Long-term occupational exposures on disability-free survival and mortality in older adults.

BACKGROUND: The impact of long-term occupational exposures on health in older adults is increasingly relevant as populations age. To date, no studies have reported their impact on survival free of disability in older adults. AIMS: We aimed to investigate the association between long-term occupational exposure and disability-free survival (DFS), all-cause mortality and cause-specific mortality in initially healthy older adults. METHODS: We analysed data from 12 215 healthy participants in the ASPirin in Reducing Events in the Elderly (ASPREE) study whose mean age was 75 years. Their work history was collated with the 'ALOHA-plus JEM' (Job Exposure Matrix) to assign occupational exposures. The primary endpoint, DFS, was a composite measure of death, dementia or persistent physical disability. The secondary endpoint, mortality, was classified according to the underlying cause. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals, adjusted for confounders. RESULTS: A total of 1835 individuals reached the DFS endpoint during the median 4.7 years follow-up period. Both ever-high and cumulative exposure to all dusts and all pesticides during a person's working years were associated with reduced DFS. Compared to no exposure, men with high exposure to dusts and pesticides had a reduced DFS. Neither of these exposures were significantly associated with all-cause mortality. Men with high occupational exposure to solvents and women exposed to dusts experienced higher all-cause and cancer-related mortality. CONCLUSIONS: Long-term occupational exposure to all dusts and pesticides was associated with a reduced DFS and increased mortality in community-dwelling healthy older adults.

Poor appetite and overeating reported by adults in Australia during the coronavirus-19 disease pandemic: a population-based study.

OBJECTIVE: As a result of the coronavirus-19 disease (COVID-19) pandemic, Australia adopted emergency measures on 22 March 2020. This study reports the effect of the COVID-19 lockdown on appetite and overeating in Australian adults during the first month of emergency measures. DESIGN: This study reports analysis of data from the population-based, self-completed survey. The main outcome measure was an item from the Patient Health Questionnaire 9 asking: 'Over the past 2 weeks, how often have you been bothered by poor appetite or overeating?'. Data on sociodemographic factors, symptoms of anxiety and depression, and the impact of COVID-19 and lockdown were also collected. Multivariable logistic regression was used to examine associations with poor appetite or overeating. SETTING: An anonymous online survey available from 3 April to 2 May 2020. PARTICIPANTS: A total of 13 829 Australian residents aged 18 years or over. RESULTS: The weighted prevalence of being bothered by poor appetite or overeating in the past 2 weeks was 53·6 %, with 11·6 % (95 % CI 10·6, 12·6) of the cohort reporting poor appetite or overeating nearly every day. High levels of anxiety, concern about contracting COVID-19, being in lockdown with children and reporting a severe impact of the lockdown were associated with increased odds of poor appetite or overeating. CONCLUSIONS: Given the widespread prevalence of being bothered by poor appetite or overeating, universal public health interventions to address emotion-focused or situational eating during periods of lockdown may be appropriate.

No difference in variability of unique hue selections and binary hue selections.

If unique hues have special status in phenomenological experience as perceptually pure, it seems reasonable to assume that they are represented more precisely by the visual system than are other colors. Following the method of Malkoc et al. (J. Opt. Soc. Am. A22, 2154 [2005]), we gathered unique and binary hue selections from 50 subjects. For these subjects we repeated the measurements in two separate sessions, allowing us to measure test-retest reliabilities (0.52≤ρ≤0.78; p≪0.01). We quantified the within-individual variability for selections of each hue. Adjusting for the differences in variability intrinsic to different regions of chromaticity space, we compared the within-individual variability for unique hues to that for binary hues. Surprisingly, we found that selections of unique hues did not show consistently lower variability than selections of binary hues. We repeated hue measurements in a single session for an independent sample of 58 subjects, using a different relative scaling of the cardinal axes of MacLeod-Boynton chromaticity space. Again, we found no consistent difference in adjusted within-individual variability for selections of unique and binary hues. Our finding does not depend on the particular scaling chosen for the Y axis of MacLeod-Boynton chromaticity space.

