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Opioid-related overdoses account for almost half of all drug overdose deaths in the United States and cause more preventable deaths every year than car crashes. Fentanyl, a highly potent mu opioid receptor (MOR) agonist and its analogues (fentalogues) are increasingly found in illicit drug samples, both where the primary drug of abuse is an opioid and where it is not. The prevalence of fentalogues in the illicit drug market is thought to be the primary driver of the increased number of opioid-related overdose deaths since 2016. In fact, fentanyl and its analogues are involved in more than 70% of opioid-related overdoses. The standard opioid overdose rescue therapy naloxone is often insufficient to reverse opioid overdoses caused by fentalogue agonists under current treatment paradigms. However, the pharmacology of many fentalogues is unknown. Moreover, within the fentalogue series of compounds, it is possible that antagonists could be identified that might be superior to naloxone as opioid overdose reversal agents. In this report, we explore the pharmacology of 70 fentalogues and identify compounds that behave as MOR antagonists in vitro and demonstrate with one of these reversals of fentanyl-induced respiratory depression in the mouse. Such compounds could provide leads for the development of effective agents for the reversal of opioid overdose.

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Esteban Ortiz-Prado, Juan Sebastian Izquierdo-Condoy, María G. Dávila-Rosero, Jorge Vásconez-González, Ana M. Diaz, Carla E. Moyano, Vanessa Arcos-Valle, Ginés Viscor, and Joshua H. West. Reduced Violence-Related Burden and Mortality at Higher Altitudes: Examining the Association between High Altitude Living and Homicide Rates in Ecuador. High Alt Med Biol. 00:000-000, 0000. Background: Homicides are a major public health concern and a leading cause of preventable deaths worldwide. The relationship between altitude and homicides remains unclear, and evidence of the possible effects of living at high altitudes on homicide rates is limited. This research aimed to investigate the mortality rates resulting from various types of aggression that culminated in homicides in Ecuador and to explore potential differences associated with altitude. Methods: An ecological analysis of homicide rates in Ecuador was conducted from 2001 to 2022. Homicide cases and the population at risk were categorized based on their place of residence according to two altitude classifications: a binary classification of low (<2,500 m) and high altitude (>2,500 m), and a detailed classification according to criteria by the International Society for Mountain Medicine, which includes low (<1,500 m), moderate (1,500-2,500 m), high (2,500-3,500 m), and very high altitude (3,500-5,500 m) categories. Both crude and directly age-sex standardized mortality rates were calculated for each altitude category. Results: We analyzed a total of 40,708 deaths attributed to aggressions (ICD-10 codes X85-Y09). The total homicide rate for men was 21.29 per 100,000 (95% confidence interval [CI]: 9.55-32.37), whereas for women, it was 2.46 per 100,000 (95% CI: 1.44-3.27). Average rates across the 22 analyzed years were higher at low altitudes (men: 13.2/100,000 and women: 1.33/100,000) as compared with high altitudes (men: 5.79/100,000 and women: 1.05/100,000). Notably, the male-to-female rate difference was more pronounced at low altitudes (898%) than at high altitudes (451%). Conclusions: Our study revealed a higher prevalence of homicides in certain provinces and significant disparities in mortality rates between men and women. Although we cannot establish a direct relationship between altitude and homicide rates, further research is needed to explore potential confounding factors and a better understanding of the underlying causes for these variations.

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PURPOSE: While progress was made towards the Vision 2020: The Right to Sight goals, Ethiopia, Ghana, and Zambia fell short of the recommended cataract surgical rate (CSR) on a national level. Post-operative cataract surgical outcomes are also lower compared to other regions. This study aimed to describe perceived barriers to cataract surgical uptake, factors related to surgeon surgical productivity, and surgical offerings in each of these countries. METHODS: An online survey was sent to ophthalmologists practicing in Ethiopia, Ghana, and Zambia. Responses were collected between June 25, 2021 and January 30, 2022. RESULTS: Responses were received from 122 ophthalmologists from Ethiopia, Ghana, and Zambia. The estimated participation rate was 47% (122/257). Distance to cataract surgical centres, lack of surgical centres, and lack of surgical equipment were among the top 10 most agreed upon barriers by respondents within each country. Many respondents reported that current financial reimbursement does not incentivise maximum productivity in themselves (56%, 68/122) or their staff (61%, 74/122). Surgeons proposed several ways to improve productivity incentives. Private practice was perceived to have the best reimbursement incentives (77%, 94/122), whereas government hospitals were least agreed upon (4%, 5/122). Discrepancies in timely post-operative refraction and eyeglasses disbursement were reported. CONCLUSIONS: Overcoming the identified barriers, improving surgeon productivity, and addressing identified deficits in cataract care will likely reduce the backlog of cataract blindness while ensuring increasingly improved patient outcomes.

