Just-in-time adaptive interventions for adolescent and young adult health and well-being: protocol for a systematic review.

INTRODUCTION: Health behaviours such as exercise and diet strongly influence well-being and disease risk, providing the opportunity for interventions tailored to diverse individual contexts. Precise behaviour interventions are critical during adolescence and young adulthood (ages 10-25), a formative period shaping lifelong well-being. We will conduct a systematic review of just-in-time adaptive interventions (JITAIs) for health behaviour and well-being in adolescents and young adults (AYAs). A JITAI is an emerging digital health design that provides precise health support by monitoring and adjusting to individual, specific and evolving contexts in real time. Despite demonstrated potential, no published reviews have explored how JITAIs can dynamically adapt to intersectional health factors of diverse AYAs. We will identify the JITAIs' distal and proximal outcomes and their tailoring mechanisms, and report their effectiveness. We will also explore studies' considerations of health equity. This will form a comprehensive assessment of JITAIs and their role in promoting health behaviours of AYAs. We will integrate evidence to guide the development and implementation of precise, effective and equitable digital health interventions for AYAs. METHODS AND ANALYSIS: In adherence to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, we will conduct a systematic search across multiple databases, including CENTRAL, MEDLINE and WHO Global Index Medicus. We will include peer-reviewed studies on JITAIs targeting health of AYAs in multiple languages. Two independent reviewers will conduct screening and data extraction of study and participant characteristics, JITAI designs, health outcome measures and equity considerations. We will provide a narrative synthesis of findings and, if data allows, conduct a meta-analysis. ETHICS AND DISSEMINATION: As we will not collect primary data, we do not require ethical approval. We will disseminate the review findings through peer-reviewed journal publication, conferences and stakeholder meetings to inform participatory research. PROSPERO REGISTRATION NUMBER: CRD42023473117.

A high fiber diet or supplementation with Lactococcus lactis subspecies cremoris to pregnant mice confers protection against intestinal injury in adult offspring.

The diet during pregnancy, or antenatal diet, influences the offspring's intestinal health. We previously showed that antenatal butyrate supplementation reduces injury in adult murine offspring with dextran sulfate sodium (DSS)-induced colitis. Potential modulators of butyrate levels in the intestine include a high fiber diet or dietary supplementation with probiotics. To test this, we supplemented the diet of pregnant mice with high fiber, or with the probiotic bacteria Lactococcus lactis subspecies cremoris or Lactobacillus rhamnosus GG. We then induced chronic colitis with DSS in their adult offspring. We demonstrate that a high fiber antenatal diet, or supplementation with Lactococcus lactis subspecies cremoris during pregnancy diminished the injury from DSS-induced colitis in offspring. These data are evidence that antenatal dietary interventions impact offspring gut health and define the antenatal diet as a therapeutic modality to enhance offspring intestinal health.

Outcomes of Surgical Repair of Aberrant Subclavian Arteries in Adults.

BACKGROUND: Symptoms, imaging characteristics, and early and midterm surgical outcomes for aberrant subclavian arteries (ASCA) are not well defined in the adult population. METHODS: A single-institution retrospective review was conducted of adults undergoing surgical repair of ASCA and descending aorta origin/Kommerell diverticulum (KD) from January 1, 2002, to December 31, 2021. Symptom improvement and differences in imaging characteristics between anatomic groups and the number of symptoms were assessed. RESULTS: Mean age was 46 ± 17 years. There were 23 of 37 left aortic arches with right ASCA (62%) and 14 of 37 right aortic arches with left ASCA (38%). Of these, 31 of 37 (84%) were symptomatic, and 19 of 37 (51%) had KD size/growth meeting criteria for surgical repair. KD aortic origin diameter was larger in more symptomatic patients: 20.60 mm (interquartile range [IQR], 16.42-30.68 mm) in patients with ≥3 symptoms vs 22.05 mm (IQR, 17.52-24.21 mm) for 2 symptoms vs 13.72 mm (IQR, 12.70-15.95 mm) for 1 symptom (P = .018). Aortic replacement was required in 22 of 37 (59%). There were no early deaths. Complications occurred in 11 of 37 (30%): vocal cord dysfunction (4 of 37 [11%]), chylothorax (3 of 37 [8%]), Horner syndrome (2 of 37 [5%]), spinal deficit (2 of 37 [5%]), stroke (1 of 37 [3%]), and temporary dialysis requirement (1 of 37 [3%]). Over a median follow-up of 2.3 years (IQR, 0.8-3.9 years), there was 1 endovascular reintervention and no reoperations. Dysphagia and shortness of breath resolved in 92% and 89%, respectively, whereas gastroesophageal reflux persisted in 47%. CONCLUSIONS: The KD aortic origin diameter correlates with the number of symptoms, and surgical repair of ASCA and descending aorta origin/KD effectively relieves symptoms, with low rates of reintervention. Given the operative complexity, surgical repair should be performed in patients meeting size criteria or with significant dysphagia or shortness of breath symptoms.

