Associations between Cerebrovascular Function and the Expression of Genes Related to Endothelial Function in Hormonal Migraine.

There is evidence to suggest that hormonal migraine is associated with altered cerebrovascular function. We aimed to investigate whether the expression of genes related to endothelial function in venous blood (1) might influence cerebrovascular function, (2) differs between hormonal migraineur and non-migraineur women, and (3) changes following resveratrol supplementation. This study utilised data obtained from 87 women (59 hormonal migraineurs and 28 controls) where RNA from venous blood was used to quantify gene expression and transcranial Doppler ultrasound was used to evaluate cerebrovascular function. Spearman's correlation analyses were performed between gene expression, cerebrovascular function, and migraine-related disability. We compared the expression of genes associated with endothelial function between migraineurs and non-migraineurs, and between resveratrol and placebo. The expression of several genes related to endothelial function was associated with alterations in cerebrovascular function. Notably, the expression of CALCA was associated with increased neurovascular coupling capacity (p = 0.013), and both CALCA (p = 0.035) and VEGF (p = 0.014) expression were associated with increased cerebral blood flow velocity in the overall study population. Additionally, VCAM1 expression correlated with decreased pulsatility index (a measure of cerebral arterial stiffness) (p = 0.009) and headache impact test-6 scores (p = 0.007) in the migraineurs. No significant differences in gene expression were observed between migraineurs and controls, or between placebo and resveratrol treatments in migraineurs. Thus, altering the expression of genes related to endothelial function may improve cerebrovascular function and decrease migraine-related disability.

The benefits of regular aerobic exercise training on cerebrovascular function and cognition in older adults.

We compared the differences in cerebrovascular and cognitive function between 13 aerobic exercise trained, older adults and 13 age-, height- and sex-matched sedentary, untrained controls. We determined whether other measures accounted for differences in cerebrovascular and cognitive function between these groups and examined the associations between these functions. Participants undertook anthropometric, mood, cardiovascular, exercise performance, strength, cerebrovascular, and cognitive measurements, and a blood collection. Transcranial Doppler ultrasonography determined cerebrovascular responsiveness (CVR) to hypercapnia and cognitive stimuli. The trained group had a higher CVR to hypercapnia (80.3 ± 7.2 vs 35.1 ± 6.7%, P < 0.001), CVR to cognitive stimuli (30.1 ± 2.9 vs 17.8 ± 1.4%, P = 0.001) and total composite cognitive score (117 ± 2 vs 98 ± 4, P < 0.001) than the controls. These parameters no longer remained statistically different between the groups following adjustments for covariates. There were positive correlations between the total composite cognitive score and CVR to hypercapnia (r = 0.474, P = 0.014) and CVR to cognitive stimuli (r = 0.685, P < 0.001). We observed a relationship between cerebrovascular and cognitive function in older adults and an interaction between regular lifelong aerobic exercise training and cardiometabolic factors that may directly influence these functions.

Geographic and demographic variation in worry about extreme heat and COVID-19 risk in summer 2020.

Extreme heat is a major health hazard that is exacerbated by ongoing human-caused climate change. However, how populations perceive the risks of heat in the context of other hazards like COVID-19, and how perceptions vary geographically, are not well understood. Here we present spatially explicit estimates of worry among the U.S. public about the risks of heat and COVID-19 during the summer of 2020, using nationally representative survey data and a multilevel regression and poststratification (MRP) model. Worry about extreme heat and COVID-19 varies both across states and across demographic groups, in ways that reflect disparities in the impact of each risk. Black or African American and Hispanic or Latino populations, who face greater health impacts from both COVID-19 and extreme heat due to institutional and societal inequalities, also tend to be much more worried about both risks than white, non-Hispanic populations. Worry about heat and COVID-19 were correlated at the individual and population level, and patterns tended to be related to underlying external factors associated with the risk environment. In the face of a changing climate there is an urgent need to address disparities in heat risk and develop responses that ensure the most at-risk populations are protected.