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We report here that expression of the ribosomal protein, RPL22, is frequently reduced in human myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML); reduced RPL22 expression is associated with worse outcomes. Mice null for Rpl22 display characteristics of an MDS-like syndrome and develop leukemia at an accelerated rate. Rpl22-deficient mice also display enhanced hematopoietic stem cell (HSC) self-renewal and obstructed differentiation potential, which arises not from reduced protein synthesis but from increased expression of the Rpl22 target, ALOX12, an upstream regulator of fatty acid oxidation (FAO). The increased FAO mediated by Rpl22-deficiency also persists in leukemia cells and promotes their survival. Altogether, these findings reveal that Rpl22 insufficiency enhances the leukemia potential of HSC via non-canonical de-repression of its target, ALOX12, which enhances FAO, a process that may serve as a therapeutic vulnerability of Rpl22 low MDS and AML leukemia cells. Highlights: RPL22 insufficiency is observed in MDS/AML and is associated with reduced survivalRpl22-deficiency produces an MDS-like syndrome and facilitates leukemogenesisRpl22-deficiency does not impair global protein synthesis by HSCRpl22 controls leukemia cell survival by non-canonical regulation of lipid oxidation eTOC: Rpl22 controls the function and transformation potential of hematopoietic stem cells through effects on ALOX12 expression, a regulator of fatty acid oxidation.

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BACKGROUND: Large-scale social and behavioral change communication (SBCC) approaches can be beneficial to achieve improvements in knowledge, attitudes, and practices (KAP). Addressing Stunting in Tanzania Early (ASTUTE) included a significant SBCC component and targeted precursors to stunting including KAP related to maternal and child health, antenatal care, WASH, childhood development, and male involvement. METHODS: Baseline, midline, and endline surveys were conducted for a total of 14,996 female caregivers and 6726 male heads of household in the Lake Zone region of Tanzania. Regression analyses were used to estimate differences in KAP from baseline to midline and endline. RESULTS: Women's knowledge of handwashing and infant/child feeding practices, and attitudes related to male involvement, consistently improved from baseline to midline and baseline to endline. Women's practices related to antenatal care, breastfeeding, and early child development improved from baseline to midline and baseline to endline. Improvements in KAP among male heads of household were varied across indicators with consistent improvement in practices related to child feeding practices from baseline to midline and baseline to endline. CONCLUSION: Many changes in KAP were observed from baseline to midline and baseline to endline and corresponded with SBCC programming in the region. These results provide support for the value of large SBCC interventions. Public health efforts in settings such as Tanzania may benefit from adopting these approaches.

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Major depressive disorder is a highly common disorder, with a lifetime prevalence in the United States of approximately 21%. Traditional antidepressant treatments are limited by a delayed onset of action and minimal efficacy in some patients. Ketamine is effective and fast-acting, but there are concerns over its abuse liability. Thus, there is a need for safe, fast-acting antidepressant drugs. The opioid buprenorphine shows promise but also has abuse liability due to its mu-agonist component. Preclinical evidence indicates that the delta-opioid system contributes to mood disorders, and delta-opioid agonists are effective in preclinical models of depression- and anxiety-like states. In this study, we test the hypothesis that the mu-opioid antagonist diprenorphine by virtue of its partial delta opioid agonist activity may offer a beneficial profile for an antidepressant medication without abuse liability. Diprenorphine was confirmed to bind with high affinity to all three opioid receptors, and functional experiments for G protein activation verified diprenorphine to be a partial agonist at delta- and kappa-opioid receptors and a mu-antagonist. Studies in C57BL/6 mice demonstrated that an acute dose of diprenorphine produced antidepressant-like effects in the tail suspension test and the novelty-induced hypophagia test that were inhibited in the presence of the delta-selective antagonist, naltrindole. Diprenorphine did not produce convulsions, a side effect of many delta agonists but rather inhibited convulsions caused by the full delta agonist SNC80; however, diprenorphine did potentiate pentylenetetrazole-induced convulsions. Diprenorphine, and compounds with a similar pharmacological profile, may provide efficient and safe rapidly acting antidepressants. SIGNIFICANCE STATEMENT: The management of major depressive disorder, particularly treatment-resistant depression, is a significant unmet medical need. Here we show that the opioid diprenorphine, a compound with mu-opioid receptor antagonist activity and delta- and kappa-opioid receptor partial agonist activities, has rapid onset antidepressant-like activity in animal models. Diprenorphine and compounds with a similar pharmacological profile to diprenorphine should be explored as novel antidepressant drugs.