Chronodentistry through orthodontic perspective: A literature review.

The human body possesses a unique set of machinery called the molecular/biological clocks that function on a regular 24-h basis forming a circadian rhythm (CR). This aids in coordinating the human biological system with ever-changing environmental conditions, thereby maintaining a balance in its functioning. The central/core component of this system is known to be in the suprachiasmatic nucleus of the hypothalamus with a few aides in the periphery. The periodontal ligament in humans, being one of the dynamic oral tissues, has been shown to exhibit this self-sustained, innate oscillatory behavior that has gained significant attention from dental surgeons. Though substantial evidence regarding its precise role in maintaining circadian periodicity is still unclear, its indispensable role in dentofacial functioning cannot be denied. This review is an attempt in bringing to light the possible role of circadian periodicity in the functioning of oral tissues in the field of orthodontics with a special focus on its role in bone remodeling, orthodontic tooth movement, orthopedic and functional appliances, pain management, and their clinical implications. This could provide a better understanding of the various physiologic and pathologic processes and help us refine our approach toward orthodontic diagnosis and therapeutics. This review would therefore serve as an overview, opening more avenues for further research on this topic that can greatly help the orthodontic fraternity.

Vertical and horizontal proportions of the face and their correlation to phi in a South Indian population.

Background: With the shift in focus from the hard to soft tissue in orthodontic diagnosis and treatment planning, the scope of orthodontic treatment has grown beyond achieving an ideal occlusion, also to achieve ideal aesthetic facial proportions. Since time immemorial, the various horizontal and vertical proportions of an ideal face is considered to follow the golden/divine ratio. Aim: The aim of this study is to assess the vertical and horizontal proportions of the face and their relation of phi in males and females of Dakshina Kannada population. Materials and Methods: The study was carried out on 100 subjects, which included 50 males and 50 females, aged between 18 and 30 years. Photographs were taken under standardized condition and adjusted to a standardized image size (5″ × 4″). Adobe Photoshop CS5.1 software was used for making all the measurements. A total of 11 vertical and horizontal ratios were independently measured for males and females, and their relation to phi was assessed. The data were subjected to Shapiro-Wilk test for testing the normality. Homogeneity of variance assumption was tested by using Levene statistic homogeneity of variance. One sample t test was used for the comparison between phi and mean vertical and horizontal ratios in males and females. Results: In males and females of the Dakshina Kannada, a statistically significant correlation was seen between all the horizontal and vertical facial proportions and phi (p < 0.05). Between male and female groups, a significant difference was noted in the intertemporal/intercanthal ratio, interalae/nose width and Intereye-soft menton/ala-soft menton (p < 0.05). Conclusion: Golden proportion can be used as a guideline in orthodontic treatment planning. However, it should not be the decisive factor in determining the facial attractiveness.

Accelerated atherosclerosis in beta-thalassemia.

