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.

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.

An in vitro study of silicone migration from intravenous fluid tubing.

Migration of particulate matter from plastic tubing and solid plastic implants has been documented in a number of studies, including some with the use of cardiac bypass, haemodialysis, and pump-assisted intravenous infusions. In order to ascertain whether silicone embolisation occurs when children have an Ivac 560 pump-assisted IV infusion, we passed 180 ml of pumped fluid through a microfilter and compared the scanning electron micrographs of those filters with unused filters and with others through which a similar volume had been passed without using the pump. The particles on the filters were analysed for their elemental content using energy-dispersive X-ray analysis. In addition, the appearance of the silicone tubing used in the pump over 3 and 72 h was assessed and compared to that of flow-only and unused tubing. More particles were found on the microfilter when fluid had been delivered via the pump than on those through which non-pumped fluid had passed or that were unused. Elemental silicon-containing particles were only found on the filter when a pump had been attached to the IV line. The flow-only and unused tubing were found to have adherent particles on the inner surface that were not seen once the tubing had been used for 3 h in the Ivac 560 pump. Also, after 72 h use, the silicone tubing had a deformed inner layer. The clinical significance of these findings is yet to be determined, but it does appear that silicone embolisation occurs during pump-assisted infusions in children.

Long-term histological response to subcutaneously injected Polytef and Bioplastique in a rat model.

OBJECTIVE: To compare the long-term carcinogenic effect of Polytef and Bioplastique in the subcutaneous space of the rat. MATERIALS AND METHODS: One hundred Sprague Dawley rats received a subcutaneous injection of one of two particulate plastics; subsequently 48 of those injected with Polytef paste containing polytetrafluoroethylene, 48 injected with silicone containing Bioplastique, and 48 control animals were available for assessment. Animals were killed when they became unwell, developed a tumour, or were 2 years of age. The injection site and all major organs and tumours were examined histologically. RESULTS: One or more tumours were found in 30 Polytef-injected rats, 34 Bioplastique-injected animals and 36 of the controls. The majority of the tumours were breast and pituitary adenomas with a similar incidence in each group. No tumours were found at the injection site of the Polytef-injected animals. Four poorly differentiated sarcomas were found on the back of Bioplastique-injected rats; three were intimately associated with silicone particles, whereas the fourth was separate from the injection site. CONCLUSION: This study would suggest that the carcinogenic risk from injectable plastics is low, but further work should be conducted with the larger particles, to ensure that their use in humans is safe.

Late follow up of autoaugmentation omentocystoplasty in a sheep model.

Four male sheep were studied 12 months after an autoaugmentation omentocystoplasty (AAOC). The omentum was lined with urothelium, but continued inflammation and/or fibrosis were seen within the subepithelial tissues associated with a failure to achieve enlargement of the bladder when compared with a control group of six animals. The median compliance value was 5.9 mL/cm H2O for the AAOC animals and 9.8 mL/cm H2O for the control group, indicating that no improvement in bladder dynamic function had been achieved with the AAOC in sheep, and no significant improvement had occurred with time when the results were compared with those seen 6 months earlier.

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.

Factors effecting the thermostability of cysteine proteinases from Carica papaya.

Thermal denaturation of four Carica papaya cysteine proteinases (papain, chymopapain, papaya proteinases 3 and 4) was studied as a function of pH using high-sensitivity differential scanning calorimetry. The ratios of calorimetric enthalpy to Van't Hoff enthalpy suggest that, for all these proteins, denaturation occurs as a non two state process, via an intermediate structure. Differences in the thermal stabilities of the proteinases; chymopapain > papaya proteinase 3 > papain > papaya proteinase 4, were correlated to their amino acid sequence to explain the observations in terms of mobility and specific residue mutation. Three-dimensional structures of papain and papaya proteinase 3 were similarly used to illustrate the influence of atomic mobility on stability.

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.

Monoclonal antibodies to the two most basic papaya proteinases.

The proteinases from Carica papaya include papain, isoenzymes of chymopapain and two proteinases A and B distinguished by their unusually high pI. The identity of one of the most basic proteinases has been questioned. The present report describes the preparation and characterisation of two monoclonal antibodies that react specifically with papaya proteinases A and B respectively and a third that identifies a common structural feature found in papain and proteinase A.

Identification of processing events in the synthesis of platelet-derived growth factor-like proteins by human osteosarcoma cells.

