Reduced food access due to a lack of money, inability to lift and lack of access to a car for food shopping : a multilevel study in Melbourne, Victoria

Objective: To describe associations between demographic and individual and arealevel socio-economic variables and restricted household food access due to lack of money, inability to lift groceries and lack of access to a car to do food shopping.Design: Multilevel study of three measures of restricted food access, i.e. running out of money to buy food, inability to lift groceries and lack of access to a car for food shopping. Multilevel logistic regression was conducted to examine the risk of each of these outcomes according to demographic and socio-economic variables.Setting: Random selection of households from fifty small areas in Melbourne, Australia, in 2003.Subjects: The main food shoppers in each household (n 2564).Results: A lack of money was significantly more likely among the young and in households with single adults. Difficultly lifting was more likely among the elderly and those born overseas. The youngest and highest age groups both reported reduced car access, as did those born overseas and single-adult households. All three factors were most likely among those with a lower individual or household socio-economic position. Increased levels of area disadvantage were independently associated with difficultly lifting and reduced car access.Conclusions: In Melbourne, households with lower individual socio-economic position and area disadvantage have restricted access to food because of a lack of money and/or having physical limitations due difficulty lifting or lack of access to a car for food shopping. Further research is required to explore the relationship between physical restrictions and food access.<br /

Sensitizing thermochemotherapy with a PARP1-inhibitor

Cis-diamminedichloroplatinum(II) (cisplatin, cDDP) is an effective chemotherapeutic agent that induces DNA double strand breaks (DSBs), primarily in replicating cells. Generally, such DSBs can be repaired by the classical or backup non-homologous end joining (c-NHEJ/b-NHEJ) or homologous recombination (HR). Therefore, inhibiting these pathways in cancer cells should enhance the efficiency of cDDP treatments. Indeed, inhibition of HR by hyperthermia (HT) sensitizes cancer cells to cDDP and in the Netherlands this combination is a standard treatment option for recurrent cervical cancer after previous radiotherapy. Additionally, cDDP has been demonstrated to disrupt c-NHEJ, which likely further increases the treatment efficacy. However, if one of these pathways is blocked, DSB repair functions can be sustained by the Poly-(ADP-ribose)-polymerase1 (PARP1)-dependent b-NHEJ. Therefore, disabling b-NHEJ should, in principle, further inhibit the repair of cDDP-induced DNA lesions and enhance the toxicity of thermochemotherapy. To explore this hypothesis, we treated a panel of cancer cell lines with HT, cDDP and a PARP1-i and measured various end-point relevant in cancer treatment. Our results demonstrate that PARP1-i does not considerably increase the efficacy of HT combined with standard, commonly used cDDP concentrations. However, in the presence of a PARP1-i, ten-fold lower concentration of cDDP can be used to induce similar cytotoxic effects. PARP1 inhibition may thus permit a substantial lowering of cDDP concentrations without diminishing treatment efficacy, potentially reducing systemic side effects

A comparison of three treatment strategies in recent onset non-systemic Juvenile Idiopathic Arthritis: Initial 3-months results of the BeSt for Kids-study

Background: Combination therapy with prednisone or etanercept may induce earlier and/or more improvement in disease activity in Disease Modifying Anti Rheumatic Drug (DMARD) naïve non-systemic Juvenile Idiopathic Arthritis (JIA) patients. Here we present three months clinical outcome of initial treatments of the BeSt-for-Kids study. Methods: Included patients were randomized to either: 1. initial DMARD-monotherapy (sulfasalazine (SSZ) or methotrexate (MTX)), 2. Initial MTX / prednisolone-bridging, 3. Initial combination MTX/etanercept. Percentage inactive disease, adjusted (a) ACR Pedi30, 50 and 70 and JADAS after 6 and 12 weeks of treatment (intention to treat analysis) and side effects are reported. Results: 94 patients (67% girls, 32 (arm 1), 32 (arm 2) and 30 (arm 3) with median (InterQuartileRange) age of 9.1 (4.7-12.9) years were included. 38% were ANA positive, 10 had oligo-articular disease, 68 polyarticular JIA and 16 psoriatic arthritis. Baseline median (IQR) ACRpedi-scores: VAS physician 49 (40-58) mm, VAS patient 54 (37-70) mm, ESR 6.5 (2-14.8)mm/hr, active joint count 8 (5-12), limited joint count 3 (1-5), CHAQ score 0.88 (0.63-1.5). In arm 1, 17 started with MTX, 15 with SSZ. After 3 months, aACR Pedi 50 was reached by 10/32 (31%), 12/32(38%) and 16/30 (53%) (p = 0.19) and aACR Pedi 70 was reached by 8/32 (25%), 6/32(19%) and 14/30(47%) in arms 1-3 (p = 0.04). Toxicity was similar. Few serious adverse events were reported. Conclusion: After 3 months of treatment in a randomized trial, patients with recent-onset JIA achieved significantly more clinical improvement (aACRPedi70) on initial combination therapy with MTX / etanercept than on initial MTX or SSZ monotherapy. Trial registration:NTR1574. Registered 3 December 2008

