Comparison of Anti-Hepatitis A Antibody Pharmacokinetics in Healthy Australian Subjects Receiving Standard or Weight-Based Dosing of Polyvalent Immunoglobulin.

This randomized controlled trial compared two dosing regimens of the polyvalent immunoglobulin available for hepatitis A post-exposure prophylaxis in Australia. Participants were randomized to receive either 270 IU (standard dose) or 3.375 IU/kg (dose by weight). Quantitative serial serum hepatitis A antibody concentrations were measured at baseline and then on days 1, 3, 7, 28, and 50. Fifteen participants completed the trial. Serum hepatitis A antibody concentrations were not different between the study groups at any time point. Pharmacokinetic parameters estimated from participant data were not different between the study groups. The hepatitis A antibody level of all participants exceeded 10 mIU/mL at day 50. While no difference between dosing regimens was found in this study, further research should examine dosing at the lower limit of current Australian recommendations before making policy decisions.

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.

Prognostic impact of elective tracheotomy in resected oral cavity squamous cell carcinoma: A nationwide cohort study.

BACKGROUND: Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in-hospital stay and long-term survival outcomes in patients with OCSCC. METHODS: A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5-year disease-specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)-matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS-matched analysis. RESULTS: Prior to PS matching, patients with tracheotomy had significantly lower 5-year DSS and OS rates compared to those without (71% vs. 82%, p < 0.0001; 62% vs. 75%, p < 0.0001, respectively). Multivariable analysis identified tracheotomy as an independent adverse prognostic factor for 5-year DSS (hazard ratio = 1.10 [1.03-1.18], p = 0.0063) and OS (hazard ratio = 1.10 [1.04-1.17], p = 0.0015). In the PS-matched cohort, the 5-year DSS was 75% for patients with tracheotomy and 76% for those without (p = 0.1488). Five-year OS rates were 66% and 67%, respectively (p = 0.0808). Prior to PS matching, patients with tracheotomy had a significantly longer mean hospital stay compared to those without (23.37 ± 10.56 days vs. 14.19 ± 8.34 days; p < 0.0001). Following PS matching, the difference in hospital stay duration between the two groups remained significant (22.34 ± 10.25 days vs. 17.59 ± 9.54 days; p < 0.0001). CONCLUSIONS: While elective tracheotomy in resected OCSCC patients may not significantly affect survival, it could be associated with prolonged hospital stays.

Sustained Inhibition of GABA-AT by OV329 Enhances Neuronal Inhibition and Prevents Development of Benzodiazepine Refractory Seizures.

γ-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the adult brain which mediates its rapid effects on neuronal excitability via ionotropic GABAA receptors. GABA levels in the brain are critically dependent upon GABA-aminotransferase (GABA-AT) which promotes its degradation. Vigabatrin, a low-affinity GABA-AT inhibitor, exhibits anticonvulsant efficacy, but its use is limited due to cumulative ocular toxicity. OV329 is a rationally designed, next-generation GABA-AT inhibitor with enhanced potency. We demonstrate that sustained exposure to OV329 in mice reduces GABA-AT activity and subsequently elevates GABA levels in the brain. Parallel increases in the efficacy of GABAergic inhibition were evident, together with elevations in electroencephalographic delta power. Consistent with this, OV329 exposure reduced the severity of status epilepticus and the development of benzodiazepine refractory seizures. Thus, OV329 may be of utility in treating seizure disorders and associated pathologies that result from neuronal hyperexcitability.

Comparing the clinical outcomes of initial surgery and primary definitive radiotherapy with a dosage of 6600 cGy or higher in cT1-2N0M0 oral cavity squamous cell carcinoma: A nationwide cohort study.

BACKGROUND: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC). METHODS: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145). RESULTS: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. CONCLUSIONS: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.

Relationship between parathyroid adenoma size, weight and histological subtypes with perioperative serum levels.

