A warm Neptune's methane reveals core mass and vigorous atmospheric mixing.

Observations of transiting gas giant exoplanets have revealed a pervasive depletion of methane1-4, which has only recently been identified atmospherically5,6. The depletion is thought to be maintained by disequilibrium processes such as photochemistry or mixing from a hotter interior7-9. However, the interiors are largely unconstrained along with the vertical mixing strength and only upper limits on the CH4 depletion have been available. The warm Neptune WASP-107b stands out among exoplanets with an unusually low density, reported low core mass10, and temperatures amenable to CH4, though previous observations have yet to find the molecule2,4. Here we present a JWST-NIRSpec transmission spectrum of WASP-107b that shows features from both SO2 and CH4 along with H2O, CO2, and CO. We detect methane with 4.2σ significance at an abundance of 1.0 ± 0.5 ppm, which is depleted by 3 orders of magnitude relative to equilibrium expectations. Our results are highly constraining for the atmosphere and interior, which indicate the envelope has a super-solar metallicity of 43 ± 8 × solar, a hot interior with an intrinsic temperature of Tint = 460 ± 40 K, and vigorous vertical mixing which depletes CH4 with a diffusion coefficient of Kzz = 1011.6±0.1 cm2 s-1. Photochemistry has a negligible effect on the CH4 abundance but is needed to account for the SO2. We infer a core mass of 11.5 - 3.6 + 3.0 M ⊕ , which is much higher than previous upper limits10, releasing a tension with core-accretion models11.

Is there a relationship between attitudes of general practitioners/family doctors and attitudes of their patients regarding industry-sponsored clinical investigations? A cross-sectional survey in a convenience sample of doctors and patients across nine European countries.

AIM: To assess the relationship between the attitudes of general practitioners/family medicine doctors (GP/FD) and of their patients toward industry-sponsored clinical research. METHODS: A cross-sectional survey included volunteer GPs/FDs who then enrolled and interviewed their patients. Data were analyzed in hierarchical models (patients nested in GPs/FDs, nested in countries/regions). RESULTS: A total of 201 GPs/FDs from nine European countries responded to the invitation and enrolled 995 of their patients. We observed mild associations between some of the GPs/FDs' attitudes (general opinion on sponsored clinical studies, appreciation of the general values of such studies, views about the importance of participant protection/privacy) and some of the patients' attitudes (appreciation of the general values and of risks associated with sponsored clinical studies, importance assigned to potential personal benefits from participation). We observed no association between GPs/FDs' attitudes and patients' willingness to participate in such studies. However, willingness to participate increased with higher patients' appreciation of the general values of sponsored studies, decreased with higher patients' appreciation of associated risks, and showed a quadratic trend across the levels of importance assigned by patients to potential personal benefits (willingness was higher when the assigned importance was very low or very high). More importance to GP/FD's advice in this respect was assigned by patients who assigned more importance to potential personal benefits, who were better educated, and who resided in rural/suburban dwellings. CONCLUSIONS: In the present convenience sample, lay-person attitudes about and willingness to participate in industry-sponsored clinical studies were associated with the attitudes of their GPs/FDs.

Adenomatoid odontogenic tumor: Features of ameloblastic-like epithelial cells differentiation, secretion, and the nature of tumor cells products.

