Increased Systemic C-Reactive Protein Is Associated With Choroidal Thinning in Intermediate Age-Related Macular Degeneration.

Purpose: C-reactive protein (CRP) and decreased choroidal thickness (CT) are risk factors for progression to advanced age-related macular degeneration (AMD). We examined the association between systemic levels of CRP and CT in patients with intermediate AMD (iAMD). Methods: Patients with iAMD in the Colorado AMD Registry were included. Baseline serum samples and multimodal imaging including spectral domain-optical coherence tomography (SD-OCT), fundus photography, and autofluorescence were obtained. Medical and social histories were surveyed. CT was obtained by manual segmentation of OCT images. High-sensitivity CRP levels were quantified in serum samples. Univariate and multivariable linear regression models accounting for the intrasubject correlation of two eyes were fit using log-transformed CT as the outcome. Results: The study included 213 eyes from 107 patients with a mean age of 76.8 years (SD, 6.8). Median CT was 200.5 µm (range, 86.5-447.0). Median CRP was 1.43 mg/L (range, 0.13-17.10). Higher CRP was associated with decreased CT in the univariate model (P = 0.01). Older age and presence of reticular pseudodrusen (RPD) were associated with decreased CT (P < 0.01), whereas gender, body mass index, and smoking were not associated with CT. Higher CRP remained significantly associated with decreased CT after adjustment for age and RPD (P = 0.01). Conclusions: Increased CRP may damage the choroid, leading to choroidal thinning and increased risk of progression to advanced AMD. Alternatively, CRP may be a marker for inflammatory events that mediate ocular disease. The results of this study further strengthen the association between inflammation and AMD. Translational Relevance: Increased CRP is associated with choroidal thinning, a clinical risk factor for AMD.

Chronic Choroidal Neovascular Membrane in Choroideremia Treated With Intravitreal Bevacizumab.

Choroidal neovascular membrane (CNVM) is a rare complication of choroideremia. The authors report a case of a 13-year-old male presenting with metamorphopsia and decreased central vision of 1-year duration. Genetic testing was significant for a pathogenic c.1437dupA mutation in the CHM gene. Fundus biomicroscopy showed a subfoveal membrane; diagnosis of CNVM was substantiated with fluorescein angiography and swept-source optical coherence tomography angiography (SS-OCTA). The patient received six injections of intravitreal bevacizumab during a 13-month period with functional and anatomic improvement. Lesion area on SS-OCTA remained stable. CNVM should be suspected in young patients with choroideremia presenting with acute decrease in central vision. Treatment with anti-vascular endothelial growth factor should be considered even in chronic cases. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e188-e192.].

Global Sensory Impairment Predicts Morbidity and Mortality in Older U.S. Adults.

OBJECTIVES: To evaluate global sensory impairment (GSI, an integrated measure of sensory dysfunction) as a predictor of physical function, cognition, overall health, and mortality. DESIGN: Prospective study. SETTING: The National Social Life, Health, and Aging Project. PARTICIPANTS: A national probability sample of 3,005 home-dwelling older U.S. adults assessed at baseline (2005-06) and 5-year follow-up (2010-11). MEASUREMENTS: Gait speed, activity, disability, cognition, overall health, 5-year mortality. RESULTS: At baseline, older adults with worse GSI were slower (Timed Up and Go times: odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.17-1.50) and had more activity of daily living deficits (≥2: OR = 1.26, 95% CI = 1.10-1.46). Five years later, they were still slower (timed walk: OR = 1.22, 95% CI = 1.05-1.42), had more disabilities (≥2 instrumental activities of daily living; OR = 1.45, 95% CI = 1.23-1.70), were less active (daytime activity according to accelerometry: ß = -2.7, 95% CI = -5.2 to -0.2), had worse cognitive function (Montreal Cognitive Assessment; ß = -0.64, 95% CI = -0.84 to -0.44), more likely to have poorer overall health (OR = 1.16, 95% CI = 1.03-1.31) and lose weight (>10%: OR = 1.31, 95% CI = 1.04-1.64), and have died (OR = 1.45, 95% CI = 1.19-1.76). All analyses were adjusted for relevant confounders at baseline, including age, sex, race and ethnicity, education, smoking, problem drinking, body mass index, comorbidities, and cognitive function. CONCLUSION: GSI predicts impaired physical function, cognitive dysfunction, significant weight loss, and mortality 5 years later in older U.S. adults. Multisensory evaluation may identify vulnerable individuals, offering the opportunity for early intervention to mitigate adverse outcomes.

Global Sensory Impairment in Older Adults in the United States.

OBJECTIVES: To determine whether there may be a common mechanism resulting in global sensory impairment of the five classical senses (vision, smell, hearing, touch, and taste) in older adults. DESIGN: Representative, population-based study. SETTING: National Social Life, Health, and Aging Project. PARTICIPANTS: Community-dwelling U.S. adults aged 57 to 85. MEASUREMENTS: The frequency with which impairment co-occurred across the five senses was estimated as an integrated measure of sensory aging. It was hypothesized that multisensory deficits would be common and reflect global sensory impairment that would largely explain the effects of age, sex, and race on sensory dysfunction. RESULTS: Two-thirds of subjects had two or more sensory deficits, 27% had just one, and 6% had none. Seventy-four percent had impairment in taste, 70% in touch, 22% in smell, 20% in corrected vision, and 18% in corrected hearing. Older adults, men, African Americans, and Hispanics had greater multisensory impairment (all P < .01). Global sensory impairment largely accounted for the effects of age, sex, and race on the likelihood of impairment in each of the five senses. CONCLUSION: Multisensory impairment is prevalent in older U.S. adults. These data support the concept of a common process that underlies sensory aging across the five senses. Clinicians assessing individuals with a sensory deficit should consider further evaluation for additional co-occurring sensory deficits.

