Effect of Menstrual Cycle and Hormonal Contraception on Musculoskeletal Health and Performance: Protocol for a Prospective Cohort Design and Cross-Sectional Comparison.

BACKGROUND: Women of reproductive age experience cyclical variation in the female sex steroid hormones 17ß-estradiol and progesterone during the menstrual cycle that is attenuated by some hormonal contraceptives. Estrogens perform a primary function in sexual development and reproduction but have nonreproductive effects on bone, muscle, and sinew tissues (ie, ligaments and tendons), which may influence injury risk and physical performance. OBJECTIVE: The purpose of the study is to understand the effect of the menstrual cycle and hormonal contraceptive use on bone and calcium metabolism, and musculoskeletal health and performance. METHODS: A total of 5 cohorts of physically active women (aged 18-40 years) will be recruited to participate: eumenorrheic, nonhormonal contraceptive users (n=20); combined oral contraceptive pill (COCP) users (n=20); hormonal implant users (n=20); hormonal intrauterine system users (n=20); and hormonal injection users (n=20). Participants must have been using the COCP and implant for at least 1 year and the intrauterine system and injection for at least 2 years. First-void urine samples and fasted blood samples will be collected for biochemical analysis of calcium and bone metabolism, hormones, and metabolic markers. Knee extensor and flexor strength will be measured using an isometric dynamometer, and lower limb tendon and stiffness, tone, and elasticity will be measured using a Myoton device. Functional movement will be assessed using a single-leg drop to assess the frontal plane projection angle and the qualitative assessment of single leg loading. Bone density and macro- and microstructure will be measured using ultrasound, dual-energy x-ray absorptiometry, and high-resolution peripheral quantitative computed tomography. Skeletal material properties will be estimated from reference point indentation, performed on the flat surface of the medial tibia diaphysis. Body composition will be assessed by dual-energy x-ray absorptiometry. The differences in outcome measures between the hormonal contraceptive groups will be analyzed in a one-way between-group analysis of covariance. Within the eumenorrheic group, the influence of the menstrual cycle on outcome measures will be assessed using a linear mixed effects model. Within the COCP group, differences across 2 time points will be analyzed using the paired-samples 2-tailed t test. RESULTS: The research was funded in January 2020, and data collection started in January 2022, with a projected data collection completion date of August 2024. The number of participants who have consented at the point of manuscript submission is 66. It is expected that all data analysis will be completed and results published by the end of 2024. CONCLUSIONS: Understanding the effects of the menstrual cycle and hormonal contraception on musculoskeletal health and performance will inform contraceptive choices for physically active women to manage injury risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT05587920; https://classic.clinicaltrials.gov/ct2/show/NCT05587920. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50542.

Design, Synthesis, and Evaluation of a New Chemotype Fluorescent Ligand for the P2Y2 Receptor.

The P2Y2 receptor (P2Y2R) is a target for diseases including cancer, idiopathic pulmonary fibrosis, and atherosclerosis. However, there are insufficient P2Y2R antagonists available for validating P2Y2R function and future drug development. Evaluation of how (R)-5-(7-chloro-2-((2-ethoxyethyl)amino)-4H-benzo[5,6]cyclohepta[1,2-d]thiazol-4-yl)-1-methyl-4-thioxo-3,4-dihydropyrimidin-2(1H)-one, a previously published thiazole-based analogue of AR-C118925, binds in a P2Y2R homology model was used to design new P2Y2R antagonist scaffolds. One P2Y2R antagonist scaffold retained millimolar affinity for the P2Y2R and upon further functionalization with terminal carboxylic acid groups affinity was improved over 100-fold. This functionalized P2Y2R antagonist scaffold was employed to develop new chemotype P2Y2R fluorescent ligands, that were attainable in a convergent five-step synthesis. One of these fluorescent ligands demonstrated micromolar affinity (pK d = 6.02 ± 0.12, n = 5) for the P2Y2R in isolated cell membranes and distinct pharmacology from an existing P2Y2R fluorescent antagonist, suggesting it may occupy a different binding site on the P2Y2R.

Sex differences in energy balance, body composition, and metabolic and endocrine markers during prolonged arduous military training.

