Qualification of a 21-valent pneumococcal urine antigen detection assay and development of clinical positivity cutoffs.

Aim: Serotype-specific assays detecting pneumococcal polysaccharides in bodily fluids are needed to understand the pneumococcal serotype distribution in non-bacteremic pneumonia. Methods: We developed a urine antigen detection assay and using urine samples from adult outpatients without pneumonia developed positivity cutoffs for both a previously published 15-valent and the new 21-valent assay. Clinical sensitivity was confirmed with samples from patients with invasive pneumococcal disease. Results: Total assay precision ranged from 7.6 to 17.8% coefficient of variation while accuracy ranged between 80 and 150% recovery, except for three serotypes where recoveries ranged from 32 to 60%. Clinical sensitivity was 86.4% and specificity was 96.5% across all 30 serotypes. Conclusion: The assay could potentially assess serotype-distribution in non-infected and infected participants with pneumococcal disease.

[Box: see text].

Neuropharmacological Evidence Implicating Drug-Induced Glutamate Receptor Dysfunction in Affective and Cognitive Sequelae of Subchronic Methamphetamine Self-Administration in Mice.

Methamphetamine (MA) is a highly addictive drug, and MA use disorder is often comorbid with anxiety and cognitive impairment. These comorbid conditions are theorized to reflect glutamate-related neurotoxicity within the frontal cortical regions. However, our prior studies of MA-sensitized mice indicate that subchronic, behaviorally non-contingent MA treatment is sufficient to dysregulate glutamate transmission in mouse brain. Here, we extend this prior work to a mouse model of high-dose oral MA self-administration (0.8, 1.6, or 3.2 g/L; 1 h sessions × 7 days) and show that while female C57BL/6J mice consumed more MA than males, MA-experienced mice of both sexes exhibited some signs of anxiety-like behavior in a behavioral test battery, although not all effects were concentration-dependent. No MA effects were detected for our measures of visually cued spatial navigation, spatial learning, or memory in the Morris water maze; however, females with a history of 3.2 g/L MA exhibited reversal-learning deficits in this task, and mice with a history of 1.6 g/L MA committed more working-memory incorrect errors and relied upon a non-spatial navigation strategy during the radial-arm maze testing. Relative to naïve controls, MA-experienced mice exhibited several changes in the expression of certain glutamate receptor-related proteins and their downstream effectors within the ventral and dorsal areas of the prefrontal cortex, the hippocampus, and the amygdala, many of which were sex-selective. Systemic pretreatment with the mGlu1-negative allosteric modulator JNJ 162596858 reversed the anxiety-like behavior expressed by MA-experienced mice in the marble-burying test, while systemic pretreatment with NMDA or the NMDA antagonist MK-801 bi-directionally affected the MA-induced reversal-learning deficit. Taken together, these data indicate that a relatively brief history of oral MA is sufficient to induce some signs of anxiety-like behavior and cognitive dysfunction during early withdrawal that reflect, at least in part, MA-induced changes in the corticolimbic expression of certain glutamate receptor subtypes of potential relevance to treating symptoms of MA use disorder.

A subchronic history of binge-drinking elicits mild, age- and sex-selective, affective, and cognitive anomalies in C57BL/6J mice.

Introduction: Alcohol abuse is a risk factor for affective and cognitive disorders, with evidence indicating that adolescent-onset excessive drinking can result in long-term deficiencies in emotional regulation and cognition, with females more susceptible to the negative emotional and cognitive consequences of excessive alcohol consumption. However, our prior examination of the interactions between sex and the age of drinking-onset indicated minimal signs of anxiety-like behavior during alcohol withdrawal, which may have related to the concurrent anxiety testing of male and female subjects. Methods: The present study addressed this potential confound by assaying for alcohol withdrawal-induced negative affect separately in males and females and expanded our investigation to include measures of spatial and working memory. Results: Following 14 days of drinking under modified Drinking-in-the-Dark procedures (10, 20, and 40% alcohol v/v; 2 h/day), adolescent and adult binge-drinking mice of both sexes exhibited, respectively, fewer and more signs of negative affect in the light-dark shuttle-box and forced swim tests than their water-drinking counterparts. Adolescent-onset binge-drinking mice also exhibited signs of impaired working memory early during radial arm maze training during early alcohol withdrawal. When tested in late (30 days) withdrawal, only adult female binge-drinking mice buried more marbles than their water-drinking counterparts. However, adolescent-onset binge-drinking mice exhibited poorer spatial memory recall in a Morris water maze. Discussion: These findings indicate that a subchronic (14-day) binge-drinking history induces mild, age- and sex-selective, changes in negative affect and cognition of potential relevance to understanding individual variability in the etiology and treatment of alcohol abuse and alcohol use disorder.