Children with beta-thalassemia (BT) present with an increase in carotid intima-medial thickness, an early sign suggestive of premature atherosclerosis. However, it is unknown if there is a direct relationship between BT and atherosclerotic disease. To evaluate this, wild-type (WT, littermates) and BT (Hbbth3/+) mice, both male and female, were placed on a 3-mo high-fat diet with low-density lipoprotein receptor suppression via overexpression of proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutation (D377Y). Mechanistically, we hypothesize that heme-mediated oxidative stress creates a proatherogenic environment in BT because BT is a hemolytic anemia that has increased free heme and exhausted hemopexin, heme's endogenous scavenger, in the vasculature. We evaluated the effect of hemopexin (HPX) therapy, mediated via an adeno-associated virus, to the progression of atherosclerosis in BT and a phenylhydrazine-induced model of intravascular hemolysis. In addition, we evaluated the effect of deferiprone (DFP)-mediated iron chelation in the progression of atherosclerosis in BT mice. Aortic en face and aortic root lesion area analysis revealed elevated plaque accumulation in both male and female BT mice compared with WT mice. Hemopexin therapy was able to decrease plaque accumulation in both BT mice and mice on our phenylhydrazine (PHZ)-induced model of hemolysis. DFP decreased atherosclerosis in BT mice but did not provide an additive benefit to HPX therapy. Our data demonstrate for the first time that the underlying pathophysiology of BT leads to accelerated atherosclerosis and shows that heme contributes to atherosclerotic plaque development in BT.NEW & NOTEWORTHY This work definitively shows for the first time that beta-thalassemia leads to accelerated atherosclerosis. We demonstrated that intravascular hemolysis is a prominent feature in beta-thalassemia and the resulting increases in free heme are mechanistically relevant. Adeno-associated virus (AAV)-hemopexin therapy led to decreased free heme and atherosclerotic plaque area in both beta-thalassemia and phenylhydrazine-treated mice. Deferiprone-mediated iron chelation led to deceased plaque accumulation in beta-thalassemia mice but provided no additive benefit to hemopexin therapy.

Rapid implementation of an emergency on-site CKRT dialysate production system during the COVID-19 pandemic.

BACKGROUND: On December 29, 2021, during the delta wave of the Coronavirus Disease 2019 (COVID-19) pandemic, the stock of premanufactured solutions used for continuous kidney replacement therapy (CKRT) at the University of New Mexico Hospital (UNMH) was nearly exhausted with no resupply anticipated due to supply chain disruptions. Within hours, a backup plan, devised and tested 18 months prior, to locally produce CKRT dialysate was implemented. This report describes the emergency implementation and outcomes of this on-site CKRT dialysate production system. METHODS: This is a single-center retrospective case series and narrative report describing and reporting the outcomes of the implementation of an on-site CKRT dialysate production system. All adults treated with locally produced CKRT dialysate in December 2021 and January 2022 at UNMH were included. CKRT dialysate was produced locally using intermittent hemodialysis machines, hemodialysis concentrate, sterile parenteral nutrition bags, and connectors made of 3-D printed biocompatible rigid material. Outcomes analyzed included dialysate testing for composition and microbiologic contamination, CKRT prescription components, patient mortality, sequential organ failure assessment (SOFA) scores, and catheter-associated bloodstream infections (CLABSIs). RESULTS: Over 13 days, 22 patients were treated with 3,645 L of locally produced dialysate with a mean dose of 20.0 mL/kg/h. Fluid sample testing at 48 h revealed appropriate electrolyte composition and endotoxin levels and bacterial colony counts at or below the lower limit of detection. No CLABSIs occurred within 7 days of exposure to locally produced dialysate. In-hospital mortality was 81.8% and 28-day mortality was 68.2%, though illness severity was high, with a mean SOFA score of 14.5. CONCLUSIONS: Though producing CKRT fluid with IHD machines is not novel, this report represents the first description of the rapid and successful implementation of a backup plan for local CKRT dialysate production at a large academic medical center in the U.S. during the COVID-19 pandemic. Though conclusions are limited by the retrospective design and limited sample size of our analysis, our experience could serve as a guide for other centers navigating similar severe supply constraints in the future.

Microbial Changes occurring during oronasal fistula wound healing.

The oral microbiome is a complex community that matures with dental development while oral health is also a recognized risk factor for systemic disease. Despite the oral cavity having a substantial microbial burden, healing of superficial oral wounds occurs quickly and with little scarring. By contrast, creation of an oro-nasal fistula (ONF), often occurring after surgery to correct a cleft palate, is a significant wound healing challenge that is further complicated by a connection of the oral and nasal microbiome. In this study, we characterized the changes in the oral microbiome of mice following a freshly inflicted wound in the oral palate that results in an open and unhealed ONF. Creation of an ONF in mice significantly lowered oral microbiome alpha diversity, with concurrent blooms of Enterococcus faecalis, Staphylococcus lentus, and Staphylococcus xylosus in the oral cavity. Treatment of mice with oral antibiotics one week prior to ONF infliction resulted in a reduction in the alpha diversity, prevented E. faecalis and S. lentus, and S. xylosus blooms, but did not impact ONF healing. Strikingly, delivery of the beneficial microbe Lactococcus lactis subsp. cremoris (LLC) to the wound bed of the freshly inflicted ONF via a PEG-MAL hydrogel vehicle resulted in rapid healing of the ONF. Healing of the ONF was associated with the maintenance of relatively high microbiome alpha diversity, and limited the abundance of E. faecalis and S. lentus, and S. xylosus in the oral cavity. These data demonstrate that a freshly inflicted ONF in the murine palate is associated with a dysbiotic oral microbiome state that may prevent ONF healing, and a bloom of opportunistic pathogens. The data also demonstrate that delivery of a specific beneficial microbe, LLC, to the ONF can boost wound healing, can restore and/or preserve oral microbiome diversity, and inhibit blooms of opportunistic pathogens.

