Anti-cytomegalovirus antibody levels stratify human immune profiles across the lifespan.

Human cytomegalovirus (hCMV) is a ubiquitous latent persistent herpesvirus infecting 60-90% of the population worldwide. hCMV carriage in immunocompetent people is asymptomatic; thus, hCMV can be considered a component of normative aging. However, hCMV powerfully modulates many features of the immune, and likely other, systems and organs. Questions remain as to how hCMV carriage affects the human host. We used anti-CMV antibody titers as a stratifying criterion to examine the impact of "intensity" of hCMV infection as a potential biomarker of aging, inflammation, and immune homeostasis in a cohort of 247 participants stratified into younger (21-40 years) and older (> 65 years of age) groups. We showed that anti-CMV antibody titers increased with age and directly correlated to increased levels of soluble tumor necrosis factor (sTNFR) I in younger but not older participants. CD8 + cell numbers were reduced in the older group due to the loss in CD8 + T naïve (Tn) cells. In CMV carriers and, in particular, in anti-CMV Ab-high participants, this loss was mitigated or reversed by an increase in the numbers of CD8 + T effector memory (Tem) and T effector memory reexpressing CD45RA (Temra) cells. Analysis of CD38, HLA-DR, and CD57 expression revealed subset (CD4 or CD8)-specific changes that correlated with anti-CMV Ab levels. In addition, anti-CMV Ab levels predicted anti-CMV CD8 T cell responsiveness to different CMV open reading frames (ORFs) selectively in older participants, which correlated to the transcriptional order of expression of specific CMV ORFs. Implications of these results for the potential predictive value of anti-CMV Ab titers during aging are discussed.

Uterine Uptake of Estrogen and Progestogen-Based Radiotracers in Rhesus Macaques with Endometriosis.

PURPOSE: Endometriosis is an estrogen-dependent disorder of menstruating primates where tissues similar to the inner lining of the uterus exist "ectopically" outside of the uterus. The ectopic endometrium, like the endometrium within the uterus, expresses estrogen receptors (ER) and progesterone receptors (PR) and undergoes hormone-dependent cell proliferation and bleeding each menstrual cycle. The goal of this study was to conduct abdominopelvic positron emission tomography (PET) scans with computed tomography (CT) imaging of rhesus macaques (Macaca mulatta) using radiotracers that target ER and PR [16α-[18F]fluoroestradiol (FES) and 12-[18F]fluoro-furanyl-nor-progesterone (FFNP)] in individuals with and without endometriosis. We also aimed to determine if menstrual cycle phase and/or the presence of endometriosis affected the uptake of these radiotracers. PROCEDURES: Rhesus macaques with either clinically diagnosed endometriosis (n = 6) or no endometriosis (n = 4) underwent PET/CT scans with FES. A subset of the animals also underwent PET/CT scans with FFNP. Standard uptake values corrected for body weight (SUVs) were obtained for each radiotracer in target and background tissues (e.g., intestinal). We performed repeated measure analysis of variance tests to determine how uterine and background uptake differed with scan time, phase of the menstrual cycle, and disease state. RESULTS: Abdominopelvic PET/CT could not resolve small, individual endometriotic lesions. However, macaques with endometriosis displayed higher uterine uptake compared to those without the disorder. Radiotracer uptake differed by menstrual cycle phase with increased uterine uptake of both radiotracers in the proliferative phase of the menstrual cycle. Background intestinal uptake of FFNP increased over time after infusion, but only during the proliferative phase. CONCLUSIONS: PET/CT with FES and FFNP support the concept that ER and PR levels are altered in individuals with endometriosis. This highlights the impact of the disease on typical reproductive tract function and may provide a novel pathway for the identification of individuals with endometriosis.

Measuring changes in chest wall motion after lung resection using structured light plethysmography: a feasibility study.

OBJECTIVES: We describe the use of structured light plethysmography (SLP)-a novel, non-contact, light-based technique for measuring tidal breathing-among a cohort of patients undergoing lung resection. In this feasibility study, we examined whether changes in chest wall motion or in asynchrony between regions of the thoraco-abdominal wall could be identified after surgery. METHODS: Fifteen patients underwent wedge resection (n = 8) or lobectomy (n = 7). All patients underwent two SLP assessments (before surgery and on Day 1 post-surgery). Each assessment captured data during 5 min of quiet (tidal) breathing. RESULTS: When data were averaged across all patients, motion on the operated side of the thorax was significantly reduced after surgery (mean change from presurgery ± standard deviation: -14.7 ± 16.5%, P = 0.01), while motion on the non-operated side increased (15.9 ± 18.5%, P = 0.01). Thoraco-abdominal asynchrony also increased (mean change ± standard deviation: 43.4 ± 55.1%, P = 0.01), but no significant difference was observed in right-left hemi-thoracic asynchrony (163.7 ± 230.3%, P = 0.08). When analysed by resection type, lobectomy was associated with reduced and increased motion on the operated and non-operated side, respectively, and with an increase in both right-left hemi-thoracic and thoraco-abdominal asynchrony. No significant changes in motion or asynchrony were identified in patients who underwent wedge resection. CONCLUSIONS: SLP was able to detect changes in chest wall motion and asynchrony after thoracic surgery. Changes in this small group of patients were consistent with the side of the incision and were most apparent in patients undergoing lobectomy.