Alcohol-drinking during later life by C57BL/6J mice induces sex- and age-dependent changes in hippocampal and prefrontal cortex expression of glutamate receptors and neuropathology markers.

Heavy drinking can induce early-onset dementia and increase the likelihood of the progression and severity of Alzheimer's Disease and related dementias (ADRD). Recently, we showed that alcohol-drinking by mature adult C57BL/6J mice induces more signs of cognitive impairment in females versus males without worsening age-related cognitive decline in aged mice. Here, we immunoblotted for glutamate receptors and protein markers of ADRD-related neuropathology within the hippocampus and prefrontal cortex (PFC) of these mice after three weeks of alcohol withdrawal to determine protein correlates of alcohol-induced cognitive decline. Irrespective of alcohol history, age-related changes in protein expression included a male-specific decline in hippocampal glutamate receptors and an increase in the expression of a beta-site amyloid precursor protein cleaving enzyme (BACE) isoform in the PFC as well as a sex-independent increase in hippocampal amyloid precursor protein. Alcohol-drinking was associated with altered expression of glutamate receptors in the hippocampus in a sex-dependent manner, while all glutamate receptor proteins exhibited significant alcohol-related increases in the PFC of both sexes. Expression of BACE isoforms and phosphorylated tau varied in the PFC and hippocampus based on age, sex, and drinking history. The results of this study indicate that withdrawal from a history of alcohol-drinking during later life induces sex- and age-selective effects on glutamate receptor expression and protein markers of ADRD-related neuropathology within the hippocampus and PFC of potential relevance to the etiology, treatment and prevention of alcohol-induced dementia and Alzheimer's Disease.

Alcohol-Drinking Under Limited-Access Procedures During Mature Adulthood Accelerates the Onset of Cognitive Impairment in Mice.

A history of heavy drinking increases vulnerability to, and the severity of, Alzheimer's disease (AD) and related dementias, with alcohol use disorder identified as the strongest modifiable risk factor for early-onset dementia. Heavy drinking has increased markedly in women over the past 10 years, particularly in mature adult women during the coronavirus (COVID-19) pandemic. This is concerning as women are more sensitive to many alcohol-related disease states, including AD and related dementias. Herein, we conducted two studies to determine if a 1-month period of binge drinking during mature adulthood (i.e., 5-9 months of age) impairs spatial and working memory to a greater extent in female vs. male C57BL/6J (B6J) mice. The anxiogenic and cognitive-impairing effects of binge drinking were also compared between mature adult and old B6J mice (18 months of age) in a third study. Throughout, females consumed more alcohol than males, indicating that a sex difference in binge drinking persists into old age. Despite the sex difference in intake, we detected no consistent sex difference in our measures of alcohol withdrawal-induced anxiety during a behavioral test battery. Although mature adult females exhibited more cognitive deficits than males, the precise outcome exhibiting a female-selective effect varied across studies. Old mice drank lower amounts of alcohol than mature adult mice, yet their blood ethanol concentrations (BECs) were within error of the 80 mg/dl criterion for binge drinking, indicative of an age-related slowing of alcohol metabolism. As expected, 18-month-old controls exhibited more signs of cognitive impairment than their 6-month-old counterparts, and binge drinking history impaired the Morris water maze performance of mice of both ages. In contrast, binge drinking history impaired the radial arm maze performance of 6-month-old mice only, and the extent of the impairment was comparable to the behavior exhibited by the older mice. We conclude from our studies that: (1) both biological sex and the age of drinking onset are subject factors that impact voluntary alcohol consumption by mice into old age; (2) binge drinking during later life elicits a negative affective state that is relatively sex-independent; (3) binge drinking during both mature adulthood and old age impairs spatial learning and memory; (4) binge drinking during mature adulthood accelerates deficits in working memory; and (5) mature adult females tend to exhibit more alcohol-induced cognitive impairments than males. If relevant to humans, these findings suggest that binge-like drinking by older adult men and women induces a negative affective state and cognitive decline, but that mature adult women, in particular, may be more sensitive to both the immediate and persistent cognitive-impairing effects of heavy drinking.

