Soviet foreign policy and the world revolution

https://stars.library.ucf.edu/prism/1787/thumbnail.jp

The American labor movement: Its past, its present and future

https://stars.library.ucf.edu/prism/1433/thumbnail.jp

What next for American labor?

https://stars.library.ucf.edu/prism/1152/thumbnail.jp

Genes of the serotonergic and dopaminergic pathways and their interaction affect the expression of Behavioural and Psychological Symptoms in Dementia (BPSD).

Although there is evidence for the involvement of genes of serotonergic and dopaminergic systems in the manifestation of the Behavioural and Psychological Symptoms in Dementia (BPSD), genetic association studies are contradictory. We used 1008 probable AD patients from the UK and applied a Multiple Indicators Multiple Causes (MIMIC) approach to investigate the effect of 11 polymorphisms in the serotonergic and dopaminergic systems, on four behavioural sub-phenotypes, namely "psychosis"," moods", "agitation" and "behavioural dyscontrol", as well as on 12 NPI items. Significant findings included the association of DRD1 A48G with "psychosis" (p=0.037), the association of DAT1 VNTR with "agitation" (p=0.006) and the association of DRD4 with "moods" sub-phenotype (p=0.008). In addition, associations were identified between DRD1 A48G and DAT1 VNTR with aberrant motor behaviour (AMB) symptoms (p=0.001 and p=0.015 respectively), between DRD4 and sleep disturbances (p=0.018) and between 5HTTLPR and apathy (p=0.033). Finally, significant interactions were observed between COMT Val158Met and 5HTTLPR with "psychosis" (p=0.026), between HTTLPR and STin2 with "psychosis" (p=0.005), between DAT1 3'UTR VNTR and COMT Val158Met with "agitation" (p=0.0001) and between DAT1 3'UTR VNTR and 5HTTLPR with the "moods" factor (p=0.0027). The complexity of the interrelations between genetic variation, behavioural symptoms and clinical variables was efficiently captured by this MIMIC model

Headache and type 2 diabetes association: a US national ambulatory case-control study

Objective We investigate the joint observation between type 2 diabetes and headache using a case-control study of a US ambulatory dataset. Background Recent whole-population cohort studies propose that type 2 diabetes may have a protective effect against headache prevalence. With headaches ranked as a leading cause of disability, headache-associated comorbidities could help identify shared molecular mechanisms. Methods We performed a case-control study using the US National Ambulatory Medical Care Survey, 2009, on the joint observation between headache and specific comorbidities, namely type 2 diabetes, hypertension and anxiety, for all patients between 18 and 65 years of age. The odds ratio of having a headache and a comorbidity were calculated using conditional logistic regression, controlling for gender and age over a study population of 3,327,947 electronic health records in the absence of prescription medication data. Results We observed estimated odds ratio of 0.89 (95% CI: 0.83-0.95) of having a headache and a record of type 2 diabetes over the population, and 0.83 (95% CI: 2.02-2.57) and 0.89 (95% CI: 3.00-3.49) for male and female, respectively. Conclusions We find that patients with type 2 diabetes are less likely to present a recorded headache indication. Patients with hypertension are almost twice as likely of having a headache indication and patients with an anxiety disorder are almost three times as likely. Given the possibility of confounding indications and prescribed medications, additional studies are recommended

Minocycline 200 mg or 400 mg versus placebo for mild Alzheimer's disease: the MADE Phase II, three-arm RCT

