Associations between serum glucose, insulin, insulin resistance and the risk of incident primary liver cancer or chronic liver disease mortality: a nested case-control study.

BACKGROUND: To evaluate the associations between pre-diagnostic levels of serum insulin, glucose and insulin resistance (HOMA-IR) and future risk of incident primary liver cancer (PLC) or chronic liver disease (CLD)-related mortality. METHODS: We used a nested case-control design to evaluate subjects over 22 years of follow-up. Glucose, insulin, and three markers of hepatitis B virus (HBV) and hepatitis C virus were measured in fasting baseline serum from 119 incident PLCs, 157 CLD-death cases and 512 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression to estimate the associations between insulin, glucose, HOMA-IR and the risk of PLC or CLD death. RESULTS: Compared with the lowest quartile of insulin, multivariable adjusted models showed that subjects in the highest quartile had elevated odds of developing PLC (ORQ4/Q1 = 2.42, 95% CI = 1.26-4.75, Ptrend = 0.007), particularly in HBV-positive subjects (Pinteraction = 0.040), and of CLD death (ORQ4/Q1 = 1.80, 95% CI = 1.02-3.21, Ptrend = 0.018). For glucose, in the HBV-positive group, subjects in the fourth quartile had an increased risk of PLC (ORQ4/Q1 = 2.18, 95% CI = 1.07-4.60, Ptrend = 0.009), and of CLD mortality (ORQ4/Q1 = 1.75, 95% CI = 0.95-3.28, Ptrend = 0.019). Subjects with the highest HOMA-IR values had a threefold risk of developing PLC (ORQ4/Q1 = 2.94, 95% CI = 1.54-5.87, Ptrend = 0.001), and a twofold risk of CLD death (ORQ4/Q1 = 2.20, 95% CI = 1.25-3.94, Ptrend = 0.005). CONCLUSIONS: We found that serum insulin and HOMA-IR could potentially be risk factors for PLC or CLD death.

Psychological Effects Of Unemployment Across The Lifespan: A Synthesis Of Relevant Literature.

Amid ongoing global economic uncertainty and long-standing efforts to tackle age discrimination and increase older workers' labor force engagement, it is pertinent to consider age differences in the individual effects of joblessness. This is paramount for informing support services, policy formulation, and research. This article is based on a literature review of international peer reviewed quantitative research that has examined the relationship between age, psychological wellbeing and unemployment. Two hundred and twenty-six studies were screened and 36 were included. No relevant qualitative studies were identified. Among the studies, there was a broad consensus that there are age differences in terms of the psychological consequences of unemployment. However, they showed mixed evidence, and critical conceptual and methodological deficiencies were identified. We conclude that the body of evidence is weak and that drawing from it for the development of practice and policy in support of jobless individuals is to be cautioned against.

CSMD1 Shows Complex Patterns of Somatic Copy Number Alterations and Expressions of mRNAs and Target Micro RNAs in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Human Cub and Sushi Multiple Domains 1 (CSMD1) is a novel candidate tumor-suppressor gene that codes for multiple domains, including complement regulatory and adhesion proteins, and has recently been shown to have alterations in multiple cancers. We investigated CSMD1 in esophageal squamous cell carcinoma (ESCC) by performing an integrated analysis on somatic copy number alterations (CNAs), including copy-number gain or loss, allelic imbalance (AI), loss of heterozygosity (LOH), and the expressions of mRNA and its target miRNAs on specimens from the same patients with ESCC. RESULTS: (i) Two-thirds of ESCC patients had all three types of alterations studied-somatic DNA alterations in 70%, and abnormal expressions of CSMD1 RNA in 69% and in target miRNAs in 66%; patterns among these alterations were complex. (ii) In total, 97% of 888 CSMD1 SNPs studied showed somatic DNA alterations, with most located near exons 4-11, 24-25, 39-40, 55-56, and 69-70. (iii) In total, 68% of SNPs with a CNA were correlated with expression of CSMD1. (iv) A total of 33 correlations between non-coding SNPs and expression of CSMD1 target miRs were found. CONCLUSIONS: Our results indicate that the CSMD1 gene may play a role in ESCC through complex patterns of DNA alterations and RNA and miRNA expressions. Alterations in some somatic SNPs in non-coding regions of CSMD1 appear to influence expression of this gene and its target miRNAs.