Structural Elucidation of Agrochemicals and Related Derivatives Using Infrared Ion Spectroscopy.

Agrochemicals frequently undergo various chemical and metabolic transformation reactions in the environment that often result in a wide range of derivates that must be comprehensively characterized to understand their toxicity profiles and their persistence and outcome in the environment. In the development phase, this typically involves a major effort in qualitatively identifying the correct chemical isomer(s) of these derivatives from the many isomers that could potentially be formed. Liquid chromatography-mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy are often used in attempts to characterize such environment transformation products. However, challenges in confidently correlating chemical structures to detected compounds in mass spectrometry data and sensitivity/selectivity limitations of NMR frequently lead to bottlenecks in identification. In this study, we use an alternative approach, infrared ion spectroscopy, to demonstrate the identification of hydroxylated derivatives of two plant protection compounds (azoxystrobin and benzovindiflupyr) contained at low levels in tomato and spinach matrices. Infrared ion spectroscopy is an orthogonal tandem mass spectrometry technique that combines the sensitivity and selectivity of mass spectrometry with structural information obtained by infrared spectroscopy. Furthermore, IR spectra can be computationally predicted for candidate molecular structures, enabling the tentative identification of agrochemical derivatives and other unknowns in the environment without using physical reference standards.

Public perceptions of the health risks of extreme heat across US states, counties, and neighborhoods.

Extreme heat is the leading weather-related cause of death in the United States. Many individuals, however, fail to perceive this risk, which will be exacerbated by global warming. Given that awareness of one's physical and social vulnerability is a critical precursor to preparedness for extreme weather events, understanding Americans' perceptions of heat risk and their geographic variability is essential for promoting adaptive behaviors during heat waves. Using a large original survey dataset of 9,217 respondents, we create and validate a model of Americans' perceived risk to their health from extreme heat in all 50 US states, 3,142 counties, and 72,429 populated census tracts. States in warm climates (e.g., Texas, Nevada, and Hawaii) have some of the highest heat-risk perceptions, yet states in cooler climates often face greater health risks from heat. Likewise, places with older populations who have increased vulnerability to health effects of heat tend to have lower risk perceptions, putting them at even greater risk since lack of awareness is a barrier to adaptive responses. Poorer neighborhoods and those with larger minority populations generally have higher risk perceptions than wealthier neighborhoods with more white residents, consistent with vulnerability differences across these populations. Comprehensive models of extreme weather risks, exposure, and effects should take individual perceptions, which motivate behavior, into account. Understanding risk perceptions at fine spatial scales can also support targeting of communication and education initiatives to where heat adaptation efforts are most needed.

Evaluation of Cognitive Performance following Fish-Oil and Curcumin Supplementation in Middle-Aged and Older Adults with Overweight or Obesity.

BACKGROUND: Obesity accelerates age-related cognitive decline, which is partly mediated by vascular dysfunction. OBJECTIVE: The aim was to test the hypothesis that supplementation with fish oil and curcumin can enhance cognitive performance by improving cerebral circulatory function in overweight or obese middle-aged to older adults. METHODS: In a 16-wk double-blind, placebo-controlled intervention trial, adults [50-80 y; BMI (kg/m2): 25-40] were randomly assigned to either fish oil (2000 mg/d DHA + 400 mg/d EPA), curcumin (160 mg/d), or a combination. Effects on cerebrovascular function (primary outcome) and cardiovascular risk factors were reported previously. Effects on cognitive performance and cerebrovascular responsiveness (CVR) to cognitive stimuli are reported herein. One-factor ANOVA with post hoc analyses was conducted between groups in the whole cohort and in males and females separately. Two-factor ANOVA was conducted to assess independent effects of fish oil and curcumin and a potential interaction. Correlations between outcomes (those obtained herein and previously reported) were also examined. RESULTS: Compared with placebo, fish oil improved CVR to a processing speed test (4.4% ± 1.9% vs. -2.2% ± 2.1%; P = 0.023) and processing speed in males only (Z-score: 0.6 ± 0.2 vs. 0.1 ± 0.2; P = 0.043). Changes in processing speed correlated inversely with changes in blood pressure (R = -0.243, P = 0.006) and C-reactive protein (R = -0.183, P = 0.046). Curcumin improved CVR in a working memory test (3.6% ± 1.2% vs. -0.2% ± 0.2%, P = 0.026) and, in males only, performance of a verbal memory test compared with placebo (Z-score: 0.2 ± 0.1 vs. -0.5 ± 0.2, P = 0.039). Combining fish oil with curcumin did not produce additional benefits. CONCLUSIONS: Improvements in processing speed following fish-oil supplementation in middle-aged to older males might be mediated by improvements in circulatory function. Mechanisms underlying the cognitive benefit seen with curcumin are unknown. As cognitive benefits were found in males only, further evaluation of sex differences in responsiveness to supplementation is warranted. This trial was registered at the Australian and New Zealand Clinical Trial Register at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370788 as ACTRN12616000732482p.

