PARACENTRAL ACUTE MIDDLE MACULOPATHY IN PURTSCHER RETINOPATHY.

PubMed

Rivera-De La Parra, David; Fromow-Guerra, Jans

2017-12-27

To describe paracentral acute middle maculopathy associated with Purtscher retinopathy, particularly in Purtscher flecken lesions as a retinal complication in a case secondary to fractures of long bones. Case report. A 16-year-old boy with bilateral paracentral scotomata presented with bilateral paracentral acute middle maculopathy as part of Purtscher retinopathy in both eyes as consequence of tibia and fibula fractures. Paracentral acute middle maculopathy is one of the optical coherence tomography findings in Purtscher retinopathy.

[The Influence of risk factors on visual performance in of phototoxic maculopathy in occupational welders].

PubMed

Li, Qingtao; Zhang, Xinfang

2014-10-01

To investigate the Influence of risk factors that cause the phototoxic maculopathy by welding arc in occupational welders. We examined randomly a group of 86 male occupational welders 172 eyes from some local metal manufacturing enterprise from August 2010 to December 2013. The ophthalmologic examination which the participants underwent thorough including the best visual acuity, fundus examination by the supplementary lens, fundus photography, and the high definition optical coherence tomography (OCT) scan. All participants of this study underwent thorough the medicine examined by a specialist of occupational who prior to the OCT. All the subjects were divided into groups according to age, protection degrees , length of service, operating time . The incidences of phototoxic maculopathy were compared within groups. The subjects was divided randomly into the lutein group and the placebo group. The examination including the best visual acuity, serum lutein concentrations, macular pigmentoptical density (MPOD), Contrast and glare Sensitivity. (1) The total incidence of phototoxic maculopathy is 32.0%. (2) The incidences of phototoxic maculopathy in the strict protection group, the randomed protective group and the nonprofessional protection group were respectively 21.4%, 36.7%, 53.6%. The incidence in the strict protection group was lower than the other two groups, the incidence was the highest in the nonprofessional protection group, and the difference was statistically significant. (3) The longer length of service, and operating time , the more incidence of phototoxic maculopathy develop. (4) The lutein group prior to the placebo group at the best visual acuity, serum lutein concentrations, macular pigmentoptical density (MPOD), Contrast and glare Sensitivity. The risk factors of phototoxic maculopathy in male occupational welders are the length of service, operating time, protection degrees and the lutein assistantly. The incidence of phototoxic maculopathy occurs

Are Long-Term Chloroquine or Hydroxychloroquine Users Being Checked Regularly for Toxic Maculopathy?

PubMed Central

Nika, Melisa; Blachley, Taylor S.; Edwards, Paul; Lee, Paul P.; Stein, Joshua D.

2014-01-01

likelihood of regular eye care (adjusted OR=1.77, CI=1.27-2.47), relative to other patients. Conclusions and Relevance In this insured population, many patients at high risk for HCQ/CQ-associated maculopathy are not undergoing routine monitoring for this serious side effect. Future studies should explore factors contributing to suboptimal adherence to expert guidelines and the potential impact on patients' vision-related outcomes. PMID:24970348

Regular examinations for toxic maculopathy in long-term chloroquine or hydroxychloroquine users.

PubMed

Nika, Melisa; Blachley, Taylor S; Edwards, Paul; Lee, Paul P; Stein, Joshua D

2014-10-01

.4% increased likelihood of regular eye care (adjusted odds ratio, 1.77; 95% CI, 1.27-2.47) relative to other patients. In this insured population, many patients at high risk for maculopathy associated with the use of chloroquine or hydroxychloroquine are not undergoing routine monitoring for this serious adverse effect. Future studies should explore factors contributing to suboptimal adherence to expert guidelines and the potential effect on patients' vision-related outcomes.

Glutathione maintenance mitigates age-related susceptibility to redox cycling agents.

PubMed

Thomas, Nicholas O; Shay, Kate P; Kelley, Amanda R; Butler, Judy A; Hagen, Tory M

2016-12-01

Isolated hepatocytes from young (4-6mo) and old (24-26mo) F344 rats were exposed to increasing concentrations of menadione, a vitamin K derivative and redox cycling agent, to determine whether the age-related decline in Nrf2-mediated detoxification defenses resulted in heightened susceptibility to xenobiotic insult. An LC 50 for each age group was established, which showed that aging resulted in a nearly 2-fold increase in susceptibility to menadione (LC 50 for young: 405μM; LC 50 for old: 275μM). Examination of the known Nrf2-regulated pathways associated with menadione detoxification revealed, surprisingly, that NAD(P)H: quinone oxido-reductase 1 (NQO1) protein levels and activity were induced 9-fold and 4-fold with age, respectively (p=0.0019 and p=0.018; N=3), but glutathione peroxidase 4 (GPX4) declined by 70% (p=0.0043; N=3). These results indicate toxicity may stem from vulnerability to lipid peroxidation instead of inadequate reduction of menadione semi-quinone. Lipid peroxidation was 2-fold higher, and GSH declined by a 3-fold greater margin in old versus young rat cells given 300µM menadione (p<0.05 and p≤0.01 respectively; N=3). We therefore provided 400µMN-acetyl-cysteine (NAC) to hepatocytes from old rats before menadione exposure to alleviate limits in cysteine substrate availability for GSH synthesis during challenge. NAC pretreatment resulted in a >2-fold reduction in cell death, suggesting that the age-related increase in menadione susceptibility likely stems from attenuated GSH-dependent defenses. This data identifies cellular targets for intervention in order to limit age-related toxicological insults to menadione and potentially other redox cycling compounds. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

[Multifocal Electroretinography in Patients with Poppers Maculopathy].

PubMed

Pahlitzsch, Milena; Salchow, Daniel; Rossel, Mirjam; Bergholz, Richard

2017-10-12

Background Maculopathy is a potential side effect of amyl nitrite or "poppers" abuse. It is characterized by a sudden, painless decrease in visual acuity. While the funduscopic changes are subtle, optical coherence tomography shows alterations of the outer retinal layers in the fovea. However, the extent of retinal dysfunction remains poorly understood. Materials/Methods We compared the multifocal electroretinogram of 6 patients with poppers maculopathy to that of a control group consisting of 6 healthy subjects. Response densities and implicit times of N1 and P1 were analyzed. Results Response densities and implicit times of both N1 and P1 were lower in the patients with poppers maculopathy than in the control group, particularly in ring 1 and rings 4 and 5. The only statistically significant finding, however, was a reduced N1 response density of one hexagon in the patient group. No significant differences were found considering the sum response or the averaged rings 1 to 5. Conclusion Compared to a healthy control group, the multifocal electroretinogram of patients with poppers maculopathy shows no relevant impairment. This contrasts the marked effect of the disease on visual acuity. In clinical practice, poppers maculopathy cannot be diagnosed by multifocal electroretinography. Georg Thieme Verlag KG Stuttgart · New York.

Pigmentary maculopathy in a patient with Wolfram syndrome.

PubMed

Dhalla, Mandeep S; Desai, Uday R; Zuckerbrod, Daniel S

2006-02-01

We describe a rare association of pigmentary maculopathy with Wolfram syndrome not previously reported in the literature. A 12-year-old boy presented to the retina service with a diagnosis of Wolfram syndrome and a history of poor central vision. The patient was found to have bilateral atrophic pigmentary maculopathy that was confirmed with fluorescein angiography. Wolfram syndrome may present with a pigmentary maculopathy and this rare finding may assist the clinician in making appropriate genetic referral when this diagnosis is suspected.

Adaptive Optics Imaging in Laser Pointer Maculopathy.

PubMed

Sheyman, Alan T; Nesper, Peter L; Fawzi, Amani A; Jampol, Lee M

2016-08-01

The authors report multimodal imaging including adaptive optics scanning laser ophthalmoscopy (AOSLO) (Apaeros retinal image system AOSLO prototype; Boston Micromachines Corporation, Boston, MA) in a case of previously diagnosed unilateral acute idiopathic maculopathy (UAIM) that demonstrated features of laser pointer maculopathy. The authors also show the adaptive optics images of a laser pointer maculopathy case previously reported. A 15-year-old girl was referred for the evaluation of a maculopathy suspected to be UAIM. The authors reviewed the patient's history and obtained fluorescein angiography, autofluorescence, optical coherence tomography, infrared reflectance, and AOSLO. The time course of disease and clinical examination did not fit with UAIM, but the linear pattern of lesions was suspicious for self-inflicted laser pointer injury. This was confirmed on subsequent questioning of the patient. The presence of linear lesions in the macula that are best highlighted with multimodal imaging techniques should alert the physician to the possibility of laser pointer injury. AOSLO further characterizes photoreceptor damage in this condition. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:782-785.]. Copyright 2016, SLACK Incorporated.

An age-related change in susceptibility of rat brain to encephalomyocarditis virus infection

PubMed Central

IKEGAMI, HISASHI; TAKEDA, MAKIO; DOI, KUNIO

1997-01-01

Rats were inoculated intraperitoneally (i.p.) or intracerebrally (i.c.) with 1 × 104 plaque forming units (PFU)/animal of the D variant of encephalomyocarditis virus (EMC-D) at 2, 4, 7, 14, 28 or 56 days of age for virological and histopathological examination. In the i.p.-inoculation study, neither viral replication nor lesions were detected in the animals inoculated at 28 and 56 days of age. In the animals inoculated when younger than 14 days of age, lesions were restricted to the brain although viral replication was detected in the brain, heart and pancreas. The brain lesions were characterized by acute meningoencephalitis with neuronal necrosis in the cerebral cortex, hippocampus and thalamus, and viral RNA was detected in degenerated and/or intact neurons. In the i.c.-inoculation study, similar age-related changes in susceptibility of rat brain to EMC-D infection were observed, but a minor difference was that viral replication and lesions were still detected in the hippocampus of some animals inoculated at 28 days of age. These results suggest that an age-related decrease in the susceptibility of rat brain to EMC virus infection may reflect an age-related change in the susceptibility of neurons themselves as well as in maturation of the immune system. PMID:9203984

PREDICTIVE FACTORS OF SURGICAL OUTCOMES IN VITRECTOMY FOR MYOPIC TRACTION MACULOPATHY.

PubMed

Hattori, Kyoko; Kataoka, Keiko; Takeuchi, Jun; Ito, Yasuki; Terasaki, Hiroko

2017-11-07

To assess predictive factors and surgical outcomes for myopic traction maculopathy. This retrospective observational case study enrolled 73 patients who underwent vitrectomy for myopic traction maculopathy. The 79 eyes obtained from our study sample were divided into 4 types: retinoschisis, lamellar macular hole (lamellar MH), foveal retinal detachment (FRD), and FRD + lamellar MH, or into 2 types according to the presence of FRD preoperatively. Dependent variables of interest were age, sex, pre- and postoperative best-corrected visual acuity (BCVA) at 6 months, and axial length. All the four types showed moderately strong-to-strong positive correlations with pre- and postoperative BCVA (retinochisisi: r = 0.61; lamellar MH: r = 0.62; FRD: r = 0.51; FRD + lamellar MH; r = 0.83). Preoperative BCVA was associated with postoperative BCVA (P < 0.0001), but age, axial length, and the types of preoperative foveal status were not. Eyes with FRD had significantly worse pre- and postoperative BCVA than eyes without FRD (P = 0.036 and P = 0.046, respectively). Postoperative full-thickness macular holes developed in 5.1% of cases and in all types but retinoschisis. Preoperative visual acuity and the presence of FRD should be considered for surgical indication of myopic traction maculopathy.

AGE-RELATED SUSCEPTIBILITY: A GENOMICS APPROACH.

EPA Science Inventory

By the year 2030 more than 70 million Americans will be over the age of 65. These older adults are a subpopulation that may have special susceptibility to toxic insult due to critical characteristics of their life-stage. Current EPA testing guidelines do not identify the elderl...

Quantifying risk over the life course - latency, age-related susceptibility, and other time-varying exposure metrics.

PubMed

Wang, Molin; Liao, Xiaomei; Laden, Francine; Spiegelman, Donna

2016-06-15

Identification of the latency period and age-related susceptibility, if any, is an important aspect of assessing risks of environmental, nutritional, and occupational exposures. We consider estimation and inference for latency and age-related susceptibility in relative risk and excess risk models. We focus on likelihood-based methods for point and interval estimation of the latency period and age-related windows of susceptibility coupled with several commonly considered exposure metrics. The method is illustrated in a study of the timing of the effects of constituents of air pollution on mortality in the Nurses' Health Study. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Paracentral acute middle maculopathy in nonischemic central retinal vein occlusion.

PubMed

Rahimy, Ehsan; Sarraf, David; Dollin, Michael L; Pitcher, John D; Ho, Allen C

2014-08-01

To better characterize a novel spectral-domain optical coherence tomography (OCT) presentation, termed paracentral acute middle maculopathy, to describe this finding in patients with nonischemic central retinal vein occlusion (CRVO), and to support a proposed pathogenesis of intermediate and deep retinal capillary ischemia. Retrospective observational case series. Clinical histories, high-resolution digital color imaging, red-free photography, fluorescein angiography, near-infrared reflectance, and spectral-domain OCT images of 484 patients with acute CRVO from 2 centers were evaluated for the presence of coexisting paracentral acute middle maculopathy. Of 484 patients diagnosed with CRVO, 25 (5.2%) demonstrated evidence of concurrent paracentral acute middle maculopathy. Patients averaged 51 years of age and presented with complaints of paracentral scotomas. All patients demonstrated hyper-reflective plaquelike lesions at the level of the inner nuclear layer by spectral-domain OCT and showed corresponding dark-gray lesions on near-infrared reflectance and perivenular deep retinal whitening on color fundus photography. There was no fluorescein angiographic correlate to these lesions. On follow-up spectral-domain OCT imaging, the lesions had resolved into areas of inner nuclear layer atrophy with persistence of scotomas. Paracentral acute middle maculopathy refers to characteristic hyper-reflective spectral-domain OCT lesions involving the middle layers of the retina at the level of the inner nuclear layer that may develop in response to ischemia of the intermediate and deep capillary plexuses. This series is the largest to describe this spectral-domain OCT finding to date, and it is the first to associate it with nonischemic CRVO. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantifying Risk Over the Life Course – Latency, Age-Related Susceptibility, and Other Time-Varying Exposure Metrics

PubMed Central

Wang, Molin; Liao, Xiaomei; Laden, Francine; Spiegelman, Donna

2016-01-01

Identification of the latency period and age-related susceptibility, if any, is an important aspect of assessing risks of environmental, nutritional and occupational exposures. We consider estimation and inference for latency and age-related susceptibility in relative risk and excess risk models. We focus on likelihood-based methods for point and interval estimation of the latency period and age-related windows of susceptibility coupled with several commonly considered exposure metrics. The method is illustrated in a study of the timing of the effects of constituents of air pollution on mortality in the Nurses’ Health Study. PMID:26750582

Uveitic crystalline maculopathy.

PubMed

Or, Chris; Kirker, Andrew W; Forooghian, Farzin

2015-01-01

The purpose of this case report is to present a novel cause of crystalline maculopathy. A 52-year-old Japanese female presented with a 4-month history of decreased vision in the left eye. Best corrected visual acuity in the left eye was 20/40. Dilated fundus examination of the right eye was unremarkable, but that of the left eye demonstrated foveal yellow-green intraretinal crystals and mild vitritis. Optical coherence tomography of the left eye revealed small intraretinal fluid cysts and intraretinal crystals. Ultra-widefield fluorescein angiography was normal in the right eye, but that of the left eye demonstrated features of intermediate uveitis. There was no history or findings to suggest any cause for the crystals other than the uveitis. We propose that this may represent a novel category of crystalline retinopathy, termed uveitic crystalline maculopathy. We hypothesize that breakdown of the blood-retinal barrier as seen in uveitis may contribute to the deposition of crystals in the macula, although the precise composition of the crystals is unknown.

Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Fisher, Diana E; Klein, Barbara E K; Wong, Tien Y; Rotter, Jerome I; Li, Xiaohui; Shrager, Sandi; Burke, Gregory L; Klein, Ronald; Cotch, Mary Frances

2016-06-01

To describe the incidence of age-related macular degeneration (AMD) and associated risk factors in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) residing in the United States. Prospective cohort study. A total of 3811 participants, aged 46 to 86 years, from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, with retinal data collected twice, on average, 8 years apart. Fundus images, taken using a digital camera through dark-adapted pupils using a standard protocol and the same equipment at both study visits, were graded centrally for early and late AMD on the basis of drusen size, type and area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Demographic, clinical, and laboratory measures were included in multivariable regression models to determine their impact on the variation in AMD incidence among racial/ethnic groups. Incident early and late AMD. The overall 8-year age- and sex-standardized incidence of early and late AMD were 4.1% and 2.3%, respectively, with incidence of early and late AMD highest in whites (5.3% and 4.1%, respectively), intermediate in Chinese (4.5% and 2.2%, respectively) and Hispanics (3.3% and 0.8%, respectively), and lowest in blacks (1.6% and 0.4%, respectively). By adjusting for age and sex, blacks had a 70% lower risk of developing early AMD than whites, and this decreased only slightly to a 67% lower risk after multivariable adjustment. By adjusting for age, sex, and race/ethnicity, hyperopia was associated with early AMD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.20), as was astigmatism (OR, 1.47; 95% CI, 1.00-2.16), but not myopia (P = 0.29). Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with

Hemisphere, gender and age-related effects on iron deposition in deep gray matter revealed by quantitative susceptibility mapping.

PubMed

Gong, Nan-Jie; Wong, Chun-Sing; Hui, Edward S; Chan, Chun-Chung; Leung, Lam-Ming

2015-10-01

The purpose of this work was to investigate the effects of hemispheric location, gender and age on susceptibility value, as well as the association between susceptibility value and diffusional metrics, in deep gray matter. Iron content was estimated in vivo using quantitative susceptibility mapping. Microstructure was probed using diffusional kurtosis imaging. Regional susceptibility and diffusional metrics were measured for the putamen, caudate nucleus, globus pallidus, thalamus, substantia nigra and red nucleus in 42 healthy adults (age range 25-78 years). Susceptibility value was significantly higher in the left than the right side of the caudate nucleus (P = 0.043) and substantia nigra (P < 0.001). Women exhibited lower susceptibility values than men in the thalamus (P < 0.001) and red nucleus (P = 0.032). Significant age-related increases of susceptibility were observed in the putamen (P < 0.001), red nucleus (P < 0.001), substantia nigra (P = 0.004), caudate nucleus (P < 0.001) and globus pallidus (P = 0.017). The putamen exhibited the highest rate of iron accumulation with aging (slope of linear regression = 0.73 × 10(-3) ppm/year), which was nearly twice those in substantia nigra (slope = 0.40 × 10(-3) ppm/year) and caudate nucleus (slope = 0.39 × 10(-3) ppm/year). Significant positive correlations between the susceptibility value and diffusion measurements were observed for fractional anisotropy (P = 0.045) and mean kurtosis (P = 0.048) in the putamen without controlling for age. Neither correlation was significant after controlling for age. Hemisphere, gender and age-related differences in iron measurements were observed in deep gray matter. Notably, the putamen exhibited the highest rate of increase in susceptibility with aging. Correlations between susceptibility value and microstructural measurements were inconclusive. These findings could provide new clues for unveiling mechanisms underlying iron-related neurodegenerative diseases. Copyright �

Poppers Maculopathy: Complete Restitution of Macular Changes in OCT after Drug Abstinence.

PubMed

Pahlitzsch, Milena; Mai, Christian; Joussen, Antonia M; Bergholz, Richard

2016-01-01

"Poppers" is a slang term for a group of alkyl nitrites that are used as recreational drugs. Their inhalative intoxication leads to muscle relaxation, analgesia, and euphoria. Maculopathy is a rare but serious side-effect. Clinical, imaging, and electrophysiological findings of seven patients with maculopathy after consumption of poppers were presented. All seven patients were male with a median age of 35 years (range 28-45 years), the median duration of periodical poppers use until the onset of symptoms was 9.8 years (one day to 25 years). Five of seven patients were HIV-positive, one patient was negative, and the HIV-status of one patient was unknown. Median average of visual acuity at presentation was 20/30 in each eye. In all patients, optical coherence tomography (OCT) showed pathognomonic alterations of the outer foveal retina. One patient showed an almost complete restitution of the maculopathy six months after cessation of drug use and following the oral intake of Lutein. Imaging alterations returned to normal and visual acuity recovered from 20/50 and 20/30 (right and left eye, respectively) to 20/20 on both eyes. Follow up of two other cases showed no relevant functional decline or improvement. Toxic maculopathy due to the consumption of poppers is an important differential diagnosis in acute visual loss without clinico-morphological correlate. Optical coherence tomography is the only reliable diagnostic tool in these cases. Complete recovery of visual function and macular morphology is rare, even after cessation of drug abuse. Oral lutein therapy may have a beneficial effect.

Pediatric Bilateral Blue Laser Pointer-Induced Maculopathy

PubMed Central

Raevis, Joseph; Shrier, Eric

2017-01-01

Background We report the first case of pediatric bilateral blue laser pointer maculopathy with complete resolution of visual symptoms. Case A 12-year-old boy presented with bilateral decreased visual acuity and central scotomata after blue laser pointer exposure. He was treated with a Medrol Dosepak and topical nonsteroidal anti-inflammatory drug (NSAID), with gradual visual acuity improved from 20/40 OU to 20/20 OU over 22 weeks, but with persistent evidence of outer retinal layer disruption from the external limiting membrane to the interdigitation zone. Conclusion Oral steroids and topical NSAIDs may be effective in improving visual outcomes in laser pointer maculopathy in the pediatric population. PMID:28611647

Incidence and evolution of subretinal precipitates in optic disc pit maculopathy.

PubMed

Chatziralli, Irini; Theodossiadis, George; Brouzas, Dimitrios; Theodossiadis, Panagiotis

2017-06-26

To study the evolution of subretinal precipitates coexistent with optic disc pit (ODP) maculopathy from their appearance at baseline examination until their absorption after successful treatment. Participants in this retrospective, multicenter study were 42 patients with ODP maculopathy, in whom complete ocular examination was performed, including visual acuity (VA) measurement, slit-lamp examination, color or red-free fundus photography, and optical coherence tomography at baseline after surgical treatment. Out of 42 cases, 17 (40.5%) cases of ODP maculopathy, which were examined between 2002 and 2015, were found to have subretinal precipitates associated with multilayer fluid accumulation at baseline. Precipitates were located at the outer part of the photoreceptor layer and remained for 3-6 months after successful treatment and absorption of subretinal fluid. The mean VA was 0.99 ± 0.21 logMAR at baseline and improved to 0.54 ± 0.25 logMAR at the final examination. Macular precipitates in association with signs of disease chronicity, such as multilayer fluid accumulation, became evident at baseline examination. Precipitates' disappearance in 15 out of 17 cases coincided with the absorption of subretinal fluid. The relative low VA at baseline probably could be attributed to the chronicity of the disease.

Automatic screening and classification of diabetic retinopathy and maculopathy using fuzzy image processing.

PubMed

Rahim, Sarni Suhaila; Palade, Vasile; Shuttleworth, James; Jayne, Chrisina

2016-12-01

Digital retinal imaging is a challenging screening method for which effective, robust and cost-effective approaches are still to be developed. Regular screening for diabetic retinopathy and diabetic maculopathy diseases is necessary in order to identify the group at risk of visual impairment. This paper presents a novel automatic detection of diabetic retinopathy and maculopathy in eye fundus images by employing fuzzy image processing techniques. The paper first introduces the existing systems for diabetic retinopathy screening, with an emphasis on the maculopathy detection methods. The proposed medical decision support system consists of four parts, namely: image acquisition, image preprocessing including four retinal structures localisation, feature extraction and the classification of diabetic retinopathy and maculopathy. A combination of fuzzy image processing techniques, the Circular Hough Transform and several feature extraction methods are implemented in the proposed system. The paper also presents a novel technique for the macula region localisation in order to detect the maculopathy. In addition to the proposed detection system, the paper highlights a novel online dataset and it presents the dataset collection, the expert diagnosis process and the advantages of our online database compared to other public eye fundus image databases for diabetic retinopathy purposes.

Screening in Primary Care for Diabetic Retinopathy, Maculopathy and Visual Loss in South Africa.

PubMed

Webb, Elizabeth M; Rheeder, Paul; Roux, Polla

2016-01-01

The aim of the study was to determine the prevalence of diabetic retinopathy, maculopathy and visual loss in primary care patients and to identify associated risk factors. We conducted a cluster randomised trial at primary care clinics in the Tshwane district in South Africa. Grades of retinopathy and maculopathy (with fundus camera) and visual acuity (Snellen chart) were assessed and, using mobile screening and teleophthalmology, clinical and biochemical testing was conducted to obtain information about glycaemic control and microvascular complications. The prevalence rates for any retinopathy, preproliferative retinopathy and proliferative retinopathy were 24.9, 19.5 and 5.5%, respectively. The prevalence rates of diabetic maculopathy, observable maculopathy and referable maculopathy were 20.8, 11.8 and 9.0%, respectively. The presence of retinopathy was associated with high body mass index, systolic blood pressure, being on insulin treatment, high HbA1c and the presence of neuropathy. High systolic blood pressure, being on insulin treatment, high HbA1c level and high low-density lipoprotein cholesterol level as well as the presence of albuminuria were significant in predicting any diabetic maculopathy. Laser photocoagulation was given to 8.3% of patients from the mobile unit and 12% of patients were referred to the nearest hospital with an outpatient eye clinic for follow-up treatment of various other eye conditions. Using the WHO categories, the study found that 78.1% of diabetes patients had normal vision, 19.3% were visually impaired and 2.2% were severely impaired or blind. High prevalence rates for diabetic retinopathy, maculopathy and visual loss were found and associations were identified. © 2016 S. Karger AG, Basel.

Next-generation sequencing analysis of the ARMS2 gene in Turkish exudative age-related macular degeneration patients.

PubMed

Bardak, H; Gunay, M; Ercalik, Y; Bardak, Y; Ozbas, H; Bagci, O

2017-01-23

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. It is a complex disease with both genetic and environmental risk factors. To improve clinical management of this condition, it is important to develop risk assessment and prevention strategies for environmental influences, and establish a more effective treatment approach. The aim of the present study was to investigate age-related maculopathy susceptibility protein 2 (ARMS2) gene sequences among Turkish patients with exudative AMD. In addition to 39 advanced exudative AMD patients, 250 healthy individuals for whom exome sequencing data were available were included as a control group. Patients with a history of known environmental and systemic AMD risk factors were excluded. Genomic DNA was isolated from peripheral blood and analyzed using next-generation sequencing. All coding exons of the ARMS2 gene were assessed. Three different ARMS2 sequence variations (rs10490923, rs2736911, and rs10490924) were identified in both the patient and control group. Within the control group, two further ARMS2 gene variants (rs7088128 and rs36213074) were also detected. Logistic regression analysis revealed a relationship between the rs10490924 polymorphism and AMD in the Turkish population.

An effective fovea detection and automatic assessment of diabetic maculopathy in color fundus images.

PubMed

Medhi, Jyoti Prakash; Dandapat, Samarendra

2016-07-01

Prolonged diabetes causes severe damage to the vision through leakage of blood and blood constituents over the retina. The effect of the leakage becomes more threatening when these abnormalities involve the macula. This condition is known as diabetic maculopathy and it leads to blindness, if not treated in time. Early detection and proper diagnosis can help in preventing this irreversible damage. To achieve this, the possible way is to perform retinal screening at regular intervals. But the ratio of ophthalmologists to patients is very small and the process of evaluation is time consuming. Here, the automatic methods for analyzing retinal/fundus images prove handy and help the ophthalmologists to screen at a faster rate. Motivated from this aspect, an automated method for detection and analysis of diabetic maculopathy is proposed in this work. The method is implemented in two stages. The first stage involves preprocessing required for preparing the image for further analysis. During this stage the input image is enhanced and the optic disc is masked to avoid false detection during bright lesion identification. The second stage is maculopathy detection and its analysis. Here, the retinal lesions including microaneurysms, hemorrhages and exudates are identified by processing the green and hue plane color images. The macula and the fovea locations are determined using intensity property of processed red plane image. Different circular regions are thereafter marked in the neighborhood of the macula. The presence of lesions in these regions is identified to confirm positive maculopathy. Later, the information is used for evaluating its severity. The principal advantage of the proposed algorithm is, utilization of the relation of blood vessels with optic disc and macula, which enhances the detection process. Proper usage of various color plane information sequentially enables the algorithm to perform better. The method is tested on various publicly available databases

Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss.

PubMed

Bonafede, Lucas; Ficicioglu, Can H; Serrano, Leona; Han, Grace; Morgan, Jessica I W; Mills, Monte D; Forbes, Brian J; Davidson, Stefanie L; Binenbaum, Gil; Kaplan, Paige B; Nichols, Charles W; Verloo, Patrick; Leroy, Bart P; Maguire, Albert M; Aleman, Tomas S

2015-12-01

To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC.

Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

PubMed Central

Bonafede, Lucas; Ficicioglu, Can H.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Mills, Monte D.; Forbes, Brian J.; Davidson, Stefanie L.; Binenbaum, Gil; Kaplan, Paige B.; Nichols, Charles W.; Verloo, Patrick; Leroy, Bart P.; Maguire, Albert M.; Aleman, Tomas S.

2015-01-01

Purpose To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Methods Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Results Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Conclusions Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC. PMID:26658511

A RESCUE THERAPY FOR PERSISTENT OPTIC DISK PIT MACULOPATHY IN PREVIOUSLY VITRECTOMIZED EYES.

PubMed

Figueroa, Marta S; Nadal, Jeroni; Contreras, Inés

2018-01-01

To report the results of vitrectomy with platelet-rich plasma (PRP) application and gas tamponade as a rescue therapy in previously vitrectomized eyes with optic disk pit (ODP) maculopathy. Three patients with visual loss due to persistent or recurrent ODP maculopathy who had undergone previous vitrectomy were offered application of PRP. Platelet-rich plasma was obtained by centrifugation of a blood sample from each patient. Surgery consisted of vitrectomy and internal limiting membrane peeling if the membrane had not been already removed (in two eyes). After fluid/air exchange, three drops of PRP were applied on the ODP followed by 8% C3F8 tamponade. Immediately after surgery, the patient remained supine for 30 minutes and then kept a face-down position for 2 weeks. Optic disk pit maculopathy improved as soon as two weeks after surgery and resolved in all eyes between six and eight months after PRP application. Patients were followed up for three years, with no recurrences. Visual acuity remained stable in one eye and improved in two eyes. Vitrectomy with PRP application may be useful as a rescue therapy in patients with refractory ODP maculopathy. Platelet-rich plasma may act by promoting the closure of the communication between the vitreous and the intraretinal/subretinal space at the pit. This treatment may avoid potentially harmful maneuvers that have been used to treat ODP maculopathy.

Epidemiology of diabetic retinopathy and maculopathy in Africa: a systematic review

PubMed Central

Burgess, P I; MacCormick, I J C; Harding, S P; Bastawrous, A; Beare, N A V; Garner, P

2013-01-01

Abstract Aim To summarize findings from studies reporting the prevalence and incidence of diabetic retinopathy and diabetic maculopathy in African countries in light of the rising prevalence of diabetes mellitus. Methods Using a predefined search strategy, we systematically searched MEDLINE, EMBASE, Science Citation index and Conference Proceedings Citation index, African Index Medicus and the grey literature database ‘OpenSIGLE’ for studies published between January 1990 and February 2011. Included studies reported prevalence or incidence of diabetic retinopathy or diabetic maculopathy of subjects with diabetes resident in African countries. Results Sixty-two studies from 21 countries were included: three population-based surveys; two cohort studies; five case–control studies; 32 diabetes clinic-based, nine eye clinic-based and 11 other hospital-based surveys. Included studies varied considerably in terms of patient selection, method of assessing the eye and retinopathy classification. In population-based studies, the reported prevalence range in patients with diabetes for diabetic retinopathy was 30.2 to 31.6%, proliferative diabetic retinopathy 0.9 to 1.3%, and any maculopathy 1.2 to 4.5%. In diabetes clinic-based surveys, the reported prevalence range for diabetic retinopathy was 7.0 to 62.4%, proliferative diabetic retinopathy 0 to 6.9%, and any maculopathy 1.2 to 31.1%. No obvious association between prevalence and income level of the country was detected. Conclusions Large, community-based cross-sectional and cohort studies are needed to investigate rates and determinants of prevalence of diabetic retinopathy, incidence and progression in Africa. Consensus is needed on the most appropriate methods of identification and classification of retinopathy for research and clinical practice. Estimates of prevalence of diabetic retinopathy, proliferative diabetic retinopathy and maculopathy are comparable with recent European and American studies. PMID:22817387

Micropulse laser for persistent optic disc pit maculopathy. A case report.

PubMed

Valdés-Lara, Carlos Andrés; Crim, Nicolás; García-Aguirre, Gerardo; Lule, Ismael Ávila; Morales-Cantón, Virgilio

2018-06-01

Optic disc pits (ODP) are rare and congenital anomalies of the optic disc, sometimes remaining asymptomatic. However, serous macular detachment or optic disc maculopathy is the most common complication, causing significant visual deterioration, without a current consensus about treatment. We describe a case of ODP maculopathy that was treated successfully with micropulse laser. A patient with ODP maculopathy remained with macular serous detachment after nine months of follow up after pars plana vitrectomy. Subthreshold micropulse laser was used to treat macular serous detachment, achieving a significant improvement in central macular thickness after one session. Subthreshold micropulse laser is designed to stimulate the retinal pigment epithelium without damage to the photoreceptors, resulting in absorption of subretinal and intraretinal fluid. Macular serous detachment in patients with ODP requires a prompt diagnosis and treatment to avoid damage to photoreceptors. Subthreshold micropulse laser is a potential treatment for eyes with ODP and macular serous detachment complication.

Reversible bull's-eye maculopathy associated with intravitreal fomivirsen therapy for cytomegalovirus retinitis.

PubMed

Stone, T W; Jaffe, G J

2000-08-01

To report two cases in which a bull's eye maculopathy developed after intravitreal injection of fomivirsen. Case reports. A 50-year-old man with acquired immunodeficiency syndrome (AIDS) and refractory cytomegalovirus retinitis developed bull's-eye pigmentary changes in the macula of the right eye after initiating therapy with fomivirsen (Vitravene; CIBA Vision, Atlanta, Georgia) intravitreal injections. These pigmentary changes resolved upon cessation of treatment. A 36-year-old man with AIDS and refractory bilateral cytomegalovirus retinitis developed bull's-eye pigmentary changes in both eyes during bilateral intravitreal treatment with fomivirsen. Vision was not affected. These changes resolved after treatment with fomivirsen was stopped. Fomivirsen, a new medication for the treatment of refractory cytomegalovirus retinitis, may cause a bull's-eye maculopathy in some patients. The bull's-eye maculopathy is reversible and does not appear to affect vision.

Operating microscope light-induced phototoxic maculopathy after transscleral sutured posterior chamber intraocular lens implantation.

PubMed

Kweon, Eui Yong; Ahn, Min; Lee, Dong Wook; You, In Cheon; Kim, Min Jung; Cho, Nam Chun

2009-01-01

The purpose of this study is to report the features of operating microscope light-induced retinal phototoxic maculopathy after transscleral sutured posterior chamber intraocular lens (TSS PC-IOL) implantation. The charts of 118 patients who underwent TSS PC-IOL implantation surgery at Chonbuk National University Hospital (Jeonju, Korea) between March 1999 and February 2008 were retrospectively reviewed. Fourteen patients underwent combined 3-port pars plana vitrectomy and TSS PC-IOL implantation (vitrectomy group), and 104 patients underwent TSS PC-IOL implantation only (nonvitrectomy group). All surgeries were performed under the same coaxial illuminated microscope. All diagnoses were confirmed through careful fundus examination and fluorescein angiography (FA). Diagnoses of retinal phototoxic maculopathy were established in 10 (8.47%) of 118 TSS PC-IOL implantation cases. Phototoxic maculopathy occurred more frequently in the vitrectomy group than in the nonvitrectomy group (6/14 versus 4/104, respectively; P < 0.001, chi-square = 24.21). Affected patients reported decreased vision and were found to have coarse alterations of the retinal pigment epithelium (RPE). In 5 of the phototoxic maculopathy cases (50%), the visual acuity was 20/200 or worse. Operating microscope light-induced retinal phototoxic maculopathy can occur more frequently after TSS PC-IOL implantation than after casual cataract surgery, especially when TSS PC-IOL is combined with vitrectomy surgery. Surgeons should take precautions to prevent retinal phototoxicity after TSS PC-IOL implantation and vitrectomy.

PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH RETINAL ARTERY OCCLUSION AFTER COSMETIC FILLER INJECTION.

PubMed

Sridhar, Jayanth; Shahlaee, Abtin; Shieh, Wen-Shi; Rahimy, Ehsan

2017-01-01

To report a single case of paracentral acute middle maculopathy in association with retinal artery occlusion in the setting of ipsilateral facial cosmetic filler injection. Case report. A 35-year-old woman presenting with sudden vision loss to finger count vision immediately after left nasal fat pad cosmetic filler injection. Dilated funduscopic examination revealed a swollen optic disc with multiple branch arterial occlusions with visible embolic material. Fluorescein angiography confirmed multiple branch arterial occlusions in addition to a focal choroidal infarction in the macula. Spectral-domain optical coherence tomography revealed middle retinal hyperreflectivity in the superotemporal macula consistent with paracentral acute middle maculopathy. En face optical coherence tomography demonstrated a superotemporal area of whitening at the level of the deep capillary plexus corresponding to the paracentral acute middle maculopathy lesion seen on spectral-domain optical coherence tomography. On twelve-month follow-up, final visual acuity was 20/100 due to optic neuropathy. Emboli from cosmetic facial filler injections may rarely result in ipsilateral arterial occlusions and now have a novel association with paracentral acute middle maculopathy likely due to deep capillary plexus feeder vessel occlusion.

Adverse ophthalmic reaction in poppers users: case series of 'poppers maculopathy'.

PubMed

Davies, A J; Kelly, S P; Naylor, S G; Bhatt, P R; Mathews, J P; Sahni, J; Haslett, R; McKibbin, M

2012-11-01

Poppers are a recreational substance of abuse belonging to the alkyl nitrite family of compounds. In the United Kingdom, where they are legal to purchase but illegal to sell for human consumption, 10% of the general population have tried them. They are considered low risk to physical and mental health. Two recent case series from France demonstrated foveal pathology in individuals associated with poppers use. A case series of seven patients presenting to four hospitals in the United Kingdom with visual impairment and maculopathy associated with inhalation of poppers. All patients experienced visual symptoms associated with poppers use. The majority had impaired visual acuity, central scotomata, distortion, or phosphenes. Clinical signs on fundoscopy ranged from normal foveal appearance to yellow, dome-shaped lesions at the foveola. Spectral domain optical coherence tomography (SD-OCT) showed varying degrees of disruption of the presumed inner segment/outer segment (IS/OS) junction. Although poppers have been in use for several decades, in 2007, following legislative changes, there was a change in the most commonly used compound from isobutyl nitrite to isopropyl nitrite. There were no reports of 'poppers maculopathy' before this. Poppers maculopathy may be missed if patients are not directly questioned about their use. The disruption or loss of the presumed IS/OS junction on SD-OCT are a characteristic feature. Further study of maculopathy in poppers users is now needed. Raising public awareness of the ocular risks associated with their use may be necessary.

Quantitative susceptibility mapping of multiple sclerosis lesions at various ages.

PubMed

Chen, Weiwei; Gauthier, Susan A; Gupta, Ajay; Comunale, Joseph; Liu, Tian; Wang, Shuai; Pei, Mengchao; Pitt, David; Wang, Yi

2014-04-01

To assess multiple sclerosis (MS) lesions at various ages by using quantitative susceptibility mapping (QSM) and conventional magnetic resonance (MR) imaging. Retrospectively selected were 32 clinically confirmed MS patients (nine men and 23 women; 39.3 years ± 10.9) who underwent two MR examinations (interval, 0.43 years ± 0.16) with three-dimensional gradient-echo sequence from August 2011 to August 2012. To estimate the ages of MS lesions, MR examinations performed 0.3-10.6 years before study examinations were studied. Hyperintensity on T2-weighted images was used to define MS lesions. QSM images were reconstructed from gradient-echo data. Susceptibility of MS lesions and temporal rates of change were obtained from QSM images. Lesion susceptibilities were analyzed by t test with intracluster correlation adjustment and Bonferroni correction in multiple comparisons. MR imaging of 32 patients depicted 598 MS lesions, of which 162 lesions (27.1%) in 23 patients were age measurable and six (1.0%) were only visible at QSM. The susceptibilities relative to normal-appearing white matter (NAWM) were 0.53 ppb ± 3.34 for acute enhanced lesions, 38.43 ppb ± 13.0 (positive; P < .01) for early to intermediately aged nonenhanced lesions, and 4.67 ppb ± 3.18 for chronic nonenhanced lesions. Temporal rates of susceptibility changes relative to cerebrospinal fluid were 12.49 ppb/month ± 3.15 for acute enhanced lesions, 1.27 ppb/month ± 2.31 for early to intermediately aged nonenhanced lesions, and -0.004 ppb/month ± 0 for chronic nonenhanced lesions. Magnetic susceptibility of MS lesions increased rapidly as it changed from enhanced to nonenhanced, it attained a high susceptibility value relative to NAWM during its initial few years (approximately 4 years), and it gradually dissipated back to susceptibility similar to that of NAWM as it aged, which may provide new insight into pathophysiologic features of MS lesions. Online supplemental material is available for this

Stellate nonhereditary idiopathic foveomacular retinoschisis concomitant to exudative maculopathies

PubMed Central

Casalino, G; Upendran, M; Bandello, F; Chakravarthy, U

2016-01-01

Purpose To report the clinical course of patients presenting with stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) concomitant with exudative maculopathies. Methods Retrospective case series. Multimodal imaging findings, including spectral-domain optical coherence tomography (SD-OCT) were reviewed. Genetic testing for the RS1 gene was performed in one patient. Results We identified two female patients who fit the definition of SNIFR and presented with concomitant neovascular age-related macular degeneration (n-AMD). In both the patients, SD-OCT showed exudative macular features and splitting (bilateral in patient 1, unilateral in patient 2) of the outer plexiform layer (OPL) in the macula with no other evidence of hereditary or an acquired predisposing condition. Genetic testing excluded mutation of RS1 gene in patient 1. The fundi of both the patients showed characteristic signs of active choroidal neovascularization (CNV) and following anti-VEGF treatment, visual acuity improved and CNV-related exudative changes resolved. However, the split along the OPL remained unaltered. Conclusions SNIFR may be associated with n-AMD. It is important to recognise the presence of retinoschisis when there is other exudative pathology as the former may be misinterpreted as intraretinal fluid, prompting unnecessary treatment. PMID:26915743

ARMS2 variants may predict the 3-year outcome of photodynamic therapy for wet age-related macular degeneration

PubMed Central

Nakai, Shunichiro; Matsumiya, Wataru; Miki, Akiko; Nakamura, Makoto

2017-01-01

Purpose To determine the association of age-related maculopathy susceptibility 2 (ARMS2) gene polymorphisms with the 3-year outcomes of photodynamic therapy (PDT) in wet age-related macular degeneration (wet AMD). Methods The single nucleotide polymorphism (SNP) at rs10490924 in the ARMS2 gene of 65 patients with wet AMD who underwent PDT was genotyped using the TaqMan assay. The clinical characteristics and the outcomes of PDT were compared among the three genotypes at rs10490924. A multivariate regression analysis was performed to evaluate the influence of the clinical cofactors on the association of rs10490924 with the visual outcome at 36 months after the first PDT. Results A significant difference was found among the genotypes in the age and the baseline lesion size. The patients with the GG genotype showed a significant improvement in vision, and the patients with the TT genotype showed a significant worsening of vision at all time points measured after the initial PDT. In the multivariate regression analysis, the number of the G allele at rs10490924 was associated with a significantly greater improvement in the baseline best-corrected visual acuity (BCVA) at 36 months after the first PDT. Conclusions ARMS2 variants are likely associated with the 3-year outcomes of PDT in patients with wet AMD. PMID:28761324

FACTORS INFLUENCING AGE AND STRAIN-RELATED SUSCEPTIBILITY TO 3-METHYLCHOLANTHRENE CARCINOGENICITY

EPA Science Inventory

Fetal mice are more sensitive to chemical carcinogens than are adults. Further, some strains of mice are more susceptible to chemical carcinogens than others. We have been conducting studies to understand the interactions between age and genetic background underlying these suscep...

Benefits, Potential Harms, and Optimal Use of Nutritional Supplementation for Preventing Progression of Age-Related Macular Degeneration.

PubMed

Rojas-Fernandez, Carlos H; Tyber, Kevin

2017-03-01

To briefly review age-related macular degeneration (AMD), the main findings from the Age Related Eye Disease Study (AREDS) report number 8 on the use of nutritional supplements for AMD, and to focus on data suggesting that supplement use should be guided using genetic testing of AMD risk genes. A literature search (January 2001 through October 26, 2016) was conducted using MEDLINE and the following MeSH terms: Antioxidants/therapeutic use, Genotype, Macular Degeneration/drug therapy, Macular degeneration/genetics, Dietary Supplements, Proteins/genetics, and Zinc Compounds/therapeutic use. Bibliographies of publications identified were also reviewed. English-language studies assessing AREDS supplement response in patients with AMD in relation to complement factor H gene ( CFH) and age-related maculopathy susceptibility 2 gene ( ARMS2) risk alleles were evaluated. Three of the 4 studies demonstrated a treatment interaction between ARMS2 and CFH genotypes and a differential response to supplements. The fourth study documented an interaction for the CFH genotype only. Reported response interactions included attenuated response, no response, and good response, whereas a subset showed increased progression of AMD. Conversely, one study reported no interactions between CFH and ARMS2 risk alleles and response to supplements. The weight of the evidence supports using genetic testing to guide selection of ocular vitamin use. This approach will avoid using supplements that could speed the progression of AMD in vulnerable patients, avoid using supplements that will have little to no effect in others, and result in appropriately using supplements in those that are likely to derive meaningful benefits.

Bull's eye and pigment maculopathy are further retinal manifestations of an abnormal Bruch's membrane in Alport syndrome.

PubMed

Savige, Judy; Wang, Yanyan; Crawford, Andrew; Smith, James; Symons, Andrew; Mack, Heather; Nicholls, Kathy; Wilson, Diane; Colville, Deb

2017-01-01

The retinal features of Alport syndrome include a central and peripheral fleck retinopathy, temporal retinal thinning, and a macular hole. Here we describe further retinal abnormalities. We identified a case of bull's eye maculopathy 20 years previously in a 68-year-old female, and reviewed archived retinal images from our cohort of X-linked (28 males, 28 females) or autosomal recessive (n = 13) Alport syndrome. All individuals had Alport syndrome confirmed on genetic testing or renal biopsy, were examined by an ophthalmologist, and underwent retinal imaging (KOWA non-mydriatic camera, Japan). The index case had the p.Q379X variant in COL4A5 and currently had renal impairment, (eGFR = 45 ml/min/1.73 m 2 ), bilateral hearing loss, and central and peripheral retinopathies. Her maculopathy had deteriorated, and she had a bilateral central visual field loss. Optical coherence tomography (Heidelberg Spectralis) demonstrated a disrupted retinal pigment epithelium and retinal atrophy. We identified a further early bull's eye maculopathy (1/69, 1.4%) from a female with autosomal recessive disease and normal renal function. We also noted a subtle pigment maculopathy associated with an abnormal retinal pigment epithelium in 27 (27/69, 39%) subjects with Alport syndrome, in both males (8/28, 29%) and females (13/28, 46%) with X-linked disease, and in autosomal recessive disease (6/13, 38%). The bull's eye and pigment maculopathies in Alport syndrome result mainly from the damaged Bruch's membrane and overlying retinal pigment epithelium. Bull's eye maculopathy affects vision and patients should undergo regular monitoring for retinal complications.

Adverse ophthalmic reaction in poppers users: case series of ‘poppers maculopathy'

PubMed Central

Davies, A J; Kelly, S P; Naylor, S G; Bhatt, P R; Mathews, J P; Sahni, J; Haslett, R; McKibbin, M

2012-01-01

Background Poppers are a recreational substance of abuse belonging to the alkyl nitrite family of compounds. In the United Kingdom, where they are legal to purchase but illegal to sell for human consumption, 10% of the general population have tried them. They are considered low risk to physical and mental health. Two recent case series from France demonstrated foveal pathology in individuals associated with poppers use. Method A case series of seven patients presenting to four hospitals in the United Kingdom with visual impairment and maculopathy associated with inhalation of poppers. Results All patients experienced visual symptoms associated with poppers use. The majority had impaired visual acuity, central scotomata, distortion, or phosphenes. Clinical signs on fundoscopy ranged from normal foveal appearance to yellow, dome-shaped lesions at the foveola. Spectral domain optical coherence tomography (SD-OCT) showed varying degrees of disruption of the presumed inner segment/outer segment (IS/OS) junction. Discussion Although poppers have been in use for several decades, in 2007, following legislative changes, there was a change in the most commonly used compound from isobutyl nitrite to isopropyl nitrite. There were no reports of ‘poppers maculopathy' before this. Poppers maculopathy may be missed if patients are not directly questioned about their use. The disruption or loss of the presumed IS/OS junction on SD-OCT are a characteristic feature. Further study of maculopathy in poppers users is now needed. Raising public awareness of the ocular risks associated with their use may be necessary. PMID:23079752

Lesion complexity drives age related cancer susceptibility in human mammary epithelial cells

DOE PAGES

Sridharan, Deepa M.; Enerio, Shiena; Stampfer, Martha M.; ...

2017-02-28

Exposures to various DNA damaging agents can deregulate a wide array of critical mechanisms that maintain genome integrity. It is unclear how these processes are impacted by one's age at the time of exposure and the complexity of the DNA lesion. To clarify this, we employed radiation as a tool to generate simple and complex lesions in normal primary human mammary epithelial cells derived from women of various ages. We hypothesized that genomic instability in the progeny of older cells exposed to complex damages will be exacerbated by age-associated deterioration in function and accentuate age-related cancer predisposition. Centrosome aberrations andmore » changes in stem cell numbers were examined to assess cancer susceptibility. Our data show that the frequency of centrosome aberrations proportionately increases with age following complex damage causing exposures. However, a dose-dependent increase in stem cell numbers was independent of both age and the nature of the insult. Phospho-protein signatures provide mechanistic clues to signaling networks implicated in these effects. Together these studies suggest that complex damage can threaten the genome stability of the stem cell population in older people. Propagation of this instability is subject to influence by the microenvironment and will ultimately define cancer risk in the older population.« less

Lesion complexity drives age related cancer susceptibility in human mammary epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sridharan, Deepa M.; Enerio, Shiena; Stampfer, Martha M.

Exposures to various DNA damaging agents can deregulate a wide array of critical mechanisms that maintain genome integrity. It is unclear how these processes are impacted by one's age at the time of exposure and the complexity of the DNA lesion. To clarify this, we employed radiation as a tool to generate simple and complex lesions in normal primary human mammary epithelial cells derived from women of various ages. We hypothesized that genomic instability in the progeny of older cells exposed to complex damages will be exacerbated by age-associated deterioration in function and accentuate age-related cancer predisposition. Centrosome aberrations andmore » changes in stem cell numbers were examined to assess cancer susceptibility. Our data show that the frequency of centrosome aberrations proportionately increases with age following complex damage causing exposures. However, a dose-dependent increase in stem cell numbers was independent of both age and the nature of the insult. Phospho-protein signatures provide mechanistic clues to signaling networks implicated in these effects. Together these studies suggest that complex damage can threaten the genome stability of the stem cell population in older people. Propagation of this instability is subject to influence by the microenvironment and will ultimately define cancer risk in the older population.« less

Age-related iron deposition in the basal ganglia of controls and Alzheimer disease patients quantified using susceptibility weighted imaging.

PubMed

Wang, Dan; Li, Yan-Ying; Luo, Jian-Hua; Li, Yue-Hua

2014-01-01

This study aimed to investigate age-related iron deposition changes in healthy subjects and Alzheimer disease patients using susceptibility weighted imaging. The study recruited 182 people, including 143 healthy volunteers and 39 Alzheimer disease patients. All underwent conventional magnetic resonance imaging and susceptibility weighted imaging sequences. The groups were divided according to age. Phase images were used to investigate iron deposition in the bilateral head of the caudate nucleus, globus pallidus and putamen, and the angle radian value was calculated. We hypothesized that age-related iron deposition changes may be different between Alzheimer disease patients and controls of the same age, and that susceptibility weighted imaging would be a more sensitive method of iron deposition quantification. The results revealed that iron deposition in the globus pallidus increased with age, up to 40 years. In the head of the caudate nucleus, iron deposition peaked at 60 years. There was a general increasing trend with age in the putamen, up to 50-70 years old. There was significant difference between the control and Alzheimer disease groups in the bilateral globus pallidus in both the 60-70 and 70-80 year old group comparisons. In conclusion, iron deposition increased with age in the globus pallidus, the head of the caudate nucleus and putamen, reaching a plateau at different ages. Furthermore, comparisons between the control and Alzheimer disease group revealed that iron deposition changes were more easily detected in the globus pallidus. Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.

Confidence Moderates the Role of Control Beliefs in the Context of Age-Related Changes in Misinformation Susceptibility.

PubMed

Auslander, Margeaux V; Thomas, Ayanna K; Gutchess, Angela H

2017-01-01

Background/Study Context: The present experiment investigated the role of confidence and control beliefs in susceptibility to the misinformation effect in young and older adults. Control beliefs are perceptions about one's abilities or competence and the extent to which one can influence performance outcomes. It was predicted that level of control beliefs would influence misinformation susceptibility and overall memory confidence. Fifty university students (ages 18-26) and 37 community-dwelling older adults (ages 62-86) were tested. Participants viewed a video, answered questions containing misinformation, and then completed a source-recognition test to determine whether the information presented was seen in the video, the questionnaire only, both, or neither. For each response, participants indicated their level of confidence. The relationship between control beliefs and memory performance was moderated by confidence. That is, individuals with lower control beliefs made more errors as confidence decreased. Additionally, the relationship between confidence and memory performance differed by age, with greater confidence related to more errors for young adults. Confidence is an important factor in how control beliefs and age are related to memory errors in the misinformation effect. This may have implications for the legal system, particularly with eyewitness testimony. The confidence of an individual should be considered if the eyewitness is a younger adult.

Role of Immune Aging in Susceptibility to West Nile Virus.

PubMed

Yao, Yi; Montgomery, Ruth R

2016-01-01

West Nile virus (WNV) can cause severe neuroinvasive disease in humans and currently no vaccine or specific treatments are available. As aging is the most prominent risk factor for WNV, age-related immune dysregulation likely plays an essential role in host susceptibility to infection with WNV. In this review, we summarize recent findings in effects of aging on immune responses to WNV infection. In particular, we focus on the age-dependent dysregulation of innate immune cell types-neutrophils, macrophages, and dendritic cells-in response to WNV infection, as well as age-related alterations in NK cells and γδ T cells that may associate with increased WNV susceptibility in older people. We also highlight two advanced technologies, i.e., mass cytometry and microRNA profiling, which significantly contribute to systems-level study of immune dysregulation in aging and should facilitate new discoveries for therapeutic intervention against WNV.

Maculopathy due to drug inhalation.

PubMed

Asensio-Sánchez, V M; Gonzalez-Buendia, L; Marcos-Fernández, M

2014-08-01

A case of maculopathy due to "poppers" is described. Poppers is a drug composed of various forms of alkyl nitrite. A 39 year-old man, who had been using poppers for years, was seen in the clinic with phosphenes, reduced visual acuity and central scotoma. The SD-OCT in the right eye showed disruption at the level of the IS/OS junction line. The SD-OCT scan in the left eye showed an outer rectangular retinal hole and an outer retinal cyst. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Predictive value of spectral-domain optical coherence tomography features in assessment of visual prognosis in eyes with acute welding arc maculopathy.

PubMed

Zhang, Chunxia; Dang, Guangfu; Zhao, Tianmei; Wang, DongLin; Su, Yan; Qu, Yi

2018-04-12

To observe spectral-domain optical coherence tomography (SD-OCT) features and to determine whether baseline OCT features can be used as predictors of visual acuity outcome in eyes with acute welding arc maculopathy. This retrospective study enrolled twenty-two eyes of eleven subjects with acute welding arc maculopathy. All subjects were evaluated by SD-OCT at baseline and final visit. The involved parameters included best-corrected visual acuity (BCVA), central macular thickness (CMT), the length of ellipsoid zone (EZ) defects, the greatest linear dimension (GLD) of outer retinal lesions, EZ reflectivity and relative EZ reflectivity (defined as the ratio of EZ reflectivity to retinal pigment epithelium reflectivity on OCT). Acute welding arc maculopathy was presented as abnormal hyperreflectivity, hyporeflectivity and defects of outer retinal layer in fovea on OCT. Compared with baseline, BCVA improved significantly accompanied by decreased GLD of outer retinal lesions and the length of EZ defects at final visit (P = 0.0004, P < 0.0001 and P < 0.0001, respectively). No significant changes were shown on CMT (P = 0.248). In multivariate regression analysis, final BCVA was associated with baseline BCVA and the length of EZ defects (P = 0.012 and P = 0.045, respectively). However, EZ reflectivity and relative EZ reflectivity were not associated with final BCVA (P > 0.05). In conclusion, SD-OCT images clearly reveal morphological changes in outer retinal layer in acute welding arc maculopathy. The baseline BCVA and length of EZ defects are the strongest predictors of final BCVA.

Age-related changes in serological susceptibility patterns to measles: results from a seroepidemiological study in Dongguan, China.

PubMed

Xiong, Yongzhen; Wang, Dong; Lin, Weiyan; Tang, Hao; Chen, Shaoli; Ni, Jindong

2014-01-01

The present study was performed to determine the seroprevalence of IgG measles antibodies in Dongguan residents (irrespective of vaccination status), to analyze the changes in age-related serological susceptibility patterns. A total of 1960 residents aged 0-60 years and 315 mother-infant pairs were studied. Serum IgG antibodies against measles virus were measured by ELISA. The overall seroprevalence was 93.4% in the general population in Dongguan, China. In subgroups aged 1-29 years who were likely vaccinated, there was a declining trend of seropositivity with age from 98.6% at 1-4 years to 85.7% at 20-29 years (P<0.0001). Seroprevalence were near or>95% in the older population (30-39 years and ≥ 40 years) who had not been immunized against measles. Age and sex were independent factors associated with seropositivity. Seroprevalence in pregnant women and their newborns was 87.0% and 84.1%, respectively. Our results suggest that the waning vaccine-induced immunity may be the main cause of increased serological susceptibility in young adults and young infants. An additional vaccination strategy that targets young adults is important for elimination of measles.

Agreement between photographic screening and hospital biomicroscopy grading of diabetic retinopathy and maculopathy.

PubMed

Healy, Rachel; Sallam, Ahmed; Jones, Vanessa; Donachie, Paul H J; Scanlon, Peter H; Stratton, Irene M; Johnston, Robert L

2014-01-01

To examine the level of agreement and reasons for disagreement between grading of diabetic retinopathy and maculopathy using mydriatic digital photographs in a diabetic retinopathy screening service (DRSS) and hospital eye service (HES). English NHS Diabetic Eye Screening Programme grades for diabetic retinopathy prospectively recorded on a hospital electronic medical record were compared to the grades from the DRSS event that prompted referral. In cases of disagreement, images were reviewed. Data for 1,501 patients (3,002 eyes) referred between 2008 and 2011 were analyzed. The HES retinopathy grades were R0 (no retinopathy) in 341 eyes, R1 (background retinopathy) in 1,712 eyes, R2 (pre-proliferative retinopathy) in 821 eyes, and R3 (proliferative retinopathy) in 128 eyes. The DRSS grades were in agreement in 2,309 eyes (76.9%), recorded a lower grade in 227 eyes, and recorded a higher grade in 466 eyes. Agreement was substantial (κ = 0.65). The commonest cause for disagreement was overgrading of R1 as R2 by hospital clinicians. The HES maculopathy grades were M0 (no maculopathy) in 2,267 eyes and M1 (maculopathy) in 735 eyes. The DRSS were in agreement in 2,111 eyes (70.2%), recorded a lower grade in 106 eyes, and recorded a higher grade in 785 eyes. Agreement was fair (κ = 0.39). The commonest cause for disagreement was hospital clinicians missing fine exudates. This study establishes a benchmark standard for agreement between HES and DRSS grading. Review of DRSS and grading reports images for newly referred patients is likely to improve levels of agreement, particularly for diabetic retinopathy, and should be strongly encouraged.

Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report

PubMed Central

Joachim, Nichole; Colijn, Johanna Maria; Kifley, Annette; Lee, Kristine E; Buitendijk, Gabriëlle H S; Klein, Barbara E K; Myers, Chelsea E; Meuer, Stacy M; Tan, Ava G; Holliday, Elizabeth G; Attia, John; Liew, Gerald; Iyengar, Sudha K; de Jong, Paulus T V M; Hofman, Albert; Vingerling, Johannes R; Mitchell, Paul; Klaver, Caroline C W; Klein, Ronald; Wang, Jie Jin

2018-01-01

Purpose To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. Design Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. Methods Retinal photography and interview with comprehensive questionnaires were conducted at each visit of three studies. AMD was assessed following the modified Wisconsin AMD grading protocol. Progression to bilateral any (early and late) or late AMD was assessed among participants with unilateral involvement only. Factors associated with the progression were assessed using logistic regression models while simultaneously adjusting for other significant risk factors. Results In any 5-year duration, 19–28% of unilateral any AMD cases became bilateral and 27–68% of unilateral late AMD became bilateral. Factors associated with the progression to bilateral involvement of any AMD were age (per year increase, adjusted OR 1.07), carrying risk alleles of the complement factor H and age-related maculopathy susceptibility 2 genes (compared with none, OR 1.76 for 1 risk allele and OR 3.34 for 2+ risk alleles), smoking (compared with non-smokers, OR 1.64 for past and OR 1.67 for current smokers), and the presence of large drusen area or retinal pigmentary abnormalities in the first eye. Conclusion One in four to one in five unilateral any AMD cases, and up to one in two unilateral late AMD cases, progressed to bilateral in 5 years. Known AMD risk factors, including smoking, are significantly associated with the progression to bilateral involvement. PMID:28108569

Blue Journal Conference. Aging and Susceptibility to Lung Disease

PubMed Central

Thannickal, Victor J.; Murthy, Mahadev; Balch, William E.; Chandel, Navdeep S.; Meiners, Silke; Eickelberg, Oliver; Selman, Moisés; Pardo, Annie; White, Eric S.; Levy, Bruce D.; Busse, Paula J.; Tuder, Rubin M.; Antony, Veena B.; Sznajder, Jacob I.

2015-01-01

The aging of the population in the United States and throughout the developed world has increased morbidity and mortality attributable to lung disease, while the morbidity and mortality from other prevalent diseases has declined or remained stable. Recognizing the importance of aging in the development of lung disease, the American Thoracic Society (ATS) highlighted this topic as a core theme for the 2014 annual meeting. The relationship between aging and lung disease was discussed in several oral symposiums and poster sessions at the annual ATS meeting. In this article, we used the input gathered at the conference to develop a broad framework and perspective to stimulate basic, clinical, and translational research to understand how the aging process contributes to the onset and/or progression of lung diseases. A consistent theme that emerged from the conference was the need to apply novel, systems-based approaches to integrate a growing body of genomic, epigenomic, transcriptomic, and proteomic data and elucidate the relationship between biologic hallmarks of aging, altered lung function, and increased susceptibility to lung diseases in the older population. The challenge remains to causally link the molecular and cellular changes of aging with age-related changes in lung physiology and disease susceptibility. The purpose of this review is to stimulate further research to identify new strategies to prevent or treat age-related lung disease. PMID:25590812

Clinical manifestations of optic pit maculopathy as demonstrated by spectral domain optical coherence tomography.

PubMed

Tzu, Jonathan H; Flynn, Harry W; Berrocal, Audina M; Smiddy, William E; Murray, Timothy G; Fisher, Yale L

2013-01-01

The purpose of this retrospective study was to evaluate the characteristic features, including spectral-domain optical coherence tomography (SD-OCT), clinical course, and outcome of treatment if given for patients with optic disc pit maculopathy. We investigated a consecutive series of patients with a diagnosis of optic pit maculopathy treated between 2001 and 2012 at the Bascom Palmer Eye Institute. Patients were divided into two main groups, ie, patients who were observed without surgery and patients who received surgical intervention. The main outcome measures were presenting and final visual acuity, and changes in SD-OCT imaging were recorded. Other data including age, gender, eye, age of onset, length of follow-up, location of optic pit, and location of fluid by OCT were also recorded. On OCT, 67% (12/18) of the eyes showed schisis-like cavities, 22% (4/18) had only subretinal fluid, and 17% (3/18) had only a schisis-like cavity without subretinal fluid. In the patients managed by observation, visual acuity was ≥20/200 in 6/8 eyes initially and 6/8 eyes at last follow-up. Ten of 18 patients received either focal laser, surgery or both. Six of 10 eyes undergoing surgery had initial visual acuity ≥ 20/200, and 8 of 10 eyes undergoing surgery had a visual acuity of ≥20/200 at last follow-up. In this study, many eyes were observed and remained stable during follow-up. In eyes with reduced vision, surgical intervention produced variable outcomes, and persistent intraretinal/subretinal fluid was a common occurrence.

Susceptibility and resilience to memory aging stereotypes: education matters more than age.

PubMed

Andreoletti, Carrie; Lachman, Margie E

2004-01-01

The authors examined whether the memory performance of young, middle-aged, and older adults would be influenced by stereotype versus counterstereotype information about age differences on a memory task. One hundred forty-nine adults from a probability sample were randomly assigned to a control group or to age-stereotype conditions. As predicted, counterstereotype information was related to higher recall compared to stereotype and control groups. This was true across all age groups, but only for those with more education. Both stereotype and counterstereotype information were related to lower recall compared to the control group across age groups for those with lower education. Results suggest those with more education are more resilient when faced with negative age stereotypes about memory and respond positively to counterstereotype information. In contrast, those with less education show greater susceptibility to the detrimental effects of age stereotypes and respond negatively to both stereotype and counterstereotype information about memory aging.

[The German program for disease management guidelines: type 2 diabetes--diabetic retinopathy/maculopathy guideline 2006. Short review].

PubMed

Ollenschläger, Günter; Kopp, Ina; Thole, Henning; Lelgemann, Monika

2007-02-15

In Germany, the first national consensus between six medical scientific associations on evidence-based recommendations for prevention and therapy of retinopathy/maculopathy in type 2 diabetes was reached in fall 2006. The recommendations' main sources are the NICE Retinopathy Guideline 2002, and existing German guidelines and reviews of recent scientific evidence. The article gives an overview on authors, sources, and key recommendations of the German National Disease Management Guideline Type 2 Diabetes-Retinopathy/Maculopathy 2006 (www.diabetes.versorgungsleitlinien.de).

Lack of Radiation Maculopathy After Palladium-103 Plaque Radiotherapy for Iris Melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yousef, Yacoub A.; Finger, Paul T., E-mail: pfinger@eyecancer.com

2012-07-15

Purpose: To report on the risk of radiation maculopathy for iris and iridociliary melanomas treated by {sup 103}Pd plaque radiotherapy. Methods and Materials: This is a retrospective clinical case series of 30 eyes in 30 patients with melanomas limited to the iris or invading the ciliary body. The main outcome measures included demographic information, laterality, tumor size, location, visual acuity, radiation dose, local control, retinal evaluation, and duration of follow-up. Results: Thirty patients were followed for a median 36 months (range, 12-90 months). Sixteen of 30 tumors (53%) were pure iris melanomas, and 14 (47%) were primary iris melanomas extendingmore » into the ciliary body. Radiation dosimetry showed that the median tumor apex dose was 85 Gy (range, 75-100 Gy), lens dose 43.5 Gy (range, 17.8-60 Gy), fovea dose 1.8 Gy (range, 1.3-5 Gy), and central optic disc dose 1.7 Gy (range, 1.3-4.7 Gy). Cataracts developed in 20 of the 28 phakic eyes (71.4%). No patient in this series developed radiation maculopathy or radiation optic neuropathy. Last best-corrected visual acuity was {>=}20/25 in 28 patients (93%) at a median 36 months' follow-up. Conclusion: Though visual acuities were transiently affected by radiation cataract, no radiation maculopathy or optic neuropathy has been noted after {sup 103}Pd treatment of iris and iridociliary melanomas.« less

Classification of Exudative Age-Related Macular Degeneration With Pachyvessels on En Face Swept-Source Optical Coherence Tomography.

PubMed

Ng, Danny Siu-Chun; Bakthavatsalam, Malini; Lai, Frank Hiu-Ping; Cheung, Carol Yim-Lui; Cheung, Gemmy Chu-Ming; Tang, Fang Yao; Tsang, Chi Wai; Lai, Timothy Yuk-Yau; Wong, Tien Yin; Brelén, Mårten Erik

2017-02-01

The purpose of this study was to classify exudative maculopathy by the presence of pachyvessels on en face swept-source optical coherence tomography (SSOCT). Consecutive patients with signs of exudative maculopathy underwent SSOCT, fluorescein and indocyanine green angiography (ICGA), ultra-widefield fundus color photography, and autofluorescence examinations. Images were analyzed in a masked fashion by two sets of four examiners in different sessions: (1) the presence of pachyvessels in en face OCT and (2) features of exudative maculopathy in conventional imaging modalities. Quantitative data obtained were subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI), which was the ratio of choroidal vessels lumen area to a specified choroidal area from binarized cross-sectional OCT scans. Pachyvessels was observed in 38 (52.1%) of 73 eyes. The pachyvessels group was associated with younger age (69.1 ± 9.4 years, odds ratio [OR] = 0.95, 95% confidence interval [95% CI] = 0.90-0.97, P = 0.04), presence of polypoidal lesions (OR = 3.27, 95% CI = 1.24-8.62, P = 0.01), increased SFCT (OR = 1.08, 95% CI = 1.02-1.14, P < 0.01), and increased CVI (65.4 ± 5.3, OR = 1.12, 95% CI = 1.02-1.23, P = 0.01). In multivariate regression, CVI significantly correlated with pachyvessels (OR = 1.24, 95% CI = 1.03-1.55, P = 0.04). Exudative maculopathy could be classified based on differences in choroidal vasculature morphology. Current results implied that choroidal hemodynamics may be relevant to variable natural history and treatment response in neovascular AMD and polypoidal choroidal vasculopathy.

An Investigation of Age-Related Iron Deposition Using Susceptibility Weighted Imaging

PubMed Central

Wang, Dan; Li, Wen-Bin; Wei, Xiao-Er; Li, Yue-Hua; Dai, Yong-Ming

2012-01-01

Aim To quantify age-dependent iron deposition changes in healthy subjects using Susceptibility Weighted Imaging (SWI). Materials and Methods In total, 143 healthy volunteers were enrolled. All underwent conventional MR and SWI sequences. Subjects were divided into eight groups according to age. Using phase images to quantify iron deposition in the head of the caudate nucleus and the lenticular nucleus, the angle radian value was calculated and compared between groups. ANOVA/Pearson correlation coefficient linear regression analysis and polynomial fitting were performed to analyze the relationship between iron deposition in the head of the caudate nucleus and lenticular nucleus with age. Results Iron deposition in the lenticular nucleus increased in individuals aged up to 40 years, but did not change in those aged over 40 years once a peak had been reached. In the head of the caudate nucleus, iron deposition peaked at 60 years (p<0.05). The correlation coefficients for iron deposition in the L-head of the caudate nucleus, R-head of the caudate nucleus, L-lenticular nucleus and R-lenticular nucleus with age were 0.67691, 0.48585, 0.5228 and 0.5228 (p<0.001, respectively). Linear regression analyses showed a significant correlation between iron deposition levels in with age groups. Conclusions Iron deposition in the lenticular nucleus was found to increase with age, reaching a plateau at 40 years. Iron deposition in the head of the caudate nucleus also increased with age, reaching a plateau at 60 years. PMID:23226360

Associations of candidate genes to age-related macular degeneration among racial/ethnic groups in the multi-ethnic study of atherosclerosis.

PubMed

Klein, Ronald; Li, Xiaohui; Kuo, Jane Z; Klein, Barbara E K; Cotch, Mary Frances; Wong, Tien Y; Taylor, Kent D; Rotter, Jerome I

2013-11-01

To describe the relationships of selected candidate genes to the prevalence of early age-related macular degeneration (AMD) in a cohort of whites, blacks, Hispanics, and Chinese Americans. Cross-sectional study. setting: Multicenter study. study population: A total of 2456 persons aged 45-84 years with genotype information and fundus photographs. procedures: Twelve of 2862 single nucleotide polymorphisms (SNPs) from 11 of 233 candidate genes for cardiovascular disease were selected for analysis based on screening with marginal unadjusted P value <.001 within 1 or more racial/ethnic groups. Logistic regression models tested for association in case-control samples. main outcome measure: Prevalence of early AMD. Early AMD was present in 4.0% of the cohort and varied from 2.4% in blacks to 6.0% in whites. The odds ratio increased from 2.3 for 1 to 10.0 for 4 risk alleles in a joint effect analysis of Age-Related Maculopathy Susceptibility 2 rs10490924 and Complement Factor H Y402H (P for trend = 4.2×10(-7)). Frequencies of each SNP varied among the racial/ethnic groups. Adjusting for age and other factors, few statistically significant associations of the 12 SNPs with AMD were consistent across all groups. In a multivariate model, most candidate genes did not attenuate the comparatively higher odds of AMD in whites. The higher frequency of risk alleles for several SNPs in Chinese Americans may partially explain their AMD frequency's approaching that of whites. The relationships of 11 candidate genes to early AMD varied among 4 racial/ethnic groups, and partially explained the observed variations in early AMD prevalence among them. Copyright © 2013 Elsevier Inc. All rights reserved.

A Case of Early Ocular Manifestation of Maculopathy in a 37 year Old Male Patient of CLL.

PubMed

Mehdi, Syed Riaz; Tandon, Nishi; Khan, Sufia Ahmad; Ahmad, Sharique

2014-09-01

B cell chronic lymphocytic leukemia (CLL) also called chronic lymphocytic leukemia is a disease of elderly, but in rare cases it can occur in young adults. Majority of patients present with no specific symptoms, and CLL is suspected on the basis of high total and relative lymphocyte counts, discovered on routine blood examination. This patient was referred from medicine outpatient in our institute, Era's Lucknow Medical College & Hospital for routine complete blood count. His total leukocyte count came out to be alarmingly high. The general blood picture and bone marrow examinations were consistent with CLL. On immunophenotyping CD5 and CD23 were positive. His cervical lymph nodes biopsy was reported as a case of CLL/small lymphocytic lymphoma. On his complaint of hazy vision his funduscopy revealed maculopathy. This makes our case a unique and rare one, as maculopathy in a young patient of CLL has not yet been reported from India.

Adherence to a Mediterranean diet, genetic susceptibility, and progression to advanced macular degeneration: a prospective cohort study.

PubMed

Merle, Bénédicte M J; Silver, Rachel E; Rosner, Bernard; Seddon, Johanna M

2015-11-01

Adherence to a Mediterranean-type diet is linked to a lower risk of mortality and chronic disease, but the association with the progression of age-related macular degeneration (AMD) and genetic susceptibility is unknown. We examined the association of adherence to the Mediterranean diet and genetic susceptibility with progression to advanced AMD. Among 2525 subjects in the AREDS (Age-Related Eye Disease Study), 1028 eyes progressed to advanced AMD over 13 y. Baseline data for demographic and behavioral covariates were collected by using questionnaires. Dietary data were collected from food-frequency questionnaires. The alternate Mediterranean diet (aMeDi) score (range: 0-9) was constructed from individual intakes of vegetables, fruit, legumes, whole grains, nuts, fish, red and processed meats, alcohol, and the ratio of monounsaturated to saturated fats. Ten genetic loci in 7 genes [complement factor H (CFH), age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 (ARMS2/HTRA1), complement component 2 (C2), complement factor B (CFB), complement component 3 (C3), collagen type VIII α 1 (COL8A1), and RAD51 paralog B (RAD51B)] were examined. Survival analysis was used to assess individual eyes for associations between incident AMD and aMeDi score, as well as interaction effects between aMeDi score and genetic variation on risk of AMD. A high aMeDi score (score of 6-9) was significantly associated with a reduced risk of progression to advanced AMD after adjustment for demographic, behavioral, ocular, and genetic covariates (HR: 0.74; 95% CI: 0.61, 0.91; P-trend = 0.007). The aMeDi score was significantly associated with a lower risk of incident advanced AMD among subjects carrying the CFH Y402H nonrisk (T) allele (P-trend = 0.0004, P-interaction = 0.04). The aMeDi score was not associated with AMD among subjects who were homozygous for the risk (C) allele. Higher adherence to a Mediterranean diet was associated with reduced risk of

MULTIMODAL IMAGING OF ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AND ADAPTIVE OPTICS SCANNING LASER OPHTHALMOSCOPY.

PubMed

Skondra, Dimitra; Nesper, Peter L; Fawzi, Amani A

2017-05-16

To report a case of acute exudative polymorphous vitelliform maculopathy including the findings of optical coherence tomography angiography and adaptive optics scanning laser ophthalmoscopy. Findings on clinical examination, color fundus photography, spectral-domain optical coherence tomography, infrared reflectance, autofluorescence, optical coherence tomography angiography, and adaptive optics scanning laser ophthalmoscopy. A 54-year-old white man with no significant medical history and history of smoking presented with bilateral multiple serous and vitelliform detachments consistent with acute exudative polymorphous vitelliform maculopathy. Extensive infectious, inflammatory, and malignancy workup was negative. Spectral-domain optical coherence tomography showed thickened, hyperreflective ellipsoid zone, subretinal fluid, and focal as well as diffuse subretinal hyperreflective material corresponding to the vitelliform lesions. Optical coherence tomography angiography showed normal retinal and choroidal vasculature, whereas adaptive optics scanning laser ophthalmoscopy showed circular focal "target" lesions at the level of the photoreceptors in the area of foveal detachment. Multimodal imaging is valuable in evaluating patients with acute exudative polymorphous vitelliform maculopathy.

Personality factors in older women's perceived susceptibility to diseases of aging.

PubMed

Gerend, Mary A; Aiken, Leona S; West, Stephen G

2004-04-01

Personality correlates of older women's perceived susceptibility to breast cancer, heart disease, and osteoporosis were examined in a community sample of 312 women aged 40-86. A latent factor of general perceived susceptibility to disease was shown to underlie disease-specific perceptions of susceptibility. Affect-related personality traits (neuroticism, extraversion, optimism, worry, and self-deceptive enhancement) and internal and chance health locus of control predicted general perceived susceptibility. Perceived disease characteristics (e.g., perceived controllability, severity) and the use of cognitive heuristics (i.e., perceived similarity to those who contract each disease) also displayed marked consistency across the three distinct diseases. Finally, our results suggested that general beliefs about the characteristics of health threats and the use of cognitive heuristics may mediate the link between personality traits and perceived risk.

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN A PERIVENULAR FERN-LIKE DISTRIBUTION WITH EN FACE OPTICAL COHERENCE TOMOGRAPHY.

PubMed

Garrity, Sean T; Tseng, Victoria L; Sarraf, David

2017-11-22

To report a case of central retinal vein occlusion resulting in a perivenular pattern of paracentral acute middle maculopathy lesions best identified with en face optical coherence tomography (OCT). Retrospective case report. Optos ultra-widefield fluorescein angiography, spectral domain OCT, en face OCT, and OCT angiography were performed. A 41-year-old man presented with decreased vision in the right eye for 2 weeks. Funduscopic examination of the affected right eye was notable for subtle retinal whitening in the macula, mild retinal venous dilation and tortuosity, and few scattered retinal dot and blot hemorrhages consistent with an acute central retinal vein occlusion. Widefield fluorescein angiography demonstrated delayed arterial and venous filling but no evidence of significant peripheral retinal vascular ischemia. En face OCT segmented at the inner nuclear layer illustrated a remarkable and precise perivenular distribution of fern-like paracentral acute middle maculopathy with periarterial sparing, whereas en face OCT segmented at the outer nuclear layer demonstrated florid cystoid macular edema. At 6-week follow-up, OCT demonstrated patchy areas of atrophic inner nuclear layer and spontaneous resolution of the cystoid macular edema. Optical coherence tomography angiography at the level of the deep capillary plexus illustrated remarkable flow reduction of the deep capillary plexus in mainly a perivenular distribution. The authors report a case of a central retinal vein occlusion with mild retinal findings associated with a remarkable perivenular pattern of paracentral acute middle maculopathy with en face OCT. Follow-up OCT angiography demonstrated significant flow reduction of the deep capillary plexus in a perivenular pattern. The perivenular pattern of paracentral acute middle maculopathy lesions with en face OCT can be an important finding suggestive of a central retinal vein occlusion.

ACUTE EXUDATIVE PARANEOPLASTIC POLYMORPHOUS VITELLIFORM MACULOPATHY DURING VEMURAFENIB AND PEMBROLIZUMAB TREATMENT FOR METASTATIC MELANOMA.

PubMed

Sandhu, Harpal S; Kolomeyer, Anton M; Lau, Marisa K; Shields, Carol L; Schuchter, Lynn M; Nichols, Charles W; Aleman, Tomas S

2017-06-13

To describe a patient with BRAF mutation-positive cutaneous melanoma who developed acute exudative polymorphous vitelliform maculopathy during vemurafenib and pembrolizumab treatment for metastatic melanoma. Retrospective case report documented with wide-field fundus imaging, spectral domain optical coherence tomography, and fundus autofluorescence imaging. A 55-year-old woman with bilateral ductal breast carcinoma and BRAF mutation-positive metastatic cutaneous melanoma complained of bilateral blurred vision within 5 days of starting vemurafenib (BRAF inhibitor). She had been on pembrolizumab (program death receptor antibody) and intermittently on dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor), and had a normal ophthalmologic examination. On presentation three weeks after the introduction of vemurafenib, her visual acuity had declined to 20/40 in both eyes. Her examination showed diffuse elevation of the fovea with multifocal yellow-white, crescent-shaped subretinal deposits within the macula of both eyes and bilateral neurosensory retinal detachments by spectral domain optical coherence tomography. Discontinuation of vemurafenib and introduction of difluprednate and dorzolamide led to a gradual resolution (over four months) of the neurosensory detachments with recovery of vision. This case report suggests that acute exudative polymorphous vitelliform maculopathy may be directly associated with the use of BRAF inhibitors as treatment for metastatic cutaneous melanoma, or indirectly by triggering autoimmune-paraneoplastic processes. Future identification of similar associations is required to unequivocally link vemurafenib and/or pembrolizumab to acute exudative polymorphous vitelliform maculopathy in metastatic melanoma.

Preliminary study on combined pharmacological and laser treatment in optic pit serous maculopathy after literature review.

PubMed

Nebbioso, M; Dapoto, L; Lenarduzzi, F; Belcaro, G; Malagola, R

2012-12-01

The pit of the optic nerve head (ON) is a rare congenital defect that sometimes presents itself with a maculopathy of various neuroretinal layers for unknown reason. This study was focused, before and after pharmacological and parasurgical treatment, on the structural and functional visual assessment in a patient with optic pit maculopathy (OPM). In order to achieve this the latest generation of hi-tech diagnostic tests were used, such as Spectral-Domain Optical Coherence Tomography (SD-OCT), Visual Evoked Potentials (VEP), full-field Electroretinography (ERG), multifocal ERG (mfERG), Microperimetry (MP-1), Standard Automated Perimetry (SAP), Fluorescein Angiography (FA) and Indocyanine Green Angiography (ICG). The research was conducted through a review of past and recent literature.

Mild Cognitive Impairment and Susceptibility to Scams in Old Age

PubMed Central

Han, S. Duke; Boyle, Patricia A.; James, Bryan D.; Yu, Lei; Bennett, David A.

2016-01-01

Background Falling victim to financial scams can have a significant impact upon social and financial wellbeing and independence. A large proportion of scam victims are older adults, but whether older victims with mild cognitive impairment (MCI) are at higher risk remains unknown. Objective We tested the hypothesis that older persons with MCI exhibit greater susceptibility to scams compared to those without cognitive impairment. Methods Seven hundred and thirty older adults without dementia were recruited from the Rush Memory and Aging Project, a community-based epidemiologic study of aging. Participants completed a five-item self-report measure of susceptibility to scams, a battery of cognitive measures, and clinical diagnostic evaluations. Results In models adjusted for age, education, and gender, the presence of MCI was associated with greater susceptibility to scams (B = 0.125, SE = 0.063, p-value = 0.047). Further, in analyses of the role of specific cognitive systems in susceptibility to scams among persons with MCI (n = 144), the level of performance in two systems, episodic memory and perceptual speed abilities, were associated with susceptibility. Conclusions Adults with MCI may be more susceptible to scams in old age than older persons with normal cognition. Lower abilities in specific cognitive systems, particularly perceptual speed and episodic memory, may contribute to greater susceptibility to scams in those with MCI. PMID:26519434

Optical coherence tomography in optic pit maculopathy managed with vitrectomy-laser-gas.

PubMed

García-Arumí, José; Guraya, Borja Corcóstegui; Espax, Ana Boixadera; Castillo, Vicente Martínez; Ramsay, Laura Sararols; Motta, R Max

2004-10-01

Optic disc pit (ODP) maculopathy has a poor visual prognosis if left to its natural course. Several therapeutic approaches have been attempted. The cases of 11 patients evaluated with optical coherence tomography (OCT) and treated with vitrectomy-laser-gas and their functional and anatomical outcomes are presented. Retrospective interventional consecutive case series, including 11 eyes with ODP maculopathy. Pre- and postoperative best-corrected visual acuity (BCVA), OCT and angiography were recorded. All patients underwent pars plana vitrectomy, posterior hyaloid dissection peripapillary diode laser prior to retinal reapplication and C(3)F(8) 15% injection. Mean preoperative BCVA was 20/126. Median preoperative BCVA was 1.0 LogMAR (range 1.3-0.4) . Eighty-two per cent of patients gained 2 or more Snellen lines of vision (mean 4.4 lines gained). Mean final BCVA was 20/32, and median final BCVA was 20/30 in Snellen VA and 0.2 in LogMAR (range 0.7-0) Preoperative OCT in all but one case confirmed the bilaminar structure of the macular detachment. Postoperative OCT helped in monitoring reabsorption of the macular detachment, which was achieved in all cases after an average of 6.5 months post-surgery. BCVA increased progressively as the subretinal fluid was reabsorbed (P=0.006). Mean duration of postoperative follow-up was 15 months. Recurrence was observed in two cases. In our series, the vitrectomy-laser-gas procedure for ODP maculopathy improved vision and achieved satisfactory anatomic results in all 11 cases. OCT was useful in the diagnosis and follow-up of this pathology. However, the low incidence of this entity makes it difficult to obtain series large enough to determine the efficacy of the vitrectomy-laser-gas procedure and other treatment modalities and be able to suggest a procedure of choice.

Magnetic susceptibility induced echo time shifts: Is there a bias in age-related fMRI studies?

PubMed Central

Ngo, Giang-Chau; Wong, Chelsea N.; Guo, Steve; Paine, Thomas; Kramer, Arthur F.; Sutton, Bradley P.

2016-01-01

Purpose To evaluate the potential for bias in functional MRI (fMRI) aging studies resulting from age-related differences in magnetic field distributions which can impact echo time and functional contrast. Materials and Methods Magnetic field maps were taken on 31 younger adults (age: 22 ± 2.9 years) and 46 older adults (age: 66 ± 4.5 years) on a 3 T scanner. Using the spatial gradients of the magnetic field map for each participant, an echo planar imaging (EPI) trajectory was simulated. The effective echo time, time at which the k-space trajectory is the closest to the center of k-space, was calculated. This was used to examine both within-subject and across-age-group differences in the effective echo time maps. The Blood Oxygenation Level Dependent (BOLD) percent signal change resulting from those echo time shifts was also calculated to determine their impact on fMRI aging studies. Result For a single subject, the effective echo time varied as much as ± 5 ms across the brain. An unpaired t-test between the effective echo time across age group resulted in significant differences in several regions of the brain (p<0.01). The difference in echo time was only approximately 1 ms, however which is not expected to have an important impact on BOLD fMRI percent signal change (< 4%). Conclusion Susceptibility-induced magnetic field gradients induce local echo time shifts in gradient echo fMRI images, which can cause variable BOLD sensitivity across the brain. However, the age-related differences in BOLD signal are expected to be small for an fMRI study at 3 T. PMID:27299727

Crystalline maculopathy: a rare complication of tamoxifen therapy.

PubMed

Srikantia, Nirmala; Mukesh, S; Krishnaswamy, Malavika

2010-01-01

Tamoxifen is a selective estrogen receptor modulator widely used in the treatment of hormone-responsive breast cancer. Tamoxifen-induced ocular complications are very rare. A post-menopausal woman, diagnosed and treated case of carcinoma of left breast, on follow-up presented with history of gradual diminution of vision in both eyes of 3 months duration. Patient was on tamoxifen therapy 20 mg daily for the last 2 years. Fundus examination showed crystalline maculopathy. Fluorescein angiography, ocular coherence tomography confirmed the diagnosis. Tamoxifen therapy was discontinued. Although ocular toxicity is rare, careful evaluation of patients with visual symptoms on tamoxifen therapy is required.

Variation in Antibiotic Susceptibility of Uropathogens by Age among Ambulatory Pediatric Patients

PubMed Central

Quach, Yennie; Bearden, David T.; Smith, David H.; Sharp, Susan E.; Guzman-Cottrill, Judith A.

2013-01-01

We compared uropathogen antibiotic susceptibility across age groups of ambulatory pediatric patients. For Escherichia coli (n=5,099) and other Gram-negative rods (n=626), significant differences (p<0.05) existed across age groups for ampicillin, cefazolin, and trimethoprim/sulfamethoxazole susceptibility. In E. coli, differences in trimethoprim/sulfamethoxazole susceptibility varied from 79% in children under 2 to 88% in ages 16–18 (p<0.001) while ampicillin susceptibility varied from 30% in children under 2 to 53% in ages 2–5 (p=0.015). Uropathogen susceptibility to common urinary anti-infectives may be lower in the youngest children. Further investigation into these differences is needed to facilitate appropriate and prudent treatment of urinary tract infections. PMID:24091131

Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration.

PubMed

Meyers, Kristin J; Liu, Zhe; Millen, Amy E; Iyengar, Sudha K; Blodi, Barbara A; Johnson, Elizabeth; Snodderly, D Max; Klein, Michael L; Gehrs, Karen M; Tinker, Lesley; Sarto, Gloria E; Robinson, Jennifer; Wallace, Robert B; Mares, Julie A

2015-11-01

Unhealthy lifestyles have been associated with increased odds for age-related macular degeneration (AMD). Whether this association is modified by genetic risk for AMD is unknown and was investigated. Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later. Women 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663). Healthy lifestyle scores (0-6 points) were assigned based on Healthy Eating Index scores, physical activity (metabolic equivalent of task hours/week), and smoking pack years assessed in 1994 and 1998. Genetic risk was based on Y402H in complement factor H (CFH) and A69S in age-related maculopathy susceptibility locus 2 (ARMS2). Additive and multiplicative interactions in odds ratios were assessed using the synergy index and a multiplicative interaction term, respectively. AMD presence and severity were assessed from grading of stereoscopic fundus photographs taken in 2001-2004. AMD was present in 337 women, 91% of whom had early AMD. The odds of AMD were 3.3 times greater (95% confidence interval [CI], 1.8-6.1) in women with both low healthy lifestyle score (0-2) and high-risk CFH genotype (CC), relative to those who had low genetic risk (TT) and high healthy lifestyle scores (4-6). There were no significant additive (synergy index [SI], 1.08; 95% CI, 0.70-1.67) or multiplicative (Pinteraction=0.94) interactions in the full sample. However, when limiting the sample to women with stable diets before AMD assessment (n=728) the odds for AMD associated with low healthy lifestyle scores and high-risk CFH genotype were strengthened (odds ratio, 4.6; 95% CI, 1.8-11.6) and the synergy index was significant (SI, 1.34; 95% CI, 1.05-1.70). Adjusting for dietary lutein and zeaxanthin attenuated, and therefore partially explained, the joint association. There were no significant additive or multiplicative interactions for ARMS2 and

A thermographic study on eyes affected by Age-related Macular Degeneration: Comparison among various forms of the pathology and analysis of risk factors

NASA Astrophysics Data System (ADS)

Matteoli, Sara; Finocchio, Lucia; Biagini, Ilaria; Giacomelli, Giovanni; Sodi, Andrea; Corvi, Andrea; Virgili, Gianni; Rizzo, Stanislao

2016-05-01

The aims of this study are to investigate (1) the ocular thermographic profiles in eyes affected by Age related Macular Degeneration (AMD) and age-matched controls to detect possible hemodynamic abnormalities that could be involved in the pathogenesis of the disease, (2) whether any risk factors associated with the disease could affect the development of a form of AMD rather than another. Thirty-four eyes with Age-Related Maculopathy (ARM), 41 eyes with dry AMD, 60 eyes affected by wet AMD, and 74 eyes with fibrotic AMD were included in the study. The control group consisted of 48 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, systemic diseases and a body temperature higher than 37.5 °C. A total of 210 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The Ocular Surface Temperature (OST) of five ocular areas was calculated by means of an image processing technique from the infrared images. Two-sample t-test, one-way ANOVA test and multivariate analysis were used for statistical analyses. ANOVA analyses showed no significant differences among AMD groups (P-value > 0.05), however, OST in AMD patients was significantly lower than in controls (P-value < 0.0001). Smokers showed higher possibility (P-value = 0.012) of developing wet AMD instead of dry AMD. Infrared thermography may be a helpful, non-invasive and not time-consuming method to be used in the management of patients with this common degenerative maculopathy.

Susceptibility to acoustic trauma in young and aged gerbils

NASA Astrophysics Data System (ADS)

Boettcher, Flint A.

2002-12-01

The effect of age on susceptibility to noise-induced hearing loss (NIHL), the effect of gender on the interaction of age-related hearing loss (ARHL) and NIHL, and the relative contributions of ARHL and NIHL to total hearing loss are poorly understood. The issues are difficult to resolve empirically in human subjects because of lack of control over extrinsic variables and for ethical reasons. Accordingly, these issues were examined in a well-studied animal model of both ARHL and NIHL, the Mongolian gerbil. Animals were exposed to an intense tone (3.5 kHz, 113 dB SPL, 1 h) either as young adults (6-8 months) or near the end of the average lifespan of the species (34-38 months). Hearing thresholds were determined with the auditory brainstem response (ABR). ARHL was approximately 5-10 dB, with slightly more observed in males at 16 kHz (p<0.05). NIHL of approximately 15-20 dB was similar for the young and old groups, suggesting no differences in susceptibility as a function of age. There were no gender differences in NIHL. The relative contributions of ARHL and NIHL to total hearing loss in aged, noise-exposed gerbils were predicted by an addition of ARHL and NIHL in dB, similar to an international standard on hearing loss allocation, ISO-1999 [Determination of Occupational Noise Exposure and Estimation of Noise-Induced Hearing Impairment (1990)]. Previous evaluations of ISO-1999 using the gerbil animal model concluded that addition of ARHL and NIHL in dB overpredicts total hearing loss. However, in these studies, ARHL was large and nearly equal to NIHL. In the current study, where ARHL was much less than NIHL, addition of the two factors in dB, as recommended by ISO-1999, results in fairly accurate predictions of total hearing loss.

Plasma Homocysteine and Asymmetrical Dimethyl-l-Arginine (ADMA) and Whole Blood DNA Methylation in Early and Neovascular Age-Related Macular Degeneration: A Pilot Study.

PubMed

Pinna, Antonio; Zinellu, Angelo; Tendas, Donatella; Blasetti, Francesco; Carru, Ciriaco; Castiglia, Paolo

2016-01-01

To compare the plasma levels of homocysteine and asymmetrical dimethyl-l-arginine (ADMA) and the degree of whole blood DNA methylation in patients with early and neovascular age-related macular degeneration (AMD) and in controls without maculopathy of any sort. This observational case-control pilot study included 39 early AMD patients, 27 neovascular AMD patients and 132 sex- and age-matched controls without maculopathy. Plasma homocysteine and ADMA concentrations and the degree of whole blood DNA methylation were measured. Quantitative variables were compared by Student's t-test or Mann-Whitney test. Logistic regression models were used to investigate the significance of the association between early or wet AMD and some variables. There were no significant differences in mean plasma homocysteine and ADMA concentrations and in the degree of whole blood DNA methylation between patients with early or neovascular AMD and their controls. Similarly, logistic regression analysis disclosed that plasma homocysteine and ADMA levels were not associated with an increased risk for early or neovascular AMD. We failed to demonstrate an association between early or neovascular AMD and increased plasma homocysteine and/or ADMA. Results also suggest that the degree of whole blood DNA methylation is not a marker of AMD.

Phototoxic maculopathy induced by quartz infrared heat lamp

PubMed Central

Zheng, Xinhua; Xie, Ping; Hu, Zizhong; Zhang, Weiwei; Liang, Kang; Wang, Xiuying; Liu, Qinghuai

2017-01-01

Abstract Rationale: A large proportion of the output of quartz infrared heat lamps is emitted as infrared radiation (IR). Retinal damage induced by IR-A and visible light on arc welders has been reported. However, case reports of retinal damage caused by quartz infrared heat lamps are rare. To the best of our knowledge, this is the first reported case of phototoxic maculopathy induced by quartz infrared heat lamps. Patient concerns: We report a female with a 1-month history of progressive blurred vision and dysmorphopsia in her right eye after improper staring at the tubes of a quartz infrared heater. Her best corrected visual acuity of the right eye was 20/32. Optical coherence tomography revealed a defect from the ellipsoid zone to retinal pigment epithelium (RPE)/Bruch's complex layer with a diameter of 360mmat its widest. P1 amplitudes in the two central concentric rings were reduced as assessed by multifocal electroretinography. Diagnoses: The patient was diagnosed with phototoxic maculopathy. Interventions: The patient was advised to cease all exposure to the infrared heater and was treated with peribulbar injections of methylprednisolone, oral Pancreatic Kininogenase, and oral Mecobalamin. Outcomes: Ten months later, her BCVA improved to 20/20. All examination results returned to normal except for a small residual defect in the interdigitation zone and RPE/Bruch's complex layer in her optical coherence tomography. Lessons: Light emitted by quartz infrared heat lamps may cause damage to the retina through photothermal and photochemical means. The public is insufficiently aware of the hazard potential of infrared heat lamps and other IR-A sources on human retina. PMID:28099337

Poppers: legal highs with questionable contents? A case series of poppers maculopathy.

PubMed

Rewbury, Rebecca; Hughes, Edward; Purbrick, Robert; Prior, Stephen; Baron, Mark

2017-11-01

Poppers are volatile alkyl nitrite compounds that are inhaled to enhance sexual experience and for their psychoactive effects. A less well-known side effect is foveal maculopathy, which has emerged following changes in their chemical composition. It is unclear if certain individuals are more susceptible to retinal damage or if there is a relationship between pattern of inhalation and brands used. A case series of 12 patients presenting to Sussex Eye Hospital, Brighton, with poppers-related visual impairment. Follow-up data were available in 10 cases, at a median time interval of 5 months (range 0-31 months). Eight samples of poppers were analysed using proton nuclear magnetic resonance spectroscopy. Patients presented with disrupted central vision occurring soon after inhalation. All demonstrated disruption of the inner segment/outer segment junction on spectral domain optical coherence tomography. Six of the brands implicated in causing visual symptoms contained isopropyl nitrite, while Jungle Juice Plus varieties, used without side effects in one case, contained amyl nitrite, 2-methyl butyl nitrite and isobutyl alcohol. In general, symptomatic resolution, alongside partial, if not full, recovery of foveal architecture was observed following abstention. On the basis of the products tested here, it seems that isopropyl nitrite is toxic to the fovea and can cause significant visual disturbance. The production of poppers is unregulated and their popularity is concerning, particularly given their exemption from the Psychoactive Substances Act 2016, which might suggest that they are harmless chemicals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The noninvasive retro-mode imaging of confocal scanning laser ophthalmoscopy in myopic maculopathy: a prospective observational study

PubMed Central

Su, Y; Zhang, X; Wu, K; Ji, Y; Zuo, C; Li, M; Wen, F

2014-01-01

Purpose To investigate the morphological features of myopic maculopathy with a new and noninvasive retro-mode imaging (RMI) technique using a confocal scanning laser ophthalmoscope. Methods A total of 42 patients (69 eyes) with myopic maculopathy were included. RMI combined with fundus photography, fundus fluorescein angiography, and optical coherence tomography together were used to observe and evaluate the morphological features of disease. Results Four in 4 eyes (100%) with macular retinoschisis were found with a characteristic pattern by RMI (firework pattern centrally with surrounding fingerprint pattern). Twenty-four in 24 eyes (100%) with pigment proliferation were found by RMI as dark plain patches, and 23 in 24 eyes with hemorrhage (95.8%) were found by RMI as gray bump. Atrophy of different degrees (12 in 14 eyes, 85.7%) was found by RMI as an area of pseudo-3D choroidal vessels or a fuzzy shadow but both without a clear boundary. Choroidal neovascularization (12 in 16 eyes, 75%) was identified laboriously by RMI as a vague raised region. Lacquer cracks were difficult to figure out in RMI. Conclusions Retinoschisis, pigment proliferation, hemorrhage, and atrophy secondary to myopic maculopathy have characteristic morphologic features in RMI; however, choroidal neovascularization and lacquer crack are not easily distinguishable in RMI. PMID:24924440

Age and Sex Related Differences in Subcortical Brain Iron Concentrations among Healthy Adults

PubMed Central

Persson, Ninni; Wu, Jianlin; Zhang, Qing; Liu, Ting; Shen, Jing; Bao, Ruyi; Ni, Mingfei; Liu, Tian; Wang, Yi; Spincemaille, Pascal

2015-01-01

Age and sex can influence brain iron levels. We studied the influence of these variables on deep gray matter magnetic susceptibilities. In 183 healthy volunteers (44.7 ± 14.2 years, range 20-69, ♀ 49%), in vivo Quantitative Susceptibility Mapping (QSM) at 1.5T was performed to estimate brain iron accumulation in the following regions of interest (ROIs): caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), pulvinar (Pul), red nucleus (Rn), substantia nigra (Sn) and the cerebellar dentate nuclei (Dn). We gauged the influence of age and sex on magnetic susceptibility by specifying a series of Structural Equation Models. The distributions of susceptibility varied in degree across the structures, conforming to histologic findings (Hallgren & Sourander, 1958), with the highest degree of susceptibility in the Gp and the lowest in the Th. Iron increase correlated across several ROIs, which may reflect an underlying age-related process. Advanced age was associated with a particularly strong linear rise of susceptibility in the striatum. Nonlinear age trends were found in the Rn, where they were the most pronounced, followed by the Pul and Sn, while minimal nonlinear trends were observed for the Pt, Th, and Dn. Moreover, sex related variations were observed, so that women showed lower levels of susceptibility in the Sn after accounting for age. Regional susceptibility of the Pul increased linearly with age in men but exhibited a nonlinear association with age in women with a leveling off starting from midlife. Women expected to be post menopause (+51 years) showed lower total magnetic susceptibility in the subcortical gray matter. The current report is consistent with previous reports of age related variations of brain iron, but also adds to the current knowledge by reporting age-related changes in less studied, smaller subcortical nuclei. This is the first in-vivo report to show lower total subcortical brain iron levels selectively in women from

Pigmentary Maculopathy Associated with Chronic Exposure to Pentosan Polysulfate Sodium.

PubMed

Pearce, William A; Chen, Rui; Jain, Nieraj

2018-05-22

To describe the clinical features of a unique pigmentary maculopathy noted in the setting of chronic exposure to pentosan polysulfate sodium (PPS), a therapy for interstitial cystitis (IC). Retrospective case series. Six adult patients evaluated by a single clinician between May 1, 2015, and October 1, 2017. Patients were identified by query of the electronic medical record system. Local records were reviewed, including results of the clinical examination, retinal imaging, and visual function assessment with static perimetry and electroretinography. Molecular testing assessed for known macular dystrophy and mitochondrial cytopathy genotypes. Mean best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution units), median cumulative PPS exposure, subjective nature of the associated visual disturbance, qualitative examination and imaging features, and molecular testing results. The median age at presentation was 60 years (range, 37-62 years). All patients received PPS for a diagnosis of IC, with a median cumulative exposure of 2263 g (range, 1314-2774 g), over a median duration of exposure of 186 months (range, 144-240 months). Most patients (4 of 6) reported difficulty reading as the most bothersome symptom. Mean BCVA was 0.1±0.18 logarithm of the minimum angle of resolution. On fundus examination, nearly all eyes showed subtle paracentral hyperpigmentation at the level of the retinal pigment epithelium (RPE) with a surrounding array of vitelliform-like deposits. Four eyes of 2 patients showed paracentral RPE atrophy, and no eyes demonstrated choroidal neovascularization. Multimodal retinal imaging demonstrated abnormality of the RPE generally contained in a well-delineated area in the posterior pole. None of the 4 patients who underwent molecular testing of nuclear DNA returned a pathogenic mutation. Additionally, all 6 patients showed negative results for pathogenic variants in the mitochondrial gene MTTL1. We describe a novel and possibly

Age and sex related differences in subcortical brain iron concentrations among healthy adults.

PubMed

Persson, Ninni; Wu, Jianlin; Zhang, Qing; Liu, Ting; Shen, Jing; Bao, Ruyi; Ni, Mingfei; Liu, Tian; Wang, Yi; Spincemaille, Pascal

2015-11-15

Age and sex can influence brain iron levels. We studied the influence of these variables on deep gray matter magnetic susceptibilities. In 183 healthy volunteers (44.7 ± 14.2 years, range 20-69, ♀ 49%), in vivo quantitative susceptibility mapping (QSM) at 1.5T was performed to estimate brain iron accumulation in the following regions of interest (ROIs): caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), pulvinar (Pul), red nucleus (Rn), substantia nigra (Sn) and the cerebellar dentate nuclei (Dn). We gauged the influence of age and sex on magnetic susceptibility by specifying a series of structural equation models. The distributions of susceptibility varied in degree across the structures, conforming to histologic findings (Hallgren and Sourander, 1958), with the highest degree of susceptibility in the Gp and the lowest in the Th. Iron increase correlated across several ROIs, which may reflect an underlying age-related process. Advanced age was associated with a particularly strong linear rise of susceptibility in the striatum. Nonlinear age trends were found in the Rn, where they were the most pronounced, followed by the Pul and Sn, while minimal nonlinear trends were observed for the Pt, Th, and Dn. Moreover, sex related variations were observed, so that women showed lower levels of susceptibility in the Sn after accounting for age. Regional susceptibility of the Pul increased linearly with age in men but exhibited a nonlinear association with age in women with a leveling off starting from midlife. Women expected to be post menopause (+51 years) showed lower total magnetic susceptibility in the subcortical gray matter. The current report not only is consistent with previous reports of age related variations of brain iron, but also adds to the current knowledge by reporting age-related changes in less studied, smaller subcortical nuclei. This is the first in-vivo report to show lower total subcortical brain iron levels selectively in women

Mediterranean Diet Score and Its Association with Age-Related Macular Degeneration: The European Eye Study.

PubMed

Hogg, Ruth E; Woodside, Jayne V; McGrath, Alanna; Young, Ian S; Vioque, Jesus L; Chakravarthy, Usha; de Jong, Paulus T; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Fletcher, Astrid E

2017-01-01

To examine associations between adherence to a Mediterranean diet and prevalence of age-related macular degeneration (AMD) in countries ranging from Southern to Northern Europe. Cross-sectional, population-based epidemiologic study. Of 5060 randomly sampled people aged 65 years or older from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain), full dietary data were available in 4753. The mean age of participants was 73.2 years (standard deviation, 5.6), and 55% were women. Participants underwent an eye examination and digital retinal color photography. The images were graded at a single center. Dietary intake during the previous 12 months was assessed by using a semiquantitative food-frequency questionnaire (FFQ). A previously published Mediterranean Diet Score (MDS) was used to classify participants according to their responses on the FFQ. Multivariable logistic regression was used to investigate the association of the MDS score and AMD, taking account of potential confounders and the multicenter study design. Images were graded according to the International Classification System for age-related maculopathy and stratified using the Rotterdam staging system into 5 exclusive stages (AMD 0-4) and a separate category of large drusen (≥125 μm). Age-related macular degeneration 4 included neovascular AMD (nvAMD) and geographic atrophy (GA). Increasing MDS was associated with reduced odds of nvAMD in unadjusted and confounder-adjusted analysis. Compared with the lowest MDS adherence (≤4 score), those in the highest category MDS adherence (>6 score) showed lower odds of nvAMD (odds ratio, 0.53; 0.27-1.04; P trend = 0.01). The association with MDS did not differ by Y204H risk allele (P = 0.89). For all early AMD (grade 1-3), there was no relationship with MDS (P trend = 0.9). There was a weak trend (P = 0.1) between MDS and large drusen; those in the highest category of MDS had 20% reduced odds compared with those in

Longitudinal atlas for normative human brain development and aging over the lifespan using quantitative susceptibility mapping.

PubMed

Zhang, Yuyao; Wei, Hongjiang; Cronin, Matthew J; He, Naying; Yan, Fuhua; Liu, Chunlei

2018-05-01

Longitudinal brain atlases play an important role in the study of human brain development and cognition. Existing atlases are mainly based on anatomical features derived from T1-and T2-weighted MRI. A 4D developmental quantitative susceptibility mapping (QSM) atlas may facilitate the estimation of age-related iron changes in deep gray matter nuclei and myelin changes in white matter. To this end, group-wise co-registered QSM templates were generated over various age intervals from age 1-83 years old. Registration was achieved by combining both T1-weighted and QSM images. Based on the proposed template, we created an accurate deep gray matter nuclei parcellation map (DGM map). Notably, we segmented thalamus into 5 sub-regions, i.e. the anterior nuclei, the median nuclei, the lateral nuclei, the pulvinar and the internal medullary lamina. Furthermore, we built a "whole brain QSM parcellation map" by combining existing cortical parcellation and white-matter atlases with the proposed DGM map. Based on the proposed QSM atlas, the segmentation accuracy of iron-rich nuclei using QSM is significantly improved, especially for children and adolescent subjects. The age-related progression of magnetic susceptibility in each of the deep gray matter nuclei, the hippocampus, and the amygdala was estimated. Our automated atlas-based analysis provided a systematic confirmation of previous findings on susceptibility progression with age resulting from manual ROI drawings in deep gray matter nuclei. The susceptibility development in the hippocampus and the amygdala follow an iron accumulation model; while in the thalamus sub-regions, the susceptibility development exhibits a variety of trends. It is envisioned that the newly developed 4D QSM atlas will serve as a template for studying brain iron deposition and myelination/demyelination in both normal aging and various brain diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Masking Period Patterns & Forward Masking for Speech-Shaped Noise: Age-related effects

PubMed Central

Grose, John H.; Menezes, Denise C.; Porter, Heather L.; Griz, Silvana

2015-01-01

Objective The purpose of this study was to assess age-related changes in temporal resolution in listeners with relatively normal audiograms. The hypothesis was that increased susceptibility to non-simultaneous masking contributes to the hearing difficulties experienced by older listeners in complex fluctuating backgrounds. Design Participants included younger (n = 11), middle-aged (n = 12), and older (n = 11) listeners with relatively normal audiograms. The first phase of the study measured masking period patterns for speech-shaped noise maskers and signals. From these data, temporal window shapes were derived. The second phase measured forward-masking functions, and assessed how well the temporal window fits accounted for these data. Results The masking period patterns demonstrated increased susceptibility to backward masking in the older listeners, compatible with a more symmetric temporal window in this group. The forward-masking functions exhibited an age-related decline in recovery to baseline thresholds, and there was also an increase in the variability of the temporal window fits to these data. Conclusions This study demonstrated an age-related increase in susceptibility to non-simultaneous masking, supporting the hypothesis that exacerbated non-simultaneous masking contributes to age-related difficulties understanding speech in fluctuating noise. Further support for this hypothesis comes from limited speech-in-noise data suggesting an association between susceptibility to forward masking and speech understanding in modulated noise. PMID:26230495

Multimodality Diagnostic Imaging in Unilateral Acute Idiopathic Maculopathy

PubMed Central

Jung, Cecilia S.; Payne, John F.; Bergstrom, Chris S.; Cribbs, Blaine E.; Yan, Jiong; Hubbard, G. Baker; Olsen, Timothy W.; Yeh, Steven

2014-01-01

Objective To describe the clinical features and imaging characteristics in unilateral acute idiopathic maculopathy (UAIM). Methods This is a retrospective review of four patients diagnosed with UAIM. Clinical characteristics (age, symptoms, Snellen visual acuity (VA), and funduscopic features) and images from spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), fluorescein (FA), and indocyanine green (ICG) angiography were analyzed. Results The median age at presentation was 31 years (range 27–52 years). The median interval between symptom onset and presentation was four weeks (range 1–20 weeks). Associated systemic findings included a viral prodrome (50%), orchitis (50%), hand-foot-mouth disease (25%), and positive Coxsackie virus titers (50%). The median presenting VA was 20/400 (range 20/70–1/400), which improved to 20/30 (range 20/20–20/60) at final follow-up. The median follow-up time was 6 weeks (range 0–8 weeks). Early in the disease course, the central macula developed irregular, circular areas of white-grey discoloration. Following recovery, the macula had a stippled retinal pigment epithelium characterized by rarefaction and hyperplasia. FA demonstrated irregular early hyperfluorescence and late subretinal hyperfluorescence. SD-OCT showed a partially reversible disruption of the outer photoreceptor layer. FAF initially revealed stippled autofluorescence that eventually became more hypoautofluorescent. ICG showed “moth-eaten” appearing choroidal vasculature, suggestive of choroidal inflammation. Conclusions The imaging characteristics highlight the structural changes during the active and resolution phases of UAIM. The visual recovery correlates with structural changes and suggests that the pathogenesis involves inflammation of the inner choroid, retinal pigment epithelium, and outer photoreceptor complex that is partially reversible. PMID:22232475

Quantitative Susceptibility Mapping after Sports-Related Concussion.

PubMed

Koch, K M; Meier, T B; Karr, R; Nencka, A S; Muftuler, L T; McCrea, M

2018-06-07

Quantitative susceptibility mapping using MR imaging can assess changes in brain tissue structure and composition. This report presents preliminary results demonstrating changes in tissue magnetic susceptibility after sports-related concussion. Longitudinal quantitative susceptibility mapping metrics were produced from imaging data acquired from cohorts of concussed and control football athletes. One hundred thirty-six quantitative susceptibility mapping datasets were analyzed across 3 separate visits (24 hours after injury, 8 days postinjury, and 6 months postinjury). Longitudinal quantitative susceptibility mapping group analyses were performed on stability-thresholded brain tissue compartments and selected subregions. Clinical concussion metrics were also measured longitudinally in both cohorts and compared with the measured quantitative susceptibility mapping. Statistically significant increases in white matter susceptibility were identified in the concussed athlete group during the acute (24 hour) and subacute (day 8) period. These effects were most prominent at the 8-day visit but recovered and showed no significant difference from controls at the 6-month visit. The subcortical gray matter showed no statistically significant group differences. Observed susceptibility changes after concussion appeared to outlast self-reported clinical recovery metrics at a group level. At an individual subject level, susceptibility increases within the white matter showed statistically significant correlations with return-to-play durations. The results of this preliminary investigation suggest that sports-related concussion can induce physiologic changes to brain tissue that can be detected using MR imaging-based magnetic susceptibility estimates. In group analyses, the observed tissue changes appear to persist beyond those detected on clinical outcome assessments and were associated with return-to-play duration after sports-related concussion. © 2018 by American Journal of

Masking Period Patterns and Forward Masking for Speech-Shaped Noise: Age-Related Effects.

PubMed

Grose, John H; Menezes, Denise C; Porter, Heather L; Griz, Silvana

2016-01-01

The purpose of this study was to assess age-related changes in temporal resolution in listeners with relatively normal audiograms. The hypothesis was that increased susceptibility to nonsimultaneous masking contributes to the hearing difficulties experienced by older listeners in complex fluctuating backgrounds. Participants included younger (n = 11), middle-age (n = 12), and older (n = 11) listeners with relatively normal audiograms. The first phase of the study measured masking period patterns for speech-shaped noise maskers and signals. From these data, temporal window shapes were derived. The second phase measured forward-masking functions and assessed how well the temporal window fits accounted for these data. The masking period patterns demonstrated increased susceptibility to backward masking in the older listeners, compatible with a more symmetric temporal window in this group. The forward-masking functions exhibited an age-related decline in recovery to baseline thresholds, and there was also an increase in the variability of the temporal window fits to these data. This study demonstrated an age-related increase in susceptibility to nonsimultaneous masking, supporting the hypothesis that exacerbated nonsimultaneous masking contributes to age-related difficulties understanding speech in fluctuating noise. Further support for this hypothesis comes from limited speech-in-noise data, suggesting an association between susceptibility to forward masking and speech understanding in modulated noise.

Preferred Retinal Loci Relationship to Macular Scotomas: A 10-Year Comparison

ERIC Educational Resources Information Center

Schoessow, Kimberly A.; Fletcher, Donald C.; Schuchard, Ronald A.

2012-01-01

Age-related maculopathy is the leading cause of vision loss among adults in developed countries, and its prevalence is expected to double over the next decade. The two forms of age-related maculopathy--exudative and nonexudative--are capable of affecting the macula, with potential symptoms including decreased contrast sensitivity, decreased visual…

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging.

PubMed

Patterson, Victoria L; Thompson, Brian S; Cherry, Catherine; Wang, Shao-Bin; Chen, Bo; Hoh, Josephine

2016-07-14

Age-related diseases are becoming increasingly prevalent and the burden continues to grow as our population ages. Effective treatments are necessary to lessen the impact of debilitating conditions but remain elusive in many cases. Only by understanding the causes and pathology of diseases associated with aging, can scientists begin to identify potential therapeutic targets and develop strategies for intervention. The most common age-related conditions are neurodegenerative disorders such as Parkinson's disease and blindness. Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Genome wide association studies have previously identified loci that are associated with increased susceptibility to this disease and identified two regions of interest: complement factor H (CFH) and the 10q26 locus, where the age-related maculopathy susceptibility 2 (ARMS2) and high-temperature requirement factor A1 (HtrA1) genes are located. CFH acts as a negative regulator of the alternative pathway (AP) of the complement system while HtrA1 is an extracellular serine protease. ARMS2 is located upstream of HtrA1 in the primate genome, although the gene is absent in mice. To study the effects of these genes, humanized knock-in mouse lines of Cfh and ARMS2, knockouts of Cfh, HtrA1, HtrA2, HtrA3 and HtrA4 as well as a conditional neural deletion of HtrA2 were generated. Of all the genetically engineered mice produced only mice lacking HtrA2, either systemically or in neural tissues, displayed clear phenotypes. In order to examine these mice thoroughly and systematically, an initial phenotyping schedule was established, consisting of a series of tests related to two main diseases of interest: AMD and Parkinson's. Genetically modified mice can be subjected to appropriate experiments to identify phenotypes that may be related to the associated diseases in humans. A phenotyping regimen with a mitochondrial focus is presented here alongside representative results

Cyclodialysis cleft with late hypotony maculopathy after inadvertent cannula detachment during cataract surgery.

PubMed

Kahawita, Shyalle; Cugati, Sudha; Casson, Robert

2015-05-01

We present the case of a 69-year-old woman who presented with hypotony several years after an inadvertent cannula detachment presumably formed a cyclodialysis cleft during phacoemulsification cataract extraction and posterior chamber intraocular lens implantation in her right eye. To our knowledge, this is the first report of late hypotony maculopathy as a result of inadvertent cannula release. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Effect of age on susceptibility to Salmonella Typhimurium infection in C57BL/6 mice.

PubMed

Ren, Zhihong; Gay, Raina; Thomas, Adam; Pae, Munkyong; Wu, Dayong; Logsdon, Lauren; Mecsas, Joan; Meydani, Simin Nikbin

2009-12-01

Ageing is associated with a decline in immune function, which predisposes the elderly to a higher incidence of infections. Information on the mechanism of the age-related increase in susceptibility to Salmonella enterica serovar Typhimurium (S. Typhimurium) is limited. In particular, little is known regarding the involvement of the immune response in this age-related change. We employed streptomycin (Sm)-pretreated C57BL/6 mice to develop a mouse model that would demonstrate age-related differences in susceptibility and immune response to S. Typhimurium. In this model, old mice inoculated orally with doses of 3 x 10(8) or 1 x 10(6) c.f.u. S. Typhimurium had significantly greater S. Typhimurium colonization in the ileum, colon, Peyer's patches, spleen and liver than young mice. Old mice had significantly higher weight loss than young mice on days 1 and 2 post-infection. In response to S. Typhimurium infection, old mice failed to increase ex vivo production of IFN-gamma and TNF-alpha in the spleen and mesenteric lymph node cells to the same degree as observed in young mice; this was associated with their inability to maintain the presence of neutrophils and macrophages at a 'youthful' level. These results indicate that Sm-pretreated C57BL/6 old mice are more susceptible to S. Typhimurium infection than young mice, which might be due to impaired IFN-gamma and TNF-alpha production as well as a corresponding change in the number of neutrophils and macrophages in response to S. Typhimurium infection compared to young mice.

Unilateral acute maculopathy associated with adult onset hand, foot and mouth disease: case report and review of literature.