BACKGROUND: This study aimed to investigate the differentiation of ameloblastic-like cells and the nature of the secreted eosinophilic materials in adenomatoid odontogenic tumors. METHODS: We studied histological and immunohistochemical characteristics of 20 cases using: cytokeratins 14 and 19, amelogenin, collagen I, laminin, vimentin, and CD34. RESULTS: Rosette cells differentiated into ameloblastic-like cells positioned face-to-face, displaying collagen I-positive material between them. Epithelial cells of the rosettes can differentiate into ameloblastic-like cells. This phenomenon probably occurs due to an induction phenomenon between these cells. The secretion of collagen I is probably a brief event. Amelogenin-positive areas were interspersed by epithelial cells in the lace-like areas, outside the rosettes and distant from the ameloblastic-like cells. CONCLUSIONS: There are at least two types of eosinophilic material in different areas within the tumor, one in the rosette and solid areas and another in lace-like areas. The secreted eosinophilic material in the rosettes and solid areas is probably a product of well-differentiated ameloblastic-like cells. It is positive for collagen I and negative for amelogenin, whereas some eosinophilic materials in the lace-like areas are positive for amelogenin. We hypothesize that the latter eosinophilic material could be a product of odontogenic cuboidal epithelial or intermediate stratum-like epithelial cells.

Prevalence of the apolipoprotein E ε4 allele in amyloid ß positive subjects across the spectrum of Alzheimer's disease.

INTRODUCTION: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid ß (Aß) pathology. METHODS: We included 3451 Aß+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. RESULTS: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aß+ cognitively normal and Aß+ mild cognitive impairment (P < .05) but not in Aß+ AD dementia (P = .66). The prevalence was highest in Northern Europe but did not vary by sex or education. DISCUSSION: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aß pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.

Molecular and Genomic Alterations in Glioblastoma Multiforme.

In recent years, important advances have been achieved in the understanding of the molecular biology of glioblastoma multiforme (GBM); thus, complex genetic alterations and genomic profiles, which recurrently involve multiple signaling pathways, have been defined, leading to the first molecular/genetic classification of the disease. In this regard, different genetic alterations and genetic pathways appear to distinguish primary (eg, EGFR amplification) versus secondary (eg, IDH1/2 or TP53 mutation) GBM. Such genetic alterations target distinct combinations of the growth factor receptor-ras signaling pathways, as well as the phosphatidylinositol 3-kinase/phosphatase and tensin homolog/AKT, retinoblastoma/cyclin-dependent kinase (CDK) N2A-p16(INK4A), and TP53/mouse double minute (MDM) 2/MDM4/CDKN2A-p14(ARF) pathways, in cells that present features associated with key stages of normal neurogenesis and (normal) central nervous system cell types. This translates into well-defined genomic profiles that have been recently classified by The Cancer Genome Atlas Consortium into four subtypes: classic, mesenchymal, proneural, and neural GBM. Herein, we review the most relevant genetic alterations of primary versus secondary GBM, the specific signaling pathways involved, and the overall genomic profile of this genetically heterogeneous group of malignant tumors.

The protein expression profile of meningioma cells is associated with distinct cytogenetic tumour subgroups.

AIMS: Limited information exists about the impact of cytogenetic alterations on the protein expression profiles of individual meningioma cells and their association with the clinicohistopathological characteristics of the disease. The aim of this study is to investigate the potential association between the immunophenotypic profile of single meningioma cells and the most relevant features of the tumour. METHODS: Multiparameter flow cytometry (MFC) was used to evaluate the immunophenotypic profile of tumour cells (n = 51 patients) and the Affymetrix U133A chip was applied for the analysis of the gene expression profile (n = 40) of meningioma samples, cytogenetically characterized by interphase fluorescence in situ hybridization. RESULTS: Overall, a close association between the pattern of protein expression and the cytogenetic profile of tumour cells was found. Thus, diploid tumours displayed higher levels of expression of the CD55 complement regulatory protein, tumours carrying isolated monosomy 22/del(22q) showed greater levels of bcl2 and PDGFRß and meningiomas carrying complex karyotypes displayed a greater proliferation index and decreased expression of the CD13 ectoenzyme, the CD9 and CD81 tetraspanins, and the Her2/neu growth factor receptor. From the clinical point of view, higher expression of CD53 and CD44 was associated with a poorer outcome. CONCLUSIONS: Here we show that the protein expression profile of individual meningioma cells is closely associated with tumour cytogenetics, which may reflect the involvement of different signalling pathways in the distinct cytogenetic subgroups of meningiomas, with specific immunophenotypic profiles also translating into a different tumour clinical behaviour.