Effects of fish oil and curcumin supplementation on cerebrovascular function in older adults: A randomized controlled trial.

BACKGROUND AND AIMS: Chronic conditions such as obesity, which contribute to endothelial dysfunction in older adults, can cause impairments in cerebrovascular perfusion, which is associated with accelerated cognitive decline. Supplementing the diet with bioactive nutrients that can enhance endothelial function, such as fish oil or curcumin, may help to counteract cerebrovascular dysfunction. METHODS AND RESULTS: A 16-week double-blind, randomized placebo-controlled trial was undertaken in 152 older sedentary overweight/obese adults (50-80 years, body mass index: 25-40 kg/m2) to investigate effects of fish oil (2000 mg docosahexaenoic acid + 400 mg eicosapentaenoic acid/day), curcumin (160 mg/day) or a combination of both on cerebrovascular function (measured by Transcranial Doppler ultrasound), systemic vascular function (blood pressure, heart rate and arterial compliance) and cardiometabolic (fasting glucose and blood lipids) and inflammatory (C-reactive protein) biomarkers. The primary outcome, cerebrovascular responsiveness to hypercapnia, was not affected by the interventions. However, cerebral artery stiffness was significantly reduced in males following fish oil supplementation (P = 0.007). Furthermore, fish oil reduced heart rate (P = 0.038) and serum triglycerides (P = 0.006) and increased HDL cholesterol (P = 0.002). Curcumin did not significantly affect these outcomes either alone or in combination with fish oil. CONCLUSION: Regular supplementation with fish oil but not curcumin improved biomarkers of cardiovascular and cerebrovascular function. The combined supplementation did not result in additional benefits. Further studies are warranted to identify an efficacious curcumin dose and to characterize (in terms of sex, BMI, cardiovascular and metabolic risk factors) populations whose cerebrovascular and cognitive functions might benefit from either intervention. CLINICAL TRIAL REGISTRATION: ACTRN12616000732482p.

Spatial heterogeneity of climate change as an experiential basis for skepticism.

We postulate that skepticism about climate change is partially caused by the spatial heterogeneity of climate change, which exposes experiential learners to climate heuristics that differ from the global average. This hypothesis is tested by formalizing an index that measures local changes in climate using station data and comparing this index with survey-based model estimates of county-level opinion about whether global warming is happening. Results indicate that more stations exhibit cooling and warming than predicted by random chance and that spatial variations in these changes can account for spatial variations in the percentage of the population that believes that "global warming is happening." This effect is diminished in areas that have experienced more record low temperatures than record highs since 2005. Together, these results suggest that skepticism about climate change is driven partially by personal experiences; an accurate heuristic for local changes in climate identifies obstacles to communicating ongoing changes in climate to the public and how these communications might be improved.

Is perfection ever attainable? Strong coupling effects in the Perfect Echo.

