Clinical Correlates of Alzheimer's Disease with and without Silent Radiographic Abnormalities

Objective: To determine whether patients with Alzheimer's disease (AD) who do not have historical or clinical evidence of stroke but who do have computed tomographic or magnetic resonance imaging evidence of noncortical lesions smaller than 2 cm or periventricular "caps" differ from other patients with AD. Methods: The computed tomographic or magnetic resonance imaging scans of 158 patients meeting criteria of the National Institute of Neurological Disorders and Stroke—Alzheimer's Disease and Related Disorders Association for probable AD were reviewed by one neuroradiologist. Two measures of disease severity—the Modified Mini-Mental State examination and the Blessed Dementia Rating Scale (Part I)—were subjected to two-way analysis of variance with scan type (computed tomography or magnetic resonance imaging) and lesion number as between-group factors and age and disease duration as covariates. Results: No relationship was seen between lesion number or periventricular caps and disease severity. Conclusion: In this cross-sectional analysis using these clinical measures, patients with AD who have well-defined radiographic abnormalities cannot be differentiated from patients with AD who do not have them

Assessing Patient Dependence in Alzheimer's Disease

Background. While cognitive and functional deficits are the hallmark of Alzheimer's disease (AD), loss of social function (and the dependence this implies) is also critical, especially in early stages of disease. Little attention has been directed to this facet of dementing disease. We describe a scale for assessing dependency in AD and present a baseline profile of dependency in a cohort of AD patients. Methods. In a study of the predictors of the course of AD, 233 patients in early stages of disease (modified MMS ≥ 30) were assessed. Psychometric properties of the dependence scale were established. To validate the scale, dependence scores at baseline were correlated with a series of measures assessing cognition and function. The course of dependency over 18 months of follow-up was also analyzed. Results. The scale shows adequate reliability (test-retest, intraclass correlation). Dependence stage was related to other measures of disease severity. Scalogram analysis shows that the dependence scale is consistent with the course of functional loss established for dementing disease. Prospective data indicate sensitivity of the scale to disease progression. Conclusion. Dependency is a distinct, measurable component of dementing disease and should be considered an important outcome in studies of AD

Multicenter Study of Predictors of Disease Course in Alzheimer Disease (the "Predictors Study"). I. Study Design, Cohort Description, and Intersite Comparisons

Clinicians should be able to provide the patient with Alzheimer disease (AD) and the family with an accurate prediction of what to expect, but the variability in the rate of disease progression precludes this. In several previous studies, specific clinical signs such as muscular rigidity, myoclonus, and hallucinations or delusions were associated with rapid progression to a more severe stage of dementia or death. The 'Predictors Study,' a longitudinal study at three independent sites, was designed to develop a predictor model of the natural history of Alzheimer disease. The study was conducted at three study sites, New York, Baltimore, and Boston in a cohort of 224 patients with early probable AD. This article describes the design and implementation of the Predictors Study, and compares features of the study cohort at baseline across sites. Patients were all at the mild stage of disease at entry and were relatively comparable across sites. Extrapyramidal signs and delusions were common, but myoclonus was rarely observed

Identification of transcriptional networks responding to pyrroloquinoline quinone dietary supplementation and their influence on thioredoxin expression, and the JAK/STAT and MAPK pathways