This study investigated sex differences in energy balance, body composition, and metabolic and endocrine markers during prolonged military training. Twenty-three trainees (14 women) completed 44-wk military training (three terms of 14 wk with 2-wk adventurous training). Dietary intake and total energy expenditure were measured over 10 days during each term by weighed food and doubly labeled water. Body composition was measured by dual-energy X-ray absorptiometry (DXA) at baseline and at the end of each term. Circulating metabolic and endocrine markers were measured at baseline and at the end of terms 2 and 3. Absolute energy intake and total energy expenditure were higher, and energy balance was lower, for men than women (P ≤ 0.008). Absolute energy intake and balance were lower, and total energy expenditure was higher, during term 2 than terms 1 and 3 (P < 0.001). Lean mass did not change with training (P = 0.081). Fat mass and body fat increased from term 1 to terms 2 and 3 (P ≤ 0.045). Leptin increased from baseline to terms 2 and 3 in women (P ≤ 0.002) but not in men (P ≥ 0.251). Testosterone and free androgen index increased from baseline to term 3 (P ≤ 0.018). Free thyroxine (T4) decreased and thyroid-stimulating hormone (TSH) increased from baseline to term 2 and term 3 (P ≤ 0.031). Cortisol decreased from baseline to term 3 (P = 0.030). IGF-I and total triiodothyronine (T3) did not change with training (P ≥ 0.148). Men experienced greater energy deficits than women during military training due to higher total energy expenditure.NEW & NOTEWORTHY Energy deficits are common in military training and can result in endocrine and metabolic disturbances. This study provides first investigation of sex differences in energy balance, body composition, and endocrine and metabolic markers in response to prolonged and arduous military training. Men experienced greater energy deficits than women due to higher energy expenditure, which was not compensated for by increased energy intake. These energy deficits were not associated with decreases in fat or lean mass or metabolic or endocrine function.

The effect of sex and protein supplementation on bone metabolism during a 36-h military field exercise in energy deficit.

This study investigated sex differences in, and the effect of protein supplementation on, bone metabolism during a 36-h military field exercise. Forty-four British Army Officer cadets (14 women) completed a 36-h field exercise. Participants consumed either their habitual diet [n = 14 women (Women) and n = 15 men (Men Controls)] or the habitual diet with an additional 46.6 g·day-1 of protein for men [n = 15 men (Men Protein)]. Women and Men Protein were compared with Men Controls to examine the effect of sex and protein supplementation. Circulating markers of bone metabolism were measured before, 24 h after (postexercise), and 96 h after (recovery) the field exercise. Beta C-telopeptide cross links of type 1 collagen and cortisol were not different between time points or Women and Men Controls (P ≥ 0.094). Procollagen type I N-terminal propeptide decreased from baseline to postexercise (P < 0.001) and recovery (P < 0.001) in Women and Men Controls. Parathyroid hormone (PTH) increased from baseline to post-exercise (P = 0.006) and decreased from postexercise to recovery (P = 0.047) in Women and Men Controls. Total 25(OH)D increased from baseline to postexercise (P = 0.038) and recovery (P < 0.001) in Women and Men Controls. Testosterone decreased from baseline to post-exercise (P < 0.001) and recovery (P = 0.007) in Men Controls, but did not change for Women (all P = 1.000). Protein supplementation in men had no effect on any marker. Men and women experience similar changes to bone metabolism-decreased bone formation and increased PTH-following a short-field exercise. Protein had no protective effect likely because of the energy deficit.NEW & NOTEWORTHY Energy deficits are common in arduous military training and can cause disturbances to bone metabolism. This study provides first evidence that short periods of severe energy deficit and arduous exercise-in the form of a 36-h military field exercise-can suppress bone formation for at least 96 h, and the suppression in bone formation was not different between men and women. Protein feeding does not offset decreases in bone formation during severe energy deficits.

Utility of a Pediatric Adaptive Sports Clinic: A Case Series Review.