The Perfect Echo sequence, originally proposed in the late 1980s, has recently been popularised with many applications in the field of small-molecule proton NMR spectroscopy. The Perfect Echo refocuses all homonuclear J-couplings for AX spin systems and refocuses magnetization in-phase for more complex weakly coupled spin systems, albeit with some intensity reduction. In contrast to suggestions in previous publications, spectra acquired in our laboratory showed that the Perfect Echo caused intensity distortions in strongly coupled systems where the chemical shift difference between the coupled spins was not large compared to the J-coupling. This paper reports experimental observations and theoretical analysis of strongly coupled spins to confirm the distortions are real and that they originate principally from transfer of magnetization caused by the final inversion pulse of the Perfect Echo. The intensity changes are not large, but because of them, identifications of coupling partners based on resonance intensities ("roofing") can no longer be relied on when the Perfect Echo is used. However, theory and experiment confirm that adding an orthogonal excitation pulse at the end of the Perfect Echo greatly reduces the distortions.

Flavonoid genistein protects bone marrow sinusoidal blood vessels from damage by methotrexate therapy in rats.

Cancer chemotherapy can cause significant damage to the bone marrow (BM) microvascular (sinusoidal) system. Investigations must now address whether and how BM sinusoidal endothelial cells (SECs) can be protected during chemotherapy. Herein we examined the potential protective effects of genistein, a soy-derived flavonoid, against BM sinusoidal damage caused by treatment with methotrexate (MTX). The groups of young adult rats were gavaged daily with genistein (20 mg/kg) or placebo. After 1 week, rats also received daily injections of MTX (0.75 mg/kg) or saline for 5 days and were killed after a further 4 days. Histological analyses showed that BM sinusoids were markedly dilated ( p < 0.001) in the MTX-alone group but were unaffected or less dilated in the genistein+MTX group. In control rats, genistein significantly enhanced expression of vascular endothelial growth factor (VEGF; p < 0.01), particularly in osteoblasts, and angiogenesis marker CD31 ( p < 0.001) in bone. In MTX-treated rats, genistein suppressed MTX-induced apoptosis of BM SECs ( p < 0.001 vs MTX alone group) and tended to increase expression of CD31 and VEGF ( p < 0.05). Our in vitro studies showed that genistein in certain concentrations protected cultured SECs from MTX cytotoxic effects. Genistein enhanced tube formation of cultured SECs, which is associated with its ability to induce expression of endothelial nitric oxide synthase and production of nitric oxide. These data suggest that genistein can protect BM sinusoids during MTX therapy, which is associated, at least partially, with its indirect effect of promoting VEGF expression in osteoblasts and its direct effect of enhancing nitric oxide production in SECs.

Repetitive hypoglycemia reduces activation of glucose-responsive neurons in C1 and C3 medullary brain regions to subsequent hypoglycemia.

The impaired ability of the autonomic nervous system to respond to hypoglycemia is termed "hypoglycemia-associated autonomic failure" (HAAF). This life-threatening phenomenon results from at least two recent episodes of hypoglycemia, but the pathology underpinning HAAF remains largely unknown. Although naloxone appears to improve hypoglycemia counterregulation under controlled conditions, hypoglycemia prevention remains the current mainstay therapy for HAAF. Epinephrine-synthesizing neurons in the rostroventrolateral (C1) and dorsomedial (C3) medulla project to the subset of sympathetic preganglionic neurons that regulate peripheral epinephrine release. Here we determined whether or not C1 and C3 neuronal activation is impaired in HAAF and whether or not 1 wk of hypoglycemia prevention or treatment with naloxone could restore C1 and C3 neuronal activation and improve HAAF. Twenty male Sprague-Dawley rats (250-300 g) were used. Plasma epinephrine levels were significantly increased after a single episode of hypoglycemia (n = 4; 5,438 ± 783 pg/ml vs. control 193 ± 27 pg/ml, P < 0.05). Repeated hypoglycemia significantly reduced the plasma epinephrine response to subsequent hypoglycemia (n = 4; 2,179 ± 220 pg/ml vs. 5,438 ± 783 pg/ml, P < 0.05). Activation of medullary C1 (n = 4; 50 ± 5% vs. control 3 ± 1%, P < 0.05) and C3 (n = 4; 45 ± 5% vs. control 4 ± 1%, P < 0.05) neurons was significantly increased after a single episode of hypoglycemia. Activation of C1 (n = 4; 12 ± 3%, P < 0.05) and C3 (n = 4; 19 ± 5%, P < 0.05) neurons was significantly reduced in the HAAF groups. Hypoglycemia prevention or treatment with naloxone did not restore the plasma epinephrine response or C1 and C3 neuronal activation. Thus repeated hypoglycemia reduced the activation of C1 and C3 neurons mediating adrenal medullary responses to subsequent bouts of hypoglycemia.