PQQ (pyrroloquinoline quinone) improves energy utilization and reproductive performance when added to rodent diets devoid of PQQ. In the present paper we describe changes in gene expression patterns and transcriptional networks that respond to dietary PQQ restriction or pharmacological administration. Rats were fed diets either deficient in PQQ (PQQ−) or supplemented with PQQ (approx. 6 nmol of PQQ/g of food; PQQ+). In addition, groups of rats were either repleted by administering PQQ to PQQ− rats (1.5 mg of PQQ intraperitoneal/kg of body weight at 12 h intervals for 36 h; PQQ−/+) or partially depleted by feeding the PQQ− diet to PQQ+ rats for 48 h (PQQ+/−). RNA extracted from liver and a Codelink® UniSet Rat I Bioarray system were used to assess gene transcript expression. Of the approx. 10000 rat sequences and control probes analysed, 238 were altered at the P<0.01 level by feeding on the PQQ− diet for 10 weeks. Short-term PQQ depletion resulted in changes in 438 transcripts (P<0.01). PQQ repletion reversed the changes in transcript expression caused by PQQ deficiency and resulted in an alteration of 847 of the total transcripts examined (P<0.01). Genes important for cellular stress (e.g. thioredoxin), mitochondriogenesis, cell signalling [JAK (Janus kinase)/STAT (signal transducer and activator of transcription) and MAPK (mitogen-activated protein kinase) pathways] and transport were most affected. qRT-PCR (quantitative real-time PCR) and functional assays aided in validating such processes as principal targets. Collectively, the results provide a mechanistic basis for previous functional observations associated with PQQ deficiency or PQQ administered in pharmacological amounts

University Students’ ,Hope, Optimism, Resilience, and Efficacy (PsyCap)nduring Covid 19 Pandemic and Its Relation to Student’s Performance Mediated by Motivation

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; It has been more than a year, covid19 pandemic has influenced our life behavior including performance reflected by students’ learning outcomes. In this situation, students have to adapt themselves to a new normal life, shifting from traditional learning styles to digital learning which is too hard for those who live in the marginal area. Therefore, the objective of this research was to try to find information on whether students still have high psychological capital and how it affects their motivation and performance as well. A causal survey was used by selecting 216 University students and there were three instruments developed which have been validated. Data were analyzed by structural equation modeling (SEM). The research results revealed that students' PsyCap and each of PsyCap dimensions, such as hope, optimism, resilience, and efficacy directly and significantly affected student’s performance and motivation. Students’ resilience has the highest path-coefficient on performance and students’ hope, significantly has the highest path-coefficient on student’s motivation. Moreover, student’s learning motivation, even during the covid19 pandemic, was significant as a good mediator between students' PsyCap and citizenship behavior which reflects student’s performance. These findings could be interpreted that, even its teaching and learning carried out fully by online methods, however, students still have remarkable hope, optimism, resilience, and efficacy significantly. Therefore, these findings have an important policy implication by developing a specific program that maintains students’ PsyCap. Improving and maintaining students’ PsyCap is not only a must, but it is a kind of responsibility hold by the university system including the university president as a campus leader. Especially in how to manage lecturers/professors for not only focus on students' cognitive aspects but their psychological conditions could not be neglected as well during the unpredictable covid19 pandemic

Identification of transcriptional networks responding to pyrroloquinoline quinone dietary supplementation and their influence on thioredoxin expression, and the JAK/STAT and MAPK pathways.

PQQ (pyrroloquinoline quinone) improves energy utilization and reproductive performance when added to rodent diets devoid of PQQ. In the present paper we describe changes in gene expression patterns and transcriptional networks that respond to dietary PQQ restriction or pharmacological administration. Rats were fed diets either deficient in PQQ (PQQ-) or supplemented with PQQ (approx. 6 nmol of PQQ/g of food; PQQ+). In addition, groups of rats were either repleted by administering PQQ to PQQ- rats (1.5 mg of PQQ intraperitoneal/kg of body weight at 12 h intervals for 36 h; PQQ-/+) or partially depleted by feeding the PQQ- diet to PQQ+ rats for 48 h (PQQ+/-). RNA extracted from liver and a Codelink(R) UniSet Rat I Bioarray system were used to assess gene transcript expression. Of the approx. 10000 rat sequences and control probes analysed, 238 were altered at the P&lt;0.01 level by feeding on the PQQ- diet for 10 weeks. Short-term PQQ depletion resulted in changes in 438 transcripts (P&lt;0.01). PQQ repletion reversed the changes in transcript expression caused by PQQ deficiency and resulted in an alteration of 847 of the total transcripts examined (P&lt;0.01). Genes important for cellular stress (e.g. thioredoxin), mitochondriogenesis, cell signalling [JAK (Janus kinase)/STAT (signal transducer and activator of transcription) and MAPK (mitogen-activated protein kinase) pathways] and transport were most affected. qRT-PCR (quantitative real-time PCR) and functional assays aided in validating such processes as principal targets. Collectively, the results provide a mechanistic basis for previous functional observations associated with PQQ deficiency or PQQ administered in pharmacological amounts

