Using environmental health dialogue in a Diné-centered approach for individualized results reporting in an environmental exposure study following the Gold King Mine Spill.

BACKGROUND: On August 5, 2015, the Gold King Mine Spill (GKMS) resulted in 3 million gallons of acid mine drainage spilling into the San Juan River impacting the Diné Bikeyah (traditional homelands of the Navajo people). The Gold King Mine Spill Diné Exposure Project was formed to understand the impacts of the GKMS on the Diné (Navajo). Reporting individualized household results in an exposure study is becoming more common; however, materials are often developed with limited community input with knowledge flowing in one direction - from researcher to participant. In this study we examined the development, dissemination, and evaluation of individualized results materials. METHODS: In August 2016, Navajo Nation Community Health Representatives (Navajo CHRs) sampled household water, dust, and soil, and resident blood and urine for lead and arsenic, respectively. From May-July 2017, iterative dialogue with a wide range of community partners and a community focus groups guided the development of a culturally-based dissemination process. In August 2017, Navajo CHRs reported individualized results and they surveyed the participants on the report-back process at that time. RESULTS: All of the 63 Diné adults (100%) who participated in the exposure study received their results by a CHR in person and 42 (67%) completed an evaluation. Most of those participants (83%) were satisfied with the result packets. Respondents ranked the individual and overall household results as the most important information they received (69% and 57%, respectively), while information on metals exposures and their health effects were the least helpful. CONCLUSIONS: Our project illustrates how a model of environmental health dialogue, defined by iterative, multidirectional communication among Indigenous community members, trusted Indigenous leaders, Indigenous researchers, non-Indigenous researchers, can improve reporting individualized study results. Findings can inform future research to encourage multi-directional environmental health dialogue to craft more culturally responsive and effective dissemination and communication materials.

Carbohydrate ingestion attenuates the reduction in complex cognitive function and cerebral blood flow during prolonged passive heat stress in humans.

PURPOSE: To determine whether carbohydrate ingestion would reduce cognitive dysfunction in humans following long duration passive heat stress (PHS) versus consuming electrolytes alone. METHODS: Fifteen young (27 ± 4 y) healthy adults were exposed to 120 min of PHS through the use of a liquid perfused suit (50 °C) on two randomized visits. Subjects consumed fluids supplemented with electrolytes (E) or electrolytes + carbohydrates (E + C). Pre- and post-heat stress, body mass (BM) and plasma osmolality (pOsm) were measured. Heart rate (HR), blood pressure (BP), Physiological Strain Index (PSI), core temperature (Tc), plasma glucose, respiration rate (RR), end-tidal CO2 (PetCO2) and internal carotid artery (ICA) blood flow were recorded at baseline and every 15 min of heat stress. Cognitive function was assessed via the Automated Neuropsychological Assessment Metric at baseline and at 30- and 120 min during heat stress. RESULTS: There were no significant differences between fluid conditions for BM, pOsm, PSI, Tc, RR or PetCO2. Plasma glucose was ∼75% greater in the E + C condition compared to the E condition after 90 min of PHS (P < 0.05). Cognitive function (120 min) was impaired following PHS only in E condition (P < 0.05) and performance on complex cognitive tasks were better by ∼22-340% in the E + C vs. E (P < 0.05). Compared to the E condition, HR and BP were lower and ICA blood flow, vascular conductance, and glucose delivery was ∼90% greater in the E + C after 90 min of PHS (P < 0.05). CONCLUSIONS: These data are the first to demonstrate that carbohydrate ingestion may have a protective effect on cognitive function during long duration PHS. Furthermore, this protection was associated with preserved ICA blood flow and glucose delivery to the brain.

Rho-kinase inhibition improves haemodynamic responses and circulating ATP during hypoxia and moderate intensity handgrip exercise in healthy older adults.