P2Y2 receptor decreases blood pressure by inhibiting ENaC.

Stimulating the Gq-coupled P2Y2 receptor (P2ry2) lowers blood pressure. Global knockout of P2ry2 increases blood pressure. Vascular and renal mechanisms are believed to participate in P2ry2 effects on blood pressure. To isolate the role of the kidneys in P2ry2 effects on blood pressure and to reveal the molecular and cellular mechanisms of this action, we test here the necessity of the P2ry2 and the sufficiency of Gq-dependent signaling in renal principal cells to the regulation of the epithelial Na+ channel (ENaC), sodium excretion, and blood pressure. Activating P2ry2 in littermate controls but not principal cell-specific P2ry2-knockout mice decreased the activity of ENaC in renal tubules. Moreover, deletion of P2ry2 in principal cells abolished increases in sodium excretion in response to stimulation of P2ry2 and compromised the normal ability to excrete a sodium load. Consequently, principal cell-specific knockout of P2ry2 prevented decreases in blood pressure in response to P2ry2 stimulation in the deoxycorticosterone acetate-salt (DOCA-salt) model of hypertension. In wild-type littermate controls, such stimulation decreased blood pressure in this model of hypertension by promoting a natriuresis. Pharmacogenetic activation of Gq exclusively in principal cells using targeted expression of Gq-designer receptors exclusively activated by designer drugs and clozapine N-oxide decreased the activity of ENaC in renal tubules, promoting a natriuresis that lowered elevated blood pressure in the DOCA-salt model of hypertension. These findings demonstrate that the kidneys play a major role in decreasing blood pressure in response to P2ry2 activation and that inhibition of ENaC activity in response to P2ry2-mediated Gq signaling lowered blood pressure by increasing renal sodium excretion.

Intestinal barrier dysfunction in murine sickle cell disease is associated with small intestine neutrophilic inflammation, oxidative stress, and dysbiosis.

The intestinal microbiome has emerged as a potential contributor to the severity of sickle cell disease (SCD). We sought to determine whether SCD mice exhibit intestinal barrier dysfunction, inflammation, and dysbiosis. Using the Townes humanized sickle cell mouse model, we found a 3-fold increase in intestinal permeability as assessed via FITC-dextran (4 kDa) assay in SS (SCD) mice compared to AA (wild type) mice (n = 4, p < 0.05). This was associated with 25 to 50% decreases in claudin-1, 3, and 15 and zonula occludens-1 gene expression (n = 8-10, p < 0.05) in the small intestine. Increased Ly6G staining demonstrated more neutrophils in the SS small intestine (3-fold, n = 5, p < 0.05) associated with increased expression of TNFα, IL-17A, CXCL1, and CD68 (2.5 to 5-fold, n = 7-10, p < 0.05). In addition, we observed 30 to 55% decreases in superoxide dismutase-1, glutathione peroxidase-1, and catalase antioxidant enzyme expression (n = 7-8, p < 0.05) concomitant to an increase in superoxide (2-fold, n = 4, p < 0.05). Importantly, all significant observations of a leaky gut phenotype and inflammation were limited to the small intestine and not observed in the colon. Finally, characterization of the composition of the microbiome within the small intestine revealed dysbiosis in SS mice compared to their AA littermates with 47 phyla to species-level significant alterations in amplicon sequence variants. We conclude that the intestinal barrier is compromised in SCD, associated with decreased gene expression of tight junction proteins, enhanced inflammation, oxidative stress, and gut microbiome dysbiosis, all specific to the small intestine.

Role of Nesprin-2 and RanBP2 in BICD2-associated brain developmental disorders.

