The link between autoimmune diseases and obsessive-compulsive and tic disorders: A systematic review.

PubMed

Pérez-Vigil, Ana; Fernández de la Cruz, Lorena; Brander, Gustaf; Isomura, Kayoko; Gromark, Caroline; Mataix-Cols, David

2016-12-01

Immunological factors are increasingly recognized as being important in a range of neuropsychiatric disorders. We aimed to summarize the disperse and often conflicting literature on the potential association between autoimmune diseases (ADs) and obsessive-compulsive disorder (OCD) and tic disorders. We searched PubMed, EMBASE, and PsycINFO for original studies evaluating the relationship between ADs and OCD/tic disorders until July, 13th 2016. Seventy-four studies met inclusion criteria. Overall, the studies were of limited methodological quality. Rates of OCD were higher in rheumatic fever patients who were also affected by its neurological manifestation, Sydenham's chorea. The literature on other ADs was scarce and the findings inconclusive. Few studies examined the association between ADs and tic disorders. A handful of family studies reported elevated rates of ADs in first-degree relatives of individuals with OCD/tic disorders, and vice versa, potentially suggesting shared genetic and/or environmental mechanisms. In conclusion, at present, there is modest evidence for a possible association and familial co-aggregation between ADs and OCD/tic disorders. We offer some suggestions for future research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions.

PubMed

Burns, Christine M; Chen, Kewei; Kaszniak, Alfred W; Lee, Wendy; Alexander, Gene E; Bandy, Daniel; Fleisher, Adam S; Caselli, Richard J; Reiman, Eric M

2013-04-23

To investigate whether higher fasting serum glucose levels in cognitively normal, nondiabetic adults were associated with lower regional cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer disease (AD). This is a cross-sectional study of 124 cognitively normal persons aged 64 ± 6 years with a first-degree family history of AD, including 61 APOEε4 noncarriers and 63 carriers. An automated brain mapping algorithm characterized and compared correlations between higher fasting serum glucose levels and lower [(18)F]-fluorodeoxyglucose-PET rCMRgl measurements. As predicted, higher fasting serum glucose levels were significantly correlated with lower rCMRgl and were confined to the vicinity of brain regions preferentially affected by AD. A similar pattern of regional correlations occurred in the APOEε4 noncarriers and carriers. Higher fasting serum glucose levels in cognitively normal, nondiabetic adults may be associated with AD pathophysiology. Findings suggest that the risk imparted by higher serum glucose levels may be independent of APOEε4 status. This study raises additional questions about the role of the metabolic process in the predisposition to AD and supports the possibility of targeting these processes in presymptomatic AD trials.

A 2000 year varve-based climate record from the central Brooks Range, Alaska

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bird, BW; Abbott, MB; Finney, BP

Varved minerogenic sediments from glacial-fed Blue Lake, northern Alaska, are used to investigate late Holocene climate variability. Varve-thickness measurements track summer temperature recorded at Atigun Pass, located 41 km east at a similar elevation (r (2) = 0.31, P = 0.08). Results indicate that climate in the Brooks Range from 10 to 730 AD (varve year) was warm with precipitation inferred to be higher than during the twentieth century. The varvetemperature relationship for this period was likely compromised and not used in our temperature reconstruction because the glacier was greatly reduced, or absent, exposing sub-glacial sediments to erosion from enhancedmore » precipitation. Varve-inferred summer temperatures and precipitation decreased after 730 AD, averaging 0.4A degrees C above the last millennial average (LMA = 4.2A degrees C) from 730 to 850 AD, and 0.1A degrees C above the LMA from 850 to 980 AD. Cooling culminated between 980 and 1030 AD with temperatures 0.7A degrees C below the LMA. Varve-inferred summer temperatures increased between 1030 and 1620 AD to the LMA, though the period between 1260 and 1350 AD was 0.2A degrees C below the LMA. Although there is no equivalent to the European Medieval Warm Period in the Blue Lake record, two warm intervals occurred from 1350 to 1450 AD and 1500 to 1620 AD (0.4 and 0.3A degrees C above the LMA, respectively). During the Little Ice Age (LIA; 1620 to 1880 AD), inferred summer temperature averaged 0.2A degrees C below the LMA. After 1880 AD, inferred summer temperature increased to 0.8A degrees C above the LMA, glaciers retreated, but aridity persisted based on a number of regional paleoclimate records. Despite warming and glacial retreat, varve thicknesses have not achieved pre-730 AD levels. This reflects limited sediment availability and transport due to a less extensive retreat compared to the first millennium, and continued relative aridity. Overall, the Blue Lake record is similar to varve records from the eastern Canadian Arctic that document a cool LIA and twentieth century warming. However, the occurrence and timing of events, such as the LIA and Medieval Warm Period, varies considerably among records, suggesting heterogeneous climatic patterns across the North American Arctic.« less

Relationship between Delusion of Theft and Cognitive Functions in Patients with Mild Alzheimer's Disease.

PubMed

Na, Hae-Ran; Kang, Dong Woo; Woo, Young-Sup; Bahk, Won-Myong; Lee, Chang-Uk; Lim, Hyun Kook

2018-04-01

Although delusion of theft (DT) is the most frequent type of delusion in Alzheimer's disease (AD), its relationship to cognitive functions remains unclear. The aim of this study was to demonstrate the relationship between DT and cognitive functions in mild AD. Two hundred eighty-nine mild AD patients were enrolled in this study. These subjects were classified into three groups: patients with no delusions (ND, n=82), patients with paranoid delusions (PD, n=114) and patients with DT (n=93). Cognitive functions and their associations with the degree of delusion were compared among the three groups. The results showed that verbal Fluency scores were significantly lower in the PD group than in the DT and ND groups. Word List Recall scores were significantly lower in the DT group than in the PD and ND groups. Interestingly, delusion severity measured with the Neuropsychiatric Inventory delusion subscale correlated negatively with the Word List Recall scores in the DT group. In this study, we demonstrated that episodic memory functions in mild AD patients were associated with DT, but not with PD. Further studies might be needed to clarify the pathophysiology of delusions associated with AD.

Relationship between Delusion of Theft and Cognitive Functions in Patients with Mild Alzheimer’s Disease

PubMed Central

Na, Hae-Ran; Kang, Dong Woo; Woo, Young-Sup; Bahk, Won-Myong; Lee, Chang-Uk; Lim, Hyun Kook

2018-01-01

Although delusion of theft (DT) is the most frequent type of delusion in Alzheimer’s disease (AD), its relationship to cognitive functions remains unclear. The aim of this study was to demonstrate the relationship between DT and cognitive functions in mild AD. Two hundred eighty-nine mild AD patients were enrolled in this study. These subjects were classified into three groups: patients with no delusions (ND, n=82), patients with paranoid delusions (PD, n=114) and patients with DT (n=93). Cognitive functions and their associations with the degree of delusion were compared among the three groups. The results showed that verbal Fluency scores were significantly lower in the PD group than in the DT and ND groups. Word List Recall scores were significantly lower in the DT group than in the PD and ND groups. Interestingly, delusion severity measured with the Neuropsychiatric Inventory delusion subscale correlated negatively with the Word List Recall scores in the DT group. In this study, we demonstrated that episodic memory functions in mild AD patients were associated with DT, but not with PD. Further studies might be needed to clarify the pathophysiology of delusions associated with AD. PMID:29669410

Shape abnormalities of the striatum in Alzheimer's disease.

PubMed

de Jong, Laura W; Ferrarini, Luca; van der Grond, Jeroen; Milles, Julien R; Reiber, Johan H C; Westendorp, Rudi G J; Bollen, Edward L E M; Middelkoop, Huub A M; van Buchem, Mark A

2011-01-01

Postmortem studies show pathological changes in the striatum in Alzheimer's disease (AD). Here, we examine the surface of the striatum in AD and assess whether changes of the surface are associated with impaired cognitive functioning. The shape of the striatum (n. accumbens, caudate nucleus, and putamen) was compared between 35 AD patients and 35 individuals without cognitive impairment. The striatum was automatically segmented from 3D T1 magnetic resonance images and automatic shape modeling tools (Growing Adaptive Meshes) were applied for morphometrical analysis. Repeated permutation tests were used to identify locations of consistent shape deformities of the striatal surface in AD. Linear regression models, corrected for age, gender, educational level, head size, and total brain parenchymal volume were used to assess the relation between cognitive performance and local surface deformities. In AD patients, differences of shape were observed on the medial head of the caudate nucleus and on the ventral lateral putamen, but not on the accumbens. The head of the caudate nucleus and ventral lateral putamen are characterized by extensive connections with the orbitofrontal and medial temporal cortices. Severity of cognitive impairment was associated with the degree of deformity of the surfaces of the accumbens, rostral medial caudate nucleus, and ventral lateral putamen. These findings provide evidence for the hypothesis that in AD primarily associative and limbic cerebral networks are affected.

Getting the hang of it: preferential gist over verbatim story recall and the roles of attentional capacity and the episodic buffer in Alzheimer disease.

PubMed

Foldi, Nancy S

2011-01-01

Story recall in Alzheimer disease (AD) is typically used as a measure of episodic memory, but the degree to which recall is dependent on available attentional resources is not fully understood. The current study investigated how measures of attention were associated to verbatim recall (exact reproduction) or gist recall (relevant semantic meaning). Sixteen participants with AD and 16 age-matched healthy older adults recalled a story on immediate free recall and recognition. Controls recalled more units overall than AD. A group X response interaction revealed more gist than verbatim recall in AD, but those with mild disease generated approximately the same number gist responses as controls. For each group, qualitatively different attentional resources were associated with recall units. In controls, verbatim units correlated positively with primacy serial position items of the California Verbal Learning Test II (CVLTII), suggesting that episodic buffer resources may be associated with story recall. In AD, gist units were positively correlated with digits forward, but inversely related to the CVLTII primacy region items, suggesting reliance on low-level capacity resources. Possible explanations of the impaired performance in AD may be a bias in favor of gist processing, poor verbatim encoding, and/or processing failure at the level of the episodic buffer.

Exploring differences in smokers' perceptions of the effectiveness of cessation media messages.

PubMed

Davis, Kevin C; Nonnemaker, James M; Farrelly, Matthew C; Niederdeppe, Jeff

2011-01-01

To examine which types of cessation-focused advertisements are associated with perceived advertisement effectiveness among smokers and to assess whether key smoker characteristics (ie, cigarette consumption, desire to quit and past quit attempts) influence perceived effectiveness of different types of cessation ads. We used data from the New York Media Tracking Survey Online, a web survey of 7060 adult smokers in New York. Participants were exposed to four categories of cessation ads: (1) why to quit--graphic images, (2) why to quit--testimonial, (3) how to quit and (4) anti-industry. Perceived ad effectiveness was measured with a four-item scale assessing the degree to which participants thought the ads made them stop and think, grabbed their attention, were believable and made them want to quit smoking. We categorised smokers based on cigarette consumption, desire to quit and past quit attempts. We used multivariable analyses to examine how smoker characteristics and category of cessation ads predict perceived ad effectiveness. Ads using the 'why to quit' strategy with either graphic images or personal testimonials were perceived as more effective than the other ad categories. Smokers who had less desire to quit or had not tried quitting in the past 12 months responded significantly less favourably to all types of cessation ads tested. Greater cigarette consumption was also associated with lower perceived effectiveness, but this association was smaller in magnitude. Tobacco control programmes that utilise cessation-focus advertising should focus relatively more on ads that adopt the 'why to quit' strategy with either graphic images or personal testimonials.

Confined phase in the real time formalism and the fate of the world behind the horizon

NASA Astrophysics Data System (ADS)

Furuuchi, Kazuyuki

2006-02-01

In the real time formulation of finite temperature field theories, one introduces an additional set of fields (type-2 fields) associated to each field in the original theory (type-1 field). In [J. M. Maldacena, J. High Energy Phys., JHEPFG, 1029-8479 04 (2003) 021., 10.1088/1126-6708/2003/04/021], in the context of the anti-de Sitter (AdS)-conformal field theories (CFT) correspondence, Maldacena interpreted type-2 fields as living on a boundary behind the black hole horizon. However, below the Hawking-Page transition temperature, the thermodynamically preferred configuration is the thermal AdS without a black hole, and hence there are no horizon and boundary behind it. This means that when the dual gauge theory is in confined phase, the type-2 fields cannot be associated with the degrees of freedom behind the black hole horizon. I argue that in this case the role of the type-2 fields is to make up bulk type-2 fields of classical closed string field theory on AdS at finite temperature in the real time formalism.

Effect of modified atmosphere packaging on the shelf life of sliced wheat flour bread.

PubMed

Rodríguez, M; Medina, L M; Jordano, R

2000-08-01

The application of modified atmospheres packaging (MAP) of sliced bread with different aw, moisture content and pH values, with or without preservative added (calcium propionate) and at different storage temperatures, has been studied with the aim of establishing the effect of MAP on the shelf-life of the selected product. Four atmospheres were tested per batch: 100% N2, 20% CO2/80% N2, 50% CO2/50% N2 and a standard air control. In samples without added preservative in CO2:N2 (50:50), the increases in shelf life were 117% and 158% at 22-25 degrees C and 15-20 degrees C, respectively. In samples with added preservative in 100% N2, shelf life was increased by 116%. Samples with added preservative in 20% CO2:80% N2 increased shelf life by 150% and 131% at 22-25 degrees C and 15-20 degrees C, respectively. By increasing the CO2 concentration to 50%, the increases in shelf life of the samples with added preservative were 167% and 195% at 22-25 degrees C and 15-20 degrees C, respectively.

Psychological, behavioral and social effects of disclosing Alzheimer's disease biomarkers to research participants: a systematic review.

PubMed

Bemelmans, S A S A; Tromp, K; Bunnik, E M; Milne, R J; Badger, S; Brayne, C; Schermer, M H; Richard, E

2016-11-10

Current Alzheimer's disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants. We performed a systematic literature search in eight scientific databases. Three independent reviewers screened the identified records and selected relevant articles. Results extracted from the included articles were aggregated and presented per effect group. Fourteen studies met the inclusion criteria and were included in the data synthesis. None of the identified studies examined the effects of disclosing nongenetic biomarkers. All studies but one concerned the disclosure of APOE genotype and were conducted in the USA. Study populations consisted largely of cognitively healthy first-degree relatives of AD patients. In this group, disclosure of an increased risk was not associated with anxiety, depression or changes in perceived risk in relation to family history. Disclosure of an increased risk did lead to an increase in specific test-related distress levels, health-related behavior changes and long-term care insurance uptake and possibly diminished memory functioning. In cognitively healthy research participants with a first-degree relative with AD, disclosure of APOE ε4-positivity does not lead to elevated anxiety and depression levels, but does increase test-related distress and results in behavior changes concerning insurance and health. We did not find studies reporting the effects of disclosing nongenetic biomarkers and only one study included people without a family history of AD. Empirical studies on the effects of disclosing nongenetic biomarkers and of disclosure to persons without a family history of AD are urgently needed. PROSPERO international prospective register for systematic reviews CRD42016035388 . Registered 19 February 2016.

Why AD Graduates Choose Their First Jobs.

ERIC Educational Resources Information Center

Smokvina, Gloria J.; Bratt, Ellen M.

Reasons for the job selections of 64 associate degree nursing graduates were examined in a pilot study at Purdue University. The basic research question was whether nursing graduates initially view "maintenance" or motivational factors as more important. Based on Herzberg's theory of motivation, information is provided on maintenance or hygiene…

False recollection of emotional pictures in Alzheimer's disease.

PubMed

Gallo, David A; Foster, Katherine T; Wong, Jessica T; Bennett, David A

2010-10-01

Alzheimer's Disease (AD) can reduce the effects of emotional content on memory for studied pictures, but less is known about false memory. In healthy adults, emotionally arousing pictures can be more susceptible to false memory effects than neutral pictures, potentially because emotional pictures share conceptual similarities that cause memory confusions. We investigated these effects in AD patients and healthy controls. Participants studied pictures and their verbal labels, and then picture recollection was tested using verbal labels as retrieval cues. Some of the test labels had been associated with a picture at study, whereas other had not. On this picture recollection test, we found that both AD patients and controls incorrectly endorsed some of the test labels that had not been studied with pictures. These errors were associated with medium to high levels of confidence, indicating some degree of false recollection. Critically, these false recollection judgments were greater for emotional compared to neutral items, especially for positively valenced items, in both AD patients and controls. Dysfunction of the amygdala and hippocampus in early AD may impair recollection, but AD did not disrupt the effect of emotion on false recollection judgments. Copyright © 2010 Elsevier Ltd. All rights reserved.

Is family history of alcohol dependence a risk factor for disturbed sleep in alcohol dependent subjects?

PubMed

Chakravorty, Subhajit; Chaudhary, Ninad S; Morales, Knashawn; Grandner, Michael A; Oslin, David W

2018-07-01

Disturbed sleep and a family history of alcohol dependence (AD) are risk factors for developing AD, yet the underlying relationship between them is unclear among individuals with AD. Understanding these inherited associations will help us not only identify risk for development of these comorbid disorders, but also individualize treatment at this interface. We evaluated whether a first-degree family history of AD (FH+) was a risk factor for sleep continuity disturbance in patients with AD. We also evaluated whether alcohol use or mood disturbance moderated the relationship between FH and sleep. We analyzed cross-sectional baseline data from an alcohol clinical trial in a sample of individuals with AD (N = 280). Their family history of AD among nuclear family members, sleep complaints, alcohol use (over the last 90 days), and mood disturbance were assessed using the Family History Interview for Substance and Mood Disorders, Medical Outcomes Study Sleep Scale, Time Line Follow-Back Interview, and Profile of Mood States-Short Form, respectively. A FH + status (65% of subjects) was significantly associated with lower model estimated mean sleep adequacy (β = - 7.05, p = 0.02) and sleep duration (β = - 0.38, p = 0.04) scale scores. FH was not associated with sleep disturbance scale. No significant moderating effect involving alcohol use or mood disturbance was seen. Family history of AD is a unique risk factor for sleep complaints in AD. Non-restorative sleep and sleep duration may be noteworthy phenotypes to help probe for underlying genotypic polymorphisms in these comorbid disorders. Published by Elsevier B.V.

Does where you shop or who you are predict what you eat?: The role of stores and individual characteristics in dietary intake.

PubMed

Vaughan, Christine A; Collins, Rebecca; Ghosh-Dastidar, Madhumita; Beckman, Robin; Dubowitz, Tamara

2017-07-01

Interventions to address diet, a modifiable risk factor for diabetes, cancer, and cardiovascular disease, have increasingly emphasized the influence of the physical environment on diet, while more traditional approaches have focused on individual characteristics. We examined environmental and individual influences on diet to understand the role of both. Household interviews were conducted in 2011 with 1372 individuals randomly selected from two low-income, predominantly African American neighborhoods in Pittsburgh, PA. Participants reported their sociodemographic characteristics, food shopping behavior, and dietary intake. Both food shopping frequency at different types of food stores and sociodemographic characteristics showed significant associations with diet in adjusted regression models. More frequent shopping at convenience and neighborhood stores and being younger, male, without a college degree, and receiving SNAP benefits were associated with greater intake of sugar-sweetened beverages (SSBs), added sugars, and discretionary fats. Being older, male, and having a college degree were associated with greater intake of fruits and vegetables. However, while food shopping behavior and sociodemographic characteristics accounted for similar amounts of nonoverlapping variance in fruit and vegetable intake, food shopping behavior accounted for much less variance, and little unique variance, in SSBs, added sugars, and discretionary fats in models with sociodemographic characteristics. The current study reinforces the need for policies and interventions at both the environmental and individual levels to improve diet in food desert residents. Individual interventions to address food choices associated with certain sociodemographic characteristics might be particularly important for curbing intake of SSBs, added sugars, and discretionary fats. Copyright © 2017 Elsevier Inc. All rights reserved.

The Trouble with Online Undergraduate Business Degrees In Traditional Regional Universities

ERIC Educational Resources Information Center

Wright, M. Keith

2014-01-01

Because of the surging demand for undergraduate business degrees and the increasing availability of effective online educational content, many traditional regional universities have added, or are now considering adding, online undergraduate business degree programs to their classroom programs. Through a review of the literature bearing on that…

Degree of Bilingualism Predicts Age of Diagnosis of Alzheimer’s Disease in Low-Education but not in Highly-Educated Hispanics

PubMed Central

Gollan, Tamar H.; Salmon, David P.; Montoya, Rosa I.; Galasko, Douglas R.

2011-01-01

The current study investigated the relationship between bilingual language proficiency and onset of probable Alzheimer’s disease (AD) in 44 Spanish-English bilinguals at the UCSD Alzheimer’s Disease Research Center. Degree of bilingualism along a continuum was measured using Boston Naming Test (BNT) scores in each language. Higher degrees of bilingualism were associated with increasingly later age-of-diagnosis (and age of onset of symptoms), but this effect was driven by participants with low education level (a significant interaction between years of education and bilingualism) most of whom (73%) were also Spanish-dominant. Additionally, only objective measures (i.e., BNT scores), not self-reported degree of bilingualism, predicted age-of-diagnosis even though objective and self-reported measures were significantly correlated. These findings establish a specific connection between knowledge of two languages and delay of AD onset, and demonstrate that bilingual effects can be obscured by interactions between education and bilingualism, and by failure to obtain objective measures of bilingualism. More generally, these data support analogies between the effects of bilingualism and “cognitive reserve” and suggest an upper limit on the extent to which reserve can function to delay dementia. PMID:22001315

Data on Second Majors in Language and Literature, 2001-13

ERIC Educational Resources Information Center

Modern Language Association, 2015

2015-01-01

Data on second majors were added to the degree completions component of the United States Department of Education's Integrated Postsecondary Education Data System (IPEDS) in 2001 and were made available on the National Science Foundation's "WebCASPAR" Web site (https://webcaspar.nsf.gov/) in 2010. The Modern Language Association's first…

Aging is associated with altered inflammatory, arachidonic acid cascade and synaptic markers, influenced by epigenetic modifications, in the human frontal cortex

PubMed Central

Keleshian, Vasken L.; Modi, Hiren R.; Rapoport, Stanley I.; Rao, Jagadeesh S.

2013-01-01

Aging is a risk factor for Alzheimer’s disease (AD) and is associated with cognitive decline. However, underlying molecular mechanisms of brain aging are not clear. Recent studies suggest epigenetic influences on gene expression in AD, since DNA methylation levels influence protein and mRNA expression in postmortem AD brain. We hypothesized that some of these changes occur with normal aging. To test this hypothesis, we measured markers of the arachidonic acid (AA) cascade, neuroinflammation, pro- and anti-apoptosis factors, and gene specific epigenetic modifications in postmortem frontal cortex from nine middle-aged (41 ± 1 (SEM) years) and ten aged subjects (70 ± 3 years). The aged compared with middle-aged brain showed elevated levels of neuroinflammatory and AA cascade markers, altered pro and anti-apoptosis factors and loss of synaptophysin. Some of these changes correlated with promoter hypermethylation of BDNF, CREB, and synaptophysin and hypomethylation of BAX. These molecular alterations in aging are different from or more subtle than changes associated with AD pathology. The degree to which they are related to changes in cognition or behavior during normal aging remains to be evaluated. PMID:23336521

Accuracy and feasibility of using an electrogoniometer for measuring simple thumb movements.

PubMed

Jonsson, Per; Johnson, Peter W; Hagberg, Mats

2007-05-01

The aim of this study was to determine the accuracy and feasibility of using an electrogoniometer (Model SG 110; Biometrics, Gwent, UK) for measuring simple thumb movements. Thumb disorders have been associated with the use of hand held devices such as mobile phones and these devices have become an integral part of modern life. In 15 young subjects, the measurements of eight flexion/extension (Flex/Ext) and adduction/abduction (Ad/Ab) thumb positions were compared between a thumb-mounted electrogoniometer and manual goniometer (which was taken as the benchmark). Group mean electrogoniometric measurement errors were below 4 degrees and 5 degrees for Ad/Ab and Flex/Ext measurements, respectively. During mobile phone use, the electrogoniometers measured differences in maximal joint angle postures, which appeared to be related to differences in mobile phone size. High movement velocities may increase the risk of musculoskeletal injury and the results indicated that Ad/Ab movements were twice the speed of Flex/Ext movements during mobile phone use. Electrogoniometers have utility for studying thumb movements during mobile phone use and may be used to evaluate other thumb-based input devices.

Development of Ag-Pd-Au-Cu alloy for multiple dental applications. Part 1. Effects of Pd and Cu contents, and addition of Ga or Sn on physical properties and bond with ultra-low fusing ceramic.

PubMed

Goto, S; Miyagawa, Y; Ogura, H

2000-09-01

Ag-Pd-Au-Cu quaternary alloys consisting of 30-50% Ag, 20-40% Pd, 10-20% Cu and 20% Au (mother alloys) were prepared. Then 5% Sn or 5% Ga was added to the mother alloy compositions, and another two alloy systems (Sn-added alloys and Ga-added alloys) were also prepared. The bond between the prepared alloys and an ultra-low fusing ceramic as well as their physical properties such as the solidus point, liquidus point and the coefficient of thermal expansion were evaluated. The solidus point and liquidus point of the prepared alloys ranged from 802 degrees C to 1142 degrees C and from 931 degrees C to 1223 degrees C, respectively. The coefficient of thermal expansion ranged from 14.6 to 17.1 x 10(-6)/degrees C for the Sn- and Ga-added alloys. In most cases, the Pd and Cu contents significantly influenced the solidus point, liquidus point and coefficient of thermal expansion. All Sn- and Ga-added alloys showed high area fractions of retained ceramic (92.1-100%), while the mother alloy showed relatively low area fractions (82.3%) with a high standard deviation (20.5%). Based on the evaluated properties, six Sn-added alloys and four Ga-added alloys among the prepared alloys were suitable for the application of the tested ultra-low fusing ceramic.

Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

PubMed Central

Gómez Ravetti, Martín; Rosso, Osvaldo A.; Berretta, Regina; Moscato, Pablo

2010-01-01

Background Alzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive. Methodology/Principal Findings We have reanalysed a microarray dataset contributed in 2004 by Blalock et al. of 31 samples corresponding to hippocampus gene expression from 22 AD subjects of varying degree of severity and 9 controls. Instead of only relying on correlations of gene expression with the associated MMSE and NFT measures, and by using modern bioinformatics methods based on information theory and combinatorial optimization, we uncovered a 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD. The signature reveals alterations in calcium, insulin, phosphatidylinositol and wnt-signalling. Among the most correlated gene probes with AD severity we found those linked to synaptic function, neurofilament bundle assembly and neuronal plasticity. Conclusions/Significance A transcription factors analysis of 1,372-probe signature reveals significant associations with the EGR/KROX family of proteins, MAZ, and E2F1. The gene homologous of EGR1, zif268, Egr-1 or Zenk, together with other members of the EGR family, are consolidating a key role in the neuronal plasticity in the brain. These results indicate a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation. PMID:20405009

New Rage on Campus: E-Commerce Degrees.

ERIC Educational Resources Information Center

Dobbs, Kevin

1999-01-01

As electronic commerce expands, higher education attempts to keep up with the demand for instruction. Some universities have added a concentration in e-commerce to their master of business administration program and others are adding majors, certifications, or degrees. (JOW)

The Evolution of General Education Requirements at Prince George's Community College.

ERIC Educational Resources Information Center

Barshay, Robert; Cant, Catherine

In August 1981, a task force was created at Maryland's Prince George's Community College (PGCC) to analyze the college's General Education (GE) requirements in terms of their appropriateness as a major component of Associate Degree (AD) programs. Rather than increase the number of GE requirements, the task force sought to identify the skills,…

Impact of solar ultraviolet radiation on atopic dermatitis symptoms in young children: A longitudinal study.

PubMed

Kim, Young-Min; Kim, Jihyun; Lee, Ji Young; Kim, Minji; Kim, Hyunmi; Jung, Kwon; Eo, Soomi; Ahn, Mijin; Ahn, Kangmo

2017-09-01

There are controversial data about the effects of sun exposure on atopic dermatitis (AD). We evaluated the association between solar ultraviolet radiation (UVR) exposure and AD symptoms in children. Eighty-two children under 6 years (48 boys and 34 girls) with AD living in Seoul, Korea, were enrolled and followed for 12 months between September 2013 and August 2014. Daily symptoms were recorded to describe the degree of itching, sleep disturbance, erythema, dryness, oozing, and edema. We assessed solar UVR by measuring radiation heat flux over the 290-400 nm wavelength range using thermopiles. A generalized linear mixed model and a generalized additive mixed model were used to evaluate the effects of UVR exposure on AD symptoms after adjusting for age, sex, outdoor temperature, outdoor humidity, and ambient air pollution. Symptom records of 12 915 person-days were analyzed. UVR showed a significantly positive relationship with AD symptoms. Over the study period, an increase in UVR by 10 W/cm 2 was associated with a 1.46% increase in AD symptoms (95% CI: 0.85-2.07) on the exposure day. An increase in the 6-day average level of UVR of the previous 5 days and the current day by 10 W/cm 2 was associated with a 3.58% (95% CI: 2.60-4.56) increase in AD symptoms. UVR exposure significantly increased AD symptoms in autumn, but decreased them in winter. Atopic dermatitis symptoms in children are likely to be affected by exposure to solar UVR with a cumulative effect, and this effect is different according to season. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Degree of bilingualism predicts age of diagnosis of Alzheimer's disease in low-education but not in highly educated Hispanics.

PubMed

Gollan, Tamar H; Salmon, David P; Montoya, Rosa I; Galasko, Douglas R

2011-12-01

The current study investigated the relationship between bilingual language proficiency and onset of probable Alzheimer's disease (AD) in 44 Spanish-English bilinguals at the UCSD Alzheimer's Disease Research Center. Degree of bilingualism along a continuum was measured using Boston Naming Test (BNT) scores in each language. Higher degrees of bilingualism were associated with increasingly later age-of-diagnosis (and age of onset of symptoms), but this effect was driven by participants with low education level (a significant interaction between years of education and bilingualism) most of whom (73%) were also Spanish-dominant. Additionally, only objective measures (i.e., BNT scores), not self-reported degree of bilingualism, predicted age-of-diagnosis even though objective and self-reported measures were significantly correlated. These findings establish a specific connection between knowledge of two languages and delay of AD onset, and demonstrate that bilingual effects can be obscured by interactions between education and bilingualism, and by failure to obtain objective measures of bilingualism. More generally, these data support analogies between the effects of bilingualism and "cognitive reserve" and suggest an upper limit on the extent to which reserve can function to delay dementia. Copyright © 2011 Elsevier Ltd. All rights reserved.

Increased Susceptibility to Oxidative Death of Lymphocytes from Alzheimer Patients Correlates with Dementia Severity

PubMed Central

Ponce, Daniela P.; Salech, Felipe; SanMartin, Carol D.; Silva, Monica; Xiong, Chengjie; Roe, Catherine M.; Henriquez, Mauricio; Quest, Andrew F.; Behrens, Maria I.

2015-01-01

We previously reported on enhanced susceptibility to death of lymphocytes from Alzheimer’s disease (AD) patients when exposed to hydrogen peroxide (H2O2)-induced oxidative stress and an increased resistance to death in those of patients with a history of skin cancer. This is consistent with our hypothesis proposing that the cellular machinery controlling cell death is deregulated in opposite directions in Alzheimer’s disease (AD) and cancer, to explain the inverse association observed in epidemiological studies. Here we investigated whether the observed increased susceptibility correlates with the degree of dementia severity. Peripheral lymphocytes from 23 AD patients, classified using the Clinical Dementia Rating (CDR) into severe dementia (CDR 3, n=10) and mild-to-moderate dementia (CDR 1–2, n=13), and 15 healthy controls (HC) (CDR 0), were exposed to H2O2 for 20 hours. Lymphocyte death was determined by flow cytometry and propidium iodide staining. The greatest susceptibility to H2O2-induced death was observed for lymphocytes from severe dementia patients, whereas those with mild-to-moderate dementia exhibited intermediate values, compared to healthy controls. A significant increase in the apoptosis/necrosis ratio was found in AD patients. Poly (ADP-ribosyl) polymerase-1 (PARP-1) inhibition significantly protected from H2O2-induced death of lymphocytes, whereby a lower degree of protection was observed in severe AD patients. Moreover, inhibition of PARP-1 abolished the differences in apoptosis/necrosis ratios observed between the three groups of patients. These results support the notion that AD is a systemic disorder, whereby enhanced susceptibility to H2O2-induced death in peripheral lymphocytes correlates with dementia severity and enhanced death in AD patients is attributable to a PARP-dependent increase in the apoptosis/necrosis ratio. PMID:25274115

Fully automated structural MRI of the brain in clinical dementia workup.

PubMed

Persson, Karin; Selbæk, Geir; Brækhus, Anne; Beyer, Mona; Barca, Maria; Engedal, Knut

2017-06-01

Background The dementia syndrome has been regarded a clinical diagnosis but the focus on supplemental biomarkers is increasing. An automatic magnetic resonance imaging (MRI) volumetry method, NeuroQuant® (NQ), has been developed for use in clinical settings. Purpose To evaluate the clinical usefulness of NQ in distinguishing Alzheimer's disease dementia (AD) from non-dementia and non-AD dementia. Material and Methods NQ was performed in 275 patients diagnosed according to the criteria of ICD-10 for AD, vascular dementia and Parkinson's disease dementia (PDD); the Winblad criteria for mild cognitive impairment; the Lund-Manchester criteria for frontotemporal dementia; and the revised consensus criteria for Lewy body dementia (LBD). Receiver operating curve (ROC) analyses with calculation of area under the curve (AUC) and regression analyses were carried out. Results Forebrain parenchyma (AUC 0.82), hippocampus (AUC 0.80), and inferior lateral ventricles (AUC 0.78) yielded the highest AUCs for AD/non-dementia discrimination. Only hippocampus (AUC 0.62) and cerebellum (AUC 0.67) separated AD from non-AD dementia. Cerebellum separated AD from PDD-LBD (AUC 0.83). Separate multiple regression analyses adjusted for age and gender, showed that memory (CERAD 10-word delayed recall) (beta 0.502, P < 0.001) was more strongly associated to the hippocampus volume than the diagnostic distinction of AD versus non-dementia (beta -0.392, P < 0.001). Conclusion NQ measures could separate AD from non-dementia fairly well but generally poorer from non-AD dementia. Degree of memory impairment, age, and gender, but not diagnostic distinction, were associated to the hippocampus volume in adjusted analyses. Surprisingly, cerebellum was found relevant in separating AD from PDD-LBD.

Perioperative fever and outcome in surgical patients with aneurysmal subarachnoid hemorrhage.

PubMed

Todd, Michael M; Hindman, Bradley J; Clarke, William R; Torner, James C; Weeks, Julie B; Bayman, Emine O; Shi, Qian; Spofford, Christina M

2009-05-01

We examined the incidence of perioperative fever and its relationship to outcome among patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial. One thousand patients with initial World Federation of Neurological Surgeons grades of I to III undergoing clipping of intracranial aneurysms after subarachnoid hemorrhage were randomized to intraoperative normothermia (36 degrees C-37 degrees C) or hypothermia (32.5 degrees C-33.5 degrees C). Fever (> or =38.5 degrees C) and other complications (including infections) occurring between admission and discharge (or death) were recorded. Functional and neuropsychologic outcomes were assessed 3 months postoperatively. The primary outcome variable for the trial was dichotomized Glasgow Outcome Scale (good outcome versus all others). Fever was reported in 41% of patients. In 97% of these, fever occurred in the postoperative period. The median time from surgery to first fever was 3 days. All measures of outcome were worse in patients who developed fever, even in those without infections or who were World Federation of Neurological Surgeons grade I. Logistic regression analyses were performed to adjust for differences in preoperative factors (e.g., age, Fisher grade, initial neurological status). This demonstrated that fever continued to be significantly associated with most outcome measures, even when infection was added to the model. An alternative stepwise model selection process including all fever-related measures from the preoperative and intraoperative period (e.g., hydrocephalus, duration of surgery, intraoperative blood loss) resulted in the loss of significance for dichotomized Glasgow Outcome Scale, but significant associations between fever and several other outcome measures remained. After adding postoperative delayed ischemic neurological deficits to the model, only worsened National Institutes of Health Stroke Scale score, Barthel Activities of Daily Living index, and discharge destination (home versus other) remained independently associated with fever. These findings suggest that fever is associated with worsened outcome in surgical subarachnoid hemorrhage patients, although, because the association between fever and the primary outcome measure for the trial is dependent on the covariates used in the analysis (particularly operative events and delayed ischemic neurological deficits), we cannot rule out the possibility that fever is a marker for other events. Only a formal trial of fever treatment or prevention can address this issue.

Gray Matter Network Disruptions and Regional Amyloid Beta in Cognitively Normal Adults.

PubMed

Ten Kate, Mara; Visser, Pieter Jelle; Bakardjian, Hovagim; Barkhof, Frederik; Sikkes, Sietske A M; van der Flier, Wiesje M; Scheltens, Philip; Hampel, Harald; Habert, Marie-Odile; Dubois, Bruno; Tijms, Betty M

2018-01-01

The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD. In this study, we examined the regional relationship between amyloid aggregation measured with positron emission tomography (PET) and gray matter network measures in elderly subjects with subjective memory complaints. Single-subject gray matter networks were extracted from T1-weigthed structural MRI in cognitively normal subjects ( n = 318, mean age 76.1 ± 3.5, 64% female, 28% amyloid positive). Degree, clustering, path length and small world properties were computed. Global and regional amyloid load was determined using [ 18 F]-Florbetapir PET. Associations between standardized uptake value ratio (SUVr) values and network measures were examined using linear regression models. We found that higher global SUVr was associated with lower clustering ( β = -0.12, p < 0.05), and small world values ( β = -0.16, p < 0.01). Associations were most prominent in orbito- and dorsolateral frontal and parieto-occipital regions. Local SUVr values showed less anatomical variability and did not convey additional information beyond global amyloid burden. In conclusion, we found that in cognitively normal elderly subjects, increased global amyloid pathology is associated with alterations in gray matter networks that are indicative of incipient network breakdown towards AD dementia.

Improving the BC Transfer Experience: Feedback from Students. Research Results

ERIC Educational Resources Information Center

British Columbia Council on Admissions and Transfer, 2012

2012-01-01

The BC Council on Admissions and Transfer is always seeking ways to improve the transfer system for the benefit of students. Doing so is often informed by research in one form or another. Questions were added to the 2011 Diploma, Associate Degree, and Certificate Student Outcomes (DACSO) survey to help us gain a better understanding of why some…

Undergraduate Observations of Separation and Position Angle of Double Stars WDS J05460+2119AB (ARY 6AD and ARY 6 AE) at Manzanita Observatory (Abstract)

NASA Astrophysics Data System (ADS)

HOffert, M. J.; Weise, E.; Clow, J.; Hirzel, J.; Leeder, B.; Molyneux, S.; Scutti, N.; Spartalis, S.; Takuhara, C.

2014-12-01

(Abstract only) Six beginning astronomy students, part of an undergraduate stellar astronomy course, one advanced undergraduate student assistant, and a professor measured the position angles and separations of Washington Double Stars (WDS) J05460+2119 (= WDS J05460+2119AB; also known as ARY 6 AD and ARY 6 AE). The measurements were made at the Manzanita Observatory (116º 20' 42" W, 32º 44' 5" N) of the Tierra Astronomical Institute on 10 Blackwood Road in Boulevard, California (www.youtube.com/watch?v=BHVdeMGBGDU), at an elevation of 4,500 ft. A Celestron 11-inch HD Edge telescope was used to measure the position angles and separations of ARY 6 AD and ARY 6 AE. The averages of our measurements are as follows: separation AD: trial 1 124.1 arcseconds and trial 2 124.5 arcseconds; separation AE: trial 1 73.3 arcseconds and trial 2 73.8 arcseconds. The averages of positon angle for AD: trial 1 159.9 degrees and trial 2 161.3 degrees, for AE: trial 1 232.6 degrees and trial 2 233.7 degrees.

Undergraduate Observations of Separation and Position Angle of Double Stars ARY 6 AD and ARY 6 AE at Manzanita Observatory

NASA Astrophysics Data System (ADS)

Hoffert, Michael J.; Weise, Eric; Clow, Jenna; Hirzel, Jacquelyn; Leeder, Brett; Molyneux, Scott; Scutti, Nicholas; Spartalis, Sarah; Tokuhara, Corey

2014-05-01

Six beginning astronomy students, part of an undergraduate stellar astronomy course, one advanced undergraduate student assistant, and a professor measured the position angles and separations of Washington Double Stars (WDS) 05460 + 2119 (also known as ARY 6 AD and ARY 6 AE). The measurements were made at the Manzanita Observatory (116° 20'42" W, 32° 44' 5" N) of the Tierra Astronomical Institute on 10 Blackwood Rd. in Boulevard, California (www.youtube.com/watch?v=BHVdcMGBGDU), at an elevation of 4,500 ft. A Celestron 11" HD Edge telescope was used to measure the position angles and separations of ARY 6 AD and ARY 6 AE. The averages of our measurements are as follows: separation AD: trial 1 124.1 arcseconds and trial 2 124.5 arcseconds. The average of separation for AE: trial 1 73.3 arcseconds and trial 2 73.8 arcseconds. The averages of position angle for AD: trial 1 159.9 degrees and trial 2 161.3 degrees. The averages of position angle for AE: trial 1 232.6 degrees and trial 2 233.7 degrees.

Concordance between (99m)Tc-ECD SPECT and 18F-FDG PET interpretations in patients with cognitive disorders diagnosed according to NIA-AA criteria.

PubMed

Ito, Kimiteru; Shimano, Yasumasa; Imabayashi, Etsuko; Nakata, Yasuhiro; Omachi, Yoshie; Sato, Noriko; Arima, Kunimasa; Matsuda, Hiroshi

2014-10-01

The purpose of this study was to clarify the concordance of diagnostic abilities and interobserver agreement between 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and brain perfusion single photon-emission computed tomography (SPECT) in patients with Alzheimer's disease (AD) who were diagnosed according to the research criteria of the National Institute of Aging-Alzheimer's Association Workshop. Fifty-five patients with "AD and mild cognitive impairment (MCI)" (n = 40) and "non-AD" (n = 15) were evaluated with 18F-FDG PET and (99m)Tc-ethyl cysteinate dimer (ECD) SPECT during an 8-week period. Three radiologists independently graded the regional uptake in the frontal, temporal, parietal, and occipital lobes as well as the precuneus/posterior cingulate cortex in both images. Kappa values were used to determine the interobserver reliability regarding regional uptake. The regions with better interobserver reliability between 18F-FDG PET and (99m)Tc-ECD SPECT were the frontal, parietal, and temporal lobes. The (99m)Tc-ECD SPECT agreement in the occipital lobes was not significant. The frontal, temporal, and parietal lobes showed good correlations between 18F-FDG PET and (99m)Tc-ECD SPECT in the degree of uptake, but the occipital lobe and precuneus/posterior cingulate cortex did not show good correlations. The diagnostic accuracy rates of "AD and MCI" ranged from 60% to 70% in both of the techniques. The degree of uptake on 18F-FDG PET and (99m)Tc-ECD SPECT showed significant correlations in the frontal, temporal, and parietal lobes. The diagnostic abilities of 18F-FDG PET and (99m)Tc-ECD SPECT for "AD and MCI," when diagnosed according to the National Institute of Aging-Alzheimer's Association Workshop criteria, were nearly identical. Copyright © 2014 John Wiley & Sons, Ltd.

Characteristics of aquaporin expression surrounding senile plaques and cerebral amyloid angiopathy in Alzheimer disease.

PubMed

Hoshi, Akihiko; Yamamoto, Teiji; Shimizu, Keiko; Ugawa, Yoshikazu; Nishizawa, Masatoyo; Takahashi, Hitoshi; Kakita, Akiyoshi

2012-08-01

Senile plaques (SPs) containing amyloid β peptide (Aβ) 1-42 are the major species present in Alzheimer disease (AD), whereas Aβ1-40 is the major constituent of arteriolar walls affected by cerebral amyloid angiopathy. The water channel proteins astrocytic aquaporin 1 (AQP1) and aquaporin 4 (AQP4) are known to be abnormally expressed in AD brains, but the expression of AQPs surrounding SPs and cerebral amyloid angiopathy has not been described in detail. Here, we investigated whether AQP expression is associated with each species of Aβ deposited in human brains affected by either sporadic or familial AD. Immunohistochemical analysis demonstrated more numerous AQP1-positive reactive astrocytes in the AD cerebral cortex than in controls, located close to Aβ42- or Aβ40-positive SPs. In AD cases, however, AQP1-positive astrocytes were not often observed in Aβ-rich areas, and there was a significant negative correlation between the levels of AQP1 and Aβ42 assessed semiquantitatively. We also found that Aβ plaque-like AQP4 was distributed in association with Aβ42- or Aβ40-positive SPs and that the degree of AQP4 expression around Aβ40-positive vessels was variable. These findings suggest that a defined population of AQP1-positive reactive astrocytes may modify Aβ deposition in the AD brain, whereas the Aβ deposition process might alter astrocytic expression of AQP4.

Abeta1-42 Detection in CSF of Alzheimer's disease is influenced by temperature: indication of reversible Abeta1-42 aggregation?

PubMed

Sancesario, Giulia M; Esposito, Zaira; Nuccetelli, Marzia; Bernardini, Sergio; Sorge, Roberto; Martorana, Alessandro; Federici, Giorgio; Bernardi, Giorgio; Sancesario, Giuseppe

2010-06-01

Amyloid-beta 1-42 (Abeta1-42), peptide detectable in cerebrospinal fluid (CSF), has been extensively studied as diagnostic marker for Alzheimer's disease; however, results are variable. We investigated whether Abeta1-42 detection in CSF may be affected by handling temperature after lumbar puncture. CSF was collected from patients affected by probable AD (n=27), other dementias (OD) (n=24), or other neurological disorders without cognitive impairment (OND) (n=23). After lumbar puncture, CSF samples were either maintained at 37 degrees C, or handled according to standard procedures and centrifuged at 4 degrees C for 10 min; thereafter, one aliquot was further stored at 4 degrees C and another at 37 degrees C, before freezing all samples 90 min later at -80 degrees C, pending analysis. Abeta1-42 and total tau were determined using a commercially available sandwich enzyme-linked immunosorbent assay ELISA. Reduced Abeta1-42 and increased total tau CSF levels were confirmed as characteristic hallmarks of the OD and AD groups, providing standard measurement in samples stored at 4 degrees C before freezing. However, avoiding cooling or reheating CSF from 4 to 37 degrees C before freezing strikingly increased the Abeta1-42 concentration detectable in the AD group (P<0.01), but not in control groups. The results indicate that a pool of Abeta1-42 cannot be detectable in the CSF of AD patients, because standard preanalytical cooling masks in some ways the epitope recognized by Abeta1-42 specific antibodies. Moreover, our study suggests that low temperature could induce Abeta1-42 conformational changes and multimeric aggregates in probable AD, but, more importantly, Abeta1-42 aggregation could be reversible. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Visual associations to retrieve episodic memory across healthy elderly, mild cognitive impairment, and patients with Alzheimer's disease.

PubMed

Meyer, Sascha R A; De Jonghe, Jos F M; Schmand, Ben; Ponds, Rudolf W H M

2018-05-16

Episodic memory tests need to determine the degree to which patients with moderate to severe memory deficits can still benefit from retrieval support. Especially in the case of Alzheimer's disease (AD), this may support health care to be more closely aligned with patients' memory capacities. We investigated whether the different measures of episodic memory of the Visual Association Test-Extended (VAT-E) can provide a more detailed and informative assessment on memory disturbances across a broad range of cognitive decline, from normal to severe impairment as seen in AD, by examining differences in floor effects. The VAT-E consists of 24 pairs of black-and-white line drawings. In a within-group design, we compared score distributions of VAT-E subtests in healthy elderly controls, mild cognitive impairment (MCI), and AD (n = 144), as well as in relation to global cognitive impairment. Paired associate recall showed a floor effect in 41% of MCI patients and 62% of AD patients. Free recall showed a floor effect in 73% of MCI patients and 84% of AD patients. Multiple-choice cued recognition did not show a floor effect in either of the patient groups. We conclude that the VAT-E covers a broad range of episodic memory decline in patients. As expected, paired associate recall was of intermediate difficulty, free recall was most difficult, and multiple-choice cued recognition was least difficult for patients. These varying levels of difficulty enable a more accurate determination of the level of retrieval support that can still benefit patients across a broad range of cognitive decline.

Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline

PubMed Central

Talbot, Konrad; Wang, Hoau-Yan; Kazi, Hala; Han, Li-Ying; Bakshi, Kalindi P.; Stucky, Andres; Fuino, Robert L.; Kawaguchi, Krista R.; Samoyedny, Andrew J.; Wilson, Robert S.; Arvanitakis, Zoe; Schneider, Julie A.; Wolf, Bryan A.; Bennett, David A.; Trojanowski, John Q.; Arnold, Steven E.

2012-01-01

While a potential causal factor in Alzheimer’s disease (AD), brain insulin resistance has not been demonstrated directly in that disorder. We provide such a demonstration here by showing that the hippocampal formation (HF) and, to a lesser degree, the cerebellar cortex in AD cases without diabetes exhibit markedly reduced responses to insulin signaling in the IR→IRS-1→PI3K signaling pathway with greatly reduced responses to IGF-1 in the IGF-1R→IRS-2→PI3K signaling pathway. Reduced insulin responses were maximal at the level of IRS-1 and were consistently associated with basal elevations in IRS-1 phosphorylated at serine 616 (IRS-1 pS616) and IRS-1 pS636/639. In the HF, these candidate biomarkers of brain insulin resistance increased commonly and progressively from normal cases to mild cognitively impaired cases to AD cases regardless of diabetes or APOE ε4 status. Levels of IRS-1 pS616 and IRS-1 pS636/639 and their activated kinases correlated positively with those of oligomeric Aβ plaques and were negatively associated with episodic and working memory, even after adjusting for Aβ plaques, neurofibrillary tangles, and APOE ε4. Brain insulin resistance thus appears to be an early and common feature of AD, a phenomenon accompanied by IGF-1 resistance and closely associated with IRS-1 dysfunction potentially triggered by Aβ oligomers and yet promoting cognitive decline independent of classic AD pathology. PMID:22476197

Cortical Iron Reflects Severity of Alzheimer’s Disease

PubMed Central

van Duijn, Sara; Bulk, Marjolein; van Duinen, Sjoerd G.; Nabuurs, Rob J.A.; van Buchem, Mark A.; van der Weerd, Louise; Natté, Remco

2017-01-01

Abnormal iron distribution in the isocortex is increasingly recognized as an in vivo marker for Alzheimer’s disease (AD). However, the contribution of iron accumulation to the AD pathology is still poorly understood. In this study, we investigated: 1) frontal cortical iron distribution in AD and normal aging and 2) the relation between iron distribution and degree of AD pathology. We used formalin fixed paraffin embedded frontal cortex from 10 AD patients, 10 elder, 10 middle aged, and 10 young controls and visualized iron with a modified Perl’s histochemical procedure. AD and elderly subjects were not different with respect to age and sex distribution. Iron distribution in the frontal cortex was not affected by normal aging but was clearly different between AD and controls. AD showed accumulation of iron in plaques, activated microglia, and, in the most severe cases, in the mid-cortical layers along myelinated fibers. The degree of altered iron accumulations was correlated to the amount of amyloid-β plaques and tau pathology in the same block, as well as to Braak stage (p < 0.001). AD and normal aging show different iron and myelin distribution in frontal cortex. These changes appear to occur after the development of the AD pathological hallmarks. These findings may help the interpretation of high resolution in vivo MRI and suggest the potential of using changes in iron-based MRI contrast to indirectly determine the degree of AD pathology in the frontal cortex. PMID:29081415

Education and occupation as proxies for reserve in aMCI converters and AD: FDG-PET evidence.

PubMed

Garibotto, V; Borroni, B; Kalbe, E; Herholz, K; Salmon, E; Holtoff, V; Sorbi, S; Cappa, S F; Padovani, A; Fazio, F; Perani, D

2008-10-21

Previous reports have shown that higher education is associated with more severe brain pathology in patients with Alzheimer disease (AD), suggesting that these individuals have a functional reserve provided by education, which masks the clinical expression of a higher degree of neurodegeneration. It is unknown if a similar reserve mechanism exists in patients with amnestic mild cognitive impairment (aMCI). The aim of this study was to assess the impact of education and occupation on brain glucose metabolism (rCMRglc) measured with FDG-PET in aMCI and in a very large sample of subjects with probable AD (pAD). A total of 242 patients with pAD, 72 with aMCI, and 144 healthy controls participated in the study. At follow-up, 21 subjects with aMCI progressed to AD. A regression analysis was conducted (SPM2), with education and occupation as independent variables, and rCMRglc as dependent variable, adjusting for demographic data, global cognitive status, and neuropsychological scores. The analysis showed a significant association between higher education/occupation and lower rCMRglc in posterior temporoparietal cortex and precuneus in pAD and aMCI converters, and no correlation in aMCI nonconverters and healthy controls. This means that, when submitted to FDG-PET for diagnostic evaluation, pAD and aMCI converters with higher education/occupation had, for comparable cognitive impairment, a more severe rCMRglc reduction than the ones with lower education/occupation. This study suggests that education and occupation may be proxies for brain functional reserve, reducing the severity and delaying the clinical expression of Alzheimer disease (AD) pathology. The results in aMCI converters suggest that functional reserve is already at play in the predementia phase of AD.

Rankings matter: nurse graduates from higher-ranked institutions have higher productivity.

PubMed

Yakusheva, Olga; Weiss, Marianne

2017-02-13

Increasing demand for baccalaureate-prepared nurses has led to rapid growth in the number of baccalaureate-granting programs, and to concerns about educational quality and potential effects on productivity of the graduating nursing workforce. We examined the association of individual productivity of a baccalaureate-prepared nurse with the ranking of the degree-granting institution. For a sample of 691 nurses from general medical-surgical units at a large magnet urban hospital between 6/1/2011-12/31/2011, we conducted multivariate regression analysis of nurse productivity on the ranking of the degree-granting institution, adjusted for age, hospital tenure, gender, and unit-specific effects. Nurse productivity was coded as "top"/"average"/"bottom" based on a computation of individual nurse value-added to patient outcomes. Ranking of the baccalaureate-granting institution was derived from the US News and World Report Best Colleges Rankings' categorization of the nurse's institution as the "first tier" or the "second tier", with diploma or associate degree as the reference category. Relative to diploma or associate degree nurses, nurses who had attended first-tier universities had three-times the odds of being in the top productivity category (OR = 3.18, p < 0.001), while second-tier education had a non-significant association with productivity (OR = 1.73, p = 0.11). Being in the bottom productivity category was not associated with having a baccalaureate degree or the quality tier. The productivity boost from a nursing baccalaureate degree depends on the quality of the educational institution. Recognizing differences in educational outcomes, initiatives to build a baccalaureate-educated nursing workforce should be accompanied by improved access to high-quality educational institutions.

Technology Assessment Requirements for Programs and Projects

NASA Technical Reports Server (NTRS)

Bilbro, James W.

2006-01-01

Program/project uncertainty can most simply be defined as the unpredictability of its outcome. As might be expected, the degree of uncertainty depends substantially on program/project type. For hi-tech programs/projects, uncertainty all too frequently translates into schedule slips, cost overruns and occasionally even to cancellations or failures - consummations root cause of such events is often attributed to inadequate definition of requirements. If such were indeed the root cause, then correcting the situation would simply be a matter of requiring better requirements definition, but since history seems frequently to repeat itself, this must not be the case - at least not in total. There are in fact many contributors to schedule slips, cost overruns, project cancellations and failures, among them lack of adequate requirements definition. The case can be made, however, that many of these contributors are related to the degree of uncertainty at the outset of the project. And further, that a dominant factor in the degree of uncertainty is the maturity of the technology required to bring the project to fruition. This presentation discusses the concept of relating degrees of uncertainty to Technology Readiness Levels (TRL) and their associated Advancement Degree of Difficulty (AD2) levels. It also briefly describes a quantifiable process to establish the appropriate TRL for a given technology and quantifies through the AD2 what is required to move it from its current TRL to the desired TRL in order to reduce risk and maximize likelihood of successfully infusing the technology.

Insights from a national survey into why substance abuse treatment units add prevention and outreach services

PubMed Central

Wells, Rebecca; Lemak, Christy Harris; D'Aunno, Thomas A

2006-01-01

Background Previous studies have found that even limited prevention-related interventions can affect health behaviors such as substance use and risky sex. Substance abuse treatment providers are ideal candidates to provide these services, but typically have little or no financial incentive to do so. The purpose of this study was therefore to explore why some substance abuse treatment units have added new prevention and outreach services. Based on an ecological framework of organizational strategy, three categories of predictors were tested: (1) environmental, (2) unit-level, and (3) unit leadership. Results A lagged cross-sectional logistic model of 450 outpatient substance abuse treatment units revealed that local per capita income, mental health center affiliation, and clinical supervisors' graduate degrees were positively associated with likelihood of adding prevention-related education and outreach services. Managed care contracts and methadone treatment were negatively associated with addition of these services. No hospital-affiliated agencies added prevention and outreach services during the study period. Conclusion Findings supported the study's ecological perspective on organizational strategy, with factors at environmental, unit, and unit leadership levels associated with additions of prevention and outreach services. Among the significant predictors, ties to managed care payers and unit leadership graduate education emerge as potential leverage points for public policy. In the current sample, units with managed care contracts were less likely to add prevention and outreach services. This is not surprising, given managed care's emphasis on cost control. However, the association with this payment source suggests that public managed care programs might affects prevention and outreach differently through revised incentives. Specifically, government payers could explicitly compensate substance abuse treatment units in managed care contracts for prevention and outreach. The effects of supervisor graduate education on likelihood of adding new prevention and outreach programs suggests that leaders' education can affect organizational strategy. Foundation and government officials may encourage prevention and outreach by funding curricular enhancements to graduate degree programs demonstrating the importance of public goods. Overall, these findings suggest that both money and professional education affect substance abuse treatment unit additions of prevention and outreach services, as well as other factors less amenable to policy intervention. PMID:16887037

Insights from a national survey into why substance abuse treatment units add prevention and outreach services.

PubMed

Wells, Rebecca; Lemak, Christy Harris; D'Aunno, Thomas A

2006-08-03

Previous studies have found that even limited prevention-related interventions can affect health behaviors such as substance use and risky sex. Substance abuse treatment providers are ideal candidates to provide these services, but typically have little or no financial incentive to do so. The purpose of this study was therefore to explore why some substance abuse treatment units have added new prevention and outreach services. Based on an ecological framework of organizational strategy, three categories of predictors were tested: (1) environmental, (2) unit-level, and (3) unit leadership. A lagged cross-sectional logistic model of 450 outpatient substance abuse treatment units revealed that local per capita income, mental health center affiliation, and clinical supervisors' graduate degrees were positively associated with likelihood of adding prevention-related education and outreach services. Managed care contracts and methadone treatment were negatively associated with addition of these services. No hospital-affiliated agencies added prevention and outreach services during the study period. Findings supported the study's ecological perspective on organizational strategy, with factors at environmental, unit, and unit leadership levels associated with additions of prevention and outreach services. Among the significant predictors, ties to managed care payers and unit leadership graduate education emerge as potential leverage points for public policy. In the current sample, units with managed care contracts were less likely to add prevention and outreach services. This is not surprising, given managed care's emphasis on cost control. However, the association with this payment source suggests that public managed care programs might affects prevention and outreach differently through revised incentives. Specifically, government payers could explicitly compensate substance abuse treatment units in managed care contracts for prevention and outreach. The effects of supervisor graduate education on likelihood of adding new prevention and outreach programs suggests that leaders' education can affect organizational strategy. Foundation and government officials may encourage prevention and outreach by funding curricular enhancements to graduate degree programs demonstrating the importance of public goods. Overall, these findings suggest that both money and professional education affect substance abuse treatment unit additions of prevention and outreach services, as well as other factors less amenable to policy intervention.

Impact of Multiple Factors on the Degree of Tinnitus Distress.

PubMed

Brüggemann, Petra; Szczepek, Agnieszka J; Rose, Matthias; McKenna, Laurence; Olze, Heidi; Mazurek, Birgit

2016-01-01

The primary cause of subjective tinnitus is a dysfunction of the auditory system; however, the degree of distress tinnitus causes depends largely on the psychological status of the patient. Our goal was to attempt to associate the grade of tinnitus-related distress with the psychological distress, physical, or psychological discomfort patients experienced, as well as potentially relevant social parameters, through a simultaneous analysis of these factors. We determined the level of tinnitus-related distress in 531 tinnitus patients using the German version of the tinnitus questionnaire (TQ). In addition, we used the Perceived Stress Questionnaire (PSQ); General Depression Scale Allgemeine Depression Skala (ADS), Berlin Mood Questionnaire (BSF); somatic symptoms inventory (BI), and SF-8 health survey as well as general information collected through a medical history. The TQ score significantly correlated with a score obtained using PSQ, ADS, BSF, BI, and SF-8 alongside psychosocial factors such as age, gender, and marital status. The level of hearing loss and the auditory properties of the specific tinnitus combined with perceived stress and the degree of depressive mood and somatic discomfort of a patient were identified as medium-strong predictors of chronic tinnitus. Social factors such as gender, age, or marital status also had an impact on the degree of tinnitus distress. The results that were obtained were implemented in a specific cortical distress network model. Using a large representative sample of patients with chronic tinnitus permitted a simultaneous statistical measurement of psychometric and audiological parameters in predicting tinnitus distress. We demonstrate that single factors can be distinguished in a manner that explains their causative association and influence on the induction of tinnitus-related distress.

Impact of Multiple Factors on the Degree of Tinnitus Distress

PubMed Central

Brüggemann, Petra; Szczepek, Agnieszka J.; Rose, Matthias; McKenna, Laurence; Olze, Heidi; Mazurek, Birgit

2016-01-01

Objective: The primary cause of subjective tinnitus is a dysfunction of the auditory system; however, the degree of distress tinnitus causes depends largely on the psychological status of the patient. Our goal was to attempt to associate the grade of tinnitus-related distress with the psychological distress, physical, or psychological discomfort patients experienced, as well as potentially relevant social parameters, through a simultaneous analysis of these factors. Methods: We determined the level of tinnitus-related distress in 531 tinnitus patients using the German version of the tinnitus questionnaire (TQ). In addition, we used the Perceived Stress Questionnaire (PSQ); General Depression Scale Allgemeine Depression Skala (ADS), Berlin Mood Questionnaire (BSF); somatic symptoms inventory (BI), and SF-8 health survey as well as general information collected through a medical history. Results: The TQ score significantly correlated with a score obtained using PSQ, ADS, BSF, BI, and SF-8 alongside psychosocial factors such as age, gender, and marital status. The level of hearing loss and the auditory properties of the specific tinnitus combined with perceived stress and the degree of depressive mood and somatic discomfort of a patient were identified as medium-strong predictors of chronic tinnitus. Social factors such as gender, age, or marital status also had an impact on the degree of tinnitus distress. The results that were obtained were implemented in a specific cortical distress network model. Conclusions: Using a large representative sample of patients with chronic tinnitus permitted a simultaneous statistical measurement of psychometric and audiological parameters in predicting tinnitus distress. We demonstrate that single factors can be distinguished in a manner that explains their causative association and influence on the induction of tinnitus-related distress. PMID:27445776

Association of stress with symptoms of atopic dermatitis.

PubMed

Oh, Sang Ho; Bae, Byung Gi; Park, Chang Ook; Noh, Ji Yeon; Park, Il Ho; Wu, Wen Hao; Lee, Kwang Hoon

2010-11-01

Psychological stress and atopic dermatitis (AD) symptoms appear to form a vicious cycle. This study compared the degree of stress and impairment of dermatology life quality between patients with AD and healthy controls, and examined for neuropeptides and neurotrophins associated with stress in AD. Questionnaires, comprising five tests evaluating depression, anxiety, interaction anxiousness, private body consciousness, and dermatology life quality, were examined in age- and sex-matched patients with AD (n = 28) and healthy controls (n = 28). Immunohistochemical staining of nerve growth factor, substance P, corticotrophin-releasing factor receptor and neuropeptide Y was performed in the AD-involved and normal skin. Patients with AD showed high scores on all of the questionnaires, including Beck Depression Inventory, state anxiety, trait anxiety, Interaction Anxiousness Scale, Private Body Consciousness subscale, and Dermatology Life Quality Index. All of the parameters, except for Beck Depression Inventory, showed higher values in AD than healthy controls (p < 0.001). Statistically significant correlations were observed between each psychological parameter and Dermatology Life Quality Index. Among the clinical parameters, only pruritus was positively correlated with state anxiety (R = 0.573, p < 0.05) and trait anxiety (R = 0.525, p < 0.05). The Eczema Area and Severity Index score did not show any significant correlations with psychological parameters. Nerve growth factor-reactive cells were observed more abundantly and intensely in both epidermis and dermis of AD involved skin (n = 4) than in healthy controls (n = 3) (p = 0.022 and 0.029, respectively). Also, the number and intensity of neuropeptide Y-positive cells was significantly greater in the entire epidermis of patients with AD than in healthy controls (n = 3) (p = 0.029 and 0.026, respectively). We conclude that anxiety may be associated with the induction of pruritus through neuro-peptide Y and nerve growth factor.

Reduced cGMP levels in CSF of AD patients correlate with severity of dementia and current depression.

PubMed

Hesse, Raphael; Lausser, Ludwig; Gummert, Pauline; Schmid, Florian; Wahler, Anke; Schnack, Cathrin; Kroker, Katja S; Otto, Markus; Tumani, Hayrettin; Kestler, Hans A; Rosenbrock, Holger; von Arnim, Christine A F

2017-03-09

Alzheimer's disease (AD) is a neurodegenerative disorder, primarily affecting memory. That disorder is thought to be a consequence of neuronal network disturbances and synapse loss. Decline in cognitive function is associated with a high burden of neuropsychiatric symptoms (NPSs) such as depression. The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) are essential second messengers that play a crucial role in memory processing as well as synaptic plasticity and are potential therapeutic targets. Biomarkers that are able to monitor potential treatment effects and that reflect the underlying pathology are of crucial interest. In this study, we measured cGMP and cAMP in cerebrospinal fluid (CSF) in a cohort of 133 subjects including 68 AD patients and 65 control subjects. To address the association with disease progression we correlated cognitive status with cyclic nucleotide levels. Because a high burden of NPSs is associated with decrease in cognitive function, we performed an exhaustive evaluation of AD-relevant marker combinations in a depressive subgroup. We show that cGMP, but not cAMP, levels in the CSF of AD patients are significantly reduced compared with the control group. Reduced cGMP levels in AD patients correlate with memory impairment based on Mini-Mental State Examination score (r = 0.17, p = 0.048) and tau as a marker of neurodegeneration (r = -0.28, p = 0.001). Moreover, we were able to show that AD patients suffering from current depression show reduced cGMP levels (p = 0.07) and exhibit a higher degree of cognitive impairment than non-depressed AD patients. These results provide further evidence for an involvement of cGMP in AD pathogenesis and accompanying co-morbidities, and may contribute to elucidating synaptic plasticity alterations during disease progression.

Cognitive Effects of Hormone Therapy Continuation or Discontinuation in a Sample of Women at Risk for Alzheimer Disease.

PubMed

Wroolie, Tonita E; Kenna, Heather A; Williams, Katherine E; Rasgon, Natalie L

2015-11-01

Use of estrogen-based hormone therapy (HT) as a protection from cognitive decline and Alzheimer disease (AD) is controversial, although cumulative data support HT use when initiated close to menopause onset with estrogen formulations containing 17β-estradiol preferable to conjugated equine estrogen formulations. Little is known regarding specific populations of women who may derive benefit from HT. Women with heightened risk for AD (aged 49-69), all of whom were taking HT for at least 1 year and most of whom initiated HT close to menopause onset, underwent cognitive assessment followed by randomization to continue or discontinue HT. Assessments were repeated at 2 years after randomization. Women who continued HT performed better on cognitive domains composed of measures of verbal memory and combined attention, working memory, and processing speed measures. Women who used 17β-estradiol versus conjugated equine estrogen, whether randomized to continue or discontinue HT, showed better verbal memory performance at the 2-year follow-up assessment. An interaction was also found with HT randomization and family history of AD in a first-degree relative. All female offspring of patients with AD declined in verbal memory; however, women who continued HT declined less than women who discontinued HT. Women without a first-degree relative with AD showed verbal memory improvement (likely because of practice effects) with continuance and declined with discontinuance of HT. Continuation of HT use appears to protect cognition in women with heightened risk for AD when initiated close to menopause onset. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease

PubMed Central

Fernández, Maria Victoria; Kim, Jong Hun; Budde, John P.; Black, Kathleen; Medvedeva, Alexandra; Saef, Ben; Del-Aguila, Jorge; Ibañez, Laura; Dube, Umber; Harari, Oscar; Norton, Joanne; Chasse, Rachel; Morris, John C.; Goate, Alison

2017-01-01

Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations. PMID:29091718

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.

PubMed

Fernández, Maria Victoria; Kim, Jong Hun; Budde, John P; Black, Kathleen; Medvedeva, Alexandra; Saef, Ben; Deming, Yuetiva; Del-Aguila, Jorge; Ibañez, Laura; Dube, Umber; Harari, Oscar; Norton, Joanne; Chasse, Rachel; Morris, John C; Goate, Alison; Cruchaga, Carlos

2017-11-01

Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.

Relationship of the method of addition and temperature of cryoprotective agents to the fertilizing capacity of cooled chicken spermatozoa.

PubMed

Sexton, T J

1975-05-01

Three experiments were conducted to determine the relationship of the method of adding (fraction or bulk) and/or holding temperature (41 degrees, 25 degrees, 10 degrees) of glycerol, dimethylsulfoxide or ethylene glycol to the fertilizing capacity of chicken spermatozoa during cooling. No significant effect on fertility was observed when sperm were washed, suspended without dilution in phosphate buffer or milk and cooled to 15 degrees in 30 min. With phosphate buffer as the medium, fertility was comparable with that of the control only when glycol was maintained at 41 degrees or 25 degrees prior to addition in fractions (3 equal parts at 10 min. intervals). Similar effects were observed when 4% DMSO at 25 degrees was added in bulk after cooling. However, when DMSO was added to sperm suspended in milk, fertility was significantly reduced regardless of treatment. None of the methods were successful in eliminating the contraceptive action of glycerol. The results indicate that a number of in vitro techniques can be used to maintain the fertilizing capacity of chicken spermatozoa in the presence of 4% ethylene glycol or DMSO.

Public School Funding and Postsecondary Outcomes in Illinois: What Is Reasonable to Expect from Illinois' School Funding Reforms? Policy Research. IERC 2018-1

ERIC Educational Resources Information Center

Houston, Derek A.

2018-01-01

This study examines the relationships between school funding and students' college preparation, postsecondary enrollment, and postsecondary degree attainment, adding to the literature on how money matters in education. The author addresses how past school funding levels among Illinois public high schools may have been associated with students'…

Changes in cassava toxicity during processing into gari and ijapu--two fermented food products.

PubMed

Sokari, T G; Karibo, P S

1992-01-01

Grated cassava to which tap water was added at levels of 25%, 50% and 75% (v/w) was held at 30 degrees C, 40 degrees C or 50 degrees C and examined over a 6 h period for cyanide content, pH and titratable acidity (TTA). During the come-up time, i.e. the time between addition of water and attainment of desired holding temperature (between 14 and 47 min), reductions in bound cyanide of ca 54-85% occurred, depending on the level of added water and holding temperature. The corresponding losses for the control samples, to which no water was added, were ca 25-33%. The biggest reduction in the bound cyanide of > 99% (from 89.0 to 0.6 ppm) occurred in grated cassava with 75% added water held at 50 degrees C. There was little or no change in pH during the period of study. The reduction of processing time for certain cassava products based on separation into detoxication and flavour development/fermentation stages is discussed.

Method of synthesis of proton conducting materials

DOEpatents

Garzon, Fernando Henry; Einsla, Melinda Lou; Mukundan, Rangachary

2010-06-15

A method of producing a proton conducting material, comprising adding a pyrophosphate salt to a solvent to produce a dissolved pyrophosphate salt; adding an inorganic acid salt to a solvent to produce a dissolved inorganic acid salt; adding the dissolved inorganic acid salt to the dissolved pyrophosphate salt to produce a mixture; substantially evaporating the solvent from the mixture to produce a precipitate; and calcining the precipitate at a temperature of from about 400.degree. C. to about 1200.degree. C.

Role of familial factors in late-onset Alzheimer disease as a function of age.

PubMed

Wu, Z; Kinslow, C; Pettigrew, K D; Rapoport, S I; Schapiro, M B

1998-09-01

Whereas early-onset Alzheimer disease (AD; usually onset at age < 50 years) has been defined with genetic mutation on chromosomes 1, 14, and 21, the degree of familial contribution to late-onset AD is unclear. Further, it is uncertain if subgroups of late-onset AD exist. To examine the influence of familial factors as a function of age in late-onset AD we investigated lifetime risks and age-specific hazard rates of AD-like illness among late-onset AD probands' and controls' first-degree relatives, using questionnaires and medical records. As part of a longitudinal study on aging and AD, we studied 78 AD probands with age of onset > or =50 years (28 "definite" and 50 "probable" AD according to NINCDS/ADRDA criteria) and 101 healthy old controls seen since 1981. Both probands and controls were screened rigorously with medical tests and brain imaging and seen regularly until autopsy. Multiple informants and medical records were used for first-degree relatives. Among first-degree relatives, 49 secondary cases of AD-like illness were found for the AD probands' relatives (391 relatives 40 years old or older) compared with 20 cases among controls' relatives (456 relatives 40 years old or older). Relatives of AD probands had a significantly increased lifetime risk of AD-like illness of 52.8+/-11.4% by age 94 years compared with a lifetime risk in relatives of controls of 22.1+/-5.8% by age 90 years. Age-specific hazard rates in relatives of AD probands increased until the 75-79-year age interval and then decreased; in contrast the age-specific hazard rates increased in relatives of controls after the 80-84-year age interval. To determine if a dividing line exist among late-onset AD, several cutoff ages were used in our study to compare cumulative risk curves of AD-like illness between relatives of late-onset probands and relatives of late-late-onset probands. Differences in the pattern of cumulative incidence of AD in relatives showed that 67-71 years is the range for a dividing line between late- and late-late-onset AD. Age-specific hazard rates of AD in relatives supported a difference between late- and late-late-onset. Whereas these rates increased until the 75-79-year age interval and then decreased in late-onset AD, the rates began increasing after the 65-69-year age interval and through the oldest age interval in both late-late-onset AD and control groups. Our results support the concept that familial factors exist in late-onset AD and that different familial factors may exist in late-onset AD subgroups.

The effect of genetic bottlenecks and inbreeding on the incidence of two major autoimmune diseases in standard poodles, sebaceous adenitis and Addison's disease.

PubMed

Pedersen, Niels C; Brucker, Lynn; Tessier, Natalie Green; Liu, Hongwei; Penedo, Maria Cecilia T; Hughes, Shayne; Oberbauer, Anita; Sacks, Ben

2015-01-01

Sebaceous adenitis (SA) and Addison's disease (AD) increased rapidly in incidence among Standard Poodles after the mid-twentieth century. Previous attempts to identify specific genetic causes using genome wide association studies and interrogation of the dog leukocyte antigen (DLA) region have been non-productive. However, such studies led us to hypothesize that positive selection for desired phenotypic traits that arose in the mid-twentieth century led to intense inbreeding and the inadvertent amplification of AD and SA associated traits. This hypothesis was tested with genetic studies of 761 Standard, Miniature, and Miniature/Standard Poodle crosses from the USA, Canada and Europe, coupled with extensive pedigree analysis of thousands more dogs. Genome-wide diversity across the world-wide population was measured using a panel of 33 short tandem repeat (STR) loci. Allele frequency data were also used to determine the internal relatedness of individual dogs within the population as a whole. Assays based on linkage between STR genomic loci and DLA genes were used to identify class I and II haplotypes and disease associations. Genetic diversity statistics based on genomic STR markers indicated that Standard Poodles from North America and Europe were closely related and reasonably diverse across the breed. However, genetic diversity statistics, internal relatedness, principal coordinate analysis, and DLA haplotype frequencies showed a marked imbalance with 30 % of the diversity in 70 % of the dogs. Standard Poodles with SA and AD were strongly linked to this inbred population, with dogs suffering with SA being the most inbred. No single strong association was found between STR defined DLA class I or II haplotypes and SA or AD in the breed as a whole, although certain haplotypes present in a minority of the population appeared to confer moderate degrees of risk or protection against either or both diseases. Dogs possessing minor DLA class I haplotypes were half as likely to develop SA or AD as dogs with common haplotypes. Miniature/Standard Poodle crosses being used for outcrossing were more genetically diverse than Standard Poodles and genetically distinguishable across the genome and in the DLA class I and II region. Ancestral genetic polymorphisms responsible for SA and AD entered Standard Poodles through separate lineages, AD earlier and SA later, and were increasingly fixed by a period of close linebreeding that was related to popular bloodlines from the mid-twentieth century. This event has become known as the midcentury bottleneck or MCB. Sustained positive selection resulted in a marked imbalance in genetic diversity across the genome and in the DLA class I and II region. Both SA and AD were concentrated among the most inbred dogs, with genetic outliers being relatively disease free. No specific genetic markers other than those reflecting the degree of inbreeding were consistently associated with either disease. Standard Poodles as a whole remain genetically diverse, but steps should be taken to rebalance diversity using genetic outliers and if necessary, outcrosses to phenotypically similar but genetically distinct breeds.

White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network.

PubMed

Lee, Seonjoo; Viqar, Fawad; Zimmerman, Molly E; Narkhede, Atul; Tosto, Giuseppe; Benzinger, Tammie L S; Marcus, Daniel S; Fagan, Anne M; Goate, Alison; Fox, Nick C; Cairns, Nigel J; Holtzman, David M; Buckles, Virginia; Ghetti, Bernardino; McDade, Eric; Martins, Ralph N; Saykin, Andrew J; Masters, Colin L; Ringman, John M; Ryan, Natalie S; Förster, Stefan; Laske, Christoph; Schofield, Peter R; Sperling, Reisa A; Salloway, Stephen; Correia, Stephen; Jack, Clifford; Weiner, Michael; Bateman, Randall J; Morris, John C; Mayeux, Richard; Brickman, Adam M

2016-06-01

White matter hyperintensities (WMHs) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically determined to develop AD. The study comprised participants (n = 299; age = 39.03 ± 10.13) from the Dominantly Inherited Alzheimer Network, including 184 (61.5%) with a mutation that results in AD and 115 (38.5%) first-degree relatives who were noncarrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent's symptom onset age from the participant's age. Baseline MRI data were analyzed for total and regional WMH. Mixed-effects piece-wise linear regression was used to examine WMH differences between carriers and noncarriers with respect to EYO. Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years before expected symptom onset. Effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years before estimated onset. Autosomal-dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMHs are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. Ann Neurol 2016;79:929-939. © 2016 American Neurological Association.

Multi-Skyrmions on AdS2 × S2, rational maps and popcorn transitions

NASA Astrophysics Data System (ADS)

Canfora, Fabrizio; Tallarita, Gianni

2017-08-01

By combining two different techniques to construct multi-soliton solutions of the (3 + 1)-dimensional Skyrme model, the generalized hedgehog and the rational map ansatz, we find multi-Skyrmion configurations in AdS2 ×S2. We construct Skyrmionic multi-layered configurations such that the total Baryon charge is the product of the number of kinks along the radial AdS2 direction and the degree of the rational map. We show that, for fixed total Baryon charge, as one increases the charge density on ∂ (AdS2 ×S2) , it becomes increasingly convenient energetically to have configurations with more peaks in the radial AdS2 direction but a lower degree of the rational map. This has a direct relation with the so-called holographic popcorn transitions in which, when the charge density is high, multi-layered configurations with low charge on each layer are favored over configurations with few layers but with higher charge on each layer. The case in which the geometry is M2 ×S2 can also be analyzed.

Impaired Long Distance Functional Connectivity and Weighted Network Architecture in Alzheimer's Disease

PubMed Central

Liu, Yong; Yu, Chunshui; Zhang, Xinqing; Liu, Jieqiong; Duan, Yunyun; Alexander-Bloch, Aaron F.; Liu, Bing; Jiang, Tianzi; Bullmore, Ed

2014-01-01

Alzheimer's disease (AD) is increasingly recognized as a disconnection syndrome, which leads to cognitive impairment due to the disruption of functional activity across large networks or systems of interconnected brain regions. We explored abnormal functional magnetic resonance imaging (fMRI) resting-state dynamics, functional connectivity, and weighted functional networks, in a sample of patients with severe AD (N = 18) and age-matched healthy volunteers (N = 21). We found that patients had reduced amplitude and regional homogeneity of low-frequency fMRI oscillations, and reduced the strength of functional connectivity, in several regions previously described as components of the default mode network, for example, medial posterior parietal cortex and dorsal medial prefrontal cortex. In patients with severe AD, functional connectivity was particularly attenuated between regions that were separated by a greater physical distance; and loss of long distance connectivity was associated with less efficient global and nodal network topology. This profile of functional abnormality in severe AD was consistent with the results of a comparable analysis of data on 2 additional groups of patients with mild AD (N = 17) and amnestic mild cognitive impairment (MCI; N = 18). A greater degree of cognitive impairment, measured by the mini-mental state examination across all patient groups, was correlated with greater attenuation of functional connectivity, particularly over long connection distances, for example, between anterior and posterior components of the default mode network, and greater reduction of global and nodal network efficiency. These results indicate that neurodegenerative disruption of fMRI oscillations and connectivity in AD affects long-distance connections to hub nodes, with the consequent loss of network efficiency. This profile was evident also to a lesser degree in the patients with less severe cognitive impairment, indicating that the potential of resting-state fMRI measures as biomarkers or predictors of disease progression in AD. PMID:23314940

Training Psychologists for Rural Practice: Exploring Opportunities and Constraints.

PubMed

Domino, Marisa Elena; Lin, Ching-Ching Claire; Morrissey, Joseph P; Ellis, Alan R; Fraher, Erin; Richman, Erica L; Thomas, Kathleen C; Prinstein, Mitchell J

2018-04-17

To examine trends in the psychologist workforce and training opportunities, including factors that may influence the decision of clinical psychologists to practice in rural settings. We use a mixed-methods approach to examine the psychologist workforce nationally and in North Carolina (NC), including (1) an analysis of the location of programs awarding doctoral degrees; (2) an analysis of the practice, demographic, and educational characteristics of the psychologist workforce; and (3) interviews with directors of doctoral programs in clinical psychology to understand where current graduates are getting jobs and why they may or may not be choosing to practice in rural communities. Fewer than 1% of programs and institutions awarding doctoral degrees in psychology in the United States are located in rural areas. In NC, approximately 80% of practicing psychologists have out-of-state degrees and about 80% of recent NC graduates are not currently licensed in the state. This juxtaposition undermines the utility of adding more in-state degree programs. While expansion of training programs within rural areas could help alleviate the shortages of mental health providers, adding new degree-granting programs alone will not necessarily increase supply. We discuss complementary recruitment and retention strategies, including greater incentives for rural training and practice as well as training in emerging technologies that don't require providers to be physically located in underserved areas, such as telemedicine. Increasing the supply of psychologists practicing in rural areas will require a thoughtful, multipronged approach to training this critical part of the behavioral health workforce. © 2018 National Rural Health Association.

