Effectiveness of an mHealth App That Uses Financial Incentives and Gamification to Promote Health Behavior Change in Adolescents and Caregivers: Protocol for a Clinic-Based Randomized Controlled Trial.

BACKGROUND: Adolescent and adult obesity continues to be a public health epidemic in the United States. Despite the popularity of mHealth apps with gamification among adolescents, there are insufficient studies to evaluate the efficacy of gamified mHealth apps and financial incentives to motivate sustained health behavior change in adolescents or their adult caregivers. OBJECTIVE: This study aims to evaluate the effectiveness of gamification techniques and financial incentives used in the novel "CommitFit" mHealth app to motivate health behavior change and improve various mental and physical health metrics in adolescents and their caregivers. METHODS: This study is a 3-month randomized controlled trial (RCT) with 30 adolescents (aged 13-15 years) and their adult caregivers (N=60). It evaluates "CommitFit," which uses gamification including points and leaderboards to motivate logging and achievement of self-selected health behavior goals (eg, more water, sleep, physical activity, fruits, or vegetables or fewer sugary beverages). The RCT had three arms, each with 10 dyads: (1) CommitFit-only users; (2) CommitFit$, where adolescents were paid US $0.05 for each point they earned; and (3) waitlist control. Intervention dyads used the app for 3 months and had the option to use it for the fourth month without prompts or extra financial incentives. User analytic software was used to evaluate the frequency of user logs and goal achievement. Monthly surveys evaluated self-reported change in the 5 CommitFit health behaviors. Changes in BMI and blood pressure were evaluated for all participants at 3 clinical visits. Mental health, gamification, and behavior economics surveys were completed during the clinical visits. RESULTS: Recruitment began in August 2023 and was completed in 10 weeks. The research team successfully recruited and enrolled 30 dyads. Researchers emailed and called 89 caregivers on a physician-approved adolescent patient list, a 33% recruitment rate. Data collection and analysis will be conducted in the spring and summer of 2024. The results of this study are anticipated to be published between late 2024 and early 2025. CONCLUSIONS: This RCT will expand knowledge of the effectiveness of gamification techniques, financial incentives, and mHealth apps to motivate sustained health behavior change among adolescents and caregivers. These results may offer new opportunities to caregivers, health insurers, health care systems, and clinicians to motivate health behavior change in adolescents and caregivers, with the ultimate goal of preventing or reducing obesity and obesity-related diseases. Additional gamification, mental health surveys, and app user analytics included in the study may provide further insight into the characteristics of adolescents or caregivers who would benefit the most from using a gamified mHealth app like CommitFit. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/63505.

A bioinspired pseudopeptide-based intracellular delivery platform enhances the cytotoxicity of a ribosome-inactivating protein through multiple death pathways.

Saporin is a 28 621 Da protein and plant toxin possessing rRNA N-glycosidase activity. Due to its potent ribosome-inactivating ability, saporin is commonly studied as an anticancer agent. However, its enzymatic activity is greatly hindered by its poor plasma membrane permeability. To overcome this barrier, we used a bioinspired intracellular delivery platform based on the pH-responsive pseudopeptide, poly(L-lysine isophthalamide) grafted with L-phenylalanine at a stoichiometric molar percentage of 50% (PP50). PP50 was co-incubated with saporin (PP50/saporin) in a mildly acidic pH environment to aid intracellular delivery and increase saporin's therapeutic potential. We demonstrated that PP50 greatly enhanced the cytotoxicity of saporin in the 2D monolayer of A549 cells and 3D A549 multicellular spheroids whilst remaining non-toxic when administered alone. To elucidate the mechanism of cell death, we assessed the activation of caspases, the inhibition of protein synthesis, the onset of apoptosis and the mechanism of PP50/saporin entry. Inhibition of protein synthesis and activation of caspases 3/7, 8 and 9 were found to occur before the onset of apoptosis and cell death. PP50/saporin was also shown to rely on micropinocytosis and caveolae-mediated endocytosis for cell entry. In addition, fluorescein isothiocyanate-labelled saporin (FITC-saporin) was localized within the cytoplasm and nuclei when delivered with Cyanine5-labelled PP50 (Cy5-PP50). Taken together, this suggests that multiple pathways are triggered to initiate apoptosis and cell death in cells treated with PP50/saporin. Therefore, these results make PP50 a potential intracellular delivery platform for the internalization of protein therapeutics.

