Effectiveness of HealthTracker for post-caesarean section surgical site infection surveillance: An intervention study.

This intervention study aimed to implement and evaluate the effectiveness of HealthTracker, a post-discharge surgical site infection surveillance system. Participants were 730 women birthing by caesarean section at a large hospital over a 6-month period. Data were downloaded from clinical data systems and HealthTracker. Receiver operating characteristics were used to assess HealthTracker. Over a 6-month period, 382 women completed HealthTracker, with 83 scoring ≥6, indicating signs and symptoms of surgical site infection. Of this 83, 58 sought advice from health professionals, 29 returned to hospital, and 45 received antibiotics. A total of 20 infections from a total population of 730 were confirmed, with 14 out of 382 respondents confirmed via HealthTracker. Receiver operating characteristics identified HealthTracker as an excellent indicator of surgical site infection. HealthTracker is a feasible mHealth option for monitoring post-discharge surgical site infection post-caesarean section. In addition, by providing alerts, advising women to monitor their symptoms and seek treatment if necessary, HealthTracker has the potential to enhance self-efficacy for surgical wound monitoring at home.

Does an electronic pathology ordering system change the volume and pattern of routine testing in hospital? An interrupted time series analysis.

AIMS: Identifying and reducing low-value care is a vital issue in Australia, with pathology test ordering a common focus in this field. This study builds on previous research and aimed to quantify the impact of the implementation of an electronic ordering (e-ordering) system on the volume of pathology testing, compared with manual (paper based) ordering. METHODS: An audit and analysis of pathology test data were conducted, using an interrupted time series design to investigate the impact of the e-ordering system on pathology ordering patterns. All medical and surgical adult inpatients at a tertiary referral hospital in Newcastle, Australia, were included over a 3-year period. RESULTS: Overall, there were no statistically significant differences in the volume of orders due to the implementation of the e-ordering system. There was a slight increase in the aggregated volume (tests per admission and tests per bed day) of tests ordered across the entire study period, reflecting a secular trend. CONCLUSIONS: Despite providing greater visibility and tracking of orders, we conclude that the implementation of an e-ordering system does not, in and of itself, reduce ordering volume. Efforts to identify and reduce low-value care will require intentional effort and specifically designed educational programmes or hard-wired algorithms.

Differentiation of brain and retinal organoids from confluent cultures of pluripotent stem cells connected by nerve-like axonal projections of optic origin.

Advances in the study of neurological conditions have been possible because of pluripotent stem cell technologies and organoids. Studies have described the generation of neural ectoderm-derived retinal and brain structures from pluripotent stem cells. However, the field is still troubled by technical challenges, including high culture costs and variability. Here, we describe a simple and economical protocol that reproducibly gives rise to the neural retina and cortical brain regions from confluent cultures of stem cells. The spontaneously generated cortical organoids are transcriptionally comparable with organoids generated by other methods. Furthermore, these organoids showed spontaneous functional network activity and proteomic analysis confirmed organoids maturity. The generation of retinal and brain organoids in close proximity enabled their mutual isolation. Suspension culture of this complex organoid system demonstrated the formation of nerve-like structures connecting retinal and brain organoids, which might facilitate the investigation of neurological diseases of the eye and brain.

Telomerase promotes formation of a telomere protective complex in cancer cells.

Telomerase is a ribonucleoprotein complex that catalyzes addition of telomeric DNA repeats to maintain telomeres in replicating cells. Here, we demonstrate that the telomerase protein hTERT performs an additional role at telomeres that is independent of telomerase catalytic activity yet essential for telomere integrity and cell proliferation. Short-term depletion of endogenous hTERT reduced the levels of heat shock protein 70 (Hsp70-1) and the telomere protective protein Apollo at telomeres, and induced telomere deprotection and cell cycle arrest, in the absence of telomere shortening. Short-term expression of hTERT promoted colocalization of Hsp70-1 with telomeres and Apollo and reduced numbers of deprotected telomeres, in a manner independent of telomerase catalytic activity. These data reveal a previously unidentified noncanonical function of hTERT that promotes formation of a telomere protective complex containing Hsp70-1 and Apollo and is essential for sustained proliferation of telomerase-positive cancer cells, likely contributing to the known cancer-promoting effects of both hTERT and Hsp70-1.