Adsorption of sterically-stabilized diblock copolymer nanoparticles at the oil-water interface: effect of charged end-groups on interfacial rheology.

The RAFT aqueous emulsion polymerization of either methyl methacrylate (MMA) or benzyl methacrylate (BzMA) is conducted at 70 °C using poly(glycerol monomethacrylate) (PGMA) as a water-soluble precursor to produce sterically-stabilized diblock copolymer nanoparticles of approximately 30 nm diameter. Carboxylic acid- or morpholine-functional RAFT agents are employed to confer anionic or cationic functionality at the ends of the PGMA stabilizer chains, with a neutral RAFT agent being used as a control. Thus the electrophoretic footprint of such minimally-charged model nanoparticles can be adjusted simply by varying the solution pH. Giant (mm-sized) aqueous droplets containing such nanoparticles are then grown within a continuous phase of n-dodecane and a series of interfacial rheology measurements are conducted. The interfacial tension between the aqueous phase and n-dodecane is strongly dependent on the charge of the terminal group on the stabilizer chains. More specifically, neutral nanoparticles produce a significantly lower interfacial tension than either cationic or anionic nanoparticles. Moreover, adsorption of neutral nanoparticles at the n-dodecane-water interface produces higher interfacial elastic moduli than that observed for charged nanoparticles. This is because neutral nanoparticles can adsorb at much higher surface packing densities owing to the absence of electrostatic repulsive forces in this case.

An international report on bacterial communities in esophageal squamous cell carcinoma.

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.

Terminal complement pathway activation drives synaptic loss in Alzheimer's disease models.

Complement is involved in developmental synaptic pruning and pathological synapse loss in Alzheimer's disease. It is posited that C1 binding initiates complement activation on synapses; C3 fragments then tag them for microglial phagocytosis. However, the precise mechanisms of complement-mediated synaptic loss remain unclear, and the role of the lytic membrane attack complex (MAC) is unexplored. We here address several knowledge gaps: (i) is complement activated through to MAC at the synapse? (ii) does MAC contribute to synaptic loss? (iii) can MAC inhibition prevent synaptic loss? Novel methods were developed and optimised to quantify C1q, C3 fragments and MAC in total and regional brain homogenates and synaptoneurosomes from WT and AppNL-G-F Alzheimer's disease model mouse brains at 3, 6, 9 and 12 months of age. The impact on synapse loss of systemic treatment with a MAC blocking antibody and gene knockout of a MAC component was assessed in Alzheimer's disease model mice. A significant increase in C1q, C3 fragments and MAC was observed in AppNL-G-F mice compared to controls, increasing with age and severity. Administration of anti-C7 antibody to AppNL-G-F mice modulated synapse loss, reflected by the density of dendritic spines in the vicinity of plaques. Constitutive knockout of C6 significantly reduced synapse loss in 3xTg-AD mice. We demonstrate that complement dysregulation occurs in Alzheimer's disease mice involving the activation (C1q; C3b/iC3b) and terminal (MAC) pathways in brain areas associated with pathology. Inhibition or ablation of MAC formation reduced synapse loss in two Alzheimer's disease mouse models, demonstrating that MAC formation is a driver of synapse loss. We suggest that MAC directly damages synapses, analogous to neuromuscular junction destruction in myasthenia gravis.

Mortality after multivitamin supplementation: Nearly 35-year follow-up of the randomized Linxian Dysplasia Nutrition Intervention Trial.