Skeletal muscle haemodynamics and circulating adenosine triphosphate (ATP) responses during hypoxia and exercise are blunted in older (OA) vs. young (YA) adults, which may be associated with impaired red blood cell (RBC) ATP release. Rho-kinase inhibition improves deoxygenation-induced ATP release from OA isolated RBCs. We tested the hypothesis that Rho-kinase inhibition (via fasudil) in vivo would improve local haemodynamic and ATP responses during hypoxia and exercise in OA. Healthy YA (25 ± 3 years; n = 12) and OA (65 ± 5 years; n = 13) participated in a randomized, double-blind, placebo-controlled, crossover study on two days (≥5 days between visits). A forearm deep venous catheter was used to administer saline/fasudil and sample venous plasma ATP ([ATP]V ). Forearm vascular conductance (FVC) and [ATP]V were measured at rest, during isocapnic hypoxia (80% SpO2${S_{{\rm{p}}{{\rm{O}}_{\rm{2}}}}}$ ), and during graded rhythmic handgrip exercise that was similar between groups (5, 15 and 25% maximum voluntary contraction (MVC)). Isolated RBC ATP release was measured during normoxia/hypoxia. With saline, ΔFVC was lower (P < 0.05) in OA vs. YA during hypoxia (∼60%) and during 15 and 25% MVC (∼25-30%), and these impairments were abolished with fasudil. Similarly, [ATP]V and ATP effluent responses from normoxia to hypoxia and rest to 25% MVC were lower in OA vs. YA and improved with fasudil (P < 0.05). Isolated RBC ATP release during hypoxia was impaired in OA vs. YA (∼75%; P < 0.05), which tended to improve with fasudil in OA (P = 0.082). These data suggest Rho-kinase inhibition improves haemodynamic responses to hypoxia and moderate intensity exercise in OA, which may be due in part to improved circulating ATP. KEY POINTS: Skeletal muscle blood flow responses to hypoxia and exercise are impaired with age. Blunted increases in circulating ATP, a vasodilator, in older adults may contribute to age-related impairments in haemodynamics. Red blood cells (RBCs) are a primary source of circulating ATP, and treating isolated RBCs with a Rho-kinase inhibitor improves age-related impairments in deoxygenation-induced RBC ATP release. In this study, treating healthy older adults systemically with the Rho-kinase inhibitor fasudil improved blood flow and circulating ATP responses during hypoxia and moderate intensity handgrip exercise compared to young adults, and also tended to improve isolated RBC ATP release. Improved blood flow regulation with fasudil was also associated with increased skeletal muscle oxygen delivery during hypoxia and exercise in older adults. This is the first study to demonstrate that Rho-kinase inhibition can significantly improve age-related impairments in haemodynamic and circulating ATP responses to physiological stimuli, which may have therapeutic implications.

Continuity of Psychopathology Throughout Adolescence and Young Adulthood.

OBJECTIVE: This study tested two opposing hypotheses on the continuity of psychopathology throughout adolescence and young adulthood; differentiation versus dynamic mutualism. Differentiation predicts that co-occurrence decreases, while dynamic mutualism predicts that co-occurrence increases due to causal interactions amongst mental health problems. METHOD: Using data from the Dutch TRacking Adolescents' Individual Lives Survey (n = 2228, 51% female), we studied the development of self-reported internalizing, externalizing, and attention problems at ages 11 to 26 across six waves. Random-intercept cross-lagged panel modeling was employed to distinguish within-person development from stable between-person processes. RESULTS: Large stable between-person associations indicated that adolescents with internalizing problems tended to have both externalizing and attention problems as well. On a within-person level, mental health problems showed partial stability and strong cross-sectional co-occurrence. Within-wave associations of internalizing with externalizing or attention problems decreased between age 11 and 16 years, after which they increased again. Little heterotypic continuity was found: age 11 externalizing predicted age 13 attention, which in turn predicted age 16 externalizing problems, and internalizing predicted externalizing problems across ages 22 to 26. Findings were similar for males and females. CONCLUSIONS: Our findings suggest co-occurrence decreases during early and middle adolescence, supporting differentiation. While co-occurrence increased again into young adulthood, this could not be labeled as dynamic mutualism because little evidence for heterotypic continuity was found in this phase of life. The strong stable links between internalizing, externalizing, and attention problems stress the importance of targeting these mental health problems and their shared risk factors together.

Self-control, Mental Health Problems, and Family Functioning in Adolescence and Young Adulthood: Between-person Differences and Within-person Effects.

Adolescents' self-control develops in the context of mental health and family functioning, but it is unclear how the interplay of self-control, mental health, and family functioning unfolds across time within individuals. Separating within-person from between-person effects, random-intercept cross-lagged panel models were applied to adolescents (from ages 11 to 26) from a Dutch cohort (n = 2228, 51% female). Adolescents with low self-control were likely to have mental health problems and poorly functioning families. Although within-person changes in the study variables were not meaningfully associated in a reciprocal manner, changes in self-control and mental health were concurrently associated. This suggests that besides stable connections between self-control, mental health, and family functioning in adolescence and young adulthood, changes in self-control and mental health are developmentally linked as well.

