Women with the Alzheimer's risk marker ApoE4 lose Aβ-specific CD4+ T cells 10–20 years before men

Adaptive immunity to self-antigens causes autoimmune disorders, such as multiple sclerosis, psoriasis and type 1 diabetes; paradoxically, T- and B-cell responses to amyloid-β (Aβ) reduce Alzheimer''s disease (AD)-associated pathology and cognitive impairment in mouse models of the disease. The manipulation of adaptive immunity has been a promising therapeutic approach for the treatment of AD, although vaccine and anti-Aβ antibody approaches have proven difficult in patients, thus far. CD4⁺ T cells have a central role in regulating adaptive immune responses to antigens, and Aβ-specific CD4⁺ T cells have been shown to reduce AD pathology in mouse models. As these cells may facilitate endogenous mechanisms that counter AD, an evaluation of their abundance before and during AD could provide important insights. Aβ-CD4see is a new assay developed to quantify Aβ-specific CD4⁺ T cells in human blood, using dendritic cells derived from human pluripotent stem cells. In tests of >50 human subjects Aβ-CD4see showed an age-dependent decline of Aβ-specific CD4⁺ T cells, which occurs earlier in women than men. In aggregate, men showed a 50% decline in these cells by the age of 70 years, but women reached the same level before the age of 60 years. Notably, women who carried the AD risk marker apolipoproteinE-ɛ4 (ApoE4) showed the earliest decline, with a precipitous drop between 45 and 52 years, when menopause typically begins. Aβ-CD4see requires a standard blood draw and provides a minimally invasive approach for assessing changes in Aβ biology that may reveal AD-related changes in physiology by a decade. Furthermore, CD4see probes can be modified to target any peptide, providing a powerful new tool to isolate antigen-specific CD4⁺ T cells from human subjects.     

Epidemiology of Traumatic Brain Injury and Subarachnoid Hemorrhage

Incidence rates of traumatic brain injury are high in both industrialized and non-industrialized countries and have been estimated variously to be between 150–250 cases per 100,000 population per year. The estimated incidence rates for subarachnoid hemorrhage (SAH) are between 10 to 25 cases per 100,000 population per year. Seasonal variation in the occurrence of subarachnoid hemorrhage has been reported in studies from different countries, with significant seasonal variations and peak periods for aneurysmal SAH differing widely. A differential racial distribution for SAH has been found as well as a higher mortality rate for women than for men. The cognitive and behavioral consequences of TBI and SAH are significant and affect the quality of life of patients and their families. Recent publications have informed of hypopituitary deficits in patients sustaining TBI or SAH. It is not clear whether the cognitive deficits found in these patients are due to the consequences of the brain injury itself or are related to the hypopituitary deficits. There is a need for research distinguishing the differential cognitive and behavioral effects of the brain injury and the endocrinological deficits in these patients, and for developing adequate treatment.     

Cyanobacterium producing cylindrospermopsin cause histopathological changes at environmentally relevant concentrations in subchronically exposed tilapia (Oreochromis niloticus)

The acute toxicity of cylindrospermopsin (CYN) has been established in rodents, based on diverse intraperitoneal an oral exposure studies and more recently in fish. But no data have been reported in fish after subchronic exposure to cyanobacterial cells containing this cyanotoxin, so far. In this work, tilapia (Oreochromis niloticus) were exposed by immersion to lyophilized Aphanizomenon ovalisporum cells added to the aquaria using two concentration levels of CYN (10 or 100 μg CYN L^?1) and deoxy‐cylindrospermopsin (deoxy‐CYN) (0.46 or 4.6 μg deoxy‐CYN L^?1), during two different exposure times: 7 or 14 d. This is the first study showing damage in the liver, kidney, hearth, intestines, and gills of tilapia after subchronic exposure to cyanobacterial cells at environmental relevant concentrations. The major histological changes observed were degenerative processes and steatosis in the liver, membranous glomerulopathy in the kidney, myofibrolysis and edema in the heart, necrotic enteritis in the gastrointestinal tract, and hyperemic processes in gill lamellae and microhemorrhages. Moreover, these histopathological findings confirm that the extent of damage is related to the CYN concentration and length of exposure. Results from the morphometric study indicated that the average of nuclear diameter of hepatocytes and cross‐sections of proximal and distal convoluted tubules are useful to evaluate the damage induced by CYN in the main targets of toxicity. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 261–277, 2015.     

Mechanical valve prosthesis is a valid option for aortic valve replacement in the elderly

BACKGROUND AND AIM OF THE STUDY: Thromboembolism and hemorrhage related to anticoagulation remain a major concern in elderly patients with mechanical valves. Clinical results following isolated aortic valve replacement (AVR) with tilting disk and bileaflet prostheses in patients aged over 70 years were analyzed and compared with results in patients aged <45 years. METHODS: Between January 1980 and August 2002, 319 consecutive older patients (group A) and 497 young patients AVR. Preoperative clinical data, early and late mortality, valve-related complications and data related to anticoagulation status (including mean INR and mean interval between INR assays) were compared between groups. RESULTS: Hospital mortality was lower in group B (3.4%) than in group A (10.7%; p <0.0001). Twelve-year actuarial survival was lower in older patients (54% in group A versus 78% in group B; p <0.001). The two groups showed similar 12-year actuarial freedom from hemorrhage (99.6% versus 99.5%; p = 0.69), endocarditis (99.6% versus 98.43%; p = 0.25) and perivalvular leak (99.6% versus 97.9%; p = 0.21). However, actuarial freedom from thromboembolism was lower in older patients (98.8% versus 99.7%; p = 0.041). CONCLUSION: Despite lower rates of long-term mortality and thromboembolism (the latter because of advanced atherosclerosis) in group A, there were no differences in rates of other valve-related complications. Hence, older age cannot be considered a contraindication to implantation of mechanical valves in the aortic position.