Detection of a Single Identical Cytomegalovirus (CMV) Strain in Recently Seroconverted Young Women

Infection with multiple CMV strains is common in immunocompromised hosts, but its occurrence in normal hosts has not been well-studied.We analyzed CMV strains longitudinally in women who acquired CMV while enrolled in a CMV glycoprotein B (gB) vaccine trial. Sequencing of four variable genes was performed in samples collected from seroconversion and up to 34 months thereafter.199 cultured isolates from 53 women and 65 original fluids from a subset of 19 women were sequenced. 51 women were infected with one strain each without evidence for genetic drift; only two women shed multiple strains. Genetic variability among strains increased with the number of sequenced genetic loci. Nevertheless, 13 of 53 women proved to be infected with an identical CMV strain based on sequencing at all four variable genes. CMV vaccine did not alter the degree of genetic diversity amongst strains.Primary CMV infection in healthy women nearly always involves shedding of one strain that remains stable over time. Immunization with CMVgB-1 vaccine strain is not selective against specific strains. Although 75% of women harbored their unique strain, or a strain shared with only one other woman, 25% shared a single common strain, suggesting that this predominant strain with a particular combination of genetic loci is advantageous in this large urban area

The EMIF-AD PreclinAD study: study design and baseline cohort overview

BACKGROUND: Amyloid pathology is the pathological hallmark in Alzheimer’s disease (AD) and can precede clinical dementia by decades. So far it remains unclear how amyloid pathology leads to cognitive impairment and dementia. To design AD prevention trials it is key to include cognitively normal subjects at high risk for amyloid pathology and to find predictors of cognitive decline in these subjects. These goals can be accomplished by targeting twins, with additional benefits to identify genetic and environmental pathways for amyloid pathology, other AD biomarkers, and cognitive decline. METHODS: From December 2014 to October 2017 we enrolled cognitively normal participants aged 60 years and older from the ongoing Manchester and Newcastle Age and Cognitive Performance Research Cohort and the Netherlands Twins Register. In Manchester we included single individuals, and in Amsterdam monozygotic twin pairs. At baseline, participants completed neuropsychological tests and questionnaires, and underwent physical examination, blood sampling, ultrasound of the carotid arteries, structural and resting state functional brain magnetic resonance imaging, and dynamic amyloid positron emission tomography (PET) scanning with [18F]flutemetamol. In addition, the twin cohort underwent lumbar puncture for cerebrospinal fluid collection, buccal cell collection, magnetoencephalography, optical coherence tomography, and retinal imaging. RESULTS: We included 285 participants, who were on average 74.8 ± 9.7 years old, 64% female. Fifty-eight participants (22%) had an abnormal amyloid PET scan. CONCLUSIONS: A rich baseline dataset of cognitively normal elderly individuals has been established to estimate risk factors and biomarkers for amyloid pathology and future cognitive declin

Cognitive function and drivers of cognitive impairment in a European and a Korean cohort of people living with HIV

Although cognitive impairments are still prevalent in the current antiretroviral therapy era, limited investigations have compared the prevalence of cognitive disorder in people living with HIV (PLWH) and its determinants in different regions and ethnicities. We compared cognitive performance across six domains using comparable batteries in 134 PLWH aged ≥45 years from the COBRA study (Netherlands, UK), and 194 PLWH aged ≥18 years from the NeuroAIDS Project (South Korea). Cognitive scores were standardized and averaged to obtain domain and global T-scores. Associations with global T-scores were evaluated using multivariable regression and the ability of individual tests to detect cognitive impairment (global T-score ≤45) was assessed using the area-under-the-receiver-operating-characteristic curve (AUROC). The median (interquartile range) age of participants was 56 (51, 62) years in COBRA (88% white ethnicity, 93% male) and 45 (37, 52) years in NeuroAIDS (100% Korean ethnicity, 94% male). The rate of cognitive impairment was 18.8% and 18.0%, respectively (p = 0.86). In COBRA, Black-African ethnicity was the factor most strongly associated with cognitive function (11.1 [7.7, 14.5] lower scores vs. white ethnicity, p < 0.01), whereas in NeuroAIDS, age (0.6 [0.1, 1.3] per 10-year, p<0.01) and education (0.7 [0.5, 0.9] per year, p<0.01) were significantly associated with cognitive function with anemia showing only a weak association (−1.2 [−2.6, 0.3], p=0.12). Cognitive domains most associated with cognitive impairment were attention (AUROC = 0.86) and executive function (AUROC = 0.87) in COBRA and processing speed (AUROC = 0.80), motor function (AUROC = 0.78) and language (AUROC = 0.78) in NeuroAIDS. Two cohorts of PLWH from different geographical regions report similar rates of cognitive impairment but different risk factors and cognitive profiles of impairment

Do people living with HIV experience greater age advancement than their HIV-negative counterparts?