AIMS: This study aims to identify associations between parathyroid adenoma (PTA) characteristics (histology, weight and size) with the change in parathyroid hormone (PTH) and calcium levels. METHODS: A historical cohort study was conducted on adult patients with solitary PTA removed in the Gold Coast Health Precinct, Australia, between 2017 and 2022. RESULTS: PTA weight is correlated with the change in day 1 PTH level (r=0.26, p=0.036), the change in day 1 corrected calcium level (r=0.20, p=0.033), and the change in follow-up corrected calcium level (r=0.47, p<0.001). The largest dimension (size) of PTA is also correlated with the change in day 1 PTH (r=0.30, p=0.011) and the change in follow-up corrected calcium level (r=0.40, p<0.001). Adjusted for age and gender, a statistically significant negative correlation was found between day 1 PTH level and adenoma size, resulting in a 0.5% change in size for every percentage change in PTH level (equating to a 5.0% increase in variance explained, p=0.038). Similarly, a negative correlation was identified in day 1 corrected calcium levels and weight, with a 4.7% change in weight for every percentage of change in day 1 corrected calcium level (an increase of 5.6% variance explained, p=0.010). In addition, a negative correlation was identified, where every 3.1% change in size (an increase of 17.4% variance explained, p<0.001) and 7.6% change in weight (an increase of 22.7% variance explained, p<0.001) was seen with every percentage change in follow-up corrected calcium levels. Clear-cell PTA had the most significant percentage fall in day 1 corrected calcium levels compared with other PTA subtypes (p=0.007). CONCLUSIONS: Preoperative calcium and PTH levels correlate with PTA weight and size. The degree of change in postoperative corrected calcium levels behaved differently in the clear-cell subtype.

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.

Hyperpolarized [1-13C]-pyruvate MRS evaluates immune potential and predicts response to radiotherapy in cervical cancer.

BACKGROUND: Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. METHODS: This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39-60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. RESULTS: The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. CONCLUSIONS: This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951921 , registered 7 July 2021. RELEVANCE STATEMENT: This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients' immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. KEY POINTS: • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients' immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy.

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.

How Promising Are "Ultraprocessed" Front-of-Package Labels? A Formative Study with US Adults.

High levels of food processing can have detrimental health effects independent of nutrient content. Experts and advocates have proposed adding information about food processing status to front-of-package labeling schemes, which currently exclusively focus on nutrient content. How consumers would perceive "ultraprocessed" labels has not yet been examined. To address this gap, we conducted a within-subjects online experiment with a convenience sample of 600 US adults. Participants viewed a product under three labeling conditions (control, "ultraprocessed" label, and "ultraprocessed" plus "high in sugar" label) in random order for a single product. The "ultraprocessed" label led participants to report thinking more about the risks of eating the product and discouraging them from wanting to buy the product more than the control, despite not grabbing more attention than the control. The "ultraprocessed" plus "high in sugar" labels grabbed more attention, led participants to think more about the risks of eating the product, and discouraged them from wanting to buy the product more than the "ultraprocessed" label alone. "Ultraprocessed" labels may constitute promising messages that could work in tandem with nutrient labels, and further research should examine how they would influence consumers' actual intentions and behaviors.

Hyperpolarized Carbon-13 Magnetic Resonance Imaging: Technical Considerations and Clinical Applications.

Hyperpolarized (HP) carbon-13 (13C) MRI represents an innovative approach for noninvasive, real-time assessment of dynamic metabolic flux, with potential integration into routine clinical MRI. The use of [1-13C]pyruvate as a probe and its conversion to [1-13C]lactate constitute an extensively explored metabolic pathway. This review comprehensively outlines the establishment of HP 13C-MRI, covering multidisciplinary team collaboration, hardware prerequisites, probe preparation, hyperpolarization techniques, imaging acquisition, and data analysis. This article discusses the clinical applications of HP 13C-MRI across various anatomical domains, including the brain, heart, skeletal muscle, breast, liver, kidney, pancreas, and prostate. Each section highlights the specific applications and findings pertinent to these regions, emphasizing the potential versatility of HP 13C-MRI in diverse clinical contexts. This review serves as a comprehensive update, bridging technical aspects with clinical applications and offering insights into the ongoing advancements in HP 13C-MRI.