BACKGROUND: The objective of this study was to update the association between multivitamin supplementation and total or cause-specific mortality in a population with a high prevalence of undernutrition in China. METHODS: The Linxian Dysplasia Nutrition Intervention Trial was a randomized, double-blind, placebo-controlled trial in which 3318 persons aged 40-69 years with esophageal squamous dysplasia were assigned to receive daily multivitamin supplementation or a placebo for 6 years and were followed for 29 years. The primary outcome was esophageal/gastric cardia cancer mortality. The data were analyzed with Cox proportional hazards regression models. Subgroup analyses were performed by common characteristics such as age and gender. RESULTS: The cumulative total mortality was 83.5%. Multivitamin supplementation did not affect total or cause-specific mortality in the participants as a whole (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.89-1.03). Subgroup analyses showed that no association between multivitamin supplementation and all-cause mortality was observed in men (HR, 0.90; 95% CI, 0.81-1.01), women (HR, 1.01; 95% CI, 0.91-1.12), younger participants (HR, 0.97; 95% CI, 0.87-1.08), or older participants (HR, 0.94; 95% CI, 0.85-1.04). Significant reductions in heart disease mortality (HR, 0.64; 95% CI, 0.47-0.87) and cerebrovascular disease mortality (HR, 0.74; 95% CI, 0.56-1.00) were seen in older men. In a subgroup of younger men and a subgroup of moderate or severe dysplasia, subjects receiving multivitamin supplementation had a lower risk of esophageal/cardia cancer mortality (HR for younger men, 0.76; 95% CI, 0.58-0.99; HR for moderate or severe dysplasia, 0.76; 95% CI, 0.58-1.00). No association between multivitamin supplementation and any cause-specific mortality was observed in a mild dysplasia population. CONCLUSIONS: Multivitamin supplementation in a population with esophageal squamous dysplasia was not associated with the risk of total mortality in the 35-year follow-up of this randomized controlled trial. In light of this and previous trials, multivitamin supplements should be used thoughtfully to improve health status of populations with esophageal squamous dysplasia. LAY SUMMARY: Multivitamin supplementation is common, yet its effect on mortality is unclear. The aim of this study was to update the long-term effects of multivitamin supplementation on total and cause-specific mortality during nearly 35 years of follow-up in the Linxian Dysplasia Nutrition Intervention Trial in China. Multivitamin supplementation in a population with esophageal squamous dysplasia was not associated with the risk of total mortality in the 35-year follow-up of this randomized controlled trial, and this indicates that multivitamin supplements should be used thoughtfully to improve health status.

Combined risk factors and risk of upper gastrointestinal cancer mortality in the Linxian general population.

We aimed to explore the association of combined risk factors with risk of death from upper gastrointestinal (UGI) cancer, including esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC) and gastric noncardia carcinoma (GNCC) in the Linxian Nutrition Intervention Trial (NIT) cohort. The NIT cohort included 29 584 healthy adults. A combined risk score (CRS) was calculated using a point system method based on 10 risk factors collected at baseline, including gender, smoking, alcohol drinking, body mass index, family history of UGI cancer, drinking tap water, tooth loss and consumption of fresh fruit, eggs and meat. Possible score ranged from 0 to 31, and higher score indicated as poorer health status. Subjects were divided into three groups by the CRS (<12 points, 12 to 20 points and >20 points). The group of CRS <12 points was considered as the reference. During the 30-year follow-up, we identified 4553 UGI cancer deaths. Compared to subjects with a CRS <12 points, the adjusted HRs for CRS of 12 to 20 points and >20 points were 1.69 (95% CI: 1.56-1.83) and 3.06 (95% CI: 2.82-3.33) for UGI cancer mortality, respectively (Ptrend < .001). Comparable associations were also observed for ESCC, GCC and GNCC mortality. Results remained similar across different age groups (Pinteraction > .05). All HRs observed in the second half follow-up period were stronger than that observed in the first half follow-up period. Our study indicated that higher CRS was associated with increased risk of UGI cancer mortality. Appropriate measures should be taken to reduce unhealthy lifestyles.

The Association Between Family History of Upper Gastrointestinal Cancer and the Risk of Death from Upper Gastrointestinal Cancer-based on Linxian Dysplasia Nutrition Intervention Trial (NIT) Cohort.

