Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis.

Tumor cells display progressive changes in metabolism that correlate with malignancy, including development of a lipogenic phenotype. How stored fats are liberated and remodeled to support cancer pathogenesis, however, remains unknown. Here, we show that the enzyme monoacylglycerol lipase (MAGL) is highly expressed in aggressive human cancer cells and primary tumors, where it regulates a fatty acid network enriched in oncogenic signaling lipids that promotes migration, invasion, survival, and in vivo tumor growth. Overexpression of MAGL in nonaggressive cancer cells recapitulates this fatty acid network and increases their pathogenicity-phenotypes that are reversed by an MAGL inhibitor. Impairments in MAGL-dependent tumor growth are rescued by a high-fat diet, indicating that exogenous sources of fatty acids can contribute to malignancy in cancers lacking MAGL activity. Together, these findings reveal how cancer cells can co-opt a lipolytic enzyme to translate their lipogenic state into an array of protumorigenic signals. PAPERFLICK:

A produce prescription program for patients with low incomes in North Carolina resulted in increased produce purchases.

OBJECTIVES: To assess if participation in a North Carolina produce prescription program for Supplemental Nutrition Assistance Program (SNAP) participants with diet-sensitive health conditions (SuperSNAP) is associated with changes in purchase composition and spending source. METHODS: This study used loyalty-card transaction data (October 2019-April 2022). We applied a linear mixed-effects model with overlap weights to perform a difference-indifferences analysis of purchases by SuperSNAP program enrollees compared to the control group. RESULTS: The sample included 1440 SuperSNAP shoppers and 45,851 control shoppers. Compared to shoppers only on SNAP, SuperSNAP shoppers spent $82.98 (95% CI (75.6, 90.3), p-value <0.001) more per month, $76.09 (95% CI (69.4, 82.8), pvalue <0.001) of which were spent strictly on food and beverage products. Among SuperSNAP shoppers, out of the $40 SuperSNAP benefit each month, an estimated $34.86 (95% CI (33.9, 35.8), p-value <0.001) of it was spent on fruits and vegetables. CONCLUSIONS: This study shows the promise of targeted produce prescription programs for SNAP participants in encouraging shifts in purchase composition.

Dietary intake of low-income adults in South Africa: ultra-processed food consumption a cause for concern.

OBJECTIVE: Given the rapidly changing food environment and proliferation of ultra-processed foods (UPF) in South Africa (SA), this study aimed to critically evaluate dietary quality and adequacy of low-income adults using the Nova classification system and WHO and World Cancer Research Fund dietary guidelines. DESIGN: Secondary household data and 1-d 24-h recalls were analysed from two cross-sectional studies conducted in 2017-2018. Foods consumed were classified according to the Nova classification system. Compliance with WHO dietary guidelines and UPF consumption trends were evaluated. SETTING: Three low-income areas (Langa, Khayalitsha and Mount Frere) in SA were included. PARTICIPANTS: In total, 2521 participants (18-50 years) were included in the study. RESULTS: Participants had a mean energy intake of 7762 kJ/d. Most participants were within the acceptable WHO guideline range for saturated fat (80·4 %), total fat (68·1 %), Na (72·7 %) and free sugar (57·3 %). UPF comprised 39·4 % of diets among the average adult participant. Only 7·0 % of all participants met the WHO guideline for fruit and vegetables and 18·8 % met the guideline for fibre. Those within the highest quartile of share of energy from UPF consumed statistically higher amounts of dietary components to limit and were the highest energy consumers overall. CONCLUSIONS: Low-income adults living in SA are consuming insufficient protective dietary components, while UPF consumption is prevalent. Higher UPF consumers consume larger amounts of nutrients linked to increased chronic disease risk. Policy measures are urgently needed in SA to protect against the proliferation of harmful UPF and to promote and enable consumption of whole and less UPF.

Indirect calorimetry directed feeding and cycling in the older ICU population: a pilot randomised controlled trial.