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The adrenomedullary chromaffin cell transduces chemical messages into outputs that regulate end organ function throughout the periphery. At least two important neurotransmitters are released by innervating preganglionic neurons to stimulate exocytosis in the chromaffin cell-acetylcholine (ACh) and pituitary adenylate cyclase activating polypeptide (PACAP). Although PACAP is widely acknowledged as an important secretagogue in this system, the pathway coupling PACAP stimulation to chromaffin cell secretion is poorly understood. The goal of this study is to address this knowledge gap. Here, it is shown that PACAP activates a Gαs-coupled pathway that must signal through phospholipase C ε (PLCε) to drive Ca2+ entry and exocytosis. PACAP stimulation causes a complex pattern of Ca2+ signals in chromaffin cells, leading to a sustained secretory response that is kinetically distinct from the form stimulated by ACh. Exocytosis caused by PACAP is associated with slower release of peptide cargo than exocytosis stimulated by ACh. Importantly, only the secretory response to PACAP, not ACh, is eliminated in cells lacking PLCε expression. The data show that ACh and PACAP, acting through distinct signaling pathways, enable nuanced and variable secretory outputs from chromaffin cells.

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A man in his 20s presented with headache and acute deterioration in visual acuity. He was found to have panuveitis and raised intracranial pressure with papilloedema. MRI and F-fluorodeoxyglucose positron emission tomography confirmed a subclinical, but active, inflammatory mastoid process. Histology of the mastoid showed immunoglobulin G4 (IgG4) cells, plasma cells and storiform fibrosis.This presentation of IgG4 disease has not been previously described.Treatment with high-dose steroids was initiated, followed by long-term immunosuppressive therapy. The patient's symptoms improved, although he remains dependent on azathioprine and low dose oral steroids for symptom control. To date, there has been no progression of the disease.

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Objectives: Stunting remains a prevalent issue in Tanzania. The consequences of stunting include reduced height, greater susceptibility to disease, and diminished cognitive ability throughout the lifespan. Lack of psychosocial stimulation is associated with increased stunting, particularly in terms of its cognitive impact. The Addressing Stunting in Tanzania Early (ASTUTE) program was a large social and behavior change communication (SBCC) intervention that aimed to reduce childhood stunting in the region by targeting early childhood development (ECD) behaviors. The purpose of this study is to report on the extent to which exposure to ASTUTE might be related to ECD behaviors. Methods: ASTUTE disseminated program messages via a mass media campaign and interpersonal communication (IPC). Logistic regression models were used to explore the relationship between exposure to TV, radio, IPC messages, and key ECD behaviors of female primary caregivers and male heads of household. Results: Among primary caregivers, IPC was positively associated with all ECD behaviors measured. Radio was associated with all behaviors except drawing with their child. TV was associated with all behaviors except playing with their child. Among heads of household, only the radio was positively associated with the ECD behaviors measured. Conclusions for practice: Findings indicate that SBCC interventions that include mass media and IPC components may be effective at promoting parental engagement in ECD behaviors. Significance: We know that ECD is important for a child's development. We know that parents play a critical role in promoting ECD behaviors. We are still exploring ways to influence parents so that they are more involved in ECD behaviors. The results presented here provide evidence for successful mass media and IPC efforts to improve parents' ECD behaviors. We hope this study will add more evidence for large interventions such as these to the literature, and we are very hopeful that governments and large international NGOs will prioritize SBCC approaches in the future, especially in locations where face-to-face interventions may be challenging.