Synthetic lethality of cytolytic HSV-1 in cancer cells with ATRX and PML deficiency.

Cancers that utilize the alternative lengthening of telomeres (ALT) mechanism for telomere maintenance are often difficult to treat and have a poor prognosis. They are also commonly deficient for expression of ATRX protein, a repressor of ALT activity, and a component of promyelocytic leukemia nuclear bodies (PML NBs) that are required for intrinsic immunity to various viruses. Here, we asked whether ATRX deficiency creates a vulnerability in ALT cancer cells that could be exploited for therapeutic purposes. We showed in a range of cell types that a mutant herpes simplex virus type 1 (HSV-1) lacking ICP0, a protein that degrades PML NB components including ATRX, was ten- to one thousand-fold more effective in infecting ATRX-deficient cells than wild-type ATRX-expressing cells. Infection of co-cultured primary and ATRX-deficient cancer cells revealed that mutant HSV-1 selectively killed ATRX-deficient cells. Sensitivity to mutant HSV-1 infection also correlated inversely with PML protein levels, and we showed that ATRX upregulates PML expression at both the transcriptional and post-transcriptional levels. These data provide a basis for predicting, based on ATRX or PML levels, which tumors will respond to a selective oncolytic herpesvirus.

A Signature of Attention-Elicited Electrocortical Activity Distinguishes Response From Non-Response to the Non-Stimulant Atomoxetine in Children and Adolescents With ADHD.

OBJECTIVE: Atomoxetine has several characteristics that make it an attractive alternative to stimulants for treating ADHD, but there are currently no tests identifying individuals for whom the medication should be a first-line option. METHOD: Within the ADHD Controlled Trial Investigation Of a Non-stimulant (ACTION) study, we examined neuro-cortical activity in 52 youth with ADHD. Baseline event-related potentials (ERP) were compared between those who subsequently responded to 6 weeks of atomoxetine versus those who did not. RESULTS: Responders were distinguished by significantly lower auditory oddball N2 amplitudes than both non-responders and typically developing controls, particularly in the right frontocentral region ( p = .002, Cohen's d = 1.1). Leave-one-out cross validation determined that N2 amplitude in this region was able to accurately predict non-responders with a specificity of 80.8%. There were no P3 differences between responders and non-responders. CONCLUSION: The N2 amplitude is a biomarker that may have utility in predicting response to atomoxetine for youth with ADHD.

Telomere sequence content can be used to determine ALT activity in tumours.

The replicative immortality of human cancer cells is achieved by activation of a telomere maintenance mechanism (TMM). To achieve this, cancer cells utilise either the enzyme telomerase, or the Alternative Lengthening of Telomeres (ALT) pathway. These distinct molecular pathways are incompletely understood with respect to activation and propagation, as well as their associations with clinical outcomes. We have identified significant differences in the telomere repeat composition of tumours that use ALT compared to tumours that do not. We then employed a machine learning approach to stratify tumours according to telomere repeat content with an accuracy of 91.6%. Importantly, this classification approach is applicable across all tumour types. Analysis of pathway mutations that were under-represented in ALT tumours, across 1,075 tumour samples, revealed that the autophagy, cell cycle control of chromosomal replication, and transcriptional regulatory network in embryonic stem cells pathways are involved in the survival of ALT tumours. Overall, our approach demonstrates that telomere sequence content can be used to stratify ALT activity in cancers, and begin to define the molecular pathways involved in ALT activation.

Extensive Proliferation of Human Cancer Cells with Ever-Shorter Telomeres.

Acquisition of replicative immortality is currently regarded as essential for malignant transformation. This is achieved by activating a telomere lengthening mechanism (TLM), either telomerase or alternative lengthening of telomeres, to counter normal telomere attrition. However, a substantial proportion of some cancer types, including glioblastomas, liposarcomas, retinoblastomas, and osteosarcomas, are reportedly TLM-negative. As serial samples of human tumors cannot usually be obtained to monitor telomere length changes, it has previously been impossible to determine whether tumors are truly TLM-deficient, there is a previously unrecognized TLM, or the assay results are false-negative. Here, we show that a subset of high-risk neuroblastomas (with ∼50% 5-year mortality) lacked significant TLM activity. Cancer cells derived from these highly aggressive tumors initially had long telomeres and proliferated for >200 population doublings with ever-shorter telomeres. This indicates that prevention of telomere shortening is not always required for oncogenesis, which has implications for inhibiting TLMs for cancer therapy.