Patterns and Outcomes of Opioid Use Before and After Hospitalization for Critical Illness: A Population-Based Cohort Study.

Background: Hospitalization represents a major access point for prescription opioids, yet little is known regarding patterns and outcomes of opioid exposures before and after hospitalization for critical illness. Methods: This is an observational, population-based cohort study of adults (≥18 years) hospitalized for critical illness from 2010 to 2019. Multivariable models assess associations between opioid exposures prior to hospitalization, classified according to the Consortium to Study Opioid Risks and Trends, and posthospitalization opioid exposures and clinical outcomes through 1-year posthospitalization. Results: Of 11 496 patients, 6318 (55%) were men with a median age of 66 (51, 79) years and 40% (n = 4623) surgical admissions. Prehospitalization opioid availability included 8449 (73%) none, 2117 (18%) short-term, 471 (4%) episodic, and 459 (4%) long-term. Thirty-nine percent (4144/10 708) of hospital survivors were discharged with opioids, with higher prescribing rates for surgical admissions (55%). Greater preadmission opioid exposures were associated with higher prevalent opioid availability at 1 year (odds ratio [95% confidence interval] 24.1 [18.3-31.8], 9.42 [7.18-12.3], and 2.55 [2.08-3.12] for long-term, episodic, and short-term exposures, respectively, vs none, P < .001). Greater preadmission opioid exposures were associated with longer hospitalizations (1.13 [1.04-1.23], 1.15 [1.06-1.25], and 1.08 [1.04-1.13] multiplicative increase in geometric mean, P < .001), more readmissions (hazard ratio [HR] 2.08 [1.74-2.49], 1.88 [1.56-2.26], and 1.48 [1.33-1.64], P < .001), and higher 1-year mortality (HR 1.59 [1.28-1.98], 1.75 [1.41-2.18], and 1.49 [1.32-1.69], P < .001). Similar associations were observed across surgical and nonsurgical admissions. Conclusions: Prehospitalization opioid exposures in survivors of critical illness are associated with clinical outcomes through 1 year and may serve as important prognostic markers.

On the energetic and magnetic stability of potassium atomic clusters doped by yttrium.

The abstract should be a single paragraph which summarises the content of the article. This study utilizes density functional theory (DFT) calculations to explore the energetic and magnetic stability of neutral and charged potassium (K) clusters doped with yttrium (Y). We aim to elucidate the influence of Y doping on the energetics and structures of these clusters, comparing them to undoped K clusters. Ground states of 64 polyhedral structures, all of them encapsulating at least one Y atom, were obtained. Y doping generally increased the spin magnetic moment, with charged clusters exhibiting the highest values. Notably, the K12Y+ cluster, possessing an icosahedral geometry and a magnetic moment of 6µB, is classified as a magnetic superatom. Additionally, we identified 14 superatoms with high magnetic robustness. The density of states (DOS) and spin density calculations additionally highlighted the substantial role played by yttrium in the electronic density of the electrons responsible for inducing magnetism in these clusters.

Community-Based Research: Interviewing Older People in Community Pharmacies.

Objective Community pharmacists play an important role in providing many essential services to older adult patients. This study aimed to assess participants' awareness and utilization of current services provided by the community pharmacy and to identify preferences for innovative strategies and services related to healthy aging. Design This is community-based research using interviews with older people in community pharmacies. Student pharmacists performed the interviews, asking 11 questions developed by the research team. The interview questions included services currently provided by the community pharmacy to determine patient awareness and use. Setting One-on-one structured interviews with participants 50 years of age and older were conducted at community pharmacies in Arizona. Results A total of 53 older people (54.7% female) participated, with most patients knowledgeable about current pharmacy services and 69.7% using at least one service. When asked if they would participate in innovative services, more than half of those interviewed (56.6%) were interested in medication side effect screening and education, and 54.7% would want to participate in medication review with drug interaction screening. Almost half were interested in lifestyle education for healthy aging in nutrition and physical activities (49.1%) and medication disposal (47.2%). Most participants preferred to communicate in person with their pharmacists, but some showed interest in mobile phone texts and calls. Conclusion Community pharmacies may be a viable setting to provide novel services to promote healthy aging among older people, particularly medication side effect and drug interaction screenings and education.