Diné (Navajo) female perspectives on mother-daughter communication and cultural assets around the transition to womanhood: a cross-sectional survey.

BACKGROUND: The inclusion of protective factors ("assets") are increasingly supported in developing culturally grounded interventions for American Indian (AI) populations. This study sought to explore AI women's cultural assets, perspectives, and teachings to inform the development of a culturally grounded, intergenerational intervention to prevent substance abuse and teenage pregnancy among AI females. METHODS: Adult self-identified AI women (N = 201) who reside on the Navajo Nation completed a cross-sectional survey between May and October 2018. The 21-question survey explored health communication around the transition to womanhood, cultural assets, perceptions of mother-daughter reproductive health communication, and intervention health topics. Univariate descriptive analyses, chi squared, and fisher's exact tests were conducted. RESULTS: Respondents ranged in age from 18 to 82 years, with a mean age of 44 ± 15.5 years. Women self-identified as mothers (95; 48%), aunts (59; 30%), older sisters (55; 28%), grandmothers (37; 19%), and/or all of the aforementioned (50; 25%). 66% (N = 95) of women admired their mother/grandmother most during puberty; 29% (N = 58) of women were 10-11 years old when someone first spoke to them about menarche; and 86% (N=172) felt their culture was a source of strength. 70% (N = 139) would have liked to learn more about reproductive health when they were a teenager; 67% (N = 134) felt Diné mothers are able to provide reproductive health education; 51% (N = 101) reported having a rite of passage event, with younger women desiring an event significantly more than older women. Responses also indicate a disruption of cultural practices due to government assimilation policies, as well as the support of male relatives during puberty. CONCLUSIONS: Results informed intervention content and delivery, including target age group, expanded caregiver eligibility criteria, lesson delivery structure and format, and protective cultural teachings. Other implications include the development of a complementary fatherhood and/or family-based intervention to prevent Native girls' substance use and teen pregnancy.

Rigorous evaluation of a substance use and teen pregnancy prevention program for American Indian girls and their female caregivers: a study protocol for a randomized controlled trial.

BACKGROUND: Early sexual initiation is associated with higher risk for sexually transmitted infection, teen pregnancy, domestic violence and substance use in later adolescence and early adulthood. Native American adolescents are more likely to have early sexual initiation compared to other racial/ethnic groups. Few programs designed with and for Native adolescents to delay sexual initiation and substance use have been tested through rigorous evaluations. This is the protocol for the randomized controlled trial of the Asdzáán Be'eena' program, a teen pregnancy and substance use prevention program for young Native girls and their female caregivers. METHODS: N = 410 female adolescents ages 10-14 and their female caregivers will be enrolled in the study and randomized to the intervention or control arm. The intervention consists of the 11-session Asdzáán Be'eena' program. The control arm consists of mailed non-monetary incentives. All participants will complete evaluations at baseline and 3 follow-up timepoints (immediate, 6 and 12 months post intervention). Evaluations include measures to assess protective factors associated with delayed sexual initiation and substance use. DISCUSSION: This is one of the first rigorous evaluations of a gender-specific, culturally tailored teen pregnancy and substance use primary prevention program for Native girls and their female caregivers. If proven efficacious, Native communities will have a culturally appropriate program for promoting protective factors associated with delayed substance use and sexual risk taking. TRIAL REGISTRATION: NCT04863729 ; April 27, 2021.

Feasibility, Acceptability, and Preliminary Impact of Asdzáán Be'eená: An Intergenerational, Strength-Based, and Culturally Grounded Program to Improve the Health of Navajo Families.

Native American youth endure a complex interplay of factors that portend greater risk-taking behaviors and contribute to marked health disparities experienced in adolescence. The Asdzáán Be'eená ("Female Pathways" in Navajo) program was developed as a primary prevention program to prevent substance use and teen pregnancy among Navajo girls. The Asdzáán Be'eená program consists of 11 lessons delivered to dyads of girls ages 8 to 11 years and their female caregivers. Feasibility, acceptability, and preliminary impact on risk and protective factors were assessed through a pre-/post study design. Data were collected from girls and their female caregivers at baseline, immediate, and 3 months postprogram completion. Forty-seven dyads enrolled in the study, and 36 completed the 3-month evaluation. At 3 months postprogram, girls reported significant increases in self-esteem, self-efficacy, parent-child relationship, social support, cultural, and sexual health knowledge. Caregivers reported increased family engagement in Navajo culture and parent-child communication and improved child functioning (fewer internalizing and externalizing behaviors). Findings suggest Asdzáán Be'eená has potential to break the cycle of substance use and teen pregnancy in Native communities by improving protective and reducing risk factors associated with these adverse health outcomes. Additional rigorous efficacy trials are necessary to establish program effectiveness.