Self-harm hospitalised morbidity and mortality risk in Australia using a matched population-based cohort

Introduction Prior and repeated self-harm hospitalisations are common risk factors for suicide. However, few studies have accounted for pre-existing comorbidities and prior hospital use when quantifying the burden of self-harm. Objectives and Approach To quantify hospitalisation in the 12 months preceding and re-hospitalisation and mortality risk in the 12 months post a self-harm hospitalisation. A population-based matched cohort study of individuals ≥18 years using linked hospitalisation and mortality records from four Australian states. Self-harm was identified using a principal diagnosis of injury (S00-T75 or T79) and an external cause of self-harm (X60-X84). The index self-harm hospitalisation was identified and 12-month pre- and post-index injury health service use was examined. The non-injured comparison cohort was randomly selected from the electoral roll and was matched 1:1 on age, gender, and postcode of residence. Comorbidities were identified using diagnosis classifications with a 1-year lookback. Negative binomial regression was used to quantify associations between self-harm and counts of hospital admissions 12-months post the index hospitalisation using rate ratios and 95%CIs. Results There were 11,597 individuals with a self-harm hospitalisation in New South Wales, South Australia, Queensland or Tasmania with a matched comparison. Mean age was 38.6 years (SD=14.9) and 57.6% were female. The self-harm cohort had a higher proportion of Charlson comorbidities, mental health diagnoses, alcohol misuse and drug-related dependence than their matched counterparts. The self-harm cohort experienced a higher proportion of health service use in the 12-months preceding (20.5% vs 10.1%) and post (21.2% vs 10.6%) the index admission and a higher mortality rate (2.9% vs 0.3%) than their matched counterparts. The adjusted rate ratios (ARR) for hospital readmission were highest for females (ARR: 2.86; 95% CI: 2.33-3.52) and individuals aged 55-64 years (ARR: 3.96; 95%CI: 2.79-5.64). Conclusion/Implications Improved hospitalisation burden quantification for self-harm can inform resource allocation for intervention and after care services for individuals at-risk of repeated self-harm. Better assessment of at-risk self-harm behaviour, appropriate referrals and improved post-discharge care, focusing on care continuity is needed

Role of Ribosomal Protein bS1 in Orthogonal mRNA Start Codon Selection

In many bacteria, the location of the mRNA start codon is determined by a short ribosome binding site sequence that base pairs with the 3'-end of 16S rRNA (rRNA) in the 30S subunit. Many groups have changed these short sequences, termed the Shine-Dalgarno (SD) sequence in the mRNA and the anti-Shine-Dalgarno (ASD) sequence in 16S rRNA, to create "orthogonal" ribosomes to enable the synthesis of orthogonal polymers in the presence of the endogenous translation machinery. However, orthogonal ribosomes are prone to SD-independent translation. Ribosomal protein bS1, which binds to the 30S ribosomal subunit, is thought to promote translation initiation by shuttling the mRNA to the ribosome. Thus, a better understanding of how the SD and bS1 contribute to start codon selection could help efforts to improve the orthogonality of ribosomes. Here, we engineered the Escherichia coli ribosome to prevent binding of bS1 to the 30S subunit and separate the activity of bS1 binding to the ribosome from the role of the mRNA SD sequence in start codon selection. We find that ribosomes lacking bS1 are slightly less active than wild-type ribosomes in vitro. Furthermore, orthogonal 30S subunits lacking bS1 do not have an improved orthogonality. Our findings suggest that mRNA features outside the SD sequence and independent of binding of bS1 to the ribosome likely contribute to start codon selection and the lack of orthogonality of present orthogonal ribosomes