Counterphase modulation flicker photometry: phenotypic and genotypic associations.

The OSCAR test, a clinical device that uses counterphase flicker photometry, is believed to be sensitive to the relative numbers of long-wavelength and middle-wavelength cones in the retina, as well as to individual variations in the spectral positions of the photopigments. As part of a population study of individual variations in perception, we obtained OSCAR settings from 1058 participants. We report the distribution characteristics for this cohort. A randomly selected subset of participants was tested twice at an interval of at least one week: the test-retest reliability (Spearman's rho) was 0.80. In a whole-genome association analysis we found a provisional association with a single nucleotide polymorphism (rs16844995). This marker is close to the gene RXRG, which encodes a nuclear receptor, retinoid X receptor γ. This nuclear receptor is already known to have a role in the differentiation of cones during the development of the eye, and we suggest that polymorphisms in or close to RXRG influence the relative probability with which long-wave and middle-wave opsin genes are expressed in human cones.

Correlates of Meal Skipping in Community Dwelling Older Adults: A Cross-Sectional Study.

In this cross-sectional analysis of 10,071 community dwelling adults aged ≥70 years, we examined factors associated with meal skipping (self-reported) using multivariable logistic regression. Prevalence of meal skipping in this study was 19.5%. The adjusted odds (aOR [95%CI]) of meal skipping were lower in those 85+ years (vs. 70-74.9 years, 0.56 [0.45-0.70]), and in those in regional areas (vs. urban area, 0.81 [0.72-0.92]). Higher odds of meal skipping were observed for those living alone (vs. living with someone, 1.84 [1.64-2.05]), current smokers (vs. non-smokers, 2.07 [1.54-2.80]), consumers of high amounts of alcohol (vs. abstainers 1.93 [1.35-2.75]), those with poor oral health (vs. excellent oral health, 1.71 [1.07 -2.73]) diabetes (vs. not 1.26 [1.06-1.50]), or frailty (vs. not, 1.63 [1.09-2.43]). This study identified socio-demographic, social, behavioural and biomedical correlates of meal skipping in later life, which may assist in targeting interventions to address meal skipping.

Self-Reported Early and Later Life Weight and the Risk of All-Cause Mortality in Older Adults.

OBJECTIVES: The extent to which body weight in early adulthood is associated with late-life mortality risk is unclear. This study aimed to determine the association between body mass index (BMI) in early adulthood (at 18 years of age) and older age (70 years and over), and the risk of mortality in later life. DESIGN: Secondary analysis of the ASPREE Longitudinal Study of Older Persons (ALSOP). SETTING, PARTICIPANTS: Data were from 14,853 relatively healthy community-dwelling Australians aged ≥ 70 years when enrolled in the study. MEASUREMENTS: Self-reported weight at age ≥ 70 years and recalled weight at age 18 years were collected at ALSOP study baseline. Height was measured with a stadiometer and was used for calculation of BMI at both timepoints. BMI at each timepoint was defined as: underweight, normal weight, overweight and obese. Individuals were categorised into one of five 'lifetime' BMI groups: normal weight (BMI between 18.5 and 24.9 at both times), overweight (25.0-29.9 at either or both times), obesity to non-obese (≥30.0 at age 18 and <30.0 ≥ 70 years), non-obese to obesity (<30.0 at age 18 and ≥30.0 at age ≥ 70 years), and early and later life obesity (≥30.0 at both times). RESULTS: During a median 4.7 years follow-up, 715 deaths occurred. Obesity at 18 years, but not in older age (p=0.44), was significantly associated with the risk of mortality in later life, even after accounting for current health status (HR: 2.35, 95% CI: 1.53-3.58, p<0.001). Compared with participants with normal BMI at both time points, being obese at both time points was associated with increased mortality risk (HR=1.99, 95% CI: 1.04-3.81, p=0.03), and the risk was even greater for individuals who were obese at 18 years but were no longer obese in older age (HR=2.92, 95% CI: 1.65-5.16, p<0.001), in fully adjusted models. Participants who were normal weight at 18 years and were obese in later life, did not have an increased mortality risk (p=0.78). CONCLUSIONS: Obesity in early adulthood, and obesity in both early and later life, were associated with increased mortality risk in later life. This highlights the importance of preventing obesity in early adulthood and maintaining a normal weight over an adult lifespan.