Executive Function and Personality Predict Instrumental Activities of Daily Living in Alzheimer Disease.

PubMed

Roy, Shumita; Ficarro, Stephanie; Duberstein, Paul; Chapman, Benjamin P; Dubovsky, Steven; Paroski, Margaret; Szigeti, Kinga; Benedict, Ralph H B

2016-11-01

Previous research shows that executive function (EF) and personality independently predict functional decline. Our objective was to determine whether personality traits predict independence with instrumental activities of daily living (IADLs), after accounting for executive dysfunction, in a mixed sample of patients with amnestic mild cognitive impairment (MCI) and Alzheimer disease (AD). In a cross-sectional analysis at a university medical center, 63 healthy older adults (median age: 67.6 years; 71% women) and 119 patients (median age: 75.0 years; 58% women) with varying degrees of AD (probable AD: 85; possible AD: 3; amnestic MCI: 31) were studied. Standardized neuropsychological measures, NEO Five-Factor Inventory (NEO-FFI), and informant-report Lawton and Brody IADL scales were used. All participants underwent neuropsychological evaluation, including administration of self- and informant-report NEO-FFI. Patients additionally underwent neurologic examination, and their informants completed the Lawton and Brody IADL scale. When testing the association between EF and personality on IADLs in the patient sample, conceptual card sorting, informant-report Openness, and informant-report Conscientiousness all significantly predicted IADLs, after accounting for age, education, and depression. In addition, a significant interaction showed that low Conscientiousness and executive dysfunction, in combination, can predict impairment of IADLs. Personality has a unique association with IADLs in patients with AD pathology that is not explained by EF. The findings confirm prior speculation that personality, in addition to cognitive dysfunction, is a risk factor for functional decline. Early identification of vulnerable individuals may allow for intervention to prolong functional independence. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Are Aβ and Its Derivatives Causative Agents or Innocent Bystanders in AD?

PubMed Central

Robakis, Nikolaos K.

2010-01-01

Alzheimer's disease (AD) is characterized by neurodegeneration in neocortical regions of the brain. Currently, Aβ-based theories, including amyloid depositions and soluble Aβ, form the basis of most therapeutic approaches to AD. It remains unclear, however, whether Aβ and its derivatives are the primary causative agents of neuronal loss in AD. Reported studies show no significant correlations between brain amyloid depositions and either degree of dementia or loss of neurons, and brain amyloid loads similar to AD are often found in normal individuals. Furthermore, behavioral abnormalities in animal models overexpressing amyloid precursor protein seem independent of amyloid depositions. Soluble Aβ theories propose toxic Aβ42 or its oligomers as the agents that promote cell death in AD. Aβ peptides, however, are normal components of human serum and CSF, and it is unclear under what conditions these peptides become toxic. Presently, there is little evidence of disease-associated abnormalities in soluble Aβ and no toxic oligomers specific to AD have been found. That familial AD mutations of amyloid precursor protein, PS1 and PS2 promote neurodegeneration suggests the biological functions of these proteins play critical roles in neuronal survival. Evidence shows that the PS/γ-secretase system promotes production of peptides involved in cell surface-to-nucleus signaling and gene expression, providing support for the hypothesis that familial AD mutations may contribute to neurodegeneration by inhibiting PS-dependent signaling pathways. PMID:20160455

The relationship of cardiovascular risk factors to Alzheimer disease in Choctaw Indians.

PubMed

Weiner, Myron F; Hynan, Linda S; Rossetti, Heidi; Womack, Kyle B; Rosenberg, Roger N; Gong, Yun-Hua; Qu, Bao-Xi

2011-05-01

To test the hypothesis that cardiovascular risk factors (CRFs) influence predisposition to and the clinical course of Alzheimer disease (AD), the authors compared Choctaw Indians, a group with known high CRF with white persons with AD. In addition to CRF history, the authors investigated the frequency of apolipoprotein E4 (apoE4) genotype andplasma homocysteine (HC) levels. The authors compared 39 Choctaw Indians with AD and 39 Choctaw Indians without AD to 39 white persons with AD with all groups similar in age. CRF history included diabetes, hypertension, high cholesterol or hypolipidemic agent use, or myocardial infarction. The authors also compared plasma HC concentration and apoE4 allele frequency. Choctaw persons with AD differed significantly from white persons with AD in history of hypertension, diabetes, and in HC values but not from Indians without AD. There was a significantly lower apoE4 allele frequency in Choctaw Indian AD than white persons with AD, and both AD groups had an affected first degree relative significantly more often than Indian controls. There was no relationship between the number of CRF and age at onset among Indians or whites, whereas HC concentration was associated with significantly earlier age of onset for Choctaw Indians but not for whites. This small study suggests that in Choctaw Indians modifiable risk factors may play more of a role in disease pathogenesis than in whites and that nonmodifiable risk factors such as apoE4 may play less of a role.

Type 2 diabetes and/or its treatment leads to less cognitive impairment in Alzheimer's disease patients.

PubMed

Domínguez, Raúl O; Marschoff, Enrique R; González, Silvia E; Repetto, Marisa G; Serra, Jorge A

2012-10-01

To evaluate the cognitive performance of a homogeneous population of Alzheimer's disease (AD), non-demented Type 2 Diabetes Mellitus (DIAB), demented with concomitant diseases (AD+DIAB) and healthy control subjects. AD is a progressive dementia disorder characterized clinically by impairment of memory, cognition and behavior. Recently, a major research interest in AD has been placed on early evaluation. Diabetes is one of the clinical conditions that represent the greatest risk of developing oxidative stress and dementia. Glucose overload, leading to the development of impaired-induced insulin secretion in DIAB and has been suggested to slow or deter AD pathogenesis. The degree of cognitive impairment was determined on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) and the Folstein's Mini Mental State Examination (MMSE); the severity of dementia was quantified applying the Clinical Dementia Rating (CDR) test; the Hamilton test was employed to evaluate depressive conditions; the final population studied was 101 subjects. The cognitive deterioration is statistically significantly lower (p<0.05) in AD+DIAB patients as compared with AD patients. In this longitudinal study the superimposed diabetic condition was associated with a lower rate of cognitive decline, while diabetic non-demented patients and controls present normal scores. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Neuroimaging correlates of neuropsychiatric symptoms in Alzheimer's disease: a review of 20 years of research.

PubMed

Boublay, N; Schott, A M; Krolak-Salmon, P

2016-10-01

Assessing morphological, perfusion and metabolic brain changes preceding or associated with neuropsychiatric symptoms (NPSs) will help in the understanding of pathophysiological underlying processes in Alzheimer's disease (AD). This review aimed to highlight the main findings on significant associations between neuroimaging and NPSs, the pathophysiology to elucidate possible underlying mechanisms, and methodological issues to aid future research. Research papers published from January 1990 to October 2015 were identified in the databases PsycInfo, Embase, PubMed and Medline, using key words related to NPSs and imaging techniques. In addition to a semi-systematic search in the databases, we also performed hand searches based on reported citations identified to be of interest. Delusions, apathy and depression symptoms were particularly associated with brain changes in AD. The majority of studies disclosed an association between frontal lobe structural and/or metabolic changes and NPSs, implicating, interestingly, for all 12 NPSs studied, the anterior cingulate cortex although temporal, subcortical and parietal regions, and insula were also involved. Given the high degree of connectivity of these brain areas, frontal change correlates of NPSs may help in the understanding of neural network participation. This review also highlights crucial methodological issues that may reduce the heterogeneity of results to enable progress on the pathophysiological mechanisms and aid research on NPS treatments in AD. Based on a broad review of the current literature, a global brain pattern to support the huge heterogeneity of neuroimaging correlates of NPSs in AD and methodological strategies are suggested to help direct future research. © 2016 EAN.

[Relationship between tobacco consumption and sport practice among health and education science university students].

PubMed

Ayán Pérez, Carlos; Molina, Antonio J; Varela Mato, Verónica; Cancela Carral, José María; Barrio Lera, Juan Pablo; Martín Sánchez, Vicente

To identify the prevalence and relationship between the practice of sports and smoking in university students enrolled on accredited qualifications related to health and/or education sciences. Cross-sectional study including 540 students (average age of 21.3±3.8 years; 68% women) of the University of Vigo registered in degree programs linked to health (Physical Therapy and Nursing), or education (Pre-School, Primary School and Physical Activity and Sport Sciences) who answered an "ad hoc" questionnaire relating sports practice and tobacco consumption. Women showed a lower habit on sports practice and a higher tobacco consumption, regardless of their academic degree. The average share of students who recognized practicing sports was significantly minor in those enrolled in health careers (37.7 vs. 57.5%). Regarding tobacco consumption, the students enrolled in health careers reported the lowest prevalence (16.7%). Among the students associated to education, this prevalence was found to be 25.9%. The bivariate analysis showed a trend towards a lower sport practice among the smokers. This association was significant only among the moderate consumers. The findings of this research show a low prevalence in sports practice among students enrolled in degrees associated to health, and a more relevant tobacco consumption among those enrolled in degrees associated to education. It seems necessary to develop strategies aimed at promoting healthy habits that should be taking into account the tobacco consumption reported by the student. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Influence of family history of dementia in the development and progression of late-onset Alzheimer's disease.

PubMed

Scarabino, Daniela; Gambina, Giuseppe; Broggio, Elisabetta; Pelliccia, Franca; Corbo, Rosa Maria

2016-03-01

Family history of dementia (FH) is a recognized risk factor for developing late-onset Alzheimer's disease (AD). We asked whether having FH increases AD risk and influences disease severity (age at onset and cognitive impairment) in 420 AD patients and 109 controls with (FH+) or without (FH-). The relationships of APOE and other AD risk genes with FH were analyzed as well. The proportion of APOE e4 allele carriers was higher among the FH+ than the FH- AD patients (49.6% vs. 38.9%; P = 0.04). The distribution of the risk genotypes of nine AD susceptibility genes previously examined (CHAT, CYP17, CYP19, ESR1, FSHR, P53, P73, P21, PPARG) did not differ between the FH+ and the FH- AD patients, indicating that none contributed significantly to familial clustering of disease. FH was associated with an increased AD risk (odds ratio [OR] 2.71, 95% confidence interval [CI] 1.44-5.09; P = 0.002) independent of carrying the APOE e4 allele (OR 2.61, 95%CI 1.53-4.44; P = 0.0004). Having a first-degree relative or a parent with dementia was significantly associated with AD risk (OR 2.9, 95%CI 1.3-6.4; P = 0.009 and OR 2.7, 95%CI 1.1-6.2; P = 0.02) but having a sibling with dementia was not (OR 1.7, 95%CI 0.2 to 14.7; P = 0.6). Among the FH+ AD patients, having one or both parents affected seemed to raise the risk of earlier onset age (P = 0.02) and greater cognitive impairment (P = 0.02) than having only an affected sibling, whereas having two or more affected relatives did not. © 2015 Wiley Periodicals, Inc.

Prevalence of atopic dermatitis in infants by domestic water hardness and season of birth: Cohort study.

PubMed

Engebretsen, Kristiane A; Bager, Peter; Wohlfahrt, Jan; Skov, Lone; Zachariae, Claus; Nybo Andersen, Anne-Marie; Melbye, Mads; Thyssen, Jacob P

2017-05-01

Atopic dermatitis (AD) appears to be more common in regions with hard domestic water and in children with a fall/winter birth. However, it is unknown whether a synergistic effect exists. We sought to evaluate the association between domestic water hardness and season of birth, respectively, with onset of AD within the first 18 months of life in a large Danish birth cohort. Of children from the Danish National Birth Cohort, 52,950 were included. History of physician-diagnosed AD and population characteristics were obtained from interviews. Birth data were obtained from the Civil Registration System, and domestic water hardness data were obtained from the Geological Survey of Denmark and Greenland. The relative prevalence (RP) of AD was calculated by using log-linear binomial regression. The prevalence of AD was 15.0% (7,942/52,950). The RP of AD was 5% (RP trend , 1.05; 95% CI, 1.03-1.07) higher for each 5° increase in domestic water hardness (range, 6.60-35.90 German degrees of hardness [118-641 mg/L]). Although the RP of AD was higher in children with a fall (RP, 1.24; 95% CI, 1.17-1.31) or winter (RP, 1.18; 95% CI, 1.11-1.25) birth, no significant interaction was observed with domestic water hardness. The population attributable risk of hard domestic water on AD was 2%. We observed that early exposure to hard domestic water and a fall/winter birth was associated with an increase in the relative prevalence of AD within the first 18 months of life. Although the 2 exposures did not interact synergistically, a dose-response relationship was observed between domestic water hardness and AD. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Genetics of Aggression in Alzheimer’s Disease (AD)

PubMed Central

Lukiw, Walter J.; Rogaev, Evgeny I.

2017-01-01

Alzheimer’s disease (AD) is a terminal, age-related neurological syndrome exhibiting progressive cognitive and memory decline, however AD patients in addition exhibit ancillary neuropsychiatric symptoms (NPSs) and these include aggression. In this communication we provide recent evidence for the mis-regulation of a small family of genes expressed in the human hippocampus that appear to be significantly involved in expression patterns common to both AD and aggression. DNA array- and mRNA transcriptome-based gene expression analysis and candidate gene association and/or genome-wide association studies (CGAS, GWAS) of aggressive attributes in humans have revealed a surprisingly small subset of six brain genes that are also strongly associated with altered gene expression patterns in AD. These genes encoded on five different chromosomes (chr) include the androgen receptor (AR; chrXq12), brain-derived neurotrophic factor (BDNF; chr11p14.1), catechol-O-methyl transferase (COMT; chr22q11.21), neuronal specific nitric oxide synthase (NOS1; chr12q24.22), dopamine beta-hydroxylase (DBH chr9q34.2) and tryptophan hydroxylase (TPH1, chr11p15.1 and TPH2, chr12q21.1). Interestingly, (i) the expression of three of these six genes (COMT, DBH, NOS1) are highly variable; (ii) three of these six genes (COMT, DBH, TPH1) are involved in DA or serotonin metabolism, biosynthesis and/or neurotransmission; and (iii) five of these six genes (AR, BDNF, COMT, DBH, NOS1) have been implicated in the development, onset and/or propagation of schizophrenia. The magnitude of the expression of genes implicated in aggressive behavior appears to be more pronounced in the later stages of AD when compared to MCI. These recent genetic data further indicate that the extent of cognitive impairment may have some bearing on the degree of aggression which accompanies the AD phenotype. PMID:28443016

Characterization of macular structure and function in two Swedish families with genetically identified autosomal dominant retinitis pigmentosa

PubMed Central

Abdulridha-Aboud, Wissam; Kjellström, Ulrika; Andréasson, Sten

2016-01-01

Purpose To study the phenotype in two families with genetically identified autosomal dominant retinitis pigmentosa (adRP) focusing on macular structure and function. Methods Clinical data were collected at the Department of Ophthalmology, Lund University, Sweden, for affected and unaffected family members from two pedigrees with adRP. Examinations included optical coherence tomography (OCT), full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Molecular genetic screening was performed for known mutations associated with adRP. Results The mode of inheritance was autosomal dominant in both families. The members of the family with a mutation in the PRPF31 (p.IVS6+1G>T) gene had clinical features characteristic of RP, with severely reduced retinal rod and cone function. The degree of deterioration correlated well with increasing age. The mfERG showed only centrally preserved macular function that correlated well with retinal thinning on OCT. The family with a mutation in the RHO (p.R135W) gene had an extreme intrafamilial variability of the phenotype, with more severe disease in the younger generations. OCT showed pathology, but the degree of morphological changes was not correlated with age or with the mfERG results. The mother, with a de novo mutation in the RHO (p.R135W) gene, had a normal ffERG, and her retinal degeneration was detected merely with the reduced mfERG. Conclusions These two families demonstrate the extreme inter- and intrafamilial variability in the clinical phenotype of adRP. This is the first Swedish report of the clinical phenotype associated with a mutation in the PRPF31 (p.IVS6+1G>T) gene. Our results indicate that methods for assessment of the central retinal structure and function may improve the detection and characterization of the RP phenotype. PMID:27212874

The impact of teachers’ modifications of an evidenced-based HIV prevention intervention on program outcomes

PubMed Central

Wang, Bo; Stanton, Bonita; Lunn, Sonja; Rolle, Glenda; Poitier, Maxwell; Adderley, Richard; Li, Xiaoming; Koci, Veronica; Deveaux, Lynette

2015-01-01

The degree to which evidence-based program outcomes are affected by modifications is a significant concern in the implementation of interventions. The ongoing national implementation of an evidence-based HIV prevention program targeting grade six students in The Bahamas [Focus on Youth in The Caribbean (FOYC)] offers an opportunity to explore factors associated with teachers’ modification of FOYC lessons and to examine the impact of types and degrees of modifications on student outcomes. Data were collected in 2012 from 155 teachers and 3646 students in 77 government elementary schools. Results indicate that teachers taught 16 of 30 core activities, 24.5 of 46 total activities and 4.7 of 8 sessions. Over one-half of the teachers made modifications to FOYC core activities; one-fourth of the teachers modified 25% or more core activities that they taught (heavily modified FOYC). Omitting core activities was the most common content modification, followed by lengthening FOYC lessons with reading, writing assignments or role-play games, shortening core activities or adding educational videos. Mixed-effects modeling revealed that omitting core activities had negative impacts on all four student outcomes. Shortening core activities and adding videos into lessons had negative impacts on HIV/AIDS knowledge and/or intention to use condom protection. Heavy modifications (>1/4 core activities) were associated with diminished program effectiveness. Heavy modifications and omitting or shortening core activities were negatively related to teachers’ level of implementation. We conclude that poorer student outcomes were associated with heavy modifications. PMID:26297497

The Impact of Teachers' Modifications of an Evidenced-Based HIV Prevention Intervention on Program Outcomes.

PubMed

Wang, Bo; Stanton, Bonita; Lunn, Sonja; Rolle, Glenda; Poitier, Maxwell; Adderley, Richard; Li, Xiaoming; Koci, Veronica; Deveaux, Lynette

2016-01-01

The degree to which evidence-based program outcomes are affected by modifications is a significant concern in the implementation of interventions. The ongoing national implementation of an evidence-based HIV prevention program targeting grade 6 students in The Bahamas [Focus on Youth in The Caribbean (FOYC)] offers an opportunity to explore factors associated with teachers' modification of FOYC lessons and to examine the impact of types and degrees of modifications on student outcomes. Data were collected in 2012 from 155 teachers and 3646 students in 77 government elementary schools. Results indicate that teachers taught 16 of 30 core activities, 24.5 of 46 total activities and 4.7 of 8 sessions. Over one-half of the teachers made modifications to FOYC core activities; one-fourth of the teachers modified 25 % or more core activities that they taught (heavily modified FOYC). Omitting core activities was the most common content modification, followed by lengthening FOYC lessons with reading, writing assignments or role-play games, and shortening core activities or adding educational videos. Mixed-effects modeling revealed that omitting core activities had negative impacts on all four student outcomes. Shortening core activities and adding videos into lessons had negative impacts on HIV/AIDS knowledge and/or intention to use condom protection. Heavy modifications (>1/4 core activities) were associated with diminished program effectiveness. Heavy modifications and omitting or shortening core activities were negatively related to teachers' level of implementation. We conclude that poorer student outcomes were associated with heavy modifications.

[Relationship between characteristic behaviors of children with AD/HD and mothers' parenting styles].

PubMed

Mano, Shoko; Uno, Hiroyuki

2007-01-01

Previous studies have revealed that mothers of children with attention-deficit/hyperactivity disorder (AD/HD) have an authoritarian parenting style. However, the psychological process of developing an authoritarian parenting style has yet to be clearly defined. To clarify this psychological process, the present study examined the hypothesis that the characteristic behaviors of children with AD/HD initially increase the mothers' parenting stress, which influences their parenting style. Thirty-six mothers of children with AD/HD (children's mean age: 8.1 years) and the same number of controls (children's mean age: 8.4 years) participated in the present study. The mothers' parenting stress was assessed using the Japanese Parenting Stress Index. Parenting styles were assessed using the TK-style scale for evaluating the relationships between parents and children. The results indicated that the mothers of children with AD/HD had significantly higher scores than controls for all parenting stress items and negative parenting style variables (dissatisfaction, reproach, strictness, interference, inconsistency and disagreement of 10 attitudes). Stepwise multiple regression analysis revealed that the characteristic behaviors of children with AD/HD were associated with the degree of attachment in mothers, which was related to the strict and reproachful parenting style in the AD/HD group. These results suggest that mothers of children with AD/HD are likely to have a strict and reproachful parenting style as a result of a lack of attachment with the child.

Brain mitochondria as a primary target in the development of treatment strategies for Alzheimer disease.

PubMed

Aliev, Gjumrakch; Palacios, Hector H; Walrafen, Brianna; Lipsitt, Amanda E; Obrenovich, Mark E; Morales, Ludis

2009-10-01

Alzheimer's disease (AD) and cerebrovascular accidents are two leading causes of age-related dementia. Increasing evidence supports the idea that chronic hypoperfusion is primarily responsible for the pathogenesis that underlies both disease processes. In this regard, hypoperfusion appears to induce oxidative stress (OS), which is largely due to reactive oxygen species (ROS), and over time initiates mitochondrial failure which is known as an initiating factor of AD. Recent evidence indicates that chronic injury stimulus induces hypoperfusion seen in vulnerable brain regions. This reduced regional cerebral blood flow (CBF) then leads to energy failure within the vascular endothelium and associated brain parenchyma, manifested by damaged mitochondrial ultrastructure (the formation of large number of immature, electron-dense "hypoxic" mitochondria) and by overproduction of mitochondrial DNA (mtDNA) deletions. Additionally, these mitochondrial abnormalities co-exist with increased redox metal activity, lipid peroxidation, and RNA oxidation. Interestingly, vulnerable neurons and glial cells show mtDNA deletions and oxidative stress markers only in the regions that are closely associated with damaged vessels, and, moreover, brain vascular wall lesions linearly correlate with the degree of neuronal and glial cell damage. We summarize the large body of evidence which indicates that sporadic, late-onset AD results from a vascular etiology by briefly reviewing mitochondrial damage and vascular risk factors associated with the disease and then we discuss the cerebral microvascular changes reason for the energy failure that occurs in normal aging and, to a much greater extent, AD.

Myoclonic epilepsy in Down syndrome and Alzheimer disease.

PubMed

Aller-Alvarez, J S; Menéndez-González, M; Ribacoba-Montero, R; Salvado, M; Vega, V; Suárez-Moro, R; Sueiras, M; Toledo, M; Salas-Puig, J; Álvarez-Sabin, J

2017-03-01

Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalized polyspike-wave discharges. We present a series of 11 patients with the diagnosis of DS or AD who developed myoclonic seizures or generalized tonic-clonic seizures. In all cases, clinical and neuroimaging studies and polygraph EEG monitoring was performed. In all cases, cognitive impairment progressed quickly after the onset of epilepsy causing an increase in the degree of dependence. The most common finding in the EEG was a slowing of brain activity with theta and delta rhythms, plus intercritical generalized polyspike-waves were objectified in eight patients. In neuroimaging studies was found cerebral cortical atrophy. The most effective drug in this series was the levetiracetam. The association of generalized epilepsy with elderly DS represents an epiphenomenon in evolution which is associated with a progressive deterioration of cognitive and motor functions. This epilepsy has some electroclinical characteristics and behaves as progressive myoclonic epilepsy, which is probably related to the structural changes that characterize the evolutionary similarity of DS with AD. Recognition of this syndrome is important, since it has prognostic implications and requires proper treatment. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Pain in Alzheimer's disease: A study of behavior and neural correlates

NASA Astrophysics Data System (ADS)

Beach, Paul Anthony

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by insidious and progressive impairment of cognition, emotion, and memory. Though pain in patients with AD is a major medical concern it is under diagnosed and under treated in patients, compared to cognitively healthy elderly. Further complicating matters, subjective self-report of pain by becomes increasingly compromised with disease progression; this often leaves clinicians and caregivers no choice but to rely on discerning pain from behavior alone. Patients also report pain at a lower frequency and intensity than healthy seniors (HS). These findings, coupled with recognition that AD pathology affects many pain processing brain regions, have prompted examination of whether AD alters pain perception. While there is evidence that AD actually predisposes heightened perception of pain, several issues remain: experimental work is limited to a handful of studies, whose results have been inconsistent; few examinations of pain in AD have included patients with advanced disease; the neural mechanism underlying altered pain in AD is not clear. I addressed these gaps in the literature by examining subjective, behavioral, and autonomic pain responses in 33 HS and 38 patients with varying severities of AD. A subset of these subjects (24 HS and 20 AD) were scanned, using fMRI. I then determined how the functional connectivity of various resting-state networks (RSNs) were associated with measured pain responses. I found that AD patients rated low-level stimuli as more painful than HS. Also, patients, regardless of severity, showed greater degrees of pain behaviors than HS - both with respect to global behaviors as measured by a clinical pain scale and facial responses as measured by an experimental tool. In contrast, autonomic responses were blunted with advancing AD. Altered pain responses in AD were associated with altered function of RSNs involved in attention and internal mentation, affect, somatosensation, and interoception (p<0.05, FWE corrected). These findings provide further evidence and an improved understanding of the neural basis for heightened pain sensitivity in patients with AD. They also emphasize the necessity to improve pain assessment and treatment strategies for a vulnerable patient population set to expand greatly in the coming decades.

Milk pH as a function of CO2 concentration, temperature, and pressure in a heat exchanger.

PubMed

Ma, Y; Barbano, D M

2003-12-01

Raw skim milk, with or without added CO2, was heated, held, and cooled in a small pilot-scale tubular heat exchanger (372 ml/min). The experiment was replicated twice, and, for each replication, milk was first carbonated at 0 to 1 degree C to contain 0 (control), 600, 1200, 1800, and 2400 ppm added CO2 using a continuous carbonation unit. After storage at 0 to 1 degree C, portions of milk at each CO2 concentration were heated to 40, 56, 72, and 80 degrees C, held at the desired temperature for 30 s (except 80 degrees C, holding 20 s) and cooled to 0 to 1 degree C. At each temperature, five pressures were applied: 69, 138, 207, 276, and 345 kPa. Pressure was controlled with a needle valve at the heat exchanger exit. Both the pressure gauge and pH probe were inline at the end of the holding section. Milk pH during heating depended on CO2 concentration, temperature, and pressure. During heating of milk without added CO2, pH decreased linearly as a function of increasing temperature but was independent of pressure. In general, the pH of milk with added CO2 decreased with increasing CO2 concentration and pressure. For milk with added CO2, at a fixed CO2 concentration, the effect of pressure on pH decrease was greater at a higher temperature. At a fixed temperature, the effect of pressure on pH decrease was greater for milk with a higher CO2 concentration. Thermal death of bacteria during pasteurization of milk without added CO2 is probably due not only to temperature but also to the decrease in pH that occurs during the process. Increasing milk CO2 concentration and pressure decreases the milk pH even further during heating and may further enhance the microbial killing power of pasteurization.

Autoimmune disease, familial clustering and thyroid carcinoma coexistent with autoimmune thyroiditis in children and adolescence: A cross-sectional study from the Czech Republic.

PubMed

Pomahacova, Renata; Zamboryova, Jana; Paterova, Petra; Fiklik, Karel; Cerna, Zdenka; Lad, Vaclav; Skalicka, Eva; Huml, Michal; Sykora, Josef

2018-06-07

The prevalence of autoimmune thyroiditis (AIT), as the most common autoimmune disease (AD) and papillary thyroid cancer (PTC) is steadily rising in children. The aim of this study was to determine the coexistence of other AD and thyroid carcinoma (TC) in AIT. The cross-sectional study conducted at a tertiary center comprised AIT children (< 19 years). Data on age/sex, thyroid function and ultrasound, autoantibodies, associated AD, familial occurence of AD and the occurence of TC for each child were collected. In total, 231 eligible patients (77% females) were included. The most common onset (66%) was during adolescence. At onset, hypothyroidism was detected in 59.3%; hashitoxicosis in 1.3%. The positivity of both autoantibodies was present in 60.6%, the negativity was in 3,5%. We confirmed a high frequency (44.6%) of AD with AIT predominance in parents and/or grandparents of patients and in siblings (7.4%). 15.2% had at least 1 comorbid AD, of which type 1 diabetes mellitus was the most common (8.5%). Over a period of 7 years TC was diagnosed in 16 patients (mean age 13.5 years) with predominance of PTC in 15 (94%) patients. AIT had concurrently 69% patients. 56% of patients had metastases (89% in AIT subjects). An invasive PTC was present in 44% (86% in AIT subjects). The prevalence rate of AD in AIT and first-degree relatives is high, and several new associations have been reported. Providers should be aware of comorbidities and TC in AIT as this would help in early diagnoses and timely interventions.

Redox-responsive solid lipid microparticles composed of octadecyl acrylate and allyl disulfide.

PubMed

Kim, Tae Hoon; Kim, Jin-Chul

2018-04-01

Redox-responsive solid lipid microparticles were prepared by an emulsification photo-polymerization method. Octadecyl acrylate (ODA) and a cross-linker (i.e. allyl disulfide (ADS) and octadiene (ODE)) were dissolved in dichloromethane, it was emulsified in poly(vinyl alcohol) solution, and the resulting O/W emulsion was irradiated with UV light. On the scanning electron microscope micrographs, the microparticles were sphere-like and they were not markedly different from the oil droplets in size. Using the atomic compositions analyzed by energy dispersive X-ray spectroscopy, the ODA to cross-linker molar ratio of ODA/ADS microparticles and ODA/ODE ones were calculated to be 1:0.13 and 1:0.15, respectively. In the FT-IR spectra of the microparticles, the signal of the vinyl group was hardly detected, implying that the monomer and the cross-linkers participated in the photo-polymerization. In differential scanning calorimetry study, ODA/ADS microparticles and ODA/ODE ones exhibited their endothermic peaks around 42.9 and 41.3 °C, respectively, possibly due to the melting of polymeric ODA. Dithiothreitol (DTT, a reducing agent) concentration had little effect on the release degree of dye loaded in ODA/ODE microparticles. Whereas, DTT concentration had a significant effect on the release degree of dye loaded in ODA/ADS microparticles. The release degree at 26 °C was weakly affected by DTT concentration. When the temperature was 37 °C, DTT concentration had a strong effect on the release degree. The disulfide cross-linker (i.e. ADS) can be broken to thiol compounds by the reducing agent, resulting in an increase in the release degree.

Melanopsin retinal ganglion cell loss in Alzheimer disease

PubMed Central

Ross‐Cisneros, Fred N.; Koronyo, Yosef; Hannibal, Jens; Gallassi, Roberto; Cantalupo, Gaetano; Sambati, Luisa; Pan, Billy X.; Tozer, Kevin R.; Barboni, Piero; Provini, Federica; Avanzini, Pietro; Carbonelli, Michele; Pelosi, Annalisa; Chui, Helena; Liguori, Rocco; Baruzzi, Agostino; Koronyo‐Hamaoui, Maya; Sadun, Alfredo A.; Carelli, Valerio

2015-01-01

Objective Melanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer disease (AD). We investigated mRGCs in AD, hypothesizing that they contribute to circadian dysfunction. Methods We assessed retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in 21 mild‐moderate AD patients, and in a subgroup of 16 we evaluated rest–activity circadian rhythm by actigraphy. We studied postmortem mRGCs by immunohistochemistry in retinas, and axons in optic nerve cross‐sections of 14 neuropathologically confirmed AD patients. We coimmunostained for retinal amyloid β (Aβ) deposition and melanopsin to locate mRGCs. All AD cohorts were compared with age‐matched controls. Results We demonstrated an age‐related optic neuropathy in AD by OCT, with a significant reduction of RNFL thickness (p = 0.038), more evident in the superior quadrant (p = 0.006). Axonal loss was confirmed in postmortem AD optic nerves. Abnormal circadian function characterized only a subgroup of AD patients. Sleep efficiency was significantly reduced in AD patients (p = 0.001). We also found a significant loss of mRGCs in postmortem AD retinal specimens (p = 0.003) across all ages and abnormal mRGC dendritic morphology and size (p = 0.003). In flat‐mounted AD retinas, Aβ accumulation was remarkably evident inside and around mRGCs. Interpretation We show variable degrees of rest–activity circadian dysfunction in AD patients. We also demonstrate age‐related loss of optic nerve axons and specifically mRGC loss and pathology in postmortem AD retinal specimens, associated with Aβ deposition. These results all support the concept that mRGC degeneration is a contributor to circadian rhythm dysfunction in AD. ANN NEUROL 2016;79:90–109 PMID:26505992

Rich club analysis in the Alzheimer's disease connectome reveals a relatively undisturbed structural core network

PubMed Central

Daianu, Madelaine; Jahanshad, Neda; Nir, Talia M.; Jack, Clifford R.; Weiner, Michael W.; Bernstein, Matthew; Thompson, Paul M.

2015-01-01

Diffusion imaging can assess the white matter connections within the brain, revealing how neural pathways break down in Alzheimer's disease (AD). We analyzed 3-Tesla whole-brain diffusion-weighted images from 202 participants scanned by the Alzheimer's Disease Neuroimaging Initiative – 50 healthy controls, 110 with mild cognitive impairment (MCI) and 42 AD patients. From whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We tested whether AD disrupts the ‘rich-club’ – a network property where high-degree network nodes are more interconnected than expected by chance. We calculated the rich-club properties at a range of degree thresholds, as well as other network topology measures including global degree, clustering coefficient, path length and efficiency. Network disruptions predominated in the low-degree regions of the connectome in patients, relative to controls. The other metrics also showed alterations, suggesting a distinctive pattern of disruption in AD, less pronounced in MCI, targeting global brain connectivity, and focusing on more remotely connected nodes rather than the central core of the network. AD involves severely reduced structural connectivity; our step-wise rich club coefficients analyze points to disruptions predominantly in the peripheral network components; other modalities of data are needed to know if this indicates impaired communication among non rich-club regions. The highly connected core was relatively preserved, offering new evidence on the neural basis of progressive risk for cognitive decline. PMID:26037224

Absence of Alzheimer Disease Neuropathologic Changes in Eyes of Subjects With Alzheimer Disease.

PubMed

Williams, Erik A; McGuone, Declan; Frosch, Matthew P; Hyman, Bradley T; Laver, Nora; Stemmer-Rachamimov, Anat

2017-05-01

Alzheimer disease (AD) is the most common cause of dementia in the elderly, and is characterized by extracellular deposition of β-amyloid and intracellular accumulation of hyperphosphorylated tau protein in the brain. These pathologic findings are identified postmortem. Various visual deficits in AD have been reported and there have been conflicting reports, through imaging and pathology studies, regarding the presence of changes in the globe that mirror Alzheimer changes in the brain. Moreover, both macular degeneration and glaucoma have been variously characterized as having AD-related features. We examined one or both eyes from 19 autopsy cases, 17 of which had varying degrees of AD-related changes, and 2 of which were age-matched controls. Three cases had glaucoma and 4 had macular degeneration. Immunohistochemistry for tau, β-amyloid, TDP-43, ubiquitin, and α-synuclein showed no evidence of inclusions, deposits or other protein accumulation in any case, in any part of the globe. This finding suggests that regardless of the severity of changes seen in the brain in AD, there are no similar changes in the globe. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Current status of renin-aldosterone angiotensin system-targeting anti-hypertensive drugs as therapeutic options for Alzheimer's disease.

PubMed

Ashby, Emma Louise; Kehoe, Patrick G

2013-10-01

Hypertension is a modifiable risk factor for Alzheimer's disease (AD) and other dementias. Yet, despite this well-documented association, few of the current strategies to treat AD are directed at this possible target. The renin-aldosterone angiotensin system (RAAS) is a centrally active modifiable pathway that is involved in cerebral blood flow regulation. Currently, three classes of RAAS-targeting drugs are licensed for treatment of peripheral hypertension--angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin II receptor blockers (ARBs) and direct renin inhibitors (DRIs). All of these are generally well tolerated and have been shown to offer varying degrees of protection on aspects of cognition and dementia, thus making them an attractive therapeutic option for AD. This review summarises existing evidence regarding the plausibility of using RAAS-targeting drugs as a strategy to treat AD and highlights unresolved aspects to such approaches, namely the potential impact of altering angiotensin II-mediated processes in the central nervous system. Continued biochemical research of the RAAS pathway in combination with formal investigation of current RAAS-modifying drugs in randomised clinical trials is now necessary to determine their therapeutic value in AD.

Are Abeta and its derivatives causative agents or innocent bystanders in AD?

PubMed

Robakis, Nikolaos K

2010-01-01

Alzheimer's disease (AD) is characterized by neurodegeneration in neocortical regions of the brain. Currently, Abeta-based theories, including amyloid depositions and soluble Abeta, form the basis of most therapeutic approaches to AD. It remains unclear, however, whether Abeta and its derivatives are the primary causative agents of neuronal loss in AD. Reported studies show no significant correlations between brain amyloid depositions and either degree of dementia or loss of neurons, and brain amyloid loads similar to AD are often found in normal individuals. Furthermore, behavioral abnormalities in animal models overexpressing amyloid precursor protein seem independent of amyloid depositions. Soluble Abeta theories propose toxic Abeta42 or its oligomers as the agents that promote cell death in AD. Abeta peptides, however, are normal components of human serum and CSF, and it is unclear under what conditions these peptides become toxic. Presently, there is little evidence of disease-associated abnormalities in soluble Abeta and no toxic oligomers specific to AD have been found. That familial AD mutations of amyloid precursor protein, PS1 and PS2 promote neurodegeneration suggests the biological functions of these proteins play critical roles in neuronal survival. Evidence shows that the PS/gamma-secretase system promotes production of peptides involved in cell surface-to-nucleus signaling and gene expression, providing support for the hypothesis that familial AD mutations may contribute to neurodegeneration by inhibiting PS-dependent signaling pathways. Copyright 2010 S. Karger AG, Basel.

Negative energy, superluminosity, and holography

NASA Astrophysics Data System (ADS)

Polchinski, Joseph; Susskind, Leonard; Toumbas, Nicolaos

1999-10-01

The holographic connection between large N super Yang-Mills (SYM) theory and gravity in anti-de Sitter (AdS) space requires unfamiliar behavior of the SYM theory in the limit that the curvature of the AdS geometry becomes small. The paradoxical behavior includes superluminal oscillations and negative energy density. These effects typically occur in the SYM description of events which take place far from the boundary of AdS when the signal from the event arrives at the boundary. The paradoxes can be resolved by assuming a very rich collection of hidden degrees of freedom of the SYM theory which store information but give rise to no local energy density. These degrees of freedom, called precursors, are needed to make possible sudden apparently acausal energy momentum flows. Such behavior would be impossible in classical field theory as a consequence of the positivity of the energy density. However we show that these effects are not only allowed in quantum field theory but that we can model them in free quantum field theory.

Bayesian network analysis reveals alterations to default mode network connectivity in individuals at risk for Alzheimer's disease.

PubMed

Li, Rui; Yu, Jing; Zhang, Shouzi; Bao, Feng; Wang, Pengyun; Huang, Xin; Li, Juan

2013-01-01

Alzheimer's disease (AD) is associated with abnormal functioning of the default mode network (DMN). Functional connectivity (FC) changes to the DMN have been found in patients with amnestic mild cognitive impairment (aMCI), which is the prodromal stage of AD. However, whether or not aMCI also alters the effective connectivity (EC) of the DMN remains unknown. We employed a combined group independent component analysis (ICA) and Bayesian network (BN) learning approach to resting-state functional MRI (fMRI) data from 17 aMCI patients and 17 controls, in order to establish the EC pattern of DMN, and to evaluate changes occurring in aMCI. BN analysis demonstrated heterogeneous regional convergence degree across DMN regions, which were organized into two closely interacting subsystems. Compared to controls, the aMCI group showed altered directed connectivity weights between DMN regions in the fronto-parietal, temporo-frontal, and temporo-parietal pathways. The aMCI group also exhibited altered regional convergence degree in the right inferior parietal lobule. Moreover, we found EC changes in DMN regions in aMCI were correlated with regional FC levels, and the connectivity metrics were associated with patients' cognitive performance. This study provides novel sights into our understanding of the functional architecture of the DMN and adds to a growing body of work demonstrating the importance of the DMN as a mechanism of aMCI.

The GAy MEn Sex StudieS: Anodyspareunia Among Belgian Gay Men.

PubMed

Vansintejan, Johan; Vandevoorde, Jan; Devroey, Dirk

2013-12-01

Anal intercourse is commonly associated with male homosexuality, but not all gay males engage in anal sex. Receptive anal intercourse can cause pain. Little is known about this sexual dysfunction. This study aims to determine the 4-week incidence of anodyspareunia (AD) in a sample of Belgian men who have sex with men (MSM) population and to assess the relevance of possible predictors such as age, relationship, and sexual behavior. An internet-based survey on sexual behavior and sexual dysfunctions, called GAy MEn Sex StudieS, was administered to the MSM aged 18 years or older, between April and December 2008. A part of the questionnaire was focusing on anal eroticism. The participants, who self-reported being human immunodeficiency virus-positive or not having anal intercourse, were excluded. Female Sexual Function Index questions on pain domain adapted for anal intercourse. A total of 1,752 Belgian MSM completed the questionnaire. Of the 1,190 (68%) participants who reported engaging in receptive anal sex in the last 4 weeks, 59% indicated having some degree of anal pain during and after sexual intercourse. For 44%, the level of pain was acceptable. Mild AD was reported by 32%, 17% had mild to moderate AD, 4% had moderate AD, and 2% had severe AD. Independent predictors for the presence of AD were age, having a steady relationship, frequency of sex with their partner, number of sex partners, number of sex partners at the same time, and massaging the anal sphincter before anal sex. The prevalence and severity of AD among the MSM were lower among older participants, the MSM who more frequently had sex with their partner, and participants with a higher number of sex partners. Inadequate lubrication and lack of oral or digitoproctic stimulation prior to penetration were the most important factors predicting pain. Unsafe anal sex was performed by 28%. One-third of the participants reported not engaging in receptive nor penetrative anal sex. The 59% of participating Belgian MSM, who had anal receptive intercourse, reported some degree of AD. These findings highlight the need for more education about anal eroticism for MSM, and more research into AD is needed. Vansintejan J, Vandevoorde J, and Devroey D. The GAy MEn Sex StudieS: Anodyspareunia among Belgian gay men. Sex Med 2013;1:87-94.

The GAy MEn Sex StudieS: Anodyspareunia Among Belgian Gay Men

PubMed Central

Vansintejan, Johan; Vandevoorde, Jan; Devroey, Dirk

2013-01-01

Introduction Anal intercourse is commonly associated with male homosexuality, but not all gay males engage in anal sex. Receptive anal intercourse can cause pain. Little is known about this sexual dysfunction. Aim This study aims to determine the 4-week incidence of anodyspareunia (AD) in a sample of Belgian men who have sex with men (MSM) population and to assess the relevance of possible predictors such as age, relationship, and sexual behavior. Methods An internet-based survey on sexual behavior and sexual dysfunctions, called GAy MEn Sex StudieS, was administered to the MSM aged 18 years or older, between April and December 2008. A part of the questionnaire was focusing on anal eroticism. The participants, who self-reported being human immunodeficiency virus-positive or not having anal intercourse, were excluded. Main Outcome Measure Female Sexual Function Index questions on pain domain adapted for anal intercourse. Results A total of 1,752 Belgian MSM completed the questionnaire. Of the 1,190 (68%) participants who reported engaging in receptive anal sex in the last 4 weeks, 59% indicated having some degree of anal pain during and after sexual intercourse. For 44%, the level of pain was acceptable. Mild AD was reported by 32%, 17% had mild to moderate AD, 4% had moderate AD, and 2% had severe AD. Independent predictors for the presence of AD were age, having a steady relationship, frequency of sex with their partner, number of sex partners, number of sex partners at the same time, and massaging the anal sphincter before anal sex. The prevalence and severity of AD among the MSM were lower among older participants, the MSM who more frequently had sex with their partner, and participants with a higher number of sex partners. Inadequate lubrication and lack of oral or digitoproctic stimulation prior to penetration were the most important factors predicting pain. Unsafe anal sex was performed by 28%. Conclusion One-third of the participants reported not engaging in receptive nor penetrative anal sex. The 59% of participating Belgian MSM, who had anal receptive intercourse, reported some degree of AD. These findings highlight the need for more education about anal eroticism for MSM, and more research into AD is needed. Vansintejan J, Vandevoorde J, and Devroey D. The GAy MEn Sex StudieS: Anodyspareunia among Belgian gay men. Sex Med 2013;1:87–94. PMID:25356292

Hippocampus-precuneus functional connectivity as an early sign of Alzheimer's disease: a preliminary study using structural and functional magnetic resonance imaging data.

PubMed

Kim, Junghoe; Kim, Yong-Hwan; Lee, Jong-Hwan

2013-02-07

Alzheimer's disease (AD) is characterized by structural atrophies in the hippocampus (HP) and aberrant patterns of functional connectivities (FC) between the hippocampus and the rest of the brain. However, the relationship between cortical atrophy levels and corresponding degrees of aberrant FC patterns has not been systematically examined. In this study, we investigated whether there was an explicit link between structural abnormalities and corresponding functional aberrances associated with AD using structural and functional magnetic resonance imaging (fMRI) data. To this end, brain regions with cortical atrophies that are associated with AD were identified in the HP in the left (L) and right (R) hemispheres using structural MRI data from volume analyses (p<0.03 for L-HP; p<0.04 for R-HP) and voxel-based morphometry analyses (p<4×10(-4) for L-HP; p<2×10(-3) for R-HP). Aberrantly reduced FC levels between the HP (with atrophy) and precuneus were also consistently observed in fMRI data from AD than HC brains that were analyzed by the Pearson's correlation coefficients (p<3×10(-4) for L-HP; and p<8×10(-5) for R-HP). In addition, the substantial negative FC levels from the HC brains between the precuneus and post central gyrus (PoCG) without structural atrophy were also significantly diminished from the AD brains (p<5×10(-5) for L-PoCG; and p<6×10(-5) for R-PoCG). The effect sizes of these aberrant FC levels associated with AD were greater than that of cortical atrophy levels when comparing using normalized Z score and Cohen's d measures, which indicates that an aberrant FC level may precede cortical atrophy. Copyright © 2012 Elsevier B.V. All rights reserved.

Skin reaction and regeneration after single sodium lauryl sulfate exposure stratified by filaggrin genotype and atopic dermatitis phenotype.

PubMed

Bandier, J; Carlsen, B C; Rasmussen, M A; Petersen, L J; Johansen, J D

2015-06-01

Filaggrin is key for the integrity of the stratum corneum. Mutations in the filaggrin gene (FLGnull) play a prominent role in atopic dermatitis (AD) pathogenesis. People with AD have increased susceptibility to irritants. However, little is known about the effect of filaggrin genotype and AD phenotype on irritant response and skin regeneration. To investigate the role of FLGnull and AD groups for skin reaction and recovery after sodium lauryl sulfate (SLS) irritation. This is a case-control study comprising 67 subjects, including healthy controls and patients with and without FLGnull and AD. Reactivity to different doses of SLS at 24, 48, 72 and 145 h after SLS application was measured by transepidermal water loss (TEWL) and laser Doppler flowmetry (LDF). Reactivity was assessed univariately and by pattern analysis. All patient groups showed a higher degree of skin-barrier disruption and inflammation than did controls in response to SLS. Assessing reactivity by the delta value of the area under the curve for both TEWL and LDF showed significant differences between healthy controls and those with the AD phenotype, irrespective of filaggrin mutation. The poorest regeneration was among those with the AD phenotype. The two AD phenotype groups were separated by multivariate technique, due to earlier inflammatory reactivity among subjects with FLGnullplus AD compared with the AD phenotype alone. Both skin reaction and regeneration were significantly different between the patient population and the healthy controls. Additionally, response severity and regeneration depended more on AD phenotype than on filaggrin genotype, whereas the response was more rapid among the FLGnullplus AD individuals. © 2015 British Association of Dermatologists.

Causes of variation in botulinal inhibition in perishable canned cured meat.

PubMed

Tompkin, R B; Christiansen, L N; Shaparis, A B

1978-05-01

Final internal processing temperatures within the range of 63 to 74 degrees C did not alter the degree of botulinal inhibition in inoculated perishable canned comminuted cured pork abused at 27 degrees C. Adding hemoglobin to the formulation reduced residual nitrite after processing and decreased botulinal inhibition. Different meats yielded different rates of botulinal outgrowth when substituted for fresh pork ham. Pork or beef heart meat showed no inhibition of the Clostridium botulinum inoculum even with a 156-microgram/g amount of sodium nitrite added to the product. This effect appears to be one of stimulating outgrowth, since residual nitrite depletion was not measurably altered.

Causes of variation in botulinal inhibition in perishable canned cured meat.

PubMed Central

Tompkin, R B; Christiansen, L N; Shaparis, A B

1978-01-01

Final internal processing temperatures within the range of 63 to 74 degrees C did not alter the degree of botulinal inhibition in inoculated perishable canned comminuted cured pork abused at 27 degrees C. Adding hemoglobin to the formulation reduced residual nitrite after processing and decreased botulinal inhibition. Different meats yielded different rates of botulinal outgrowth when substituted for fresh pork ham. Pork or beef heart meat showed no inhibition of the Clostridium botulinum inoculum even with a 156-microgram/g amount of sodium nitrite added to the product. This effect appears to be one of stimulating outgrowth, since residual nitrite depletion was not measurably altered. PMID:350156

Electrochemical pretreatment of waste activated sludge: effect of process conditions on sludge disintegration degree and methane production.

PubMed

Ye, Caihong; Yuan, Haiping; Dai, Xiaohu; Lou, Ziyang; Zhu, Nanwen

2016-11-01

Waste activated sludge (WAS) requires a long digestion time because of a rate-limiting hydrolysis step - the first phase of anaerobic digestion (AD). Pretreatment can be used prior to AD to facilitate the hydrolysis step and improve the efficiency of WAS digestion. This study evaluated a novel application of electrochemical (EC) technology employed as the pretreatment method prior to AD of WAS, focusing on the effect of process conditions on sludge disintegration and subsequent AD process. A superior process condition of EC pretreatment was obtained by reaction time of 30 min, electrolysis voltage of 20 V, and electrode distance of 5 cm, under which the disintegration degree of WAS ranged between 9.02% and 9.72%. In the subsequent batch AD tests, 206 mL/g volatile solid (VS) methane production in EC pretreated sludge was obtained, which was 20.47% higher than that of unpretreated sludge. The AD time was 19 days shorter for EC pretreated sludge compared to the unpretreated sludge. Additionally, the EC + AD reactor achieved 41.84% of VS removal at the end of AD. The analysis of energy consumption showed that EC pretreatment could be effective in enhancing sludge AD with reduced energy consumption when compared to other pretreatment methods.

Prevalence and clinicoradiological analyses of patients with Alzheimer disease coexisting multiple microbleeds.

PubMed

Nagasawa, Junpei; Kiyozaka, Tetsuhito; Ikeda, Ken

2014-10-01

Pathologic findings of cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD) coexist frequently. Both diseases are associated with β-amyloid deposition and dementia. We aimed to evaluate frequency and clinicoradiological profile of AD patients with multiple microbleeds (MBs). We reviewed clinical records and magnetic resonance imaging (MRI) findings in patients with probable AD diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria from 2009 to 2012. Brain MRI was performed at 1.5-T superconducting system, including T2*-weighted gradient-echo imaging. MBs were defined as rounded, hypointense foci less than or equal to 10 mm in size in the brain parenchyma. MBs topography was divided into the lobar (L) and the deep/infratentorial (D/I) region. Multiple MBs were defined as the number greater than or equal to 8 in the L and the D/I territory, respectively. White matter hyperintensities (WMHs) were assessed using the age-related white matter changes scale. Clinicoradiological findings were examined for 1 year. Prevalence and clinicoradiological profiles were studied in patients with multiple L or D/I MBs. Five hundred fifty patients (238 men and 312 women) participated in the present study. Mean age (standard deviation) was 78.4 (7.7) years, 78.3 (8.1) years in men and 78.6 (7.5) years in women. A total of 132 patients (55 men and 78 women) had at least 1 MB. Prevalence of MB ≥ 1 was 24%, 23 in men and 25 in women. The ratio of L and D/I MBs were 1.1, .6 in men and 1.8 in women. Multiple MBs were detected in 93 patients (17%), 38 (16%) men and 55 (17%) in women. L distribution was found in 49 patients (9%), 15 men (6%) and 34 women (11%), and D/I distribution in 44 patients (8%), 23 men (10%) and 21 women (7%). Multiple L MBs was associated with faster progression of dementia, cerebral hemorrhage, and increased number of MBs. Multiple D/I MBs were linked to hypertension and WMH scores. The present study indicated that the prevalence of multiple MBs was 17% in Japanese AD patients. The clinicoradiological profile suggested severe degree of CAA in patients with multiple L MBs (9%) and hypertension and aged changes in patients with multiple D/I MBs (8%). T2*-weighted imaging is a useful tool for evaluating degree of CAA and hypertensive vascular changes. We should pay more attention to management and care in AD patients with multiple MBs. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Factors determining disease duration in Alzheimer's disease: a postmortem study of 103 cases using the Kaplan-Meier estimator and Cox regression.

PubMed

Armstrong, R A

2014-01-01

Factors associated with duration of dementia in a consecutive series of 103 Alzheimer's disease (AD) cases were studied using the Kaplan-Meier estimator and Cox regression analysis (proportional hazard model). Mean disease duration was 7.1 years (range: 6 weeks-30 years, standard deviation = 5.18); 25% of cases died within four years, 50% within 6.9 years, and 75% within 10 years. Familial AD cases (FAD) had a longer duration than sporadic cases (SAD), especially cases linked to presenilin (PSEN) genes. No significant differences in duration were associated with age, sex, or apolipoprotein E (Apo E) genotype. Duration was reduced in cases with arterial hypertension. Cox regression analysis suggested longer duration was associated with an earlier disease onset and increased senile plaque (SP) and neurofibrillary tangle (NFT) pathology in the orbital gyrus (OrG), CA1 sector of the hippocampus, and nucleus basalis of Meynert (NBM). The data suggest shorter disease duration in SAD and in cases with hypertensive comorbidity. In addition, degree of neuropathology did not influence survival, but spread of SP/NFT pathology into the frontal lobe, hippocampus, and basal forebrain was associated with longer disease duration.

Negative specific heat of black-holes from fluid-gravity correspondence

NASA Astrophysics Data System (ADS)

Bhattacharya, Swastik; Shankaranarayanan, S.

2017-04-01

Black holes in asymptotically flat space-times have negative specific heat—they get hotter as they loose energy. A clear statistical mechanical understanding of this has remained a challenge. In this work, we address this issue using fluid-gravity correspondence which aims to associate fluid degrees of freedom to the horizon. Using linear response theory and the teleological nature of event horizon, we show explicitly that the fluctuations of the horizon-fluid lead to negative specific heat for a Schwarzschild black Hole. We also point out how the specific heat can be positive for Kerr-Newman or AdS black holes. Our approach constitutes an important advance as it allows us to apply the canonical ensemble approach to study thermodynamics of asymptotically flat black hole space-times.

A study on Korean nursing students' educational outcomes

PubMed Central

Oh, Kasil; Lee, Hyang-Yeon; Lee, Sook-Ja; Kim, In-Ja; Choi, Kyung-Sook; Ko, Myung-Sook

2011-01-01

The purpose of this study was to describe outcome indicators of nursing education including critical thinking, professionalism, leadership, and communication and to evaluate differences among nursing programs and academic years. A descriptive research design was employed. A total of 454 students from four year baccalaureate (BS) nursing programs and two three-year associate degree (AD) programs consented to complete self-administered questionnaires. The variables were critical thinking, professionalism, leadership and communication. Descriptive statistics, χ2-test, t-tests, ANOVA, and the Tukey test were utilized for the data analysis. All the mean scores of the variables were above average for the test instruments utilized. Among the BS students, those in the upper classes tended to attain higher scores, but this tendency was not identified in AD students. There were significant differences between BS students and AD students for the mean scores of leadership and communication. These findings suggested the need for further research to define properties of nursing educational outcomes, and to develop standardized instruments for research replication and verification. PMID:21602914

CCD Measurements of Star Systems 00152+2722 J 868 and 05413+5329 BUP 82AD

NASA Astrophysics Data System (ADS)

Luberto, Judah; Priest, Stephen; Jackman, Max; Splettstoeszer, Annaclare; Blankenbiller, Craig; Priest, Allen

2018-01-01

Position angle (Theta) and separation (Rho) measurements were acquired through images of WDS 00152+2722 (J 868) and WDS 05413+5329 (BUP 82AD) using T7, a 17-inch telescope in Nerpio, Spain, through the iTelescope network, and a 10-inch telescope near San Diego, California. Image data was analyzed using MaxIm DL Pro 6 and Mira Pro x64 software tools. J 868 has an angle of 231.158 degrees and a separation of 6.205 arcseconds. BUP 82AD has an angle of 283.404 degrees and a separation of 699.842 arcseconds. Measurements of J 868 follow its proposed orbit, but it is likely the two stars are not gravitationally bound. Measurements on BUP 82AD suggest this pair is an optical binary.

Lost and forgotten? Orientation versus memory in Alzheimer's disease and frontotemporal dementia.

PubMed

Yew, Belinda; Alladi, Suvarna; Shailaja, Mekala; Hodges, John R; Hornberger, Michael

2013-01-01

Recent studies suggest that significant memory problems are not specific to Alzheimer's disease (AD) but can be also observed in other neurodegenerative conditions, such as behavioral variant frontotemporal dementia (bvFTD). We investigated whether orientation (spatial & temporal) information is a better diagnostic marker for AD compared to memory and whether their atrophy correlates of orientation and memory differ. A large sample (n = 190) of AD patients (n = 73), bvFTD patients (n = 54), and healthy controls (n = 63) underwent testing. A subset of the patients (n = 72) underwent structural imaging using voxel-based morphometry analysis of magnetic resonance brain imaging. Orientation and memory scores from the Addenbrooke's Cognitive Examination showed that AD patients had impaired orientation and memory, while bvFTD patients performing at control level for orientation but had impaired memory. A logistic regression showed that 78% of patients could be classified on the basis of orientation and memory scores alone at clinic presentation. Voxel-based morphometry analysis was conducted using orientation and memory scores as covariates, which showed that the neural correlates for orientation and memory also dissociated with posterior hippocampus cortex being related to orientation in AD, while the anterior hippocampus was associated with memory performance in the AD and bvFTD patients. Orientation and memory measures discriminate AD and bvFTD to a high degree and tap into different hippocampal regions. Disorientation and posterior hippocampus appears therefore specific to AD and will allow clinicians to discriminate AD patients from other neurodegenerative conditions with similar memory deficits at clinic presentation.

Predicting MCI outcome with clinically available MRI and CSF biomarkers

PubMed Central

Heister, D.; Brewer, J.B.; Magda, S.; Blennow, K.

2011-01-01

Objective: To determine the ability of clinically available volumetric MRI (vMRI) and CSF biomarkers, alone or in combination with a quantitative learning measure, to predict conversion to Alzheimer disease (AD) in patients with mild cognitive impairment (MCI). Methods: We stratified 192 MCI participants into positive and negative risk groups on the basis of 1) degree of learning impairment on the Rey Auditory Verbal Learning Test; 2) medial temporal atrophy, quantified from Food and Drug Administration–approved software for automated vMRI analysis; and 3) CSF biomarker levels. We also stratified participants based on combinations of risk factors. We computed Cox proportional hazards models, controlling for age, to assess 3-year risk of converting to AD as a function of risk group and used Kaplan-Meier analyses to determine median survival times. Results: When risk factors were examined separately, individuals testing positive showed significantly higher risk of converting to AD than individuals testing negative (hazard ratios [HR] 1.8–4.1). The joint presence of any 2 risk factors substantially increased risk, with the combination of greater learning impairment and increased atrophy associated with highest risk (HR 29.0): 85% of patients with both risk factors converted to AD within 3 years, vs 5% of those with neither. The presence of medial temporal atrophy was associated with shortest median dementia-free survival (15 months). Conclusions: Incorporating quantitative assessment of learning ability along with vMRI or CSF biomarkers in the clinical workup of MCI can provide critical information on risk of imminent conversion to AD. PMID:21998317

Clustering of dystonia in some pedigrees with autosomal dominant essential tremor suggests the existence of a distinct subtype of essential tremor

PubMed Central

2010-01-01

Background There is an ongoing debate whether essential tremor (ET) represents a monosymptomatic disorder or other neurologic symptoms are compatible with the diagnosis of ET. Many patients with clinically definite ET develop dystonia. It remains unknown whether tremor associated with dystonia represent a subtype of ET. We hypothesized that ET with dystonia represents a distinct subtype of ET. Methods We studied patients diagnosed with familial ET and dystonia. We included only those patients whose first-degree relatives met diagnostic criteria for ET or dystonia with tremor. This cohort was ascertained for the presence of focal, segmental, multifocal, hemidystonia or generalized dystonia, and ET. Results We included 463 patients from 97 kindreds with autosomal dominant mode of inheritance (AD), defined by the vertical transmission of the disease. ET was the predominant phenotype in every ascertained family and each was phenotypically classified as AD ET. "Pure" ET was present in 365 individuals. Focal or segmental dystonia was present in 98 of the 463 patients; 87 of the 98 patients had ET associated with dystonia, one had dystonic tremor and ten had isolated dystonia. The age of onset and tremor severity did not differ between patients with "pure" ET and ET associated with dystonia. We did not observe a random distribution of dystonia in AD ET pedigrees and all patients with dystonia associated with ET were clustered in 28% of all included pedigrees (27/97, p < 0.001). Conclusions Our results suggest that familial ET associated with dystonia may represent a distinct subtype of ET. PMID:20670416

Rethinking Teacher Evaluation: A Conversation about Statistical Inferences and Value-Added Models

ERIC Educational Resources Information Center

Callister Everson, Kimberlee; Feinauer, Erika; Sudweeks, Richard R.

2013-01-01

In this article, the authors provide a methodological critique of the current standard of value-added modeling forwarded in educational policy contexts as a means of measuring teacher effectiveness. Conventional value-added estimates of teacher quality are attempts to determine to what degree a teacher would theoretically contribute, on average,…

Plasma cytokine IL-6 levels and subjective cognitive decline: preliminary findings.

PubMed

Keegan, Andrew P; Paris, Daniel; Luis, Cheryl A; Abdullah, Laila; Ait-Ghezala, Ghania; Beaulieu-Abdelahad, David; Pryor, Makenzie; Chaykin, Jillian; Crynen, Gogce; Crawford, Fiona; Mullan, Michael

2018-02-01

Detection of Alzheimer's disease (AD) prior to clinical inception will be paramount for introducing disease modifying treatments. We have begun collecting baseline characteristics of a community cohort for longitudinal assessment and testing of antecedent blood-based biomarkers. We describe the baseline visit from the first 131 subjects in relationship to a commonly described cytokine, interleukin 6 (IL-6). Subjects from the community presented for a free memory screening with varying degrees of memory concern. We quantified the baseline plasma levels of the cytokine IL-6 and assessed cognition (Montreal Cognitive Assessment, MoCA) and mood (Geriatric Depression Scale, GDS) in relationship to their memory concern. Baseline MoCA scores were inversely related to age, and this association was influenced by an AD risk factor, Apolipoprotein E (APOE4) carrier status. The degree of subjective cognitive decline correlated with GDS and was inversely related to MoCA scores. Interleukin 6 levels were related to age, body mass index, and years of education. It will be important to assess how these baseline IL-6 levels and forthcoming novel biomarkers relate to future cognitive decline. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Abnormal degree centrality in Alzheimer's disease patients with depression: A resting-state functional magnetic resonance imaging study.

PubMed

Guo, Zhongwei; Liu, Xiaozheng; Hou, Hongtao; Wei, Fuquan; Liu, Jian; Chen, Xingli

2016-06-15

Depression is common in Alzheimer's disease (AD) and occurs in AD patients with a prevalence of up to 40%. It reduces cognitive function and increases the burden on caregivers. Currently, there are very few medications that are useful for treating depression in AD patients. Therefore, understanding the brain abnormalities in AD patients with depression (D-AD) is crucial for developing effective interventions. The aim of this study was to investigate the intrinsic dysconnectivity pattern of whole-brain functional networks at the voxel level in D-AD patients based on degree centrality (DC) as measured by resting-state functional magnetic resonance imaging (R-fMRI). Our study included 32 AD patients. All patients were evaluated using the Neuropsychiatric Inventory and Hamilton Depression Rating Scale and further divided into two groups: 15 D-AD patients and 17 non-depressed AD (nD-AD) patients. R-fMRI datasets were acquired from these D-AD and nD-AD patients. First, we performed a DC analysis to identify voxels that showed altered whole brain functional connectivity (FC) with other voxels. We then further investigated FC using the abnormal DC regions to examine in more detail the connectivity patterns of the identified DC changes. D-AD patients had lower DC values in the right middle frontal, precentral, and postcentral gyrus than nD-AD patients. Seed-based analysis revealed decreased connectivity between the precentral and postcentral gyrus to the supplementary motor area and middle cingulum. FC also decreased in the right middle frontal, precentral, and postcentral gyrus. Thus, AD patients with depression fit a 'network dysfunction model' distinct from major depressive disorder and AD. Copyright © 2016. Published by Elsevier Inc.

Nonclassical properties and teleportation in the two-mode photon-added displaced squeezed states

NASA Astrophysics Data System (ADS)

Hoai, Nguyen Thi Xuan; Duc, Truong Minh

2016-01-01

In this paper, we study the nonclassical properties and find out the effect of photon addition on these properties as well as the process of teleportation in the two-mode photon-added displaced squeezed (TMPADS) states. We derive the analytic expressions of the Wigner function, the photon number distribution and the intermode photon antibunching for these states. We show that photon addition operation not only makes the Wigner function become negative but also leads to increase the degree of antibunching. The peak of the photon number distribution becomes flatter and shifts to the greater number of photons by adding photons to both modes simultaneously. Furthermore, it is proved that the degree of intermodal entanglement becomes bigger and bigger through increasing the number of photons added to both modes. As expected, when using these states as an entanglement resource to teleport a state, the average fidelity of teleportation process is also improved by increasing the number of added photons.

Postoperative shoulder imbalance in Lenke Type 1A adolescent idiopathic scoliosis and related factors.

PubMed

Matsumoto, Morio; Watanabe, Kota; Kawakami, Noriaki; Tsuji, Taichi; Uno, Koki; Suzuki, Teppei; Ito, Manabu; Yanagida, Haruhisa; Minami, Shohei; Akazawa, Tsutomu

2014-11-05

The purpose of this study was to investigate the occurrence and factors associated with postoperative shoulder imbalance (PSI) in Lenke type 1A curve. This study included 106 patients with Lenke Type 1A curve who were followed up more than two years after posterior correction surgery. Pedicle screw (PS) constructs were used in 84 patients, and hybrid constructs in 22. The upper instrumented vertebra was rostral to the upper-end vertebra (UEV) in 70 patients, at UEV in 26, and below UEV in 10. The clavicle angle and T1 tilt angle were measured as PSI indicators, and correlations between radiographic parameters of shoulder balance and other radiographic parameters and associations between PSI and clinical parameters were investigated. For statistical analyses, paired and unpaired t-tests were used. The mean Cobb angles of the main and proximal thoracic curves were 54.6 ± 9.5 and 26.7 ± 7.9 degrees before surgery, 14.5 ± 7.5, and 14.9 ± 7.1 at follow-up. Clavicle angle and T1 tilt angle were -2.9 ± 2.8 and -2.6 ± 6.3 before surgery, 2.4 ± 2.8 and 4.4 ± 4.3 immediately after surgery, and 1.8 ± 2.1 and 3.4 ± 5.5 at follow-up. Twenty patients developed distal adding-on. Clavicle angle at follow-up correlated weakly but significantly with preoperative clavicle angle (r = 0.34, p = 0.001) and with the correction rates of the main thoracic curve (r = 0.34, p = 0.001); it correlated negatively with the proximal curve spontaneous correction rate (r=-0.21, p = 0.034). The clavicle angle at follow-up was significantly larger in patients with PS-only constructs (PS 2.1 degrees vs. hybrid 0.9, p = 0.02), and tended to be smaller in patients with distal adding-on (adding-on 1.1 vs. non adding-on 2.0, p = 0.09). PSI was more common with better correction of the main curve (using PS constructs), in patients with a larger preoperative clavicle angle, and with a larger and more rigid proximal curve. Distal adding-on may compensate for PSI.

Nurse Value-Added and Patient Outcomes in Acute Care

PubMed Central

Yakusheva, Olga; Lindrooth, Richard; Weiss, Marianne

2014-01-01

Objective The aims of the study were to (1) estimate the relative nurse effectiveness, or individual nurse value-added (NVA), to patients’ clinical condition change during hospitalization; (2) examine nurse characteristics contributing to NVA; and (3) estimate the contribution of value-added nursing care to patient outcomes. Data Sources/Study Setting Electronic data on 1,203 staff nurses matched with 7,318 adult medical–surgical patients discharged between July 1, 2011 and December 31, 2011 from an urban Magnet-designated, 854-bed teaching hospital. Study Design Retrospective observational longitudinal analysis using a covariate-adjustment value-added model with nurse fixed effects. Data Collection/Extraction Methods Data were extracted from the study hospital's electronic patient records and human resources databases. Principal Findings Nurse effects were jointly significant and explained 7.9 percent of variance in patient clinical condition change during hospitalization. NVA was positively associated with having a baccalaureate degree or higher (0.55, p = .04) and expertise level (0.66, p = .03). NVA contributed to patient outcomes of shorter length of stay and lower costs. Conclusions Nurses differ in their value-added to patient outcomes. The ability to measure individual nurse relative value-added opens the possibility for development of performance metrics, performance-based rankings, and merit-based salary schemes to improve patient outcomes and reduce costs. PMID:25256089

Epidemiology and Clinical Features of Atopic Dermatitis in Kerman, a Desert Area of Iran

PubMed Central

Esfandiarpour, Iraj; Sedaghatmanesh, Maryam; Saviz, Mahdieh

2014-01-01

Background Epidemiologic studies of atopic dermatitis (AD) in desert areas are still lacking. Objective The aim of this study was to investigate the epidemiology of AD in children in Kerman city, a desert area in Iran. Methods We evaluated preschool children (age, 2 to 7 years) and primary school students (age, greater than 7 up to 12 years) in Kerman. We selected 865 students to estimate the prevalence and assess other features of AD such as distribution of lesions, personal history, family history of atopy, aggravating factors, associated symptoms, and morphological variants. Results The prevalence of AD was 9.1% in our study population. The prevalence of AD was 9.17% and 9.09% in males and females, respectively. The prevalence of AD in the age range of 2 to 7 years was 13.53% and 8.33% among children aged greater than 7 up to 12 years. In total, 82.27% of the patients were in chronic stage of the disease, and 31.6% had a personal history of other atopic diseases. At least one first-degree family member with atopy was seen in 46.83% of the patients. The most common sites of involvement were the head and neck. The most involved areas in the limbs were extensor surfaces. The most frequent morphological variant of AD was the common type. Conclusion The prevalence of AD in Kerman was higher than in other Iranian cities but lower than that in developed countries. Diversity in the clinical features of AD has been observed among different studies, and the diagnostic criteria of AD should be adapted in proportion to the studied area. PMID:24648683

Alcohol and Alzheimer's Disease-Does Alcohol Dependence Contribute to Beta-Amyloid Deposition, Neuroinflammation and Neurodegeneration in Alzheimer's Disease?

PubMed

Venkataraman, Ashwin; Kalk, Nicola; Sewell, Gavin; Ritchie, Craig W; Lingford-Hughes, Anne

2017-03-09

To investigate the underlying neurobiology between alcohol use, misuse and dependence and cognitive impairment, particularly Alzheimer's disease (AD). Review of the literature using searches of Medline, Pubmed, EMBASE, PsycInfo, and meeting abstracts and presentations. The role of alcohol as a risk factor and contributor for cognitive decline associated with AD has received little attention. This is despite the high prevalence of alcohol use, the potential reversibility of a degree of cognitive impairment and the global burden of AD. Until now the focus has largely been on the toxic effects of alcohol, neuronal loss and the role of thiamine. We propose alcohol adds to the cognitive burden seen in dementia through additional mechanisms to neurodegenerative processes or may contribute at various mechanistic points in the genesis and sustenance of AD pathology via neuroinflammation. We describe the common underlying neurobiology in alcohol and AD, and examine ways alcohol likely contributes to neuroinflammation directly via stimulation of Toll-like receptors and indirectly from small bowel changes, hepatic changes, withdrawal and traumatic brain injury to the pathogenesis of AD. Alcohol use, misuse and dependence cause cognitive impairment. We propose alcohol adds to the cognitive burden seen in dementia through additional mechanisms to neurodegenerative processes or may contribute at various mechanistic points in the genesis and sustenance of AD pathology via neuroinflammation. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Importance of hypolimnetic cycling in aging of "new" mercury in a northern temperate lake.

PubMed

Chadwick, Shawn P; Babiarz, Christopher L; Hurley, James P; Armstrong, David E

2013-03-15

The aging of "new" mercury (Hg) was investigated in Experimental Lake 658 as part of the Mercury Experiment To Assess Atmospheric Loading In Canada and the United States (METAALICUS). Mercury enriched in (202)Hg was added to the epilimnion over a three-year period to simulate direct atmospheric deposition. We evaluated the aging of newly added mercury (HgLake) in the water column using chemical methods and experiments to examine differences in phase partitioning and transport compared to the ambient pool, HgAmb. Aging was sufficiently slow to observe differences in the partitioning characteristics of HgLake and HgAmb. Amended HgLake initially partitioned to a greater extent to epilimnetic particulate matter (log Kd of HgLake=5.08; log Kd of HgAmb=4.9). HgLake was transported rapidly to the hypolimnion by settling particulate matter. Partitioning became more similar after amended Hg was recycled within the hypolimnion through redox processes. Experiments showed the removal of Hg from the aqueous phase by Fe and/or Mn oxyhydroxide-organic matter complexes. Separations using the anion exchange resin DEAE indicated that both HgLake and HgAmb were associated mainly with dissolved organic matter (DOM) and with partial association with sulfide in anoxic waters, but the degree of association of HgLake with DOM was higher in oxic (epilimnetic) waters. In the solid phase, chemical fractionation indicated greater association of HgLake with organic matter, while HgAmb showed greater association with oxyhydroxide and inert phases. Overall, the results suggest that "new" Hg added from the atmosphere is initially more particle-reactive than ambient Hg in the epilimnion, where initial sorption/partitioning occurs mainly to plankton and detrital particles. Once Hg has been deposited at the sediment-water interface, extended equilibration time in combination with microbial and chemical redox processes "age" the "new" Hg, and particle partitioning becomes similar for the added isotope and ambient pools. Copyright © 2012 Elsevier B.V. All rights reserved.

"Push-Through" Rod Passage Technique for the Improvement of Lumbar Lordosis and Sagittal Balance in Minimally Invasive Adult Degenerative Scoliosis Surgery.

PubMed

Haque, Raqeeb M; Uddin, Omar M; Ahmed, Yousef; El Ahmadieh, Tarek Y; Hashmi, Sohaib Z; Shah, Amir; Fessler, Richard G

2016-10-01

Traditional open surgical techniques for correction of adult degenerative scoliosis (ADS) are often associated with increased blood loss, postoperative pain, and complications. Minimally invasive (MIS) techniques have been utilized to address these issues; however, concerns regarding improving certain alignment parameters have been raised. A new "push-through" technique for MIS correction of ADS has been developed wherein a rod is bent before its placement into the screw heads and then contoured further to yield improved correction of radiographic parameters. Preoperative and postoperative radiographic measurements of 3 patients who underwent MIS correction of scoliosis using the "push-through" technique were compared with 22 prior patients who had received traditional MIS correction. All patients received staged correction of scoliosis. The first stage involved insertion of lateral lumbar interbodies. Standing x-rays were then evaluated for overall global balance. The second stage involved appropriate MIS facetectomies, facet fusions, posterior transforaminal interbodies at lower lumbar segments, and finally the placement of rods.TECHNIQUE OVERVIEW:: (1) A long rod composed of titanium is bent with a mild lordosis and passed through the extensions of the screw heads cephalad to caudad. (2) The rod is passed fully through the incision so it extrudes from the caudal end of the construct. At this point, further lordosis is bent into the rods. (3) The rod is then pulled back into the appropriate position. (4) The unnecessary cephalad rod is then cut to appropriate length with a circular saw. (5) Rod reducers are then sequentially lowered and tightened to achieve the desired correction. Mean age for all patients was 66.02 years. Preoperative coronal Cobb, sagittal vertical axis (SVA), and pelvic incidence (PI) were similar in all patients, whereas lumbar lordosis (LL) was smaller (15.27 vs. 29.85 degrees, P=0.00389) and pelvic tilt (PT) was larger (37.00 vs. 27.00 degrees, P=0.00011) in "push-through" patients. Postoperatively, "pushthrough" patients experienced greater correction of LL (21.93 vs. 3.70 degrees, P=0.00001), PI-LL (-18.57 vs. -0.26 degrees, P=0.00471), PT (-7.67 vs. -0.40 degrees, P=0.00341), SVA (-40.67 mm vs. 0.95 mm, P=0.05846), and coronal Cobb (-20.23 vs. -18.76 degrees, P=0.75). This new method of contouring a rod enables improved LL. This technique is easy to perform and can be a valuable tool in treating ADS using MIS techniques.

Long-term recall of social relationships related to addiction and HIV risk behaviors.

PubMed

Stout, R L; Janssen, T; Braciszewski, J M; Vose-O'Neal, A

2017-08-01

Social relationships have been demonstrated as a key predictor of relapse among addicted persons and are likely to be important determinants of HIV risk behaviors also. However, the degree to which this population can reliably and consistently identify important people (IPs) in retrospect has been understudied. Using the modified Important People and Activities questionnaire, we investigated to what degree IPs were dropped, added, or retained, and whether data about individual IPs were reported accurately on 6- and 12-month follow up periods using a sample of 50 drug or alcohol abusing participants. We found that IPs were largely retained, and that those retained versus dropped/added differed by their reaction to participant alcohol/drug use, as well as frequency of contact. We further found that there were differences in reliability of data describing specific IPs. While both 6- and 12-month follow up periods led to reliabilities ranging from excellent to fair, we found poorer reliability on responses to recall of "frequency of contact" and "reactions to drinking", as well as "reactions to drug use". Future investigations of reliability of social relationships recalled retrospectively should attempt to examine possible systematic biases in addition to the reliability of specific IP data. More sophisticated studies are needed on factors associated with systematic variation in reporting of aspects of social relationships that are associated with addictions or HIV risk outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases.

PubMed

Youssef, S A; Capucchio, M T; Rofina, J E; Chambers, J K; Uchida, K; Nakayama, H; Head, E

2016-03-01

According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with molecular and morphological changes but also leads to different degrees of behavioral and cognitive dysfunction. Common age-related brain lesions in humans include brain atrophy, neuronal loss, amyloid plaques, cerebrovascular amyloid angiopathy, vascular mineralization, neurofibrillary tangles, meningeal osseous metaplasia, and accumulation of lipofuscin. In aging humans, the most common neurodegenerative disorder is Alzheimer's disease (AD), which progressively impairs cognition, behavior, and quality of life. Pathologic changes comparable to the lesions of AD are described in several other animal species, although their clinical significance and effect on cognitive function are poorly documented. This review describes the commonly reported age-associated neurologic lesions in domestic and laboratory animals and the relationship of these lesions to cognitive dysfunction. Also described are the comparative interspecies similarities and differences to AD and other human neurodegenerative diseases including Parkinson's disease and progressive supranuclear palsy, and the spontaneous and transgenic animal models of these diseases. © The Author(s) 2016.

Could Better Phenotyping Small Vessel Disease Provide New Insights into Alzheimer Disease and Improve Clinical Trial Outcomes?

PubMed

Marnane, Michael; Hsiung, Ging-Yuek R

2016-01-01

Alzheimer Disease (AD) is the most common primary cause of dementia with a burgeoning epidemic as life expectancy and general medical care improve worldwide. Recent data from pathologic studies has shown that the cooccurrence of other neurodegenerative and vascular pathologies is in fact the rule rather than the exception. In late onset AD, cerebral small vessel disease (SVD) is almost invariably co-existent to a greater or lesser extent and is known to promote cognitive deterioration. Previous observational studies and clinical trials have largely sought to divide dementia based on predominant neurodegenerative or vascular mechanisms. Given the high degree of overlap, findings from such studies may be difficult to interpret and apply to population cohorts. Additionally opportunities may be lost for uncovering novel interventions that target interactions between co-existent vascular and neurodegenerative pathologies. In the current review, we consider potential pathophysiologic mechanisms through which SVD may be associated with and promote AD pathology. In particular we explore shared environmental and genetic associations and how these may converge via neuroinflammatory pathways potentially providing novel therapeutic targets. SVD has heterogenous manifestations on cerebral imaging and at pathology. We discuss how studying SVD topography may enable us to better identify those at risk for more rapid cognitive decline and improve future clinical trial design.

Perioperative complications and safety of type II thyroplasty (TPII) for adductor spasmodic dysphonia.

PubMed

Mizoguchi, Kenji; Hatakeyama, Hiromitsu; Yanagida, Saori; Nishizawa, Noriko; Oridate, Nobuhiko; Fukuda, Satoshi; Homma, Akihiro

2017-05-01

Type II thyroplasty (TPII) is one of the surgical options offered in the management of adductor spasmodic dysphonia (AdSD); however, there have been no detailed reports of its safety and associated complications during the perioperative period. Our aim was to assess the complications and safety of TPII. TPII was performed for consecutive 15 patients with AdSD from April 2012 through May 2014. We examined retrospectively the perioperative complications, the degree of surgical invasion, and recovery process from surgery. All patients underwent successful surgery under only local anesthesia. Vocal fold erythema was observed in 14 patients and vocal fold edema in 10 patients; however, all of them showed complete resolution within 1 month. No patient experienced severe complications such as acute airway distress or hemorrhage. Fourteen patients were able to have oral from the 1st postoperative morning, with the remaining patient able to have oral intake from the 2nd postoperative day. In addition, no patient experienced aspiration postoperatively. In conclusion, only minor complications were observed in association with TPII in this study. No dysphagia was observed postoperatively, which is an advantage over other treatments. The results of our study suggest that TPII is a safe surgical treatment for AdSD.

Acceptance of sugar reduction in flavored yogurt.

PubMed

Chollet, M; Gille, D; Schmid, A; Walther, B; Piccinali, P

2013-09-01

To investigate what level of sugar reduction is accepted in flavored yogurt, we conducted a hedonic test focusing on the degree of liking of the products and on optimal sweetness and aroma levels. For both flavorings (strawberry and coffee), consumers preferred yogurt containing 10% added sugar. However, yogurt containing 7% added sugar was also acceptable. On the just-about-right scale, yogurt containing 10% sugar was more often described as too sweet compared with yogurt containing 7% sugar. On the other hand, the sweetness and aroma intensity for yogurt containing 5% sugar was judged as too low. A second test was conducted to determine the effect of flavoring concentration on the acceptance of yogurt containing 7% sugar. Yogurts containing the highest concentrations of flavoring (11% strawberry, 0.75% coffee) were less appreciated. Additionally, the largest percentage of consumers perceived these yogurts as "not sweet enough." These results indicate that consumers would accept flavored yogurts with 7% added sugar instead of 10%, but 5% sugar would be too low. Additionally, an increase in flavor concentration is undesirable for yogurt containing 7% added sugar. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Possible impacts of early-11th-, middle-12th-, and late-13th-century droughts on western Native Americans and the Mississippian Cahokians

USGS Publications Warehouse

Benson, L.V.; Berry, M.S.; Jolie, E.A.; Spangler, J.D.; Stahle, D.W.; Hattori, E.M.

