COVID-19 stressors on mental health and quality of life. The mean (SD) age of the study population was 70.3 (7.8) years and 321 (38.0%) were women. The linear regression effect estimate of the association of COVID-19 stressors with mental health was most pronounced in women, highly educated people, people with advanced PD and people prone to distancing or seeking social support. Smaller effect estimates were found in people scoring high on confrontive coping or planful problem solving. The parametric G-formula method was used to calculate the effects of hypothetical interventions on COVID-19 stressors. An intervention reducing stressors with 50% in people with above median MDS-UPDRS-II decreased the Beck Depression Inventory in this group from 14.7 to 10.6, the State-Trait Anxiety Inventory from 81.6 to 73.1 and the Parkinson's Disease Quality of Life Questionnaire from 35.0 to 24.3. Insights from this cross-sectional study help to inform tailored care interventions to subgroups of people with PD most vulnerable to the impact of COVID-19 on mental health and quality of life.
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Although richness and distribution of woody species in the Cerrado physiognomies have been extensively studied, the shifts of woody species from savanna physiognomies to dry forests have not yet been addressed. Here, we investigate the effect of soil physical-chemical traits on the woody species turnover between adjacent cerrado stricto sensu and dry forest physiognomies. Woody species were surveyed, and soil and topographic variables measured, in 30 10×40 m plots systematically distributed, with 15 plots in each physiognomy. We found a spatially structured distribution of woody species, and differences of soil traits between cerrado stricto sensu and dry forest areas, mainly related to the aluminum saturation, base saturation, and available phosphorus. Aluminum saturation increased toward the savanna area, while base saturation increased toward the dry forest. Most woody species predominated in one physiognomy, such as Callisthene major in the cerrado stricto sensu and Anadenanthera colubrina in the dry forest. Only 20% of the species were widely distributed across both physiognomies or, not often, restricted to the intermediary values of the soil gradient. General results indicate that contrasting soil traits between cerrado stricto sensu and dry forest produce a strongly spatially organized and sharp transition in terms of species distribution between these physiognomies.
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Pradaria , Solo , Brasil , Florestas , ÁrvoresRESUMO
The cerebellum is increasingly recognised for its role in modulation of cognition, behaviour, and affect. The present study examined the relation between structural cerebellar damage (grey matter volume (GMV), white matter hyperintensities (WMHs), lacunar infarcts (LIs) and microbleeds (MBs)) and measures of cognitive, psychological (i.e. symptoms of depression and apathy) and general daily functioning in a population of community-dwelling older persons with mild cognitive deficits, but without dementia. In 194 participants of the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden, the association between cerebellar GMV, WMHs, LIs and MBs and measures of cognitive, psychological and general daily functioning was analysed with linear regression analysis, adjusted for age, sex, education and cerebral volume. Cerebellar GMV was associated with the overall cognition score (standardised beta 0.20 [95% CI, 0.06-0.33]). Specifically, posterior cerebellar GMV was associated with executive function (standardised beta 0.18 [95% CI, 0.03-0.16]). No relation was found between vascular pathology and cognition. Also, no consistent associations were found on the cerebellar GMV and vascular pathology measures and psychological and general daily functioning. In this population of community-dwelling elderly, less posterior cerebellar GMV but not vascular pathology was associated with worse cognitive function, specifically with poorer executive function. No relation was found between cerebellar pathology and psychological and general daily functioning.
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Cerebelo/patologia , Transtornos Cognitivos/patologia , Substância Cinzenta/patologia , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Vasos Sanguíneos/patologia , Cognição , Transtornos Cognitivos/psicologia , Disfunção Cognitiva/patologia , Disfunção Cognitiva/psicologia , Função Executiva , Feminino , Humanos , Vida Independente , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
OBJECTIVE: Episodic memory is impaired in Alzheimer's disease (AD) dementia but thought to be relatively spared in behavioral variant frontotemporal dementia (bvFTD). This view is challenged by evidence of memory impairment in bvFTD. This study investigated differences in recognition memory performance between bvFTD and AD. METHOD: We performed a retrospective analysis on the recognition trial of the Rey Auditory Verbal Learning Test in patients with bvFTD (n = 85), AD (n = 55), and control participants (n = 59). Age- and education-adjusted between-group analysis was performed on the total score and indices of discriminative ability and response bias. Correlations between recognition and measures of memory, language, executive functioning, and construction were examined. RESULTS: Patients with AD had a significantly lower total recognition score than patients with bvFTD (control 28.8 ± 1.5; bvFTD 24.8 ± 4.5; AD 23.4 ± 3.6, p < .01). Both bvFTD and AD had worse discriminative ability than controls (A' control 0.96 ± 0.03; bvFTD 0.87 ± 0.03; AD 0.84 ± 0.10, p < .01), but there was no difference in response bias (B" control 0.9 ± 0.2; bvFTD 1.6 ± 1.47; AD 1.4± 1.4, p < .01). AD had worse discriminability than bvFTD (p < .05). Discriminability was associated with memory for both patient groups (median correlation coefficient r = .34) and additionally associated with language (r = .31), but not executive functioning (r = -.03) in bvFTD. Response bias was unrelated to other cognitive functions (r = -.02). CONCLUSIONS: Discriminability, but not response bias, differentiated patients with bvFTD from AD. The presence of an impaired discrimination index suggests a "pure" (recognition) memory deficit in bvFTD.