Self-reported oral health status, edentulism and all-cause mortality risk in 12 809 Australian older adults: a prospective cohort study.

OBJECTIVE: To investigate the association between oral health status and all-cause mortality in older adults using prospective cohort study design. SETTING AND PARTICIPANTS: In total, 12 809 adults aged ≥70 years (54.3% females) were participants of the ASPREE Longitudinal Study of Older Persons (ALSOP). METHODS: Participants self-reported the presence of natural teeth and oral health status. The association of self-reported oral health, edentulism and the integrative measure of the two with all-cause mortality were explored using the Cox-regression models adjusted for age, gender, socio-economic status, health-related behaviours, weight status, aspirin and polypharmacy. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. RESULTS: In total, 22.2% of participants reported edentulism and 13.8% had fair/poor oral health. After adjustment for confounders, risk of all-cause mortality was higher among those with edentulism (vs. no edentulism) HR (95% CI) 1.43 (1.18, 1.73); and those with edentulism and reporting poor/fair oral health HR (95% CI) 1.69 (1.02, 2.82), or with no edentulism but reporting poor/fair oral health HR (95% CI) 1.46 (1.19-1.80) vs. no edentulism and reporting good/very good/excellent oral health. No association was observed between self-reported oral health alone and all-cause mortality. CONCLUSIONS: The risk of all-cause mortality was 69% higher among older adults reporting both edentulism and poor/fair oral health compared with those with teeth and more favourable self-reported oral health. © 2023 Australian Dental Association.

Simian sarcoma virus--transformed cells secrete a mitogen identical to platelet-derived growth factor.

Normal rat kidney (NRK) cells transformed by simian sarcoma virus (SSV) release into the culture medium a biologically active mitogen with properties identical to those of human platelet-derived growth factor (PDGF). Like PDGF, the growth factor derived from SSV-NRK cells was shown to be stable to heat and sensitive to reducing agents. It was capable of inhibiting binding of labeled PDGF to the receptor on human fibroblasts. It also stimulated the phosphorylation of the same membrane protein (185 kilodaltons) in isolated plasma membranes from human fibroblasts. Immunoprecipitation of metabolically labeled proteins released by SSV-NRK cells showed that a 34-kilodalton protein was specifically precipitated by antiserum to PDGF. Upon reduction, this protein had a molecular size of 17 kilodaltons. PDGF has been shown to consist of two 14- to 18-kilodalton proteins linked by disulfide bonds.

Detection of c-sis transcripts and synthesis of PDGF-like proteins by human osteosarcoma cells.

Platelet-derived growth factor (PDGF) has been previously shown to be homologous to the transforming gene of simian sarcoma virus (v-sis), and inappropriate expression of the cellular counterpart of the v-sis gene (c-sis) has been implicated in the generation of mesenchymal tumors. The U-2 OS human osteosarcoma line was shown to contain multiple c-sis transcripts. Immunoprecipitation experiments with antiserum to PDGF identified a variety of polypeptides ranging in size from 18,000 to 165,000 daltons that were immunoprecipitated specifically from U-2 OS cell extracts. The osteosarcoma also was shown to secrete a 29,000-dalton protein having the serological and structural characteristics of PDGF.

Inertia or inaction? Blood pressure management and cardiovascular risk in diabetes.