BACKGROUND: Limited funding is available for athletes with disabilities in the United Kingdom. This compounds the barriers to participation and development that already exist. METHOD: To combat this growing problem, a Multi-Disciplinary Pediatric Adaptive Sports Clinic was formed. RESULT: Fifteen athletes with disabilities attended the Clinic from November 2017 to November 2019. In our cohort, there were 10 males and 5 females (age range: 13-18 years). Most athletes participated at a grassroots level (n = 9). The range of diagnoses included cerebral palsy, Ehlers Danlos syndrome and congenital hand differences. Forty-four appointments were made after the initial meeting with a 95% attendance rate. Improvements beyond the minimal clinically important differences (MCID) for the Patient Specific Functional Scale, Numerical Pain Rating Scale, and Medical Research Council Manual Muscle Testing Scale were noted in over half of cases. CONCLUSION: With a focus on injury prevention and strength and conditioning techniques, this clinic supported athletes to successfully compete from a recreational to an elite level across all types of sports and adolescent ages by providing patient-specific regimens. Our case series provides preliminary evidence to suggest the formation of similar clinics that can support athletes with disabilities across a range of sports.

Wayfinding and path integration deficits detected using a virtual reality mobile app in patients with traumatic brain injury.

The ability to navigate is supported by a wide network of brain areas which are particularly vulnerable to disruption brain injury, including traumatic brain injury (TBI). Wayfinding and the ability to orient back to the direction you have recently come (path integration) may likely be impacted in daily life but have so far not been tested with patients with TBI. Here, we assessed spatial navigation in thirty-eight participants, fifteen of whom had a history of TBI, and twenty-three control participants. Self-estimated spatial navigation ability was assessed using the Santa Barbara Sense of Direction (SBSOD) scale. No significant difference between TBI patients and a control group was identified. Rather, results indicated that both participant groups demonstrated 'good' self-inferred spatial navigational ability on the SBSOD scale. Objective navigation ability was tested via the virtual mobile app test Sea Hero Quest (SHQ), which has been shown to predict real-world navigation difficulties and assesses (a) wayfinding across several environments and (b) path integration. Compared to a sub-sample of 13 control participants, a matched subsample of 10 TBI patients demonstrated generally poorer performance on all wayfinding environments tested. Further analysis revealed that TBI participants consistently spent a shorter duration viewing a map prior to navigating to goals. Patients showed mixed performance on the path integration task, with poor performance evident when proximal cues were absent. Our results provide preliminary evidence that TBI impacts both wayfinding and, to some extent, path integration. The findings suggest long-lasting clinical difficulties experienced in TBI patients affect both wayfinding and to some degree path integration ability.

Neurodevelopmental outcomes in children exposed to newer antiseizure medications: A systematic review.

As prenatal exposure to certain older antiseizure medications (ASMs) has been linked with poorer neurodevelopmental outcomes in children, the use of newer ASMs throughout pregnancy has increased. The current review aimed to delineate the impact of in utero exposure to these newer ASMs on child neurodevelopment. A systematic search of MEDLINE, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature Plus, and PsycINFO was conducted, limiting results to articles available in English and published after the year 2000. Studies investigating neurodevelopmental outcomes following in utero exposure to the following ASMs were eligible for inclusion in the review: eslicarbazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, topiramate, and zonisamide. Thirty-five publications were identified, and a narrative synthesis was undertaken. Methodological quality was variable, with distinct patterns of strengths/weaknesses attributable to design. Most studies examined lamotrigine exposure and reported nonsignificant effects on child neurodevelopment. Comparatively fewer high-quality studies were available for levetiracetam, limiting conclusions regarding findings to date. Data for topiramate, gabapentin, and oxcarbazepine were so limited that firm conclusions could not be drawn. Concerningly, no studies investigated eslicarbazepine, lacosamide, perampanel, or zonisamide. Exposure to certain newer ASMs, such as lamotrigine and levetiracetam, does not thus far appear to impact certain aspects of neurodevelopment, but further delineation across the different neurodevelopmental domains and dosage levels is required. A lack of data cannot be inferred to represent safety of newer ASMs, which are yet to be investigated.

Parental Support, Parent-Adolescent Conflict, and Substance Use of Native Hawaiian and Other Pacific Islander Youth: Ethnic Differences in Stress-Buffering and Vulnerability Effects.