Limiting Thymic Precursor Supply Increases the Risk of Lymphoid Malignancy in Murine X-Linked Severe Combined Immunodeficiency.

In early gene therapy trials for SCID-X1, using γ-retroviral vectors, T cell leukemias developed in a subset of patients secondary to insertional proto-oncogene activation. In contrast, we have reported development of T cell leukemias in SCID-X1 mice following lentivirus-mediated gene therapy independent of insertional mutagenesis. A distinguishing feature in our study was that only a proportion of transplanted γc-deficient progenitors were transduced and therefore competent for reconstitution. We hypothesized that reconstitution of SCID-X1 mice with limiting numbers of hematopoietic progenitors might be a risk factor for lymphoid malignancy. To test this hypothesis, in the absence of transduction, SCID-X1 mice were reconstituted with serially fewer wild-type hematopoietic progenitors. A robust inverse correlation between hematopoietic progenitor cell dose and T-lymphoid malignancy was observed, with earlier disease onset at lower cell doses. Malignancies were of donor origin and carried activating Notch1 mutations. These findings align with emerging evidence that thymocyte self-renewal induced by progenitor deprivation carries an oncogenic risk that is modulated by intra-thymic competition from differentiation-committed cells. Although insertional proto-oncogene activation is required for the development of malignancy in humans, failure of γc-deficient thymocytes to effectively compete with this at-risk cell population may have also contributed to oncogenesis observed in early SCID-X1 trials.

Automated classification and characterization of the mitotic spindle following knockdown of a mitosis-related protein.

BACKGROUND: Cell division (mitosis) results in the equal segregation of chromosomes between two daughter cells. The mitotic spindle plays a pivotal role in chromosome alignment and segregation during metaphase and anaphase. Structural or functional errors of this spindle can cause aneuploidy, a hallmark of many cancers. To investigate if a given protein associates with the mitotic spindle and regulates its assembly, stability, or function, fluorescence microscopy can be performed to determine if disruption of that protein induces phenotypes indicative of spindle dysfunction. Importantly, functional disruption of proteins with specific roles during mitosis can lead to cancer cell death by inducing mitotic insult. However, there is a lack of automated computational tools to detect and quantify the effects of such disruption on spindle integrity. RESULTS: We developed the image analysis software tool MatQuantify, which detects both large-scale and subtle structural changes in the spindle or DNA and can be used to statistically compare the effects of different treatments. MatQuantify can quantify various physical properties extracted from fluorescence microscopy images, such as area, lengths of various components, perimeter, eccentricity, fractal dimension, satellite objects and orientation. It can also measure textual properties including entropy, intensities and the standard deviation of intensities. Using MatQuantify, we studied the effect of knocking down the protein clathrin heavy chain (CHC) on the mitotic spindle. We analysed 217 microscopy images of untreated metaphase cells, 172 images of metaphase cells transfected with small interfering RNAs targeting the luciferase gene (as a negative control), and 230 images of metaphase cells depleted of CHC. Using the quantified data, we trained 23 supervised machine learning classification algorithms. The Support Vector Machine learning algorithm was the most accurate method (accuracy: 85.1%; area under the curve: 0.92) for classifying a spindle image. The Kruskal-Wallis and Tukey-Kramer tests demonstrated that solidity, compactness, eccentricity, extent, mean intensity and number of satellite objects (multipolar spindles) significantly differed between CHC-depleted cells and untreated/luciferase-knockdown cells. CONCLUSION: MatQuantify enables automated quantitative analysis of images of mitotic spindles. Using this tool, researchers can unambiguously test if disruption of a protein-of-interest changes metaphase spindle maintenance and thereby affects mitosis.

Differential response of epiblast stem cells to Nodal and Activin signalling: a paradigm of early endoderm development in the embryo.