The aging profile of the Portuguese population: a principal component analysis.

In the last 5 years the resident population of Portugal has increased 2.3%, along with a progressive ageing. This study aims assessing the social dependence and frailty, as well as social and familial support needs of the elderly. In an observational, cross-sectional community based study (EPEPP study), a total of 2,672 people, aged 55 or more, were submitted to an enquiry and several variables were studied among three age groups: 55-64 years old (37%), 65-74 years old (37%) and ≥ 75 years old (26%), encompassing a total of 57% women and 43% men. A questionnaire including items such as physical autonomy, locomotion, falls, health/medical complaints, instrumental autonomy, physical activity, health self-evaluation and emotional status was applied. The strong correlations among the studied scores allowed the identification of people groups with common characteristics when a principal component analysis was used: "autonomy" (scores of instrumental autonomy, locomotion and physical autonomy) and "perception of health and emotional status" (scores of health self-evaluation and emotional status), were present in the three age groups. The component analysis evidences that a good autonomy, a good perception of health and emotional status are determinant to a good quality of life in elderly. Although health status and self-rated health have a propensity to deteriorate with aging, older Portuguese consider their state of health satisfactory and tend to underestimate their decline. In what concerns the analysis of gender with the same age and in contrast to what has been reported, older women alike to men, experience a good mobility and health self-evaluation.

Work-related stress in Medical and Dentistry programs.

Introduction: Stress occurs more frequently in groups in which the degree of responsibility and decision-making power play notable roles in society, such as professors and health professionals. Objectives: To measure and understand the stress of professors in the undergraduate course of Medicine and Dentistry of a private educational institution in northeastern Brazil. Methods: Observational, descriptive and exploratory study with a quantitative approach was conducted between November 2018 and September 2019. A total of 184 professors participated in the study, answering the following instruments: demographic sociodata questionnaire, Stress Symptoms Inventory and the Preliminary Burnout Identification Questionnaire. The Post-Traumatic Stress Symptoms Scale was applied to the 60 professors with stress. The data obtained were submitted to data analysis through Pearson's chi-square test and logistic regression. Results: Stress was present in 40.3% of the professors, with a predominance of the resistance phase (85%) and signs indicative of burnout. There was a significant correlation between the presence of stress and the time of traumatic event either with the individual himself or with some relative and/or close friend. There was no correlation between the traumatic events and Post Traumatic Stress Disorder, although a significant correlation was observed between Post Traumatic Stress Disorder and burnout. Conclusions: The results point to the need to properly identify and manage stress so that the teaching experience is healthy and conducive to the teaching-learning process.

Introdução: O estresse ocorre de forma mais recorrente em grupos em que o grau de responsabilidade e poder de decisão perpetram notáveis papéis na sociedade, tais como docentes e profissionais de saúde. Objetivos: Mensurar e compreender o estresse docente dos cursos de graduação de Medicina e Odontologia de uma instituição de ensino privada do Nordeste do Brasil. Métodos: Tratou-se de um estudo observacional, descritivo, analítico e exploratório, com abordagem quantitativa no período de novembro de 2018 a setembro de 2019. Participaram do estudo 184 docentes, respondendo aos seguintes instrumentos: um questionário sociodemográfico, o Inventário de Sintomas de Estresse e o Questionário Preliminar de Identificação de Burnout. Já a Escala de Sintomas de Estresse Pós-Traumático foi aplicada nos 60 docentes com estresse. Foi realizada a análise de dados através do teste de qui-quadrado de Pearson e de regressão logística. Resultados: O estresse estava presente em 40,3% dos docentes, com predomínio da fase de resistência (85%) e sinais indicativos de burnout. Houve correlação significativa entre estresse e tempo de acontecimento traumático, seja com o próprio indivíduo ou com algum familiar e/ou amigo próximo. Não houve correlação entre o acontecimento traumático e o transtorno de estresse pós-traumático, embora tenha sido observada correlação significativa de transtorno de estresse pós-traumático e burnout. Conclusões: Os resultados apontam para a necessidade de identificar e manejar adequadamente o estresse para que a experiência docente seja salutar e propícia ao processo de ensino-aprendizagem.