Living Act 31: Perspectives From Bayfield, Wisconsin

In this article, we discuss the teaching of Indigenous land sovereignty, history, and culture, commonly referred to as Act 31, in the School District of Bayfield in Bayfield, Wisconsin. Since the legislative mandate in 1991, the Wisconsin Department of Public Instruction has strongly recommended that Wisconsin students receive instruction related to Act 31 twice in elementary school and once in high school. However, because Act 31 is not strictly enforced, there is uneven implementation throughout the state. At the School District of Bayfield, teaching Act 31 is mainstreamed in the curriculum. Here, five teachers offer their vignette, or story, on infusing Act 31 into their instruction. This scholarship emerged from a collaboration between the School District of Bayfield and the University of Wisconsin-Platteville’s School of Education

Hospital service use for young people with chronic health conditions : a population-based matched retrospective cohort study

Aim: This study aims to identify the hospitalised morbidity associated with three common chronic health conditions among young people using a population-based matched cohort. Methods: A population-level matched case-comparison retrospective cohort study of young people aged ≤18 years hospitalised with asthma, type 1 diabetes (T1D) or epilepsy during 2005–2018 in New South Wales, Australia using linked birth, health and mortality records. The comparison cohort was matched on age, sex and residential postcode. Adjusted rate ratios (ARR) were calculated by sex and age group. Results: There were 65 055 young people hospitalised with asthma, 6648 with epilepsy, and 2209 with T1D. Young people with epilepsy (ARR 10.95; 95% confidence interval (CI) 9.98–12.02), T1D (ARR 8.64; 95% CI 7.72–9.67) or asthma (ARR 4.39; 95% CI 4.26–4.53) all had a higher risk of hospitalisation than matched peers. Admission risk was highest for males (ARR 11.00; 95% CI 9.64–12.56) and females with epilepsy (ARR 10.83; 95% CI 9.54–12.29) compared to peers. The highest admission risk by age group was for young people aged 10–14 years (ARR 5.50; 95% CI 4.77–6.34) living with asthma, children aged ≤4 years (ARR 12.68; 95% CI 11.35–14.17) for those living with epilepsy, and children aged 5–9 years (ARR 9.12; 95% CI 7.69–10.81) for those living with T1D compared to peers. Conclusions: The results will guide health service planning and highlight opportunities for better management of chronic health conditions, such as further care integration between acute, primary and community health services for young people

Impact of chronic health conditions and injury on school performance and health outcomes in New South Wales, Australia : a retrospective record linkage study protocol

Introduction: Children who have sustained a serious injury or who have a chronic health condition, such as diabetes or epilepsy, may have their school performance adversely impacted by the condition, treatment of the condition and/or time away from school. Examining the potential adverse impact requires the identification of children most likely to be affected and the use of objective measures of education performance. This may highlight educational disparities that could be addressed with learning support. This study aims to examine education performance, school completion and health outcomes of children in New South Wales (NSW), Australia, who were hospitalised with an injury or a chronic health condition compared with children who have not been hospitalised for these conditions. Method and analysis This research will be a retrospective population-level case-comparison study of hospitalised injured or chronically ill children (ie, diabetes, epilepsy, asthma or mental health conditions) aged ≤18 years in NSW, Australia, using linked health and education administrative data collections. It will examine the education performance, school completion and health outcomes of children who have been hospitalised in NSW with an injury or a chronic health condition compared with children randomly drawn from the NSW population (matched on gender, age and residential postcode) who have not been hospitalised for these conditions. Ethics and dissemination The study received ethics approval from the NSW Population Health Services Research Ethics Committee (2018HRE0904). Findings from the research will be published in peer-reviewed journals and presented at scientific conferences