PubMed

Agrawal, Rupesh; Bhan, Kanchan; Balaggan, Kam; Lee, Richard Wj; Pavesio, Carlos E; Addison, Peter Kf

2015-01-01

Acute maculopathy is a rare condition of unknown aetiology and Coxsackie virus is known to be associated with this macular chorioretinitis. We report a case of acute unilateral maculopathy in a 35-year-old woman with concurrent hand foot and mouth disease. Furthermore, we display multimodal imaging (colour fundus photographs, autofluorescence, spectral domain ocular coherence tomography, fluorescein angiography and indocyanine green angiography) charting the course of the disease. The source of the virus was thought to be the patient's child. Empirical treatment with oral corticosteroids was commenced and the inflammation resolved, leaving a residual macular scar. We present this case combined with the review of literature of adult onset Coxsackie-virus-associated retinitis. This case reiterates the fact that Coxsackie virus is an uncommon but important consideration in the differential diagnosis of chorioretinitis and posterior uveitis with atypical retinopathy.

Quantitative Susceptibility Mapping by Inversion of a Perturbation Field Model: Correlation with Brain Iron in Normal Aging

PubMed Central

Poynton, Clare; Jenkinson, Mark; Adalsteinsson, Elfar; Sullivan, Edith V.; Pfefferbaum, Adolf; Wells, William

2015-01-01

There is increasing evidence that iron deposition occurs in specific regions of the brain in normal aging and neurodegenerative disorders such as Parkinson's, Huntington's, and Alzheimer's disease. Iron deposition changes the magnetic susceptibility of tissue, which alters the MR signal phase, and allows estimation of susceptibility differences using quantitative susceptibility mapping (QSM). We present a method for quantifying susceptibility by inversion of a perturbation model, or ‘QSIP’. The perturbation model relates phase to susceptibility using a kernel calculated in the spatial domain, in contrast to previous Fourier-based techniques. A tissue/air susceptibility atlas is used to estimate B0 inhomogeneity. QSIP estimates in young and elderly subjects are compared to postmortem iron estimates, maps of the Field-Dependent Relaxation Rate Increase (FDRI), and the L1-QSM method. Results for both groups showed excellent agreement with published postmortem data and in-vivo FDRI: statistically significant Spearman correlations ranging from Rho = 0.905 to Rho = 1.00 were obtained. QSIP also showed improvement over FDRI and L1-QSM: reduced variance in susceptibility estimates and statistically significant group differences were detected in striatal and brainstem nuclei, consistent with age-dependent iron accumulation in these regions. PMID:25248179

Redox responses are preserved across muscle fibres with differential susceptibility to aging.

PubMed

Smith, Neil T; Soriano-Arroquia, Ana; Goljanek-Whysall, Katarzyna; Jackson, Malcolm J; McDonagh, Brian

2018-04-15

Age-related loss of muscle mass and function is associated with increased frailty and loss of independence. The mechanisms underlying the susceptibility of different muscle types to age-related atrophy are not fully understood. Reactive oxygen species (ROS) are recognised as important signalling molecules in healthy muscle and redox sensitive proteins can respond to intracellular changes in ROS concentrations modifying reactive thiol groups on Cysteine (Cys) residues. Conserved Cys residues tend to occur in functionally important locations and can have a direct impact on protein function through modifications at the active site or determining protein conformation. The aim of this work was to determine age-related changes in the redox proteome of two metabolically distinct murine skeletal muscles, the quadriceps a predominantly glycolytic muscle and the soleus which contains a higher proportion of mitochondria. To examine the effects of aging on the global proteome and the oxidation state of individual redox sensitive Cys residues, we employed a label free proteomics approach including a differential labelling of reduced and reversibly oxidised Cys residues. Our results indicate the proteomic response to aging is dependent on muscle type but redox changes that occur primarily in metabolic and cytoskeletal proteins are generally preserved between metabolically distinct tissues. Skeletal muscle containing fast twitch glycolytic fibres are more susceptible to age related atrophy compared to muscles with higher proportions of oxidative slow twitch fibres. Contracting skeletal muscle generates reactive oxygen species that are required for correct signalling and adaptation to exercise and it is also known that the intracellular redox environment changes with age. To identify potential mechanisms for the distinct response to age, this article combines a global proteomic approach and a differential labelling of reduced and reversibly oxidised Cysteine residues in two

In vitro susceptibility of thioredoxins and glutathione to redox modification and aging-related changes in skeletal muscle

PubMed Central

Dimauro, Ivan; Pearson, Timothy; Caporossi, Daniela; Jackson, Malcolm J.

2012-01-01

Thioredoxins (Trx's) regulate redox signaling and are localized to various cellular compartments. Specific redox-regulated pathways for adaptation of skeletal muscle to contractions are attenuated during aging, but little is known about the roles of Trx's in regulating these pathways. This study investigated the susceptibility of Trx1 and Trx2 in skeletal muscle to oxidation and reduction in vitro and the effects of aging and contractions on Trx1, Trx2, and thioredoxin reductase (TrxR) 1 and 2 contents and nuclear and cytosolic Trx1 and mitochondrial Trx2 redox potentials in vivo. The proportions of cytosolic and nuclear Trx1 and mitochondrial Trx2 in the oxidized or reduced forms were analyzed using redox Western blotting. In myotubes, the mean redox potentials were nuclear Trx1, −251 mV; cytosolic Trx1, −242 mV; mitochondrial Trx2, −346 mV, data supporting the occurrence of differing redox potentials between cell compartments. Exogenous treatment of myoblasts and myotubes with hydrogen peroxide or dithiothreitol modified glutathione redox status and nuclear and cytosolic Trx1, but mitochondrial Trx2 was unchanged. Tibialis anterior muscles from young and old mice were exposed to isometric muscle contractions in vivo. Aging increased muscle contents of Trx1, Trx2, and TrxR2, but neither aging nor endogenous ROS generated during contractions modified Trx redox potentials, although oxidation of glutathione and other thiols occurred. We conclude that glutathione redox couples in skeletal muscle are more susceptible to oxidation than Trx and that Trx proteins are upregulated during aging, but do not appear to modulate redox-regulated adaptations to contractions that fail during aging. PMID:23022873

AGING AND SUSCEPTIBILITY TO TOLUENE IN RATS: A PHARMACOKINETIC, BIOMARKER, AND PHYSIOLOGICAL APPROACH.

EPA Science Inventory

Aging adults are a growing segment of the U.S. population and are likely to exhibit increased susceptibility to many environmental toxicants. However, there is little information on the susceptibility of the aged to toxicants. The toxicity of toluene has been well characterized i...

BRAZILIAN BOOTY RETINOPATHY: PURTSCHER-LIKE RETINOPATHY WITH PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH PMMA INJECTION INTO BUTTOCKS.

PubMed

Khatibi, Azadeh

2018-01-01

To report a case of Purtscher-like retinopathy with paracentral acute middle maculopathy preceded by febrile illness after filler injection into the buttock muscles bilaterally for cosmesis to achieve a "Brazilian booty." Retrospective case report. A 35-year-old female presented with febrile illness and then decreased vision after repeat polymethyl methacrylate injections into her buttock muscles in Mexico. Examination was significant for retinal whitening, especially in the perifoveal areas, and intraretinal hemorrhages. Optical coherence tomography and fluorescein angiography imaging were consistent with small-vessel ischemic disease in the retina and choroid. Once systemic infection was ruled out, patient was treated with high-dose intravenous and then oral steroids. Vision recovery was good, with retinal atrophy on optical coherence tomography in the previous areas of retinal whitening. A Purtscher-like retinopathy with paracentral acute middle maculopathy and loss of vision may occur after filler injection below the neck, not just the face. This is the first report of vision loss caused by filler injected outside the face.

Torpedo maculopathy: Two case reports and a literature review.

PubMed

de Manuel-Triantafilo, S; Gili, P; Bañuelos Bañuelos, J

2016-08-01

The cases concern a 4 year-old boy and 25 year-old female with 20/20 visual acuity, who presented with a unilateral non-pigmented macular lesion, temporal to the fovea, a torpedo shaped defect in the retinal pigment epithelium (RPE). Optical coherence tomography showed attenuation of the RPE signal, and in the second patient there proved to be a neurosensory detachment, RPE atrophy, and thinning of the retinal layers. The lesion was hypoautofluorescent and hyperfluorescent on fluorescein angiography. Torpedo maculopathy is an asymptomatic characteristic lesion which should be considered in the differential diagnosis of macular lesions in children and young patients. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Aging dynamics in the polymer glass of poly(2-chlorostyrene): Dielectric susceptibility and volume

NASA Astrophysics Data System (ADS)

Fukao, Koji; Tahara, Daisuke

2009-11-01

Aging dynamics was investigated in the glassy states of poly(2-chlorostyrene) by measuring the complex electrical capacitance during aging below the glass transition temperature. The variations with time and temperature of the ac dielectric susceptibility and volume could be determined by simply measuring the variation in the complex electrical capacitance. Isothermal aging at a given temperature for several hours after an intermittent stop in constant-rate cooling is stored in the deviations of both the real and imaginary parts of the complex ac dielectric susceptibility and volume. During cooling after isothermal aging, the deviation of the ac dielectric susceptibility from the reference value decreases and almost vanishes at room temperature. By contrast, the deviation in volume induced during isothermal aging remains almost constant during cooling. The simultaneous measurement of ac dielectric susceptibility and volume clearly revealed that the ac dielectric susceptibility exhibits a full rejuvenation effect, whereas the volume does not show any rejuvenation effects. We discuss a plausible model that can reproduce the present experimental results.

Gene-diet interactions in age-related macular degeneration

USDA-ARS?s Scientific Manuscript database

Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50% of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation...

SCARB1 rs5888 is associated with the risk of age-related macular degeneration susceptibility and an impaired macular area.

PubMed

Stanislovaitiene, Daiva; Zaliuniene, Dalia; Krisciukaitis, Algimantas; Petrolis, Robertas; Smalinskiene, Alina; Lesauskaite, Vita; Tamosiunas, Abdonas; Lesauskaite, Vaiva

2017-01-01

Age-related macular degeneration (ARMD), a progressive retinal disease, is responsible for an impaired central vision in about 180 million people worldwide. Current options for ARMD prevention and treatment are limited due to an incomplete understanding of disease etiopathogenesis. We aimed to test the hypothesis that the single nucleotide polymorphism rs5888 of SCARB1 gene reflecting lipid and antioxidant micronutrient metabolism pathways is associated with ARMD susceptibility and to evaluate if there is any relation between SCARB1 rs5888 and the macular lesion area. The prospective case-control study included patients with ARMD (n = 215) and the reference group (n = 238) drawn from a random sample of the Lithuanian population (n = 1436). The genotyping test of SCARB1 rs5888 was carried out using the real-time polymerase chain reaction method. Regression analysis adjusted by gender and age demonstrated that SCARB1 rs5888 TT genotype significantly decreased the odds for ARMD development (OR: 0.61, 95%; CI: 0.380-0.981, p = 0.04). A smoking habit and leading an outdoor life are associated with larger macular lesion areas in ARMD patients (0.54 (0.00-39.06) vs. 3.09 (0.02-19.30) and 0.27 (0.00-34.57) vs. 0.75 (0.00-39.06), respectively). In late stage ARMD subjects with CT genotype, the macular lesion area was larger than in TT carriers (7.64 (0.49-39.06) mm 2 vs. 5.02 (0.03-37.06) mm 2 , p = 0.006). SCARB1 rs5888 and environmental oxidative stress have a prominent role in ARMD susceptibility, early ARMD progression to advanced stage disease and even in the outcome of the disease-an area of macular lesion.

Phototoxic maculopathy induced by quartz infrared heat lamp: A clinical case report.

PubMed

Zheng, Xinhua; Xie, Ping; Hu, Zizhong; Zhang, Weiwei; Liang, Kang; Wang, Xiuying; Liu, Qinghuai

2017-01-01

A large proportion of the output of quartz infrared heat lamps is emitted as infrared radiation (IR). Retinal damage induced by IR-A and visible light on arc welders has been reported. However, case reports of retinal damage caused by quartz infrared heat lamps are rare. To the best of our knowledge, this is the first reported case of phototoxic maculopathy induced by quartz infrared heat lamps. We report a female with a 1-month history of progressive blurred vision and dysmorphopsia in her right eye after improper staring at the tubes of a quartz infrared heater. Her best corrected visual acuity of the right eye was 20/32. Optical coherence tomography revealed a defect from the ellipsoid zone to retinal pigment epithelium (RPE)/Bruch's complex layer with a diameter of 360mmat its widest. P1 amplitudes in the two central concentric rings were reduced as assessed by multifocal electroretinography. The patient was diagnosed with phototoxic maculopathy. The patient was advised to cease all exposure to the infrared heater and was treated with peribulbar injections of methylprednisolone, oral Pancreatic Kininogenase, and oral Mecobalamin. Ten months later, her BCVA improved to 20/20. All examination results returned to normal except for a small residual defect in the interdigitation zone and RPE/Bruch's complex layer in her optical coherence tomography. Light emitted by quartz infrared heat lamps may cause damage to the retina through photothermal and photochemical means. The public is insufficiently aware of the hazard potential of infrared heat lamps and other IR-A sources on human retina.

Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition.

PubMed

Salami, Alireza; Eriksson, Johan; Nilsson, Lars-Göran; Nyberg, Lars

2012-03-01

Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n=287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease. Copyright © 2011 Elsevier B.V. All rights reserved.

Prevalence of Early and Late Age-Related Macular Degeneration in India: The INDEYE Study

PubMed Central

Krishnan, Tiruvengada; Ravindran, Ravilla D.; Murthy, Gudlavalleti V. S.; Vashist, Praveen; Fitzpatrick, Kathryn E.; Thulasiraj, R. Duraisami; John, Neena; Maraini, Giovanni; Camparini, Monica; Chakravarthy, Usha

2010-01-01

Purpose. To estimate the prevalence of early and late age-related macular degeneration (AMD) in India. Methods. Of 7518 people aged 60 years and older identified from randomly sampled villages in North and South India, 5853 (78%) attended an eye examination including fundus photography. Fundus images were graded according to the Wisconsin Age-Related Maculopathy Grading System. Results. Fundus images were ungradable in 1587 people, mainly because of cataract. People 80 years of age and older were less likely to attend the eye examination and more likely to have ungradable images. For ages 60 to 79 years, the percent prevalence (95% confidence interval [CI]) were late AMD 1.2 (0.8–1.5); and early AMD: grade 1 (soft distinct drusen or pigmentary irregularities), 39.3 (37.2–41.5); grade 2 (soft distinct drusen with pigmentary irregularities or soft indistinct or reticular drusen), 6.7 (5.8–7.6); and grade 3 (soft indistinct or reticular drusen with pigmentary irregularities), 0.2 (0.1–0.4). For ages 80 and older, the respective percent prevalence was: late AMD, 2.5 (0.4–4.7); and early AMD: grade 1, 43.1(35.7–50.6); grade 2, 8.1 (4.3–12.0); and grade 3, 0.5 (0–1.5). Conclusions. The prevalence of early AMD (grades 1 and 2) is similar to that observed in Western populations, but grade 3 appears to be lower. The prevalence of late AMD is comparable to that in Western populations in the age group 60 to 79 years. It is likely that the prevalence in the 80 and older age group is underestimated. PMID:19696177

«Poppers maculopathy?» in Spain. A new ophthalmological disease.

PubMed

García-Bella, J; Donate, J; Gallego-Pinazo, R; Benítez Del Castillo, J M

2016-08-01

The term «poppers» refers to products made of volatile alkyl nitrites used for recreational practices. 40 year old man reported blurred vision in both eyes and photophobia, and admitted regular use of «poppers». Best corrected visual acuity was 0.63/1 in both eyes. Bilateral yellowish vitelliform macular lesions were present in both eyes in the funduscopy, as well as a disruption of the IS/OS line in the optical coherence tomography. This is the first case of «poppers maculopathy» registered in Spain. Clinical findings and symptoms are similar to previous reported cases. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Prevalence and risk factors for age-related macular degeneration in Indians: a comparative study in Singapore and India.

PubMed

Gemmy Cheung, Chui Ming; Li, Xiang; Cheng, Ching-Yu; Zheng, Yingfeng; Mitchell, Paul; Wang, Jie Jin; Jonas, Jost B; Nangia, Vinay; Wong, Tien Yin

2013-04-01

To compare the prevalence and risk factors for age-related macular degeneration (AMD) in 2 Indian populations, 1 living in urban Singapore and 1 in rural central India. Population-based, cross-sectional studies of Indians aged 40+ years. Our analysis included 3337 Singapore-residing participants and 3422 India-residing participants. All participants underwent comprehensive systemic and ocular examinations and retinal photography. AMD was graded from retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System. Systemic and ocular risk factors were assessed for association with AMD. Singapore-residing participants were older (mean age 57.8 years vs 53.8 years) and, after adjusting for age and sex, were more likely to have previous cataract surgery, higher body mass index, hypertension, diabetes, previous myocardial infarction, higher cholesterol, and lower creatinine levels, but less likely to be current smokers, than India-residing participants. The age-standardized prevalence of early and late AMD was 4.45% and 0.34%, respectively, in Singapore and 5.80% and 0.16%, respectively, in India. Shorter axial length was associated with early AMD in both Singapore and India, whereas previous cataract surgery, higher body mass index, hypertension, and lower cholesterol were associated with early AMD in Singapore but not in India. The prevalence of AMD was similar among Indian adults living in urban Singapore and rural India, despite differences in cardiovascular risk factor profile and demographics. Copyright © 2013 Elsevier Inc. All rights reserved.

Circulating anti-retinal antibodies as immune markers in age-related macular degeneration

PubMed Central

Patel, Nishal; Ohbayashi, Masahara; Nugent, Alex K; Ramchand, Kanchan; Toda, Masako; Chau, Kai-Yin; Bunce, Catey; Webster, Andrew; Bird, Alan C; Ono, Santa Jeremy; Chong, Victor

2005-01-01

Age-related macular maculopathy (ARM) and age-related macular degeneration (AMD) are the leading causes of blindness in the Western world. Despite the magnitude of this clinical problem, very little is known about the pathogenesis of the disease. In this study, we analysed the sera (using indirect immunohistochemistry and Western blot analysis) from a very large cohort of such patients and normal age-matched controls to detect circulating anti-retinal antibodies. Patients with bilateral drusen (n = 64) and with chorioretinal neovascularization (CNV) (n = 51) were recruited in addition to age-matched control subjects (n = 39). The sera were analysed for anti-retinal immunoglobulins on retinal sections. The data were then correlated with the clinical features graded according to the International Classification and Grading System of ARM and AMD. The sera of patients with drusen (93·75%) and CNV (82·27%) were found to have a significantly (P = 0·02) higher titre of autoantibodies to the retina in comparison with controls (8·69%), indicating significant evidence of involvement of the immune process in early stages of AMD. Subsequent statistical analysis of the drusen group showed significant progressive staining (P = 0·0009) in the nuclei layers from early to late stages of ARM. Western blotting confirmed the presence of anti-retinal immunoglobulins to retinal antigens. As anti-retinal immunoglobulins are present in patients with bilateral drusen and exudative AMD, these antibodies could play a significant role in the pathogenesis of AMD. Whilst we do not have evidence that these antibodies precede disease onset, the possibility that their presence might contribute to disease progression needs to be investigated. Finally, the eventual identification of the target antigens detected by these antibodies may permit the future development of new diagnostic methods for ARM and AMD. PMID:15946260

Age-related susceptibility to infection with diarrheagenic E. coli in infants from peri-urban areas of Lima, Peru

PubMed Central

Ochoa, Theresa J.; Ecker, Lucie; Barletta, Francesca; Mispireta, Mónica L.; Gil, Ana I.; Contreras, Carmen; Molina, Margarita; Amemiya, Isabel; Verastegui, Hector; Hall, Eric R.; Cleary, Thomas G.; Lanata, Claudio F.

2009-01-01

Background Diarrheagenic E. coli are being recognized as important pediatric enteropathogens worldwide. However, it is unclear whether there are differences in age-related susceptibility to specific agents, especially among infants. Methods We conducted a passive surveillance diarrhea cohort study of 1034 children from 2 to 12 months of age in Lima, Perú. Control stool samples were collected from randomly selected children without diarrhea. All samples were analyzed for common enteric pathogens and for the diarrheagenic E. coli by a multiplex real-time PCR. Results The most commonly isolated pathogens from 1065 diarrheal episodes were the diarrheagenic E. coli (31%), including enteroaggregative (15.1%) and enteropathogenic E. coli (EPEC) (7.6%). Diarrheagenic E. coli, Campylobacter and rotavirus were more frequently isolated from infants ≥ 6m. Diffusely adherent E. coli and enterotoxigenic E. coli (ETEC) were more frequently isolated in diarrheal samples than in controls in older infants (p<0.05). Children ≥ 6m infected with ETEC had a 4.56-fold increased risk for diarrhea (95% CI, 1.20 to 17.28). Persistent diarrhea was more frequent in infants < 6m (13.5% vs. 3.6%, p<0.001). Among diarrheagenic E. coli positive samples, co-infections with other pathogens were more common in diarrhea than in controls (40.1% vs. 15.6%, p<0.001). Conclusions Diarrheagenic E. coli were more frequently isolated in older infants. In this setting with high frequency of pathogen exposure and high frequency of breastfeeding, we hypothesize that the major age-related differences result from decreased exposure to milk protective factors and with increased exposure to contaminated food and water. PMID:19857163

Retinal vascular caliber, iris color, and age-related macular degeneration in the Irish Nun Eye Study.

PubMed

McGowan, Amy; Silvestri, Giuliana; Moore, Evelyn; Silvestri, Vittorio; Patterson, Christopher C; Maxwell, Alexander P; McKay, Gareth J

2014-12-18

To evaluate the relationship between retinal vascular caliber (RVC), iris color, and age-related macular degeneration (AMD) in elderly Irish nuns. Data from 1233 participants in the cross-sectional observational Irish Nun Eye Study were assessed from digital photographs with a standardized protocol using computer-assisted software. Macular images were graded according to the modified Wisconsin Age-related Maculopathy Grading System. Regression models were used to assess associations, adjusting for age, mean arterial blood pressure, body mass index, refraction, and fellow RVC. In total, 1122 (91%) participants had gradable retinal images of sufficient quality for vessel assessment (mean age: 76.3 years [range, 56-100 years]). In an unadjusted analysis, we found some support for a previous finding that individuals with blue iris color had narrower retinal venules compared to those with brown iris color (P < 0.05), but this was no longer significant after adjustment. Age-related macular degeneration status was categorized as no AMD, any AMD, and late AMD only. Individuals with any AMD (early or late AMD) had significantly narrower arterioles and venules compared to those with no AMD in an unadjusted analysis, but this was no longer significant after adjustment. A nonsignificant reduced risk of any AMD or late AMD only was observed in association with brown compared to blue iris color, in both unadjusted and adjusted analyses. Retinal vascular caliber was not significantly associated with iris color or early/late AMD after adjustment for confounders. A lower but nonsignificant AMD risk was observed in those with brown compared to blue iris color. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Multicenter study of pars plana vitrectomy for optic disc pit maculopathy: MACPIT study.

PubMed

Avci, R; Kapran, Z; Ozdek, Ş; Teke, M Y; Oz, O; Guven, D; Yilmaz, S; Kaderli, B; Durukan, A H; Sobaci, G; Unver, Y B; Akduman, L; Kaynak, S; Dogan, I; Inan, U U

2017-09-01

PurposeTo evaluate surgical intervention with pars plana vitrectomy (PPV) for correction of optic disc pit maculopathy (ODP-M).Patients and methodsRetrospective chart review from 13 centres of 51 eyes of 50 patients with ODP-M who underwent PPV between 2002-2014. Anatomic and final best-corrected visual acuity (BCVA) outcomes were evaluated for all cases with different adjuvant techniques.ResultsThere were 23 males and 27 females with median age 25.5 (6-68) years. Preoperative median foveal thickness was 694.5 (331-1384) μm and improved to 252.5 (153-1405) μm. Median BCVA improved from 20/200 (20/20000 to 20/40) to 20/40 (20/2000 to 20/20) with 20/40 or better in 31 eyes. Complete retinal reattachment was achieved in 44 eyes (86.3%) at 7.1 (5.9) months. The good surgical outcomes were achieved in different adjuvant groups. Median follow-up was 24 (6 to 120) months.ConclusionsThese results confirm the long-term effectiveness of PPV for ODP-M. Prospective studies are needed to determine the effectiveness of any adjuvant technique in improving the success of PPV for ODP-M.

Premise and Prediction – How Optic Nerve Head Biomechanics Underlies the Susceptibility and Clinical Behavior of the Aged Optic Nerve Head

PubMed Central

Burgoyne, Claude F.; Downs, J. Crawford

2009-01-01

We propose that age-related alterations in optic nerve head (ONH) biomechanics underlie the clinical behavior and increased susceptibility of the aged ONH to glaucomatous damage. The literature which suggests that the aged ONH is more susceptible to glaucomatous damage at all levels of intraocular pressure is reviewed. The relevant biomechanics of the aged ONH are discussed and a biomechanical explanation for why, on average, the stiffened peripapillary scleral and lamina cribrosa connective tissues of the aged eye should lead to a shallow (senile sclerotic) form of cupping is proposed. A logic for why age-related axon loss and the optic neuropathy of glaucoma in the aged eye may overlap is discussed. Finally, we argue for a need to characterize all forms of clinical cupping into prelaminar and laminar components so as to add precision to the discussion of clinical cupping which does not currently exist. Such characterization may lead to the early detection of ONH axonal and connective tissue pathology in ocular hypertension and eventually aid in the assessment of etiology in all forms of optic neuropathy including those that may be purely age-related. PMID:18552618

Risk Factors for Four-Year Incidence and Progression of Age-Related Macular Degeneration: The Los Angeles Latino Eye Study

PubMed Central

CHOUDHURY, FARZANA; VARMA, ROHIT; MCKEAN-COWDIN, ROBERTA; KLEIN, RONALD; AZEN, STANLEY P.

2011-01-01

PURPOSE To identify risk factors for 4-year incidence and progression of age-related macular degeneration (AMD) in adult Latinos. DESIGN Population-based prospective cohort study. METHODS Participants, aged 40 or older, from The Los Angeles Latino Eye Study (LALES) underwent standardized comprehensive ophthalmologic examinations at baseline and at 4 years of follow-up. Age-related macular degeneration was detected by grading 30-degree stereoscopic fundus photographs using the modified Wisconsin Age-Related Maculopathy Grading System. Multivariate stepwise logistic regression was used to examine the independent association of incidence and progression of AMD and baseline sociodemographic, behavioral, clinical, and ocular characteristics. RESULTS Multivariate analyses revealed that older age (OR per decade of age: 1.52; 95% CI: 1.29, 1.85) and higher pulse pressure (OR per 10 mm Hg: 2.54; 95% CI: 1.36, 4.76) were independently associated with the incidence of any AMD. The same factors were associated with early AMD, soft indistinct drusen, and retinal pigmentary abnormalities. Additionally, presence of clinically diagnosed diabetes mellitus was independently associated with increased retinal pigment (OR: 1.66; 95% CI: 1.01, 2.85), and male gender was associated with retinal pigment epithelial depigmentation (OR 2.50; 95% CI: 1.48, 4.23). Older age (OR per decade of age: 2.20; 95% CI: 1.82, 2.67) and current smoking (OR: 2.85; 95% CI: 1.66, 4.90) were independently associated with progression of AMD. CONCLUSIONS Several modifiable risk factors were associated with 4-year incidence and progression of AMD in Latinos. The results suggest that interventions aimed at reducing pulse pressure and promoting smoking cessation may reduce incidence and progression of AMD, respectively. PMID:21679916

Three-dimensional Optical Coherence Tomography Imaging and Treatment of Glaucomatous Optic Nerve Head Defects Associated with Schisis-like Maculopathy

PubMed Central

Öztaş, Zafer; Menteş, Jale; Ateş, Halil; Nalçacı, Serhad

2017-01-01

We present the three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) findings of schisis-like maculopathy associated with structural changes of the optic nerve (ON) head as well as the treatment outcomes of a case of advanced glaucoma. In addition to ophthalmological examination, B-scan and 3D-SD-OCT images of the ON head, peripapillary retina, and the macula were obtained. The B-scan images only detected typical retinoschisis findings. However, the 3D-SD-OCT images of the ON head revealed defects of various sizes, shapes, and depths at the outer wall of the prelaminar and laminar regions of the ON canal. The 3D images were able to establish that these defects were both adjacent to and interconnected with the retinal layers. The patient successfully received 3D-SD-OCT-guided thermal laser treatment that is used in congenital optic disc pits complicated with macular schisis. In brief, 3D-SD-OCT is very useful for demonstrating the ON head defects that can lead to schisis-like maculopathy in cases of advanced glaucoma. PMID:28405489

Increased susceptibility of aging gastric mucosa to injury: The mechanisms and clinical implications

PubMed Central

Tarnawski, Andrzej S; Ahluwalia, Amrita; Jones, Michael K

2014-01-01

This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-“aging gastropathy”-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2

FOUR-YEAR INCIDENCE AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION: THE LOS ANGELES LATINO EYE STUDY

PubMed Central

Varma, Rohit; Foong, Athena W.P.; Lai, Mei-Ying; Choudhury, Farzana; Klein, Ronald; Azen, Stanley P.

2011-01-01

Purpose To estimate 4-year incidence and progression of early and advanced age-related macular degeneration (AMD). Design Population-based cohort study. Methods A comprehensive ophthalmologic examination including stereoscopic fundus photography was performed on adult Latinos at baseline and follow-up. Photographs were graded using a modified Wisconsin Age-Related Maculopathy Grading System. For estimations of incidence and progression of AMD, the Age Related Eye Disease Study Scale was used. Main outcome measures are incidence and progression of early AMD (drusen type, drusen size, and retinal pigmentary abnormalities) and advanced AMD (exudative AMD and geographic atrophy). Results 4,658/6100 (76%) completed the follow-up examination. The 4-year incidence of early AMD was 7.5% (95%CI:6.6,8.4) and advanced AMD was 0.2% (95%CI:0.1,0.4). Progression of any AMD occurred in 9.3% (95%CI:8.4,10.3) of at-risk participants. Incidence and progression increased with age. Incidence of early AMD in the second eye (10.8%) was higher than incidence in the first eye (6.9%). Baseline presence of soft indistinct large drusen≥250μm in diameter was more likely to predict the 4-year incidence of pigmentary abnormalities, geographic atrophy, and exudative AMD than smaller or hard or soft distinct drusen. Conclusions Age-specific incidence and progression of AMD in Latinos are lower than in non-Hispanic whites. While incident early AMD is more often unilateral, the risk of its development in the second is higher than in the first eye. Older persons and those with soft indistinct large drusen had a higher risk of developing advanced AMD compared to those who were younger and did not have soft indistinct large drusen. PMID:20399926

Long-term outcomes of pars plana vitrectomy without internal limiting membrane peeling for optic disc pit maculopathy.

PubMed

Avci, R; Yilmaz, S; Inan, U U; Kaderli, B; Kurt, M; Yalcinbayir, O; Yildiz, M; Yucel, A

2013-12-01

To evaluate the results of surgical treatment of maculopathy secondary to congenital optic pit anomaly with pars plana vitrectomy (PPV), endolaser to the temporal edge of the optic disc and C3F8 tamponade without internal limiting membrane (ILM) peeling. Thirteen eyes of 12 patients with serous macular detachment and/or macular retinoschisis secondary to congenital optic disc pit (ODP) were included in the study. All eyes underwent PPV, posterior hyaloid removal, endolaser photocoagulation on the temporal margin of the optic disc and 12% C3F8 gas tamponade. Anatomic success and functional outcome determined retrospectively by optical coherence tomography and measurement of best corrected visual acuity (BCVA), respectively were the main outcome parameters. Two lines or more improvement in BCVA was obtained in 11 eyes and 6 of these eyes had 20/40 or better BCVA at the final visit. Subretinal or intraretinal fluid was completely resorbed postoperatively in 12 eyes but a little intraretinal fluid persisted in one eye at the 16-month follow-up. Better visual improvement was observed in patients treated by earlier surgical intervention. PPV, C3F8 gas tamponade and endolaser to the optic disc margin without ILM peeling may yield favourable results in the treatment of ODP maculopathy.

Age-related behavioral effects of methomyI in Brown Norway rats.

EPA Science Inventory

Methomyl is a cholinesterase-inhibiting carbamate pesticide that is used in the field on cotton and a variety of fruits and vegetables. Concerns have been raised generally about age-related differences in susceptibility to cholinesterase-inhibiting pesticides, especially for chil...

Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice.

PubMed

Montalvo-Ortiz, Janitza L; Fisher, Daniel W; Rodríguez, Guadalupe; Fang, Deyu; Csernansky, John G; Dong, Hongxin

2017-08-01

Older patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility. In this study, we treated young (2-3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects. In addition, we pretreated separate groups of young and aged mice with histone deacetylase (HDAC) inhibitors valproic acid (VPA) or entinostat (MS-275) and then administered HAL. Our results show that the motor side effects of HAL are exaggerated in aged mice as compared to young mice and that HDAC inhibitors are able to reverse the severity of these deficits. HAL-induced motor deficits in aged mice are associated with an age- and drug-dependent decrease in striatal D2R protein levels and functionality. Further, histone acetylation was reduced while histone tri-methylation was increased at specific lysine residues of H3 and H4 within the Drd2 promoter in the striatum of aged mice. HDAC inhibitors, particularly VPA, restored striatal D2R protein levels and functionality and reversed age- and drug-related histone modifications at the Drd2 promoter. These results suggest that epigenetic changes at the striatal Drd2 promoter drive age-related increases in antipsychotic side effect susceptibility, and HDAC inhibitors may be an effective adjunct treatment strategy to reduce side effects in aged populations.

Reduced mitochondrial mass and function add to age-related susceptibility toward diet-induced fatty liver in C57BL/6J mice.

PubMed

Lohr, Kerstin; Pachl, Fiona; Moghaddas Gholami, Amin; Geillinger, Kerstin E; Daniel, Hannelore; Kuster, Bernhard; Klingenspor, Martin

2016-10-01

Nonalcoholic fatty liver disease (NAFLD) is a major health burden in the aging society with an urging medical need for a better understanding of the underlying mechanisms. Mitochondrial fatty acid oxidation and mitochondrial-derived reactive oxygen species (ROS) are considered critical in the development of hepatic steatosis, the hallmark of NAFLD. Our study addressed in C57BL/6J mice the effect of high fat diet feeding and age on liver mitochondria at an early stage of NAFLD development. We therefore analyzed functional characteristics of hepatic mitochondria and associated alterations in the mitochondrial proteome in response to high fat feeding in adolescent, young adult, and middle-aged mice. Susceptibility to diet-induced obesity increased with age. Young adult and middle-aged mice developed fatty liver, but not adolescent mice. Fat accumulation was negatively correlated with an age-related reduction in mitochondrial mass and aggravated by a reduced capacity of fatty acid oxidation in high fat-fed mice. Irrespective of age, high fat diet increased ROS production in hepatic mitochondria associated with a balanced nuclear factor erythroid-derived 2 like 2 (NFE2L2) dependent antioxidative response, most likely triggered by reduced tethering of NFE2L2 to mitochondrial phosphoglycerate mutase 5. Age indirectly influenced mitochondrial function by reducing mitochondrial mass, thus exacerbating diet-induced fat accumulation. Therefore, consideration of age in metabolic studies must be emphasized. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Susceptibility to distraction during reading in young, young-old, and old-old adults.

PubMed

McGinnis, Debra

2012-01-01

BACKGROUND/STUDY CONTEXT: Susceptibility to distraction during reading may increase with age, resulting in comprehension errors. Neurological integrity and cognitive reserve are possible covariates of age-related distraction susceptibility. The current study investigated distraction susceptibility in three age groups (young, young-old, and old-old), and examined the covariation patterns of variable sets associated with neurological integrity and cognitive reserve. Participants responded to comprehension questions after reading stories that included semantically related or semantically unrelated distractors. Neurological integrity measures consisted of Mini-Mental State Examination, Selective Reminding, and Category Fluency. Cognitive reserve measures consisted of education and vocabulary. Old-old adults were more likely than young and young-old adults to select distractors when responding to comprehension questions (24.02%, 11.95%, 3.68%, respectively). Age-related distraction variance significantly overlapped neurological variance, and became more transparent after cognitive reserve variance was controlled. This study augments previous age-related distraction research by highlighting (a) the increase in distraction susceptibility in adults over 79, particularly when distractors are semantically related; (b) the influence of age-related neurological integrity on distraction; and (c) the possibility that education and verbal experience may decrease distraction susceptibility, consistent with cognitive reserve frameworks.

AGING-RELATED CARBARYL EFFECTS IN BROWN NORWAY RATS

EPA Science Inventory

The rapid increase in older adults in the population highlights the importance ofunderstanding the role of aging in susceptibility to environmental contaminants. Aspart of a larger research program on life-stage susceptibility, this experiment determined the effect of the carbama...

Age-Related Macular Degeneration: Genetics and Biology Coming Together

PubMed Central

Fritsche, Lars G.; Fariss, Robert N.; Stambolian, Dwight; Abecasis, Gonçalo R.; Curcio, Christine A.

2014-01-01

Genetic and genomic studies have enhanced our understanding of complex neurodegenerative diseases that exert a devastating impact on individuals and society. One such disease, age-related macular degeneration (AMD), is a major cause of progressive and debilitating visual impairment. Since the pioneering discovery in 2005 of complement factor H (CFH) as a major AMD susceptibility gene, extensive investigations have confirmed 19 additional genetic risk loci, and more are anticipated. In addition to common variants identified by now-conventional genome-wide association studies, targeted genomic sequencing and exome-chip analyses are uncovering rare variant alleles of high impact. Here, we provide a critical review of the ongoing genetic studies and of common and rare risk variants at a total of 20 susceptibility loci, which together explain 40–60% of the disease heritability but provide limited power for diagnostic testing of disease risk. Identification of these susceptibility loci has begun to untangle the complex biological pathways underlying AMD pathophysiology, pointing to new testable paradigms for treatment. PMID:24773320

The Hayflick Limit and Age-Related Adaptive Immune Deficiency.

PubMed

Gill, Zoe; Nieuwoudt, Martin; Ndifon, Wilfred

2018-01-01

The adaptive immune system (AIS) acquires significant deficiency during chronological ageing, making older individuals more susceptible to infections and less responsive to vaccines compared to younger individuals. At the cellular level, one of the most striking features of this ageing-related immune deficiency is the dramatic loss of T-cell diversity that occurs in elderly humans. After the age of 70 years, there is a sharp decline in the diversity of naïve T cells, including a >10-fold decrease in the CD4+ compartment and a >100-fold decrease in the CD8+ compartment. Such changes are detrimental because the AIS relies on a diverse naïve T-cell pool to respond to novel pathogens. Recent work suggests that this collapse of naïve T-cell diversity results from T cells reaching the Hayflick limit and being eliminated through both antigen-dependent and -independent pathways. The progressive attrition of telomeres is the molecular mechanism that underlies this Hayflick limit. Therefore, we propose that by measuring the telomere lengths of T cells with high resolution, it is possible to develop a unique biomarker of immune deficiency, potentially much better correlated with individual susceptibility to diseases compared to chronological age alone. © 2017 S. Karger AG, Basel.

Scharioth Macula Lens: A new intraocular implant for low-vision patients with stabilized maculopathy- first experience.

PubMed

Nekolova, Jana; Rozsival, Pavel; Sin, Martin; Jiraskova, Nada

2017-06-01

To present the initial results of Scharioth Macula Lens (SML) implantation. The SML is a new add-on intraocular lens designed to increase uncorrected near visual acuity (UCVA) in patients with stabilized maculopathy. Eight patients were included in the study. All met the indication criteria before SML implantation. An SML was implanted in the better seeing eye. Near and distance visual acuity were tested. Possible complications and patient complaints were recorded and patients were asked about their quality of vision after SML implantation. The examination was carried out on day 1, 1 week, 1, 3 and 6 months after surgery. Six-month-results are presented. Apart from one, all patients with the SML had good near visual acuity at a recommended reading distance of 15 cm. Preoperatively, the mean (min-max) near UCVA was J13 (J8-J16), mean distance BCVA was 0.27. Postoperatively, the best results were after 1 month - near UCVA was J2.5 (J1-J7), distance BCVA was 0.26. Three months after surgery, this decreased to J4.5 (J1-J8); distance VA remained 0.25. Six months postoperatively - near vision was J4 (J1-J8) and distance VA was unchanged. Patients reported problems with reading speed and reading distance. Daily exercise improved their reading ability. One patient converted to wet AMD 3 months post-implantation. The SML is a new hope for low-vision patients. It acts as a magnifier in the eye. It is a suitable method for increasing near visual acuity in patients with inactive maculopathy.

The Minnesota Grading System using fundus autofluorescence of eye bank eyes: a correlation to age-related macular degeneration (an AOS thesis).

PubMed

Olsen, Timothy W

2008-01-01

To establish a grading system of eye bank eyes using fundus autofluorescence (FAF) and identify a methodology that correlates FAF to age-related macular degeneration (AMD) with clinical correlation to the Age-Related Eye Disease Study (AREDS). Two hundred sixty-two eye bank eyes were evaluated using a standardized analysis of FAF. Measurements were taken with the confocal scanning laser ophthalmoscope (cSLO). First, high-resolution, digital, stereoscopic, color images were obtained and graded according to AREDS criteria. With the neurosensory retina removed, mean FAF values were obtained from cSLO images using software analysis that excludes areas of atrophy and other artifact, generating an FAF value from a grading template. Age and AMD grade were compared to FAF values. An internal fluorescence reference standard was tested. Standardization of the cSLO machine demonstrated that reliable data could be acquired after a 1-hour warm-up. Images obtained prior to 1 hour had falsely elevated levels of FAF. In this initial analysis, there was no statistical correlation of age to mean FAF. There was a statistically significant decrease in FAF from AREDS grade 1, 2 to 3, 4 (P < .0001). An internal fluorescent standard may serve as a quantitative reference. The Minnesota Grading System (MGS) of FAF (MGS-FAF) establishes a standardized methodology for grading eye bank tissue to quantify FAF compounds in the retinal pigment epithelium and correlate these findings to the AREDS. Future studies could then correlate specific FAF to the aging process, histopathology AMD phenotypes, and other maculopathies, as well as to analyze the biochemistry of autofluorescent fluorophores.

Refractive Error and the Risk of Age-Related Macular Degeneration in the South Korean Population.

PubMed

Lin, Shuai-Chun; Singh, Kuldev; Chao, Daniel L; Lin, Shan C

2016-01-01

We investigated the association between refractive error and the prevalence of age-related macular degeneration (AMD) in a population-based study. This was a cross-sectional study. Right eyes were included from 14,067 participants aged 40 years and older with gradable fundus photographs and refraction data from the fourth and the fifth Korea National Health and Nutrition Examination Survey 2008 to 2011. Early and late AMD was graded based on the International Age-Related Maculopathy Epidemiological Study Group grading system. Autorefraction data were collected to calculate spherical equivalent refraction in diopters (D) and classified into 4 groups: hyperopia (≥1.0 D), emmetropia (-0.99 to 0.99 D), mild myopia (-1.0 to -2.99 D), and moderate to high myopia (≤-3.0 D). After adjustment for potential confounders, each diopter increase in spherical equivalent was associated with a 16% [odds ratio (OR), 1.16; 95% confidence interval (CI), 1.08-1.25] and 18% (OR, 1.18; 95% CI, 1.10-1.27) increased risk of any (early + late) and early AMD, respectively. Mild and moderate to high myopia were associated with lower odds of any and early AMD compared with hyperopia (any AMD: OR, 0.62; 95% CI, 0.4-0.95 for mild myopia; OR, 0.41; 95% CI, 0.21-0.81 for moderate to high myopia; early AMD: OR, 0.63; 95% CI, 0.4-0.99 for mild myopia; OR, 0.36; 95% CI, 0.16-0.77 for moderate to high myopia group). There was no association between refractive status and the likelihood of late AMD (P = 0.91). Myopia is associated with lower odds of any and early AMD, but not with late AMD in the South Korean population.

Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and Proteasomal Dysfunction and Immune Activation in Human Thyroid

PubMed Central

Cho, Byuri Angela; Yoo, Seong-Keun; Song, Young Shin; Kim, Su-jin; Lee, Kyu Eun; Shong, Minho

2018-01-01

Background: Elucidating aging-related transcriptomic changes in human organs is necessary to understand the aging physiology and mechanisms, but little is known regarding the thyroid gland. We investigated aging-related transcriptomic alterations in the human thyroid gland and characterized the related molecular functions. Methods: Publicly available RNA sequencing data of 322 thyroid tissue samples from the Genotype-Tissue Expression project were analyzed. In addition, our own 64 RNA sequencing data of normal thyroid tissue samples were used as a validation set. To comprehensively evaluate the associations between aging and transcriptomic changes, we performed a weighted gene coexpression network analysis and pathway enrichment analysis. The thyroid differentiation score was then used for further analysis, defining the correlations between thyroid differentiation and aging. Results: The most significant aging-related transcriptomic change in thyroid was the downregulation of genes related to the mitochondrial and proteasomal functions (p = 3 × 10−6). Moreover, genes that are associated with immune processes were significantly upregulated with age (p = 3 × 10−4), and all of them overlapped with the upregulated genes in the thyroid glands affected by lymphocytic thyroiditis. Furthermore, these aging-related changes were not significantly different according to sex, but in terms of the thyroid differentiation, females were more susceptible to aging-related changes (p for trend = 0.03). Conclusions: Aging-related transcriptomic changes in the thyroid gland were associated with mitochondrial and proteasomal dysfunction, loss of differentiation, and activation of autoimmune processes. Our results provide clues to better understanding the age-related decline in thyroid function and higher susceptibility to autoimmune thyroid disease. PMID:29652618

Prevalence and Cardiovascular Associations of Diabetic Retinopathy and Maculopathy: Results from the Gutenberg Health Study.

PubMed

Raum, Philipp; Lamparter, Julia; Ponto, Katharina A; Peto, Tunde; Hoehn, René; Schulz, Andreas; Schneider, Astrid; Wild, Philipp S; Pfeiffer, Norbert; Mirshahi, Alireza

2015-01-01

Diabetic retinopathy (DR) is the leading cause of blindness in people of working age. The purpose of this paper is to report the prevalence and cardiovascular associations of diabetic retinopathy and maculopathy (DMac) in Germany. The Gutenberg Health Study (GHS) is a population-based study with 15,010 participants aged between 35 at 74 years from the city of Mainz and the district of Mainz-Bingen. We determined the weighted prevalence of DR and DMac by assessing fundus photographs of persons with diabetes from the GHS data base. Diabetes was defined as HbA1c ≥ 6.5%, known diagnosis diabetes mellitus or known diabetes medication. Furthermore, we analysed the association between DR and cardiovascular risk factors and diseases. Overall, 7.5% (1,124/15,010) of the GHS cohort had diabetes. Of these, 27.7% were unaware of their disease and thus were newly diagnosed by their participation in the GHS. The prevalence of DR and DMac was 21.7% and 2.3%, respectively among patients with diabetes. Vision-threatening disease was present in 5% of the diabetic cohort. In the multivariable analysis DR (all types) was associated with age (Odds Ratio [95% confidence interval]: 0.97 [0.955-0.992]; p = 0.006) arterial hypertension (1.90 [1.190-3.044]; p = 0.0072) and vision-threatening DR with obesity (3.29 [1.504-7.206]; p = 0.0029). DR (all stages) and vision-threatening DR were associated with duration of diabetes (1.09 [1.068-1.114]; p<0.0001 and 1.18 [1.137-1.222]; p<0.0001, respectively). Our calculations suggest that approximately 142 000 persons aged between 35 and 74 years have vision threatening diabetic retinal disease in Germany [corrected].Prevalence of DR was lower in the GHS compared to East-Asian studies. Associations were found with age, arterial hypertension, obesity, and duration of diabetes mellitus.

Markers of inflammation, oxidative stress, and endothelial dysfunction and the 20-year cumulative incidence of early age-related macular degeneration: the Beaver Dam Eye Study.

PubMed

Klein, Ronald; Myers, Chelsea E; Cruickshanks, Karen J; Gangnon, Ronald E; Danforth, Lorraine G; Sivakumaran, Theru A; Iyengar, Sudha K; Tsai, Michael Y; Klein, Barbara E K

2014-04-01

IMPORTANCE Modifying levels of factors associated with age-related macular degeneration (AMD) may decrease the risk for visual impairment in older persons. OBJECTIVE To examine the relationships of markers of inflammation, oxidative stress, and endothelial dysfunction to the 20-year cumulative incidence of early AMD. DESIGN, SETTING, AND PARTICIPANTS This longitudinal population-based cohort study involved a random sample of 975 persons in the Beaver Dam Eye Study without signs of AMD who participated in the baseline examination in 1988-1990 and up to 4 follow-up examinations in 1993-1995, 1998-2000, 2003-2005, and 2008-2010. EXPOSURES Serum markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, interleukin-6, and white blood cell count), oxidative stress (8-isoprostane and total carbonyl content), and endothelial dysfunction (soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1) were measured. Interactions with complement factor H (rs1061170), age-related maculopathy susceptibility 2 (rs10490924), complement component 3 (rs2230199), and complement component 2/complement factor B (rs4151667) were examined using multiplicative models. Age-related macular degeneration was assessed from fundus photographs. MAIN OUTCOMES AND MEASURES Early AMD defined by the presence of any size drusen and the presence of pigmentary abnormalities or by the presence of large-sized drusen (≥125-μm diameter) in the absence of late AMD. RESULTS The 20-year cumulative incidence of early AMD was 23.0%. Adjusting for age, sex, and other risk factors, high-sensitivity C-reactive protein (odds ratio comparing fourth with first quartile, 2.18; P = .005), tumor necrosis factor-α receptor 2 (odds ratio, 1.78; P = .04), and interleukin-6 (odds ratio, 1.78; P = .03) were associated with the incidence of early AMD. Increased incidence of early AMD was associated with soluble vascular cell adhesion molecule

MRI Estimates of Brain Iron Concentration in Normal Aging Using Quantitative Susceptibility Mapping

PubMed Central

Bilgic, Berkin; Pfefferbaum, Adolf; Rohlfing, Torsten; Sullivan, Edith V.; Adalsteinsson, Elfar

2011-01-01

FDRI, which again yielded perfect rank ordering of iron by brain structure. The final means of validation was to assess how well each in vivo method detected known age-related differences in regional iron concentrations measured in the same young and elderly healthy adults. Both QSM methods and FDRI were consistent in identifying higher iron concentrations in striatal and brain stem ROIs (i.e., caudate nucleus, putamen, globus pallidus, red nucleus, and substantia nigra) in the older than in the young group. The two QSM methods appeared more sensitive in detecting age differences in brain stem structures as they revealed differences of much higher statistical significance between the young and elderly groups than did FDRI. However, QSM values are influenced by factors such as the myelin content, whereas FDRI is a more specific indicator of iron content. Hence, FDRI demonstrated higher specificity to iron yet yielded noisier data despite longer scan times and lower spatial resolution than QSM. The robustness, practicality, and demonstrated ability of predicting the change in iron deposition in adult aging suggest that regularized QSM algorithms using single-field-strength data are possible alternatives to tissue iron estimation requiring two field strengths. PMID:21925274

Bevacizumab Therapy and Multimodal Ultra-widefield Imaging in Immunogammopathy Maculopathy Secondary to Waldenstrom’s Macroglobulinemia

PubMed Central

Xu, Lucy T.; Courtney, Robert J.; Ehlers, Justis P

2015-01-01

Waldenstrom’s macroglobulinemia (WM) is associated with retinal findings of hyperviscosity such as venous dilation, and findings of immunogammopathy maculopathy such as serous macular detachment. The report describes a case of bilateral serous macular detachment with intraretinal schisis-like fluid in a patient with WM. Enhanced depth imaging OCT revealed a thickened choroid with hyper-reflective accumulations in the RPE layer. The ultra-widefield fundus autofluorescence demonstrated a central area of hyperautofluorescence corresponding to the area of serous macular detachment. Ultra-widefield fluorescein angiography was characteristically silent. Intravitreal bevacizumab therapy resulted in significant reduction in intraretinal fluid, but minimal change in subretinal fluid. Long-term follow-up demonstrated alterations in retinal architecture and improved serous detachments. PMID:25707055

Novel quantitative assessment of metamorphopsia in maculopathy.

PubMed

Wiecek, Emily; Lashkari, Kameran; Dakin, Steven C; Bex, Peter

2014-11-18

Patients with macular disease often report experiencing metamorphopsia (visual distortion). Although typically measured with Amsler charts, more quantitative assessments of perceived distortion are desirable to effectively monitor the presence, progression, and remediation of visual impairment. Participants with binocular (n = 33) and monocular (n = 50) maculopathy across seven disease groups, and control participants (n = 10) with no identifiable retinal disease completed a modified Amsler grid assessment (presented on a computer screen with eye tracking to ensure fixation compliance) and two novel assessments to measure metamorphopsia in the central 5° of visual field. A total of 81% (67/83) of participants completed a hyperacuity task where they aligned eight dots in the shape of a square, and 64% (32/50) of participants with monocular distortion completed a spatial alignment task using dichoptic stimuli. Ten controls completed all tasks. Horizontal and vertical distortion magnitudes were calculated for each of the three assessments. Distortion magnitudes were significantly higher in patients than controls in all assessments. There was no significant difference in magnitude of distortion across different macular diseases. There were no significant correlations between overall magnitude of distortion among any of the three measures and no significant correlations in localized measures of distortion. Three alternative quantifications of monocular spatial distortion in the central visual field generated uncorrelated estimates of visual distortion. It is therefore unlikely that metamorphopsia is caused solely by retinal displacement, but instead involves additional top-down information, knowledge about the scene, and perhaps, cortical reorganization. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Locally Learning Biomedical Data Using Diffusion Frames

DTIC Science & Technology

2012-01-01

age - related macular degeneration (AMD) patients. All eye- related data were collected by our collaborators at the...in Table 2. 6.2. Age - related macular degeneration Age - related macular degeneration is the most common cause of blindness among the elderly population...maculopathy and age - related macular degeneration . The international ARM epidemiological study group. Surv. Ophthalmol. 39, 367–374.

Human plasma paraoxonase 1 (PON1) arylesterase activity during aging: correlation with susceptibility of LDL oxidation.

PubMed

Mehdi, Mohammad Murtaza; Rizvi, Syed Ibrahim

2012-08-01

The role of free radicals has long been proposed as a cause for the aging process. Oxidative stress is considered a major factor for altering many physiological processes and enzymatic activities during aging and is also known to play a major role in the development of several age-dependent diseases. Paraoxonase 1 (PON1) is an anti-atherosclerotic enzyme that mainly prevents accumulation of lipoperoxides and inhibits the lipid oxidation in low-density lipoproteins (LDL). This study was undertaken to investigate the antioxidant behavior of PON1 by measuring its arylesterase activity. The susceptibility of LDL for oxidation and the radical scavenging activity of plasma were also measured during aging in humans. Arylesterase activity of PON1 was measured in plasma of human subjects between 20 and 81 years of age of both genders. The susceptibility of LDL for oxidation and radical scavenging activity were measured in plasma. Decrease in plasma arylesterase activity of PON1, increase in susceptibility of LDL for oxidation and decrease in plasma radical scavenging activity were observed as a function of human age. The study provides evidence of a relationship between PON1 activity, LDL oxidation and free radical scavenging activity of plasma. The present results emphasize the dependency of PON1 activity to prevailing oxidative stress during human aging. Our findings assume significance in view of the possible categorization of PON1 as a longevity gene. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

Epigenetic susceptibility factors for prostate cancer with aging.

PubMed

Damaschke, N A; Yang, B; Bhusari, S; Svaren, J P; Jarrard, D F

2013-12-01

Increasing age is a significant risk factor for prostate cancer. The prostate is exposed to environmental and endogenous stress that may underlie this remarkable incidence. DNA methylation, genomic imprinting, and histone modifications are examples of epigenetic factors known to undergo change in the aging and cancerous prostate. In this review we examine the data linking epigenetic alterations in the prostate with aging to cancer development. An online search of current and past peer reviewed literature on epigenetic changes with cancer and aging was performed. Relevant articles were analyzed. Epigenetic changes are responsible for modifying expression of oncogenes and tumor suppressors. Several of these changes may represent a field defect that predisposes to cancer development. Focal hypermethylation occurs at CpG islands in the promoters of certain genes including GSTP1, RARβ2, and RASSF1A with both age and cancer, while global hypomethylation is seen in prostate cancer and known to occur in the colon and other organs. A loss of genomic imprinting is responsible for biallelic expression of the well-known Insulin-like Growth Factor 2 (IGF2) gene. Loss of imprinting (LOI) at IGF2 has been documented in cancer and is also known to occur in benign aging prostate tissue marking the presence of cancer. Histone modifications have the ability to dictate chromatin structure and direct gene expression. Epigenetic changes with aging represent molecular mechanisms to explain the increased susceptibly of the prostate to develop cancer in older men. These changes may provide an opportunity for diagnostic and chemopreventive strategies given the epigenome can be modified. © 2013 Wiley Periodicals, Inc.

Age-related effects of dexamethasone administration in adrenal zona reticularis.

PubMed

Almeida, Henrique; Matos, Liliana; Ferreira, Jorge; Neves, Delminda

2006-05-01

Suppression of adrenocorticotropic hormone results in reduced adrenal steroid output, adrenocortical cell atrophy, and apoptosis in young rats. To verify such effects during aging, dexamethasone was injected into rats for 3 days at five different ages; at day 4, adrenals and blood were collected for morphologic and corticosterone assay. Adrenal structure was similar at all ages, but in dexamethasone-injected animals there were ultrastructural features of apoptosis and a higher percentage of TUNEL and caspase-3-labeled nuclei and cytoplasm; their corticosterone decreased significantly. In both groups, there was age-related decrease in the percentage of apoptotic cells, significant only in dexamethasone-injected rats. The data suggest that aged adrenocortical cells are less susceptible to the lack of adrenocorticotropic hormone (ACTH), possibly as a result of their decreased functional ability.

The Minnesota Grading System Using Fundus Autofluorescence of Eye Bank Eyes: A Correlation To Age-Related Macular Degeneration (An AOS Thesis)

PubMed Central

Olsen, Timothy W.

2008-01-01

Purpose To establish a grading system of eye bank eyes using fundus autofluorescence (FAF) and identify a methodology that correlates FAF to age-related macular degeneration (AMD) with clinical correlation to the Age-Related Eye Disease Study (AREDS). Methods Two hundred sixty-two eye bank eyes were evaluated using a standardized analysis of FAF. Measurements were taken with the confocal scanning laser ophthalmoscope (cSLO). First, high-resolution, digital, stereoscopic, color images were obtained and graded according to AREDS criteria. With the neurosensory retina removed, mean FAF values were obtained from cSLO images using software analysis that excludes areas of atrophy and other artifact, generating an FAF value from a grading template. Age and AMD grade were compared to FAF values. An internal fluorescence reference standard was tested. Results Standardization of the cSLO machine demonstrated that reliable data could be acquired after a 1-hour warm-up. Images obtained prior to 1 hour had falsely elevated levels of FAF. In this initial analysis, there was no statistical correlation of age to mean FAF. There was a statistically significant decrease in FAF from AREDS grade 1, 2 to 3, 4 (P < .0001). An internal fluorescent standard may serve as a quantitative reference. Conclusions The Minnesota Grading System (MGS) of FAF (MGS-FAF) establishes a standardized methodology for grading eye bank tissue to quantify FAF compounds in the retinal pigment epithelium and correlate these findings to the AREDS. Future studies could then correlate specific FAF to the aging process, histopathology AMD phenotypes, and other maculopathies, as well as to analyze the biochemistry of autofluorescent fluorophores. PMID:19277247

[Analysis of measles immunity level and serological susceptibility among Yunnan residents aged ≥20 years].

PubMed

Zhao, Z X; Zhou, R R; Li, L Q; Yu, W; Li, Q F; Hu, P

2018-01-06

Objective: To evaluate the population immunity to measles and explore the factors associated with measles susceptibility in Yunnan residents aged ≥20 years. Methods: 2 689 residents aged ≥20 years were selected by multistage stratified systematic randomized sampling in 252 villages of 42 counties in Yunnan Province between June and September in 2015. Each subject was surveyed by the same questionnaire, including general information, measles contained vaccine history, measles history, and 5 ml blood sample of each subject was collected. Serum IgG antibodies against measles virus were measured by ELISA. Positive was defined as the antibody concentration ≥250 mU/ml, and negative as <250 mU/ml. Non-conditional logistic regression model was used analyze the factors associated with measles susceptibility in adults. Results: Among 2 689 subjects, 1 214 were males (45.15%), and the overall positive rate of measles IgG antibody was 89.77%. Compared with subjects from the region where economic development was low, subjects from the region where economic development was moderate were likely to be susceptible to measles virus ( OR= 1.81, 95 %CI: 1.33-2.47). Four age groups had higher risk of being susceptible to measles virus (compared with ≥40 years: 20-24 years old, OR= 2.04, 95 %CI: 1.26-3.31; 25-29 years old, OR= 3.72, 95 %CI: 2.37-5.86; 30-34 years old, OR= 1.94, 95 %CI: 1.22-3.09; 35-39 years old, OR= 1.81, 95 %CI: 1.07-3.05). Conclusion: Our results suggest that the serological susceptibility in adults (20-39 years), especially adults from the regions where the economic development was moderate, should be concerned. The additional vaccination strategy targeting young adults is important for reducing the risk of measles infection.