Promoting Healthier Purchases: Ultraprocessed Food Taxes and Minimally Processed Foods Subsidies for the Low Income.

INTRODUCTION: Fiscal policies can shift relative food prices to encourage the purchase and consumption of minimally processed foods while discouraging the purchase and consumption of unhealthy ultraprocessed foods, high in calories and nutrients of concern (sodium, sugar, and saturated fats), especially for low-income households. METHODS: The 2017-2018 packaged food purchase data among U.S. households were used to derive household income- and composition-specific demand elasticities across 22 food and beverage categories. Policy simulations, conducted in 2022-2023, assessed the impact of national taxes on unhealthy ultraprocessed food and beverage purchases, both separately and alongside subsidies for minimally processed foods and beverages targeted to low-income households. Resultant nutritional implications are reported on the basis of changes in purchased calories and nutrients of concern. In addition, financial implications for both households and the federal government are projected. RESULTS: A sugar-based tax on sugar-sweetened beverages would lower both volume and calories purchased with the largest impact on low-income households without children. Meanwhile, targeted subsidies would increase fruit, vegetable, and healthier drink purchases without substantially increasing calories. Under tax simulations, low-income households would make larger reductions in their absolute volume and calorie purchases of taxed foods and beverages than their higher-income counterparts, suggesting that these policies, if implemented, could help narrow nutritional disparities. CONCLUSIONS: Levying national taxes on unhealthy ultraprocessed foods/beverages and offering targeted subsidies for minimally processed foods/beverages could promote healthier food choices among low-income households. Such policies have the potential to benefit low-income households financially and at a relatively low cost for the federal government annually.

Special Supplemental Nutrition Program for Women, Infants, and Children Participant Grocery Store Purchases during the COVID-19 Pandemic in North Carolina.

Background: Families participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) experienced barriers to accessing healthy food during the COVID-19 pandemic, but we do not yet understand how WIC participant food purchases shifted during the pandemic. Objectives: We aimed to describe the association between the initial shock of the pandemic in March 2020 and WIC shoppers' food purchases and changes in purchases before and during the pandemic at a top grocery chain and examine differences in these relationships by duration of WIC use. Methods: We used longitudinal food transaction data from WIC shoppers (n = 2,989,116 shopper-month observations from 175,081 unique WIC shoppers) from 496 stores in a top grocery store chain in North Carolina between October 2019 and May 2021. We used an interrupted time series design to describe the following: 1) the relationship between the initial shock of the pandemic and WIC shopper food purchases and 2) differences in purchases before and during the pandemic. To assess differences in purchases between shoppers consistently using WIC electronic benefit transfer (EBT) cards and shoppers starting or stopping WIC EBT use during the pandemic, we used models stratified by WIC group. Primary outcomes were share (%) of total calories purchased from fruits, vegetables, nuts, and legumes (FV), processed foods, and sugar-sweetened beverages (SSBs). Results: We observed small decreases in the share of total calories from FV (-0.4%) and small increases in the share of calories from processed food (1.1%) and SSBs (0.5%) purchased at this retailer when comparing the pre and post March 2020 periods. Compared with shoppers that started or stopped using WIC benefits during the pandemic, shoppers that used WIC benefits consistently had slightly higher FV and lower processed food and SSB purchases at this retailer. Conclusions: Future studies should examine whether additional supports for nutrient-dense food choices may be needed for families with low incomes in public health emergencies.

Impact of the Philadelphia Beverage Tax on Perceived Beverage Healthfulness, Tax Awareness, and Tax Opinions.