This research study examined the overall and ethnic-specific effects of parental emotional and instrumental support, parent-adolescent interpersonal conflict, and negative life events (i.e., major life stressors, such as parental job loss or school suspension) on the substance use of Caucasian, Asian-American, Filipino, and Native Hawaiian and other Pacific Islander (NHOPI) youth in Hawai'i. Adolescents (N = 3,561) from 10 public middle/intermediate schools completed paper/pencil surveys, and multiple regression and structural equation models were developed to examine overall and ethnic-specific effects. Parental support was found to buffer against the influence of negative life events on substance use in the overall sample; however, this effect was not observed for either Caucasian or NHOPI youth in ethnic-specific analyses. The impact of parent-adolescent conflict and negative life events on substance use was more pronounced for both Filipino and NHOPI youth. While the study may have had some limitations related to regional specificity and measurement, the findings nonetheless point to the differential effects of risk and protective factors for NHOPI youth, compared with other youth ethnic groups in Hawai'i. Implications of these findings for culturally specific, family-focused prevention research and practice for NHOPI youth are discussed.

Hippocampal and prefrontal processing of network topology to simulate the future.

Topological networks lie at the heart of our cities and social milieu. However, it remains unclear how and when the brain processes topological structures to guide future behaviour during everyday life. Using fMRI in humans and a simulation of London (UK), here we show that, specifically when new streets are entered during navigation of the city, right posterior hippocampal activity indexes the change in the number of local topological connections available for future travel and right anterior hippocampal activity reflects global properties of the street entered. When forced detours require re-planning of the route to the goal, bilateral inferior lateral prefrontal activity scales with the planning demands of a breadth-first search of future paths. These results help shape models of how hippocampal and prefrontal regions support navigation, planning and future simulation.

The effects of perceived racism on psychological distress mediated by venting and disengagement coping in Native Hawaiians.

BACKGROUND: Studies have linked perceived racism to psychological distress via certain coping strategies in several different racial and ethnic groups, but few of these studies included indigenous populations. Elucidating modifiable factors for intervention to reduce the adverse effects of racism on psychological well-being is another avenue to addressing health inequities. METHODS: We examined the potential mediating effects of 14 distinct coping strategies on the relationship between perceived racism and psychological distress in a community-based sample of 145 Native Hawaiians using structural equation modeling. RESULTS: Perceived racism had a significant indirect effect on psychological distress, mediated through venting and behavioral disengagement coping strategies, with control for age, gender, educational level, and marital status. DISCUSSION: The findings suggest that certain coping strategies may exacerbate the deleterious effects of racism on a person's psychological well-being. CONCLUSION: Our study adds Native Hawaiians to the list of U.S. racial and ethnic minorities whose psychological well-being is adversely affected by racism.

Longitudinal study of e-cigarette use and onset of cigarette smoking among high school students in Hawaii.

OBJECTIVE: Use of electronic cigarettes (e-cigarettes) is prevalent among adolescents, but there is little knowledge about the consequences of their use. We examined, longitudinally, how e-cigarette use among adolescents is related to subsequent smoking behaviour. METHODS: Longitudinal school-based survey with a baseline sample of 2338 students (9th and 10th graders, mean age 14.7 years) in Hawaii surveyed in 2013 (time 1, T1) and followed up 1 year later (time 2, T2). We assessed e-cigarette use, tobacco cigarette use, and psychosocial covariates (demographics, parental support and monitoring, and sensation seeking and rebelliousness). Regression analyses including the covariates tested whether e-cigarette use was related to the onset of smoking among youth who had never smoked cigarettes, and to change in smoking frequency among youth who had previously smoked cigarettes. RESULTS: Among T1 never-smokers, those who had used e-cigarettes at T1 were more likely to have smoked cigarettes at T2; for a complete-case analysis, adjusted OR=2.87, 95% CI 2.03 to 4.05, p<0.0001. Among ever-smokers at T1, using e-cigarettes was not related to significant change in their frequency of smoking at T2. Uptake of e-cigarette use among T1 never-users of either product was predicted by age, Caucasian or Native Hawaiian (vs Asian-American) ethnicity, lower parental education and parental support, higher rebelliousness, and perception of e-cigarettes as healthier. CONCLUSIONS: Adolescents who use e-cigarettes are more likely to start smoking cigarettes. This result together with other findings suggests that policies restricting adolescents' access to e-cigarettes may have a rationale from a public health standpoint.