Immunophenotypic identification and characterization of tumor cells and infiltrating cell populations in meningiomas.

Meningiomas are primary tumors of the central nervous system composed of both neoplastic and other infiltrating cells. We determined the cellular composition of 51 meningioma samples by multiparameter flow cytometric (MFC) immunophenotyping and investigated the potential relationship between mRNA and protein expression levels of neoplastic cells. For immunophenotypic, morphologic, and cytogenetic characterization of individual cell populations, a large panel of markers was used together with phagocytic/endocytic functional assays and MFC sorting. Overall, our results revealed coexistence of CD45(-) neoplastic cells and CD45(+) immune infiltrating cells in all meningiomas. Infiltrating cells included tissue macrophages, with an HLA-DR(+)CD14(+)CD45(+)CD68(+)CD16(-/+)CD33(-/+) phenotype and high phagocytic/endocytic activity, and a small proportion of cytotoxic lymphocytes (mostly T CD8(+) and natural killer cells). Tumor cells expressed multiple cell adhesion proteins, tetraspanins, HLA-I/HLA-DR molecules, complement regulatory proteins, cell surface ectoenzymes, and growth factor receptors. Noteworthy, the relationship between mRNA and protein levels was variable, depending on the proteins evaluated and the level of infiltration by immune cells. In summary, our results indicate that MFC immunophenotyping provides a reliable tool for the characterization of the patterns of protein expression of different cell populations coexisting in meningioma samples, with a more accurate measure of gene expression profiles of tumor cells at the functional/protein level than conventional mRNA microarray, independently of the degree of infiltration of the tumor by immune cells.

Salmonella detection with LAMP and qPCR and identification of serovars of interest by multiplex qPCR in poultry carcasses.

Salmonella is present in the poultry production chain and is a major challenge in terms of food safety and animal health. The early Salmonella detection is one of the main tools to control and prevent the transmission of this pathogen. Microbiological isolation and serotyping to identify and differentiate Salmonella serovars are laborious processes, time-consuming, and expensive. Therefore, molecular diagnostic methods can be rapid and efficient alternatives to the detection of this pathogen. Thus, the aim herein was to standardize and evaluate the use of loop-mediated isothermal amplification (LAMP) in comparison with real-time PCR (qPCR) for detection of Salmonella associated with a multiplex qPCR for simultaneous identification and differentiation of S. Enteritidis, S. Typhimurium, S. Pullorum, and S. Gallinarum. The LAMP, qPCR, and multiplex qPCR assays were comparable in specificity. The three techniques were evaluated for specificity for 16 different serovars of Salmonella and for 37 strains of the serovars of interest. The limit of detection and the efficiency of the LAMP, qPCR, and multiplex qPCR reactions were determined. The techniques were applied to 33 samples of chicken carcasses and compared to the results of conventional microbiology for validation. As results, LAMP was specific in the detection of different Salmonella serovars but presented lower limit of detection ranging from 101 to 104 CFU/reaction. In comparison, qPCR could detect less cells (100 to 102 CFU/reaction), reaching equal specificity and better repeatability in the assays. The qPCR multiplexing for identification of the different serovars also showed good specificity, with the detection threshold between entre 101 and 102 CFU/reaction. The results obtained in the analyses on poultry carcasses suggested a correspondence between the results obtained in molecular methods and in conventional microbiology. Thus, the proposed assays are promising for the diagnosis of Salmonella in poultry carcasses, already proved to be faster and more efficient than conventional diagnostics techniques, being of great interest for poultry production, animal, and public health.