Cognitive and neuropsychological underpinnings of relational and conjunctive working memory binding across age.

PubMed

van Geldorp, Bonnie; Parra, Mario A; Kessels, Roy P C

2015-01-01

The ability to form associations (i.e., binding) is critical for memory formation. Recent studies suggest that aging specifically affects relational binding (associating separate features) but not conjunctive binding (integrating features within an object). Possibly, this dissociation may be driven by the spatial nature of the studies so far. Alternatively, relational binding may simply require more attentional resources. We assessed relational and conjunctive binding in three age groups and we included an interfering task (i.e., an articulatory suppression task). Binding was examined in a working memory (WM) task using non-spatial features: shape and colour. Thirty-one young adults (mean age = 22.35), 30 middle-aged adults (mean age = 54.80) and 30 older adults (mean age = 70.27) performed the task. Results show an effect of type of binding and an effect of age but no interaction between type of binding and age. The interaction between type of binding and interference was significant. These results indicate that aging affects relational binding and conjunctive binding similarly. However, relational binding is more susceptible to interference than conjunctive binding, which suggests that relational binding may require more attentional resources. We suggest that a general decline in WM resources associated with frontal dysfunction underlies age-related deficits in WM binding.

Prevalence and determinants of age-related macular degeneration in the 50 years and older population: A hospital based study in Maharashtra, India

PubMed Central

Kulkarni, Sucheta R; Aghashe, Supriya R; Khandekar, Rajiv B; Deshpande, Madan D

2013-01-01

Background: We present the magnitude and determinants of age-related macular degeneration (ARMD) among the 50 year and older population that visited our hospital. Materials and Methods: This was a cohort of eye patients with ARMD, seen from 2006 to 2009. Optometrist noted the best-corrected vision. Ophthalmologists examined eyes using a slit-lamp bio-microscope. The ARMD was confirmed by fluoresceine angiography and optical coherent tomography. The age, sex, history of smoking, sun exposure, family history of ARMD, diet, body mass index (BMI), hypertension, and diabetes were associated with ARMD. Result: Of the 19,140 persons of ≥ 50 years of age-attending eye clinic in our hospital, 302 persons had ARMD in at least one eye. The proportion of overall ARMD was 1.38% (95% CI 1.21--1.55). The proportion of age-related maculopathy (ARM) and late ARMD was 1.14% (95% CI 0.99--1.29) and 0.24% (95% CI 0.21–0.24) respectively. ARM was unilateral and bilateral in 64 (29.2%) and 155 (70.8%) persons respectively. Dry ARMD was found in 47.8%. On regression analysis, old age (OR = 1.05), male (OR = 0.54), and history of smoking (OR = 2.32) were significant risk factors of ARMD. A total of 4.2% of persons with ARMD were blind (vision <3/60). Only 43% of persons with ARMD had J6 grade of the best-corrected near vision. Conclusion: ARMD does not seem to be of public health magnitude in the study area. Early stages of ARMD were common among patients. ge, being male, and history of smoking were significant risk factors for ARMD. PMID:23571245

Susceptibility to varicella-zoster infection in individuals 1 to 29 years of age in Mexico.

PubMed

Alvarez y Muñoz, M T; Torres, J; Damasio-Santana, L; Gómez, A; Fernández-Quintanilla, G; Tapia-Conyer, R; Muñoz, O

1999-01-01

The prevalence of varicella zoster virus (VZV) infection has been poorly studied in Latin America. The aim of this work was to study the seroprevalence of antibody to VZV infection in Mexico. Infection was determined in 3,737 individuals. Samples were collected during a national serologic survey performed during 1987-1988 and represented individuals 1- to 29-years-old from all socioeconomic levels and from rural and urban communities throughout the country. Antibodies anti-VZV were measured with a commercially available enzyme-linked immunosorbent assay (VARELISA Merck, Germany). In the population studied, 464 individuals (12.4%) were seronegative or susceptible to infection, whereas about 17.0% of individuals 1- to 19-years-old were susceptible to infection. Between the ages of 20 to 24 years, 8.4% were susceptible and between 25 to 29 years, 5.0% of persons were still susceptible to infection. Socioeconomic level, density of population, crowding, and gender were not found as risk factors for susceptibility to VZV infection in adolescents and young adults. Low educational level was found as a risk factor for susceptibility. High proportions of adolescents and young adults in Mexico are susceptible to VZV infection and should receive special attention when designing vaccination programs.

Assessing age-dependent susceptibility to measles in Japan.

PubMed

Kinoshita, Ryo; Nishiura, Hiroshi

2017-06-05

Routine vaccination against measles in Japan started in 1978. Whereas measles elimination was verified in 2015, multiple chains of measles transmission were observed in 2016. We aimed to reconstruct the age-dependent susceptibility to measles in Japan so that future vaccination strategies can be elucidated. An epidemiological model was used to quantify the age-dependent immune fraction using datasets of vaccination coverage and seroepidemiological survey. The second dose was interpreted in two different scenarios, i.e., booster and random shots. The effective reproduction number, the average number of secondary cases generated by a single infected individual, and the age at infection were explored using the age-dependent transmission model and the next generation matrix. While the herd immunity threshold of measles likely ranges from 90% to 95%, assuming that the basic reproductive number ranges from 10 to 20, the estimated immune fraction in Japan was below those thresholds in 2016, despite the fact that the estimates were above 80% for all ages. If the second dose completely acted as the booster shot, a proportion immune above 90% was achieved only among those aged 5years or below in 2016. Alternatively, if the second dose was randomly distributed regardless of primary vaccination status, a proportion immune over 90% was achieved among those aged below 25years. The effective reproduction number was estimated to range from 1.50 to 3.01 and from 1.50 to 3.00, respectively, for scenarios 1 and 2 in 2016; if the current vaccination schedule were continued, the reproduction number is projected to range from 1.50 to 3.01 and 1.39 to 2.78, respectively, in 2025. Japan continues to be prone to imported cases of measles. Supplementary vaccination among adults aged 20-49years would be effective if the chains of transmission continue to be observed in that age group. Copyright © 2017 Elsevier Ltd. All rights reserved.

How sex and age affect immune responses, susceptibility to infections, and response to vaccination

PubMed Central

Giefing-Kröll, Carmen; Berger, Peter; Lepperdinger, Günter; Grubeck-Loebenstein, Beatrix

2015-01-01

Do men die young and sick, or do women live long and healthy? By trying to explain the sexual dimorphism in life expectancy, both biological and environmental aspects are presently being addressed. Besides age-related changes, both the immune and the endocrine system exhibit significant sex-specific differences. This review deals with the aging immune system and its interplay with sex steroid hormones. Together, they impact on the etiopathology of many infectious diseases, which are still the major causes of morbidity and mortality in people at old age. Among men, susceptibilities toward many infectious diseases and the corresponding mortality rates are higher. Responses to various types of vaccination are often higher among women thereby also mounting stronger humoral responses. Women appear immune-privileged. The major sex steroid hormones exhibit opposing effects on cells of both the adaptive and the innate immune system: estradiol being mainly enhancing, testosterone by and large suppressive. However, levels of sex hormones change with age. At menopause transition, dropping estradiol potentially enhances immunosenescence effects posing postmenopausal women at additional, yet specific risks. Conclusively during aging, interventions, which distinctively consider the changing level of individual hormones, shall provide potent options in maintaining optimal immune functions. PMID:25720438

AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON BRAIN OXIDATIVE STRESS PARAMETERS IN BROWN NORWAY RATS.

EPA Science Inventory

The influence of aging on susceptibility to environmental contaminants is poorly understood. The objectives of this study were to test whether oxidative stress (OS) is a potential toxicity pathway following toluene exposure and to determine if these effects are age-dependent. We ...

Prevalence of Undiagnosed Age-Related Macular Degeneration in Primary Eye Care.

PubMed

Neely, David C; Bray, Kevin J; Huisingh, Carrie E; Clark, Mark E; McGwin, Gerald; Owsley, Cynthia

2017-06-01

Age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment in older adults in the United States, yet little is known about whether AMD is appropriately diagnosed in primary eye care. To examine the prevalence of eyes with AMD in patients seen in primary eye care clinics who purportedly have normal macular health per their medical record and the association of AMD with patient and physician characteristics. In this cross-sectional study of primary eye care practices in Birmingham, Alabama, 644 persons 60 years or older with normal macular health per medical record based on their most recent dilated comprehensive eye examination by a primary eye care ophthalmologist or optometrist were enrolled from May 1, 2009, through December 31, 2011. Data analysis was performed from May 1, 2016, through December 20, 2016. Presence of AMD as defined by the Clinical Age-Related Maculopathy Staging system based on color fundus photography and a masked grader. Types of AMD-associated lesions were noted. Patient health and physician characteristics were collected. The sample consisted of 1288 eyes from 644 participants (231 [35.9%] male and 413 [64.1%] female; mean [SD] age, 69.4 [6.1] years; 611 white [94.9%]) seen by 31 primary eye care ophthalmologists or optometrists. A total of 968 eyes (75.2%) had no AMD, in agreement with their medical record; 320 (24.8%) had AMD despite no diagnosis of AMD in the medical record. Among eyes with undiagnosed AMD, 32 (10.0%) had hyperpigmentation, 43 (13.4%) had hypopigmentation, 249 (77.8%) had small drusen, 250 (78.1%) had intermediate drusen, and 96 (30.0%) had large drusen. Undiagnosed AMD was associated with older patient age (odds ratio [OR], 1.06; 95% CI, 1.04-1.09; P < .001), male sex (age-adjusted OR, 1.39; 95% CI, 1.02-1.91; P = .04), and less than a high school education (age-adjusted OR, 2.40; 95% CI, 1.03-5.62; P = .04). Prevalence of undiagnosed AMD was not different for

3H/3He age data in assessing the susceptibility of wells to contamination

USGS Publications Warehouse

Manning, Andrew H.; Solomon, D. Kip; Thiros, Susan A.

2005-01-01

Regulatory agencies are becoming increasingly interested in using young–ground water dating techniques, such as the 3H/3He method, in assessing the susceptibility of public supply wells (PSWs) to contamination. However, recent studies emphasize that ground water samples of mixed age may be the norm, particularly from long-screened PSWs, and tracer-based “apparent” ages can differ substantially from actual mean ages for mixed-age samples. We present age and contaminant data from PSWs in Salt Lake Valley, Utah, that demonstrate the utility of 3H and 3He measurements in evaluating well susceptibility, despite potential age mixing. Initial 3H concentrations (measured 3H + measured tritiogenic 3He) are compared to those expected based on the apparent 3H/3He age and the local precipitation 3H record. This comparison is used to determine the amount of modern water (recharged after ∼1950) vs. prebomb water (recharged before ∼1950) samples might contain. Concentrations of common contaminants were also measured using detection limits generally lower than those used for regulatory purposes. A clear correlation exists between the potential magnitude of the modern water fraction and both the occurrence and concentration of contaminants. For samples containing dominantly modern water based on their initial 3H concentrations, potential discrepancies between apparent 3H/3He ages and mean ages are explored using synthetic samples that are random mixtures of different modern waters. Apparent ages can exceed mean ages by up to 13 years for these samples, with an exponential age distribution resulting in the greatest discrepancies.

Assessing Susceptibility to Age-Related Macular Degeneration With Genetic Markers and Environmental Factors

PubMed Central

Chen, Yuhong; Zeng, Jiexi; Zhao, Chao; Wang, Kevin; Trood, Elizabeth; Buehler, Jeanette; Weed, Matthew; Kasuga, Daniel; Bernstein, Paul S.; Hughes, Guy; Fu, Victoria; Chin, Jessica; Lee, Clara; Crocker, Maureen; Bedell, Matthew; Salasar, Francesca; Yang, Zhenglin; Goldbaum, Michael; Ferreyra, Henry; Freeman, William R.; Kozak, Igor; Zhang, Kang

2014-01-01

Objectives To evaluate the independent and joint effects of genetic factors and environmental variables on advanced forms of age-related macular degeneration (AMD), including geographic atrophy and choroidal neovascularization, and to develop a predictive model with genetic and environmental factors included. Methods Demographic information, including age at onset, smoking status, and body mass index, was collected for 1844 participants. Genotypes were evaluated for 8 variants in 5 genes related to AMD. Unconditional logistic regression analyses were performed to generate a risk predictive model. Results All genetic variants showed a strong association with AMD. Multivariate odds ratios were 3.52 (95% confidence interval, 2.08-5.94) for complement factor H, CFH rs1061170 CC, 4.21 (2.30-7.70) for CFH rs2274700 CC, 0.46 (0.27-0.80) for C2 rs9332739 CC/CG, 0.44 (0.30-0.66) for CFB rs641153 TT/CT, 10.99 (6.04-19.97) for HTRA1/LOC387715 rs10490924 TT, and 2.66 (1.43-4.96) for C3 rs2230199 GG. Smoking was independently associated with advanced AMD after controlling for age, sex, body mass index, and all genetic variants. Conclusion CFH confers more risk to the bilaterality of geographic atrophy, whereas HTRA1/LOC387715 contributes more to the bilaterality of choroidal neovascularization. C3 confers more risk for geographic atrophy than choroidal neovascularization. Risk models with combined genetic and environmental factors have notable discrimination power. Clinical Relevance Early detection and risk prediction of AMD could help to improve the prognosis of AMD and to reduce the outcome of blindness. Targeting high-risk individuals for surveillance and clinical interventions may help reduce disease burden. PMID:21402993

SPECTRAL DOMAIN VERSUS SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE RETINAL CAPILLARY PLEXUSES IN SICKLE CELL MACULOPATHY.

PubMed

Jung, Jesse J; Chen, Michael H; Frambach, Caroline R; Rofagha, Soraya; Lee, Scott S

2018-01-01

To compare the spectral domain and swept source optical coherence tomography angiography findings in two cases of sickle cell maculopathy. A 53-year-old man and a 24-year-old man both with sickle cell disease (hemoglobin SS) presented with no visual complaints; Humphrey visual field testing demonstrated asymptomatic paracentral scotomas that extended nasally in the involved eyes. Clinical examination and multimodal imaging including spectral domain and swept source optical coherence tomography, and spectral domain optical coherence tomography angiography and swept source optical coherence tomography angiography (Carl Zeiss Meditec Inc, Dublin, CA) were performed. Fundus examination of both patients revealed subtle thinning of the macula. En-face swept source optical coherence tomography confirmed the extent of the thinning correlating with the functional paracentral scotomas on Humphrey visual field. Swept source optical coherence tomography B-scan revealed multiple confluent areas of inner nuclear thinning and significant temporal retinal atrophy. En-face 6 × 6-mm spectral domain optical coherence tomography angiography of the macula demonstrated greater loss of the deep capillary plexus compared with the superficial capillary plexus. Swept source optical coherence tomography angiography 12 × 12-mm imaging captured the same macular findings and loss of both plexuses temporally outside the macula. In these two cases of sickle cell maculopathy, deep capillary plexus ischemia is more extensive within the macula, whereas both the superficial capillary plexus and deep capillary plexus are involved outside the macula likely due to the greater oxygen demands and watershed nature of these areas. Swept source optical coherence tomography angiography clearly demonstrates the angiographic extent of the disease correlating with the Humphrey visual field scotomas and confluent areas of inner nuclear atrophy.

Age- and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters

PubMed Central

Kang, Seok Kyu; Markowitz, Geoffrey J.; Kim, Shin Tae; Johnston, Michael V.; Kadam, Shilpa D.

2015-01-01

Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB), with NKCC1 antagonist bumetanide (BTN) as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in post-natal day 7, 10, and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs) quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy. PMID:26029047

Age- and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters.

PubMed

Kang, Seok Kyu; Markowitz, Geoffrey J; Kim, Shin Tae; Johnston, Michael V; Kadam, Shilpa D

2015-01-01

Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB), with NKCC1 antagonist bumetanide (BTN) as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in post-natal day 7, 10, and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs) quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.

Impact of Host Age and Parity on Susceptibility to Severe Urinary Tract Infection in a Murine Model

PubMed Central

Kline, Kimberly A.; Schwartz, Drew J.; Gilbert, Nicole M.; Lewis, Amanda L.

2014-01-01

The epidemiology and bacteriology of urinary tract infection (UTI) varies across the human lifespan, but the reasons for these differences are poorly understood. Using established monomicrobial and polymicrobial murine UTI models caused by uropathogenic Escherichia coli (UPEC) and/or Group B Streptococcus (GBS), we demonstrate age and parity as inter-related factors contributing to UTI susceptibility. Young nulliparous animals exhibited 10–100-fold higher bacterial titers compared to older animals. In contrast, multiparity was associated with more severe acute cystitis in older animals compared to age-matched nulliparous controls, particularly in the context of polymicrobial infection where UPEC titers were ∼1000-fold higher in the multiparous compared to the nulliparous host. Multiparity was also associated with significantly increased risk of chronic high titer UPEC cystitis and ascending pyelonephritis. Further evidence is provided that the increased UPEC load in multiparous animals required TLR4-signaling. Together, these data strongly suggest that the experience of childbearing fundamentally and permanently changes the urinary tract and its response to pathogens in a manner that increases susceptibility to severe UTI. Moreover, this murine model provides a system for dissecting these and other lifespan-associated risk factors contributing to severe UTI in at-risk groups. PMID:24835885

Impact of host age and parity on susceptibility to severe urinary tract infection in a murine model.

PubMed

Kline, Kimberly A; Schwartz, Drew J; Gilbert, Nicole M; Lewis, Amanda L

2014-01-01

The epidemiology and bacteriology of urinary tract infection (UTI) varies across the human lifespan, but the reasons for these differences are poorly understood. Using established monomicrobial and polymicrobial murine UTI models caused by uropathogenic Escherichia coli (UPEC) and/or Group B Streptococcus (GBS), we demonstrate age and parity as inter-related factors contributing to UTI susceptibility. Young nulliparous animals exhibited 10-100-fold higher bacterial titers compared to older animals. In contrast, multiparity was associated with more severe acute cystitis in older animals compared to age-matched nulliparous controls, particularly in the context of polymicrobial infection where UPEC titers were ∼1000-fold higher in the multiparous compared to the nulliparous host. Multiparity was also associated with significantly increased risk of chronic high titer UPEC cystitis and ascending pyelonephritis. Further evidence is provided that the increased UPEC load in multiparous animals required TLR4-signaling. Together, these data strongly suggest that the experience of childbearing fundamentally and permanently changes the urinary tract and its response to pathogens in a manner that increases susceptibility to severe UTI. Moreover, this murine model provides a system for dissecting these and other lifespan-associated risk factors contributing to severe UTI in at-risk groups.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT AT 2-MONTH INTERVALS REDUCES FOVEAL AVASCULAR ZONE ENLARGEMENT AND VISION LOSS IN RADIATION MACULOPATHY: A Pilot Study.

PubMed

Daruich, Alejandra; Matet, Alexandre; Schalenbourg, Ann; Zografos, Leonidas

2018-05-03

To evaluate, in eyes with radiation maculopathy, the effect of 2-month-interval anti-vascular endothelial growth factor therapy on best-corrected visual acuity and foveal avascular zone (FAZ) enlargement using optical coherence tomography angiography. Consecutive treatment-naive patients with radiation maculopathy after proton beam irradiation for choroidal melanoma were retrospectively included. Clinical and optical coherence tomography angiography data at baseline and the 6-month visit were recorded. Two independent observers measured FAZ area manually on 3 × 3-mm optical coherence tomography angiography images of the superficial capillary plexus and deep capillary plexus. Patients were encouraged to follow strictly a 2-month-interval intravitreal anti-vascular endothelial growth factor treatment by either bevacizumab or ranibizumab. Findings were analyzed based on the adherence to the treatment scheme. According to the adherence to the bimonthly anti-vascular endothelial growth factor treatment protocol, patients were categorized into 3 groups: treatment protocol (n = 19, strict adherence), variable intervals (n = 11, intervals other than 2 months), and no treatment (n = 11). The estimated radiation dose to the foveola in each group was 49 ± 16, 46 ± 17, and 46 ± 18 cobalt gray equivalent, respectively (P = 0.85). For the entire cohort, best-corrected visual acuity loss (P < 0.02) and FAZ enlargement (P < 0.0001) were observed over 6 months. Best-corrected visual acuity loss was significantly less pronounced in the treatment-protocol group than in the variable-interval and no-treatment groups (P = 0.007 and P = 0.004). The FAZ enlargement was lower in the treatment-protocol group compared with the variable-interval group for both superficial capillary plexus (P = 0.029) and deep capillary plexus (P = 0.03), and to the no-treatment group for the deep capillary plexus only (P = 0.016). Decrease in best-corrected visual acuity and FAZ enlargement on optical

Prevalence of and susceptibility to cigarette smoking among female students aged 13 to 15 years in Vietnam, 2007.

PubMed

Minh, Hoang Van; Hai, Phan Thi; Giang, Kim Bao; Kinh, Ly Ngoc

2010-01-01

Recent reports show a sharp increase in smoking rates among girls. We describe prevalence of cigarette smoking and susceptibility to cigarette smoking among female students aged 13 to 15 years in Vietnam and examine the associated factors. We used data from female secondary school students aged 13 to 15 years (grades 8-10) from the 2007 Global Youth Tobacco Survey that was conducted in 9 provinces in Vietnam. We used multivariate logistic regression analysis to determine associations between independent variables with smoking status and susceptibility to smoking. Prevalence of cigarette smoking among girls was 1.2% (95% confidence interval [CI], 0.9-1.5), and 1.5% (95% CI, 1.2-1.9) of girls were susceptible to smoking. Having friends who smoke was the strongest predictor of both smoking status and susceptibility to smoking. Attendance at school classes that described the harmful effects of smoking had significant effects in reducing cigarette smoking. Girls who were exposed to billboard cigarette advertising were more likely to be susceptible to smoking than were those who had not seen advertisements. Our findings highlight the need for pursuing school-based intervention programs in Vietnam and for countering tobacco advertising and marketing practices that target young women.

Sex differences in metabolic aging of the brain: insights into female susceptibility to Alzheimer's disease.

PubMed

Zhao, Liqin; Mao, Zisu; Woody, Sarah K; Brinton, Roberta D

2016-06-01

Despite recent advances in the understanding of clinical aspects of sex differences in Alzheimer's disease (AD), the underlying mechanisms, for instance, how sex modifies AD risk and why the female brain is more susceptible to AD, are not clear. The purpose of this study is to elucidate sex disparities in brain aging profiles focusing on 2 major areas-energy and amyloid metabolism-that are most significantly affected in preclinical development of AD. Total RNA isolated from hippocampal tissues of both female and male 129/C57BL/6 mice at ages of 6, 9, 12, or 15 months were comparatively analyzed by custom-designed Taqman low-density arrays for quantitative real-time polymerase chain reaction detection of a total of 182 genes involved in a broad spectrum of biological processes modulating energy production and amyloid homeostasis. Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains. In female brains, 44.2% of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation. In contrast, in male brains, only 5.4% of genes were significantly altered at this age transition. Subsequent changes in female brains were at a much smaller magnitude, including 10.9% from 9 months to 12 months and 6.1% from 12 months to 15 months. In male brains, most changes occurred from 12 months to 15 months and the majority were upregulated. Furthermore, gene network analysis revealed that clusterin appeared to serve as a link between the overall decreased bioenergetic metabolism and increased amyloid dyshomeostasis associated with the earliest transition in female brains. Together, results from this study indicate that: (1) female and male brains follow profoundly dissimilar trajectories as they age; (2) female brains undergo age-related changes much earlier than male brains; (3) early changes in female brains signal the onset of a hypometabolic phenotype at risk for AD. These

Age and prior blood feeding of Anopheles gambiae influences their susceptibility and gene expression patterns to ivermectin-containing blood meals.

PubMed

Seaman, Jonathan A; Alout, Haoues; Meyers, Jacob I; Stenglein, Mark D; Dabiré, Roch K; Lozano-Fuentes, Saul; Burton, Timothy A; Kuklinski, Wojtek S; Black, William C; Foy, Brian D

2015-10-15

Ivermectin has been proposed as a novel malaria transmission control tool based on its insecticidal properties and unique route of acquisition through human blood. To maximize ivermectin's effect and identify potential resistance/tolerance mechanisms, it is important to understand its effect on mosquito physiology and potential to shift mosquito population age-structure. We therefore investigated ivermectin susceptibility and gene expression changes in several age groups of female Anopheles gambiae mosquitoes. The effect of aging on ivermectin susceptibility was analyzed in three age groups (2, 6, and 14-days) of colonized female Anopheles gambiaemosquitoes using standard survivorship assays. Gene expression patterns were then analyzed by transcriptome sequencing on an Illumina HiSeq 2500 platform. RT-qPCR was used to validate transcriptional changes and also to examine expression in a different, colonized strain and in wild mosquitoes, both of which blood fed naturally on an ivermectin-treated person. Mosquitoes of different ages and blood meal history died at different frequencies after ingesting ivermectin. Mortality was lowest in 2-day old mosquitoes exposed on their first blood meal and highest in 6-day old mosquitoes exposed on their second blood meal. Twenty-four hours following ivermectin ingestion, 101 and 187 genes were differentially-expressed relative to control blood-fed, in 2 and 6-day groups, respectively. Transcription patterns of select genes were similar in membrane-fed, colonized, and naturally-fed wild vectors. Transcripts from several unexpected functional classes were highly up-regulated, including Niemann-Pick Type C (NPC) genes, peritrophic matrix-associated genes, and immune-response genes, and these exhibited different transcription patterns between age groups, which may explain the observed susceptibility differences. Niemann-Pick Type 2 genes were the most highly up-regulated transcripts after ivermectin ingestion (up to 160 fold) and

Exposure to Atomic Bomb Radiation and Age-Related Macular Degeneration in Later Life: The Hiroshima-Nagasaki Atomic Bomb Survivor Study.

PubMed

Itakura, Katsumasa; Takahashi, Ikuno; Nakashima, Eiji; Yanagi, Masahide; Kawasaki, Ryo; Neriishi, Kazuo; Wang, Jie Jin; Wong, Tien Yin; Hida, Ayumi; Ohishi, Waka; Kiuchi, Yoshiaki

2015-08-01

To investigate the association between radiation exposure from the atomic bombings and the prevalence of age-related macular degeneration (AMD) among older residents of Hiroshima and Nagasaki. The Adult Health Study is a cohort study of atomic bomb survivors living in Hiroshima and Nagasaki, comprising 2153 participants who underwent examinations with retinal fundus photographs in 2006-2008. The radiation dose to the eye for the analysis was estimated with the revised dosimetry system (DS02). The retinal photographs were graded according to the Wisconsin Age-Related Maculopathy Grading System modified for nonstereoscopic retinal images. Early and late AMD were defined according to the type of lesion detected in the worse eye of the participants. Person-specific data were analyzed by using a logistic regression model to assess the association between radiation dose and AMD. Among the 1824 subjects with gradable retinal images (84.7% of the overall participants), the estimated eye dose was widely distributed, with a mean of 0.45 Gy and standard deviation of 0.74 Gy. The prevalence of early and late AMD was 10.5% and 0.3%, respectively. There were no significant associations between radiation dose and AMD, with each 1-Gy increase in exposure, adjusted odds ratio was 0.93 (95% confidence interval [CI], 0.75-1.15) for early AMD and 0.79 (95% CI, 0.21-2.94) for late AMD. No significant associations were found between atomic bomb irradiation early in life and the prevalence of early or late AMD later in life among Japanese atomic bomb survivors.

Polymorphisms in ARMS2/HTRA1 and Complement Genes and Age-Related Macular Degeneration in India: Findings from the INDEYE Study

PubMed Central

Sundaresan, Periasamy; Vashist, Praveen; Ravindran, Ravilla D.; Shanker, Ashwini; Nitsch, Dorothea; Nonyane, Bareng A. S.; Smeeth, Liam; Chakravarthy, Usha; Fletcher, Astrid E.

2012-01-01

Purpose. Association between genetic variants in complement factor H (CFH), factor B (CFB), component 2 (C2), and in the ARMS2/HTRA1 region with age-related macular degeneration (AMD) comes mainly from studies of European ancestry and case-control studies of late-stage disease. We investigated associations of both early and late AMD with these variants in a population-based study of people aged 60 years and older in India. Methods. Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System and participants assigned to one of four mutually exclusive stages based on the worse affected eye (0 = no AMD, 1–3 = early AMD, 4 = late AMD). Multinomial logistic regression was used to derive risk ratios (RR) accounting for sampling method and adjusting for age, sex, and study center. Results. Of 3569 participants, 53.2% had no signs of AMD, 45.6% had features of early AMD, and 1.2% had late AMD. CFH (rs1061170), C2 (rs547154), or CFB (rs438999) was not associated with early or late AMD. In the ARMS2 locus, rs10490924 was associated with both early (adjusted RR 1.22, 95% confidence interval [CI]: 1.13–1.33, P < 0.0001) and late AMD (adjusted RR 1.81, 95% CI: 1.15–2.86; P = 0.01); rs2672598 was associated only with early AMD (adjusted RR 1.12, 95% CI: 1.02–1.23; P = 0.02); rs10490923 was not associated with early or late AMD. Conclusions. Two variants in ARMS2/HTRA1 were associated with increased risk of early AMD, and for one of these, the increased risk was also evident for late AMD. The study provides new insights into the role of these variants in early stages of AMD in India. PMID:23060141

Age-related variation in limb bone diaphyseal structure among Inuit foragers from Point Hope, northern Alaska.

PubMed

Wallace, I J; Nesbitt, A; Mongle, C; Gould, E S; Grine, F E

2014-01-01

Age-related deterioration of limb bone diaphyseal structure is documented among precontact Inuit foragers from northern Alaska. These findings challenge the concept that bone loss and fracture susceptibility among modern Inuit stem from their transition away from a physically demanding traditional lifestyle toward a more sedentary Western lifestyle. Skeletal fragility is rare among foragers and other traditional-living societies, likely due to their high physical activity levels. Among modern Inuit, however, severe bone loss and fractures are apparently common. This is possibly because of recent Western influences and increasing sedentism. To determine whether compromised bone structure and strength among the Inuit are indeed aberrant for a traditional-living group, data were collected on age-related variation in limb bone diaphyseal structure from a group predating Western influences. Skeletons of 184 adults were analyzed from the Point Hope archaeological site. Mid-diaphyseal structure was measured in the humerus, radius, ulna, femur, and tibia using CT. Structural differences were assessed between young, middle-aged, and old individuals. In all bones examined, both females and males exhibited significant age-related reductions in bone quantity. With few exceptions, total bone (periosteal) area did not significantly increase between young and old age in either sex, nor did geometric components of bending rigidity (second moments of area). While the physically demanding lifestyles of certain traditional-living groups may protect against bone loss and fracture susceptibility, this is not the case among the Inuit. It remains possible, however, that Western characteristics of the modern Inuit lifestyle exacerbate age-related skeletal deterioration.

CHARACTERIZING AND PROVIDING ADEQUATE PROTECTION FOR SUSCEPTIBLE SUBPOPULATIONS: SUSCEPTIBLE POPULATIONS: SUSCEPTIBILITY ASSOCIATED WITH THE AGED

EPA Science Inventory

SUMMARY: An important Agency mandate is to identify subpopulations particularly susceptible to adverse effects associated with exposure to environmental contaminants. For example, a critical public health question is the extent to which exposure to environmental contaminants cont...

Glycomics and glycoproteomics focused on aging and age-related diseases--Glycans as a potential biomarker for physiological alterations.

PubMed

Miura, Yuri; Endo, Tamao

2016-08-01

Since glycosylation depends on glycosyltransferases, glycosidases, and sugar nucleotide donors, it is susceptible to the changes associated with physiological and pathological conditions. Therefore, alterations in glycan structures may be good targets and biomarkers for monitoring health conditions. Since human aging and longevity are affected by genetic and environmental factors such as diseases, lifestyle, and social factors, a scale that reflects various environmental factors is required in the study of human aging and longevity. We herein focus on glycosylation changes elucidated by glycomic and glycoproteomic studies on aging, longevity, and age-related diseases including cognitive impairment, diabetes mellitus, and frailty. We also consider the potential of glycan structures as biomarkers and/or targets for monitoring physiological and pathophysiological changes. Glycan structures are altered in age-related diseases. These glycans and glycoproteins may be involved in the pathophysiology of these diseases and, thus, be useful diagnostic markers. Age-dependent changes in N-glycans have been reported previously in cohort studies, and characteristic N-glycans in extreme longevity have been proposed. These findings may lead to a deeper understanding of the mechanisms underlying aging as well as the factors influencing longevity. Alterations in glycosylation may be good targets and biomarkers for monitoring health conditions, and be applicable to studies on age-related diseases and healthy aging. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of Aging on Periodontal Inflammation, Microbial Colonization, and Disease Susceptibility

PubMed Central

Wu, Y.; Dong, G.; Xiao, W.; Xiao, E.; Miao, F.; Syverson, A.; Missaghian, N.; Vafa, R.; Cabrera-Ortega, A.A.; Rossa, C.; Graves, D.T.

2016-01-01

Periodontitis is a chronic inflammatory disease induced by a biofilm that forms on the tooth surface. Increased periodontal disease is associated with aging. We investigated the effect of aging on challenge by oral pathogens, examining the host response, colonization, and osteoclast numbers in aged versus young mice. We also compared the results with mice with lineage-specific deletion of the transcription factor FOXO1, which reduces dendritic cell (DC) function. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in young (4 to 5 mo) and aged (14 to 15 mo) mice. Aged mice as well as mice with reduced DC function had decreased numbers of DCs in lymph nodes, indicative of a diminished host response. In vitro studies suggest that reduced DC numbers in lymph nodes of aged mice may involve the effect of advanced glycation end products on DC migration. Surprisingly, aged mice but not mice with genetically altered DC function had greater production of antibody to P. gingivalis, greater IL-12 expression, and more plasma cells in lymph nodes following oral inoculation as compared with young mice. The greater adaptive immune response in aged versus young mice was linked to enhanced levels of P. gingivalis and reduced bacterial diversity. Thus, reduced bacterial diversity in aged mice may contribute to increased P. gingivalis colonization following inoculation and increased periodontal disease susceptibility, reflected by higher TNF levels and osteoclast numbers in the periodontium of aged versus young mice. PMID:26762510

The effects of blueberry and strawberry serum metabolites on age-related oxidative and inflammatory signaling in vitro

USDA-ARS?s Scientific Manuscript database

Age-related decrements in cognition are thought to result from the increased susceptibility to and accumulating effects of oxidative stress and inflammation. Berry fruits contain a variety of bioactive polyphenolic compounds, such as anthocyanins, that exhibit potent antioxidant and anti-inflammator...

Association of Single-Nucleotide Polymorphisms in Age-Related Macular Degeneration With Pseudodrusen: Secondary Analysis of Data From the Comparison of AMD Treatments Trials.

PubMed

Lin, Lisa Y; Zhou, Qiang; Hagstrom, Stephanie; Maguire, Maureen G; Daniel, Ebenezer; Grunwald, Juan E; Martin, Daniel F; Ying, Gui-Shuang

2018-06-01

Previous studies investigating the association of single-nucleotide polymorphisms (SNPs) that confer increased risk of age-related macular degeneration (AMD) with pseudodrusen have yielded conflicting results and have not evaluated other AMD SNPs or pseudodrusen subtypes. To determine the association of SNPs in the complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), HtrA serine peptidase 1 (HTRA1), complement C2 (C2), complement C3 (C3), lipase C (LIPC), and complement factor B (CFB) genes with the presence of pseudodrusen and pseudodrusen subtypes (ie, dot, reticular, and confluent). In this post hoc analysis of cross-sectional data from US participants in the Comparison of AMD Treatments Trials, genotyping was performed in 835 participants with TaqMan assays for the SNPs rs1061170 (Y402H variant in CFH), rs800292 (I62V variant in CFH), rs10490924 (A69S variant in ARMS2), rs11200638 (HTRA1), rs547154 (C2), rs2230199 (R102G variant in C3), rs10468017 (LIPC), and rs4151667 (L9H variant in CFB). Presence and subtype of baseline pseudodrusen in either eye determined using color fundus photography, red-free images, and fluorescein angiograms. Among 835 participants enrolled for genotyping, 755 (90.4%) were evaluated for pseudodrusen. Of these, 471 (62.4%) were female and 750 (99.3%) were white, and the mean (SD) age was 78.3 (7.5) years. A total of 213 of 755 participants (28.2%) had pseudodrusen (107 [14.2%] had dot pseudodrusen, 180 [23.8%] had reticular pseudodrusen, and 102 [13.5%] had confluent pseudodrusen). After adjusting for age, sex, and smoking status, the ARMS2 risk allele T was associated with higher risk of pseudodrusen (odds ratio [OR], 1.93; 95% CI, 1.19-3.12) for TT vs GG (P = .04). A similar association was found for HTRA1 (OR, 2.04; 95% CI, 1.26-3.31) for AA vs GG (P = .03). The CFH Y402H risk allele C was associated with lower risk of pseudodrusen (OR, 0.61; 95% CI, 0.38-0.97) for CC vs TT but was not statistically

Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity.

PubMed

Perez, Geovanny F; Jain, Amisha; Kurdi, Bassem; Megalaa, Rosemary; Pancham, Krishna; Huseni, Shehlanoor; Isaza, Natalia; Rodriguez-Martinez, Carlos E; Rose, Mary C; Pillai, Dinesh; Nino, Gustavo

2016-10-20

Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children). Sixty-seven percent of these hospitalizations occurred in children born full-term (>37 weeks), 12% in preterm (32-37 weeks) and 21% in severely premature children (<32 weeks). The most common viruses identified were rhinovirus (RV; 60%) and respiratory syncytial virus (RSV; 17%). Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life.

Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity

PubMed Central

Perez, Geovanny F.; Jain, Amisha; Kurdi, Bassem; Megalaa, Rosemary; Pancham, Krishna; Huseni, Shehlanoor; Isaza, Natalia; Rodriguez-Martinez, Carlos E.; Rose, Mary C.; Pillai, Dinesh; Nino, Gustavo

2016-01-01

Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children). Sixty-seven percent of these hospitalizations occurred in children born full-term (>37 weeks), 12% in preterm (32–37 weeks) and 21% in severely premature children (<32 weeks). The most common viruses identified were rhinovirus (RV; 60%) and respiratory syncytial virus (RSV; 17%). Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life. PMID:27775602

Susceptibility of the aging Brown Norway rat to carbaryl, an anti-cholinesterase-based insecticide: Thermoregulatory and cardiovascular responses.

EPA Science Inventory

The proportion of aged in the United States is projected to expand markedly for the next several decades. Hence, the U.S.EPA is assessing if the aged are more susceptible to environmental toxicants. The thermoregulatory and cardiovascular responses of young adult, mature adult, a...

Effect of Aging on Periodontal Inflammation, Microbial Colonization, and Disease Susceptibility.

PubMed

Wu, Y; Dong, G; Xiao, W; Xiao, E; Miao, F; Syverson, A; Missaghian, N; Vafa, R; Cabrera-Ortega, A A; Rossa, C; Graves, D T

2016-04-01

Periodontitis is a chronic inflammatory disease induced by a biofilm that forms on the tooth surface. Increased periodontal disease is associated with aging. We investigated the effect of aging on challenge by oral pathogens, examining the host response, colonization, and osteoclast numbers in aged versus young mice. We also compared the results with mice with lineage-specific deletion of the transcription factor FOXO1, which reduces dendritic cell (DC) function. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in young (4 to 5 mo) and aged (14 to 15 mo) mice. Aged mice as well as mice with reduced DC function had decreased numbers of DCs in lymph nodes, indicative of a diminished host response. In vitro studies suggest that reduced DC numbers in lymph nodes of aged mice may involve the effect of advanced glycation end products on DC migration. Surprisingly, aged mice but not mice with genetically altered DC function had greater production of antibody to P. gingivalis, greater IL-12 expression, and more plasma cells in lymph nodes following oral inoculation as compared with young mice. The greater adaptive immune response in aged versus young mice was linked to enhanced levels of P. gingivalis and reduced bacterial diversity. Thus, reduced bacterial diversity in aged mice may contribute to increased P. gingivalis colonization following inoculation and increased periodontal disease susceptibility, reflected by higher TNF levels and osteoclast numbers in the periodontium of aged versus young mice. © International & American Associations for Dental Research 2016.

Ability of university-level education to prevent age-related decline in emotional intelligence

PubMed Central

Cabello, Rosario; Navarro Bravo, Beatriz; Latorre, José Miguel; Fernández-Berrocal, Pablo

2014-01-01

Numerous studies have suggested that educational history, as a proxy measure of active cognitive reserve, protects against age-related cognitive decline and risk of dementia. Whether educational history also protects against age-related decline in emotional intelligence (EI) is unclear. The present study examined ability EI in 310 healthy adults ranging in age from 18 to 76 years using the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT). We found that older people had lower scores than younger people for total EI and for the EI branches of perceiving, facilitating, and understanding emotions, whereas age was not associated with the EI branch of managing emotions. We also found that educational history protects against this age-related EI decline by mediating the relationship between age and EI. In particular, the EI scores of older adults with a university education were higher than those of older adults with primary or secondary education, and similar to those of younger adults of any education level. These findings suggest that the cognitive reserve hypothesis, which states that individual differences in cognitive processes as a function of lifetime intellectual activities explain differential susceptibility to functional impairment in the presence of age-related changes and brain pathology, applies also to EI, and that education can help preserve cognitive-emotional structures during aging. PMID:24653697

Effects of tissue susceptibility on brain temperature mapping.

PubMed

Maudsley, Andrew A; Goryawala, Mohammed Z; Sheriff, Sulaiman

2017-02-01

A method for mapping of temperature over a large volume of the brain using volumetric proton MR spectroscopic imaging has been implemented and applied to 150 normal subjects. Magnetic susceptibility-induced frequency shifts in gray- and white-matter regions were measured and included as a correction in the temperature mapping calculation. Additional sources of magnetic susceptibility variations of the individual metabolite resonance frequencies were also observed that reflect the cellular-level organization of the brain metabolites, with the most notable differences being attributed to changes of the N-Acetylaspartate resonance frequency that reflect the intra-axonal distribution and orientation of the white-matter tracts with respect to the applied magnetic field. These metabolite-specific susceptibility effects are also shown to change with age. Results indicate no change of apparent brain temperature with age from 18 to 84 years old, with a trend for increased brain temperature throughout the cerebrum in females relative for males on the order of 0.1°C; slightly increased temperatures in the left hemisphere relative to the right; and a lower temperature of 0.3°C in the cerebellum relative to that of cerebral white-matter. This study presents a novel acquisition method for noninvasive measurement of brain temperature that is of potential value for diagnostic purposes and treatment monitoring, while also demonstrating limitations of the measurement due to the confounding effects of tissue susceptibility variations. Copyright © 2016 Elsevier Inc. All rights reserved.

Adolescents' Susceptibility to Peer Pressure: Relations to Parent-Adolescent Relationship and Adolescents' Emotional Autonomy from Parents

ERIC Educational Resources Information Center

Chan, Siu Mui; Chan, Kwok-Wai

2013-01-01

Studies on factors affecting susceptibility to peer pressure are not plentiful although this susceptibility has been found to be associated with youth problems such as substance use and risky sexual behavior. The present study examined how adolescents' susceptibility to peer pressure is related to their relationships with mothers and emotional…

Pars plana vitrectomy with juxtapapillary laser photocoagulation versus vitrectomy without juxtapapillary laser photocoagulation for the treatment of optic disc pit maculopathy: the results of the KKESH International Collaborative Retina Study Group.

PubMed

Abouammoh, Marwan A; Alsulaiman, Sulaiman M; Gupta, Vishali S; Mousa, Ahmed; Hirakata, Akito; Berrocal, Maria H; Chenworth, Megan; Chhablani, Jay; Oshima, Yusuke; AlZamil, Waseem M; Casella, Antonio Marcelo; Papa-Oliva, Gabriela; Banker, Alay S; Arevalo, J Fernando

2016-04-01

To compare the functional and anatomic outcomes of pars plana vitrectomy (PPV) with juxtapapillary laser photocoagulation (JLP) versus vitrectomy without JLP in optic disc pit maculopathy. This was a multicentre, retrospective study of 46 consecutive patients with optic disc pit maculopathy presenting at tertiary eye centres between 1992 and 2012. Indications for surgery included distorted or decreased vision. Surgical intervention included PPV, posterior vitreous detachment, with or without gas tamponade. Twenty-four patients received laser photocoagulation at the temporal edge of the optic disc pit (group A) and 22 patients had no laser (group B). Postoperative best-corrected visual acuity (BCVA) and optical coherence tomography findings were the main outcome measures. Mean follow-up was 44 months (range 12-98 months). BCVA in group A improved significantly from 0.7 logMAR (20/100) preoperatively to 0.5 logMAR (20/60) postoperatively (p=0.017). In group B, BCVA improved from 0.7 logMAR (20/100) preoperatively to 0.4 logMAR (20/40) postoperatively (p=0.014). The difference in final BCVA between groups was not statistically significant (p=0.693). The mean central macular thickness (CMT) in group A improved significantly from 750 μm preoperatively to 309 μm at last follow-up (p<0.0001). The mean CMT in group B improved from 616 μm preoperatively to 291 μm at last follow-up (p=0.028). The difference in final CMT between groups was not statistically significant (p=0.747). PPV with JLP for optic disc pit maculopathy had similar functional and anatomic outcomes compared with vitrectomy without JLP. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Age-related Changes in the Hepatic Microcirculation in Mice

PubMed Central

Ito, Yoshiya; Sørensen, Karen K.; Bethea, Nancy W.; Svistounov, Dmitri; McCuskey, Margaret K.; Smedsrød, Bård H.; McCuskey, Robert S.

2007-01-01

Aging of the liver is associated with impaired metabolism of drugs, adverse drug interactions, and susceptibility to toxins. Since reduced hepatic blood flow is suspected to contribute this impairment, we examined age-related alterations in hepatic microcirculation.. Livers of C57Bl/6 mice were examined at 0.8 (pre-pubertal), 3 (young adult), 14 (middle-aged) and 27 (senescent) months of age using in vivo and electron microscopic methods. The results demonstrated a 14% reduction in the numbers of perfused sinusoids between 0.8 and 27 month mice associated with 35% reduction in sinusoidal blood flow. This was accompanied by an inflammatory response evidenced by a 5-fold increase in leukocyte adhesion in 27 month mice, up-regulated expression of ICAM-1, and increases in intrahepatic macrophages. Sinusoidal diameter decreased 6-10%. Liver sinusoidal endothelial cell (LSEC) dysfunction was seen as early as 14 months when there was a 3-fold increase in the numbers of swollen LSEC. The endocytotic capacity of LSEC also was found to be reduced in older animals. The sinusoidal endothelium in 27 month old mice exhibited pseudocapillarization. In conclusion, the results suggest that leukocyte accumulation in the sinusoids and narrowing of sinusoidal lumens due to pseudocapillarization and dysfunction of LSEC reduce sinusoidal blood flow in aged livers. PMID:17582718

Disease spread in age structured populations with maternal age effects.

PubMed

Clark, Jessica; Garbutt, Jennie S; McNally, Luke; Little, Tom J

2017-04-01

Fundamental ecological processes, such as extrinsic mortality, determine population age structure. This influences disease spread when individuals of different ages differ in susceptibility or when maternal age determines offspring susceptibility. We show that Daphnia magna offspring born to young mothers are more susceptible than those born to older mothers, and consider this alongside previous observations that susceptibility declines with age in this system. We used a susceptible-infected compartmental model to investigate how age-specific susceptibility and maternal age effects on offspring susceptibility interact with demographic factors affecting disease spread. Our results show a scenario where an increase in extrinsic mortality drives an increase in transmission potential. Thus, we identify a realistic context in which age effects and maternal effects produce conditions favouring disease transmission. © 2017 The Authors Ecology Letters published by CNRS and John Wiley & Sons Ltd.

Ursodeoxycholic acid decreases age-related adiposity and inflammation in mice

PubMed Central

Oh, Ah-Reum; Bae, Jin-Sik; Lee, Junghoon; Shin, Eunji; Oh, Byung-Chul; Park, Sang-Chul; Cha, Ji-Young

2016-01-01

Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-γ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli. [BMB Reports 2016; 49(2): 105-110] PMID:26350747

Molecular inflammation: underpinnings of aging and age-related diseases.

PubMed

Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan

2009-01-01

Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) upregulation of pro-inflammatory mediators (e.g., TNF-alpha, IL-1beta, IL-6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-kappaB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity.

Molecular Inflammation: Underpinnings of Aging and Age-related Diseases

PubMed Central

Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan

2013-01-01

Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) up-regulation of pro-inflammatory mediators (e.g., TNF-α, IL-1β, 6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-κB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity. PMID:18692159

Assessment of Groundwater Susceptibility to Non-Point Source Contaminants Using Three-Dimensional Transient Indexes.

PubMed

Zhang, Yong; Weissmann, Gary S; Fogg, Graham E; Lu, Bingqing; Sun, HongGuang; Zheng, Chunmiao

2018-06-05

Groundwater susceptibility to non-point source contamination is typically quantified by stable indexes, while groundwater quality evolution (or deterioration globally) can be a long-term process that may last for decades and exhibit strong temporal variations. This study proposes a three-dimensional (3- d ), transient index map built upon physical models to characterize the complete temporal evolution of deep aquifer susceptibility. For illustration purposes, the previous travel time probability density (BTTPD) approach is extended to assess the 3- d deep groundwater susceptibility to non-point source contamination within a sequence stratigraphic framework observed in the Kings River fluvial fan (KRFF) aquifer. The BTTPD, which represents complete age distributions underlying a single groundwater sample in a regional-scale aquifer, is used as a quantitative, transient measure of aquifer susceptibility. The resultant 3- d imaging of susceptibility using the simulated BTTPDs in KRFF reveals the strong influence of regional-scale heterogeneity on susceptibility. The regional-scale incised-valley fill deposits increase the susceptibility of aquifers by enhancing rapid downward solute movement and displaying relatively narrow and young age distributions. In contrast, the regional-scale sequence-boundary paleosols within the open-fan deposits "protect" deep aquifers by slowing downward solute movement and displaying a relatively broad and old age distribution. Further comparison of the simulated susceptibility index maps to known contaminant distributions shows that these maps are generally consistent with the high concentration and quick evolution of 1,2-dibromo-3-chloropropane (DBCP) in groundwater around the incised-valley fill since the 1970s'. This application demonstrates that the BTTPDs can be used as quantitative and transient measures of deep aquifer susceptibility to non-point source contamination.

Age-related susceptibility to epileptogenesis and neuronal loss in male Fischer rats exposed to soman and treated with medical countermeasures.

PubMed

Marrero-Rosado, Brenda; Rossetti, Franco; Rice, Matthew W; Moffett, Mark C; Lee, Robyn; Stone, Michael F; Lumley, Lucille A

2018-03-27

Elderly individuals compose a large percentage of the world population; however, few studies have addressed the efficacy of current medical countermeasures (MCM) against the effects of chemical warfare nerve agent exposure in aged populations. We evaluated the efficacy of the anticonvulsant diazepam in an old adult rat model of soman (GD) poisoning and compared the toxic effects to those observed in young adult rats when anticonvulsant treatment is delayed. After determining their respective median lethal dose (LD50) of GD, we exposed young adult and old adult rats to an equitoxic 1.2 LD50 dose of GD followed by treatment with atropine sulfate and the oxime HI-6 at one minute after exposure, and diazepam at 30 minutes after seizure onset. Old adult rats that presented with status epilepticus were more susceptible to developing spontaneous recurrent seizures (SRS). Neuropathological analysis revealed that in rats of both age groups that developed SRS, there was a significant reduction in the density of mature neurons in the piriform cortex, thalamus, and amygdala, with more pronounced neuronal loss in the thalamus of old adult rats compared to young adult rats. Furthermore, old adult rats displayed a reduced density of cells expressing glutamic acid decarboxylase 67, a marker of GABAergic interneurons, in the basolateral amygdala and piriform cortex, and a reduction of astrocyte activation in the piriform cortex. Our observations demonstrate the reduced effectiveness of current MCM in an old adult animal model of GD exposure and strongly suggest the need for countermeasures that are more tailored to the vulnerabilities of an aging population.

Grey matter correlates of susceptibility to scams in community-dwelling older adults.

PubMed

Duke Han, S; Boyle, Patricia A; Yu, Lei; Arfanakis, Konstantinos; James, Bryan D; Fleischman, Debra A; Bennett, David A

2016-06-01

Susceptibility to scams is a significant issue among older adults, even among those with intact cognition. Age-related changes in brain macrostructure may be associated with susceptibility to scams; however, this has yet to be explored. Based on previous work implicating frontal and temporal lobe functioning as important in decision making, we tested the hypothesis that susceptibility to scams is associated with smaller grey matter volume in frontal and temporal lobe regions in a large community-dwelling cohort of non-demented older adults. Participants (N = 327, mean age = 81.55, mean education = 15.30, 78.9 % female) completed a self-report measure used to assess susceptibility to scams and an MRI brain scan. Results indicated an inverse association between overall grey matter and susceptibility to scams in models adjusted for age, education, and sex; and in models further adjusted for cognitive function. No significant associations were observed for white matter, cerebrospinal fluid, or total brain volume. Models adjusted for age, education, and sex revealed seven clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, left middle temporal, left orbitofrontal, right ventromedial prefrontal, right middle temporal, right precuneus, and right dorsolateral prefrontal regions. In models further adjusted for cognitive function, results revealed three significant clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, right hippocampal, and right middle temporal regions. Lower grey matter concentration in specific brain regions may be associated with susceptibility to scams, even after adjusting for cognitive ability. Future research is needed to determine whether grey matter reductions in these regions may be a biomarker for susceptibility to scams in old age.

Comparative susceptibility of Salmonella Typhimurium biofilms of different ages to disinfectants.

PubMed

Wong, Hui San; Townsend, Kirsty M; Fenwick, Stan G; Maker, Garth; Trengove, Robert D; O'Handley, Ryan M

2010-10-01

There is a general consensus that with increasing age a biofilm shows increased resistance to antimicrobials. In this study the susceptibility of 3-, 5- and 7-day-old Salmonella enterica serovar Typhimurium biofilms to disinfectants was evaluated. It was hypothesized that 7-day-old biofilms would be more resistant to disinfectants compared to 3- and 5-day-old biofilms. Biofilms were formed using the MBEC™ system and treated with six chemical disinfectants for 1 and 5 min. Four disinfectants at the highest concentration available showed 100% reduction in viable cells from all ages of biofilms after exposure for 5 min, and ethanol at 70% v/v was the least effective against biofilms, followed by chlorhexidine gluconate (CG). At the recommended user concentrations, only sodium hypochlorite showed 100% reduction in viable cells from all ages of biofilms. Benzalkonium chloride and CG were the least effective against biofilms, followed by quaternary ammonium compound which only showed 100% reduction in viable cells from 5-day-old biofilms. Overall, the results from this study do not display enhanced resistance in 7-day-old biofilms compared to 3- and 5-day-old biofilms. It is concluded that under the conditions of this study, the age of biofilm did not contribute to resistance towards disinfectants. Rather, the concentration of disinfectant and an increased contact time were both shown to play a role in successful sanitization.

Cuprizone-induced demyelination in mice: age-related vulnerability and exploratory behavior deficit.

PubMed

Wang, Hongkai; Li, Chengren; Wang, Hanzhi; Mei, Feng; Liu, Zhi; Shen, Hai-Ying; Xiao, Lan

2013-04-01

Schizophrenia is a mental disease that mainly affects young individuals (15 to 35 years old) but its etiology remains largely undefined. Recently, accumulating evidence indicated that demyelination and/or dysfunction of oligodendrocytes is an important feature of its pathogenesis. We hypothesized that the vulnerability of young individuals to demyelination may contribute to the onset of schizophrenia. In the present study, three different age cohorts of mice, i.e. juvenile (3 weeks), young-adult (6 weeks) and middle-aged (8 months), were subjected to a 6-week diet containing 0.2% cuprizone (CPZ) to create an animal model of acute demyelination. Then, age-related vulnerability to CPZ-induced demyelination, behavioral outcomes, and myelination-related molecular biological changes were assessed. We demonstrated: (1) CPZ treatment led to more severe demyelination in juvenile and young-adult mice than in middle-aged mice in the corpus callosum, a region closely associated with the pathophysiology of schizophrenia; (2) the higher levels of demyelination in juvenile and young-adult mice were correlated with a greater reduction of myelin basic protein, more loss of CC-1-positive mature oligodendrocytes, and higher levels of astrocyte activation; and (3) CPZ treatment resulted in a more prominent exploratory behavior deficit in juvenile and young-adult mice than in middle-aged mice. Together, our data demonstrate an age-related vulnerability to demyelination with a concurrent behavioral deficit, providing supporting evidence for better understanding the susceptibility of the young to the onset of schizophrenia.

Stem Cell Ophthalmology Treatment Study II

ClinicalTrials.gov

2018-02-01

Retinal Disease; Age-Related Macular Degeneration; Retinitis Pigmentosa; Stargardt Disease; Optic Neuropathy; Nonarteritic Ischemic Optic Neuropathy; Optic Atrophy; Optic Nerve Disease; Glaucoma; Leber Hereditary Optic Neuropathy; Blindness; Vision Loss Night; Vision Loss Partial; Vision, Low; Retinopathy; Maculopathy; Macular Degeneration; Retina Atrophy

Genetic and Functional Dissection of HTRA1 and LOC387715 in Age-Related Macular Degeneration

PubMed Central

Zeng, Jiexi; Lu, Fang; Sun, Xufang; Zhao, Chao; Wang, Kevin; Davey, Lisa; Chen, Haoyu; London, Nyall; Muramatsu, Daisuke; Salasar, Francesca; Carmona, Ruben; Kasuga, Daniel; Wang, Xiaolei; Bedell, Matthew; Dixie, Manjuxia; Zhao, Peiquan; Yang, Ruifu; Gibbs, Daniel; Liu, Xiaoqi; Li, Yan; Li, Cai; Li, Yuanfeng; Campochiaro, Betsy; Constantine, Ryan; Zack, Donald J.; Campochiaro, Peter; Fu, Yinbin; Li, Dean Y.; Katsanis, Nicholas; Zhang, Kang

2010-01-01

A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD) and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X) in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits. PMID:20140183

Working memory, age, and hearing loss: susceptibility to hearing aid distortion.

PubMed

Arehart, Kathryn H; Souza, Pamela; Baca, Rosalinda; Kates, James M

2013-01-01

Hearing aids use complex processing intended to improve speech recognition. Although many listeners benefit from such processing, it can also introduce distortion that offsets or cancels intended benefits for some individuals. The purpose of the present study was to determine the effects of cognitive ability (working memory) on individual listeners' responses to distortion caused by frequency compression applied to noisy speech. The present study analyzed a large data set of intelligibility scores for frequency-compressed speech presented in quiet and at a range of signal-to-babble ratios. The intelligibility data set was based on scores from 26 adults with hearing loss with ages ranging from 62 to 92 years. The listeners were grouped based on working memory ability. The amount of signal modification (distortion) caused by frequency compression and noise was measured using a sound quality metric. Analysis of variance and hierarchical linear modeling were used to identify meaningful differences between subject groups as a function of signal distortion caused by frequency compression and noise. Working memory was a significant factor in listeners' intelligibility of sentences presented in babble noise and processed with frequency compression based on sinusoidal modeling. At maximum signal modification (caused by both frequency compression and babble noise), the factor of working memory (when controlling for age and hearing loss) accounted for 29.3% of the variance in intelligibility scores. Combining working memory, age, and hearing loss accounted for a total of 47.5% of the variability in intelligibility scores. Furthermore, as the total amount of signal distortion increased, listeners with higher working memory performed better on the intelligibility task than listeners with lower working memory did. Working memory is a significant factor in listeners' responses to total signal distortion caused by cumulative effects of babble noise and frequency compression

Age-related differences in pulmonary effects of acute and ...

EPA Pesticide Factsheets

Ozone (O3) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O3-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O3 are uncertain. In this study, we examined age-related susceptibility to O3 using 1 mo (adolescent), 4 mo (young adult), 12 mo (adult) and 24 mo (senescent) male Brown Norway rats exposed to filtered air or O3 (0.25and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O3-induced pulmonary effects.Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24 mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O3 exposures. PenH was increased in all groups with an augmented response in the 4 mo rats following the subchronic O3 exposures. O3 led to increased breathing frequency and minute volume in the 1 and 4 mo animals. Markers ofpulmonary permeability were increased in all age groups. Elevations in BALF γ-glutamyl transferase activity and lung inflammation following an acute O3 exposure were noted in only the 1 and 4 mo rats, which likely received an increased effective O3 dose. These data demonstrate that ado

Lack of association of CFD polymorphisms with advanced age-related macular degeneration.