Objective: Explore the influence of family history of upper gastrointestinal (UGI) cancer on UGI cancer death, based on the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort. Methods: Family history of UGI cancer was defined as at least one first-degree relative (parent, child, or sibling) had a history of esophageal or gastric cancer. Cancer death was carried out by ICD-10 code. Family history information was collected at baseline and cancer deaths were assessed at each annual follow-up. The COX proportional risk model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). We compared the positive family history group with the negative to determine the risk of family history on UGI cancer death. The effect of category of relatives, number of relatives with UGI cancer, and diagnosis age of relatives on the UGI death risk were further analyzed. Interaction and stratification analyses were done to see the subgroup effects. Sensitivity analyses were also conducted by exclusion of individuals who were followed up less than three years. We considered controlling of covariates including: gender, age (continuity), community, education level, number of siblings (continuity), BMI (continuity), smoking, alcohol use, fresh fruit intake, fresh vegetable intake, hot beverage intake, edible oil intake, meat intake, and moldy staple food intake. All food intake variables were converted into categorical variables. Results: From1985 to2015, we followed up total 3,318 individuals with 898 UGI cancer deaths (537 from ESCC, 77 from GNCC, and 284 from GCC). In a single factor analysis, family history of UGI cancer increased the risk of death of esophageal squamous cell carcinoma (ESCC) by 27% (HR=1.270, 95%CI1.072-1.504). No associations were observed in gastric cardia carcinoma (GCC) and gastric non-cardia carcinoma (GNCC). After adjusting for multi-factor, a family history of UGI cancer risk of death increased by 31.9% from ESCC (HR=1.319,95%CI:1.110-1.567). Subgroup analysis of different types of relatives with UGI cancers, UGI cancers in the mother (HR=1.457,95%CI:1.200-1.768), brother (HR=1.522,95%CI:1.117-2.073), and sister (HR=1.999,95%CI:1.419-2.817) were independent risk factors for ESCC death, while the father was not. In addition, 2 relatives with UGI cancer (HR=1.495, 95%, CI:1.110-2.013) and ≥3 relatives with UGI cancer (HR=2.836, 95%CI:1.842-4.367) significantly increased the risk of ESCC death, and the trend test was statistically significant (P<0.001). Relatives' diagnostic age of 51-60 years (HR=1.322, 95%CI:1.046-1.672) and 41-50 years (HR=1.442, 95%CI:1.078-1.930) were the risk factors for ESCC death, with statistical significance in the trend test (P=0.010). No statistically significant result of the family history effect on the risk of death from GCC or GNCC was found. Sensitivity analysis of 80% of subjects, randomly selected, did not change the results. Conclusion: A family history of UGI cancer may predict the risk of death from ESCC but not from GCC or GNCC. UGI cancer in the mother may predict the risk of death from ESCC, but not father, which indicates gender differences. Gender and smoking are the interaction items with family history in a similar extent. In the subgroup, the risk of ESCC death is more distinct by family history in younger, female, and better-lifestyle individuals, which indicates the unique role of genetic factors.

Hard-to-soft transition-enhanced piezoelectricity in poly(vinylidene fluoride) via relaxor-like secondary crystals activated by high-power ultrasonication.

Although high piezoelectric coefficients have recently been observed in poly(vinylidene fluoride-co-trifluoroethylene) [P(VDF-TrFE)] random copolymers, they have low Curie temperatures, which makes their piezoelectricity thermally unstable. It has been challenging to achieve high piezoelectric performance from the more thermally stable PVDF homopolymer. In this report, we describe how high-power ultrasonic processing was used to induce a hard-to-soft piezoelectric transition and improve the piezoelectric coefficient d31 in neat PVDF. After high-power ultrasonication for 20 min, a uniaxially stretched and poled PVDF film exhibited a high d31 of 50.2 ± 1.7 pm V-1 at room temperature. Upon heating to 65 °C, the d31 increased to a maximum value of 76.2 ± 1.2 pm V-1, and the high piezoelectric performance persisted up to 110 °C. The enhanced piezoelectricity was attributed to the relaxor-like secondary crystals in the oriented amorphous fraction, broken off from the primary crystals by ultrasonication, as suggested by differential scanning calorimetry and broadband dielectric spectroscopy studies.

Relationships between serum iron and liver diseases in nutrition intervention trials: A nested case-control study.

BACKGROUND: Serum iron is associated with the risk of several diseases. However, limited prospective studies have been performed between serum iron and the subsequent risk of chronic liver disease (CLD) and primary liver cancer (PLC) incidence. METHODS: We performed a nested case-control study using data from the Linxian Nutrition Intervention Trials among participants who developed PLC incidence or died from CLD over 22-years of follow-up. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the risk of PLC incidence or CLD death in different quintile of baseline serum iron using logistic regression. RESULTS: Individuals with serum iron in the highest quintile, compared to those in the second quintile (the reference), had an increased risk of CLD mortality (OR=2.02, 95% CI=1.27-3.27, Ptrend=0.011). The association was stronger among HCV-positive participants (Pinteraction=0.005). For PLC incidence, the risk estimates were above one, but not statistically significant (all P > 0.05). CONCLUSIONS: A significant positive association was found between serum iron and the risk of CLD-related mortality, especially in HCV-positive subjects. Our results suggest that serum iron plays a risk role in CLD death but not in PLC incidence.