Carbohydrate ingestion attenuates cognitive dysfunction following long-duration exercise in the heat in humans.

INTRODUCTION: To determine if electrolyte or carbohydrate supplementation vs. water would limit the magnitude of dehydration and decline in cognitive function in humans following long-duration hyperthermic-exercise. METHODS: 24 subjects performed 3 visits of 2 h walking (3mph/7% grade) in an environmental chamber (33 °C/10% relative humidity). In random order, subjects consumed water (W), electrolytes (Gatorade Zero; E), or electrolytes+carbohydrates (Gatorade; E+C). Throughout exercise (EX), subjects carried a 23 kg pack and drank ad-libitum. Pre-and post-EX, body mass (BM) and plasma osmolality (pOsm) were measured. Physiological Strain Index (PSI) and core temperature (TC) were recorded every 15 min. Plasma glucose (GLU) was measured every 30 min. Cognitive processing (SCWT) was measured post-EX and compared to baseline (BL). A subset of 8 subjects performed a normothermic (N) protocol (21 °C/ambient humidity) to ascertain how the exercise stimulus influenced hydration status and cognition without heat. RESULTS: There were no significant differences between fluid conditions (W, E, E+C) for BM loss (Δ2.5 ± 0.2, 2.5 ± 0.2, 2.3 ± 0.2 kg), fluid consumption (1.9 ± 0.2, 1.9 ± 0.2, 1.8 ± 0.2L), pOsm (Δ1.5 ± 2.7, 2.2 ± 2.4, 2.0 ± 1.5 mmol/L), peak-PSI (7.5 ± 0.4, 7.0 ± 0.6, 7.9 ± 0.5), and peak-TC (38.7 ± 0.1, 38.6 ± 0.2, 38.8 ± 0.2 °C). GLU decreased significantly in W and E, whereas it increased above BL in E+C at 60, 90, and 120 min (P < 0.05). Compared to BL values (43.6 ± 26 ms), SCWT performance significantly decreased in all conditions (463 ± 93, 422 ± 83, 140 ± 52 ms, P < 0.05). Importantly, compared to W and E, the impairment in SCWT was significantly attenuated in E+C (P < 0.05). As expected, when compared to the heat-stress protocol (W, E, E+C), N resulted in lower BM loss, fluid consumption, and peak-PSI (1.1 ± 0.1 kg, 1.2 ± 0.7L, 4.8, respectively), and improved SCWT performance. CONCLUSIONS: These data are the first to suggest that, independent of supplementation variety, cognitive processing significantly decreases immediately following long-duration exercise in the heat in healthy humans. Compared to water and fluids supplemented with only electrolytes, fluids supplemented with carbohydrates significantly blunts this decrease in cognitive function.

Social Withdrawal and Romantic Relationships: A Longitudinal Study in Early Adulthood.

Involvement in romantic relationships is a salient developmental task in late adolescence and early adulthood, and deviations from normative romantic development are linked to adverse outcomes. This study investigated to what extent social withdrawal contributed to deviations from normative romantic development, and vice versa, and the interplay between withdrawal and couples' relationship perceptions. The sample included 1710 young adults (55-61% female) from the Tracking Adolescents' Individual Lives Survey cohort and their romantic partners. Data were collected across 4 waves, covering romantic relationships from ages 17 to 29 years. The results showed that higher withdrawal predicted a higher likelihood of romantic non-involvement by adulthood, consistently being single at subsequent waves, and entering one's first relationship when older. Withdrawal moderately decreased when youth entered their first relationship. Male's withdrawal in particular affected romantic relationship qualities and dynamics. These results provide new insights into the developmental sequelae of withdrawn young adults' romantic relationship development.

KIR channel activation links local vasodilatation with muscle fibre recruitment during exercise in humans.