PubMed

Zeng, Jiexi; Chen, Yuhong; Tong, Zongzhong; Zhou, Xinrong; Zhao, Chao; Wang, Kevin; Hughes, Guy; Kasuga, Daniel; Bedell, Matthew; Lee, Clara; Ferreyra, Henry; Kozak, Igor; Haw, Weldon; Guan, Jean; Shaw, Robert; Stevenson, William; Weishaar, Paul D; Nelson, Mark H; Tang, Luosheng; Zhang, Kang

2010-11-03

Age-related macular degeneration (AMD) is the most common cause of irreversible central vision loss worldwide. Research has linked AMD susceptibility with dysregulation of the complement cascade. Typically, complement factor H (CFH), complement factor B (CFB), complement component 2 (C2), and complement component 3 (C3) are associated with AMD. In this paper, we investigated the association between complement factor D (CFD), another factor of the complement system, and advanced AMD in a Caucasian population. Six single nucleotide polymorphisms (SNPs), rs1683564, rs35186399, rs1683563, rs3826945, rs34337649, and rs1651896, across the region covering CFD, were chosen for this study. One hundred and seventy-eight patients with advanced AMD and 161 age-matched normal controls were genotyped. Potential positive signals were further tested in another independent 445 advanced AMD patients and 190 controls. χ2 tests were performed to compare the allele frequencies between case and control groups. None of the six SNPs of CFD was found to be significantly associated with advanced AMD in our study. Our findings suggest that CFD may not play a major role in the genetic susceptibility to AMD because no association was found between the six SNPs analyzed in the CFD region and advanced AMD.

Factors that Impact Susceptibility to Fiber-Induced Health Effects

PubMed Central

Below, Jennifer E.; Cox, Nancy J.; Fukagawa, Naomi K.; Hirvonen, Ari; Testa, Joseph R.

2011-01-01

Asbestos and related fibers are associated with a number of adverse health effects, including malignant mesothelioma (MM), an aggressive cancer that generally develops in the surface serosal cells of the pleural, pericardial, and peritoneal cavities. Although approximately 80% of individuals with MM are exposed to asbestos, fewer than 5% of asbestos workers develop MM. In addition to asbestos, other mineralogical, environmental, genetic, and possibly viral factors might contribute to MM susceptibility. Given this complex etiology of MM, understanding susceptibility to MM needs to be a priority for investigators in order to reduce exposure of those most at risk to known environmental carcinogens. In this review, the current body of literature related to fiber-associated disease susceptibility including age, sex, nutrition, genetics, asbestos, and other mineral exposure is addressed with a focus on MM, and critical areas for further study are recommended. PMID:21534090

Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice.

PubMed

Gioscia-Ryan, Rachel A; LaRocca, Thomas J; Sindler, Amy L; Zigler, Melanie C; Murphy, Michael P; Seals, Douglas R

2014-06-15

Age-related arterial endothelial dysfunction, a key antecedent of the development of cardiovascular disease (CVD), is largely caused by a reduction in nitric oxide (NO) bioavailability as a consequence of oxidative stress. Mitochondria are a major source and target of vascular oxidative stress when dysregulated. Mitochondrial dysregulation is associated with primary ageing, but its role in age-related endothelial dysfunction is unknown. Our aim was to determine the efficacy of a mitochondria-targeted antioxidant, MitoQ, in ameliorating vascular endothelial dysfunction in old mice. Ex vivo carotid artery endothelium-dependent dilation (EDD) to increasing doses of acetylcholine was impaired by ∼30% in old (∼27 months) compared with young (∼8 months) mice as a result of reduced NO bioavailability (P < 0.05). Acute (ex vivo) and chronic (4 weeks in drinking water) administration of MitoQ completely restored EDD in older mice by improving NO bioavailability. There were no effects of age or MitoQ on endothelium-independent dilation to sodium nitroprusside. The improvements in endothelial function with MitoQ supplementation were associated with the normalization of age-related increases in total and mitochondria-derived arterial superoxide production and oxidative stress (nitrotyrosine abundance), as well as with increases in markers of vascular mitochondrial health, including antioxidant status. MitoQ also reversed the age-related increase in endothelial susceptibility to acute mitochondrial damage (rotenone-induced impairment in EDD). Our results suggest that mitochondria-derived oxidative stress is an important mechanism underlying the development of endothelial dysfunction in primary ageing. Mitochondria-targeted antioxidants such as MitoQ represent a promising novel strategy for the preservation of vascular endothelial function with advancing age and the prevention of age-related CVD. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological

Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice

PubMed Central

Gioscia-Ryan, Rachel A; LaRocca, Thomas J; Sindler, Amy L; Zigler, Melanie C; Murphy, Michael P; Seals, Douglas R

2014-01-01

Age-related arterial endothelial dysfunction, a key antecedent of the development of cardiovascular disease (CVD), is largely caused by a reduction in nitric oxide (NO) bioavailability as a consequence of oxidative stress. Mitochondria are a major source and target of vascular oxidative stress when dysregulated. Mitochondrial dysregulation is associated with primary ageing, but its role in age-related endothelial dysfunction is unknown. Our aim was to determine the efficacy of a mitochondria-targeted antioxidant, MitoQ, in ameliorating vascular endothelial dysfunction in old mice. Ex vivo carotid artery endothelium-dependent dilation (EDD) to increasing doses of acetylcholine was impaired by ∼30% in old (∼27 months) compared with young (∼8 months) mice as a result of reduced NO bioavailability (P < 0.05). Acute (ex vivo) and chronic (4 weeks in drinking water) administration of MitoQ completely restored EDD in older mice by improving NO bioavailability. There were no effects of age or MitoQ on endothelium-independent dilation to sodium nitroprusside. The improvements in endothelial function with MitoQ supplementation were associated with the normalization of age-related increases in total and mitochondria-derived arterial superoxide production and oxidative stress (nitrotyrosine abundance), as well as with increases in markers of vascular mitochondrial health, including antioxidant status. MitoQ also reversed the age-related increase in endothelial susceptibility to acute mitochondrial damage (rotenone-induced impairment in EDD). Our results suggest that mitochondria-derived oxidative stress is an important mechanism underlying the development of endothelial dysfunction in primary ageing. Mitochondria-targeted antioxidants such as MitoQ represent a promising novel strategy for the preservation of vascular endothelial function with advancing age and the prevention of age-related CVD. PMID:24665093

From lymphopoiesis to plasma cells differentiation, the age-related modifications of B cell compartment are influenced by "inflamm-ageing".

PubMed

Bulati, Matteo; Caruso, Calogero; Colonna-Romano, Giuseppina

2017-07-01

Ageing is a complex process characterized by a general decline in physiological functions with increasing morbidity and mortality. The most important aspect of ageing is the chronic inflammatory status, named "inflamm-ageing", strictly associated with the deterioration of the immune function, termed "immunosenescence". Both are causes of increased susceptibility of elderly to infectious diseases, cancer, dementia, cardiovascular diseases and autoimmunity, and of a decreased response to vaccination. It has been widely demonstrated that ageing has a strong impact on the remodelling of the B cell branch of immune system. The first evident effect is the significant decrease in circulating B cells, primarily due to the reduction of new B cell coming from bone marrow (BM) progenitors, as inflammation directly impacts on B lymphopoiesis. Besides, in aged individuals, there is a shift from naïve to memory immunoglobulins production, accompanied by the impaired ability to produce high affinity protective antibodies against newly encountered antigens. This is accompanied by the increase of expanded clones of B cells, which correlates with poor health status. Age-related modifications also occur in naïve/memory B cells subsets. Indeed, in the elderly, there is a reduction of naïve B cells, accompanied by the expansion of memory B cells that show a senescence-associated phenotype. Finally, elderly show the impaired ability of memory B cells to differentiate into plasma cells. It can be concluded that inflammation is the leading cause of the age-related impairment of B cell compartment, which play certainly a key role in the development of age-related diseases. This makes study of B cells in the aged an important tool for monitoring immunosenescence, chronic inflammatory disorders and the effectiveness of vaccines or pharmacological therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Ethnic Differences in the Association Between Age-Related Macular Degeneration and Vision-Specific Functioning

PubMed Central

Fenwick, Eva K.; Man, Ryan E. K.; Cheung, Chui Ming Gemmy; Sabanayagam, Charumathi; Cheng, Ching-Yu; Neelam, Kumari; Chua, Jacqueline; Gan, Alfred T. L.; Mitchell, Paul; Wong, Tien Y.

2017-01-01

Importance Understanding the link between ethnicity and health is critical to making appropriate public policy decisions. Few population-level data are available about this connection, however, including the influence of ethnicity on the association between age-related macular degeneration (AMD) and vision-specific functioning (VSF). Objective To identify the influence of ethnicity on VSF among Chinese, Malay, and Indian patients with AMD. Design, Setting, and Participants This cross-sectional, population-based study relied on patients and their data from 3 population-based studies in 3 ethnic groups: Chinese, Malay and Indian. Of 10 033 Chinese, Malay, and Indian adults who participated in the study, 9962 (99.3%) who had gradable fundus images and Visual Function Index (VF-11) data available were included in the analyses for the present study. Uniocular presenting distance visual acuity was measured using the logMAR chart. Separate multiple linear regression models examined the association between AMD and VSF in the 3 ethnic groups, adjusting for age, sex, presenting visual acuity in the better-seeing eye, educational level, income, smoking status, hypertension, diabetes, cardiovascular disease, total cholesterol level, and other eye conditions. Data were collected between January 20, 2004, and December 19, 2011; data analysis was conducted between November 12, 2015, and December 28, 2016. Exposures Age-related macular degeneration according to fundus photographs graded using a modified Wisconsin Age-Related Maculopathy Grading System. Main Outcomes and Measures Rasch analysis was used to convert VF-11 questionnaire scores to estimated interval measures of VSF. Results Of the 9962 participants, the mean (SD) age was 58.8 (10.4) years; 4909 (49.3%) were male; 590 (5.9%) had early AMD (241 Chinese, 161 Malays, and 188 Indians) and 60 (0.6%) had late AMD (25 Chinese, 21 Malays, and 14 Indians). In the adjusted models, compared with no AMD, early AMD was

Correlates of Susceptibility to Scams in Older Adults Without Dementia

PubMed Central

James, Bryan D.; Boyle, Patricia A.; Bennett, David A.

2013-01-01

This study examined correlates of susceptibility to scams in 639 community-dwelling older adults without dementia from a cohort study of aging. Regression models adjusted for age, sex, education, and income were used to examine associations between susceptibility to scams, measured by 5-item self-report measure, and a number of potential correlates. Susceptibility was positively associated with age and negatively associated with income, cognition, psychological well being, social support, and literacy. Fully adjusted models indicated that older age and lower levels of cognitive function, decreased psychological well-being, and lower literacy in particular may be markers of susceptibility to financial victimization in old age. PMID:24499279

Relative stress corrosion susceptibilities of alloys 690 and 600 in simulated boiling water reactor environments

NASA Astrophysics Data System (ADS)

Page, R. A.; McMinn, A.

1986-05-01

The relative susceptibilities of alloys 600 and 690 to intergranular stress corrosion cracking (IGSCC) in pure water and a simulated resin intrusion environment at 288 °C were evaluated. A combination of creviced and noncreviced slow-strain-rate, and precracked fracture mechanics tests were employed in the evaluation. Susceptibility was determined as a function of dissolved oxygen content, degree of sensitization, and crevice condition. The results indicated that alloy 600 was susceptible to various degrees of IGSCC in oxygen containing pure water when creviced, and immune to IGSCC when uncreviced. Alloy 690 was immune to IGSCC under all pure water conditions examined. Alloy 600 and alloy 690 were both susceptible to cracking in the simulated resin intrusion environment. Alloy 690, however, exhibited the greatest resistance to SCC of the two alloys.

[Prevention and preventive therapy of age-related macular degeneration through the beneficial effect of treatment of endothelial dysfunction].

PubMed

Fischer, Tamás

2006-12-24

The beneficial effect achieved by the treatment of endothelial dysfunction in chronic cardiovascular diseases is already an evidence belonging to the basic treatment of the disease. Given the fact that the vascular system is uniform and consubstantial both physiologically, pathophysiologically and in terms of therapy, and that it plays a key role in age-related macular degeneration (AMD) - a disease leading to tragic loss of vision with its etiology and therapy being unknown -, endothelial dysfunction should be treated. The pleiotropic effects of ACE-inhibitors, AR-blockers and statins help to restitute the balance between vasodilators and vasoconstrictors in endothelial dysfunction caused by oxidative stress, the balance of growth factors and their inhibitors, pro- and anti-inflammatory substances and prothrombotic and fibrinolytic factors, inhibit the formation of oxidative stress and its harmful effects; while aspirin with its pleiotropic effects acting as an antiaggregation substance on platelets helps to set the endothelial layer back to its normal balance regarding its vasodilating, antithrombotic, anti-adhesive and anti-inflammatory functions. For the above reasons it is suggested that, as a part of long term primary and/or secondary prevention, the following groups of patients with AMD receive - taking into consideration all possible side effects - ACE-inhibitor and/or AR-blocker and statin and aspirin treatment: 1) those without maculopathy but being over the age of 50 and having risk factors inducing endothelial dysfunction; 2) those, who already developed AMD in one eye as a prevention in the second, unaffected eye; and 3) those patients who developed AMD in both eyes in order to ameliorate or merely slow the progression of the disease. Besides, it is advisory to inhibit AMD risk factors inducing oxidative stress with consecutive endothelial dysfunction.

History of the Pasamonte achondrite: Relative susceptibility of the SmNd, RbSr, and UPb systems to metamorphic events

USGS Publications Warehouse

Unruh, D.M.; Nakamura, N.; Tatsumoto, M.

1977-01-01

The RbSr, SmNd, and UPb systematics of the eucrite Pasamonte have been studied in order to investigate the relative susceptibility of the different systems to post-crystallization events and to determine the age and history of the meteorite. The RbSr and 238U-206Pb data of mineral separates do not define an isochron but the SmNd data define an internal isochron which corresponds to the formation age of 4.58 ?? 0.12 b.y. (109 years). The 207Pb-206Pb data of mineral separates define an apparent age of 4.53 ?? 0.03 b.y., however we conclude that this age, while in agreement with the SmNd age, is not strictly valid since the UPb data indicate at least three stages of evolution. The UPb data indicate that the parent body of the meteorite experienced brecciation shortly after the formation of the parent body surface (???4.2-4.45 b.y. ago) and a recent disturbance (collision?) 6 ?? 30 m.y. ago. The latter age is within the range of cosmic ray exposure ages for achondrites. ?? 1977.

Dengue related maculopathy and foveolitis.

PubMed

Juanarita, Jaafar; Azmi, Mohd Noor Raja; Azhany, Yaakub; Liza-Sharmini, Ahmad Tajudin

2012-09-01

A 24 year-old Malay lady presented with high grade fever, myalgia, generalized rashes, severe headache and was positive for dengue serology test. Her lowest platelet count was 45 × 10(9) cells/L. She complained of sudden onset of painlessness, profound loss of vision bilaterally 7 days after the onset of fever. On examination, her right eye best corrected vision was 6/30 and left eye was 6/120. Her anterior segment examination was unremarkable. Funduscopy revealed there were multiple retinal haemorrhages found at posterior pole of both fundi and elevation at fovea area with subretinal fluid. Systemic examination revealed normal findings except for residual petechial rashes. She was managed conservatively. Her vision improved tremendously after 2 months. The retinal hemorrhages and foveal elevation showed sign of resolving. Ocular manifestations following dengue fever is rare. However, bilateral visual loss can occur if both fovea are involved.

Nasopharyngeal carriage and antimicrobial susceptibility of Haemophilus influenzae among children younger than 5 years of age in Beijing, China.

PubMed

Zhu, Hongbin; Wang, Aihua; Tong, Jingjing; Yuan, Lin; Gao, Wei; Shi, Wei; Yu, Sangjie; Yao, Kaihu; Yang, Yonghong

2015-02-04

Haemophilus influenzae is one of the main pathogens that cause community-acquired respiratory infections in children. Our previous study showed that H. influenzae is the second most common pathogen causing pneumonia and accounts for 30-50% of bacterial meningitis among Chinese children. H. influenzae carriage in children and its resistance to commonly used antimicrobials varies widely both geographically and over time. Surveys of the nasopharyngeal carriage of H. influenzae in children younger than 5 years of age with acute respiratory tract infection (ARI) were conducted in Beijing Children's Hospital, China in 2000, 2002, 2010, and 2012. The overall annual carriage rates of H. influenzae among children younger than 5 years of age with ARI were 35.5%, 20.6%, 14.4%, and 18.7%, and the percentages of H. influenzae isolates producing β-lactamase were 4%, 13%, 27.1%, and 31%, respectively. The percentages of susceptibility to ampicillin progressively decreased from 96% (2000) to 87% (2002) to 63% (2010) to 61% (2012). All of the ampicillin-resistant isolates were found to be beta-lactamase producers. The susceptibility to tetracycline increased from 54% (2000) to 60% (2002) to 91.5% (2010) to 94.5% (2012). No statistically significant differences were observed in the susceptibility to cefaclor, cefuroxime, sulfamethoxazole, and chloramphenicol. Amoxicillin/clavulanic acid and ceftriaxone were the most effective antimicrobials for the isolates of H. influenzae across the 10-year period. This report on the H. influenzae carriage rates in children and the susceptibility of these bacteria to commonly used antibiotics showed that H. influenzae carriage decreased from 2000 to 2012. Additionally, the percentage of β-lactamase-producing isolates increased while their susceptibility to ampicillin progressively decreased during this time. These results indicate that the appropriate empirical antimicrobial therapy should be changed for pediatric patients in China.

RODENT MODELS OF SUSCEPTIBILITY: WHAT IS THEIR PLACE IN INHALATION TOXICOLOGY

EPA Science Inventory

Abstract: There is renewed interest in inhalation toxicology regarding "susceptibility" as associated with host variables, including genetics, age, diet, and disease. This interest derives from epidemiology that shows air pollution-related human mortality/morbidity, especially a...

Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction

PubMed Central

Christensen, Mark H.; Ishibashi, Masaru; Nielsen, Michael L.; Leonard, Christopher S.; Kohlmeier, Kristi A.

2015-01-01

The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on several parameters affecting LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7-P15), nicotine was found to induce larger intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15-P34). Nicotine increased neuronal firing of cholinergic cells to a greater degree in younger animals, possibly linked to development associated differences found in nicotinic effects on action potential shape and afterhyperpolarization. We conclude that in addition to age-associated alterations of several properties expected to affect resting cell excitability, parameters affecting cell excitability are altered by nicotine differentially across ontogeny. Taken together, our data suggest that nicotine induces a larger excitatory response in cholinergic LDT neurons from the youngest animals, which could result in a greater excitatory output from these cells to target regions involved in development of addiction. Such output would be expected to be promotive of addiction; therefore, ontogenetic differences in nicotine-mediated increases in the excitability of the LDT could contribute to the differential susceptibility to nicotine addiction seen across age. PMID:24863041

MR Measurement of Alloy Magnetic Susceptibility: Towards Developing Tissue-Susceptibility Matched Metals

PubMed Central

Astary, Garrett W.; Peprah, Marcus K.; Fisher, Charles R.; Stewart, Rachel L.; Carney, Paul R.; Sarntinoranont, Malisa; Meisel, Mark W.; Manuel, Michele V.; Mareci, Thomas H.

2013-01-01

Magnetic resonance imaging (MRI) can be used to relate structure to function mapped with high-temporal resolution electrophysiological recordings using metal electrodes. Additionally, MRI may be used to guide the placement of electrodes or conductive cannula in the brain. However, the magnetic susceptibility mismatch between implanted metals and surrounding brain tissue can severely distort MR images and spectra, particularly in high magnetic fields. In this study, we present a modified MR method of characterizing the magnetic susceptibility of materials that can be used to develop biocompatible, metal alloys that match the susceptibility of host tissue in order to eliminate MR distortions proximal to the implant. This method was applied at 4.7 T and 11.1 T to measure the susceptibility of a model solid-solution alloy of Cu and Sn, which is inexpensive but not biocompatible. MR-derived relative susceptibility values of four different compositions of Cu-Sn alloy deviated by less than 3.1% from SQUID magnetometry absolute susceptibility measurements performed up to 7 T. These results demonstrate that the magnetic susceptibility varies linearly with atomic percentage in these solid-solution alloys, but are not simply the weighted average of Cu and Sn magnetic susceptibilities. Therefore susceptibility measurements are necessary when developing susceptibility-matched, solid-solution alloys for the elimination of susceptibility artifacts in MR. This MR method does not require any specialized equipment and is free of geometrical constraints, such as sample shape requirements associated with SQUID magnetometry, so the method can be used at all stages of fabrication to guide the development of a susceptibility matched, biocompatible device. PMID:23727587

Exocarp Properties and Transcriptomic Analysis of Cucumber (Cucumis sativus) Fruit Expressing Age-Related Resistance to Phytophthora capsici

PubMed Central

Ando, Kaori; Carr, Kevin M.; Colle, Marivi; Mansfeld, Ben N.; Grumet, Rebecca

2015-01-01

Very young cucumber (Cucumis sativus) fruit are highly susceptible to infection by the oomycete pathogen, Phytophthora capsici. As the fruit complete exponential growth, at approximately 10–12 days post pollination (dpp), they transition to resistance. The development of age-related resistance (ARR) is increasingly recognized as an important defense against pathogens, however, underlying mechanisms are largely unknown. Peel sections from cucumber fruit harvested at 8 dpp (susceptible) and 16 dpp (resistant) showed equivalent responses to inoculation as did whole fruit, indicating that the fruit surface plays an important role in defense against P. capsici. Exocarp from 16 dpp fruit had thicker cuticles, and methanolic extracts of peel tissue inhibited growth of P. capsici in vitro, suggesting physical or chemical components to the ARR. Transcripts specifically expressed in the peel vs. pericarp showed functional differentiation. Transcripts predominantly expressed in the peel were consistent with fruit surface associated functions including photosynthesis, cuticle production, response to the environment, and defense. Peel-specific transcripts that exhibited increased expression in 16 dpp fruit relative to 8 dpp fruit, were highly enriched (P<0.0001) for response to stress, signal transduction, and extracellular and transport functions. Specific transcripts included genes associated with potential physical barriers (i.e., cuticle), chemical defenses (flavonoid biosynthesis), oxidative stress, penetration defense, and molecular pattern (MAMP)-triggered or effector-triggered (R-gene mediated) pathways. The developmentally regulated changes in gene expression between peels from susceptible- and resistant- age fruits suggest programming for increased defense as the organ reaches full size. PMID:26528543

Exocarp Properties and Transcriptomic Analysis of Cucumber (Cucumis sativus) Fruit Expressing Age-Related Resistance to Phytophthora capsici.

PubMed

Ando, Kaori; Carr, Kevin M; Colle, Marivi; Mansfeld, Ben N; Grumet, Rebecca

2015-01-01

Very young cucumber (Cucumis sativus) fruit are highly susceptible to infection by the oomycete pathogen, Phytophthora capsici. As the fruit complete exponential growth, at approximately 10-12 days post pollination (dpp), they transition to resistance. The development of age-related resistance (ARR) is increasingly recognized as an important defense against pathogens, however, underlying mechanisms are largely unknown. Peel sections from cucumber fruit harvested at 8 dpp (susceptible) and 16 dpp (resistant) showed equivalent responses to inoculation as did whole fruit, indicating that the fruit surface plays an important role in defense against P. capsici. Exocarp from 16 dpp fruit had thicker cuticles, and methanolic extracts of peel tissue inhibited growth of P. capsici in vitro, suggesting physical or chemical components to the ARR. Transcripts specifically expressed in the peel vs. pericarp showed functional differentiation. Transcripts predominantly expressed in the peel were consistent with fruit surface associated functions including photosynthesis, cuticle production, response to the environment, and defense. Peel-specific transcripts that exhibited increased expression in 16 dpp fruit relative to 8 dpp fruit, were highly enriched (P<0.0001) for response to stress, signal transduction, and extracellular and transport functions. Specific transcripts included genes associated with potential physical barriers (i.e., cuticle), chemical defenses (flavonoid biosynthesis), oxidative stress, penetration defense, and molecular pattern (MAMP)-triggered or effector-triggered (R-gene mediated) pathways. The developmentally regulated changes in gene expression between peels from susceptible- and resistant- age fruits suggest programming for increased defense as the organ reaches full size.

The DrugAge database of aging-related drugs.

PubMed

Barardo, Diogo; Thornton, Daniel; Thoppil, Harikrishnan; Walsh, Michael; Sharifi, Samim; Ferreira, Susana; Anžič, Andreja; Fernandes, Maria; Monteiro, Patrick; Grum, Tjaša; Cordeiro, Rui; De-Souza, Evandro Araújo; Budovsky, Arie; Araujo, Natali; Gruber, Jan; Petrascheck, Michael; Fraifeld, Vadim E; Zhavoronkov, Alexander; Moskalev, Alexey; de Magalhães, João Pedro

2017-06-01

Aging is a major worldwide medical challenge. Not surprisingly, identifying drugs and compounds that extend lifespan in model organisms is a growing research area. Here, we present DrugAge (http://genomics.senescence.info/drugs/), a curated database of lifespan-extending drugs and compounds. At the time of writing, DrugAge contains 1316 entries featuring 418 different compounds from studies across 27 model organisms, including worms, flies, yeast and mice. Data were manually curated from 324 publications. Using drug-gene interaction data, we also performed a functional enrichment analysis of targets of lifespan-extending drugs. Enriched terms include various functional categories related to glutathione and antioxidant activity, ion transport and metabolic processes. In addition, we found a modest but significant overlap between targets of lifespan-extending drugs and known aging-related genes, suggesting that some but not most aging-related pathways have been targeted pharmacologically in longevity studies. DrugAge is freely available online for the scientific community and will be an important resource for biogerontologists. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Perspectives on human clinical trials of therapies using iPS cells in Japan: reaching the forefront of stem-cell therapies.

PubMed

Song, Peipei; Inagaki, Yoshinori; Sugawara, Yasuhiko; Kokudo, Norihiro

2013-06-01

A research project involving sheets of retinal pigment epithelium constructed from iPS cells derived from patients with age-related maculopathy is one step closer to being approved for clinical trials by the Japanese Government. Now is the time to make therapies using iPS cells clinically available.

Relative Age

NASA Image and Video Library

2010-06-04

In some regions of Mars the relative ages of different materials can be determined. In this image, captured by NASA 2001 Mars Odyssey, the younger lava flows of Daedalia Planum are on top of the older Terra Sirenum materials.

Growth of ponderosa pine stands in relation to mountain pine beetle susceptibility

Treesearch

R. A. Obedzinski; J. M. Schmid; S. A. Mata; W. K. Olsen; R. R. Kessler

1999-01-01

Ten-year diameter and basal area growth were determined for partially cut stands at 4 locations. Average diameters in the partially cut plots generally increased by 1 inch or more, while average diameter in the uncut controls increased by 0.9 inches or less. Individual tree growth is discussed in relation to potential susceptibility to mountain pine beetle infestation...

[Age-related changes in swallowing. Physiology and pathophysiology].

PubMed

Muhle, P; Wirth, R; Glahn, J; Dziewas, R

2015-04-01

The term presbyphagia refers to all changes of swallowing physiology that are manifested with increasing age. Alterations in the pattern of deglutition that are part of healthy aging are called primary presbyphagia. Primary presbyphagia is not an illness in itself but contributes to a more pervasive naturally diminished functional reserve, making older adults more susceptible to dysphagia. If disorders in swallowing occur in the elderly as a comorbidity of a specific disease, for example stroke or neurodegenerative disorders, this is called secondary presbyphagia. Increasing age has an impact on each stage of deglutition. In the oral preparatory phase a diminished input for smell and taste as well as a usually multifactorial cause of dry mouth are the most important influencing factors. Sarcopenia, the degenerative loss of skeletal muscle mass, strength and quality associated with aging, interferes in particular with the oropharyngeal phase. A decreased sensory feedback from the oropharyngeal mucosa leads to a delayed triggering of the swallowing reflex. Finally, a reduction in connective tissue elasticity and changes of the axial skeleton lead to various modifications of the swallowing pattern with advanced age.

Age-Related Susceptibility to Apoptosis in Human Retinal Pigment Epithelial Cells Is Triggered by Disruption of p53–Mdm2 Association

PubMed Central

Bhattacharya, Sujoy; Chaum, Edward; Johnson, Dianna A.; Johnson, Leonard R.

2012-01-01

Purpose. Relatively little is known about the contribution of p53/Mdm2 pathway in apoptosis of retinal pigment epithelial (RPE) cells or its possible link to dysfunction of aging RPE or to related blinding disorders such as age-related macular degeneration (AMD). Methods. Age-associated changes in p53 activation were evaluated in primary RPE cultures from human donor eyes of various ages. Apoptosis was evaluated by activation of caspases and DNA fragmentation. Gene-specific small interfering RNA was used to knock down expression of p53. Results. We observed that the basal rate of p53-dependent apoptosis increased in an age-dependent manner in human RPE. The age-dependent increase in apoptosis was linked to alterations in several aspects of the p53 pathway. p53 phosphorylation Ser15 was increased through the stimulation of ATM-Ser1981. p53 acetylation Lys379 was increased through the inhibition of SIRT1/2. These two posttranslational modifications of p53 blocked the sequestration of p53 by Mdm2, thus resulting in an increase in free p53 and of p53 stimulation of apoptosis through increased expression of PUMA (p53 upregulated modulator of apoptosis) and activation of caspase-3. Aged RPE also had reduced expression of antiapoptotic Bcl-2, which contributed to the increase in apoptosis. Of particular interest in these studies was that pharmacologic treatments to block p53 phosphorylation, acetylation, or expression were able to protect RPE cells from apoptosis. Conclusions. Our studies suggest that aging in the RPE leads to alterations of specific checkpoints in the apoptotic pathway, which may represent important molecular targets for the treatment of RPE-related aging disorders such as AMD. PMID:23139272

Genetic studies of Age-related macular degeneration: lessons, challenges and opportunities for disease management

PubMed Central

Ratna Priya, Rinki; Chew, Emily Y.; Swaroop, Anand

2012-01-01

Age-related macular degeneration (AMD) is a common cause of visual impairment in individuals over 55 years of age worldwide. The varying clinical phenotypes of AMD result from contributions of genetic, epigenetic and non-genetic (environmental) factors. Genetic studies of AMD have come of age as a direct result of tremendous gains from human genome project, genomewide association studies and identification of numerous susceptibility loci. These findings have implicated immune response, high-density lipoprotein cholesterol metabolism, extracellular matrix, and angiogenesis signaling pathways in disease pathophysiology. Here, we address how the wealth of genetic findings in AMD is expected to impact the practice of medicine, providing opportunities for improved risk assessment, molecular diagnosis, preventive and therapeutic intervention. We propose that the potential of using genetic variants for monitoring treatment response (pharmacogenetics) may usher a new era of personalized medicine in the clinical management of AMD. PMID:23009893

Risk Factors for Varicella Susceptibility Among Refugees to Toronto, Canada.

PubMed

Cadieux, Geneviève; Redditt, Vanessa; Graziano, Daniela; Rashid, Meb

2017-02-01

Several outbreaks of varicella have occurred among refugees. We aimed to estimate the prevalence of varicella susceptibility among refugees, and identify risk factors for varicella susceptibility. All refugees rostered at Crossroads Clinic in Toronto, Canada in 2011-2014 were included in our study. Varicella serology was assessed at the initial visit. Refugees' age, sex, education, time since arrival, and climate and population density of birth country were abstracted from the chart. Multivariate logistic regression was used to identify risk factors for varicella susceptibility. 1063 refugees were rostered at Crossroads Clinic during the study; 7.9 % (95 % CI 6.1, 9.7) were susceptible to varicella. Tropical climate (OR 3.20, 95 % CI 1.53, 6.69) and younger age (OR per year of age 0.92, 95 % CI 0.88-0.96) were associated with increased varicella susceptibility. These risk factors for varicella susceptibility should be taken into account to maximize the cost-effectiveness of varicella prevention strategies among refugees.

EFFECTS OF TOLUENE ON BRAIN OXIDATIVE STRESS PARAMETERS IN AGING BROWN NORWAY RATS

EPA Science Inventory

Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for tol...

Susceptibility of Diabetic Rats to Pulmonary and Systemic Effects of Inhaled Photochemically-Aged Atmosphere and Ozone (O3)

EPA Science Inventory

Susceptibility of Diabetic Rats to Pulmonary and Systemic Effects of Inhaled Photochemically-Aged Atmosphere and Ozone (O3)MC Schladweiler1, SJ Snow2, QT Krantz1, C King1, JD Krug2, N Modak2, A Henriquez3, V Bass4, DJ Miller3, JE Richards1, EH Boykin1, R Jaskot1, MI Gilmour1 and ...

Diabetic eye disease among adults in Fiji with previously undiagnosed diabetes.

PubMed

Brian, Garry; Sikivou, Biu; Fischer-Harder, Konstanze; Szetu, John; Qoqonokana, Mundi Qalo; Ramke, Jacqueline

2011-01-01

To determine the prevalence and severity of diabetic eye disease among adults aged ≥40 years with unrecognized diabetes in Fiji. Population-based cross-sectional survey using multistage cluster random sampling. 1381 (=73.0% participation). Interview-based questionnaire; visual acuity measured; dilated ocular examination performed; glycosylated haemoglobin (HbA1c) concentration determined. Prevalence and grade of diabetic retinopathy/maculopathy. Sample prevalence of diabetes was 44.8% (95%CI 42.2-47.5%), with 63.4% (95%CI 59.5-67.1%) previously undiagnosed (384/606). Predictors of undiagnosed compared with previously diagnosed diabetes were female gender (P = 0.001), rural residence (P = 0.049) and not having a relative with known diabetes (P < 0.001). Twenty-two retinae of participants with previously undiagnosed diabetes were unexaminable (predominantly cataract). Of the remaining 746 eyes, 3.5% (95%CI 2.4-5.1%) had diabetic retinopathy/maculopathy, 1 (0.1%) had proliferative retinopathy and 4 (0.5%) had active significant maculopathy. Of eyes with diabetic disease, two (7.7%, 95%CI 1.0-25.3%) had diabetes-related vision impairment (3/60; 6/60). Sixteen previously undiagnosed participants (4.2%, 95%CI 2.5-6.7%) had diabetic disease evident in at least one eye: for four (all Melanesian women aged >50 years), this was vision-threatening (1.0%; 95%CI 0.3-2.8). Mean HbA1c (10.7 ± 2.6%) of participants undiagnosed and with diabetes eye disease was higher (P < 0.001) than that of those undiagnosed and without. The prevalence of diabetic eye disease was low among this cohort, but where present, severe vision-threatening retinopathy/maculopathy was relatively common. If diabetic eye disease is to be avoided or ameliorated in Fiji, then community awareness of and access to diabetes diagnostic services must improve, particularly for women and rural dwellers. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of

Susceptibility to mortality related to temperature and heat and cold wave duration in the population of Stockholm County, Sweden

PubMed Central

Rocklöv, Joacim; Forsberg, Bertil; Ebi, Kristie; Bellander, Tom

2014-01-01

Background Ambient temperatures can cause an increase in mortality. A better understanding is needed of how health status and other factors modify the risk associated with high and low temperatures, to improve the basis of preventive measures. Differences in susceptibility to temperature and to heat and cold wave duration are relatively unexplored. Objectives We studied the associations between mortality and temperature and heat and cold wave duration, stratified by age and individual and medical factors. Methods Deaths among all residents of Stockholm County between 1990 and 2002 were linked to discharge diagnosis data from hospital admissions, and associations were examined using the time stratified case-crossover design. Analyses were stratified by gender, age, pre-existing disease, country of origin, and municipality level wealth, and adjusted for potential confounding factors. Results The effect on mortality by heat wave duration was higher for lower ages, in areas with lower wealth, for hospitalized patients younger than age 65. Odds were elevated among females younger than age 65, in groups with a previous hospital admission for mental disorders, and in persons with previous cardiovascular disease. Gradual increases in summer temperatures were associated with mortality in people older than 80 years, and with mortality in groups with a previous myocardial infarction and with chronic obstructive pulmonary disease (COPD) in the population younger than 65 years. During winter, mortality was associated with a decrease in temperature particularly in men and with the duration of cold spells for the population older than 80. A history of hospitalization for myocardial infarction increased the odds associated with cold temperatures among the population older than 65. Previous mental disease or substance abuse increased the odds of death among the population younger than 65. Conclusion To increase effectiveness, we suggest preventive efforts should not assume

Selective breeding for susceptibility to myopia reveals a gene-environment interaction.

PubMed

Chen, Yen-Po; Hocking, Paul M; Wang, Ling; Povazay, Boris; Prashar, Ankush; To, Chi-Ho; Erichsen, Jonathan T; Feldkaemper, Marita; Hofer, Bernd; Drexler, Wolfgang; Schaeffel, Frank; Guggenheim, Jeremy A

2011-06-08

Purpose. To test whether the interanimal variability in susceptibility to visually induced myopia is genetically determined. Methods. Monocular deprivation of sharp vision (DSV) was induced in outbred White Leghorn chicks aged 4 days. After 4 days' DSV, myopia susceptibility was quantified by the relative changes in axial length and refraction. Chicks in the extreme tails of the distribution of susceptibility to DSV were kept and paired for breeding (high- and low-susceptibility lines). A second round of selection was then performed. The third generation of chicks, derived from the selected parents, was assessed after either monocular DSV (4 or 10 days) or lens wear. Results. After two rounds of selective breeding, the chicks from the high-susceptibility line developed approximately twice as much myopia in response to 4 days' DSV as did those from the low-susceptibility line (P < 0.001). All ocular component dimensions differed significantly (P < 0.001) between the two selected lines, both before treatment and in the responses of the treated eye. When DSV was conducted for 10 days, the relative changes in axial length and refractive error were still significantly different between the high and low lines (P < 0.001). The chicks bred for high or low susceptibility to DSV also showed significantly different responses to minus lens wear, but not to plus lens wear. Additive genetic effects explained ∼50% of the interanimal variability in response to DSV. Conclusions. Genes and environment interact to shape refractive development in chicks.

Quantitative susceptibility map analysis in preterm neonates with germinal matrix-intraventricular hemorrhage.

PubMed

Tortora, Domenico; Severino, Mariasavina; Sedlacik, Jan; Toselli, Benedetta; Malova, Mariya; Parodi, Alessandro; Morana, Giovanni; Fato, Marco Massimo; Ramenghi, Luca Antonio; Rossi, Andrea

2018-05-10

Germinal matrix-intraventricular hemorrhage (GMH-IVH) is a common form of intracranial hemorrhage occurring in preterm neonates that may affect normal brain development. Although the primary lesion is easily identified on MRI by the presence of blood products, its exact extent may not be recognizable with conventional sequences. Quantitative susceptibility mapping (QSM) quantify the spatial distribution of magnetic susceptibility within biological tissues, including blood degradation products. To evaluate magnetic susceptibility of normal-appearing white (WM) and gray matter regions in preterm neonates with and without GMH-IVH. Retrospective case-control. A total of 127 preterm neonates studied at term equivalent age: 20 had mild GMH-IVH (average gestational age 28.7 ± 2.1 weeks), 15 had severe GMH-IVH (average gestational age 29.3 ± 1.8 weeks), and 92 had normal brain MRI (average gestational age 29.8 ± 1.8 weeks). QSM at 1.5 Tesla. QSM analysis was performed for each brain hemisphere with a region of interest-based approach including five WM regions (centrum semiovale, frontal, parietal, temporal, and cerebellum), and a subcortical gray matter region (basal ganglia/thalami). Changes in magnetic susceptibility were explored using a one-way analysis of covariance, according to GMH-IVH severity (P < 0.05). In preterm neonates with normal brain MRI, all white and subcortical gray matter regions had negative magnetic susceptibility values (diamagnetic). Neonates with severe GMH-IVH showed higher positive magnetic susceptibility values (i.e. paramagnetic) in the centrum semiovale (0.0019 versus -0.0014 ppm; P < 0.001), temporal WM (0.0011 versus -0.0012 ppm; P = 0.037), and parietal WM (0.0005 versus -0.0001 ppm; P = 0.002) compared with controls. No differences in magnetic susceptibility were observed between neonates with mild GMH-IVH and controls (P = 0.236). Paramagnetic susceptibility changes occur in several normal

AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON PROTEIN CARBONYL CONTENT IN FRONTAL CORTEX AND CEREBELLUM OF BROWN NORWAY RATS.

EPA Science Inventory

The influence of aging on susceptibility to environmental contaminants is poorly understood, largely due to a lack of data on exposures in older adults and adequate animal models. We examined the acute effects of the volatile organic compound, toluene, in a study investigating m...

Genome-wide analysis of disease progression in age-related macular degeneration.

PubMed

Yan, Qi; Ding, Ying; Liu, Yi; Sun, Tao; Fritsche, Lars G; Clemons, Traci; Ratnapriya, Rinki; Klein, Michael L; Cook, Richard J; Liu, Yu; Fan, Ruzong; Wei, Lai; Abecasis, Gonçalo R; Swaroop, Anand; Chew, Emily Y; Weeks, Daniel E; Chen, Wei

2018-03-01

Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related macular degeneration (AMD), one of the first batch and most successful examples of genome-wide association study. However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization or geographic atrophy). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study. To our knowledge, this is the first genome-wide association study of disease progression (bivariate survival outcome) in AMD genetic studies, thus providing novel insights to AMD genetics. We used a robust Cox proportional hazards model to appropriately account for between-eye correlation when analyzing the progression time in the two eyes of each participant. We identified four previously reported susceptibility loci showing genome-wide significant association with AMD progression: ARMS2-HTRA1 (P = 8.1 × 10-43), CFH (P = 3.5 × 10-37), C2-CFB-SKIV2L (P = 8.1 × 10-10) and C3 (P = 1.2 × 10-9). Furthermore, we detected association of rs58978565 near TNR (P = 2.3 × 10-8), rs28368872 near ATF7IP2 (P = 2.9 × 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression to choroidal neovascularization but not geographic atrophy. Secondary analysis limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also associated with AMD progression (P < 0.0015). Our genome-wide analysis thus expands the genetics in both development and progression of AMD and should assist in early identification of high risk individuals.

Genetic polymorphism of interleukin-6 influences susceptibility to HBV-related hepatocellular carcinoma in a male Chinese Han population.

PubMed

Tang, Shengli; Yuan, Yufeng; He, Yueming; Pan, Dingyu; Zhang, Yongxi; Liu, Yuanyuan; Liu, Quanyan; Zhang, Zhonglin; Liu, Zhisu

2014-04-01

As a multifunctional cytokine, interleukin-6 (IL-6) plays a key role in chronic inflammation as well as tumor growth and progression of hepatitis B virus (HBV) infection. Recent studies have implicated that single nucleotide polymorphism (SNP) -572C>G (rs1800796) located within the promoter region of IL-6 gene was associated with susceptibility to several diseases. Here, a case-control study was undertaken to investigate the association between this polymorphism and HBV-related hepatocellular carcinoma (HCC) susceptibility in a Chinese Han population. A total of 900 patients with chronic HBV infection, including 505 HBV-related HCC patients and 395 HBV infected patients without HCC were enrolled, and rs1800796 polymorphism was genotyped by the TaqMan method and DNA sequencing technology. The results indicated no significant association between rs1800796 polymorphism and the risk of HBV-related HCC in all subjects; however, a significant difference was identified in male subjects. Under the dominant model, male subjects with the G allele (CG/GG) have higher susceptibility to HBV-related HCC than those with CC genotype after adjusting confounding factors (P=0.012, odds ratio [OR] 1.68, 95% confidence interval [95% CI] 1.15-2.42). Our results suggested that rs1800796 polymorphism of IL-6 gene was associated with susceptibility to HBV-related HCC in a male Chinese Han population. Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: the Nutritional AMD Treatment 2 study.

PubMed

Souied, Eric H; Delcourt, Cécile; Querques, Giuseppe; Bassols, Ana; Merle, Bénédicte; Zourdani, Alain; Smith, Theodore; Benlian, Pascale

2013-08-01

To evaluate the efficacy of docosahexaenoic acid (DHA)-enriched oral supplementation in preventing exudative age-related macular degeneration (AMD). The Nutritional AMD Treatment 2 study was a randomized, placebo-controlled, double-blind, parallel, comparative study. Two hundred sixty-three patients 55 years of age or older and younger than 85 years with early lesions of age-related maculopathy and visual acuity better than 0.4 logarithm of minimum angle of resolution units in the study eye and neovascular AMD in the fellow eye. Patients were assigned randomly to receive either 840 mg/day DHA and 270 mg/day eicosapentaenoic acid (EPA) from fish oil capsules or the placebo (olive oil capsules) for 3 years. The primary outcome measure was time to occurrence of choroidal neovascularization (CNV) in the study eye. Secondary outcome measures in the study eye were: incidence of CNV developing in patients, changes in visual acuity, occurrence and progression of drusen, and changes in EPA plus DHA level in red blood cell membrane (RBCM). Time to occurrence and incidence of CNV in the study eye were not significantly different between the DHA group (19.5±10.9 months and 28.4%, respectively) and the placebo group (18.7±10.6 months and 25.6%, respectively). In the DHA group, EPA plus DHA levels increased significantly in RBCM (+70%; P<0.001), suggesting that DHA easily penetrated cells, but this occurred unexpectedly also in the placebo group (+9%; P = 0.007). In the DHA-allocated group, patients steadily achieving the highest tertile of EPA plus DHA levels in RBCM had significantly lower risk (-68%; P = 0.047; hazard ratio, 0.32; 95% confidence interval, 0.10-0.99) of CNV developing over 3 years. No marked changes from baseline in best-corrected visual acuity, drusen progression, or geographic atrophy in the study eye were observed throughout the study in either group. In patients with unilateral exudative AMD, 3 years of oral DHA-enriched supplementation had the same

Environmental cadmium and lead exposures and age-related macular degeneration in U.S. adults: The National Health and Nutrition Examination Survey 2005 to 2008

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Erin W.; Schaumberg, Debra A.; Center for Translational Medicine, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT

Age-related macular degeneration (AMD) is a complex disease resulting from the interplay of genetic predisposition and environmental exposures, and has been linked to oxidative stress and inflammatory mechanisms. Lead and cadmium can accumulate in human retinal tissues and may damage the retina through oxidative stress, and may thereby play a role in the development of AMD. We examined associations between blood lead, blood cadmium, and urinary cadmium concentrations and the presence of AMD in 5390 participants aged 40 years and older with blood lead and blood cadmium measures and a subsample of 1548 with urinary cadmium measures in the 2005–2008more » National Health and Nutrition Examination Surveys. AMD was identified by grading retinal photographs with a modification of the Wisconsin Age-Related Maculopathy Grading System. The weighted prevalence of AMD was 6.6% (n=426). Controlling for age, gender, race/ethnicity, education and body mass index, adults in the highest blood cadmium quartile had higher odds of AMD compared to the lowest quartile (odds ratio [OR], 1.56; 95% CI, 1.02–2.40), with a significant trend across quartiles (p-trend=0.02). After further adjustment for pack-years of cigarette smoking, estimates were somewhat attenuated (OR, 1.43; 95% CI, 0.91–2.27; p-trend=0.08). Similar associations were found with urinary cadmium. The association between urinary cadmium and AMD was stronger in non-Hispanic whites (NHW) than in non-Hispanic blacks (NHB) (OR, 3.31; 95% CI, 1.37–8.01 for levels above versus below the median among NHW; OR,1.45; 95% CI, 0.40–5.32 for levels above versus below the median among NHB; p-interaction=0.03). We found no association between blood lead levels and AMD. Higher cadmium body burden may increase risk of AMD, particularly among non-Hispanic white individuals; however, additional studies are needed before firm conclusions can be drawn. - Highlights: • We examined the association of cadmium and lead with age-related

Human Gut Microbiota Predicts Susceptibility to Vibrio cholerae Infection.

PubMed

Midani, Firas S; Weil, Ana A; Chowdhury, Fahima; Begum, Yasmin A; Khan, Ashraful I; Debela, Meti D; Durand, Heather K; Reese, Aspen T; Nimmagadda, Sai N; Silverman, Justin D; Ellis, Crystal N; Ryan, Edward T; Calderwood, Stephen B; Harris, Jason B; Qadri, Firdausi; David, Lawrence A; LaRocque, Regina C

2018-04-12

Cholera is a public health problem worldwide and the risk factors for infection are only partially understood. We prospectively studied household contacts of cholera patients to compare those who were infected with those who were not. We constructed predictive machine learning models of susceptibility using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio cholerae infection and tested these taxa for interactions with V. cholerae in vitro. We found that machine learning models based on gut microbiota predicted V. cholerae infection as well as models based on known clinical and epidemiological risk factors. A 'predictive gut microbiota' of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota structure, clinical outcome, and age were also linked. These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility.

Association of Age Related Macular Degeneration and Age Related Hearing Impairment

PubMed Central

Ghasemi, Hassan; Pourakbari, Malihe Shahidi; Entezari, Morteza; Yarmohammadi, Mohammad Ebrahim

2016-01-01

Purpose: To evaluate the association between age-related macular degeneration (ARMD) and sensory neural hearing impairment (SHI). Methods: In this case-control study, hearing status of 46 consecutive patients with ARMD were compared with 46 age-matched cases without clinical ARMD as a control group. In all patients, retinal involvements were confirmed by clinical examination, fluorescein angiography (FA) and optical coherence tomography (OCT). All participants were examined with an otoscope and underwent audiological tests including pure tone audiometry (PTA), speech reception threshold (SRT), speech discrimination score (SDS), tympanometry, reflex tests and auditory brainstem response (ABR). Results: A significant (P = 0.009) association was present between ARMD, especially with exudative and choroidal neovascularization (CNV) components, and age-related hearing impairment primarily involving high frequencies. Patients had higher SRT and lower SDS against anticipated presbycusis than control subjects. Similar results were detected in exudative, CNV and scar patterns supporting an association between late ARMD with SRT and SDS abnormalities. ABR showed significantly prolonged wave I and IV latency times in ARMD (P = 0.034 and 0.022, respectively). Average latency periods for wave I in geographic atrophy (GA) and CNV, and that for wave IV in drusen patterns of ARMD were significantly higher than controls (P = 0.030, 0.007 and 0.050, respectively). Conclusion: The association between ARMD and age-related SHI may be attributed to common anatomical components such as melanin in these two sensory organs. PMID:27195086

Consequences of Age-Related Cognitive Declines

PubMed Central

Salthouse, Timothy

2013-01-01

Adult age differences in a variety of cognitive abilities are well documented, and many of those abilities have been found to be related to success in the workplace and in everyday life. However, increased age is seldom associated with lower levels of real-world functioning, and the reasons for this lab-life discrepancy are not well understood. This article briefly reviews research concerned with relations of age to cognition, relations of cognition to successful functioning outside the laboratory, and relations of age to measures of work performance and achievement. The final section discusses several possible explanations for why there are often little or no consequences of age-related cognitive declines in everyday functioning. PMID:21740223

Age-related aspects of addiction

PubMed Central

Koechl, Birgit; Unger, Annemarie; Fischer, Gabriele

2013-01-01

Research has shown that substance use, abuse and addiction are not limited to a specific age group. Problems related to substance addiction are an important cause of morbidity in the population aged 65 and above, especially the abuse of prescription drugs and legal substances. A lack of evidence-based studies and tailored treatment options for the aging population is evident. Appropriate and effective health-care is an important goal to improve health-related quality of life of elderly people. Research in the increasingly aging population needs to include an age- and gender-sensitive approach. PMID:22722821

Risk factors for persisting measles susceptibility: a case-control study among unvaccinated orthodox Protestants.

PubMed

de Munter, Anne C; Tostmann, Alma; Hahné, Susan J M; Spaan, D Henri; van Ginkel, Rijk; Ruijs, Wilhelmina L M

2018-04-30

Measles is an infectious disease providing lifelong immunity. Epidemics periodically occur among unvaccinated orthodox Protestants in the Netherlands. During the 2013/2014 epidemic, 17% of the reported patients was over 14 years old. Apparently, they did not catch measles during the previous 1999/2000 epidemic and remained susceptible. We wanted to identify risk factors for this so-called persisting measles susceptibility, and thus risk factors for acquiring measles at older age with increased risk of complications. A case-control study was performed among unvaccinated orthodox Protestants born between 1988 and 1998; cases had measles in 2013/2014, controls during or before 1999/2000. Associations between demographic, geographical and religion-related determinants and persisting measles susceptibility were determined using univariate and multivariable logistic regression. Analyses were stratified in two age-groups: infants/toddlers and primary school-aged children during the 1999/2000 measles epidemic. In total, 204 cases and 563 controls were included. Risk factors for persisting measles susceptibility for infants/toddlers in 1999/2000 were belonging to a moderately conservative church, absence of older siblings and residency outside low vaccination coverage (LVC)-municipalities. Risk factors for primary school-aged children were residency outside LVC-municipalities and attendance of non-orthodox Protestant primary school. Unvaccinated orthodox Protestant adolescents and adults who resided outside the LVC-municipalities, did not attend an orthodox Protestant primary school, had no older siblings and belonged to a moderately conservative church were at risk for persisting measles susceptibility and, thus, for acquiring measles at older age with increased risk of complications. For this subgroup of orthodox Protestants targeted information on vaccination is recommended.

Clinical Trials Targeting Aging and Age-Related Multimorbidity

PubMed Central

Crimmins, Eileen M; Grossardt, Brandon R; Crandall, Jill P; Gelfond, Jonathan A L; Harris, Tamara B; Kritchevsky, Stephen B; Manson, JoAnn E; Robinson, Jennifer G; Rocca, Walter A; Temprosa, Marinella; Thomas, Fridtjof; Wallace, Robert; Barzilai, Nir

2017-01-01

Abstract Background There is growing interest in identifying interventions that may increase health span by targeting biological processes underlying aging. The design of efficient and rigorous clinical trials to assess these interventions requires careful consideration of eligibility criteria, outcomes, sample size, and monitoring plans. Methods Experienced geriatrics researchers and clinical trialists collaborated to provide advice on clinical trial design. Results Outcomes based on the accumulation and incidence of age-related chronic diseases are attractive for clinical trials targeting aging. Accumulation and incidence rates of multimorbidity outcomes were developed by selecting at-risk subsets of individuals from three large cohort studies of older individuals. These provide representative benchmark data for decisions on eligibility, duration, and assessment protocols. Monitoring rules should be sensitive to targeting aging-related, rather than disease-specific, outcomes. Conclusions Clinical trials targeting aging are feasible, but require careful design consideration and monitoring rules. PMID:28364543

The etiology of human age-related cataract. Proteins don't last forever.

PubMed

Truscott, Roger J W; Friedrich, Michael G

2016-01-01

It is probable that the great majority of human cataract results from the spontaneous decomposition of long-lived macromolecules in the human lens. Breakdown/reaction of long-lived proteins is of primary importance and recent proteomic analysis has enabled the identification of the particular crystallins, and their exact sites of amino acid modification. Analysis of proteins from cataractous lenses revealed that there are sites on some structural proteins that show a consistently greater degree of deterioration than age-matched normal lenses. The most abundant posttranslational modification of aged lens proteins is racemization. Deamidation, truncation and crosslinking, each arising from the spontaneous breakdown of susceptible amino acids within proteins, are also present. Fundamental to an understanding of nuclear cataract etiology, it is proposed that once a certain degree of modification at key sites occurs, that protein-protein interactions are disrupted and lens opacification ensues. Since long-lived proteins are now recognized to be present in many other sites of the body, such as the brain, the information gleaned from detailed analyses of degraded proteins from aged lenses will apply more widely to other age-related human diseases. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Shape-related characteristics of age-related differences in subcortical structures.

PubMed

Madan, Christopher R

2018-01-11

With an increasing aging population, it is important to understand biological markers of aging. Subcortical volume is known to differ with age; additionally considering shape-related characteristics may provide a better index of age-related differences. Fractal dimensionality is more sensitive to age-related differences, but is borne out of mathematical principles, rather than neurobiological relevance. We considered four distinct measures of shape and how they relate to aging and fractal dimensionality: surface-to-volume ratio, sphericity, long-axis curvature, and surface texture. Structural MRIs from a combined sample of over 600 healthy adults were used to measure age-related differences in the structure of the thalamus, putamen, caudate, and hippocampus. For each, volume and fractal dimensionality were calculated, as well as four distinct shape measures. These measures were examined for their utility in explaining age-related variability in brain structure. The four shape measures were able to account for 80%-90% of the variance in fractal dimensionality. Of the distinct shape measures, surface-to-volume ratio was the most sensitive biomarker. Though volume is often used to characterize inter-individual differences in subcortical structures, our results demonstrate that additional measures can be useful complements. Our results indicate that shape characteristics are useful biological markers of aging.

A Comprehensive Survey of Sequence Variation in the ABCA4 (ABCR) Gene in Stargardt Disease and Age-Related Macular Degeneration

PubMed Central

Rivera, Andrea; White, Karen; Stöhr, Heidi; Steiner, Klaus; Hemmrich, Nadine; Grimm, Timo; Jurklies, Bernhard; Lorenz, Birgit; Scholl, Hendrik P. N.; Apfelstedt-Sylla, Eckhart; Weber, Bernhard H. F.

2000-01-01

Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the ABCA4 gene. In addition, we have assessed the proposed role for ABCA4 in age-related macular degeneration (AMD), a common cause of late-onset blindness, by studying 200 affected individuals with late-stage disease. Using a screening strategy based primarily on denaturing gradient gel electrophoresis, we have identified in the three study groups a total of 127 unique alterations, of which 90 have not been previously reported, and have classified 72 as probable pathogenic mutations. Of the 288 STGD chromosomes studied, mutations were identified in 166, resulting in a detection rate of ∼58%. Eight different alleles account for 61% of the identified disease alleles, and at least one of these, the L541P-A1038V complex allele, appears to be a founder mutation in the German population. When the group with AMD and the control group were analyzed with the same methodology, 18 patients with AMD and 12 controls were found to harbor possible disease-associated alterations. This represents no significant difference between the two groups; however, for detection of modest effects of rare alleles in complex diseases, the analysis of larger cohorts of patients may be required. PMID:10958763

A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration.

PubMed

Rivera, A; White, K; Stöhr, H; Steiner, K; Hemmrich, N; Grimm, T; Jurklies, B; Lorenz, B; Scholl, H P; Apfelstedt-Sylla, E; Weber, B H

2000-10-01

Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the ABCA4 gene. In addition, we have assessed the proposed role for ABCA4 in age-related macular degeneration (AMD), a common cause of late-onset blindness, by studying 200 affected individuals with late-stage disease. Using a screening strategy based primarily on denaturing gradient gel electrophoresis, we have identified in the three study groups a total of 127 unique alterations, of which 90 have not been previously reported, and have classified 72 as probable pathogenic mutations. Of the 288 STGD chromosomes studied, mutations were identified in 166, resulting in a detection rate of approximately 58%. Eight different alleles account for 61% of the identified disease alleles, and at least one of these, the L541P-A1038V complex allele, appears to be a founder mutation in the German population. When the group with AMD and the control group were analyzed with the same methodology, 18 patients with AMD and 12 controls were found to harbor possible disease-associated alterations. This represents no significant difference between the two groups; however, for detection of modest effects of rare alleles in complex diseases, the analysis of larger cohorts of patients may be required.

Counteracting Age Stereotypes: A Self-Awareness Manipulation

ERIC Educational Resources Information Center

Chen, Yiwei; Pethtel, Olivia; Ma, Xiaodong

2010-01-01

The major goals of the present study were to (a) examine age differences in susceptibility to age stereotypes and (b) test a self-awareness manipulation in counteracting age stereotypes. Young and older adults read two sets of descriptors that only differed in the to-be-ignored age-related information. In the high self-awareness condition,…

Systematic analysis of the gerontome reveals links between aging and age-related diseases

PubMed Central

Fernandes, Maria; Wan, Cen; Tacutu, Robi; Barardo, Diogo; Rajput, Ashish; Wang, Jingwei; Thoppil, Harikrishnan; Thornton, Daniel; Yang, Chenhao; Freitas, Alex

2016-01-01

Abstract In model organisms, over 2,000 genes have been shown to modulate aging, the collection of which we call the ‘gerontome’. Although some individual aging-related genes have been the subject of intense scrutiny, their analysis as a whole has been limited. In particular, the genetic interaction of aging and age-related pathologies remain a subject of debate. In this work, we perform a systematic analysis of the gerontome across species, including human aging-related genes. First, by classifying aging-related genes as pro- or anti-longevity, we define distinct pathways and genes that modulate aging in different ways. Our subsequent comparison of aging-related genes with age-related disease genes reveals species-specific effects with strong overlaps between aging and age-related diseases in mice, yet surprisingly few overlaps in lower model organisms. We discover that genetic links between aging and age-related diseases are due to a small fraction of aging-related genes which also tend to have a high network connectivity. Other insights from our systematic analysis include assessing how using datasets with genes more or less studied than average may result in biases, showing that age-related disease genes have faster molecular evolution rates and predicting new aging-related drugs based on drug-gene interaction data. Overall, this is the largest systems-level analysis of the genetics of aging to date and the first to discriminate anti- and pro-longevity genes, revealing new insights on aging-related genes as a whole and their interactions with age-related diseases. PMID:28175300

The microbiota and microbiome in aging: potential implications in health and age-related diseases.