Intensive sex partying with gamma-hydroxybutyrate: factors associated with using gamma-hydroxybutyrate for chemsex among Australian gay and bisexual men – results from the Flux Study

Background: Gamma-hydroxybutyrate (GHB) use among gay and bisexual men (GBM) has increased in recent years. It is commonly cited as a sexual enhancement drug. There is, however, little evidence for factors associated with GHB use or the consequences of its use among GBM. Aim: We examine factors associated with GHB use, its relationship to sexual risk behaviour, and the contexts, consequences, and motivations for its use. Methods: The Following Lives Undergoing Change (Flux) study is an online prospective observational study of Australian GBM. At baseline, a total of 3190 GBM provided details about their use of GHB. We collected data on frequency, methods, pleasures and consequences for their drug use, alongside key demographic variables. Results: Mean age was 35.0 years. One in five men (19.5%) had a history of GHB use and 5.4% reported use within the previous six months, with 2.7% having used it monthly or more frequently. 14.7% had experienced drug overdose, which was more common among men who used GHB at least monthly. Being HIV-positive, having more gay friends, greater social engagement with gay men who use drugs, a greater number of sexual partners, group sex, and condomless anal intercourse with casual partners were independently associated with GHB use in the previous six months. Greater social engagement with gay men who use drugs and group sex were independently associated with at least monthly use. More frequent GHB use was independently associated with experiencing overdose among GHB users. Conclusion: Most men used GHB infrequently and often explicitly to enhance sexual experiences, often in the context of intensive sex partying. Men who used GHB frequently, were at greater risk of overdose and other negative health outcomes. GHB use should be considered alongside other drugs that have been implicated in sexual risk behaviour and HIV transmission. Harm reduction interventions need to consider the particular impact of frequent GHB use

Tailored combination prevention packages and PrEP for young key populations

Introduction: Young key populations, defined in this article as men who have sex with men, transgender persons, people who sell sex and people who inject drugs, are at particularly high risk for HIV. Due to the often marginalized and sometimes criminalized status of young people who identify as members of key populations, there is a need for HIV prevention packages that account for the unique and challenging circumstances they face. Pre-exposure prophylaxis (PrEP) is likely to become an important element of combination prevention for many young key populations. Objective: In this paper, we discuss important challenges to HIV prevention among young key populations, identify key components of a tailored combination prevention package for this population and examine the role of PrEP in these prevention packages. Methods: We conducted a comprehensive review of the evidence to date on prevention strategies, challenges to prevention and combination prevention packages for young key populations. We focused specifically on the role of PrEP in these prevention packages and on young people under the age of 24, and 18 in particular. Results and discussion: Combination prevention packages that include effective, acceptable and scalable behavioural, structural and biologic interventions are needed for all key populations to prevent new HIV infections. Interventions in these packages should meaningfully involve beneficiaries in the design and implementation of the intervention, and take into account the context in which the intervention is being delivered to thoughtfully address issues of stigma and discrimination. These interventions will likely be most effective if implemented in conjunction with strategies to facilitate an enabling environment, including increasing access to HIV testing and health services for PrEP and other prevention strategies, decriminalizing key populations’ practices, increasing access to prevention and care, reducing stigma and discrimination, and fostering community empowerment. PrEP could offer a highly effective, time-limited primary prevention for young key populations if it is implemented in combination with other programs to increase access to health services and encourage the reliable use of PrEP while at risk of HIV exposure. Conclusions: Reductions in HIV incidence will only be achieved through the implementation of combinations of interventions that include biomedical and behavioural interventions, as well as components that address social, economic and other structural factors that influence HIV prevention and transmission