Objectives: Despite successful antiretroviral therapy, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers of aging in PLWH, appropriately chosen HIV-negative individuals, and blood donors, and explored factors associated with biological age advancement. Design: Cross-sectional analysis of 134 PLWH on suppressive antiretroviral therapy, 79 lifestyle-comparable HIV-negative controls aged 45 years or older from the Co-mor- Bidity in Relation to AIDS (COBRA) cohort, and 35 age-matched blood donors. Methods: Biological age was estimated using a validated algorithm based on 10 biomarkers. Associations between ‘age advancement’ (biological minus chronological age) and HIV status/parameters, lifestyle, cytomegalovirus (CMV), hepatitis B (HBV) and hepatitis C virus (HCV) infections were investigated using linear regression. Results: The average (95% CI) age advancement was greater in both HIV-positive [13.2 (11.6–14.9) years] and HIV-negative [5.5 (3.8–7.2) years] COBRA participants compared with blood donors [7.0 (4.1 to 9.9) years, both P’s<0.001)], but also in HIV-positive compared with HIV-negative participants (P<0.001). Chronic HBV, higher anti-CMV IgG titer and CD8þ T-cell count were each associated with increased age advancement, independently of HIV-status/group. Among HIV-positive participants, age advancement was increased by 3.5 (0.1–6.8) years among those with nadir CD4þ T-cell count less than 200 cells/ml and by 0.1 (0.06–0.2) years for each additional month of exposure to saquinavir

Homocystinuria presenting as central retinal artery occlusion and longstanding thromboembolic disease.

A case of central retinal artery occlusion in a patient with a 10-year history of unexplained thromboembolic disease due to a secondary hypercoagulable state is presented. Ophthalmological examination led to the final diagnosis

Use of a new intraocular spectral domain optical coherence tomography in vitreoretinal surgery

Purpose To describe the use of a novel intra-ocular side-scanning probe enabling the acquisition of spectral-domain optical coherence tomography (SD-OCT) images during surgery in a series of patients with complex forms of retinal detachment. Methods A 23-gauge, side-scanning SD-OCT probe (C7 System; LightLab Imaging, Inc/St Jude Medical, St. Paul, MN, USA) in a 20-gauge catheter, was used to acquire the intra-operative OCT images in seven patients with vitreoretinal diseases. Twenty-five gauge pars plana vitrectomy (PPV) was performed in every patient in a standard fashion. After enlarging the temporal sclerotomy to a 20-gauge port, all the patients were scanned with intra-ocular side-scanning SD-OCT, during different steps of the surgery based on surgeon needs. Scans were recorded real time and directly evaluated on a screen during surgery. Optical coherence tomography (OCT) scans were judged beneficial when they would recognize structures otherwise not seen on biomicroscopy. Results The intra-ocular SD-OCT has been helpful in acquiring extra information during vitreoretinal surgery such as the detection of the presence of otherwise invisible membranes (epiretinal membrane, subretinal membrane), the location of small tears and the identification of the retinal plane under suboptimal conditions for visualization. Conclusion The use of an intra-ocular SD-OCT can expand upon visual cues during surgery, helping in the decision-making process and allowing additional deliberate surgical manoeuvres aimed at improving surgical outcomes

In vivo 3D determination of peripapillary scleral and retinal layer architecture using polarization-sensitive optical coherence tomography

Purpose: The purpose of this paper was to determine the architecture of the collagen fibers of the peripapillary sclera, the retinal nerve fiber layer (RNFL), and Henle’s fiber layer in vivo in 3D using polarization-sensitive optical coherence tomography (PS-OCT). Methods: Seven healthy volunteers were imaged with our in-house built PS-OCT system. PS-OCT imaging included intensity, local phase retardation, relative optic axis, and optic axis uniformity (OAxU). Differential Mueller matrix calculus was used for the first time in ocular tissues to visualize local orientations that varied with depth, incorpo-rating a correction method for the fiber orientation in preceding layers. Results: Scleral collagen fiber orientation images clearly showed an inner layer with an orientation parallel to the RNFL orientation, and a deeper layer where the collagen was circularly oriented. RNFL orientation images visualized the nerve fibers leaving the optic nerve head (ONH) in a radial pattern. The phase retardation and orientation of Henle’s fiber layer were visualized locally for the first time. Conclusions: PS-OCT successfully showed the orientation of the retinal nerve fibers, sclera, and Henle’s fiber layer, and is to the extent of our knowledge the only technique able to do so in 3D in vivo. Translational Relevance: In vivo 3D imaging of scleral collagen architecture and the retinal neural fibrous structures can improve our understanding of retinal biomechanics and structural alterations in different disease stages of myopia and glaucoma