BACKGROUND: Older critically ill patients experience rapid muscle loss during stay in an intensive care unit (ICU) due to physiological stress and increased catabolism. This may lead to increased ICU length of stay, delayed weaning from ventilation and persistent functional limitations. We hypothesized that with optimal nutrition and early physical therapy acting in synergism, we can reduce muscle mass loss and improve functional outcomes. METHODS: This was a prospective, single blinded randomized, controlled single-center pilot study to compare the lean muscle mass (measured at bilateral quadriceps femoris using ultrasound) of older ICU patients at 4 time points over 14 days between the control and intervention groups. The control group received standard weight-based empiric feeding and standard ICU physiotherapy. The intervention group received indirect calorimetry directed feeding adjusted daily and 60 min per day of cycle ergometry. 21 patients were recruited and randomized with 11 patients in the control arm and 10 patients in the intervention arm. Secondary outcome measures included ICU and hospital mortality, length of stay, functional assessments of mobility and assessment of strength. RESULTS: Median age was 64 in the control group and 66 in the intervention group. Median calories achieved was 24.5 kcal/kg per day in the control group and 23.3 kcal/kg per day in the intervention group. Cycle ergometry was applied to patients in the intervention group for a median of 60 min a day and a patient had a median of 8.5 sessions in 14 days. Muscle mass decreased by a median of 4.7cm2 in the right quadriceps femoris in the control group and 1.8cm2 in the intervention group (p = 0.19), while the left quadriceps femoris decreased by 1.9cm2 in the control group and 0.1cm2 in the intervention group (p = 0.51). CONCLUSION: In this pilot study, we found a trend towards decrease muscle loss in bilateral quadriceps femoris with our combined interventions. However, it did not reach statistical significance likely due to small number of patients recruited in the study. However, we conclude that the intervention is feasible and potentially beneficial and may warrant a larger scale study to achieve statistical significance. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov on 30th May 2018 with identifier NCT03540732.

Comparison of skin cancer risk between renal transplant recipients and patients with glomerular diseases in rural Queensland.

INTROUDCTION: There is increased risk of skin cancer in patients with gloermular disease or those with renal transplant. OBJECTIVES: To compare the risk of skin cancer between kidney recipients (KTRs) and patients with glomerular disease (GD). DESIGN: The cohort comprised patients with KTRs (n = 61) and GD (n = 51) in Central and Central West Queensland, Australia. A quantitative cohort study was undertaken to study the risk of skin cancer in rural communities between two subgroups of patients with kidney diseases in relationship to immunosuppression. Statistical analyses of the differences in incidence of skin cancers between the two groups were done by chi-square test, Fisher's exact test, independent t-test and McNemar's test. FINDINGS: KTRs with non-melanoma skin carcinoma (NMSC) increased significantly after treatment with immunosuppressants (pre-transplantation, n = 11 [18.0%], post-transplantation, n = 28 [45.9%]; p < 0.001). There were no differences in number of patients with NMSC observed in the GD group (pre-diagnosis, n = 6 [11.8%], post-diagnosis, n = 7 [13.7%]; p = 1.000). Compared to the risks at 1 year post-immunosuppressants, the incidence of NMSC of KTRs increased significantly at 3 years (20.3% vs. 35.4%, p < 0.001) and 5 years (20.3% vs. 62.2%, p < 0.001) post-immunosuppressants, whereas the increased incidence of NMSC was observed only at 5 years (2.1% vs. 11.8%, p = 0.012) in the GD cohort. The mean cumulative number of NMSC in KTRs increased significantly at 3 years (p = 0.011), and 5 years (p = 0.001) post-immunosuppressants, compared to the risks at 1 year post-immunosuppressants, however, no differences were noted in the GD cohort. DISCUSSION: Immunosuppressants increased the risk of NMSC in KTRs. The increased risk is likely dependent on the intensity and duration of immunosuppressants. CONCLUSION: In patients with a high risk of NMSC, reducing skin cancer risk should be considered in conjunction with the optimisation of treatment.

Religious Belief Among Women in Australia: Characteristics and Role in Influencing Children's Health-Related Quality of Life and Lifestyle.

Religiosity can be an important factor in women's health-related behaviour, attitudes, and decision-making. Evidence however, regarding the religiosity of mothers and its influence on child health, is scarce. Based on a large population-based cohort in Australia, we aim to examine the religiosity of women in Australia and the association of maternal religiosity with children's health-related quality of life (HRQOL) and lifestyle. Our findings indicate that (1) maternal religious involvement was higher for women with higher education levels, ascertained religious values in decision-making, and abstinence from binge drinking in the household, (2) maternal religiosity positively influenced their children's HRQOL, (3) children of mothers who were more religious had less worries or fewer school-work problems, but the children of mothers with stronger religious beliefs used more internet/computer during the week but had less time playing games on weekends. This study provides additional specificity to inform future health interventions in religious community contexts to enhance the positive influence of maternal religious belief for better development of their children.