2007-01-01

One or more of three intense and persistent droughts impacted some Native American cultures in the early-11th, middle-12th and late-13th centuries, including the Anasazi, Fremont, Lovelock, and Mississippian (Cahokian) prehistorical cultures. Tree-ring-based reconstructions of precipitation and temperature indicate that warm drought periods occurred between AD 990 and 1060, AD 1135 and 1170, and AD 1276 and 1297. These droughts occurred during minima in the Pacific Decadal Oscillation and may have been associated with positive values of the Atlantic Multidecadal Oscillation. Each of the Native American cultures was supported, to a greater or lesser degree, by precipitation-dependent resources. Both the Four Corners region and Cahokia were sites of intense growth between about AD 1050 and 1130, and by AD 1150, cultures in both regions were undergoing stress. By AD 1300 the Anasazi and Fremont cultures had collapsed and their residual populations had either left their homelands or withered. In the case of Fremont populations, the AD 990-1060 drought may have had the greatest impact. This drought also may have affected the Anasazi, for it was at the end of this drought that some people from Chaco migrated to the San Juan River valley and founded the Salmon Ruin great house. Detailed data do not exist on the number of Lovelock habitation sites or populations over time; however, Lovelock populations appear to have retreated from the western Great Basin to California by AD 1300 or shortly thereafter.

Amyloid deposits and response to shunt surgery in idiopathic normal-pressure hydrocephalus.

PubMed

Hiraoka, Kotaro; Narita, Wataru; Kikuchi, Hirokazu; Baba, Toru; Kanno, Shigenori; Iizuka, Osamu; Tashiro, Manabu; Furumoto, Shozo; Okamura, Nobuyuki; Furukawa, Katsutoshi; Arai, Hiroyuki; Iwata, Ren; Mori, Etsuro; Yanai, Kazuhiko

2015-09-15

In previous studies, patients with idiopathic normal-pressure hydrocephalus (iNPH) occasionally showed Alzheimer's pathology in frontal lobe cortical biopsy during cerebrospinal fluid shunt surgery or intracranial pressure monitoring. In clinical practice, the differential diagnosis of iNPH from Alzheimer's disease (AD) can be problematic, particularly because some iNPH cases exhibit AD comorbidity. In this study, we evaluated amyloid deposition in the brains of patients with iNPH before shunt surgery, and investigated the association between brain amyloid deposits and clinical improvement following the surgery. Amyloid imaging was performed in patients with iNPH or AD and also in healthy control subjects by using positron emission tomography (PET) and a radiolabeled pharmaceutical compound, (11)C-BF227. Using the cerebellar hemispheres as reference regions, the standard uptake value ratio (SUVR) of the neocortex was estimated and used as an index for amyloid deposition. In patients with iNPH, clinical symptoms were assessed before shunt surgery and 3 months after surgery. Five of the 10 patients with iNPH had neocortical SUVRs that were as high as those of AD subjects, whereas the SUVRs of the 5 patients were as low as those of healthy controls. A significant inverse correlation between neocortical SUVRs and cognitive improvements after shunt surgery was observed in iNPH. The amount of amyloid deposits ranges widely in the brains of patients with iNPH and is associated with the degree of cognitive improvement after shunt surgery. Copyright © 2015 Elsevier B.V. All rights reserved.

Degradation kinetics of the antioxidant additive ascorbic acid in packed table olives during storage at different temperatures.

PubMed

Montaño, A; Casado, F J; Rejano, L; Sanchez, A H; de Castro, A

2006-03-22

The kinetics of ascorbic acid (AA) loss during storage of packed table olives with two different levels of added AA was investigated. Three selected storage temperatures were assayed: 10 degrees C, ambient (20-24 degrees C), and 40 degrees C. The study was carried out in both pasteurized and unpasteurized product. The effect of pasteurization treatment alone on added AA was not significant. In the pasteurized product, in general AA degraded following a first-order kinetics. The activation energy calculated by using the Arrhenius model averaged 9 kcal/mol. For each storage temperature, the increase in initial AA concentration significantly decreased the AA degradation rate. In the unpasteurized product, AA was not detected after 20 days in samples stored at room temperature and AA degradation followed zero-order kinetics at 10 degrees C, whereas at 40 degrees C a second-order reaction showed the best fit. In both pasteurized and unpasteurized product, the low level of initial dehydroascorbic acid disappeared during storage. Furfural appeared to be formed during storage, mainly at 40 degrees C, following zero-order kinetics.

Disclosing Pleiotropic Effects during Genetic Risk Assessment for Alzheimer’s Disease: A Randomized, Controlled Trial

PubMed Central

Christensen, Kurt D.; Roberts, J. Scott; Whitehouse, Peter J.; Royal, Charmaine D. M.; Obisesan, Thomas O.; Cupples, L. Adrienne; Vernarelli, Jacqueline A.; Bhatt, Deepak L.; Linnenbringer, Erin; Butson, Melissa B.; Fasaye, Grace-Ann; Uhlmann, Wendy R.; Hiraki, Susan; Wang, Na; Cook-Deegan, Robert; Green, Robert C.

2016-01-01

Background Increasing use of genetic testing raises questions about disclosing secondary findings, including pleiotropic information. Objective To determine the safety and behavioral impact of disclosing modest associations between APOE genotype and coronary artery disease (CAD) risk during APOE-based genetic risk assessments for Alzheimer’s disease (AD). Design Randomized, multicenter equivalence clinical trial Setting Four teaching hospitals Participants 257 asymptomatic adults enrolled, 69% with one AD-affected first degree relative Intervention Disclosing AD and CAD genetic risk information (AD+CAD) versus disclosing only AD genetic risk (AD-only) Measurements Co-primary outcomes were Beck Anxiety Index (BAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores at 12 months. Secondary outcomes included test-related distress at 12 months, all measures at 6 weeks and 6 months, and health behavior changes at 12 months. Results 12 months after disclosure, mean BAI scores were 3.5 and 3.5 in AD-only and AD+CAD arms (Δ=0.0, 95%CI: −1.0 to 1.0), and mean CES-D scores were 6.4 and 7.1 in AD-only and AD+CAD arms (Δ=0.7, 95%CI: −1.0 to 2.4). Both confidence bounds fell within the equivalence margin of +/−5 points. Among ε4-positive participants, distress was lower in AD+CAD arms than AD-only arms (Δ=−4.8, 95%CI: −8.6 to −1.0) (p=0.031 for disclosure arm x APOE genotype). AD+CAD participants also reported more health behavior changes, regardless of APOE genotype. Limitations Outcomes were self-reported from volunteers without severe anxiety, severe depression, or cognitive problems. Analyses omitted 33 randomized participants. Conclusion Disclosing pleiotropic information did not increase anxiety or depression, and may have decreased distress among those at increased risk for two conditions. Providing risk modification information regarding CAD improved health behaviors. Findings highlight potential benefits of secondary genetic findings disclosure when options exist for decreasing risk. PMID:26810768

Impact of an automated dispensing system in outpatient pharmacies.

PubMed

Humphries, Tammy L; Delate, Thomas; Helling, Dennis K; Richardson, Bruce

2008-01-01

To evaluate the impact of an automated dispensing system (ADS) on pharmacy staff work activities and job satisfaction. Cross-sectional, retrospective study. Kaiser Permanente Colorado (KPCO) outpatient pharmacies in September 2005. Pharmacists and technicians from 18 outpatient pharmacies. All KPCO outpatient pharmacists (n = 136) and technicians (n = 160) were surveyed regarding demographics and work activities and pharmacist job satisfaction. Work activities and job satisfaction were compared between pharmacies with and without ADS. Historical prescription purchase records from ADS pharmacies were assessed for pre-ADS to post-ADS changes in productivity. Self-reported pharmacy staff work activities and pharmacist job satisfaction. Pharmacists who responded to the demographic questionnaire (n = 74) were primarily women (60%), had a bachelor's degree in pharmacy (68%), and had been in practice for 10 years or more (53%). Responding technicians (n = 72) were predominantly women (80%) with no postsecondary degree (90%) and fewer than 10 years (68%) in practice. Pharmacists in ADS pharmacies who responded to the work activities questionnaire (n = 50) reported equivalent mean hours spent in patient care activities and filling medication orders compared with non-ADS pharmacists (n = 33; P > 0.05). Similarly, technicians in ADS pharmacies who responded to the work activities questionnaire (n = 64) reported equivalent mean hours spent in filling medication orders compared with non-ADS technicians (n = 38; P > 0.05). An equivalent proportion of ADS pharmacists reported satisfaction with their current job compared with non-ADS pharmacies (P > 0.05). Mean productivity did not increase appreciably after automation (P >0.05). By itself, installing an ADS does not appear to shift pharmacist work activities from dispensing to patient counseling or to increase job satisfaction. Shifting pharmacist work activities from dispensing to counseling and monitoring drug therapy outcomes may be warranted in ADS pharmacies.

Poisson-Lie duals of the η deformed symmetric space sigma model

NASA Astrophysics Data System (ADS)

Hoare, Ben; Seibold, Fiona K.

2017-11-01

Poisson-Lie dualising the η deformation of the G/H symmetric space sigma model with respect to the simple Lie group G is conjectured to give an analytic continuation of the associated λ deformed model. In this paper we investigate when the η deformed model can be dualised with respect to a subgroup G0 of G. Starting from the first-order action on the complexified group and integrating out the degrees of freedom associated to different subalgebras, we find it is possible to dualise when G0 is associated to a sub-Dynkin diagram. Additional U1 factors built from the remaining Cartan generators can also be included. The resulting construction unifies both the Poisson-Lie dual with respect to G and the complete abelian dual of the η deformation in a single framework, with the integrated algebras unimodular in both cases. We speculate that extending these results to the path integral formalism may provide an explanation for why the η deformed AdS5 × S5 superstring is not one-loop Weyl invariant, that is the couplings do not solve the equations of type IIB supergravity, yet its complete abelian dual and the λ deformed model are.

Operative vaginal delivery in case of persistent occiput posterior position after manual rotation failure: a 6-month follow-up on pelvic floor function.

PubMed

Guerby, Paul; Parant, Olivier; Chantalat, Elodie; Vayssiere, Christophe; Vidal, Fabien

2018-07-01

To compare the short- and long-term perineal consequences (at 6 months postpartum) and short-term neonatal consequences of instrumental rotation (IR) to those induced by assisted delivery (AD) in the occiput posterior (OP) position, in case of manual rotation failure. A prospective observational cohort study; tertiary referral hospital including all women presenting with persistent OP position who delivered vaginally after manual rotation failure with attempted IR or AD in OP position from September 2015 to October 2016. Maternal and neonatal outcomes of all attempted IR deliveries were compared with OP operative vaginal deliveries. Main outcomes measured were pelvic floor function at 6 months postpartum including Wexner score for anal incontinence and ICIQ-FLUTS for urinary symptoms. Perineal morbidity comprised severe perineal tears, corresponding to third and fourth degree lacerations. Fetal morbidity parameters comprised low neonatal Apgar scores, acidaemia, major and minor fetal injuries and neonatal intensive care unit admissions. Among 5265 women, 495 presented with persistent OP positions (9.4%) and 111 delivered after manual rotation failure followed by AD delivery: 58 in the IR group and 53 in the AD in OP group. The incidence of anal sphincter injuries was significantly reduced after IR attempt (1.7% vs. 24.5%; p < 0.001) without increasing neonatal morbidity. At 6 months postpartum, AD in OP position was associated with higher rate of anal incontinence (30% vs. 5.5%, p = 0.001) and with more urinary symptoms, dyspareunia and perineal pain. OP operative deliveries are associated with significant perineal morbidity and pelvic floor dysfunction at 6 months postpartum.

Advanced figure sensor operations and maintenance manual

NASA Technical Reports Server (NTRS)

Robertson, H. J.

1972-01-01

This manual contains procedures for installing, operating, and maintaining the optical figure sensor and its associated electronic controls. The optical figure sensor, a system of integrated components, comprises: (1) a phase measuring modified interferometer employing a single frequency 6328 A laser, and a Vidissector; (2) a two-axis automatic thermal compensation control mount; (3) a five degree of freedom manual adjustment stand; and (4) a control console. This instrument provides real time output data of optical figure errors for spherical mirrors, and is also capable of measuring aspherical mirrors if a null corrector is added.

Chitosan/lecithin liposomal nanovesicles as an oral insulin delivery system.

PubMed

Al-Remawi, Mayyas; Elsayed, Amani; Maghrabi, Ibrahim; Hamaidi, Mohammad; Jaber, Nisrein

2017-05-01

In the present work, insulin-chitosan polyelectrolyte complexes associated to lecithin liposomes were investigated as a new carrier for oral delivery of insulin. The preparation was characterized in terms of particle size, zeta potential and encapsulation efficiency. Surface tension measurements revealed that insulin-chitosan polyelectrolyte complexes have some degree of hydrophobicity and should be added to lecithin liposomal dispersion and not the vice versa to prevent their adsorption on the surface. Stability of insulin was enhanced when it was associated to liposomes. Significant reduction of blood glucose levels was noticed after oral administration of liposomal preparation to streptozotocin diabetic rats compared to control. The hypoglycemic activity was more prolonged compared to subcutaneously administered insulin.

Apolipoprotein E-epsilon 4 allele and familial risk in Alzheimer's disease.

PubMed

Li, G; Silverman, J M; Altstiel, L D; Haroutunian, V; Perl, D P; Purohit, D; Birstein, S; Lantz, M; Mohs, R C; Davis, K L

1996-01-01

Recent studies have found an association between presence of apolipoprotein E (APOE) epsilon 4 allele and Alzheimer's disease (AD). The present study compared the cumulative risk of primary progressive dementia (PPD) in relatives of AD probands carrying at least one copy of the epsilon 4 allele with the relatives of AD probands not carrying epsilon 4 and with relatives of non-demented controls. Our aim was to determine whether the familial aggregation of PPD in relatives of AD probands is primarily due to those carrying epsilon 4. Seventy-seven neuropathologically diagnosed AD patients were obtained as probands through our Alzheimer's Disease Research Center Brain Bank. AD probands were genotyped for APOE. As a comparison group, 198 non-demented probands were also included. Through family informants, demographic and diagnostic data were collected on 382 first-degree relatives (age > or = 45 years) of AD probands and 848 relatives of the controls. We found that the cumulative risk of PPD in both relatives of AD probands with and without the epsilon 4 allele was significantly higher than that in the relatives of non-demented controls. However, the increased risk in the relatives of AD probands with the epsilon 4 allele was marginally, but not significantly, lower than the risk in the relatives of probands without epsilon 4. A greater likelihood of death by heart diseases over developing PPD in relatives of AD probands with epsilon 4 (3.1-fold increase) was found compared to relatives of probands without epsilon 4 (1.7-fold increase), especially prior to age 70, although the difference was not statistically significant. The increased familial risk for PPD in the relatives of AD probands with the APOE-epsilon 4 allele relative to controls suggests that familial factors in addition to APOE-epsilon 4 are risk factors for AD. Differential censorship from increased mortality of heart diseases may have prevented a higher incidence of PPD among the relatives of probands with epsilon 4.

The impact of lignin source on its self-assembly in solution

DOE PAGES

Ratnaweera, Dilru R.; Saha, Dipendu; Pingali, Sai Venkatesh; ...

2015-07-30

Recently, there has been a growing interest in developing value added uses for lignin, including the utilization of lignins as a precursor for carbon materials. Proper understanding of the association behavior of lignins during solution processing provides important structural information that is needed to rationally optimize the use of lignins in industry in a range of value added applications. In this paper, we follow the assembly of lignin molecules from a variety of sources in dimethyl sulfoxide, a good solvent for lignins, using small angle neutron scattering. In order to mimic industrial processing conditions, concentrations of lignins were kept abovemore » the overlap concentration. At small length scales, short lignin segments with ~4–10 monolignol units associate to form rigid rod-like/cylindrical building blocks, where the number of repeat units in a cylindrical segment decreases with increasing lignin concentration. These cylindrical building blocks associate to form aggregates with low cross-linking densities and a random coil or network like structures from highly branched lignin structures. The degree of branching of the base lignin molecule, which varies with source, plays a crucial role in determining their association behavior. Finally, the overall sizes of the aggregates decrease with increasing concentration at low cross-linking densities, whereas the opposite trend is observed for highly branched lignins.« less

Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahara, Kiyoshi; Ii, Masaaki, E-mail: masaii@art.osaka-med.ac.jp; Inamoto, Teruo

2014-04-18

Highlights: • AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells. • AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway. • High expression of the TGF-β1 gene in AdSCs. - Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferationmore » of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.« less

Prevalence and comorbidities in adults with psoriasis compared to atopic eczema.

PubMed

Radtke, M A; Schäfer, I; Glaeske, G; Jacobi, A; Augustin, M

2017-01-01

Most data suggesting an association between psoriasis and cardiovascular disease (CVD) have come from specialized populations at either low or high risk of CVD. Atopic dermatitis (AD) has been associated with a number of modifiable risk factors, particularly obesity. There has been a recent controversy on the suggestion that associations with comorbidities in psoriasis may be due to overreporting or biased by disease severity and therefore not necessarily representative of the general psoriasis population. To evaluate the prevalence of AD and psoriasis and to compare the prevalence rates of comorbidities based on a large sample of health insurance data. Data were collected from a database of non-selected individuals from a German statutory health insurance organization that covers all geographic regions. Individuals identified by International Classification of Diseases (ICD)-10 codes applied to all outpatient and inpatient visits in the year 2009. Comorbidities were evaluated by ICD-10 diagnoses. The database consisted of 1 642 852 members of a German statutory health insurance. Of 1 349 671 data sets analyzed, 37 456 patients ≥18 years were diagnosed with psoriasis (prevalence 2.78%), and 48 140 patients ≥18 years of age were diagnosed with AD, equivalent to a prevalence of 3.67%. Patients with psoriasis showed increased rates of comorbidities in all age groups. Comorbidities related to the metabolic syndrome including arterial hypertension [prevalence ratio (PR), 1.94; 95% confidence interval (CI), 1.90-1.98], hyperlipidaemia (PR, 1.77; 95% CI, 1.73-1.81), obesity (PR, 1.74; 95% CI, 1.69-1.79) and diabetes mellitus (PR, 1.88; 95% CI, 1.83-1.94) were significantly more common among patients with psoriasis compared to AD. Diseases forming part of the metabolic syndrome showed significant lower prevalence rates in patients with AD than in patients with psoriasis. Within the limitations of secondary healthcare data, our study disproves the suggestion that associations with comorbidities in psoriasis may be biased by a higher degree of severity or overreporting. © 2016 European Academy of Dermatology and Venereology.

Salivary chromogranin A levels correlate with disease severity but do not reflect anxiety or personality of adult patients with atopic dermatitis.

PubMed

Kaneko, Sakae; Liu, Lijuan; Kakamu, Takeyasu; Minami-Hori, Masako; Morita, Eishin

2017-08-01

Stress-induced scratching is an issue in patients with adult atopic dermatitis (AD). Although itching and stress are believed to be intimately related, no objective index is available; therefore, most evaluations are subjective. Using saliva, which is easily collected, we investigated the degree to which AD severity and patient stress levels are reflected in stress proteins in the saliva. Here, we evaluated the severity (Scoring Atopic Dermatitis [SCORAD] score), stress (State-Trait Anxiety Index [STAI] score), personality (Tokyo University Egogram [TEG] II score) and quality of life (Dermatology Life Quality Index [DLQI] score) of 51 patients with AD who were examined in the Department of Dermatology of Shimane University between April and December 2015. We collected saliva and measured salivary chromogranin A (CgA), amylase and cortisol. The amount of salivary CgA per protein in patients with AD was correlated with their SCORAD score (r = 0.458, P < 0.001). There was no correlation between cortisol or amylase levels and SCORAD score. SCORAD score was correlated with DLQI (r = 0.390, P = 0.006). CgA per protein was correlated with DLQI (r = 0.393, P = 0.004). There was no correlation between scores for the anxiety component of the STAI, TEG II or DLQI. Our results suggested that patients with more severe AD may have high stress levels. The personalities of these patients with AD tended to involve elevated anxiety levels. © 2017 Japanese Dermatological Association.

Minimal massive 3D gravity

NASA Astrophysics Data System (ADS)

Bergshoeff, Eric; Hohm, Olaf; Merbis, Wout; Routh, Alasdair J.; Townsend, Paul K.

2014-07-01

We present an alternative to topologically massive gravity (TMG) with the same ‘minimal’ bulk properties; i.e. a single local degree of freedom that is realized as a massive graviton in linearization about an anti-de Sitter (AdS) vacuum. However, in contrast to TMG, the new ‘minimal massive gravity’ has both a positive energy graviton and positive central charges for the asymptotic AdS-boundary conformal algebra.

Sleep Modifies the Relation of APOE to the Risk of Alzheimer Disease and Neurofibrillary Tangle Pathology

PubMed Central

Lim, Andrew S.P.; Yu, Lei; Kowgier, Matthew; Schneider, Julie A.; Buchman, Aron S.; Bennett, David A.

2013-01-01

IMPORTANCE The Apolipoprotein E (APOE) ε4 allele is a common and well-established genetic risk factor for Alzheimer Disease (AD). Sleep consolidation is also associated with AD risk and previous work suggests that APOE genotype and sleep may interact to influence cognitive function. OBJECTIVE To determine whether better sleep consolidation attenuates the relation of the APOE genotype to the risk of incident AD and the burden of AD pathology. DESIGN Prospective longitudinal cohort study with up to 6 years of follow-up. SETTING Community-based. PARTICIPANTS We studied a volunteer sample of 698 community dwelling older adults without dementia (average age 81.7 years; 77% female) in the Rush Memory and Aging Project followed for up to 6 years. EXPOSURES We used up to 10 days of actigraphic recording to quantify the degree of sleep consolidation, and ascertained APOE genotype. MAIN OUTCOME MEASURES Subjects underwent annual evaluation for AD over a follow-up period of up to 6 years. Autopsies were performed on 201 deceased participants, and Aβ and neurofibrillary tangle (NFT) pathology were identified by immunohistochemistry and quantified. RESULTS Over a follow-up period, 98 individuals developed AD. In a series of Cox proportional hazards models, better sleep consolidation attenuated the effect of the ε4 allele on the risk of incident AD (HR 0.67 95%CI 0.46–0.97 p=0.036 per allele per 1SD increase in sleep consolidation). In a series of linear mixed effect models, better sleep consolidation also attenuated the effect of the ε4 allele on the annual rate of cognitive decline (interaction estimate +0.048 SE=0.012 p<0.001). In deceased individuals, better sleep consolidation attenuated the effect of the ε4 allele on NFT density (interaction estimate −0.42 SE=0.17 p=0.016), which accounted for the effect of sleep consolidation on the association between APOE genotype and cognition proximate to death. CONCLUSIONS AND RELEVANCE Better sleep consolidation attenuates the effect of APOE genotype on incident AD and NFT pathology. Assessment of sleep consolidation may identify APOE positive individuals at high risk for incident AD, and interventions to enhance sleep consolidation should be studied as potentially useful means to reduce the risk of AD and NFT pathology in APOE ε4+ individuals. PMID:24145819

Column temperature programming in enantioseparation of dihydropyrimidinone compounds using derivatized cellulose and amylose chiral stationary phases.

PubMed

Wang, Fang; Yeung, David; Han, Jun; Semin, David; McElvain, James S; Cheetham, Janet

2008-03-01

We report the application of column temperature programs as a tool to examine unusual temperature-induced behaviors of polysaccharide chiral stationary phases (CSPs). Using dihydropyrimidinone (DHP) compounds as probes we observed the heating (10-50 degrees C) and cooling (50-10 degrees C) van't Hoff plots of retention factors and/or selectivities of DHP compounds were not superimposable on AD, IA, and AS-H columns solvated with ethanol (EtOH)/n-hexane (n-Hex) mobile phases. The plots were not superimposable on AD, IB, and AS-H columns solvated with 2-propanol (2-PrOH)/n-Hex mobile phases. The thermally induced path-dependant behaviors were caused by slow equilibration as evidenced by the disappearance of the hysteresis in the second heating to cooling cycle and in a cooling to heating cycle. From the step-temperature program (10-50-10 degrees C), only EtOH solvated AD and AS-H phases showed the change of retention factors and/or selectivities with time while only 2-PrOH solvated AS-H phase showed similar behaviors.

Fever: exchange of shivering by nonshivering pyrogenesis in cold-acclimated guinea pigs.

PubMed

Blatteis, C M

1976-01-01

The pyrogenic response of adult, unanesthetized guinea pigs to 2 mug/kg iv of Salmonella enteritidis endotoxin was measured at 27 and 7 degrees C ambient temperatures, both before and after an 8-wk exposure to 7 degrees C. There were no significant differences between the onset, maximum height, and total duration of the fevers produced before and after cold acclimation in both thermal environments. However, in 27 degrees C, before cold acclimation, fever production was associated with vigorous shivering activity; two temperature maxima typically developed. After cold acclimation, visible shivering was not detectable during pyrogenesis; moreover, only a single maximum occurred, culminating during the interval between the two rises previously. In 7 degrees C, shivering occurred in both the non-cold- and cold-acclimated endotoxin-treated guinea pigs, but the increase in oxygen consumption was significantly greater in the latter. These results indicated, therefore, that nonshivering (NST) replaces shivering thermogenesis (ST) in a thermoneutral, while ST is added onto NST in a cold, environment in cold-acclimated guinea pigs in supplying the necessary heat for fever production, and that these effects involve alterations in the character of the febrile course.

Degree of Bilingualism Predicts Age of Diagnosis of Alzheimer's Disease in Low-Education but Not in Highly Educated Hispanics

ERIC Educational Resources Information Center

Gollan, Tamar H.; Salmon, David P.; Montoya, Rosa I.; Galasko, Douglas R.

2011-01-01

The current study investigated the relationship between bilingual language proficiency and onset of probable Alzheimer's disease (AD) in 44 Spanish-English bilinguals at the UCSD Alzheimer's Disease Research Center. Degree of bilingualism along a continuum was measured using Boston Naming Test (BNT) scores in each language. Higher degrees of…

The MLA Survey of Postsecondary Entrance and Degree Requirements for Languages Other Than English, 2009-10

ERIC Educational Resources Information Center

Lusin, Natalia

2012-01-01

Since 1953, the MLA has conducted a survey of entrance and degree requirements for languages other than English. The surveys reveal trends over time and show how colleges and universities in the United States have added, dropped, or changed their requirements. Entrance and degree requirements are one measure of the value that an institution…

Memory of myself: autobiographical memory and identity in Alzheimer's disease.

PubMed

Addis, Donna Rose; Tippett, Lynette J

2004-01-01

A number of theories posit a relationship between autobiographical memory and identity. To test this we assessed the status of autobiographical memory and identity in 20 individuals with Alzheimer's disease (AD) and 20 age-matched controls, and investigated whether degree of autobiographical memory impairment was associated with changes in identity. Two tests of autobiographical memory (Autobiographical Memory Interview, autobiographical fluency) and two measures of identity (Twenty Statements Test, identity items of the Tennessee Self Concept Scale) were administered. AD participants exhibited significant impairments on both memory tests, and changes in the strength, quality, and direction of identity relative to controls. Impairments of some components of autobiographical memory, particularly autobiographical memory for childhood and early adulthood, were related to changes in the strength and quality of identity. These findings support the critical role of early adulthood autobiographical memories (16-25 years) in identity, and suggest autobiographical memory loss affects identity.

Noninvasive fractal biomarker of clock neurotransmitter disturbance in humans with dementia

PubMed Central

Hu, Kun; Harper, David G.; Shea, Steven A.; Stopa, Edward G.; Scheer, Frank A. J. L.

2013-01-01

Human motor activity has a robust, intrinsic fractal structure with similar patterns from minutes to hours. The fractal activity patterns appear to be physiologically important because the patterns persist under different environmental conditions but are significantly altered/reduced with aging and Alzheimer's disease (AD). Here, we report that dementia patients, known to have disrupted circadian rhythmicity, also have disrupted fractal activity patterns and that the disruption is more pronounced in patients with more amyloid plaques (a marker of AD severity). Moreover, the degree of fractal activity disruption is strongly associated with vasopressinergic and neurotensinergic neurons (two major circadian neurotransmitters) in postmortem suprachiasmatic nucleus (SCN), and can better predict changes of the two neurotransmitters than traditional circadian measures. These findings suggest that the SCN impacts human activity regulation at multiple time scales and that disrupted fractal activity may serve as a non-invasive biomarker of SCN neurodegeneration in dementia. PMID:23863985

Assortativity and leadership emerge from anti-preferential attachment in heterogeneous networks.

PubMed

Sendiña-Nadal, I; Danziger, M M; Wang, Z; Havlin, S; Boccaletti, S

2016-02-18

Real-world networks have distinct topologies, with marked deviations from purely random networks. Many of them exhibit degree-assortativity, with nodes of similar degree more likely to link to one another. Though microscopic mechanisms have been suggested for the emergence of other topological features, assortativity has proven elusive. Assortativity can be artificially implanted in a network via degree-preserving link permutations, however this destroys the graph's hierarchical clustering and does not correspond to any microscopic mechanism. Here, we propose the first generative model which creates heterogeneous networks with scale-free-like properties in degree and clustering distributions and tunable realistic assortativity. Two distinct populations of nodes are incrementally added to an initial network by selecting a subgraph to connect to at random. One population (the followers) follows preferential attachment, while the other population (the potential leaders) connects via anti-preferential attachment: they link to lower degree nodes when added to the network. By selecting the lower degree nodes, the potential leader nodes maintain high visibility during the growth process, eventually growing into hubs. The evolution of links in Facebook empirically validates the connection between the initial anti-preferential attachment and long term high degree. In this way, our work sheds new light on the structure and evolution of social networks.

Assortativity and leadership emerge from anti-preferential attachment in heterogeneous networks

NASA Astrophysics Data System (ADS)

Sendiña-Nadal, I.; Danziger, M. M.; Wang, Z.; Havlin, S.; Boccaletti, S.

2016-02-01

Real-world networks have distinct topologies, with marked deviations from purely random networks. Many of them exhibit degree-assortativity, with nodes of similar degree more likely to link to one another. Though microscopic mechanisms have been suggested for the emergence of other topological features, assortativity has proven elusive. Assortativity can be artificially implanted in a network via degree-preserving link permutations, however this destroys the graph’s hierarchical clustering and does not correspond to any microscopic mechanism. Here, we propose the first generative model which creates heterogeneous networks with scale-free-like properties in degree and clustering distributions and tunable realistic assortativity. Two distinct populations of nodes are incrementally added to an initial network by selecting a subgraph to connect to at random. One population (the followers) follows preferential attachment, while the other population (the potential leaders) connects via anti-preferential attachment: they link to lower degree nodes when added to the network. By selecting the lower degree nodes, the potential leader nodes maintain high visibility during the growth process, eventually growing into hubs. The evolution of links in Facebook empirically validates the connection between the initial anti-preferential attachment and long term high degree. In this way, our work sheds new light on the structure and evolution of social networks.

AD620SQ/883B Total Ionizing Dose Radiation Lot Acceptance Report for RESTORE-LEO

NASA Technical Reports Server (NTRS)

Burton, Noah; Campola, Michael

2017-01-01

A Radiation Lot Acceptance Test was performed on the AD620SQ/883B, Lot 1708D, in accordance with MIL-STD-883, Method 1019, Condition D. Using a Co-60 source 4 biased parts and 4 unbiased parts were irradiated at 10 mrad/s (0.036 krad/hr) in intervals of approximately 1 krad from 3-10 krads, and ones of 5 krads from 10-25 krads, where it was annealed while unbiased at 25 degrees Celsius, for 2 days, and then, subsequently, annealed while biased at 25 degrees celsius, for another 7 days.

The prognostic value of family history among patients with urinary bladder cancer.

PubMed

Egbers, Lieke; Grotenhuis, Anne J; Aben, Katja K; Alfred Witjes, J; Kiemeney, Lambertus A; Vermeulen, Sita H

2015-03-01

A history of urinary bladder cancer (UBC) in first-degree relatives increases UBC risk by twofold. The influence of positive family history on UBC prognosis is unknown. Here, we investigated association of first-degree UBC family history with clinicopathological characteristics and prognosis of UBC patients. Detailed clinical data of 1,465 non-muscle-invasive bladder cancer (NMIBC) and 250 muscle-invasive or metastatic bladder cancer (MIBC) patients, diagnosed from 1995 to 2010, were collected through medical file review. Competing risk analyses were used to compare recurrence-free survival (RFS) and progression-free survival (PFS) of NMIBC patients according to self-reported UBC family history. Overall survival in MIBC patients was estimated using Kaplan-Meier analysis. The added value of family history in prediction of NMIBC prognosis was quantified with Harrell's concordance-index. Hundred (6.8%) NMIBC and 14 (5.6%) MIBC patients reported UBC in first-degree relatives. Positive family history was statistically significantly associated with smaller tumor size and non-significantly with more favorable distribution of other tumor characteristics. In univariable analyses, positive family history correlated with longer RFS (p = 0.11) and PFS (p = 0.04). Hazard ratios for positive vs. negative family history after adjustment for clinicopathological characteristics were 0.75 (95% CI = 0.53-1.07) and 0.45 (95% CI = 0.18-1.12) for RFS and PFS, respectively. Five familial and 48 sporadic MIBC patients (Kaplan-Meier 10-year risk: 41% and 25%) died within 10 years. Family history did not improve the c-index of prediction models. This study shows that a first-degree family history of UBC is not clearly associated with NMIBC prognosis. Family history does not aid in prediction of NMIBC recurrence or progression. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Untimed Design Fluency in Aging and Alzheimer's Disease: Psychometrics and Normative Data.

PubMed

Sunderaraman, Preeti; Sokolov, Elisaveta; Cines, Sarah; Sullo, Elizabeth; Orly, Aidan; Lerer, Bianca; Karlawish, Jason; Huey, Edward; Cosentino, Stephanie

2015-01-01

Design fluency tests, commonly used in both clinical and research contexts to evaluate nonverbal concept generation, have the potential to offer useful information in the differentiation of healthy versus pathological aging. Although normative data for older adults (OAs) are available for multiple timed versions of this test, similar data have been unavailable for a previously published untimed test, the Graphic Pattern Generation Test (GPG). Time constraints common to almost all of the available design fluency tests may cloud interpretation of higher-level executive abilities-for example, in individuals with slow processing speed. The current study examined the psychometric properties of the GPG and presents normative data in a sample of 167 healthy OAs and 110 individuals diagnosed with Alzheimer's disease (AD). Results suggest that a brief version of the GPG can be administered reliably and that this short form has high test-retest and interrater reliability. Number of perseverations was higher in individuals with AD as compared with OAs. A cutoff score of 4 or more perseverations showed a moderate degree of sensitivity (76%) and specificity (37%) in distinguishing individuals with AD and OAs. Finally, perseverations were associated with nonmemory indexes, thereby underscoring the nonverbal nature of this error in OAs and individuals with AD.

The Graphic Pattern Generation Test in Healthy Aging and Alzheimer's Disease: Psychometric Properties and Normative Data

PubMed Central

Sunderaraman, Preeti; Sokolov, Elisaveta; Cines, Sarah; Sullo, Elizabeth; Orly, Aidan; Lerer, Bianca; Karlawish, Jason; Huey, Edward; Cosentino, Stephanie

2015-01-01

Design fluency tests, commonly used in both clinical and research contexts to evaluate nonverbal concept generation, have the potential to offer useful information in the differentiation of healthy versus pathological aging. While normative data for older adults are available for multiple timed versions of this test, similar data have been unavailable for a previously published untimed task, the Graphic Pattern Generation Task (GPG). Time constraints common to almost all of the available design fluency tests may cloud interpretation of higher level executive abilities, for example in individuals with slow processing speed. The current study examined the psychometric properties of the GPG and presents normative data in a sample of 167 healthy older adults (OAs) and 110 individuals diagnosed with Alzheimer's disease (AD). Results suggest that a brief version of the GPG can be administered reliably, and that this short form has high test-retest and inter-rater reliability. Number of perseverations was higher in individuals with AD as compared to OAs. A cut-off score of 4 or more perseverations showed a moderate degree of sensitivity (76%) and specificity (37%) in distinguishing individuals with AD and OAs. Finally, perseverations were associated with nonmemory indices, underscoring the nonverbal nature of this error in OAs and individuals with AD. PMID:25679880

Optimal Control Design Advantages Utilizing Two-Degree-of-Freedom Controllers

DTIC Science & Technology

1993-12-01

AFrTIGAE/ENYIV3D-27 AD--A273 839 D"TIC OPTIMAL CONTROL DESIGN ADVANTAGES UTILIZING TWO-DEGREE-OF-FREEDOM CONTROLLERS THESIS Michael J. Stephens...AFIT/GAE/ENY/93D-27 OPTIMAL CONTROL DESIGN ADVANTAGES UTILIZING TWO-DEGREE-OF-FREEDOM CONTROLLERS THESIS Presented to the Faculty of the Graduate...measurement noises compared to the I- DOF model. xvii OPTIMAL CONTROL DESIGN ADVANTAGES UTILIZING TWO-DEGREE-OF-FREEDOM CONTROLLERS I. Introduction L1

The effects of potato and rice starch as substitutes for phosphate in and degree of comminution on the technological, instrumental and sensory characteristics of restructured ham.

PubMed

Resconi, Virginia C; Keenan, Derek F; García, Elisa; Allen, Paul; Kerry, Joe P; Hamill, Ruth M

2016-11-01

The effects of sodium tripolyphosphate (STPP), two sources of starch (potato starch: PS and rice starch: RS) and comminution degree (CD) on the technological, instrumental and sensory characteristics of reformed hams were studied using response surface methodology. Both starches reduced cook loss and decreased ham flavour intensity, but RS had stronger effects on instrumental measures of texture, while PS was associated with improved juiciness when low/no added STPP was included. Coarsely ground meat, processed 100% with the kidney plate was associated with slightly increased cook loss, reduced texture profile analysis parameters and a more intense ham flavour compared to the other treatment (80% ground with a kidney plate plus 20% with a 9mm plate). STPP was the sole factor affecting overall liking. If starch is included in the formulation, the standard level of STPP (0.3%) can be reduced by half with no increase in cook losses, but some decline in sensory quality cannot be avoided. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oblique perspective, due east by 70 degrees. Note concrete pier, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Oblique perspective, due east by 70 degrees. Note concrete pier, added CA. 1930's. Other piers and abutments are heavily mortared rubble stone. - Watson Mill Bridge, Spanning South Fork Broad River, Watson Mill Road, Watson Mill Bridge State Park, Comer, Madison County, GA

Enhancing Engineering Education through Engineering Management

ERIC Educational Resources Information Center

Pence, Kenneth R.; Rowe, Christopher J.

2012-01-01

Engineering Management courses are added to a traditional engineering curriculum to enhance the value of an undergraduate's engineering degree. A four-year engineering degree often leaves graduates lacking in business and management acumen. Engineering management education covers topics enhancing the value of new graduates by teaching management…

Methods for synthesizing semiconductor quality chalcopyrite crystals for nonlinear optical and radiation detection applications and the like

DOEpatents

Stowe, Ashley; Burger, Arnold

2016-05-10

A method for synthesizing I-III-VI.sub.2 compounds, including: melting a Group III element; adding a Group I element to the melted Group III element at a rate that allows the Group I and Group III elements to react thereby providing a single phase I-III compound; and adding a Group VI element to the single phase I-III compound under heat, with mixing, and/or via vapor transport. The Group III element is melted at a temperature of between about 200 degrees C. and about 700 degrees C. Preferably, the Group I element consists of a neutron absorber and the group III element consists of In or Ga. The Group VI element and the single phase I-III compound are heated to a temperature of between about 700 degrees C. and about 1000 degrees C. Preferably, the Group VI element consists of S, Se, or Te. Optionally, the method also includes doping with a Group IV element activator.

Amyloid β-Derived Diffusible Ligands (ADDLs) Induce Abnormal Autophagy Associated with Aβ Aggregation Degree.

PubMed

Wen, Jie; Fang, Fang; Guo, Shu-Han; Zhang, Ying; Peng, Xiang-Lei; Sun, Wei-Min; Wei, Xiao-Ran; He, Jin-Sheng; Hung, Tao

2018-02-01

Autophagy is disturbed in Alzheimer's disease (AD) and maintaining normal autophagy homeostasis is a new therapeutic strategy for AD treatment. Amyloid β-derived diffusible ligands (ADDLs), the most toxic species of which are oligomeric forms of amyloid β peptide (Aβ) that originate from amyloid β precursor protein (APP) via autophagy; however, whether ADDLs are involved in autophagy-related AD pathogenesis remains unclear. In this study, we primarily defined the specific subsets of ADDLs, A-0, A-12, A-24, and A-48, which were generated from ADDL aggregation mixtures at different time courses of assembly. The secondary structures of ADDL subsets were detected by circular dichroism (CD). Neuronal or non-neuronal cells were exposed to the subsets of ADDLs in vitro, and then, autophagic markers were detected. Our results first showed that exogenous or endogenous LC3 puncta (autophagosomes) were induced in the cytoplasm of cells exposed to ADDLs and that the LC3 puncta were the strongest with A-24 exposure. Then, the CD spectroscopy data also indicated that the proportion of α-helices decreased, whereas the proportion of β-strands and β-turns increased during ADDL assembly from 0 to 24 h. In addition, the quantitative Western blot data demonstrated that the ratio of LC3B-II/I was significantly increased, and SQSTM1/p62 decreased over time. Finally, our results indicated that the level of phosphorylated p70 S6 kinase (p-p70 S6 kinase), which is a substrate protein in the MTOR pathway, and the ratio of p-p70 S6 kinase/p70 S6 kinase significantly decreased following A-24 exposure. Taken together, our data suggest that ADDL-induced abnormal autophagy is correlated with Aβ aggregation degree and the MTOR pathway, which might contribute to ADDL-induced AD pathogenesis.

Use of and Self-Perceived Need for Assistive Devices in Individuals with Disabilities in Taiwan

PubMed Central

Yeung, Kwok-Tak; Lin, Chung-Hui; Teng, Ya-Ling; Chen, Fen-Fen; Lou, Shu-Zon; Chen, Chiung-Ling

2016-01-01

Assistive devices (ADs) can help individuals with disabilities achieve greater independence, and it can enhance the quality of their lives. This study investigated the use of and self-perceived need for ADs in individuals with disabilities, and determined the influence of gender, age as well as type and degree of disability on the use of and self-perceived need for ADs. This descriptive study utilized a cross-sectional survey design with a convenience sample of participants. A total of 1018 subjects with disabilities who visited an exhibition of assistive technology and two ADs research and development centers completed a questionnaires either by themselves or via a caregiver who completed the questionnaire on behalf of the subject or via interviewers trained specifically for this study. The Mann-Whitney U test and Kruskal-Wallis test were used to determine the influence of participant characteristics on the use of ADs. The results showed that 77.2% and 83.3% of the participants reported that they used and needed AD(s) to engage in activities of daily living. The mean quantity of the use of and self-perceived need for total types of ADs were 3.0 and 5.3, respectively. Participants with different disabilities reported different percentages of the use of various types of ADs. No difference was found between genders and among the age groups in the use of quantity of ADs. Individuals with different types and degrees of disability used different quantities of ADs. Participants with physical, visual and multiple disabilities used significantly more ADs compared to participants with intellectual disability. The total quantity of ADs used increased significantly with increased severity of disability. The mean use of assistive devices was lower compared to the mean need of individuals with disabilities. Further study is required to determine why patients feel the need for but not currently use a specific assistive device. PMID:27023276

Symmetry operators of Killing spinors and superalgebras in AdS5

NASA Astrophysics Data System (ADS)

Ertem, Ümit

2016-04-01

We construct the first-order symmetry operators of Killing spinor equation in terms of odd Killing-Yano forms. By modifying the Schouten-Nijenhuis bracket of Killing-Yano forms, we show that the symmetry operators of Killing spinors close into an algebra in AdS5 spacetime. Since the symmetry operator algebra of Killing spinors corresponds to a Jacobi identity in extended Killing superalgebras, we investigate the possible extensions of Killing superalgebras to include higher-degree Killing-Yano forms. We found that there is a superalgebra extension but no Lie superalgebra extension of the Killing superalgebra constructed out of Killing spinors and odd Killing-Yano forms in AdS5 background.

Assessment of the information provided by the medical specialist on Alzheimer's disease and that retained by the patient caregivers.

PubMed

Molinuevo, J L; Hernández, B

2012-10-01

There is evidence of insufficient communication abilities by medical specialists as well as of the limited retentive capacities of patients with Alzheimer disease (AD) and their caregivers. The main reasons for this include the personal limitations of the physician, as well as external, emotional and social-cultural factors associated with the patients and their caregivers. The aim of this study is to compare the clinical information on AD provided by the physicians and that perceived by caregivers and to assess factors associated with differences in perception. We carried out an observational national multicentre study based on questionnaires assessing the information provided by the physician and that retained by the caregiver for 17 items of information. The study involved 61 researchers and included a total of 679 patients who met the selection criteria. We evaluated the factors associated with the difference in perception of the information that was transmitted. Participating caregivers had a mean age of 57.2 ± 14.8 years, with an average care time of 27.6 ± 28.0 months. Approximately half (50.9%) were children of the AD patient and most lived in the same household (64.9%). Caregivers assigned significantly higher ratings to information on concept of disease, aetiology, pathogenesis, dosage and treatment recommendations and adherence, while doctors assigned significantly higher ratings to information related to demystification and correcting preconceived notions, possible complications, adverse events and/or iatrogenesis, family associations, and emotional/psychological support to caregivers (P<.05). Concordance between the information provided and that received was classified between poor and weak (inter-rater agreement ≤ 0.27). The degree of disease progression using the Global Deterioration Scale (GDS) was a factor significantly associated with professional-carer information discrepancy (P=.002). Many areas of information showed large differences in perception between physicians and caregivers of AD patients, which highlights the need to improve the communication process in order to achieve higher quality. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

A Model of Consumer Response to Over-the-Counter Drug Advertising: Antecedents and Influencing Factors.

PubMed

Huh, Jisu; Delorme, Denise E; Reid, Leonard N

2016-01-01

Given the importance of over-the-counter (OTC) drugs in the health care marketplace and lack of systematic research on OTC drug advertising (OTCA) effects, this study tested a theory-based, product category-specific OTCA effects model. Structural equation modeling analysis of data for 1 OTC drug category, analgesics, supported the proposed model, explaining the OTCA effect process from key consumer antecedents to ad involvement, from ad involvement to ad attention, from ad attention to cognitive responses, then to affective/evaluative responses, leading to the final behavioral outcome. Several noteworthy patterns also emerged: (a) Product involvement was directly linked to ad attention, rather than exerting an indirect influence through ad involvement; (b) ad attention was significantly related to both cognitive and affective/evaluative responses to different degrees, with stronger links to cognitive responses; and (c) ad-prompted actions were influenced by both ad trust and ad attitude.

Prototype learning and dissociable categorization systems in Alzheimer's disease.

PubMed

Heindel, William C; Festa, Elena K; Ott, Brian R; Landy, Kelly M; Salmon, David P

2013-08-01

Recent neuroimaging studies suggest that prototype learning may be mediated by at least two dissociable memory systems depending on the mode of acquisition, with A/Not-A prototype learning dependent upon a perceptual representation system located within posterior visual cortex and A/B prototype learning dependent upon a declarative memory system associated with medial temporal and frontal regions. The degree to which patients with Alzheimer's disease (AD) can acquire new categorical information may therefore critically depend upon the mode of acquisition. The present study examined A/Not-A and A/B prototype learning in AD patients using procedures that allowed direct comparison of learning across tasks. Despite impaired explicit recall of category features in all tasks, patients showed differential patterns of category acquisition across tasks. First, AD patients demonstrated impaired prototype induction along with intact exemplar classification under incidental A/Not-A conditions, suggesting that the loss of functional connectivity within visual cortical areas disrupted the integration processes supporting prototype induction within the perceptual representation system. Second, AD patients demonstrated intact prototype induction but impaired exemplar classification during A/B learning under observational conditions, suggesting that this form of prototype learning is dependent on a declarative memory system that is disrupted in AD. Third, the surprisingly intact classification of both prototypes and exemplars during A/B learning under trial-and-error feedback conditions suggests that AD patients shifted control from their deficient declarative memory system to a feedback-dependent procedural memory system when training conditions allowed. Taken together, these findings serve to not only increase our understanding of category learning in AD, but to also provide new insights into the ways in which different memory systems interact to support the acquisition of categorical knowledge. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prototype Learning and Dissociable Categorization Systems in Alzheimer’s Disease

PubMed Central

Heindel, William C.; Festa, Elena K.; Ott, Brian R.; Landy, Kelly M.; Salmon, David P.

2015-01-01

Recent neuroimaging studies suggest that prototype learning may be mediated by at least two dissociable memory systems depending on the mode of acquisition, with A/Not-A prototype learning dependent upon a perceptual representation system located within posterior visual cortex and A/B prototype learning dependent upon a declarative memory system associated with medial temporal and frontal regions. The degree to which patients with Alzheimer’s disease (AD) can acquire new categorical information may therefore critically depend upon the mode of acquisition. The present study examined A/Not-A and A/B prototype learning in AD patients using procedures that allowed direct comparison of learning across tasks. Despite impaired explicit recall of category features in all tasks, patients showed differential patterns of category acquisition across tasks. First, AD patients demonstrated impaired prototype induction along with intact exemplar classification under incidental A/Not-A conditions, suggesting that the loss of functional connectivity within visual cortical areas disrupted the integration processes supporting prototype induction within the perceptual representation system. Second, AD patients demonstrated intact prototype induction but impaired exemplar classification during A/B learning under observational conditions, suggesting that this form of prototype learning is dependent on a declarative memory system that is disrupted in AD. Third, the surprisingly intact classification of both prototypes and exemplars during A/B learning under trial-and-error feedback conditions suggests that AD patients shifted control from their deficient declarative memory system to a feedback-dependent procedural memory system when training conditions allowed. Taken together, these findings serve to not only increase our understanding of category learning in AD, but to also provide new insights into the ways in which different memory systems interact to support the acquisition of categorical knowledge. PMID:23751172

Diagnostics and therapy of Alzheimer's disease.

PubMed

Mikiciuk-Olasik, Elzbieta; Szymański, Paweł; Zurek, Elzbieta

2007-04-01

Alzheimer's Disease (AD) is described as a degenerative disease of the central nervous system characterized by a noticeable cognitive decline defined by a loss of memory and learning ability, together with a reduced ability to perform basic activities of daily living. In the brain of an AD patients is the dramatic decrease in cholinergic innervation in the cortex and hippocampus due to the loss of neurons in the basal forebrain. The above findings led to the development of the cholinergic hypothesis, which proposes that the cognitive loss associated with AD is related to decreased cortical cholinergic neurotransmission. In brain of Alzheimer's patient's one ascertained presence of neuritic plaques containing the beta-amyloid peptide and protein tau. Biochemical and genetics studies implicated a central role for beta-amyloid in the pathological cascade of events in AD. The most therapeutic strategies in AD have been directed to two main targets: the beta-amyloid peptide and the cholinergic neurotransmission. The first approach is to act on the amyloid precursor protein (APP) processing. The second main approach is to slow of decline of neuronal degeneration or increasing cholinergic transmission. Diagnosis of AD is very difficult and to date no specific diagnostic tests of the disease are available. Intellectual function testing to determine the degree of cognitive status during routine medical examination is a useful supplementary method of diagnosing dementia. The permissible result, come down from radiopharmacy, which is an integral part of a nuclear medicine. A radiopharmaceutical may be defined as a pharmaceutical substance containing radioactive atoms. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are capable of mapping the distribution of radionuclides in three dimensions, producing maps of brain biochemical and physiological processes. The techniques are reasonably sensitive and specific in differentiating AD from other dementias.

Insulin dysfunction and Tau pathology.

PubMed

El Khoury, Noura B; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

2014-01-01

The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.

Insulin dysfunction and Tau pathology

PubMed Central

El Khoury, Noura B.; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

2013-01-01

The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia. PMID:24574966

Examining the Pathways between Self-Awareness and Well-Being in Mild-Moderate Alzheimer’s Disease

PubMed Central

Cines, Sarah; Farrell, Meagan; Steffener, Jason; Sullo, Liz; Huey, Ted; Karlawish, Jason; Cosentino, Stephanie

2015-01-01

Objective To investigate the relationship between awareness of memory loss and psychological well-being in a non-clinically depressed sample of participants with mild-moderate Alzheimer’s disease. Method Study participants (n=104) enrolled through Columbia University Medical Center and the University of Pennsylvania completed clinical and cognitive assessments. Participants were rated with regard to their degree of awareness of memory deficits and completed questionnaires relating to their psychological well-being, including mood and quality of life (QOL). Mediating models were used to establish the relationship between awareness, depression, and QOL, as well as to examine potential mediators of awareness and depression including psychological distress, objective memory deficits, and negative self-ratings. Results There was a direct association between awareness of memory deficits and depressed mood, but not awareness and QOL. However, there was an indirect association between awareness and QOL through depression. Neither psychological distress, memory deficits, nor negative self-ratings mediated the relationship between awareness and depression. Conclusions Awareness is associated with depressed mood in non-clinically depressed participants with mild to moderate AD. However, depressed mood does not appear to reflect the direct psychological reaction to awareness of memory loss. Moreover, awareness has only an indirect association with QOL via depressed mood. These results suggest that preserved awareness does not have a direct negative impact on overall psychological well-being in AD. PMID:26560509

Evaluating the Patterns of Aging-Related Tau Astrogliopathy Unravels Novel Insights Into Brain Aging and Neurodegenerative Diseases.

PubMed

Kovacs, Gabor G; Robinson, John L; Xie, Sharon X; Lee, Edward B; Grossman, Murray; Wolk, David A; Irwin, David J; Weintraub, Dan; Kim, Christopher F; Schuck, Theresa; Yousef, Ahmed; Wagner, Stephanie T; Suh, Eunran; Van Deerlin, Vivianna M; Lee, Virginia M-Y; Trojanowski, John Q

2017-04-01

The term "aging-related tau astrogliopathy" (ARTAG) describes pathological accumulation of abnormally phosphorylated tau protein in astrocytes. We evaluated the correlates of ARTAG types (i.e., subpial, subependymal, white and gray matter, and perivascular) in different neuroanatomical regions. Clinical, neuropathological, and genetic (eg, APOE ε4 allele, MAPT H1/H2 haplotype) data from 628 postmortem brains from subjects were investigated; most of the patients had been longitudinally followed at the University of Pennsylvania. We found that (i) the amygdala is a hotspot for all ARTAG types; (ii) age at death, male sex, and presence of primary frontotemporal lobar degeneration (FTLD) tauopathy are significantly associated with ARTAG; (iii) age at death, greater degree of brain atrophy, ventricular enlargement, and Alzheimer disease (AD)-related variables are associated with subpial, white matter, and perivascular ARTAG types; (iv) AD-related variables are associated particularly with lobar white matter ARTAG; and (v) gray matter ARTAG in primary FTLD-tauopathies appears in areas without neuronal tau pathology. We provide a reference map of ARTAG types and propose at least 5 constellations of ARTAG. Furthermore, we propose a conceptual link between primary FTLD-tauopathy and ARTAG-related astrocytic tau pathologies. Our observations serve as a basis for etiological stratification and definition of progression patterns of ARTAG. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Impact of APOE4-CSF Aβ interaction on hippocampal volume loss over 1 year in MCI

PubMed Central

Chiang, G.C.; Insel, P.S.; Tosun, D.; Schuff, N.; Truran-Sacrey, D.; Raptentsetsang, S.T.; Thompson, P.M.; Reiman, E.M.; Jack, C.R.; Fox, N.C.; Jagust, W.J.; Harvey, D.J.; Beckett, L.A.; Gamst, A.; Aisen, P.S.; Petersen, R.C.; Weiner, M.W.

2011-01-01

Background The majority of studies relating amyloid pathology with brain volumes have been cross-sectional. Apolipoprotein E4 (APOE4), a genetic risk factor for Alzheimer’s disease (AD), is also associated with hippocampal volume loss. No studies have considered the effects of amyloid pathology and APOE4 together on longitudinal volume loss. Methods We evaluated whether an abnormal level of cerebrospinal fluid beta-amyloid (CSF Aβ) and APOE4 carrier status were independently associated with greater hippocampal volume loss over 1 year. We then assessed whether APOE4 status and CSF Aβ acted synergistically, testing the significance of an interaction term in the regression analysis. We included 297 participants: 77 cognitively normal (NC), 144 with mild cognitive impairment (MCI), and 76 with AD. Results An abnormal CSF Aβ level was found to be associated with greater hippocampal volume loss over 1 year in each group. APOE4 was associated with hippocampal volume loss only in the NC and MCI groups. APOE4 carriers with abnormal CSF Aβ in the MCI group acted synergistically to produce disproportionately greater volume loss than noncarriers. Conclusion Baseline CSF Aβ predicts progression of hippocampal volume loss. APOE4 carrier status amplifies the degree of neurodegeneration in MCI. Understanding the effect of interactions between genetic risk and amyloid pathology will be important in clinical trials and our understanding of the disease process. PMID:21889115

Relationships among plasma granzyme B level, pruritus and dermatitis in patients with atopic dermatitis.

PubMed

Kamata, Yayoi; Kimura, Utako; Matsuda, Hironori; Tengara, Suhandy; Kamo, Atsuko; Umehara, Yoshie; Iizumi, Kyoichi; Kawasaki, Hiroaki; Suga, Yasushi; Ogawa, Hideoki; Tominaga, Mitsutoshi; Takamori, Kenji

2016-12-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H 1 -antihistamines. Granzymes (Gzms) are a family of serine proteases expressed by cytotoxic T lymphocytes and natural killer cells that have been shown to modulate inflammation. However, the relationship between Gzms and pathology in AD remains unclear. This study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients. Plasma was collected from 46 patients with AD, 24 patients with psoriasis, and 30 healthy controls. AD severity was assessed with the scoring atopic dermatitis (SCORAD) index, psoriasis severity with the psoriasis area and severity index (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB and gastrin releasing peptide (GRP) levels were measured by enzyme-linked immunosorbent assays. Plasma GzmB concentrations were significantly higher in patients with AD and psoriasis than in healthy controls. Correlation analyses showed that plasma GzmB concentrations positively correlated with SCORAD and serum levels of severity markers such as thymus and activation-regulated chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of GRP, an itch-related peptide, were higher in patients with AD, positively correlating with VAS score and plasma GzmB level. In addition, plasma GzmB concentration was significantly lower in the treatment group than the untreated group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score and PASI score in patients with psoriasis. In contrast to the results of plasma GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups, and showed no correlations with VAS score and SCORAD index in patients with AD. Plasma GzmB levels may reflect the degree of pruritus and dermatitis in patients with AD. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Impact of control for air pollution and respiratory epidemics on the estimated associations of temperature and daily mortality.

PubMed

O'Neill, Marie S; Hajat, Shakoor; Zanobetti, Antonella; Ramirez-Aguilar, Matiana; Schwartz, Joel

2005-11-01

We assessed the influence of control for air pollution and respiratory epidemics on associations between apparent temperature (AT) and daily mortality in Mexico City and Monterrey. Poisson regressions were fit to mortality among all ages, children (ages 0-14 years) and the elderly (ages >or=65 years). Predictors included mean daily AT, season, day of week and public holidays for the base model. Respiratory epidemics and air pollution (particulate matter <10 microm in aerodynamic diameter and O3) were added singly and then jointly for a fully adjusted model. Percent changes in mortality were calculated for days of relatively extreme temperatures [cold (10-11 degrees C) for both cities and heat (35-36 degrees C) for Monterrey], compared to days at the overall mean temperature in each city (15 degrees C in Mexico City, 25 degrees C in Monterrey). In Mexico City, total mortality increased 12.4% [95% confidence interval (CI) 10.5%, 14.5%] on cold days (fully adjusted). Among children, the adjusted association was similar [10.9% (95% CI: 5.4%, 16.7%)], but without control for pollution and epidemics, was nearly twice as large [19.7% (95% CI: 13.9%, 25.9)]. In Monterrey, the fully adjusted heat effect for all deaths was 18.7% (95% CI: 11.7%, 26.1%), a third lower than the unadjusted estimate; the heat effect was lower among children [5.5% (95% CI: -10.1%, 23.8%)]. Cold had a similar effect on all-age mortality as in Mexico City [11.7% (95% CI: 3.7%, 20.3%)]. Responses of the elderly differed little from all-ages responses in both cities. Associations between weather and health persisted even with control for air pollution and respiratory epidemics in two Mexican cities, but risk assessments and climate change adaptation programs are best informed by analyses that account for these potential confounders.

Method for high specific bioproductivity of .alpha.,.omega.-alkanedicarboxylic acids

DOEpatents

Mobley, David Paul; Shank, Gary Keith

2000-01-01

This invention provides a low-cost method of producing .alpha.,.omega.-alkanedicarboxylic acids. Particular bioconversion conditions result in highly efficient conversion of fatty acid, fatty acid ester, or alkane substrates to diacids. Candida tropicalis AR40 or similar yeast strains are grown in a medium containing a carbon source and a nitrogen source at a temperature of 31.degree. C. to 38.degree. C., while additional carbon source is continuously added, until maximum cell growth is attained. Within 0-3 hours of this point, substrate is added to the culture to initiate conversion. An .alpha.,.omega.-alkanedicarboxylic acid made according to this method is also provided.

In silico development of new acetylcholinesterase inhibitors.

PubMed

Pascoini, A L; Federico, L B; Arêas, A L F; Verde, B A; Freitas, P G; Camps, I

2018-04-19

In this work, we made use of fragment-based drug design (FBDD) and de novo design to obtain more powerful acetylcholinesterase (AChE) inhibitors. AChE is associated with Alzheimer's disease (AD). It was found that the cholinergic pathways in the cerebral cortex are compromised in AD and the accompanying cholinergic deficiency contributes to the cognitive deterioration of AD patients. In the FBDD approach, fragments are docked into the active site of the protein. As fragments are molecular groups with a low number of atoms, it is possible to study their interaction with localized amino acids. Once the interactions are measured, the fragments are organized by affinity and then linked together to form new molecules with a high degree of interaction with the active site. In the other approach, we used the de novo design technique starting from reference drugs used in the AD treatment. These drugs were broken into fragments (seeds). In the growing strategy, fragments were added to each seed, growing new molecules. In the linking strategy, two or more separated seeds were linked with different fragments. Both strategies combined produced a library of more than 2 million compounds. This library was filtered using absorption, distribution, metabolism, and excretion properties. The resulting library with around six thousand compounds was filtered again. In this case, structures with Tanimoto coefficients >.85 were discarded. The final library with 1500 compounds was submitted to docking studies. As a result, 10 compounds with better interaction energy than the reference drugs were obtained.

Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.

PubMed

Lampert, Erika J; Roy Choudhury, Kingshuk; Hostage, Christopher A; Petrella, Jeffrey R; Doraiswamy, P Murali

2013-01-01

A positive family history (FH) is a risk factor for late-onset Alzheimer's disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum. Cross-sectional analyses of data from a national biomarker study. The Alzheimer's Disease Neuroimaging Initiative national study. 257 subjects (ages 55-89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data. Cerebrospinal fluid (CSF) Aβ42, tau, and tau/Aβ42 ratio, MRI-measured hippocampal volumes. Univariate and multivariate analyses. In MCI, CSF Aβ42 was lower (p = .005), t-tau was higher (p = 0.02) and t-tau/Aβ42 ratio was higher (p = 0.002) in FH+ than FH- subjects. A significant residual effect of FH on pathologic markers in MCI remained after adjusting for ApoE4 (p<0.05). Among CN, 47% of FH+ exhibited "pathologic signature of AD" (CSF t-tau/Aβ42 ratio >0.39) versus 21% of FH- controls (p = 0.03). The FH effect was not significant in AD subjects. Hippocampal and intracranial volumes did not differ between FH+ and FH- subjects in any group. A positive family history of late-onset AD is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in MCI. The unexplained genetic heritability in family history is about the half the size of the ApoE4 effect. Longitudinal studies are warranted to more definitively examine this issue.

Awareness of Mild Cognitive Impairment and Mild Alzheimer's Disease Dementia Diagnoses Associated With Lower Self-Ratings of Quality of Life in Older Adults.

PubMed

Stites, Shana D; Karlawish, Jason; Harkins, Kristin; Rubright, Jonathan D; Wolk, David

2017-10-01

This study examined how awareness of diagnostic label impacted self-reported quality of life (QOL) in persons with varying degrees of cognitive impairment. Older adults (n = 259) with normal cognition, Mild Cognitive Impairment (MCI), or mild Alzheimer's disease dementia (AD) completed tests of cognition and self-report questionnaires that assessed diagnosis awareness and multiple domains of QOL: cognitive problems, activities of daily living, physical functioning, mental wellbeing, and perceptions of one's daily life. We compared measures of QOL by cognitive performance, diagnosis awareness, and diagnostic group. Persons with MCI or AD who were aware of their diagnosis reported lower average satisfaction with daily life (QOL-AD), basic functioning (BADL Scale), and physical wellbeing (SF-12 PCS), and more difficulties in daily life (DEM-QOL) than those who were unaware (all p ≤ .007). Controlling for gender, those expecting their condition to worsen over time reported greater depression (GDS), higher stress (PSS), lower quality of daily life (QOL-AD, DEM-QOL), and more cognitive difficulties (CDS) compared to others (all p < .05). Persons aware of their diagnostic label-either MCI or AD-and its prognosis report lower QOL than those unaware of these facts about themselves. These relationships are independent of the severity of cognitive impairment. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

An Item Response Theory (IRT) analysis of the Short Inventory of Problems-Alcohol and Drugs (SIP-AD) among non-treatment seeking men-who-have-sex-with-men: evidence for a shortened 10-item SIP-AD.

PubMed

Hagman, Brett T; Kuerbis, Alexis N; Morgenstern, Jon; Bux, Donald A; Parsons, Jeffrey T; Heidinger, Bram E

2009-11-01

The Short Inventory of Problems-Alcohol and Drugs (SIP-AD) is a 15-item measure that assesses concurrently negative consequences associated with alcohol and illicit drug use. Current psychometric evaluation has been limited to classical test theory (CTT) statistics, and it has not been validated among non-treatment seeking men-who-have-sex-with-men (MSM). Methods from Item Response Theory (IRT) can improve upon CTT by providing an in-depth analysis of how each item performs across the underlying latent trait that it is purported to measure. The present study examined the psychometric properties of the SIP-AD using methods from both IRT and CTT among a non-treatment seeking MSM sample (N=469). Participants were recruited from the New York City area and were asked to participate in a series of studies examining club drug use. Results indicated that five items on the SIP-AD demonstrated poor item misfit or significant differential item functioning (DIF) across race/ethnicity and HIV status. These five items were dropped and two-parameter IRT analyses were conducted on the remaining 10 items, which indicated a restricted range of item location parameters (-.15 to -.99) plotted at the lower end of the latent negative consequences severity continuum, and reasonably high discrimination parameters (1.30 to 2.22). Additional CTT statistics were compared between the original 15-item SIP-AD and the refined 10-item SIP-AD and suggest that the differences were negligible with the refined 10-item SIP-AD indicating a high degree of reliability and validity. Findings suggest the SIP-AD can be shortened to 10 items and appears to be a non-biased reliable and valid measure among non-treatment seeking MSM.

Attitudes toward Advertisements of the Older Adults

ERIC Educational Resources Information Center

Estrada, M.; Moliner, M. A.; Sanchez, J.

2010-01-01

In this study we will analyze the attitude of older adults to advertisements, differentiating between advertisements that contain rhetorical figures (trope ads) and those that do not (explicit ads). We will also study their attitude toward the brand advertised according to their degree of involvement with the product. In the course of the…

Physical activity attenuates age-related biomarker alterations in preclinical AD

PubMed Central

Schultz, Stephanie A.; Oh, Jennifer M.; Larson, Jordan; Edwards, Dorothy; Cook, Dane; Koscik, Rebecca; Gallagher, Catherine L.; Dowling, N.M.; Carlsson, Cynthia M.; Bendlin, Barbara B.; LaRue, Asenath; Rowley, Howard A.; Christian, Brad T.; Asthana, Sanjay; Hermann, Bruce P.; Johnson, Sterling C.; Sager, Mark A.

2014-01-01

Objective: To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Methods: Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer's Prevention underwent T1 MRI; a subset also underwent 11C-Pittsburgh compound B–PET (n = 186) and 18F-fluorodeoxyglucose–PET (n = 152) imaging. Participants' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity. Results: There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group. Conclusions: In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life. PMID:25298312

Physical activity attenuates age-related biomarker alterations in preclinical AD.

PubMed

Okonkwo, Ozioma C; Schultz, Stephanie A; Oh, Jennifer M; Larson, Jordan; Edwards, Dorothy; Cook, Dane; Koscik, Rebecca; Gallagher, Catherine L; Dowling, N M; Carlsson, Cynthia M; Bendlin, Barbara B; LaRue, Asenath; Rowley, Howard A; Christian, Brad T; Asthana, Sanjay; Hermann, Bruce P; Johnson, Sterling C; Sager, Mark A

2014-11-04

To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer's Prevention underwent T1 MRI; a subset also underwent (11)C-Pittsburgh compound B-PET (n = 186) and (18)F-fluorodeoxyglucose-PET (n = 152) imaging. Participants' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity. There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group. In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life. © 2014 American Academy of Neurology.

Neurogenesis in the adult brain: implications for Alzheimer's disease.

PubMed

Galvan, Veronica; Bredesen, Dale E

2007-10-01

The function of neurogenesis in the adult brain is still unknown. Interventions such as environmental enrichment and exercise impinge on neurogenesis, suggesting that the process is regulated by experience. Conversely, a role for neurogenesis in learning has been proposed through 'cellular plasticity', a process akin to synaptic plasticity but operating at the network level. Although neurogenesis is stimulated by acute injury, and possibly by neurodegenerative processes such as Alzheimer's disease (AD), it does not suffice to restore function. While the role and direction of change in the neurogenic response at different stages of AD is still a matter of debate, it is possible that a deficit in neurogenesis may contribute to AD pathogenesis since at least one of the two regions ostensibly neurogenic in the adult human brain (the subgranular zone of the dentage gyrus and the ventriculo-olfactory neurogenic system) support high-level functions affected in early AD (associative memory and olfaction respectively). The age of onset and the rate of progression of sporadic forms of AD are highly variable. Sporadic AD may have a component of insufficient neurogenic replacement or insufficient neurogenic stimulation that is correlated with traits of personal history; the rate of neurogenesis and the survival of replicating progenitors is strongly modified by behavioral interventions known to impinge on the rate of neurogenesis and the probability of survival of newly born neurons--exercise, enriched experience, and learning. This view is consistent with epidemiological data suggesting that higher education and increased participation in intellectual, social and physical aspects of daily life are associated with slower cognitive decline in healthy elderly ("cognitive reserve") and may reduce the risk of AD. Although neurogenesis can be modulated exogenously by growth factors, stimulation of neurogenesis as a mean to treat neurodegeneration is still for the most part speculative. Moreover, it is possible that different roles of neurogenesis during the course of AD are dictated by the degree of permissibility of the environment in which the process is taking place. A unique opportunity may exist in which the therapeutic stimulation of neurogenesis might contribute to functional 'repair' of the adult diseased brain, before damage to whole neuronal networks has ensued. In spite of the considerable gaps in our knowledge of neurogenesis, and of the considerable limitations that will need to be overcome before we can intervene in the process, that new neurons are added continuously to the adult mammalian brain is a discovery that has already changed the way we think about neurobiology, and may soon change the way we understand and approach neurodegenerative diseases such as AD.

Effects of combined fine motor skill and cognitive therapy to cognition, degree of dementia, depression, and activities of daily living in the elderly with Alzheimer's disease.

PubMed

Lee, Jin; Lee, ByoungHee; Park, YuHyung; Kim, Yumi

2015-10-01

[Purpose] This study evaluated the effects of combined fine motor skill and cognitive therapies on cognition, depression, and activities of daily living in elderly patients with Alzheimer's disease (AD). [Subjects and Methods] Twenty-six participants comprised 2 groups. The experimental group (n=13) received combined fine motor skill and cognitive therapy, and the control group (n=13) received only general medical care. [Results] The experimental group showed improvements in cognition, degree of dementia, depression, and activities of daily living compared to the control group. However, there were no significant differences between the two groups. [Conclusion] These results suggest that combined fine motor skill and cognitive therapy improves cognition, degree of dementia, depression, and daily living in elderly patients with AD. These therapies would therefore be effective as general medical care strategies.

A key heterogeneous structure of fractal networks based on inverse renormalization scheme

NASA Astrophysics Data System (ADS)

Bai, Yanan; Huang, Ning; Sun, Lina

2018-06-01

Self-similarity property of complex networks was found by the application of renormalization group theory. Based on this theory, network topologies can be classified into universality classes in the space of configurations. In return, through inverse renormalization scheme, a given primitive structure can grow into a pure fractal network, then adding different types of shortcuts, it exhibits different characteristics of complex networks. However, the effect of primitive structure on networks structural property has received less attention. In this paper, we introduce a degree variance index to measure the dispersion of nodes degree in the primitive structure, and investigate the effect of the primitive structure on network structural property quantified by network efficiency. Numerical simulations and theoretical analysis show a primitive structure is a key heterogeneous structure of generated networks based on inverse renormalization scheme, whether or not adding shortcuts, and the network efficiency is positively correlated with degree variance of the primitive structure.

Reduced levels of protein recoding by A-to-I RNA editing in Alzheimer's disease

PubMed Central

Khermesh, Khen; D'Erchia, Anna Maria; Barak, Michal; Annese, Anita; Wachtel, Chaim; Levanon, Erez Y.; Picardi, Ernesto; Eisenberg, Eli

2016-01-01

Adenosine to inosine (A-to-I) RNA editing, catalyzed by the ADAR enzyme family, acts on dsRNA structures within pre-mRNA molecules. Editing of the coding part of the mRNA may lead to recoding, amino acid substitution in the resulting protein, possibly modifying its biochemical and biophysical properties. Altered RNA editing patterns have been observed in various neurological pathologies. Here, we present a comprehensive study of recoding by RNA editing in Alzheimer's disease (AD), the most common cause of irreversible dementia. We have used a targeted resequencing approach supplemented by a microfluidic-based high-throughput PCR coupled with next-generation sequencing to accurately quantify A-to-I RNA editing levels in a preselected set of target sites, mostly located within the coding sequence of synaptic genes. Overall, editing levels decreased in AD patients’ brain tissues, mainly in the hippocampus and to a lesser degree in the temporal and frontal lobes. Differential RNA editing levels were observed in 35 target sites within 22 genes. These results may shed light on a possible association between the neurodegenerative processes typical for AD and deficient RNA editing. PMID:26655226

Vaccine-induced T cells Provide Partial Protection Against High-dose Rectal SIVmac239 Challenge of Rhesus Macaques

PubMed Central

Lasaro, Marcio O; Haut, Larissa H; Zhou, Xiangyang; Xiang, Zhiquan; Zhou, Dongming; Li, Yan; Giles-Davis, Wynetta; Li, Hua; Engram, Jessica C; DiMenna, Lauren J; Bian, Ang; Sazanovich, Marina; Parzych, Elizabeth M; Kurupati, Raj; Small, Juliana C; Wu, Te-Lang; Leskowitz, Rachel M; Klatt, Nicole R; Brenchley, Jason M; Garber, David A; Lewis, Mark; Ratcliffe, Sarah J; Betts, Michael R; Silvestri, Guido; Ertl, Hildegund C

2011-01-01

Despite enormous efforts by the scientific community, an effective HIV vaccine remains elusive. To further address to what degree T cells in absence of antibodies may protect against simian immunodeficiency virus (SIV) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239. Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed only a modest reduction of viral loads, their overall survival was improved, in association with a substantial protection from the loss of CD4+ T cells. In addition, the two vaccinated Mamu-A*01+ macaques controlled viral loads to levels below detection within weeks after challenge. These data strongly suggest that T cells, while unable to affect SIV acquisition upon high-dose rectal infection, can reduce disease progression. Induction of potent T-cell responses should thus remain a component of our efforts to develop an efficacious vaccine to HIV-1. PMID:21081905

Vaccine-induced T cells provide partial protection against high-dose rectal SIVmac239 challenge of rhesus macaques.

PubMed

Lasaro, Marcio O; Haut, Larissa H; Zhou, Xiangyang; Xiang, Zhiquan; Zhou, Dongming; Li, Yan; Giles-Davis, Wynetta; Li, Hua; Engram, Jessica C; Dimenna, Lauren J; Bian, Ang; Sazanovich, Marina; Parzych, Elizabeth M; Kurupati, Raj; Small, Juliana C; Wu, Te-Lang; Leskowitz, Rachel M; Klatt, Nicole R; Brenchley, Jason M; Garber, David A; Lewis, Mark; Ratcliffe, Sarah J; Betts, Michael R; Silvestri, Guido; Ertl, Hildegund C

2011-02-01

Despite enormous efforts by the scientific community, an effective HIV vaccine remains elusive. To further address to what degree T cells in absence of antibodies may protect against simian immunodeficiency virus (SIV) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239. Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed only a modest reduction of viral loads, their overall survival was improved, in association with a substantial protection from the loss of CD4(+) T cells. In addition, the two vaccinated Mamu-A*01(+) macaques controlled viral loads to levels below detection within weeks after challenge. These data strongly suggest that T cells, while unable to affect SIV acquisition upon high-dose rectal infection, can reduce disease progression. Induction of potent T-cell responses should thus remain a component of our efforts to develop an efficacious vaccine to HIV-1.

Effects of physical activity on colorectal cancer risk among family history and body mass index subgroups: a systematic review and meta-analysis.

PubMed

Shaw, Eileen; Farris, Megan S; Stone, Chelsea R; Derksen, Jeroen W G; Johnson, Rhys; Hilsden, Robert J; Friedenreich, Christine M; Brenner, Darren R

2018-01-11

Physical activity is consistently associated with a reduced risk of colorectal cancer in epidemiologic studies. This association among higher risk subgroups, such as those with a first-degree family history of colorectal cancer or high body mass index remains unclear. We searched MEDLINE for studies examining physical activity and colorectal cancer risk among higher risk subgroups through July 11, 2017. Fifteen and three studies were eligible for inclusion for body mass index and first-degree family history of colorectal cancer subgroups, respectively. Estimates of the highest to lowest comparison of physical activity for each subgroup of risk were pooled using random-effects models. The pooled associations of physical activity and colorectal cancer risk for those without and with a first-degree family history of colorectal cancer were 0.56 (95% confidence interval (CI) = 0.39-0.80) and 0.72 (95% CI = 0.39-1.32), respectively (p heterogeneity  = 0.586). The pooled associations of physical activity and colorectal cancer risk for the low and high body mass index groups were 0.74 (95% CI = 0.66-0.83) and 0.65 (95% CI = 0.53-0.79), respectively (p heterogeneity  = 0.389). Overall, a stronger relative risk of physical activity on colorectal cancer risk was observed in the higher body mass index group, although the difference was not statistically significant, suggesting an added benefit of physical activity as a cancer prevention strategy in population groups with strong risk factors for colorectal cancer. Additional research among these subgroups is warranted.

Influence of thermal processing conditions on flavor stability in fluid milk: benzaldehyde.

PubMed

Potineni, R V; Peterson, D G

2005-01-01

Flavor loss in dairy products has been associated with enzymatic degradation by xanthine oxidase. This study was conducted to investigate the influence of milk thermal processing conditions (or xanthine oxidase inactivation) on benzaldehyde stability. Benzaldehyde was added to whole milk which had been thermally processed at 4 levels: (1) none or raw, (2) high temperature, short time (HTST) pasteurization, (3) HTST pasteurization, additionally heated to 100 degrees C (PAH), and (4) UHT sterilized. Additionally, PAH and UHT milk samples containing benzaldehyde (with and without ferrous sulfate) were spiked with xanthine oxidase. Azide was added as an antimicrobial agent (one additional pasteurized sample without) and the microbial load (total plate count) was determined on d 0, 2, and 6. The concentration of benzaldehyde and benzoic acid in all milk samples were determined at d 0, 1, 2, 4, and 6 (stored at 5 degrees C) by gas chromatography/mass spectrometry in selective ion monitory mode. Over the 6-d storage period, more than 80% of the benzaldehyde content was converted (oxidized) to benzoic acid in raw and pasteurized milk, whereas no change in the benzaldehyde concentration was found in PAH or UHT milk samples. Furthermore, the addition of xanthine oxidase or xanthine oxidase plus ferrous sulfate to PAH or UHT milk samples did not result in benzaldehyde degradation over the storage period.

Cognitive impact after short-term exposure to different proton pump inhibitors: assessment using CANTAB software.

PubMed

Akter, Sanjida; Hassan, Md Rajib; Shahriar, Mohammad; Akter, Nahia; Abbas, Md Golam; Bhuiyan, Mohiuddin Ahmed

2015-12-27

Studies have shown that proton pump inhibitors (PPIs) increase the brain burden of amyloid-beta (Aβ) and also create vitamin B12 deficiency. However, these two phenomena have deleterious effect on cognition and Alzheimer's disease (AD). Since the use of PPIs has increased tremendously for the last few years, it is of great public health importance to investigate the cognitive impact of PPIs. Hence, the purpose of this study was to investigate the degree of neuropsychological association of each PPI with different cognitive functions. Sixty volunteers of either gender were recruited and divided randomly into six groups: five test groups for five classes of PPIs and one control group. All the groups participated in the five computerized neuropsychological tests (nine subtests) of the Cambridge Neuropsychological Test Automated Battery twice: at the beginning of the study and 7 days thereafter. We found statistically and clinically significant impairment in visual memory, attention, executive function, and working and planning function. One-way analysis of variance findings showed that all PPIs had a similar negative impact on cognition. However, paired-samples t tests indicated that omeprazole showed significant (p < 0.05) results in seven subtests; lansoprazole and pantoprazole showed significant results in five subtests; and rabeprazole showed significant results in four subtests. Among five classes of PPIs, esomeprazole showed comparatively less impact on cognitive function with significant results in three subtests. The present study reveals for the first time that different PPIs have varying degrees of influence on different cognitive domains and have associations with AD. These findings should be considered when balancing the risks and benefits of prescribing these medications. A study done for a longer period of time with a larger sample size might yield better results.

Voluntary fluid intake and core temperature responses in adolescent tennis players: sports beverage versus water.