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There are no Food and Drug Administration-approved medications for cocaine use disorder, including relapse. The µ-opioid receptor (MOPr) partial agonist buprenorphine alone or in combination with naltrexone has been shown to reduce cocaine-positive urine tests and cocaine seeking in rodents. However, there are concerns over the abuse liability of buprenorphine. Buprenorphine's partial agonist and antagonist activity at the nociception receptor (NOPr) and κ-opioid receptor (KOPr), respectively, may contribute to its ability to inhibit cocaine seeking. Thus, we hypothesized that a buprenorphine derivative that exhibits antagonist activity at MOPr and KOPr with enhanced agonist activity at the NOPr could provide a more effective treatment. Here we compare the pharmacology of buprenorphine and two analogs, BU10119 and BU12004, in assays for antinociception and for cocaine- and stress-primed reinstatement in the conditioned place preference paradigm. In vitro and in vivo assays showed that BU10119 acts as an antagonist at MOPr, KOPr, and δ-opioid receptor (DOPr) and a partial agonist at NOPr, whereas BU12004 showed MOPr partial agonist activity and DOPr, KOPr, and NOPr antagonism. BU10119 and buprenorphine but not BU12004 lessened cocaine-primed reinstatement. In contrast, BU10119, BU12004, and buprenorphine blocked stress-primed reinstatement. The selective NOPr agonist SCH221510 but not naloxone decreased cocaine-primed reinstatement. Together, these findings are consistent with the concept that NOPr agonism contributes to the ability of BU10119 and buprenorphine to attenuate reinstatement of cocaine-conditioned place preference in mice. The findings support the development of buprenorphine analogs lacking MOPr agonism with increased NOPr agonism for relapse prevention to cocaine addiction. SIGNIFICANCE STATEMENT: There are no Food and Drug Administration-approved medications for cocaine use disorder. Buprenorphine has shown promise as a treatment for cocaine relapse prevention; however, there are concerns over the abuse liability of buprenorphine. Here we show a buprenorphine analogue, BU10119, which lacks µ-opioid receptor agonism and inhibits cocaine-primed and stress-primed reinstatement in a conditioned place-preference paradigm. The results suggest the development of BU10119 for the management of relapse to cocaine seeking.

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BACKGROUND: Diarrhea remains a major cause of morbidity and mortality among children in Tanzania. The purpose of this study was to explore associations between diarrheal disease and water, sanitation, and hygiene (WASH) related behaviors and determine care-seeking predictors for diarrheal disease. METHODS: Data from 9996 female primary caregivers were collected as part of a larger integrated nutrition program. Logistic regression was used to measure associations between predictor and dependent variables and diarrheal and care-seeking outcomes. RESULTS: Knowledge of the importance of handwashing after assisting a child who has defecated (OR 0.79, CI 0.72-0.87), before preparing food (OR 0.88, CI 0.80-0.97), and before feeding a child (OR 0.89, CI 0.81-0.99) were each associated with not having a child with diarrhea in the past two weeks. Fathers or male caregivers (OR 0.65, CI 0.48-0.89) were less likely to seek medical care for a child with diarrhea. No associations were found between WASH-related knowledge or behavior and seeking medical care for a child with diarrhea. CONCLUSIONS: Findings indicate that knowledge of handwashing importance was significant in washing hands after assisting a child who has defecated, before preparing food, and prior to feeding a child. These findings demonstrate the value of parental involvement to lower morbidity and mortality among children.

