Erdahl Teber

Tau haplotypes regulate transcription and are associated with Parkinson's disease

A primary haplotype (H1) of the microtubule‐associated protein Tau (MAPT) gene is associated with Parkinsons disease (PD). However, the mechanism for disease susceptibility remains unknown. We examined the promoter region of MAPT and identified single nucleotide polymorphisms and insertions of 1 to 11 nucleotides. These polymorphisms corresponded to the previously characterized haplotypes, H1 and H2, as well as a novel variant of the H1 haplotype, H1′. As observed in other studies, we demonstrated a significant association with the H1/H1 promoter genotype and PD in a cohort of 206 idiopathic late‐onset cases. This is in contrast with a panel of 13 early‐onset PD patients, for whom we did not detect any mutations in MAPT. By examining single nucleotide polymorphisms in adjacent genes, we showed that linkage disequilibrium does not extend beyond the MAPT haplotype to neighboring genes. To define the mechanism of disease susceptibility, we examined the transcriptional activity of the promoter haplotypes using a luciferase reporter assay. We demonstrated in two human cell lines, SK‐N‐MC and 293, that the H1 haplotype was more efficient at driving gene expression than the H2 haplotype. Our data suggest that an increase in expression of the MAPT gene is a susceptibility factor in idiopathic PD.

The Transcriptional and Functional Properties of Mouse Epiblast Stem Cells Resemble the Anterior Primitive Streak

Mouse epiblast stem cells (EpiSCs) can be derived from a wide range of developmental stages. To characterize and compare EpiSCs with different origins, we derived a series of EpiSC lines from pregastrula stage to late-bud-stage mouse embryos. We found that the transcriptomes of these cells are hierarchically distinct from those of the embryonic stem cells, induced pluripotent stem cells (iPSCs), and epiblast/ectoderm. The EpiSCs display globally similar gene expression profiles irrespective of the original developmental stage of the source tissue. They are developmentally similar to the ectoderm of the late-gastrula-stage embryo and behave like anterior primitive streak cells when differentiated in vitro and in vivo. The EpiSC lines that we derived can also be categorized based on a correlation between gene expression signature and predisposition to differentiate into particular germ-layer derivatives. Our findings therefore highlight distinct identifying characteristics of EpiSCs and provide a foundation for further examination of EpiSC properties and potential.

Severity of age-related hearing loss is associated with impaired activities of daily living

BACKGROUND age-related hearing loss is a common chronic condition; hence, it is important to understand its influence on the functional status of older adults. We assessed the association between hearing impairment with activity limitations as assessed by the activities of daily living (ADL) scale. METHODS a total of 1,952 Blue Mountains Hearing Study participants aged ≥60 years had their hearing levels measured using pure-tone audiometry. A survey instrument with questions on functional status as determined by the Older Americans Resources and Services ADL scale was administered. RESULTS one hundred and sixty-four (10.4%) participants reported ADL difficulty. A higher proportion of hearing impaired than non-impaired adults reported difficulties in performing three out of the seven basic ADL and six out of the seven instrumental ADL tasks. After multivariable adjustment, increased severity of hearing loss was associated with impaired ADL (P(trend )= 0.001). Subjects with moderate to severe hearing loss compared with those without, had a 2.9-fold increased likelihood of reporting difficulty in ADL, multivariate-adjusted odds ratio (OR): 2.87 [95% confidence interval (CI): 1.59-5.19]. Participants aged <75 years with hearing loss compared with those without, had 2-fold higher odds of impaired ADL. Having worn or wearing a hearing aid was also associated with a 2-fold increased likelihood of impaired ADL. CONCLUSION functional status as measured by a common ADL scale is diminished in older hearing impaired adults. Our findings suggest that severely diminished hearing could make the difference between independence and the need for formal support services or placement.

Incidence and Predictors of Hearing Aid Use and Ownership Among Older Adults With Hearing Loss

PURPOSE The reasons are not clear as to why people who need hearing aids and possess them do not use them. We aimed to describe the incidence and predictors of hearing aid ownership and use among older adults. METHODS We included 2,015 Blue Mountains Hearing Study participants aged ≥55 years who were examined between 1997 and 1999 and 2002 and 2004. Hearing levels were measured with pure-tone audiometry. RESULTS The 5-year incidence of hearing aid use and ownership was 8.1% and 8.5%, respectively. Age was associated with incident hearing aid ownership and use, multivariable-adjusted odds ratio (OR) per decade increase in age of 1.79 (95% confidence interval [CI], 1.21-2.64) and of 1.66 (95% CI, 1.15-2.40), respectively. Any level of hearing loss (HL) at baseline predicted a 2.8-fold increased likelihood of using a hearing aid at follow-up. Hearing handicap was associated with 7% increased likelihood of incident aid use. Key reasons provided for not obtaining/using a hearing aid were: not recommended one (8.0%), its high cost (1.7%), and believing that they did not need one (9.0%). CONCLUSIONS Incident hearing aid ownership and usage was relatively low among hearing impaired adults. Age, question-defined hearing handicap, and measured HL were significant predictors of incident hearing aid use/ownership.