1. Diabetes is a significant risk factor for cardiovascular disease (CVD), but the presence of comorbidities, such as hypertension, markedly increases CVD risk. The aim of the present study was to determine the effectiveness of hypertension management in patients with diabetes. 2. The cvTRAC Study was a cross-sectional study of CVD risk factors in primary care practices across Australia. General medical practitioners enrolled patients they considered to be at increased risk of CVD and reported on cardiovascular disease history, CVD risk factor levels and current therapy. 3. In all, 9857 men and 8332 women with diabetes participated in the study, with > 85% having at least two CVD risk factors in addition to diabetes and 68% having a history of hypertension. Lost therapeutic benefit in diabetes patients with hypertension was seen in those who were failing to meet targets on antihypertensive drug therapy (therapeutic inertia: > 73% of the hypertensive cohort), with a smaller proportion accounted for by those who met prescribing guidelines but were not being treated pharmacologically (treatment gap: 5.4% of the hypertensive cohort). Lack of compliance with lifestyle guidelines was estimated to account for over 8% of those not meeting blood pressure targets. Age (odds ratio (OR) 0.983, 95% confidence interval (CI) 0.980-0.986; P < 0.001), compliance with physical activity guidelines (OR 1.219, 95% CI 1.088-1.366; P = 0.001) and compliance with dietary guidelines (OR 1.298, 95% CI 1.188-1.420; P < 0.001) were independent predictors of target blood pressure attainment in the diabetic population. 4. Deficiencies in pharmacological and lifestyle-related therapeutic strategies contribute to suboptimal hypertension management in diabetes. Therapeutic inertia is a greater contributor to lost therapeutic benefit than treatment gap in this population.

An exploratory factor analysis of visual performance in a large population.

A factor analysis was performed on 25 visual and auditory performance measures from 1060 participants. The results revealed evidence both for a factor relating to general perceptual performance, and for eight independent factors that relate to particular perceptual skills. In an unrotated PCA, the general factor for perceptual performance accounted for 19.9% of the total variance in the 25 performance measures. Following varimax rotation, 8 consistent factors were identified, which appear to relate to (1) sensitivity to medium and high spatial frequencies, (2) auditory perceptual ability (3) oculomotor speed, (4) oculomotor control, (5) contrast sensitivity at low spatial frequencies, (6) stereo acuity, (7) letter recognition, and (8) flicker sensitivity. The results of a hierarchical cluster analysis were consistent with our rotated factor solution. We also report correlations between the eight performance factors and other (non-performance) measures of perception, demographic and anatomical measures, and questionnaire items probing other psychological variables.

Evidence that a human osteosarcoma cell line which secretes a mitogen similar to platelet-derived growth factor requires growth factors present in platelet-poor plasma.

A human osteosarcoma-derived cell line, 2T, grows almost as well in medium supplemented with platelet-poor plasma (PPP) as it does in medium containing fetal bovine serum. Human diploid fibroblasts, in contrast, will not grow in medium containing PPP unless human platelet-derived growth factor (PDGF) is added. PPP treated with carboxymethyl-Sephadex at pH 7.4 was able to support 2T cell proliferation, although at a reduced rate compared to untreated PPP. Addition of PDGF to carboxymethyl-Sephadex-treated PPP did not restore the growth rate. However, insulin-like growth factor isolated from human plasma did partially restore the activity of carboxy-methyl-Sephadex-treated PPP. Medium conditioned by 2T cells was mitogenic for quiescent BALB/c3T3 cells and human diploid fibroblasts. Antiserum to human PDGF blocked the mitogenic activity of the conditioned medium. Partial characterization confirmed the biochemical similarity to PDGF. The data are consistent with the hypothesis that these osteosarcoma-derived cells have growth factor requirements similar to those of normal mesenchymal cells but are able to overcome the normal growth limitations by autocrine secretion of PDGF-like mitogens.

Evidence for functional platelet-derived growth factor receptors on MG-63 human osteosarcoma cells.

The specific interaction of platelet-derived growth factor (PDGF) with the human osteosarcoma cell line MG-63 was studied. Scatchard analysis of 125I-PDGF binding to MG-63 cells indicated there were 32,000 specific PDGF-binding sites per cell with a Kd of 2.4 X 10(-11) M. Unlabeled PDGF blocked the specific binding of labeled PDGF to MG-63 cells at concentrations greater than 1 ng/ml. When assayed for phosphorylation of MG-63 membrane vesicles, PDGF was shown to stimulate a dose-dependent phosphorylation of a protein (phosphoprotein with a molecular weight of 185,000) which was stable in 1 M NaOH. In the absence of PDGF, a prominent alkali-stable phosphoprotein with a molecular weight of 116,000 was noted. PDGF also stimulated a dose-dependent increase in [3H]aminoisobutyric acid uptake, [3H]thymidine incorporation, and cell proliferation. When tested for secretion of PDGF-like factors, the mitogenic activity of MG-63-conditioned serum-free medium was not blocked by anti-PDGF antiserum. Concentrated MG-63-conditioned medium did not compete with 125I-PDGF for specific receptor sites on diploid fibroblasts. Therefore, MG-63 osteosarcoma cells have functional PDGF receptors and do not secrete PDGF-like mitogens.