Olfactory function in Wave 2 of the National Social Life, Health, and Aging Project.

OBJECTIVE: To investigate the sense of smell, including sensitivity and odor identification, and characterize the U.S. national prevalence of olfactory dysfunction in older adults, thereby facilitating further investigation of the substantial risks for older adults associated with this basic sensory ability. METHOD: The sense of smell was evaluated using the Olfactory Function Field Exam (OFFE), a measure designed specifically for field research, which assesses 3 components of olfaction: sensitivity to n-butanol (a standard testing odorant) and androstadienone (AND, a key social odor produced by humans), as well as the ability to identify odors. Respondents were randomly selected from the National Social Life, Health, and Aging Project Wave 2 sample to receive the OFFE (n = 2,304), and 2,212 consented to participate. RESULTS: In the U.S. population aged 62-90, n-butanol detection ability was significantly worse at older ages (ordinal logistic regression, p < .001); however, there was no difference in detection ability between genders (p = .60). AND detection ability was also significantly worse at older ages (p = .003), but in contrast to n-butanol, women outperformed men (p = .001). As expected, odor identification ability was worse in older people than in younger (p < .001), and women were more accurate than men (p = .001). DISCUSSION: We report for the first time 3 facets of olfactory function and its association with age and gender in a representative sample of U.S. older adults. Future analyses of these data are needed to elucidate the sense of smell's role in physical, social, and mental health with aging.

Sensory function: insights from Wave 2 of the National Social Life, Health, and Aging Project.

OBJECTIVES: Sensory function, a critical component of quality of life, generally declines with age and influences health, physical activity, and social function. Sensory measures collected in Wave 2 of the National Social Life, Health, and Aging Project (NSHAP) survey focused on the personal impact of sensory function in the home environment and included: subjective assessment of vision, hearing, and touch, information on relevant home conditions and social sequelae as well as an improved objective assessment of odor detection. METHOD: Summary data were generated for each sensory category, stratified by age (62-90 years of age) and gender, with a focus on function in the home setting and the social consequences of sensory decrements in each modality. RESULTS: Among both men and women, older age was associated with self-reported impairment of vision, hearing, and pleasantness of light touch. Compared with women, men reported significantly worse hearing and found light touch less appealing. There were no gender differences for vision. Overall, hearing loss seemed to have a greater impact on social function than did visual impairment. DISCUSSION: Sensory function declines across age groups, with notable gender differences for hearing and light touch. Further analysis of sensory measures from NSHAP Wave 2 may provide important information on how sensory declines are related to health, social function, quality of life, morbidity, and mortality in this nationally representative sample of older adults.

Induction of megakaryocyte differentiation drives nuclear accumulation and transcriptional function of MKL1 via actin polymerization and RhoA activation.

How components of the cytoskeleton regulate complex cellular responses is fundamental to understanding cellular function. Megakaryoblast leukemia 1 (MKL1), an activator of serum response factor (SRF) transcriptional activity, promotes muscle, neuron, and megakaryocyte differentiation. In muscle cells, where MKL1 subcellular localization is one mechanism by which cells control SRF activity, MKL1 translocation from the cytoplasm to the nucleus in response to actin polymerization is critical for its function as a transcriptional regulator. MKL1 localization is cell-type specific; it is predominantly cytoplasmic in unstimulated fibroblasts and some muscle cell types and is constitutively nuclear in neuronal cells. In the present study, we report that in megakaryocytes, subcellular localization and regulation of MKL1 is dependent on RhoA activity and actin organization. Induction of megakaryocytic differentiation of human erythroleukemia cells by 12-O-tetradecanoylphorbol-13-acetate and primary megakaryocytes by thrombopoietin promotes MKL1 nuclear localization. This MKL1 localization is blocked by drugs inhibiting RhoA activity or actin polymerization.We also show that nuclear-localized MKL1 activates the transcription of SRF target genes. This report broadens our knowledge of the molecular mechanisms regulating megakaryocyte differentiation.

Optimization of the matrix solid phase dispersion extraction procedure for the analysis of polybrominated diphenyl ethers in human placenta.

Characterization of prenatal exposure to hazardous chemicals most often relies upon the analysis of cord blood. However, human placenta is an appropriate tissue alternative with noteworthy advantages. Owing to analytical challenges, reports on placental levels of toxic chemicals are limited. The purpose of this study was to establish a reliable, cost-effective, and relatively fast and simple method to extract polybrominated diphenyl ethers (PBDEs) from human placenta for analysis using gas chromatography coupled with mass spectrometry (GC/MS). The matrix solid phase dispersion (MSPD) method was optimized for the extraction and analysis of 43 PBDEs (including BDE209) from human placenta samples. Different sorbents, sample conditions, grinding methods, elution solvents, and single and repeated extractions were compared for their effects on the extraction efficiency. The performance of the optimized method was validated by analyzing spiked placenta samples and a standard reference material of fish tissue. Congener specific PBDE recovery ranged from 91% to 114% for the spiked samples and 89% to 115% for a standard reference material (SRM) of fish tissue. The optimized MSPD procedure was compared with two conventional extraction methods. The extraction efficiency of MSPD was found to be comparable with that of the traditional Soxhlet method and superior to that using a liquid extraction method. Twenty two PBDEs were detected in all of the five samples collected in Chicago in 2008. This is the first description of PBDEs detected in human placentas in the U.S.