Correction of Visual Impairment by Cataract Surgery and Improved Survival in Older Persons: The Blue Mountains Eye Study Cohort

OBJECTIVE We assessed whether correction of visual impairment (VI) by cataract surgery was associated with improved long-term survival in an older Australian population. DESIGN Population-based cohort study. PARTICIPANTS In the Blue Mountains Eye Study, 354 participants, aged ≥ 49 years, had both cataract and VI or had undergone cataract surgery before baseline examinations. They were subsequently examined after 5- and 10-year follow-ups. METHODS Associations between the mortality risk and the surgical correction of VI (visual acuity [VA] <20/40, attributable to cataract) were assessed in Cox proportional hazard regression models, after multivariate adjustment, using time-dependent variables for the study factor. MAIN OUTCOME MEASURES All-cause mortality. RESULTS The 15-year crude mortality of participants who had undergone cataract surgery at baseline with no subsequent VI (71.8%) was relatively similar to that in participants with cataract-related VI who had not yet undergone surgery (79.4%). However, after adjusting for age and sex, participants who underwent cataract surgery before baseline or during follow-up and no longer had VI had significantly lower long-term mortality risk (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46-0.77) than participants with VI due to cataract who had not undergone cataract surgery. This lower mortality risk in the group with surgically corrected VI (HR, 0.54; 95% CI, 0.41-0.73) persisted after further adjustment for smoking, body mass index, home ownership, qualifications, poor self-rated health, the presence of poor mobility, hypertension, diabetes, self-reported history of angina, myocardial infarction, stroke, cancer, asthma, and arthritis. This finding remained significant (HR, 0.55; 95% CI, 0.41-0.73) after additional adjustment for the number of medications taken (continuous variable) and the number (≥ 5 vs. <5) of comorbid conditions (poor mobility, hypertension, diabetes, angina, myocardial infarction, stroke, cancer, asthma, or arthritis) as indicators of frailty. CONCLUSIONS Surgical correction of VI due to cataract was associated with significantly better long-term survival of older persons after accounting for known cataract and mortality risk factors, and indicators of general health. Whether some uncontrolled factors (frailty or general health) could have influenced decisions not to perform cataract surgery in some participants is unknown. However, this finding strongly supports many previous reports linking VI with poor survival. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Blood pressure is associated with retinal vessel signs in preadolescent children.

Objective Few studies have examined the effect of blood pressure (BP) on the retinal microvasculature in children. We examined the relationship between BP and retinal vessel caliber in a sample of preadolescent schoolchildren. Methods Eligible high school students [2353/3144 (response 75.3%); mean age, 12.7 years] from 21 randomly selected schools in Sydney, Australia, were examined during 2004–2005. Retinal vessel caliber was quantified from digital retinal images using well known computer-based programs. BP was measured using a standard protocol and high BP was defined according to published guidelines for this age group. Results After adjusting for age, sex, ethnicity, BMI, iris color, axial length, birth weight and the fellow retinal vascular caliber, children in the highest quartiles of SBP, DBP or mean arterial BP had approximately 5 μm narrower mean retinal arteriolar caliber than those in the lowest quartiles of all three BP measures (all P for trend <0.0001). Children classified as having high BP had approximately 2.0 μm narrower mean retinal arteriolar caliber than normotensive children (P = 0.002). In boys, each 10-mmHg increase in SBP was associated with a 2.19-μm increase in the mean retinal venular caliber (P = 0.0003), but no similar significant association was evident in girls. Conclusion Elevated BP is associated with narrower retinal arterioles in preadolescent boys and girls, and also with wider retinal venules in boys. These data provide further evidence of early microvascular changes associated with high BP in older children.