Joint frailty modeling of time-to-event data to elicit the evolution pathway of events: a generalized linear mixed model approach.

Multimorbidity constitutes a serious challenge on the healthcare systems in the world, due to its association with poorer health-related outcomes, more complex clinical management, increases in health service utilization and costs, but a decrease in productivity. However, to date, most evidence on multimorbidity is derived from cross-sectional studies that have limited capacity to understand the pathway of multimorbid conditions. In this article, we present an innovative perspective on analyzing longitudinal data within a statistical framework of survival analysis of time-to-event recurrent data. The proposed methodology is based on a joint frailty modeling approach with multivariate random effects to account for the heterogeneous risk of failure and the presence of informative censoring due to a terminal event. We develop a generalized linear mixed model method for the efficient estimation of parameters. We demonstrate the capacity of our approach using a real cancer registry data set on the multimorbidity of melanoma patients and document the relative performance of the proposed joint frailty model to the natural competitor of a standard frailty model via extensive simulation studies. Our new approach is timely to advance evidence-based knowledge to address increasingly complex needs related to multimorbidity and develop interventions that are most effective and viable to better help a large number of individuals with multiple conditions.

Early relapse is an adverse prognostic factor for survival outcomes in patients with oral cavity squamous cell carcinoma: results from a nationwide registry study.

BACKGROUND: The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC. METHODS: Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse. RESULTS: The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p < 0.0001 (AHR: 3.10 [2.69 - 3.57]) and OS: 49% versus 22%, p < 0.0001 (AHR: 3.32 [2.89 - 3.81]). CONCLUSION: After adjustment for potential confounders and PS matching, early relapse was an adverse prognostic factor for survival outcomes in patients with OCSCC. Our findings may have significant implications for risk stratification.

Using T1 mapping indices to evaluate muscle function and predict conservative treatment outcomes in diabetic patients with peripheral arterial disease.

OBJECTIVES: To investigate interstitial muscle fibrosis via T1 mapping indices and its relationships with muscle function and conservative treatment outcomes. METHODS: A total of 49 DM patients with PAD were prospectively recruited from 2016 to 2017. All PAD patients underwent pre-treatment MRI with conservative treatment via a rehabilitation program and antiplatelet therapy. The need to require percutaneous transluminal angioplasty intervention was recorded as intolerance to conservative treatment outcomes. We quantified calf interstitial muscle fibrosis using T1 mapping indices (native T1, post-contrast T1, and the extracellular volume fraction [ECV]). Muscle function was evaluated using a 6-min walking test (6MWT) and a 3-min stepping test (3MST). PAD patients were divided into two groups according to their tolerance or intolerance of the conservative treatment. Pearson's correlation, reproducibility, and multivariable Cox hazard analyses were performed with p < 0.05 indicating statistical significance. RESULTS: Among the T1 mapping indices in the posterior compartment of the calf in PAD patients, the native T1 value was significantly correlated with 6MWT (r = -0.422, p = 0.010) and 3MST (r = -0.427, p = 0.009). All T1 mapping indices showed excellent intra-observer and inter-observer correlations. ECV was an independent predictor of conservative treatment intolerance (average ECV, hazard ratio: 1.045, 95% confidence interval: 1.011-1.079, p = 0.009). CONCLUSIONS: T1 mapping measurements are reproducible with excellent intra-observer and inter-observer correlations. T1 mapping indices may be predictive of treatment and functional outcomes and carry promise in patient evaluation. TRIAL REGISTRATION: Clinical Trials Identifier: NCT02850432 . KEY POINTS: • T1 mapping measurements of the calf muscles are reproducible with excellent intra-observer and inter-observer correlations (0.98 and 0.95 for anterior and posterior compartment muscle extracellular volume matrix [ECV] measurements, respectively). • ECV is shown to independently predict conservative treatment intolerance. • T1 mapping indices may be predictive of treatment and functional outcomes and carry promise in patient evaluation.

Fully automated segmentation and radiomics feature extraction of hypopharyngeal cancer on MRI using deep learning.