KEY POINTS: During exercise, blood flow to working skeletal muscle increases in parallel with contractile activity such that oxygen delivery is sufficient to meet metabolic demand. K+ released from active skeletal muscle fibres could facilitate vasodilatation in proportion to the degree of muscle fibre recruitment. Once released, K+ stimulates inwardly rectifying K+ (KIR ) channels on the vasculature to elicit an increase in blood flow. In the present study, we demonstrate that KIR channels mediate the rapid vasodilatory response to an increase in exercise intensity. We also show that KIR channels augment vasodilatation during exercise which demands greater muscle fibre recruitment independent of the total amount of work performed. These results suggest that K+ plays a key role in coupling the magnitude of vasodilatation to the degree of contractile activity. Ultimately, the findings from this study help us understand the signalling mechanisms that regulate muscle blood flow in humans. ABSTRACT: Blood flow to active skeletal muscle is augmented with greater muscle fibre recruitment. We tested whether activation of inwardly rectifying potassium (KIR ) channels underlies vasodilatation with elevated muscle fibre recruitment when work rate is increased (Protocol 1) or held constant (Protocol 2). We assessed forearm vascular conductance (FVC) during rhythmic handgrip exercise under control conditions and during local inhibition of KIR channels (intra-arterial BaCl2 ). In Protocol 1, healthy volunteers performed mild handgrip exercise for 3 min, then transitioned to moderate intensity for 30 s. BaCl2 eliminated vasodilatation during the first contraction at the moderate workload (ΔFVC, BaCl2 : -1 ± 17 vs. control: 30 ± 28 ml min-1  100 mmHg-1 ; n = 9; P = 0.004) and attenuated the 30 s area under the curve by 56 ± 14% (n = 9; P < 0.0001). In Protocol 2, participants performed two exercise bouts in which muscle fibre recruitment was manipulated while total contractile work was held constant via reciprocal changes in contraction frequency: (1) low fibre recruitment, with contractions at 12.5% maximal voluntary contraction once every 4 s and (2) high fibre recruitment, with contractions at 25% maximal voluntary contraction once every 8 s. Under control conditions, steady-state FVC was augmented in high vs. low fibre recruitment (211 ± 90 vs. 166 ± 73 ml min-1 ⋅100 mmHg-1 ; n = 10; P = 0.0006), whereas BaCl2 abolished the difference between high and low fibre recruitment (134 ± 59 vs. 134 ± 63 ml min-1  100 mmHg-1 ; n = 10; P = 0.85). These findings demonstrate that KIR channel activation is a key mechanism linking local vasodilatation with muscle fibre recruitment during exercise.

Augmentation of endothelium-dependent vasodilatory signalling improves functional sympatholysis in contracting muscle of older adults.

KEY POINTS: The ability of contracting skeletal muscle to attenuate sympathetic vasoconstriction (functional sympatholysis) is critical for maintaining blood flow during exercise-mediated sympathoexcitation. Functional sympatholysis and endothelial function are impaired with ageing, resulting in compromised blood flow and oxygen delivery to contracting skeletal muscle during exercise. In the present study, intra-arterial infusion of ACh or ATP to augment endothelium-dependent signalling during exercise attenuated α1 -adrenergic vasoconstriction in the contracting muscle of older adults. The vascular signalling mechanisms capable of functional sympatholysis are preserved in healthy ageing, and thus the age-related impairment in functional sympatholysis probably results from the loss of a functional signal (e.g. plasma [ATP]) as opposed to an intrinsic endothelial dysfunction. ABSTRACT: The ability of contracting skeletal muscle to attenuate sympathetic α-adrenergic vasoconstriction ('functional sympatholysis') is impaired with age. In young adults, increasing endothelium-dependent vasodilatory signalling during mild exercise augments sympatholysis. In the present study, we tested the hypothesis that increasing endothelium-dependent signalling during exercise in older adults can improve sympatholysis. In 16 older individuals (Protocol 1, n = 8; Protocol 2, n = 8), we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (FVC) to local intra-arterial infusion of phenylephrine (PE; α1 -agonist) during (i) infusion of an endothelium-dependent vasodilator alone (Protocol 1: ACh or Protocol 2: low dose ATP); (ii) mild handgrip exercise (5% maximum voluntary contraction; MVC); (iii) moderate handgrip exercise (15% MVC); and (iv) mild or moderate handgrip exercise + infusion of ACh or ATP to augment endothelium-dependent signalling. PE caused robust vasoconstriction in resting skeletal muscle during control vasodilator infusions (ΔFVC: ACh: -31 ± 3 and ATP: -30 ± 4%). PE-mediated vasoconstriction was not attenuated by mild or moderate intensity exercise (ΔFVC: 5% MVC: -30 ± 9; 15% MVC: -33 ± 8%; P > 0.05 vs. control ACh and ATP), indicative of impaired sympatholysis, and ACh or ATP infusion during mild exercise did not impact this response. However, augmentation of endothelium-dependent signalling via infusion of ACh or ATP during moderate intensity exercise attenuated PE-mediated vasoconstriction (ΔFVC: -13 ± 1 and -19 ± 5%, respectively; P < 0.05 vs. all conditions). Our findings demonstrate that, given a sufficient stimulus, endothelium-dependent sympatholysis remains intact in older adults. Strategies aimed at activating such pathways represent a viable approach for improving sympatholysis and thus tissue blood flow and oxygen delivery in older adults.