OBJECTIVE: To assess the impact of the Philadelphia Beverage Tax on perceived beverage healthfulness, and awareness and opinions of the tax. DESIGN: Natural experiment SETTING: Small independent stores in Philadelphia (n = 61) and Baltimore (untaxed control site; n = 65) PARTICIPANTS: Shoppers in Philadelphia (n = 2,731) and Baltimore (n = 4,600) pre- and post-tax implementation. MAIN OUTCOME MEASURES: Perceptions of 4 beverages (unhealthy vs healthy/neutral), tax awareness, and tax opinions (oppose vs favor/neutral). ANALYSIS: Mixed-effects linear probability models estimated changes in perceived beverage healthfulness in Philadelphia, relative to Baltimore, following a difference-in-differences approach. Mixed-effects linear probability models estimated pre-post changes in tax awareness and opinions in Philadelphia-only. RESULTS: The probability of perceiving taxed beverages as unhealthy increased 2-years post-tax relative to Baltimore (regular soda: 5.7% [95% confidence interval (CI), 0.9-10.6], P = 0.02; diet soda: 7.7% [95% CI, 1.5-13.8], P < 0.001; sports drinks: 6.4% [95% CI, 0.4-12.4], P = 0.04), with similar changes at 1-year post-tax, whereas perceived healthfulness of untaxed 100% fruit juice did not change. Tax awareness was high at baseline (72%) and increased post-implementation; however, the probability of opposing the tax (22%) also increased over time. CONCLUSIONS AND IMPLICATIONS: Decreases in the perceived healthfulness of taxed beverages suggest the tax had a health-signaling effect. Consumer awareness and health education efforts could complement tax policies to enhance understanding of health risks.

Should sub-millimeter margins be deemed positive in oral cavity squamous cell carcinoma?

BACKGROUND: While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm. METHODS: Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted. RESULTS: The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398). CONCLUSIONS: OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins.

A Qualitative Exploration of Spanish-Speaking Latina Women's Experiences Participating in WIC Before and During the COVID-19 Pandemic.

BACKGROUND: More than one-third of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) participants identify as Latino, but participation has been declining and individuals who speak predominantly Spanish face additional barriers to participation. During the COVID-19 pandemic, there were changes in WIC eligibility and benefits that may have been differentially accessible to Spanish-speaking Latina participants due to factors such as language barriers and lack of awareness of changes. Understanding Spanish-speaking Latinas' experiences with the WIC program generally and during the pandemic can inform efforts to equitably implement future emergency food response policies and improve the WIC program and Latina participant enrollment more broadly. OBJECTIVE: This study aimed to understand the perceptions and experiences of Spanish-speaking Latina WIC participants with the WIC program generally and with COVID-19 pandemic-related policy changes made to the WIC program. DESIGN: Qualitative in-depth interviews were conducted virtually in Spanish in August 2022 using a semi-structured guide. PARTICIPANTS/SETTING: Study participants were 18 Spanish-speaking Latina adult WIC participants living in North Carolina recruited using convenience sampling. ANALYSIS: All interviews were recorded, transcribed, and coded in Spanish. Thematic analysis with inductive coding was used to derive key themes. RESULTS: Perceptions about the WIC program in this sample were mixed. Participants felt positively about the healthfulness of foods included in the WIC food packages but expressed concern about the monthly benefit amounts being too low and the cultural appropriateness of food options. Pandemic policy changes, such as remote appointments and the Cash Value Benefit increase were perceived positively; however, barriers to using benefits during this time included limited communication from WIC agencies, food shortages, and concerns about not being granted US citizenship or permanent resident status due to use of WIC (ie, public charge rule). Social networks played an important role in learning about and enrolling in WIC and navigating food shortages during the pandemic. CONCLUSIONS: Concerns about the cultural appropriateness of foods provided, communication challenges, and the public charge rule emphasized the need for resources dedicated in the WIC program to improving Spanish-speaking Latina women's experiences with WIC.

Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts.