On the energetic and magnetic stability of neutral and charged lithium clusters doped with one and two yttrium atoms.

DFT calculations were performed to study the effect on energetic and magnetic stability when clusters with up to 24 lithium atoms were doped with one and two atoms of yttrium. In this, the effect of the charge was considered. As a result, some stable structures were identified as possible magnetic superatoms, among them, the YLi12+ cluster with an icosahedron geometry with a spin magnetic moment of 4 bohr magnetons. The participation of yttrium in the electron density of the unpaired electrons providing magnetism in clusters was corroborated at the level of a density of states (DOS) calculation and a spin density calculation. In particular, in the Y2Li12+ superatom, it was found that the encapsulated yttrium atom participates with 35.02% and the second yttrium atom with 15.04%. These percentages, with a contribution from p orbitals, but to a greater extent by d orbitals. The complementation to these percentages is due to the participation of the s and p orbitals of the lithium atoms. In general, doping with a second yttrium atom allowed to obtain a greater amount of high magnetic moments, and considering charged clusters allowed to obtain also high magnetic moments.

Tracking gastrointestinal nematode risk on cattle farms through pasture contamination mapping.

Gastrointestinal nematode (GIN) parasites in grazing cattle are a major cause of production loss and their control is increasingly difficult due to anthelmintic resistance and climate change. Rotational grazing can support control and decrease reliance on chemical intervention, but is often complex due to the need to track grazing periods and infection levels, and the effect of weather on larval availability. In this paper, a simulation model was developed to predict the availability of infective larvae of the bovine GIN, Ostertagia ostertagi, at the level of individual pastures. The model was applied within a complex rotational grazing system and successfully reproduced observed variation in larval density between fields and over time. Four groups of cattle in their second grazing season (n = 44) were followed throughout the temperate grazing season with regular assessment of GIN faecal egg counts, which were dominated by O. ostertagi, animal weight and recording of field rotations. Each group of cattle was rotationally grazed on six group-specific fields throughout the 2019 grazing season. Maps and calendars were produced to illustrate the change in pasture infectivity (density of L3 on herbage) across the 24 separate grazing fields. Simulations predicted differences in pasture contamination levels in relation to the timing of grazing and the return period. A proportion of L3 was predicted to persist on herbage over winter, declining to similar intensities across fields before the start of the following grazing season, irrespective of contamination levels in the previous year. Model predictions showed good agreement with pasture larval counts. The model also simulated differences in seasonal pasture infectivity under rotational grazing in systems that differed in temperature and rainfall profiles. Further application could support individual farm decisions on evasive grazing and refugia management, and improved regional evaluation of optimal grazing strategies for parasite control. The integration of weather and livestock movement is inherent to the model, and facilitates consideration of climate change adaptation through improved disease control.

Comparing gradient boosting machine and Bayesian threshold BLUP for genome-based prediction of categorical traits in wheat breeding.

Genomic selection (GS) is a predictive methodology that is changing plant breeding. Genomic selection trains a statistical machine-learning model using available phenotypic and genotypic data with which predictions are performed for individuals that were only genotyped. For this reason, some statistical machine-learning methods are being implemented in GS, but in order to improve the selection of new genotypes early in the prediction process, the exploration of new statistical machine-learning algorithms must continue. In this paper, we performed a benchmarking study between the Bayesian threshold genomic best linear unbiased predictor model (TGBLUP; popular in GS) and the gradient boosting machine (GBM). This comparison was done using four real wheat (Triticum aestivum L.) data sets with categorical traits measured in terms of two metrics: the proportion of cases correctly classified (PCCC) and the Kappa coefficient in the testing set. Under 10 random partitions with four different sizes of testing proportions (20, 40, 60, and 80%), we compared the two algorithms and found that in three of the four data sets, the GBM outperformed the TGBLUP model in terms of both metrics (PCCC and Kappa coefficient). In the larger data sets (Data Sets 3 and 4), the gain in terms of prediction accuracy of the GBM was considerably significant. For this reason, we encourage more research using the GBM in GS to evaluate its virtues in terms of prediction performance in the context of GS.