Drug repurposing: phosphate prodrugs of anticancer and antiviral FDA-approved nucleosides as novel antimicrobials.

OBJECTIVES: Following a drug repurposing approach, we aimed to investigate and compare the antibacterial and antibiofilm activities of different classes of phosphate prodrugs (HepDirect, cycloSal, SATE and mix SATE) of antiviral and anticancer FDA-approved nucleoside drugs [zidovudine (AZT), floxouridine (FUDR) and gemcitabine (GEM)] against a variety of pathogenic Gram-positive and -negative bacteria. METHODS: Ten prodrugs were synthesized and screened for antibacterial activity against seven Gram-negative and two Gram-positive isolates fully susceptible to traditional antibiotics, alongside six Gram-negative and five Gram-positive isolates with resistance mechanisms. Their ability to prevent and eradicate biofilms of different bacterial pathogens in relation to planktonic growth inhibition was also evaluated, together with their effect on proliferation, viability and apoptosis of different eukaryotic cells. RESULTS: The prodrugs showed decreased antibacterial activity compared with the parent nucleosides. cycloSal-GEM-monophosphate (MP) prodrugs 20a and 20b were the most active agents against Gram-positive bacteria (Enterococcus faecalis and Staphylococcus aureus) and retained their activity against antibiotic-resistant isolates. cycloSal-FUDR-MP 21a partially retained good activity against the Gram-positive bacteria E. faecalis, Enterococcus faecium and S. aureus. Most of the prodrugs tested displayed very potent preventive antibiofilm specific activity, but not curative. In terms of cytotoxicity, AZT prodrugs did not affect apoptosis or cell viability at the highest concentration tested, and only weak effects on apoptosis and/or cell viability were observed for GEM and FUDR prodrugs. CONCLUSIONS: Among the different prodrug approaches, the cycloSal prodrugs appeared the most effective. In particular, cycloSal (17a) and mix SATE (26) AZT prodrugs combine the lowest cytotoxicity with high and broad antibacterial and antibiofilm activity against Gram-negative bacteria.

A common-mesocosm experiment recreates sawgrass (Cladium jamaicense) phenotypes from Everglades marl prairies and peat marshes.

PREMISE: The southern Florida Everglades landscape sustains wetlands of national and international importance. Sawgrass (Cladium jamaicense), the dominant macrophyte in the Everglades, has two phenotypes that vary in size and density between Everglades marl prairies and peat marshes. Marl prairies have recently been hypothesized to be a newly formed habitat developed after European colonization as a result of landscape-scale hydrologic modifications, implying that sawgrass marl phenotypes developed in response to the marl habitat. We examined whether sawgrass wetland phenotypes are plastic responses to marl and peat soils. METHODS: In a common-mesocosm experiment, seedlings from a single Everglades population were grown outdoors in field-collected marl or peat soils. Growth and morphology of plants were measured over 14 mo, while soil and leaf total nitrogen, total phosphorus, total carbon, and plant biomass and biomass allocation were determined in a final harvest. RESULTS: Sawgrass plant morphology diverged in marl vs. peat soils, and variations in morphology and density of mesocosm-grown plants resembled differences seen in sawgrass plants growing in marl and peat habitats in Everglades wetlands. Additionally, sawgrass growing in marl made abundant dauciform roots, while dauciform root production of sawgrass growing in peat was correlated with soil total phosphorus. CONCLUSIONS: Sawgrass from a single population grown in marl or peat soils can mimic sawgrass phenotypes associated with marl vs. peat habitats. This plasticity is consistent with the hypothesis that Everglades marl prairies are relatively new habitats that support plant communities assembled after European colonization and subsequent landscape modifications.

The social withdrawal and social anxiety feedback loop and the role of peer victimization and acceptance in the pathways.