Empowerment-based nutrition interventions on blood pressure: a randomized comparative effectiveness trial.

Introduction: Empowerment lifestyle programs are needed to reduce the risk of hypertension. Our study compared the effectiveness of two empowerment-based approaches toward blood pressure (BP) reduction: salt reduction-specific program vs. healthy lifestyle general program. Methods: Three hundred and eleven adults (median age of 44 years, IQR 34-54 years) were randomly assigned to a salt reduction (n = 147) or a healthy lifestyle program (n = 164). The outcome measures were urinary sodium (Na+) and potassium (K+) excretion, systolic (SBP) and diastolic (DBP) blood pressure, weight, and waist circumference. Results: There were no significant differences in primary and secondary outcomes between the two program groups. When comparing each program to baseline, the program focused on salt reduction was effective in lowering BP following a 12-week intervention with a mean change of -2.5 mm Hg in SBP (95% CI, -4.1 to -0.8) and - 2.7 mm Hg in DBP (95% CI, -3.8 to -1.5) in the intention-to-treat (ITT) analysis. In the complete-case (CC) analysis, the mean change was -2.1 mm Hg in SBP (95% CI, -3.7 to -0.5) and - 2.3 mm Hg in DBP (95% CI, -3.4 to -1.1). This effect increases in subjects with high-normal BP or hypertension [SBP - 7.9 mm Hg (95% CI, -12.5 to -3.3); DBP - 7.3 mm Hg (95% CI, -10.2 to -4.4)]. The healthy lifestyle group also exhibited BP improvements after 12 weeks; however, the changes were less pronounced compared to the salt reduction group and were observed only for DBP [mean change of -1.5 mm Hg (95% CI, -2.6 to -0.4) in ITT analysis and - 1.4 mm Hg (95% CI, -2.4 to -0.3) in CC analysis, relative to baseline]. Overall, improvements in Na+/K+ ratio, weight, and Mediterranean diet adherence resulted in clinically significant SBP decreases. Importantly, BP reduction is attributed to improved dietary quality, rather than being solely linked to changes in the Na+/K+ ratio. Conclusion: Salt-focused programs are effective public health tools mainly in managing individuals at high risk of hypertension. Nevertheless, in general, empowerment-based approaches are important strategies for lowering BP, by promoting health literacy that culminates in adherence to the Mediterranean diet and weight reduction.

miRNA-31 Improves Cognition and Abolishes Amyloid-ß Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by progressive memory impairment, behavioral changes, and, ultimately, loss of consciousness and death. Recently, microRNA (miRNA) dysfunction has been associated with increased production and impaired clearance of amyloid-ß (Aß) peptides, whose accumulation is one of the most well-known pathophysiological markers of this disease. In this study, we identified several miRNAs capable of targeting key proteins of the amyloidogenic pathway. The expression of one of these miRNAs, miR-31, previously found to be decreased in AD patients, was able to simultaneously reduce the levels of APP and Bace1 mRNA in the hippocampus of 17-month-old AD triple-transgenic (3xTg-AD) female mice, leading to a significant improvement of memory deficits and a reduction in anxiety and cognitive inflexibility. In addition, lentiviral-mediated miR-31 expression significantly ameliorated AD neuropathology in this model, drastically reducing Aß deposition in both the hippocampus and subiculum. Furthermore, the increase of miR-31 levels was enough to reduce the accumulation of glutamate vesicles in the hippocampus to levels found in non-transgenic age-matched animals. Overall, our results suggest that miR-31-mediated modulation of APP and BACE1 can become a therapeutic option in the treatment of AD.

Oral melanomas in HIV-positive patients: Report of two cases and review of the literature.