Effect of obesity on retinal vascular structure in pre-adolescent children

UNLABELLED OBJECTIVES. In adults, obesity is linked to changes in the retinal microvasculature. Limited research has been conducted into this association in children. We examined in a cohort of pre-adolescents the relationship between body mass index (BMI) and retinal vascular structure, including retinal vessel diameter and retinal vessel fractals, a measure of geometric patterns reflecting vessel density. METHODS A population-based study among school children (2 353/3 144 [75.3%], median age, 12.7 years) recruited from a random cluster sample of 21 schools was conducted during 2004-5. Retinal images were taken and vessel diameter and fractal dimension were quantified using computer-based programs following standardized protocols. Anthropometric measures (weight, height, waist circumference, and BMI) were obtained and defined using standardized protocols. RESULTS Children with the highest quartile of BMI had narrower retinal arteriolar diameter (2.8 μm narrower, p<0.0001) and wider venular caliber (4.2 μm wider, p=0.001) than those with BMI in the lowest quartile, after adjusting for age, sex, ethnicity, mean arterial blood pressure, iris color, axial length, birth weight and fellow retinal vessel caliber. Obese children had narrower retinal arteriolar diameter (2.8 μm narrower, p=0.01) and wider venular diameter (4.5 μm wider, p=0.01) than in non-overweight/obese children. Retinal fractal dimension was not significantly associated with BMI. Increasing quartiles of waist circumference were also associated with retinal vessel diameter. CONCLUSIONS Our data provide evidence of adverse retinal microvascular caliber changes in obese pre-adolescent children, well before the onset of metabolic and cardiovascular disease in adulthood, and support an early, generalized adverse effect of adiposity on microvascular structure.

Influence of physical activity and screen time on the retinal microvasculature in young children.

Objective—It is not clear whether physical activity and sedentary behavior affect retinal microvascular caliber. We investigated associations among physical activity (outdoor and indoor sporting activities), sedentary behaviors (including screen time, television [TV] viewing, and computer and videogame usage), and retinal microvascular caliber in schoolchildren. Methods and Results—Six-year-old students (1765/2238) from a random cluster sample of 34 Sydney schools were examined. Parents completed questionnaires about physical and sedentary activities. Retinal images were taken, and retinal vessel caliber was quantified. After adjusting for age, sex, ethnicity, eye color, axial length, body mass index, birth weight, and mean arterial blood pressure, children who spent more time in outdoor sporting activities (in the highest tertile of activity) had 2.2 &mgr;m (95% CI 0.65 to 3.71) wider mean retinal arteriolar caliber than those in the lowest tertile (Ptrend=0.004). Increasing quartiles of time spent watching TV were associated with narrower mean retinal arteriolar caliber ≈2.3 &mgr;m (95% CI 0.73 to 3.92), Ptrend=0.003. Conclusion—These data suggest that physical activity could have a beneficial influence, whereas screen time has a potential adverse influence on retinal microvascular structure. The magnitude of arteriolar narrowing associated with each hour daily of TV viewing is similar to that associated with a 10-mm Hg increase in systolic blood pressure in children.

Prevalence and 5-Year Incidence of Dual Sensory Impairment in an Older Australian Population

PURPOSE To report prevalence and 5-year incidence of dual sensory impairment (DSI), and associated risk factors, in an older population. METHODS We included 2015 Blue Mountains Hearing Study participants aged ≥55 years, examined between 1997 and 1999 (baseline) and 2002 and 2004. Hearing thresholds were measured with the use of pure-tone audiometry. Visual acuity was measured with a LogMar chart while the subject wore distance glasses, if they owned a pair. DSI was defined as combined presenting visual acuity (better eye) <20/40, and PTA(0.5-4 kHz) (better ear) >25 dB HL. The incidence of DSI was considered by the use of two at-risk subpopulations: (i) participants with no sensory impairment and; (ii) with one type of sensory impairment at baseline. RESULTS The prevalence of DSI was 6% at baseline, increasing from 0% for ages <60 years to 26.8% for ages 80+ years (p for trend <.0001). Five-year DSI incidence was 1.6% in persons with no sensory impairment and 11.3% in those with a single sensory impairment, a 7-fold difference. Among participants with either no sensory impairment or a single sensory impairment at baseline, a significant age-related increase in incident DSI was found (p for trend <.0001 and .0004, respectively). Low education was a significant risk factor for DSI among those with no sensory impairment and those with single sensory impairment, multivariable-adjusted odds ratio (OR, 6.62; 95% confidence interval [95% CI], 1.79-24.4) and OR, 2.55 (95% CI, 1.36-4.79), respectively. CONCLUSIONS Aging population trends and the age-related prevalence and incidence of DSI support the implementation of collaborative efforts in service provision between hearing and vision professionals. Active case-finding among older persons with single-sensory impairments may help identify those with DSI and provide timely and appropriate services.

Smaller Birth Size is Associated With Narrower Retinal Arterioles in Early Adolescence

Please cite this paper as: Gopinath, Baur, Wang, Teber, Liew, Cheung, Wong and Mitchell (2010). Smaller Birth Size is Associated With Narrower Retinal Arterioles in Early Adolescence. Microcirculation17(8), 660–668.