Social withdrawal and social anxiety are believed to have a bidirectional influence on one another, but it is unknown if their relationship is bidirectional, especially within person, and if peer experiences influence this relationship. We investigated temporal sequencing and the strength of effects between social withdrawal and social anxiety, and the roles of peer victimization and acceptance in the pathways. Participants were 2,772 adolescents from the population-based and clinically referred cohorts of the Tracking Adolescents' Individual Lives Survey. Self- and parent-reported withdrawal, and self-reported social anxiety, peer victimization, and perceived peer acceptance were assessed at 11, 13, and 16 years. Random-intercept cross-lagged panel models were used to investigate within-person associations between these variables. There was no feedback loop between withdrawal and social anxiety. Social withdrawal did not predict social anxiety at any age. Social anxiety at 11 years predicted increased self-reported withdrawal at 13 years. Negative peer experiences predicted increased self- and parent-reported withdrawal at 13 years and increased parent-reported withdrawal at 16 years. In turn, self-reported withdrawal at 13 years predicted negative peer experiences at 16 years. In conclusion, adolescents became more withdrawn when they became more socially anxious or experienced greater peer problems, and increasing withdrawal predicted greater victimization and lower acceptance.

A Qualitative Evaluation of a Community Based, Culturally Relevant Intervention to Promote Healthy Food Access in American Indian Communities.

In response to a need for healthy, affordable food, Johns Hopkins Center for American Indian Health and three rural indigenous communities launched the "Feast for the Future," (FFF) to promote access to healthy foods and the transfer of traditional food-based knowledge from farmers/elders to youth. To assess program impact, 43 in-depth interviews were conducted with participating farmers, elders, and Community Advisory Board members. Interviews were recorded, transcribed, and analyzed in Atlas.ti. Common themes from qualitative analyses included: FFF programs support farming/gardening revitalization and cultural connectedness/identity; FFF has supported positive behavior change among interviewees and their families; There is a need to revitalize traditional food systems; Farming/gardening is central to cultural identity; and Responsibility for food choices. The interviews revealed that the community-based program is perceived by key stakeholders as reaffirming cultural identity and promoting healthy eating. As a CAB member shared.

Self-selected fluid volume and flavor strength does not alter fluid intake, body mass loss, or physiological strain during moderate-intensity exercise in the heat.

INTRODUCTION: The purpose of this study was to determine the effects of ad libitum flavor and fluid intake on changes in body mass (BM) and physiological strain during moderate intensity exercise in the heat. METHODS: Ten subjects (24±3yrs, 7M/3F) performed 60 min of treadmill walking at 1.3 m/s and 7% grade in an environmental chamber set to 33 °C and 10% relative humidity while carrying a 22.7 kg pack on two different occasions. Subjects consumed either plain water or water plus flavor (Infuze), ad libitum, at each visit. Pre and post exercise, fluid consumption (change in fluid reservoir weight) and BM (nude) were measured. During exercise, heart rate (HR), systolic blood pressure (SBP), rate of perceived exertion (RPE), oxygen consumption (VO2), respiratory exchange ratio (RER), core temperature (TC), and physiological strain index (PSI) were recorded every 15 min during exercise. RESULTS: No significant differences were observed for fluid consumption between fluid conditions (512 ± 97.2 mL water vs. 414.3 ± 62.5 mL Infuze). Despite a significant decrease from baseline, there were no significant differences in overall change of BM (Δ -1.18 vs. -0.64 Kg) or percent body weight loss for water and Infuze conditions, respectively (1.58 ± 0.6 and 0.79 ± 0.2%). Furthermore, there were no significant differences in HR (144 ± 6 vs. 143 ± 8 bpm), SBP (157 ± 5 vs. 155 ± 5 mmHg), RPE, VO2 (27.4 ± 0.9 vs. 28.1 ± 1.2 ml/Kg/min), RER, TC (38.1 ± 0.1 vs. 37.0 ± 0.1 °C), and peak PSI (5.4 ± 0.4 vs. 5.7 ± 0.8) between conditions. CONCLUSIONS: Offering individuals the choice to actively manipulate flavor strength did not significantly influence ad libitum fluid consumption, fluid loss, or physiological strain during 60 min of moderate intensity exercise in the heat.

Amplification of endothelium-dependent vasodilatation in contracting human skeletal muscle: role of KIR channels.