PubMed

Zapata, Heidi J; Quagliarello, Vincent J

2015-04-01

Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Motion sickness susceptibility related to ACTH, ADH and TSH

NASA Technical Reports Server (NTRS)

Kohl, R. L.; Leach, C.; Homick, J. L.; Larochelle, F. T.

1983-01-01

The hypothesis that endogenous levels of certain hormones might be indicative of an individual's susceptibility to stressful motion is tested in a comparison of subjects classified as less prone to motion sickness with those of higher susceptibility. The levels of ACTH and vasopressin measured before exposure to stressful motion were twice as high in the less-suceptible group. No significant differences were noted in the levels of angiotensin, aldosterone, or TSH. The differences between the two groups were greater for a given hormone than for any of the changes induced by exposure to stressful motion.

Age-related regulation of genes: slow homeostatic changes and age-dimension technology

NASA Astrophysics Data System (ADS)

Kurachi, Kotoku; Zhang, Kezhong; Huo, Jeffrey; Ameri, Afshin; Kuwahara, Mitsuhiro; Fontaine, Jean-Marc; Yamamoto, Kei; Kurachi, Sumiko

2002-11-01

Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named “age-dimension technology (ADT)”. ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.

Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults

PubMed Central

Tong, Ann-Jay; Kollmann, Tobias R.; Smale, Stephen T.

2015-01-01

A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development. PMID:26147648

Age-related DNA methylation changes for forensic age-prediction.

PubMed

Yi, Shao Hua; Jia, Yun Shu; Mei, Kun; Yang, Rong Zhi; Huang, Dai Xin

2015-03-01

There is no available method of age-prediction for biological samples. The accumulating evidences indicate that DNA methylation patterns change with age. Aging resembles a developmentally regulated process that is tightly controlled by specific epigenetic modifications and age-associated methylation changes exist in human genome. In this study, three age-related methylation fragments were isolated and identified in blood of 40 donors. Age-related methylation changes with each fragment was validated and replicated in a general population sample of 65 donors over a wide age range (11-72 years). Methylation of these fragments is linearly correlated with age over a range of six decades (r = 0.80-0.88). Using average methylation of CpG sites of three fragments, a regression model that explained 95 % of the variance in age was built and is able to predict an individual's age with great accuracy (R (2 )= 0.93). The predicted value is highly correlated with the observed age in the sample (r = 0.96) and has great accuracy of average 4 years difference between predicted age and true age. This study implicates that DNA methylation can be an available biological marker of age-prediction. Further measurement of relevant markers in the genome could be a tool in routine screening to predict age of forensic biological samples.

Age-related changes of task-specific brain activity in normal aging.

PubMed

Ho, Ming-Chung; Chou, Chia-Yi; Huang, Chin-Fei; Lin, Yu-Te; Shih, Ching-Sen; Han, Shiang-Yi; Shen, Ming-Hsun; Chen, Tsung-Ching; Liang, Chi-lin; Lu, Ming-Chi; Liu, Chia-Ju

2012-01-17

An important question in healthcare for older patients is whether age-related changes in cortical reorganization can be measured with advancing age. This study investigated the factors behind such age-related changes, using time-frequency analysis of event-related potentials (ERPs). We hypothesized that brain rhythms was affected by age-related changes, which could be reflected in the ERP indices. An oddball task was conducted in two experimental groups, namely young participants (N=15; mean age 23.7±2.8 years) and older participants (N=15; mean age 70.1±7.9 years). Two types of stimuli were used: the target (1 kHz frequency) and standard (2 kHz frequency). We scrutinized three ERP indices: event-related spectral power (ERPSP), inter-trial phase-locking (ITPL), and event-related cross-phase coherence (ERPCOH). Both groups performed equally well for correct response rate. However, the results revealed a statistically significant age difference for inter-trial comparison. Compared with the young, the older participants showed the following age-related changes: (a) power activity decreased; however, an increase was found only in the late (P3, 280-450 ms) theta (4-7 Hz) component over the bilateral frontal and temporo-frontal areas; (b) low phase-locking in the early (N1, 80-140 ms) theta band over the parietal/frontal (right) regions appeared; (c) the functional connections decreased in the alpha (7-13 Hz) and beta (13-30 Hz) bands, but no difference emerged in the theta band between the two groups. These results indicate that age-related changes in task-specific brain activity for a normal aging population can be depicted using the three ERP indices. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

CHANGES IN NEUROTRANSMITTER GENE EXPRESSION IN THE AGING RETINA.

EPA Science Inventory

To understand mechanisms of neurotoxicity in susceptible populations, we examined age-related changes in constitutive gene expression in the retinas of young (4mos), middle-aged (11 mos) and aged (23 mos) male Long Evans rats. Derived from a pouch of the forebrain during develop...

Differential susceptibility in steelhead trout populations to an emergent MD strain of infectious hematopoietic necrosis virus

USGS Publications Warehouse

Breyta, R.; Jones, Amelia; Kurath, Gael

2014-01-01

A significant emergence of trout-adapted MD subgroup infectious hematopoietic necrosis virus (IHNV) began in the coastal region of Washington State, USA, in 2007. This emergence event lasted until 2011 and caused both asymptomatic adult fish infection and symptomatic epidemic disease and mortality in juvenile fish. Incidence of virus during this emergence demonstrated a heterogeneous distribution among rivers of the coastal region, leaving fish populations of some rivers apparently untouched while others suffered significant and recurrent infection and mortality (Breyta et. al. 2013; Dis Aquat Org 104:179-195). In this study, we examined the possible contribution of variations in susceptibility of fish populations, age-related resistance, and virus virulence to the observed landscape heterogeneity. We found that the most significant variable was host susceptibility: by controlled experimental challenge studies steelhead trout populations with no history of IHNV infection were 1 to 3 orders of magnitude more sensitive than a fish population with a long history of IHNV infection. In addition, 2 fish populations from the same river, which descended relatively recently from a common ancestral population, demonstrated 1 to 2 orders of magnitude difference in susceptibility. Fish age-related development of resistance was most evident in the more susceptible of 2 related fish populations. Finally, the strain of virus involved in the 2007 coastal Washington emergence had high virulence but was within the range of other known M group viruses tested. These results suggest that one major driver of landscape heterogeneity in the 2007 coastal Washington IHNV emergence was variation in fish population susceptibility and that this trait may have a heritable component.

Ex-vivo quantitative susceptibility mapping of human brain hemispheres

PubMed Central

Kotrotsou, Aikaterini; Tamhane, Ashish A.; Dawe, Robert J.; Kapasi, Alifiya; Leurgans, Sue E.; Schneider, Julie A.; Bennett, David A.; Arfanakis, Konstantinos

2017-01-01

Ex-vivo brain quantitative susceptibility mapping (QSM) allows investigation of brain characteristics at essentially the same point in time as histopathologic examination, and therefore has the potential to become an important tool for determining the role of QSM as a diagnostic and monitoring tool of age-related neuropathologies. In order to be able to translate the ex-vivo QSM findings to in-vivo, it is crucial to understand the effects of death and chemical fixation on brain magnetic susceptibility measurements collected ex-vivo. Thus, the objective of this work was twofold: a) to assess the behavior of magnetic susceptibility in both gray and white matter of human brain hemispheres as a function of time postmortem, and b) to establish the relationship between in-vivo and ex-vivo gray matter susceptibility measurements on the same hemispheres. Five brain hemispheres from community-dwelling older adults were imaged ex-vivo with QSM on a weekly basis for six weeks postmortem, and the longitudinal behavior of ex-vivo magnetic susceptibility in both gray and white matter was assessed. The relationship between in-vivo and ex-vivo gray matter susceptibility measurements was investigated using QSM data from eleven older adults imaged both antemortem and postmortem. No systematic change in ex-vivo magnetic susceptibility of gray or white matter was observed over time postmortem. Additionally, it was demonstrated that, gray matter magnetic susceptibility measured ex-vivo may be well modeled as a linear function of susceptibility measured in-vivo. In conclusion, magnetic susceptibility in gray and white matter measured ex-vivo with QSM does not systematically change in the first six weeks after death. This information is important for future cross-sectional ex-vivo QSM studies of hemispheres imaged at different postmortem intervals. Furthermore, the linear relationship between in-vivo and ex-vivo gray matter magnetic susceptibility suggests that ex-vivo QSM captures

Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.

PubMed

Ishii, Makoto; Iadecola, Costantino

2016-05-01

Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibility.

PubMed

Melikian, George L; Rhee, Soo-Yon; Taylor, Jonathan; Fessel, W Jeffrey; Kaufman, David; Towner, William; Troia-Cancio, Paolo V; Zolopa, Andrew; Robbins, Gregory K; Kagan, Ron; Israelski, Dennis; Shafer, Robert W

2012-05-01

Determining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs have highly variable dynamic susceptibility ranges, making it difficult to determine the relative effect of an RT mutation on susceptibility to different NRTIs. In this study, we analyzed 1,273 genotyped HIV-1 isolates for which phenotypic results were obtained using the PhenoSense assay (Monogram, South San Francisco, CA). We used a parsimonious feature selection algorithm, LASSO, to assess the possible contributions of 177 mutations that occurred in 10 or more isolates in our data set. We then used least-squares regression to quantify the impact of each LASSO-selected mutation on each NRTI. Our study provides a comprehensive view of the most common NRTI resistance mutations. Because our results were standardized, the study provides the first analysis that quantifies the relative phenotypic effects of NRTI resistance mutations on each of the NRTIs. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation.

Intra- and inter-rater agreement between an ophthalmologist and mid-level ophthalmic personnel to diagnose retinal diseases based on fundus photographs at a primary eye center in Nepal: the Bhaktapur Retina Study.

PubMed

Thapa, Raba; Bajimaya, Sanyam; Bouman, Renske; Paudyal, Govinda; Khanal, Shankar; Tan, Stevie; Thapa, Suman S; van Rens, Ger

2016-07-18

Early detection can reduce irreversible blindness from retinal diseases. This study aims to assess the intra- and inter-rater agreement of retinal pathologies observed on fundus photographs between an ophthalmologist and two-mid level ophthalmic personnel (MLOPs). A population-based, cross-sectional study was conducted among subjects 60 years and above in the Bhaktapur district of Nepal. Fundus photographs of 500 eyes of 500 subjects were assessed. The macula-centered 45-degree photographs were graded twice by one ophthalmologist and two MLOPs. Intra-rater and inter-rater agreements were assessed for the ophthalmologist and the MLOPs. Mean age was 70.22 years ± 6.94 (SD). Retinal pathologies were observed in 55.6 % of photographs (age-related macular degeneration: 34.2 %; diabetic retinopathy: 4.2 %; retinal vein occlusion: 3.8 %). Twelve (2.4 %) fundus pictures were non-gradable. The intra-rater agreement for overall retinal pathologies, retinal hemorrhage, and maculopathy were substantial both for the ophthalmologist as well as for the MLOPs. There was moderate inter-rater agreement between the ophthalmologist and the first MLOP on second rating for overall retinal pathologies, [kappa (k); 95 % CI = 0.59 (0.51-0.66)], retinal hemorrhage [k; 95 % CI = 0.60 (0.41-0.78)], and maculopathy [k; 95 % CI = 0.52 (0.43-0.60)]. Inter-rater agreement between the ophthalmologist and the second MLOP for second rating was moderate for overall retinal pathologies [k; 95 % CI = 0.52 (0.44-0.60)], substantial agreement for retinal hemorrhage [k; 95 % CI = 0. 68 (0.52-0.84)], moderate agreement for maculopathy [k; 95 % CI = 0.59 (0.50-0.67)]. There is moderate agreement between the MLOPs and the ophthalmologist in grading fundus photographs for retinal hemorrhages and maculopathy.

Nutrition and age-related eye diseases

USDA-ARS?s Scientific Manuscript database

Vision loss among the elderly is an important health problem. Approximately one person in three has some form of vision-reducing eye disease by the age of 65 [1]. Age-related cataract, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma are the major diseases resulting in visu...

Age-related epigenetic drift and phenotypic plasticity loss: implications in prevention of age-related human diseases

PubMed Central

Li, Yuanyuan; Tollefsbol, Trygve O

2016-01-01

Aging is considered as one of the most important developmental processes in organisms and is closely associated with global deteriorations of epigenetic markers such as aberrant methylomic patterns. This altered epigenomic state, referred to ‘epigenetic drift’, reflects deficient maintenance of epigenetic marks and contributes to impaired cellular and molecular functions in aged cells. Epigenetic drift-induced abnormal changes during aging are scantily repaired by epigenetic modulators. This inflexibility in the aged epigenome may lead to an age-related decline in phenotypic plasticity at the cellular and molecular levels due to epigenetic drift. This perspective aims to provide novel concepts for understanding epigenetic effects on the aging process and to provide insights into epigenetic prevention and therapeutic strategies for age-related human disease. PMID:27882781

Splicing regulatory factors, ageing and age-related disease.

PubMed

Latorre, Eva; Harries, Lorna W

2017-07-01

Alternative splicing is a co-transcriptional process, which allows for the production of multiple transcripts from a single gene and is emerging as an important control point for gene expression. Alternatively expressed isoforms often have antagonistic function and differential temporal or spatial expression patterns, yielding enormous plasticity and adaptability to cells and increasing their ability to respond to environmental challenge. The regulation of alternative splicing is critical for numerous cellular functions in both pathological and physiological conditions, and deregulated alternative splicing is a key feature of common chronic diseases. Isoform choice is controlled by a battery of splicing regulatory proteins, which include the serine arginine rich (SRSF) proteins and the heterogeneous ribonucleoprotein (hnRNP) classes of genes. These important splicing regulators have been implicated in age-related disease, and in the ageing process itself. This review will outline the important contribution of splicing regulator proteins to ageing and age-related disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Age-related differences in acquisiton, steady-state performance and carbaryl effects on the operant behavior of Brown Norway rats.

EPA Science Inventory

The rapid increase in older adults in the population highlights the importance of understanding the role of aging in susceptibility to environmental contaminants. As part of a larger program on life-stage susceptibility, this experiment determined the effect of the carbamate pest...

Genetic studies of age-related macular degeneration: lessons, challenges, and opportunities for disease management.

PubMed

Priya, Rinki Ratna; Chew, Emily Y; Swaroop, Anand

2012-12-01

Age-related macular degeneration (AMD) is a common cause of visual impairment in individuals >55 years of age worldwide. The varying clinical phenotypes of AMD result from contributions of genetic, epigenetic, and nongenetic (environmental) factors. Genetic studies of AMD have come of age as a direct result of tremendous gains from the human genome project, genome-wide association studies, and identification of numerous susceptibility loci. These findings have implicated immune response, high-density lipoprotein cholesterol metabolism, extracellular matrix, and angiogenesis signaling pathways in disease pathophysiology. Herein, we address how the wealth of genetic findings in AMD is expected to impact the practice of medicine, providing opportunities for improved risk assessment, molecular diagnosis, preventive, and therapeutic intervention. We propose that the potential of using genetic variants for monitoring treatment response (pharmacogenetics) may usher in a new era of personalized medicine in the clinical management of AMD. Proprietary or commercial disclosures may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

A sensory origin for color-word stroop effects in aging: simulating age-related changes in color-vision mimics age-related changes in Stroop.

PubMed

Ben-David, Boaz M; Schneider, Bruce A

2010-11-01

An increase in Stroop effects with age can be interpreted as reflecting age-related reductions in selective attention, cognitive slowing, or color-vision. In the present study, 88 younger adults performed a Stroop test with two color-sets, saturated and desaturated, to simulate an age-related decrease in color perception. This color manipulation with younger adults was sufficient to lead to an increase in Stroop effects that mimics age-effects. We conclude that age-related changes in color perception can contribute to the differences in Stroop effects observed in aging. Finally, we suggest that the clinical applications of Stroop take this factor into account.

Molecular-level insights into aging processes of skin elastin.

PubMed

Mora Huertas, Angela C; Schmelzer, Christian E H; Hoehenwarter, Wolfgang; Heyroth, Frank; Heinz, Andrea

2016-01-01

Skin aging is characterized by different features including wrinkling, atrophy of the dermis and loss of elasticity associated with damage to the extracellular matrix protein elastin. The aim of this study was to investigate the aging process of skin elastin at the molecular level by evaluating the influence of intrinsic (chronological aging) and extrinsic factors (sun exposure) on the morphology and susceptibility of elastin towards enzymatic degradation. Elastin was isolated from biopsies derived from sun-protected or sun-exposed skin of differently aged individuals. The morphology of the elastin fibers was characterized by scanning electron microscopy. Mass spectrometric analysis and label-free quantification allowed identifying differences in the cleavage patterns of the elastin samples after enzymatic digestion. Principal component analysis and hierarchical cluster analysis were used to visualize differences between the samples and to determine the contribution of extrinsic and intrinsic aging to the proteolytic susceptibility of elastin. Moreover, the release of potentially bioactive peptides was studied. Skin aging is associated with the decomposition of elastin fibers, which is more pronounced in sun-exposed tissue. Marker peptides were identified, which showed an age-related increase or decrease in their abundances and provide insights into the progression of the aging process of elastin fibers. Strong age-related cleavage occurs in hydrophobic tropoelastin domains 18, 20, 24 and 26. Photoaging makes the N-terminal and central parts of the tropoelastin molecules more susceptible towards enzymatic cleavage and, hence, accelerates the age-related degradation of elastin. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Senescent Cells: A Novel Therapeutic Target for Aging and Age-Related Diseases

PubMed Central

Naylor, RM; Baker, DJ; van Deursen, JM

2014-01-01

Aging is the main risk factor for most chronic diseases, disabilities, and declining health. It has been proposed that senescent cells—damaged cells that have lost the ability to divide—drive the deterioration that underlies aging and age-related diseases. However, definitive evidence for this relationship has been lacking. The use of a progeroid mouse model (which expresses low amounts of the mitotic checkpoint protein BubR1) has been instrumental in demonstrating that p16Ink4a-positive senescent cells drive age-related pathologies and that selective elimination of these cells can prevent or delay age-related deterioration. These studies identify senescent cells as potential therapeutic targets in the treatment of aging and age-related diseases. Here, we describe how senescent cells develop, the experimental evidence that causally implicates senescent cells in age-related dysfunction, the chronic diseases and disorders that are characterized by the accumulation of senescent cells at sites of pathology, and the therapeutic approaches that could specifically target senescent cells. PMID:23212104

Oral medicine and the ageing population.

PubMed

Yap, T; McCullough, M

2015-03-01

The oral cavity is subject to age related processes such as cellular ageing and immunosenescence. The ageing population bears an increased burden of intraoral pathology. In oral medicine, the majority of presenting patients are in their fifth to seventh decade of life. In this review, we discuss the ageing population's susceptibility to mucosal disorders and the increased prevalence of potentially malignant disorders and oral squamous cell carcinoma, as well as dermatoses including oral lichen planus and immunobullous conditions. We also address the ageing population's susceptibility to oral discomfort and explore salivary secretion, ulceration and the symptoms of oral burning. Finally, we will describe orofacial pain conditions which are more likely encountered in an older population. This update highlights clinical presentations which are more likely to be encountered in the ageing population in a general practice setting and the importance of screening both new and long-term patients. © 2015 Australian Dental Association.

Neuroanatomical Substrates of Age-Related Cognitive Decline

ERIC Educational Resources Information Center

Salthouse, Timothy A.

2011-01-01

There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the…

Relative susceptibility of pecan germplasm to blackmargined aphid

USDA-ARS?s Scientific Manuscript database

The blackmargined aphid, Monellia caryella (Fitch), is an important phytophage in the pecan, Carya illinoinensis (Wangenh.) K. Koch, agroecosystem where it often is treated with insecticide. Pecan cultivars released by the USDA Pecan Breeding Program vary in susceptibility and risk of damage from t...

Estimation of the Population Susceptibility Against Measles in Slovakia.

PubMed

Zibolenová, Jana; Chladná, Zuzana; Švihrová, Viera; Baška, Tibor; Waczulíková, Iveta; Hudečková, Henrieta

2017-03-01

In Slovakia, thanks to a highly effective vaccination programme, no domestic cases of measles have been reported since 1999. However, there are several outbreaks of measles currently hitting some countries in Europe. Difficulties in reaching the goal of measles elimination make it necessary to monitor the status of the population susceptibility to prevent similar outbreaks in the future. We hypothesize that immunity wanes overtime, which can substantially impact the population susceptibility. This work introduces a model that estimates a proportion of individuals susceptible to measles in the Slovak population in 2015. Our analysis is based on an age-cohort model that incorporates waning immunity, vaccination schedule and changes in demographic structure. The inputs of the model are data on the vaccination coverage, last seroprevalence survey in 2002 and age structure of the population. In a short-term horizon, waning immunity does not affect the estimated proportion of the susceptible population. However, in a long-term horizon, the antibody titers can fall below the level of protection, which would result in a substantial transfer of initially immune individuals to the compartment of the susceptible ones. Incorporating of waning immunity in the cohort model has indicated that the most susceptible cohorts are not-vaccinated youngest children and cohorts born between 1969 and 1986. Applying the model to the current situation shows that people aged 30-45 years and unvaccinated infants represent the most susceptible groups. Model partially replaces missing seroprevalence survey, but, because the parameters of model and phenomenon of waning immunity are not exactly known, we suggest reintroducing the regular national serosurveys in order to empirically determine the level of susceptibility for measles in Slovakia. Copyright© by the National Institute of Public Health, Prague 2017

Age-Related Changes in Immunological Factors and Their Relevance in Allergic Disease Development During Childhood.

PubMed

Chang, Woo Sung; Kim, Eun Jin; Lim, Yeon Mi; Yoon, Dankyu; Son, Jo Young; Park, Jung Won; Hong, Soo Jong; Cho, Sang Heon; Lee, Joo Shil

2016-07-01

Allergic diseases are triggered by Th2-mediated immune reactions to allergens and orchestrated by various immunological factors, including immune cells and cytokines. Although many reports have suggested that childhood is the critical period in the onset of allergic diseases and aging leads to alter the susceptibility of an individual to allergic diseases, age-related changes in various immunological factors in healthy individuals as well as their difference between healthy and allergic children have not yet been established. We investigated the ratio of Th1/Th2 cells and the levels of 22 allergy-related cytokines across all age groups in individuals who were classified as clinically non-atopic and healthy. We also examined their differences between healthy and allergic children to evaluate immunological changes induced by the development of allergic diseases during childhood. The Th1/Th2 ratio rose gradually during the growth period including childhood, reaching peak values in the twenties-thirties age group. Th1/Th2 ratios were significantly lower in allergic children than in healthy controls, whereas 14 of 22 cytokines were significantly higher in allergic children than in healthy controls. On the other hand, there were no differences in Th1/Th2 ratios and cytokines between healthy and allergic adolescents. In this study, age-related changes in Th1/Th2 ratios were found in normal controls across all age groups, and decreases in Th1/Th2 ratio were observed with increasing of 14 cytokines in allergic children. The results of this study may be helpful as reference values for both monitoring immunological changes according to aging in healthy individuals and distinguishing between normal and allergic subjects in terms of immune cells and soluble factors.

SU-F-I-24: Feasibility of Magnetic Susceptibility to Relative Electron Density Conversion Method for Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ito, K; Kadoya, N; Chiba, M

2016-06-15

Purpose: The aim of this study is to develop radiation treatment planning using magnetic susceptibility obtained from quantitative susceptibility mapping (QSM) via MR imaging. This study demonstrates the feasibility of a method for generating a substitute for a CT image from an MRI. Methods: The head of a healthy volunteer was scanned using a CT scanner and a 3.0 T MRI scanner. The CT imaging was performed with a slice thickness of 2.5 mm at 80 and 120 kV (dual-energy scan). These CT images were converted to relative electron density (rED) using the CT-rED conversion table generated by a previousmore » dual-energy CT scan. The CT-rED conversion table was generated using the conversion of the energy-subtracted CT number to rED via a single linear relationship. One T2 star-weighted 3D gradient echo-based sequence with four different echo times images was acquired using the MRI scanner. These T2 star-weighted images were used to estimate the phase data. To estimate the local field map, a Laplacian unwrapping of the phase and background field removal algorithm were implemented to process phase data. To generate a magnetic susceptibility map from the local field map, we used morphology enabled dipole inversion method. The rED map was resampled to the same resolution as magnetic susceptibility, and the magnetic susceptibility-rED conversion table was obtained via voxel-by-voxel mapping between the magnetic susceptibility and rED maps. Results: A correlation between magnetic susceptibility and rED is not observed through our method. Conclusion: Our results show that the correlation between magnetic susceptibility and rED is not observed. As the next step, we assume that the voxel of the magnetic susceptibility map comprises two materials, such as water (0 ppm) and bone (-2.2 ppm) or water and marrow (0.81ppm). The elements of each voxel were estimated from the ratio of the two materials.« less

Relative age-related participation and dropout trends in German youth sports clubs.

PubMed

Wattie, Nick; Tietjens, Maike; Cobley, Stephen; Schorer, Jörg; Baker, Joseph; Kurz, Dietrich

2014-01-01

Relative age describes a youth's age within their age group cohort. Compared to relatively younger peers, relatively older youth in an annual age group cohort have been found more likely to be selected to sports teams, and to receive higher grades in education. This study examined the influence of youth sport participants' relative age on participation and dropout. Using data from the 1995 German Youth Sport Survey (N total=2612), comparisons (stratified by gender and sport type) were made between the relative age of current and former participants. Analyses also considered the type of school youths were enrolled in while exploring the influence of relative age on sport participations. No relative age effects for dropout emerged among males in team or individual sport contexts. Female dropouts were more likely to be relatively older (Q1, OR adjusted: 0.52, 95% CI: 0.34-0.80; Q2, OR adjusted: 0.55, 95% CI: 0.36-0.84; Q3, OR adjusted: 0.59, 95% CI: 0.39-0.89), an effect that was mirrored among 'artistic' sport participants. Boys and girls in schools that were for children of higher academic proficiency were more likely to be currently participating in sport. Findings suggest that relative age-related dropout effects may be context sensitive and different for males and females. For the most part, relative age did not appear to have any relationship with dropout in this sample, with some notable exceptions for females. Overall, factors such as the type of school youths were enrolled in appear to be a more salient influence on sport participation than relative age.

MR susceptibility imaging

NASA Astrophysics Data System (ADS)

Duyn, Jeff

2013-04-01

This work reviews recent developments in the use of magnetic susceptibility contrast for human MRI, with a focus on the study of brain anatomy. The increase in susceptibility contrast with modern high field scanners has led to novel applications and insights into the sources and mechanism contributing to this contrast in brain tissues. Dedicated experiments have demonstrated that in most of healthy brain, iron and myelin dominate tissue susceptibility variations, although their relative contribution varies substantially. Local variations in these compounds can affect both amplitude and frequency of the MRI signal. In white matter, the myelin sheath introduces an anisotropic susceptibility that has distinct effects on the water compartments inside the axons, between the myelin sheath, and the axonal space, and renders their signals dependent on the angle between the axon and the magnetic field. This offers opportunities to derive tissue properties specific to these cellular compartments.

Effects of dietary L-carnitine and coenzyme Q10 at different supplemental ages on growth performance and some immune response in ascites-susceptible broilers.

PubMed

Geng, Ailian; Li, Baoming; Guo, Yuming

2007-02-01

Effects of dietary L-carnitine and coenzyme Q10 (CoQ10) at different supplemental ages on performance and some immune response were investigated in ascites-susceptible broilers. A 3 x 2 x 2 factorial design was used consisting of L-carnitine supplementation (0, 75, and 100 mg/kg), CoQ10 supplementation (0 and 40 mg/kg) and different supplemental ages (from day 1 on and from day 10 on). A total of 480 one-day-old Arbor Acre male broiler chicks were randomly allocated to 12 groups, every group had five replicates, each with eight birds. The birds were fed a corn-soybean based diet for six weeks. From day 10-21, all the birds were exposed to a low ambient temperature (12-15 degrees C) to increase the susceptibility to ascites. No significant effects were observed on growth performance by L-carnitine, CoQ10 supplementation, and different supplemental ages. Packed cell volume was significantly decreased by L-carnitine supplementation alone, and ascites heart index and ascites mortality were decreased by L-carnitine, CoQ10 supplementation alone, and L-carnitine + CoQ10 supplementation together (p < 0.05). Heart index of broilers was significantly improved by L-carnitine, CoQ10 supplementation alone during 0-3 week. Serum IgG content was improved by L-carnitine supplementation alone (p < 0.05), but lysozyme activity was increased by L-carnitine + CoQ10 supplementation together (p < 0.05). A significant L-carnitine by supplemental age interaction was observed in lysozyme activity. L-carnitine supplementation alone had no effects on the peripheral blood lymphocyte (PBL) proliferation in response to concanavalin A (ConA) and lipopolysaccharide, but supplemental CoQ10 alone and L-carnitine+ CoQ10 together decreased the PBL proliferation in response to ConA (p < 0.05). The present study suggested that L-carnitine + CoQ10 supplementation together had positive effects on some immune response of ascites-susceptible broilers, which might benefit for the reduction of broilers

The Role of Astrocyte Mitochondria in Differential Regional Susceptibility to Environmental Neurotoxicants: Tools for Understanding Neurodegeneration

PubMed Central

Kubik, Laura L.; Philbert, Martin A.

2015-01-01

In recent decades, there has been a significant expansion in our understanding of the role of astrocytes in neuroprotection, including spatial buffering of extracellular ions, secretion of metabolic coenzymes, and synaptic regulation. Astrocytic neuroprotective functions require energy, and therefore require a network of functional mitochondria. Disturbances to astrocytic mitochondrial homeostasis and their ability to produce ATP can negatively impact neural function. Perturbations in astrocyte mitochondrial function may accrue as the result of physiological aging processes or as a consequence of neurotoxicant exposure. Hydrophobic environmental neurotoxicants, such as 1,3-dinitrobenzene and α-chlorohydrin, cause regionally specific spongiform lesions mimicking energy deprivation syndromes. Astrocyte involvement includes mitochondrial damage that either precedes or is accompanied by neuronal damage. Similarly, environmental neurotoxicants that are implicated in the etiology of age-related neurodegenerative conditions cause regionally specific damage in the brain. Based on the regioselective nature of age-related neurodegenerative lesions, chemically induced models of regioselective lesions targeting astrocyte mitochondria can provide insight into age-related susceptibilities in astrocyte mitochondria. Most of the available research to date focuses on neuronal damage in cases of age-related neurodegeneration; however, there is a body of evidence that supports a central mechanistic role for astrocyte mitochondria in the expression of neural injury. Regional susceptibility to neuronal damage induced by aging by exposure to neurotoxicants may be a reflection of highly variable regional energy requirements. This review identifies region-specific vulnerabilities in astrocyte mitochondria in examples of exposure to neurotoxicants and in age-related neurodegeneration. PMID:25740792

Relative susceptibility of titanium alloys to hot-salt stress-corrosion

NASA Technical Reports Server (NTRS)

Gray, H. R.

1971-01-01

Susceptibility of titanium alloys to hot-salt stress-corrosion cracking increased as follows: Ti-2Al-11Sn-5Zr-0.2Si(679), Ti-6Al-2Sn-4Zr-2Mo(6242), Ti-6Al-4V(64), Ti-6Al-4V-3Co(643), Ti-8Al-1Mo-1V(811), and Ti-13V-11Cr-3A1(13-11-3). The Ti-5Al-6Sn-2Zr-1Mo-0.25Si(5621S) alloy was both the least and most susceptible depending on heat treatment. Such rankings can be drastically altered by heat-to-heat and processing variations. Residual compressive stresses and cyclic exposures also reduce susceptibility to stress-corrosion. Simulated turbine-engine compressor environmental variables such as air velocity, pressure, dewpoint, salt concentration, and salt deposition temperature have only minor effects. Detection of substantial concentrations of hydrogen in all corroded alloys confirmed the existence of a hydrogen embrittlement mechanism.

NUTRITIONAL SUPPLEMENTATION IN AGE-RELATED MACULAR DEGENERATION.

PubMed

Parodi, Maurizio Battaglia; Zucchiatti, Ilaria; Cicinelli, Maria Vittoria; Cascavilla, Maria Lucia; Bandello, Francesco

2016-06-01

To evaluate the rate of adherence to prescribed nutritional supplementation in patients affected by age-related macular degeneration, in an Italian tertiary referral tertiary center. Patients with age-related macular degeneration, age-related eye disease study Categories 3 and 4, were recruited and underwent an 11-item questionnaire. The study included a total of 193 patients meeting the age-related eye disease study nutritional supplementation criteria (174 patients with age-related eye disease study Category 4 and 19 with Category 3). Seventy-seven (40%) were taking oral supplementation, 70 of whom (90%) 1 tablet/day. Oral supplementation was recommended by the personal ophthalmologist in 85 patients (44%), including all those currently receiving it. Eight patients of 85 (9.4%) rejected supplementation despite it being recommended, mostly because they were already taking other medicines. Ninety-four patients (48%) claimed they had not received any information from their ophthalmologist. Our data reveal that Italian patients with age-related eye disease study Categories 3 and 4 have a low adherence to nutritional supplementation. In 65% of cases, patients were not adequately informed by their ophthalmologist of the potential benefits of oral supplementation for age-related macular degeneration; indeed, 108 patients (56%) were not even aware such nutritional treatments are available. Ophthalmologists should be aware of the importance of giving advice to persons with age-related macular degeneration regarding the benefits of oral supplements.

Analysis of plasma microRNA expression profiles revealed different cancer susceptibility in healthy young adult smokers and middle-aged smokers

PubMed Central

Shi, Bing; Gao, Hongmin; Zhang, Tianyang; Cui, Qinghua

2016-01-01

Cigarette smoking is a world-wide habit and an important risk factor for cancer. It was known that cigarette smoking can change the expression of circulating microRNAs (miRNAs) in healthy middle-aged adults. However, it remains unclear whether cigarette smoking can change the levels of circulating miRNAs in young healthy smokers and whether there are differences in cancer susceptibility for the two cases. In this study, the miRNA expression profiles of 28 smokers and 12 non-smokers were determined by Agilent human MicroRNA array. We further performed bioinformatics analysis for the differentially expressed miRNAs. The result showed that 35 miRNAs were differentially expressed. Among them, 24 miRNAs were up-regulated and 11 miRNAs were down-regulated in smokers. Functional enrichment analysis showed that the deregulated miRNAs are related to immune system and hormones regulation. Strikingly, the up-regulated miRNAs are mostly associated with hematologic cancers, such as lymphoma, leukemia. As a comparison, the up-regulated plasma miRNAs in middle-aged smokers are mostly associated with solid cancers, such as hepatocellular carcinoma and lung cancer, suggesting that smoking could have different influences on young adults and middle-aged adults. In a conclusion, we identified the circulating miRNAs deregulated by cigarette smoking and revealed that the age-dependent deregulated miRNAs tend to be mainly involved in different types of human cancers. PMID:26943588

Analysis of plasma microRNA expression profiles revealed different cancer susceptibility in healthy young adult smokers and middle-aged smokers.

PubMed

Shi, Bing; Gao, Hongmin; Zhang, Tianyang; Cui, Qinghua

2016-04-19

Cigarette smoking is a world-wide habit and an important risk factor for cancer. It was known that cigarette smoking can change the expression of circulating microRNAs (miRNAs) in healthy middle-aged adults. However, it remains unclear whether cigarette smoking can change the levels of circulating miRNAs in young healthy smokers and whether there are differences in cancer susceptibility for the two cases. In this study, the miRNA expression profiles of 28 smokers and 12 non-smokers were determined by Agilent human MicroRNA array. We further performed bioinformatics analysis for the differentially expressed miRNAs. The result showed that 35 miRNAs were differentially expressed. Among them, 24 miRNAs were up-regulated and 11 miRNAs were down-regulated in smokers. Functional enrichment analysis showed that the deregulated miRNAs are related to immune system and hormones regulation. Strikingly, the up-regulated miRNAs are mostly associated with hematologic cancers, such as lymphoma, leukemia. As a comparison, the up-regulated plasma miRNAs in middle-aged smokers are mostly associated with solid cancers, such as hepatocellular carcinoma and lung cancer, suggesting that smoking could have different influences on young adults and middle-aged adults. In a conclusion, we identified the circulating miRNAs deregulated by cigarette smoking and revealed that the age-dependent deregulated miRNAs tend to be mainly involved in different types of human cancers.

TOLUENE EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF YOUNG-ADULT, MIDDLE-AGE AND SENESCENT BROWN NORWAY RATS

EPA Science Inventory

Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for tol...

Aging on a different scale--chronological versus pathology-related aging.

PubMed

Melis, Joost P M; Jonker, Martijs J; Vijg, Jan; Hoeijmakers, Jan H J; Breit, Timo M; van Steeg, Harry

2013-10-01

In the next decades the elderly population will increase dramatically, demanding appropriate solutions in health care and aging research focusing on healthy aging to prevent high burdens and costs in health care. For this, research targeting tissue-specific and individual aging is paramount to make the necessary progression in aging research. In a recently published study we have attempted to make a step interpreting aging data on chronological as well as pathological scale. For this, we sampled five major tissues at regular time intervals during the entire C57BL/6J murine lifespan from a controlled in vivo aging study, measured the whole transcriptome and incorporated temporal as well as physical health aspects into the analyses. In total, we used 18 different age-related pathological parameters and transcriptomic profiles of liver, kidney, spleen, lung and brain and created a database that can now be used for a broad systems biology approach. In our study, we focused on the dynamics of biological processes during chronological aging and the comparison between chronological and pathology-related aging.

Disconnected Aging: Cerebral White Matter Integrity and Age-Related Differences in Cognition

PubMed Central

Bennett, Ilana J.; Madden, David J.

2013-01-01

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. PMID:24280637

Cholesteryl Ester Transfer Protein Intimately Involved in Dyslipidemia-Related Susceptibility to Cognitive Deficits in Type 2 Diabetic Patients.

PubMed

Sun, Jie; Cai, Rongrong; Huang, Rong; Wang, Pin; Tian, Sai; Sun, Haixia; Xia, Wenqing; Wang, Shaohua

2016-08-01

Cholesteryl ester transfer protein (CETP) is involved in diabetic dyslipidemia. We aim to test the hypothesis that CETP might be of importance in mediating dyslipidemia-related susceptibility to cognitive deficits in diabetic patients. We recruited 190 type 2 diabetic patients and divided them into two groups according to the Montreal Cognitive Assessment (MoCA) score. The association between CETP and cognitive decline was analyzed with logistic regression and stratification. There were 110 diabetic patients with mild cognition impairment (MCI) and 80 healthy cognition subjects as controls. Dyslipidemia is more common among diabetic patients with MCI; they had a significant increase of serum CETP concentrations, which was negatively correlated with MoCA (r = -0.638; p < 0.001). Negative correlations were also found between the serum CETP concentration with the Auditory Verbal Learning Test (r = -0.266; p = 0.008), indicating memory deficit. Logistic regression analysis revealed that CETP concentration was an independent factor of diabetic MCI (p < 0.001). Further stratification study showed that high serum levels of CETP was an independent risk factor of MCI in diabetic patients with a low density lipoproteins level ≥2.59 mmol/L, or high density lipoproteins level ≤1.0 mmol/L for men and ≤1.3 mmol/L for women, or TG level ≥1.7 mmol/L, after adjusting for age, sex, education, and glucose control (all ps < 0.05). CETP was intimately involved in dyslipidemia-related susceptibility to cognitive decline, especially memory function in type 2 diabetic patients.

Confidant Relations of the Aged.

ERIC Educational Resources Information Center

Tigges, Leann M.; And Others

The confidant relationship is a qualitatively distinct dimension of the emotional support system of the aged, yet the composition of the confidant network has been largely neglected in research on aging. Persons (N=940) 60 years of age and older were interviewed about their socio-environmental setting. From the enumeration of their relatives,…

Th17-related genes and celiac disease susceptibility.

PubMed

Medrano, Luz María; García-Magariños, Manuel; Dema, Bárbara; Espino, Laura; Maluenda, Carlos; Polanco, Isabel; Figueredo, M Ángeles; Fernández-Arquero, Miguel; Núñez, Concepción

2012-01-01

Th17 cells are known to be involved in several autoimmune or inflammatory diseases. In celiac disease (CD), recent studies suggest an implication of those cells in disease pathogenesis. We aimed at studying the role of genes relevant for the Th17 immune response in CD susceptibility. A total of 101 single nucleotide polymorphisms (SNPs), mainly selected to cover most of the variability present in 16 Th17-related genes (IL23R, RORC, IL6R, IL17A, IL17F, CCR6, IL6, JAK2, TNFSF15, IL23A, IL22, STAT3, TBX21, SOCS3, IL12RB1 and IL17RA), were genotyped in 735 CD patients and 549 ethnically matched healthy controls. Case-control comparisons for each SNP and for the haplotypes resulting from the SNPs studied in each gene were performed using chi-square tests. Gene-gene interactions were also evaluated following different methodological approaches. No significant results emerged after performing the appropriate statistical corrections. Our results seem to discard a relevant role of Th17 cells on CD risk.

Stereotypes, Warnings, and Identity-Related Variables Influence Older Adults' Susceptibility to Associative False Memory Errors.

PubMed

Smith, Amy M; Gallo, David A; Barber, Sarah J; Maddox, Keith B; Thomas, Ayanna K

2017-08-01

Activating ageist stereotypes can impair older adults' ability to remember information. This effect has been shown to be strongest for older adults who possess certain characteristics (e.g., young-old, highly educated). The present study extended this line of research to investigate the relationship between stereotyping and false memory susceptibility in older adults. We first presented older adults with lists of associated words in an incidental learning paradigm. Afterward, we manipulated whether participants were presented with stereotypes about aging and whether they were given warnings about the associative nature of the lists. Participants then completed a yes/no recognition test and answered demographic questions. Older adults in the stereotyped group were more likely to falsely recognize non-presented theme words than older adults in the control group. Further, those who were highly educated and/or retired were most likely to experience this false memory susceptibility. Similar to the research on veridical memory, these findings suggest that the effects of ageist stereotyping on older adults' false memory susceptibility may be best understood in terms of the individual differences that older adults possess. Identifying the types of people who are at risk of experiencing stereotype threat is an important step toward helping older adults avoid memory impairment in the presence of common stereotypes. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The role of hydrogen sulfide in aging and age-related pathologies.

PubMed

Perridon, Bernard W; Leuvenink, Henri G D; Hillebrands, Jan-Luuk; van Goor, Harry; Bos, Eelke M

2016-09-27

When humans grow older, they experience inevitable and progressive loss of physiological function, ultimately leading to death. Research on aging largely focuses on the identification of mechanisms involved in the aging process. Several proposed aging theories were recently combined as the 'hallmarks of aging'. These hallmarks describe (patho-)physiological processes that together, when disrupted, determine the aging phenotype. Sustaining evidence shows a potential role for hydrogen sulfide (H 2 S) in the regulation of aging. Nowadays, H 2 S is acknowledged as an endogenously produced signaling molecule with various (patho-) physiological effects. H 2 S is involved in several diseases including pathologies related to aging. In this review, the known, assumed and hypothetical effects of hydrogen sulfide on the aging process will be discussed by reviewing its actions on the hallmarks of aging and on several age-related pathologies.

Deregulation of CRTCs in Aging and Age-related Disease Risk

PubMed Central

Escoubas, Caroline C.; Silva-García, Carlos G.; Mair, William B.

2017-01-01

Advances in public health in the last century have seen a sharp increase in human life expectancy. With these changes have come increased incidence of age-related pathologies and health burdens in the elderly. Patient age is the biggest risk factor for multiple chronic conditions that often occur simultaneously within one individual. An alternative to disease centric therapeutic approaches is that of ‘geroscience’, which aims to define molecular mechanisms that link age to overall disease risk. One such mechanism is deregulation of CREB-regulated transcriptional coactivators, CRTCs. Initially identified for their role in modulating CREB transcription, the last five years has seen an expansion in knowledge of new cellular regulators and roles of CRTCs beyond CREB. CRTCs have been shown to modulate organismal aging in C. elegans and to impact age-related diseases in humans. Here, we discuss CRTC deregulation as a new driver of aging, and integrating link between age and disease risk. PMID:28365140

Human susceptibility to legionnaires' disease.

PubMed

Berrington, William R; Hawn, Thomas R

2013-01-01

Legionella pneumophila is a facultative intracellular pathogen that is an important cause of pneumonia. Although host factors that may predispose to acquisition of Legionnaire's Disease (LD) include comorbid illnesses (e.g., diabetes, chronic lung disease), age, male sex, and smoking, many individuals have no identifiable risk factors. Some studies suggest that genetic factors may enhance susceptibility to LD. In this chapter we discuss current techniques and scientific methods to identify genetic susceptibility factors. These genetic studies provide insight into the human immune response to intracellular pathogens and may improve strategies for treatment and vaccine development.

Red Blood Cell Susceptibility to Pneumolysin

PubMed Central

Bokori-Brown, Monika; Petrov, Peter G.; Khafaji, Mawya A.; Mughal, Muhammad K.; Naylor, Claire E.; Shore, Angela C.; Gooding, Kim M.; Casanova, Francesco; Mitchell, Tim J.; Titball, Richard W.; Winlove, C. Peter

2016-01-01

This study investigated the effect of the biochemical and biophysical properties of the plasma membrane as well as membrane morphology on the susceptibility of human red blood cells to the cholesterol-dependent cytolysin pneumolysin, a key virulence factor of Streptococcus pneumoniae, using single cell studies. We show a correlation between the physical properties of the membrane (bending rigidity and surface and dipole electrostatic potentials) and the susceptibility of red blood cells to pneumolysin-induced hemolysis. We demonstrate that biochemical modifications of the membrane induced by oxidative stress, lipid scrambling, and artificial cell aging modulate the cell response to the toxin. We provide evidence that the diversity of response to pneumolysin in diabetic red blood cells correlates with levels of glycated hemoglobin and that the mechanical properties of the red blood cell plasma membrane are altered in diabetes. Finally, we show that diabetic red blood cells are more resistant to pneumolysin and the related toxin perfringolysin O relative to healthy red blood cells. Taken together, these studies indicate that the diversity of cell response to pneumolysin within a population of human red blood cells is influenced by the biophysical and biochemical status of the plasma membrane and the chemical and/or oxidative stress pre-history of the cell. PMID:26984406

Do advanced glycation end-products play a role in malaria susceptibility?

PubMed Central

Traoré, Karim; Arama, Charles; Médebielle, Maurice; Doumbo, Ogobara; Picot, Stéphane

2016-01-01

There are growing data supporting the differences in susceptibility to malaria described between sympatric populations with different lifestyles. Evidence has also been growing for some time that nutritional status and the host’s metabolism are part of the complex mechanisms underlying these differences. The role of dietary advanced glycation end-products (AGEs) in the modulation of immune responses (innate and adaptive responses) and chronic oxidative stress has been established. But less is known about AGE implication in naturally acquired immunity and susceptibility to malaria. Since inflammatory immune responses and oxidative events have been demonstrated as the hallmark of malaria infection, it seems crucial to investigate the role of AGE in susceptibility or resistance to malaria. This review provides new insight into the relationship between nutrition, metabolic disorders, and infections, and how this may influence the mechanisms of susceptibility or resistance to malaria in endemic areas. PMID:27012162

Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

PubMed

Bennett, I J; Madden, D J

2014-09-12

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

The role of hydrogen sulfide in aging and age-related pathologies

PubMed Central

Perridon, Bernard W.; Leuvenink, Henri G.D.; Hillebrands, Jan-Luuk; van Goor, Harry; Bos, Eelke M.

2016-01-01

When humans grow older, they experience inevitable and progressive loss of physiological function, ultimately leading to death. Research on aging largely focuses on the identification of mechanisms involved in the aging process. Several proposed aging theories were recently combined as the ‘hallmarks of aging’. These hallmarks describe (patho-)physiological processes that together, when disrupted, determine the aging phenotype. Sustaining evidence shows a potential role for hydrogen sulfide (H2S) in the regulation of aging. Nowadays, H2S is acknowledged as an endogenously produced signaling molecule with various (patho-) physiological effects. H2S is involved in several diseases including pathologies related to aging. In this review, the known, assumed and hypothetical effects of hydrogen sulfide on the aging process will be discussed by reviewing its actions on the hallmarks of aging and on several age-related pathologies. PMID:27683311

Relation of motion sickness susceptibility to vestibular and behavioral measures of orientation

NASA Technical Reports Server (NTRS)

Peterka, Robert J.

1995-01-01

The objective is to determine the relationship of motion sickness susceptibility to vestibulo-ocular reflexes (VOR), motion perception, and behavioral utilization of sensory orientation cues for the control of postural equilibrium. The work is focused on reflexes and motion perception associated with pitch and roll movements that stimulate the vertical semicircular canals and otolith organs of the inner ear. This work is relevant to the space motion sickness problem since 0 g related sensory conflicts between vertical canal and otolith motion cues are a likely cause of space motion sickness.

What is normal in normal aging? Effects of Aging, Amyloid and Alzheimer’s Disease on the Cerebral Cortex and the Hippocampus

PubMed Central

Fjell, Anders M.; McEvoy, Linda; Holland, Dominic; Dale, Anders M.; Walhovd, Kristine B

2015-01-01

What can be expected in normal aging, and where does normal aging stop and pathological neurodegeneration begin? With the slow progression of age-related dementias such as Alzheimer’s Disease (AD), it is difficult to distinguish age-related changes from effects of undetected disease. We review recent research on changes of the cerebral cortex and the hippocampus in aging and the borders between normal aging and AD. We argue that prominent cortical reductions are evident in fronto-temporal regions in elderly even with low probability of AD, including regions overlapping the default mode network. Importantly, these regions show high levels of amyloid deposition in AD, and are both structurally and functionally vulnerable early in the disease. This normalcy-pathology homology is critical to understand, since aging itself is the major risk factor for sporadic AD. Thus, rather than necessarily reflecting early signs of disease, these changes may be part of normal aging, and may inform on why the aging brain is so much more susceptible to AD than is the younger brain. We suggest that regions characterized by a high degree of life-long plasticity are vulnerable to detrimental effects of normal aging, and that this age-vulnerability renders them more susceptible to additional, pathological AD-related changes. We conclude that it will be difficult to understand AD without understanding why it preferably affects older brains, and that we need a model that accounts for age-related changes in AD-vulnerable regions independently of AD-pathology. PMID:24548606

X-82 to Treat Age-related Macular Degeneration

ClinicalTrials.gov

2018-05-30

Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

Men and mice: Relating their ages.

PubMed

Dutta, Sulagna; Sengupta, Pallav

2016-05-01

Since the late 18th century, the murine model has been widely used in biomedical research (about 59% of total animals used) as it is compact, cost-effective, and easily available, conserving almost 99% of human genes and physiologically resembling humans. Despite the similarities, mice have a diminutive lifespan compared to humans. In this study, we found that one human year is equivalent to nine mice days, although this is not the case when comparing the lifespan of mice versus humans taking the entire life at the same time without considering each phase separately. Therefore, the precise correlation of age at every point in their lifespan must be determined. Determining the age relation between mice and humans is necessary for setting up experimental murine models more analogous in age to humans. Thus, more accuracy can be obtained in the research outcome for humans of a specific age group, although current outcomes are based on mice of an approximate age. To fill this gap between approximation and accuracy, this review article is the first to establish a precise relation between mice age and human age, following our previous article, which explained the relation in ages of laboratory rats with humans in detail. Copyright © 2015 Elsevier Inc. All rights reserved.

Bodacious Berry, Potency Wood and the Aging Monster: Gender and Age Relations in Anti-Aging Ads

ERIC Educational Resources Information Center

Calasanti, Toni

2007-01-01

This paper situates age discrimination within a broader system of age relations that intersects with other inequalities, and then uses that framework to analyze internet advertisements for the anti-aging industry. Such ads reinforce age and gender relations by positing old people as worthwhile only to the extent that they look and act like those…

Age-related changes in cognitive conflict processing: an event-related potential study.

PubMed

Mager, Ralph; Bullinger, Alex H; Brand, Serge; Schmidlin, Maria; Schärli, Heinz; Müller-Spahn, Franz; Störmer, Robert; Falkenstein, Michael

2007-12-01

Cognitive tasks involving conflicting stimuli and responses are associated with an early age-related decline in performance. Conflict and conflict-induced interference can be stimulus- or response-related. In classical stimulus-response compatibility tasks, such as the Stroop task, the event-related potential (ERP) usually reveals a greater negativity on incongruent versus congruent trials which has often been linked with conflict processing. However, it is unclear whether this negativity is related to stimulus- or response-related conflict, thus rendering the meaning of age-related changes inconclusive. In the present study, a modified Stroop task was used to focus on stimulus-related interference processes while excluding response-related interference. Since we intended to study work-relevant effects ERPs and performance were determined in young (about 30 years old) and middle-aged (about 50 years old) healthy subjects (total n=80). In the ERP, a broad negativity developed after incongruent versus congruent stimuli between 350 and 650 ms. An age-related increase of the latency and amplitude of this negativity was observed. These results indicate age-related alterations in the processing of conflicting stimuli already in middle age.

Aquifer susceptibility in Virginia, 1998-2000

USGS Publications Warehouse

Nelms, David L.; Harlow, George E.; Plummer, Niel; Busenberg, Eurybiades

2003-01-01

and springs in the fractured-rock terrains (the Appalachian Plateaus, Valley and Ridge, Blue Ridge, and Piedmont regional aquifer systems) contained concentrations of CFCs and 3H greater than one or both of the thresholds. Because all of the water samples exceeded at least one of the threshold values, young water is present throughout most of these regional aquifer systems; therefore, water supplies developed in these systems are susceptible to contamination from near-surface sources. No relation between well depth and presence of CFCs is evident from samples in the fractured-rock terrains. More than 95 percent of the samples for which the dating methods were applicable contained waters with apparent ages less than 35 years. About 5 percent of these samples, most of which were from the Blue Ridge and Piedmont regional aquifer systems, contained young waters with apparent ages of less than 5 years. Most of the samples from the Valley and Ridge Carbonate, Blue Ridge, and Piedmont regional aquifer systems had young water fractions of more than 50 percent, whereas samples from the Coastal Plain Shallow and Appalachian Plateaus regional aquifer systems contained less than 40 percent young waters. Concentrations of CFCs in excess of air-water equilibrium, which can indicate that nonatmospheric sources (such as sewage effluent) have introduced CFCs into the ground-water system, were measured in 6 and 48 percent of the water samples from the Coastal Plain and fractured-rock regional aquifer systems, respectively. The nitrate (NO3) concentrations greater than the USGS detection level of 0.05 milligrams per liter generally increase as the apparent age of the young water fraction decreases, with the highest NO3 concentrations for samples in which one or more of the CFCs are above modern atmospheric mixing ratios (commonly referred to as 'contaminated' for ground-water dating purposes). Most of the samples in which NO3 was detected w

The relative age effect in soccer: a match-related perspective.

PubMed

Vaeyens, Roel; Philippaerts, Renaat M; Malina, Robert M

2005-07-01

Asymmetries in the distributions of birth dates in senior professional and youth soccer players have been interpreted as evidence for systematic discrimination against individuals born shortly before the cut-off date in assigning youth to specific age groups. This concept is known as the "relative age effect". The results of a longitudinal study of birth date distritubions of 2757 semi-professional and amateur senior soccer players in Belgium are presented. Records for competitive games were available in official statistics provided by the Royal Belgian Football Association. The chi-square statistic was used to examine differences between observed and expected birth date distributions. Regression analyses indicated a shift of bias when two different start dates were compared. Players born in the early part of the new age band (January to March) were over-represented compared with players born late in the new selection period (October to December). However, players with birthdays at the start of the old selection year (August) were still represented. In a retrospective analysis of 2138 players, variables indicative of match involvement, number of selections for matches, and time played were examined in relation to the relative age effect. The group of semi-professional and amateur senior soccer players born in the first quarter of the selected age band received more playing opportunities. Comparisons of birth date distributions (traditional approach to relative age effect) with match-related variables gave similar, though not entirely consistent, results. However, there were no differences for the mean number of selections and for playing minutes between players born at the start or the end of the selection year. Our findings suggest that match-based variables may provide a more reliable indication of the relative age effect in soccer.

Susceptibility for thin ideal media and eating styles.

PubMed

Anschutz, Doeschka J; Engels, Rutger C M E; Van Strien, Tatjana

2008-03-01

This study examined the relations between susceptibility for thin ideal media and restrained, emotional and external eating, directly and indirectly through body dissatisfaction. Thin ideal media susceptibility, body dissatisfaction and eating styles were measured in a sample of 163 female students. Structural equation modelling was used for analyses, controlling for BMI. Higher susceptibility for thin ideal media was directly related to higher scores on all eating styles, and indirectly related to higher restrained and emotional eating through elevated levels of body dissatisfaction. So, thin ideal media susceptibility was not only related to restraint through body dissatisfaction, but also directly. Emotional eaters might be more vulnerable for negative affect, whereas external eaters might be more sensitive to external cues in general.

Quantitative susceptibility mapping of human brain at 3T: a multisite reproducibility study.

PubMed

Lin, P-Y; Chao, T-C; Wu, M-L

2015-03-01

Quantitative susceptibility mapping of the human brain has demonstrated strong potential in examining iron deposition, which may help in investigating possible brain pathology. This study assesses the reproducibility of quantitative susceptibility mapping across different imaging sites. In this study, the susceptibility values of 5 regions of interest in the human brain were measured on 9 healthy subjects following calibration by using phantom experiments. Each of the subjects was imaged 5 times on 1 scanner with the same procedure repeated on 3 different 3T systems so that both within-site and cross-site quantitative susceptibility mapping precision levels could be assessed. Two quantitative susceptibility mapping algorithms, similar in principle, one by using iterative regularization (iterative quantitative susceptibility mapping) and the other with analytic optimal solutions (deterministic quantitative susceptibility mapping), were implemented, and their performances were compared. Results show that while deterministic quantitative susceptibility mapping had nearly 700 times faster computation speed, residual streaking artifacts seem to be more prominent compared with iterative quantitative susceptibility mapping. With quantitative susceptibility mapping, the putamen, globus pallidus, and caudate nucleus showed smaller imprecision on the order of 0.005 ppm, whereas the red nucleus and substantia nigra, closer to the skull base, had a somewhat larger imprecision of approximately 0.01 ppm. Cross-site errors were not significantly larger than within-site errors. Possible sources of estimation errors are discussed. The reproducibility of quantitative susceptibility mapping in the human brain in vivo is regionally dependent, and the precision levels achieved with quantitative susceptibility mapping should allow longitudinal and multisite studies such as aging-related changes in brain tissue magnetic susceptibility. © 2015 by American Journal of Neuroradiology.

Incentive relativity in middle aged rats.

PubMed

Justel, N; Mustaca, A; Boccia, M; Ruetti, E

2014-01-24

Response to a reinforcer is affected by prior experience with different reward values of that reward, a phenomenon known as incentive relativity. Two different procedures to study this phenomenon are the incentive downshift (ID) and the consummatory anticipatory negative contrast (cANC), the former is an emotional-cognitive protocol and the latter cognitive one. Aged rodents, as also well described in aged humans, exhibit alterations in cognitive functions. The main goal of this work was to evaluate the effect of age in the incentive' assessment using these two procedures. The results indicated that aged rats had an adequate assessment of the rewards but their performance is not completely comparable to that of young subjects. They recover faster from the ID and they had a cognitive impairment in the cANC. The results are discussed in relation to age-related changes in memory and emotion. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Detection of relatively penicillin G-resistant Neisseria meningitidis by disk susceptibility testing.

PubMed Central

Campos, J; Mendelman, P M; Sako, M U; Chaffin, D O; Smith, A L; Sáez-Nieto, J A

1987-01-01

Beginning in 1985, relatively penicillin G-resistant (Penr) meningococci which did not produce beta-lactamase were isolated from the blood and cerebrospinal fluid of patients in Spain. We identified 16 Penr (mean MIC, 0.3 microgram/ml; range, 0.1 to 0.7 microgram/ml) and 12 penicillin-susceptible (Pens; mean MIC, less than or equal to 0.06 microgram/ml) strains of Neisseria meningitidis by the agar dilution technique using an inoculum of 10(4) CFU and questioned which disk susceptibility test would best differentiate these two populations. We compared the disk susceptibility of these strains using disks containing 2 (P2) and 10 (P10) U of penicillin G, 2 (Am2) and 10 (Am10) micrograms of ampicillin, and 1 microgram of oxacillin (OX1). We also investigated susceptibility with disks containing 30 micrograms of each of cephalothin (CF30), cefoxitin (FOX30), cefuroxime (CXM30), and cefotaxime (CTX30) and 75 micrograms of cefoperazone (CFP75) and determined by cluster analysis any correlation with the zone diameters obtained with P2 disks. Using the P2 and AM2 disks (in contrast to the P10 and AM10 disks), we correctly differentiated all the Penr from Pens isolates. In addition, the zone diameters with the P2 disk gave the best correlation with the penicillin G MIC determinations. All 16 Penr strains and 3 of 12 Pens strains showed zone diameters of 6 mm around OX1 disks, limiting the usefulness of OX1 disks. The zone diameters obtained with CF30, CXM30, and OX1 disks correlated with those obtained with the P2 disk, which suggests that these antibiotics have similar effects on these strains. In contrast, the data obtained with FOX30, CTX30, and CFP75 disks did not cluster with those obtained with the P2 disk, which suggests that there was a difference in the bacterial target or reflects their greater activity. We conclude that the P2 disk tests more readily identify Penr meningococci than do the standard P10 disk tests. PMID:3124729

Autophagy and ageing: implications for age-related neurodegenerative diseases.