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Doença de Alzheimer/psicologia , Demência Frontotemporal/psicologia , Transtornos da Memória/diagnóstico , Testes de Memória e Aprendizagem , Idoso , Cognição/fisiologia , Função Executiva/fisiologia , Feminino , Humanos , Masculino , Memória Episódica , Rememoração Mental/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Reconhecimento Psicológico , Estudos RetrospectivosRESUMO
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INTRODUCTION: Trials to test disease-modifying treatments for frontotemporal dementia are eagerly awaited and sensitive instruments to assess potential treatment effects are increasingly urgent, yet lacking thus far. We aimed to identify gene-specific instruments assessing clinical onset and disease progression by comparing cognitive functioning between bvFTD patients across genetic mutations. METHODS: We examined differences in 7 cognitive domains between bvFTD patients with GRN (n = 20), MAPT (n = 29) or C9orf72 (n = 31) mutations, and non-carriers (n = 24), and described longitudinal (M = 22.6 months, SD = 16.6) data in a subsample (n = 27). RESULTS: Patients showed overall cognitive impairment, except memory recall, working memory and visuoconstruction. GRN patients performed lower on executive function (mean difference - 2.1; 95%CI - 4.1 to - 0.5) compared to MAPT and lower on attention compared to MAPT (mean difference - 2.5; 95%CI - 4.7 to - 0.3) and C9orf72 (mean difference - 2.4; 95%CI - 4.5 to - 0.3). Only MAPT patients were impaired on delayed recall (mean difference - 1.4; 95%CI - 2.1 to - 0.7). GRN patients declined rapidly on attention and memory, MAPT declined in confrontation naming, whereas C9orf72 patients were globally impaired but remained relatively stable over time on all cognitive domains. DISCUSSION: This study shows gene-specific cognitive profiles in bvFTD, which underlines the value of neuropsychological tests as outcome measures in upcoming trials for genetic bvFTD.
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Atenção/fisiologia , Função Executiva/fisiologia , Demência Frontotemporal/genética , Demência Frontotemporal/fisiopatologia , Rememoração Mental/fisiologia , Desempenho Psicomotor/fisiologia , Idoso , Proteína C9orf72/genética , Feminino , Demência Frontotemporal/classificação , Humanos , Estudos Longitudinais , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Proteínas tau/genéticaRESUMO
STUDY QUESTION: Is it possible to differentiate primary human testicular platelet-derived growth factor receptor alpha positive (PDGFRα+) cells into functional Leydig cells? SUMMARY ANSWER: Although human testicular PDGFRα+ cells are multipotent and are capable of differentiating into steroidogenic cells with Leydig cell characteristics, they are not able to produce testosterone after differentiation. WHAT IS KNOWN ALREADY: In rodents, stem Leydig cells (SLCs) that have been identified and isolated using the marker PDGFRα can give rise to adult testosterone-producing Leydig cells after appropriate differentiation in vitro. Although PDGFRα+ cells have also been identified in human testicular tissue, so far there is no evidence that these cells are true human SLCs that can differentiate into functional Leydig cells in vitro or in vivo. STUDY DESIGN, SIZE, DURATION: We isolated testicular cells enriched for interstitial cells from frozen-thawed fragments of testicular tissue from four human donors. Depending on the obtained cell number, PDGFRα+-sorted cells of three to four donors were exposed to differentiation conditions in vitro to stimulate development into adipocytes, osteocytes, chondrocytes or into Leydig cells. We compared their cell characteristics with cells directly after sorting and cells in propagation conditions. To investigate their differentiation potential in vivo, PDGFRα+-sorted cells were transplanted in the testis of 12 luteinizing hormone receptor-knockout (LuRKO) mice of which 6 mice received immunosuppression treatment. An additional six mice did not receive cell transplantation and were used as a control. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human testicular interstitial cells were cultured to Passage 3 and FACS sorted for HLA-A,B,C+/CD34-/PDGFRα+. We examined their mesenchymal stromal cell (MSC) membrane protein expression by FACS analyses. Furthermore, we investigated lineage-specific staining and gene expression after MSC trilineage differentiation. For the differentiation into Leydig cells, PDGFRα+-sorted cells were cultured in either proliferation or differentiation medium for 28 days, after which they were stimulated either with or without hCG, forskolin or dbcAMP for 24 h to examine the increase in gene expression of steroidogenic enzymes using qPCR. In addition, testosterone, androstenedione and progesterone levels were measured in the culture medium. We also transplanted human PDGFRα+-sorted testicular interstitial cells into the testis of LuRKO mice. Serum was collected at several time points after transplantation, and testosterone was measured. Twenty weeks after transplantation testes were collected for histological examination. MAIN RESULTS AND THE ROLE OF CHANCE: From primary cultured human testicular interstitial cells at Passage 3, we could obtain a population of HLA-A,B,C+/CD34-/PDGFRα+ cells by FACS. The sorted cells showed characteristics of MSC and were able to differentiate into adipocytes, chondrocytes and osteocytes. Upon directed differentiation into Leydig cells in vitro, we observed a significant increase in the expression of HSD3B2 and INSL3. After 24 h stimulation with forskolin or dbcAMP, a significantly increased expression of STAR and CYP11A1 was observed. The cells already expressed HSD17B3 and CYP17A1 before differentiation but the expression of these genes were not significantly increased after differentiation and stimulation. Testosterone levels could not be detected in the medium in any of the stimulation conditions, but after stimulation with forskolin or dbcAMP, androstenedione and progesterone were detected in culture medium. After transplantation of the human cells into the testes of LuRKO mice, no significant increase in serum testosterone levels was found compared to the controls. Also, no human cells were identified in the interstitium of mice testes 20 weeks after transplantation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study was performed using tissue from only four donors because of limitations in donor material. Because of the need of sufficient cell numbers, we first propagated cells to passage 3 before FACS of the desired cell population was performed. We cannot rule out this propagation of the cells resulted in loss of stem cell properties. WIDER IMPLICATIONS OF THE FINDINGS: A lot of information on Leydig cell development is obtained from rodent studies, while the knowledge on human Leydig cell development is very limited. Our study shows that human testicular interstitial PDGFRα+ cells have different characteristics compared to rodent testicular PDGFRα+ cells in gene expression levels of steroidogenic enzymes and potential to differentiate in adult Leydig cells under comparable culture conditions. This emphasizes the need for confirming results from rodent studies in the human situation to be able to translate this knowledge to the human conditions, to eventually contribute to improvements of testosterone replacement therapies or establishing alternative cell therapies in the future, potentially based on SLCs. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Amsterdam UMC, location AMC, Amsterdam, the Netherlands. All authors declare no competing interests.
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Diferenciação Celular/genética , Células Intersticiais do Testículo/metabolismo , Células-Tronco Multipotentes/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Espermatogênese/genética , Idoso , Animais , Técnicas de Cultura de Células/métodos , Células Cultivadas , Meios de Cultura , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Receptores do LH/genética , Testosterona/sangueRESUMO
Cytogenomic investigations of haematological neoplasms, including chromosome banding analysis, fluorescence in situ hybridisation (FISH) and microarray analyses have become increasingly important in the clinical management of patients with haematological neoplasms. The widespread implementation of these techniques in genetic diagnostics has highlighted the need for guidance on the essential criteria to follow when providing cytogenomic testing, regardless of choice of methodology. These recommendations provide an updated, practical and easily available document that will assist laboratories in the choice of testing and methodology enabling them to operate within acceptable standards and maintain a quality service.