KEY POINTS: In humans, the vasodilatory response to skeletal muscle contraction is mediated in part by activation of inwardly rectifying potassium (KIR ) channels. Evidence from animal models suggest that KIR channels serve as electrical amplifiers of endothelium-dependent hyperpolarization (EDH). We found that skeletal muscle contraction amplifies vasodilatation to the endothelium-dependent agonist ACh, whereas there was no change in the vasodilatory response to sodium nitroprusside, an endothelium-independent nitric oxide donor. Blockade of KIR channels reduced the exercise-induced amplification of ACh-mediated vasodilatation. Conversely, pharmacological activation of KIR channels in quiescent muscle via intra-arterial infusion of KCl independently amplified the vasodilatory response to ACh. This study is the first in humans to demonstrate that specific endothelium-dependent vasodilatory signalling is amplified in the vasculature of contracting skeletal muscle and that KIR channels may serve as amplifiers of EDH-like vasodilatory signalling in humans. ABSTRACT: The local vasodilatory response to muscle contraction is due in part to the activation of inwardly rectifying potassium (KIR ) channels. Evidence from animal models suggest that KIR channels function as 'amplifiers' of endothelium-dependent vasodilators. We tested the hypothesis that contracting muscle selectively amplifies endothelium-dependent vasodilatation via activation of KIR channels. We measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (FVC) to local intra-arterial infusion of ACh (endothelium-dependent dilator) during resting conditions, handgrip exercise (5% maximum voluntary contraction) or sodium nitroprusside (SNP; endothelium-independent dilator) which served as a high-flow control condition (n = 7, young healthy men and women). Trials were performed before and after blockade of KIR channels via infusion of barium chloride. Exercise augmented peak ACh-mediated vasodilatation (ΔFVC saline: 117 ± 14; exercise: 236 ± 21 ml min-1 (100 mmHg)-1 ; P < 0.05), whereas SNP did not impact ACh-mediated vasodilatation. Blockade of KIR channels attenuated the exercise-induced augmentation of ACh. In eight additional subjects, SNP was administered as the experimental dilator. In contrast to ACh, exercise did not alter SNP-mediated vasodilatation (ΔFVC saline: 158 ± 35; exercise: 121 ± 22 ml min-1 (100 mmHg)-1 ; n.s.). Finally, in a subset of six subjects, direct pharmacological activation of KIR channels in quiescent muscle via infusion of KCl amplified peak ACh-mediated vasodilatation (ΔFVC saline: 97 ± 15, KCl: 142 ± 16 ml min-1  (100 mmHg)-1 ; respectively; P < 0.05). These findings indicate that skeletal muscle contractions selectively amplify endothelium-dependent vasodilatory signalling via activation of KIR channels, and this may be an important mechanism contributing to the normal vasodilatory response to exercise in humans.

Multicenter Clinical Evaluation of Etest Meropenem-Vaborbactam (bioMérieux) for Susceptibility Testing of Enterobacterales (Enterobacteriaceae) and Pseudomonas aeruginosa.

Meropenem-vaborbactam (MEV) is a novel carbapenem-beta-lactamase inhibitor combination antibiotic approved by the U.S. Food and Drug Administration (FDA) for treatment of complicated urinary tract infections, including pyelonephritis, in adults. In this study, we evaluated the performance of Etest MEV (bioMérieux, Marcy l'Etoile, France) compared to that of broth microdilution for 629 Enterobacterales and 163 Pseudomonas aeruginosa isolates. According to CLSI/FDA breakpoints, 13 Enterobacterales isolates (12 clinical and 1 challenge) were resistant to MEV. Overall, Etest MEV demonstrated 92.4% essential agreement (EA), 99.2% category agreement (CA), 0% very major errors (VME), 0% major errors (ME), and 0.8% minor errors (mE) with clinical and challenge isolates of Enterobacterales Individual species demonstrated EA rates of ≥80%, with the exception of Proteus mirabilis, for which clinical and challenge isolates demonstrated 34.3% EA, 97.1% CA, 0% ME, and 2.9% mE, precluding the use of Etest MEV with this species. Excluding P. mirabilis, MEV Etest MEV demonstrated 95.8% EA, 99.3% CA, 0% VME, 0% ME, and 0.7% mE with Enterobacterales isolates. When evaluated using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, Etest MEV performance with clinical (16 MEV resistant) and challenge (12 MEV resistant) isolates of Enterobacterales (excluding P. mirabilis) and P. aeruginosa demonstrated an unacceptably high VME rate of 7.1% despite 95.2% EA, 99.2% CA, and 0.5% ME compared to the reference method. In conclusion, we report that Etest MEV is accurate and reproducible for MEV susceptibility testing for P. aeruginosa and Enterobacterales, with the exception of P. mirabilis, using CLSI/FDA breakpoints. Etest MEV should not be used with P. mirabilis due to unacceptable analytical performance.