OBJECTIVES: To use convolutional neural network for fully automated segmentation and radiomics features extraction of hypopharyngeal cancer (HPC) tumor in MRI. METHODS: MR images were collected from 222 HPC patients, among them 178 patients were used for training, and another 44 patients were recruited for testing. U-Net and DeepLab V3 + architectures were used for training the models. The model performance was evaluated using the dice similarity coefficient (DSC), Jaccard index, and average surface distance. The reliability of radiomics parameters of the tumor extracted by the models was assessed using intraclass correlation coefficient (ICC). RESULTS: The predicted tumor volumes by DeepLab V3 + model and U-Net model were highly correlated with those delineated manually (p < 0.001). The DSC of DeepLab V3 + model was significantly higher than that of U-Net model (0.77 vs 0.75, p < 0.05), particularly in those small tumor volumes of < 10 cm3 (0.74 vs 0.70, p < 0.001). For radiomics extraction of the first-order features, both models exhibited high agreement (ICC: 0.71-0.91) with manual delineation. The radiomics extracted by DeepLab V3 + model had significantly higher ICCs than those extracted by U-Net model for 7 of 19 first-order features and for 8 of 17 shape-based features (p < 0.05). CONCLUSION: Both DeepLab V3 + and U-Net models produced reasonable results in automated segmentation and radiomic features extraction of HPC on MR images, whereas DeepLab V3 + had a better performance than U-Net. CLINICAL RELEVANCE STATEMENT: The deep learning model, DeepLab V3 + , exhibited promising performance in automated tumor segmentation and radiomics extraction for hypopharyngeal cancer on MRI. This approach holds great potential for enhancing the radiotherapy workflow and facilitating prediction of treatment outcomes. KEY POINTS: • DeepLab V3 + and U-Net models produced reasonable results in automated segmentation and radiomic features extraction of HPC on MR images. • DeepLab V3 + model was more accurate than U-Net in automated segmentation, especially on small tumors. • DeepLab V3 + exhibited higher agreement for about half of the first-order and shape-based radiomics features than U-Net.

Determinants of health-related quality of life in people with Human Immunodeficiency Virus, failing first-line treatment in Africa.

BACKGROUND: Antiretroviral treatment improves health related quality of life (HRQoL) of people with human immunodeficiency virus (PWH). However, one third initiating first-line treatment experience virological failure and the determinants of HRQoL in this key population are unknown. Our study aims to identify determinants of among PWH failing antiretroviral treatment in sub-Saharan Africa. METHODS: We analysed data from a cohort of PWH having virological failure (> 1,000 copies/mL) on first-line ART in South Africa and Uganda. We measured HRQoL using the EuroQOL EQ-5D-3L and used a two-part regression model to obtain by-country analyses for South Africa and Uganda. The first part identifies risk factors that were associated with the likelihood of participants reporting perfect health (utility = 1) versus non-perfect health (utility < 1). The second part identifies risk factors that were associated with the EQ-5 L-3L utility scores for participants reporting non-perfect health. We performed sensitivity analyses to compare the results between the two-part model using tobit models and ordinary least squares regression. RESULTS: In both countries, males were more likely to report perfect health and participants with at least one comorbidity were less likely to report perfect health. In South Africa, participants with side effects and in Uganda those with opportunistic infections were also less likely to report perfect health. In Uganda, participants with 100% ART adherence were more likely to report perfect health. In South Africa, high HIV viral load, experiencing ART side effects, and the presence of opportunistic infections were each associated with lower HRQoL, whereas participants with 100% ART adherence reported higher HRQoL. In Uganda participants with lower CD4 count had lower HRQoL. CONCLUSION: Markers of advanced disease (opportunistic infection, high viral load, low CD4), side effects, comorbidities and lack of ART adherence negatively impacted HRQoL for PWH experiencing virological failure. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02787499.

Delirium is significantly associated with hospital frailty risk score derived from administrative data.

