Vascular α1A Adrenergic Receptors as a Potential Therapeutic Target for IPAD in Alzheimer's Disease.

Drainage of interstitial fluid from the brain occurs via the intramural periarterial drainage (IPAD) pathways along the basement membranes of cerebral capillaries and arteries against the direction of blood flow into the brain. The cerebrovascular smooth muscle cells (SMCs) provide the motive force for driving IPAD, and their decrease in function may explain the deposition of amyloid-beta as cerebral amyloid angiopathy (CAA), a key feature of Alzheimer's disease. The α-adrenoceptor subtype α1A is abundant in the brain, but its distribution in the cerebral vessels is unclear. We analysed cultured human cerebrovascular SMCs and young, old and CAA human brains for (a) the presence of α1A receptor and (b) the distribution of the α1A receptor within the cerebral vessels. The α1A receptor was present on the wall of cerebrovascular SMCs. No significant changes were observed in the vascular expression of the α1A-adrenergic receptor in young, old and CAA cases. The pattern of vascular staining appeared less punctate and more diffuse with ageing and CAA. Our results show that the α1A-adrenergic receptor is preserved in cerebral vessels with ageing and in CAA and is expressed on cerebrovascular smooth muscle cells, suggesting that vascular adrenergic receptors may hold potential for therapeutic targeting of IPAD.

An observational study to evaluate three pilot programmes of retesting chlamydia-positive individuals within 6†months in the South West of England.

OBJECTIVES: To evaluate 3 pilot chlamydia retesting programmes in South West England which were initiated prior to the release of new National Chlamydia Screening Programme (NCSP) guidelines recommending retesting in 2014. METHODS: Individuals testing positive between August 2012 and July 2013 in Bristol (n=346), Cornwall (n=252) and Dorset (n=180) programmes were eligible for inclusion in the retesting pilots. The primary outcomes were retest within 6 months (yes/no) and repeat diagnosis at retest (yes/no), adjusted for area, age and gender. RESULTS: Overall 303/778 (39.0%) of participants were retested within 6 months and 31/299 (10.4%) were positive at retest. Females were more likely to retest than males and Dorset had higher retesting rates than the other areas. CONCLUSIONS: More than a third of those eligible were retested within the time frame of the study. Chlamydia retesting programmes appear feasible within the context of current programmes to identify individuals at continued risk of infection with relatively low resource and time input.

Chlamydia screening, retesting and repeat diagnoses in Cornwall, UK 2003-2009.

OBJECTIVES: This study aims to describe the patterns of testing and retesting for chlamydia in Cornwall during the first 5 years of the National Chlamydia Screening Programme. We evaluate the factors associated with retesting and estimate the incidence of chlamydia diagnosis and repeat diagnosis. STUDY DESIGN: Secondary database analysis. SELECTION CRITERIA: men and women tested for chlamydia between March 2003 and January 2009 in Cornwall, aged ≥12 years and ≤25 years at the first test. The factors associated with retesting in those with at least one known test result and at least 14 days follow-up time were analysed using Cox regression and the incidence of diagnosis and repeat diagnosis were calculated. RESULTS: The final dataset consisted of 71 066 records from 49 941 individuals; of whom 59.0% were female and 75.4% were only tested once. There were 48 375 individuals with at least one known test result (negative or positive) and at least 14 days follow-up, included in the Cox regression analysis. Factors associated with testing more than once were (adjusted HR, 95% CI): being female (2.24; 2.14 to 2.34) and initially testing positive (1.43; 1.35 to 1.51). The positivity at first episode declined from 13.2% (1077 cases) in 2003/2004 to 5.8% (843 cases) in 2008/2009. The incidence of diagnosis at the second test was 5.9 per 100 person years in those testing negative at the first test compared with 18.1 per 100 person years in those initially positive. DISCUSSION: Most individuals in this analysis were tested only once, but the testing volume and proportion of repeat tests were highest at the end of the study period. As the testing rate stabilises to 30% coverage, maintaining retesting rates in those previously tested and especially in those previously diagnosed with chlamydia will be necessary for the sustainability of the screening programme. CONCLUSIONS: A key feature of the next 5 years of the screening programme will be to maintain screening and rescreening.

HIV and bone health.

Bones are the foundation of our bodies; without healthy bones, we can become vulnerable to poor overall health. People with HIV are susceptible to bone loss, and to a condition called osteoporosis that may lead to fractures. In addition, as people with HIV are living longer due to effective antiretroviral therapy, bone complications may worsen as a result of aging and long-term HIV disease. Aging, antiretroviral drugs, traditional bone loss risk factors, and lifestyle all contribute to bone deterioration in the setting of HIV.