Potential intracellular target proteins of the anticarcinogenic Bowman Birk protease inhibitor identified by affinity chromatography.

The soybean-derived Bowman Birk inhibitor (BBI) has been shown to inhibit carcinogenesis in both in vitro and in vivo model systems. In the present study, we have utilized a BBI affinity column to determine whether cellular enzymes, present in C3H/10T1/2 cells, specifically interact with this inhibitor. Using this technique, we have identified three proteins with masses of about 70, 60, and 50 kilodaltons. Cell fractionation experiments demonstrate that the 60- and 50-kilodalton proteins are present in the 10,000 x g pellet (lysosomal/golgi fraction) of C3H/10T1/2 cell homogenates. We have also identified two proteins with masses of 60 and 50 kilodaltons which bind to the BBI affinity column in fibroblasts from patients having Bloom syndrome. BBI as well as several other protease inhibitors has been shown previously to reduce the frequency of spontaneous chromosomal aberrations in these cells. Our results indicate that the 50- and 60-kilodalton proteins we have identified by affinity chromatography are present in both mouse and human cells and further suggest that these proteins are potential intracellular targets of the BBI in these cells.

Kinetic analysis of papaya proteinase omega.

Papaya proteinase omega (pp omega) has been purified from dried latex both by immunoaffinity and traditional methods. Kinetic analysis revealed that (1), the pp omega-catalysed hydrolysis of N-benzoyl-L-arginine p-nitroanilide (BApNA) has a lower specificity (kcat/Km) than the same reaction catalysed by papain; (2), the pp omega-catalysed hydrolysis of a tripeptide substrate having phenylalanine at the second position (S2-site) showed a more similar specificity to that catalysed by papain; (3), the significant difference between the two enzymes is that steady state kinetics with both L-BApNA and a tripeptide enables the identification in pp omega of other ionizations affecting binding. The active sites of papain and pp omega can therefore be distinguished by pH-dependence of kcat/Km.

Low plasma vitamin E levels in major depression: diet or disease?

OBJECTIVE: Levels of vitamin E have been reported to be lower in patients suffering major depression, but whether this is due to inadequate dietary intake or the pathophysiology of depression is not known, and was the subject of the present study. SETTING: Wollongong, Australia. METHODS: Plasma vitamin E (alpha-tocopherol) was measured in 49 adults with major depression, age (mean+/-s.d.): 47+/-12 y. In a subset (n=19) usual dietary intake of vitamin E was determined by diet history. RESULTS: Subjects had significantly lower plasma alpha-tocopherol (4.71+/-0.13 mumol/mmol cholesterol) than has previously been reported for healthy Australians, and plasma alpha-tocopherol was inversely related to depression score (by Beck Depression Inventory) (r=-0.367, P<0.009). Diet analysis indicated that 89% of subjects met or exceeded the recommended intake for vitamin E, and dietary intake was not related to plasma alpha-tocopherol level in this subset. CONCLUSION: These findings suggest that plasma levels of alpha-tocopherol are lower in depression, but this is not likely to be the result of inability to meet recommended dietary intake. .

A population study of binocular function.

As part of a genome-wide association study (GWAS) of perceptual traits in healthy adults, we measured stereo acuity, the duration of alternative percepts in binocular rivalry and the extent of dichoptic masking in 1060 participants. We present the distributions of the measures, the correlations between measures, and their relationships to other psychophysical traits. We report sex differences, and correlations with age, interpupillary distance, eye dominance, phorias, visual acuity and personality. The GWAS, using data from 988 participants, yielded one genetic association that passed a permutation test for significance: The variant rs1022907 in the gene VTI1A was associated with self-reported ability to see autostereograms. We list a number of other suggestive genetic associations (p<10(-5)).