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BACKGROUND: Water access, sanitation, and hygiene (WASH) remain a public health concern in Indonesia. Proper WASH practices can decrease risk of stunting, wasting, and disease in children under the age of 2. OBJECTIVE: The purpose of our study is to examine if using technology to access health information and services among Indonesian women affects knowledge and behaviors regarding handwashing and defecation practices. METHODS: Our study is an interview-based cross-sectional survey. Participants included 1734 mothers of children under 2 years of age. These women were randomly selected and interviewed as part of a 3-stage cluster sampling technique. Our study uses data regarding WASH knowledge which includes benefits of handwashing with soap, 5 critical times of handwashing, risks of open defecation, media of disease transmission, defecation locations, and risks of open defecation. Data regarding WASH behaviors were also included: handwashing with soap, type of latrine used at home, and where defecation took place. This investigation used adjusted and unadjusted logistic and linear regression models to determine differences in WASH outcomes between those who use technology to access health information and services and those who did not. RESULTS: One result is that Indonesian women with children under 2 years of age who use technology to access health information and services are more likely to know the advantages of proper handwashing (odds ratio [OR] 2.603, 95% CI 1.666-4.067) and know the 5 critical times of handwashing (OR 1.217, 95% CI 0.969-1.528). Women who use technology to access health information are also more likely to know the risks of open defecation (OR 1.627, 95% CI 1.170-2.264) and use a type of toilet (such as a gooseneck or squat toilet) that limits risk (OR 3.858, 95% CI 2.628-5.665) compared to women who did not use technology to access health information. CONCLUSIONS: Using technology to access health information and services was associated with an increase in handwashing and defecation knowledge. In the future, promoting mothers of children under 2 years of age to access health information through technology might be used to increase handwashing and defecation knowledge as well as safe defecation practices. However, further research should be done to determine how technology may increase the frequency of recommended handwashing behaviors.

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BACKGROUND: The purpose of this study was to examine the extent to which a national nutrition communication campaign (NNCC) intervention providing interpersonal communication (IPC) was associated with improved knowledge and behaviors related to feeding practices among mothers with children under two years of age in rural Indonesia. METHODS: Data came from a follow-up, cross-sectional survey of 1734 mothers. Key outcomes of interest were minimum meal frequency, minimum dietary diversity and minimum acceptable diet, as defined by the World Health Organization. Associations between exposure to the NNCC intervention and infant and young child feeding (IYCF) knowledge and behaviors were analyzed using adjusted linear and logistic regression, controlling for age, education, and income. RESULTS: A total of 525 mothers reported exposure to IPC interventions (30.3%). Participation in IPC was associated with increased knowledge of feeding practices (p < .0001). Separately, knowledge of feeding practices was related to achieving recommended behavioral practices of minimum meal frequency (p = 0.019), dietary diversity (p = 0.013), adequate diet (p < .001). CONCLUSION: These findings underscore the value of increasing maternal knowledge of IYCF practices through IPC interventions as a way to improve behavioral practices and address stunting in rural Indonesia.

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Background: Water, sanitation, and hygiene (WASH) behaviors play a significant role in stunting. Knowledge and behaviors regarding WASH among caregivers are critical to providing children with chances to survive and thrive. The purpose of this study is to determine if exposure to a national communication campaign using media and interpersonal communication (IPC) is associated with WASH-related knowledge and behaviors among Indonesian mothers with children under the age of two. Methods: Data came from a cross-sectional survey of 1734 mothers with children under the age of two. The measures included exposure to two different interventions: media messages (media) and interpersonal communication strategies (IPC) and WASH-related knowledge and behavior. Multiple logistic regression was used to examine the association between intervention exposure and study variables. Results: Exposure to both media and IPC interventions was associated with participants having a higher knowledge of appropriate defecation practices (p < 0.001), higher knowledge of proper handwashing practices (p < 0.001), and higher self-reported handwashing at critical times (p < 0.001) but was not associated with reported practicing of appropriate defecation (OR = 0.780, 95% CI: 0.566-1.101). Mothers exposed to only media interventions were more likely to have knowledge of appropriate defecation practices (p < 0.001) and to have reported practicing appropriate defecation behaviors (OR = 1.539, 95% CI: 1.173-2.019). Mothers exposed to only IPC interventions were more likely to have reported handwashing at critical times (p = 0.009). Conclusions: Exposure to both media and IPC interventions was associated with increased knowledge and optimal behaviors related to WASH. These findings demonstrate the value of communications campaigns that use mass media coupled with IPC to improve WASH knowledge and behavior.