PubMed

Bergeron, M F; Waller, J L; Marinik, E L

2006-05-01

To examine differences in ad libitum fluid intake, comparing a 6% carbohydrate/electrolyte drink (CHO-E) and water, and associated differences in core temperature and other selected physiological and perceptual responses in adolescent athletes during tennis training in the heat. Fourteen healthy, fit, young tennis players (nine male; five female; mean (SD) age 15.1 (1.4) years; weight 60.6 (8.3) kg; height 172.8 (8.6) cm) completed two 120 minute tennis specific training sessions on separate days (randomised, crossover design) in a warm environment (wet bulb globe temperature: CHO-E, 79.3 (2.6) degrees F; water, 79.9 (2.2) degrees F; p>0.05). There were no significant differences (p>0.05) between the trials with respect to fluid intake, urine volume, fluid retention, sweat loss, perceived exertion, thirst, or gastrointestinal discomfort. However, there was a difference (p<0.05) in the percentage body weight change after training (CHO-E, -0.5 (0.7)%; water, -0.9 (0.6)%). Urine specific gravity before training (CHO-E, 1.024 (0.006); water, 1.025 (0.005)) did not correlate significantly (p>0.05) with any of these measurements or with core body temperature. In examining the main effect for trial, the CHO-E trial showed a significantly lower (p<0.001) mean body temperature (irrespective of measurement time) than the water trial. However, the mean body temperature in each trial was not associated (p>0.05) with fluid intake, fluid retention, sweat loss, or percentage body weight change. Ad libitum consumption of a CHO-E drink may be more effective than water in minimising fluid deficits and mean core temperature responses during tennis and other similar training in adolescent athletes.

Nutrient Intakes Linked to Better Health Outcomes Are Associated with Higher Diet Costs in the US

PubMed Central

Aggarwal, Anju; Monsivais, Pablo; Drewnowski, Adam

2012-01-01

Purpose Degrees of nutrient intake and food groups have been linked to differential chronic disease risk. However, intakes of specific nutrients may also be associated with differential diet costs and unobserved differences in socioeconomic status (SES). The present study examined degrees of nutrient intake, for every key nutrient in the diet, in relation to diet cost and SES. Methods Socio-demographic data for a stratified random sample of adult respondents in the Seattle Obesity Study were obtained through telephone survey. Dietary intakes were assessed using food frequency questionnaire (FFQ) (n = 1,266). Following standard procedures, nutrient intakes were energy-adjusted using the residual method and converted into quintiles. Diet cost for each respondent was estimated using Seattle supermarket retail prices for 384 FFQ component foods. Results Higher intakes of dietary fiber, vitamins A, C, D, E, and B12, beta carotene, folate, iron, calcium, potassium, and magnesium were associated with higher diet costs. The cost gradient was most pronounced for vitamin C, beta carotene, potassium, and magnesium. Higher intakes of saturated fats, trans fats and added sugars were associated with lower diet costs. Lower cost lower quality diets were more likely to be consumed by lower SES. Conclusion Nutrients commonly associated with a lower risk of chronic disease were associated with higher diet costs. By contrast, nutrients associated with higher disease risk were associated with lower diet costs. The cost variable may help somewhat explain why lower income groups fail to comply with dietary guidelines and have highest rates of diet related chronic disease. PMID:22662168

Abdominal adipose tissue thickness measured using magnetic resonance imaging is associated with lumbar disc degeneration in a Chinese patient population.

PubMed

Yang, Lili; Mu, Liangshan; Huang, Kaiyu; Zhang, Tianyi; Mei, Zihan; Zeng, Wenrong; He, Jiawei; Chen, Wei; Liu, Xiaozheng; Ye, Xinjian; Yan, Zhihan

2016-12-13

The relationship between abdominal adiposity and disc degeneration remains largely uninvestigated. Here, we investigated the association between abdominal adipose tissue thickness and lumbar disc degeneration in a cross-sectional study of 2415 participants from The Second Affiliated Hospital of Wenzhou Medical University. All subjects were scanned with a 3T Magnetic Resonance Imaging system to evaluate the degree of lumbar disc degeneration. Multiple logistic regression analysis revealed that men in the highest quartiles for abdominal diameter (AD), sagittal diameter (SAD), and ventral subcutaneous thickness (VST) were at higher odds ratio for severe lumbar disc degeneration than men in the lowest quartiles. The adjusted model revealed that women in the highest quartiles for AD and SAD were also at higher odds ratio for severe lumbar disc degeneration than women in the lowest quartiles. Our results suggest that abdominal obesity might be one of underlying mechanisms of lumbar disc degeneration, and preventive strategies including weight control could be useful to reduce the incidence of lumbar disc degeneration. Prospective studies are needed to this confirm these results and to identify more deeper underlying mechanisms.

The self-association of acebutolol: Conductometry and light scattering

NASA Astrophysics Data System (ADS)

Ruso, Juan M.; López-Fontán, José L.; Prieto, Gerardo; Sarmiento, Félix

2003-04-01

The association characteristics of an amphiphilic beta-blocker drug, acebutolol hydrochloride, in aqueous solution containing high concentrations of electrolyte and at different temperatures have been examined by static and dynamic light scattering and electrical conductivity. Time averaged light scattering measurements on aqueous solutions of acebutolol at 298.15 K in the presence of added electrolyte (0.4-1.0 mol kg-1 NaCl) have shown discontinuities which reflect the appearance of aggregates. The critical micelle concentration, aggregation numbers, effective micelle charges, and degree of micellar ionization were calculated. Dynamic light scattering has shown an increase in micellar size with increase in concentration of added electrolyte. Data have been interpreted using the DLVO theory to quantify the interaction between the drug aggregates and the colloidal stability. Critical micelle concentrations in water have been calculated from conductivity measurements over the temperature range 288.15-313.15 K. The variation in critical concentration with temperature passes through a minimum close to 294 K. Thermodynamic parameters of aggregate formation (ΔGm0,ΔHm0,ΔSm0) were obtained from a variation of the mass action model applicable to systems of low aggregation number.

White matter hyperintensities and the mediating role of cerebral amyloid angiopathy in dominantly-inherited Alzheimer's disease.

PubMed

Lee, Seonjoo; Zimmerman, Molly E; Narkhede, Atul; Nasrabady, Sara E; Tosto, Giuseppe; Meier, Irene B; Benzinger, Tammie L S; Marcus, Daniel S; Fagan, Anne M; Fox, Nick C; Cairns, Nigel J; Holtzman, David M; Buckles, Virginia; Ghetti, Bernardino; McDade, Eric; Martins, Ralph N; Saykin, Andrew J; Masters, Colin L; Ringman, John M; Fӧrster, Stefan; Schofield, Peter R; Sperling, Reisa A; Johnson, Keith A; Chhatwal, Jasmeer P; Salloway, Stephen; Correia, Stephen; Jack, Clifford R; Weiner, Michael; Bateman, Randall J; Morris, John C; Mayeux, Richard; Brickman, Adam M

2018-01-01

White matter hyperintensity (WMH) volume on MRI is increased among presymptomatic individuals with autosomal dominant mutations for Alzheimer's disease (AD). One potential explanation is that WMH, conventionally considered a marker of cerebrovascular disease, are a reflection of cerebral amyloid angiopathy (CAA) and that increased WMH in this population is a manifestation of this vascular form of primary AD pathology. We examined whether the presence of cerebral microbleeds, a marker of CAA, mediates the relationship between WMH and estimated symptom onset in individuals with and without autosomal dominant mutations for AD. Participants (n = 175, mean age = 41.1 years) included 112 with an AD mutation and 63 first-degree non-carrier controls. We calculated the estimated years from expected symptom onset (EYO) and analyzed baseline MRI data for WMH volume and presence of cerebral microbleeds. Mixed effects regression and tests of mediation were used to examine microbleed and WMH differences between carriers and non-carriers and to test the whether the association between WMH and mutation status is dependent on the presence of microbleeds. Mutation carriers were more likely to have microbleeds than non-carriers (p<0.05) and individuals with microbleeds had higher WMH volume than those without (p<0.05). Total WMH volume was increased in mutation carriers compared with non-carriers, up to 20 years prior to EYO, after controlling for microbleed status, as we demonstrated previously. Formal testing of mediation demonstrated that 21% of the association between mutation status and WMH was mediated by presence of microbleeds (p = 0.03) but a significant direct effect of WMH remained (p = 0.02) after controlling for presence of microbleeds. Although there is some co-dependency between WMH and microbleeds, the observed increases in WMH among mutation carriers does not appear to be fully mediated by this marker of CAA. The findings highlight the possibility that WMH represent a core feature of AD independent of vascular forms of beta amyloid.

A novel DYRK1A (dual specificity tyrosine phosphorylation-regulated kinase 1A) inhibitor for the treatment of Alzheimer's disease: effect on Tau and amyloid pathologies in vitro.

PubMed

Coutadeur, Séverine; Benyamine, Hélène; Delalonde, Laurence; de Oliveira, Catherine; Leblond, Bertrand; Foucourt, Alicia; Besson, Thierry; Casagrande, Anne-Sophie; Taverne, Thierry; Girard, Angélique; Pando, Matthew P; Désiré, Laurent

2015-05-01

The dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) gene is located within the Down Syndrome (DS) critical region on chromosome 21 and is implicated in the generation of Tau and amyloid pathologies that are associated with the early onset Alzheimer's Disease (AD) observed in DS. DYRK1A is also found associated with neurofibrillary tangles in sporadic AD and phosphorylates key AD players (Tau, amyloid precursor, protein, etc). Thus, DYRK1A may be an important therapeutic target to modify the course of Tau and amyloid beta (Aβ) pathologies. Here, we describe EHT 5372 (methyl 9-(2,4-dichlorophenylamino) thiazolo[5,4-f]quinazoline-2-carbimidate), a novel, highly potent (IC50 = 0.22 nM) DYRK1A inhibitor with a high degree of selectivity over 339 kinases. Models in which inhibition of DYRK1A by siRNA reduced and DYRK1A over-expression induced Tau phosphorylation or Aβ production were used. EHT 5372 inhibits DYRK1A-induced Tau phosphorylation at multiple AD-relevant sites in biochemical and cellular assays. EHT 5372 also normalizes both Aβ-induced Tau phosphorylation and DYRK1A-stimulated Aβ production. DYRK1A is thus as a key element of Aβ-mediated Tau hyperphosphorylation, which links Tau and amyloid pathologies. EHT 5372 and other compounds in its class warrant in vivo investigation as a novel, high-potential therapy for AD and other Tau opathies. Inhibition of the dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is a new high-potential therapeutic approach for Alzheimer disease. Here we describe EHT 5372, a novel potent and selective DYRK1A inhibitor. EHT 5372 inhibits DYRK1A-induced Tau phosphorylation, Aβ production and Aβ effects on phospho-Tau, including Tau aggregation. © 2014 International Society for Neurochemistry.

The fluidity of Chinese hamster ovary cell and bull sperm membranes after cholesterol addition.

PubMed

Purdy, P H; Fox, M H; Graham, J K

2005-08-01

Cell plasma membrane fluidity is affected by membrane lipid and protein composition as well as temperature. Altering the cholesterol content of a membrane can change membrane fluidity at different temperatures and this may affect cell survival during cryopreservation. In these experiments, we examined the effect that adding cholesterol to the membranes of Chinese hamster ovary cells (CHO) and bull sperm had on cell plasma membrane fluidity and cell survival when cells were cooled to 5 degrees C or were cryopreserved. Cells were treated with 0, 1.5 or 5.0mg cholesterol-loaded cyclodextrin (CLC), stained with N-((4-(6-phenyl-1,3,5-hexatrienyl)phenyl)propyl)trimethylammonium-p-toluenesulfonate (TMAP-DPH) to evaluate membrane fluidity and with propidium iodide to evaluate cell viability, prior to analysis by flow cytometry at 23, 5 degrees C, and after cryopreservation. CHO cells exhibited a single cell population with all cells having similar membrane fluidity. Membrane fluidity did not change when temperature had been reduced and then returned to 23 degrees C (P<0.05), however, adding cholesterol to the cells induced membranes to become more rigid (P<0.05). Bull sperm samples consisted of two cell subpopulations, one having relatively higher membrane fluidity than the other, regardless of cholesterol treatment or temperature. In addition, cells possessing the highest membrane fluidity did not survive cooling or cryopreservation efficiently. CLC treatment did not significantly alter membrane fluidity after temperature changes, but did maintain higher percentages of spermatozoa surviving cooling to 5 degrees C and cryopreservation (P<0.05). In conclusion, adding cholesterol to cell resulted in detectable membrane fluidity changes in CHO cells and increased survival of bull sperm after cooling to 5 degrees C and after cryopreservation.

Stability of picrotoxin during yogurt manufacture and storage.

PubMed

Jablonski, J E; Jackson, L S

2008-10-01

Picrotoxin is a neurotoxin found in the berries of Anamirta cocculus, a plant native to Southeast Asia. Picrotoxin has potential for being used as a biological weapon since the toxin is relatively easy to isolate and purify. Limited information exists on the stability and detection of picrotoxin added to foods before or after processing. The objective of this study was to determine the stability of picrotoxin during yogurt manufacture and storage. Direct, cup-set yogurt was produced by using methods that mimic the conditions used in full-scale production of yogurt. Milk (full-fat or low-fat) was pasteurized at 85 degrees C for 30 min, and then cooled to 43 degrees C. Yogurt starter culture (thermophilic culture or thermophilic + probiotic culture) and picrotoxin (200 mug/mL milk) were added. Samples of yogurt during fermentation (5 to 6 h, 43 degrees C) and during 30 d refrigerated (4 to 6 degrees C) storage were analyzed for pH, titratable acidity, and picrototoxin levels. Regardless of starter culture used or fat content of milk, there were no significant differences in the pH and titratable acidities of the picrotoxin-spiked yogurt and the control yogurt (no added picrotoxin) during fermentation and up to 4 wk of refrigerated storage. The color or texture of the yogurt was not affected by addition of picrotoxin. Levels of picrotoxinin and picrotin (components of picrotoxin) in yogurt, as measured by LC/MS (APCI(+)/SIR) did not change significantly during fermentation and storage. A separate experiment determined that addition of picrotoxin to milk before pasteurization (85 degrees C, 30 min) did not affect picrotoxin stability. These results indicate that picrotoxin is stable in yogurt during manufacture and storage.

Osmotic tolerance limits and membrane permeability characteristics of stallion spermatozoa treated with cholesterol.

PubMed

Glazar, Amanda I; Mullen, Steven F; Liu, Jun; Benson, James D; Critser, John K; Squires, Edward L; Graham, James K

2009-10-01

Stallion spermatozoa exhibit osmotic damage during the cryopreservation process. Recent studies have shown that the addition of cholesterol to spermatozoal membranes increases the cryosurvival of bull, ram and stallion spermatozoa, but the exact mechanism by which added cholesterol improves cryosurvival is not understood. The objectives of this study were to determine if adding cholesterol to stallion sperm membranes alters the osmotic tolerance limits and membrane permeability characteristics of the spermatozoa. In experiment one, stallion spermatozoa were treated with cholesterol-loaded cyclodextrin (CLC), subjected to anisotonic solutions and spermatozoal motility analyzed. The spermatozoa were then returned to isotonic conditions and the percentages of motile spermatozoa again determined. CLC treatment increased the osmotic tolerance limit of stallion spermatozoa in anisotonic solutions and when returned to isotonic conditions. The second and third experiments utilized an electronic particle counter to determine the plasma membrane characteristics of stallion spermatozoa. In experiment two, stallion spermatozoa were determined to behave as linear osmometers. In experiment three, spermatozoa were treated with CLC, incubated with different cryoprotectants (glycerol, ethylene glycol or dimethyl formamide) and their volume excursions measured during cryoprotectant removal at 5 degrees and 22 degrees C. Stallion spermatozoa were less permeable to the cryoprotectants at 5 degrees C than 22 degrees C. Glycerol was the least permeable cryoprotectant in control cells. The addition of CLC's to spermatozoa increased the permeability of stallion spermatozoa to the cryoprotectants. Therefore, adding cholesterol to spermatozoal membranes reduces the amount of osmotic stress endured by stallion spermatozoa during cryopreservation.

Climatic factors are associated with childhood eczema prevalence in US

PubMed Central

Silverberg, Jonathan I.; Hanifin, Jon; Simpson, Eric L.

2013-01-01

Atopic dermatitis (AD, atopic eczema) is driven by a complex relationship between genetic predisposition and environmental exposures. We sought to determine the impact of specific climatic factors on the US prevalence of AD. We used a merged analysis of the 2007 National Survey of Children's Health from a representative sample of 91,642 children age 0–17 years and the 2006–2007 National Climate Data Center and Weather Service measurements of relative humidity (%), indoor heating degree days (HDD), clear sky UV indices ozone levels, and outdoor air temperature. As a proxy for AD, we used an affirmative response to the NSCH survey question asking whether the participant’s child has been given a doctor diagnosis of “eczema or any other kind of skin allergy” in the previous 12 months. In multivariate models controlling for sex, race/ethnicity, age and household income, eczema prevalence was significantly lower with highest-quartile mean annual relative humidity (logistic regression, adjusted odds ratio [95% confidence interval]=0.82 [0.71–0.96], P=0.01) and issued UV index (0.73 [0.64–0.84], P<0.0001), and with two other factors associated with increased UV exposure. Eczema prevalence was decreased with highest-quartile air temperature (0.80 [0.70–0.92], P=0.002), but increased with 3rd–quartile mean annual HDD (1.26 [1.11–1.43], P=0.0003). This study provides evidence of climate influences on the US prevalence of childhood eczema. PMID:23334343

Gray matter network disruptions and amyloid beta in cognitively normal adults.

PubMed

Tijms, Betty M; Kate, Mara Ten; Wink, Alle Meije; Visser, Pieter Jelle; Ecay, Mirian; Clerigue, Montserrat; Estanga, Ainara; Garcia Sebastian, Maite; Izagirre, Andrea; Villanua, Jorge; Martinez Lage, Pablo; van der Flier, Wiesje M; Scheltens, Philip; Sanz Arigita, Ernesto; Barkhof, Frederik

2016-01-01

Gray matter networks are disrupted in Alzheimer's disease (AD). It is unclear when these disruptions start during the development of AD. Amyloid beta 1-42 (Aβ42) is among the earliest changes in AD. We studied, in cognitively healthy adults, the relationship between Aβ42 levels in cerebrospinal fluid (CSF) and single-subject cortical gray matter network measures. Single-subject gray matter networks were extracted from structural magnetic resonance imaging scans in a sample of cognitively healthy adults (N = 185; age range 39-79, mini-mental state examination >25, N = 12 showed abnormal Aβ42 < 550 pg/mL). Degree, clustering coefficient, and path length were computed at whole brain level and for 90 anatomical areas. Associations between continuous Aβ42 CSF levels and single-subject cortical gray matter network measures were tested. Smoothing splines were used to determine whether a linear or nonlinear relationship gave a better fit to the data. Lower Aβ42 CSF levels were linearly associated at whole brain level with lower connectivity density, and nonlinearly with lower clustering values and higher path length values, which is indicative of a less-efficient network organization. These relationships were specific to medial temporal areas, precuneus, and the middle frontal gyrus (all p < 0.05). These results suggest that mostly within the normal spectrum of amyloid, lower Aβ42 levels can be related to gray matter networks disruptions. Copyright © 2016 Elsevier Inc. All rights reserved.

Processing conditions and endpoint temperature effects on development of pink defect without pink-generating ligands in cooked ground turkey breast.

PubMed

Claus, James R; Jeong, Jong Youn

2018-02-01

This study was conducted to characterize the pink pigments associated with storing presalted (2%) and ground turkey breast trim at different processing conditions. Four treatments included: treatment (no NaCl, stored for 7 d before being cooked), treatment 2 (NaCl added and stored for 7 d before being cooked), treatment 3 (NaCl added and immediately cooked), and treatment 4 (stored for 7 d before NaCl added and cooked). All treatments were cooked to 4 endpoint temperatures (71.1, 73.9, 76.7, and 79.4°C). Processing conditions affected the pink defect in cooked ground turkey breast. Undenatured myoglobin in salted meat (treatment 2, 3, 4) still remained (17 to 19%) after cooking. Salted and stored ground turkey (treatment 2) produced a cooked product with the most reducing condition (lowest oxidation-reduction potential, ORP) and one of the most red coloration (CIE a* values). Final internal temperature had limited effects on pigment properties. ORP was similar across cooking temperatures but CIE a* values decreased with temperature. Even at 79.4°C, 15% undenatured myoglobin remained. Cooking yield decreased with temperature as expected (92.8 to 89.5%). Results indicate that to limit the degree of the pink color development processors should avoid storage of ground turkey, particularly when mixed with salt, as it favors the formation of nicotinamide-denatured globin hemochrome. © 2017 Poultry Science Association Inc.

Optimal Designs for Performance Assessments: The Subject Factor.

ERIC Educational Resources Information Center

Parkes, Jay

Much speculation abounds concerning how expensive performance assessments are or are going to be. Recent projections indicate that, in order to achieve an acceptably high generalizability coefficient, many additional tasks may need to be added, which will enlarge costs. Such projections are, to some degree, correct, and to some degree simplistic.…

Neuropathology of Autosomal Dominant Alzheimer Disease in the National Alzheimer Coordinating Center Database.

PubMed

Ringman, John M; Monsell, Sarah; Ng, Denise W; Zhou, Yan; Nguyen, Andy; Coppola, Giovanni; Van Berlo, Victoria; Mendez, Mario F; Tung, Spencer; Weintraub, Sandra; Mesulam, Marek-Marsel; Bigio, Eileen H; Gitelman, Darren R; Fisher-Hubbard, Amanda O; Albin, Roger L; Vinters, Harry V

2016-03-01

Alzheimer disease (AD) represents a genetically heterogeneous entity. To elucidate neuropathologic features of autosomal dominant AD ([ADAD] due to PSEN1, APP, or PSEN2 mutations), we compared hallmark AD pathologic findings in 60 cases of ADAD and 120 cases of sporadic AD matched for sex, race, ethnicity, and disease duration. Greater degrees of neuritic plaque and neurofibrillary tangle formation and cerebral amyloid angiopathy (CAA) were found in ADAD (p values < 0.01). Moderate to severe CAA was more prevalent in ADAD (63.3% vs. 39.2%, p = 0.003), and persons with PSEN1 mutations beyond codon 200 had higher average Braak scores and severity and prevalence of CAA than those with mutations before codon 200. Lewy body pathology was less extensive in ADAD but was present in 27.1% of cases. We also describe a novel pathogenic PSEN1 mutation (P267A). The finding of more severe neurofibrillary pathology and CAA in ADAD, particularly in carriers of PSEN1 mutations beyond codon 200, warrants consideration when designing trials to treat or prevent ADAD. The finding of Lewy body pathology in a substantial minority of ADAD cases supports the assertion that development of Lewy bodies may be in part driven by abnormal β-amyloid protein precursor processing. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Intergenerational Pattern of Interference and Internally-Motivated Changes in Cajun French

ERIC Educational Resources Information Center

Dubois, Sylvie; Noetzel, Sibylle

2005-01-01

We examine the variable use of locative prepositions in Cajun French, adding two dimensions to existing studies: real-time evidence, adding a diachronic descriptive perspective, and a methodological tool, measuring the degree of exposure to French (MDI). The goal of this paper is to determine the origins and the directions of language change…

Effect of light-enhanced bleaching on in vitro surface and intrapulpal temperature rise.

PubMed

Baik, J W; Rueggeberg, F A; Liewehr, F R

2001-01-01

This study investigated the effect of the presence, absence, and aging of a heat-enhancing compound (colorant) added to bleaching gel on the temperature rise of the gel itself, as well as the temperature rise within the pulp chamber, when a tooth was exposed to a variety of light-curing units in vitro. An extracted human upper central incisor was fitted with thermocouples placed in the pulp chamber as well as on the facial tooth surface. A temperature-controlled simulated intrapulpal fluid flow was provided to the tooth, and bleaching agent (Opalesence XTRA, Ultradent) containing heat-enhancing colorant, aged colorant, or no colorant was applied to the facial surface. The tooth and light-curing unit were placed in a thermostatically controlled oven at 37 degrees C, and real-time gel and intrapulpal temperature values were recorded digitally. Light-curing units used were a plasma arc light (PAC) (PowerPac, ADT), a conventional quartz tungsten halogen source (QTH) (Optilux 501, Demetron/Kerr), the QTH light used in high-power (bleaching) mode, and an argon ion laser (AccuCure 3000, LaserMed). An exposure scenario simulating light-enhanced bleaching of 10 upper teeth was developed. Temperature rise over the pre-exposure, baseline value associated with the last light exposure in the bleaching sequence was calculated for each curing and bleaching combination. Five replications for each test condition were made. Temperature rise values were compared using analysis of variance (ANOVA) at a preset alpha of 0.05. When fresh colorant-containing bleach was used, the PAC light increased bleach temperature 39.3 degrees C above baseline. With no added colorant, temperature rise was 37.1 degrees C. The QTH light in bleach mode resulted in gel temperature 24.8 degrees C above baseline, whereas the temperature increase was only 11.5 degrees C when no colorant was used. Conventional QTH light use increased fresh bleach temperature by 17.7 degrees C, whereas an increase of only 11.1 degrees C was measured without colorant. The argon ion laser produced equivalent temperature rise regardless of the presence or freshness of the colorant, approximately 9.4 degrees C. Intrapulpal temperatures were all significantly lower than those recorded in the bleaching gel and ranged from 5 degrees to 8 degrees C. As a rule, the presence of fresh heat-enhancing colorant in the bleaching gel resulted in a significant intrapulpal temperature increase (approximately 1 degrees C) over that reached using other lights. The PAC and the QTH light used in bleach mode induced greater intrapulpal temperature rise than the laser. Freshness of bleaching agent incorporating light-activated, heat-enhancing colorant influences temperature rise of bleaching gel and also may increase intrapulpal temperature values. Use of intense lights does elevate bleach temperature and also results in increased intrapulpal temperature that may further impact on patient sensitivity and pulpal health resulting from this treatment.

Comparison of imaging biomarkers for Alzheimer's disease: amyloid imaging with [18F]florbetapir positron emission tomography and magnetic resonance imaging voxel-based analysis for entorhinal cortex atrophy.

PubMed

Tateno, Amane; Sakayori, Takeshi; Kawashima, Yoshitaka; Higuchi, Makoto; Suhara, Tetsuya; Mizumura, Sunao; Mintun, Mark A; Skovronsky, Daniel M; Honjo, Kazuyoshi; Ishihara, Keiichi; Kumita, Shinichiro; Suzuki, Hidenori; Okubo, Yoshiro

2015-05-01

We compared amyloid positron emission tomography (PET) and magnetic resonance imaging (MRI) in subjects clinically diagnosed with Alzheimer's disease (AD), mild cognitive impairment (MCI), and older healthy controls (OHC) in order to test how these imaging biomarkers represent cognitive decline in AD. Fifteen OHC, 19 patients with MCI, and 19 patients with AD were examined by [(18)F]florbetapir PET to quantify the standard uptake value ratio (SUVR) as the degree of amyloid accumulation, by MRI and the voxel-based specific regional analysis system for AD to calculate z-score as the degree of entorhinal cortex atrophy, and by mini-mental state examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive component--Japanese version (ADAS-Jcog) for cognitive functions. Both cutoff values for measuring AD-like levels of amyloid (1.099 for SUVR) and entorhinal cortex atrophy (1.60 for z-score) were well differentially diagnosed and clinically defined AD from OHC (84.2% for SUVR and 86.7% for z-score). Subgroup analysis based on beta-amyloid positivity revealed that z-score significantly correlated with MMSE (r = -0.626, p < 0.01) and ADAS-Jcog (r = 0.691, p < 0.01) only among subjects with beta-amyloid. This is the first study to compare [(18)F]florbetapir PET and MRI voxel-based analysis of entorhinal cortex atrophy for AD. Both [(18)F]florbetapir PET and MRI detected changes in AD compared with OHC. Considering that entorhinal cortex atrophy correlated well with cognitive decline only among subjects with beta-amyloid, [18F]florbetapir PET makes it possible to detect AD pathology in the early stage, whereas MRI morphometry for subjects with beta-amyloid provides a good biomarker to assess the severity of AD in the later stage. Copyright © 2014 John Wiley & Sons, Ltd.

A comprehensive analysis on preservation patterns of gene co-expression networks during Alzheimer's disease progression.

PubMed

Ray, Sumanta; Hossain, Sk Md Mosaddek; Khatun, Lutfunnesa; Mukhopadhyay, Anirban

2017-12-20

Alzheimer's disease (AD) is a chronic neuro-degenerative disruption of the brain which involves in large scale transcriptomic variation. The disease does not impact every regions of the brain at the same time, instead it progresses slowly involving somewhat sequential interaction with different regions. Analysis of the expression patterns of the genes in different regions of the brain influenced in AD surely contribute for a enhanced comprehension of AD pathogenesis and shed light on the early characterization of the disease. Here, we have proposed a framework to identify perturbation and preservation characteristics of gene expression patterns across six distinct regions of the brain ("EC", "HIP", "PC", "MTG", "SFG", and "VCX") affected in AD. Co-expression modules were discovered considering a couple of regions at once. These are then analyzed to know the preservation and perturbation characteristics. Different module preservation statistics and a rank aggregation mechanism have been adopted to detect the changes of expression patterns across brain regions. Gene ontology (GO) and pathway based analysis were also carried out to know the biological meaning of preserved and perturbed modules. In this article, we have extensively studied the preservation patterns of co-expressed modules in six distinct brain regions affected in AD. Some modules are emerged as the most preserved while some others are detected as perturbed between a pair of brain regions. Further investigation on the topological properties of preserved and non-preserved modules reveals a substantial association amongst "betweenness centrality" and "degree" of the involved genes. Our findings may render a deeper realization of the preservation characteristics of gene expression patterns in discrete brain regions affected by AD.

Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging.

PubMed

Woodward, Matthew R; Hafeez, Muhammad Ubaid; Qi, Qianya; Riaz, Ahmed; Benedict, Ralph H B; Yan, Li; Szigeti, Kinga

2018-04-19

To explore whether the ability to recognize specific odorant items is differentially affected in aging versus Alzheimer disease (AD); to refine olfactory identification deficit (OID) as a biomarker of prodromal and early AD. Prospective multicenter cross-sectional study with a longitudinal arm. Outpatient memory diagnostic clinics in New York and Texas. Adults aged 65 and older with amnestic mild cognitive impairment (aMCI) and AD and healthy aging (HA) subjects in the comparison group. Participants completed the University of Pennsylvania Smell Identification Test (UPSIT) and neuropsychological testing. AD-associated odorants (AD-10) were selected based on a model of ordinal logistic regression. Age-associated odorants (Age-10) were identified using a linear model. For the 841 participants (234 HA, 192 aMCI, 415 AD), AD-10 was superior to Age-10 in separating HA and AD. AD-10 was associated with a more widespread cognitive deficit across multiple domains, in contrast to Age-10. The disease- and age-associated odorants clustered separately in age and AD. AD-10 predicted conversion from aMCI to AD. Nonoverlapping UPSIT items were identified that were individually associated with age and disease. Despite a modest predictive value of the AD-specific items for conversion to AD, the AD-specific items may be useful in enriching samples to better identify those at risk for AD. Further studies are needed with monomolecular and unilateral stimulation and orthogonal biomarker validation to further refine disease- and age-associated signals. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Polar lunar power ring: Propulsion energy resource

NASA Technical Reports Server (NTRS)

Galloway, Graham Scott

1990-01-01

A ring shaped grid of photovoltaic solar collectors encircling a lunar pole at 80 to 85 degrees latitude is proposed as the primary research, development, and construction goal for an initial lunar base. The polar Lunar Power Ring (LPR) is designed to provide continuous electrical power in ever increasing amounts as collectors are added to the ring grid. The LPR can provide electricity for any purpose indefinitely, barring a meteor strike. The associated rail infrastructure and inherently expandable power levels place the LPR as an ideal tool to power an innovative propulsion research facility or a trans-Jovian fleet. The proposed initial output range is 90 Mw to 90 Gw.

Double dissociation of social functioning in frontotemporal dementia

PubMed Central

Rankin, Katherine P.; Kramer, Joel H.; Mychack, Paula; Miller, Bruce L.

2009-01-01

Background Efforts to characterize changes in social functioning in frontotemporal dementia (FTD) have failed to elicit clear dissociation between frontal and temporal variants of the disease based on behavioral measures. Methods This study obtained premorbid and current first-degree relative ratings using an established measure of interpersonal functioning, the Interpersonal Adjectives Scales, to measure personality change in 16 patients with frontal variant (FLV) and 13 with temporal variant (TLV) FTD, and in a control group of 16 patients with AD. Results All three groups showed significant change over time in multiple domains, including increased introversion (FG) and submissiveness (HI). However, patients with both FTD subtypes evidenced significantly greater increases in overall interpersonal pathology vector length [VL] than did patients with AD, who remained within the normal range on all scores. Patients with FLV showed a 2 SD increase in submissiveness (HI), but their cold-heartedness (DE) change scores were not significantly different from those of patients with AD. Conversely, the TLV cold-heartedness (DE) score increased 2 SD compared to minimal change for the AD and FLV groups, yet change in submissiveness (HI) did not differentiate between AD and TLV groups. Conclusions The Interpersonal Adjectives Scales differentiated both FTD groups from patients with AD on the basis of both degree and direction of personality change. Also, the two subtypes of FTD showed distinctly different patterns of change in social functioning: patients with temporal variant shifted toward severe interpersonal coldness with mild loss of dominance, whereas patients with frontal variant showed the opposite pattern. PMID:12552042

Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II+VII+X activity in subjects infused with the drug. Influence of time and temperature.

PubMed

Thorsen, Sixtus; Teisner, Ane; Jensen, Søren Astrup; Philips, Malou; Dalhoff, Kim; Bendtsen, Flemming

2009-01-01

The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences the accuracy of the plasma PT assay. The accuracy of Nycotest PT was studied using plasma added NAC in vitro and plasma from subjects infused with NAC. The latter results were compared with those obtained by analysis of PT by CoaguChek S. Therapeutic NAC concentrations added to plasma in vitro decreased factor II+VII+X activity at 37 degrees C in a time-dependent manner. This effect was quenched at temperatures <24 degrees C. Activity lost at 37 degrees C could partly be recovered by subsequent incubation at 5 or 20 degrees C. Incubation at 37 degrees C prior to assay led to a significant additional depression of factor II+VII+X activity in plasma from subjects infused with NAC during the first 3h of infusion indicating that it contained reactive NAC. The risk that this NAC interfered with the accuracy of the PT assay was considered minimal with samples stored below 24 degrees C. This was supported by similarity of results obtained by analysis of appropriately stored plasma and simultaneously drawn blood by CoaguChek S. Residual reactive NAC does not interfere with the accuracy of the PT assay of plasma stored below 24 degrees C, but NAC-induced loss in activity at 37 degrees C may be partly recovered during subsequent storage below 24 degrees C.

Constructing an explicit AdS/CFT correspondence with Cartan geometry

NASA Astrophysics Data System (ADS)

Hazboun, Jeffrey S.

2018-04-01

An explicit AdS/CFT correspondence is shown for the Lie group SO (4 , 2). The Lie symmetry structures allow for the construction of two physical theories through the tools of Cartan geometry. One is a gravitational theory that has anti-de Sitter symmetry. The other is also a gravitational theory but is conformally symmetric and lives on 8-dimensional biconformal space. These "extra" four dimensions have the degrees of freedom used to construct a Yang-Mills theory. The two theories, based on AdS or conformal symmetry, have a natural correspondence in the context of their Lie algebras alone where neither SUSY, nor holography, is necessary.

The General Education Initiative in Hong Kong: Organized Contradictions and Emerging Tensions

ERIC Educational Resources Information Center

Jaffee, David

2012-01-01

In 2012 all Hong Kong universities will be extending the length of the undergraduate degree from 3 to 4 years and adding General Education as a degree requirement. This reform initiative represents a unique case of comprehensive organizational change of higher education on an unprecedented scale. This paper examines several of the most significant…

Baccalaureate Time-to-Degree for Montana University System Two-Year College Transfer Students

ERIC Educational Resources Information Center

Gallagher, Thomas Patrick

2017-01-01

Two-year college transfer education has been promoted as a cost-effective path for achieving the baccalaureate, but increased time-to-degree could nullify this assumption. The Montana University System (MUS) recently expanded the mission for its two-year college system by adding the transfer function. This non-experimental quantitative research…

Female Stereotyping in Advertising: An Experiment on Male-Female Perceptions of Leadership.

ERIC Educational Resources Information Center

Kilbourne, William E.

1990-01-01

Examines the impact of sex role stereotyping in advertising on the perception of the degree to which women possess managerial attributes considered requisite for success in business. Finds that depicting women in professional roles in magazine ads results in higher evaluations by male subjects of the degree to which the nonrole female possessed…

Genetics of psychosis of Alzheimer disease.

PubMed

Shah, Chintan; DeMichele-Sweet, Mary Ann A; Sweet, Robert A

2017-01-01

Psychotic symptoms, comprised of delusions and hallucinations, occur in about half of individuals with Alzheimer disease (AD with psychosis, AD+P). These individuals have greater agitation, aggression, depression, functional impairment, and mortality than individuals without psychosis (AD-P). Although the exact etiopathogenesis of AD+P is unclear, the rapidly developing field of genomics continues to expand our understanding of this disease. Several independent studies have demonstrated familial aggregation and heritability of AD+P. Linkage studies have been suggestive of loci on several chromosomes associated with AD+P. Association studies examining apolipoprotein E gene, the best established genetic risk factor for late-onset AD, did not find any significant association of this gene with AD+P. Other candidate gene studies focusing on monoamine neurotransmitter systems have yielded equivocal results. A genome-wide association study and studies examining copy number variations recently have detected suggestive associations, but have been underpowered. Approaches to increase sizes of AD+P samples for genome wide association studies are discussed. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Emotional quotient in frontotemporal dementia vs. Alzheimer's disease: the role of socioemotional agnosia.

PubMed

Carr, Andrew R; Samimi, Mersal S; Paholpak, Pongsatorn; Jimenez, Elvira E; Mendez, Mario F

2017-01-01

Socioemotional dysfunction distinguishes behavioural variant frontotemporal dementia (bvFTD) from other dementias. Patients with bvFTD not only have early social impairment and emotional blunting, but they also have agnosia of their socioemotional dysfunction. To investigate the relationship between agnosia and dysfunction, we assessed self-knowledge of socioemotional dysfunction with an emotional quotient (EQ) scale administered to 12 patients with bvFTD and a comparison group of 12 age-matched patients with Alzheimer's disease (AD), and compared these self-ratings to caregiver ratings of social dysfunction and emotional blunting. The bvFTD patients self-rated as having higher EQs than the AD patients, particularly higher self-ratings of their Social Skills, an EQ subscale which correlated with increased emotional blunting. On within-groups analysis, the bvFTD patients' high self-ratings of their EQ Appraisal of Emotions correlated with increased socioemotional dysfunction, whereas all of the AD patients' self-ratings correlated appropriately with their degree of dysfunction. Large socioemotional agnosia scores (EQ minus function) distinguishes bvFTD from AD. Additionally, in bvFTD, agnosia specifically for their ability to appreciate others' emotions correlates with the degree of socioemotional dysfunction, suggesting a role for socioemotional agnosia in increasing socioemotional dysfunction.

Perfect fluidity of a dissipative system: Analytical solution for the Boltzmann equation in AdS 2 Ⓧ S 2

DOE PAGES

Noronha, Jorge; Denicol, Gabriel S.

2015-12-30

In this paper we obtain an analytical solution of the relativistic Boltzmann equation under the relaxation time approximation that describes the out-of-equilibrium dynamics of a radially expanding massless gas. This solution is found by mapping this expanding system in flat spacetime to a static flow in the curved spacetime AdS 2 Ⓧ S 2. We further derive explicit analytic expressions for the momentum dependence of the single-particle distribution function as well as for the spatial dependence of its moments. We find that this dissipative system has the ability to flow as a perfect fluid even though its entropy density doesmore » not match the equilibrium form. The nonequilibrium contribution to the entropy density is shown to be due to higher-order scalar moments (which possess no hydrodynamical interpretation) of the Boltzmann equation that can remain out of equilibrium but do not couple to the energy-momentum tensor of the system. Furthermore, in this system the slowly moving hydrodynamic degrees of freedom can exhibit true perfect fluidity while being totally decoupled from the fast moving, nonhydrodynamical microscopic degrees of freedom that lead to entropy production.« less

Hospitalization in people with dementia with Lewy bodies: Frequency, duration, and cost implications.

PubMed

Mueller, Christoph; Perera, Gayan; Rajkumar, Anto P; Bhattarai, Manorama; Price, Annabel; O'Brien, John T; Ballard, Clive; Stewart, Robert; Aarsland, Dag

2018-01-01

Increased hospitalization is a major component of dementia impact on individuals and cost, but has rarely been studied in dementia with Lewy bodies (DLB). Our aim was to describe the risk and duration of hospital admissions in patients with DLB, and compare these to those in Alzheimer's disease (AD) and the general population. A large database of mental health and dementia care in South London was used to assemble a cohort of patients diagnosed with DLB. These were 1:4 matched with patients diagnosed with AD on age, gender, and cognitive status. Rates of hospital admissions in the year after dementia diagnosis were significantly higher in 194 patients with DLB than in 776 patients with AD (crude incidence rate ratio 1.50; 95% confidence interval: 1.28-1.75) or the catchment population (indirectly standardized hospitalization rate 1.22; 95% confidence interval: 1.06-1.39). Patients with DLB had on average almost four additional hospital days per person-year than patients with AD. Multivariate Poisson regression models indicated poorer physical health early in the disease course as the main driver of this increased rate of hospitalization, whereby neuropsychiatric symptoms additionally explained the higher number of hospital days. Patients with DLB are more frequently admitted to general hospitals and utilize inpatient care to a substantially higher degree than patients with AD or the general elderly population. These data highlight an opportunity to reduce hospital days by identifying DLB earlier and providing more targeted care focused on the specific triggers for hospitalization and associations of prolonged stay.

Association of Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 with pathological diagnosis of Alzheimer disease.

PubMed

Yu, Lei; Chibnik, Lori B; Srivastava, Gyan P; Pochet, Nathalie; Yang, Jingyun; Xu, Jishu; Kozubek, James; Obholzer, Nikolaus; Leurgans, Sue E; Schneider, Julie A; Meissner, Alexander; De Jager, Philip L; Bennett, David A

2015-01-01

Recent large-scale genome-wide association studies have discovered several genetic variants associated with Alzheimer disease (AD); however, the extent to which DNA methylation in these AD loci contributes to the disease susceptibility remains unknown. To examine the association of brain DNA methylation in 28 reported AD loci with AD pathologies. Ongoing community-based clinical pathological cohort studies of aging and dementia (the Religious Orders Study and the Rush Memory and Aging Project) among 740 autopsied participants 66.0 to 108.3 years old. DNA methylation levels at individual CpG sites generated from dorsolateral prefrontal cortex tissue using a bead assay. Pathological diagnosis of AD by National Institute on Aging-Reagan criteria following a standard postmortem examination. Overall, 447 participants (60.4%) met the criteria for pathological diagnosis of AD. Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 was associated with pathological AD. The association was robustly retained after replacing the binary trait of pathological AD with 2 quantitative and molecular specific hallmarks of AD, namely, Aβ load and paired helical filament tau tangle density. Furthermore, RNA expression of transcripts of SORL1 and ABCA7 was associated with paired helical filament tau tangle density, and the expression of BIN1 was associated with Aβ load. Brain DNA methylation in multiple AD loci is associated with AD pathologies. The results provide further evidence that disruption of DNA methylation is involved in the pathological process of AD.

Advantages and risks of using steel slag in preparing composts from raw organic waste.

PubMed

Tu, Xuefei; Aneksampant, Apichaya; Kobayashi, Shizusa; Tanaka, Atsushi; Nishimoto, Ryo; Fukushima, Masami

2017-01-02

It had been reported that iron and manganese oxides in steel slag enhanced the production of humic acid (HA) from low-molecular-weight compounds, such as phenolic acids, amino acids, and saccharides. In the present study, this function of steel slag was applied to the composting of raw organic wastes (ROWs). The degree of humification of HAs is an important factor in evaluating compost quality. Thus, HAs were extracted from the prepared composts and the humification parameters were determined, in terms of elemental compositions, acidic functional group contents, molecular weights, spectroscopic parameters from UV-vis absorption and 13 C NMR spectra. The timing for adding steel slag affected the degree of humification of HAs in the composts. The weight average molecular weight of a HA when slag was added initially (29 kDa) was significantly higher than when slag was added after elevating the temperature of the compost pile (17-18 kDa). These results show that ROWs are decomposed to low-molecular-weight compounds after the pile temperature is elevated and the presence of slag enhances the polycondensation of these compounds to produce HAs with a higher degree of humification. Because the slag used in the present study contained several-tens ng g -1 to several μg g -1 of toxic elements (B, Cu, Cr, and Zn), leaching tests for these elements from the prepared composts were carried out. Levels for leaching boron from composts prepared by adding slag (0.2-0.4 mg L -1 ) were obviously higher than the corresponding levels without slag (0.05 mg L -1 ).

3D Shape Perception in Posterior Cortical Atrophy: A Visual Neuroscience Perspective

PubMed Central

Gillebert, Céline R.; Schaeverbeke, Jolien; Bastin, Christine; Neyens, Veerle; Bruffaerts, Rose; De Weer, An-Sofie; Seghers, Alexandra; Sunaert, Stefan; Van Laere, Koen; Versijpt, Jan; Vandenbulcke, Mathieu; Salmon, Eric; Todd, James T.; Orban, Guy A.

2015-01-01

Posterior cortical atrophy (PCA) is a rare focal neurodegenerative syndrome characterized by progressive visuoperceptual and visuospatial deficits, most often due to atypical Alzheimer's disease (AD). We applied insights from basic visual neuroscience to analyze 3D shape perception in humans affected by PCA. Thirteen PCA patients and 30 matched healthy controls participated, together with two patient control groups with diffuse Lewy body dementia (DLBD) and an amnestic-dominant phenotype of AD, respectively. The hierarchical study design consisted of 3D shape processing for 4 cues (shading, motion, texture, and binocular disparity) with corresponding 2D and elementary feature extraction control conditions. PCA and DLBD exhibited severe 3D shape-processing deficits and AD to a lesser degree. In PCA, deficient 3D shape-from-shading was associated with volume loss in the right posterior inferior temporal cortex. This region coincided with a region of functional activation during 3D shape-from-shading in healthy controls. In PCA patients who performed the same fMRI paradigm, response amplitude during 3D shape-from-shading was reduced in this region. Gray matter volume in this region also correlated with 3D shape-from-shading in AD. 3D shape-from-disparity in PCA was associated with volume loss slightly more anteriorly in posterior inferior temporal cortex as well as in ventral premotor cortex. The findings in right posterior inferior temporal cortex and right premotor cortex are consistent with neurophysiologically based models of the functional anatomy of 3D shape processing. However, in DLBD, 3D shape deficits rely on mechanisms distinct from inferior temporal structural integrity. SIGNIFICANCE STATEMENT Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visuoperceptual dysfunction and most often an atypical presentation of Alzheimer's disease (AD) affecting the ventral and dorsal visual streams rather than the medial temporal system. We applied insights from fundamental visual neuroscience to analyze 3D shape perception in PCA. 3D shape-processing deficits were affected beyond what could be accounted for by lower-order processing deficits. For shading and disparity, this was related to volume loss in regions previously implicated in 3D shape processing in the intact human and nonhuman primate brain. Typical amnestic-dominant AD patients also exhibited 3D shape deficits. Advanced visual neuroscience provides insight into the pathogenesis of PCA that also bears relevance for vision in typical AD. PMID:26377458

Policy Statements for the Associate Degree, the Associate in Applied Science Degree, and the Associate Degree in Nursing.

ERIC Educational Resources Information Center

American Association of Community and Junior Colleges, Washington, DC.

The policy statements contained in this document present the position of the American Association of Community and Junior Colleges (AACJC) on the Associate Degree, the Associate in Applied Science Degree (AAS), and the Associate Degree in Nursing. In its statement on the Associate Degree, the AACJC: (1) stresses the responsibility of faculty and…

Financial and health literacy predict incident AD dementia and AD pathology

PubMed Central

Yu, Lei; Wilson, Robert S.; Schneider, Julie A.; Bennett, David A.; Boyle, Patricia A.

2017-01-01

Background Domain specific literacy is a multidimensional construct that requires multiple resources including cognitive and non-cognitive factors. Objective We test the hypothesis that domain specific literacy is associated with AD dementia and AD pathology after controlling for cognition. Methods Participants were community based older persons who completed a baseline literacy assessment, underwent annual clinical evaluations for up to 8 years and agreed to organ donation after death. Financial and health literacy was measured using 32 questions and cognition was measured using 19 tests. Annual diagnosis of AD dementia followed standard criteria. AD pathology was examined post-mortem by quantifying plaques and tangles. Cox models examined the association of literacy with incident AD dementia. Performance of model prediction for incident AD dementia was assessed using indices for integrated discrimination improvement and continuous net reclassification improvement. Linear regression models examined the independent association of literacy with AD pathology in autopsied participants. Results All 805 participants were free of dementia at baseline and 102 (12.7%) developed AD dementia during the follow-up. Lower literacy was associated with higher risk for incident AD dementia (p<0.001), and the association persisted after controlling for cognition (Hazard Ratio=1.50, p=0.004). The model including the literacy measure had better predictive performance than the one with demographics and cognition only. Lower literacy also was associated with higher burden of AD pathology after controlling for cognition (β=0.07, p=0.035). Conclusion Literacy predicts incident AD dementia and AD pathology in community-dwelling older persons, and the association is independent of traditional measures of cognition. PMID:28157101

In vitro granulocyte adherence and in vivo margination: two associated complement-dependent functions. Studies based on the acute neutropenia of filtration leukophoresis.

PubMed

Fehr, J; Jacob, H S

1977-09-01

To study mechanisms and mediators regulating the distribution of intravascular granulocytes between circulating and marginated pools, a human model with extreme transient margination, the neutropenia of continuous flow filtration leukophoresis, was analyzed. Studies in animals demonstrated the existence of a complement (C)-derived granulocytopenia-inducing factor. Thus, autologous plasma, exposed to nylon fibers (NF) of the filtration system, produced an acute selective decrement of circulating granulocytes and monocytes. This phenomenon was blocked by decomplementing plasma, by pretreatment of plasma with EDTA or hydrazine, and by preheating at 56 degrees C, but did occur after recombination of heat-inactivated and hydrazine-treated plasma before NF exposure. Preheating plasma at 50 degrees C did not inhibit the neutropenic response, suggesting involvement of the classical pathway of C activation. Ultrafiltration studies indicated that the NF-provoked neutropenia-inducing factor has a mol wt in the range of 10,000-30,000, and is heat stable (56 degrees C). To analyze the hypothesis that C- induced neutrophil margination might be consequent to increased cell adhesiveness to endothelial surfaces, the role of C in promoting granulocyte adherence was evaluated in vitro. Measured with a plastic Petridish assay, granulocyte adherence was significantly reduced in heat- inactivated (56 degrees C) and hydrazine-treated plasma, but adherence promoting capacity was restored by mixing the two plasmas, or by adding purified C3 to hydrazine-treated plasma. After exposure to activated C, neutrophils showed significantly increased adhesiveness which was maintained when cells were resuspended in heat-inactivated plasma, but progressively lost when resuspended in fresh plasma. On the basis of these results we conclude that granulocyte adhesiveness in vitro and margination in vivo are closely associated, C-dependent phenomena.

Probing spatial locality in ionic liquids with the grand canonical adaptive resolution molecular dynamics technique

NASA Astrophysics Data System (ADS)

Shadrack Jabes, B.; Krekeler, C.; Klein, R.; Delle Site, L.

2018-05-01

We employ the Grand Canonical Adaptive Resolution Simulation (GC-AdResS) molecular dynamics technique to test the spatial locality of the 1-ethyl 3-methyl imidazolium chloride liquid. In GC-AdResS, atomistic details are kept only in an open sub-region of the system while the environment is treated at coarse-grained level; thus, if spatial quantities calculated in such a sub-region agree with the equivalent quantities calculated in a full atomistic simulation, then the atomistic degrees of freedom outside the sub-region play a negligible role. The size of the sub-region fixes the degree of spatial locality of a certain quantity. We show that even for sub-regions whose radius corresponds to the size of a few molecules, spatial properties are reasonably reproduced thus suggesting a higher degree of spatial locality, a hypothesis put forward also by other researchers and that seems to play an important role for the characterization of fundamental properties of a large class of ionic liquids.

Relation of genomic variants for Alzheimer disease dementia to common neuropathologies

PubMed Central

Yu, Lei; Buchman, Aron S.; Schneider, Julie A.; De Jager, Philip L.; Bennett, David A.

2016-01-01

Objective: To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. Methods: This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 × 10−8) for pathologic AD for all variants. Results: APOE ε4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67–5.46, p = 1.9 × 10−13), while ε2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30–0.61, p = 3.1 × 10−6). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Conclusions: Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. PMID:27371493

Relation of genomic variants for Alzheimer disease dementia to common neuropathologies.

PubMed

Farfel, Jose M; Yu, Lei; Buchman, Aron S; Schneider, Julie A; De Jager, Philip L; Bennett, David A

2016-08-02

To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 × 10(-8)) for pathologic AD for all variants. APOE ε4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67-5.46, p = 1.9 × 10(-13)), while ε2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30-0.61, p = 3.1 × 10(-6)). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. © 2016 American Academy of Neurology.

Trajectories of Preparation for Future Care among First-Degree Relatives of Alzheimer's Disease Patients: An Ancillary Study of ADAPT

ERIC Educational Resources Information Center

Mak, Wingyun; Sorensen, Silvia

2012-01-01

Purpose: This study examines the longitudinal patterns of Preparation for Future Care (PFC), defined as Awareness, Avoidance, Gathering Information, Decision Making, and Concrete Plans, in first-degree relatives of people with Alzheimer's disease (AD). Design and Methods: Eight time points across 6.5 years from a subsample of adults aged 70 years…

Gender Difference Added? Institutional Variations in the Gender Gap in First Class Degree Awards in Mathematical Sciences

ERIC Educational Resources Information Center

Simonite, Vanessa

2005-01-01

This article shows how multilevel modelling can be used to study institutional variations in the gender differences in achievement. The results presented are from analyses of the degree classifications of 22,433 individuals who graduated in mathematical sciences, from universities in the UK, between 1994/95 and 1999/2000. The analyses were…

Effects of Cooking and Screw-Pressing on Functional Properties of Protein in Milkweed (Asclepias spp.) Seed Meals and Press Cakes

USDA-ARS?s Scientific Manuscript database

This study determined the effects of oil processing conditions on functional properties of milkweed seed proteins to evaluate their potential for value-added uses. Flaked milkweed seeds were cooked at 82 degrees C (180 degrees F) for 30, 60 or 90 min in the seed conditioner, and then screw-pressed ...

Method for conversion of carbohydrate polymers to value-added chemical products

DOEpatents

Zhang, Zongchao C [Norwood, NJ; Brown, Heather M [Kennewick, WA; Su, Yu [Richland, WA

2012-02-07

Methods are described for conversion of carbohydrate polymers in ionic liquids, including cellulose, that yield value-added chemicals including, e.g., glucose and 5-hydroxylmethylfurfural (HMF) at temperatures below 120.degree. C. Catalyst compositions that include various mixed metal halides are described that are selective for specified products with yields, e.g., of up to about 56% in a single step process.

Cappuccino and Specific Heat versus Heat of Vaporization

ERIC Educational Resources Information Center

Hidden, Frits; Boomsma, Jorn; Schins, Anton; van den Berg, Ed

2012-01-01

A cappuccino is prepared by adding about 50 mL frothing, foaming milk to a cup of espresso. Whole milk is best for foaming and the ideal milk temperature when adding it to the espresso is 65 [degrees]C. The espresso itself may be warmer than that. During the heating the milk should not burn, as that would spoil the taste. The best way is to heat…

The Impact of Awareness of and Concern About Memory Performance on the Prediction of Progression From Mild Cognitive Impairment to Alzheimer Disease Dementia.

PubMed

Munro, Catherine E; Donovan, Nancy J; Amariglio, Rebecca E; Papp, Kate V; Marshall, Gad A; Rentz, Dorene M; Pascual-Leone, Alvaro; Sperling, Reisa A; Locascio, Joseph J; Vannini, Patrizia

2018-05-03

To investigate the relationship of awareness of and concern about memory performance to progression from mild cognitive impairment (MCI) to Alzheimer disease (AD) dementia. Participants (n = 33) had a diagnosis of MCI at baseline and a diagnosis of MCI or AD dementia at follow-up. Participants were categorized as "Stable-MCI" if they retained an MCI diagnosis at follow-up (mean follow-up = 18.0 months) or "Progressor-MCI" if they were diagnosed with AD dementia at follow-up (mean follow-up = 21.6 months). Awareness was measured using the residual from regressing a participant's objective memory score onto their subjective complaint score (i.e., residual<0 indicates overestimation of performance). Concern was assessed using a questionnaire examining the degree of concern when forgetting. Logistic regression was used to determine whether the presence of these syndromes could predict future diagnosis of AD dementia, and repeated measures analysis of covariance tests were used to examine longitudinal patterns of these syndromes. Baseline anosognosia was apparent in the Progressor-MCI group, whereas participants in the Stable-MCI group demonstrated relative awareness of their memory performance. Baseline awareness scores successfully predicted whether an individual would progress to AD-dementia. Neither group showed change in awareness of performance over time. Neither group showed differences in concern about memory performance at baseline or change in concern about performance over time. These data suggest that anosognosia may appear prior to the onset of AD dementia, while anosodiaphoria likely does not appear until later in the AD continuum. Additionally, neither group showed significant changes in awareness or concern over time, suggesting that change in these variables may happen over longer periods. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Dissociable Effects of Aging and Mild Cognitive Impairment on Bottom-Up Audiovisual Integration.

PubMed

Festa, Elena K; Katz, Andrew P; Ott, Brian R; Tremont, Geoffrey; Heindel, William C

2017-01-01

Effective audiovisual sensory integration involves dynamic changes in functional connectivity between superior temporal sulcus and primary sensory areas. This study examined whether disrupted connectivity in early Alzheimer's disease (AD) produces impaired audiovisual integration under conditions requiring greater corticocortical interactions. Audiovisual speech integration was examined in healthy young adult controls (YC), healthy elderly controls (EC), and patients with amnestic mild cognitive impairment (MCI) using McGurk-type stimuli (providing either congruent or incongruent audiovisual speech information) under conditions differing in the strength of bottom-up support and the degree of top-down lexical asymmetry. All groups accurately identified auditory speech under congruent audiovisual conditions, and displayed high levels of visual bias under strong bottom-up incongruent conditions. Under weak bottom-up incongruent conditions, however, EC and amnestic MCI groups displayed opposite patterns of performance, with enhanced visual bias in the EC group and reduced visual bias in the MCI group relative to the YC group. Moreover, there was no overlap between the EC and MCI groups in individual visual bias scores reflecting the change in audiovisual integration from the strong to the weak stimulus conditions. Top-down lexicality influences on visual biasing were observed only in the MCI patients under weaker bottom-up conditions. Results support a deficit in bottom-up audiovisual integration in early AD attributable to disruptions in corticocortical connectivity. Given that this deficit is not simply an exacerbation of changes associated with healthy aging, tests of audiovisual speech integration may serve as sensitive and specific markers of the earliest cognitive change associated with AD.

Do Talkativeness and Vocal Loudness Correlate With Laryngeal Pathology? A Study of the Vocal Overdoer/Underdoer Continuum.

PubMed

Bastian, Robert W; Thomas, James P

2016-09-01

Assess the correlation between self-rating scales of talkativeness and loudness with various types of voice disorders. This is a retrospective study. A total of 974 patients were analyzed. The cohort study included 430 consecutive patients presenting to the senior author with voice complaints from December 1995 to December 1998. The case-control study added 544 consecutive patients referred to the same examiner from January 1988 to December 1998 for vocal fold examination before thyroid, parathyroid, and carotid surgery. Patient responses on seven-point Likert self-rating scales of talkativeness and loudness were compared with laryngeal disease. Mucosal lesions clearly associated with vibratory trauma are strongly associated with a high self-rating of talkativeness. Laryngeal deconditioning disorders were associated with a low self-rating of talkativeness. Use of a simple self-rating scale of vocal loudness and talkativeness during history taking can reliably orient the examiner to the types of voice disorders likely to be diagnosed subsequently during vocal capability testing and visual laryngeal examination. The high degree of talkativeness and loudness seen in vocal overdoers correlates well with mucosal disorders such as nodules, polyps, capillary ectasia, epidermoid inclusion cysts, and hemorrhage. A lower degree of talkativeness correlates with muscle deconditioning disorders such as vocal fold bowing, atrophy, presbyphonia, and vocal fatigue syndrome. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Abundant stable gauge field hair for black holes in anti-de Sitter space.

PubMed

Baxter, J E; Helbling, Marc; Winstanley, Elizabeth

2008-01-11

We present new hairy black hole solutions of SU(N) Einstein-Yang-Mills (EYM) theory in asymptotically anti-de Sitter (AdS) space. These black holes are described by N+1 independent parameters and have N-1 independent gauge field degrees of freedom. Solutions in which all gauge field functions have no zeros exist for all N, and for a sufficiently large (and negative) cosmological constant. At least some of these solutions are shown to be stable under classical, linear, spherically symmetric perturbations. Therefore there is no upper bound on the amount of stable gauge field hair with which a black hole in AdS can be endowed.

Evaluating Alzheimer's disease biomarkers as mediators of age-related cognitive decline.

PubMed

Hohman, Timothy J; Tommet, Doug; Marks, Shawn; Contreras, Joey; Jones, Rich; Mungas, Dan

2017-10-01

Age-related changes in cognition are partially mediated by the presence of neuropathology and neurodegeneration. This manuscript evaluates the degree to which biomarkers of Alzheimer's disease, (AD) neuropathology and longitudinal changes in brain structure, account for age-related differences in cognition. Data from the AD Neuroimaging Initiative (n = 1012) were analyzed, including individuals with normal cognition and mild cognitive impairment. Parallel process mixed effects regression models characterized longitudinal trajectories of cognitive variables and time-varying changes in brain volumes. Baseline age was associated with both memory and executive function at baseline (p's < 0.001) and change in memory and executive function performances over time (p's < 0.05). After adjusting for clinical diagnosis, baseline, and longitudinal changes in brain volume, and baseline levels of cerebrospinal fluid biomarkers, age effects on change in episodic memory and executive function were fully attenuated, age effects on baseline memory were substantially attenuated, but an association remained between age and baseline executive function. Results support previous studies that show that age effects on cognitive decline are fully mediated by disease and neurodegeneration variables but also show domain-specific age effects on baseline cognition, specifically an age pathway to executive function that is independent of brain and disease pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

The effect of glycerol-related osmotic changes on post-thaw motility and acrosomal integrity of ram spermatozoa.

PubMed

Fiser, P S; Fairfull, R W

1989-02-01

Ram semen, collected by artificial vagina, was diluted and processed for long-term storage as described by P. S. Fiser, L. Ainsworth, and R. W. Fairfull (Canad. J. Anim. Sci. 62, 425-428, 1982). The concentration of the cryoprotectant, glycerol, was adjusted to 4% in the diluted semen prior to freezing by a one-step addition at 30 degrees C (Method 1), by cooling the semen to 5 degrees C and addition of the glycerol gradually over 30 min (Method 2), by one-step addition of glycerol prior to equilibration for 2 hr (Method 3), or by cooling to 5 degrees C, followed by a holding period of 2 hr at 5 degrees C, and the one-step addition of glycerol just prior to freezing (Method 4). After thawing, the glycerol concentration of the semen was reduced by stepwise dilution from 4 to 0.4% over 15 or 30 min or by a one-step ten-fold dilution. The average post-thaw percentage of motile spermatozoa was significantly lower after addition of glycerol by Method 1 (39.9%) than when the glycerol was added by the other three methods (range, 44.0-46.4% averaged over the glycerol dilution). The average post-thaw percentage of intact acrosomes (61.2%), highest in semen in which the glycerol was added by Method 2, was not significantly different from those in which glycerol was added to semen by Methods 3 and 4, but it was significantly higher than that found in semen in which the glycerol was added by Method 1 (54.4%). However, when averaged over the method of glycerolation, the post-thaw percentage of motile spermatozoa (range, 43.7-44.2%) and the percentage of intact acrosomes (range, 56.8-59.5%) did not differ significantly in semen subjected to gradual decrease in glycerol concentration and diluent osmolality (over 15 and 30 min) or by a one-step, 10-fold dilution. These data indicate that post-thaw survival of spermatozoa can be influenced by the way in which glycerol is added prior to freezing. However, post-thaw spermatozoa motility and acrosomal integrity can be maintained even after a rapid decrease in glycerol concentration such as that which accompanies insemination or dilution of semen for assessment of motility.

[Effects of sulphur compounds on the volatile characteristics of heavy metals in fly ash from the MSW and sewage sludge co-combustion plant during the disposal process with higher temperature].

PubMed

Liu, Jing-Yong; Sun, Shui-Yu

2012-11-01

Fly ash sample was collected from a MSW co-combustion with sewage sludge plant and the volatilization of heavy metals Pb, Cd, Cu and Zn was investigated before and after the water washing of fly ash, meanwhile, the influence of adding different sulphur compounds (S, NaS, Na2 SO3, Na2 SO4) on the volatilization of heavy metals was studied. The results showed that the contents of Zn, Pb and Mn were high, the Ni content was low and the Cd content reached 29.4 mg x kg(1). The contents of Pb, Cu, Zn increased, while that of Cd reduced in the fly ash after water washing. TG-DTG curves of fly ash showed highest weight loss in ranges of 579-732 degrees C and 949-1 200 degrees C, with 690 degrees C and 1 154 degrees C as the inflection point temperatures. The volatilization of different heavy metals showed great difference in the volatilization rate, following the order of Pb > Cd > Zn > Cu, in which the volatilization rate of Pb was more than 80% and that of Cu was less than 30%. After water washing, the volatilization of different heavy metals showed great difference in the volatilization rate, with the order of Zn > Pb > Cd > Cu, in which the volatilization rate of Zn was more than 20%. With the pretreatment of adding Na2 SO3 and Na2 SO4, the evaporation rates of heavy metals (Cu, Pb, Zn, Cd) were significantly decreased. After adding S, the evaporation rate of Zn was reduced, whereas the addition of Na2S reduced the evaporation rates of Cd and Zn. The evaporation rates of the four heavy metals were all reduced after adding Na2S in the washed fly ash. The evaporation rates of Cu and Zn were reduced with addition of S and Na2SO3 and the evaporation rate of Cd was reduced by adding the four sulfides. The results can provide a basis for the harmless disposal and maximized resource utilization and recycling of fly ash.

The Road Ahead to Cure Alzheimer’s Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations

PubMed Central

Cavedo, E.; Lista, S.; Khachaturian, Z.; Aisen, P.; Amouyel, P.; Herholz, K.; Jack, C.R.; Sperling, R.; Cummings, J.; Blennow, K.; O’Bryant, S.; Frisoni, G.B.; Khachaturian, A.; Kivipelto, M.; Klunk, W.; Broich, K.; Andrieu, S.; de Schotten, M. Thiebaut; Mangin, J.-F.; Lammertsma, A.A.; Johnson, K.; Teipel, S.; Drzezga, A.; Bokde, A.; Colliot, O.; Bakardjian, H.; Zetterberg, H.; Dubois, B.; Vellas, B.; Schneider, L.S.; Hampel, H.

2015-01-01

Alzheimer’s disease (AD) is a slowly progressing non-linear dynamic brain disease in which pathophysiological abnormalities, detectable in vivo by biological markers, precede overt clinical symptoms by many years to decades. Use of these biomarkers for the detection of early and preclinical AD has become of central importance following publication of two international expert working group’s revised criteria for the diagnosis of AD dementia, mild cognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequence of matured research evidence six AD biomarkers are sufficiently validated and partly qualified to be incorporated into operationalized clinical diagnostic criteria and use in primary and secondary prevention trials. These biomarkers fall into two molecular categories: biomarkers of amyloid-beta (Aβ) deposition and plaque formation as well as of tau-protein related hyperphosphorylation and neurodegeneration. Three of the six gold-standard (“core feasible) biomarkers are neuroimaging measures and three are cerebrospinal fluid (CSF) analytes. CSF Aβ1-42 (Aβ1-42), also expressed as Aβ1-42 : Aβ1-40 ratio, T-tau, and P-tau Thr181 & Thr231 proteins have proven diagnostic accuracy and risk enhancement in prodromal MCI and AD dementia. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. Magnetic resonance imaging (MRI) at increasing field strength and resolution allows detecting the evolution of distinct types of structural and functional abnormality pattern throughout early to late AD stages. Anatomical or volumetric MRI is the most widely used technique and provides local and global measures of atrophy. The revised diagnostic criteria for “prodromal AD” and “mild cognitive impairment due to AD” include hippocampal atrophy (as the fourth validated biomarker), which is considered an indicator of regional neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in regions of interest, such as the hippocampus and in an exploratory fashion, observer and hypothesis-indedendent, throughout the entire brain. Evolving modalities such as diffusion-tensor imaging (DTI) and advanced tractography as well as resting-state functional MRI provide useful additionally useful measures indicating the degree of fiber tract and neural network disintegration (structural, effective and functional connectivity) that may substantially contribute to early detection and the mapping of progression. These modalities require further standardization and validation. The use of molecular in vivo amyloid imaging agents (the fifth validated biomarker), such as the Pittsburgh Compound-B and markers of neurodegeneration, such as fluoro-2-deoxy-D-glucose (FDG) (as the sixth validated biomarker) support the detection of early AD pathological processes and associated neurodegeneration. How to use, interpret, and disclose biomarker results drives the need for optimized standardization. Multimodal AD biomarkers do not evolve in an identical manner but rather in a sequential but temporally overlapping fashion. Models of the temporal evolution of AD biomarkers can take the form of plots of biomarker severity (degree of abnormality) versus time. AD biomarkers can be combined to increase accuracy or risk. A list of genetic risk factors is increasingly included in secondary prevention trials to stratify and select individuals at genetic risk of AD. Although most of these biomarker candidates are not yet qualified and approved by regulatory authorities for their intended use in drug trials, they are nonetheless applied in ongoing clinical studies for the following functions: (i) inclusion/exclusion criteria, (ii) patient stratification, (iii) evaluation of treatment effect, (iv) drug target engagement, and (v) safety. Moreover, novel promising hypothesis-driven, as well as exploratory biochemical, genetic, electrophysiological, and neuroimaging markers for use in clinical trials are being developed. The current state-of-the-art and future perspectives on both biological and neuroimaging derived biomarker discovery and development as well as the intended application in prevention trials is outlined in the present publication. PMID:26478889

Financial and Health Literacy Predict Incident Alzheimer's Disease Dementia and Pathology.

PubMed

Yu, Lei; Wilson, Robert S; Schneider, Julie A; Bennett, David A; Boyle, Patricia A

2017-01-01

Domain specific literacy is a multidimensional construct that requires multiple resources including cognitive and non-cognitive factors. We test the hypothesis that domain specific literacy is associated with Alzheimer's disease (AD) dementia and AD pathology after controlling for cognition. Participants were community-based older persons who completed a baseline literacy assessment, underwent annual clinical evaluations for up to 8 years, and agreed to organ donation after death. Financial and health literacy was measured using 32 questions and cognition was measured using 19 tests. Annual diagnosis of AD dementia followed standard criteria. AD pathology was examined postmortem by quantifying plaques and tangles. Cox models examined the association of literacy with incident AD dementia. Performance of model prediction for incident AD dementia was assessed using indices for integrated discrimination improvement and continuous net reclassification improvement. Linear regression models examined the independent association of literacy with AD pathology in autopsied participants. All 805 participants were free of dementia at baseline and 102 (12.7%) developed AD dementia during the follow-up. Lower literacy was associated with higher risk for incident AD dementia (p < 0.001), and the association persisted after controlling for cognition (hazard ratio = 1.50, p = 0.004). The model including the literacy measure had better predictive performance than the one with demographics and cognition only. Lower literacy also was associated with higher burden of AD pathology after controlling for cognition (β= 0.07, p = 0.035). Literacy predicts incident AD dementia and AD pathology in community-dwelling older persons, and the association is independent of traditional measures of cognition.

Between simplicity and accuracy: Effect of adding modeling details on quarter vehicle model accuracy.

PubMed

Soong, Ming Foong; Ramli, Rahizar; Saifizul, Ahmad

2017-01-01

Quarter vehicle model is the simplest representation of a vehicle that belongs to lumped-mass vehicle models. It is widely used in vehicle and suspension analyses, particularly those related to ride dynamics. However, as much as its common adoption, it is also commonly accepted without quantification that this model is not as accurate as many higher-degree-of-freedom models due to its simplicity and limited degrees of freedom. This study investigates the trade-off between simplicity and accuracy within the context of quarter vehicle model by determining the effect of adding various modeling details on model accuracy. In the study, road input detail, tire detail, suspension stiffness detail and suspension damping detail were factored in, and several enhanced models were compared to the base model to assess the significance of these details. The results clearly indicated that these details do have effect on simulated vehicle response, but to various extents. In particular, road input detail and suspension damping detail have the most significance and are worth being added to quarter vehicle model, as the inclusion of these details changed the response quite fundamentally. Overall, when it comes to lumped-mass vehicle modeling, it is reasonable to say that model accuracy depends not just on the number of degrees of freedom employed, but also on the contributions from various modeling details.

Effect of xylan and lignin removal by batch and flowthrough pretreatment on the enzymatic digestibility of corn stover cellulose.

PubMed

Yang, Bin; Wyman, Charles E

2004-04-05

Compared with batch systems, flowthrough and countercurrent reactors have important potential advantages for pretreating cellulosic biomass, including higher hemicellulose sugar yields, enhanced cellulose digestibility, and reduced chemical additions. Unfortunately, they suffer from high water and energy use. To better understand these trade-offs, comparative data are reported on xylan and lignin removal and enzymatic digestibility of cellulose for corn stover pretreated in batch and flowthrough reactors over a range of flow rates between 160 degrees and 220 degrees C, with water only and also with 0.1 wt% sulfuric acid. Increasing flow with just water enhanced the xylan dissolution rate, more than doubled total lignin removal, and increased cellulose digestibility. Furthermore, adding dilute sulfuric acid increased the rate of xylan removal for both batch and flowthrough systems. Interestingly, adding acid also increased the lignin removal rate with flow, but less lignin was left in solution when acid was added in batch. Although the enzymatic hydrolysis of pretreated cellulose was related to xylan removal, as others have shown, the digestibility was much better for flowthrough compared with batch systems, for the same degree of xylan removal. Cellulose digestibility for flowthrough reactors was related to lignin removal as well. These results suggest that altering lignin also affects the enzymatic digestibility of corn stover. Copyright 2004 Wiley Periodicals, Inc.

Between simplicity and accuracy: Effect of adding modeling details on quarter vehicle model accuracy

PubMed Central

2017-01-01

Quarter vehicle model is the simplest representation of a vehicle that belongs to lumped-mass vehicle models. It is widely used in vehicle and suspension analyses, particularly those related to ride dynamics. However, as much as its common adoption, it is also commonly accepted without quantification that this model is not as accurate as many higher-degree-of-freedom models due to its simplicity and limited degrees of freedom. This study investigates the trade-off between simplicity and accuracy within the context of quarter vehicle model by determining the effect of adding various modeling details on model accuracy. In the study, road input detail, tire detail, suspension stiffness detail and suspension damping detail were factored in, and several enhanced models were compared to the base model to assess the significance of these details. The results clearly indicated that these details do have effect on simulated vehicle response, but to various extents. In particular, road input detail and suspension damping detail have the most significance and are worth being added to quarter vehicle model, as the inclusion of these details changed the response quite fundamentally. Overall, when it comes to lumped-mass vehicle modeling, it is reasonable to say that model accuracy depends not just on the number of degrees of freedom employed, but also on the contributions from various modeling details. PMID:28617819

Vitrification of waste

DOEpatents

Wicks, George G.

1999-01-01

A method for encapsulating and immobilizing waste for disposal. Waste, preferably, biologically, chemically and radioactively hazardous, and especially electronic wastes, such as circuit boards, are placed in a crucible and heated by microwaves to a temperature in the range of approximately 300.degree. C. to 800.degree. C. to incinerate organic materials, then heated further to a temperature in the range of approximately 1100.degree. C. to 1400.degree. C. at which temperature glass formers present in the waste will cause it to vitrify. Glass formers, such as borosilicate glass, quartz or fiberglass can be added at the start of the process to increase the silicate concentration sufficiently for vitrification.

Bacterial pattern and antibiotic sensitivity in children and adolescents with infected atopic dermatitis

NASA Astrophysics Data System (ADS)

Samosir, C. T.; Ruslie, R. H.; Rusli, R. E.

2018-03-01

Atopic dermatitis (AD) is a pruritic and chronic inflammatory skin disease which affected approximately 20% in children. Bacterial infection is common in AD patients and correlates directly with AD severity. A cross-sectional study was conducted to evaluate the prevalence of bacterial skin infection in AD patients and its relation with severity of AD and also to study bacteria in the infected AD and its antibiotic sensitivity. Samples were 86 children and adolescents with an AD in Helvetia Community Health Center Medan from March 2016 until February 2017. Index of SCORing Atopic Dermatitis (SCORAD) was used to evaluate the severity of AD. Lesion and nonlesional skinwere swabbed to take sterile cultures. All bacteria noted and tested for antibiotic sensitivity. Datawere by using Chi-Square and Mann Whitney test with 95% CI and p-value<0.05 was considered statistically significant. Fifty-six AD patients (65.1%) were bacterial infected. There was a significant relationship between severity of AD and bacterial infection (p = 0.006). Staphylococcus aureus was the leading bacteria from all degrees of AD severity. Isolated Staphylococcus aureuswas sensitive to amoxicillin-clavulanate (93.3%), clindamycin (90%), erythromycin (90%), and gentamicin (90%), while sensitivity to tetracycline was low (20%).

Alcohol Dependence and Its Relationship With Insomnia and Other Sleep Disorders.

PubMed

Chakravorty, Subhajit; Chaudhary, Ninad S; Brower, Kirk J

2016-11-01

Sleep-related complaints are widely prevalent in those with alcohol dependence (AD). AD is associated not only with insomnia, but also with multiple sleep-related disorders as a growing body of literature has demonstrated. This article will review the various aspects of insomnia associated with AD. In addition, the association of AD with other sleep-related disorders will be briefly reviewed. The association of AD with insomnia is bidirectional in nature. The etiopathogenesis of insomnia has demonstrated multiple associations and is an active focus of research. Treatment with cognitive behavioral therapy for insomnia is showing promise as an optimal intervention. In addition, AD may be associated with circadian abnormalities, short sleep duration, obstructive sleep apnea, and sleep-related movement disorder. The burgeoning knowledge on insomnia associated with moderate-to-severe alcohol use disorder has expanded our understanding of its underlying neurobiology, clinical features, and treatment options. Copyright © 2016 by the Research Society on Alcoholism.

Influence of government controls over the currency exchange rate in the evolution of Hurst's exponent: An autonomous agent-based model

NASA Astrophysics Data System (ADS)

Chávez Muñoz, Pablo; Fernandes da Silva, Marcus; Vivas Miranda, José; Claro, Francisco; Gomez Diniz, Raimundo

2007-12-01

We have studied the performance of the Hurst's index associated with the currency exchange rate in Brazil and Chile. It is shown that this index maps the degree of government control in the exchange rate. A model of supply and demand based in an autonomous agent is proposed, that simulates a virtual market of sale and purchase, where buyer or seller are forced to negotiate through an intermediary. According to this model, the average of the price of daily transactions correspond to the theoretical balance proposed by the law of supply and demand. The influence of an added tendency factor is also analyzed.

Assessing the Potential of Using Value-Added Estimates of Teacher Job Performance for Making Tenure Decisions. Working Paper 31

ERIC Educational Resources Information Center

Goldhaber, Dan; Hansen, Michael

2010-01-01

Reforming teacher tenure is an idea that appears to be gaining traction with the underlying assumption being that one can infer to a reasonable degree how well a teacher will perform over her career based on estimates of her early-career effectiveness. Here we explore the potential for using value-added models to estimate performance and inform…

Big Missiles and Big Decks: The Viability of Aircraft Carriers in an A2/AD World

DTIC Science & Technology

2016-06-01

RESEARCH DESIGN This thesis centers on a historical case study of two periods in which the United States and its carrier fleet faced some degree...19 3. Lessons Learned ...........................................................................21 C. APPLICABILITY OF CASE STUDIES ...employed the strategic concepts behind A2/AD since the Persian War of 480 BC. In his analysis of several historic case studies , Tangredi notes that a

Nutritional status of community-dwelling elderly with newly diagnosed Alzheimer's disease: prevalence of malnutrition and the relation of various factors to nutritional status.

PubMed

Droogsma, E; van Asselt, D Z B; Schölzel-Dorenbos, C J M; van Steijn, J H M; van Walderveen, P E; van der Hooft, C S

2013-07-01

To determine the prevalence of malnutrition and its relation to various factors in community-dwelling elderly with newly diagnosed Alzheimer's disease (AD). Retrospective cross-sectional study. Memory clinic in a rural part of the Netherlands. 312 Community-dwelling AD patients, aged 65 years or older, were included. At the time the diagnosis AD was made, socio-demographic characteristics and data on nutritional status (Mini Nutritional Assessment (MNA)), cognitive function (Mini Mental State Examination (MMSE), Cambridge Cognitive Examination (Camcog)), functional status (Interview for Deterioration in Daily Living Activities in Dementia (IDDD), Barthel Index (BI)) and behaviour (Revised Memory and Behaviour Problems Checklist (RMBPC)) were assessed. Characteristics of well-nourished patients (MNA score >23.5) were compared to characteristics of patients at risk of malnutrition (MNA score 17-23.5). Linear regression analysis was performed to assess the effect of various factors on nutritional status. The prevalence of malnutrition was 0% and 14.1% was at risk of malnutrition. AD patients at risk of malnutrition were more impaired in basic and complex daily functioning than well-nourished AD patients (median IDDD score 41.5 [25th -75th percentile 38.8-48.0] versus median IDDD score 40.0 [25th -75th percentile 37.0-43.0], p = 0.028). The degree of impairment in basic and complex daily functioning (IDDD) was independently related to nutritional status (MNA) (p = 0.001, B = -0.062). One in seven community-dwelling elderly with newly diagnosed AD is at risk of malnutrition. The degree of impairment in daily functioning is independently related to nutritional status. Therefore, assessment of the nutritional status should be included in the comprehensive assessment of AD patients. The relation between daily functioning, nutritional status and AD warrants further investigation.