Emotional self-control and dysregulation: A dual-process analysis of pathways to externalizing/internalizing symptomatology and positive well-being in younger adolescents.

OBJECTIVES: There is little knowledge about how emotional regulation contributes to vulnerability versus resilience to substance use disorder. With younger adolescents, we studied the pathways through which emotion regulation attributes are related to predisposing factors for disorder. METHODS: A sample of 3561 adolescents (M age 12.5 years) was surveyed. Measures for emotional self-control (regulation of sadness and anger), emotional dysregulation (angerability, affective lability, and rumination about sadness or anger), and behavioral self-control (planfulness and problem solving) were obtained. A structural model was analyzed with regulation attributes related to six intermediate variables that are established risk or protective factors for adolescent substance use (e.g., academic involvement, stressful life events). Criterion variables were externalizing and internalizing symptomatology and positive well-being. RESULTS: Indirect pathways were found from emotional regulation to symptomatology through academic competence, stressful events, and deviance-prone attitudes and cognitions. Direct effects were also found: from emotional dysregulation to externalizing and internalizing symptomatology; emotional self-control to well-being; and behavioral self-control (inverse) to externalizing symptomatology. Emotional self-control and emotional dysregulation had independent effects and different types of pathways. CONCLUSIONS: Adolescents scoring high on emotional dysregulation are at risk for substance dependence because of more externalizing and internalizing symptomatology. Independently, youth with better behavioral and emotional self-control are at lower risk. This occurs partly through relations of regulation constructs to environmental variables that affect levels of symptomatology (e.g., stressful events, poor academic performance). Effects of emotion regulation were found at an early age, before the typical onset of substance disorder.

Technological Analysis of the World's Earliest Shamanic Costume: A Multi-Scalar, Experimental Study of a Red Deer Headdress from the Early Holocene Site of Star Carr, North Yorkshire, UK.

Shamanic belief systems represent the first form of religious practice visible within the global archaeological record. Here we report on the earliest known evidence of shamanic costume: modified red deer crania headdresses from the Early Holocene site of Star Carr (c. 11 kya). More than 90% of the examples from prehistoric Europe come from this one site, establishing it as a place of outstanding shamanistic/cosmological significance. Our work, involving a programme of experimental replication, analysis of macroscopic traces, organic residue analysis and 3D image acquisition, metrology and visualisation, represents the first attempt to understand the manufacturing processes used to create these artefacts. The results produced were unexpected--rather than being carefully crafted objects, elements of their production can only be described as expedient.

Impact of brief self-affirmation manipulations on university students' reactions to risk information about binge drinking.

OBJECTIVES: Binge drinking is associated with an array of negative health consequences and is particularly prevalent in university students. Health-risk messages about alcohol may fail to change such behaviour because they are dismissed or derogated. The present study sought to compare the effect of three brief self-affirmation manipulations on message processing, message acceptance, and subsequent alcohol-related behaviour in university students. DESIGN: Participants (N = 307) were randomly allocated to condition (kindness questionnaire, values essay, attributes questionnaire, control questionnaire) before reading a health-risk message about binge drinking. METHODS: After reading the message, participants completed measures of message processing (message reactance, message evaluation, counter-arguing) and message acceptance (perceived risk, intention, plans) as well as a manipulation check. Alcohol consumption was assessed 1 week later. RESULTS: Participants in all three self-affirmation conditions scored significantly higher than participants in the control condition on the manipulation check measure. All other self-affirmation effects were non-significant. CONCLUSIONS: While the three self-affirmation manipulations were found to be self-affirming, they failed to impact on measures of message processing, message acceptance, or subsequent behaviour. The findings concur with previous research that questions the use of self-affirmation to reduce alcohol consumption in university students. Current self-affirmation manipulations may not be strong enough to overcome defensive processing of health-risk messages about alcohol in students and/or prime social goals that are related to the domain under threat (i.e., alcohol consumption), thereby nullifying any positive self-affirmation effects. Statement of contribution What is already known on this subject? Health-risk messages to reduce alcohol consumption (e.g., binge drinking) in university students may fail due to defensive processing (e.g., message derogation). Self-affirmation has been proposed as a technique to bolster one's self-integrity and promote open-minded processing of health-risk messages. Most previous studies that have presented health-risk messages about alcohol to university students have used a values essay to self-affirm participants with equivocal results. What does this study add? There are few studies that have directly compared different self-affirmation manipulations. All three self-affirmation manipulations were found by participants to be self-affirming, consistent with the idea that there are multiple ways individuals can self-affirm, but had no significant effects on message processing, message acceptance, or behaviour. Self-affirmation manipulations may lead individuals to reflect on interpersonal values that are related to alcohol consumption in students and may therefore prime the very cognitions and behaviour that they seek to reduce.