Bicaudal D2 (BICD2) is responsible for recruiting cytoplasmic dynein to diverse forms of subcellular cargo for their intracellular transport. Mutations in the human BICD2 gene have been found to cause an autosomal dominant form of spinal muscular atrophy (SMA-LED2), and brain developmental defects. Whether and how the latter mutations are related to roles we and others have identified for BICD2 in brain development remains little understood. BICD2 interacts with the nucleoporin RanBP2 to recruit dynein to the nuclear envelope (NE) of Radial Glial Progenitor cells (RGPs) to mediate their well-known but mysterious cell-cycle-regulated interkinetic nuclear migration (INM) behavior, and their subsequent differentiation to form cortical neurons. We more recently found that BICD2 also mediates NE dynein recruitment in migrating post-mitotic neurons, though via a different interactor, Nesprin-2. Here, we report that Nesprin-2 and RanBP2 compete for BICD2-binding in vitro. To test the physiological implications of this behavior, we examined the effects of known BICD2 mutations using in vitro biochemical and in vivo electroporation-mediated brain developmental assays. We find a clear relationship between the ability of BICD2 to bind RanBP2 vs. Nesprin-2 in controlling of nuclear migration and neuronal migration behavior. We propose that mutually exclusive RanBP2-BICD2 vs. Nesprin-2-BICD2 interactions at the NE play successive, critical roles in INM behavior in RGPs and in post-mitotic neuronal migration and errors in these processes contribute to specific human brain malformations.

Association of a variant upstream of growth differentiation factor 11 (GDF11) on carcass traits in crossbred beef cattle.

The mature peptide of growth differentiation factor 11 (GDF11) in Bos taurus breeds, shares 90% amino acid sequence similarity to myostatin (MSTN), where loss-of-function mutations result in muscular hyperplasia causing a phenotype known as double-muscling. Mutations in the MSTN coding sequence increase muscle mass and reduce fat and bone tissues, but also confer poor fertility, reduced stress tolerance, and increased calf mortality. GDF11 influences skeletal muscle development in mice, and muscular atrophy can be induced by exogenous GDF11 treatment. To date, there are no reports of GDF11's role in bovine carcass traits. To determine associations between GDF11 and carcass quality in beef cattle, bovine GDF11 was examined in crossbred Canadian beef cattle populations during finishing. Few coding variants were found in this functionally important gene, but an upstream variant c.1-1951C > T (rs136619751) with a minor allele frequency of 0.31 was identified and further genotyped in two separate populations of crossbred steers (n = 415 and 450). CC animals had lower backfat thickness, marbling percentage, and yield score than CT or TT animals (P < 0.001 and < 0.05). These data suggest a role of GDF11 in carcass quality in beef cattle and may provide a selection tool to improve carcass traits in cattle.

The effect of a multi-component school-based social network intervention on children's body mass index: a four-arm intervention study.

Objective: Schools are considered an important setting for stimulating healthy weight. The current study is unique in examining effects of a multi-component school-based social network intervention on children's body mass index z-scores (zBMI).Methods: Four schools were randomly allocated to one of four conditions: a social network intervention using influence agents focusing on water consumption, physical activity, a combination of the two, or a passive control condition. Participants included a total of 201 6- to-11-year-old children (53.7% girls; Mage = 8.51, SDage = 0.93). At baseline, 149 (76.0%) participants had a healthy weight, 29 (14.8%) had overweight and 18 (9.2%) had obesity.Results: Linear mixed effect models indicated that a multi-component school-based social network intervention targeting both water consumption and physical activity was most effective in decreasing children's zBMI.Conclusion: This study suggests that schools can contribute to the intervention of childhood obesity-even without involving the parents-by targeting both children's water consumption and physical activity through influential peers, but more research is needed to identify mechanisms of change.

Automated hand hygiene compliance system's audible alert reminder increases healthcare worker hand hygiene compliance.