Background: Minocycline is an anti-inflammatory drug and protects against the toxic effects of β-amyloid in vitro and in animal models of Alzheimer’s disease. To the best of our knowledge, no randomised placebo-controlled clinical trials in patients with Alzheimer’s disease looking at the efficacy and tolerability of minocycline have been carried out. Objectives: The trial investigated whether or not minocycline was superior to placebo in slowing down the rate of decline in cognitive and functional ability over 2 years. The safety and tolerability of minocycline were also assessed. Design: A Phase II, three-arm, randomised, double-blind, multicentre trial with a semifactorial design. Participants continued on trial treatment for up to 24 months. Setting: Patients were identified from memory services, both within the 32 participating NHS trusts and within the network of memory services supported by the Dementias and Neurodegenerative Diseases Research Network (also known as DeNDRoN). Participants: Patients with standardised Mini Mental State Examination scores of > 23 points and with Alzheimer’s disease assessed by the National Institute on Aging–Alzheimer’s Association’s criteria were identified from memory services. Intervention: Patients with mild Alzheimer’s disease were randomly allocated 1 : 1 : 1 to receive one of three treatments: arm 1 – 400 mg per day of minocycline; arm 2 – 200 mg per day of minocycline; or arm 3 – placebo. Patients continued treatment for 24 months. Participants, investigators and outcome assessors were blind to treatment allocation. Main outcome measures: Primary outcome measures were decline in standardised Mini Mental State Examination and Bristol Activities of Daily Living Scale scores of combined minocycline treatment arms versus placebo, as analysed by intention-to-treat repeated measures regression. Results: Between 23 May 2014 and 14 April 2016, 554 participants were randomised. Of the 544 eligible participants, the mean age was 74.3 years and the average standardised Mini Mental State Examination score was 26.4 points. A total of 252 serious adverse events were reported, with the most common categories being neuropsychiatric and cardiocirculatory. Significantly fewer participants completed treatment with 400 mg of minocycline [29% (53/184)] than 200 mg [62% (112/181)] or placebo [64% (114/179)] (p < 0.0001), mainly because of gastrointestinal symptoms (p = 0.0008), dermatological side effects (p = 0.02) and dizziness (p = 0.01). Assessment rates were also lower in the 400-mg treatment arm: 68% (119 of 174 expected) for standardised Mini Mental State Examination scores at 24 months, compared with 82% (144/176) for the 200-mg treatment arm and 84% (140/167) for the placebo arm. Decline in standardised Mini Mental State Examination scores over the 24-month study period in the combined minocycline arms was similar to that in the placebo arm (4.1- vs. 4.3-point reduction; p = 0.9), as was the decline in the 400- and 200-mg treatment arms (3.3 vs. 4.7 points; p = 0.08). Likewise, worsening of Bristol Activities of Daily Living Scale scores over 24 months was similar in all trial arms (5.7, 6.6 and 6.2 points in the 400-mg treatment arm, 200-mg treatment arm and placebo arm, respectively; a p-value of 0.57 for minocycline vs. placebo and a p-value of 0.77 for 400 vs. 200 mg of minocycline). Results were similar in different patient subgroups and in sensitivity analyses adjusting for missing data. Limitations: Potential limitations of the study include that biomarkers were not used to confirm the diagnosis of Alzheimer’s disease, as these and apolipoprotein E (APOE) genotyping are not routinely available within the NHS. Compliance was also worse than expected and differential follow-up rates were observed, with fewer assessments obtained for the 400-mg treatment arm than for the 200-mg treatment and placebo arms. Conclusions: Minocycline does not delay the progress of cognitive or functional impairment in people with mild Alzheimer’s disease over a 2-year period. Minocycline at a dose of 400 mg is poorly tolerated in this population. Future work: The Minocycline in mild Alzheimer’s DiseasE (MADE) study provides a framework for a streamlined trial design that can be usefully applied to test other disease-modifying therapies

Plasma protein biomarkers for the prediction of CSF amyloid and Tau and [18F]-Flutemetamol PET scan result

Background: Blood biomarkers may aid in recruitment to clinical trials of Alzheimer’s disease (AD) modifying therapeutics by triaging potential trials participants for amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) Aβ and tau tests. Objective: To discover a plasma proteomic signature associated with CSF and PET measures of AD pathology. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based proteomics were performed in plasma from participants with subjective memory impairment (SMC), mild cognitive impairment (MCI) and AD, recruited to the Amsterdam Dementia Cohort, stratified by CSF Tau/Aβ42 (n=50). Technical replication and independent validation were performed by immunoassay in plasma from SMC, MCI and AD participants recruited to the Amsterdam Dementia Cohort with CSF measures (n=100), MCI participants enrolled in the GE067-005 study with [18F] Flutemetamol PET amyloid measures (n=173), and AD, MCI and cognitively healthy participants from the EMIF 500 study with CSF Aβ42 measurements (n=494). Results: 25 discovery proteins were nominally associated with CSF Tau/Aβ42 (P < 0.05) with associations of ficolin-2 (FCN2), apolipoprotein C-IV and fibrinogen β chain confirmed by immunoassay (P < 0.05). In the GE067-005 cohort, FCN2 was nominally associated with PET amyloid (P < 0.05) replicating the association with CSF Tau/Aβ42. There were nominally significant associations of complement component 3 with PET amyloid, and apolipoprotein(a), apolipoprotein A-I, ceruloplasmin, and PPY with MCI conversion to AD (all P < 0.05). In the EMIF 500 cohort FCN2 was trending towards a significant relationship with CSF Aβ42 (P ≈ 0.05), while both A1AT and clusterin were nominally significantly associated with CSF Aβ42 (both P < 0.05). Conclusion: Associations of plasma proteins with multiple measures of AD pathology and progression are demonstrated. To our knowledge this is the first study to report an association of FCN2 with AD pathology. Further testing of the proteins in larger independent cohorts will be important

Alzheimer's disease in humans and other animals; a consequence of post-reproductive lifespan and longevity rather than ageing

Research in the author’s laboratories is supported by the NIHR, MRC, ARUK, Alzheimer’s Society, Wellcome Trust and the EUIntroduction Alzheimer's disease and diabetes mellitus are linked by epidemiology, genetics, and molecular pathogenesis. They may also be linked by the remarkable observation that insulin signaling sets the limits on longevity. In worms, flies, and mice, disrupting insulin signaling increases life span leading to speculation that caloric restriction might extend life span in man. It is our contention that man is already a long-lived organism, specifically with a remarkably high postfertility life span, and that it is this that results in the prevalence of Alzheimer's disease and diabetes. Methods We review evidence for this hypothesis that carries specific predictions including that other animals with exceptionally long postreproductive life span will have increased risk of both diabetes and Alzheimer's disease. Results and Conclusions We present novel evidence that Dolphin, like man, an animal with exceptional longevity, might be one of the very few natural models of Alzheimer's disease.PostprintPeer reviewe