E-cigarette use and willingness to smoke: a sample of adolescent non-smokers.

OBJECTIVE: There is little evidence on the consequences of using electronic cigarettes (e-cigarette) in adolescence. With a multiethnic sample of non-smokers, we assessed the relation between e-cigarette use and social-cognitive factors that predict smoking of combustible cigarettes. METHODS: School-based cross-sectional survey of 2309 high school students (mean age 14.7 years). Participants reported on e-cigarette use and cigarette use; on smoking-related cognitions (smoking expectancies, prototypes of smokers) and peer smoker affiliations; and on willingness to smoke cigarettes. Regression analyses conducted for non-cigarette smokers tested the association between e-cigarette use and willingness to smoke cigarettes, controlling for demographics, parenting, academic and social competence, and personality variables. Structural equation modelling (SEM) analysis tested whether the relation between e-cigarette use and willingness to smoke was mediated through any of the three smoking-related variables. RESULTS: Non-smokers who had used e-cigarettes (18% of the total sample) showed more willingness to smoke cigarettes compared with those who had never used any tobacco product; the adjusted OR was 2.35 (95% CI 1.73 to 3.19). SEM showed that the relation between e-cigarette use and willingness to smoke was partly mediated through more positive expectancies about smoking, but there was also a direct path from e-cigarette use to willingness. CONCLUSIONS: Among adolescent non-smokers, e-cigarette use is associated with willingness to smoke, a predictor of future cigarette smoking. The results suggest that use of e-cigarettes by adolescents is not without attitudinal risk for cigarette smoking. These findings have implications for formulation of policy about access to e-cigarettes by adolescents.

Insights in public health: Electronic cigarettes: marketing to Hawai'i's adolescents.

Electronic cigarettes (e-cigarettes) are an emerging phenomenon that is becoming increasingly popular among adolescents. Current e-cigarette use among adolescents has more than doubled in the past few years nationally and more than tripled in Hawai'i, despite the fact that safety in terms of health and injury from use is widely unknown. The use of e-cigarettes among adolescents is of particular concern because they may act as a gateway to smoking conventional tobacco cigarettes, substitute for cigarettes where smoking would normally not be allowed, and weaken the effect of clean air policies, and displace effective smoking cessation treatments. Additionally, the use of e-cigarettes may lead to the use of conventional cigarettes. There is special concern that e-cigarette companies are recruiting adolescents who would not have otherwise tried smoking by using tactics such as offering e-cigarettes in attractive flavorings and using the same successful strategies to market their product as tobacco companies have used for conventional cigarettes in past decades. It has been shown that exposure to cigarette marketing is related to initiation and progression in adolescent smoking. Yet, there remains no regulation on the marketing of e-cigarettes to adolescents. It can be extrapolated that expanded regulation that includes limits on the marketing of e-cigarettes may help decrease use among adolescents and prevent the possible increase of smoking rates.

Risk factors for exclusive e-cigarette use and dual e-cigarette use and tobacco use in adolescents.