Genomic-enabled prediction was used for categorical traits to capture data patterns in different environments. Two different genome-based models were used for predicting categorical traits. Genome-based prediction with genotype × environment interaction was used.

Disparities in Hypoxemia Detection by Pulse Oximetry Across Self-Identified Racial Groups and Associations With Clinical Outcomes.

OBJECTIVES: To assess disparities in hypoxemia detection by pulse oximetry across self-identified racial groups and associations with clinical outcomes. DESIGN: Observational cohort study from May 5, 2018, to December 31, 2020. SETTING: Three academic medical centers in the United States. PATIENTS: Adults greater than or equal to 18 years who self-identified as White, Black, Asian, or American Indian admitted to the ICU or undergoing surgery during inpatient hospitalization with simultaneous measurements of pulse oximetry-estimated oxygen saturation and arterial blood gas-derived oxygen saturation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Multivariable models were employed to assess the relationships between race, occult hypoxemia (i.e., arterial blood gas-derived oxygen saturation < 88% despite pulse oximetry-estimated oxygen saturation ≥ 92%), and clinical outcomes of hospital mortality and hospital-free days. One-hundred twenty-eight-thousand two-hundred eighty-five paired pulse oximetry-estimated oxygen saturation-arterial blood gas-derived oxygen saturation measurements were included from 26,603 patients. Pulse oximetry-estimated oxygen saturation on average overestimated arterial blood gas-derived oxygen saturation by 1.57% (1.54-1.61%). Black, Asian, and American Indian patients were more likely to experience occult hypoxemia during hospitalization (estimated probability 6.2% [5.1-7.6%], 6.6% [4.9-8.8%], and 6.6% [4.4-10.0%], respectively) compared with White patients (3.6% [3.4-3.8%]). Black patients had increased odds of occult hypoxemia compared with White patients after adjustment (odds ratio, 1.65; 1.28-2.14; p < 0.001). Differences in occult hypoxemia between Asian and American Indian patients compared with White patients were not significant after adjustment (odds ratio, 1.53; 0.95-2.47; p = 0.077 and odds ratio, 1.31; 0.80-2.16; p = 0.288, respectively). Occult hypoxemia was associated with increased odds of mortality in surgical (odds ratio, 2.96; 1.20-7.28; p = 0.019) and ICU patients (1.36; 1.03-1.80; p = 0.033). Occult hypoxemia was associated with fewer hospital-free days in surgical (-2.5 d [-3.9 to -1.2 d]; p < 0.001) but not ICU patients (0.4 d [-0.7 to 1.4 d]; p = 0.500). CONCLUSIONS: Occult hypoxemia is more common in Black patients compared with White patients and is associated with increased mortality, suggesting potentially important outcome implications for undetected hypoxemia. It is imperative to validate pulse oximetry with expanded racial inclusion.

Calculation of the EPR g-tensor from auxiliary density functional theory.

The working equations for the calculation of the electron paramagnetic resonance (EPR) g-tensor within the framework of the auxiliary density functional theory (ADFT) are presented. The scheme known as gauge including atomic orbitals (GIAOs) is employed to treat the gauge origin problem. This ADFT-GIAO formulation possesses an inherent high computational performance, allowing for the calculation of the EPR g-tensor of molecules containing some hundreds of atoms in reasonable computational time employing moderate computational resources. The effect of the use of a gauge independent auxiliary density on the quality of the g-tensor calculation for the evaluation of the exchange-correlation contribution is analyzed in this work. The best agreement with the experiment is obtained with the BLYP functional (Becke 1988 exchange and Lee-Yang-Parr correlation) in combination with a double-ζ basis set, in particular aug-cc-pVDZ. Furthermore, models of endohedral fullerenes N@Cn, with n = {60, 70, 100, 180, 240}, were used for benchmarking its computational performance.

Small molecule delivery through nanofibrous scaffolds for musculoskeletal regenerative engineering.