OBJECTIVES: Delirium is highly prevalent in hospitalised older adults, under-diagnosed and associated with poor outcomes. We aim to determine (i) association of frailty measured using Hospital Frailty Risk Score (HFRS) with delirium, (ii) impact of delirium on mortality, 30-days readmission, extended length of stay (eLOS) and cost (eCOST). METHODS: Retrospective cohort study was conducted on 902 older adults ≥75 years discharged from an academic tertiary hospital between March and September 2021. Data was obtained from hospital administrative database. RESULTS: Delirium was prevalent in 39.1%, 58.1% were female with mean age 85.3 ± 6.2 years. Patients with delirium were significantly older, had higher HFRS, pneumonia, urinary tract infection (UTI), E.coli and Klebsiella infection, constipation, dehydration, stroke and intracranial bleed, with comorbidities including dementia, diabetes, hypertension, hyperlipidaemia and chronic kidney disease. In-hospital mortality, 30-days mortality, 30-days readmission, median LOS and cost was significantly higher. Delirium was significantly associated with at least intermediate frailty (OR = 3.52; CI = 2.48-4.98), dementia (OR = 2.39; CI = 1.61-3.54), UTI (OR = 1.95; CI = 1.29-2.95), constipation (OR = 2.49; CI = 1.43-4.33), Klebsiella infection (OR = 3.06; CI = 1.28-7.30), dehydration (OR = 2.01; CI = 1.40 - 2.88), 30-day mortality (OR = 2.52; CI = 1.42-4.47), 30-day readmission (OR = 2.18; CI = 1.36-3.48), eLOS (OR = 1.80; CI = 1.30-2.49) and eCOST (OR = 1.67; CI = 1.20-2.35). CONCLUSIONS: Delirium was highly prevalent in older inpatients, and associated with dementia, frailty, increased cost, LOS, 30-day readmissions and mortality. Hospital Frailty Risk Score had robust association with delirium and can be auto-populated from electronic medical records. Prospective studies are needed on multicomponent delirium preventive measures in high-risk groups identified by HFRS in acute care settings.

A cross-sectional study of symptoms and health-related quality of life in menopausal-aged women in China.

OBJECTIVE: To measure symptoms and health-related quality of life in a cross-sectional cohort of menopausal-aged women in China. METHOD: A cross-sectional survey was conducted in a general population cohort of 2,000 Chinese females over the age of 45 years. Patients completed the Chinese version of the EuroQol-5D five level (EQ5D5L) health-related quality of life instrument via Personal Digital Assistant. Raw scores were converted to utility tariffs using value sets for China. Statistical analysis included Pearson's chi-square test, z test for multiple comparisons with adjustment by the Bonferroni method, independent-sample t-test, ANOVA, and adjustment by the Tukey method for multiple comparison. Results were considered statistically significant when p < 0.05 and the study was reported according to the STROBE recommendations. RESULTS: In a cohort of 2000 women, 732 (37%) were premenopausal, 798 (40%) were perimenopausal and 470 (23%) were postmenopausal. Perimenopausal women reported significantly more symptoms (91%) compared to premenopausal (77%) and postmenopausal (81%) women. Health-related quality of life was significantly lower in symptomatic perimenopausal women compared to premenopausal (0.919, p < 0.05) and postmenopausal (0.877, p < 0.05) women. Within each group there was a statistically significant difference between the health-related quality of life of women with symptoms compared to without symptoms. CONCLUSION: The perimenopausal phase of menopause is associated with significantly more symptoms and significantly lower HRQoL compared to premenopausal and postmenopausal phases.

Why is this study needed?• It is important to understand the impact of menopausal symptoms on women's quality of life so that decisions can be made about what healthcare services to provide and what treatments to fund.• Currently there are only a few older studies investigating menopausal symptoms in the perimenopausal phase, which is characterised by hormone fluctuations and symptoms likely to impact quality of life, and lasts up to four years. What is the key problem this manuscript addresses?• This research measures symptoms and the impact on quality of life of menopausal women in China. What are your main results and what do they mean?• Women in the perimenopausal phase are disproportionately affected by symptoms compared to premenopausal and postmenopausal women.• Perimenopausal women have significantly lower HRQoL compared to premenopausal and postmenopausal women.• This information is critical to informing pharmacoeconomic decisions about healthcare provision and publicly funded treatments in China.

Sociodemographic disparities in purchases of fruit drinks with policy relevant front-of-package nutrition claims.