Adding School to Work-Family Balance: The Role of Support for Portuguese Working Mothers Attending a Master's Degree

ERIC Educational Resources Information Center

Andrade, Cláudia; Matias, Marisa

2017-01-01

This qualitative study examines the work, family, and study experiences of Portuguese professional women in two different career stages: early career and mid-career. Using semi-structured interviews with a sample of 22 working mothers enrolled in a master's degree, this study explores their experiences of combining the roles of mother, worker and…

Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals

PubMed Central

Ghani, Mahdi; Reitz, Christiane; Cheng, Rong; Vardarajan, Badri Narayan; Jun, Gyungah; Sato, Christine; Naj, Adam; Rajbhandary, Ruchita; Wang, Li-San; Valladares, Otto; Lin, Chiao-Feng; Larson, Eric B.; Graff-Radford, Neill R.; Evans, Denis; De Jager, Philip L.; Crane, Paul K.; Buxbaum, Joseph D.; Murrell, Jill R.; Raj, Towfique; Ertekin-Taner, Nilufer; Logue, Mark; Baldwin, Clinton T.; Green, Robert C.; Barnes, Lisa L.; Cantwell, Laura B.; Fallin, M. Daniele; Go, Rodney C. P.; Griffith, Patrick A.; Obisesan, Thomas O.; Manly, Jennifer J.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Lopez, Oscar L.; Bennett, David A.; Hendrie, Hugh; Hall, Kathleen S.; Goate, Alison M.; Byrd, Goldie S.; Kukull, Walter A.; Foroud, Tatiana M.; Haines, Jonathan L.; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Lee, Joseph H.; Schellenberg, Gerard D.; St. George-Hyslop, Peter; Mayeux, Richard; Rogaeva, Ekaterina

2015-01-01

IMPORTANCE Mutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays. OBJECTIVE To evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals. DESIGN, SETTING, AND PARTICIPANTS Case-control study of a large African American data set previously genotyped on different genome-wide SNP arrays conducted from December 2013 to January 2015. Global and locus-based ROH measurements were analyzed using raw or imputed genotype data. We studied the raw genotypes from 2 case-control subsets grouped based on SNP array: Alzheimer’s Disease Genetics Consortium data set (871 cases and 1620 control individuals) and Chicago Health and Aging Project–Indianapolis Ibadan Dementia Study data set (279 cases and 1367 control individuals). We then examined the entire data set using imputed genotypes from 1917 cases and 3858 control individuals. MAIN OUTCOMES AND MEASURES The ROHs larger than 1 Mb, 2 Mb, or 3 Mb were investigated separately for global burden evaluation, consensus regions, and gene-based analyses. RESULTS The African American cohort had a low degree of inbreeding (F ~ 0.006). In the Alzheimer’s Disease Genetics Consortium data set, we detected a significantly higher proportion of cases with ROHs greater than 2 Mb (P = .004) or greater than 3 Mb (P = .02), as well as a significant 114-kilobase consensus region on chr4q31.3 (empirical P value 2 = .04; ROHs >2 Mb). In the Chicago Health and Aging Project–Indianapolis Ibadan Dementia Study data set, we identified a significant 202-kilobase consensus region on Chr15q24.1 (empirical P value 2 = .02; ROHs >1 Mb) and a cluster of 13 significant genes on Chr3p21.31 (empirical P value 2 = .03; ROHs >3 Mb). A total of 43 of 49 nominally significant genes common for both data sets also mapped to Chr3p21.31. Analyses of imputed SNP data from the entire data set confirmed the association of AD with global ROH measurements (12.38 ROHs >1 Mb in cases vs 12.11 in controls; 2.986 Mb average size of ROHs >2 Mb in cases vs 2.889 Mb in controls; and 22% of cases with ROHs >3 Mb vs 19% of controls) and a gene-cluster on Chr3p21.31 (empirical P value 2 = .006-.04; ROHs >3 Mb). Also, we detected a significant association between AD and CLDN17 (empirical P value 2 = .01; ROHs >1 Mb), encoding a protein from the Claudin family, members of which were previously suggested as AD biomarkers. CONCLUSIONS AND RELEVANCE To our knowledge, we discovered the first evidence of increased burden of ROHs among patients with AD from an outbred African American population, which could reflect either the cumulative effect of multiple ROHs to AD or the contribution of specific loci harboring recessive mutations and risk haplotypes in a subset of patients. Sequencing is required to uncover AD variants in these individuals. PMID:26366463

A link-adding strategy for transport efficiency of complex networks

NASA Astrophysics Data System (ADS)

Ma, Jinlong; Han, Weizhan; Guo, Qing; Wang, Zhenyong; Zhang, Shuai

2016-12-01

The transport efficiency is one of the critical parameters to evaluate the performance of a network. In this paper, we propose an improved efficient (IE) strategy to enhance the network transport efficiency of complex networks by adding a fraction of links to an existing network based on the node’s local degree centrality and the shortest path length. Simulation results show that the proposed strategy can bring better traffic capacity and shorter average shortest path length than the low-degree-first (LDF) strategy under the shortest path routing protocol. It is found that the proposed strategy is beneficial to the improvement of overall traffic handling and delivering ability of the network. This study can alleviate the congestion in networks, and is helpful to design and optimize realistic networks.

Decarbonization process for carbothermically produced aluminum

DOEpatents

Bruno, Marshall J.; Carkin, Gerald E.; DeYoung, David H.; Dunlap, Sr., Ronald M.

2015-06-30

A method of recovering aluminum is provided. An alloy melt having Al.sub.4C.sub.3 and aluminum is provided. This mixture is cooled and then a sufficient amount of a finely dispersed gas is added to the alloy melt at a temperature of about 700.degree. C. to about 900.degree. C. The aluminum recovered is a decarbonized carbothermically produced aluminum where the step of adding a sufficient amount of the finely dispersed gas effects separation of the aluminum from the Al.sub.4C.sub.3 precipitates by flotation, resulting in two phases with the Al.sub.4C.sub.3 precipitates being the upper layer and the decarbonized aluminum being the lower layer. The aluminum is then recovered from the Al.sub.4C.sub.3 precipitates through decanting.

Plutonium dissolution process

DOEpatents

Vest, Michael A.; Fink, Samuel D.; Karraker, David G.; Moore, Edwin N.; Holcomb, H. Perry

1996-01-01

A two-step process for dissolving plutonium metal, which two steps can be carried out sequentially or simultaneously. Plutonium metal is exposed to a first mixture containing approximately 1.0M-1.67M sulfamic acid and 0.0025M-0.1M fluoride, the mixture having been heated to a temperature between 45.degree. C. and 70.degree. C. The mixture will dissolve a first portion of the plutonium metal but leave a portion of the plutonium in an oxide residue. Then, a mineral acid and additional fluoride are added to dissolve the residue. Alteratively, nitric acid in a concentration between approximately 0.05M and 0.067M is added to the first mixture to dissolve the residue as it is produced. Hydrogen released during the dissolution process is diluted with nitrogen.

Disease-related microglia heterogeneity in the hippocampus of Alzheimer's disease, dementia with Lewy bodies, and hippocampal sclerosis of aging.

PubMed

Bachstetter, Adam D; Van Eldik, Linda J; Schmitt, Frederick A; Neltner, Janna H; Ighodaro, Eseosa T; Webster, Scott J; Patel, Ela; Abner, Erin L; Kryscio, Richard J; Nelson, Peter T

2015-05-23

Neuropathological, genetic, and biochemical studies have provided support for the hypothesis that microglia participate in Alzheimer's disease (AD) pathogenesis. Despite the extensive characterization of AD microglia, there are still many unanswered questions, and little is known about microglial morphology in other common forms of age-related dementia: particularly, dementia with Lewy bodies (DLB) and hippocampal sclerosis of aging (HS-Aging). In addition, no prior studies have attempted to compare and contrast the microglia morphology in the hippocampus of various neurodegenerative conditions. Here we studied cases with pathologically-confirmed AD (n = 7), HS-Aging (n = 7), AD + HS-aging (n = 4), DLB (n = 12), and normal (cognitively intact) controls (NC) (n = 9) from the University of Kentucky Alzheimer's Disease Center autopsy cohort. We defined five microglia morphological phenotypes in the autopsy samples: ramified, hypertrophic, dystrophic, rod-shaped, and amoeboid. The Aperio ScanScope digital neuropathological tool was used along with two well-known microglial markers: IBA1 (a marker for both resting and activated microglia) and CD68 (a lysosomal marker in macrophages/microglia associated with phagocytic cells). Hippocampal staining analyses included studies of subregions within the hippocampal formation and nearby white matter. Using these tools and methods, we describe variation in microglial characteristics that show some degree of disease specificity, including, (1) increased microglia density and number in HS-aging and AD + HS-aging; (2) low microglia density in DLB; (3) increased number of dystrophic microglia in HS-aging; and (4) increased proportion of dystrophic to all microglia in DLB. We conclude that variations in morphologies among microglial cells, and cells of macrophage lineage, can help guide future work connecting neuroinflammatory mechanisms with specific neurodegenerative disease subtypes.

How redesigning AD clinical trials might increase study partners’ willingness to participate

PubMed Central

Karlawish, Jason; Cary, Mark S.; Rubright, Jonathan; TenHave, Tom

2008-01-01

Background: Timely recruiting and retaining participants into Alzheimer disease (AD) clinical trials is a challenge. We used conjoint analysis to identify how alterations in attributes of clinical trial design improve willingness to participate: risk, home visits, car service, or increased chance of receiving intervention. Method: A total of 108 study partners of patients with very mild to severe stage AD rated willingness to allow their relative to participate in eight clinical trials that varied combinations of the four attributes. Results: The highest utility was for home visits (0.89) which essentially compensated for the disutility of high risk (−0.85). The combination of home visits and car service was redundant, with almost no increase in utility over home visits alone. Seventeen percent were willing to participate in a trial with no amenities; the addition of home visits increased predicted willingness to participate to 27%; low risk, home visits, and higher chance of active treatment increased predicted willingness to 60%. The value of reducing the hassles of travel correlated well with measures of AD severity (activities of daily living r = 0.41, p < 0.001; basic activities of daily living r = 0.38, p < 0.001; Neuropsychiatric Inventory severity p = 0.24, p = 0.01; Neuropsychiatric Inventory distress r = 0.23, p < 0.02). No association was found between degree of study partner burden and willingness to tolerate risk of an intervention. Conclusion: Clinical trials that reduce travel inconvenience may offset the disincentive of study features such as the risk of intervention and may also increase willingness to participate. Redesigning trials may also help recruit patients with more severe Alzheimer disease. Shorter recruitment periods and increased retention rates may offset costs of these changes. GLOSSARY AD = Alzheimer disease; BLUP = best linear unbiased prediction; RAQ = Research Attitude Questionnaire. PMID:19047560

Horizontal and Vertical Cultural Differences in the Content of Advertising Appeals

PubMed Central

Shavitt, Sharon; Johnson, Timothy P.; Zhang, Jing

2014-01-01

The distinction between vertical (emphasizing hierarchy) and horizontal (valuing equality) cultures yields novel predictions regarding the prevalence of advertising appeals. A content analysis of 1211 magazine advertisements in five countries (Denmark, Korea, Poland, Russia, U.S.) revealed differences in ad content that underscore the value of this distinction. Patterns in the degree to which ads emphasized status benefits and uniqueness benefits corresponded to the countries' vertical/horizontal cultural classification. These and other patterns of ad benefits are analyzed and the predictions afforded by the vertical/horizontal distinction versus the broader individualism-collectivism distinction are compared and tested. PMID:25554720

Horizontal and Vertical Cultural Differences in the Content of Advertising Appeals.

PubMed

Shavitt, Sharon; Johnson, Timothy P; Zhang, Jing

2011-05-01

The distinction between vertical (emphasizing hierarchy) and horizontal (valuing equality) cultures yields novel predictions regarding the prevalence of advertising appeals. A content analysis of 1211 magazine advertisements in five countries (Denmark, Korea, Poland, Russia, U.S.) revealed differences in ad content that underscore the value of this distinction. Patterns in the degree to which ads emphasized status benefits and uniqueness benefits corresponded to the countries' vertical/horizontal cultural classification. These and other patterns of ad benefits are analyzed and the predictions afforded by the vertical/horizontal distinction versus the broader individualism-collectivism distinction are compared and tested.

TNF-alpha and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects.

PubMed

Kamer, Angela R; Craig, Ronald G; Pirraglia, Elizabeth; Dasanayake, Ananda P; Norman, Robert G; Boylan, Robert J; Nehorayoff, Andrea; Glodzik, Lidia; Brys, Miroslaw; de Leon, Mony J

2009-11-30

The associations of inflammation/immune responses with clinical presentations of Alzheimer's disease (AD) remain unclear. We hypothesized that TNF-alpha and elevated antibodies to periodontal bacteria would be greater in AD compared to normal controls (NL) and their combination would aid clinical diagnosis of AD. Plasma TNF-alpha and antibodies against periodontal bacteria were elevated in AD patients compared with NL and independently associated with AD. The number of positive IgG to periodontal bacteria incremented the TNF-alpha classification of clinical AD and NL. This study shows that TNF-alpha and elevated numbers of antibodies against periodontal bacteria associate with AD and contribute to the AD diagnosis.

Eating quality of lamb meat: effects of breed, sex, degree of maturity and nutritional management.

PubMed

Arsenos, G; Banos, G; Fortomaris, P; Katsaounis, N; Stamataris, C; Tsaras, L; Zygoyiannis, D

2002-04-01

The eating quality of lamb meat of three indigenous Greek dairy breeds of sheep, reared under different nutritional management conditions, was assessed by Taste Panel Tests (TPT). Lean samples from the leg joints of 69 lamb carcasses of the Boutsko (B), Serres (S) and Karagouniko (K) breed were used. For the first TPT, 24 lambs (four males and four females of each breed) were reared in individual pens on a concentrate ration fed ad libitum. For the second TPT, 27 individual penned male lambs were fed on Lucerne hay ad libitum and on three different levels of concentrate: High (H), Medium, (M) and Low (L). For the third TPT, 18 male lambs were used; initially the groups were fed indoors for 63 days on three different levels of concentrate (H, M and L) together with ad libitum Lucerne hay, and subsequently finished on irrigated, sown pasture. For TPT 1, leg joints were obtained from lambs that had been slaughtered at 30, 45, 60 or 90% of mature weight (PMW) for each breed. For TPT 2, lambs were slaughtered at 23, 28 or 33 kg target slaughter live weights (TSLW), common for all breeds. For TPT 3, lambs were slaughtered at 48 or 55% of PMW for each breed. Panellists assessed warm, roasted lean samples of leg joints and rated Flavour, Juiciness, Tenderness and Overall Acceptability. In TPT 1, degree of maturity significantly affected Flavour, Tenderness and Overall Acceptability whereas sex affected only Flavour. In TPT 2, breed and concentrate level significantly affected the quality characteristics, but concentrate level had no significant effect in TPT 3. Effects associated with slaughter weight were significant for most characteristics in all TPT, with decreasing acceptability for older/heavier lambs. Significant interactions were found between breed and the other factors in TPT 2 and TPT 3 for most quality characteristics. Results from these studies suggest changing traditional production systems may enhance the eating quality of lamb meat.

Association between mast cells, tissue remodelation and parasite burden in the skin of dogs with visceral leishmaniasis.

PubMed

Cardoso, Jamille Mirelle de Oliveira; Ker, Henrique Gama; Aguiar-Soares, Rodrigo Dian de Oliveira; Moreira, Nádia das Dores; Mathias, Fernando Augusto Siqueira; Reis, Levi Eduardo Soares; Roatt, Bruno Mendes; Vieira, Paula Melo de Abreu; Coura-Vital, Wendel; Carneiro, Cláudia Martins; Reis, Alexandre Barbosa

2017-08-30

Canine visceral leishmaniosis (CVL) is a zoonosis of major public health impact caused by organisms of the genus Leishmania which is transmitted to human and animals by phlebotomine sand flies. The skin is the first point of contact with Leishmania parasites for sandy fly vectors and it is considered an important reservoir compartment in infected dogs. The aim of this study was to determine the main histophatologic alterations in ear skin of dogs naturally infected by Leishmania infantum with different clinical status and different degrees of parasitism. Therefore, thirty-four dogs naturally infected with L. infantum were grouped according to their clinical status in asymptomatic (AD, n=11), oligosymptomatic (OD, n=11) and symptomatic dogs (SD, n=12) as well as their degrees of parasite load in the skin as low (LP, n=11), median (MP, n=11) and high (HP, n=12) parasitism. Additionally, ten dogs were used as control (CD, n=10). At necropsy, skin samples were collected for further histological and parasitological analysis. The OD and SD groups presented higher parasite burden than AD group. The inflammation was higher in SD group when compared to OD and AD. The LP, MP and HP groups showed an increasing inflammatory process, indicating that a great parasite load is accompanied by a major inflammatory process in the skin. The number of mast cells was higher in the OD and LP groups than CD group, suggesting that these cells may be involved in tissue remodeling, since that an increase of type III collagen fibers and decrease type I collagen fibers were observed in these groups. Taken together, our results enable a better understanding of the alterations in skin of CVL dogs and consequently new insights about the pathogenesis of CVL. Copyright © 2017. Published by Elsevier B.V.

Effects of added polyacrylamide on changes in water states during the composting of kitchen waste.

PubMed

Yang, Yu-Qiang; Chen, Zhuo-Xian; Zhang, Xue-Qing; Hu, Li-Fang; Shen, Dong-Sheng; Long, Yu-Yang

2015-02-01

The effects of adding polyacrylamide (PAM), to attempt to delay the loss of capillary water and achieve a better level of organic matter humification, in the composting of kitchen waste were evaluated. Four treatments, with initial moisture content of 60 % were used: 0.1 % PAM added before the start of composting (R1), 0.1 % PAM added when the thermophilic phase of composting became stable (at >50 °C) (R2), 0.1 % PAM added when the moisture content significantly decreased (R3), and no PAM added (R4). The introduction of PAM in R1 and R2 significantly increased the capillary force and delayed the loss of moisture content and capillary water. The introduction of PAM in R2 and R3 improved the composting process, in terms of the degradation of biochemical fractions and the humification degree. These results show that the optimal time for adding PAM was the initial stage of the thermophilic phase.

Authoritative parenting and issue involvement as indicators of ad recall: an empirical investigation of anti-drug ads for parents.

PubMed

Quick, Brian L; Stephenson, Michael T

2007-01-01

This investigation explores the role of authoritative parenting and issue involvement in regard to the recall of parental anti-drug ads encouraging child monitoring. In addition, the study tested whether issue involvement mediates the association between authoritative parenting and recall of parental anti-drug television ads among parents (N = 185) with adolescents in Grades 6, 7, and 8. The results indicate that (a) authoritative parenting is positively associated with favorable attitudes toward monitoring children and issue involvement regarding adolescent drug use, (b) issue involvement is associated with ad recall, (c) issue involvement mediates the relationship between authoritative parenting and ad recall, (d) ad recall is not associated with favorable attitudes toward parental monitoring, and (e) favorable attitudes regarding parental monitoring are positively associated with intentions to engage in monitoring within the next 6 months.

Differences between sexes in rectal cooling rates after exercise-induced hyperthermia.

PubMed

Lemire, Bruno B; Gagnon, Daniel; Jay, Ollie; Kenny, Glen P

2009-08-01

We evaluated differences between sexes in core cooling rates during cold water immersion after exercise-induced hyperthermia. Ten male (M) and nine female (F) participants, matched for body surface area-to-mass ratio (AD/M) (F: 268 +/- 19 vs M: 261 +/- 16 cm2 x kg(-1)), were recruited for the study. Participants exercised until rectal temperature reached 39.5 degrees C and were subsequently immersed in a 2.0 degrees C circulated water bath until rectal temperature decreased to 37.5 degrees C. Rectal and mean skin temperatures and the relative rate of nonevaporative heat loss (W x m(-2)) were measured continuously during the immersion period. Males were heavier, had a lower body fat percentage, and had a greater amount of lean body mass compared with females (P < or = 0.05). Significant differences were found in the overall cooling rate for rectal temperature (F: 0.22 +/- 0.07 vs M: 0.12 +/- 0.03 degrees C x min(-1), P = 0.001) and in the overall immersion times (F: 10.89 +/- 4.49 vs M: 18.13 +/- 4.47 min, P = 0.003). Mean skin temperature was lower in females compared with that in males during the immersion period (P < 0.001), although there were no differences between sexes in the rate of nonevaporative heat loss (P = 0.180). Although females had a similar AD/M and greater body adiposity, they had approximately 1.7-fold greater rectal cooling rate. Because AD/M and body adiposity do not seem to influence rectal cooling rates in previously hyperthermic individuals, the greater cooling rates in females may be attributed to physical differences in lean body mass.

Effect of water phase salt content and storage temperature on Listeria monocytogenes survival in chum salmon (Oncorhynchus keta) roe and caviar (ikura).

PubMed

Shin, Joong-Han; Rasco, Barbara A

2007-06-01

Salmon caviar, or ikura, is a ready-to-eat food prepared by curing the salmon roe in a brine solution. Other seasonings or flavorants may be added, depending upon the characteristics of the product desired. Listeria monocytogenes growth is a potential risk, since it can grow at high salt concentrations (>10%) and in some products at temperatures as low as 3 degrees C. Ikura was prepared from chum salmon (Oncorhynchus keta) roe by adding food-grade NaCl to yield water phase salt contents (WPS) of 0.22% (no added salt), 2.39%+/- 0.18%, 3.50%+/- 0.19%, and 4.36%+/- 0.36%. A cocktail containing L. monocytogenes (ATCC 19114, 7644, 19113) was incorporated into the ikura at 2 inoculum levels (log 2.4 and 4.2 CFU/g), and stored at 3 or 7 degrees C for up to 30 d. L. monocytogenes was recovered by plating onto modified Oxford media. Aerobic microflora were analyzed on plate count agar. Samples were tested at 0, 5, 10, 20, and 30 d. L. monocytogenes did not grow in chum salmon ikura held at 3 degrees C during 30 d at any salt level tested; however, the addition of salt at these levels did little to inhibit Listeria growth at 7 degrees C and counts reached 5 to 6 logs CFU/g. Components in the salmon egg intracellular fluid appear to inhibit the growth of L. monocytogenes. Total aerobic microflora levels were slightly lower in products with higher salt contents. These results indicate that temperature control is critical for ikura and similar products, but that products with lower salt contents can be safe, as long as good refrigeration is maintained.

Association between atopic dermatitis and attention deficit hyperactivity disorder in U.S. children and adults*

PubMed Central

Strom, M.A.; Fishbein, A.B.; Paller, A.S.; Silverberg, J.I.

2016-01-01

Summary Background Atopic dermatitis (AD) is associated with chronic itch, allergic disease and sleep disturbance, all of which might increase the risk of attention deficit (hyperactivity) disorder (ADD/ADHD). Previous analyses have found a consistent association between AD and ADD/ADHD, although the underlying factors contributing to such an association remain underexplored. Additionally, the relationship has been underexplored in adults. Objectives To determine if childhood and adult AD and AD severity are associated with ADD/ADHD and to delineate the factors contributing to such an association. Methods We analysed data on 354 416 children aged 2–17 years and 34 613 adults age 18+ years from 19 U.S. population-based surveys, including the National Health Interview Survey 1997–2013 and the National Survey of Children’s Health 2003/4 and 2007/8. Results In multivariate models adjusting for age, sex, sociodemographics, allergic disease and healthcare utilization, AD was associated with ADD/ADHD in both children [adjusted odds ratio (95% confidence interval), 1·14 (1·03–1·26)] and adults [1·61 (1·25–2·06)]. Children with both severe AD and only 0–3 nights of adequate sleep per week had much higher odds of ADD/ADHD [16·83 (7·02–40·33)] than those with 0–3 nights of adequate sleep per week [1·83 (1·47–2·26)] or mild–moderate AD alone [1·56 (1·22–1·99)]. AD was most strongly associated with severe ADHD. AD unaccompanied by other allergic disease was also associated with increased risk of ADD/ADHD in children. Among children with AD, history of anaemia, headaches and obesity were associated with even higher odds of ADD/ADHD. Asthma, insomnia and headaches increased the odds of ADHD in adults with AD, although underweight body mass index was protective. Conclusions Atopic dermatitis is associated with increased odds of ADD/ADHD in adults and children. Several factors increase the risk of ADHD in adults and children with AD. PMID:27105659

Frontal lobe function in elderly patients with Alzheimer's disease and caregiver burden.

PubMed

Hashimoto, Akiko; Matsuoka, Kiwamu; Yasuno, Fumihiko; Takahashi, Masato; Iida, Junzo; Jikumaru, Kiyoko; Kishimoto, Toshifumi

2017-07-01

Understanding of the relationship between caregiver burden and the degree of behavioural deficits in patients with Alzheimer's disease (AD) is relatively limited. Therefore, it is worthwhile to examine the correlations between the various relevant factors to improve the efficacy of care for patients with AD. The aim of this study was to investigate the specific contributions of frontal lobe dysfunction in AD patients to caregiver burden, while controlling for other predictor variables. Participants included 30 pairs of caregivers and patients with AD. The Zarit Burden Interview and Frontal Assessment Battery were used to measure the caregiver burden and patients' frontal lobe function, respectively. To investigate the effects of frontal lobe dysfunction on caregiver burden, hierarchical regression equations with steps incorporating additional predictor variables were fitted. We also performed a correlation analysis between the individual subdomains of the Zarit Burden Interview and the predictor variables. Our study suggests that the degree of frontal lobe dysfunction in AD patients predicts their caregiver burden, when other factors of daily functional limitations and neuropsychiatric symptoms are controlled. Daily functional limitations and neuropsychiatric symptoms affected caregivers' psychosocial burden, whereas frontal lobe dysfunction affected caregivers' burden due to the increase in the dependency of the patients. Our findings indicate that to ameliorate the disabilities of patients and reduce caregiver burden, there is a need for interventions that focus on psychosocial burdens, as shown in previous studies, as well as on excessive dependency due to frontal lobe dysfunction. © 2017 Japanese Psychogeriatric Society.

White matter hyperintensities and the mediating role of cerebral amyloid angiopathy in dominantly-inherited Alzheimer’s disease

PubMed Central

Lee, Seonjoo; Zimmerman, Molly E.; Narkhede, Atul; Nasrabady, Sara E.; Tosto, Giuseppe; Meier, Irene B.; Benzinger, Tammie L. S.; Marcus, Daniel S.; Fagan, Anne M.; Fox, Nick C.; Cairns, Nigel J.; Holtzman, David M.; Buckles, Virginia; Ghetti, Bernardino; McDade, Eric; Martins, Ralph N.; Saykin, Andrew J.; Masters, Colin L.; Ringman, John M.; Fӧrster, Stefan; Schofield, Peter R.; Sperling, Reisa A.; Johnson, Keith A.; Chhatwal, Jasmeer P.; Salloway, Stephen; Correia, Stephen; Jack, Clifford R.; Weiner, Michael; Bateman, Randall J.; Morris, John C.; Mayeux, Richard

2018-01-01

Introduction White matter hyperintensity (WMH) volume on MRI is increased among presymptomatic individuals with autosomal dominant mutations for Alzheimer’s disease (AD). One potential explanation is that WMH, conventionally considered a marker of cerebrovascular disease, are a reflection of cerebral amyloid angiopathy (CAA) and that increased WMH in this population is a manifestation of this vascular form of primary AD pathology. We examined whether the presence of cerebral microbleeds, a marker of CAA, mediates the relationship between WMH and estimated symptom onset in individuals with and without autosomal dominant mutations for AD. Participants and methods Participants (n = 175, mean age = 41.1 years) included 112 with an AD mutation and 63 first-degree non-carrier controls. We calculated the estimated years from expected symptom onset (EYO) and analyzed baseline MRI data for WMH volume and presence of cerebral microbleeds. Mixed effects regression and tests of mediation were used to examine microbleed and WMH differences between carriers and non-carriers and to test the whether the association between WMH and mutation status is dependent on the presence of microbleeds. Results Mutation carriers were more likely to have microbleeds than non-carriers (p<0.05) and individuals with microbleeds had higher WMH volume than those without (p<0.05). Total WMH volume was increased in mutation carriers compared with non-carriers, up to 20 years prior to EYO, after controlling for microbleed status, as we demonstrated previously. Formal testing of mediation demonstrated that 21% of the association between mutation status and WMH was mediated by presence of microbleeds (p = 0.03) but a significant direct effect of WMH remained (p = 0.02) after controlling for presence of microbleeds. Discussion Although there is some co-dependency between WMH and microbleeds, the observed increases in WMH among mutation carriers does not appear to be fully mediated by this marker of CAA. The findings highlight the possibility that WMH represent a core feature of AD independent of vascular forms of beta amyloid. PMID:29742105

Alzheimer biomarkers and clinical Alzheimer disease were not associated with increased cerebrovascular disease in a memory clinic population.

PubMed

Spies, Petra E; Verbeek, Marcel M; Sjogren, Magnus J C; de Leeuw, Frank-Erik; Claassen, Jurgen A H R

2014-01-01

Preclinical and post-mortem studies suggest that Alzheimer disease (AD) causes cerebrovascular dysfunction, and therefore may enhance susceptibility to cerebrovascular disease (CVD). The objective of this study was to investigate this association in a memory clinic population. The AD biomarkers CSF amyloid β42, amyloid β40 and APOE-ε4 status have all been linked to increased CVD risk in AD, and therefore the first aim of this study was to analyze the association between these biomarkers and CVD. In 92 memory clinic patients the cross-sectional association between AD biomarkersand the severity of CVD was investigated with linear regression analysis. Additionally, we studied whether AD biomarkers modified the relation between vascular risk factors and CVD. CVD was assessed on MRI through a visual rating scale.Analyses were adjusted for age. The second aim of this study was to investigate the association between clinical AD and CVD, where 'clinical AD' was defined as follows: impairment in episodic memory, hippocampal atrophy and an aberrant concentration of cerebrospinal fluid (CSF) biomarkers. 47 of the 92 patients had AD. No association between CSF amyloid β42, amyloid β40 or APOE-ε4 status and CVD severity was found, nor did these AD biomarkers modify the relation between vascular risk factors and CVD. Clinical AD was not associated with CVD severity (p=0.83). Patients with more vascular risk factors had more CVD, but this relationship was not convincingly modified by AD (p=0.06). In this memory clinic population, CVD in patients with AD was related to vascular risk factors and age, comparable to patients without AD. Therefore, in our study, the preclinical and post-mortem evidence that AD would predispose to CVD could not be translated clinically. Further work, including replication of this work in a different and larger sample, is warranted.

Association of monoamine oxidase A gene polymorphism with Alzheimer's disease and Lewy body variant.

PubMed

Takehashi, Masanori; Tanaka, Seigo; Masliah, Eliezer; Ueda, Kunihiro

2002-07-19

The association between (GT)n dinucleotide repeats in monoamine oxidase gene loci, monoamine oxidase A (MAOA) and B (MAOB), and Parkinson's disease (PD), Alzheimer's disease (AD), and Lewy body variant (LBV) of AD were determined. MAOA-GT polymorphisms were significantly associated with pure AD and LBV. MAOA-GT allele 113 was excessively represented in pure AD and LBV compared with controls. Furthermore, the frequency of females homozygous for MAOA-GT allele 113 was higher in pure AD and LBV than controls by 2.79- and 2.77-fold, respectively. In contrast, there was no association between MAOA-GT or MAOB-GT polymorphisms and PD. These results suggest that polymorphisms within the MAOA gene may have implication in AD pathology shared by pure AD and LBV.

Maternal and anaesthesia-related risk factors and incidence of spinal anaesthesia-induced hypotension in elective caesarean section: A multinomial logistic regression.

PubMed

Fakherpour, Atousa; Ghaem, Haleh; Fattahi, Zeinabsadat; Zaree, Samaneh

2018-01-01

Although spinal anaesthesia (SA) is nowadays the preferred anaesthesia technique for caesarean section (CS), it is associated with considerable haemodynamic effects, such as maternal hypotension. This study aimed to evaluate a wide range of variables (related to parturient and anaesthesia techniques) associated with the incidence of different degrees of SA-induced hypotension during elective CS. This prospective study was conducted on 511 mother-infant pairs, in which the mother underwent elective CS under SA. The data were collected through preset proforma containing three parts related to the parturient, anaesthetic techniques and a table for recording maternal blood pressure. It was hypothesized that some maternal (such as age) and anaesthesia-related risk factors (such as block height) were associated with occurance of SA-induced hypotension during elective CS. The incidence of mild, moderate and severe hypotension was 20%, 35% and 40%, respectively. Eventually, ten risk factors were found to be associated with hypotension, including age >35 years, body mass index ≥25 kg/m 2 , 11-20 kg weight gain, gravidity ≥4, history of hypotension, baseline systolic blood pressure (SBP) <120 mmHg and baseline heart rate >100 beats/min in maternal modelling, fluid preloading ≥1000 ml, adding sufentanil to bupivacaine and sensory block height >T 4 in anaesthesia-related modelling ( P < 0.05). Age, body mass index, weight gain, gravidity, history of hypotension, baseline SBP and heart rate, fluid preloading, adding sufentanil to bupivacaine and sensory block hieght were the main risk factors identified in the study for SA-induced hypotension during CS.

Associations between added sugar (solid vs. liquid) intakes, diet quality, and adiposity indicators in Canadian children.

PubMed

Wang, JiaWei; Shang, Lei; Light, Kelly; O'Loughlin, Jennifer; Paradis, Gilles; Gray-Donald, Katherine

2015-08-01

Little is known about the influence of different forms of added sugar intake on diet quality or their association with obesity among youth. Dietary intake was assessed by three 24-h recalls in 613 Canadian children (aged 8-10 years). Added sugars (mean of 3-day intakes) were categorized according to source (solid or liquid). Dietary intake and the Canadian Healthy Eating Index (« HEI-C ») were compared across tertiles of solid and liquid added sugars separately as were adiposity indicators (body mass index (BMI), fat mass (dual-energy X-ray absorptiometry), and waist circumference). Cross-sectional associations were examined in linear regression models adjusting for age, sex, energy intake, and physical activity (7-day accelerometer). Added sugar contributed 12% of total energy intake (204 kcal) on average, of which 78% was from solid sources. Higher consumption of added sugars from either solid or liquid source was associated with higher total energy, lower intake of micronutrients, vegetables and fruit, and lower HEI-C score. Additionally liquid sources were associated with lower intake of dairy products. A 10-g higher consumption of added sugars from liquid sources was associated with 0.4 serving/day lower of vegetables and fruit, 0.4-kg/m(2) higher BMI, a 0.5-kg higher fat mass, and a 0.9-cm higher waist circumference whereas the associations of added sugars from solid sources and adiposity indicators tended to be negative. In conclusion, higher consumption of added sugar from either solid or liquid sources was associated with lower overall diet quality. Adiposity indicators were only positively associated with added sugars from liquid sources.

Genome-wide association study of Alzheimer's disease with psychotic symptoms.

PubMed

Hollingworth, P; Sweet, R; Sims, R; Harold, D; Russo, G; Abraham, R; Stretton, A; Jones, N; Gerrish, A; Chapman, J; Ivanov, D; Moskvina, V; Lovestone, S; Priotsi, P; Lupton, M; Brayne, C; Gill, M; Lawlor, B; Lynch, A; Craig, D; McGuinness, B; Johnston, J; Holmes, C; Livingston, G; Bass, N J; Gurling, H; McQuillin, A; Holmans, P; Jones, L; Devlin, B; Klei, L; Barmada, M M; Demirci, F Y; DeKosky, S T; Lopez, O L; Passmore, P; Owen, M J; O'Donovan, M C; Mayeux, R; Kamboh, M I; Williams, J

2012-12-01

Psychotic symptoms occur in ~40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysis of three genome-wide association studies (GWASs) to identify loci that (1) increase susceptibility to an AD and subsequent psychotic symptoms; or (2) modify risk of psychotic symptoms in the presence of neurodegeneration caused by AD. In all, 1299 AD cases with psychosis (AD+P), 735 AD cases without psychosis (AD-P) and 5659 controls were drawn from Genetic and Environmental Risk in AD Consortium 1 (GERAD1), the National Institute on Aging Late-Onset Alzheimer's Disease (NIA-LOAD) family study and the University of Pittsburgh Alzheimer Disease Research Center (ADRC) GWASs. Unobserved genotypes were imputed to provide data on >1.8 million single-nucleotide polymorphisms (SNPs). Analyses in each data set were completed comparing (1) AD+P to AD-P cases, and (2) AD+P cases with controls (GERAD1, ADRC only). Aside from the apolipoprotein E (APOE) locus, the strongest evidence for association was observed in an intergenic region on chromosome 4 (rs753129; 'AD+PvAD-P' P=2.85 × 10(-7); 'AD+PvControls' P=1.11 × 10(-4)). SNPs upstream of SLC2A9 (rs6834555, P=3.0 × 10(-7)) and within VSNL1 (rs4038131, P=5.9 × 10(-7)) showed strongest evidence for association with AD+P when compared with controls. These findings warrant further investigation in larger, appropriately powered samples in which the presence of psychotic symptoms in AD has been well characterized.

Genetics of Psychosis in Alzheimer Disease.

PubMed

DeMichele-Sweet, Mary Ann A; Sweet, Robert A

2014-03-01

Psychosis occurs in approximately half of patients with Alzheimer disease (AD with psychosis, AD+P). AD+P patients have more rapid cognitive decline, greater behavioral symptoms, and higher mortality than do AD patients without psychosis. Studies in three independent cohorts have shown that psychosis in AD aggregates in families, with estimated heritability of 29.5 - 60.8%. These findings have motivated studies to investigate and uncover the genes responsible for the development of psychosis, with the ultimate goal of identifying potential biologic mechanisms that may serve as leads to specific therapies. Linkage analyses have implicated loci on chromosomes 2, 6, 7, 8, 15, and 21 with AD+P. Association studies of APOE do not support it as a risk gene for psychosis in AD. No other candidate genes, such as neurodegenerative and monoamine genes, show conclusive evidence of association with AD+P. However, a recent genome-side association study has produced some promising leads, including among them genes that have been associated with schizophrenia. This review summarizes the current knowledge of the genetic basis of AD+P.

Convergent and divergent intranetwork and internetwork connectivity patterns in patients with remitted late-life depression and amnestic mild cognitive impairment.

PubMed

Chen, Jiu; Shu, Hao; Wang, Zan; Zhan, Yafeng; Liu, Duan; Liao, Wenxiang; Xu, Lin; Liu, Yong; Zhang, Zhijun

2016-10-01

Both remitted late-life depression (rLLD) and amnesiac mild cognitive impairment (aMCI) alter brain functions in specific regions of the brain. They are also disconnection syndromes that are associated with a high risk of developing Alzheimer's disease (AD). Resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) was performed to define the shared and distinct aberrant patterns in intranetwork and internetwork connectivity between rLLD and aMCI and to determine how knowledge of these differences might contribute to our essential understanding of the altered sequences involved in functional systems both inside and outside of resting-state networks. We used rs-fcMRI to investigate in five functionally well-defined brain networks in two large cohorts of subjects at high risk for AD (55 rLLD and 87 aMCI) and 114 healthy controls (HC). A reduced degree of functional connectivity was observed in the bilateral inferior temporal cortex and supplemental motor area, and reduced correlations were observed within the sensory-motor network (SMN) and in the default mode network (DMN)-control network (CON) pair in the rLLD group than the HC group. The aMCI group showed only focal functional changes in regions of interest pairs, a trend toward increased correlations within the salience network and SMN, and a trend toward a reduced correlation in the DMN-CON pair. Furthermore, the rLLD group exhibited more severely altered functional connectivity than the aMCI group. Interestingly, these altered connectivities were associated with specific multi-domain cognitive and behavioral functions in both rLLD and aMCI. The degree of functional connectivity in the right primary auditory areas was negatively correlated with Hamilton Depression Scale scores in rLLD. Notably, altered connectivity between the right middle temporal cortex and the posterior cerebellum was negatively correlated with Mattis Dementia Rating Scale scores in both rLLD and aMCI. These results demonstrate that rLLD and aMCI may share convergent and divergent aberrant intranetwork and internetwork connectivity patterns as a potential continuous spectrum of the same disease. They further suggest that dysfunctions in the right specific temporal-cerebellum neural circuit may contribute to the similarities observed in rLLD and aMCI conversion to AD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Word associations contribute to machine learning in automatic scoring of degree of emotional tones in dream reports.

PubMed

Amini, Reza; Sabourin, Catherine; De Koninck, Joseph

2011-12-01

Scientific study of dreams requires the most objective methods to reliably analyze dream content. In this context, artificial intelligence should prove useful for an automatic and non subjective scoring technique. Past research has utilized word search and emotional affiliation methods, to model and automatically match human judges' scoring of dream report's negative emotional tone. The current study added word associations to improve the model's accuracy. Word associations were established using words' frequency of co-occurrence with their defining words as found in a dictionary and an encyclopedia. It was hypothesized that this addition would facilitate the machine learning model and improve its predictability beyond those of previous models. With a sample of 458 dreams, this model demonstrated an improvement in accuracy from 59% to 63% (kappa=.485) on the negative emotional tone scale, and for the first time reached an accuracy of 77% (kappa=.520) on the positive scale. Copyright © 2011 Elsevier Inc. All rights reserved.

Interaction between Cytomegalovirus and Herpes Simplex Virus Type 1 Associated with the Risk of Alzheimer's Disease Development.

PubMed

Lövheim, Hugo; Olsson, Jan; Weidung, Bodil; Johansson, Anders; Eriksson, Sture; Hallmans, Göran; Elgh, Fredrik

2018-01-01

Several environmental factors, including infectious agents, have been suggested to cause Alzheimer's disease (AD). Cytomegalovirus (CMV) has been associated with AD in several recent studies. To investigate whether carriage of CMV, alone or in combination with Herpes simplex virus (HSV), increased the risk of developing AD. Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years), taken an average of 9.6 years before AD diagnosis, and 360 age-, sex-, cohort-, and sampling date matched dementia-free controls were analyzed to detect anti-CMV (immunoglobulin [Ig] G and IgM), group-specific anti-HSV (IgG and IgM), and specific anti-HSV1 and HSV2 IgG antibodies by enzyme-linked immunosorbent assays. AD cases and dementia-free controls were compared using conditional logistic regression analyses. The presence of anti-CMV IgG antibodies did not increase the risk of AD (odds ratio [OR], 0.857; p = 0.497). Among AD cases, an association between CMV and HSV1 carriage was detected (OR 7.145, p < 0.001); in a conditional logistic regression model, the interaction between CMV and HSV1 was associated with AD development (OR 5.662; p = 0.007). The present findings do not support a direct relationship between CMV infection and the development of AD; however, an interaction between CMV and HSV1 was found to be associated significantly with AD development. These findings suggest that CMV infection facilitates the development of HSV1-associated AD, possibly via its effects on the immune system.

Subjective memory complaints are associated with poorer cognitive performance in adults with HIV.

PubMed

Kamkwalala, Asante; Hulgan, Todd; Newhouse, Paul

2017-05-01

With successful antiretroviral therapy in the US, HIV-positive adults now routinely survive into old age. However, increased life expectancy with HIV introduces the added complication of age-related cognitive decline. Aging with HIV has been associated with poorer cognitive outcomes compared to HIV-negative adults. While up to 50% of older HIV-positive adults will develop some degree of cognitive impairment over their lifetime, cognitive symptoms are often not consistently monitored, until those symptoms are significant enough to impair daily life. In this study we found that subjective memory complaint (SMC) ratings correlated with measurable memory performance impairments in HIV-positive adults, but not HIV-negative adults. As the HIV-positive population ages, structured subjective cognitive assessment may be beneficial to identify the early signs of cognitive impairment, and subsequently allow for earlier interventions to maintain cognitive performance as these adults continue to survive into old age.

Adolescents' perceptions of print cigarette advertising: a case for counteradvertising.

PubMed

Hawkins, K; Hane, A C

2000-01-01

Cigarette smoking is a major preventable cause of serious chronic disease. The majority of smokers begin smoking during their adolescent years. Print cigarette advertising plays an influential role in encouraging young people to smoke. Eight hundred and forty-three middle/junior high-school-aged students from a large midwestern metropolitan area participated in this study of adolescents' recognition of and belief in messages associated with print cigarette advertising. Results indicated no significant difference between smokers and nonsmokers in their recognition of messages associated with print cigarette advertising. However, smokers and nonsmokers differed significantly in the degree to which they believed the messages communicated by print cigarette advertising. Consistent with social cognitive theory, students who smoke at least occasionally were more likely to believe messages conveyed by print cigarette ads than were students who had never smoked. Implications of these findings for research and practice are discussed, including specification of guidelines for effective counteradvertising.

Risk of Cardiac Events Associated With Antidepressant Therapy in Patients With Long QT Syndrome.

PubMed

Wang, Meng; Szepietowska, Barbara; Polonsky, Bronislava; McNitt, Scott; Moss, Arthur J; Zareba, Wojciech; Auerbach, David S

2018-01-15

Patients with long QT syndrome (LQTS) are at a high risk of cardiac events. Many patients with LQTS are treated with antidepressant drugs (ADs). We investigated the LQTS genotype-specific risk of recurrent cardiac arrhythmic events (CAEs) associated with AD therapy. The study included 59 LQT1 and 72 LQT2 patients from the Rochester-based LQTS Registry with corrected QT (QT c ) prolongation and a history of AD therapy. Using multivariate Anderson-Gill models, we estimated the LQTS genotype-specific risk of recurrent CAEs (ventricular tachyarrhythmias, aborted cardiac arrest, or sudden cardiac death) associated with time-dependent ADs. Specifically, we examined the risk associated with all ADs, selective serotonin reuptake inhibitor (SSRI), and ADs classified on the CredibleMeds list (www.CredibleMeds.org) as "Conditional" or "Known risk of Torsades de pointes (TdP)." After adjusting for baseline QT c duration, sex, and time-dependent beta-blocker usage, there was an increased risk of recurrent CAEs associated with ADs in LQT1 patients (hazard ratio = 3.67, 95% confidence interval 1.98-6.82, p < 0.001) but not in LQT2 patients (hazard ratio = 0.89, 95% confidence interval 0.49-1.64, p = 0.716; LQT1 vs LQT2 interaction, p < 0.001). Similarly, LQT1 patients who were on SSRIs or ADs with "Known risk of TdP" had a higher risk of recurrent CAEs than those patients off all ADs, whereas there was no association in LQT2 patients. ADs with "Conditional risk of TdP" were not associated with the risk of recurrent CAEs in any of the groups. In conclusion, the risk of recurrent CAEs associated with time-dependent ADs is higher in LQT1 patients but not in LQT2 patients. Results suggest a LQTS genotype-specific effect of ADs on the risk of arrhythmic events. Copyright © 2017 Elsevier Inc. All rights reserved.

A Hamiltonian approach for the Thermodynamics of AdS black holes

NASA Astrophysics Data System (ADS)

Baldiotti, M. C.; Fresneda, R.; Molina, C.

2017-07-01

In this work we study the Thermodynamics of D-dimensional Schwarzschild-anti de Sitter (SAdS) black holes. The minimal Thermodynamics of the SAdS spacetime is briefly discussed, highlighting some of its strong points and shortcomings. The minimal SAdS Thermodynamics is extended within a Hamiltonian approach, by means of the introduction of an additional degree of freedom. We demonstrate that the cosmological constant can be introduced in the thermodynamic description of the SAdS black hole with a canonical transformation of the Schwarzschild problem, closely related to the introduction of an anti-de Sitter thermodynamic volume. The treatment presented is consistent, in the sense that it is compatible with the introduction of new thermodynamic potentials, and respects the laws of black hole Thermodynamics. By demanding homogeneity of the thermodynamic variables, we are able to construct a new equation of state that completely characterizes the Thermodynamics of SAdS black holes. The treatment naturally generates phenomenological constants that can be associated with different boundary conditions in underlying microscopic theories. A whole new set of phenomena can be expected from the proposed generalization of SAdS Thermodynamics.

Degree of free fatty acid saturation influences chocolate rejection in human assessors.

PubMed

Running, Cordelia A; Hayes, John E; Ziegler, Gregory R

2017-02-01

In foods, free fatty acids (FFAs) traditionally have been viewed as contributing an odor, yet evidence has accumulated that FFAs also contribute a unique taste ("oleogustus"). However, minimal work has been conducted using actual foods to test the contribution of FFA to taste preferences. Here, we investigate flavor, taste, and aroma contributions of added FFA in chocolate, as some commercial manufacturers already use lipolysis of triglycerides to generate unique profiles. We hypothesized that small added concentrations of FFAs would increase preferences for chocolate, whereas higher added concentrations would decrease preferences. We also hypothesized a saturated fatty acid (stearic C18) would have a lesser effect than a monounsaturated (oleic C18:1), which would have a lesser effect than a polyunsaturated (linoleic C18:2) fatty acid. For each, paired preference tests were conducted for 10 concentrations (0.04% to 2.25%) of added FFAs compared with the control chocolate without added FFAs. Stearic acid was tested for flavor (tasting and nares open), whereas the unsaturated fatty acids were tested for both aroma (orthonasal only and no tasting) and taste (tasting with nares blocked to eliminate retronasal odor). We found no preference for any added FFA chocolate; however, rejection was observed independently for both taste and aroma of unsaturated fatty acids, with linoleic acid reaching rejection at lower concentrations than oleic acid. These data indicate that degree of unsaturation influences rejection of both FFA aroma and taste in chocolate. Thus, alterations of FFA profiles in foods should be approached cautiously to avoid shifting concentrations of unsaturated fatty acids to hedonically unacceptable levels. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Compatible Goals: Defense and Environmental Protection

DTIC Science & Technology

1984-03-22

Remedial Action Site. AD-P004 146 Treatment of Wastewater (Red Water ) Resulti g from TNT Trinitrotoluene) Purification. AD-P004 147 Location of Volatile... Availabilit C040e3 _Vafl" -,ior OEC 5 1984 Ths document has been appeoved Dist Spool.A distribution.Is unlimiedL..... .. . COMFATABLE GOALS : DEFENSE AND...surface water to the same good biological quality as the water entering the installation. 4. Conserve fossil fuel energy to the highest degree possi

76 FR 2842 - Airworthiness Directives; Eurocopter France (Eurocopter) Model SA-365N, SA-365N1, AS-365N2, AS...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-18

... initial and recurring inspections of the inner angles and flanges of the 9-degree frame on the right-hand... further flight, repairing the frame. This proposed AD is prompted by the discovery of a crack in the 9-degree frame of a Eurocopter Model AS-365N2 helicopter. These cracks could also develop on the other...

The impact of salient advertisements on reading and attention on web pages.

PubMed

Simola, Jaana; Kuisma, Jarmo; Oörni, Anssi; Uusitalo, Liisa; Hyönä, Jukka

2011-06-01

Human vision is sensitive to salient features such as motion. Therefore, animation and onset of advertisements on Websites may attract visual attention and disrupt reading. We conducted three eye tracking experiments with authentic Web pages to assess whether (a) ads are efficiently ignored, (b) ads attract overt visual attention and disrupt reading, or (c) ads are covertly attended with distraction showing up indirectly in the reading performance. The Web pages contained an ad above a central text and another ad to the right of the text. In Experiments 1, 2, and 3A the task was to read for comprehension. Experiment 1 examined whether the degree of animation affects attention toward the ads. The results showed that ads were overtly attended during reading and that the dwell times on ads were the longest when the ad above was static and the other ad was animated. In Experiments 2 and 3, the ads appeared abruptly after a random time interval. The results showed that attention (i.e., the time when the eyes first entered an ad) was related to the ad onset time. This happened especially for the ad to the right, indicating that ads appearing close to the text region capture overt attention. In Experiment 3B the participants browsed the Web pages according to their own interest. The study demonstrated that salient ads attract overt visual attention and disrupt reading, but during free browsing, ads were viewed more frequently and for longer time than during reading.

Tech-Prep/Associate Degree Program Guide: Tech Prep Associate Degree Program, Business Administration Associate Degree Program, Office Administration Associate Degree Program, Allied Health Associate Degree Program.

ERIC Educational Resources Information Center

Marmaras, Judy; Neri, Pat

The Tech-Prep Associate Degree Program (TPAD) at the Community College of Rhode Island (CCRI) in Warwick, is a high school/community college partnership providing high school students with an alternative program of study focused on goal setting, basic academic skills development, and the skills needed to pursue a career in a technical, business or…

Polygenic Overlap Between C-Reactive Protein, Plasma Lipids, and Alzheimer Disease.

PubMed

Desikan, Rahul S; Schork, Andrew J; Wang, Yunpeng; Thompson, Wesley K; Dehghan, Abbas; Ridker, Paul M; Chasman, Daniel I; McEvoy, Linda K; Holland, Dominic; Chen, Chi-Hua; Karow, David S; Brewer, James B; Hess, Christopher P; Williams, Julie; Sims, Rebecca; O'Donovan, Michael C; Choi, Seung Hoan; Bis, Joshua C; Ikram, M Arfan; Gudnason, Vilmundur; DeStefano, Anita L; van der Lee, Sven J; Psaty, Bruce M; van Duijn, Cornelia M; Launer, Lenore; Seshadri, Sudha; Pericak-Vance, Margaret A; Mayeux, Richard; Haines, Jonathan L; Farrer, Lindsay A; Hardy, John; Ulstein, Ingun Dina; Aarsland, Dag; Fladby, Tormod; White, Linda R; Sando, Sigrid B; Rongve, Arvid; Witoelar, Aree; Djurovic, Srdjan; Hyman, Bradley T; Snaedal, Jon; Steinberg, Stacy; Stefansson, Hreinn; Stefansson, Kari; Schellenberg, Gerard D; Andreassen, Ole A; Dale, Anders M

2015-06-09

Epidemiological findings suggest a relationship between Alzheimer disease (AD), inflammation, and dyslipidemia, although the nature of this relationship is not well understood. We investigated whether this phenotypic association arises from a shared genetic basis. Using summary statistics (P values and odds ratios) from genome-wide association studies of >200 000 individuals, we investigated overlap in single-nucleotide polymorphisms associated with clinically diagnosed AD and C-reactive protein (CRP), triglycerides, and high- and low-density lipoprotein levels. We found up to 50-fold enrichment of AD single-nucleotide polymorphisms for different levels of association with C-reactive protein, low-density lipoprotein, high-density lipoprotein, and triglyceride single-nucleotide polymorphisms using a false discovery rate threshold <0.05. By conditioning on polymorphisms associated with the 4 phenotypes, we identified 55 loci associated with increased AD risk. We then conducted a meta-analysis of these 55 variants across 4 independent AD cohorts (total: n=29 054 AD cases and 114 824 healthy controls) and discovered 2 genome-wide significant variants on chromosome 4 (rs13113697; closest gene, HS3ST1; odds ratio=1.07; 95% confidence interval=1.05-1.11; P=2.86×10(-8)) and chromosome 10 (rs7920721; closest gene, ECHDC3; odds ratio=1.07; 95% confidence interval=1.04-1.11; P=3.38×10(-8)). We also found that gene expression of HS3ST1 and ECHDC3 was altered in AD brains compared with control brains. We demonstrate genetic overlap between AD, C-reactive protein, and plasma lipids. By conditioning on the genetic association with the cardiovascular phenotypes, we identify novel AD susceptibility loci, including 2 genome-wide significant variants conferring increased risk for AD. © 2015 American Heart Association, Inc.

A Wind-Tunnel Investigation of a Transonic-Transport Configuration Utilizing Drag-Reducing Devices at Mach Numbers from 0.20 to 1.03

NASA Technical Reports Server (NTRS)

Loving, Donald L.

1961-01-01

The static longitudinal stability and control and lateral characteristics of a transonic-transport model, incorporating recent drag-reducing devices, has been investigated in the Langley 8-foot transonic pressure tunnel. The wing was cambered, had a thickened root and a taper ratio of 0.3. Wing sweepback angles of 45 degrees and 40 degrees were investigated with corresponding aspect ratios of 7 and 8, respectively. Modifications to the model for reducing the drag were: a forward fuselage addition and special bodies (four big enough to house jet engines) added to the upper surface of the wing. Other components and changes investigated included an empennage, a wing-tip body, wing fences, wing trailing-edge flaps, horizontal-tail settings, and wing dihedral angle. The investigation covered the Mach number range from 0.20 to 1.03 for the angle-of-attack range from -5 degrees to 15.4 degrees, and a sideslip angle of -5 degrees, in the Reynolds number range from 0.52 times 10(exp 6) to 1.94 times 10(exp 6) based on the wing mean aerodynamic chord. The various fuselage and wing additions delayed the drag-rise Mach number and greatly reduced the drag beyond the drag rise. The wing bodies markedly alleviated unstable pitch tendencies throughout the test Mach number range. At low landing speeds, the wing bodies exhibited little interference with the ability of trailing-edge flaps to increase the lift near maximum lift coefficient; and the use of fences greatly reduced the severe longitudinal instability trend at landing attitudes. The model with a 6 degree dihedral angle exhibited positive lateral and directional stability characteristics in the presence of the fuselage and wing additions. An increase in drag-rise Mach number associated with the fuselage and wing additions on the 40 degree sweptback wing combination was similar to that for the comparable 45 degree combination. These additions did, however, reduce the drag of the 40 degree sweptback configurations more than the 45 degree configurations in the transonic speed range.

3D Shape Perception in Posterior Cortical Atrophy: A Visual Neuroscience Perspective.

PubMed

Gillebert, Céline R; Schaeverbeke, Jolien; Bastin, Christine; Neyens, Veerle; Bruffaerts, Rose; De Weer, An-Sofie; Seghers, Alexandra; Sunaert, Stefan; Van Laere, Koen; Versijpt, Jan; Vandenbulcke, Mathieu; Salmon, Eric; Todd, James T; Orban, Guy A; Vandenberghe, Rik

2015-09-16

Posterior cortical atrophy (PCA) is a rare focal neurodegenerative syndrome characterized by progressive visuoperceptual and visuospatial deficits, most often due to atypical Alzheimer's disease (AD). We applied insights from basic visual neuroscience to analyze 3D shape perception in humans affected by PCA. Thirteen PCA patients and 30 matched healthy controls participated, together with two patient control groups with diffuse Lewy body dementia (DLBD) and an amnestic-dominant phenotype of AD, respectively. The hierarchical study design consisted of 3D shape processing for 4 cues (shading, motion, texture, and binocular disparity) with corresponding 2D and elementary feature extraction control conditions. PCA and DLBD exhibited severe 3D shape-processing deficits and AD to a lesser degree. In PCA, deficient 3D shape-from-shading was associated with volume loss in the right posterior inferior temporal cortex. This region coincided with a region of functional activation during 3D shape-from-shading in healthy controls. In PCA patients who performed the same fMRI paradigm, response amplitude during 3D shape-from-shading was reduced in this region. Gray matter volume in this region also correlated with 3D shape-from-shading in AD. 3D shape-from-disparity in PCA was associated with volume loss slightly more anteriorly in posterior inferior temporal cortex as well as in ventral premotor cortex. The findings in right posterior inferior temporal cortex and right premotor cortex are consistent with neurophysiologically based models of the functional anatomy of 3D shape processing. However, in DLBD, 3D shape deficits rely on mechanisms distinct from inferior temporal structural integrity. Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visuoperceptual dysfunction and most often an atypical presentation of Alzheimer's disease (AD) affecting the ventral and dorsal visual streams rather than the medial temporal system. We applied insights from fundamental visual neuroscience to analyze 3D shape perception in PCA. 3D shape-processing deficits were affected beyond what could be accounted for by lower-order processing deficits. For shading and disparity, this was related to volume loss in regions previously implicated in 3D shape processing in the intact human and nonhuman primate brain. Typical amnestic-dominant AD patients also exhibited 3D shape deficits. Advanced visual neuroscience provides insight into the pathogenesis of PCA that also bears relevance for vision in typical AD. Copyright © 2015 Gillebert, Schaeverbeke et al.

The Influence of Academic Momentum and Associate Degree Credit Requirements on Community College Student Degree Completion

ERIC Educational Resources Information Center

Knox, Daniel

2017-01-01

This study addresses gaps in the theoretical and policy literature by examining the relationship between associate degree program credit requirements and four student outcomes: associate degree attainment, time to degree, final associate degree grade point average, and persistence. Using student unit record data, a longitudinal quantitative study…

Anxious distress in depressed outpatients: Prevalence, comorbidity, and incremental validity.

PubMed

Rosellini, Anthony J; Bourgeois, Michelle L; Correa, Jeannette; Tung, Esther S; Goncharenko, Svetlana; Brown, Timothy A

2018-05-08

The goals of this study were to estimate the prevalence of the DSM-5 anxious distress specifier (AD) among depressed outpatients, to examine associations of AD with comorbid diagnoses, and to test the incremental validity of AD over comorbidity in predicting functional impairment and severity of anxiety and depression symptoms. The sample was 237 outpatients diagnosed with major depressive disorder (MDD) or persistent depressive disorder (PDD), with and without AD, using the Anxiety and Related Disorders Interview Schedule for DSM-5. Outpatients also completed self-report questionnaires assessing functional impairment and anxiety, stress, and depression symptom severity. Two-by-two contingency tables were used to examine the associations of AD with comorbidity. Two-thirds (66.2%) of outpatients were assigned AD, with similar rates among those with MDD and PDD. Outpatients with AD were significantly more likely than those without AD to have a comorbid GAD diagnosis (OR = 2.47). Hierarchical multiple regressions were used to test the incremental validity of AD in predicting functional impairment and symptom outcomes beyond comorbid disorders. Controlling for comorbid disorders, AD was significantly associated with more severe functional impairment, autonomic arousal, stress, panic, generalized anxiety, and depression. The strongest incremental association were observed between AD and autonomic arousal (f 2  = 0.12-0.18) and generalized anxiety (f 2  = 0.17). These findings add to a growing literature that AD is common among outpatients and associated with important clinical outcomes, suggesting that AD should be routinely assessed in patients with mood disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Carbohydrate Dehydration Demonstrations.

ERIC Educational Resources Information Center

Dolson, David A.; And Others

1995-01-01

Discusses the impact of various factors on the "charring reaction" of a carbohydrate with concentrated sulfuric acid including the type of sugar, the degree of fineness of the sugar crystals, and the amount of water added. (JRH)

Separation by solvent extraction

DOEpatents

Holt, Jr., Charles H.

1976-04-06

17. A process for separating fission product values from uranium and plutonium values contained in an aqueous solution, comprising adding an oxidizing agent to said solution to secure uranium and plutonium in their hexavalent state; contacting said aqueous solution with a substantially water-immiscible organic solvent while agitating and maintaining the temperature at from -1.degree. to -2.degree. C. until the major part of the water present is frozen; continuously separating a solid ice phase as it is formed; separating a remaining aqueous liquid phase containing fission product values and a solvent phase containing plutonium and uranium values from each other; melting at least the last obtained part of said ice phase and adding it to said separated liquid phase; and treating the resulting liquid with a new supply of solvent whereby it is practically depleted of uranium and plutonium.

The location discrimination reversal task in mice is sensitive to deficits in performance caused by aging, pharmacological and other challenges.

PubMed

Graf, Radka; Longo, Jami L; Hughes, Zoë A

2018-06-01

Deficits in hippocampal-mediated pattern separation are one aspect of cognitive function affected in schizophrenia (SZ) or Alzheimer's disease (AD). To develop novel therapies, it is beneficial to explore this specific aspect of cognition preclinically. The location discrimination reversal (LDR) task is a hippocampal-dependent operant paradigm that evaluates spatial learning and cognitive flexibility using touchscreens. Here we assessed baseline performance as well as multimodal disease-relevant manipulations in mice. Mice were trained to discriminate between the locations of two images where the degree of separation impacted performance. Administration of putative pro-cognitive agents was unable to improve performance at narrow separation. Furthermore, a range of disease-relevant manipulations were characterized to assess whether performance could be impaired and restored. Pertinent to the cholinergic loss in AD, scopolamine (0.1 mg/kg) produced a disruption in LDR, which was attenuated by donepezil (1 mg/kg). Consistent with NMDA hypofunction in cognitive impairment associated with SZ, MK-801 (0.1 mg/kg) also disrupted performance; however, this deficit was not modified by rolipram. Microdeletion of genes associated with SZ (22q11) resulted in impaired performance, which was restored by rolipram (0.032 mg/kg). Since aging and inflammation affect cognition and are risk factors for AD, these aspects were also evaluated. Aged mice were slower to acquire the task than young mice and did not reach the same level of performance. A systemic inflammatory challenge (lipopolysaccharide (LPS), 1 mg/kg) produced prolonged (7 days) deficits in the LDR task. These data suggest that LDR task is a valuable platform for evaluating disease-relevant deficits in pattern separation and offers potential for identifying novel therapies.

[Profile of the informal carer associated with the clinical management of the Alzheimer's disease patient refractory to symptomatic treatment of the disease].

PubMed

Molinuevo, J L; Hernández, B

2011-11-01

Many factors influence the satisfaction and quality of life of informal caregivers of non-responder patients with Alzheimer disease (AD). Among these include, the course of the disease, cognitive impairment and behavioural disturbances of the patient, the level of family support and caregiver inherent factors such as, time commitment, psychological status and awareness of the disease. The aim of this work is to determine the profile of informal caregivers of non-responder AD patients and to evaluate the different factors that affect their quality of life, burden and overall satisfaction with treatment. We carried out a prospective and multicentre study in Spain that included a total of 249 AD patients unresponsive to anticholinesterase treatment, and their informal caregivers. We evaluated caregivers' quality of life with the SF-36 questionnaire and their associated burden with the Zarit scale, both validated for Spain. The severity and progression of the disease was quantified according to Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE). Caregiver burden showed a significant increase with the time elapsed since the start of the study, while treatment satisfaction increased slightly with this factor. Caregiver burden is highly correlated with CDR scale on patient symptoms, both in the initial visit (p<.0001) and final visit (p=.0001). Caregiver satisfaction with treatment was mainly affected by the degree of change in cognitive deterioration experienced by the patient between the two visits (p=.021). Overall satisfaction with the treatment stated by the caregiver does not correlate with compliance to treatment, but it does so with the changes in patient's cognitive impairment, a factor that also influences caregiver's burden. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Stability of mycotoxins during food processing.

PubMed

Bullerman, Lloyd B; Bianchini, Andreia

2007-10-20

The mycotoxins that commonly occur in cereal grains and other products are not completely destroyed during food processing operations and can contaminate finished processed foods. The mycotoxins most commonly associated with cereal grains are aflatoxins, ochratoxin A, fumonisins, deoxynivalenol and zearalenone. The various food processes that may have effects on mycotoxins include sorting, trimming, cleaning, milling, brewing, cooking, baking, frying, roasting, canning, flaking, alkaline cooking, nixtamalization, and extrusion. Most of the food processes have variable effects on mycotoxins, with those that utilize the highest temperatures having greatest effects. In general the processes reduce mycotoxin concentrations significantly, but do not eliminate them completely. However, roasting and extrusion processing show promise for lowering mycotoxin concentrations, though very high temperatures are needed to bring about much of a reduction in mycotoxin concentrations. Extrusion processing at temperatures greater than 150 degrees C are needed to give good reduction of zearalenone, moderate reduction of alfatoxins, variable to low reduction of deoxynivalenol and good reduction of fumonisins. The greatest reductions of fumonisins occur at extrusion temperatures of 160 degrees C or higher and in the presence of glucose. Extrusion of fumonisin contaminated corn grits with 10% added glucose resulted in 75-85% reduction in Fumonisin B(1) levels. Some fumonisin degredation products are formed during extrusion, including small amounts of hydrolyzed Fumonisin B(1) and N-(Carboxymethyl) - Fumonisin B(1) and somewhat higher amounts of N-(1-deoxy-d-fructos-1-yl) Fumonisin B(1) in extruded grits containing added glucose. Feeding trial toxicity tests in rats with extruded fumonisin contaminated corn grits show some reduction in toxicity of grits extruded with glucose.

Carbollide solubility and chemical compatibility summary

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCabe, D.J.

1993-08-17

This report examines the value of the cobalt dicarbollide anion as an effective form of in-tank precipitation. The cobalt dicarbollide anion (CDC) has been investigated for the possible replacement of tetraphenyl borate anion (TPB) for precipitation of cesium in SRS High Level Waste (HLW). The solubility of the cesium CDC in 5 M salt solutions and the reactivity with caustic have been studied extensively. The solubility of CSCDC in a mixture of 4 M sodium nitrate and 1 m sodium hydroxide is {approximately}2 {times} 10{sup {minus}3} M at 40{degrees}C. Furthermore, the CDC decomposes in 1 M sodium hydroxide solution withmore » apparent first order kinetics with a half-life of 7.3 days at 60 {degrees}C and 94 days at 40{degrees}C. Tank temperatures are currently estimated to approach 60{degrees}C during the ITP filtration cycle. This solubility and rapid decomposition of the CDC under highly alkaline conditions and high temperature would require increasing the quantity of CDC and nonradioactive cesium which must be added, increasing the cost of production. Increasing the quantity of CDC would necessitate recovery of the material, probably using a solvent extraction system. Due to the large amount of nonradioactive cesium which must be added, the total amount of precipitate formed exceeds that for TPB precipitation. Also, formation of sodium and/or potassium precipitates compete with cesium salt precipitation in 5 M salt solutions at lower temperature (<30{degrees}C). Decomposition generates hydrogen, which may lead to process complications.« less

Effects of PVA(Polyvinyl Alcohol) on Supercooling Phenomena of Water

NASA Astrophysics Data System (ADS)

Kumano, Hiroyuki; Saito, Akio; Okawa, Seiji; Takizawa, Hiroshi

In this paper, effects of polymer additive on supercooling of water were investigated experimentally. Poly-vinyl alcohol (PVA) were used as the polymer, and the samples were prepared by dissolving PVA in ultra pure water. Concentration, degree of polymerization and saponification of PVA were varied as the experimental parameters. The sample was cooled, and the temperature at the instant when ice appears was measured. Since freezing of supercooled water is statistical phenomenon, many experiments were carried out and average degrees of supercooling were obtained for each experimental condition. As the result, it was found that PVA affects nucleation of supercooling and the degree of supercooling increases by adding the PVA. Especially, it is found that the average degree of supercooling increases and the standard deviation of average degree of supercooling decreases with increase of degree of saponification of PVA. However, the average degree of supercooling are independent of the degree of polymerization of PVA in the range of this study.

Increased resting-state brain entropy in Alzheimer's disease.

PubMed

Xue, Shao-Wei; Guo, Yonghu

2018-03-07

Entropy analysis of resting-state functional MRI (R-fMRI) is a novel approach to characterize brain temporal dynamics and facilitates the identification of abnormal brain activity caused by several disease conditions. However, Alzheimer's disease (AD)-related brain entropy mapping based on R-fMRI has not been assessed. Here, we measured the sample entropy and voxel-wise connectivity of the network degree centrality (DC) of the intrinsic brain activity acquired by R-fMRI in 26 patients with AD and 26 healthy controls. Compared with the controls, AD patients showed increased entropy in the middle temporal gyrus and the precentral gyrus and also showed decreased DC in the precuneus. Moreover, the magnitude of the negative correlation between local brain activity (entropy) and network connectivity (DC) was increased in AD patients in comparison with healthy controls. These findings provide new evidence on AD-related brain entropy alterations.

Generalizing the transition from amplitude to oscillation death in coupled oscillators.

PubMed

Zou, Wei; Senthilkumar, D V; Koseska, Aneta; Kurths, Jürgen

2013-11-01

Amplitude death (AD) and oscillation death (OD) are two structurally different oscillation quenching types in coupled nonlinear oscillators. The transition from AD to OD has been recently realized due to the interplay between heterogeneity and coupling strength [A. Koseska et al., Phys. Rev. Lett. 111, 024103 (2013)]. We identify here the transition from AD to OD in nonlinear oscillators with couplings of distinct natures. It is demonstrated that the presence of time delay in the coupling cannot induce such a transition in identical oscillators, but it can indeed facilitate its occurrence with a low degree of heterogeneity. Moreover, it is further shown that the AD to OD transition is reliably observed in identical oscillators with dynamic and conjugate couplings. The coexistence of AD and OD and rich stable OD configurations after the transition are revealed, which are of great significance for potential applications in physics, biology, and control studies.

Association of Alzheimer's disease GWAS loci with MRI markers of brain aging.

PubMed

Chauhan, Ganesh; Adams, Hieab H H; Bis, Joshua C; Weinstein, Galit; Yu, Lei; Töglhofer, Anna Maria; Smith, Albert Vernon; van der Lee, Sven J; Gottesman, Rebecca F; Thomson, Russell; Wang, Jing; Yang, Qiong; Niessen, Wiro J; Lopez, Oscar L; Becker, James T; Phan, Thanh G; Beare, Richard J; Arfanakis, Konstantinos; Fleischman, Debra; Vernooij, Meike W; Mazoyer, Bernard; Schmidt, Helena; Srikanth, Velandai; Knopman, David S; Jack, Clifford R; Amouyel, Philippe; Hofman, Albert; DeCarli, Charles; Tzourio, Christophe; van Duijn, Cornelia M; Bennett, David A; Schmidt, Reinhold; Longstreth, William T; Mosley, Thomas H; Fornage, Myriam; Launer, Lenore J; Seshadri, Sudha; Ikram, M Arfan; Debette, Stephanie

2015-04-01

Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta ± SE = -0.047 ± 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons. Copyright © 2015 Elsevier Inc. All rights reserved.

CR1 rs3818361 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Chinese Population.

PubMed

Li, Yongning; Song, Dongjing; Jiang, Yongshuai; Wang, Jingwei; Feng, Rennan; Zhang, Liangcai; Wang, Guangyu; Chen, Zugen; Wang, Renzhi; Jiang, Qinghua; Liu, Guiyou

2016-08-01

Recent genome-wide association studies (GWAS) reported CR1 rs3818361 polymorphism to be an Alzheimer's disease (AD) susceptibility variant in European ancestry. Three independent studies investigated this association in Chinese population. However, these studies reported weak or no significant association. Here, we reinvestigated the association using all the samples from three independent studies in Chinese population (N = 4047, 1244 AD cases and 2803 controls). We also selected three independent studies in European ancestry population (N = 11787, 3939 AD cases and 7848 controls) to evaluate the effect of rs3818361 polymorphism on AD risk in different ethnic backgrounds. In Chinese population, we did not identified significant heterogeneity using additive, recessive, and dominant genetic models. Meta-analysis showed significant association between rs3818361 and AD with P = 6.00E-03 and P = 5.00E-03. We further identified no heterogeneity of rs3818361 polymorphism between Chinese and European populations. We found that rs3818361 polymorphism contributed to AD with similar genetic risk in Chinese and European populations. In summary, this is the first study to show significant association between rs3818361 polymorphism and AD in Chinese population by a meta-analysis method. Our findings indicate that the effect of CR1 rs3818361 polymorphism on AD risk in Chinese cohorts is consistent with the increased risk observed in European AD cohorts.

Magnetic resonance imaging traits in siblings discordant for Alzheimer disease.

PubMed

Cuenco, Karen T; Green, Robert C; Zhang, J; Lunetta, Kathryn; Erlich, Porat M; Cupples, L Adrienne; Farrer, Lindsay A; DeCarli, Charles

2008-07-01

Magnetic resonance imaging (MRI) can aid clinical assessment of brain changes potentially correlated with Alzheimer disease (AD). MRI traits may improve our ability to identify genes associated with AD-outcomes. We evaluated semi-quantitative MRI measures as endophenotypes for genetic studies by assessing their association with AD in families from the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) Study. Discordant siblings from multiple ethnicities were ascertained through a single affected proband. Semi-quantitative MRI measures were obtained for each individual. The association between continuous/ordinal MRI traits and AD were analyzed using generalized estimating equations. Medical history and Apolipoprotein E (APOE)epsilon4 status were evaluated as potential confounders. Comparisons of 214 affected and 234 unaffected subjects from 229 sibships revealed that general cerebral atrophy, white matter hyperintensities (WMH), and mediotemporal atrophy differed significantly between groups (each at P < .0001) and varied by ethnicity. Age at MRI and duration of AD confounded all associations between AD and MRI traits. Among unaffected sibs, the presence of at least one APOEepsilon4 allele and MRI infarction was associated with more WMH after adjusting for age at MRI. The strong association between MRI traits and AD suggests that MRI traits may be informative endophenotypes for basic and clinical studies of AD. In particular, WMH may be a marker of vascular disease that contributes to AD pathogenesis.

Electrical conductivity of San Carlos olivine along [100] under oxygen- and pyroxene-buffered conditions and implications for defect equilibria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wanamaker, B.J.; Duba, A.G.

1993-01-10

The electrical conductivity along [100] of single crystal San Carlos olivine was measured as a function of temperature between 1100[degrees] and 1200[degrees]C and oxygen fugacity between 10[sup [minus]6] and 10[sup +0.5] Pa (at 1200[degrees]C), and either with (pyroxene-buffered) or without (self-buffered) an added natural pyroxene buffer from a San Carlos Iherzolite. Under these temperature and fO[sub 2] conditions, electrical conduction in the self-buffered sample is attributed to polarons (Fe[sup [sm bullet

Cancer linked to Alzheimer disease but not vascular dementia

PubMed Central

Roe, C M.; Fitzpatrick, A L.; Xiong, C; Sieh, W; Kuller, L; Miller, J P.; Williams, M M.; Kopan, R; Behrens, M I.; Morris, J C.

2010-01-01

Objective: To investigate whether cancer is associated with Alzheimer disease (AD) and vascular dementia (VaD). Methods: Cox proportional hazards models were used to test associations between prevalent dementia and risk of future cancer hospitalization, and associations between prevalent cancer and risk of subsequent dementia. Participants in the Cardiovascular Health Study–Cognition Substudy, a prospective cohort study, aged 65 years or older (n = 3,020) were followed a mean of 5.4 years for dementia and 8.3 years for cancer. Results: The presence of any AD (pure AD + mixed AD/VaD; hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.20–0.84) and pure AD (HR = 0.31, 95% CI = 0.12–0.86) was associated with a reduced risk of future cancer hospitalization, adjusted for demographic factors, smoking, obesity, and physical activity. No significant associations were found between dementia at baseline and rate of cancer hospitalizations for participants with diagnoses of VaD. Prevalent cancer was associated with reduced risk of any AD (HR = 0.72; 95% CI = 0.52–0.997) and pure AD (HR = 0.57; 95% CI = 0.36–0.90) among white subjects after adjustment for demographics, number of APOE ε4 alleles, hypertension, diabetes, and coronary heart disease; the opposite association was found among minorities, but the sample size was too small to provide stable estimates. No significant association was found between cancer and subsequent development of VaD. Conclusions: In white older adults, prevalent Alzheimer disease (AD) was longitudinally associated with a reduced risk of cancer, and a history of cancer was associated with a reduced risk of AD. Together with other work showing associations between cancer and Parkinson disease, these findings suggest the possibility that cancer is linked to neurodegeneration. GLOSSARY 3MSE = modified Mini-Mental State Examination; AD = Alzheimer disease; ADDTC = Alzheimer Disease Diagnostic and Treatment Centers; CHD = coronary heart disease; CHS = Cardiovascular Health Study; CI = confidence interval; HR = hazard ratio; ICD-9 = International Classification of Diseases–Ninth Revision; MCI = mild cognitive impairment; NINCDS-ADRDA = National Institute of Neurological and Communicative Diseases and Stroke–Alzheimer's Disease and Related Disorders Association; PD = Parkinson disease; VaD = vascular dementia. PMID:20032288

Added sugars and risk factors for obesity, diabetes and heart disease.

PubMed

Rippe, J M; Angelopoulos, T J

2016-03-01

The effects of added sugars on various chronic conditions are highly controversial. Some investigators have argued that added sugars increase the risk of obesity, diabetes and cardiovascular disease. However, few randomized controlled trials are available to support these assertions. The literature is further complicated by animal studies, as well as studies which compare pure fructose to pure glucose (neither of which is consumed to any appreciable degree in the human diet) and studies where large doses of added sugars beyond normal levels of human consumption have been administered. Various scientific and public health organizations have offered disparate recommendations for upper limits of added sugar. In this article, we will review recent randomized controlled trials and prospective cohort studies. We conclude that the normal added sugars in the human diet (for example, sucrose, high-fructose corn syrup and isoglucose) when consumed within the normal range of normal human consumption or substituted isoenergetically for other carbohydrates, do not appear to cause a unique risk of obesity, diabetes or cardiovascular disease.

Fibrin deposited in the Alzheimer’s disease brain promotes neuronal degeneration

PubMed Central

Cortes-Canteli, Marta; Mattei, Larissa; Richards, Allison T.; Norris, Erin H.; Strickland, Sidney

2014-01-01

Alzheimer’s disease (AD) is the most common form of dementia and has no effective treatment. Besides the well-known pathological characteristics, this disease also has a vascular component, and substantial evidence shows increased thrombosis as well as a critical role for fibrin(ogen) in AD. This molecule has been implicated in neuroinflammation, neurovascular damage, blood brain barrier permeability, vascular amyloid deposition, and memory deficits that are observed in AD. Here we present evidence demonstrating that fibrin deposition increases in the AD brain and correlates with the degree of pathology. Moreover, we show that fibrin(ogen) is present in areas of dystrophic neurites and that a modest decrease in fibrinogen levels improves neuronal health and ameliorates amyloid pathology in the subiculum of AD mice. Our results further characterize the important role of fibrin(ogen) in this disease and support the design of therapeutic strategies aimed at blocking the interaction between fibrinogen and Aβ and/or normalizing the increased thrombosis present in AD. PMID:25475538

HLA similarities indicate shared genetic risk in 21-hydroxylase autoantibody positive South African and United States Addison's disease.

PubMed

Ross, I L; Babu, S; Armstrong, T; Zhang, L; Schatz, D; Pugliese, A; Eisenbarth, G; Baker Ii, P

2014-10-01

Genetic similarities between patients from the United States and South African (SA) Addison's Disease (AD) strengthen evidence for genetic association. SA-AD (n = 73), SA healthy controls (N = 78), and US-AD patients (N = 83) were genotyped for DQA1, DQB1, DRB1, and HLA-B alleles. Serum was tested for the quantity of 21OH-AA and IFNα-AA at the Barbara Davis Center. Although not as profound as in US-AD, in SA-AD 21OH-AA + subjects the predominantly associated risk haplotypes were DRB1*0301-DQB1*0201 (DR3), DRB1*04xx-DQB1*0302 (DR4), and the combined DR3/4 genotype. DQB1*0302 associated DRB1*04xx haplotypes conferred higher risk than those DRB1*04xx haplotypes associated with other DQB1 alleles. We found negative association in 21OH-AA + SA-AD for DQA1*0201-DQB1*0202 and DQA1*0101-DQB1*0501 vs SA controls, and positive association for DQA1*0401-DQB1*0402 vs US-AD. Apart from the class II DR3 haplotype, HLA-B8 did not have an independent effect; however together DR3 and HLA-B8 conferred the highest risk vs 21OH-AA negative SA-AD and SA-controls. HLA-B7 (often with DR4) conferred novel risk in 21OH-AA + SA-AD vs controls. This study represents the first comparison between South African and United States AD populations utilizing genotyping and serology performed at the same center. SA-AD and US-AD 21OH-AA + patients share common HLA risk haplotypes including DR4 (with HLA-B7) and DR3 (with HLA-B8), strengthening previously described HLA associations and implicating similar genetic etiology. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tomato growth as affected by root-zone temperature and the addition of gibberellic acid and kinetin to nutrient solutions

NASA Technical Reports Server (NTRS)

Bugbee, B.; White, J. W.; Salisbury, F. B. (Principal Investigator)

1984-01-01

The effect of root-zone temperature on young tomato plants (Lycopersicon esculentum Mill. cv. Heinz 1350) was evaluated in controlled environments using a recirculating solution culture system. Growth rates were measured at root-zone temperatures of 15 degrees, 20 degrees, 25 degrees, and 30 degrees C in a near optimum foliar environment. Optimum growth occurred at 25 degrees to 30 degrees during the first 4 weeks of growth and 20 degrees to 25 degrees during the 5th and 6th weeks. Growth was severely restricted at 15 degrees. Four concentrations of gibberellic acid (GA3) and kinetin were added to the nutrient solution in a separate trial; root-zone temperature was maintained at 15 degrees and 25 degrees. Addition of 15 micromoles GA3 to solutions increased specific leaf area, total leaf area, and dry weight production of plants in both temperature treatments. GA3-induced growth stimulation was greater at 15 degrees than at 25 degrees. GA3 may promote growth by increasing leaf area, enhancing photosynthesis per unit leaf area, or both. Kinetic was not useful in promoting growth at either temperature.