OBJECTIVE: To evaluate the effectiveness of an automated hand hygiene compliance system (AHHCS) audible alert and vibration for increasing hand hygiene compliance. DESIGN: A nonrandomized, before-and-after, quasi-experimental study of an AHHCS was implemented in several inpatient units. Over a 51-day period, the system's real-time audible alert was turned on, off, and back on. Overall, hand hygiene compliance was compared between days with activated and deactivated alerts and vibration. SETTING: This study was conducted at a level 1 trauma center, a regional academic health system with 1,564 beds. PARTICIPANTS: The AHHCS was implemented in 9 inpatient units: 3 adult medical-surgical step-down units, and 6 adult intensive care units. The AHHCS badges were assigned to patient care assistants, registered nurses, physical therapists, occupational therapists, speech therapists, respiratory therapists, and physicians. INTERVENTION: In the 9 inpatient units, selected healthcare staff were issued wearable badges that detected entry into and exit from a patient room. The audible alert was turned on for 16 days, turned off for 17 days, and then turned back on for 18 days, for a total of 51 days. RESULTS: Utilization of the AHHCS real-time audible alert reminder resulted in sustained HH compliance ≥90%. When the alert and vibration were deactivated, HH compliance dropped to an average of 74% (range, 62%-78%). Once the alert resumed, HH compliance returned to ≥90%. CONCLUSION: Utilization of an AHHCS with real-time reminder audible alerts may be an effective method to increase healthcare worker HH compliance to ≥90%. Users of AHHCSs should consider the use of real-time reminders to improve HH compliance.

Understanding the behavioral determinants of adolescents' water consumption: A cross-country comparative study.

Substituting the consumption of sugar-sweetened beverages (SSB) with that of water can have a positive effect on adolescents' health. However, despite the attention on this topic in the Global North, it is relatively understudied in other regions of the world, such as the Caribbean. To guide the development of future interventions, understanding the factors determining water consumption among Caribbean adolescents is important. This study examined the behavioral determinants of water consumption among adolescents in Aruba (the Caribbean) and compared them to those in the Netherlands (Western Europe). We used a theoretical model that integrates the dominant theoretical perspectives in the field of public health, including theories of planned behavior, social norms, and intrinsic motivation. This cross-country study included 1,584 adolescents from Aruba and the Netherlands (52% girls; M = 12.34 years; SD = 2.14). The data were analyzed using regression analyses. This study found that in Aruba, adolescents with higher scores of intrinsic motivation, friends' descriptive norms, attitudes, and behavioral control regarding water consumption drank more water. Moreover, the associations between water consumption and both intrinsic motivation as well as friends' descriptive norms for adolescents in Aruba were stronger than those found in the Netherlands. These associations imply that it is even more important for Aruban adolescents than Dutch adolescents to be intrinsically motivated or to perceive their friends often consuming water to drink more water. The cross-country comparison implies that future interventions in Aruba aimed at increasing adolescents' water consumption as an alternative to SSB should focus on enhancing their intrinsic motivation while considering their friends' social norms.

Incidence and Outcomes of Advanced Heart Failure in Adults With Congenital Heart Disease.

BACKGROUND: There are limited data about the stage D heart failure (advanced HF) in adults with congenital heart disease. Our study objectives were (1) to determine the incidence of new-onset advanced HF in patients and the relationship between advanced HF and all-cause mortality and (2) to determine the relationship between therapies for advanced HF and all-cause mortality. METHODS: Retrospective cohort study of adults with congenital heart disease at Mayo Clinic (2003-2019). We defined advanced HF using the European Society of Cardiology diagnostic criteria for advanced HF. Therapies received by the patients with advanced HF were classified into 3 mutually exclusive groups (treatment pathways): (1) conventional cardiac intervention, (2) transplant listing, and (3) palliative care. RESULTS: Of 5309 patients without advanced HF at baseline assessment, 432 (8%) developed advanced HF during follow-up (1.1%/y), and the incidence of advanced HF was higher in patients with severe or complex congenital heart disease. Onset of advanced HF was associated with 6-fold increase in the risk of mortality. Conventional cardiac intervention was associated with significantly higher risk of mortality as compared to transplant listing. The longer the interval from the initial onset of advanced HF to transplant evaluation, the lower the odds of being listed for transplant. CONCLUSIONS: Based on these data, we postulate that early identification of patients with advanced HF, and a timely referral for transplant evaluation (instead of conventional cardiac intervention) may offer the best chance of survival for these critically ill patients. Further studies are required to validate this postulation.

NOXA1-dependent NADPH oxidase 1 signaling mediates angiotensin II activation of the epithelial sodium channel.