Mouse epiblast stem cells (EpiSCs) display temporal differences in the upregulation of Mixl1 expression during the initial steps of in vitro differentiation, which can be correlated with their propensity for endoderm differentiation. EpiSCs that upregulated Mixl1 rapidly during differentiation responded robustly to both Activin A and Nodal in generating foregut endoderm and precursors of pancreatic and hepatic tissues. By contrast, EpiSCs that delayed Mixl1 upregulation responded less effectively to Nodal and showed an overall suboptimal outcome of directed differentiation. The enhancement in endoderm potency in Mixl1-early cells may be accounted for by a rapid exit from the progenitor state and the efficient response to the induction of differentiation by Nodal. EpiSCs that readily differentiate into the endoderm cells are marked by a distinctive expression fingerprint of transforming growth factor (TGF)-ß signalling pathway genes and genes related to the endoderm lineage. Nodal appears to elicit responses that are associated with transition to a mesenchymal phenotype, whereas Activin A promotes gene expression associated with maintenance of an epithelial phenotype. We postulate that the formation of definitive endoderm (DE) in embryoid bodies follows a similar process to germ layer formation from the epiblast, requiring an initial de-epithelialization event and subsequent re-epithelialization. Our results show that priming EpiSCs with the appropriate form of TGF-ß signalling at the formative phase of endoderm differentiation impacts on the further progression into mature DE-derived lineages, and that this is influenced by the initial characteristics of the cell population. Our study also highlights that Activin A, which is commonly used as an in vitro surrogate for Nodal in differentiation protocols, does not elicit the same downstream effects as Nodal, and therefore may not effectively mimic events that take place in the mouse embryo.

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.

The use of soluble protein structures in modeling helical proteins in a layered membrane.

Major advances have been made in the prediction of soluble protein structures, led by the knowledge-based modeling methods that extract useful structural trends from known protein structures and incorporate them into scoring functions. The same cannot be reported for the class of transmembrane proteins, primarily due to the lack of high-resolution structural data for transmembrane proteins, which render many of the knowledge-based method unreliable or invalid. We have developed a method that harnesses the vast structural knowledge available in soluble protein data for use in the modeling of transmembrane proteins. At the core of the method, a set of transmembrane protein decoy sets that allow us to filter and train features recognized from soluble proteins for transmembrane protein modeling into a set of scoring functions. We have demonstrated that structures of soluble proteins can provide significant insight into transmembrane protein structures. A complementary novel two-stage modeling/selection process that mimics the two-stage helical membrane protein folding was developed. Combined with the scoring function, the method was successfully applied to model 5 transmembrane proteins. The root mean square deviations of the predicted models ranged from 5.0 to 8.8 Å to the native structures.

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.

Symmetry of optic nerve head parameters measured by the heidelberg retina tomograph 3 in healthy eyes: the Blue Mountains Eye study.

PURPOSE: To assess the symmetry of optic nerve head parameters measured by the Heidelberg Retina Tomograph 3 (HRT 3) between fellow eyes in a normal elderly population. DESIGN: Cross-sectional population-based study. METHODS: Participants of the Blue Mountains Eye Study 10-year follow-up who did not have optic disc disease, including glaucoma, were included. Optic nerve head parameters measured by HRT 3 were compared between fellow eyes. The normal range of interocular asymmetry (larger disc minus smaller disc) was determined by the 2.5th and 97.5th percentiles. RESULTS: A total of 1276 eligible participants had HRT scans of both eyes. HRT measurements in right eyes differed slightly in rim steepness and rim volume from those in left eyes (P < .05). The 2.5th and 97.5th percentile of interocular asymmetry limits were -0.41 and 0.45 for cup-to-disc ratio and -0.19 and 0.22 for cup-to-disc area ratio, respectively. The highest interocular correlation was found in disc area and cup area (r ranged from 0.74-0.76), whereas mean cup depth, cup volume, and retinal nerve fiber layer thickness had the poorest correlation (r ≤ 0.07). Greater optic disc area asymmetry was associated with a larger interocular difference in the other optic nerve head parameters. CONCLUSIONS: There was minimal interocular difference and substantial interocular correlation in optic nerve head parameters measured by HRT 3. Interocular asymmetry greater than 0.2 for cup-to-disc area ratio was considered outside the normal range.

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.

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.

Influence of parental history of hypertension on screen time and physical activity in young offspring.