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BACKGROUND: Mountain biking is an aerobic physical activity that has experienced rapid growth. The emergence of the electric pedal-assist mountain bike (eMTB), while not without its critics, presents the potential for an even larger segment of the population to enjoy the health benefits of mountain biking. Although the research focused on the use of e-bikes generally is growing, there is limited research specifically targeting eMTB use. Research is needed exploring the potential exercise response of riding an eMTB, together with the beliefs and perceptions of mountain bikers who have and have not experienced eMTB riding. OBJECTIVE: This study aimed to compare conventional mountain bike and eMTB use. This was done by investigating 2 questions: (1) What proportion of exercise response is retained for an experienced mountain biker while using an eMTB when compared with a conventional mountain bike? and (2) What are the perceptions and beliefs of experienced mountain bikers toward eMTBs both before and after riding an eMTB? METHODS: A convergent mixed methods data collection approach was used in the study. Participants completed both a pre- and postride questionnaire, and data regarding heart rate were collected. Heart rates from each ride were compared against each other. RESULTS: The average heart rate during eMTB use was 94% (31/33) of the average heart rate during conventional mountain bike use. Therefore, eMTB use in this study achieved a majority of the exercise response and exceeded established biometric thresholds for cardiovascular fitness. Paired t test statistics were calculated to compare beliefs of conventional mountain bikes and eMTBs and to compare mean heart rate and speed between conventional mountain bike and eMTB use on the study loop. Participants overwhelmingly perceived the potential impact of eMTB use to be positive on both pre- and post-eMTB ride questionnaires. CONCLUSIONS: Despite the measured benefit, participants' perceived exertion while riding the eMTB was low.

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The importance of water, sanitation and hygiene (WASH) behaviors in low- and middle-income countries in preventing childhood illness is well established. Tanzania is known to have high rates of chronic malnutrition and childhood stunting-both of which have been linked to poor WASH practices. Interviews were conducted with 5000 primary caregivers of children aged 0-23 months. Four composite WASH knowledge variables were created to assess the relationship between WASH knowledge and access to different forms of media, such as television, radio, and mobile phones. WASH knowledge variables measure knowledge of when to wash hands, the need for soap when washing hands, when to wash a baby's hands, and how eating soil or chicken feces can affect a baby's health. Logistic and linear regression analyses were conducted to measure the association between media access and WASH knowledge. Having watched television was positively associated with higher WASH knowledge indicators (all p < 0.05). Higher WASH knowledge was positively associated with more frequent handwashing after cleaning a baby's bottom (all p < 0.0001). The quantity of media access also had a positive linear effect on handwashing; more media items owned was associated with increases in handwashing. Study findings indicate media access is associated with WASH knowledge among caregivers in resource-poor settings.

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Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are associated with a variety of cellular alterations that mitigate cardiovascular disease. However, pinpointing the positive therapeutic effects is challenging due to inconsistent clinical trial results and overly simplistic in vitro studies. Here we aimed to develop realistic models of n-3 PUFA effects on platelet function so that preclinical results can better align with and predict clinical outcomes. Human platelets incubated with the n-3 PUFAs docosahexaenoic acid and eicosapentaenoic acid were stimulated with agonist combinations mirroring distinct regions of a growing thrombus. Platelet responses were then monitored in a number of ex-vivo functional assays. Furthermore, intravital microscopy was used to monitor arterial thrombosis and fibrin deposition in mice fed an n-3 PUFA-enriched diet. We found that n-3 PUFA treatment had minimal effects on many basic ex-vivo measures of platelet function using agonist combinations. However, n-3 PUFA treatment delayed platelet-derived thrombin generation in both humans and mice. This impaired thrombin production paralleled a reduced platelet accumulation within thrombi formed in either small arterioles or larger arteries of mice fed an n-3 PUFA-enriched diet, without impacting P-selectin exposure. Despite an apparent lack of robust effects in many ex-vivo assays of platelet function, increased exposure to n-3 PUFAs reduces platelet-mediated thrombin generation and attenuates elements of thrombus formation. These data support the cardioprotective value of-3 PUFAs and strongly suggest that they modify elements of platelet function in vivo.