The activity of the epithelial Na+ channel (ENaC) in principal cells of the distal nephron fine-tunes renal Na+ excretion. The renin-angiotensin-aldosterone system modulates ENaC activity to control blood pressure, in part, by influencing Na+ excretion. NADPH oxidase activator 1-dependent NADPH oxidase 1 (NOXA1/NOX1) signaling may play a key role in angiotensin II (ANG II)-dependent activation of ENaC. The present study aimed to explore the role of NOXA1/NOX1 signaling in ANG II-dependent activation of ENaC in renal principal cells. Patch-clamp electrophysiology and principal cell-specific Noxa1 knockout (PC-Noxa1 KO) mice were used to determine the role of NOXA1/NOX1 signaling in ANG II-dependent activation of ENaC. The activity of ENaC in the luminal plasma membrane of principal cells was quantified in freshly isolated split-opened tubules using voltage-clamp electrophysiology. ANG II significantly increased ENaC activity. This effect was robust and observed in response to both acute (40 min) and more chronic (48-72 h) ANG II treatment of isolated tubules and mice, respectively. Inhibition of ANG II type 1 receptors with losartan abolished ANG II-dependent stimulation of ENaC. Similarly, treatment with ML171, a specific inhibitor of NOX1, abolished stimulation of ENaC by ANG II. Treatment with ANG II failed to increase ENaC activity in principal cells in tubules isolated from the PC-Noxa1 KO mouse. Tubules from wild-type littermate controls, though, retained their ability to respond to ANG II with an increase in ENaC activity. These results indicate that NOXA1/NOX1 signaling mediates ANG II stimulation of ENaC in renal principal cells. As such, NOXA1/NOX1 signaling in the distal nephron plays a central role in Na+ homeostasis and control of blood pressure, particularly as it relates to regulation by the renin-ANG II axis.NEW & NOTEWORTHY Activity of the epithelial Na+ channel (ENaC) in the distal nephron fine-tunes renal Na+ excretion. Angiotensin II (ANG II) has been reported to enhance ENaC activity. Emerging evidence suggests that NADPH oxidase (NOX) signaling plays an important role in the stimulation of ENaC by ANG II in principal cells. The present findings indicate that NOX activator 1/NOX1 signaling mediates ANG II stimulation of ENaC in renal principal cells.

Motivating Social Influencers to Engage in Health Behavior Interventions.

Social influencers are widely known as the promotors of purchase behavior as well as for their potential to change health behaviors among individuals in their social networks. For social influencers to be successful in changing behaviors, it is essential that they convey their message in an authentic, original, credible, and persistent manner. In the context of health behavior interventions, this requires a focus on the motivation of social influencers to engage in the intervention. This perspective article describes the importance of motivating social influencers to engage in the desired health behaviors themselves and to promote it within their social network. We briefly describe the current state of knowledge and our empirical experience in implementing health interventions with social influencers. Using insights from self-determination theory, we demonstrate how social influencers can be motivated optimally in health behavior interventions and, thereby, improving the success of the intervention. To illustrate these insights and guide intervention practice, we provide concrete examples of techniques that can be applied in health interventions involving social influencers. We conclude with directions for further research and intervention practice to improve the delivery of health behavior interventions.

Development and evaluation of a survey instrument to assess veterinary medical record suitability for multi-center research studies.

Here we describe the development and evaluation of a survey instrument to assess the research suitability of veterinary electronic medical records (EMRs) through the conduct of two studies as part of the Dog Aging Project (DAP). In study 1, four reviewers used the instrument to score a total of 218 records in an overlapping matrix of pairs to assess inter-rater agreement with respect to appropriate format (qualification), identification match (verification), and record quality. Based upon the moderate inter-rater agreement with respect to verification and the relatively large number of records that were incorrectly rejected the instrument was modified and more specific instructions were provided. In study 2, a modified instrument was again completed by four reviewers to score 100 different EMRs. The survey scores were compared to a gold standard of board-certified specialist review to determine receiver operating curve statistics. The refined survey had substantial inter-rater agreement across most qualification and verification questions. The cut-off value identified had a sensitivity of 95 and 96% (by reviewer 1 and reviewer 2, respectively) and a specificity of 82% and 91% (by reviewer 1 and reviewer 2, respectively) to predict gold standard acceptance or rejection of the record. Using just qualification and verification questions within the instrument (as opposed to full scoring) minimally impacted sensitivity and specificity and resulted in substantial time savings in the review process.