OBJECTIVE: Our objectives were to describe sociodemographic characteristics associated with the purchase of (1) any fruit drinks and (2) fruit drinks with specific front-of-package (FOP) nutrition claims. DESIGN: Cross-sectional. SETTING: USA. PARTICIPANTS: We merged fruit drink purchasing data from 60 712 household-months from 5233 households with children 0-5 years participating in Nielsen Homescan in 2017 with nutrition claims data. We examined differences in predicted probabilities of purchasing any fruit drinks by race/ethnicity, income and education. We constructed inverse probability (IP) weights based on likelihood of purchasing any fruit drinks. We used IP-weighted multivariable logistic regression models to examine predicted probabilities of purchasing fruit drinks with specific FOP claims. RESULTS: One-third of households with young children purchased any fruit drinks. Non-Hispanic (NH) Black (51·6 %), Hispanic (36·3 %), lower-income (39·3 %) and lower-educated households (40·9 %) were more likely to purchase any fruit drinks than NH White (31·3 %), higher-income (25·8 %) and higher-educated households (30·3 %) (all P < 0·001). In IP-weighted analyses, NH Black households were more likely to purchase fruit drinks with 'Natural' and fruit or fruit flavour claims (6·8 % and 3·7 %) than NH White households (4·5 % and 2·7 %) (both P < 0·01). Lower- and middle-income (15·0 % and 13·8 %) and lower- and middle-educated households (15·4 % and 14·5 %) were more likely to purchase fruit drinks with '100 % Vitamin C' claims than higher-income (10·8 %) and higher-educated households (12·9 %) (all P < 0·025). CONCLUSIONS: We found a higher likelihood of fruit drink purchases in lower-income, lower-educated, NH Black and Hispanic households. Experimental studies should determine if nutrition claims may be contributing to disparities in fruit drink consumption.

Clinical and economic burden of benign and malignant skin lesions in renal transplant recipients.

BACKGROUND: Studies evaluating the economic burden of dermatological care in the transplant setting are currently not available in Australia. AIMS: To evaluate the clinical and economic burden of benign and malignant skin lesions in renal transplant recipients in Central Queensland. METHODS: A bottom-up approach was used to determine the clinical burden and direct costs from patient-level Medicare data obtained from Service Australia for skin lesions. RESULTS: Seventy-six percent of the renal transplant population in Central Queensland participated in this study. The median age was 57.0 years (standard deviation ± 13.6) and the majority (61.8%) of participants were men. The mean duration after transplant surgery was 99.9 months (interquartile range, 73.2-126.6 months). During a 2-year follow-up, 22 (40%) patients were diagnosed with benign skin lesions, 21 (38%) with nonmelanoma skin carcinoma (NMSC) and one (2%) with melanoma. There was a total of 231 visits to clinicians for diagnostic and therapeutic skin procedures and the direct costs to Medicare was $48 806 Australian Dollars (AUD) or $30 427 US Dollars (USD). Approximately 86% of the total direct costs was spent for nonNMSC and mean direct costs for NMSC was $763 AUD (or $476 USD). CONCLUSION: This Medicare data-based study provides further insight into the burgeoning clinical and economic burden of the care for benign and malignant skin lesions in the renal transplantation setting in Australia.

Higher well-being individuals are more receptive to cultivated meat: An investigation of their reasoning for consuming cultivated meat.

It is evident that over-consumption of meat can contribute to the emission of hazardous greenhouse gases. One viable way to address such climate impact is to make people become more aware of more sustainable diet options, such as cultivated meat. However, it is challenging to instigate change in people's meat-eating habit, and empirical works have been examining the psychological factors that are related to consumers' willingness to consume cultivated meat. Research has suggested that psychological well-being can play a role in the meaning-making of food consumption, with higher well-being individuals showing more recognition of other sociocultural benefits of consuming food beyond just fulfilling their sustenance needs. As existing works have yet to understand the link between well-being and consumption of novel foods, the current research set out to fill this gap by examining the relationship between people's psychological well-being and their willingness to consume cultivated meat via different reasons (mediators) for consuming cultivated meat. We recruited a representative sample of 948 adults in Singapore to complete an online survey. The study offered the first evidence that there is a positive relationship between people's psychological well-being and their willingness to consume cultivated meat. Further, results revealed that their higher willingness can be motivated by the perception that cultivated meat is as healthy and nutritious, as safe as, and has the same sensory quality as real meat, and is beneficial to the society. This investigation adds to the growing literature on consumer acceptance of cultivated meat by showing the novel finding that well-being and receptivity to cultivated meat is positively linked, and such a positive link can be explained by people's better recognition of the prospective benefits offered by this alternative food.

KCC2 is required for the survival of mature neurons but not for their development.