Comparison between measured and perceived weight status in a nationally representative sample of Australian adults.

BACKGROUND: Many individuals may not accurately perceive whether their weight status poses a health risk. This paper aimed to determine how accurately Australians perceived their weight status compared to objective measurements, and to determine what factors were associated with underestimating weight status. METHODS: Participants were 7947 non-pregnant adults from the 2011 to 2012 Australian National Nutrition and Physical Activity Survey, with complete data for self-reported and measured weight status. Multivariate logistic regression was used to examine associations between individual characteristics and accuracy of perceived weight status. RESULTS: Overall, 25.5% of the sample underestimated and 3.8% overestimated their weight status. Men were almost twice as likely as women to underestimate (34.0% vs 17.7%, p<0.001). In both sexes, underestimating weight status was strongly associated with higher waist circumference, satisfaction with weight and older age. In men, underestimation was associated with low education levels and being on a diet, and in women, underestimating weight status was associated with being born overseas and area-level disadvantage. CONCLUSIONS: At least a quarter of the adult population misperceives their weight status as healthy when in fact they are at increased risk of morbidity and mortality due to overweight and obesity. This may present a major barrier to prevention efforts.

Jamie's Ministry of Food: quasi-experimental evaluation of immediate and sustained impacts of a cooking skills program in Australia.

OBJECTIVE: To evaluate the immediate and sustained effectiveness of the first Jamie's Ministry of Food Program in Australia on individuals' cooking confidence and positive cooking/eating behaviours. METHODS: A quasi- experimental repeated measures design was used incorporating a wait-list control group. A questionnaire was developed and administered at baseline (T1), immediately post program (T2) and 6 months post completion (T3) for participants allocated to the intervention group, while wait -list controls completed it 10 weeks prior to program commencement (T1) and just before program commencement (T2). The questionnaire measured: participants' confidence to cook, the frequency of cooking from basic ingredients, and consumption of vegetables, vegetables with the main meal, fruit, ready-made meals and takeaway. Analysis used a linear mixed model approach for repeated measures using all available data to determine mean differences within and between groups over time. SUBJECTS: All adult participants (≥18 years) who registered and subsequently participated in the program in Ipswich, Queensland, between late November 2011- December 2013, were invited to participate. RESULTS: In the intervention group: 694 completed T1, 383 completed T1 and T2 and 214 completed T1, T2 and T3 assessments. In the wait-list group: 237 completed T1 and 149 completed T1 and T2 assessments. Statistically significant increases within the intervention group (P<0.001) and significant group*time interaction effects (P<0.001) were found in all cooking confidence measures between T1 and T2 as well as cooking from basic ingredients, frequency of eating vegetables with the main meal and daily vegetable intake (0.52 serves/day increase). Statistically significant increases at T2 were sustained at 6 months post program in the intervention group. CONCLUSIONS: Jamie's Ministry of Food Program, Australia improved individuals' cooking confidence and cooking/eating behaviours contributing to a healthier diet and is a promising community-based strategy to influence diet quality.

Wider impacts of a 10-week community cooking skills program--Jamie's Ministry of Food, Australia.

BACKGROUND: Jamie's Ministry of Food (JMoF) Australia is a 10-week community-based cooking skills program which is primarily aimed at increasing cooking skills and confidence and the promotion of eating a more nutritious diet. However, it is likely that the program influences many pathways to behaviour change. This paper explores whether JMoF impacted on known precursors to healthy cooking and eating (such as attitudes, knowledge, beliefs, cooking enjoyment and satisfaction and food purchasing behaviour) and whether there are additional social and health benefits which arise from program participation. METHODS: A mixed method, quasi-experimental longitudinal evaluation with a wait-list control was conducted. Intervention participants were measured using repeated questionnaires at three time points; before and after the program and at six-month follow-up. Control participants completed the questionnaire 10 weeks before their program and at program commencement. Quantitative analysis used a linear mixed model approach and generalised linear models for repeated measures using all available data. Qualitative methods involved 30-minute repeated semi-structured interviews with a purposively selected sample, analysed thematically. RESULTS: Statistically significant differences between groups and over time were found for a reduction of take away/fast food weekly purchasing (P = 0.004), and increases in eating meals at the dinner table (P = 0.01), cooking satisfaction (P = 0.01), and the ability to prepare a meal in 30 minutes (P < 0.001) and from basics that was low in cost (P < 0.001). The qualitative findings supported the quantitative results. Repeat qualitative interviews with fifteen participants indicated increased confidence and skills gained from the program to prepare meals from scratch as well as increases in family involvement in cooking and meal times at home. CONCLUSIONS: Jamie's Ministry of Food, Australia resulted in improvements in participants' food and cooking attitudes and knowledge, food purchasing behaviours and social interactions within the home environment, which were sustained six months after the program. TRIAL REGISTRATION: Australian and New Zealand Trial registration number: ACTRN12611001209987.