Oral melanoma in HIV-positive patients is exceedingly rare, with only two cases reported in the literature published in English. Herein, we report two additional cases of oral melanomas which occurred as oral masses in the upper gingiva and hard palate in 35- and 27-year-old HIV-positive women. Significant thrombocytopenia, anemia, reduced CD4 cells, and high HIV load occurred in both patients. Microscopically, the lesions showed a variable proliferation of fusiform and epithelioid-pigmented cells, with cellular pleomorphism and high mitotic index. The diagnosis of melanoma was supported by positive immunoreactivity for S-100, MelanA, and HMB-45. Both cases had an unfavorable outcome, and the patients died a few months after the initial diagnosis. Because of its rarity, oral melanoma occurring in HIV-positive patients can pose problems in diagnosis and should be clinically distinguished from Kaposi's sarcoma, which is more common in the context of the immunodeficiency syndrome.

Development of an analytical methodology for simultaneous determination of vincristine and doxorubicin in pharmaceutical preparations for oncology by HPLC-UV.

A high-performance liquid chromatography-UV methodology (lambda=230 nm) was developed and validated for the simultaneous determination of vincristine and doxorubicin in pharmaceutical preparations used in oncology. The chromatography was carried out on a C18 column using acetonitrile 90% in water-potassium hydrogenphosphate buffer 50 mM, pH 3.2+/-0.1 (32:68, v/v) as mobile phase at a flow rate of 1.5 mL/min. The method proved to be specific, exact, and accurate, in accordance with the ICH standards, presenting linearity in the 1-5 microg/mL and 5-100 microg/mL intervals, and detection (0.19x0.51 microg/mL) and quantification (0.63x1.7 microg/mL) limits for vincristine and doxorubicin, respectively.

Quantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid Biomarkers.

Cerebrospinal fluid (CSF) biomarkers have been extensively investigated in the Alzheimer's disease (AD) field, and are now being applied in clinical practice. CSF amyloid-beta (Aß1-42), total tau (t-tau), and phosphorylated tau (p-tau) reflect disease pathology, and may be used as quantitative traits for genetic analyses, fostering the identification of new genetic factors and the proposal of novel biological pathways of the disease. In patients, the concentration of CSF Aß1-42 is decreased due to the accumulation of Aß1-42 in amyloid plaques in the brain, while t-tau and p-tau levels are increased, indicating the extent of neuronal damage. To better understand the biological mechanisms underlying the regulation of AD biomarkers, and its relation to AD, we examined the association between 36 selected single nucleotide polymorphisms (SNPs) and AD biomarkers Aß1-42, t-tau, and p-tau in CSF in a cohort of 672 samples (571 AD patients and 101 controls) collected within 10 European consortium centers.Our results highlighted five genes, APOE, LOC100129500, PVRL2, SNAR-I, and TOMM40, previously described as main players in the regulation of CSF biomarkers levels, further reinforcing a role for these in AD pathogenesis. Three new AD susceptibility loci, INPP5D, CD2AP, and CASS4, showed specific association with CSF tau biomarkers. The identification of genes that specifically influence tau biomarkers point out to mechanisms, independent of amyloid processing, but in turn related to tau biology that may open new venues to be explored for AD treatment.

Association of Cerebral Amyloid-ß Aggregation With Cognitive Functioning in Persons Without Dementia.

Importance: Cerebral amyloid-ß aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials. Objective: To investigate whether amyloid-ß aggregation is associated with cognitive functioning in persons without dementia. Design, Setting, and Participants: This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017. Main Outcomes and Measures: Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype. Results: Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P < .001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P < .001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years. Conclusions and Relevance: Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.

Lunar astrobiology: a review and suggested laboratory equipment.

In October of 2005, the European Space Agency (ESA) and Alcatel Alenia Spazio released a "call to academia for innovative concepts and technologies for lunar exploration." In recent years, interest in lunar exploration has increased in numerous space programs around the globe, and the purpose of our study, in response to the ESA call, was to draw on the expertise of researchers and university students to examine science questions and technologies that could support human astrobiology activity on the Moon. In this mini review, we discuss astrobiology science questions of importance for a human presence on the surface of the Moon and we provide a summary of key instrumentation requirements to support a lunar astrobiology laboratory.

Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes.

Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., Aß42, total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF Aß42 levels inversely correlated to VV/TIV in the whole study population (Aß42: r = -0.28; p < 0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p < 0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF Aß42 alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF Aß42 levels.

Mitochondrial dysfunction and caspase activation in rat cortical neurons treated with cocaine or amphetamine.

Drug abuse is associated with brain dysfunction and neurodegeneration, and various recreational drugs induce apoptotic cell death. This study examined the role of the mitochondrial apoptotic pathway in psychostimulant-induced neuronal dysfunction. Using primary neuronal cultures, we observed that amphetamine (IC50=1.40 mM) was more potent than cocaine (IC50=4.30 mM) in inducing cell toxicity. Apoptotic cell death was further evaluated using cocaine and amphetamine concentrations that moderately decreased cell reduction capacity but did not affect plasma membrane integrity. Compared to cocaine, amphetamine highly decreased the mitochondrial membrane potential, as determined using the fluorescent probe rhodamine-123, whereas both drugs decreased mitochondrial cytochrome c. In contrast to amphetamine, cocaine cytotoxicity was partly mediated through effects on the electron transport chain, since cocaine toxicity was ameliorated in mitochondrial DNA-depleted cells lacking mitochondrially encoded electron transport chain subunits. Cocaine and amphetamine induced activation of caspases-2, -3 and -9 but did not affect activity of caspases-6 or -8. In addition, amphetamine, but not cocaine, was associated with the appearance of evident nuclear apoptotic morphology. These events were not accompanied by differences in the release of the apoptosis-inducing factor (AIF) from mitochondria. Our results demonstrate that although both amphetamine and cocaine activate the mitochondrial apoptotic pathway in cortical neurons, amphetamine is more likely to promote apoptosis.

Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers.

INTRODUCTION: Core cerebrospinal fluid (CSF) biomarkers - Aß42, Tau, and phosphorylated Tau (pTau) - have been recently incorporated in the revised criteria for Alzheimer's disease (AD). However, their widespread clinical application lacks standardization. Pre-analytical sample handling and storage play an important role in the reliable measurement of these biomarkers across laboratories. AIM: In this study, we aim to surpass the efforts from previous studies, by employing a multicenter approach to assess the impact of less studied CSF pre-analytical confounders in AD-biomarkers quantification. METHODS: Four different centers participated in this study and followed the same established protocol. CSF samples were analyzed for three biomarkers (Aß42, Tau, and pTau) and tested for different spinning conditions [temperature: room temperature (RT) vs. 4°C; speed: 500 vs. 2000 vs. 3000 g], storage volume variations (25, 50, and 75% of tube total volume), as well as freezing-thaw cycles (up to five cycles). The influence of sample routine parameters, inter-center variability, and relative value of each biomarker (reported as normal/abnormal) was analyzed. RESULTS: Centrifugation conditions did not influence biomarkers levels, except for samples with a high CSF total protein content, where either non-centrifugation or centrifugation at RT, compared to 4°C, led to higher Aß42 levels. Reducing CSF storage volume from 75 to 50% of total tube capacity decreased Aß42 concentration (within analytical CV of the assay), whereas no change in Tau or pTau was observed. Moreover, the concentration of Tau and pTau appears to be stable up to five freeze-thaw cycles, whereas Aß42 levels decrease if CSF is freeze-thawed more than three times. CONCLUSION: This systematic study reinforces the need for CSF centrifugation at 4°C prior to storage and highlights the influence of storage conditions in Aß42 levels. This study contributes to the establishment of harmonized standard operating procedures that will help reducing inter-lab variability of CSF-AD biomarkers evaluation.