Modified eQTL and Somatic DNA Segment Alterations in Esophageal Squamous Cell Carcinoma for Genes Related to Immunity, DNA Repair, and Inflammation.

We integrated ESCC expression and GWAS genotyping, to investigate eQTL and somatic DNA segment alterations, including somatic copy number alteration, allelic imbalance (AI), and loss of heterozygosity (LOH) in ESCC. First, in eQTL analysis, we used a classical approach based on genotype data from GWAS and expression signals in normal tissue samples, and then used a modified approach based on fold change in the tumor vs. normal samples. We focused on the genes in three pathways: inflammation, DNA repair, and immunity. Among the significant (p < 0.05) SNP-probe pairs from classical and modified eQTL analyses, 24 genes were shared by the two approaches, including 18 genes that showed the same numbers of SNPs and probes and 6 genes that had the different numbers of SNPs and probes. For these 18 genes, we found 28 SNP-probe pairs were correlated in opposite directions in the two approaches, indicating an intriguing difference between the classical and modified eQTL approaches. Second, we analyzed the somatic DNA segment alterations. Across the 24 genes, abnormal gene expression on mRNA arrays was seen in 19-95% of cases and 26-78% showed somatic DNA segment alterations on Affymetrix GeneChip Human Mapping Arrays. The results suggested that this strategy could identify gene expression and somatic DNA segment alterations for biological markers (genes) by combining classical and modified eQTLs and somatic DNA evaluation on SNP arrays. Thus, this study approach may allow us to understand functionality indicative of potentially relevant biomarkers in ESCC.

Design and qualification of a bench-scale model for municipal waste-to-energy combustion.

This paper reports the design and qualification of the first purpose-built, bench-scale reactor system to model the municipal waste-to-energy combustion of fluorinated polymers. Using the principle of similarity, the gas-phase combustion zone of a typical municipal waste-to-energy plant has been scaled down to the bench with a focus on chemical similarity. Chemical similarity is achieved in large part through the use of methanol as a surrogate for municipal solid waste (MSW). Review of prior research shows that methanol is one of the major volatile products expected during MSW thermal conversion in the fuel bed of waste-to-energy plants. Like full-scale waste-energy plants, the design of the bench-scale model includes a flame zone and a post-flame zone. Maintaining steady methanol vapor flow premixed with air to the model reactor system ensures stable combustion resulting in bench-scale CO emission levels comparable to those of full-scale waste-to-energy plants. Since investigation of fluorinated polymer combustion includes trace analysis of exhaust gas for perfluorooctanoic acid (PFOA), qualification testing focused on PFOA collection efficiency. High PFOA collection efficiency (>90%) demonstrated the capability of the reactor system in transporting and absorbing PFOA that may be generated during high-temperature combustion testing of fluorinated polymers. Overall, the bench-scale system is qualified for its intended use to investigate potential generation of PFOA from combustion of fluorinated polymers under conditions representative of waste-to-energy combustion.Implications: Decision-makers depend on environmental researchers to provide reliable predictions of pollutant emissions from waste combustion of polymers at end of product life. Reliable predictions are especially important with regard to questions about potential PFOA emissions from municipal waste combustion of fluorinated polymers. Results from qualification testing confirm that the novel bench-scale model reactor system is capable of representing gas-phase municipal waste combustion behavior upstream of air pollution control and generating representative exhaust gas samples for off-line trace-level analysis of PFOA.

Sterically Stabilized Diblock Copolymer Nanoparticles Enable Convenient Preparation of Suspension Concentrates Comprising Various Agrochemical Actives.