Musculoskeletal regenerative engineering approach using small bioactive molecules in conjunction with advanced materials has emerged as a highly promising strategy for musculoskeletal repair and regeneration. Advanced biomaterials technologies have revealed nanofiber-based scaffolds for musculoskeletal tissue engineering as vehicles for the controlled delivery of small molecule drugs. This review article highlights recent advances in nanofiber-based delivery of small molecules for musculoskeletal regenerative engineering. The article concludes with perspectives on the challenges and future directions. FROM THE CLINICAL EDITOR: In this review, advances in nanofiber-based delivery of small molecules are discussed from the standpoint of their potential role in musculoskeletal regenerative engineering, highlighting both future directions and current challenges.

Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications.

Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. However, common limitations with protein growth factors, such as high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host reduce potential clinical applications. New strategies for bone regeneration that involve inexpensive and stable small molecules can obviate these problems and have a significant impact on the treatment of skeletal injury and diseases. Over the past decade, a large number of small molecules with the potential of regenerating skeletal tissue have been reported in the literature. Here, we review this literature, paying specific attention to the prospects for small molecule-based bone-regenerative engineering. We also review the preclinical study of small molecules associated with bone regeneration.

Long-term oral contraceptive treatment, metabolic syndrome and measures of cardiovascular risk in pre-menopausal women: National Health and Nutrition Examination Survey 1999-2004.

AIM: Differences in subclinical cardiometabolic measures were examined as a function of oral contraceptive pills (OCP) treatment duration to compare never-treated women with four OCP-treatment groups (<1, 1-5, 5-10 and >10 years). METHODS: The NHANES (1999-2004) database was used to evaluate 2089 healthy, pre-menopausal women, aged 18-55 years, with or without OCP history, no other hormonal treatment or history of systemic conditions. Outcome measures included body mass, central obesity, blood pressure, glycemia, insulinemia, lipid profile and inflammation. Analyses evaluated differences in prevalence of Metabolic Syndrome (MetS), constituent MetS and other clinical risk criteria, as well as outcome magnitudes. Analyses controlled for demographic and health-related variables, and study-eligible conditions. RESULTS: Relative to other groups, women with >10 years OCP-use, and to some extent those with 5-10 years treatment, displayed no differences in prevalence of MetS and most risk criteria. Further analysis showed that, relative to women treated for <5 years, those with more prolonged OCP treatment displayed lower body mass and fasting glycemia with higher HDL-c levels, but more elevated LDL-c and total cholesterol. CONCLUSIONS: The findings of both beneficial and detrimental subclinical cardiometabolic differences with more long-term OCP-treatment reinforces the need to monitor changes in these factors within the context of the treated patient's risk-benefit profile. However, because the magnitude of these differences was small, relative to normative ranges, it may be concluded that OCPs, as used in recent decades, are unlikely to markedly affect cardiometabolic risk.

Prevalence and prediction of previously unknown MRSA carriage on admission to a geriatric hospital.

OBJECTIVES: to determine the prevalence and characteristics of previously unknown methicillin-resistant Staphylococcus aureus (MRSA) carriers at admission. DESIGN: two prospective case-control studies. SUBJECTS: 1,621 elderly patients were screened for MRSA carriage within 24 hours after admission to a geriatric hospital in Geneva, Switzerland. METHODS: risk factors associated with previously unknown MRSA carriage were determined in the derivation group, and the resulting risk score was evaluated in the validation cohort using logistic regression analysis. RESULTS: prevalence of MRSA carriage at admission increased from 7.3% (53/724 patients) in 2001 to 8.7% (78/897 patients) in 2003, with a corresponding prevalence of unknown MRSA carriers of 4.6 and 5.8%, respectively. Three variables were independently associated with previously unknown MRSA carriage: recent antibiotic treatment (adjusted OR (aOR) 2.3; 95% CI 1.0-5.1), intra-hospital transfer (aOR 2.5; 95% CI 1.2-5.3), and hospitalization in the past 2 years (aOR 2.7; 95% CI 1.1-6.7). In the validation cohort, the probability of MRSA carriage increased across risk scores: 0 point, 4% prevalence (6/146); 1 point, 15% (21/136); and $2 points, 31% (21/68; P<0.001). The risk score showed good discrimination and calibration in both groups. CONCLUSIONS: our risk score, which used a simple additive point system to estimate the likelihood of unknown MRSA carriage, had good accuracy and generalised well in an independent sample of patients. Once validated in a clinical trial, our risk score may be used as a tool to optimise MRSA control.