Autoaugmentation gastrocystoplasty and demucosalized gastrocystoplasty in a sheep model.

OBJECTIVES: To compare the normal sheep bladder at 6 and 12 months with bladders subjected to either an autoaugmentation gastrocystoplasty or a clam demucosalized gastrocystoplasty. METHODS: Twenty male lambs aged between 8 and 10 weeks had an autoaugmentation gastrocystoplasty in which de-epithelialized stomach muscle was added to an intact urothelium. The functional, radiologic, and histologic outcomes were compared with 11 animals who underwent a clam demucosalized gastrocystoplasty and 14 control animals. A total of 18 operated animals had a urodynamic study at 6 months and 9 at 12 months. RESULTS: The average bladder volume for the autoaugmentation gastrocystoplasty group at 12 months was greater than that of the control group (401 +/- 120 mL versus 205 +/- 77 mL). The demucosalized clam bladders had been less effectively enlarged (286 +/- 77 mL). The compliance values for autoaugmentation gastrocystoplasty animals were 14.7 +/- 11.3 mL/cm water (H2O) compared with 9.0 +/- 4.8 mL/cm H2O in the demucosalized gastrocystoplasty group, and 9.1 +/- 3.7 mL/cm H2O for the control animals. CONCLUSIONS: The addition of the autoaugmentation procedure improves the prospect of enlarging the normal sheep bladder when using demucosalized gastric muscle.

Zonisamide as a neuroprotective agent in an adult gerbil model of global forebrain ischemia: a histological, in vivo microdialysis and behavioral study.

Brief periods of global cerebral ischemia are known to produce characteristic patterns of neuronal injury both in human studies and in experimental animal models. Ischemic damage to vulnerable areas such as the CA1 sector of the hippocampus is thought to result from excitotoxic amino acid neurotransmission. The objective of this study was to determine the ability of a novel sodium channel blocking compound, zonisamide, to reduce neuronal damage by preventing the ischemia-associated accumulation of extracellular glutamate. Using a gerbil model, animals were subjected to 5 min ischemic insults. Both pre- and post-ischemic drug administration (zonisamide 150 mg/kg) were studied. Histological brain sections were prepared using a silver stain at 7 and 28 days post ischemia. The animals sacrificed at 28 days also underwent behavioral testing using a modified Morris water maze. In vivo microdialysis was performed on a separate group of animals in order to determine the patterns of ischemia-induced glutamate accumulation in the CA1 sector of the hippocampus. Pyramidal cell damage scores in the CA1 region of the hippocampus were significantly reduced in animals pre-treated with zonisamide compared to saline-treated controls, both at 7 days (drug pre-treated: 0.812 +/- 0.28, n = 8; controls: 1.625 +/- 0.24, n = 8; *P < 0.05) and 28 (drug pre-treated: 0.833 +/- 0.22, n = 12; controls: 1.955 +/- 0.26, n = 11; **P < 0.01) days post ischemia. However, animals receiving zonisamide post-treatment did not display significant differences from controls. Behavioral studies also showed significant preservation of function in drug-treated animals. Microdialysis studies confirmed a reduction in glutamate release in drug-treated animals compared to saline-treated controls. Our data suggest that zonisamide is effective in reducing neuronal damage by a mechanism involving decreased ischemia-induced extracellular glutamate accumulation and interruption of excitotoxic pathways.

Drug delivery systems for cyclosporine: achievements and complications.

The review deals with the preparation, properties, and analysis of different kinds of cyclosporine delivery systems, such as solid formulations, liposomes, emulsions and microemulsions and targeted cyclosporine formulations. The review points out a key role of delivery systems in increasing the therapeutic effectiveness of cyclosporine. Comparative studies of the prior marketed formulation, Sandimmune, with a new microemulsion formulation, Neoral, are discussed including some data on clinical development of Neoral.