PubMed

Carroll, Bernadette; Hewitt, Graeme; Korolchuk, Viktor I

2013-01-01

Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our 'ageing' world.

Plasma phospholipid fatty acids and fish-oil consumption in relation to osteoporotic fracture risk in older adults: the Age, Gene/Environment Susceptibility Study.

PubMed

Harris, Tamara B; Song, Xiaoling; Reinders, Ilse; Lang, Thomas F; Garcia, Melissa E; Siggeirsdottir, Kristin; Sigurdsson, Sigurdur; Gudnason, Vilmundur; Eiriksdottir, Gudny; Sigurdsson, Gunnar; Steingrimsdottir, Laufey; Aspelund, Thor; Brouwer, Ingeborg A; Murphy, Rachel A

2015-05-01

Polyunsaturated fatty acids (PUFAs) may play a role in fracture, but studies have been largely confined to estimates of dietary intake. We aimed to examine associations between fatty acids measured in late life and fish-oil consumption in early life, midlife, and late life with osteoporotic fracture risk. Osteoporotic fractures were determined from medical records over 5-9 y of follow-up in men and women aged 66-96 y. Data were analyzed from 1438 participants including 898 participants who were randomly selected from the Age, Gene/Environment Susceptibility Study, which is an observational study, and 540 participants with incident fracture. Plasma phospholipid fatty acids were assessed by using gas chromatography. Fish-oil consumption was assessed by using validated questionnaires as never (referent), less than daily, or daily. HRs and 95% CIs adjusted for age, education, height, weight, diabetes, physical activity, and medications were estimated by using Cox regression. In men, the highest tertile of PUFAs, n-3 (ω-3), and eicosapentaenoic acid were associated with decreased fracture risk [HRs (95% CIs): 0.60 (95% CI: 0.41, 0.89), 0.66 (0.45, 0.95), and 0.59 (0.41, 0.86), respectively]. In women, PUFAs tended to be inversely associated with fracture risk (P-trend = 0.06), but tertiles 2 and 3 were not independently associated with risk. Tertile 2 of n-6 and arachidonic acid was associated with fracture risk in women [HRs (95% CIs): 1.43 (1.10, 1.85) and 1.42 (1.09, 1.85), respectively]. Daily fish-oil consumption in late life was associated with lower fracture risk in men (HR: 0.64; 95% CI: 0.45, 0.91). Daily fish-oil consumption in midlife was associated with lower fracture risk in women (HR: 0.75; 95% CI: 0.58, 0.98). Greater PUFA concentrations may be associated with lower osteoporotic fracture risk in older adults, particularly in men. Critical time periods for n-3 fatty acid consumption may differ by sex. © 2015 American Society for Nutrition.

Depressive Symptom Trajectories, Aging-Related Stress, and Sexual Minority Stress Among Midlife and Older Gay Men: Linking Past and Present.

PubMed

Wight, Richard G; Harig, Frederick; Aneshensel, Carol S; Detels, Roger

2016-05-01

We concatenate 28 years of historical depressive symptoms data from a longitudinal cohort study of U.S. gay men who are now midlife and older (n = 312), with newly collected survey data to analyze trajectories of depressive symptomatology over time and their impact on associations between current stress and depressive symptoms. Symptoms are high over time, on average, and follow multiple trajectories. Aging-related stress, persistent life-course sexual minority stress, and increasing sexual minority stress are positively associated with depressive symptoms, net of symptom trajectories. Men who had experienced elevated and increasing trajectories of depressive symptoms are less susceptible to the damaging effects of aging-related stress than those who experienced a decrease in symptoms over time. Intervention efforts aimed at assisting gay men as they age should take into account life-course depressive symptom histories to appropriately contextualize the health effects of current social stressors. © The Author(s) 2015.

Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

PubMed Central

Rea, Irene Maeve; Gibson, David S.; McGilligan, Victoria; McNerlan, Susan E.; Alexander, H. Denis; Ross, Owen A.

2018-01-01

Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called “inflamm-aging.” Despite research there is no clear understanding about the causes of “inflamm-aging” that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer’s disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with “inflammageing” or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis. PMID:29686666

Susceptibility to Heat-Related Fluid and Electrolyte Imbalance Emergency Department Visits in Atlanta, Georgia, USA.

PubMed

Heidari, Leila; Winquist, Andrea; Klein, Mitchel; O'Lenick, Cassandra; Grundstein, Andrew; Ebelt Sarnat, Stefanie

2016-10-02

Identification of populations susceptible to heat effects is critical for targeted prevention and more accurate risk assessment. Fluid and electrolyte imbalance (FEI) may provide an objective indicator of heat morbidity. Data on daily ambient temperature and FEI emergency department (ED) visits were collected in Atlanta, Georgia, USA during 1993-2012. Associations of warm-season same-day temperatures and FEI ED visits were estimated using Poisson generalized linear models. Analyses explored associations between FEI ED visits and various temperature metrics (maximum, minimum, average, and diurnal change in ambient temperature, apparent temperature, and heat index) modeled using linear, quadratic, and cubic terms to allow for non-linear associations. Effect modification by potential determinants of heat susceptibility (sex; race; comorbid congestive heart failure, kidney disease, and diabetes; and neighborhood poverty and education levels) was assessed via stratification. Higher warm-season ambient temperature was significantly associated with FEI ED visits, regardless of temperature metric used. Stratified analyses suggested heat-related risks for all populations, but particularly for males. This work highlights the utility of FEI as an indicator of heat morbidity, the health threat posed by warm-season temperatures, and the importance of considering susceptible populations in heat-health research.

Susceptibility to Heat-Related Fluid and Electrolyte Imbalance Emergency Department Visits in Atlanta, Georgia, USA

PubMed Central

Heidari, Leila; Winquist, Andrea; Klein, Mitchel; O’Lenick, Cassandra; Grundstein, Andrew; Ebelt Sarnat, Stefanie

2016-01-01

Identification of populations susceptible to heat effects is critical for targeted prevention and more accurate risk assessment. Fluid and electrolyte imbalance (FEI) may provide an objective indicator of heat morbidity. Data on daily ambient temperature and FEI emergency department (ED) visits were collected in Atlanta, Georgia, USA during 1993–2012. Associations of warm-season same-day temperatures and FEI ED visits were estimated using Poisson generalized linear models. Analyses explored associations between FEI ED visits and various temperature metrics (maximum, minimum, average, and diurnal change in ambient temperature, apparent temperature, and heat index) modeled using linear, quadratic, and cubic terms to allow for non-linear associations. Effect modification by potential determinants of heat susceptibility (sex; race; comorbid congestive heart failure, kidney disease, and diabetes; and neighborhood poverty and education levels) was assessed via stratification. Higher warm-season ambient temperature was significantly associated with FEI ED visits, regardless of temperature metric used. Stratified analyses suggested heat-related risks for all populations, but particularly for males. This work highlights the utility of FEI as an indicator of heat morbidity, the health threat posed by warm-season temperatures, and the importance of considering susceptible populations in heat-health research. PMID:27706089

Immunology of age-related macular degeneration.

PubMed

Ambati, Jayakrishna; Atkinson, John P; Gelfand, Bradley D

2013-06-01

Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population.

Transcriptomic and metabolomic analyses of cucumber fruit peels reveal a developmental increase in terpenoid glycosides associated with age-related resistance to Phytophthora capsici

PubMed Central

Mansfeld, Ben N; Colle, Marivi; Kang, Yunyan; Jones, A Daniel; Grumet, Rebecca

2017-01-01

The oomycete, Phytophthora capsici, infects cucumber (Cucumis sativus L.) fruit. An age-related resistance (ARR) to this pathogen was previously observed in fruit of cultivar ‘Vlaspik’ and shown to be associated with the peel. Young fruits are highly susceptible, but develop resistance at ~10–12 days post pollination (dpp). Peels from resistant (16 dpp) versus susceptible (8 dpp) age fruit are enriched with genes associated with defense, and methanolic extracts from resistant age peels inhibit pathogen growth. Here we compared developing fruits from ‘Vlaspik’ with those of ‘Gy14’, a line that does not exhibit ARR. Transcriptomic analysis of peels of the two lines at 8 and 16 dpp identified 80 genes that were developmentally upregulated in resistant ‘Vlaspik’ 16 dpp versus 8 dpp, but not in susceptible ‘Gy14’ at 16 dpp. A large number of these genes are annotated to be associated with defense and/or specialized metabolism, including four putative resistance (R) genes, and numerous genes involved in flavonoid and terpenoid synthesis and decoration. Untargeted metabolomic analysis was performed on extracts from 8 and 16 dpp ‘Vlaspik’ and ‘Gy14’ fruit peels using Ultra-Performance Liquid Chromatography and Quadrupole Time-of-Flight Mass Spectrometry. Multivariate analysis of the metabolomes identified 113 ions uniquely abundant in resistant ‘Vlaspik’ 16 dpp peel extracts. The most abundant compounds in this group had relative mass defects consistent with terpenoid glycosides. Two of the three most abundant ions were annotated as glycosylated nor-terpenoid esters. Together, these analyses reveal potential mechanisms by which ARR to P. capsici may be conferred. PMID:28580151

Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics

NASA Technical Reports Server (NTRS)

Dijk, D. J.; Duffy, J. F.

1999-01-01

The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed.

Age‐related alterations in immune responses to West Nile virus infection

PubMed Central

2016-01-01

Summary West Nile virus (WNV) is the most important causative agent of viral encephalitis worldwide and an important public health concern in the United States due to its high prevalence, severe disease, and the absence of effective treatments. Infection with WNV is mainly asymptomatic, but some individuals develop severe, possibly fatal, neurological disease. Individual host factors play a role in susceptibility to WNV infection, including genetic polymorphisms in key anti‐viral immune genes, but age is the most well‐defined risk factor for susceptibility to severe disease. Ageing is associated with distinct changes in immune cells and a decline in immune function leading to increased susceptibility to infection and reduced responses to vaccination. WNV is detected by pathogen recognition receptors including Toll‐like receptors (TLRs), which show reduced expression and function in ageing. Neutrophils, monocyte/macrophages and dendritic cells, which first recognize and respond to infection, show age‐related impairment of many functions relevant to anti‐viral responses. Natural killer cells control many viral infections and show age‐related changes in phenotype and functional responses. A role for the regulatory receptors Mertk and Axl in blood–brain barrier permeability and in facilitating viral uptake through phospholipid binding may be relevant for susceptibility to WNV, and age‐related up‐regulation of Axl has been noted previously in human dendritic cells. Understanding the specific immune parameters and mechanisms that influence susceptibility to symptomatic WNV may lead to a better understanding of increased susceptibility in elderly individuals and identify potential avenues for therapeutic approaches: an especially relevant goal, as the world's populating is ageing. PMID:27612657

AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

EPA Science Inventory

The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), i...

Age-Related Changes in Creative Thinking

ERIC Educational Resources Information Center

Roskos-Ewoldsen, Beverly; Black, Sheila R.; Mccown, Steven M.

2008-01-01

Age-related differences in cognitive processes were used to understand age-related declines in creativity. According to the Geneplore model (Finke, Ward, & Smith, 1992), there are two phases of creativity--generating an idea and exploring the implications of the idea--each with different underlying cognitive processes. These two phases are…

Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats.

PubMed

MacPhail, R C; Farmer, J D; Jarema, K A

2012-01-01

Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have compared toxicant susceptibility across a broad range of life stages. Results are presented for behavioral evaluations of male Brown Norway rats obtained as adolescents (1 month), or young (4 months), middle-age (12 months) and senescent (24 months) adults. Motor activity was evaluated in photocell devices during 30-min sessions. Age-related baseline characteristics and sensitivity to toluene (0, 300, 650, or 1000mg/kg, p.o.) were determined. In Experiment 1, young-adult, middle-age and senescent rats were treated with corn-oil vehicle before five weekly test sessions. Baselines of horizontal and vertical activity decreased with age, but each age-group's averages remained stable across weeks of testing. Baseline activity of older rats was more variable than that of the young adults; older rats were also more variable individually from week to week. Toluene (1000mg/kg) increased horizontal activity proportionately more in senescent rats (ca. 300% of control) than in middle-age or young-adult rats (ca.145-175% of control). Experiment 2 established toluene dose-effect functions in individual adolescent, young-adult, middle-age and senescent rats; each rat received all treatments, counterbalanced across four weekly sessions. Toluene produced dose-related increases in horizontal activity that increased proportionately with age. Experiment 3 replicated the effects of toluene (1000mg/kg) in Experiment 1, showing that toluene-induced increases in horizontal activity were greatest in the oldest rats. Collectively, the results show that aging increased susceptibility to toluene and also increased variability in toluene response. Given the rapid growth of the aged population, further research is

The morphology of human hyoid bone in relation to sex, age and body proportions.

PubMed

Urbanová, P; Hejna, P; Zátopková, L; Šafr, M

2013-06-01

Morphological aspects of the human hyoid bone are, like many other skeletal elements in human body, greatly affected by individual's sex, age and body proportions. Still, the known sex-dependent bimodality of a number of body size characteristics overshadows the true within-group patterns. Given the ambiguity of the causal effects of age, sex and body size upon hyoid morphology the present study puts the relationship between shape of human hyoid bone and body proportions (height and weight) under scrutiny of a morphological study. Using 211 hyoid bones and landmark-based methods of geometric morphometrics, it was shown that the size of hyoid bones correlated positively with measured body dimensions but showed no correlation if the individual's sex was controlled for. For shape variables, our results revealed that hyoid morphology is clearly related to body size as expressed in terms of the height and weight. Yet, the hyoid shape was shown to result primarily from the sex-related bimodal distribution of studied body size descriptors which, in the case of the height-dependent model, exhibited opposite trends for males and females. Apart from the global hyoid shape given by spatial arrangements of the greater horns, body size dependency was translated into size and position of the hyoid body. None of the body size characters had any impact on hyoid asymmetry. Ultimately, sexually dimorphic variation was revealed for age-dependent changes in both size and shape of hyoid bones as male hyoids tend to be more susceptible to modifications with age than female bones. Copyright © 2013 Elsevier GmbH. All rights reserved.

Evaluation of new and established age-related macular degeneration susceptibility genes in the Women's Health Initiative Sight Exam (WHI-SE) Study

USDA-ARS?s Scientific Manuscript database

To assess whether established and newly reported genetic variants, independent of known lifestyle factors, are associated with the risk of age-related macular degeneration (AMD) among women participating in the Women's Health Initiative Sight Exam (WHI-SE) Genetic Ancillary Study. This is a multice...

Immunology of age-related macular degeneration

PubMed Central

Ambati, Jayakrishna; Atkinson, John P.; Gelfand, Bradley D.

2014-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. PMID:23702979

Morphological Characteristics of Motor Neurons Do Not Determine Their Relative Susceptibility to Degeneration in a Mouse Model of Severe Spinal Muscular Atrophy

PubMed Central

Mutsaers, Chantal A.; Thomson, Derek; Hamilton, Gillian; Parson, Simon H.; Gillingwater, Thomas H.

2012-01-01

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice – including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA. PMID:23285108

Leaders and followers in adolescent close friendships: Susceptibility to peer influence as a predictor of risky behavior, friendship instability, and depression

PubMed Central

ALLEN, JOSEPH P.; PORTER, MARYFRANCES R.; MCFARLAND, F. CHRISTY

2006-01-01

Adolescents’ susceptibility to peer influence was examined as a marker of difficulties in the general process of autonomy development that was likely to be related to deficits across multiple domains of psychosocial functioning. A laboratory-based assessment of susceptibility to peer influence in interactions with a close friend was developed and examined in relation to corollary reports obtained from adolescents, their mothers, and close peers at ages 13 and 14. As hypothesized, observed susceptibility to peer influence with a close friend predicted future responses to negative peer pressure, but it was also related to broader markers of problems in functioning, including decreases in popularity, and increasing levels of depressive symptoms, over time. Susceptibility to peer influence was also linked to higher concurrent levels of substance use, externalizing behavior, and sexual activity. Results are interpreted as reflecting the central role of establishing autonomy with peers in psychosocial development. PMID:16478557

Higher mortality and impaired elimination of bacteria in aged mice after intracerebral infection with E. coli are associated with an age-related decline of microglia and macrophage functions.

PubMed

Schütze, Sandra; Ribes, Sandra; Kaufmann, Annika; Manig, Anja; Scheffel, Jörg; Redlich, Sandra; Bunkowski, Stephanie; Hanisch, Uwe-Karsten; Brück, Wolfgang; Nau, Roland

2014-12-30

Incidence and mortality of bacterial meningitis are strongly increased in aged compared to younger adults demanding new strategies to improve prevention and therapy of bacterial central nervous system (CNS) infections the elderly. Here, we established a geriatric mouse model for an intracerebral E. coli infection which reflects the clinical situation in aged patients: After intracerebral challenge with E. coli K1, aged mice showed a higher mortality, a faster development of clinical symptoms, and a more pronounced weight loss. Elimination of bacteria and systemic inflammatory response were impaired in aged mice, however, the number of infiltrating leukocytes and microglial cells in the CNS of aged and young mice did not differ substantially. In vitro, primary microglial cells and peritoneal macrophages from aged mice phagocytosed less E. coli and released less NO and cyto-/chemokines compared to cells from young mice both without activation and after stimulation by agonists of TLR 2, 4, and 9. Our results suggest that the age-related decline of microglia and macrophage functions plays an essential role for the higher susceptibility of aged mice to intracerebral infections. Strategies to improve the phagocytic potential of aged microglial cells and macrophages appear promising for prevention and treatment of CNS infections in elderly patients.

Hypertensive renal disease: susceptibility and resistance in inbred hypertensive rat lines.

PubMed

Braun, Michael C; Herring, Stacy M; Gokul, Nisha; Monita, Monique; Bell, Rebecca; Hicks, M John; Wenderfer, Scott E; Doris, Peter A

2013-10-01

Spontaneously hypertensive rat (SHR) lines differ in their susceptibility to hypertensive end-organ disease and may provide an informative model of genetic risk of disease. Lines derived from the original SHR-B and SHR-C clades are highly resistant to hypertensive end-organ disease, whereas lines derived from the SHR-A clade were selected for stroke susceptibility and experience hypertensive renal disease. Here we characterize the temporal development of progressive renal injury in SHR-A3 animals consuming 0.3% sodium in the diet and drinking water. SHR-A3 rats demonstrate albuminuria, glomerular damage, tubulointerstitial injury, and renal fibrosis that emerge at 18 weeks of age and progress. Mortality of SHR-A3 animals was 50% at 40 weeks of age, and animals surviving to this age had reduced renal function. In contrast SHR-B2, which are 87% genetically identical to SHR-A3, are substantially protected from renal injury and demonstrate only moderate changes in albuminuria and renal histological injury over this time period. At 40 weeks of age, electron microscopy of the renal glomerulus revealed severe podocyte effacement in SHR-A3, but slit diaphragm architecture in SHR-B2 at this age was well preserved. Renal injury traits in the F1 and F2 progeny of an intercross between SHR-A3 and SHR-B2 were measured to determine heritability of renal injury in this model. Heritability of albuminuria, glomerular injury, and tubulointerstitial injury were estimated at 48.9, 66.5 and 58.6%, respectively. We assessed the relationship between blood pressure and renal injury measures in the F2 animals and found some correlation between these variables that explain up to 26% of the trait variation. Quantitative trait locus (QTL) mapping was performed using over 200 single nucleotide polymorphism markers distributed across the 13% of the genome that differs between these two closely related lines. Mapping of albuminuria, tubulointerstitial injury, and renal fibrosis failed to

Working-age adults with diabetes experience greater susceptibility to seasonal influenza: a population-based cohort study.

PubMed

Lau, Darren; Eurich, Dean T; Majumdar, Sumit R; Katz, Alan; Johnson, Jeffrey A

2014-04-01

The aim of this work was to compare the incidence of illness attributable to influenza in working-age adults (age <65 years) with and without diabetes. We performed a cohort study using administrative data from Manitoba, Canada, between 2000 and 2008. All working-age adults with diabetes were identified and matched with up to two non-diabetic controls. We analysed the rates of influenza-like illness physician visits and hospitalisations, pneumonia and influenza hospitalisations, and all-cause hospitalisations. Multivariable regressions were used to estimate the influenza-attributable rate of each outcome. We included 745,777 person-years of follow-up among 166,715 subjects. The median age was 50-51 years and 48-49% were women; adults with diabetes had more comorbidities and were more likely to be vaccinated for influenza than those without diabetes. Compared with similar adults without diabetes, those with diabetes had a 6% greater (RR 1.06, 95% CI 1.02, 1.10; absolute risk difference 6 per 1,000 adults per year) increase in all-cause hospitalisations associated with influenza, representing a total of 54 additional hospitalisations. There were no differences in the influenza-attributable rates of influenza-like illness (p = 0.06) or pneumonia and influenza (p = 0.11). Guidelines calling for influenza vaccinations in diabetic, in addition to elderly, adults implicitly single out working-age adults with diabetes. The evidence supporting such guidelines has hitherto been scant. We found that working-age adults with diabetes appear more susceptible to serious influenza-attributable illness. These findings represent the strongest available evidence for targeting diabetes as an indication for influenza vaccination, irrespective of age.

Life stress, glucocorticoid signaling, and the aging epigenome: Implications for aging-related diseases.

PubMed

Gassen, Nils C; Chrousos, George P; Binder, Elisabeth B; Zannas, Anthony S

2017-03-01

Life stress has been associated with accelerated cellular aging and increased risk for developing aging-related diseases; however, the underlying molecular mechanisms remain elusive. A highly relevant process that may underlie this association is epigenetic regulation. In this review, we build upon existing evidence to propose a model whereby exposure to life stress, in part via its effects on the hypothalamic-pituitary axis and the glucocorticoid signaling system, may alter the epigenetic landscape across the lifespan and, consequently, influence genomic regulation and function in ways that are conducive to the development of aging-related diseases. This model is supported by recent studies showing that life stressors and stress-related phenotypes can accelerate epigenetic aging, a measure that is based on DNA methylation prediction of chronological age and has been associated with several aging-related disease phenotypes. We discuss the implications of this model for the prevention and treatment of aging-related diseases, as well as the challenges and limitations of this line of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Geohydrology and susceptibility of major aquifers to surface contamination in Alabama, area 7

USGS Publications Warehouse

Mooty, W.S.

1987-01-01

The geohydrology and susceptibility of the seven major aquifers to surface contamination in Area 7 - Bibb, Dallas, Hale, Perry, and Wilcox Counties, are described. Aquifers in the northern part of the study area are in Paleozoic limestones and dolomite formations. Deposits in the central part of the study area are predominately of Cretaceous age and contain the Coker, Gordo, and Eutaw aquifers. Although the southern part of the study area has many deposits of Tertiary age, the Ripley Formation of Cretaceous age is the major aquifer. Contamination of any of the major aquifers is improbable because the majority of the recharge area for the primary aquifers is woodland, pasture, or farmland. Downdip from their outcrops, the major aquifers in the study area are protected from land surface contamination by relatively impermeable layers of clay and chalk. The aquifers that are highly susceptible to contamination are the ones in the limestone and dolomite formations in northern Bibb County. Sinkholes exist in the recharge area of these formations and could provide a direct link for contaminates from the land surface to the water table. An area northeast of the Selma well field is also highly susceptible to contamination. The Eutaw Formation in this area is overlain by alluvial deposits that could increase recharge to the aquifer by slowing the runoff rate of surface water. (USGS)

Regulation of age-related macular degeneration-like pathology by complement factor H

PubMed Central

Toomey, Christopher B.; Kelly, Una; Saban, Daniel R.; Bowes Rickman, Catherine

2015-01-01

Complement factor H (CFH) is a major susceptibility gene for age-related macular degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here, the role of CFH in the development of AMD pathology in vivo was interrogated by analyzing aged Cfh+/− and Cfh−/− mice fed a high-fat, cholesterol-enriched diet. Strikingly, decreased levels of CFH led to increased sub-retinal pigmented epithelium (sub-RPE) deposit formation, specifically basal laminar deposits, following high-fat diet. Mechanistically, our data show that deposits are due to CFH competition for lipoprotein binding sites in Bruch’s membrane. Interestingly and despite sub-RPE deposit formation occurring in both Cfh+/− and Cfh−/− mice, RPE damage accompanied by loss of vision occurred only in old Cfh+/− mice. We demonstrate that such pathology is a function of excess complement activation in Cfh+/− mice versus complement deficiency in Cfh−/− animals. Due to the CFH-dependent increase in sub-RPE deposit height, we interrogated the potential of CFH as a previously unidentified regulator of Bruch’s membrane lipoprotein binding and show, using human Bruch’s membrane explants, that CFH removes endogenous human lipoproteins in aged donors. Thus, advanced age, high-fat diet, and decreased CFH induce sub-RPE deposit formation leading to complement activation, which contributes to RPE damage and visual function impairment. This new understanding of the complicated interactions of CFH in AMD-like pathology provides an improved foundation for the development of targeted therapies for AMD. PMID:25991857

Accuracy of magnetic resonance based susceptibility measurements

NASA Astrophysics Data System (ADS)

Erdevig, Hannah E.; Russek, Stephen E.; Carnicka, Slavka; Stupic, Karl F.; Keenan, Kathryn E.

2017-05-01

Magnetic Resonance Imaging (MRI) is increasingly used to map the magnetic susceptibility of tissue to identify cerebral microbleeds associated with traumatic brain injury and pathological iron deposits associated with neurodegenerative diseases such as Parkinson's and Alzheimer's disease. Accurate measurements of susceptibility are important for determining oxygen and iron content in blood vessels and brain tissue for use in noninvasive clinical diagnosis and treatment assessments. Induced magnetic fields with amplitude on the order of 100 nT, can be detected using MRI phase images. The induced field distributions can then be inverted to obtain quantitative susceptibility maps. The focus of this research was to determine the accuracy of MRI-based susceptibility measurements using simple phantom geometries and to compare the susceptibility measurements with magnetometry measurements where SI-traceable standards are available. The susceptibilities of paramagnetic salt solutions in cylindrical containers were measured as a function of orientation relative to the static MRI field. The observed induced fields as a function of orientation of the cylinder were in good agreement with simple models. The MRI susceptibility measurements were compared with SQUID magnetometry using NIST-traceable standards. MRI can accurately measure relative magnetic susceptibilities while SQUID magnetometry measures absolute magnetic susceptibility. Given the accuracy of moment measurements of tissue mimicking samples, and the need to look at small differences in tissue properties, the use of existing NIST standard reference materials to calibrate MRI reference structures is problematic and better reference materials are required.

Pattern of susceptibility to measles in Italy. Serological Study Group.

PubMed Central

Salmaso, S.; Gabutti, G.; Rota, M. C.; Giordano, C.; Penna, C.; Mandolini, D.; Crovari, P.

2000-01-01

On the basis of seroprevalence and incidence data we describe the distribution of individuals susceptible and immune to measles in Italy in 1996-97. In regions where vaccination coverage was at least 70%, approximately 10% of 3-year-old children were susceptible to measles, whereas 40% were in this category in regions with lower vaccination coverage. Seroprevalence among children older than 4 years was similar for the two groups of regions; in the age group 20-39 years it was approximately 95%. During 1990-96 in the regions with lower vaccination coverage the incidence was highest among children aged 4-6 years, and the median age of cases was 7 years; in the regions with higher vaccination coverage, however, the incidence remained at around 5% for the age group 4-16 years, and the overall median age was 10 years. These data confirm the partial reduction in measles incidence in Italy, although transmission has still not been interrupted. The size and geographical distribution of the current pool of susceptible individuals can be expected to present an obstacle to measles elimination if appropriate vaccination strategies, such as catch-up campaigns, are not adopted. PMID:10994277

Influence of Sex and Age on Natural Resistance to St. Louis Encephalitis Virus Infection in Mice

PubMed Central

Andersen, Arthur A.; Hanson, Robert P.

1974-01-01

A difference was observed in susceptibility of adult male and female mice to St. Louis encephalitis (SLE) virus as measured by the death rate after intravenous challenge. Female mice that had susceptibility similar to that of males at 2 months of age had increased resistance to SLE virus at 3 and 4 months of age. The increased resistance occurred after sexual maturity, indicating that the resistance factor possibly was related to an aging process in the female. The susceptibility of male mice remained unchanged over the 2- to 4-month period. Neither pregnancy nor castration had any effect on resistance of adult mice to St. Louis encephalitis virus. PMID:4857422

Ozone Effects on Protein Carbonyl Content in the Frontal Cortex and Cerebellum of Young-Adult, Middle Age, and Senescent Brown Norway Rats

EPA Science Inventory

Oxidative stress (OS) plays an important role in susceptibility and disease in old age. Understanding age-related susceptibility is a critical part of community-based human health risk assessment of chemical exposures. There is growing concern over a common air pollutant, ozone ...

Rabbits and men: relating their ages.

PubMed

Dutta, Sulagna; Sengupta, Pallav

2018-04-19

Rabbit, a member of the Lagomorpha order, is the closest phylogenetic relative to humans, next to primates. It possesses greater acceptability as a laboratory mammal than primates in terms of husbandry, breeding ease, cost effectiveness, and legal ethical conveniences. Moreover, as a laboratory animal, the rabbit also owns its advantages over mice or rats, in terms of phylogenetic resemblance to human, size, blood volume, responsiveness, and other congruences enabling them to better imitate human physiological characteristics in biomedical research. A specific research aspires to effectuate its outcome on a particular human age group, for which it is pivotal to select a laboratory rabbit of exact age, which will correlate with that specific age of a human, which is currently based on mere approximation. This article is the first ever scientific venture, focused to swap this approximation of laboratory rabbit age with accuracy by relating it with that of humans analyzing different phases of life individually. Considering the diminutive lifespan of rabbits compared to humans, the correlation of their age with respect to the entire lifespan, which we found out to be 45.625 days compared to one human year, is not enough. Thereby, like our previous articles that formulated concise relation of age of laboratory rats and mice with human age, in this article also, we aim to aid biomedical research specificity in the selection of laboratory model age, separately correlating different life phases of humans with that of rabbits, the second mostly used mammal in 2016 in the United States.

Dissection of Genomewide-Scan Data in Extended Families Reveals a Major Locus and Oligogenic Susceptibility for Age-Related Macular Degeneration

PubMed Central

Iyengar, Sudha K.; Song, Danhong; Klein, Barbara E. K.; Klein, Ronald; Schick, James H.; Humphrey, Jennifer; Millard, Christopher; Liptak, Rachel; Russo, Karlie; Jun, Gyungah; Lee, Kristine E.; Fijal, Bonnie; Elston, Robert C.

2004-01-01

To examine the genetic basis of age-related macular degeneration (ARMD), a degenerative disease of the retinal pigment epithelium and neurosensory retina, we conducted a genomewide scan in 34 extended families (297 individuals, 349 sib pairs) ascertained through index cases with neovascular disease or geographic atrophy. Family and medical history was obtained from index cases and family members. Fundus photographs were taken of all participating family members, and these were graded for severity by use of a quantitative scale. Model-free linkage analysis was performed, and tests of heterogeneity and epistasis were conducted. We have evidence of a major locus on chromosome 15q (GATA50C03 multipoint P=1.98×10-7; empirical P⩽1.0×10-5; single-point P=3.6×10-7). This locus was present as a weak linkage signal in our previous genome scan for ARMD, in the Beaver Dam Eye Study sample (D15S659, multipoint P=.047), but is otherwise novel. In this genome scan, we observed a total of 13 regions on 11 chromosomes (1q31, 2p21, 4p16, 5q34, 9p24, 9q31, 10q26, 12q13, 12q23, 15q21, 16p12, 18p11, and 20q13), with a nominal multipoint significance level of P⩽.01 or LOD ⩾1.18. Family-by-family analysis of the data, performed using model-free linkage methods, suggests that there is evidence of heterogeneity in these families. For example, a single family (family 460) individually shows linkage evidence at 8 loci, at the level of P<.0001. We conducted tests for heterogeneity, which suggest that ARMD susceptibility loci on chromosomes 9p24, 10q26, and 15q21 are not present in all families. We tested for mutations in linked families and examined SNPs in two candidate genes, hemicentin-1 and EFEMP1, in subsamples (145 and 189 sib pairs, respectively) of the data. Mutations were not observed in any of the 11 exons of EFEMP1 nor in exon 104 of hemicentin-1. The SNP analysis for hemicentin-1 on 1q31 suggests that variants within or in very close proximity to this gene cause ARMD

Parainflammation, chronic inflammation, and age-related macular degeneration.

PubMed

Chen, Mei; Xu, Heping

2015-11-01

Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. © Society for Leukocyte Biology.

Decorin expression is important for age-related changes in tendon structure and mechanical properties

PubMed Central

Dunkman, Andrew A.; Buckley, Mark R.; Mienaltowski, Michael J.; Adams, Sheila M.; Thomas, Stephen J.; Satchell, Lauren; Kumar, Akash; Pathmanathan, Lydia; Beason, David P.; Iozzo, Renato V.; Birk, David E.; Soslowsky, Louis J.

2013-01-01

The aging population is at an increased risk of tendon injury and tendinopathy. Elucidating the molecular basis of tendon aging is crucial to understanding the age-related changes in structure and function in this vulnerable tissue. In this study, the structural and functional features of tendon aging are investigated. In addition, the roles of decorin and biglycan in the aging process were analyzed using transgenic mice at both mature and aged time points. Our hypothesis is that the increase in tendon injuries in the aging population is the result of altered structural properties that reduce the biomechanical function of the tendon and consequently increase susceptibility to injury. Decorin and biglycan are important regulators of tendon structure and therefore, we further hypothesized that decreased function in aged tendons is partly the result of altered decorin and biglycan expression. Biomechanical analyses of mature (day 150) and aged (day 570) patellar tendons revealed deteriorating viscoelastic properties with age. Histology and polarized light microscopy demonstrated decreased cellularity, alterations in tenocyte shape, and reduced collagen fiber alignment in the aged tendons. Ultrastructural analysis of fibril diameter distributions indicated an altered distribution in aged tendons with an increase of large diameter fibrils. Aged wild type tendons maintained expression of decorin which was associated with the structural and functional changes seen in aged tendons. Aged patellar tendons exhibited altered and generally inferior properties across multiple assays. However, decorin-null tendons exhibited significantly decreased effects of aging compared to the other genotypes. The amelioration of the functional deficits seen in the absence of decorin in aged tendons was associated with altered tendon fibril structure. Fibril diameter distributions in the decorin-null aged tendons were comparable to those observed in the mature wild type tendon with the absence

C-Reactive Protein as a Therapeutic Target in Age-Related Macular Degeneration.

PubMed

Molins, Blanca; Romero-Vázquez, Sara; Fuentes-Prior, Pablo; Adan, Alfredo; Dick, Andrew D

2018-01-01

Age-related macular degeneration (AMD), a retinal degenerative disease, is the leading cause of central vision loss among the elderly population in developed countries and an increasing global burden. The major risk is aging, compounded by other environmental factors and association with genetic variants for risk of progression. Although the etiology of AMD is not yet clearly understood, several pathogenic pathways have been proposed, including dysfunction of the retinal pigment epithelium, inflammation, and oxidative stress. The identification of AMD susceptibility genes encoding complement factors and the presence of complement and other inflammatory mediators in drusen, the hallmark deposits of AMD, support the concept that local inflammation and immune-mediated processes play a key role in AMD pathogenesis that may be accelerated through systemic immune activation. In this regard, increased levels of circulating C-reactive protein (CRP) have been associated with higher risk of AMD. Besides being a risk marker for AMD, CRP may also play a role in the progression of the disease as it has been identified in drusen, and we have recently found that its monomeric form (mCRP) induces blood retinal barrier disruption in vitro . In this review, we will address recent evidence that links CRP and AMD pathogenesis, which may open new therapeutic opportunities to prevent the progression of AMD.

Similarity-based interference in a working memory numerical updating task: age-related differences between younger and older adults.

PubMed

Pelegrina, Santiago; Borella, Erika; Carretti, Barbara; Lechuga, M Teresa

2012-01-01

Similarity among representations held simultaneously in working memory (WM) is a factor which increases interference and hinders performance. The aim of the current study was to investigate age-related differences between younger and older adults in a working memory numerical updating task, in which the similarity between information held in WM was manipulated. Results showed a higher susceptibility of older adults to similarity-based interference when accuracy, and not response times, was considered. It was concluded that older adults' WM difficulties appear to be due to the availability of stored information, which, in turn, might be related to the ability to generate distinctive representations and to the process of binding such representations to their context when similar information has to be processed in WM.

Gadd45 proteins: Relevance to aging, longevity and age-related pathologies

PubMed Central

Moskalev, Alexey A.; Smit-McBride, Zeljka; Shaposhnikov, Mikhail V.; Plyusnina, Ekaterina N.; Zhavoronkov, Alex; Budovsky, Arie; Tacutu, Robi; Fraifeld, Vadim E.

2013-01-01

The Gadd45 proteins have been intensively studied, in view of their important role in key cellular processes. Indeed, the Gadd45 proteins stand at the crossroad of the cell fates by controlling the balance between cell (DNA) repair, eliminating (apoptosis) or preventing the expansion of potentially dangerous cells (cell cycle arrest, cellular senescence), and maintaining the stem cell pool. However, the biogerontological aspects have not thus far received sufficient attention. Here we analyzed the pathways and modes of action by which Gadd45 members are involved in aging, longevity and age-related diseases. Because of their pleiotropic action, a decreased inducibility of Gadd45 members may have far-reaching consequences including genome instability, accumulation of DNA damage, and disorders in cellular homeostasis – all of which may eventually contribute to the aging process and age-related disorders (promotion of tumorigenesis, immune disorders, insulin resistance and reduced responsiveness to stress). Most recently, the dGadd45 gene has been identified as a longevity regulator in Drosophila. Although further wide-scale research is warranted, it is becoming increasingly clear that Gadd45s are highly relevant to aging, age-related diseases (ARDs) and to the control of life span, suggesting them as potential therapeutic targets in ARDs and pro-longevity interventions. PMID:21986581

Age-related differences in human skin proteoglycans.

PubMed

Carrino, David A; Calabro, Anthony; Darr, Aniq B; Dours-Zimmermann, Maria T; Sandy, John D; Zimmermann, Dieter R; Sorrell, J Michael; Hascall, Vincent C; Caplan, Arnold I

2011-02-01

Previous work has shown that versican, decorin and a catabolic fragment of decorin, termed decorunt, are the most abundant proteoglycans in human skin. Further analysis of versican indicates that four major core protein species are present in human skin at all ages examined from fetal to adult. Two of these are identified as the V0 and V1 isoforms, with the latter predominating. The other two species are catabolic fragments of V0 and V1, which have the amino acid sequence DPEAAE as their carboxyl terminus. Although the core proteins of human skin versican show no major age-related differences, the glycosaminoglycans (GAGs) of adult skin versican are smaller in size and show differences in their sulfation pattern relative to those in fetal skin versican. In contrast to human skin versican, human skin decorin shows minimal age-related differences in its sulfation pattern, although, like versican, the GAGs of adult skin decorin are smaller than those of fetal skin decorin. Analysis of the catabolic fragments of decorin from adult skin reveals the presence of other fragments in addition to decorunt, although the core proteins of these additional decorin catabolic fragments have not been identified. Thus, versican and decorin of human skin show age-related differences, versican primarily in the size and the sulfation pattern of its GAGs and decorin in the size of its GAGs. The catabolic fragments of versican are detected at all ages examined, but appear to be in lower abundance in adult skin compared with fetal skin. In contrast, the catabolic fragments of decorin are present in adult skin, but are virtually absent from fetal skin. Taken together, these data suggest that there are age-related differences in the catabolism of proteoglycans in human skin. These age-related differences in proteoglycan patterns and catabolism may play a role in the age-related changes in the physical properties and injury response of human skin.

Cardiac and Carotid Markers Link With Accelerated Brain Atrophy: The AGES-Reykjavik Study (Age, Gene/Environment Susceptibility-Reykjavik).

PubMed

Sabayan, Behnam; van Buchem, Mark A; Sigurdsson, Sigurdur; Zhang, Qian; Meirelles, Osorio; Harris, Tamara B; Gudnason, Vilmundur; Arai, Andrew E; Launer, Lenore J

2016-11-01

Pathologies in the heart-brain axis might, independently or in combination, accelerate the process of brain parenchymal loss. We aimed to investigate the association of serum N-terminal brain natriuretic peptide (NT-proBNP), as a marker of cardiac dysfunction, and carotid intima media thickness (CIMT), as a marker of carotid atherosclerosis burden, with structural brain changes. In the longitudinal population-based AGES-Reykjavik study (Age, Gene/Environment Susceptibility-Reykjavik), we included 2430 subjects (mean age, 74.6 years; 41.4% men) with baseline data on NT-proBNP and CITM (assessed by ultrasound imaging). Participants underwent a high-resolution brain magnetic resonance imaging at baseline and 5 years later to assess total brain (TBV), gray matter, and white matter volumes. Each unit higher log-transformed NT-proBNP was associated with 3.6 mL (95% confidence interval [CI], -6.0 to -1.1) decline in TBV and 3.5 mL (95% CI, -5.7 to -1.3) decline in gray matter volume. Likewise, each millimeter higher CIMT was associated with 10.8 mL (95% CI, -17.3 to -4.2) decline in TBV and 8.6 mL (95% CI, -14.4 to -2.8) decline in gray matter volume. There was no association between NT-proBNP and CIMT and changes in white matter volume. Compared with participants with low NT-proBNP and CIMT, participants with both high NT-proBNP and CIMT had 3.8 mL (95% CI, -6.0 to -1.6) greater decline in their TBV and 4 mL (95% CI, -6.0 to -2.0) greater decline in GMW. These associations were independent of sociodemographic and cardiovascular factors. Older subjects with both cardiac dysfunction and carotid atherosclerosis are at an increased risk for brain parenchymal loss. Accumulated pathologies in the heart-brain axis might accelerate brain atrophy. © 2016 American Heart Association, Inc.

The application of information theory for the research of aging and aging-related diseases.

PubMed

Blokh, David; Stambler, Ilia

2017-10-01

This article reviews the application of information-theoretical analysis, employing measures of entropy and mutual information, for the study of aging and aging-related diseases. The research of aging and aging-related diseases is particularly suitable for the application of information theory methods, as aging processes and related diseases are multi-parametric, with continuous parameters coexisting alongside discrete parameters, and with the relations between the parameters being as a rule non-linear. Information theory provides unique analytical capabilities for the solution of such problems, with unique advantages over common linear biostatistics. Among the age-related diseases, information theory has been used in the study of neurodegenerative diseases (particularly using EEG time series for diagnosis and prediction), cancer (particularly for establishing individual and combined cancer biomarkers), diabetes (mainly utilizing mutual information to characterize the diseased and aging states), and heart disease (mainly for the analysis of heart rate variability). Few works have employed information theory for the analysis of general aging processes and frailty, as underlying determinants and possible early preclinical diagnostic measures for aging-related diseases. Generally, the use of information-theoretical analysis permits not only establishing the (non-linear) correlations between diagnostic or therapeutic parameters of interest, but may also provide a theoretical insight into the nature of aging and related diseases by establishing the measures of variability, adaptation, regulation or homeostasis, within a system of interest. It may be hoped that the increased use of such measures in research may considerably increase diagnostic and therapeutic capabilities and the fundamental theoretical mathematical understanding of aging and disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Shared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Muscles

PubMed Central

Valdez, Gregorio; Tapia, Juan C.; Lichtman, Jeff W.; Fox, Michael A.; Sanes, Joshua R.

2012-01-01

Normal aging and neurodegenerative diseases both lead to structural and functional alterations in synapses. Comparison of synapses that are generally similar but respond differently to insults could provide the basis for discovering mechanisms that underlie susceptibility or resistance to damage. Here, we analyzed skeletal neuromuscular junctions (NMJs) in 16 mouse muscles to seek such differences. We find that muscles respond in one of three ways to aging. In some, including most limb and trunk muscles, age-related alterations to NMJs are progressive and extensive during the second postnatal year. NMJs in other muscles, such as extraocular muscles, are strikingly resistant to change. A third set of muscles, including several muscles of facial expression and the external anal sphinter, succumb to aging but not until the third postnatal year. We asked whether susceptible and resistant muscles differed in rostrocaudal or proximodistal position, source of innervation, motor unit size, or fiber type composition. Of these factors, muscle innervation by brainstem motor neurons correlated best with resistance to age-related decline. Finally, we compared synaptic alterations in normally aging muscles to those in a mouse model of amyotrophic lateral sclerosis (ALS). Patterns of resistance and susceptibility were strikingly correlated in the two conditions. Moreover, damage to NMJs in aged muscles correlated with altered expression and distribution of CRMP4a and TDP-43, which are both altered in motor neurons affected by ALS. Together, these results reveal novel structural, regional and molecular parallels between aging and ALS. PMID:22485182

Age-Related Differences in Multiple Task Monitoring

PubMed Central

Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

2014-01-01

Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age. PMID:25215609

Age-related differences in multiple task monitoring.

PubMed

Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

2014-01-01

Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

NAD+ Deficits in Age-Related Diseases and Cancer.

PubMed

Garrido, Amanda; Djouder, Nabil

2017-08-01

The phenomenon of aging has gained widespread attention in recent times. Although significant advances have been made to better understand aging and its related pathologies including cancer, there is not yet a clear mechanism explaining why diseases and cancer are inherent parts of the aging process. Finding a unifying equation that could bridge aging and its related diseases would allow therapeutic development and solve an immense human health problem to live longer and better. In this review, we discuss NAD + reduction as the central mechanism that may connect aging to its related pathologies and cancer. NAD + boosters would ensure and ameliorate health quality during aging. Copyright © 2017 Elsevier Inc. All rights reserved.

mTOR is a key modulator of ageing and age-related disease

PubMed Central

Johnson, Simon C.; Rabinovitch, Peter S.; Kaeberlein, Matt

2013-01-01

Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans. PMID:23325216

Age-related changes in ultra-triathlon performances

PubMed Central

2012-01-01

Background The age-related decline in performance has been investigated in swimmers, runners and triathletes. No study has investigated the age-related performance decline in ultra-triathletes. The purpose of this study was to analyse the age-related declines in swimming, cycling, running and overall race time for both Triple Iron ultra-triathlon (11.4-km swimming, 540-km cycling and 126.6-km running) and Deca Iron ultra-triathlon (38-km swimming, 1,800-km cycling and 420-km running). Methods The age and performances of 423 male Triple Iron ultra-triathletes and 119 male Deca Iron ultra-triathletes were analysed from 1992 to 2010 using regression analyses and ANOVA. Results The mean age of the finishers was significantly higher for Deca Iron ultra-triathletes (41.3 ± 3.1 years) compared to a Triple Iron ultra-triathletes (38.5 ± 3.3 years) (P < 0.05). For both ultra-distances, the fastest overall race times were achieved between the ages of 25 and 44 years. Deca Iron ultra-triathletes achieved the same level of performance in swimming and cycling between 25 and 54 years of age. Conclusions The magnitudes of age-related declines in performance in the three disciplines of ultra-triathlon differ slightly between Triple and Deca Iron ultra-triathlon. Although the ages of Triple Iron ultra-triathletes were on average younger compared to Deca Iron ultra-triathletes, the fastest race times were achieved between 25 and 44 years for both distances. Further studies should investigate the motivation and training of ultra-triathletes to gain better insights in ultra-triathlon performance. PMID:23849327

Differential age-related effects on conjunctive and relational visual short-term memory binding.

PubMed

Bastin, Christine

2017-12-28

An age-related associative deficit has been described in visual short-term binding memory tasks. However, separate studies have suggested that ageing disrupts relational binding (to associate distinct items or item and context) more than conjunctive binding (to integrate features within an object). The current study directly compared relational and conjunctive binding with a short-term memory task for object-colour associations in 30 young and 30 older adults. Participants studied a number of object-colour associations corresponding to their individual object span level in a relational task in which objects were associated to colour patches and a conjunctive task where colour was integrated into the object. Memory for individual items and for associations was tested with a recognition memory test. Evidence for an age-related associative deficit was observed in the relational binding task, but not in the conjunctive binding task. This differential impact of ageing on relational and conjunctive short-term binding is discussed by reference to two underlying age-related cognitive difficulties: diminished hippocampally dependent binding and attentional resources.

Review of nutrient actions on age-related macular degeneration.

PubMed

Zampatti, Stefania; Ricci, Federico; Cusumano, Andrea; Marsella, Luigi Tonino; Novelli, Giuseppe; Giardina, Emiliano

2014-02-01

The actions of nutrients and related compounds on age-related macular degeneration (AMD) are explained in this review. The findings from 80 studies published since 2003 on the association between diet and supplements in AMD were reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility include carotenoids (lutein and zeaxanthin, β-carotene), vitamins (vitamin A, E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids [monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA and omega-6 PUFA), saturated fatty acids and cholesterol], and dietary carbohydrates. The literature revealed that many of these antioxidants and nutrients exert a protective role by functioning synergistically. Specifically, the use of dietary supplements with targeted actions can provide minimal benefits on the onset or progression of AMD; however, this does not appear to be particularly beneficial in healthy people. Furthermore, some supplements or nutrients have demonstrated discordant effects on AMD in some studies. Since intake of dietary supplements, as well as exposure to damaging environmental factors, is largely dependent on population habits (including dietary practices) and geographical localization, an overall healthy diet appears to be the best strategy in reducing the risk of developing AMD. As of now, the precise mechanism of action of certain nutrients in AMD prevention remains unclear. Thus, future studies are required to examine the effects that nutrients have on AMD and to determine which factors are most strongly correlated with reducing the risk of AMD or preventing its progression. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of solar and laser macula retinal injury using scanning laser ophthalmoscopy spectral imaging

NASA Astrophysics Data System (ADS)

Zwick, Harry; Gagliano, Donald A.; Stuck, Bruce E.; Lund, David J.

1994-07-01

Both solar and laser sources may induce punctate foveal retinal damage. Unprotected viewing of the sun or bright blue sky represent potential solar radiation causes of photic maculopathy that may induce punctate foveal damage. Laser induced macular retinal damage is another more recent kind of photic maculopathy. Most documented cases of laser photic maculopathy have involved acute laser exposure generally from Q-switched visible or nonvisible near IR laser systems. In our comparison of these types of photic maculopathies, we have employed conventional as well as spectral and confocal scanning laser ophthalomoscopy to evaluate the depth of the photic maculopathy. Functionally, we have observed a tritan color vision loss present in nearly all photic maculopathies.

Age-related Deterioration of Hematopoietic Stem Cells.

PubMed

Kim, Mi Jung; Kim, Min Hwan; Kim, Seung Ah; Chang, Jae Suk

2008-11-01

Aging is the process of system deterioration over time in the whole body. Stem cells are self-renewing and therefore have been considered exempt from the aging process. Earlier studies by Hayflick showed that there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, and cycling kinetics and ontogeny-related studies strongly suggest that even the most primitive stem cell functions exhibit a certain degree of aging. Despite these findings, studies on the effects of aging on stem cell functions are inconclusive. Here we review the age-related properties of hematopoietic stem cells in terms of intrinsic and extrinsic alterations, proliferative potential, signaling molecules, telomere and telomerase, senescence and cancer issues, regenerative potential and other indications of stem cell aging are discussed in detail.

Age-related Deterioration of Hematopoietic Stem Cells

PubMed Central

Kim, Mi Jung; Kim, Min Hwan; Kim, Seung Ah; Chang, Jae Suk

2008-01-01

Aging is the process of system deterioration over time in the whole body. Stem cells are self-renewing and therefore have been considered exempt from the aging process. Earlier studies by Hayflick showed that there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, and cycling kinetics and ontogeny-related studies strongly suggest that even the most primitive stem cell functions exhibit a certain degree of aging. Despite these findings, studies on the effects of aging on stem cell functions are inconclusive. Here we review the age-related properties of hematopoietic stem cells in terms of intrinsic and extrinsic alterations, proliferative potential, signaling molecules, telomere and telomerase, senescence and cancer issues, regenerative potential and other indications of stem cell aging are discussed in detail. PMID:24855509

The Digital Ageing Atlas: integrating the diversity of age-related changes into a unified resource.

PubMed

Craig, Thomas; Smelick, Chris; Tacutu, Robi; Wuttke, Daniel; Wood, Shona H; Stanley, Henry; Janssens, Georges; Savitskaya, Ekaterina; Moskalev, Alexey; Arking, Robert; de Magalhães, João Pedro

2015-01-01

Multiple studies characterizing the human ageing phenotype have been conducted for decades. However, there is no centralized resource in which data on multiple age-related changes are collated. Currently, researchers must consult several sources, including primary publications, in order to obtain age-related data at various levels. To address this and facilitate integrative, system-level studies of ageing we developed the Digital Ageing Atlas (DAA). The DAA is a one-stop collection of human age-related data covering different biological levels (molecular, cellular, physiological, psychological and pathological) that is freely available online (http://ageing-map.org/). Each of the >3000 age-related changes is associated with a specific tissue and has its own page displaying a variety of information, including at least one reference. Age-related changes can also be linked to each other in hierarchical trees to represent different types of relationships. In addition, we developed an intuitive and user-friendly interface that allows searching, browsing and retrieving information in an integrated and interactive fashion. Overall, the DAA offers a new approach to systemizing ageing resources, providing a manually-curated and readily accessible source of age-related changes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

AIDS susceptibility in a migrant population: perception and behavior.

PubMed

McBride, D C; Weatherby, N L; Inciardi, J A; Gillespie, S A

1999-01-01

Within the framework of the Health Belief Model, this paper examines correlates of perception of AIDS susceptibility among 846 drug-using migrant farm workers and their sex partners. Significant but relatively small differences by ethnicity and gender were found. The data showed a consistent significant statistical relationship between frequency of drug use, high-risk sexual behavior, and perception of AIDS susceptibility. Perception of AIDS susceptibility was significantly related to a subsequent reduction in sexual risk behaviors. Consistent with the Health Belief Model, the data suggest that increasing perception of AIDS susceptibility may be an important motivator in reducing high-risk behaviors.

Age-related differences in temporomandibular disorder diagnoses.

PubMed

Guarda-Nardini, Luca; Piccotti, Fabio; Mogno, Giorgia; Favero, Lorenzo; Manfredini, Daniele

2012-04-01

The purpose of the current study was to evaluate the pattern of age distribution of temporomandibular disorders (TMD) and to identify prevalence peaks for the different diagnoses. The study sample (N = 383; F:M ratio = 3.9; mean age range 41.7 +/- 17 years) consisted of patients seeking treatment for TMD and who were assessed in accordance with the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) version 1.0 guidelines. The sample was divided into four age groups on the basis of percentile-derived intervals to compare prevalence of different diagnoses in relation to age. The pattern of clinical diagnoses changed with increasing age. The peculiar distribution of RDC/TMD axis I diagnoses, with relation to age, mainly affected the disorders trend of groups II and III, with the former decreasing with age from about 62% to 40% and the latter increasing from 75% to almost 95%. Two distinct age peaks were identified for the prevalence of the main clinical marker of group III diagnosis of arthrosis/arthritis, viz., joint crepitus sounds (N = 104, mean age range 51.9 +/- 14.5), and for the prevalence of all other diagnoses in patients without joint crepitus (N = 279, mean age range 37.9 +/- 16.4). The hypothesis that TMD patient populations may be composed of at least two diagnostic subgroups in relation to age, and that the presence of clinically diagnosed degenerative joint disorders may be a key discriminating factor, was supported. The external validity of the results from this investigation needs to be confirmed by multicenter and cross-cultural studies.

Sex-specific predictors of hearing-aid use in older persons: The age, gene/environment susceptibility - Reykjavik study

PubMed Central

Fisher, Diana E.; Li, Chuan-Ming; Hoffman, Howard J.; Chiu, May S.; Themann, Christa L.; Petersen, Hannes; Jonsson, Palmi V.; Jonsson, Helgi; Jonasson, Fridbert; Sverrisdottir, Johanna Eyrun; Launer, Lenore J.; Eiriksdottir, Gudny; Gudnason, Vilmundur; Cotch, Mary Frances

2015-01-01

Objective We estimate the prevalence of hearing-aid use in Iceland and identify sex-specific factors associated with use. Design Population-based cohort study. Study sample A total of 5172 age, gene/environment susceptibility - Reykjavik study (AGES-RS) participants, aged 67 to 96 years (mean age 76.5 years), who completed air-conduction and pure-tone audiometry. Results Hearing-aid use was reported by 23.0% of men and 15.9% of women in the cohort, although among participants with at least moderate hearing loss in the better ear (pure-tone average [PTA] of thresholds at 0.5, 1, 2, and 4 kHz ≥ 35 dB hearing level [HL]) it was 49.9% and did not differ by sex. Self-reported hearing loss was the strongest predictor of hearing-aid use in men [OR: 2.68 (95% CI: 1.77, 4.08)] and women [OR: 3.07 (95% CI: 1.94, 4.86)], followed by hearing loss severity based on audiometry. Having diabetes or osteoarthritis were significant positive predictors of use in men, whereas greater physical activity and unimpaired cognitive status were important in women. Conclusions Hearing-aid use was comparable in Icelandic men and women with moderate or greater hearing loss. Self-recognition of hearing loss was the factor most predictive of hearing-aid use; other influential factors differed for men and women. PMID:25816699

Erythrocyte Osmotic Fragility Testing and the Prediction of Canine Malignant Hyperthermia Susceptibility

PubMed Central

Cribb, Peter H.; Olfert, Ernest A.; Reynolds, F. Barry

1986-01-01

A Doberman-German Shepherd cross-bred male dog, previously diagnosed as malignant hyperthermia susceptible, was mated to an unrelated nonsusceptible German Shepherd cross-bred female. The resultant litter was subjected to hematological, biochemical and erythrocyte osmotic fragility testing in an endeavor to predict the susceptibility of individuals to malignant hyperthermia. Laboratory evaluations were repeated at one year of age and the litter subjected to the halothane challenge test. No significant difference in erythrocyte osmotic fragility was found between malignant hyperthermia susceptible and nonsusceptible siblings at six weeks or at one year of age. Erythrocyte osmotic fragility, in both malignant hyperthermia susceptible and nonsusceptible animals, increased between six weeks and one year of age. Dantrolene sodium was an effective treatment for malignant hyperthermia in the dog when administered early in an episode and in adequate dosage. The initial sign of a malignant hyperthermia episode was a very rapid increase in end tidal partial pressure of carbon dioxide. This finding reinforces the value of capnographic monitoring in anesthesia. PMID:17422730

Prevalence and Determinants of Susceptibility to Tobacco Smoking among Students in The Gambia.

PubMed

Jallow, Isatou K; Britton, John; Langley, Tessa

2018-06-20

Smoking is the biggest preventable cause of death, and kills about 7 million people annually. As smoking prevalence is falling in developed countries, tobacco businesses are turning to low and middle-income countries (LMICs) to generate new tobacco markets. To prevent young people from initiating smoking and becoming regular smokers it is important to understand the causes of susceptibility to smoking. In this study we report a nationwide survey of the prevalence and risk factors of smoking susceptibility among students aged 12-20 in The Gambia. We used two-stage cluster random sampling to select students in secondary schools throughout The Gambia, and questionnaire to collect data on demographic characteristics and indicators on susceptibility to initiating smoking. Among the total sample of 10,289 students, 9831(96%; 55.6% girls and 44.4% boys, (aged 12-20 years) non-smokers were included in the analysis. Of these, 3,333 (33.9%) were found to be susceptible to smoking. Smoking susceptibility was more common among students attending grant-aided schools, non-Muslims, who had smoking allowed at home, had family members or friends who smoke, were sent to purchase cigarettes, had poor knowledge of the harmful effects of smoking, noticed point-of-sale tobacco advertisements and who had positive attitudes towards smoking. This study shows that susceptibility to smoking is common among students and associated with preventable exposures. Although based on cross-sectional data these findings suggest that raising students' awareness of the harmful effects of smoking and reducing the prevalence of adult smoking, extending tobacco advertising restrictions to include point-of-sale, are all important to preventing the uptake of smoking among students. This is the first study to provide detailed data on smoking susceptibility and risk factors in a nationally representative sample of young people in The Gambia. Our findings show that susceptibility to smoking is relatively high

CREB Overexpression Ameliorates Age-related Behavioral and Biophysical Deficits

NASA Astrophysics Data System (ADS)

Yu, Xiao-Wen

Age-related cognitive deficits are observed in both humans and animals. Yet, the molecular mechanisms underlying these deficits are not yet fully elucidated. In aged animals, a decrease in intrinsic excitability of pyramidal neurons from the CA1 sub-region of hippocampus is believed to contribute to age-related cognitive impairments, but the molecular mechanism(s) that modulate both these factors has yet to be identified. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents has been shown to facilitate cognition, and increase intrinsic excitability of their neurons. However, how CREB changes with age, and how that impacts cognition in aged animals, is not clear. Therefore, we first systematically characterized age- and training-related changes in CREB levels in dorsal hippocampus. At a remote time point after undergoing behavioral training, levels of total CREB and activated CREB (phosphorylated at S133, pCREB) were measured in both young and aged rats. We found that pCREB, but not total CREB was significantly reduced in dorsal CA1 of aged rats. Importantly, levels of pCREB were found to be positively correlated with short-term spatial memory in both young and aged rats i.e. higher pCREB in dorsal CA1 was associated with better spatial memory. These findings indicate that an age-related deficit in CREB activity may contribute to the development of age-related cognitive deficits. However, it was still unclear if increasing CREB activity would be sufficient to ameliorate age-related cognitive, and biophysical deficits. To address this question, we virally overexpressed CREB in CA1, where we found the age-related deficit. Young and aged rats received control or CREB virus, and underwent water maze training. While control aged animals exhibited deficits in long-term spatial memory, aged animals with CREB overexpression performed at levels comparable to young animals. Concurrently, aged neurons

Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging.