The human osteosarcoma-derived cell line U-2 OS expresses c-sis mRNA and synthesizes platelet-derived growth factor (PDGF)-like proteins. Pulse-chase experiments indicate that proteins of 23 kDa and 180 kDa are synthesized first. The 23-kDa protein undergoes dimerization and proteolysis, giving rise to the 30-kDa dimeric protein secreted by the cells. The 180-kDa protein is proteolytically cleaved in a complex series of steps that give rise to several intracellular species. It is also the likely precursor of high molecular mass PDGF-like or PDGF-associated proteins secreted by these cells. The processing and secretion of the 180-kDa protein is slower than that of the 23-kDa protein. Subcellular fractionation and studies with the antibiotic monensin indicate that the processing events occur in the Golgi-endoplasmic reticulum compartment of U-2 OS cells.

Platelet-derived growth factor stimulates rapid polyphosphoinositide breakdown in fetal human fibroblasts.

The addition of human platelet-derived growth factor (PDGF) to confluent, quiescent cultures of human diploid fibroblasts induced the rapid breakdown of cellular polyphosphoinositides. The levels of 32P-labeled phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP), and phosphatidylinositol (PI) decreased by 30 to 40% within 1 min after exposure of the cells to PDGF. The levels of PIP and PIP2 returned to their initial values within 3 and 10 min, respectively, after PDGF addition. The level of PI continued to increase after it had returned to control values and was up threefold within 30 min after PDGF addition. In cells prelabeled with myo-[3H]inositol PDGF caused an eightfold increase in the levels of inositol trisphosphate (IP3) within 2 min. Lesser increases, twofold and 1.3-fold, respectively, were seen in levels of inositol bisphosphate (IP2) and inositol monophosphate (IP). Within 10 min after PDGF addition the levels of all three inositol phosphates had decreased to control values. The levels of IP3 measured 2 min after PDGF addition depended on the PDGF concentration and were maximal at 5-10 ng/ml of PDGF. Similar concentrations of PDGF stimulate maximal cell growth and DNA synthesis in these cells.

Demonstration of receptors for a PDGF-like mitogen on human osteosarcoma cells.

U-2 OS human osteosarcoma cells synthesize, process and secrete a platelet-derived growth factor (PDGF)-like mitogen. Incubation of these cells with 1 mM suramin unmasks PDGF receptor sites which are normally occupied or down regulated by the secreted endogenous PDGF-like mitogen. Partially purified preparations of metabolically labelled U-2 OS conditioned medium binds to U-2 OS cells and binding is inhibited by excess PDGF. These findings suggest that U-2 OS cells are capable of autocrine stimulation.

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.

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.

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.

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.

Human platelet-derived growth factor stimulates amino acid transport and protein synthesis by human diploid fibroblasts in plasma-free media.

Purified human platelet-derived growth factor (PDGF) induces an increase in amino acid uptake via system A in quiescent human diploid fibroblasts. Cells must be exposed to PDGF for 45 min to obtain maximum transport stimulation. Transport stimulation requires protein synthesis. Transient exposure to PDGF, alone, in the absence of plasma components can stimulate transport. Acid-insoluble [3H]leucine incorporation is also stimulated by PDGF treatment, and this event also does not require the presence of plasma components. Finally, antiserum to PDGF that blocks PDGF-stimulated DNA synthesis in these cells also blocks PDGF-stimulated amino acid uptake and protein synthesis. Increased amino acid uptake and protein synthesis that occur soon after addition of fresh serum to quiescent cells can be attributed to the action of PDGF acting alone and should be useful as markers for the investigation of early cellular events caused by PDGF.

Growth factors and regulation of cell growth.

A new class of polypeptide hormones known collectively as growth factors has been identified. These polypeptides are able to stimulate DNA synthesis and mitosis of cells cultured in vitro. Growth factors have been isolated from several sources, including platelets, submaxillary glands, pituitary, brain, and medium conditioned by cells grown in vitro. Growth factors appear to behave like classic polypeptide hormones. In the cases of epidermal growth factor and nerve growth factor, specific cell membrane receptors have been studied in detail and partially purified. Platelet-derived growth factor and somatomedin-C interact synergistically and apparently, sequentially to promote cell proliferation in vitro. These studies suggest that cell proliferation is controlled by a synergistic interaction among several growth factors and, perhaps, other hormones. Several in vivo roles for growth factors and a role for tumor-cell-derived growth factors in neoplasia have been suggested.