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BACKGROUND: The emergence of electric pedal-assist bicycles (e-bikes) presents an opportunity to increase active transportation by minimizing personal barriers of engaging in physical activity. OBJECTIVES: The aim of this study was to assess the beliefs of individuals using e-bikes for active transport and report preliminary biometric measurements while using e-bikes for physical activity compared with conventional bikes. METHODS: Participants used both conventional bicycles and e-bikes to compare energy expenditure while riding on the study route. Apple smart watches were used to track each participant's heart rate, distance, speed, and time while riding both bicycles. A total of 3 survey instruments were used to estimate beliefs: one administered before riding the bicycles, a second administered after riding a conventional bike, and the final survey completed after riding an e-bike. Survey instruments were constructed using constructs from the theory of planned behavior. RESULTS: The study sample (N=33) included adults aged between 19 and 28 years. Paired t test analysis revealed that participants believed a conventional bike was more likely than an e-bike to benefit their physical health (P=.002) and save them money (P=.005), while an e-bike was perceived to be more likely than a conventional bike to save them time (P<.001). Paired t test analysis revealed participants significantly agreed more with the statement that they could ride an e-bike most days (P=.006) compared with a conventional bike. After participants traveled approximately 10 miles on each type of bicycle, participants' mean average heart rate while riding the e-bike was 6.21 beats per minute lower than when riding the conventional bike (P=.04), but both were significantly higher than resting heart rate (P<.001). CONCLUSIONS: This pilot study suggests that e-bikes are an active form of transportation capable of providing much of the cardiovascular health benefits obtained during conventional bike use. E-bikes may help reduce some of the obstacles to conventional bike use, such as increased transportation time, decreased convenience, and physical fatigue.

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BACKGROUND: Mental and emotional self-help apps have emerged as potential mental illness prevention and treatment tools. The health behavior theory mechanisms by which these apps influence mental health-related behavior change have not been thoroughly examined. OBJECTIVE: The objective of this study was to examine the association between theoretical behavior change mechanisms and use of mental and emotional self-help apps and whether the use of such apps is associated with mental health behaviors. METHODS: This study utilized a cross-sectional survey of 150 users of mental or emotional health apps in the past 6 months. Survey questions included theory-based items, app engagement and likeability items, and behavior change items. Stata version 14 was used to calculate all statistics. Descriptive statistics were calculated for each of the demographic, theory, engagement, and behavior variables. Multiple regression analysis was used to identify factors associated with reported changes in theory and separately for reported changes in actual behavior after controlling for potentially confounding variables. RESULTS: Participants reported that app use increased their motivation, desire to set goals, confidence, control, and intentions to be mentally and emotionally healthy. Engagement (P<.001) was positively associated with the reported changes in theory items, whereas perceived behavior change was positively associated with theory (P<.001), engagement (P=.004), frequency of use of apps (P=.01), and income (P=.049). CONCLUSIONS: Participants reported that app use increased their motivation, desire to set goals, confidence, control, and intentions to be mentally and emotionally healthy. This increase in perceptions, beliefs, and attitudes surrounding their mental and emotional health was considerably associated with perceived change in behavior. There was a positive association between the level of engagement with the app and the impact on theory items. Future efforts should consider the value of impacting key theoretical constructs when designing mental and emotional health apps. As apps are evaluated and additional theory-based apps are created, cost-effective self-help apps may become common preventative and treatment tools in the mental health field.

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BACKGROUND: Physical activity apps are commonly used to increase levels of activity and health status. To date, the focus of research has been to determine the potential of apps to influence behavior, to ascertain the efficacy of a limited number of apps to change behavior, and to identify the characteristics of apps that users prefer. OBJECTIVE: The purpose of this study was to identify the mechanisms by which the use of physical activity apps may influence the users' physical activity behavior. METHODS: This study used a cross-sectional survey of users of health-related physical activity apps during the past 6 months. An electronic survey was created in Qualtrics' Web-based survey software and deployed on Amazon Mechanical Turk. Individuals who had used at least one physical activity app in the past 6 months were eligible to respond. The final sample comprised 207 adults living in the United States. 86.0% (178/207) of respondents were between the ages of 26 and 54 years, with 51.2% (106/207) of respondents being female. Behavior change theory informed the creation of 20 survey items relating to the mechanisms of behavior change. Respondents also reported about engagement with the apps, app likeability, and physical activity behavior. RESULTS: Respondents reported that using a physical activity app in the past 6 months resulted in a change in their attitudes, beliefs, perceptions, and motivation. Engagement with the app (P<.001), frequency of app use (P=.03), and app price (P=.01) were related to the reported impact of the behavior change theory or mechanisms of change. The mechanisms of change were associated with self-reported physical activity behaviors (P<.001). CONCLUSIONS: The findings from this study provide an overview of the mechanisms by which apps may impact behavior. App developers may wish to incorporate these mechanisms in an effort to increase impact. Practitioners should consider the extent to which behavior change theory is integrated into a particular app when they consider making recommendations to others wishing to increase levels of physical activity.