The K+/Cl- cotransporter KCC2 (SLC12A5) allows mature neurons in the CNS to maintain low intracellular Cl- levels that are critical in mediating fast hyperpolarizing synaptic inhibition via type A γ-aminobutyric acid receptors (GABAARs). In accordance with this, compromised KCC2 activity results in seizures, but whether such deficits directly contribute to the subsequent changes in neuronal structure and viability that lead to epileptogenesis remains to be assessed. Canonical hyperpolarizing GABAAR currents develop postnatally, which reflect a progressive increase in KCC2 expression levels and activity. To investigate the role that KCC2 plays in regulating neuronal viability and architecture, we have conditionally ablated KCC2 expression in developing and mature neurons. Decreasing KCC2 expression in mature neurons resulted in the rapid activation of the extrinsic apoptotic pathway. Intriguingly, direct pharmacological inhibition of KCC2 in mature neurons was sufficient to rapidly induce apoptosis, an effect that was not abrogated via blockade of neuronal depolarization using tetrodotoxin (TTX). In contrast, ablating KCC2 expression in immature neurons had no discernable effects on their subsequent development, arborization, or dendritic structure. However, removing KCC2 in immature neurons was sufficient to ablate the subsequent postnatal development of hyperpolarizing GABAAR currents. Collectively, our results demonstrate that KCC2 plays a critical role in neuronal survival by limiting apoptosis, and mature neurons are highly sensitive to the loss of KCC2 function. In contrast, KCC2 appears to play a minimal role in mediating neuronal development or architecture.

The Influence of Front-of-Package Nutrition Labeling on Consumer Behavior and Product Reformulation.

Countries worldwide have implemented mandatory or voluntary front-of-package nutrition labeling systems. We provide a narrative review of (a) real-world evaluations of front-of-package nutrition labels that analyze objective sales data and (b) studies that objectively assess product reformulation in response to a front-of-package nutrition label implementation. We argue that there is sufficient scientific evidence to recommend that governments implement mandatory front-of-package nutrition labeling systems to improvepopulation health. We also present a conceptual framework to describe front-of-package label influence and provide recommendations for the optimal label design, emphasizing that labeling systems should be highly visible and salient, be simple and easy to understand, leverage automatic associations, and integrate informational and emotional messaging. The existing research suggests that Guideline Daily Amount labels should be avoided and that the Health Star Rating and Nutri-Score systems are promising but that systems with warning labels like the one in Chile are likely to produce the largest public health benefits.

Clinical Outcomes of Taiwanese Patients with Resected Oral Cavity Squamous Cell Carcinoma Who Underwent Reconstruction with Free Versus Local Flaps.

BACKGROUND: We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps. METHODS: From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable. RESULTS: Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age < 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin > 4 mm, extranodal extension (ENE), and adjuvant therapy (all p < 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079). CONCLUSIONS: After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.

Junk Food Intake Among Adults in the United States.

BACKGROUND: There is no consensus on how to define "junk food." In 2016, Chile implemented the most comprehensive set of obesity-preventive regulations in the world, including criteria to define unhealthy foods. OBJECTIVES: The objective of this study was to examine the amount of energy, sodium, sugar, and saturated fat consumed by US adults defined as junk food using the Chilean criteria. METHODS: We used 2 nationally representative surveys of food intake in 10,001 US adults: NHANES 2015-2016 and NHANES 2017-2018. The main outcome measures were the contributions of energy, total sugars, saturated fat, and sodium deriving from junk food sources. Mean intake and proportion of energy, sugar, saturated fat, and sodium for junk food overall and each food category were calculated. RESULTS: Overall, 47% of energy, 75% of total sugar, 46% of sodium, and 48% of saturated fat consumed by US adults derived from junk food sources. Sugar-sweetened beverages (SSBs) were responsible for more than 40% of total sugar intake deriving from junk foods. Non-Hispanic black adults had the highest mean energy, total sugar, and sodium intake deriving from junk foods, with non-Hispanic white adults having the highest saturated fat intake. Non-Hispanic black adults had the highest intake of total sugar deriving from junk food sources of SSBs (26.7 g/d), with SSBs representing >40% of total sugar intake deriving from junk food sources for all race/ethnic groups. CONCLUSIONS: Foods that meet the Chilean criteria for junk food provide approximately half or more daily energy and food components to limit in the diet of US adults, with important differences observed between race/ethnic groups. Policy efforts to reduce junk food intake, particularly the intake of SSBs, must be expanded to improve the cardiometabolic health equitably in the United States.