Methods for the evaluation of the Jamie Oliver Ministry of Food program, Australia.

BACKGROUND: Community-based programs aimed at improving cooking skills, cooking confidence and individual eating behaviours have grown in number over the past two decades. Whilst some evidence exists to support their effectiveness, only small behavioural changes have been reported and limitations in study design may have impacted on results.This paper describes the first evaluation of the Jamie Oliver Ministry of Food Program (JMoF) Australia, in Ipswich, Queensland. JMoF Australia is a community-based cooking skills program open to the general public consisting of 1.5 hour classes weekly over a 10 week period, based on the program of the same name originating in the United Kingdom. METHODS/DESIGN: A mixed methods study design is proposed. Given the programmatic implementation of JMoF in Ipswich, the quantitative study is a non-randomised, pre-post design comparing participants undergoing the program with a wait-list control group. There will be two primary outcome measures: (i) change in cooking confidence (self-efficacy) and (ii) change in self-reported mean vegetable intake (serves per day). Secondary outcome measures will include change in individual cooking and eating behaviours and psycho-social measures such as social connectedness and self-esteem. Repeated measures will be collected at baseline, program completion (10 weeks) and 6 months follow up from program completion. A sample of 250 participants per group will be recruited for the evaluation to detect a mean change of 0.5 serves a day of vegetables at 80% power (0.5% significance level). Data analysis will assess the magnitude of change of these variables both within and between groups and use sub group analysis to explore the relationships between socio-demographic characteristics and outcomes.The qualitative study will be a longitudinal design consisting of semi-structured interviews with approximately 10-15 participants conducted at successive time points. An inductive thematic analysis will be conducted to explore social, attitudinal and behavioural changes experienced by program participants. DISCUSSION: This evaluation will contribute to the evidence of whether cooking programs work in terms of improving health and wellbeing and the underlying mechanisms which may lead to positive behaviour change. TRIAL REGISTRATION: Australian and New Zealand Trial registration number: ACTRN12611001209987.

The cost-effectiveness of a successful community-based obesity prevention program: the be active eat well program.

OBJECTIVE: To examine the cost-effectiveness of Be Active Eat Well (BAEW), a large, multifaceted, community-based capacity-building demonstration program that promoted healthy eating and physical activity for Australian children aged 4-12 years between 2003 and 2006. DESIGN AND METHODS: A quasi-experimental, longitudinal design was used with anthropometric data collected at baseline (1001 children-intervention; 1183-comparator) and follow-up. A societal perspective was employed, with intervention resource use measured retrospectively based on process evaluation reports, school newsletters, reports, and key stakeholder interviews, and valued in 2006 Australian dollars (AUD). Outcomes were measured as Body Mass Index (BMI) units saved and Disability Adjusted Life Years (DALYs) averted over the predicted cohort lifetime, and reported as incremental cost-effectiveness ratios (with 95% uncertainty intervals). RESULTS: The intervention cost AUD0.34M ($0.31M; $0.38M) annually, and resulted in savings of 547 (-104; 1209) BMI units and 10.2 (-0.19; 21.6) DALYs. This translated to modest cost offsets of AUD27 311 (-$1803; $58 242) and a net cost per DALY saved of AUD29 798 (dominated; $0.26M). CONCLUSIONS: BAEW was affordable and cost-effective, and generated substantial spin-offs in terms of activity beyond funding levels. Elements fundamental to its success and any potential cost efficiencies associated with scaling-up now require identification.