Newly diagnosed T1 diabetes presenting with hypoglycemia due to simultaneous co-existence of Addison disease.

PubMed

Glynn, Nigel; Bashir, Mohammed; Smith, Diarmuid; Thompson, Christopher J

2014-09-01

Type 1 diabetes mellitus (TIDM) classically presents with symptomatic hyperglycemia and many patients develop diabetic ketoacidosis prior to their diagnosis. However, non-classical presentation or co-presentation with associated diseases may delay diagnosis or lead to challenges in acute, clinical management. An 18-yr-old girl presented to hospital with severe, symptomatic hypoglycemia. Clinical history and serum electrolyte concentrations suggested a diagnosis of adrenal insufficiency. She remained hypoglycemic until glucocorticoid replacement was commenced, at which point she developed persistent hyperglycemia requiring insulin therapy. Subsequent follow up confirmed the diagnosis of Addison's disease (AD), the treatment of which unmasked co-existing type 1 diabetes. Autoimmune diseases often cluster together in affected patients and first-degree relatives. Approximately 1 in 200 patients with T1DM develop AD. However, months or more commonly years usually elapse between the presentation of different autoimmune conditions. The co-diagnosis T1DM and AD in the acute setting is rare. Moreover, the first presentation of T1DM with severe hypoglycemia is even more exceptional. This case highlights the need for vigilance during the acute, emergency management of patients with autoimmune conditions and, in particular, to consider the possibility of concurrent antibody-mediated diseases which may need to be addressed during resuscitation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Examination of the Clinicopathologic Continuum of Alzheimer Disease in the Autopsy Cohort of the National Alzheimer Coordinating Center

PubMed Central

Serrano-Pozo, Alberto; Qian, Jing; Monsell, Sarah E.; Frosch, Matthew P.; Betensky, Rebecca A.; Hyman, Bradley T.

2014-01-01

To test the hypothesis that Alzheimer disease (AD) is a clinical and pathologic continuum between normal aging and end-stage dementia, we selected a convenience sample of subjects from the National Alzheimer Coordinating Center 2005 to 2012 autopsy cohort (n = 2,083) with the last clinical evaluation within 2 years before autopsy and no other primary neuropathologic diagnosis. Demographic and neuropathologic characteristics were correlated with the Clinical Dementia Rating–Sum of Boxes in the 835 subjects meeting these criteria. Both neuritic plaques and neurofibrillary tangles independently predicted Clinical Dementia Rating–Sum of Boxes. Severe small-vessel disease, severe amyloid angiopathy, and hippocampal sclerosis were also independently associated with the degree of cognitive impairment. By contrast, education was a strong independent protective factor against cognitive deficits. The cause of mild to moderate dementia remained uncertain in 14% of the patients. Inverse probability weighting suggests the generalizability of these results to nonautopsied cohorts. These data indicate that plaques and tangles independently contribute to cognitive impairment, that concurrent vascular disease strongly correlates with cognitive dysfunction even in a sample selected to represent the AD pathologic continuum, and that education further modifies clinical expression. Thus, multiple concomitant etiologies of brain damage and premorbid characteristics contribute to the uncertainty of AD clinicopathologic correlations based only on tangles and plaques. PMID:24226270

Magnetic record associated with tree ring density: Possible climate proxy

PubMed Central

Kletetschka, Gunther; Pruner, Petr; Venhodova, Daniela; Kadlec, Jaroslav

2007-01-01

A magnetic signature of tree rings was tested as a potential paleo-climatic indicator. We examined wood from sequoia tree, located in Mountain Home State Forest, California, whose tree ring record spans over the period 600 – 1700 A.D. We measured low and high-field magnetic susceptibility, the natural remanent magnetization (NRM), saturation isothermal remanent magnetization (SIRM), and stability against thermal and alternating field (AF) demagnetization. Magnetic investigation of the 200 mm long sequoia material suggests that magnetic efficiency of natural remanence may be a sensitive paleoclimate indicator because it is substantially higher (in average >1%) during the Medieval Warm Epoch (700–1300 A.D.) than during the Little Ice Age (1300–1850 A.D.) where it is <1%. Diamagnetic behavior has been noted to be prevalent in regions with higher tree ring density. The mineralogical nature of the remanence carrier was not directly detected but maghemite is suggested due to low coercivity and absence of Verwey transition. Tree ring density, along with the wood's magnetic remanence efficiency, records the Little Ice Age (LIA) well documented in Europe. Such a record suggests that the European LIA was a global phenomenon. Magnetic analysis of the thermal stability reveals the blocking temperatures near 200 degree C. This phenomenon suggests that the remanent component in this tree may be thermal in origin and was controlled by local thermal condition. PMID:17381844

Examination of the clinicopathologic continuum of Alzheimer disease in the autopsy cohort of the National Alzheimer Coordinating Center.

PubMed

Serrano-Pozo, Alberto; Qian, Jing; Monsell, Sarah E; Frosch, Matthew P; Betensky, Rebecca A; Hyman, Bradley T

2013-12-01

To test the hypothesis that Alzheimer disease (AD) is a clinical and pathologic continuum between normal aging and end-stage dementia, we selected a convenience sample of subjects from the National Alzheimer Coordinating Center 2005 to 2012 autopsy cohort (n = 2,083) with the last clinical evaluation within 2 years before autopsy and no other primary neuropathologic diagnosis. Demographic and neuropathologic characteristics were correlated with the Clinical Dementia Rating-Sum of Boxes in the 835 subjects meeting these criteria. Both neuritic plaques and neurofibrillary tangles independently predicted Clinical Dementia Rating-Sum of Boxes. Severe small-vessel disease, severe amyloid angiopathy, and hippocampal sclerosis were also independently associated with the degree of cognitive impairment. By contrast, education was a strong independent protective factor against cognitive deficits. The cause of mild to moderate dementia remained uncertain in 14% of the patients. Inverse probability weighting suggests the generalizability of these results to nonautopsied cohorts. These data indicate that plaques and tangles independently contribute to cognitive impairment, that concurrent vascular disease strongly correlates with cognitive dysfunction even in a sample selected to represent the AD pathologic continuum, and that education further modifies clinical expression. Thus, multiple concomitant etiologies of brain damage and premorbid characteristics contribute to the uncertainty of AD clinicopathologic correlations based only on tangles and plaques.

Death of the Escherichia coli K-12 strain W3110 in soil and water.

PubMed Central

Bogosian, G; Sammons, L E; Morris, P J; O'Neil, J P; Heitkamp, M A; Weber, D B

1996-01-01

Whether Escherichia coli K-12 strain W3110 can enter the "viable but nonculturable" state was studied with sterile and nonsterile water and soil at various temperatures. In nonsterile river water, the plate counts of added E. coli cells dropped to less than 10 CFU/ml in less than 10 days. Acridine orange direct counts, direct viable counts, most-probable-number estimates, and PCR analyses indicated that the added E. coli cells were disappearing from the water in parallel with the number of CFU. Similar results were obtained with nonsterile soil, although the decline of the added E. coli was slower. In sterile water or soil, the added E. coli persisted for much longer, often without any decline in the plate counts even after 50 days. In sterile river water at 37 degrees C and sterile artificial seawater at 20 and 37 degrees C, the plate counts declined by 3 to 5 orders of magnitude, while the acridine orange direct counts remained unchanged. However, direct viable counts and various resuscitation studies all indicated that the nonculturable cells were nonviable. Thus, in either sterile or nonsterile water and soil, the decline in plate counts of E. coli K-12 strain W3110 is not due to the cells entering the viable but nonculturable state, but is simply due to their death. PMID:8900002

The effect of ad hominem attacks on the evaluation of claims promoted by scientists.

PubMed

Barnes, Ralph M; Johnston, Heather M; MacKenzie, Noah; Tobin, Stephanie J; Taglang, Chelsea M

2018-01-01

Two experiments were conducted to determine the relative impact of direct and indirect (ad hominem) attacks on science claims. Four hundred and thirty-nine college students (Experiment 1) and 199 adults (Experiment 2) read a series of science claims and indicated their attitudes towards those claims. Each claim was paired with one of the following: A) a direct attack upon the empirical basis of the science claim B) an ad hominem attack on the scientist who made the claim or C) both. Results indicate that ad hominem attacks may have the same degree of impact as attacks on the empirical basis of the science claims, and that allegations of conflict of interest may be just as influential as allegations of outright fraud.

The effect of ad hominem attacks on the evaluation of claims promoted by scientists

PubMed Central

2018-01-01

Two experiments were conducted to determine the relative impact of direct and indirect (ad hominem) attacks on science claims. Four hundred and thirty-nine college students (Experiment 1) and 199 adults (Experiment 2) read a series of science claims and indicated their attitudes towards those claims. Each claim was paired with one of the following: A) a direct attack upon the empirical basis of the science claim B) an ad hominem attack on the scientist who made the claim or C) both. Results indicate that ad hominem attacks may have the same degree of impact as attacks on the empirical basis of the science claims, and that allegations of conflict of interest may be just as influential as allegations of outright fraud. PMID:29381757

Added sugars: consumption and associated factors among adults and the elderly. São Paulo, Brazil.

PubMed

Bueno, Milena Baptista; Marchioni, Dirce Maria Lobo; César, Chester Luis Galvão; Fisberg, Regina Mara

2012-06-01

To investigate added sugar intake, main dietary sources and factors associated with excessive intake of added sugar. A population-based household survey was carried out in São Paulo, the largest city in Brazil. Cluster sampling was performed and the study sample comprised 689 adults and 622 elderly individuals. Dietary intake was estimated based on a 24-hour food recall. Usual nutrient intake was estimated by correcting for the within-person variance of intake using the Iowa State University (ISU) method. Linear regression analysis was conducted to identify factors associated with added sugar intake. Average of energy intake (EI) from added sugars was 9.1% (95% CI: 8.9%; 9.4%) among adults and 8.4% (95% CI: 8.2%; 8.7%) among the elderly (p < 0.05). Average added sugar intake (% EI) was higher among women than among men (p < 0.05). Soft drink was the main source of added sugar among adults, while table sugar was the main source of added sugar among the elderly. Added sugar intake increased with age among adults. Moreover, higher socioeconomic level was associated with added sugar intake in the same group. Added sugar intake is higher among younger adults of higher socioeconomic level. Soft drink and table sugar accounted for more than 50% of the sugar consumed.

Graph theoretic analysis of structural connectivity across the spectrum of Alzheimer's disease: The importance of graph creation methods

PubMed Central

Phillips, David J.; McGlaughlin, Alec; Ruth, David; Jager, Leah R.; Soldan, Anja

2015-01-01

Graph theory is increasingly being used to study brain connectivity across the spectrum of Alzheimer's disease (AD), but prior findings have been inconsistent, likely reflecting methodological differences. We systematically investigated how methods of graph creation (i.e., type of correlation matrix and edge weighting) affect structural network properties and group differences. We estimated the structural connectivity of brain networks based on correlation maps of cortical thickness obtained from MRI. Four groups were compared: 126 cognitively normal older adults, 103 individuals with Mild Cognitive Impairment (MCI) who retained MCI status for at least 3 years (stable MCI), 108 individuals with MCI who progressed to AD-dementia within 3 years (progressive MCI), and 105 individuals with AD-dementia. Small-world measures of connectivity (characteristic path length and clustering coefficient) differed across groups, consistent with prior studies. Groups were best discriminated by the Randić index, which measures the degree to which highly connected nodes connect to other highly connected nodes. The Randić index differentiated the stable and progressive MCI groups, suggesting that it might be useful for tracking and predicting the progression of AD. Notably, however, the magnitude and direction of group differences in all three measures were dependent on the method of graph creation, indicating that it is crucial to take into account how graphs are constructed when interpreting differences across diagnostic groups and studies. The algebraic connectivity measures showed few group differences, independent of the method of graph construction, suggesting that global connectivity as it relates to node degree is not altered in early AD. PMID:25984446

Cognitive effects of hormone therapy continuation or discontinuation in a sample of women at risk for Alzheimer’s disease

PubMed Central

Wroolie, Tonita E.; Kenna, Heather A.; Williams, Katherine E.; Rasgon, Natalie L.

2015-01-01

Use of estrogen-based hormone therapy (HT), as a protection from cognitive decline and Alzheimer’s disease, is controversial although cumulative data supports HT use when initiated close to menopause onset with estrogen formulations containing 17β-estradiol (17β-E) being preferable to conjugated equine estrogen formulations. Little is known regarding specific populations of women who may derive benefit from HT. Women with heightened risk for AD (aged 49-69), all of whom were taking HT for at least one year, most of whom initiated HT close to menopause onset, underwent cognitive assessment followed by randomization to continue or discontinue HT. Assessments were repeated at two years after randomization. Women who continued HT performed better on cognitive domains composed of measures of verbal memory, and combined attention, working memory, and processing speed measures. Women who used 17β-E versus conjugated equine estrogen, whether randomized to continue or discontinue HT showed better verbal memory performance at the 2-year follow-up assessment. An interaction was also found with HT randomization and family history of AD in a first degree relative. All women offspring of patients with AD declined in verbal memory however, women who continued HT declined less than women who discontinued HT. Women without a first-degree relative with AD showed verbal memory improvement (likely due to practice effects) with continuance and declined with discontinuance of HT. Continuation of HT use appears to protect cognition in women with heightened risk for AD when initiated close to menopause onset. PMID:26209223

Effect of pH on subunit association and heat protection of soybean alpha-galactosidase

NASA Technical Reports Server (NTRS)

Porter, J. E.; Sarikaya, A.; Herrmann, K. M.; Ladisch, M. R.; Mitchell, C. A. (Principal Investigator)

1992-01-01

Soybeans contain the enzyme alpha-galactosidase, which hydrolyzes alpha-1, 6 linkages in stachyose and raffinose to give sucrose and galactose. We have found that galactose, a competitive product inhibitor of alpha-galactosidase, strongly promotes the heat stability of the tetrameric form of the enzyme at pH 4.0 and at temperatures of up to 70 degrees C for 60 min. Stachyose and raffinose also protect alpha-galactosidase from denaturation at pH 4.0 although to a lesser extent. Glucose and mannose have little effect. At pH 7.0 the enzyme is a monomer, and galactose has no effect on the heat stability of the enzyme. In the absence of heat protection of the enzyme by added sugars, a series deactivation mechanism was found to describe the deactivation data. In comparison, a unimolecular, non-first order deactivation model applies at pH 4.0, where heat protection effects were observed. At a temperature above 60 degrees C, simple deactivation is a suitable model. The results suggest that alpha-galactosidase conformation and heat stability are directly related.

A growth model for directed complex networks with power-law shape in the out-degree distribution

PubMed Central

Esquivel-Gómez, J.; Stevens-Navarro, E.; Pineda-Rico, U.; Acosta-Elias, J.

2015-01-01

Many growth models have been published to model the behavior of real complex networks. These models are able to reproduce several of the topological properties of such networks. However, in most of these growth models, the number of outgoing links (i.e., out-degree) of nodes added to the network is constant, that is all nodes in the network are born with the same number of outgoing links. In other models, the resultant out-degree distribution decays as a poisson or an exponential distribution. However, it has been found that in real complex networks, the out-degree distribution decays as a power-law. In order to obtain out-degree distribution with power-law behavior some models have been proposed. This work introduces a new model that allows to obtain out-degree distributions that decay as a power-law with an exponent in the range from 0 to 1. PMID:25567141

Prospective association between added sugars and frailty in older adults.

PubMed

Laclaustra, Martin; Rodriguez-Artalejo, Fernando; Guallar-Castillon, Pilar; Banegas, Jose R; Graciani, Auxiliadora; Garcia-Esquinas, Esther; Ordovas, Jose; Lopez-Garcia, Esther

2018-05-01

Sugar-sweetened beverages and added sugars (monosaccharides and disaccharides) in the diet are associated with obesity, diabetes, and cardiovascular disease, which are all risk factors for decline in physical function among older adults. The aim of this study was to examine the association between added sugars in the diet and incidence of frailty in older people. Data were taken from 1973 Spanish adults ≥60 y old from the Seniors-ENRICA cohort. In 2008-2010 (baseline), consumption of added sugars (including those in fruit juices) was obtained using a validated diet history. Study participants were followed up until 2012-2013 to assess frailty based on Fried's criteria. Statistical analyses were performed with logistic regression adjusted for age, sex, education, smoking status, body mass index, energy intake, self-reported comorbidities, Mediterranean Diet Adherence Score (excluding sweetened drinks and pastries), TV watching time, and leisure-time physical activity. Compared with participants consuming <15 g/d added sugars (lowest tertile), those consuming ≥36 g/d (highest tertile) were more likely to develop frailty (OR: 2.27; 95% CI: 1.34, 3.90; P-trend = 0.003). The frailty components "low physical activity" and "unintentional weight loss" increased dose dependently with added sugars. Association with frailty was strongest for sugars added during food production. Intake of sugars naturally appearing in foods was not associated with frailty. The consumption of added sugars in the diet of older people was associated with frailty, mainly when present in processed foods. The frailty components that were most closely associated with added sugars were low level of physical activity and unintentional weight loss. Future research should determine whether there is a causal relation between added sugars and frailty.

Assessing Understanding of the Learning Cycle: The ULC

NASA Astrophysics Data System (ADS)

Marek, Edmund A.; Maier, Steven J.; McCann, Florence

2008-08-01

An 18-item, multiple choice, 2-tiered instrument designed to measure understanding of the learning cycle (ULC) was developed and field-tested from the learning cycle test (LCT) of Odom and Settlage ( Journal of Science Teacher Education, 7, 123 142, 1996). All question sets of the LCT were modified to some degree and 5 new sets were added, resulting in the ULC. The ULC measures (a) understandings and misunderstandings of the learning cycle, (b) the learning cycle’s association with Piaget’s ( Biology and knowledge theory: An essay on the relations between organic regulations and cognitive processes, 1975) theory of mental functioning, and (c) applications of the learning cycle. The resulting ULC instrument was evaluated for internal consistency with Cronbach’s alpha, yielding a coefficient of .791.

Cardiorespiratory Fitness is Associated with Atrophy in Alzheimer’s and Aging Over Two Years

PubMed Central

Vidoni, Eric D.; Honea, Robyn A.; Billinger, Sandra A.; Swerdlow, Russel H.; Burns, Jeffrey M.

2011-01-01

We sought to describe change in cardiorespiratory (CR) fitness over 2 years in those with early–stage Alzheimer’s disease (AD) and nondemented aging and assess the relationship of CR fitness with cognitive decline, brain atrophy and dementia progression. Individuals with early-stage AD (n=37) and without dementia (n=53) attended clinical evaluations, cognitive and exercise tests, and MRI at baseline and 2 years later. CR fitness was lower in those with AD over the study period. Lower baseline CR fitness was associated with progression of dementia severity in AD. Declining CR fitness over 2 years was associated with brain atrophy in AD, especially in the parahippocampus. In nondemented participants, there was a trend for lower baseline fitness to be related to cognitive decline. Both lower baseline CR fitness and declining CR fitness over 2 years were associated with regional brain atrophy. We conclude that CR fitness is chronically reduced in those with AD. Further in those with AD, CR fitness is associated with progression of dementia severity and brain atrophy in AD, suggesting a link between progression of dementia severity and cardiorespiratory health. PMID:21531480

Commercial complementary food consumption is prospectively associated with added sugar intake in childhood.

PubMed

Foterek, Kristina; Buyken, Anette E; Bolzenius, Katja; Hilbig, Annett; Nöthlings, Ute; Alexy, Ute

2016-06-01

Given that commercial complementary food (CF) can contain high levels of added sugar, a high consumption may predispose to a preference for sweet taste later in life. This study examined cross-sectional associations between commercial CF consumption and added sugar intake in infancy as well as its prospective relation to added sugar intake in pre-school and primary-school age children. In all, 288 children of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study with 3-d weighed dietary records at 0·5 and 0·75 (infancy), 3 and 4 (pre-school age) and 6 and 7 years of age (primary-school age) were included in this analysis. Individual commercial CF consumption as percentage of total commercial CF (%cCF) was averaged at 0·5 and 0·75 years. Individual total added sugar intake (g/d, energy percentage/d) was averaged for all three age groups. Multivariable logistic and linear regression models were used to analyse associations between %cCF and added sugar intake. In infancy, a higher %cCF was associated with odds for high added sugar intake from CF and for high total added sugar intake (>75th percentile, P<0·033). Prospectively, a higher %cCF was related to higher added sugar intake in both pre-school (P<0·041) and primary-school age children (P<0·039), although these associations were attenuated in models adjusting for added sugar intake in infancy. A higher %cCF in infancy may predispose to higher added sugar intake in later childhood by virtue of its added sugar content. Therefore, offering home-made CF or carefully chosen commercial CF without added sugar might be one strategy to reduce sugar intake in infancy and later on.

Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

PubMed

Østergaard, Søren D; Mukherjee, Shubhabrata; Sharp, Stephen J; Proitsi, Petroula; Lotta, Luca A; Day, Felix; Perry, John R B; Boehme, Kevin L; Walter, Stefan; Kauwe, John S; Gibbons, Laura E; Larson, Eric B; Powell, John F; Langenberg, Claudia; Crane, Paul K; Wareham, Nicholas J; Scott, Robert A

2015-06-01

Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR). We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49), fasting glucose (NSNPs = 36), insulin resistance (NSNPs = 10), body mass index (BMI, NSNPs = 32), total cholesterol (NSNPs = 73), HDL-cholesterol (NSNPs = 71), LDL-cholesterol (NSNPs = 57), triglycerides (NSNPs = 39), systolic blood pressure (SBP, NSNPs = 24), smoking initiation (NSNPs = 1), smoking quantity (NSNPs = 3), university completion (NSNPs = 2), and years of education (NSNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3)). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8)). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3)), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this study include the small proportion of intermediate trait variance explained by genetic variants and other implicit limitations of MR analyses. Inherited lifetime exposure to higher SBP is associated with lower AD risk. These findings suggest that higher blood pressure--or some environmental exposure associated with higher blood pressure, such as use of antihypertensive medications--may reduce AD risk.

Adenovirus 36 seropositivity is strongly associated with race and gender, but not obesity, among US military personnel.

PubMed

Broderick, M P; Hansen, C J; Irvine, M; Metzgar, D; Campbell, K; Baker, C; Russell, K L

2010-02-01

Although several studies have shown a positive association between evidence of anti-adenovirus 36 (Ad-36) antibodies (Ad-36 exposure) and (1) obesity and (2) serum cholesterol in animals, there is limited research demonstrating this association in humans. There is also limited research on transmission, presentation and demographics of Ad-36 infection. (1) Body mass (body mass index (BMI)), (2) fasting serum cholesterol and triglyceride levels and (3) demographic characteristics were compared between Ad-36 seropositive and seronegative groups. The majority of subjects were matched as cases versus controls on a number of demographic variables. A total of 150 obese and 150 lean active-duty military personnel were studied. Subjects completed a questionnaire regarding demographic and behavioral characteristics. Subject serum samples were tested by serum neutralization assay for the presence of anti-Ad-36 antibodies. In all, 34% of obese and 39% of lean subjects had Ad-36 exposure, an insignificant difference. Serum cholesterol and triglyceride levels were significantly higher among the obese subjects than among the lean, but there were no associations between serum cholesterol and triglyceride levels and Ad-36 exposure. Positive associations were found between Ad-36 exposure and age, race and gender. The study stands in contrast to previous work that has shown a positive relationship between Ad-36 exposure and (1) obesity, and (2) levels of serum cholesterol and triglycerides. In this study there was no association in either case. Unanticipated relationships between Ad-36 exposure and age, race and gender were found, and this is the first time that such a link between Ad-36 exposure and demographics has been found.

HIGHER SERUM TOTAL CHOLESTEROL LEVELS IN LATE MIDDLE AGE ARE ASSOCIATED WITH GLUCOSE HYPOMETABOLISM IN BRAIN REGIONS AFFECTED BY ALZHEIMER’S DISEASE AND NORMAL AGING

PubMed Central

Reiman, Eric M.; Chen, Kewei; Langbaum, Jessica B.S.; Lee, Wendy; Reschke, Cole; Bandy, Daniel; Alexander, Gene E.; Caselli, Richard J.

2010-01-01

Epidemiological studies suggest that higher midlife serum total cholesterol levels are associated with an increased risk of Alzheimer’s disease (AD). Using fluorodeoxyglucose positron emission tomography (PET) in the study of cognitively normal late-middle-aged people, we demonstrated an association between apolipoprotein E (APOE) ε4 gene dose, the major genetic risk factor for late-onset AD, and lower measurements of the cerebral metabolic rate for glucose (CMRgl) in AD-affected brain regions, we proposed using PET as a presymptomatic endophenotype to evaluate other putative AD risk modifiers, and we then used it to support an aggregate cholesterol-related genetic risk score in the risk of AD. In the present study, we used PET to investigate the association between serum total cholesterol levels and cerebral metabolic rate for glucose metabolism (CMRgl) in 117 cognitively normal late middle-aged APOE ε4 homozygotes, heterozygotes and noncarriers. Higher serum total cholesterol levels were associated with lower CMRgl bilaterally in precuneus, parietotemporal and prefrontal regions previously found to be preferentially affected by AD, and in additional frontal regions previously found to be preferentially affected by normal aging. The associations were greater in APOE ε4 carriers than non-carriers in some of the AD-affected brain regions. We postulate the higher midlife serum total cholesterol levels accelerate brain processes associated with normal aging and conspire with other risk factors in the predisposition to AD. We propose using PET in proof-of-concept randomized controlled trials to rapidly evaluate the effects of midlife cholesterol-lowering treatments on the brain changes associated with normal aging and AD. PMID:19631758

Perceived Effectiveness of Antismoking Ads and Association with Quit Attempts Among Smokers: Evidence from the Tips From Former Smokers Campaign.

PubMed

Davis, Kevin C; Duke, Jennifer; Shafer, Paul; Patel, Deesha; Rodes, Robert; Beistle, Diane

2017-08-01

Measures of perceived effectiveness (PE) of ads have been validated to predict changes in cognitive precursors of quit attempts, but a relationship between PE and actual quit attempts has not been shown in population-based studies. We analyzed smokers' PE ratings of ads from the national Tips From Former Smokers (Tips) campaign to (1) establish the validity of PE in predicting quit attempts in a large, nationally representative sample of smokers; (2) identify behavioral and demographic correlates of PE among respondents; and (3) examine whether PE is influenced by matching the race/ethnicity of ad participants with that of the ad viewer. We used survey data from two waves (baseline and follow-up) of a longitudinal online cohort of adult U.S. cigarette smokers. Respondents were shown one or more of 14 Tips campaign ads and were asked to assess each ad in terms of PE. We used multivariate models to estimate the association between baseline PE and prospective quit attempts; cross-sectional associations between PE and various respondent characteristics, including race/ethnicity, desire to quit, and health conditions; and the association between race/ethnicity of respondents and Tips ad participants. Higher PE at baseline was associated with increased odds of a quit attempt at follow-up. Higher PE scores were associated with non-Hispanic black race, Hispanic ethnicity, higher desire to quit, presence of a chronic health condition, and presence of a mental health condition. There was no relationship between PE scores and matched race/ethnicity of the respondent and Tips ad participants. This is the first study to demonstrate an association between PE scores for antismoking ads and prospective quit attempts in a large, nationally representative sample of smokers. Our findings also provide strong evidence that racial/ethnic minority subpopulations, including non-Hispanic blacks and Hispanics, react more favorably to Tips campaign ads irrespective of race/ethnicity of the ad participant. This suggests that message characteristics (e.g., graphic visuals and emotional content) may play a more important role in PE than race/ethnicity of ad participants.

Body composition is associated with physical activity in daily life as measured using a triaxial accelerometer in both men and women.

PubMed

den Hoed, M; Westerterp, K R

2008-08-01

Activity-related energy expenditure is the most variable component of total energy expenditure and thus an important determinant of energy balance. To determine whether body composition is related to physical activity in both men and women. A total of 134 healthy participants were recruited (80 women, 54 men; aged 21+/-2 years; body mass index, 22.0+/-2.4). Physical activity was measured for a period of 2 weeks using a triaxial accelerometer for movement registration (Tracmor). Percentage body fat (%BF) was determined by underwater weighing and deuterium dilution according to Siri's three-compartment model. The participant characteristics-body mass, height and gender together explained a substantial part of the variation in %BF (R(2)=0.75, SEE=4.0%). Adding physical activity to the model increased the explained variation in %BF with 4% (R(2)=0.79, SEE=3.7%, P<0.001). Taking seasonality into account by adding the number of daylight hours as an independent variable further increased the explained variation with 1% (R(2)=0.80, SEE=3.7%, P<0.05). In analogy, the association was evaluated for both genders separately. In women, %BF and physical activity were significantly associated (P<0.001). In men, %BF was only associated with physical activity when seasonality was taken into account as well (P<0.05). This probably resulted from men participating more in season bound sports, because an association was found without adjusting for seasonality when only men with a consistent year-round participation in sports were considered. Evidence was found for an association between body composition and physical activity in both genders. A consistent year-round degree of physical activity appears to be a prerequisite to reveal the association. Moreover, Tracmor-assessed physical activity improves the estimate of %BF when a participant's characteristics are taken into account.

Decreased Glucose Metabolism in Medial Prefrontal Areas is Associated with Nutritional Status in Patients with Prodromal and Early Alzheimer's Disease.

PubMed

Sugimoto, Taiki; Nakamura, Akinori; Kato, Takashi; Iwata, Kaori; Saji, Naoki; Arahata, Yutaka; Hattori, Hideyuki; Bundo, Masahiko; Ito, Kengo; Niida, Shumpei; Sakurai, Takashi

2017-01-01

Weight loss is frequently observed in patients with Alzheimer's disease (AD); however, the underlying mechanisms are not well understood. To clarify the associations between nutritional status and AD-related brain changes using Pittsburgh Compound-B (PiB)-PET, fluorodeoxyglucose (FDG)-PET, and structural MRI. The subjects were 34 amyloid-β (Aβ)-positive individuals with mild cognitive impairment or early AD (prodromal/early AD), and 55 Aβ-negative cognitively normal (CN) subjects who attended the Multimodal Neuroimaging for AD Diagnosis (MULNIAD) study. Nutritional status of the subjects was assessed by body mass index and waist to height ratio (waist circumference/height). The associations between nutritional status and brain changes were examined by multiple regression analysis using statistical parametric mapping. In the prodromal/early AD group, nutritional status was significantly positively correlated with regional cerebral glucose metabolism (rCGM) in the medial prefrontal cortices, while different topographical associations were seen in the CN group, suggesting these changes were AD-specific. Aβ deposition and gray matter volume were not significantly associated with nutritional status. Sub-analysis in the prodromal/early AD group demonstrated that fat mass index, but not fat-free mass index, was positively correlated with rCGM in the medial prefrontal areas. This present study provides preliminary results suggesting that hypometabolism in the medial prefrontal areas is specifically associated with AD-related weight loss, and decrease in fat mass may have a key role.

Polymorphisms of CHAT but not TFAM or VR22 are Associated with Alzheimer Disease Risk.

PubMed

Gao, Lili; Zhang, Yan; Deng, Jinghua; Yu, Wenbing; Yu, Yunxia

2016-06-07

BACKGROUND Alzheimer disease (AD) is a chronic neurodegenerative disease that is one of the most prevalent health problems among seniors. The cause of AD has not yet been elucidated, but many risk factors have been identified that might contribute to the pathogenesis and prognosis of AD. We conducted a meta-analysis of studies involving CHAT, TFAM, and VR22 polymorphisms and AD susceptibility to further understand the pathogenesis of AD. MATERIAL AND METHODS PubMed/Medline, Embase, Web of Science, the Cochrane Library, and Google Scholar were searched for relevant articles. Rs1880676, rs2177369, rs3810950, and rs868750 of CHAT; rs1937 and rs2306604 of TFAM; and rs10997691 and rs7070570 of VR22 are studied in this meta-analysis. RESULTS A total of 51 case-control studies with 16 446 cases and 16 057 controls were enrolled. For CHAT, rs2177369 (G>A) in whites and rs3810950 (G>A) in Asians were found to be associated with AD susceptibility. No association was detected between rs1880676 and rs868750 and AD risk. For TFAM and VR22, no significant association was detected in studied single-nucleotide polymorphisms (SNPs). CONCLUSIONS Rs2177369 and rs3810950 of CHAT are associated with AD susceptibility, but rs1880676 and rs868750 are not. Rs1937 and rs2306604 of TFAM, and rs10997691 and rs7070570 of VR22 are not significantly associated with AD risk.

Visualizing Hyperactivation in Neurodegeneration Based on Prefrontal Oxygenation: A Comparative Study of Mild Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls

PubMed Central

Yap, Kah Hui; Ung, Wei Chun; Ebenezer, Esther G. M.; Nordin, Nadira; Chin, Pui See; Sugathan, Sandheep; Chan, Sook Ching; Yip, Hung Loong; Kiguchi, Masashi; Tang, Tong Boon

2017-01-01

Background: Cognitive performance is relatively well preserved during early cognitive impairment owing to compensatory mechanisms. Methods: We explored functional near-infrared spectroscopy (fNIRS) alongside a semantic verbal fluency task (SVFT) to investigate any compensation exhibited by the prefrontal cortex (PFC) in Mild Cognitive Impairment (MCI) and mild Alzheimer's disease (AD). In addition, a group of healthy controls (HC) was studied. A total of 61 volunteers (31 HC, 12 patients with MCI and 18 patients with mild AD) took part in the present study. Results: Although not statistically significant, MCI exhibited a greater mean activation of both the right and left PFC, followed by HC and mild AD. Analysis showed that in the left PFC, the time taken for HC to achieve the activation level was shorter than MCI and mild AD (p = 0.0047 and 0.0498, respectively); in the right PFC, mild AD took a longer time to achieve the activation level than HC and MCI (p = 0.0469 and 0.0335, respectively); in the right PFC, HC, and MCI demonstrated a steeper slope compared to mild AD (p = 0.0432 and 0. 0107, respectively). The results were, however, not significant when corrected by the Bonferroni-Holm method. There was also found to be a moderately positive correlation (R = 0.5886) between the oxygenation levels in the left PFC and a clinical measure [Mini-Mental State Examination (MMSE) score] in MCI subjects uniquely. Discussion: The hyperactivation in MCI coupled with a better SVFT performance may suggest neural compensation, although it is not known to what degree hyperactivation manifests as a potential indicator of compensatory mechanisms. However, hypoactivation plus a poorer SVFT performance in mild AD might indicate an inability to compensate due to the degree of structural impairment. Conclusion: Consistent with the scaffolding theory of aging and cognition, the task-elicited hyperactivation in MCI might reflect the presence of compensatory mechanisms and hypoactivation in mild AD could reflect an inability to compensate. Future studies will investigate the fNIRS parameters with a larger sample size, and their validity as prognostic biomarkers of neurodegeneration. PMID:28919856

Method for creating high carbon content products from biomass oil

DOEpatents

Parker, Reginald; Seames, Wayne

2012-12-18

In a method for producing high carbon content products from biomass, a biomass oil is added to a cracking reactor vessel. The biomass oil is heated to a temperature ranging from about 100.degree. C. to about 800.degree. C. at a pressure ranging from about vacuum conditions to about 20,700 kPa for a time sufficient to crack the biomass oil. Tar is separated from the cracked biomass oil. The tar is heated to a temperature ranging from about 200.degree. C. to about 1500.degree. C. at a pressure ranging from about vacuum conditions to about 20,700 kPa for a time sufficient to reduce the tar to a high carbon content product containing at least about 50% carbon by weight.

Differences in STEM degree attainment by region, ethnicity, and degree type

NASA Astrophysics Data System (ADS)

Koledoye, Kimberly A.

Purpose One purpose of this study was to determine the extent to which a difference was present in the STEM degree attainment of all students and particularly of URMs between the 2001 and the 2009 academic year. The second purpose of this study was to determine the extent to which a difference was present in the attainment of STEM associate degrees and bachelor degrees of all students and particularly of URMs awarded between the 2001 and the 2009 academic year. Another purpose of this study was to determine the extent to which a difference existed in STEM associate degree and STEM bachelor degree attainment among geographic regions between the 2001 and the 2009 academic years. The extent to which a difference existed in the STEM bachelor degree and associate degree attainment of URMs among geographic regions between the 2001 to the 2009 academic year was ascertained. The final purpose of this study was to determine the extent to which a difference was present in STEM associate degree and bachelor degree attainment of all students and particularly URMs as a function of degree type between the 2001 academic year and the 2009 academic year. Methodology Archival data from the Integrated Postsecondary Education Data System were utilized to compare STEM degree attainment for regions, regions for URMs, STEM degree attainment overall and for URMs, STEM degree attainment classified by associate degrees and bachelor degrees for all students and URMs, and STEM degree attainment of associate degrees and bachelor degrees for all students and URMs by specific degree type between 2001 and 2009. Findings In this non-experimental causal comparative investigation, statistically significant differences were revealed in 95 of the 165 comparisons. Declining associate degree attainment was concerning, particularly in the computer and information sciences and engineering and engineering technologies. Moderate increases were determined in bachelor degree attainment with statistically significant differences identified in all STEM degree areas. Women had more increases than other URMs, and degree attainment by geographic region varied widely. Given the strong national need for more STEM graduates, reason for concerns are raised by the results of this investigation. KEY WORDS: STEM degrees, Associate, Bachelor, IPEDS

Effects of curing sodium nitrite additive and natural meat fat on growth control of Listeria monocytogenes by the bacteriocin-producing Lactobacillus curvatus strain CWBI-B28.

PubMed

Kouakou, P; Ghalfi, H; Destain, J; Dubois-Dauphin, R; Evrard, P; Thonart, P

2009-09-01

In realistic model meat systems, the separate and combined effects of fat content and sodium nitrite on the antilisterial activity of the bacteriocin of Lactobacillus curvatus CWBI-B28 were studied. In laboratory fermentations where Listeria monocytogenes was co-cultured at 4 degrees C with bacteriocin-producing CWBI-B28 in lean pork meat (fat content: 13%) without added nitrite, a strong antilisterial effect was observed after one week. The effect was maintained for an additional week, after which a slight and very gradual rebound was observed. Both added nitrite (20 ppm) and a high-fat content (43%) were found to antagonise this antilisterial effect, the Listeria cfu count reached after six weeks being 200 times as high in high-fat meat with added nitrite than in lean meat without nitrite. This antagonism could not be attributed to slower growth of the bacteriocin-producing strain, since CWBI-B28 grew optimally in fat-rich meat with 20 ppm sodium nitrite. Bacteriocin activity was also measured in the samples. The observed activity levels are discussed in relation to the degree of antilisterial protection conferred.

Optimized synthesis of lipase-catalyzed hexyl acetate in n-hexane by response surface methodology.

PubMed

Shieh, C J; Chang, S W

2001-03-01

Hexyl acetate, a short-chain ester with fruity odor, is a significant green note flavor compound and widely used in the food industry. The ability for immobilized lipase from Mucor miehei (Lipozyme IM-77) to catalyze the transesterification of hexanol with triacetin was investigated in this study. Response surface methodology and five-level-five-factor central composite rotatable design were adopted to evaluate the effects of synthesis variables, such as reaction time (2-10 h), temperature (25-65 degrees C), enzyme amount (10-50%; 0.024-0.118 BAUN), substrate molar ratio of triacetin to hexanol (1:1 to 3:1), and added water content (0-20%) on percentage molar conversion of hexyl acetate. The results showed that reaction temperature and substrate molar ratio were the most important parameters and that added water content had less of an effect on percent molar conversion. On the basis of canonical analysis, optimum synthesis conditions were as follows: reaction time, 7.7 h; temperature, 52.6 degrees C; enzyme amount, 37.1% (0.089 BAUN); substrate molar ratio, 2.7:1; and added water, 12.5%. The predicted value was 88.9% molar conversion, and the actual experimental value was 86.6% molar conversion.

The effect of increased genetic risk for Alzheimer’s disease on hippocampal and amygdala volume

PubMed Central

Lupton, Michelle K.; Strike, Lachlan; Hansell, Narelle K.; Wen, Wei; Mather, Karen A.; Armstrong, Nicola J.; Thalamuthu, Anbupalam; McMahon, Katie L.; de Zubicaray, Greig I.; Assareh, Amelia A.; Simmons, Andrew; Proitsi, Petroula; Powell, John F.; Montgomery, Grant W.; Hibar, Derrek P.; Westman, Eric; Tsolaki, Magda; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Velas, Bruno; Lovestone, Simon; Brodaty, Henry; Ames, David; Trollor, Julian N.; Martin, Nicholas G.; Thompson, Paul M.; Sachdev, Perminder S.; Wright, Margaret J.

2016-01-01

Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer’s disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive impairment [MCI]) and 467 young (16–30 years) adults. An AD polygenic risk score combining common risk variants excluding apolipoprotein E (APOE), and a single nucleotide polymorphism in TREM2, were both associated with reduced hippocampal volume in healthy older adults and those with MCI. APOE ɛ4 was associated with hippocampal and amygdala volume in those with AD and MCI but was not associated in healthy older adults. No associations were found in young adults. Genetic risk for AD affects the hippocampus before the clinical symptoms of AD, reflecting a neurodegenerative effect before clinical manifestations in older adults. PMID:26973105

Differential brain responses to cries of infants with autistic disorder and typical development: an fMRI study.

PubMed

Venuti, Paola; Caria, Andrea; Esposito, Gianluca; De Pisapia, Nicola; Bornstein, Marc H; de Falco, Simona

2012-01-01

This study used fMRI to measure brain activity during adult processing of cries of infants with autistic disorder (AD) compared to cries of typically developing (TD) infants. Using whole brain analysis, we found that cries of infants with AD compared to those of TD infants elicited enhanced activity in brain regions associated with verbal and prosodic processing, perhaps because altered acoustic patterns of AD cries render them especially difficult to interpret, and increased activity in brain regions associated with emotional processing, indicating that AD cries also elicit more negative feelings and may be perceived as more aversive and/or arousing. Perceived distress engendered by AD cries related to increased activation in brain regions associated with emotional processing. This study supports the hypothesis that cry is an early and meaningful anomaly displayed by children with AD. It could be that cries associated with AD alter parent-child interactions much earlier than the time that reliable AD diagnosis normally occurs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Maternal and anaesthesia-related risk factors and incidence of spinal anaesthesia-induced hypotension in elective caesarean section: A multinomial logistic regression

PubMed Central

Fakherpour, Atousa; Ghaem, Haleh; Fattahi, Zeinabsadat; Zaree, Samaneh

2018-01-01

Background and Aims: Although spinal anaesthesia (SA) is nowadays the preferred anaesthesia technique for caesarean section (CS), it is associated with considerable haemodynamic effects, such as maternal hypotension. This study aimed to evaluate a wide range of variables (related to parturient and anaesthesia techniques) associated with the incidence of different degrees of SA-induced hypotension during elective CS. Methods: This prospective study was conducted on 511 mother–infant pairs, in which the mother underwent elective CS under SA. The data were collected through preset proforma containing three parts related to the parturient, anaesthetic techniques and a table for recording maternal blood pressure. It was hypothesized that some maternal (such as age) and anaesthesia-related risk factors (such as block height) were associated with occurance of SA-induced hypotension during elective CS. Results: The incidence of mild, moderate and severe hypotension was 20%, 35% and 40%, respectively. Eventually, ten risk factors were found to be associated with hypotension, including age >35 years, body mass index ≥25 kg/m2, 11–20 kg weight gain, gravidity ≥4, history of hypotension, baseline systolic blood pressure (SBP) <120 mmHg and baseline heart rate >100 beats/min in maternal modelling, fluid preloading ≥1000 ml, adding sufentanil to bupivacaine and sensory block height >T4in anaesthesia-related modelling (P < 0.05). Conclusion: Age, body mass index, weight gain, gravidity, history of hypotension, baseline SBP and heart rate, fluid preloading, adding sufentanil to bupivacaine and sensory block hieght were the main risk factors identified in the study for SA-induced hypotension during CS. PMID:29416149

Thermodynamic study on competitive solubilization of cholesterol and beta-sitosterol in bile salt micelles.

PubMed

Matsuoka, Keisuke; Hirosawa, Takashi; Honda, Chikako; Endo, Kazutoyo; Moroi, Yoshikiyo; Shibata, Osamu

2007-07-01

Differences in the preferential solubilization of cholesterol and competitive solubilizates (beta-sitosterol and aromatic compounds) in bile salt micelles was systematically studied by changing the molar ratio of cholesterol to competitive solubilizates. The cholesterol solubility in a mixed binary system (cholesterol and beta-sitosterol) was almost half that of the cholesterol alone system, regardless of the excess beta-sitosterol quantity added. On the other hand, the mutual solubilities of cholesterol and pyrene were not inhibited by their presence in binary mixed crystals. Finally, the cholesterol solubility was measured by changing the alkyl chain length of n-alkylbenzenes. When tetradecylbenzene was added to the bile solution, the cholesterol solubility decreased slightly and was below the original cholesterol solubility. Based on Gibbs energy change (DeltaG degrees ) for solubilization, chemicals that inhibit cholesterol solubility in their combined crystal systems showed a larger negative DeltaG degrees value than cholesterol alone.

[Effect of three kinds of rare earth oxides on chromaticity and mechanical properties of zirconia ceramic].

PubMed

Huang, Hui; Zhang, Fu-qiang; Sun, Jing; Gao, Lian

2006-06-01

To evaluate the colouration of zirconia ceramic by adding three kinds of rare earth oxides. The influence of the pigments concentration on the mechanical properties and the microstructure was also analyzed. Added different concentrations of CeO(2), Er(2)O(3) and Pr(6)O(11) in tetragonal zirconia poly crystals stabilized with 3 mol% yttria (3Y-T2P) powder, compacted at 200 MPa using cold isostatic pressure, and sintered to 1 400 degrees C. The heating rate was 150 degrees C/h and the dwelling time was 2 hours. The chromaticity of sintered bodies was measured with chroma meter. The relative density, hardness, flexure strength and fracture toughness were investigated as well. The phase stability of the colorized and pure zirconia was evaluated by X-ray diffraction (XRD) using an automated diffractometer. The microstructures of the specimens were evaluated by scanning electron microscope (SEM). Several kinds of color achieved by the different pigments praseodym oxide, cerium oxide and erbium oxide were presented in the CIELab system. The a* value increased with the added amount of Er(2)O(3), while b* value rose with the increasing amount of CeO(2) and Pr(6)O(11). However, three pigments failed to decrease L* value and the sintered body appeared too bright. Adding three pigments influenced flexure strength of zirconia ceramic significantly, but had little influence on the hardness and fracture toughness. Microscopy revealed the relationship between the porosity and shapes of grains was correlated to strength of the diphase ceramics. No additional phase could be detected by XRD, except t-ZrO(2) in all colorized samples after sintering at 1 400 degrees C for 120 min. Zirconia ceramic can be colorized by CeO(2), Er(2)O(3), and Pr(6)O(11). Pigments even in a small amount influence the mechanical properties of the colorized zirconia material, which necessitates further investigation.

Control of pyrite addition in coal liquefaction process

DOEpatents

Schmid, Bruce K.; Junkin, James E.

1982-12-21

Pyrite addition to a coal liquefaction process (22, 26) is controlled (118) in inverse proportion to the calcium content of the feed coal to maximize the C.sub.5 --900.degree. F. (482.degree. C.) liquid yield per unit weight of pyrite added (110). The pyrite addition is controlled in this manner so as to minimize the amount of pyrite used and thus reduce pyrite contribution to the slurry pumping load and disposal problems connected with pyrite produced slag.

Material and method for promoting the growth of anaerobic bacteria

DOEpatents

Adler, Howard I.

1984-01-01

A material and method for promoting the growth of anaerobic bacteria which includes a nutrient media containing a hydrogen donor and sterile membrane fragments of bacteria having an electron transfer system which reduces oxygen to water. Dissolved oxygen in the medium is removed by adding the sterile membrane fragments to the nutrient medium and holding the medium at a temperature of about 10.degree. to about 60.degree. C. until the dissolved oxygen is removed.

A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin.

PubMed

Deming, Yuetiva; Xia, Jian; Cai, Yefei; Lord, Jenny; Holmans, Peter; Bertelsen, Sarah; Holtzman, David; Morris, John C; Bales, Kelly; Pickering, Eve H; Kauwe, John; Goate, Alison; Cruchaga, Carlos

2016-01-01

Genome-wide association studies have associated clusterin (CLU) variants with Alzheimer's disease (AD). However, the role of CLU on AD pathogenesis is not totally understood. We used cerebrospinal fluid (CSF) and plasma CLU levels as endophenotypes for genetic studies to understand the role of CLU in AD. CSF, but not plasma, CLU levels were significantly associated with AD status and CSF tau/amyloid-beta ratio, and highly correlated with CSF apolipoprotein E (APOE) levels. Several loci showed almost genome-wide significant associations including LINC00917 (p = 3.98 × 10(-7)) and interleukin 6 (IL6, p = 9.94 × 10(-6), in the entire data set and in the APOE ε4- individuals p = 7.40 × 10(-8)). Gene ontology analyses suggest that CSF CLU levels may be associated with wound healing and immune response which supports previous functional studies that demonstrated an association between CLU and IL6. CLU may play a role in AD by influencing immune system changes that have been observed in AD or by disrupting healing after neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

A potential endophenotype for Alzheimer’s disease: cerebrospinal fluid clusterin

PubMed Central

Deming, Yuetiva; Xia, Jian; Cai, Yefei; Lord, Jenny; Holmans, Peter; Bertelsen, Sarah; Holtzman, David; Morris, John C; Bales, Kelly; Pickering, Eve H; Kauwe, John; Goate, Alison; Cruchaga, Carlos

2016-01-01

Genome-wide association studies have associated clusterin (CLU) variants with Alzheimer’s disease (AD). However the role of CLU on AD pathogenesis is not totally understood. We used CSF and plasma CLU levels as endophenotypes for genetic studies to understand the role of CLU in AD. CSF, but not plasma, CLU levels were significantly associated with AD status and CSF tau/Aβ ratio, and highly correlated with CSF apolipoprotein E (APOE) levels. Several loci showed almost genome-wide significant associations including LINC00917 (p=3.98×10−7) and interleukin 6 (IL6, p=9.94×10−6, in the entire dataset and in the APOE ε4- individuals p=7.40×10−8). Gene-ontology analyses suggest that CSF CLU levels may be associated with wound healing and immune response which supports previous functional studies that demonstrated an association between CLU and IL6. CLU may play a role in AD by influencing immune system changes that have been observed in AD or by disrupting healing after neurodegeneration. PMID:26545630

Stability of ondansetron hydrochloride injection in various beverages.

PubMed

Yamreudeewong, W; Danthi, S N; Hill, R A; Fox, J L

1995-09-15

The stability of ondansetron hydrochloride injection in beverages likely to be acceptable to patients was studied. Ondansetron hydrochloride injection (containing ondansetron 2 mg/mL) was added to apple juice, fruit punch, cherry-flavored drink, carbonated soft drinks, and hot tea to provide a nominal ondansetron concentration of 32.8, 64.5, or 95.2 micrograms/mL. Samples were stored at -3 to 28 degrees C (noncarbonated-beverage mixtures except tea), 2 to 28 degrees C (carbonated-beverage mixtures), and 25 degrees C (tea) and assayed for ondansetron concentration by high-performance liquid chromatography at 6, 24, 48, and 72 hours (noncarbonated-beverage mixtures except tea); 6, 24, and 48 hours (carbonated-beverage mixtures); and 1 hour (tea). More than 95% of the initial ondansetron concentration was retained in apple juice, fruit punch, cherry-flavored drink, Sprite, and Diet Coke throughout the periods studied. A precipitate formed immediately after ondansetron was added to hot tea, but the drug was chemically stable for at least one hour in this preparation. Ondansetron hydrochloride injection 32.7, 64.5, and 95.2 micrograms/mL (expressed as free base) was stable in various beverages when stored at -3 to 28 degrees C for up to 72 hours. Ondansetron at these same concentrations precipitated in hot tea preparations but was chemically stable for at least one hour.

Effect of storage conditions on quality of prebiotic dark chocolate.

PubMed

Norhayati, H; Rasma, Suzielawanis I; Mohd, Khan A

2013-04-01

A prebiotic such as inulin is a well-known functional plant food ingredient. It is capable of stimulating growth of beneficial bifidobacteria in the intestine thus protecting against intestinal infections, preventing constipation, increasing mineral absorption, reducing the incidence of colon cancer, and producing B vitamins. Inulin added to food therefore has to be stable during food processing especially against heat treatment, low pH and Maillard reaction. Newly developed dark chocolate, DC-1, containing inulin (replacing sugar component) as an added value, was stored at 18 degrees C, 60% relative humidity and 25 degrees C, 80% relative humidity (RH) to determine shelf life stability compared to control dark chocolate, DC-0 (with high content of sugar). Sensory evaluation (quantitative descriptive analysis), water activity (a(w)), microbiological content and presence of inulin after storage of the prebiotic chocolate under both conditions were evaluated to determine shelf life. The DC-1 chocolate had at least 12 months of shelf life at 18 degrees C, 60% RH with better acceptance than DC-0; moreover, it did not experience microbiological and inulin content changes. At 25 degrees C, 80% RH, the growth of Aspergillus sp. was observed on the surface of both DC-0 and DC-1 with a(w) > 0.50 after a 2-month storage. Shelf life stability of DC-1 is almost similar to DC-0.

Economic burden associated with alcohol dependence in a German primary care sample: a bottom-up study.

PubMed

Manthey, Jakob; Laramée, Philippe; Parrott, Steve; Rehm, Jürgen

2016-08-31

A considerable economic burden has been repeatedly associated with alcohol dependence (AD) - mostly calculated using aggregate data and alcohol-attributable fractions (top-down approach). However, this approach is limited by a number of assumptions, which are hard to test. Thus, cost estimates should ideally be validated with studies using individual data to estimate the same costs (bottom-up approach). However, bottom-up studies on the economic burden associated with AD are lacking. Our study aimed to fill this gap using the bottom-up approach to examine costs for AD, and also stratified the results by the following subgroups: sex, age, diagnostic approach and severity of AD, as relevant variations could be expected by these factors. 1356 primary health care patients, representative for two German regions. AD was diagnosed by a standardized instrument and treating physicians. Individual costs were calculated by combining resource use and productivity data representing a period of six months prior to the time of interview, with unit costs derived from the literature or official statistics. The economic burden associated with AD was determined via excess costs by comparing utilization of various health care resources and impaired productivity between people with and without AD, controlling for relevant confounders. Additional analyses for several AD characteristics were performed. Mean costs among alcohol dependent patients were 50 % higher compared to the remaining patients, resulting in 1836 € excess costs per alcohol dependent patient in 6 months. More than half of these excess costs incurred through increased productivity loss among alcohol dependent patients. Treatment for alcohol problems represents only 6 % of these costs. The economic burden associated with AD incurred mainly among males and among 30 to 49 year old patients. Both diagnostic approaches were significantly related to the economic burden, while costs increased with alcohol use disorder severity but not with other AD severity indicators. Our study confirms previous studies using top-down approaches to estimate the economic burden associated with AD. Further, we highlight the need for efforts aimed at preventing adverse outcomes for health and occupational situation associated with alcohol dependence based on factors associated with particularly high economic burden.

Sugars and risk of mortality in the NIH-AARP Diet and Health Study.

PubMed

Tasevska, Natasha; Park, Yikyung; Jiao, Li; Hollenbeck, Albert; Subar, Amy F; Potischman, Nancy

2014-05-01

Although previous studies have linked intake of sugars with incidence of cancer and other chronic diseases, its association with mortality remains unknown. We investigated the association of total sugars, added sugars, total fructose, added fructose, sucrose, and added sucrose with the risk of all-cause, cardiovascular disease, cancer, and other-cause mortality in the NIH-AARP Diet and Health Study. The participants (n = 353,751), aged 50-71 y, were followed for up to 13 y. Intake of individual sugars over the previous 12 mo was assessed at baseline by using a 124-item NIH Diet History Questionnaire. In fully adjusted models (fifth quartile compared with first quartile), all-cause mortality was positively associated with the intake of total sugars [HR (95% CI): 1.13 (1.06, 1.20); P-trend < 0.0001], total fructose [1.10 (1.04, 1.17); P-trend < 0.0001], and added fructose [1.07 (1.01, 1.13); P-trend = 0.005) in women and total fructose [1.06 (1.01, 1.10); P-trend = 0.002] in men. In men, a weak inverse association was found between other-cause mortality and dietary added sugars (P-trend = 0.04), sucrose (P-trend = 0.03), and added sucrose (P-trend = 0.006). Investigation of consumption of sugars by source showed that the positive association with mortality risk was confined only to sugars from beverages, whereas the inverse association was confined to sugars from solid foods. In this large prospective study, total fructose intake was weakly positively associated with all-cause mortality in both women and men, whereas added sugar, sucrose, and added sucrose intakes were inversely associated with other-cause mortality in men. In our analyses, intake of added sugars was not associated with an increased risk of mortality. The NIH-AARP Diet and Health Study was registered at clinicaltrials.gov as NCT00340015.

Sugars and risk of mortality in the NIH-AARP Diet and Health Study1234

PubMed Central

Tasevska, Natasha; Park, Yikyung; Jiao, Li; Hollenbeck, Albert; Subar, Amy F; Potischman, Nancy

2014-01-01

Background: Although previous studies have linked intake of sugars with incidence of cancer and other chronic diseases, its association with mortality remains unknown. Objective: We investigated the association of total sugars, added sugars, total fructose, added fructose, sucrose, and added sucrose with the risk of all-cause, cardiovascular disease, cancer, and other-cause mortality in the NIH-AARP Diet and Health Study. Design: The participants (n = 353,751), aged 50–71 y, were followed for up to 13 y. Intake of individual sugars over the previous 12 mo was assessed at baseline by using a 124-item NIH Diet History Questionnaire. Results: In fully adjusted models (fifth quartile compared with first quartile), all-cause mortality was positively associated with the intake of total sugars [HR (95% CI): 1.13 (1.06, 1.20); P-trend < 0.0001], total fructose [1.10 (1.04, 1.17); P-trend < 0.0001], and added fructose [1.07 (1.01, 1.13); P-trend = 0.005) in women and total fructose [1.06 (1.01, 1.10); P-trend = 0.002] in men. In men, a weak inverse association was found between other-cause mortality and dietary added sugars (P-trend = 0.04), sucrose (P-trend = 0.03), and added sucrose (P-trend = 0.006). Investigation of consumption of sugars by source showed that the positive association with mortality risk was confined only to sugars from beverages, whereas the inverse association was confined to sugars from solid foods. Conclusions: In this large prospective study, total fructose intake was weakly positively associated with all-cause mortality in both women and men, whereas added sugar, sucrose, and added sucrose intakes were inversely associated with other-cause mortality in men. In our analyses, intake of added sugars was not associated with an increased risk of mortality. The NIH-AARP Diet and Health Study was registered at clinicaltrials.gov as NCT00340015. PMID:24552754

Atopic dermatitis: Interaction between genetic variants of GSTP1, TNF, TLR2, and TLR4 and air pollution in early life.

PubMed

Hüls, Anke; Klümper, Claudia; MacIntyre, Elaina A; Brauer, Michael; Melén, Erik; Bauer, Mario; Berdel, Dietrich; Bergström, Anna; Brunekreef, Bert; Chan-Yeung, Moira; Fuertes, Elaine; Gehring, Ulrike; Gref, Anna; Heinrich, Joachim; Standl, Marie; Lehmann, Irina; Kerkhof, Marjan; Koppelman, Gerard H; Kozyrskyj, Anita L; Pershagen, Göran; Carlsten, Christopher; Krämer, Ursula; Schikowski, Tamara

2018-04-06

Associations between traffic-related air pollution (TRAP) and childhood atopic dermatitis (AD) remain inconsistent, possibly due to unexplored gene-environment interactions. The aim of this study was to examine whether a potential effect of TRAP on AD prevalence in children is modified by selected single nucleotide polymorphisms (SNPs) related to oxidative stress and inflammation. Doctor-diagnosed AD up to age 2 years and at 7-8 years, as well as AD symptoms up to age 2 years, was assessed using parental-reported questionnaires in six birth cohorts (N = 5685). Associations of nitrogen dioxide (NO 2 ) estimated at the home address of each child at birth and nine SNPs within the GSTP1, TNF, TLR2, or TLR4 genes with AD were examined. Weighted genetic risk scores (GRS) were calculated from the above SNPs and used to estimate combined marginal genetic effects of oxidative stress and inflammation on AD and its interaction with TRAP. GRS was associated with childhood AD and modified the association between NO 2 and doctor-diagnosed AD up to the age of 2 years (P(interaction) = .029). This interaction was mainly driven by a higher susceptibility to air pollution in TNF rs1800629 minor allele (A) carriers. TRAP was not associated with the prevalence of AD in the general population. The marginal genetic association of a weighted GRS from GSTP1, TNF, TLR2, and TLR4SNPs and its interaction with air pollution supports the role of oxidative stress and inflammation in AD. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Added Sugars and Cardiovascular Disease Risk in Children: A Scientific Statement From the American Heart Association.

PubMed

Vos, Miriam B; Kaar, Jill L; Welsh, Jean A; Van Horn, Linda V; Feig, Daniel I; Anderson, Cheryl A M; Patel, Mahesh J; Cruz Munos, Jessica; Krebs, Nancy F; Xanthakos, Stavra A; Johnson, Rachel K

2017-05-09

Poor lifestyle behaviors are leading causes of preventable diseases globally. Added sugars contribute to a diet that is energy dense but nutrient poor and increase risk of developing obesity, cardiovascular disease, hypertension, obesity-related cancers, and dental caries. For this American Heart Association scientific statement, the writing group reviewed and graded the current scientific evidence for studies examining the cardiovascular health effects of added sugars on children. The available literature was subdivided into 5 broad subareas: effects on blood pressure, lipids, insulin resistance and diabetes mellitus, nonalcoholic fatty liver disease, and obesity. Associations between added sugars and increased cardiovascular disease risk factors among US children are present at levels far below current consumption levels. Strong evidence supports the association of added sugars with increased cardiovascular disease risk in children through increased energy intake, increased adiposity, and dyslipidemia. The committee found that it is reasonable to recommend that children consume ≤25 g (100 cal or ≈6 teaspoons) of added sugars per day and to avoid added sugars for children <2 years of age. Although added sugars most likely can be safely consumed in low amounts as part of a healthy diet, few children achieve such levels, making this an important public health target. © 2017 American Heart Association, Inc.

Message content of alcohol moderation TV commercials: impact of corporate versus nonprofit sponsorship.

PubMed

Lavack, A M

1999-01-01

This content analysis examines a sample of 203 alcohol-related North American TV commercials dealing with alcohol moderation and driving under the influence (DUI), in order to determine whether the type of ad sponsor has an impact on the message content. Corporate sponsors, such as breweries and distillers, are compared to nonprofit sponsors such as governments and nonprofit organizations. Findings show that ads from corporate sponsors are less likely to make mention of threats or negative consequences, and are also less likely to use fear arousal. However, DUI/alcohol moderation ads from corporate sponsors and nonprofit sponsors do not differ in the degree to which they use humor or positive approaches.

Microporous crystals and synthesis schemes

DOEpatents

Tumas, William; Ott, Kevin C.; McCleskey, T. Mark; Yates, Matthew Z.; Birnbaum, Eva R.

2008-04-22

Novel zeolites are produced by combining a polar solute, a silicon or phosphorous source, and a structure directing agent. Surfactants and a hydrophobic solvent are added to the previously mixed three species and shaken to disperse the surfactants. The reverse microemulsion is stirred overnight, at about room temperature and then iced for five to ten minutes. A metal source is added vigorously shaken for about two minutes. The mixture is then aged for about two hours at about room temperature. A mineralizer is added and the resultant mixture aged for about two hours at about room temperature. The mixture is heated to about 180.degree. C., for a suitable time period. The final novel product is then isolated.

Microporous crystals and synthesis schemes

DOEpatents

Tumas, William; Ott, Kevin C.; McCleskey, T. Mark; Yates, Matthew Z.; Birnbaum, Eva R.

2005-09-27

Novel zeolites are produced by combining a polar solute, a silicon or phosphorous source, and a structure directing agent. Surfactants and a hydrophobic solvent are added to the previously mixed three species and shaken to disperse the surfactants. The reverse microemulsion is stirred overnight, at about room temperature and then iced for five to ten minutes. A metal source is added vigorously shaken for about two minutes. The mixture is then aged for about two hours at about room temperature. A mineralizer is added and the resultant mixture aged for about two hours at about room temperature. The mixture is heated to about 180.degree. C., for a suitable time period. The final novel product is then isolated.

Tin-silver-bismuth solders for electronics assembly

DOEpatents

Vianco, Paul T.; Rejent, Jerome A.

1995-01-01

A lead-free solder alloy for electronic assemblies composed of a eutectic alloy of tin and silver with a bismuth addition, x, of 0

Single Degree-of-Freedom Exoskeleton Mechanism Design for Thumb Rehabilitation*

PubMed Central

Yihun, Yimesker; Miklos, Robert; Perez-Gracia, Alba; Reinkensmeyer, David J.; Denney, Keith; Wolbrecht, Eric T.

2014-01-01

This paper presents the kinematic design of a spatial, 1-degree-of-freedom closed linkage to be used as an exoskeleton for thumb motion. Together with an already-designed finger mechanism, it forms a robotic device for hand therapy. The goal for the exoskeleton is to generate the desired grasping and pinching path of the thumb with one degree of freedom, rather than using a system actuating all its joints independently. In addition to the path of the thumb, additional constraints are added in order to control the position and size of the exoskeleton, reducing physical and sensory interference with the user. PMID:23366289

Research on the co-movement between high-end talent and economic growth: A complex network approach

NASA Astrophysics Data System (ADS)

Zhang, Zhen; Wang, Minggang; Xu, Hua; Zhang, Wenbin; Tian, Lixin

2018-02-01

The major goal of this paper is to focus on the co-movement between high-end talent and economic growth by a complex network approach. Firstly, the national high-end talent development efficiency from 1990 to 2015 is taken as the quantitative index to measure the development of high-end talent. The added values of the primary industry, secondary industry, tertiary industry are selected as economic growth indexes, and all the selected sample data are standardized by the mean value processing method. Secondly, let seven months as the length of the sliding window, and one month as the sliding step, then the grey correlation degrees between systems are measured using the slope correlation degrees, and the grey correlation degree sequence is mapped into the symbol series composed by three symbols { Y , O , N } based on the coarse graining method. Let three characters as a mode, the nodes are obtained by the modes according to the time sequence. Let the transformation between the modal be the edge, and the times of the transformation be weight, then the co-movement networks between national high-end talent development efficiency and the added values of the primary industry, secondary industry, tertiary industry are built respectively. Finally, the dynamic characteristics of the networks are analysed by the node strength, strength distribution, weighted clustering coefficient, conversion cycle of the modes and the transition between the co-movement modes. The results indicate that there are mutual influence and promotion relations between the national high-end talent development efficiency and the added values of the primary, secondary and tertiary industry.

Growth inhibition of heat-injured Enterococcus faecium by oligophosphates in a cured meat model.

PubMed

Houben, J H; Tjeerdsma-van Bokhoven, J L M

2004-12-01

Cells of two heat-resistant strains of Enterococcus faecium were heated and incubated in meat suspensions containing curing ingredients. The concentrations of the curing ingredients were those frequently used for pasteurized ham-type products, except that the concentrations of the oligophosphates (triphosphate and diphosphate) varied. Heating tests at 69 degrees C were performed with inoculated meat suspensions in heat-sealed plastic pouches. Numbers of bacteria were counted immediately after heating and in parallel series of heated pouches incubated at 37 degrees C. Plating was performed in Tryptone Dextrose Yeast Meat Peptonised Milk Agar (TDYMP); in TDYMP Agar to which the curing ingredients were added; and in TDYMP Agar to which the curing ingredients except oligophosphates were added. The inclusion of oligophosphates in the heating medium increased the heat-injury sustained by the E. faecium cells, and in combination with rather severe heat treatment even completely blocked the growth of surviving organisms in the meat suspension incubated at 37 degrees C. The presence of oligophosphates in the culture medium TDYMP Agar severely reduced the counts of freshly heated cells; however, this effect disappeared after repair and growth of the surviving organisms in the meat suspension.

Blending of palm oil, palm stearin and palm kernel oil in the preparation of table and pastry margarine.

PubMed

Norlida, H M; Md Ali, A R; Muhadhir, I

1996-01-01

Palm oil (PO ; iodin value = 52), palm stearin (POs1; i.v. = 32 and POs2; i.v. = 40) and palm kernel oil (PKO; i.v. = 17) were blended in ternary systems. The blends were then studied for their physical properties such as melting point (m.p.), solid fat content (SFC), and cooling curve. Results showed that palm stearin increased the blends melting point while palm kernel oil reduced it. To produce table margarine with melting point (m.p.) below 40 degrees C, the POs1 should be added at level of < or = 16%, while POs2 at level of < or = 20%. At 10 degrees C, eutectic interaction occur between PO and PKO which reach their maximum at about 60:40 blending ratio. Within the eutectic region, to maintain the SFC at 10 degrees C to be < or = 50%, POs1 may be added at level of < or = 7%, while POs2 at level of < or = 12%. The addition of palm stearin increased the blends solidification Tmin and Tmax values, while PKO reduced them. Blends which contained high amount of palm stearin showed melting point and cooling curves quite similar to that of pastry margarine.

Characteristics of Associate's Degree Attainers and Time to Associate's Degree. Web Tables. NCES 2012-271

ERIC Educational Resources Information Center

Green, Caitlin; Radwin, David

2012-01-01

The number of associate's degrees conferred by U.S. postsecondary institutions increased 30 percent from 1997 to 2007, from 571,000 to 745,000, and is projected to grow another 30 percent by 2020, a faster pace than the actual and projected growth in bachelor's degrees awarded. Despite the growing prevalence of associate's degrees, however, there…

Time to Degree: A National View of the Time Enrolled and Elapsed for Associate and Bachelor's Degree Earners. (Signature Report No. 11)

ERIC Educational Resources Information Center

Shapiro, Doug; Dundar, Afet; Wakhungu, Phoebe Khasiala; Yuan, Xin; Nathan, Angel; Hwang, Youngsik

2016-01-01

This report examines time to degree completion for a cohort of students who earned an associate degree as their first and only postsecondary degree or a bachelor's degree as their first four-year degree between July 1, 2014, and June 30, 2015. Overall, the average time enrolled for associate and bachelor's degree earners was 3.3 years and 5.1…

Effect of the nature of the counterion on the properties of anionic surfactants. 5. Self-association behavior and micellar properties of ammonium dodecyl sulfate.

PubMed

Tcacenco, Celize M; Zana, Raoul; Bales, Barney L

2005-08-25

Micelles formed in water from ammonium dodecyl sulfate (AmDS) are characterized using time-resolved fluorescence quenching (TRFQ), electron paramagnetic resonance (EPR), conductivity, Krafft temperature, and density measurements. TRFQ was used to measure the aggregation number, N, and the quenching rate constant of pyrene by dodecylpyridinium chloride, k(Q). N depends only on the concentration (C(aq)) of ammonium ions in the aqueous phase whether these counterions are derived from the surfactant alone or from the surfactant plus added ammonium chloride as follows: N = N0(C(aq)/cmc0)(gamma), where N0 is the aggregation number at the critical micelle concentration in the absence of added salt, cmc0, and is equal to 77, 70, and 61 at 16, 25, and 35 degrees C, respectively. The exponent gamma = 0.22 is independent of temperature in the range 16 to 35 degrees C. The fact that N depends only on C(aq) permits the determination of the micelle ionization degree (alpha) by employing various experimental approaches to exploit a recent suggestion (J. Phys. Chem. B 2001, 105, 6798) that N depends only on C(aq). Utilizing various combinations of salt and surfactant, values of alpha were obtained by finding common curves as a function of C(aq) of the following experimental results: the Krafft temperature, N, k(Q), the microviscosity of the Stern layer determined from the rotational correlation time of a spin probe, 5-doxyl stearic acid methyl ester, and the spin-probe sensed hydration of the micelle surface. The values of alpha, determined from applying the aggregation number-based definition of alpha to all of these quantities, were within experimental uncertainty of the values alpha = 0.19, 0.20, and 0.21 derived from conductivity measurements at 16, 25, and 35 degrees C, respectively. The volume fraction of the Stern layer occupied by water decreases as N increases. For AmDS micelles, both the hydration and its decrease are predicted by a simple theory of micelle hydration by fixing the parameters of the theory for sodium dodecyl sulfate and employing no further adjustable parameters. For a given value of N, the hydration decreases as the temperature increases.

A Frequency-Domain Substructure System Identification Algorithm

NASA Technical Reports Server (NTRS)

Blades, Eric L.; Craig, Roy R., Jr.

1996-01-01

A new frequency-domain system identification algorithm is presented for system identification of substructures, such as payloads to be flown aboard the Space Shuttle. In the vibration test, all interface degrees of freedom where the substructure is connected to the carrier structure are either subjected to active excitation or are supported by a test stand with the reaction forces measured. The measured frequency-response data is used to obtain a linear, viscous-damped model with all interface-degree of freedom entries included. This model can then be used to validate analytical substructure models. This procedure makes it possible to obtain not only the fixed-interface modal data associated with a Craig-Bampton substructure model, but also the data associated with constraint modes. With this proposed algorithm, multiple-boundary-condition tests are not required, and test-stand dynamics is accounted for without requiring a separate modal test or finite element modeling of the test stand. Numerical simulations are used in examining the algorithm's ability to estimate valid reduced-order structural models. The algorithm's performance when frequency-response data covering narrow and broad frequency bandwidths is used as input is explored. Its performance when noise is added to the frequency-response data and the use of different least squares solution techniques are also examined. The identified reduced-order models are also compared for accuracy with other test-analysis models and a formulation for a Craig-Bampton test-analysis model is also presented.

Antimicrobial effect of herb extracts against Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella typhimurium associated with beef.

PubMed

Cutter, C N

2000-05-01

The effects of plant extracts against pathogenic bacteria in vitro are well known, yet few studies have addressed the effects of these compounds against pathogens associated with muscle foods. A series of experiments was conducted to determine the effectiveness of a commercially available, generally recognized as safe, herb extract dispersed in sodium citrate (Protecta One) or sodium chloride (Protecta Two) against Escherichia coli O157:H7, Salmonella typhimurium, and Listeria monocytogenes associated with beef. In the first experiment, E. coli O157:H7, Salmonella typhimurium, and L. monocytogenes inoculated onto beef and subjected to surface spray treatments with 2.5% solutions of Protecta One or Protecta Two were not affected by immediate application (day 0) of the herbal extracts. However, after 7 days of storage at 4 degrees C, E. coli O157:H7 was reduced by >1.3 log10 CFU/cm2 by Protecta Two; L. monocytogenes was reduced by 1.8 and 1.9 log10 CFU/cm2 by Protecta One and Protecta Two, respectively; Salmonella typhimurium was not reduced >0.3 log10 CFU/cm2 by either extract by day 7. In the second experiment, 2.5% Protecta Two (wt/vol or wt/wt) added to inoculated lean and adipose beef trim, processed, and packaged as ground beef chubs (80% lean, 20% adipose), did not reduce pathogen populations >0.5 log10 CFU/g up to 14 days at 4 degrees C. In the third experiment, surface spray treatments of beef with 2.5% lactic acid or 2.5% solutions of Protecta One or Protecta Two, vacuum packaged, and stored up to 35 days at 4 degrees C did reduce E. coli O157:H7, L. monocytogenes, and Salmonella Typhimurium slightly. These studies suggest that the use of herb extracts may afford some reductions of pathogens on beef surfaces; however, the antimicrobial activity may be diminished in ground beef by adipose components.

Diurnal Salivary Alpha-amylase Dynamics among Dementia Family Caregivers

PubMed Central

Liu, Yin; Granger, Douglas A.; Kim, Kyungmin; Klein, Laura C.; Almeida, David M.; Zarit, Steven H.

2016-01-01

Objective The study examined diurnal regulation of salivary alpha-amylase (sAA) in association with daily stressors, adult day services (ADS) use, and other caregiving characteristics. Methods A sample of 165 family caregivers of individuals with dementia (IWD) completed an 8-day diary study. Caregivers provided 5 saliva samples across the 8 days. On some days, caregivers provided all or most of the care. On other days, their relative attended ADS for part of the day. A 3-level unconditional linear spline model was fit to describe the typical sAA diurnal rhythms. Predictors were then added to the unconditional model to test the hypotheses on ADS use and daily stressors. Results Daily ADS use did not have an effect on diurnal sAA regulation. However, controlling for daily ADS use, greater ADS use over the 8 days was associated with a more prominent rise between 30 minutes after wake-up and before lunch, and a more prominent decline between before lunch and late afternoon. Fewer ADS days were associated with a more flattened sAA diurnal rhythm. Additionally, greater daily care-related stressor exposures had a within-person association with lower sAA levels in the late afternoon. Care-related stressor exposures had significant within- and between-person associations with sAA diurnal slopes. Furthermore, daily positive experiences had a significant between-person association with sAA diurnal slopes. Conclusions Caring for a disabled family member may heighten the vulnerability to potential physiological conditions. Respite from care stressors from ADS use may have some biobehavioral benefits on sAA regulations. PMID:27786517

Diurnal salivary alpha-amylase dynamics among dementia family caregivers.

PubMed

Liu, Yin; Granger, Douglas A; Kim, Kyungmin; Klein, Laura C; Almeida, David M; Zarit, Steven H

2017-02-01

The study examined diurnal regulation of salivary alpha-amylase (sAA) in association with daily stressors, adult day services (ADS) use, and other caregiving characteristics. A sample of 165 family caregivers of individuals with dementia (IWD) completed an 8-day diary study. Caregivers provided 5 saliva samples across the 8 days. On some days, caregivers provided all or most of the care. On other days, their relative attended ADS for part of the day. A 3-level unconditional linear spline model was fit to describe the typical sAA diurnal rhythms. Predictors were then added to the unconditional model to test the hypotheses on ADS use and daily stressors. Daily ADS use did not have an effect on diurnal sAA regulation. However, controlling for daily ADS use, greater ADS use over the 8 days was associated with a more prominent rise between 30 min after wake-up and before lunch, and a more prominent decline between before lunch and late afternoon. Fewer ADS days were associated with a more flattened sAA diurnal rhythm. Additionally, greater daily care-related stressor exposures had a within-person association with lower sAA levels in the late afternoon. Care-related stressor exposures had significant within- and between-person associations with sAA diurnal slopes. Furthermore, daily positive experiences had a significant between-person association with sAA diurnal slopes. Caring for a disabled family member may heighten the vulnerability to potential physiological conditions. Respite from care stressors from ADS use may have some biobehavioral benefits on sAA regulations. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study

PubMed Central

Østergaard, Søren D.; Mukherjee, Shubhabrata; Sharp, Stephen J.; Proitsi, Petroula; Lotta, Luca A.; Day, Felix; Perry, John R. B.; Boehme, Kevin L.; Walter, Stefan; Kauwe, John S.; Gibbons, Laura E.; Larson, Eric B.; Powell, John F.; Langenberg, Claudia; Crane, Paul K.; Wareham, Nicholas J.; Scott, Robert A.

2015-01-01

Background Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR). Methods and Findings We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, N SNPs = 49), fasting glucose (N SNPs = 36), insulin resistance (N SNPs = 10), body mass index (BMI, N SNPs = 32), total cholesterol (N SNPs = 73), HDL-cholesterol (N SNPs = 71), LDL-cholesterol (N SNPs = 57), triglycerides (N SNPs = 39), systolic blood pressure (SBP, N SNPs = 24), smoking initiation (N SNPs = 1), smoking quantity (N SNPs = 3), university completion (N SNPs = 2), and years of education (N SNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP–AD associations from the International Genomics of Alzheimer’s Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62–0.91]; p = 3.4 × 10−3). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10−8). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51–0.89]; p = 6.5 × 10−3), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this study include the small proportion of intermediate trait variance explained by genetic variants and other implicit limitations of MR analyses. Conclusions Inherited lifetime exposure to higher SBP is associated with lower AD risk. These findings suggest that higher blood pressure—or some environmental exposure associated with higher blood pressure, such as use of antihypertensive medications—may reduce AD risk. PMID:26079503

Relationship between cardiac autonomic function and cognitive function in Alzheimer's disease.

PubMed

Nonogaki, Zen; Umegaki, Hiroyuki; Makino, Taeko; Suzuki, Yusuke; Kuzuya, Masafumi

2017-01-01

Alzheimer's disease (AD) affects many central nervous structures and neurotransmitter systems. These changes affect not only cognitive function, but also cardiac autonomic function. However, the functional relationship between cardiac autonomic function and cognition in AD has not yet been investigated. The objective of the present study was to evaluate the association between cardiac autonomic function measured by heart rate variability and cognitive function in AD. A total of 78 AD patients were recruited for this study. Cardiac autonomic function was evaluated using heart rate variability analysis. Multiple linear regression analysis was used to model the association between heart rate variability and cognitive function (global cognitive function, memory, executive function and processing speed), after adjustment for covariates. Global cognitive function was negatively associated with sympathetic modulation (low-to-high frequency power ratio). Memory performance was positively associated with parasympathetic modulation (high frequency power) and negatively associated with sympathetic modulation (low-to-high frequency power ratio). These associations were independent of age, sex, educational years, diabetes, hypertension and cholinesterase inhibitor use. Cognitive function, especially in the areas of memory, is associated with cardiac autonomic function in AD. Specifically, lower cognitive performance was found to be associated with significantly higher cardiac sympathetic and lower parasympathetic function in AD. Geriatr Gerontol Int 2017; 17: 92-98. © 2015 Japan Geriatrics Society.

The Amateur Scientist.

ERIC Educational Resources Information Center

Walker, Jearl

1982-01-01

Discusses the thermodynamics of heating and boiling water, including the mechanics of bubble formation. Indicates that when salt was added to boiling water (when cooking pasta) the water temperature rose less than a degree, concluding that salt serves only as a seasoning. (Author/JN)

Intake of added sugars is not associated with weight measures in children 6 to 18 years: NHANES 2003–2006

USDA-ARS?s Scientific Manuscript database

The association between intakes of added sugars and weight measures in children continues to be under scrutiny because the evidence is inconclusive. This study examined the association between intake of added sugars and five weight measures using a nationally representative sample of children. NHANE...

Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by adaptive optics retinal imaging

PubMed Central

Song, Hongxin; Rossi, Ethan A; Stone, Edwin; Latchney, Lisa; Williams, David; Dubra, Alfredo; Chung, Mina

2018-01-01

Purpose Several genes causing autosomal-dominant cone-rod dystrophy (AD-CRD) have been identified. However, the mechanisms by which genetic mutations lead to cellular loss in human disease remain poorly understood. Here we combine genotyping with high-resolution adaptive optics retinal imaging to elucidate the retinal phenotype at a cellular level in patients with AD-CRD harbouring a defect in the GUCA1A gene. Methods Nine affected members of a four-generation AD-CRD pedigree and three unaffected first-degree relatives underwent clinical examinations including visual acuity, fundus examination, Goldmann perimetry, spectral domain optical coherence tomography and electroretinography. Genome-wide scan followed by bidirectional sequencing was performed on all affected participants. High-resolution imaging using a custom adaptive optics scanning light ophthalmoscope (AOSLO) was performed for selected participants. Results Clinical evaluations showed a range of disease severity from normal fundus appearance in teenaged patients to pronounced macular atrophy in older patients. Molecular genetic testing showed a mutation in in GUCA1A segregating with disease. AOSLO imaging revealed that of the two teenage patients with mild disease, one had severe disruption of the photoreceptor mosaic while the other had a normal cone mosaic. Conclusions AOSLO imaging demonstrated variability in the pattern of cone and rod cell loss between two teenage cousins with early AD-CRD, who had similar clinical features and had the identical disease-causing mutation in GUCA1A. This finding suggests that a mutation in GUCA1A does not lead to the same degree of AD-CRD in all patients. Modifying factors may mitigate or augment disease severity, leading to different retinal cellular phenotypes. PMID:29074494

Enhancement of mercury capture by the simultaneous addition of hydrogen bromide (HBr) and fly ashes in a slipstream facility.

PubMed

Cao, Yan; Wang, Quan-Hai; Li, Jun; Cheng, Jen-Chieh; Chan, Chia-Chun; Cohron, Marten; Pan, Wei-Ping

2009-04-15

Low halogen content in tested Powder River Basin (PRB) coals and low loss of ignition content (LOI) in PRB-derived fly ash were likely responsible for higher elemental mercury content (averaging about 75%) in the flue gas and also lower mercury capture efficiency by electrostatic precipitator (ESP) and wet-FGD. To develop a cost-effective approach to mercury capture in a full-scale coal-fired utility boiler burning PRB coal, experiments were conducted adding hydrogen bromide (HBr) or simultaneously adding HBr and selected fly ashes in a slipstream reactor (0.152 x 0.152 m) under real flue gas conditions. The residence time of the flue gas inside the reactorwas about 1.4 s. The average temperature of the slipstream reactor was controlled at about 155 degrees C. Tests were organized into two phases. In Phase 1, only HBr was added to the slipstream reactor, and in Phase 2, HBr and selected fly ash were added simultaneously. HBr injection was effective (>90%) for mercury oxidation at a low temperature (155 degrees C) with an HBr addition concentration of about 4 ppm in the flue gas. Additionally, injected HBr enhanced mercury capture by PRB fly ash in the low-temperature range. The mercury capture efficiency, attesting conditions of the slipstream reactor, reached about 50% at an HBr injection concentration of 4 ppm in the flue gas. Compared to only the addition of HBr, simultaneously adding bituminous-derived fly ash in a minimum amount (30 lb/MMacf), together with HBr injection at 4 ppm, could increase mercury capture efficiency by 30%. Injection of lignite-derived fly ash at 30 lb/MMacf could achieve even higher mercury removal efficiency (an additional 35% mercury capture efficiency compared to HBr addition alone).

Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by adaptive optics retinal imaging.

PubMed

Song, Hongxin; Rossi, Ethan A; Stone, Edwin; Latchney, Lisa; Williams, David; Dubra, Alfredo; Chung, Mina

2018-01-01

Several genes causing autosomal-dominant cone-rod dystrophy (AD-CRD) have been identified. However, the mechanisms by which genetic mutations lead to cellular loss in human disease remain poorly understood. Here we combine genotyping with high-resolution adaptive optics retinal imaging to elucidate the retinal phenotype at a cellular level in patients with AD-CRD harbouring a defect in the GUCA1A gene. Nine affected members of a four-generation AD-CRD pedigree and three unaffected first-degree relatives underwent clinical examinations including visual acuity, fundus examination, Goldmann perimetry, spectral domain optical coherence tomography and electroretinography. Genome-wide scan followed by bidirectional sequencing was performed on all affected participants. High-resolution imaging using a custom adaptive optics scanning light ophthalmoscope (AOSLO) was performed for selected participants. Clinical evaluations showed a range of disease severity from normal fundus appearance in teenaged patients to pronounced macular atrophy in older patients. Molecular genetic testing showed a mutation in in GUCA1A segregating with disease. AOSLO imaging revealed that of the two teenage patients with mild disease, one had severe disruption of the photoreceptor mosaic while the other had a normal cone mosaic. AOSLO imaging demonstrated variability in the pattern of cone and rod cell loss between two teenage cousins with early AD-CRD, who had similar clinical features and had the identical disease-causing mutation in GUCA1A . This finding suggests that a mutation in GUCA1A does not lead to the same degree of AD-CRD in all patients. Modifying factors may mitigate or augment disease severity, leading to different retinal cellular phenotypes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns.

PubMed

Habes, M; Janowitz, D; Erus, G; Toledo, J B; Resnick, S M; Doshi, J; Van der Auwera, S; Wittfeld, K; Hegenscheid, K; Hosten, N; Biffar, R; Homuth, G; Völzke, H; Grabe, H J; Hoffmann, W; Davatzikos, C

2016-04-05

We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20-90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q<0.001). ABA patterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD.

Weak independent association signals between IDE polymorphisms, Alzheimer's disease and cognitive measures.

PubMed

Mueller, Jakob C; Riemenschneider, Matthias; Schoepfer-Wendels, Andreas; Gohlke, Henning; Konta, Lidija; Friedrich, Patricia; Illig, Thomas; Laws, Simon M; Förstl, Hans; Kurz, Alexander

2007-05-01

Functional and genetic studies suggest that insulin-degrading enzyme (IDE) may be a strong functional and positional candidate. As there is a lack of consensus in regards to the level and location of IDE association signals we aimed to clarify these discrepancies through genotyping 28 SNPs in a large case-control collective together with quantitative measures of cognitive ability (MMSE). Four SNPs (rs11187007, rs2149632_ide12, rs11187033, rs11187040) were found to be associated with AD (nominal p<0.01). Tests with MMSE scores adjusted for disease duration identified associations, with the most significant result for rs1999763 (nominal p=0.008). Similarly, different reconstructed IDE haplotypes were associated with AD and higher MMSE scores. The association signals are only borderline significant after adjustment for multiple testing, but add further evidence to previous published results on the association between IDE and AD or MMSE. A subgroup analysis indicated more prominent associations with AD in younger, and with MMSE in older patients. There may be two independent effects mediated by IDE variants, risk for AD and modification of disease progression.

Association between energy intake and viewing television, distractibility, and memory for advertisements12345

PubMed Central

Martin, Corby K; Coulon, Sandra M; Markward, Nathan; Greenway, Frank L; Anton, Stephen D

2009-01-01

Background: The effect of television viewing (TVV) with and without advertisements (ads) on energy intake is unclear. Objective: The objectives were to test 1) the effect of TVV, with and without ads, on energy intake compared with a control and reading condition and 2) the association of distractibility and memory for ads with energy intake and body weight. Design: Forty-eight (26 female) adults (age: 19–54 y) with a body mass index (in kg/m2) of 20–35 completed this laboratory-based study. All participants completed 4 buffet-style meals in random order in the following conditions: 1) control, 2) while reading, 3) while watching TV with food and nonfood ads (TV-ads), and 4) while watching TV with no ads (TV-no ads). Energy intake was quantified by weighing foods. Distractibility and memory for ads in the TV-ads condition were quantified with a norm-referenced test and recognition task, respectively. Results: Repeated-measures analysis of variance indicated that energy and macronutrient intake did not differ significantly among the 4 conditions (P > 0.65). Controlling for sex, memory for ads was associated with body weight (r = 0.36, P < 0.05) and energy intake but only when viewing TV (r = 0.39, P < 0.05 during the TV-no ads condition, and r = 0.29, P = 0.06 during the TV-ads condition). Controlling for sex, distractibility was associated with body weight (r = 0.36, P < 0.05) but not energy intake. Distractibility, however, accounted for 13% of the variance in men's energy intake (P = 0.11). Conclusions: TVV did not affect energy intake, but individual characteristics (memory for ads) were associated with body weight and energy intake in certain conditions. These characteristics should be considered in food intake and intervention studies. PMID:19056603

Late-onset Alzheimer disease genetic variants in posterior cortical atrophy and posterior AD.

PubMed

Carrasquillo, Minerva M; Khan, Qurat ul Ain; Murray, Melissa E; Krishnan, Siddharth; Aakre, Jeremiah; Pankratz, V Shane; Nguyen, Thuy; Ma, Li; Bisceglio, Gina; Petersen, Ronald C; Younkin, Steven G; Dickson, Dennis W; Boeve, Bradley F; Graff-Radford, Neill R; Ertekin-Taner, Nilüfer

2014-04-22

To investigate association of genetic risk factors for late-onset Alzheimer disease (LOAD) with risk of posterior cortical atrophy (PCA), a syndrome of visual impairment with predominant Alzheimer disease (AD) pathology in posterior cortical regions, and with risk of "posterior AD" neuropathology. We assessed 81 participants with PCA diagnosed clinically and 54 with neuropathologic diagnosis of posterior AD vs 2,523 controls for association with 11 significant single nucleotide polymorphisms (SNPs) from published LOAD risk genome-wide association studies. There was highly significant association with APOE ε4 and increased risk of PCA (p = 0.0003, odds ratio [OR] = 3.17) and posterior AD (p = 1.11 × 10(-17), OR = 6.43). No other locus was significant after corrections for multiple testing, although rs11136000 near CLU (p = 0.019, OR = 0.60) and rs744373 near BIN1 (p = 0.025, OR = 1. 63) associated nominally significantly with posterior AD, and rs3851179 at the PICALM locus had significant association with PCA (p = 0.0003, OR = 2.84). ABCA7 locus SNP rs3764650, which was also tested under the recessive model because of Hardy-Weinberg disequilibrium, also had nominally significant association with PCA risk. The direction of association at APOE, CLU, and BIN1 loci was the same for participants with PCA and posterior AD. The effects for all SNPs, except rs3851179, were consistent with those for LOAD risk. We identified a significant effect for APOE and nominate CLU, BIN1, and ABCA7 as additional risk loci for PCA and posterior AD. Our findings suggest that at least some of the genetic risk factors for LOAD are shared with these atypical conditions and provide effect-size estimates for their future genetic studies.

The effects of noncoding aquaporin-4 single-nucleotide polymorphisms on cognition and functional progression of Alzheimer's disease.

PubMed

Burfeind, Kevin G; Murchison, Charles F; Westaway, Shawn K; Simon, Matthew J; Erten-Lyons, Deniz; Kaye, Jeffrey A; Quinn, Joseph F; Iliff, Jeffrey J

2017-09-01

The glymphatic system is a brain-wide perivascular network that facilitates clearance of proteins, including amyloid β, from the brain interstitium through the perivascular exchange of cerebrospinal fluid and interstitial fluid. The astrocytic water channel aquaporin-4 (AQP4) is required for glymphatic system function, and impairment of glymphatic function in the aging brain is associated with altered AQP4 expression and localization. In human cortical tissue, alterations in AQP4 expression and localization are associated with Alzheimer's disease (AD) status and pathology. Although this suggests a potential role for AQP4 in the development or progression of AD, the relationship between of naturally occurring variants in the human AQP4 gene and cognitive function has not yet been evaluated. Using data from several longitudinal aging cohorts, we investigated the association between five AQP4 single-nucleotide polymorphisms (SNPs) and the rate of cognitive decline in participants with a diagnosis of AD. None of the five SNPs were associated with different rates of AD diagnosis, age of dementia onset in trial subjects. No association between AQP4 SNPs with histological measures of AD pathology, including Braak stage or neuritic plaque density was observed. However, AQP4 SNPs were associated with altered rates of cognitive decline after AD diagnosis, with two SNPS (rs9951307 and rs3875089) associated with slower cognitive decline and two (rs3763040 and rs3763043) associated with more rapid cognitive decline after AD diagnosis. These results provide the first evidence that variations in the AQP4 gene, whose gene product AQP4 is vital for glymphatic pathway function, may modulate the progression of cognitive decline in AD.

Community pharmacists' knowledge of Alzheimer disease care in high- and low-income Chicago.

PubMed

Marvanova, Marketa; Henkel, Paul Jacob

This pilot study examined community pharmacists' knowledge to provide care and services for persons with Alzheimer disease (AD) and area income-based disparities in knowledge and availability of cognitive enhancers. A cross-sectional telephone survey of pharmacies (n = 137) in high- and low-income areas in Chicago was conducted on pharmacists' degree, experience, and continuing education, as well as knowledge of AD disease and treatment expectations, adverse effects (AEs) of donepezil, and self-care recommendations for insomnia. Pharmacies were selected from highest- and lowest-income zip code areas, defined using household area median incomes from the 2008-2012 American Community Survey 5-Year Estimates. In-stock availability of select cognitive enhancers was obtained. Chi-square, Fisher exact test, and simple and multiple logistic regression analyses were performed with the use of Stata 10.1. Odds were 70% lower that pharmacists in low-income areas would say there was nothing to reverse the course of AD (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.13-0.70) and 7 times greater that they would recommend a medication to reverse the course of AD (OR 7.04, 95% CI 2.19-22.62) compared with pharmacists in high-income areas. Odds were more than 50% lower that pharmacists in low-income areas would name at least 1 adverse effect for donepezil (OR 0.42, 95% CI 0.19-0.92) compared with peers in high-income areas. Pharmacies in low-income areas had lower odds of having 4 of the 5 surveyed formulations of cognitive enhancers in stock. It is concerning that 20%-30% of pharmacists recommended a medication to "reverse" the course of AD, about one-half of pharmacists could not mention a single adverse effect of donepezil, and more than one-fourth of pharmacists made an inappropriate self-care sleep aid recommendation for a person with AD who was using rivastigmine patch. Although overall results regarding pharmacists' knowledge were poor, performance was significantly poorer in low-income areas. As our AD population increases, we need to strengthen pharmacists' knowledge on and competencies important for pharmacy-related AD care. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Atherosclerosis risk factors in American Indians with Alzheimer disease: preliminary findings.

PubMed

Weiner, Myron F; Rosenberg, Roger N; Womack, Kyle B; Svetlik, Doris A; Fuller, Carey; Fields, Julie; Hynan, Linda S

2008-01-01

Factors predisposing to and associated with atherosclerosis may impact the onset and progression of Alzheimer disease (AD). The high prevalence of atherosclerosis and associated risk factors in American Indians makes them ideal subjects to test this association. We compared frequency of history of hypertension, myocardial infarction, stroke, diabetes, and high cholesterol in 34 American Indians with AD with 34 age-matched American Indian controls, and 34 age-matched whites with probable AD. We also measured waist size, height, and weight, and acquired blood for determination of plasma homocysteine and apolipoprotein E genotype. The 3 groups did not differ significantly in age or sex. History of hypertension and diabetes was significantly more common among American Indian AD patients than Indian controls or whites with AD. The 3 groups did not differ in history of stroke or myocardial infarction. Body mass index was significantly greater in both Indian groups than the white AD group. Plasma homocysteine levels were greater, but not significantly so, in the Indian AD than the Indian control group. Thus, there is preliminary evidence of a modest association between history of hypertension and diabetes and AD in a small sample of American Indians. This suggests that changes in lifestyle factors could influence the expression of AD in American Indians.

Decreased C-reactive protein levels in Alzheimer disease.

PubMed

O'Bryant, Sid E; Waring, Stephen C; Hobson, Valerie; Hall, James R; Moore, Carol B; Bottiglieri, Teodoro; Massman, Paul; Diaz-Arrastia, Ramon

2010-03-01

C-reactive protein (CRP) is an acute-phase reactant that has been found to be associated with Alzheimer disease (AD) in histopathological and longitudinal studies; however, little data exist regarding serum CRP levels in patients with established AD. The current study evaluated CRP levels in 192 patients diagnosed with probable AD (mean age = 75.8 +/- 8.2 years; 50% female) as compared to 174 nondemented controls (mean age = 70.6 +/- 8.2 years; 63% female). Mean CRP levels were found to be significantly decreased in AD (2.9 microg/mL) versus controls (4.9 microg/mL; P = .003). In adjusted models, elevated CRP significantly predicted poorer (elevated) Clinical Dementia Rating Scale sum of boxes (CDR SB) scores in patients with AD. In controls, CRP was negatively associated with Mini-Mental State Examination (MMSE) scores and positively associated with CDR SB scores. These findings, together with previously published results, are consistent with the hypothesis that midlife elevations in CRP are associated with increased risk of AD development though elevated CRP levels are not useful for prediction in the immediate prodrome years before AD becomes clinically manifest. However, for a subgroup of patients with AD, elevated CRP continues to predict increased dementia severity suggestive of a possible proinflammatory endophenotype in AD.

Decreased C-Reactive Protein Levels in Alzheimer Disease

PubMed Central

O’Bryant, Sid E.; Waring, Stephen C.; Hobson, Valerie; Hall, James R.; Moore, Carol B.; Bottiglieri, Teodoro; Massman, Paul; Diaz-Arrastia, Ramon

2011-01-01

C-reactive protein (CRP) is an acute-phase reactant that has been found to be associated with Alzheimer disease (AD) in histo-pathological and longitudinal studies; however, little data exist regarding serum CRP levels in patients with established AD. The current study evaluated CRP levels in 192 patients diagnosed with probable AD (mean age = 75.8 ± 8.2 years; 50% female) as compared to 174 nondemented controls (mean age = 70.6 ± 8.2 years; 63% female). Mean CRP levels were found to be significantly decreased in AD (2.9 µg/mL) versus controls (4.9 µg/mL; P = .003). In adjusted models, elevated CRP significantly predicted poorer (elevated) Clinical Dementia Rating Scale sum of boxes (CDR SB) scores in patients with AD. In controls, CRP was negatively associated with Mini-Mental State Examination (MMSE) scores and positively associated with CDR SB scores. These findings, together with previously published results, are consistent with the hypothesis that midlife elevations in CRP are associated with increased risk of AD development though elevated CRP levels are not useful for prediction in the immediate prodrome years before AD becomes clinically manifest. However, for a subgroup of patients with AD, elevated CRP continues to predict increased dementia severity suggestive of a possible proinflammatory endophenotype in AD. PMID:19933496

Genetic Aspects of Alzheimer Disease

PubMed Central

Williamson, Jennifer; Goldman, Jill; Marder, Karen S.

2011-01-01

Background Alzheimer disease (AD) is a genetically complex disorder. Mutations in 3 genes, presenilin 1, amyloid precursor protein, and presenilin 2, lead to early-onset familial AD in rare families with onset of disease occurring prior to age 65. Specific polymorphisms in apolipoprotein E are associated with the more common, late-onset AD occurring after age 65. In this review, we discuss current advances in AD genetics, the implications of the known AD genes, presenilin 1, presenilin 2, amyloid precursor protein, and apolipoprotein E, and other possible genes on the clinical diagnosis, treatment, and genetic counseling of patients and families with early- and late-onset AD. Review Summary In addition to the mutations in 4 known genes associated with AD, mutations in other genes may be implicated in the pathogenesis of the disease. Most recently, 2 different research groups have reported genetic association between 2 genes, sortilin-related receptor and GAB2, and AD. These associations have not changed the diagnostic and medical management of AD. Conclusions New research in the genetics of AD have implicated novel genes as having a role in the disease, but these findings have not been replicated nor have specific disease causing mutations been identified. To date, clinical genetic testing is limited to familial early-onset disease for symptomatic individuals and asymptomatic relatives and, although not recommended, amyloid precursor protein apolipoprotein E testing as an adjunct to diagnosis of symptomatic individuals. PMID:19276785

A Claims-Based Examination of Health Care Costs Among Spouses of Patients With Alzheimer's Disease.

PubMed

Gilden, Daniel M; Kubisiak, Joanna M; Kahle-Wrobleski, Kristin; Ball, Daniel E; Bowman, Lee

2017-06-01

Spouses of Alzheimer's disease patients (AD spouses) may experience substantial health effects associated with their partner's chronic cognitive and behavioral dysfunction. Studies examining associations between the medical experiences of AD spouses in the period before and after their partner's AD diagnosis are limited, particularly those which measure health care resource use and cost. AD patients were identified through multiple Medicare claims containing an AD diagnostic code. Their spouses were identified through special coding in the Medicare eligibility records. The AD spouses were matched demographically to the spouses of Medicare beneficiaries without a history of AD. Longitudinal and annual cross-sectional Medicare cost comparisons utilized log-transformed linear regression. The longitudinal period of observation began 12 months before the AD patient's initial claim listing AD and continued for up to 38 months afterwards. The study identified 16,322 AD spouses. Total per person costs were 24% higher in AD spouses than in the controls ($694/month vs $561/month). AD spouses' excess costs began 3 months before their partners' AD diagnoses and continued for ≥30 months. Being an AD spouse predicted 29% higher Medicare costs after adjustment for chronic health status (P < .001). Increasing AD patient care complexity had a substantial impact on AD spouse Medicare costs (P < .001). This study documents a link between the health status of AD spouses and AD patients. Additional research is required to elicit the mechanism behind the association between AD spouse and AD patient diagnosis. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Biometric parameters in different stages of primary angle closure using low-coherence interferometry.

PubMed

Yazdani, Shahin; Akbarian, Shadi; Pakravan, Mohammad; Doozandeh, Azadeh; Afrouzifar, Mohsen

2015-03-01

To compare ocular biometric parameters using low-coherence interferometry among siblings affected with different degrees of primary angle closure (PAC). In this cross-sectional comparative study, a total of 170 eyes of 86 siblings from 47 families underwent low-coherence interferometry (LenStar 900; Haag-Streit, Koeniz, Switzerland) to determine central corneal thickness, anterior chamber depth (ACD), aqueous depth (AD), lens thickness (LT), vitreous depth, and axial length (AL). Regression coefficients were applied to show the trend of the measured variables in different stages of angle closure. To evaluate the discriminative power of the parameters, receiver operating characteristic curves were used. Best cutoff points were selected based on the Youden index. Sensitivity, specificity, positive and negative predicative values, positive and negative likelihood ratios, and diagnostic accuracy were determined for each variable. All biometric parameters changed significantly from normal eyes to PAC suspects, PAC, and PAC glaucoma; there was a significant stepwise decrease in central corneal thickness, ACD, AD, vitreous depth, and AL, and an increase in LT and LT/AL. Anterior chamber depth and AD had the best diagnostic power for detecting angle closure; best levels of sensitivity and specificity were obtained with cutoff values of 3.11 mm for ACD and 2.57 mm for AD. Biometric parameters measured by low-coherence interferometry demonstrated a significant and stepwise change among eyes affected with various degrees of angle closure. Although the current classification scheme for angle closure is based on anatomical features, it has excellent correlation with biometric parameters.

Differential transesophageal echocardiographic diagnosis between linear artifacts and intraluminal flap of aortic dissection or disruption.

PubMed

Vignon, P; Spencer, K T; Rambaud, G; Preux, P M; Krauss, D; Balasia, B; Lang, R M

2001-06-01

The relatively low specificity of transesophageal echocardiography (TEE) for the diagnosis of aortic dissection (AD) or traumatic disruption of the aorta (TDA) has been attributed to linear artifacts. We sought to determine the incidence of intra-aortic linear artifacts in a cohort of patients with suspected AD or TDA, to establish the differential TEE diagnostic criteria between these artifacts and true aortic flaps, and to evaluate their impact on TEE diagnostic accuracy. During an 8-year period, patients at high risk of AD (n = 261) or TDA (n = 90) who underwent a TEE study and had confirmed final diagnoses were studied. In an initial retrospective series, linear artifacts were observed within the ascending and descending aorta in 59 of 230 patients (26%) and 17 of 230 patients (7%), respectively. TEE findings associated with linear artifacts in the ascending aorta were as follows: displacement parallel to aortic walls; similar blood flow velocities on both sides; angle with the aortic wall > 85 degrees; and thickness > 2.5 mm. Diagnostic criteria of reverberant images in the descending aorta were as follows: displacement parallel to aortic walls, overimposition of blood flow, and similar blood flow velocities on both sides of the image. In a subsequent prospective series (n = 121), systematic use of these diagnostic criteria resulted in improved TEE specificity for the identification of true intra-aortic flaps. Misleading intra-aortic linear artifacts are frequently observed in patients undergoing a TEE study for suspected AD or TDA. Routine use of the herein-proposed diagnostic criteria promises to further improve TEE diagnostic accuracy in the setting of severely ill patients with potential need for prompt surgery.

How redesigning AD clinical trials might increase study partners' willingness to participate.

PubMed

Karlawish, Jason; Cary, Mark S; Rubright, Jonathan; Tenhave, Tom

2008-12-02

Timely recruiting and retaining participants into Alzheimer disease (AD) clinical trials is a challenge. We used conjoint analysis to identify how alterations in attributes of clinical trial design improve willingness to participate: risk, home visits, car service, or increased chance of receiving intervention. A total of 108 study partners of patients with very mild to severe stage AD rated willingness to allow their relative to participate in eight clinical trials that varied combinations of the four attributes. The highest utility was for home visits (0.89) which essentially compensated for the disutility of high risk (-0.85). The combination of home visits and car service was redundant, with almost no increase in utility over home visits alone. Seventeen percent were willing to participate in a trial with no amenities; the addition of home visits increased predicted willingness to participate to 27%; low risk, home visits, and higher chance of active treatment increased predicted willingness to 60%. The value of reducing the hassles of travel correlated well with measures of AD severity (activities of daily living r = 0.41, p < 0.001; basic activities of daily living r = 0.38, p < 0.001; Neuropsychiatric Inventory severity p = 0.24, p = 0.01; Neuropsychiatric Inventory distress r = 0.23, p < 0.02). No association was found between degree of study partner burden and willingness to tolerate risk of an intervention. Clinical trials that reduce travel inconvenience may offset the disincentive of study features such as the risk of intervention and may also increase willingness to participate. Redesigning trials may also help recruit patients with more severe Alzheimer disease. Shorter recruitment periods and increased retention rates may offset costs of these changes.

Applicability of digital analysis and imaging technology in neuropathology assessment.

PubMed

Dunn, William D; Gearing, Marla; Park, Yuna; Zhang, Lifan; Hanfelt, John; Glass, Jonathan D; Gutman, David A

2016-06-01

Alzheimer's disease (AD) is a progressive neurological disorder that affects more than 30 million people worldwide. While various dementia-related losses in cognitive functioning are its hallmark clinical symptoms, ultimate diagnosis is based on manual neuropathological assessments using various schemas, including Braak staging, CERAD (Consortium to Establish a Registry for Alzheimer's Disease) and Thal phase scoring. Since these scoring systems are based on subjective assessment, there is inevitably some degree of variation between readers, which could affect ultimate neuropathology diagnosis. Here, we report a pilot study investigating the applicability of computer-driven image analysis for characterizing neuropathological features, as well as its potential to supplement or even replace manually derived ratings commonly performed in medical settings. In this work, we quantitatively measured amyloid beta (Aβ) plaque in various brain regions from 34 patients using a robust digital quantification algorithm. We next verified these digitally derived measures to the manually derived pathology ratings using correlation and ordinal logistic regression methods, while also investigating the association with other AD-related neuropathology scoring schema commonly used at autopsy, such as Braak and CERAD. In addition to successfully verifying our digital measurements of Aβ plaques with respective categorical measurements, we found significant correlations with most AD-related scoring schemas. Our results demonstrate the potential for digital analysis to be adapted to more complex staining procedures commonly used in neuropathological diagnosis. As the efficiency of scanning and digital analysis of histology images increases, we believe that the basis of our semi-automatic approach may better standardize quantification of neuropathological changes and AD diagnosis, ultimately leading to a more comprehensive understanding of neurological disorders and more efficient patient care. © 2015 Japanese Society of Neuropathology.

Applicability of digital analysis and imaging technology in neuropathology assessment

PubMed Central

Dunn, William D.; Gearing, Marla; Park, Yuna; Zhang, Lifan; Hanfelt, John; Glass, Jonathan D.; Gutman, David A.

2017-01-01

Alzheimer’s disease (AD) is a progressive neurological disorder that affects more than 30 million people worldwide. While various dementia-related losses in cognitive functioning are its hallmark clinical symptoms, ultimate diagnosis is based on manual neuropathological assessments using various schemas, including Braak staging, CERAD (Consortium to Establish a Registry for Alzheimer’s Disease) and Thal phase scoring. Since these scoring systems are based on subjective assessment, there is inevitably some degree of variation between readers, which could affect ultimate neuropathology diagnosis. Here, we report a pilot study investigating the applicability of computer-driven image analysis for characterizing neuropathological features, as well as its potential to supplement or even replace manually derived ratings commonly performed in medical settings. In this work, we quantitatively measured amyloid beta (Aβ) plaque in various brain regions from 34 patients using a robust digital quantification algorithm. We next verified these digitally derived measures to the manually derived pathology ratings using correlation and ordinal logistic regression methods, while also investigating the association with other AD-related neuropathology scoring schema commonly used at autopsy, such as Braak and CERAD. In addition to successfully verifying our digital measurements of Aβ plaques with respective categorical measurements, we found significant correlations with most AD-related scoring schemas. Our results demonstrate the potential for digital analysis to be adapted to more complex staining procedures commonly used in neuropathological diagnosis. As the efficiency of scanning and digital analysis of histology images increases, we believe that the basis of our semi-automatic approach may better standardize quantification of neuropathological changes and AD diagnosis, ultimately leading to a more comprehensive understanding of neurological disorders and more efficient patient care. PMID:26577803

Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without Alzheimer's dementia.

PubMed

Sabbagh, Marwan N; Chen, Kewei; Rogers, Joseph; Fleisher, Adam S; Liebsack, Carolyn; Bandy, Dan; Belden, Christine; Protas, Hillary; Thiyyagura, Pradeep; Liu, Xiaofen; Roontiva, Auttawut; Luo, Ji; Jacobson, Sandra; Malek-Ahmadi, Michael; Powell, Jessica; Reiman, Eric M

2015-08-01

Down syndrome (DS) is associated with amyloid b (Ab) deposition. We characterized imaging measurements of regional fibrillar Ab burden, cerebral metabolic rate for glucose (rCMRgl), gray matter volumes (rGMVs), and age associations in 5 DS with dementia (DS/AD1), 12 DS without dementia (DS/AD2), and 9 normal controls (NCs). There were significant group differences in mean standard uptake value ratios (SUVRs) for florbetapir with DS/AD1 having the highest, followed by DS/AD2, followed by NC. For [18F]-fluorodeoxyglucose positron emission tomography, posterior cingulate rCMRgl in DS/AD1 was significantly reduced compared with DS/AD2 and NC. For volumetric magnetic resonance imaging (vMRI), hippocampal volumes were significantly reduced for the DS/AD1 compared with DS/AD2 and NC. Age-related SUVR increases and rCMRgl reductions were greater in DS participants than in NCs. DS is associated with fibrillar Ab, rCMRgl, and rGMV alterations in the dementia stage and before the presence of clinical decline. This study provides a foundation for the studies needed to inform treatment and prevention in DS. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Dextran and gelatin based photocrosslinkable tissue adhesive.

PubMed

Wang, Tao; Nie, Jun; Yang, Dongzhi

2012-11-06

A two-component tissue adhesive based on biocompatible and bio-degradable polymers (oxidized urethane dextran (Dex-U-AD) and gelatin) was prepared and photocrosslinked under the ultraviolet (UV) irradiation. The adhesive could adhere to surface of gelatin, which simulated the human tissue steadily. The structures of above Dex-U-AD were characterized by FTIR, (1)H NMR spectroscopy and XRD. The adhesion property of result products was evaluated by lap-shear test. The maximum adhesion strength could reach to 4.16±0.72 MPa which was significantly higher than that of fibrin glue. The photopolymerization process of Dex-U-AD/gelatin was monitored by real time infrared spectroscopy (RTIR). It took less than 5 min to complete the curing process. The cytotoxicity of Dex-U-AD/gelatin also was evaluated which indicated that Dex-U-AD/gelatin gels were nontoxic to L929 cell. The relationship between all the above-mentioned properties and degree of oxidization of Dex-U-AD was assessed. The obtained products have the potential to serve as tissue adhesive in the future. Copyright © 2012 Elsevier Ltd. All rights reserved.

Loss of VGLUT1 and VGLUT2 in the prefrontal cortex is correlated with cognitive decline in Alzheimer disease.

PubMed

Kashani, Alireza; Lepicard, Eve; Poirel, Odile; Videau, Catherine; David, Jean Philippe; Fallet-Bianco, Catherine; Simon, Axelle; Delacourte, André; Giros, Bruno; Epelbaum, Jacques; Betancur, Catalina; El Mestikawy, Salah

2008-11-01

Several lines of evidence suggest that the glutamatergic system is severely impaired in Alzheimer disease (AD). Here, we assessed the status of glutamatergic terminals in AD using the first available specific markers, the vesicular glutamate transporters VGLUT1 and VGLUT2. We quantified VGLUT1 and VGLUT2 in the prefrontal dorsolateral cortex (Brodmann area 9) of controls and AD patients using specific antiserums. A dramatic decrease in VGLUT1 and VGLUT2 was observed in AD using Western blot. Similar decreases were observed in an independent group of subjects using immunoautoradiography. The VGLUT1 reduction was highly correlated with the degree of cognitive impairment, assessed with the clinical dementia rating (CDR) score. A significant albeit weaker correlation was also observed with VGLUT2. These findings provide evidence indicating that glutamatergic systems are severely impaired in the A9 region of AD patients and that this impairment is strongly correlated with the progression of cognitive decline. Our results suggest that VGLUT1 expression in the prefrontal cortex could be used as a valuable neurochemical marker of dementia in AD.

Additional freeze hardiness in wheat acquired by exposure to -3 degreesC is associated with extensive physiological, morphological, and molecular changes.

PubMed

Herman, Eliot M; Rotter, Kelsi; Premakumar, Ramaswamy; Elwinger, G; Bae, Hanhong; Bae, Rino; Ehler-King, Linda; Chen, Sixue; Livingston, David P

2006-01-01

Cold-acclimated plants acquire an additional 3-5 degrees C increase in freezing tolerance when exposed to -3 degrees C for 12-18 h before a freezing test (LT50) is applied. The -3 degrees C treatment replicates soil freezing that can occur in the days or weeks leading to overwintering by freezing-tolerant plants. This additional freezing tolerance is called subzero acclimation (SZA) to differentiate it from cold acclimation (CA) that is acquired at above-freezing temperatures. Using wheat as a model, results have been obtained indicating that SZA is accompanied by changes in physiology, cellular structure, the transcriptome, and the proteome. Using a variety of assays, including DNA arrays, reverse transcription-polymerase chain reaction (RT-PCR), 2D gels with mass spectroscopic identification of proteins, and electron microscopy, changes were observed to occur as a consequence of SZA and the acquisition of added freezing tolerance. In contrast to CA, SZA induced the movement of intracellular water to the extracellular space. Many unknown and stress-related genes were upregulated by SZA including some with obvious roles in SZA. Many genes related to photosynthesis and plastids were downregulated. Changes resulting from SZA often appeared to be a loss of rather than an appearance of new proteins. From a cytological perspective, SZA resulted in alterations of organelle structure including the Golgi. The results indicate that the enhanced freezing tolerance of SZA is correlated with a wide diversity of changes, indicating that the additional freezing tolerance is the result of complex biological processes.

Falls, Cognitive Impairment, and Gait Performance: Results From the GOOD Initiative

PubMed Central

Allali, Gilles; Launay, Cyrille P.; Blumen, Helena M.; Callisaya, Michele L.; De Cock, Anne-Marie; Kressig, Reto W.; Srikanth, Velandai; Steinmetz, Jean-Paul; Verghese, Joe; Beauchet, Olivier

2017-01-01

Objectives Falls are highly prevalent in individuals with cognitive decline. The complex relationship between falls and cognitive decline (including both subtype and severity of dementia) and the influence of gait disorders have not been studied. This study aimed to examine the association between the subtype (Alzheimer disease [AD] versus non-AD) and the severity (from preclinical to moderate dementia) of cognitive impairment and falls, and to establish an association between falls and gait parameters during the course of dementia. Design Multicenter cross-sectional study. Setting “Gait, cOgnitiOn & Decline” (GOOD) initiative. Participants A total of 2496 older adults (76.6 ± 7.6 years; 55.0% women) were included in this study (1161 cognitively healthy individuals [CHI], 529 patients with mild cognitive impairment [MCI], 456 patients with mild dementia, and 350 with moderate dementia) from 7 countries. Measurements Falls history was collected retrospectively at baseline in each study. Gait speed and stride time variability were recorded at usual walking pace with the GAITRite system. Results The prevalence of individuals who fall was 50% in AD and 64% in non-AD; whereas it was 25% in CHIs. Only mild and moderate non-AD dementia were associated with an increased risk for falls in comparison with CHI. Higher stride time variability was associated with falls in older adults without dementia (CHI and each MCI subgroup) and mild non-AD dementia, whereas lower gait speed was associated with falls in all participant groups, except in mild AD dementia. When gait speed was adjusted for, higher stride time variability was associated with falls only in CHIs (odds ratio 1.14; P = .012), but not in MCI or in patients with dementia. Conclusions These findings suggest that non-AD, but not AD dementia, is associated with increased falls in comparison with CHIs. The association between gait parameters and falls also differs across cognitive status, suggesting different mechanisms leading to falls in older individuals with dementia in comparison with CHIs who fall. PMID:27914848

Aqueous phase removal of nitrogen from nitrogen compounds

DOEpatents

Fassbender, Alex G.

1993-01-01

A method is disclosed for denitrification of compounds containing nitrogen present in aqueous waste streams. The method comprises the steps of (1) identifying the types of nitrogen compounds present in a waste stream, (2) determining the concentrations of nitrogen compounds, (3) balancing oxidized and reduced form of nitrogen by adding a reactant, and (4) heating the mixture to a predetermined reaction temperature from about 300.degree. C. to about 600.degree. C., thereby resulting in less harmful nitrogen and oxygen gas, hydroxides, alcohols, and hydrocarbons.

Phase change material for temperature control and material storage

NASA Technical Reports Server (NTRS)

Wessling, Jr., Francis C. (Inventor); Blackwood, James M. (Inventor)

2011-01-01

A phase change material comprising a mixture of water and deuterium oxide is described, wherein the mole fraction of deuterium oxide is selected so that the mixture has a selected phase change temperature within a range between 0.degree. C. and 4.degree. C. The mixture is placed in a container and used for passive storage and transport of biomaterials and other temperature sensitive materials. Gels, nucleating agents, freezing point depression materials and colorants may be added to enhance the characteristics of the mixture.

Preparation of reactive beta-dicalcium silicate

DOEpatents

Shen, Ming-Shing; Chen, James M.; Yang, Ralph T.

1982-01-01

This invention relates to the preparation of fine particles of reactive beta-dicalcium silicate by means of a solid state process which comprises firing a mixture of calcium sulfate, silica and a reducing additive selected from the group consisting of calcium sulfide, carbon, carbon monoxide, methane and hydrogen, at a temperature of about 850.degree.-1000.degree. C. A carrier gas such as nitrogen or carbon dioxide may also be added, if desired. A high concentration of sulfur dioxide is a by-product of this process.

Emissivity Measurements of Additively Manufactured Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morgan, Robert Vaughn; Reid, Robert Stowers; Baker, Andrew M.

The emissivity of common 3D printing materials such as ABS and PLA were measured using a reflectivity meter and have the measured value of approximately 0.92. Adding a conductive material to the filament appears to cause a decrease in the emissivity of the surface. The angular dependence of the emissivity and the apparent temperature was measured using a FLIR infrared camera showing that the emissivity does not change much for shallow angles less than 40 angular degrees, and drops off dramatically after 70 angular degrees.

Prevalence and risk factors of maladaptive behaviour in young children with Autistic Disorder

PubMed Central

Hartley, S. L.; Sikora, D. M.; McCoy, R.

2010-01-01

Background Children with Autistic Disorder (AD) evidence more co-occurring maladaptive behaviours than their typically developing peers and peers with intellectual disability because of other aetiologies. The present study investigated the prevalence of Clinically Significant maladaptive behaviours during early childhood and identified at-risk subgroups of young children with AD. Method Parents rated their child’s maladaptive behaviours on the Child Behaviour Checklist (CBCL) in 169 children with AD aged 1.5 to 5.8 years. Results One-third of young children with AD had a CBCL Total Problems score in the Clinically Significant range. The highest percentage of Clinically Significant scores were in the Withdrawal, Attention, and Aggression CBCL syndrome scales. There was a high degree of co-morbidity of Clinically Significant maladaptive behaviours. Several subject characteristic risk factors for maladaptive behaviours were identified. Conclusions Findings highlight the need to include behavioural management strategies aimed at increasing social engagement, sustained attention and decreasing aggressive behaviour in comprehensive intervention programmes for young children with AD. PMID:18444989

[Effects of Lime on Seedling Growth,Yield and Volatile Constituents of Atractylodes lancea].

PubMed

Zhang, Yan; Miki, Sakurai; Chen, Mei-lan; Takeda, Xiuji; Zhao, Dong-yue; Kang, Li-ping; Guo, Lan-ping

2015-03-01

To investigate the effects of different amounts of lime on yield and quality of Atractylodes lancea, and to provide reference for the herb growing site soil improvement and self-poisoning ease. Add different gradients of lime, and then measure their growth targets, yield and four kinds of volatile constituents content(hinesol, atractylone, β-eudesmol and atractylodin). Volatile constituents yield per plant was calculated. Adding 160 g/m2 lime had a significant role in promoting the growth and yield of herb; Adding 80 g/m2 lime was conducive to the volatile constituents production, and adding lime decreased the atractylone and atractylodin content, while increased the hinesol and β-eudesmol content; Adding 160 g/m2 lime promoted the volatile constituents yield per plant. Adding lime plays a role of neutralize soil pH, antibacteria and prevention incognita, and has a certain degree of ease autotoxicity and obstacle,and then promotes the yield and volatile constituents production of Atractylodes lancea.

On the Selection of Non-Invasive Methods Based on Speech Analysis Oriented to Automatic Alzheimer Disease Diagnosis

PubMed Central

López-de-Ipiña, Karmele; Alonso, Jesus-Bernardino; Travieso, Carlos Manuel; Solé-Casals, Jordi; Egiraun, Harkaitz; Faundez-Zanuy, Marcos; Ezeiza, Aitzol; Barroso, Nora; Ecay-Torres, Miriam; Martinez-Lage, Pablo; de Lizardui, Unai Martinez

2013-01-01

The work presented here is part of a larger study to identify novel technologies and biomarkers for early Alzheimer disease (AD) detection and it focuses on evaluating the suitability of a new approach for early AD diagnosis by non-invasive methods. The purpose is to examine in a pilot study the potential of applying intelligent algorithms to speech features obtained from suspected patients in order to contribute to the improvement of diagnosis of AD and its degree of severity. In this sense, Artificial Neural Networks (ANN) have been used for the automatic classification of the two classes (AD and control subjects). Two human issues have been analyzed for feature selection: Spontaneous Speech and Emotional Response. Not only linear features but also non-linear ones, such as Fractal Dimension, have been explored. The approach is non invasive, low cost and without any side effects. Obtained experimental results were very satisfactory and promising for early diagnosis and classification of AD patients. PMID:23698268

Atropinic burden of prescriptions forms in patients with Alzheimer disease: a cross-sectional study in a French PharmacoVigilance Database.

PubMed

Montastruc, François; Rouanet, Sarah; Gardette, Virginie; Rousseau, Vanessa; Bagheri, Haleh; Montastruc, Jean-Louis

2015-07-01

Atropinic drugs in patients with Alzheimer disease (AD) can decrease the effects of anticholinesterase drugs and/or induce adverse drug reactions (ADRs). Several atropinic risk scales defining an atropinic burden of drugs were proposed but were little used in AD patients. All ADRs' notifications of AD patients registered in the Midi-Pyrénées PharmacoVigilance Database between 1999 and 2013 were analyzed using Anticholinergic Drug Scale (ADS) and Anticholinergic Duran's list. The primary objective was to quantify atropinic burden in AD patients and the secondary one to investigate associated factors. Among the 475 notifications, at least one atropinic drug was found in 282 notifications (59.4%) according to ADS and 214 (45.1%) according to Duran. Mean number of atropinics per notifications was 0.9 ± 0.9 (ADS) and 0.7 ± 0.9 (Duran). Mean atropinic burden per notifications was 1.2 ± 1.5 (ADS) and 0.9 ± 1.3 (Duran). Atropinic burden ≥ 3 was found in 87 notifications (18.2%) according to ADS and 50 (10.5%) according to Duran. There was no association between atropinic burden and age of patients. The number of drugs is associated to a high atropinic burden. The present work found an association between an atropinic drug and an anticholinesterase agent in around 1 out of 2 AD patients and a clinically significant atropinic burden (≥ 3) in around 1 to 2 AD patients out of 10. The benefit harm balance of atropinic drugs must be discussed before each prescription in AD patients.

Biomarkers in Sporadic and Familial Alzheimer's Disease.

PubMed

Lista, Simone; O'Bryant, Sid E; Blennow, Kaj; Dubois, Bruno; Hugon, Jacques; Zetterberg, Henrik; Hampel, Harald

2015-01-01

Most forms of Alzheimer's disease (AD) are sporadic (sAD) or inherited in a non-Mendelian fashion, and less than 1% of cases are autosomal-dominant. Forms of sAD do not exhibit familial aggregation and are characterized by complex genetic and environmental interactions. Recently, the expansion of genomic methodologies, in association with substantially larger combined cohorts, has resulted in various genome-wide association studies that have identified several novel genetic associations of AD. Currently, the most effective methods for establishing the diagnosis of AD are defined by multi-modal pathways, starting with clinical and neuropsychological assessment, cerebrospinal fluid (CSF) analysis, and brain-imaging procedures, all of which have significant cost- and access-to-care barriers. Consequently, research efforts have focused on the development and validation of non-invasive and generalizable blood-based biomarkers. Among the modalities conceptualized by the systems biology paradigm and utilized in the "exploratory biomarker discovery arena", proteome analysis has received the most attention. However, metabolomics, lipidomics, transcriptomics, and epigenomics have recently become key modalities in the search for AD biomarkers. Interestingly, biomarker changes for familial AD (fAD), in many but not all cases, seem similar to those for sAD. The integration of neurogenetics with systems biology/physiology-based strategies and high-throughput technologies for molecular profiling is expected to help identify the causes, mechanisms, and biomarkers associated with the various forms of AD. Moreover, in order to hypothesize the dynamic trajectories of biomarkers through disease stages and elucidate the mechanisms of biomarker alterations, updated and more sophisticated theoretical models have been proposed for both sAD and fAD.

An integrative examination of general personality dysfunction in a large community sample.

PubMed

Hengartner, Michael Pascal; De Fruyt, Filip; Rodgers, Stephanie; Müller, Mario; Rössler, Wulf; Ajdacic-Gross, Vladeta

2014-10-01

Recently, the severity of general personality dysfunction has gained broad interest in personality disorder (PD) research. We analysed data of 511 participants aged 20-41 years from a comprehensive psychiatric survey in the general population of Zurich, Switzerland. We added the trait-scores from all DSM-IV PDs, as assessed by a self-report questionnaire, to provide a measure of general personality dysfunction. Adjusting for the Big Five personality domains as a proxy for stylistic PD elements, this composite PD score exhibited strong associations with neuroticism and schizotypy. General personality dysfunction additionally revealed a moderate detrimental association with psychosocial functioning and a strong effect on coping resources, on heavy drinking and drug use and on most psychopathological syndromes. Of particular interest is the strong association with total psychopathological distress and co-occurrence of multiple disorders, suggesting that increasing PD severity relates to the degree of global impairment independent of specific PD traits. Discussed herein are implications for public mental health policies, classification, conceptualization and treatment of PDs. Copyright © 2014 John Wiley & Sons, Ltd.

Lower Choline and Myo-Inositol in Temporo-Parietal Cortex Is Associated With Apathy in Amnestic MCI.

PubMed

Tumati, Shankar; Opmeer, Esther M; Marsman, Jan-Bernard C; Martens, Sander; Reesink, Fransje E; De Deyn, Peter P; Aleman, André

2018-01-01

Apathy is a common symptom in patients with amnestic mild cognitive impairment (aMCI) and is associated with an increased risk of progression to Alzheimer's disease (AD). The neural substrates underlying apathy in aMCI may involve multiple brain regions, including the anterior cingulate cortex and the temporo-parietal region. Here we investigated neurometabolites in brain regions that may underlie apathy in aMCI patients using proton magnetic resonance spectroscopy ( 1 H-MRS). Twenty-eight aMCI patients with varying degrees of apathy and 20 matched controls underwent 1 H-MRS. Spectra were acquired from single voxels in the posterior cingulate cortex (PCC), dorsal anterior cingulate cortex (DACC), right dorsolateral prefrontal cortex (DLPFC), and right temporo-parietal cortex (TPC). Apathy was measured with the Apathy Evaluation Scale (AES). Spearman partial correlations between metabolite concentrations in each region and severity of apathy were determined. Additionally, analyses of covariance (ANCOVA) were performed to determine whether metabolite changes differed between patients with or without clinically-diagnosed apathy. The degree of apathy was found to be negatively correlated with choline and myo-inositol (mI) in the TPC. Additional exploratory analyses suggested that N-acetylaspartate (NAA)/mI ratio was reduced in aMCI without clinical apathy but not in aMCI with clinical apathy. In the DACC, glutamate and glutamine (Glx) levels tended to be higher in the aMCI with apathy group compared to controls and reduced in association with depression scores. In conclusion, apathy in aMCI patients was associated with neurometabolite changes indicative of altered membranal integrity and glial function in the right TPC. Findings also indicated that in a clinically-diagnosed aMCI cohort, apathy symptoms may be suggestive of neural changes that are distinct from aMCI without apathy.

Kinematic and Pressure Features of Handwriting and Drawing: Preliminary Results Between Patients with Mild Cognitive Impairment, Alzheimer Disease and Healthy Controls

PubMed Central

Garre-Olmo, Josep; Faúndez-Zanuy, Marcos; López-de-Ipiña, Karmele; Calvó-Perxas, Laia; Turró-Garriga, Oriol

2017-01-01

Background: Alzheimer’s disease (AD) is the most common neurodegenerative dementia of old age, and the leading chronic disease contributor to disability and dependence among older people worldwide. Clinically, AD is characterized by a progressive cognitive decline that interferes with the abil-ity to perform the activities of daily living. Handwriting and drawing are complex human activities that entail an intricate blend of cognitive, kinesthetic, and perceptual-motor features. Objective: To compare the kinematic characteristics of handwriting and drawing between patients with AD, patients with mild cognitive impairment (MCI) and healthy controls. Methods: We used a cross-sectional and observational design to assess the kinematic and pressure fea-tures of handwriting and drawing using a computerized system. Participants were asked to copy one sen-tence, write a dictated sentence and an own sentence, copy two and-three dimensions drawings, and to execute the clock drawing test. By means of discriminant analyses, we explored the value of several kin-ematic features in order to classify participants depending on their degree of cognitive functioning. Results: The sample consisted of 52 participants (23 AD, 12 MCI, and 17 healthy controls) with a mean age of 69.7 years (SD=8.11). The degree of correct classification was largely dependent on the nature of the groups to be classified and the specific task, and ranged between 63.5% and 100%. Diagnostic accu-racy based on kinematic measures showed higher specificity values for distinguishing between normal and impaired cognition (MCI and AD), and higher sensitivity was obtained when distinguishing between impaired cognition levels (MCI vs. AD). Conclusion: The kinematic features of writing and drawing procedures, rather than the final product, may be a useful and objective complement to the clinical assessment of patients with cognitive impairment. PMID:28290244

Kinematic and Pressure Features of Handwriting and Drawing: Preliminary Results Between Patients with Mild Cognitive Impairment, Alzheimer Disease and Healthy Controls.

PubMed

Garre-Olmo, Josep; Faúndez-Zanuy, Marcos; López-de-Ipiña, Karmele; Calvó-Perxas, Laia; Turró-Garriga, Oriol

2017-01-01

Alzheimer's disease (AD) is the most common neurodegenerative dementia of old age, and the leading chronic disease contributor to disability and dependence among older people worldwide. Clinically, AD is characterized by a progressive cognitive decline that interferes with the ability to perform the activities of daily living. Handwriting and drawing are complex human activities that entail an intricate blend of cognitive, kinesthetic, and perceptual-motor features. To compare the kinematic characteristics of handwriting and drawing between patients with AD, patients with mild cognitive impairment (MCI) and healthy controls. We used a cross-sectional and observational design to assess the kinematic and pressure features of handwriting and drawing using a computerized system. Participants were asked to copy one sentence, write a dictated sentence and an own sentence, copy two and-three dimensions drawings, and to execute the clock drawing test. By means of discriminant analyses, we explored the value of several kinematic features in order to classify participants depending on their degree of cognitive functioning. The sample consisted of 52 participants (23 AD, 12 MCI, and 17 healthy controls) with a mean age of 69.7 years (SD=8.11). The degree of correct classification was largely dependent on the nature of the groups to be classified and the specific task, and ranged between 63.5% and 100%. Diagnostic accuracy based on kinematic measures showed higher specificity values for distinguishing between normal and impaired cognition (MCI and AD), and higher sensitivity was obtained when distinguishing between impaired cognition levels (MCI vs. AD). The kinematic features of writing and drawing procedures, rather than the final product, may be a useful and objective complement to the clinical assessment of patients with cognitive impairment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Downregulation of peptide transporter genes in cell lines transformed with the highly oncogenic adenovirus 12

PubMed Central

1994-01-01

The expression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and correlates with the high oncogenicity of this virus. In primary embryonal fibroblasts from transgenic mice that express both endogenous H-2 genes and a miniature swine class I gene (PD1), Ad12- mediated transformation results in suppression of cell surface expression of all class I antigens. Although class I mRNA levels of PD1 and H-2Db are similar to those in nonvirally transformed cells, recognition of newly synthesized class I molecules by a panel of monoclonal antibodies is impaired, presumably as a result of inefficient assembly and transport of the class I molecules. Class I expression can be partially induced by culturing cells at 26 degrees C, or by coculture of cells with class I binding peptides at 37 degrees C. Analysis of steady state mRNA levels of the TAP1 and TAP2 transporter genes for Ad12-transformed cell lines revealed that they both are significantly reduced, TAP2 by about 100-fold and TAP1 by 5-10-fold. Reconstitution of PD1 and H-2Db, but not H-2Kb, expression is achieved in an Ad12-transformed cell line by stable transfection with a TAP2, but not a TAP1, expression construct. From these data it may be concluded that suppressed expression of peptide transporter genes, especially TAP2, in Ad12-transformed cells inhibits cell surface expression of class I molecules. The failure to fully reconstitute H- 2Db and H-2Kb expression indicates that additional factors are involved in controlling class I gene expression in Ad12-transformed cells. Nevertheless, these results suggest that suppression of peptide transporter genes might be an important mechanism whereby virus- transformed cells escape immune recognition in vivo. PMID:7519239

Association between intake of total vs added sugar on diet quality: a systematic review.

PubMed

Louie, Jimmy Chun Yu; Tapsell, Linda C

2015-12-01

Given its potential effect on nutrient and energy density, the sugar content of the diet is a subject of controversy. The aim of this review was to examine the cross-sectional or prospective evidence for associations between the intake of total sugar or added sugar (high vs low intakes) and diet quality or nutrient intakes in the general population. The following databases were searched for English-language articles published between 1972 and 2012: CINAHL Plus, EBM Reviews, ERIC, MEDLINE, PREMEDLINE, PsycINFO, PubMed, and ScienceDirect. The search identified studies that examined the association between intake of total sugar and/or added sugar and diet quality (n = 22) or nutrient intakes (n = 30). The following data were extracted: sample size and population, dietary assessment method, source of added sugar data, source of funding, comparator, association between total sugar or added sugar and diet quality, and the direction and magnitude of the association. Of 22 studies, all except 1 found a higher intake of added sugar to be associated with poorer diet quality, and the exceptional study did not adjust for total energy intake. Twenty-one of 30 studies found a negative association between added sugar and micronutrient intakes. The same association was not found for total sugar intake. Any negative association between dietary sugar and diet quality is better exposed by referring to added sugar rather than total sugar. There was substantial variation in features of study quality, including sample size, so the magnitude of the observed effect was generally small and may not be of clinical significance. Furthermore, the positive influence that core foods such as fruit and milk exert on total sugar values may bias the association between total sugar and diet quality. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

FRED: Exergame to Prevent Dependence and Functional Deterioration Associated with Ageing. A Pilot Three-Week Randomized Controlled Clinical Trial.

PubMed

Mugueta-Aguinaga, Iranzu; Garcia-Zapirain, Begonya

2017-11-23

Introduction: Frailty syndrome and advanced age may decrease the acceptance of illness and quality of life, and worsen patients' existing health conditions, as well as leading to an increase in health care expenses. Purpose: The purpose of this study is to reduce frailty risk via the use of a FRED game which has been expressly designed and put together for the study. Materials and methods: A total of 40 frail volunteers with a score of <10 points in the short physical performance battery (SPPB) took part in a feasibility study in order to validate the FRED game. Following randomisation, the study group (20 subjects) took part in nine sessions of 20 min each over a three-week period. The control group (19 subjects) continued to lead their daily lives in the course of which they had no physical activity scheduled; Results: After three weeks and having taken part in nine physical activity sessions with the FRED game, 60% of subjects from the study group (12/20) obtained a score of ≥10 points at the end of the study, i.e., less risk of evidencing frailty. This result proved to be statistically significant ( p < 0.001). The degree of compliance with and adherence to the game was confirmed by 100% attendance of the sessions. Discussion: Our findings support the hypothesis that FRED, an ad hoc designed exergame, significantly reduced the presence and severity of frailty in a sample of sedentary elders, thus potentially modifying their risk profile. Conclusions: The FRED game is a tool that shows a 99% certain improvement in the degree of frailty in frail elderly subjects. The effectiveness of the design of ad hoc games in a certain pathology or population group is therefore evidenced.

FRED: Exergame to Prevent Dependence and Functional Deterioration Associated with Ageing. A Pilot Three-Week Randomized Controlled Clinical Trial

PubMed Central

Garcia-Zapirain, Begonya

2017-01-01

Introduction: Frailty syndrome and advanced age may decrease the acceptance of illness and quality of life, and worsen patients’ existing health conditions, as well as leading to an increase in health care expenses. Purpose: The purpose of this study is to reduce frailty risk via the use of a FRED game which has been expressly designed and put together for the study. Materials and Methods: A total of 40 frail volunteers with a score of <10 points in the short physical performance battery (SPPB) took part in a feasibility study in order to validate the FRED game. Following randomisation, the study group (20 subjects) took part in nine sessions of 20 min each over a three-week period. The control group (19 subjects) continued to lead their daily lives in the course of which they had no physical activity scheduled; Results: After three weeks and having taken part in nine physical activity sessions with the FRED game, 60% of subjects from the study group (12/20) obtained a score of ≥10 points at the end of the study, i.e., less risk of evidencing frailty. This result proved to be statistically significant (p < 0.001). The degree of compliance with and adherence to the game was confirmed by 100% attendance of the sessions. Discussion: Our findings support the hypothesis that FRED, an ad hoc designed exergame, significantly reduced the presence and severity of frailty in a sample of sedentary elders, thus potentially modifying their risk profile. Conclusions: The FRED game is a tool that shows a 99% certain improvement in the degree of frailty in frail elderly subjects. The effectiveness of the design of ad hoc games in a certain pathology or population group is therefore evidenced. PMID:29168787

A hyperosmolar-colloidal additive to the CPB-priming solution reduces fluid load and fluid extravasation during tepid CPB.

PubMed

Kvalheim, V; Farstad, M; Haugen, O; Brekke, H; Mongstad, A; Nygreen, E; Husby, P

2008-01-01

Cardiopulmonary bypass(CPB) is associated with fluid overload. We hypothesized that fluid gain during CPB could be reduced by substituting parts of a crystalloid prime with 7.2% hypertonic saline and 6% poly (O-2-hydroxyethyl) starch solution (HyperHaes). 14 animals were randomized to a control group (Group C) or to Group H. CPB-prime in Group C was Ringer's solution. In group H, 4 ml/kg of Ringer's solution was replaced by the hypertonic saline/hydroxyethyl starch solution. After 60 min stabilization, CPB was initiated and continued for 120 min. All animals were allowed drifting of normal temperature (39.0 degrees C) to about 35.0 degrees C. Fluid was added to the CPB circuit as needed to maintain a 300-ml level in the venous reservoir. Blood chemistry, hemodynamic parameters, fluid balance, plasma volume, fluid extravasation rate (FER), tissue water content and acid-base parameters were measured/calculated. Total fluid need during 120 min CPB was reduced by 60% when hypertonic saline/hydroxyethyl starch solution was added to the CPB prime (p < 0.01). The reduction was related to a lowered FER. The effect was most pronounced during the first 30 min on CPB, with 0.6 (0.43) (Group H) compared with 1.5 (0.40) ml/kg/min (Group C) (p < 0.01). Hemodynamics and laboratory parameters were similar in both groups. Serum concentrations of sodium and chloride increased to maximum levels of 148 (1.5) and 112 (1.6) mmol/l in Group H. To conclude: addition of 7.2% hypertonic saline and 6% poly (O-2-hydroxyethyl) starch solution to crystalloid CPB prime reduces fluid needs and FER during tepid CPB.

Tissue dissolution by sodium hypochlorite: effect of concentration, temperature, agitation, and surfactant.

PubMed

Stojicic, Sonja; Zivkovic, Slavoljub; Qian, Wei; Zhang, Hui; Haapasalo, Markus

2010-09-01

Sodium hypochlorite is the most commonly used endodontic irrigant because of its antimicrobial and tissue-dissolving activity. The aim of this study was to evaluate and compare the effects of concentration, temperature, and agitation on the tissue-dissolving ability of sodium hypochlorite. In addition, a hypochlorite product with added surface active agent was compared with conventional hypochlorite solutions. Three sodium hypochlorite solutions from two different manufacturers in concentrations of 1%, 2%, 4%, and 5.8% were tested at room temperature, 37 degrees C, and 45 degrees C with and without agitation by ultrasonic and sonic energy and pipetting. Distilled and sterilized tap water was used as controls. Pieces of bovine muscle tissue (68 +/- 3 mg) were placed in 10 mL of each solution for five minutes. In selected samples, agitation was performed for one, two, or four 15-second periods per each minute. The tissue specimens were weighed before and after treatment, and the percentage of weight loss was calculated. The contact angle on dentin of the three solutions at concentrations of 1% and 5.8% was measured. Weight loss (dissolution) of the tissue increased almost linearly with the concentration of sodium hypochlorite. Higher temperatures and agitation considerably enhanced the efficacy of sodium hypochlorite. The effect of agitation on tissue dissolution was greater than that of temperature; continuous agitation resulted in the fastest tissue dissolution. Hypochlorite with added surface active agent had the lowest contact angle on dentin and was most effective in tissue dissolution in all experimental situations. Optimizing the concentration, temperature, flow, and surface tension can improve the tissue-dissolving effectiveness of hypochlorite even 50-fold. Copyright 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The transobturator suburethral sling: a safe and effective option for all degrees of post prostatectomy urinary incontinence.

PubMed

Sullivan, John F; Stassen, Paul N; Moran, Diarmuid; Bolton, Eva M; Smyth, Lisa G; Browne, Cliodhna M; Forde, James C; Tal, Raanan; Lynch, Thomas H

2018-04-01

Male stress urinary incontinence (SUI) after radical prostatectomy (RP) is common. The surgical standard of care traditionally has been placement of an artificial urinary sphincter (AUS) but since its introduction the transobturator male sling has been shown to have particular unique advantages. Our aim was to assess outcomes of a consecutive series of suburethral sling insertions in men presenting with all degrees of post RP SUI. A consecutive cohort of men undergoing AdVance sling insertion following RP were studied. Parameters assessed included pre and postoperative urinary function, 24 hour pad use, quality of life (QoL) outcomes, complications and further treatments. Degree of incontinence was categorized as mild (1-2), moderate (3-5) or severe (≥ 6) depending on daily pad use. Patients were reviewed at 1, 4 and 6 months. The International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) was used to assess symptom severity and QoL outcomes. Seventy-seven patients were included, mean age 68 and mean time to sling post RP 34 (8-113) months. Preoperative degree of incontinence: mild 22%, moderate 58%, severe 20%. Fourteen percent had undergone post RP radiation therapy (RT). In total 73% experienced complete resolution of symptoms post sling, 12% significant improvement, 15% no reduction in pad use. Sixty percent with severe incontinence were classified as cured (no pad or 1 dry pad for security reasons). When patients with preoperative RT were excluded, cure rate rose to 82%. On follow up survey at 30 months (mean), the ICIQ-SF score decreased from baseline 17.7 (9-21.0) to 8.0 (0-20) (p < 0.0001), CI 95% (8-12). Suburethral slings are effective and safe for all degrees of post RP incontinence, are associated with improved QoL parameters and with appropriate selection and counseling are a viable option for more severe degrees of post RP SUI.

CDK5RAP2 gene and tau pathophysiology in late-onset sporadic Alzheimer's disease.

PubMed

Miron, Justin; Picard, Cynthia; Nilsson, Nathalie; Frappier, Josée; Dea, Doris; Théroux, Louise; Poirier, Judes

2018-06-01

Because currently known Alzheimer's disease (AD) single-nucleotide polymorphisms only account for a small fraction of the genetic variance in this disease, there is a need to identify new variants associated with AD. Our team performed a genome-wide association study in the Quebec Founder Population isolate to identify novel protective or risk genetic factors for late-onset sporadic AD and examined the impact of these variants on gene expression and AD pathology. The rs10984186 variant is associated with an increased risk of developing AD and with a higher CDK5RAP2 mRNA prevalence in the hippocampus. On the other hand, the rs4837766 variant, which is among the best cis-expression quantitative trait loci in the CDK5RAP2 gene, is associated with lower mild cognitive impairment/AD risk and conversion rate. The rs10984186 risk and rs4837766 protective polymorphic variants of the CDK5RAP2 gene might act as potent genetic modifiers for AD risk and/or conversion by modulating the expression of this gene. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Higher brain BDNF gene expression is associated with slower cognitive decline in older adults.

PubMed

Buchman, Aron S; Yu, Lei; Boyle, Patricia A; Schneider, Julie A; De Jager, Philip L; Bennett, David A

2016-02-23

We tested whether brain-derived neurotrophic factor (BDNF) gene expression levels are associated with cognitive decline in older adults. Five hundred thirty-five older participants underwent annual cognitive assessments and brain autopsy at death. BDNF gene expression was measured in the dorsolateral prefrontal cortex. Linear mixed models were used to examine whether BDNF expression was associated with cognitive decline adjusting for age, sex, and education. An interaction term was added to determine whether this association varied with clinical diagnosis proximate to death (no cognitive impairment, mild cognitive impairment, or dementia). Finally, we examined the extent to which the association of Alzheimer disease (AD) pathology with cognitive decline varied by BDNF expression. Higher brain BDNF expression was associated with slower cognitive decline (p < 0.001); cognitive decline was about 50% slower with the 90th percentile BDNF expression vs 10th. This association was strongest in individuals with dementia. The level of BDNF expression was lower in individuals with pathologic AD (p = 0.006), but was not associated with macroscopic infarcts, Lewy body disease, or hippocampal sclerosis. BDNF expression remained associated with cognitive decline in a model adjusting for age, sex, education, and neuropathologies (p < 0.001). Furthermore, the effect of AD pathology on cognitive decline varied by BDNF expression such that the effect was strongest for high levels of AD pathology (p = 0.015); thus, in individuals with high AD pathology (90th percentile), cognitive decline was about 40% slower with the 90th percentile BDNF expression vs 10th. Higher brain BDNF expression is associated with slower cognitive decline and may also reduce the deleterious effects of AD pathology on cognitive decline. © 2016 American Academy of Neurology.

Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients.

PubMed

Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya

2016-01-19

Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide.

Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients

PubMed Central

Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya

2016-01-01

Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide. PMID:26784730

Associations Between Genetic Variants in 19p13 and 19q13 Regions and Susceptibility to Alzheimer Disease: A Meta-Analysis.

PubMed

Bao, Jie; Wang, Xiao-jie; Mao, Zong-fu

2016-01-22

Alzheimer disease (AD) has become an epidemic within the growing elderly population and effective therapies of AD have not been discovered. Genetic factors accounted for over 70% of the incidence of AD and the disease-related polymorphisms are located on chromosome 19, which is one of several prominent chromosomes related to the development of AD. Many inconsistent associations between polymorphisms in ABCA7, CD33, and TOMM40 genes and the susceptibility to AD have been suggested by several independent studies. A comprehensive literature search for studies involving the association between gene polymorphisms and AD was performed, and we finally selected 3 genes (4 polymorphisms) for the meta-analysis: ABCA7 (rs3764650), CD33 (rs3865444), and TOMM40 (rs157580, rs2075650). A total of 25 articles investigating 3 genes (4 polymorphisms) were included in the meta-analysis. The pooled results of 4 polymorphisms were all significantly associated with the susceptibility to AD. The pooled effect of ABCA7 rs3764605 allele G was significantly associated with an increased the risk of AD (OR=1.20, 95% CI: 1.14-1.26, P value <0.001). Similarly, our evidence suggested that allele A of TOMM40 rs2075650 polymorphism was a risk factor for AD (OR=2.87, 95% CI: 2.46-3.34, P value <0.001). Alleles A of CD33 rs3865444 and A of TOMM40 rs157580 were both protective factors for AD onset (OR=0.94, 95% CI: 0.90-0.98, P value=0.003; OR=0.62, 95% CI: 0.57-0.66, P value <0.001). CONCLUSIONS" Results from the meta-analysis revealed that the pooled ABCA7 rs376465, CD33 rs3865444, TOMM40 rs157580, and rs2075650 variants were significantly associated with the susceptibility to AD. However, the association differed significantly between Asian and Caucasian groups for SNPs of CD33 rs3865444, TOMM40 rs157580, and rs2075650.

Rare TREM2 variants associated with Alzheimer's disease display reduced cell surface expression.

PubMed

Sirkis, Daniel W; Bonham, Luke W; Aparicio, Renan E; Geier, Ethan G; Ramos, Eliana Marisa; Wang, Qing; Karydas, Anna; Miller, Zachary A; Miller, Bruce L; Coppola, Giovanni; Yokoyama, Jennifer S

2016-09-02

Rare variation in TREM2 has been associated with greater risk for Alzheimer's disease (AD). TREM2 encodes a cell surface receptor expressed on microglia and related cells, and the R47H variant associated with AD appears to affect the ability of TREM2 to bind extracellular ligands. In addition, other rare TREM2 mutations causing early-onset neurodegeneration are thought to impair cell surface expression. Using a sequence kernel association (SKAT) analysis in two independent AD cohorts, we found significant enrichment of rare TREM2 variants not previously characterized at the protein level. Heterologous expression of the identified variants showed that novel variants S31F and R47C displayed significantly reduced cell surface expression. In addition, we identified rare variant R136Q in a patient with language-predominant AD that also showed impaired surface expression. The results suggest rare TREM2 variants enriched in AD may be associated with altered TREM2 function and that AD risk may be conferred, in part, from altered TREM2 surface expression.

Association Between Adolescent Viewership and Alcohol Advertising on Cable Television

PubMed Central

Garfield, Craig F.; Elliott, Marc N.; Ostroff, Joshua; Ross, Craig; Jernigan, David H.; Vestal, Katherine D.; Schuster, Mark A.

2010-01-01

Objectives. We examined whether alcohol advertising on cable television is associated with adolescent viewership. Methods. Using Nielsen data for every national cable alcohol advertisement from 2001 to 2006 (608 591 ads), we examined whether ad incidence in a given advertising time slot was associated with adolescent viewership (i.e., the percentage of the audience that was aged 12–20 years) after we controlled for other demographic variables. Results. Almost all alcohol ads appeared in time slots with audiences made up of 30% or fewer underage viewers. In these time slots (standardized by duration and number of viewers), each 1-percentage-point increase in adolescent viewership was associated with more beer (7%), spirits (15%), and alcopop (or low-alcohol refresher; 22%) ads, but fewer wine (−8%) ads (P < .001 for all). For spirits and alcopops, associations were stronger among adolescent girls than among adolescent boys (P < .001 for each). Conclusions. Ad placements for beer, spirits, and alcopops increased as adolescent viewership rose from 0% to 30%, especially for female viewers. Alcohol advertising practices should be modified to limit exposure of underage viewers. PMID:19696391

Association between adolescent viewership and alcohol advertising on cable television.

PubMed

Chung, Paul J; Garfield, Craig F; Elliott, Marc N; Ostroff, Joshua; Ross, Craig; Jernigan, David H; Vestal, Katherine D; Schuster, Mark A

2010-03-01

We examined whether alcohol advertising on cable television is associated with adolescent viewership. Using Nielsen data for every national cable alcohol advertisement from 2001 to 2006 (608 591 ads), we examined whether ad incidence in a given advertising time slot was associated with adolescent viewership (i.e., the percentage of the audience that was aged 12-20 years) after we controlled for other demographic variables. Almost all alcohol ads appeared in time slots with audiences made up of 30% or fewer underage viewers. In these time slots (standardized by duration and number of viewers), each 1-percentage-point increase in adolescent viewership was associated with more beer (7%), spirits (15%), and alcopop (or low-alcohol refresher; 22%) ads, but fewer wine (-8%) ads (P < .001 for all). For spirits and alcopops, associations were stronger among adolescent girls than among adolescent boys (P < .001 for each). Ad placements for beer, spirits, and alcopops increased as adolescent viewership rose from 0% to 30%, especially for female viewers. Alcohol advertising practices should be modified to limit exposure of underage viewers.

Genetic association between ghrelin polymorphisms and Alzheimer's disease in a Japanese population.

PubMed

Shibata, Nobuto; Ohnuma, Tohru; Kuerban, Bolati; Komatsu, Miwa; Arai, Heii

2011-01-01

Ghrelin has been reported to enter the hippocampus and to bind to the neurons of the hippocampal formation. This peptide also affects neuronal glucose uptake and decreases tau hyperphosphorylation. There is increasing evidence suggesting an association between ghrelin and Alzheimer's disease (AD) pathology. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) of the ghrelin gene are associated with AD. The SNPs were genotyped using TaqMan technology and were analyzed using a case-control study design. Our case-control dataset consisted of 182 AD patients and 143 age-matched controls. Hardy-Weinberg equilibrium and linkage disequilibrium analyses suggest that the region in and around the gene is highly polymorphic. One SNP, rs4684677 (Leu90Gln), showed a marginal association with age of AD onset. We did not detect any association between the other SNPs of the ghrelin gene and AD. There have been few genetic studies on the relationship between circulating ghrelin and functional SNPs. Further multifactorial studies are needed to clarify the relationship between ghrelin and AD. Copyright © 2011 S. Karger AG, Basel.

Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study.

PubMed

Varma, Vijay R; Oommen, Anup M; Varma, Sudhir; Casanova, Ramon; An, Yang; Andrews, Ryan M; O'Brien, Richard; Pletnikova, Olga; Troncoso, Juan C; Toledo, Jon; Baillie, Rebecca; Arnold, Matthias; Kastenmueller, Gabi; Nho, Kwangsik; Doraiswamy, P Murali; Saykin, Andrew J; Kaddurah-Daouk, Rima; Legido-Quigley, Cristina; Thambisetty, Madhav

2018-01-01

The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression. Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180) assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA) (N = 44, mean age = 81.33, % female = 36.36) from AD (N = 15), control (CN; N = 14), and "asymptomatic Alzheimer's disease" (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15) participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes-sphingolipids and glycerophospholipids-that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer's Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63) and preclinical (BLSA) (N = 207, mean age = 78.68, % female = 42.63) AD, in which we tested their associations with magnetic resonance imaging (MRI) measures of AD-related brain atrophy, cerebrospinal fluid (CSF) biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that summarized the relative importance of each metabolite to severity of AD pathology and disease progression (Endophenotype Association Score in Early Alzheimer's Disease [EASE-AD]). Finally, we mapped the main metabolite classes emerging from our analyses to key biological pathways implicated in AD pathogenesis. We found that distinct sphingolipid species including sphingomyelin (SM) with acyl residue sums C16:0, C18:1, and C16:1 (SM C16:0, SM C18:1, SM C16:1) and hydroxysphingomyelin with acyl residue sum C14:1 (SM (OH) C14:1) were consistently associated with severity of AD pathology at autopsy and AD progression across prodromal and preclinical stages. Higher log-transformed blood concentrations of all four sphingolipids in cognitively normal individuals were significantly associated with increased risk of future conversion to incident AD: SM C16:0 (hazard ratio [HR] = 4.430, 95% confidence interval [CI] = 1.703-11.520, p = 0.002), SM C16:1 (HR = 3.455, 95% CI = 1.516-7.873, p = 0.003), SM (OH) C14:1 (HR = 3.539, 95% CI = 1.373-9.122, p = 0.009), and SM C18:1 (HR = 2.255, 95% CI = 1.047-4.855, p = 0.038). The sphingolipid species identified map to several biologically relevant pathways implicated in AD, including tau phosphorylation, amyloid-β (Aβ) metabolism, calcium homeostasis, acetylcholine biosynthesis, and apoptosis. Our study has limitations: the relatively small number of brain tissue samples may have limited our power to detect significant associations, control for heterogeneity between groups, and replicate our findings in independent, autopsy-derived brain samples. We present a novel framework to identify biologically relevant brain and blood metabolites associated with disease pathology and progression during the prodromal and preclinical stages of AD. Our results show that perturbations in sphingolipid metabolism are consistently associated with endophenotypes across preclinical and prodromal AD, as well as with AD pathology at autopsy. Sphingolipids may be biologically relevant biomarkers for the early detection of AD, and correcting perturbations in sphingolipid metabolism may be a plausible and novel therapeutic strategy in AD.

Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study

PubMed Central

Oommen, Anup M.; Varma, Sudhir; Casanova, Ramon; An, Yang; O’Brien, Richard; Pletnikova, Olga; Kastenmueller, Gabi; Doraiswamy, P. Murali; Kaddurah-Daouk, Rima; Thambisetty, Madhav

2018-01-01

Background The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression. Methods and findings Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180) assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA) (N = 44, mean age = 81.33, % female = 36.36) from AD (N = 15), control (CN; N = 14), and “asymptomatic Alzheimer’s disease” (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15) participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes—sphingolipids and glycerophospholipids—that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer’s Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63) and preclinical (BLSA) (N = 207, mean age = 78.68, % female = 42.63) AD, in which we tested their associations with magnetic resonance imaging (MRI) measures of AD-related brain atrophy, cerebrospinal fluid (CSF) biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that summarized the relative importance of each metabolite to severity of AD pathology and disease progression (Endophenotype Association Score in Early Alzheimer’s Disease [EASE-AD]). Finally, we mapped the main metabolite classes emerging from our analyses to key biological pathways implicated in AD pathogenesis. We found that distinct sphingolipid species including sphingomyelin (SM) with acyl residue sums C16:0, C18:1, and C16:1 (SM C16:0, SM C18:1, SM C16:1) and hydroxysphingomyelin with acyl residue sum C14:1 (SM (OH) C14:1) were consistently associated with severity of AD pathology at autopsy and AD progression across prodromal and preclinical stages. Higher log-transformed blood concentrations of all four sphingolipids in cognitively normal individuals were significantly associated with increased risk of future conversion to incident AD: SM C16:0 (hazard ratio [HR] = 4.430, 95% confidence interval [CI] = 1.703–11.520, p = 0.002), SM C16:1 (HR = 3.455, 95% CI = 1.516–7.873, p = 0.003), SM (OH) C14:1 (HR = 3.539, 95% CI = 1.373–9.122, p = 0.009), and SM C18:1 (HR = 2.255, 95% CI = 1.047–4.855, p = 0.038). The sphingolipid species identified map to several biologically relevant pathways implicated in AD, including tau phosphorylation, amyloid-β (Aβ) metabolism, calcium homeostasis, acetylcholine biosynthesis, and apoptosis. Our study has limitations: the relatively small number of brain tissue samples may have limited our power to detect significant associations, control for heterogeneity between groups, and replicate our findings in independent, autopsy-derived brain samples. Conclusions We present a novel framework to identify biologically relevant brain and blood metabolites associated with disease pathology and progression during the prodromal and preclinical stages of AD. Our results show that perturbations in sphingolipid metabolism are consistently associated with endophenotypes across preclinical and prodromal AD, as well as with AD pathology at autopsy. Sphingolipids may be biologically relevant biomarkers for the early detection of AD, and correcting perturbations in sphingolipid metabolism may be a plausible and novel therapeutic strategy in AD. PMID:29370177

Genetically-Predicted Adult Height and Alzheimer's Disease.

PubMed

Larsson, Susanna C; Traylor, Matthew; Burgess, Stephen; Markus, Hugh S

2017-01-01

Observational studies have linked increased adult height with better cognitive performance and reduced risk of Alzheimer's disease (AD). It is unclear whether the associations are due to shared biological processes that influence height and AD or due to confounding by early life exposures or environmental factors. To use a genetic approach to investigate the association between adult height and AD. We selected 682 single nucleotide polymorphisms (SNPs) associated with height at genome-wide significance (p < 5×10-8) in the Genetic Investigation of ANthropometric Traits (GIANT) consortium. Summary statistics for each of these SNPs on AD were obtained from the International Genomics of Alzheimer's Project (IGAP) of 17,008 individuals with AD and 37,154 controls. The estimate of the association between genetically predicted height and AD was calculated using the inverse-variance weighted method. The odds ratio of AD was 0.91 (95% confidence interval, 0.86-0.95; p = 9.8×10-5) per one standard deviation increase (about 6.5 cm) in genetically predicted height based on 682 SNPs, which were clustered in 419 loci. In an analysis restricted to one SNP from each height-associated locus (n = 419 SNPs), the corresponding OR was 0.92 (95% confidence interval, 0.86-0.97; p = 4.8×10-3). This finding suggests that biological processes that influence adult height may have a role in the etiology of AD.

The Association between Potential Exposure to Magazine Ads with Voluntary Health Warnings and the Perceived Harmfulness of Electronic Nicotine Delivery Systems (ENDS)

PubMed Central

Weaver, Scott R.; Zahra, Nahleen; Huang, Jidong; Cheng, Kai-Wen; Chaloupka, Frank J.

2018-01-01

(1) Background: Several brands of electronic nicotine delivery systems (ENDS) carry voluntary health warning messages. This study examined how potential exposure to ENDS magazine ads with these voluntary health warnings were associated with the perceived harmfulness of ENDS. (2) Methods: Risk perception measures and self-reported exposure to ENDS ads were obtained from the 2014 Georgia State University (GSU) Tobacco Products and Risk Perceptions Survey of a nationally representative sample of U.S. adults. We examined the association between potential exposure to magazine ads with warnings and the perceived harms of ENDS relative to cigarettes, using binary logistic regressions and controlling for general ENDS ad exposure and socio-demographic characteristics. (3) Results: Potential exposure to ENDS magazine ads with warnings was associated with a lower probability of considering ENDS to be more or equally harmful compared to cigarettes, particularly among non-smokers (OR = 0.16; 95% CI: 0.04–0.77). In addition, ad exposure, ENDS use history, race/ethnicity, gender, education, and income were also associated with harm perceptions. (4) Conclusions: This study did not find evidence that magazine ads with warnings increased misperceptions that ENDS are equally or more harmful than cigarettes. With more ENDS advertisements carrying warnings, more research is needed to determine how the warnings in advertisements convey relative harm information to consumers and the public. PMID:29570638

The Association between Potential Exposure to Magazine Ads with Voluntary Health Warnings and the Perceived Harmfulness of Electronic Nicotine Delivery Systems (ENDS).