It is well known that sterically stabilized diblock copolymer nanoparticles can be readily prepared using polymerization-induced self-assembly. Recently, we reported that such nanoparticles can be employed as a dispersant to prepare micron-sized particles of a widely used fungicide (azoxystrobin) via ball milling. In the present study, we examine the effect of varying the nature of the steric stabilizer block, the mean nanoparticle diameter, and the glass transition temperature (Tg) of the core-forming block on the particle size and colloidal stability of such azoxystrobin microparticles. In addition, the effect of crosslinking the nanoparticle cores is also investigated. Laser diffraction studies indicated the formation of azoxystrobin microparticles of approximately 2 µm diameter after milling for between 15 and 30 min at 6000 rpm. Diblock copolymer nanoparticles comprising a non-ionic steric stabilizer, rather than a cationic or anionic steric stabilizer, were determined to be more effective dispersants. Furthermore, nanoparticles of up to 51 nm diameter enabled efficient milling and ensured overall suspension concentrate stability. Moreover, crosslinking the nanoparticle cores and adjusting the Tg of the core-forming block had little effect on the milling of azoxystrobin. Finally, we show that this versatile approach is also applicable to five other organic crystalline agrochemicals, namely pinoxaden, cyproconazole, difenoconazole, isopyrazam and tebuconazole. TEM studies confirmed the adsorption of sterically stabilized nanoparticles at the surface of such agrochemical microparticles. The nanoparticles are characterized using TEM, DLS, aqueous electrophoresis and 1H NMR spectroscopy, while the final aqueous' suspension concentrates comprising microparticles of the above six agrochemical actives are characterized using optical microscopy, laser diffraction and electron microscopy.

Combined Lifestyle Factors and Risk of All-Cause and Cause-Specific Mortality Among Participants in the Linxian Nutrition Intervention Trial: A Cohort, Observational Study.

BACKGROUND: Several studies have indicated that combinations of lifestyle and dietary factors are associated with risk of total mortality and death from cardiovascular disease and cancer, but limited data are available from long-term follow-up studies in China. METHODS: This study was a observational cohort study. We prospectively examined the associations of combined lifestyle factors and risk of total and cause-specific mortality in the Linxian General Population Nutrition Intervention Trial (NIT) cohort that included 29,584 healthy adults. A points system method was used to calculate a combined risk score of five lifestyle factors, including smoking, alcohol drinking, body mass index, vegetable intake and fruit intake. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: Overall, adjusted hazard ratios for mortality increased progressively with an increasing combined risk score. Compared to individuals with a score of zero or one, HRs (95%CIs) for a score of five or above were 1.59 (1.44-1.75) for all-cause mortality, 1.67 (1.48-1.88) for heart disease, 1.69 (1.52-1.88) for stroke, and 1.34 (1.21, 1.47) for cancer. This association for mortality was seen consistently, regardless of gender and age at baseline. CONCLUSIONS: A higher combined risk score was positively associated with risk of total, heart disease, stroke, and cancer mortality. These findings could provide further evidence for the idea that healthy lifestyle is the optimal way to reduce the risk of premature death, and encourage behavior change.

3R Blackboard: A platform for animal and organ sharing.

Since the embedding of the principles of the 3Rs (Replacement, Reduction and Refinement) in national and international regulations on the use of animals, scientists have been challenged to find ways to reduce the number of animals in their research. Here, we present a digital platform, called '3R Backboard', linked to a laboratory animal management system, which facilitates sharing of surplus biological materials from animals (e.g. tissues, organs and cells) to other research teams. Based on information provided, such as genotype, age and sex, other animal workers were able to indicate their interest in collecting specific tissues and to communicate with the person providing the animals. A short pilot study of this approach conducted in a limited academic environment presented strong evidence of its effectiveness and resulted in a notable reduction of the number of mice used. In addition, the use of 3R Blackboard led to resource saving, knowledge exchange and even establishment of new collaboration.

Oxylipin metabolism is controlled by mitochondrial ß-oxidation during bacterial inflammation.

Oxylipins are potent biological mediators requiring strict control, but how they are removed en masse during infection and inflammation is unknown. Here we show that lipopolysaccharide (LPS) dynamically enhances oxylipin removal via mitochondrial ß-oxidation. Specifically, genetic or pharmacological targeting of carnitine palmitoyl transferase 1 (CPT1), a mitochondrial importer of fatty acids, reveal that many oxylipins are removed by this protein during inflammation in vitro and in vivo. Using stable isotope-tracing lipidomics, we find secretion-reuptake recycling for 12-HETE and its intermediate metabolites. Meanwhile, oxylipin ß-oxidation is uncoupled from oxidative phosphorylation, thus not contributing to energy generation. Testing for genetic control checkpoints, transcriptional interrogation of human neonatal sepsis finds upregulation of many genes involved in mitochondrial removal of long-chain fatty acyls, such as ACSL1,3,4, ACADVL, CPT1B, CPT2 and HADHB. Also, ACSL1/Acsl1 upregulation is consistently observed following the treatment of human/murine macrophages with LPS and IFN-γ. Last, dampening oxylipin levels by ß-oxidation is suggested to impact on their regulation of leukocyte functions. In summary, we propose mitochondrial ß-oxidation as a regulatory metabolic checkpoint for oxylipins during inflammation.