OBJECTIVE: Epidemiological data on the relationship between parental hypertension and lifestyle factors among children are limited. We assessed the associations between positive parental history of hypertension with a range of indicators of sedentariness (television viewing, computer and videogame usage) and physical activity (outdoor and indoor activity) among prepubertal children. METHODS: Six-year-old (1765 of 2238 eligible) students from a random cluster sample of 34 Sydney schools were examined. Parents completed questionnaires about their medical conditions and the child's activities. If the biological mother and/or father had hypertension, then this was classified as positive parental history of hypertension. RESULTS: Parents of 160 (9.2%) children gave a positive family history of hypertension. After adjusting for age, sex, ethnicity, parental education and employment and exposure to passive smoking, children with, compared with those without, a family history of hypertension were more likely to spend above the median time (hours/day) watching television and playing videogames [odds ratio (OR) 1.41, 95% confidence interval (CI) 1.02-1.96; OR 1.52, CI 1.12-2.06, respectively]. The offspring of hypertensive parents were more likely to spend above the median time in total physical activity (OR 1.67, 95% CI 1.23-2.27). Maternal (but not paternal) hypertension was associated with increased time spent watching television (P = 0.03) and in outdoor activity (P = 0.01). CONCLUSION: Parental hypertension influences the time that prepubertal offspring spend in both active and sedentary pursuits. These findings highlight potential factors that could be addressed in the development of cardiovascular disease-preventive measures starting early in life among the offspring of hypertensive parents.

Exposure to workplace noise and the risk of cardiovascular disease events and mortality among older adults.

BACKGROUND: We aimed to examine whether cross-sectional (prevalence) and longitudinal relationships (5-year incidence and 10-year mortality) exist between workplace noise exposure and cardiovascular diseases (CVD). METHODS: 2942 participants aged 55+years of the Blue Mountains Eye Study, Australia (1997-9 and 2002-4). Participants self-reported workplace noise exposure, hearing protector use and physician diagnosed CVD. CVD deaths were confirmed using the Australian National Death Index. RESULTS: 133 and 937 participants self-reported workplace noise exposure, and use or non-use of hearing protection devices, respectively. After multivariate adjustment, those who did not use hearing protection devices were 53% and 75% more likely to have prevalent CVD and angina, respectively, compared to those never exposed to workplace noise. Exposure to severe workplace noise for less than 1 to 5 years versus no exposure was associated with incident stroke OR 3.44 (95% CI 1.11-10.63). The mortality rate of CVD was 0.94% per year in people unexposed to workplace noise. Participants reporting less than 1 to 5 years versus those with no workplace noise exposure had a higher risk of CVD mortality, hazard ratio, HR, 1.60 (95% CI 1.10-2.33). DISCUSSION: These data highlight the public health impact of workplace noise exposure on the vascular health of older adults.

Parental history of hypertension is associated with narrower retinal arteriolar caliber in young girls.

We aimed to assess the associations between parental history of hypertension and indicators of cardiovascular risk (retinal vessel diameter, presence of obesity, and elevated blood pressure) in prepubertal children. There were 1739 (77.7% of those eligible) 6-year-old students (863 girls and 876 boys) who were examined from a random cluster sample of 34 Sydney schools. Parents completed questionnaires about their medical conditions, including whether they have/had hypertension. Retinal images were taken with a digital fundus camera, and retinal vessel caliber was quantified using computer software. Anthropometric (height, weight, percentage of body fat, and body mass index) and blood pressure measures were collected. There were 160 children (9.2%) with a positive parental history of hypertension (either biological mother and/or father). Children with a positive versus negative parental history of hypertension had significantly higher body mass index (16.8 versus 16.5 kg/m(2); P=0.04) and systolic blood pressure (101.3 versus 99.8 mm Hg; P=0.01). Girls with positive versus negative parental history of hypertension had significantly higher diastolic blood pressure (≈3.1 mm Hg; P=0.01) and narrower retinal arteriolar caliber (≈4.3 µm; P=0.0004). Positive parental history of hypertension was not associated with mean retinal vascular caliber among boys. We show that a positive parental history of hypertension in healthy prepubertal girls, but not boys, is associated with narrower retinal arteriolar vessels, likely conveying a predisposition to develop hypertension later in life. These findings may indicate the need for cardiovascular disease prevention measures starting early in life among offspring of hypertensive parents.