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Neoplasias Hematológicas/genética , Bandeamento Cromossômico , Humanos , Hibridização in Situ Fluorescente , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide Aguda/genética , Linfoma/genética , Análise em Microsséries , Mieloma Múltiplo/genética , Síndromes MielodisplásicasRESUMO
INTRODUCTION: Patients with complete occlusion of the internal carotid artery (CAO) are vulnerable to cerebral hypoperfusion. Since cerebral hypoperfusion is associated with accelerated cognitive decline, patients with CAO may have an increased risk of cognitive impairment. We aimed to assess the prevalence and profile of cognitive impairment in patients with CAO and to explore the relation between hemodynamic impairment and cognitive functioning. METHODS: We systematically searched Medline and EMBASE for studies including patients with symptomatic or asymptomatic CAO subjected to cognitive testing that were published between 1980 and 2017. We did not include patients with carotid stenosis. We obtained data on type of study, patient characteristics, cerebral imaging and neuropsychological testing. In addition, we extracted data on potential causes of systemic hemodynamic impairment and the presence and stage of cerebral hemodynamic impairment. We assessed methodological quality of included studies with the Newcastle-Ottawa Scale. RESULTS: We found eight studies comprising 244 patients (mean age 61â¯years, 76% male, 93% symptomatic CAO). The proportion of patients with cognitive impairment ranged from 54 to 71% in four studies; in the other four studies patients with CAO performed worse on cognitive testing than controls, but results were not quantified. Impairment was reported in all cognitive domains. We found no data on the association between systemic hemodynamic impairment and cognitive functioning. Studies that assessed whether cerebral hemodynamic impairment was associated with cognitive functioning showed conflicting results. CONCLUSION: In patients with CAO, cognitive impairment is present in about half to two-thirds of patients and is not restricted to specific cognitive domains. The effect of systemic and cerebral hemodynamic impairment on cognitive functioning in patients with CAO deserves further study.
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Estenose das Carótidas/complicações , Transtornos Cognitivos/etiologia , Bases de Dados Bibliográficas/estatística & dados numéricos , HumanosRESUMO
AIMS: Type 2 diabetes mellitus is associated with cognitive dysfunction, but the underlying structural brain correlates are uncertain. This study examined the association between cognitive functioning and structural brain abnormalities in people with long-standing Type 2 diabetes. METHODS: Ninety-three people with Type 2 diabetes (age 62.3 ± 5.4 years, diabetes duration 9.7 ± 6.7 years; HbA1c 65 ± 10 mmol/mol, 8.1 ± 1.3%) were included. Cognitive functioning was assessed by a test battery covering the domains memory, processing speed and executive functioning. Brain tissue volumes and white matter hyperintensity volumes were automatically determined on MRI. Linear regression analyses were performed adjusted for age, sex and education. RESULTS: In people with Type 2 diabetes, increased white matter hyperintensity volume was associated with decreased processing speed [regression B coefficient = -0.22 (-0.38 to -0.06), P = 0.009], but not with memory or executive function (P > 0.05). Brain tissue volumes were not significantly related to cognitive functioning (P > 0.05). CONCLUSIONS: In people with long-standing, less strictly controlled Type 2 diabetes, white matter hyperintensities volumes were associated with decreased processing speed. This suggests that cerebral small vessel disease is an underlying disease mechanism of cognitive dysfunction in these individuals.
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Encéfalo/patologia , Cognição/fisiologia , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/psicologia , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Encefalopatias Metabólicas/diagnóstico , Encefalopatias Metabólicas/etiologia , Encefalopatias Metabólicas/patologia , Estudos de Casos e Controles , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Testes Neuropsicológicos , Tamanho do ÓrgãoRESUMO
BACKGROUND: Several genetic causes of ectopia lentis (EL), with or without systemic features, are known. The differentiation between syndromic and isolated EL is crucial for further treatment, surveillance and counseling of patients and their relatives. Next generation sequencing (NGS) is a powerful tool enabling the simultaneous, highly-sensitive analysis of multiple target genes. OBJECTIVE: The aim of this study was to evaluate the diagnostic yield of our NGS panel in EL patients. Furthermore, we provide an overview of currently described mutations in ADAMTSL4, the main gene involved in isolated EL. METHODS: A NGS gene panel was analysed in 24 patients with EL. RESULTS: A genetic diagnosis was confirmed in 16 patients (67%). Of these, four (25%) had a heterozygous FBN1 mutation, 12 (75%) were homozygous or compound heterozygous for ADAMTSL4 mutations. The known European ADAMTSL4 founder mutation c.767_786del was most frequently detected. CONCLUSION: The diagnostic yield of our NGS panel was high. Causative mutations were exclusively identified in ADAMTSL4 and FBN1. With this approach the risk of misdiagnosis or delayed diagnosis can be reduced. The value and clinical implications of establishing a genetic diagnosis in patients with EL is corroborated by the description of two patients with an unexpected underlying genetic condition.