Quantitative evaluation of radon, tobacco use and lung cancer association in an occupational cohort with 27 follow-up years.

BACKGROUND: Occupational radon cohorts provide important information about exposure at residential level, which are difficult to observe prospectively. However, evidence about radon-related lung cancer risks from initial exposure in childhood or interaction between radon and smoking is still limited. METHODS: A total of 6017 tin miners with at least 10 years of underground radon exposure were enrolled beginning in 1992 and followed for up to 27 years. Lung cancer risks were estimated by modeling total and intensity of radon exposure. RESULTS: A total of 933 lung cancer cases occurred in this cohort over 89,092 person-years of follow up. Excess relative risk increased by 0.96% per cumulative working level month (WLM). A unique aspect of this population was the early age at first radon exposure for workers. Results showed that lung cancer risk from initial radon exposure in childhood (<13 years old) was greater than risk when first exposure occurred at later ages (13-17, 18-24, and ≥ 25 years old). Moreover, risk declined with years since last exposure and attained age, but increased with age at last exposure. Importantly, these patterns were stable after adjustment for tobacco use or arsenic exposure. For joint effects of radon and other agents, our results support sub-multiplicative as the most likely model for interaction between radon and tobacco use or arsenic exposure. CONCLUSION: This study highlights the possible importance of radon exposure in childhood in cancer etiology and suggests another potential strategy to mitigate the global lung cancer burden.

Indicators of job quality in the Australian aged care workforce: A scoping review.

OBJECTIVE: As governments grapple with ageing populations, there is a need to understand more about the aged care workforce and how it is managed. METHODS: We undertook a scoping review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Scopus and PubMed were used to identify papers published between 2010 and 2020. We mapped the breadth and scale of the evidence base according to the QuInnE indicators of job quality. RESULTS: Out of 642 titles and abstracts that were screened, 122 were selected. Outcomes were measured across a range of domains, including wages, employment quality, education and training, working conditions, work/life balance and consultative participation and collective representation. These were distributed unevenly, revealing evidence gaps. CONCLUSIONS: We identified significant knowledge gaps regarding Australia's aged care workforce at a time when the sector is coming under fresh scrutiny and projections indicate that it will face critical labour shortfalls going forward.

Arsenic, tobacco use, and lung cancer: An occupational cohort with 27 follow-up years.

BACKGROUND: We explored the shape of the exposure-response relationship of arsenic-related lung cancer and the interaction between arsenic and tobacco use. METHODS: A total of 3278 tin miners with at least 10 years of arsenic exposure were enrolled since 1992 and followed up for 27 years. After excluding radon-exposed miners and former smokers, 1620 miners were included into the sub-cohort. Lung cancer risks were estimated by modeling total exposure and intensity of arsenic exposure. RESULTS: The cohort experienced 73,866 person-years and 414 lung cancer cases. Firstly, the ERR/mg/m3-year was 0.0033 (95% CI: 0.0014-0.0045) in arsenic concentration <3 mg/m3 and 0.0056 (95% CI: 0.0035-0.0073) in arsenic concentration ≥3 mg/m3. After adjusting for cumulative arsenic exposure, and the ERR/mg/m3 increased with increasing intensity (0.129 (95% CI: 0.039, 0.189)). Secondly, an unique aspect of this population was the early age at first arsenic exposure for workers. Results showed that lung cancer incidence risk from exposed in childhood (<13 years) was non-significantly greater than those in other age groups (13-17 and ≥ 18 years). Finally, the most likely joint effects of inhaled arsenic and tobacco use was sub-multiplicative. CONCLUSION: This study enlightened us that for fixed cumulative arsenic exposure, higher concentration over shorter duration might be more deleterious than lower concentration over longer duration. Substantial reductions in the lung cancer burden of smokers exposed to arsenic could be achieved by reductions in either exposure.