OBJECTIVE: To describe electronic cigarette (e-cigarette) use and cigarette use among adolescents and determine whether established risk factors for smoking discriminate user categories. METHODS: School-based survey of 1941 high school students (mean age 14.6 years) in Hawaii; data collected in 2013. The survey assessed e-cigarette use and cigarette use, alcohol and marijuana use, and psychosocial risk and protective variables (eg, parental support, academic involvement, smoking expectancies, peer smoking, sensation seeking). Analysis of variance and multinomial regression examined variation in risk and protective variables across the following categories of ever-use: e-cigarette only, cigarette only, dual use (use of both products), and nonuser (never used either product). RESULTS: Prevalence for the categories was 17% (e-cigarettes only), 12% (dual use), 3% (cigarettes only), and 68% (nonusers). Dual users and cigarette-only users were highest on risk status (elevated on risk factors and lower on protective factors) compared with other groups. E-cigarette only users were higher on risk status than nonusers but lower than dual users. E-cigarette only users and dual users more often perceived e-cigarettes as healthier than cigarettes compared with nonusers. CONCLUSIONS: This study reports a US adolescent sample with one of the largest prevalence rates of e-cigarette only use in the existing literature. Dual use also had a substantial prevalence. The fact that e-cigarette only users were intermediate in risk status between nonusers and dual users raises the possibility that e-cigarettes are recruiting medium-risk adolescents, who otherwise would be less susceptible to tobacco product use.

The hippocampus and entorhinal cortex encode the path and Euclidean distances to goals during navigation.

BACKGROUND: Despite decades of research on spatial memory, we know surprisingly little about how the brain guides navigation to goals. While some models argue that vectors are represented for navigational guidance, other models postulate that the future path is computed. Although the hippocampal formation has been implicated in processing spatial goal information, it remains unclear whether this region processes path- or vector-related information. RESULTS: We report neuroimaging data collected from subjects navigating London's Soho district; these data reveal that both the path distance and the Euclidean distance to the goal are encoded by the medial temporal lobe during navigation. While activity in the posterior hippocampus was sensitive to the distance along the path, activity in the entorhinal cortex was correlated with the Euclidean distance component of a vector to the goal. During travel periods, posterior hippocampal activity increased as the path to the goal became longer, but at decision points, activity in this region increased as the path to the goal became closer and more direct. Importantly, sensitivity to the distance was abolished in these brain areas when travel was guided by external cues. CONCLUSIONS: The results indicate that the hippocampal formation contains representations of both the Euclidean distance and the path distance to goals during navigation. These findings argue that the hippocampal formation houses a flexible guidance system that changes how it represents distance to the goal depending on the fluctuating demands of navigation.

Allocentric directional processing in the rodent and human retrosplenial cortex.

Head direction (HD) cells in the rodent brain have been investigated for a number of years, providing us with a detailed understanding of how the rodent brain codes for allocentric direction. Allocentric direction refers to the orientation of the external environment, independent of one's current (egocentric) orientation. The presence of neural activity related to allocentric directional coding in humans has also been noted but only recently directly tested. Given the current status of both fields, it seems beneficial to draw parallels between this rodent and human research. We therefore discuss how findings from the human retrosplenial cortex (RSC), including its "translational function" (converting egocentric to allocentric information) and ability to code for permanent objects, compare to findings from the rodent RSC. We conclude by suggesting critical future experiments that derive from a cross-species approach to understanding the function of the human RSC.

Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production.

Economic feasibility of biosynthetic fuel and chemical production hinges upon harnessing metabolism to achieve high titre and yield. Here we report a thorough genotypic and phenotypic optimization of an oleaginous organism to create a strain with significant lipogenesis capability. Specifically, we rewire Yarrowia lipolytica's native metabolism for superior de novo lipogenesis by coupling combinatorial multiplexing of lipogenesis targets with phenotypic induction. We further complete direct conversion of lipid content into biodiesel. Tri-level metabolic control results in saturated cells containing upwards of 90% lipid content and titres exceeding 25 g l(-1) lipids, which represents a 60-fold improvement over parental strain and conditions. Through this rewiring effort, we advance fundamental understanding of lipogenesis, demonstrate non-canonical environmental and intracellular stimuli and uncouple lipogenesis from nitrogen starvation. The high titres and carbon-source independent nature of this lipogenesis in Y. lipolytica highlight the potential of this organism as a platform for efficient oleochemical production.