In many cancers, mortality is associated with the emergence of relapse with multidrug resistance (MDR). Thus far, the investigation of cancer relapse mechanisms has largely focused on acquired genetic mutations. Using acute myeloid leukemia (AML) patient-derived xenografts (PDX), we systematically elucidated a basis of MDR and identified drug sensitivity in relapsed AML. We derived pharmacologic sensitivity for 22 AML PDX models using dynamic BH3 profiling (DBP), together with genomics and transcriptomics. Using in vivo acquired resistant PDXs, we found that resistance to unrelated, narrowly targeted agents in distinct PDXs was accompanied by broad resistance to drugs with disparate mechanisms. Moreover, baseline mitochondrial apoptotic priming was consistently reduced regardless of the class of drug-inducing selection. By applying DBP, we identified drugs showing effective in vivo activity in resistant models. This study implies evasion of apoptosis drives drug resistance and demonstrates the feasibility of the DBP approach to identify active drugs for patients with relapsed AML. SIGNIFICANCE: Acquired resistance to targeted therapy remains challenging in AML. We found that reduction in mitochondrial priming and common transcriptomic signatures was a conserved mechanism of acquired resistance across different drug classes in vivo. Drugs active in vivo can be identified even in the multidrug resistant state by DBP.

Predicting suicidality in late-life depression by 3D convolutional neural network and cross-sample entropy analysis of resting-state fMRI.

BACKGROUND: Predicting suicide is a pressing issue among older adults; however, predicting its risk is difficult. Capitalizing on the recent development of machine learning, considerable progress has been made in predicting complex behavior such as suicide. As depression remained the strongest risk for suicide, we aimed to apply deep learning algorithms to identify suicidality in a group with late-life depression (LLD). METHODS: We enrolled 83 patients with LLD, 35 of which were non-suicidal and 48 were suicidal, including 26 with only suicidal ideation and 22 with past suicide attempts, for resting-state functional magnetic resonance imaging (MRI). Cross-sample entropy (CSE) analysis was conducted to examine the complexity of MRI signals among brain regions. Three-dimensional (3D) convolutional neural networks (CNNs) were used, and the classification accuracy in each brain region was averaged to predict suicidality after sixfold cross-validation. RESULTS: We found brain regions with a mean accuracy above 75% to predict suicidality located mostly in default mode, fronto-parietal, and cingulo-opercular resting-state networks. The models with right amygdala and left caudate provided the most reliable accuracy in all cross-validation folds, indicating their neurobiological importance in late-life suicide. CONCLUSION: Combining CSE analysis and the 3D CNN, several brain regions were found to be associated with suicidality.

Cognitive protection and brain entropy changes from omega-3 polyunsaturated fatty acids supplement in late-life depression: A 52-week randomized controlled trial.

BACKGROUND: Late-life depression (LLD) is associated with risk of dementia, yet intervention of LLD provides an opportunity to attenuate subsequent cognitive decline. Omega-3 polyunsaturated fatty acids (PUFAs) supplement is a potential intervention due to their beneficial effect in depressive symptoms and cognitive function. To explore the underlying neural mechanism, we used resting-state functional MRI (rs-fMRI) before and after omega-3 PUFAs supplement in older adults with LLD. METHODS: A 52-week double-blind randomized controlled trial was conducted. We used multi-scale sample entropy to analyze rs-fMRI data. Comprehensive cognitive tests and inflammatory markers were collected to correlate with brain entropy changes. RESULTS: A total of 20 patients completed the trial with 11 under omega-3 PUFAs and nine under placebo. While no significant global cognitive improvement was observed, a marginal enhancement in processing speed was noted in the omega-3 PUFAs group. Importantly, participants receiving omega-3 PUFAs exhibited decreased brain entropy in left posterior cingulate gyrus (PCG), multiple visual areas, the orbital part of the right middle frontal gyrus, and the left Rolandic operculum. The brain entropy changes of the PCG in the omega-3 PUFAs group correlated with improvement of language function and attenuation of interleukin-6 levels. LIMITATIONS: Sample size is small with only marginal clinical effect. CONCLUSION: These findings suggest that omega-3 PUFAs supplement may mitigate cognitive decline in LLD through anti-inflammatory mechanisms and modulation of brain entropy. Larger clinical trials are warranted to validate the potential therapeutic implications of omega-3 PUFAs for deterring cognitive decline in patients with late-life depression.