PubMed

Lin, Jonathan B; Sene, Abdoulaye; Santeford, Andrea; Fujiwara, Hideji; Sidhu, Rohini; Ligon, Marianne M; Shankar, Vikram A; Ban, Norimitsu; Mysorekar, Indira U; Ory, Daniel S; Apte, Rajendra S

2018-06-11

Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Middle-Aged Diabetic Females and Males Present Distinct Susceptibility to Alzheimer Disease-like Pathology.

PubMed

Candeias, E; Duarte, A I; Sebastião, I; Fernandes, M A; Plácido, A I; Carvalho, C; Correia, S; Santos, R X; Seiça, R; Santos, M S; Oliveira, C R; Moreira, P I

2017-10-01

Type 2 diabetes (T2D) is a highly concerning public health problem of the twenty-first century. Currently, it is estimated that T2D affects 422 million people worldwide with a rapidly increasing prevalence. During the past two decades, T2D has been widely shown to have a major impact in the brain. This, together with the cognitive decline and increased risk for dementia upon T2D, may arise from the complex interaction between normal brain aging and central insulin signaling dysfunction. Among the several features shared between T2D and some neurodegenerative disorders (e.g., Alzheimer disease (AD)), the impairment of insulin signaling may be a key link. However, these may also involve changes in sex hormones' function and metabolism, ultimately contributing to the different susceptibilities between females and males to some pathologies. For example, female sex has been pointed as a risk factor for AD, particularly after menopause. However, less is known on the underlying molecular mechanisms or even if these changes start during middle-age (perimenopause). From the above, we hypothesized that sex differentially affects hormone-mediated intracellular signaling pathways in T2D brain, ultimately modulating the risk for neurodegenerative conditions. We aimed to evaluate sex-associated alterations in estrogen/insulin-like growth factor-1 (IGF-1)/insulin-related signaling, oxidative stress markers, and AD-like hallmarks in middle-aged control and T2D rat brain cortices. We used brain cortices homogenates obtained from middle-aged (8-month-old) control Wistar and non-obese, spontaneously T2D Goto-Kakizaki (GK) male and female rats. Peripheral characterization of the animal models was done by standard biochemical analyses of blood, plasma, or serum. Steroid sex hormones, oxidative stress markers, and AD-like hallmarks were given by specific ELISA kits and colorimetric techniques, whereas the levels of intracellular signaling proteins were determined by Western blotting

Restoration of the photoreceptor layer and improvement of visual acuity in successfully treated optic disc pit maculopathy: a long follow-up study by optical coherence tomography.

PubMed

Theodossiadis, George P; Grigoropoulos, Vlassis G; Liarakos, Vasilis S; Rouvas, Alexandros; Emfietzoglou, Ioannis; Theodossiadis, Panagiotis G

2012-07-01

To investigate by optical coherence tomography (OCT) the evolution of the photoreceptor layer and its association with best-corrected visual acuity (BCVA) in optic disc pit (ODP) maculopathy after successful surgical treatment. Fourteen eyes of 14 patients were included in this study, and followed up from 36 to 95 months (mean 57.36 ± 18.32 months). The follow-up period started at the time of complete subretinal fluid absorption. Examination was performed by time-domain OCT before and after treatment. Spectral-domain OCT was used after treatment. Parameters assessed were type of elevation, central foveal thickness, time elapsed from onset to treatment, type of treatment, BCVA, and inner segment outer segment (IS/OS) junction line. The IS/OS junction was characterized after treatment as intact, interrupted, or absent (not distinguishable). Significant restoration of the IS/OS junction line was first noticed between 6 and 12 months after fluid absorption (p = 0.02; Wilcoxon signed rank test). Restoration was continuous up to the 24th month of postoperative examination after fluid absorption (p = 0.14; Wilcoxon signed rank test). BCVA was 0.99 ± 0.38 logMar before treatment, 0.81 ± 0.26 logMar (p = 0.011; paired t-test) immediately after fluid absorption and 0.61 ± 0.33 logMar (p = 0.026; one-way ANOVA) 24 months after fluid resolution. BCVA was significantly positively correlated with the integrity of the IS/OS junction line during follow-up (Pearson r = 0.775; p < 0.001). The IS/OS junction restoration cannot be detected immediately after fluid resolution in the majority of cases. It became evident 6-12 months later and was completed 24 months after fluid absorption. Improvement in BCVA was noticed only during the first 2 years of follow-up. No significant changes were noticed in BCVA or the IS/OS line after 2 years. Among the studied variables, the final photoreceptor layer condition and BCVA immediately after fluid absorption

Quantitative Susceptibility Mapping in Parkinson's Disease.

PubMed

Langkammer, Christian; Pirpamer, Lukas; Seiler, Stephan; Deistung, Andreas; Schweser, Ferdinand; Franthal, Sebastian; Homayoon, Nina; Katschnig-Winter, Petra; Koegl-Wallner, Mariella; Pendl, Tamara; Stoegerer, Eva Maria; Wenzel, Karoline; Fazekas, Franz; Ropele, Stefan; Reichenbach, Jürgen Rainer; Schmidt, Reinhold; Schwingenschuh, Petra

2016-01-01

Quantitative susceptibility mapping (QSM) and R2* relaxation rate mapping have demonstrated increased iron deposition in the substantia nigra of patients with idiopathic Parkinson's disease (PD). However, the findings in other subcortical deep gray matter nuclei are converse and the sensitivity of QSM and R2* for morphological changes and their relation to clinical measures of disease severity has so far been investigated only sparsely. The local ethics committee approved this study and all subjects gave written informed consent. 66 patients with idiopathic Parkinson's disease and 58 control subjects underwent quantitative MRI at 3T. Susceptibility and R2* maps were reconstructed from a spoiled multi-echo 3D gradient echo sequence. Mean susceptibilities and R2* rates were measured in subcortical deep gray matter nuclei and compared between patients with PD and controls as well as related to clinical variables. Compared to control subjects, patients with PD had increased R2* values in the substantia nigra. QSM also showed higher susceptibilities in patients with PD in substantia nigra, in the nucleus ruber, thalamus, and globus pallidus. Magnetic susceptibility of several of these structures was correlated with the levodopa-equivalent daily dose (LEDD) and clinical markers of motor and non-motor disease severity (total MDS-UPDRS, MDS-UPDRS-I and II). Disease severity as assessed by the Hoehn & Yahr scale was correlated with magnetic susceptibility in the substantia nigra. The established finding of higher R2* rates in the substantia nigra was extended by QSM showing superior sensitivity for PD-related tissue changes in nigrostriatal dopaminergic pathways. QSM additionally reflected the levodopa-dosage and disease severity. These results suggest a more widespread pathologic involvement and QSM as a novel means for its investigation, more sensitive than current MRI techniques.

Age-Related Macular Degeneration.

PubMed

Mehta, Sonia

2015-09-01

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision. Copyright © 2015 Elsevier Inc. All rights reserved.

Aged spontaneously hypertensive rats (SHRs) are predisposed to ultrafine carbon particle (UfCP) mediated cardiovascular impairment.

EPA Science Inventory

Background: Elderly individuals are considered to be more susceptible to particulate matter (PM) related cardiovascular (CV) health effects. In this study we investigated UfCP mediated CV effects on aged SHRs and compared the findings to that of adult SHRs to identify age related...

Rubella susceptibility in pregnant women and results of a postpartum immunization strategy in Catalonia, Spain.

PubMed

Vilajeliu, Alba; García-Basteiro, Alberto L; Valencia, Salomé; Barreales, Saul; Oliveras, Laura; Calvente, Valentín; Goncé, Anna; Bayas, José M

2015-04-08

Elimination of congenital rubella syndrome depends not only on effective childhood immunization but also on the identification and immunization of rubella susceptible women. We assessed rubella susceptibility among pregnant women and evaluated the adherence and response to postpartum immunization with measles, mumps and rubella (MMR) vaccine. Cross-sectional study of women who gave birth at the Hospital Clinic de Barcelona (Spain) between January 2008 and December 2013. Antenatal serological screening for rubella was performed in all women during pregnancy. In rubella-susceptible women, two doses of MMR vaccine were recommended following birth. We evaluated rubella serological response to MMR vaccination in mothers who complied with the recommendations. A total of 22,681 pregnant women were included in the study. The mean age was 32.3 years (SD 5.6), and 73.6% were primipara. The proportion of immigrants ranged from 43.4% in 2010 to 38.5% in 2012. The proportion of women susceptible to rubella was 5.9% (1328). Susceptibility to rubella declined with increasing maternal age. Immigrant pregnant women were more susceptible to rubella (7.6%) than women born in Spain (4.6%). Multivariate analyses showed that younger age (≤19 years) aOR 1.7 (95% CI 1.1-2.5), primiparas aOR 1.3 (95% CI 1.1-1.5) and immigrant women aOR 1.6 (95% CI 1.4-1.8) were more likely to be susceptible. The second dose of MMR vaccine was received by 57.2% (718/1256) of rubella-susceptible women, with the highest proportion being immigrant women compared with women born in Spain. After vaccination, all women showed rubella immunity. The higher rubella susceptibility found in the three youngest age groups and in immigrant women highlights the relevance of antenatal screening, in order to ensure identification and postpartum immunization. The postpartum immunization strategy is an opportunity to protect women of childbearing age and consequently prevent occurrence of CRS, and to increase vaccination

Statins for age-related macular degeneration

PubMed Central

Gehlbach, Peter; Li, Tianjing; Hatef, Elham

2013-01-01

Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries (Congdon 2003). Recent epidemiologic, genetic and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives To examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and/or progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 9), MEDLINE (January 1950 to September 2011), EMBASE (January 1980 to September 2011), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to September 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 16 September 2011. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis Two authors independently evaluated the search results against the selection criteria. Two Italian speaking colleagues extracted data. One author entered data. We did not perform a meta-analysis because only one completed RCT was identified. Main results Two studies met the selection criteria. One trial reported insufficient details to assess the risk of bias; the other trial is ongoing. Of the completed trial, the

A Strong Immune Response in Young Adult Honeybees Masks Their Increased Susceptibility to Infection Compared to Older Bees

PubMed Central

Bull, James C.; Ryabov, Eugene V.; Prince, Gill; Mead, Andrew; Zhang, Cunjin; Baxter, Laura A.; Pell, Judith K.; Osborne, Juliet L.; Chandler, Dave

2012-01-01

Honeybees, Apis mellifera, show age-related division of labor in which young adults perform maintenance (“housekeeping”) tasks inside the colony before switching to outside foraging at approximately 23 days old. Disease resistance is an important feature of honeybee biology, but little is known about the interaction of pathogens and age-related division of labor. We tested a hypothesis that older forager bees and younger “house” bees differ in susceptibility to infection. We coupled an infection bioassay with a functional analysis of gene expression in individual bees using a whole genome microarray. Forager bees treated with the entomopathogenic fungus Metarhizium anisopliae s.l. survived for significantly longer than house bees. This was concomitant with substantial differences in gene expression including genes associated with immune function. In house bees, infection was associated with differential expression of 35 candidate immune genes contrasted with differential expression of only two candidate immune genes in forager bees. For control bees (i.e. not treated with M. anisopliae) the development from the house to the forager stage was associated with differential expression of 49 candidate immune genes, including up-regulation of the antimicrobial peptide gene abaecin, plus major components of the Toll pathway, serine proteases, and serpins. We infer that reduced pathogen susceptibility in forager bees was associated with age-related activation of specific immune system pathways. Our findings contrast with the view that the immunocompetence in social insects declines with the onset of foraging as a result of a trade-off in the allocation of resources for foraging. The up-regulation of immune-related genes in young adult bees in response to M. anisopliae infection was an indicator of disease susceptibility; this also challenges previous research in social insects, in which an elevated immune status has been used as a marker of increased disease

Age-related patterns in work-related injury claims from older New Zealanders, 2009-2013: Implications of injury for an aging workforce.

PubMed

Lilley, Rebbecca; Jaye, Chrystal; Davie, Gabrielle; Keeling, Sally; Waters, Debra; Egan, Richard

2018-01-01

This study describes the incidence, nature and cause of work-related injuries in older New Zealand workers to understand the risks of work-related injury in this rapidly aging population. Data for the period 2009-2013 from 25,455 injured workers aged 55-79 years, extracted from national work-related injury entitlement claims, were stratified by age group and analysed by sex, industry, injury type and cause. Age-specific claims rates were calculated by year, sex and ethnicity. Patterns of injury differed by age: 70-79 year olds had the highest injury rates and proportion of claims due to falls (45%), for the self-employed (32%), for the agriculture sector (24%), and for fatal injuries (5%). The burden of work-related injuries in older workers, particularly in those aged over 70, will increase with their increasing participation in work. Workplace injury prevention strategies and interventions need to consider the specific characteristics and vulnerabilities of older workers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human genetic susceptibility and infection with Leishmania peruviana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaw, M.A.; Davis, C.R.; Collins, A.

1995-11-01

Racial differences, familial clustering, and murine studies are suggestive of host genetic control of Leishmania infections. Complex segregation analysis has been carried out by use of the programs POINTER and COMDS and data from a total population survey, comprising 636 nuclear families, from an L. perurviana endemic area. The data support genetic components controlling susceptibility to clinical leishmaniasis, influencing severity of disease and resistance to disease among healthy individuals. A multifactorial model is favored over a sporadic model. Two-locus models provided the best fit to the data, the optimal model being a recessive gene (frequency .57) plus a modifier locus.more » Individuals infected at an early age and with recurrent lesions are genetically more susceptible than those infected with a single episode of disease at a later age. Among people with no lesions, those with a positive skin-test response are genetically less susceptible than those with a negative response. The possibility of the involvement of more than one gene together with environmental effects has implications for the design of future linkage studies. 31 refs., 7 tabs.« less

Parental smoking, rejection of parental smoking, and smoking susceptibility and behaviors in Hong Kong adolescents.

PubMed

Chen, Jianjiu; Ho, Sai Yin; Wang, Man Ping; Lam, Tai Hing

2018-07-01

We explored the role of rejection of parental smoking in the association between parental smoking and smoking in adolescents. In 2010-11 cross-sectional survey, 61,810 Hong Kong secondary school students (mean age 14.6 years, 50.5% boys) reported their smoking (never, not susceptible; never, susceptible; ever, not current; current), paternal and maternal smoking, and whether they accepted paternal and maternal smoking (acceptance/rejection). We used multinomial logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of students' smoking in relation to acceptance and rejection of parental smoking, compared with no parental smoking. The OR (95% CI) of "never, susceptible", "ever, not current", and "current", compared with "never, not susceptible", in relation to acceptance of paternal smoking was 1.81 (1.67-1.96), 2.46 (2.25-2.69), and 2.79 (2.51-3.10), respectively. The corresponding ORs for rejection were 0.70 (0.64-0.76), 1.23 (1.13-1.35), and 0.47 (0.40-0.56). The OR (95% CI) of "never, susceptible", "ever, not current", and "current", compared with "never, not susceptible", in relation to acceptance of maternal smoking was 2.05 (1.80-2.33), 2.57 (2.29-2.88), and 6.33 (5.39-7.44), respectively. The corresponding ORs for rejection were 0.85 (0.69-1.05), 1.59 (1.39-1.81), and 2.14 (1.71-2.68). No overlapping was observed between the 95% CIs for acceptance and rejection of paternal or maternal smoking. While adolescent smoking was associated with parental smoking, especially in those who accepted parental smoking, the association was attenuated or reversed in those who rejected parental smoking. Copyright © 2018 Elsevier Ltd. All rights reserved.

Environmental and physiological effects on grouping of drought-tolerant and susceptible rice varieties related to rice (Oryza sativa) root hydraulics under drought

PubMed Central

Henry, Amelia; Wehler, Regina; Grondin, Alexandre; Franke, Rochus; Quintana, Marinell

2016-01-01

Background and Aims Root hydraulic limitations (i.e. intra-plant restrictions to water movement) may be related to crop performance under drought, and groupings in the hydraulic function of drought-tolerant and drought-susceptible rice (Oryza sativa) varieties have been previously reported. This study aimed to better understand the environmental and physiological relationships with rice root hydraulics under drought. Methods Xylem sap bleeding rates in the field (gsap g–1 shoot) were measured on seasonal and diurnal time frames, during which time environmental conditions were monitored and physiological measurements were conducted. Complementary experiments on the effects of vapour pressure deficit (VPD) on root hydraulic conductivity and on transpiration rates of de-rooted tillers were conducted in growth chambers. Key Results The diurnal effects on bleeding rate were more closely related to irradiance than VPD, and VPD effects on root hydraulic conductivity measured on 21-day-old plants were due to effects on plant growth including root surface area, maximum root depth and root:shoot ratio. Leaf osmotic potential was related to the grouping of drought-tolerant and drought-susceptible varieties in rice root hydraulics, and these groupings were independent of differences in phenology. Low single-tiller bleeding rates were observed under high evapo-transpirational demand, higher bleeding rates were observed at more negative leaf osmotic potentials in drought-susceptible varieties, and drought-tolerant and susceptible varieties differed in the VPD-induced increase in transpiration rates of de-rooted tillers. Low root suberin amounts in some of the drought-susceptible varieties may have resulted in higher ion transport, as evidenced by higher sap K+ concentration and higher bleeding rates in those varieties. Conclusions These results provide evidence of the environmental effects on shoots that can influence root hydraulics. The consistent groupings of drought

Environmental and physiological effects on grouping of drought-tolerant and susceptible rice varieties related to rice (Oryza sativa) root hydraulics under drought.

PubMed

Henry, Amelia; Wehler, Regina; Grondin, Alexandre; Franke, Rochus; Quintana, Marinell

2016-05-02

Root hydraulic limitations (i.e. intra-plant restrictions to water movement) may be related to crop performance under drought, and groupings in the hydraulic function of drought-tolerant and drought-susceptible rice (Oryza sativa) varieties have been previously reported. This study aimed to better understand the environmental and physiological relationships with rice root hydraulics under drought. Xylem sap bleeding rates in the field (g sap g -1 shoot ) were measured on seasonal and diurnal time frames, during which time environmental conditions were monitored and physiological measurements were conducted. Complementary experiments on the effects of vapour pressure deficit (VPD) on root hydraulic conductivity and on transpiration rates of de-rooted tillers were conducted in growth chambers. The diurnal effects on bleeding rate were more closely related to irradiance than VPD, and VPD effects on root hydraulic conductivity measured on 21-day-old plants were due to effects on plant growth including root surface area, maximum root depth and root:shoot ratio. Leaf osmotic potential was related to the grouping of drought-tolerant and drought-susceptible varieties in rice root hydraulics, and these groupings were independent of differences in phenology. Low single-tiller bleeding rates were observed under high evapo-transpirational demand, higher bleeding rates were observed at more negative leaf osmotic potentials in drought-susceptible varieties, and drought-tolerant and susceptible varieties differed in the VPD-induced increase in transpiration rates of de-rooted tillers. Low root suberin amounts in some of the drought-susceptible varieties may have resulted in higher ion transport, as evidenced by higher sap K + concentration and higher bleeding rates in those varieties. These results provide evidence of the environmental effects on shoots that can influence root hydraulics. The consistent groupings of drought-tolerant and susceptible varieties suggest that traits

Nutritional considerations for healthy aging and reduction in age-related chronic disease

USDA-ARS?s Scientific Manuscript database

A projected doubling in the global population of people aged >/= 60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifes...

Oral exposure to Listeria monocytogenes in aged IL-17RKO mice: A possible murine model to study listeriosis in susceptible populations.

PubMed

Alam, Mohammad S; Costales, Matthew; Cavanaugh, Christopher; Pereira, Marion; Gaines, Dennis; Williams, Kristina

2016-10-01

Foodborne Listeria monocytogenes (LM) is a cause of serious illness and death in the US. The case-fatality rate of invasive LM infection in the elderly population is >50%. The goal of this study is to establish a murine model of oral LM infection that can be used as a surrogate for human foodborne listeriosis in the geriatric population. Adult C57BL/6 (wild-type, WT) and adult or old IL17R-KO (knock-out) mice were gavaged with a murinized LM strain (Lmo-InlA m ) and monitored for body-weight loss and survivability. Tissues were collected and assayed for bacterial burden, histology, and cytokine responses. When compared to WT mice, adult IL17R-KO mice are more susceptible to LM infection and showed increased LM burden and tissue pathology and a higher mortality rate. Older LM-infected KO-mice lost significantly (p < 0.02, ANOVA) more body-weight and had a higher bacterial burden in the liver (p = 0.03) and spleen as compared to adult mice. Uninfected, aged KO-mice showed a higher baseline pro-inflammatory response when compared to uninfected adult-KO mice. After infection, the pro-inflammatory cytokine, IFN-γ, mRNA in the liver was higher in the adult mice as compared to the old mice. The anti-inflammatory cytokine, IL-10, mRNA and regulatory T-cells (CD4 + CD25 +h or CD4 + Foxp3 + ) cells in the aged mice increased significantly after infection as compared to adult mice. Expression of the T-cell activation marker, CD25 (IL-2Rα) in the aged mice did not increase significantly over baseline. These data suggest that aged IL17R-KO mice can be used as an in vivo model to study oral listeriosis and that aged mice are more susceptible to LM infection due to dysregulation of pro- and anti-inflammatory responses compared to adult mice, resulting in a protracted clearance of the infection. Published by Elsevier Ltd.

INVESTIGATIONS INTO AGE-RELATED SUSCEPTIBILITY TO ARSENIC CARCONOGENICITY

EPA Science Inventory

Environmental Issue. Arsenic compounds are ubiquitous throughout the environment and are a major health problem in many parts of the world. Human exposure to arsenic has been identified from both natural and anthropogenic sources. Most chronic exposure comes from drinking water, ...

Prioritization of Disease Susceptibility Genes Using LSM/SVD.

PubMed

Gong, Lejun; Yang, Ronggen; Yan, Qin; Sun, Xiao

2013-12-01

Understanding the role of genetics in diseases is one of the most important tasks in the postgenome era. It is generally too expensive and time consuming to perform experimental validation for all candidate genes related to disease. Computational methods play important roles for prioritizing these candidates. Herein, we propose an approach to prioritize disease genes using latent semantic mapping based on singular value decomposition. Our hypothesis is that similar functional genes are likely to cause similar diseases. Measuring the functional similarity between known disease susceptibility genes and unknown genes is to predict new disease susceptibility genes. Taking autism as an instance, the analysis results of the top ten genes prioritized demonstrate they might be autism susceptibility genes, which also indicates our approach could discover new disease susceptibility genes. The novel approach of disease gene prioritization could discover new disease susceptibility genes, and latent disease-gene relations. The prioritized results could also support the interpretive diversity and experimental views as computational evidence for disease researchers.

Molecular inflammation as an underlying mechanism of the aging process and age-related diseases.

PubMed

Chung, H Y; Lee, E K; Choi, Y J; Kim, J M; Kim, D H; Zou, Y; Kim, C H; Lee, J; Kim, H S; Kim, N D; Jung, J H; Yu, B P

2011-07-01

Aging is a biological process characterized by time-dependent functional declines that are influenced by changes in redox status and by oxidative stress-induced inflammatory reactions. An organism's pro-inflammatory status may underlie the aging process and age-related diseases. In this review, we explore the molecular basis of low-grade, unresolved, subclinical inflammation as a major risk factor for exacerbating the aging process and age-related diseases. We focus on the redox-sensitive transcription factors, NF-κB and FOXO, which play essential roles in the expression of pro-inflammatory mediators and anti-oxidant enzymes, respectively. Major players in molecular inflammation are discussed with respect to the age-related up-regulation of pro-inflammatory cytokines and adhesion molecules, cyclo-oxygenase-2, lipoxygenase, and inducible nitric oxide synthase. The molecular inflammation hypothesis proposed by our laboratory is briefly described to give further molecular insights into the intricate interplay among redox balance, pro-inflammatory gene activation, and chronic age-related inflammatory diseases. The final section discusses calorie restriction as an aging-retarding intervention that also exhibits extraordinarily effective anti-inflammatory activity by modulating GSH redox, NF-κB, SIRT1, PPARs, and FOXOs.

An increasing, potentially measles-susceptible population over time after vaccination in Korea.

PubMed

Kang, Hae Ji; Han, Young Woo; Kim, Su Jin; Kim, You-Jin; Kim, A-Reum; Kim, Joo Ae; Jung, Hee-Dong; Eom, Hye Eun; Park, Ok; Kim, Sung Soon

2017-07-24

In Korea, measles occurs mainly in infants <12months of age, who are unvaccinated. In addition, vaccine populations, including adolescents and young adults, can become infected though importation. Thus, the question arises whether the current level of herd immunity in Korea is now insufficient for protecting against measles infection. Age-specific measles seroprevalence was evaluated by performing enzyme immunoassays and plaque reduction-neutralization tests on 3050 subjects aged 0-50years (birth cohort 1964-2014) and 480 subjects aged 2-30years (birth cohort 1984-2012). The overall seropositivity and measles antibody concentrations were 71.5% and 1366mIU/mL, respectively. Progressive decline in antibody levels and seropositivity were observed over time after vaccination in infants, adolescents, and young adults. The accumulation of potentially susceptible individuals in the population was confirmed by comparing data from 2010 and 2014 seroprevalence surveys. The statistical correlation between measles incidence and measles seronegativity was determined. Waning levels of measles antibodies with increasing time post-vaccination suggests that measles susceptibility is potentially increasing in Korea. This trend may be related to limitations of vaccine-induced immunity in the absence of natural boosting by the wild virus, compared to naturally acquired immunity triggered by measles infection. This study provides an important view into the current measles herd immunity in Korea. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Quantitative Susceptibility Mapping Reveals an Association between Brain Iron Load and Depression Severity

PubMed Central

Yao, Shun; Zhong, Yi; Xu, Yuhao; Qin, Jiasheng; Zhang, Ningning; Zhu, Xiaolan; Li, Yuefeng

2017-01-01

Previous studies have detected abnormal serum ferritin levels in patients with depression; however, the results have been inconsistent. This study used quantitative susceptibility mapping (QSM) for the first time to examine brain iron concentration in depressed patients and evaluated whether it is related to severity. We included three groups of age- and gender-matched participants: 30 patients with mild-moderate depression (MD), 14 patients with major depression disorder (MDD) and 20 control subjects. All participants underwent MR scans with a 3D gradient-echo sequence reconstructing for QSM and performed the 17-item Hamilton Depression Rating Scale (HDRS) test. In MDD, the susceptibility value in the bilateral putamen was significantly increased compared with MD or control subjects. In addition, a significant difference was also observed in the left thalamus in MDD patients compared with controls. However, the susceptibility values did not differ between MD patients and controls. The susceptibility values positively correlated with the severity of depression as indicated by the HDRS scores. Our results provide evidence that brain iron deposition may be associated with depression and may even be a biomarker for investigating the pathophysiological mechanism of depression. PMID:28900391

Age-ordered shirt numbering reduces the selection bias associated with the relative age effect.

PubMed

Mann, David L; van Ginneken, Pleun J M A

2017-04-01

When placed into age groups for junior sporting competition, the relative differences in age between children leads to a bias in who is evaluated as being talented. While the impact of this relative age effect (RAE) is clear, until now there has been no evidence to show how to reduce it. The aim of this study was to determine whether the selection bias associated with the RAE could be reduced. Talent scouts from an elite football club watched junior games and ranked players on the basis of their potential. Scouts were allocated to one of three groups provided with contrasting information about the age of the players: (1) no age information, (2) players' birthdates or (3) knowledge that the numbers on the playing shirts corresponded to the relative age of the players. Results revealed a significant selection bias for the scouts in the no-age information group, and that bias remained when scouts knew the players' dates-of-birth. Strikingly though, the selection bias was eliminated when scouts watched the games knowing the shirt numbers corresponded to the relative ages of the players. The selection bias associated with the RAE can be reduced if information about age is presented appropriately.

Sociodemographic and economic characteristics of susceptibility to rubella among women preparing for pregnancy in rural China.

PubMed

Liu, Fangchao; Zhang, Shikun; Liu, Jue; Wang, Qiaomei; Shen, Haiping; Zhang, Yiping; Liu, Min

2017-09-01

Infection with rubella virus during pregnancy can result in congenital defects and adverse pregnancy outcomes. The risk of rubella infection is greatly determined by the level of rubella antibodies in the serum. A survey of rubella antibody seronegativity rates was conducted in 780 000 women in rural China who were planning a pregnancy, in order to evaluate the herd susceptibility in different age groups and by high, middle, and low GDP per capita regions. In order to evaluate the herd susceptibility to rubella, a nationwide population-based study of rural Chinese women who were planning to have a baby and who were aged 21-49 years was instigated. As a part of the National Free Pre-conception Health Examination Project covering 29 provinces in 2012, a physical check-up program was provided to women who planned to become pregnant within the next 6 months. All medical data were from serological samples tested by ELISA, and the participants' immunity status was categorized based on levels of rubella antibodies. Economic data were also collected to explore the association between herd susceptibility and socioeconomic characteristics in the women of childbearing age. A total 264 306 of 782 293 recruited women preparing for pregnancy tested susceptible to rubella (33.79%). The seronegativity rate in women with a history of vaccination was significantly lower than that in women who had not received the vaccination or did not know their vaccination history (23.76%, 33.70%, and 35.68%, respectively). The seronegativity rates were 26.89%, 37.86%, and 32.61% in high, middle, and low GDP per capita areas, respectively. After stratified analysis and adjusting for other factors by multiple logistic regression, the lower seronegativity rates in women in high GDP per capita regions compared to women in middle and low GDP per capita regions remained in the different age groups and subgroups of immunization history. There is a clear difference in rubella-specific susceptibility

Plasma Protein Pentosidine and Carboxymethyllysine, Biomarkers for Age-related Macular Degeneration*

PubMed Central

Ni, Jiaqian; Yuan, Xianglin; Gu, Jiayin; Yue, Xiuzhen; Gu, Xiaorong; Nagaraj, Ram H.; Crabb, John W.

2009-01-01

Age-related macular degeneration (AMD) causes severe vision loss in the elderly; early identification of AMD risk could help slow or prevent disease progression. Toward the discovery of AMD biomarkers, we quantified plasma protein Nε-carboxymethyllysine (CML) and pentosidine from 58 AMD and 32 control donors. CML and pentosidine are advanced glycation end products that are abundant in Bruch membrane, the extracellular matrix separating the retinal pigment epithelium from the blood-bearing choriocapillaris. We measured CML and pentosidine by LC-MS/MS and LC-fluorometry, respectively, and found higher mean levels of CML (∼54%) and pentosidine (∼64%) in AMD (p < 0.0001) relative to normal controls. Plasma protein fructosyl-lysine, a marker of early glycation, was found by amino acid analysis to be in equal amounts in control and non-diabetic AMD donors, supporting an association between AMD and increased levels of CML and pentosidine independent of other diseases like diabetes. Carboxyethylpyrrole (CEP), an oxidative modification from docosahexaenoate-containing lipids and also abundant in AMD Bruch membrane, was elevated ∼86% in the AMD cohort, but autoantibody titers to CEP, CML, and pentosidine were not significantly increased. Compellingly higher mean levels of CML and pentosidine were present in AMD plasma protein over a broad age range. Receiver operating curves indicate that CML, CEP adducts, and pentosidine alone discriminated between AMD and control subjects with 78, 79, and 88% accuracy, respectively, whereas CML in combination with pentosidine provided ∼89% accuracy, and CEP plus pentosidine provided ∼92% accuracy. Pentosidine levels appeared slightly altered in AMD patients with hypertension and cardiovascular disease, indicating further studies are warranted. Overall this study supports the potential utility of plasma protein CML and pentosidine as biomarkers for assessing AMD risk and susceptibility, particularly in combination with CEP

COUNTERACTING AGE STEREOTYPES: A SELF-AWARENESS MANIPULATION

PubMed Central

Chen, Yiwei; Pethtel, Olivia; Ma, Xiaodong

2014-01-01

The major goals of the present study were to (a) examine age differences in susceptibility to age stereotypes and (b) test a self-awareness manipulation in counteracting age stereotypes. Young and older adults read two sets of descriptors that only differed in the to-be-ignored age-related information. In the high self-awareness condition, participants saw themselves via a computer video camera. In the low self-awareness condition, they saw prerecorded images of a stranger. Overall, older adults were more likely than young adults to make age-stereotypical judgments in the low self-awareness condition. No age differences were found in the high self-awareness condition. PMID:24443629

Colorectal cancer-susceptibility single-nucleotide polymorphisms in Korean population.

PubMed

Hong, Sung Noh; Park, Changho; Kim, Jong-Il; Kim, Duk-Hwan; Kim, Hee Cheol; Chang, Dong Kyung; Rhee, Poong-Lyul; Kim, Jae J; Rhee, Jong Chul; Son, Hee Jung; Kim, Young-Ho

2015-05-01

Considering the significant racial and ethnic diversity in genetic variation, it is unclear whether the genome-wide association studies-identified colorectal cancer (CRC)-susceptibility single-nucleotide polymorphisms (SNPs) discovered in European populations are also relevant to the Korean population. However, studies on CRC-susceptibility SNPs in Koreans are limited. To investigate the racial and ethnic diversity of CRC-susceptibility genetic variants, we genotyped for the established European CRC-susceptibility SNPs in 198 CRC cases and 329 controls in Korea. To identify novel genetic variants using genome-wide screening in Korea, Illumina HumanHap 370K/610K BeadChips were performed on 105 CRC patients, and candidate CRC-susceptibility SNPs were selected. Subsequently, genotyping for replication was done in 189 CRC cases and 190 controls. Among the European CRC-susceptibility SNPs, rs4939827 in SMAD7 was associated with a significant decreased risk of Korean CRC (age-/gender-adjusted odds ratio [95% confidence interval]: additive model, 0.67 [95% CI, 0.47-0.95]; dominant model, 0.59 [95% CI, 0.39-0.91]). rs4779584 and rs10795668 were associated with CRC risk in females and males, respectively. Among candidate CRC-susceptibility SNPs selected from genome-wide screening, novel SNP, rs17051076, was found to be associated with a significantly increased risk of microsatellite instability-high CRC (age-/gender-adjusted odds ratio [95% confidence interval]: additive model, 4.25 [95% CI, 1.51-11.98]; dominant model, 3.52 [95% CI, 1.13-10.94]) in the replication study. rs4939827, rs4779584, and rs10795668 may contribute to the risk of CRC in the Korean population as well as in European populations. Novel rs17051076 could be associated with microsatellite instability-high CRC in Koreans. These associations support the ethnic diversity of CRC-susceptibility SNPs and should be taken into account in large-scale studies. © 2013 Journal of Gastroenterology and Hepatology

Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis

PubMed Central

Mora, Ana L.; Rojas, Mauricio

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a chronic age-related lung disease with high mortality that is characterized by abnormal scarring of the lung parenchyma. There has been a recent attempt to define the age-associated changes predisposing individuals to develop IPF. Age-related perturbations that are increasingly found in epithelial cells and fibroblasts from IPF lungs compared with age-matched cells from normal lungs include defective autophagy, telomere attrition, altered proteostasis, and cell senescence. These divergent processes seem to converge in mitochondrial dysfunction and metabolic distress, which potentiate maladaptation to stress and susceptibility to age-related diseases such as IPF. Therapeutic approaches that target aging processes may be beneficial for halting the progression of disease and improving quality of life in IPF patients. PMID:28145905

Are there age-related differences in social suggestibility to central and peripheral misinformation?

PubMed

Daneman, Meredyth; Thannikkotu, Cheyenne; Chen, Zhijian

2013-01-01

BACKGROUND/STUDY CONTEXT: Dalton and Daneman ( 2006 , Memory, 14, 486-501) showed that young adults can be induced to accept misinformation from a co-witness, even if it contradicts central features of a previously witnessed event. This study investigated whether older adults are also susceptible to social suggestion, and if so, whether to the same or different degree as their younger counterparts. The study also investigated whether participants were more likely to succumb to suggestions delivered by a peer or an older figure. Younger and older adults viewed an action video in the presence of a younger or older confederate co-witness. During a postevent discussion, the confederate introduced misinformation about central and peripheral features of the co-witnessed event. Finally, participants responded to true-false statements about the event and rated how confident they were in their decisions. Older adults were able to correctly reject false statements about an event that had been mentioned during the discussion by the confederate less often than they were able to correctly reject false statements that had not been mentioned, even if the misstatements contradicted central features of the previously witnessed event. However, older adults were no more susceptible to a co-witness's misleading suggestions than were their younger counterparts, and the age of the confederate did not influence the size of the suggestibility effect for younger or older adults. When baseline memory accuracy (correct rejection rates for unmentioned false information) is controlled, older adults are no more susceptible to misleading suggestions from a co-witness than are their younger counterparts. Age of the confederate did not influence the size of the suggestibility effect and thus provided no support for the predictions that participants are more likely to succumb to misleading suggestions delivered by a peer or by an older authority figure.

Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats.

EPA Science Inventory

Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have...

Age-related mutations and chronic myelomonocytic leukemia

PubMed Central

Mason, CC; Khorashad, JS; Tantravahi, SK; Kelley, TW; Zabriskie, MS; Yan, D; Pomicter, AD; Reynolds, KR; Eiring, AM; Kronenberg, Z; Sherman, RL; Tyner, JW; Dalley, BK; Dao, K-H; Yandell, M; Druker, BJ; Gotlib, J; O’Hare, T; Deininger, MW

2016-01-01

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy nearly confined to the elderly. Previous studies to determine incidence and prognostic significance of somatic mutations in CMML have relied on candidate gene sequencing, although an unbiased mutational search has not been conducted. As many of the genes commonly mutated in CMML were recently associated with age-related clonal hematopoiesis (ARCH) and aged hematopoiesis is characterized by a myelomonocytic differentiation bias, we hypothesized that CMML and aged hematopoiesis may be closely related. We initially established the somatic mutation landscape of CMML by whole exome sequencing followed by gene-targeted validation. Genes mutated in ⩾ 10% of patients were SRSF2, TET2, ASXL1, RUNX1, SETBP1, KRAS, EZH2, CBL and NRAS, as well as the novel CMML genes FAT4, ARIH1, DNAH2 and CSMD1. Most CMML patients (71%) had mutations in ⩾ 2 ARCH genes and 52% had ⩾ 7 mutations overall. Higher mutation burden was associated with shorter survival. Age-adjusted population incidence and reported ARCH mutation rates are consistent with a model in which clinical CMML ensues when a sufficient number of stochastically acquired age-related mutations has accumulated, suggesting that CMML represents the leukemic conversion of the myelomonocytic-lineage-biased aged hematopoietic system. PMID:26648538

Amniotic Epithelial Cells: A New Tool to Combat Aging and Age-Related Diseases?

PubMed Central

Di Germanio, Clara; Bernier, Michel; de Cabo, Rafael; Barboni, Barbara

2016-01-01

The number of elderly people is growing at an unprecedented rate and this increase of the aging population is expected to have a direct impact on the incidence of age-related diseases and healthcare-associated costs. Thus, it is imperative that new tools are developed to fight and slow age-related diseases. Regenerative medicine is a promising strategy for the maintenance of health and function late in life; however, stem cell-based therapies face several challenges including rejection and tumor transformation. As an alternative, the placenta offers an extraordinary source of fetal stem cells, including the amniotic epithelial cells (AECs), which retain some of the characteristics of embryonic stem cells, but show low immunogenicity, together with immunomodulatory and anti-inflammatory activities. Because of these characteristics, AECs have been widely utilized in regenerative medicine. This perspective highlights different mechanisms triggered by transplanted AECs that could be potentially useful for anti-aging therapies, which include: Graft and differentiation for tissue regeneration in age-related settings, anti-inflammatory behavior to combat “inflammaging,” anti-tumor activity, direct lifespan and healthspan extension properties, and possibly rejuvenation in a manner reminiscent of heterochronic parabiosis. Here, we critically discuss benefits and limitation of AECs-based therapies in age-related diseases. PMID:27921031

Relation of motion sickness susceptibility to vestibular and behavioral measures of orientation

NASA Technical Reports Server (NTRS)

Peterka, Robert J.

1994-01-01

The objective of this proposal is to determine the relationship of motion sickness susceptibility to vestibulo-ocular reflexes (VOR), motion perception, and behavioral utilization of sensory orientation cues for the control of postural equilibrium. The work is focused on reflexes and motion perception associated with pitch and roll movements that stimulate the vertical semicircular canals and otolith organs of the inner ear. This work is relevant to the space motion sickness problem since 0 g related sensory conflicts between vertical canal and otolith motion cues are a likely cause of space motion sickness. Results of experimentation are summarized and modifications to a two-axis rotation device are described. Abstracts of a number of papers generated during the reporting period are appended.

Retinal Structure Measurements as Inclusion Criteria for Stem Cell-Based Therapies of Retinal Degenerations.

PubMed

Jacobson, Samuel G; Matsui, Rodrigo; Sumaroka, Alexander; Cideciyan, Artur V

2016-04-01

We reviewed and illustrated the most optimal retinal structural measurements to make in stem cell clinical trials. Optical coherence tomography (OCT) and autofluorescence (AF) imaging were used to evaluate patients with severe visual loss from nonsyndromic and syndromic retinitis pigmentosa (RP), ABCA4-Stargardt disease, and nonneovascular age-related macular degeneration (AMD). Outer nuclear layer (ONL), rod outer segment (ROS) layer, inner retina, ganglion cell layer (GCL), and nerve fiber layer (NFL) thicknesses were quantified. All patients had severely reduced visual acuities. Retinitis pigmentosa patients had limited visual fields; maculopathy patients had central scotomas with retained peripheral function. For the forms of RP illustrated, there was detectable albeit severely reduced ONL across the scanned retina, and normal or hyperthick GCL and NFL. Maculopathy patients had no measurable ONL centrally; it became detectable with eccentricity. Some maculopathy patients showed unexpected GCL losses. Autofluorescence imaging illustrated central losses of RPE integrity. A hypothetical scheme to relate patient data with different phases of retinal remodeling in animal models of retinal degeneration was presented. Stem cell science is advancing, but it is not too early to open the discussion of criteria for patient selection and monitoring. Available clinical tools, such as OCT and AF imaging, can provide inclusion/exclusion criteria and robust objective outcomes. Accepting that early trials may not lead to miraculous cures, we should be prepared to know why-scientifically and clinically-so we can improve subsequent trials. We also must determine if retinal remodeling is an impediment to efficacy.

Aging of Cerebral White Matter

PubMed Central

Liu, Huan; Yang, Yuanyuan; Xia, Yuguo; Zhu, Wen; Leak, Rehana K.; Wei, Zhishuo; Wang, Jianyi; Hu, Xiaoming

2016-01-01

White matter (WM) occupies a large volume of the human cerebrum and is mainly composed of myelinated axons and myelin-producing glial cells. The myelinated axons within WM are the structural foundation for efficient neurotransmission between cortical and subcortical areas. Similar to neuron-enriched gray matter areas, WM undergoes a series of changes during the process of aging. WM malfunction can induce serious neurobehavioral and cognitive impairments. Thus, age-related changes in WM may contribute to the functional decline observed in the elderly. In addition, aged WM becomes more susceptible to neurological disorders, such as stroke, traumatic brain injury (TBI), and neurodegeneration. In this review, we summarize the structural and functional alterations of WM in natural aging and speculate on the underlying mechanisms. We also discuss how age-related WM changes influence the progression of various brain disorders, including ischemic and hemorrhagic stroke, TBI, Alzheimer’s disease, and Parkinson’s disease. Although the physiology of WM is still poorly understood relative to gray matter, WM is a rational therapeutic target for a number of neurological and psychiatric conditions. PMID:27865980

Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset.

PubMed

Nichols, W C; Pankratz, N; Marek, D K; Pauciulo, M W; Elsaesser, V E; Halter, C A; Rudolph, A; Wojcieszek, J; Pfeiffer, R F; Foroud, T

2009-01-27

To characterize sequence variation within the glucocerebrosidase (GBA) gene in a select subset of our sample of patients with familial Parkinson disease (PD) and then to test in our full sample whether these sequence variants increased the risk for PD and were associated with an earlier onset of disease. We performed a comprehensive study of all GBA exons in one patient with PD from each of 96 PD families, selected based on the family-specific lod scores at the GBA locus. Identified GBA variants were subsequently screened in all 1325 PD cases from 566 multiplex PD families and in 359 controls. Nine different GBA variants, five previously reported, were identified in 21 of the 96 PD cases sequenced. Screening for these variants in the full sample identified 161 variant carriers (12.2%) in 99 different PD families. An unbiased estimate of the frequency of the five previously reported GBA variants in the familial PD sample was 12.6% and in the control sample was 5.3% (odds ratio 2.6; 95% confidence interval 1.5-4.4). Presence of a GBA variant was associated with an earlier age at onset (p = 0.0001). On average, those patients carrying a GBA variant had onset with PD 6.04 years earlier than those without a GBA variant. This study suggests that GBA is a susceptibility gene for familial Parkinson disease (PD) and patients with GBA variants have an earlier age at onset than patients with PD without GBA variants.

Age-related macular degeneration: genome-wide association studies to translation.

PubMed

Black, James R M; Clark, Simon J

2016-04-01

In recent years, genome-wide association studies (GWAS), which are able to analyze the contribution to disease of genetic variations that are common within a population, have attracted considerable investment. Despite identifying genetic variants for many conditions, they have been criticized for yielding data with minimal clinical utility. However, in this regard, age-related macular degeneration (AMD), the most common form of blindness in the Western world, is a striking exception. Through GWAS, common genetic variants at a number of loci have been discovered. Two loci in particular, including genes of the complement cascade on chromosome 1 and the ARMS2/HTRA1 genes on chromosome 10, have been shown to convey significantly increased susceptibility to developing AMD. Today, although it is possible to screen individuals for a genetic predisposition to the disease, effective interventional strategies for those at risk of developing AMD are scarce. Ongoing research in this area is nonetheless promising. After providing brief overviews of AMD and common disease genetics, we outline the main recent advances in the understanding of AMD, particularly those made through GWAS. Finally, the true merit of these findings and their current and potential translational value is examined.Genet Med 18 4, 283-289.

Dietary Approaches that Delay Age-Related Diseases

PubMed Central

Everitt, Arthur V; Hilmer, Sarah N; Brand-Miller, Jennie C; Jamieson, Hamish A; Truswell, A Stewart; Sharma, Anita P; Mason, Rebecca S; Morris, Brian J; Le Couteur, David G

2006-01-01

Reducing food intake in lower animals such as the rat decreases body weight, retards many aging processes, delays the onset of most diseases of old age, and prolongs life. A number of clinical trials of food restriction in healthy adult human subjects running over 2–15 years show significant reductions in body weight, blood cholesterol, blood glucose, and blood pressure, which are risk factors for the development of cardiovascular disease and diabetes. Lifestyle interventions that lower energy balance by reducing body weight such as physical exercise can also delay the development of diabetes and cardiovascular disease. In general, clinical trials are suggesting that diets high in calories or fat along with overweight are associated with increased risk for cardiovascular disease, type 2 diabetes, some cancers, and dementia. There is a growing literature indicating that specific dietary constituents are able to influence the development of age-related diseases, including certain fats (trans fatty acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular disease, glycemic index and fiber for diabetes, fruits and vegetables for cardiovascular disease, and calcium and vitamin D for osteoporosis and bone fracture. In addition, there are dietary compounds from different functional foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols that may affect the development of age-related diseases. Long-term prospective clinical trials will be needed to confirm these diet—disease relationships. On the basis of current research, the best diet to delay age-related disease onset is one low in calories and saturated fat and high in wholegrain cereals, legumes, fruits and vegetables, and which maintains a lean body weight. Such a diet should become a key component of healthy aging, delaying age-related diseases and perhaps intervening in the aging process itself. Furthermore, there are studies suggesting that nutrition in childhood

Absolute and Relative Socioeconomic Health Inequalities across Age Groups

PubMed Central

van Zon, Sander K. R.; Bültmann, Ute; Mendes de Leon, Carlos F.; Reijneveld, Sijmen A.

2015-01-01

Background The magnitude of socioeconomic health inequalities differs across age groups. It is less clear whether socioeconomic health inequalities differ across age groups by other factors that are known to affect the relation between socioeconomic position and health, like the indicator of socioeconomic position, the health outcome, gender, and as to whether socioeconomic health inequalities are measured in absolute or in relative terms. The aim is to investigate whether absolute and relative socioeconomic health inequalities differ across age groups by indicator of socioeconomic position, health outcome and gender. Methods The study sample was derived from the baseline measurement of the LifeLines Cohort Study and consisted of 95,432 participants. Socioeconomic position was measured as educational level and household income. Physical and mental health were measured with the RAND-36. Age concerned eleven 5-years age groups. Absolute inequalities were examined by comparing means. Relative inequalities were examined by comparing Gini-coefficients. Analyses were performed for both health outcomes by both educational level and household income. Analyses were performed for all age groups, and stratified by gender. Results Absolute and relative socioeconomic health inequalities differed across age groups by indicator of socioeconomic position, health outcome, and gender. Absolute inequalities were most pronounced for mental health by household income. They were larger in younger than older age groups. Relative inequalities were most pronounced for physical health by educational level. Gini-coefficients were largest in young age groups and smallest in older age groups. Conclusions Absolute and relative socioeconomic health inequalities differed cross-sectionally across age groups by indicator of socioeconomic position, health outcome and gender. Researchers should critically consider the implications of choosing a specific age group, in addition to the indicator of

Nutritional Considerations for Healthy Aging and Reduction in Age-Related Chronic Disease.

PubMed

Shlisky, Julie; Bloom, David E; Beaudreault, Amy R; Tucker, Katherine L; Keller, Heather H; Freund-Levi, Yvonne; Fielding, Roger A; Cheng, Feon W; Jensen, Gordon L; Wu, Dayong; Meydani, Simin N

2017-01-01

A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of "nutritional frailty," which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high. This review highlights the role of nutrition science in promoting healthy aging and in improving the prognosis in cases of age-related diseases. It serves to identify key knowledge gaps and implementation challenges to support adequate nutrition for healthy aging, including applicability of metrics used in body-composition and diet adequacy for older adults and mechanisms to reduce nutritional frailty and to promote diet resilience. This review also discusses management recommendations for several leading chronic conditions common in aging populations, including cognitive decline and dementia, sarcopenia, and compromised immunity to infectious disease. The role of health systems in incorporating nutrition care routinely for those aged ≥60 y and living independently and current actions to address nutritional status before hospitalization and the development of disease are discussed. © 2017 American Society for Nutrition.

Thalamic structures and associated cognitive functions: Relations with age and aging.

PubMed

Fama, Rosemary; Sullivan, Edith V

2015-07-01

The thalamus, with its cortical, subcortical, and cerebellar connections, is a critical node in networks supporting cognitive functions known to decline in normal aging, including component processes of memory and executive functions of attention and information processing. The macrostructure, microstructure, and neural connectivity of the thalamus changes across the adult lifespan. Structural and functional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) have demonstrated, regional thalamic volume shrinkage and microstructural degradation, with anterior regions generally more compromised than posterior regions. The integrity of selective thalamic nuclei and projections decline with advancing age, particularly those in thalamofrontal, thalamoparietal, and thalamolimbic networks. This review presents studies that assess the relations between age and aging and the structure, function, and connectivity of the thalamus and associated neural networks and focuses on their relations with processes of attention, speed of information processing, and working and episodic memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sex-Related and Age-Related Differences in Knee Strength of Basketball Players Ages 11–17 Years

PubMed Central

Vardaxis, Vassilios G.

2003-01-01

Objective: To assess hamstrings and quadriceps strength of basketball players ages 11–13 and 15–17 years. Design and Setting: This cross-sectional study occurred during the 2000 American Youth Basketball Tour National Tournament. We investigated whether sex- or age-related strength differences existed among study participants. Subjects: Forty-one tournament participants (22 girls, 19 boys; 11–13 or 15–17 years old) who reported no history of knee sprain or surgery were recruited. Measurements: We used a Cybex II dynamometer to obtain isokinetic concentric peak torques relative to body mass (Nm/kg) at 60°/s for hamstrings and quadriceps bilaterally. From average peak torques, we determined ipsilateral hamstrings:quadriceps and homologous muscle-group ratios. Results: Correlations between hamstrings and quadriceps strength measures ranged from 0.78 to 0.97. Players 15–17 years old had greater relative hamstrings and quadriceps strength than 11- to 13-year-old athletes. Age and sex interacted significantly for quadriceps strength. The quadriceps strength of 15- to 17-year-old girls did not differ from that of 11- to 13-year-old girls, whereas 15- to 17-year-old boys had stronger quadriceps than 11- to 13-year-old boys. Boys 15–17 years old had greater quadriceps strength than girls 15–17 years old. Conclusions: This study is unique in providing normative data for the hamstrings and quadriceps strength of basketball players 11–13 and 15–17 years old. Age-related strength differences did not occur consistently between the sexes, as girls 11–13 and 15–17 years old had similar relative quadriceps strength. PMID:14608433

Markers of Oxidant Stress that are Clinically Relevant in Aging and Age-related Disease

PubMed Central

Jacob, Kimberly D.; Hooten, Nicole Noren; Trzeciak, Andrzej R.; Evans, Michele K.

2013-01-01

Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant. PMID:23428415

iPSCs, aging and age-related diseases.

PubMed

Isobe, Ken-Ichi; Cheng, Zhao; Nishio, Naomi; Suganya, Thanasegan; Tanaka, Yuriko; Ito, Sachiko

2014-09-25

Human histocompatibility antigens are quite heterogeneous and promote the rejection of transplanted tissue. Recent advances in stem cell research that enable the use of a patient's own stem cells for transplantation are very important because rejection could be avoided. In particular, Yamanaka's group in Japan gave new hope to patients with incurable diseases when they developed induced murine pluripotent stem cells (iPSCs) in 2006 and human iPSCs in 2007. Whereas embryonic stem cells (ESCs) are derived from the inner cell mass and are supported in culture by LIF, iPSCs are derived from fetal or adult somatic cells. Through the application of iPSC technology, adult somatic cells can develop a pluripotent state. One advantage of using iPSCs instead of ESCs in regenerative medicine is that (theoretically) immune rejection could be avoided, although there is some debate about immune rejection of a patient's own iPSCs. Many diseases occur in elderly patients. In order to use regenerative medicine with the elderly, it is important to demonstrate that iPSCs can indeed be generated from older patients. Recent findings have shown that iPSCs can be established from aged mice and aged humans. These iPSCs can differentiate to cells from all three germ layers. However, it is not known whether iPSCs from aged mice or humans show early senescence. Before clinical use of iPSCs, issues related to copy number variation, tumorigenicity and immunogenicity must be resolved. It is particularly important that researchers have succeeded in generating iPSCs that have differentiated to somatic cells related to specific diseases of the elderly, including atherosclerosis, diabetes, Alzheimer's disease and Parkinson's disease. These efforts will facilitate the use of personalized stem cell transplantation therapy for currently incurable diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Hyperhomocysteinemia and Age-related Macular Degeneration: Role of Inflammatory Mediators and Pyroptosis; A Proposal.

PubMed

Singh, Mahavir; Tyagi, Suresh C

2017-08-01

Age-related macular degeneration (AMD) and pyroptosis cause irreversible vascular changes in the eyes leading to central vision loss in patients. It is the most common eye disease affecting millions of people aged 50years or older, and is slowly becoming a major health problem worldwide. The disease mainly affects macula lutea, an oval-shaped pigmented area surrounding fovea near the center of retina, a region responsible for visual acuity. It is fairly a complex disease as genetics of patients, environmental triggers as well as risk factors such as age, family history of CVDs, diabetes, gender, obesity, race, hyperopia, iris color, smoking, diabetes, exposure to sun light and pyroptosis have all been clubbed together as probable causes of macular degeneration. Among genes that are known to play a role include variant polymorphisms in the complement cascade components such as CFH, C2, C3, and CFB as potential genetic risk factors. So far, AMD disease hypothesized theories have not resulted into the anticipated impact towards the development of effective or preventive therapies in order to help alleviate patients' suffering because, as of today, it is still unclear what actually initiates or leads to this dreaded eye condition. Based upon our extensive work on the metabolism of homocysteine (Hcy) in various disease conditions we, therefore, are proposing a novel hypothesis for AMD pathogenesis as we strongly believe that Hcy and events such as pyroptosis make a greater contribution to the overall etiology of AMD disease in a target population of susceptible hosts by inciting and accelerating the inherent inflammatory changes in the retina of these patients (Fig. 2). In this context, we further state that Hcy and pyroptosis should be considered as legitimate and valuable markers of retinal dysfunction as they not only aid and abet in the development but also in the progression of AMD in older people as discussed in this paper. This discussion should open up new

Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

PubMed Central

Ardeljan, Daniel; Chan, Chi-Chao

2013-01-01

Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

Segregation of a Latent High Adiposity Phenotype in Families with a History of Type 2 Diabetes Mellitus Implicates Rare Obesity-Susceptibility Genetic Variants with Large Effects in Diabetes-Related Obesity

PubMed Central

Jenkins, Arthur B.; Batterham, Marijka; Samocha-Bonet, Dorit; Tonks, Katherine; Greenfield, Jerry R.; Campbell, Lesley V.

2013-01-01

Background We recently reported significantly greater weight gain in non-diabetic healthy subjects with a 1st degree family history (FH+) of type 2 diabetes mellitus (T2DM) than in a matched control group without such history (FH−) during voluntary overfeeding, implying co-inheritance of susceptibilities to T2DM and obesity. We have estimated the extent and mode of inheritance of susceptibility to increased adiposity in FH+. Methods Normoglycaemic participants were categorised either FH+ (≥1 1st degree relative with T2DM, 50F/30M, age 45±14 (SD) yr) or FH− (71F/51M, age 43±14 yr). Log-transformed anthropometric measurements (height, hip and waist circumferences) and lean, bone and fat mass (Dual Energy X-ray Absorptiometry) data were analysed by rotated Factor Analysis. The age- and gender-adjusted distributions of indices of adiposity in FH+ were assessed by fits to a bimodal model and by relative risk ratios (RR, FH+/FH−) and interpreted in a purely genetic model of FH effects. Results The two orthogonal factors extracted, interpretable as Frame and Adiposity accounted for 80% of the variance in the input data. FH+ was associated with significantly higher Adiposity scores (p<0.01) without affecting Frame scores. Adiposity scores in FH+ conformed to a bimodal normal distribution, consistent with dominant expression of major susceptibility genes with 59% (95% CI 40%, 74%) of individuals under the higher mode. Calculated risk allele frequencies were 0.09 (0.02, 0.23) in FH−, 0.36 (0.22, 0.48) in FH+ and 0.62 (0.36, 0.88) in unobserved T2DM-affected family members. Conclusions The segregation of Adiposity in T2DM-affected families is consistent with dominant expression of rare risk variants with major effects, which are expressed in over half of FH+ and which can account for most T2DM-associated obesity in our population. The calculated risk allele frequency in FH− suggests that rare genetic variants could also account for a substantial fraction of the

Age-related macular degeneration.

PubMed

Cheung, Lily K; Eaton, Angie

2013-08-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. © 2013 Pharmacotherapy Publications, Inc.

Relative Age Effects in Dutch Adolescents: Concurrent and Prospective Analyses

PubMed Central

Jeronimus, Bertus F.; Stavrakakis, Nikolaos; Veenstra, René; Oldehinkel, Albertine J.

2015-01-01

The literature on relative age position effects is rather inconsistent. In this study we examined intra-classroom age position (or relative age) effects on Dutch adolescents’ school progress and performance (as rated by teachers), physical development, temperamental development (fear and frustration), and depressive symptoms, all adjusted for age at the time of measurement. Data were derived from three waves of Tracking Adolescents' Individuals Lives Survey (TRAILS) of 2230 Dutch adolescents (baseline mean age 11.1, SD = 0.6, 51% girls). Albeit relative age predicted school progress (grade retention ORs = 0.83 for each month, skipped grade OR = 1.47, both p<.001), our key observation is the absence of substantial developmental differences as a result of relative age position in Dutch adolescents with a normative school trajectory, in contrast to most literature. For adolescents who had repeated a grade inverse relative age effects were observed, in terms of physical development and school performance, as well as on depressive symptoms, favoring the relatively young. Cross-cultural differences in relative age effect may be partly explained by the decision threshold for grade retention. PMID:26076384

Potential Susceptibility Loci Identified for Renal Cell Carcinoma by Targeting Obesity-Related Genes.

PubMed