PubMed

Shang, Ce; Weaver, Scott R; Zahra, Nahleen; Huang, Jidong; Cheng, Kai-Wen; Chaloupka, Frank J

2018-03-23

(1) Background: Several brands of electronic nicotine delivery systems (ENDS) carry voluntary health warning messages. This study examined how potential exposure to ENDS magazine ads with these voluntary health warnings were associated with the perceived harmfulness of ENDS. (2) Methods: Risk perception measures and self-reported exposure to ENDS ads were obtained from the 2014 Georgia State University (GSU) Tobacco Products and Risk Perceptions Survey of a nationally representative sample of U.S. adults. We examined the association between potential exposure to magazine ads with warnings and the perceived harms of ENDS relative to cigarettes, using binary logistic regressions and controlling for general ENDS ad exposure and socio-demographic characteristics. (3) Results: Potential exposure to ENDS magazine ads with warnings was associated with a lower probability of considering ENDS to be more or equally harmful compared to cigarettes, particularly among non-smokers (OR = 0.16; 95% CI: 0.04-0.77). In addition, ad exposure, ENDS use history, race/ethnicity, gender, education, and income were also associated with harm perceptions. (4) Conclusions: This study did not find evidence that magazine ads with warnings increased misperceptions that ENDS are equally or more harmful than cigarettes. With more ENDS advertisements carrying warnings, more research is needed to determine how the warnings in advertisements convey relative harm information to consumers and the public.

Quantification of Butyrylcholinesterase Activity as a Sensitive and Specific Biomarker of Alzheimer's Disease.

PubMed

Macdonald, Ian R; Maxwell, Selena P; Reid, George A; Cash, Meghan K; DeBay, Drew R; Darvesh, Sultan

2017-01-01

Amyloid-β (Aβ) plaques are a neuropathological hallmark of Alzheimer's disease (AD); however, a significant number of cognitively normal older adults can also have Aβ plaques. Thus, distinguishing AD from cognitively normal individuals with Aβ plaques (NwAβ) based on Aβ plaque detection is challenging. It has been observed that butyrylcholinesterase (BChE) accumulates in plaques preferentially in AD. Thus, detecting BChE-associated plaques has the potential as an improved AD biomarker. We present Aβ, thioflavin-S, and BChE quantification of 26 postmortem brain tissues; AD (n = 8), NwAβ (n = 6), cognitively normal without plaques (n = 8), and other common dementias including corticobasal degeneration, frontotemporal dementia with tau, dementia with Lewy bodies, and vascular dementia. Pathology burden in the orbitofrontal cortex, entorhinal cortex, amygdala, and hippocampal formation was determined and compared. The predictive value of Aβ and BChE quantification was determined, via receiver-operating characteristic plots, to evaluate their AD diagnostic performance using sensitivity, specificity, and area under curve (AUC) metrics. In general, Aβ and BChE-associated pathology were greater in AD, particularly in the orbitofrontal cortex. In this region, the largest increase (9.3-fold) was in BChE-associated pathology, observed between NwAβ and AD, due to the virtual absence of BChE-associated plaques in NwAβ brains. Furthermore, BChE did not associate with pathology of the other dementias. In this sample, BChE-associated pathology provided better diagnostic performance (AUC = 1.0, sensitivity/specificity = 100% /100%) when compared to Aβ (AUC = 0.98, 100% /85.7%). These findings highlight the predictive value of BChE as a biomarker for AD that could facilitate timely disease diagnosis and management.

Anxiety symptoms in amnestic mild cognitive impairment are associated with medial temporal atrophy and predict conversion to Alzheimer disease.

PubMed

Mah, Linda; Binns, Malcolm A; Steffens, David C

2015-05-01

To test the hypothesis that anxiety in amnestic mild cognitive impairment (aMCI) increases rates of conversion to Alzheimer disease (AD) and to identify potential neural mechanisms underlying such an association. Participants (N = 376) with aMCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were studied over a median period of 36 months. A Cox proportional-hazards model was used to assess the association between anxiety severity ratings on the Neuropsychiatric Inventory Questionnaire and AD risk. Other variables were depression, memory loss, and MRI-derived AD-related regions of interest (ROIs), including hippocampal, amygdalar, entorhinal cortical (EC) volumes, and EC thickness, In addition, a linear regression model was used to determine the effect of anxiety in aMCI on rates of atrophy within ROIs. Anxiety severity increased rate of aMCI conversion to AD, after controlling for depression and cognitive decline. The association between anxiety and AD remained significant even with inclusion of ROI baseline values or atrophy rates as explanatory variables. Further, anxiety status predicted greater rates of decrease in EC volume. An association between anxiety and EC thickness missed significance. Anxiety symptoms in aMCI predict conversion to AD, over and beyond the effects of depression, memory loss, or atrophy within AD neuroimaging biomarkers. These findings, together with the greater EC atrophy rate predicted by anxiety, are compatible with the hypothesis that anxiety is not a prodromal noncognitive feature of AD but may accelerate decline toward AD through direct or indirect effects on EC. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

High precision redundant robotic manipulator

DOEpatents

Young, Kar-Keung David

1998-01-01

A high precision redundant robotic manipulator for overcoming contents imposed by obstacles or imposed by a highly congested work space. One embodiment of the manipulator has four degrees of freedom and another embodiment has seven degreed of freedom. Each of the embodiments utilize a first selective compliant assembly robot arm (SCARA) configuration to provide high stiffness in the vertical plane, a second SCARA configuration to provide high stiffness in the horizontal plane. The seven degree of freedom embodiment also utilizes kinematic redundancy to provide the capability of avoiding obstacles that lie between the base of the manipulator and the end effector or link of the manipulator. These additional three degrees of freedom are added at the wrist link of the manipulator to provide pitch, yaw and roll. The seven degrees of freedom embodiment uses one revolute point per degree of freedom. For each of the revolute joints, a harmonic gear coupled to an electric motor is introduced, and together with properly designed based servo controllers provide an end point repeatability of less than 10 microns.

Evaluation of genetic association between an ITGAM non-synonymous SNP (rs1143679) and multiple autoimmune diseases.

PubMed

Anaya, Juan-Manuel; Kim-Howard, Xana; Prahalad, Sampath; Cherñavsky, Alejandra; Cañas, Carlos; Rojas-Villarraga, Adriana; Bohnsack, John; Jonsson, Roland; Bolstad, Anne Isine; Brun, Johan G; Cobb, Beth; Moser, Kathy L; James, Judith A; Harley, John B; Nath, Swapan K

2012-02-01

Many autoimmune diseases (ADs) share similar underlying pathology and have a tendency to cluster within families, supporting the involvement of shared susceptibility genes. To date, most of the genetic variants associated with systemic lupus erythematosus (SLE) susceptibility also show association with others ADs. ITGAM and its associated 'predisposing' variant (rs1143679, Arg77His), predicted to alter the tertiary structures of the ligand-binding domain of ITGAM, may play a key role for SLE pathogenesis. The aim of this study is to examine whether the ITGAM variant is also associated with other ADs. We evaluated case-control association between rs1143679 and ADs (N=18,457) including primary Sjögren's syndrome, systemic sclerosis, multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis, celiac disease, and type-1 diabetes. We also performed meta-analyses using our data in addition to available published data. Although the risk allele 'A' is relatively more frequent among cases for each disease, it was not significantly associated with any other ADs tested in this study. However, the meta-analysis for systemic sclerosis was associated with rs1143679 (p(meta)=0.008). In summary, this study explored the role of ITGAM in general autoimmunity in seven non-lupus ADs, and only found association for systemic sclerosis when our results were combined with published results. Thus ITGAM may not be a general autoimmunity gene but this variant may be specifically associated with SLE and systemic sclerosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Lack of genetic association between TREM2 and Alzheimer's disease in East Asian population: a systematic review and meta-analysis.

PubMed

Huang, Man; Wang, Dejun; Xu, Zhijun; Xu, Yongshan; Xu, Xiaoping; Ma, Yuefeng; Xia, Zheng

2015-09-01

Large-scale genome-wide association studies have identified TREM2 variants to be significantly associated with Alzheimer's disease (AD) in caucasian population. The goal of this systematic study and meta-analysis was to assess the association between Triggering receptor expressed on myeloid cells 2 (TREM2) variants and AD in East Asian population. In this study, literatures were searched in PubMed, MEDLINE, EMBASE, and the Cochrane library to screen citations from January 1990 to June 2014. Data analysis was done by using the Stata 12 software. Twelve studies were considered for analysis. A total of 13 535 patients with AD and 22 976 healthy controls were studied. The results showed that rs75932628 variant was significantly associated with AD in caucasian population (P < .001, odds ratio ¼ 3.17, 95% confidence interval 2.45-4.09). However, the association was not found in East Asian population. In our study, we found that TREM2 variant is likely not associated with AD in East Asian population.

Pediatric advance directives: parents' knowledge, experience, and preferences.

PubMed

Liberman, Danica B; Pham, Phung K; Nager, Alan L

2014-08-01

To explore parents' and caregivers' experience, knowledge, and preferences regarding advance directives (ADs) for children who have chronic illness. We conducted a prospective, cross-sectional survey of parents and caregivers of children who have chronic illness. During ambulatory medical visits, participants were asked about previous AD experience and knowledge, future preferences regarding AD discussions, their child's past and current health status, and family demographics. Among 307 participants surveyed, previous AD experience was low, with 117 (38.1%) having heard of an AD, 54 (17.6%) having discussed one, and 77 (25.1%) having known someone who had an AD. Furthermore, 27 (8.8%) participants had an AD or living will of their own, and 8 (2.6%) reported that their chronically ill child had an AD. Previous AD knowledge was significantly more likely among parents and caregivers who had a college degree than those who did not have a high school diploma, yet significantly less likely among primarily Spanish-speaking parents and caregivers than those primarily English-speaking. Interest in creating an AD for the child was reported by 151 (49.2%) participants, and was significantly more likely among families who had more frequent emergency department visits over the previous year. The limited AD experience and knowledge of parents and caregivers of children who have chronic illness and their interest in creating an AD suggest an unmet need among families of children who have chronic illness, and an opportunity to enhance communication between families and medical teams regarding ADs and end-of-life care. Copyright © 2014 by the American Academy of Pediatrics.

GAB2 as an Alzheimer disease susceptibility gene: follow-up of genomewide association results.

PubMed

Schjeide, Brit-Maren M; Hooli, Basavaraj; Parkinson, Michele; Hogan, Meghan F; DiVito, Jason; Mullin, Kristina; Blacker, Deborah; Tanzi, Rudolph E; Bertram, Lars

2009-02-01

Genomewide association (GWA) studies have recently implicated 4 novel Alzheimer disease (AD) susceptibility loci (GAB2, GOLM1, and 2 uncharacterized loci to date on chromosomes 9p and 15q). To our knowledge, these findings have not been independently replicated. To assess these GWA findings in 4 large data sets of families affected by AD. Follow-up of genetic association findings in previous studies. Academic research. More than 4000 DNA samples from almost 1300 families affected with AD. Genetic association analysis testing of 4 GWA signals (rs7101429 [GAB2], rs7019241 [GOLM1], rs10519262 [chromosome 15q], and rs9886784 [chromosome 9p]) using family-based methods. In the combined analyses, only rs7101429 in GAB2 yielded significant evidence of association with the same allele as in the original GWA study (P =.002). The results are in agreement with recent meta-analyses of this and other GAB2 polymorphisms suggesting approximately a 30% decrease in risk for AD among carriers of the minor alleles. None of the other 3 tested loci showed consistent evidence for association with AD across the investigated data sets. GAB2 contains genetic variants that may lead to a modest change in the risk for AD. Despite these promising results, more data from independent samples are needed to better evaluate the potential contribution of GAB2 to AD risk in the general population.

Effects of Family History and APOE ε4 Status on Cognitive Decline in the Absence of AD: The Cache County Study

PubMed Central

Hayden, Kathleen M.; Zandi, Peter P.; West, Nancy A.; Tschanz, JoAnn T.; Norton, Maria C.; Corcoran, Chris; Breitner, John C. S.; Welsh-Bohmer, Kathleen A.

2010-01-01

Context Studies have shown that the APOE ε4 genotype is associated with cognitive decline and increased risk of Alzheimer’s dementia (AD). Other genes are probably associated with both outcomes. Family history of AD (FhxAD) may represent genetic factors or shared environmental factors that increase the risk of cognitive decline. Objective To evaluate the influences of FhxAD and APOE ε4 on cognitive decline. Design, Setting, and Participants Residents of Cache County, Utah, aged 65+ were invited to participate. At baseline 2,957 participants provided DNA for genotyping at APOE and a detailed family history of AD. They also completed the Modified Mini-Mental State Examination (3MS). Cognitive status was re-examined after three and seven years. We used mixed models to examine the association between FhxAD, APOE ε4, and cognitive trajectories. Main Outcome Measure 3MS score trajectories over time. Results Compared with participants who had neither APOE ε4 nor FhxAD, those with APOE ε4 scored lower at baseline (−0.70 points on 3MS, 95% confidence interval (CI) −1.15 to −0.24). Participants with both FhxAD and APOE ε4 differed less, if at all, in baseline score (−0.46, 95% CI −1.09 to 0.16) but declined faster over 7 years (− 9.75, CI −10.82 -- 8.67) vs.(−2.91, CI −3.37 to −2.44). After exclusion of participants who developed prodromal AD or incident dementia, the group with FhxAD and APOE ε4 declined much less over 7 years (−1.54, CI −2.59 to −0.50). Conclusions These results suggest that much of the association between FhxAD, APOE ε4, and cognitive decline is attributed to undetected incipient (latent) disease. Absent this association, the two factors do not appear individually to be associated with cognitive decline although they may be additive. PMID:19901170

An optimized method for extraction and detection of Coconut cadang-cadang viroid(CCCVd) from oil palm.

PubMed

Mohammadi, M R; Vadamalai, G; Joseph, H

2010-01-01

Coconut cadong-cadong viroid (CCCVd) causes the Lethal cadang-cadang disease of coconut palms in the Philippines and it is recently reported to be associated with the orange spotting disease on oil palm in Malaysia. The low concentration of the viroid RNA in oil palm as well as the high content of polyphenols and polysaccharides in this plant which interfere with the purification steps makes it difficult to extract and detect this viroid from oil palm. A previously described method was modified and optimized for extraction and detection of CCCVd from infected oil palms. Briefly, 7 g of leaf material was homogenized in a mortar or a blender using liquid nitrogen. 10 ml of extraction buffer (100 mM Tris-HCl pH 7.5, 100 mM NaCl, 10 mM EDTA) along with 100 mM 2-mercaptoethanol and 10 ml water saturated phenol was added to the frozen powder. After centrifuging at 4 degrees C, 4000 g for 30 min, the aqueous phase was extracted once more with phenol then once with chloroform-isoamyl alcohol (24:1). After adding sodium acetate, pH 5.6 to 200 mM, the mixture was precipitated with 2.5 vol ethanol overnight in -20 freezer and then the pellet was washed with 70% ethanol and air-dried. One milliliter of 8 M LiCl was added to the dried pellet and after shaking overnight at 4 degrees C and another centrifugation step the supernatant was collected and precipitated again with ethanol and then the resulting pellet was washed and air-dried. To carry out northern blotting, samples equivalent to 40 g of plant tissue were mixed with formamide buffer and loaded onto a 12% polyacrylamide gel containing 7 M urea and after separation by electrophoresis, were electroblotted onto membrane and fixed by UV cross-linking. Pre-hybridization and hybridization using hybridization buffer (50% formamide, 25%SSPE, 0.1% Ficol and PVP, 0.1 % SDS, 0.02 % DNA (5mg/ml)) was carried out at 45 degrees C for 90 min and 16 h, respectively followed by two low stringency washes (0.5 X SSC, 0.1% SDS, at room temperature for 5 min) and one high stringency wash (0.1X SSC, 0.1% SDS at 60 degrees C for 1 hour). In vitro synthesized DIG-labeled full-length CCCVd(-) RNA probe was used in hybridization step. DIG Nucleic Acid Detection Kit (Roche) instructions were followed for detection procedure and as a result the blue bands corresponding to the position of the viroid were appeared on the membrane. The result of this study showed the ability of DIG labeled probe in detection of the viroid and also provided a suitable extraction and hybridization method for the detection of CCCVd from oil palm.

Is it possible to automatically distinguish resting EEG data of normal elderly vs. mild cognitive impairment subjects with high degree of accuracy?

PubMed

Rossini, Paolo M; Buscema, Massimo; Capriotti, Massimiliano; Grossi, Enzo; Rodriguez, Guido; Del Percio, Claudio; Babiloni, Claudio

2008-07-01

It has been shown that a new procedure (implicit function as squashing time, IFAST) based on artificial neural networks (ANNs) is able to compress eyes-closed resting electroencephalographic (EEG) data into spatial invariants of the instant voltage distributions for an automatic classification of mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects with classification accuracy of individual subjects higher than 92%. Here we tested the hypothesis that this is the case also for the classification of individual normal elderly (Nold) vs. MCI subjects, an important issue for the screening of large populations at high risk of AD. Eyes-closed resting EEG data (10-20 electrode montage) were recorded in 171 Nold and in 115 amnesic MCI subjects. The data inputs for the classification by IFAST were the weights of the connections within a nonlinear auto-associative ANN trained to generate the instant voltage distributions of 60-s artifact-free EEG data. The most relevant features were selected and coincidently the dataset was split into two halves for the final binary classification (training and testing) performed by a supervised ANN. The classification of the individual Nold and MCI subjects reached 95.87% of sensitivity and 91.06% of specificity (93.46% of accuracy). These results indicate that IFAST can reliably distinguish eyes-closed resting EEG in individual Nold and MCI subjects. IFAST may be used for large-scale periodic screening of large populations at risk of AD and personalized care.

Experimental hyperphenylalaninemia in the pregnant guinea pig: possible phenylalanine teratogenesis and p-chlorophenylalanine embryotoxicity.

PubMed

Kronick, J B; Whelan, D T; McCallion, D J

1987-10-01

Maternal hyperphenylalaninemia (HPH) due to deficient phenylalanine (Phe) hydroxylation is a recognized human teratogen associated with an increased incidence of intrauterine growth retardation, microcephaly, congenital heart disease, and mental retardation. There are no previous reports of experimental HPH during organogenesis. Sustained HPH was produced in pregnant guinea pigs by adding 3.5% Phe and 1.0% parachlorophenylalanine (pCPA), an inhibitor of Phe hydroxylase, to standard guinea pig chow. Animals consumed the supplemented test diets from gestation day 1 until killed on gestation day 17. Examination of day 17 embryos revealed that embryonic mortality was associated only with maternal pCPA administration and was independent of the degree of maternal HPH. Embryonic malformation was associated with maternal HPH as well as maternal pCPA administration. Both maternal HPH and pCPA administration were associated with embryonic growth retardation. There was no association between maternal food intake or plasma tyrosine levels and embryonic abnormality or mortality. Both Phe and tyrosine were found to be concentrated in gestation day 17 yolk sac fluid when compared to maternal plasma Phe and tyrosine. The association of embryonic malformation and maternal HPH is consistent with human data. The embryotoxicity of pCPA requires further study and highlights the necessity of appropriate controls in models of experimental HPH.

A Gadamerian Phenomenological Study Examining the Meaning of Having a Bachelor's Degree Expressed by Associate Degree Nurses (ADN) Who Educationally Transitioned to a Baccalaureate Degree in Nursing (BSN)

ERIC Educational Resources Information Center

Sauld, Jill Pierpont

2017-01-01

Since the inception of associate degree nursing programs, professional nursing conversations and debate have grappled with reckoning differences between the associate degree in nursing (ADN) and the bachelor's degree in nursing (BSN). Research reporting better patient outcomes with more baccalaureate prepared nurses has been a driving force for…

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and childhood atopic dermatitis: a prospective birth cohort study.

PubMed

Chen, Qian; Huang, Rong; Hua, Li; Guo, Yifeng; Huang, Lisu; Zhao, Yanjun; Wang, Xia; Zhang, Jun

2018-01-17

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been reported to suppress immune function. However, previous studies on prenatal exposure to PFASs and allergic disorders in offspring provided inconsistent results. We aimed to examine the association between prenatal exposure to PFASs and childhood atopic dermatitis (AD) in offspring up to 24 months of age. A prospective birth cohort study involving 1056 pregnant women was conducted in two hospitals in Shanghai from 2012 to 2015. Prenatal information was collected by an interview with the women and from medical records. Fetal umbilical cord blood was collected at birth. Cord blood plasma PFASs were measured. Children were followed at 6, 12 and 24 months and information on the development of AD was recorded. AD was diagnosed by 2 dermatologists independently based on the questionnaires. Multiple logistic regression was used to compute odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between AD and each PFASs, adjusting for potential confounders. A total of 687 children completed a 2-year follow-up visit and had PFASs measurement. AD was diagnosed in 173 (25.2%) children during the first 24 months. In female children, a log-unit increase in perfluorooctanoic acid (PFOA) was associated with a 2.1-fold increase in AD risk (AOR 2.07, 95% CI 1.13-3.80) after adjusting for potential confounders. The corresponding risk was 2.22 (1.07-4.58) for perfluorononanoic acid (PFNA). The highest PFOA quartile was significantly associated with AD (2.52, 1.12-5.68) compared with the lowest quartile. The highest quartile of PFNA, perfluorodecanoic acid (PFDA) and perfluorohexane sulfonic acid (PFHxS) were associated with AD with AOR (95% CI) being 2.14 (0.97-4.74), 2.14 (1.00-4.57), and 2.30 (1.03-5.15), respectively. Additionally, the second quartile of perfluorododecanoic acid (PFDoA) was associated with a 3.2-fold increase in AD risk (3.24, 1.44-7.27). However, no significant associations were found in male children. Prenatal exposure to PFOA, PFDA, PFDoA and PFHxS significantly increased the risk of childhood AD in female children during the first 24 months of life. In addition, the associations between AD with prenatal exposure to PFNA were close to statistical significance.

A comprehensive multiomics approach toward understanding the relationship between aging and dementia.

PubMed

Currais, Antonio; Goldberg, Joshua; Farrokhi, Catherine; Chang, Max; Prior, Marguerite; Dargusch, Richard; Daugherty, Daniel; Armando, Aaron; Quehenberger, Oswald; Maher, Pamela; Schubert, David

2015-11-01

Because age is the greatest risk factor for sporadic Alzheimer's disease (AD), phenotypic screens based upon old age-associated brain toxicities were used to develop the potent neurotrophic drug J147. Since certain aspects of aging may be primary cause of AD, we hypothesized that J147 would be effective against AD-associated pathology in rapidly aging SAMP8 mice and could be used to identify some of the molecular contributions of aging to AD. An inclusive and integrative multiomics approach was used to investigate protein and gene expression, metabolite levels, and cognition in old and young SAMP8 mice. J147 reduced cognitive deficits in old SAMP8 mice, while restoring multiple molecular markers associated with human AD, vascular pathology, impaired synaptic function, and inflammation to those approaching the young phenotype. The extensive assays used in this study identified a subset of molecular changes associated with aging that may be necessary for the development of AD.

Effect of Treating Anxiety Disorders on Cognitive Deficits and Behaviors Associated with Attention Deficit Hyperactivity Disorder: A Preliminary Study.

PubMed

Denis, Isabelle; Guay, Marie-Claude; Foldes-Busque, Guillaume; BenAmor, Leila

2016-06-01

Twenty-five percent of children with ADHD also have an anxiety disorder (AD). As per Quay and in light of Barkley's model, anxiety may have a protective effect on cognitive deficits and behaviors associated with ADHD. This study aimed to evaluate the effect of treating AD on cognitive deficits and behaviors associated with ADHD in children with both disorders. Twenty-four children with ADHD and AD were divided into two groups: treatment for AD, and wait list. Participants were assessed at pre-treatment, post-treatment, and 6-month follow-up with the ADIS-C, the CBCL, and neuropsychological measures. The results revealed a significant improvement in automatic response inhibition and flexibility, and a decrease in inattention/hyperactivity behaviors following the treatment for AD. No significant differences were observed in motor response inhibition, working memory, or attention deficits. The results do not seem to support Quay's hypothesis: treating AD did not exacerbate cognitive deficits and behaviors associated with ADHD in our sample.

Verbal fluency in bilingual Spanish/English Alzheimer's disease patients.

PubMed

Salvatierra, Judy; Rosselli, Monica; Acevedo, Amarilis; Duara, Ranjan

2007-01-01

Studies have demonstrated that in verbal fluency tests, monolinguals with Alzheimer's disease (AD) show greater difficulties retrieving words based on semantic rather than phonemic rules. The present study aimed to determine whether this difficulty was reproduced in both languages of Spanish/English bilinguals with mild to moderate AD whose primary language was Spanish. Performance on semantic and phonemic verbal fluency of 11 bilingual AD patients was compared to the performance of 11 cognitively normal, elderly bilingual individuals matched for gender, age, level of education, and degree of bilingualism. Cognitively normal subjects retrieved significantly more items under the semantic condition compared to the phonemic, whereas the performance of AD patients was similar under both conditions, suggesting greater decline in semantic verbal fluency tests. This pattern was produced in both languages, implying a related semantic decline in both languages. Results from this study should be considered preliminary because of the small sample size.

Using pictures and words to understand recognition memory deterioration in amnestic mild cognitive impairment and Alzheimer’s disease: A review

PubMed Central

Ally, Brandon A.

2012-01-01

Difficulty recognizing previously encountered stimuli is one of the earliest signs of incipient Alzheimer’s disease (AD). Work over the last 10 years has focused on how patients with AD and those in the prodromal stage of amnestic mild cognitive impairment (aMCI) make recognition decisions for visual and verbal stimuli. Interestingly, both groups of patients demonstrate markedly better memory for pictures over words, to a degree that is significantly greater in magnitude than their healthy older counterparts. Understanding this phenomenon not only helps to conceptualize how memory breaks down in AD, but also potentially provides the basis for future interventions. The current review will critically examine recent recognition memory work using pictures and words in the context of the dual-process theory of recognition and current hypotheses of cognitive breakdown in the course of very early AD. PMID:22927024

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data

PubMed Central

Gibson, J; Russ, T C; Adams, M J; Clarke, T-K; Howard, D M; Hall, L S; Fernandez-Pujals, A M; Wigmore, E M; Hayward, C; Davies, G; Murray, A D; Smith, B H; Porteous, D J; Deary, I J; McIntosh, A M

2017-01-01

Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in older age and frequently co-occur. Numerous phenotypic studies based on clinical diagnoses suggest that a history of depression increases risk of subsequent AD, although the basis of this relationship is uncertain. Both illnesses are polygenic, and shared genetic risk factors could explain some of the observed association. We used genotype data to test whether MDD and AD have an overlapping polygenic architecture in two large population-based cohorts, Generation Scotland's Scottish Family Health Study (GS:SFHS; N=19 889) and UK Biobank (N=25 118), and whether age of depression onset influences any relationship. Using two complementary techniques, we found no evidence that the disorders are influenced by common genetic variants. Using linkage disequilibrium score regression with genome-wide association study (GWAS) summary statistics from the International Genomics of Alzheimer's Project, we report no significant genetic correlation between AD and MDD (rG=−0.103, P=0.59). Polygenic risk scores (PRS) generated using summary data from International Genomics of Alzheimer's Project (IGAP) and the Psychiatric Genomics Consortium were used to assess potential pleiotropy between the disorders. PRS for MDD were nominally associated with participant-recalled AD family history in GS:SFHS, although this association did not survive multiple comparison testing. AD PRS were not associated with depression status or late-onset depression, and a survival analysis showed no association between age of depression onset and genetic risk for AD. This study found no evidence to support a common polygenic structure for AD and MDD, suggesting that the comorbidity of these disorders is not explained by common genetic variants. PMID:28418403

Risk of Hip Fracture in Benzodiazepine Users With and Without Alzheimer Disease.

PubMed

Saarelainen, Laura; Tolppanen, Anna-Maija; Koponen, Marjaana; Tanskanen, Antti; Sund, Reijo; Tiihonen, Jari; Hartikainen, Sirpa; Taipale, Heidi

2017-01-01

To investigate the association between benzodiazepine and related drug (BZDR) use and hip fracture as well as postfracture mortality and duration of hospital stay in community-dwellers with and without Alzheimer disease (AD). Retrospective cohort study. The register-based Medication Use and Alzheimer's disease (MEDALZ) study, including all community-dwelling persons diagnosed with AD in Finland during 2005-2011 (n = 70,718) and their matched comparison persons without AD. Persons without BZDR use during the year preceding the AD diagnosis or the corresponding matching date as well as persons without history of hip fracture were included in this study. We investigated the risk of hip fracture associated with BZDR use compared with nonuse separately in persons with and without AD. Further, we investigated the association between BZDR use during hip fracture and 1-year mortality as well as longer than a 4-month hospital stay after hip fracture. Associations were reported as hazard ratios and odds ratios with 95% confidence intervals (CI). BZDR use was associated with an increased risk of hip fracture in persons with and without AD (adjusted hazard ratio 1.4 [95% CI 1.2-1.7] and 1.6 [95% CI 1.3-1.9], respectively). BZDR use during hip fracture was associated with longer than 4-month postfracture hospital stay in persons with AD [adjusted odds ratio 1.9 (95% CI 1.3-2.8)] but not in comparison persons. One-year mortality was not associated with BZDR use during hip fracture. Higher threshold in prescribing BZDRs for neuropsychiatric symptoms might decrease the hip fracture rate and affect the length of hospital stay in persons with AD. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data.

PubMed

Gibson, J; Russ, T C; Adams, M J; Clarke, T-K; Howard, D M; Hall, L S; Fernandez-Pujals, A M; Wigmore, E M; Hayward, C; Davies, G; Murray, A D; Smith, B H; Porteous, D J; Deary, I J; McIntosh, A M

2017-04-18

Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in older age and frequently co-occur. Numerous phenotypic studies based on clinical diagnoses suggest that a history of depression increases risk of subsequent AD, although the basis of this relationship is uncertain. Both illnesses are polygenic, and shared genetic risk factors could explain some of the observed association. We used genotype data to test whether MDD and AD have an overlapping polygenic architecture in two large population-based cohorts, Generation Scotland's Scottish Family Health Study (GS:SFHS; N=19 889) and UK Biobank (N=25 118), and whether age of depression onset influences any relationship. Using two complementary techniques, we found no evidence that the disorders are influenced by common genetic variants. Using linkage disequilibrium score regression with genome-wide association study (GWAS) summary statistics from the International Genomics of Alzheimer's Project, we report no significant genetic correlation between AD and MDD (r G =-0.103, P=0.59). Polygenic risk scores (PRS) generated using summary data from International Genomics of Alzheimer's Project (IGAP) and the Psychiatric Genomics Consortium were used to assess potential pleiotropy between the disorders. PRS for MDD were nominally associated with participant-recalled AD family history in GS:SFHS, although this association did not survive multiple comparison testing. AD PRS were not associated with depression status or late-onset depression, and a survival analysis showed no association between age of depression onset and genetic risk for AD. This study found no evidence to support a common polygenic structure for AD and MDD, suggesting that the comorbidity of these disorders is not explained by common genetic variants.

Atopic dermatitis and the hygiene hypothesis revisited.

PubMed

Flohr, Carsten; Yeo, Lindsey

2011-01-01

We published a systematic review on atopic dermatitis (AD) and the hygiene hypothesis in 2005. Since then, the body of literature has grown significantly. We therefore repeated our systematic review to examine the evidence from population-based studies for an association between AD risk and specific infections, childhood immunizations, the use of antibiotics and environmental exposures that lead to a change in microbial burden. Medline was searched from 1966 until June 2010 to identify relevant studies. We found an additional 49 papers suitable for inclusion. There is evidence to support an inverse relationship between AD and endotoxin, early day care, farm animal and dog exposure in early life. Cat exposure in the presence of skin barrier impairment is positively associated with AD. Helminth infection at least partially protects against AD. This is not the case for viral and bacterial infections, but consumption of unpasteurized farm milk seems protective. Routine childhood vaccinations have no effect on AD risk. The positive association between viral infections and AD found in some studies appears confounded by antibiotic prescription, which has been consistently associated with an increase in AD risk. There is convincing evidence for an inverse relationship between helminth infections and AD but no other pathogens. The protective effect seen with early day care, endotoxin, unpasteurized farm milk and animal exposure is likely to be due to a general increase in exposure to non-pathogenic microbes. This would also explain the risk increase associated with the use of broad-spectrum antibiotics. Future studies should assess skin barrier gene mutation carriage and phenotypic skin barrier impairment, as gene-environment interactions are likely to impact on AD risk. Copyright © 041_ S. Karger AG, Basel.

Accumulation of subcutaneous fat, but not visceral fat, is a predictor of adiponectin levels in preterm infants at term-equivalent age.

PubMed

Nakano, Yuya; Itabashi, Kazuo; Sakurai, Motoichiro; Aizawa, Madoka; Dobashi, Kazushige; Mizuno, Katsumi

2014-05-01

Preterm infants have altered fat tissue development, including a higher percentage of fat mass and increased volume of visceral fat. They also have altered adiponectin levels, including a lower ratio of high-molecular-weight adiponectin (HMW-Ad) to total adiponectin (T-Ad) at term-equivalent age, compared with term infants. The objective of this study was to investigate the association between adiponectin levels and fat tissue accumulation or distribution in preterm infants at term-equivalent age. Cross-sectional clinical study. Study subjects were 53 preterm infants born at ≤34weeks gestation with a mean birth weight of 1592g. Serum levels of T-Ad and HMW-Ad were measured and a computed tomography (CT) scan was performed at the level of the umbilicus at term-equivalent age to analyze how fat tissue accumulation or distribution was correlated with adiponectin levels. T-Ad (r=0.315, p=0.022) and HMW-Ad levels (r=0.338, p=0.013) were positively associated with subcutaneous fat area evaluated by performing CT scan at term-equivalent age, but were not associated with visceral fat area in simple regression analyses. In addition, T-Ad (β=0.487, p=0.003) and HMW-Ad levels (β=0.602, p<0.001) were positively associated with subcutaneous fat tissue area, but they were not associated with visceral fat area also in multiple regression analyses. Subcutaneous fat accumulation contributes to increased levels of T-Ad and HMW-Ad, while visceral fat accumulation does not influence adiponectin levels in preterm infants at term-equivalent age. Copyright © 2014 Elsevier Ltd. All rights reserved.

The CLU gene rs11136000 variant is significantly associated with Alzheimer's disease in Caucasian and Asian populations.

PubMed

Liu, Guiyou; Wang, Haiyang; Liu, Jiafeng; Li, Jingbo; Li, Hali; Ma, Guoda; Jiang, Yongshuai; Chen, Zugen; Zhao, Bin; Li, Keshen

2014-03-01

Large-scale genomewide association studies have reported that the CLU rs11136000 polymorphism is significantly associated with Alzheimer's disease (AD) in people of Caucasian ancestry. Recently, this association was investigated in Asian populations (Chinese, Japanese, and Korean). However, these studies reported either a weak association or no association between the rs11136000 polymorphism and AD. We believe that this discrepancy may be caused by the relatively small sample size of the previous studies and the genetic heterogeneity of the rs11136000 polymorphism in AD among different populations. For this study, we searched the PubMed and AlzGene databases. We selected 18 independent studies (6 studies of Asian populations and 12 of populations of Caucasian ancestry) that evaluated the association between the rs11136000 polymorphism and AD using a case-control experimental design. We evaluated the genetic heterogeneity of the rs11136000 polymorphism in Caucasian and Asian populations. We then investigated the rs11136000 polymorphism by a meta-analysis in Asian populations using allele, dominant, and recessive models. We identified a significant association between rs11136000 and AD with the allele model (P = 2.00 × 10(-4)) and the dominant model (P = 5.00 × 10(-3)). Meanwhile, a similar genetic risk of the rs11136000 polymorphism in AD was observed in Asian and Caucasian populations. Further meta-analysis in pooled Asian and Caucasian populations indicated a more significant association with the allele (P = 8.30 × 10(-24)), dominant (P = 4.46 × 10(-17)), and recessive (P = 3.92 × 10(-12)) models. Collectively, our findings from this meta-analysis indicate that the effect of the CLU rs11136000 polymorphism on AD risk in Asian cohorts (Chinese, Japanese, and Korean) is consistent with the protective effect observed in Caucasian AD cohorts.

Postmenopausal hormone therapy and Alzheimer disease

PubMed Central

Tuppurainen, Marjo; Rikkonen, Toni; Kivipelto, Miia; Soininen, Hilkka; Kröger, Heikki; Tolppanen, Anna-Maija

2017-01-01

Objective: To explore the association between postmenopausal hormone therapy (HT) and Alzheimer disease (AD). Methods: Twenty-year follow-up data from the Kuopio Osteoporosis Risk Factor and Prevention study cohort were used. Self-administered questionnaires were sent to all women aged 47–56 years, residing in Kuopio Province starting in 1989 until 2009, every 5th year. Register-based information on HT prescriptions was available since 1995. Probable AD cases, based on DSM-IV and National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria, were identified from the special reimbursement register (1999–2009). The study population included 8,195 women (227 cases of incident AD). Results: Postmenopausal estrogen use was not associated with AD risk in register-based or self-reported data (hazard ratio/95% confidence interval 0.92/0.68–1.2, 0.99/0.75–1.3, respectively). Long-term self-reported postmenopausal HT was associated with reduced AD risk (0.53/0.31–0.91). Similar results were obtained with any dementia diagnosis in the hospital discharge register as an outcome. Conclusions: Our results do not provide strong evidence for a protective association between postmenopausal HT use and AD or dementia, although we observed a reduced AD risk among those with long-term self-reported HT use. PMID:28202700

Gravity and large black holes in Randall-Sundrum II braneworlds.

PubMed

Figueras, Pau; Wiseman, Toby

2011-08-19

We show how to construct low energy solutions to the Randall-Sundrum II (RSII) model by using an associated five-dimensional anti-de Sitter space (AdS(5)) and/or four-dimensional conformal field theory (CFT(4)) problem. The RSII solution is given as a perturbation of the AdS(5)-CFT(4) solution, with the perturbation parameter being the radius of curvature of the brane metric compared to the AdS length ℓ. The brane metric is then a specific perturbation of the AdS(5)-CFT(4) boundary metric. For low curvatures the RSII solution reproduces 4D general relativity on the brane. Recently, AdS(5)-CFT(4) solutions with a 4D Schwarzschild boundary metric were numerically constructed. We modify the boundary conditions to numerically construct large RSII static black holes with radius up to ~20ℓ. For a large radius, the RSII solutions are indeed close to the associated AdS(5)-CFT(4) solution. © 2011 American Physical Society

The role of clusterin in Alzheimer's disease: pathways, pathogenesis, and therapy.

PubMed

Yu, Jin-Tai; Tan, Lan

2012-04-01

Genetic variation in clusterin gene, also known as apolipoprotein J, has been associated with Alzheimer's disease (AD) through replicated genome-wide studies, and plasma clusterin levels are associated with brain atrophy, baseline prevalence and severity, and rapid clinical progression in patients with AD, highlighting the importance of clusterin in AD pathogenesis. Emerging data suggest that clusterin contributes to AD through various pathways, including amyloid-β aggregation and clearance, lipid metabolism, neuroinflammation, and neuronal cell cycle control and apoptosis. Moreover, epigenetic regulation of the clusterin expression also seems to play an important role in the pathogenesis of AD. Emerging knowledge of the contribution of clusterin to the pathogenesis of AD presents new opportunities for AD therapy.

Parkinson disease and Alzheimer disease: environmental risk factors.

PubMed

Campdelacreu, J

2014-01-01

The purpose of this review is to update and summarise available evidence on environmental risk factors that have been associated with risk of Parkinson disease (PD) or Alzheimer disease (AD) and discuss their potential mechanisms. Evidence consistently suggests that a higher risk of PD is associated with pesticides and that a higher risk of AD is associated with pesticides, hypertension and high cholesterol levels in middle age, hyperhomocysteinaemia, smoking, traumatic brain injury and depression. There is weak evidence suggesting that higher risk of PD is associated with high milk consumption in men, high iron intake, chronic anaemia and traumatic brain injury. Weak evidence also suggests that a higher risk of AD is associated with high aluminium intake through drinking water, excessive exposure to electromagnetic fields from electrical grids, DM and hyperinsulinaemia, obesity in middle age, excessive alcohol consumption and chronic anaemia. Evidence consistently suggests that a lower risk of PD is associated with hyperuricaemia, tobacco and coffee use, while a lower risk of AD is associated with moderate alcohol consumption, physical exercise, perimenopausal hormone replacement therapy and good cognitive reserve. Weak evidence suggests that lower risk of PD is associated with increased vitamin E intake, alcohol, tea, NSAIDs, and vigorous physical exercise, and that lower risk of AD is associated with the Mediterranean diet, coffee and habitual NSAID consumption. Several environmental factors contribute significantly to risk of PD and AD. Some may already be active in the early stages of life, and some may interact with other genetic factors. Population-based strategies to modify such factors could potentially result in fewer cases of PD or AD. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Effect of Ternary Solutes on the Evolution of Structure and Gel Formation in Amphiphilic Copolymer Solutions

NASA Astrophysics Data System (ADS)

Meznarich, Norman Anthony Kang

Aqueous solutions of polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) amphiphilic triblock copolymers (commercially known as Pluronic surfactants) undergo reversible and temperature-dependent micellization and arrangement into cubic ordered lattices known as "micelle gels". The macroscopic behavior of the ordering is a transition from a liquid to a gel. While the phase behavior and gel structure of pure Pluronic surfactant solutions have been well studied, less is known about the effects of added ternary solutes. In this dissertation, a comprehensive investigation into the effects of the added pharmaceutical methylparaben on solutions of F127 ranging from 10 to 30 wt% was conducted in order to better understand the behavior of F127 in multicomponent pharmaceutical formulations. The viscoelastic properties of F127 gel formation were studied using rheometry, where heating rates of 0.1, 1, and 10 degrees C/min were also used to probe the kinetics of the gel transition. In solutions containing methylparaben, F127 gelation occurred at up to 15 degrees C lower temperatures and was accelerated by a factor of three to four. Small angle x-ray scattering (SAXS) was used to characterize the structure of the ordered domains, and how they were affected by the presence of dissolved pharmaceuticals. It was found that ordered domain formation changed from heterogeneous nucleation and growth to possible homogeneous nucleation and growth. A roughly 2% reduction in the cubic lattice parameter was also observed for solutions containing methylparaben. Differential scanning calorimetry (DSC) experiments were performed on a series of different Pluronic surfactants in order to characterize the micellization behavior as a function of PPO center block length and PEO/PPO ratio. Added methylparaben suppressed the micellization endotherm, the degree of suppression depending linearly on the amount of added methylparaben, as well as the length of the PPO center block and PEO/PPO ratio. This dissertation yielded a thorough characterization of the changes in micellization and gelation behavior in F127 gels as a result of added pharmaceuticals. Previously unobserved behavior such as the onset of ordered domain formation in F127 gels was observed, and a greater understanding of the interactions between amphiphilic copolymer solutions and dissolved solutes was achieved.

Genetic association between Alzheimer disease and the alpha-synuclein gene.

PubMed

Matsubara, M; Yamagata, H; Kamino, K; Nomura, T; Kohara, K; Kondo, I; Miki, T

2001-01-01

alpha-Synuclein has been isolated as a component of amyloid in addition to the major A beta peptide in Alzheimer disease (AD). However, there are conflicting reports regarding the association of alpha-synuclein gene polymorphism with AD. Using a novel and common polymorphism in intron 3, we examined the relationship between AD and alpha-synuclein and apolipoprotein E (ApoE) genes in 183 Japanese AD patients and 210 controls. Carriers of the alpha-synuclein deletion (D) allele had a 2.2-fold increased risk of developing AD than noncarriers in women. The odds ratio for the ApoE epsilon 4 and the alpha-synuclein D allele was 11.4 in women. The results showed that the alpha-synuclein gene is associated with sporadic AD in women, independent of ApoE epsilon 4 status. Copyright 2001 S. Karger AG, Basel

The dopamine transporter gene may not contribute to susceptibility and the specific personality traits of amphetamine dependence.

PubMed

Tzeng, Nian-Sheng; Lu, Ru-Band; Yeh, Hui-Wen; Yeh, Yi-Wei; Huang, Chang-Chih; Yen, Che-Hung; Kuo, Shin-Chang; Chen, Chun-Yen; Chang, Hsin-An; Ho, Pei-Shen; Cheng, Serena; Shih, Mei-Chen; Huang, San-Yuan

2015-04-01

A substantial amount of evidence suggests that dysfunction of the dopamine transporter may be involved in the pathophysiology of amphetamine dependence (AD). The aim of this study was to examine whether the dopamine transporter gene (DAT1, SLC6A3) is associated with development of AD and whether this gene influences personality traits in patients with AD. Eighteen polymorphisms of the DAT1 gene were analyzed in a case-control study that included 909 Han Chinese men (568 patients with AD and 341 control subjects). The patients fulfilled the DSM-IV-TR criteria for AD. The Tridimensional Personality Questionnaire (TPQ) was used to assess personality traits and to examine the association between these traits and DAT1 gene variants. A weak association was found between the rs27072 polymorphism and development of AD, but these borderline associations were unconfirmed by logistic regression and haplotype analysis. Although harm avoidance and novelty seeking scores were significantly higher in patients than in controls, DAT1 polymorphisms did not influence these scores. This study suggests that high harm avoidance and novelty seeking personality traits may be a risk factor for the development of AD. However, the DAT1 gene may not contribute to AD susceptibility and specific personality traits observed in AD among Han Chinese men. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Association between added sugar intake and dental caries in Yup'ik children using a novel hair biomarker.

PubMed

Chi, Donald L; Hopkins, Scarlett; O'Brien, Diane; Mancl, Lloyd; Orr, Eliza; Lenaker, Dane

2015-10-09

Dental caries (tooth decay) is a significant public health problem in Alaska Native children. Dietary added sugars are considered one of the main risk factors. In this cross-sectional pilot study, we used a validated hair-based biomarker to measure added sugar intake in Alaska Native Yup'ik children ages 6-17 years (N = 51). We hypothesized that added sugar intake would be positively associated with tooth decay. A 66-item parent survey was administered, a hair sample was collected from each child, and a dental exam was conducted. Added sugar intake (grams/day) was measured from hair samples using a linear combination of carbon and nitrogen ratios. We used linear and log-linear regression models with robust standard errors to test our hypothesis that children with higher added sugar intake would have a higher proportion of carious tooth surfaces. The mean proportion of carious tooth surfaces was 30.8 % (standard deviation: 23.2 %). Hair biomarker-based added sugar intake was associated with absolute (6.4 %; 95 % CI: 1.2 %, 11.6 %; P = .02) and relative increases in the proportion of carious tooth surfaces (24.2 %; 95 % CI: 10.6 %, 39.4 %; P < .01). There were no associations between self-reported measures of sugar-sweetened food and beverage intake and tooth decay. Added sugar intake as assessed by hair biomarker was significantly and positively associated with tooth decay in our sample of Yup'ik children. Self-reported dietary measures were not associated tooth decay. Most added sugars were from sugar-sweetened fruit drinks consumed at home. Future dietary interventions aimed at improving the oral health of Alaska Native children should consider use of objective biomarkers to assess and measure changes in home-based added sugar intake, particularly sugar-sweetened fruit drinks.

Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias.

PubMed

Beecham, Gary W; Hamilton, Kara; Naj, Adam C; Martin, Eden R; Huentelman, Matt; Myers, Amanda J; Corneveaux, Jason J; Hardy, John; Vonsattel, Jean-Paul; Younkin, Steven G; Bennett, David A; De Jager, Philip L; Larson, Eric B; Crane, Paul K; Kamboh, M Ilyas; Kofler, Julia K; Mash, Deborah C; Duque, Linda; Gilbert, John R; Gwirtsman, Harry; Buxbaum, Joseph D; Kramer, Patricia; Dickson, Dennis W; Farrer, Lindsay A; Frosch, Matthew P; Ghetti, Bernardino; Haines, Jonathan L; Hyman, Bradley T; Kukull, Walter A; Mayeux, Richard P; Pericak-Vance, Margaret A; Schneider, Julie A; Trojanowski, John Q; Reiman, Eric M; Schellenberg, Gerard D; Montine, Thomas J

2014-09-01

Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs), and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), hippocampal sclerosis of the elderly (HS), and vascular brain injury (VBI). Genome-wide significance was observed for clinico-pathologic AD dementia, NPs, NFTs, CAA, and LBD with a number of variants in and around the apolipoprotein E gene (APOE). GalNAc transferase 7 (GALNT7), ATP-Binding Cassette, Sub-Family G (WHITE), Member 1 (ABCG1), and an intergenic region on chromosome 9 were associated with NP score; and Potassium Large Conductance Calcium-Activated Channel, Subfamily M, Beta Member 2 (KCNMB2) was strongly associated with HS. Twelve of the 21 non-APOE genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample: CR1, BIN1, CLU, MS4A6A, PICALM, ABCA7, CD33, PTK2B, SORL1, MEF2C, ZCWPW1, and CASS4 with 9 of these 12 loci showing larger odds ratio in the clinico-pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for NFTs or NPs showed positive correlation, while those for risk of VBI showed a moderate negative correlation. The other co-morbid neuropathologic features showed only nominal association with the known AD loci. Our results discovered new genetic associations with specific neuropathologic features and aligned known genetic risk for AD dementia with specific neuropathologic changes in the largest brain autopsy study of AD and related dementias.

Association of usual intake of added sugars with nutrient adequacy

USDA-ARS?s Scientific Manuscript database

Recommendations for intakes of added sugars have varied considerably and the scientific basis supporting these recommendations has been inconsistent. The goal of this study was to examine the association of usual intake (UI) of added sugars and nutrient adequacy in those participating in NHANES 2009...

Associations of Spatial Disparities of Alzheimer's Disease Mortality Rates with Soil Selenium and Sulfur Concentrations and Four Common Risk Factors in the United States.

PubMed

Sun, Hongbing

2017-01-01

Associations between environmental factors and spatial disparity of mortality rates of Alzheimer's disease (AD) in the US are not well understood. To find associations between 41 trace elements, four common risk factors, and AD mortality rates in the48 contiguous states. Isopleth maps of AD mortality rates of the 48 states and associated factors were examined. Correlations between state average AD mortality rates and concentrations of 41 soil elements, wine consumption, percentage of current smokers, obesity, and diagnosed diabetes of the 48 states between 1999 and 2014 were analyzed. Among 41 elements, soil selenium concentrations have the most significant inverse correlations with AD mortality rates. Rate ratio (RR) of the 6 states with the lowest product of soil selenium and sulfur concentrations is 53% higher than the 6 states with the highest soil selenium sulfur product in the 48 states (RR = 1.53, CI95% 1.51-1.54). Soil tin concentrations have the most significant inverse correlation with AD mortality growth rates between 1999 and 2014, followed by soil sulfur concentrations. Percentages of obesity, diagnosed diabetes, smoking, and wine consumption per capita also correlate significantly with AD mortality growth rates. High soil selenium and sulfur concentrations and wine consumption are associated with low AD mortality rates. Given that average soil selenium and sulfur concentrations are indicators of their intakes from food, water, and air by people in a region, long-term exposure to high soil selenium and sulfur concentrations might be beneficial to AD mortality rate reduction in a region.

Vascular risk factors and the effect of white matter lesions on extrapyramidal signs in Alzheimer's disease.

PubMed

Park, Moon Ho; Min, Joo Young; Kwon, Do-Young; Lee, Seung Hwan; Na, Hae Ri; Cho, Sung Tae; Na, Duk L

2011-06-01

Extrapyramidal signs (EPSs), which are important characteristics of Parkinson's disease (PD), occur frequently in Alzheimer's disease (AD). Although AD and PD share common clinical features such as EPSs, these diseases vary with respect to vascular risk factors. The presence of vascular risk factors increases the risk of AD; however, these factors have been known to be inversely associated with PD. We aimed to assess the effect of vascular risk factors and white matter lesions (WMLs) on EPSs in AD. We recruited 1,187 AD patients and 333 controls with neither cognitive impairment nor EPSs. All participants underwent detailed clinical evaluations which included assessments of vascular risk factors, cognitive function, and EPSs, as well as WMLs on brain MRIs. EPS subtypes were classified into tremor-dominant, postural instability gait difficulty, or indeterminate; WMLs subtypes were classified into periventricular WML (pvWML) or deep WML (dWML). EPSs were present in 17.9% of subjects with AD and were significantly associated with vascular risk factors such as age, male gender, diabetes mellitus, and WMLs. Additionally, a multivariate logistic regression analysis showed that EPSs in AD were associated with pvWML (odds ratio (OR), 1.61-2.52), not with dWML. With respect to EPS subtypes, the majority (78.4%) of EPSs in AD were postural instability gait difficulty, which was also associated with WMLs (OR 1.84-2.41), pvWML (OR 2.09-3.14), and dWML (OR 1.83-3.42). EPSs in AD are associated with selected vascular risk factors as well as WMLs.

Hand eczema and atopic dermatitis in adolescents: a prospective cohort study from the BAMSE project.

PubMed

Grönhagen, C; Lidén, C; Wahlgren, C-F; Ballardini, N; Bergström, A; Kull, I; Meding, B

2015-11-01

There is a well-known association between atopic dermatitis (AD) and hand eczema but less is known about how age at onset, persistence and severity of AD influence the risk of developing hand eczema. To examine the role of AD in the occurrence of hand eczema in adolescence. In addition, associations between asthma and rhinoconjunctivitis, sensitization to common airborne and food allergens, and hand eczema were studied. From the population-based birth cohort BAMSE, 2927 adolescents who had been followed up repeatedly concerning allergy-related disease were included. Questionnaires identified adolescents with hand eczema at 16 years, and their blood was analysed for specific IgE. A total of 152 (5·2%) adolescents had hand eczema at the age of 16 years. Many of these adolescents had a history of AD (n = 111; 73·0%) and asthma and/or rhinitis (n = 83; 54·6%), respectively. Children with AD (aged 0-16 years) had more than threefold increased odds ratios (OR) for having hand eczema; those with persistent or severe AD had a crude OR of 6·1 [95% confidence interval (CI) 4·0-9·1] and 5·3 (95% CI 2·9-9·6), respectively. We confirm a strong association between AD during childhood and hand eczema in adolescence. Children with persistent or more severe AD are at greater risk of developing hand eczema. Asthma and/or rhinoconjunctivitis, positive specific IgE or age at onset of AD are not associated with hand eczema in adolescence. © 2015 British Association of Dermatologists.

Timing of Advance Directive Completion and Relationship to Care Preferences.

PubMed

Enguidanos, Susan; Ailshire, Jennifer

2017-01-01

Given recent Medicare rules reimbursing clinicians for engaging in advance care planning, there is heightened need to understand factors associated with the timing of advance directive (AD) completion before death and how the timing impacts care decisions. The purpose of this study was to investigate patterns in timing of AD completion and the relationship between timing and documented care preferences. We hypothesize that ADs completed late in the course of illness or very early in the disease trajectory will reflect higher preferences for aggressive care. We conducted a retrospective study using logistic regressions to analyze data from the Health and Retirement Study, a nationally representative longitudinal survey of older adults. The analytic sample included exit interviews conducted from 2000 to 2012 among 2904 proxy reporters of deceased participants who had an AD. Nearly three-quarters (71%) of ADs were completed a year or more before death. Being younger or a racial/ethnic minority, and having lower education, a diagnosis of cancer or lung disease, and an expected death were associated with completing an AD within the three months before death, while having the lowest quartile of assets and memory problems were inversely associated with AD completion. Minorities, those with lower education, expected death, and timing of AD completion were associated with electing aggressive care. Early documentation of care wishes may not be associated with an increased likelihood of electing aggressive care; however, ADs completed in the last months of life have higher rates of election of aggressive care. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Association between Diabetes and Risk of Aortic Dissection: A Case-Control Study in a Chinese Population.

PubMed

He, Xingwei; Liu, Xintian; Liu, Wanjun; Wang, Bei; Liu, Yujian; Li, Zhuxi; Wang, Tao; Tan, Rong; Gao, Bo; Zeng, Hesong

2015-01-01

It is well-recognized that diabetes represents a powerful independent risk factor for cardiovascular diseases. However, very few studies have investigated the relationship between diabetes and risk of aortic dissection (AD). The aim of this case-control study was to evaluate the association between diabetes and risk of AD in Chinese population. A hospital-based case-control study, consisting of 2160 AD patients and 4320 controls, was conducted in a Chinese population. Demographic, clinical characteristics and risk factors were collected. Diabetes rate of patients with overall AD, Stanford type A AD and type B AD group was compared with that of corresponding matched control groups. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) for relationship between diabetes and AD risk. The prevalence of diabetes was lower in AD cases than that of control subjects, whether it is the overall AD, type A AD or type B AD group (4.7% vs. 10.0%, 2.9% vs. 8.8%, 5.9% vs. 10.9%, all P<0.001). Furthermore, in multivariate model, diabetes was found to be associated with lower AD risk, which not only applies to the overall AD (OR = 0.2, 95%CI: 0.15-0.26), but also type A AD (OR = 0.12, 95% CI: 0.07-0.20) and type B AD (OR = 0.25, 95%CI: 0.18-0.33). We observed the paradoxical inverse relationship between DM and risk of AD in the Chinese population. These results suggest diabetes may play a protective role in the development of AD. However, further studies are needed to enrich related evidence, especially with regard to underlying mechanisms for these trends.

Association between genes encoding components of the IL-4/IL-4 receptor pathway and dermatitis in children.

PubMed

Hussein, Yousri M; Shalaby, Sally M; Nassar, Amani; Alzahrani, Saad S; Alharbi, Ayman S; Nouh, Maha

2014-07-25

To determine whether IL-4, IL-4Rα and STAT6 polymorphisms are associated with susceptibility to dermatitis in Egyptian children. We genotyped three groups of children, consisting of 106 atopic dermatitis (AD) children, 95 non-AD children, and 100 of healthy controls, for IL-4 (-590 C/T), (-33 C/T), IL-4Rα (I50V), (Q576R) and STAT6 (2964 G/A), (2892 C/T) gene polymorphisms using PCR-RFLP assay. Total serum IgE and serum IL-4 levels were detected by ELISA. There was a non-significant association of IL-4 -590 C/T, -33 C/T polymorphisms in the children with non-AD or those with AD when compared with the controls. We identified a significant association between IL-4Rα I50V, Q576R polymorphisms and dermatitis susceptibility in AD (p=0.002, <0.001 respectively), whereas no such association was observed in non-AD group (p=0.52, 0.99 respectively). A significant association between STAT6 polymorphisms and both types of dermatitis was found. Patients who were carriers of IL4 -590C, IL-4Rα I50V G, STAT6 2964 A and STAT6 2892 T had an increased risk of AD [OR and 95% CI: 3.2 (2.5-4.2), p=0.005]. Furthermore, there was no relation between each polymorphism and serum IL-4 level (p>0.05 for each) while homozygosity for the risk alleles of IL-4, IL-4Rα and STAT6 SNPs were significantly associated with increased total IgE levels in all subjects. In Egyptian children, the IL-4Rα and the STAT6 polymorphism may play a role in susceptibility to AD. In addition, gene-gene interaction between the IL-4, the IL-4Rα and the STAT6 significantly increases an individual's susceptibility to AD. Copyright © 2014 Elsevier B.V. All rights reserved.

[Conservative treatment of metacarpal fracture].

PubMed

Prokop, A; Helling, H J; Kulus, S; Rehm, K E

2002-01-01

Conservative treatment of meatacarpale fracture is recommended if there are no joint displacement, rotation failures, displacement over 30 degrees ad axim and shortening over 5 mm. Operative procedures should be done in open fractures and serial of fractures of metacarpale bones. Early functionally treatment should be done in stable, not displaced fractures. Cast can be used only for a short time in full extended position of fingers and flexion in metacarpo-phalangeal joint in 60-90 degrees. Twin-tapes after reduction of edema allowed free range of motion by fixed rotation. Closed reduction of displaced fractures of fifth metacarpal bone (boxer's fracture) isn't successful. Cases with displacement over 30 degrees may be operatively treated by intramedullary stabilization.

[Treatment of metacarpal fractures].

PubMed

Prokop, A; Jubel, A; Helling, H J; Kulus, S; Rehm, K E

2002-09-01

Conservative treatment of metacarpal fractures is recommended if there is no joint displacement, malrotation, displacement of over 30 degrees ad axim and shortening of over 5 mm. Surgery should be performed in open fractures and serial fractures of metacarpal bone. Early functional treatment should be carried out in stable, not displaced fractures. A cast can be used for a short period in full extended position of fingers and flexion in metacarpo-phalangeal joint in 60 - 90 degrees. Twin-tape fixation allows functional treatment after soft-tissue swelling has disappeared. Closed reduction of displaced fractures of the fifth metacarpal bone (boxer's fracture) is not successful. Cases with displacement of over 30 degrees may be treated surgically by intramedullary stabilisation.

Associations between dietary fiber and colorectal polyp risk differ by polyp type and smoking status.

PubMed

Fu, Zhenming; Shrubsole, Martha J; Smalley, Walter E; Ness, Reid M; Zheng, Wei

2014-05-01

The association of dietary fiber intake with colorectal cancer risk is established. However, the association may differ between cigarette smokers and nonsmokers. We evaluated this hypothesis in a large colonoscopy-based case-control study. Dietary fiber intakes were estimated by self-administered food frequency questionnaire. Unconditional logistic regression analysis was used to estimate ORs and 95% CIs with adjustment for potential confounders. Analysis also was stratified by cigarette smoking and sex. High dietary fiber intake was associated with reduced risk of colorectal polyps (P-trend = 0.003). This association was found to be stronger among cigarette smokers (P-trend = 0.006) than nonsmokers (P-trend = 0.21), although the test for multiplicative interaction was not statistically significant (P = 0.11). This pattern of association was more evident for high-risk adenomatous polyps (ADs), defined as advanced or multiple ADs (P-interaction smoking and dietary fiber intake = 0.09). Among cigarette smokers who smoked ≥23 y, a 38% reduced risk of high-risk ADs was found to be associated with high intake of dietary fiber compared with those in the lowest quartile fiber intake group (P-trend = 0.004). No inverse association with dietary fiber intake was observed for low-risk ADs, defined as single nonadvanced ADs. Cigarette smoking may modify the association of dietary fiber intake with the risk of colorectal polyps, especially high-risk ADs, a well-established precursor of colorectal cancer.

Development of Polyethylene Glycol and Hard Fat-Based Mucoadhesive Tablets Containing Various Types of Polyvinyl Alcohols as Mucoadhesive Polymers for Buccal Application.

PubMed

Ikeuchi-Takahashi, Yuri; Kobayashi, Ayaka; Onishi, Hiraku

2017-06-01

Topical drug application has the advantage of avoiding systemic side effects. We attempted to develop a long-acting matrix-type tablet containing indomethacin (IM) with low physical stimulus and potent mucoadhesive force to treat pain caused by oral aphtha. A mixture of polyethylene glycol (PEG) and hard fat was used as the tablet base. Ethylcellulose was added to the base in an attempt to control drug release. Tablets with PEG as a base were also prepared for comparison. Polyvinyl alcohols (PVAs) with various degrees of saponification were added to increase the mucoadhesive force. From the optical microscopic observations, formulations using PEG and hard fat exhibit PEG/hard fat dispersions caused by the stabilizing effects of PVA. Although the tablets using PEG and hard fat showed sufficient adhesiveness and sustained drug release, those using PEG as the base did not. Drug release was controlled by the amount of hard fat and the saponification degree of PVA. The drug release rate was most increased in a tablet containing PVA with an intermediate degree of saponification, PEG and hard fat. From differential scanning calorimetry and powder X-ray diffraction, IM was considered to exist in the molecular phase. From the results of buccal administration of tablets to rats, highest tissue concentrations were observed in the tablet containing PVA with the intermediate degree of saponification using PEG and hard fat, and the plasma concentrations were sufficiently low in comparison.

Elevated serum pesticide levels and risk for Alzheimer disease.

PubMed

Richardson, Jason R; Roy, Ananya; Shalat, Stuart L; von Stein, Richard T; Hossain, Muhammad M; Buckley, Brian; Gearing, Marla; Levey, Allan I; German, Dwight C

2014-03-01

The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer's Disease Research Center and the University of Texas Southwestern Medical School's Alzheimer's Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases. Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status. Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54-5.82; P < .001) and lower Mini-Mental State Examination scores (-1.605; range, -3.095 to -0.114; P < .0001). The Mini-Mental State Examination scores in the highest tertile of DDE were -1.753 points lower in the subpopulation carrying an APOE ε4 allele compared with those carrying an APOE ε3 allele (P interaction = .04). Serum levels of DDE were highly correlated with brain levels of DDE (ρ = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein. Elevated serum DDE levels are associated with an increased risk for AD and carriers of an APOE4 ε4 allele may be more susceptible to the effects of DDE. Both DDT and DDE increase amyloid precursor protein levels, providing mechanistic plausibility for the association of DDE exposure with AD. Identifying people who have elevated levels of DDE and carry an APOE ε4 allele may lead to early identification of some cases of AD.

Genome-wide association study identifies two loci influencing plasma neurofilament light levels.

PubMed

Li, Jie-Qiong; Yuan, Xiang-Zhen; Li, Hai-Yan; Cao, Xi-Peng; Yu, Jin-Tai; Tan, Lan; Chen, Wei-An

2018-05-10

Plasma neurofilament light (NFL) is a promising biomarker for Alzheimer disease (AD), which increases in the early stage of AD and is associated with the progression of AD. We performed a genome-wide association study (GWAS) of plasma NFL in Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) cohort to identify novel variants associated with AD. This study included 179 cognitively healthy controls (HC), 176 patients with mild cognitive impairment (MCI), and 172 patients with AD. All subjects were restricted to non-Hispanic Caucasian derived from the ADNI cohort and met all quality control (QC) criteria. Association of plasma NFL with the genetic variants was assessed using PLINK with an additive genetic model, i.e.dose-dependent effect of the minor alleles. The influence of a genetic variant associated with plasma NFL (rs7943454) on brain structure was further assessed using PLINK with a linear regression model. The minor allele (T) of rs7943454 in leucine zipper protein 2 gene (LUZP2) was associated with higher plasma NFL at suggestive levels (P = 1.39 × 10 - 6 ) in a dose-dependent fashion. In contrast, the minor allele (G) of rs640476 near GABRB2 was associated with lower plasma NFL at suggestive levels (P = 6.71 × 10 - 6 ) in a dose-dependent effect in all diagnostic groups except the MCI group. Furthermore, the minor allele (T) of rs7943454 within LUZP2 increased the onset risk of AD (odds ratio = 1.547, confidence interval 95% = 1.018-2.351) and was associated with atrophy of right middle temporal gyrus in the whole cohort in the longitudinal study (P = 0.0234). GWAS found the associations of two single nucleotide polymorphisms (rs7943454 and rs640476) with plasma NFL at suggestive levels. Rs7943454 in LUZP2 was associated with the onset risk of AD and atrophy of right middle temporal gyrusin the whole cohort. Using an endophenotype-based approach, we identified rs7943454 as a new AD risk locus.

Non-Alzheimer's contributions to dementia and cognitive resilience in The 90+ Study.

PubMed

Robinson, John L; Corrada, Maria M; Kovacs, Gabor G; Dominique, Myrna; Caswell, Carrie; Xie, Sharon X; Lee, Virginia M-Y; Kawas, Claudia H; Trojanowski, John Q

2018-06-18

The diagnosis of Alzheimer's disease (AD) in the oldest-old is complicated by the increasing prevalence of age-related neurofibrillary tangles, plaques and non-AD pathologies such as cerebrovascular disease (CVD), hippocampal sclerosis (HS), aging-related tau astrogliopathy (ARTAG), as well as TDP-43 and Lewy pathology. The contribution of these non-AD pathologies to dementia and cognitive resilience is unclear. We assessed the level of AD neuropathologic change (ADNPC) and non-AD pathology in 185 participants enrolled in The 90+ Study with available cognitive assessments and brain tissue. Logistic regression models-adjusting for age, sex and education-determined the association between each pathology and dementia or between subgroups. 53% had dementia, primarily AD or mixed AD; 23% had cognitive impairment without dementia (CIND); 23% were not impaired. Both AD and non-AD pathology was prevalent. 100% had tangles, 81% had plaques, and both tangles and plaques associated with dementia. ARTAG distributed across limbic (70%), brainstem (39%) and cortical regions (24%). 49% had possible CVD and 26% had definite CVD, while HS was noted in 15%. Cortical ARTAG, CVD and HS were each associated with dementia, but limbic and brainstem ARTAGs were not. TDP-43 and Lewy pathologies were found in 36 and 17% and both associated with dementia. No pathology distinguished CIND and the not impaired. By NIA-AA criteria and dementia status, the cohort was subdivided into four groups: those with minimal ADNPC included the not dementia (ND) and Not AD dementia groups; and those with significant ADNPC included the Resilient without dementia and AD dementia groups. Compared to the ND group, the Not AD dementia group had more HS, cortical ARTAG, TDP-43, and Lewy pathology. Compared to the AD dementia group, the Resilient group had less CVD, no HS and less cortical ARTAG, TDP-43 and Lewy pathology. Our findings imply that reductions in non-AD pathologies including CVD contribute to cognitive resilience in the oldest-old.

Backus Effect on a Perpendicular Errors in Harmonic Models of Real vs. Synthetic Data

NASA Technical Reports Server (NTRS)

Voorhies, C. V.; Santana, J.; Sabaka, T.

1999-01-01

Measurements of geomagnetic scalar intensity on a thin spherical shell alone are not enough to separate internal from external source fields; moreover, such scalar data are not enough for accurate modeling of the vector field from internal sources because of unmodeled fields and small data errors. Spherical harmonic models of the geomagnetic potential fitted to scalar data alone therefore suffer from well-understood Backus effect and perpendicular errors. Curiously, errors in some models of simulated 'data' are very much less than those in models of real data. We analyze select Magsat vector and scalar measurements separately to illustrate Backus effect and perpendicular errors in models of real scalar data. By using a model to synthesize 'data' at the observation points, and by adding various types of 'noise', we illustrate such errors in models of synthetic 'data'. Perpendicular errors prove quite sensitive to the maximum degree in the spherical harmonic expansion of the potential field model fitted to the scalar data. Small errors in models of synthetic 'data' are found to be an artifact of matched truncation levels. For example, consider scalar synthetic 'data' computed from a degree 14 model. A degree 14 model fitted to such synthetic 'data' yields negligible error, but amplifies 4 nT (rmss) added noise into a 60 nT error (rmss); however, a degree 12 model fitted to the noisy 'data' suffers a 492 nT error (rmms through degree 12). Geomagnetic measurements remain unaware of model truncation, so the small errors indicated by some simulations cannot be realized in practice. Errors in models fitted to scalar data alone approach 1000 nT (rmss) and several thousand nT (maximum).

Development of an HPLC method for determination of metabolic compounds in myocardial tissue.

PubMed

Volonté, M G; Yuln, G; Quiroga, P; Consolini, A E

2004-05-28

The determination of adenine nucleotides and creatine compounds has great importance in the characterization of ischemic myocardial injury and post-ischemic recovery. It was developed by an HPLC method for the quantification of creatine (Cr), creatine phosphate (CrP), hypoxanthine (HX), AMP, adenosine (Ad), ADP and ATP in isolated perfused rat hearts. The chromatographic conditions were: RP 18 column; mobile phase composed by KH(2)PO(4) (215 mM), tetrabutylammonium hydrogen sulfate (2.3mM), acetonitrile (4%) and KOH (1M 0.4%); flow rate 1 ml min(-1); temperature 25 degrees C; injection volume 20 microl; detection at 220 nm and height peak (HP) as the integration parameter. The method was validated by means of linearity and sensitivity evaluations, using calibration curves done with five concentration levels of each compound. The limits of quantification (LOQ) were also determined. The system precision was calculated as the coefficient of variation for five injections for each compound tested. The purity of the peaks was established using enzymatic peak shift analysis with hexokinase and creatine kinase and also comparing HP at various wavelengths. Frozen hearts were homogenized with a mechanical homogenizer for 3 min at 0 degrees C added with 5 ml of 0.4N HCLO(4). After precipitation with 0.8 ml of 2M KOH the extract was shaked for 2 min and later centrifuged at 0 degrees C for 10 min. The supernatant was kept on ice, filtrated and injected into the HPLC system. The results show that the method for the determination of Cr, CrP, HX, AMP, Ad, ADP and ATP by HPLC here described has good linearity, LOQ, precision, specificity and is simple and rapid to perform.

Association between an Alzheimer's Disease-Related Index and APOE ε4 Gene Dose.

PubMed

Schraml, Frank; Chen, Kewei; Ayutyanont, Napatkamon; Auttawut, Roontiva; Langbaum, Jessica B S; Lee, Wendy; Liu, Xiaofen; Bandy, Dan; Reeder, Stephanie Q; Alexander, Gene E; Caselli, Richard J; Fleisher, Adam S; Reiman, Eric M

2013-01-01

We introduced a hypometabolic convergence index (HCI) to characterize in a single measurement the extent to which a person's fluorodeoxyglucose positron emission tomogram (FDG PET) corresponds to that in Alzheimer's disease (AD). Apolipoprotein E ε4 (APOE ε4) gene dose is associated with three levels of risk for late-onset AD. We explored the association between gene dose and HCI in cognitively normal ε4 homozygotes, heterozygotes, and non-carriers. An algorithm was used to characterize and compare AD-related HCIs in cognitively normal individuals, including 36 ε4 homozygotes, 46 heterozygotes, and 78 non-carriers. These three groups differed significantly in their HCIs (ANOVA, p = 0.004), and there was a significant association between HCIs and gene dose (linear trend, p = 0.001). The HCI is associated with three levels of genetic risk for late-onset AD. This supports the possibility of using a single FDG PET measurement to help in the preclinical detection and tracking of AD.

Association of Platelet Serotonin Levels in Alzheimer's Disease with Clinical and Cerebrospinal Fluid Markers.

PubMed

Tajeddinn, Walid; Fereshtehnejad, Seyed-Mohammad; Seed Ahmed, Mohammed; Yoshitake, Takashi; Kehr, Jan; Shahnaz, Tasmin; Milovanovic, Micha; Behbahani, Homira; Höglund, Kina; Winblad, Bengt; Cedazo-Minguez, Angel; Jelic, Vesna; Järemo, Petter; Aarsland, Dag

2016-05-04

Serotonin (5-HT) is involved in the pathology of Alzheimer's disease (AD). We aimed to measure 5-HT level in platelets in AD and explore its association with cerebrospinal fluid (CSF), AD biomarkers (amyloid-β 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau)), and clinical symptoms. 15 patients with AD and 20 patients with subjective cognitive impairment (SCI) were included. 5-HT metabolites were measured, in a specific fraction, using high performance liquid chromatography with electrochemical detection (HPLC-ECD). Significantly lower 5-HT concentrations were observed in AD patients compared to SCI patients both after normalization against total protein (p = 0.008) or platelet count (p = 0.019). SCI patients with lower 5-HT level have higher AD CSF biomarkers, total tau (p = 0.026) and tau/Aβ42 ratio (p = 0.001), compared to those with high 5-HT levels. AD patients have reduced platelet 5-HT levels. In SCI, lower 5-HT content was associated with a higher AD-CSF biomarker burden.

Analyzing the genes related to Alzheimer's disease via a network and pathway-based approach.

PubMed

Hu, Yan-Shi; Xin, Juncai; Hu, Ying; Zhang, Lei; Wang, Ju

2017-04-27

Our understanding of the molecular mechanisms underlying Alzheimer's disease (AD) remains incomplete. Previous studies have revealed that genetic factors provide a significant contribution to the pathogenesis and development of AD. In the past years, numerous genes implicated in this disease have been identified via genetic association studies on candidate genes or at the genome-wide level. However, in many cases, the roles of these genes and their interactions in AD are still unclear. A comprehensive and systematic analysis focusing on the biological function and interactions of these genes in the context of AD will therefore provide valuable insights to understand the molecular features of the disease. In this study, we collected genes potentially associated with AD by screening publications on genetic association studies deposited in PubMed. The major biological themes linked with these genes were then revealed by function and biochemical pathway enrichment analysis, and the relation between the pathways was explored by pathway crosstalk analysis. Furthermore, the network features of these AD-related genes were analyzed in the context of human interactome and an AD-specific network was inferred using the Steiner minimal tree algorithm. We compiled 430 human genes reported to be associated with AD from 823 publications. Biological theme analysis indicated that the biological processes and biochemical pathways related to neurodevelopment, metabolism, cell growth and/or survival, and immunology were enriched in these genes. Pathway crosstalk analysis then revealed that the significantly enriched pathways could be grouped into three interlinked modules-neuronal and metabolic module, cell growth/survival and neuroendocrine pathway module, and immune response-related module-indicating an AD-specific immune-endocrine-neuronal regulatory network. Furthermore, an AD-specific protein network was inferred and novel genes potentially associated with AD were identified. By means of network and pathway-based methodology, we explored the pathogenetic mechanism underlying AD at a systems biology level. Results from our work could provide valuable clues for understanding the molecular mechanism underlying AD. In addition, the framework proposed in this study could be used to investigate the pathological molecular network and genes relevant to other complex diseases or phenotypes.

A 2,000-year record of mercury and ancient civilizations in seal hairs from King George Island, West Antarctica.

PubMed

Sun, Liguang; Yin, Xuebin; Liu, Xiaodong; Zhu, Renbin; Xie, Zhouqing; Wang, Yuhong

2006-09-01

The concentrations of total mercury (Hg(T)) and three bio-essential elements (phosphor, potassium, sodium) were analyzed in Antarctic seal hairs from a lake core spanning the past 2,000 years and collected from King George Island (63 degrees 23'S, 57 degrees 00'W), West Antarctica. The Hg(T) concentration shows a significant fluctuation while the levels of the three bio-essential elements remain almost constant. The rise and fall of the Hg(T) concentration in the seal hairs are found to be closely coincided with ancient activities of gold and silver mining using Hg-amalgamation process around the world, especially in the Southern Hemisphere. Briefly, Hg(T) levels are high during five episodes of extensive gold and silver mining activities--Rome Empire and China Han Dynasty (approximately 18-300 A.D.), Maya period and China Tang (750-900 A.D.), Incas civilization and Christian Kingdom (1200-1500 A.D.), New world (1650-1800 A.D.), and modern industry period (1840 A.D.-present); they are low during four time periods of reduced gold and silver mining activities--the China Han and Rome fall (since 300 A.D.), Maya fall and Wartime period in China (1050-1250 A.D.), Pizarro coming (ca. 1532 A.D.) and Independence War of South America (1800-1830 A.D.). Two profiles of Hg(T) in other two lake cores, one affected by seal excrements and the other by penguin droppings, from the same region are similar to the one in seal hairs. The Hg concentration profile in the seal hairs is significantly correlated with the one in a peat bog of Southern Chile near King George Island. Since Hg is existent mainly at the form of methyl-mercury in seal hairs, this correlation supports a relationship and link between atmospheric mercury concentration and methyl-mercury production. Comparing with samples from American and European continents, the Antarctic seal hairs provide an archive of total mercury concentration in surface seawater of the South Ocean less affected by regional human activities, and this archive may provide a good reference for assessing the global Hg emissions, depositions and recycling in the past thousand years.

Gender-specific association of ATP-binding cassette transporter 1 (ABCA1) polymorphisms with the risk of late-onset Alzheimer's disease.

PubMed

Sundar, Purnima Desai; Feingold, Eleanor; Minster, Ryan L; DeKosky, Steven T; Kamboh, M Ilyas

2007-06-01

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder caused by a complex interaction of genetic and environmental factors. Increasing evidence highlights a potential role for cholesterol in the pathophysiology of AD. The ABCA1 gene, located in close vicinity to the 9q linkage peaks identified by genome-wide AD linkage studies, plays an important role in cellular cholesterol efflux, and is likely a good candidate gene. However, results from published genetic association studies between ABCA1 and AD are ambiguous. In the present study, we examined the role of two ABCA1 polymorphisms, R219K (rs2230806) and G-17C (rs2740483) in modifying the risk of late-onset AD (LOAD) in a large American white cohort of 992 AD cases and 699 controls. We observed significant gender x R219K interaction (p=0.00008). Female carriers of the 219K allele showed a 1.75-fold increased risk of developing AD compared to non-219K carrier females (95% CI 1.34-2.29; p=0.00004). The overall two-site haplotype distribution was also significant between female AD cases and controls (p=0.017). The risk associated with the R219K polymorphism was independent of the recently reported significant association in the ubiquilin (UBQLN1) gene in this region on chromosome 9q. Our data suggest a gender-specific and APOE and UBQLN1 independent association between the ABCA1/R219K polymorphism and LOAD.

ASSOCIATION BETWEEN GAB2 HAPLOTYPE AND HIGHER GLUCOSE METABOLISM IN ALZHEIMER'S DISEASE-AFFECTED BRAIN REGIONS IN COGNITIVELY NORMAL APOEε4 CARRIERS

PubMed Central

Liang, Winnie S.; Chen, Kewei; Lee, Wendy; Sidhar, Kunal; Corneveaux, Jason J.; Allen, April N.; Myers, Amanda; Villa, Stephen; Meechoovet, Bessie; Pruzin, Jeremy; Bandy, Daniel; Fleisher, Adam S.; Langbaum, Jessica B.S.; Huentelman, Matthew J.; Jensen, Kendall; Dunckley, Travis; Caselli, Richard J.; Kaib, Susan; Reiman, Eric M.

2010-01-01

In a genome-wide association study (GWAS) of late-onset Alzheimer's disease (AD), we found an association between common haplotypes of the GAB2 gene and AD risk in carriers of the apolipoprotein E (APOE) ε4 allele, the major late-onset AD susceptibility gene. We previously proposed the use of fluorodeoxyglucose positron emission tomography (FDG-PET) measurements as a quantitative presymptomatic endophenotype, more closely related to disease risk than the clinical syndrome itself, to help evaluate putative genetic and non-genetic modifiers of AD risk. In this study, we examined the relationship between the presence or absence of the relatively protective GAB2 haplotype and PET measurements of regional-to-whole brain FDG uptake in several AD-affected brain regions in 158 cognitively normal late-middle-aged APOEε4 homozygotes, heterozygotes, and non-carriers. GAB2 haplotypes were characterized using Affymetrix Genome-Wide Human SNP 6.0 Array data from each of these subjects. As predicted, the possibly protective GAB2 haplotype was associated with higher regional-to-whole brain FDG uptake in AD-affected brain regions in APOEε4 carriers. While additional studies are needed, this study supports the association between the possibly protective GAB2 haplotype and the risk of late-onset AD in APOEε4 carriers. It also supports the use of brain-imaging endophenotypes to help assess possible modifiers of AD risk. PMID:20888920