Suppression of Protonated Organic Solvents in NMR Spectroscopy Using a Perfect Echo Low-Pass Filtration Pulse Sequence.

Proton NMR spectra are usually acquired using deuterated solvents, but in many cases it is necessary to obtain spectra on samples in protonated solvents. In these cases, the intense resonances of the protonated solvents need to be suppressed to maximize sensitivity and spectral quality. A wide range of highly effective solvent suppression methods have been developed, but additional measures are needed to suppress the 13C satellites of the solvent. Because the satellites represent 1.1% of the original solvent signal, they remain problematic if unsuppressed. The recently proposed DISPEL pulse sequences suppress 13C satellites extremely effectively, and this Technical Note demonstrates that combining DISPEL and presaturation results in exceptionally effective solvent suppression. An important element in the effectiveness is volume selection, which is inherent within the DISPEL sequence. Spectra acquired in protonated dimethlysulfoxide and tetrahydrofuran show that optimum results are obtained by modifying the phase cycle, cycling the pulse-field gradients, and using broadband 13C inversion pulses to reduce the effects of radiofrequency offset and inhomogeneity.

Comparison of two low-fat diets, differing in protein and carbohydrate, on psychological wellbeing in adults with obesity and type 2 diabetes: a randomised clinical trial.

BACKGROUND: Although higher-protein diets (HP) can assist with weight loss and glycemic control, their effect on psychological wellbeing has not been established. The objective of this study was to compare the effects of a HP and a higher-carbohydrate diet (HC), combined with regular exercise, on psychological wellbeing both during weight loss (WL) and weight maintenance phases (WM). METHODS: In a parallel RCT, 61 adults with T2D (mean ± SD: BMI 34.3 ± 5.1 kg/m2, aged 55 ± 8 years) consumed a HP diet (29% protein, 34% carbohydrate, 31% fat) or an isocaloric HC diet (21%:48%:24%), with moderate intensity exercise, for 12 weeks of WL and 12 weeks of WM. Secondary data evaluating psychological wellbeing was assessed using: Problems Areas in Diabetes (PAID); Diabetes-39 Quality of Life (D-39); Short Form Health Survey (SF-36); Perceived Stress Scale-10 (PSS-10) and the Leeds Sleep Evaluation Questionnaire (LSEQ) at Weeks 0, 12 and 24 and evaluated with mixed models analysis. RESULTS: Independent of diet, improvements for PAID; D-39 diabetes control; D-39 severity of diabetes; SF-36 physical functioning and SF-36 general health were found following WL (d = 0.30 to 0.69, P ≤ 0.04 for all) which remained after 12 weeks of WM. SF-36 vitality improved more in the HP group (group x time interaction P = 0.03). Associations were seen between HbA1c and D-39 severity of diabetes rating (r = 0.30, P = 0.01) and SF-36 mental health (r = - 0.32, P = 0.003) and between weight loss and PAID (r = 0.30, P = 0.01). CONCLUSION: Several improvements in diabetes-related and general psychological wellbeing were seen similarly for both diets following weight loss and a reduction in HbA1c with most of these improvements remaining when weight loss was sustained for 12 weeks. A HP diet may provide additional increases in vitality. TRIAL REGISTRATION: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12613000008729 ) on 4 January 2013.

The Effect of Geographic Proximity to Unconventional Oil and Gas Development on Public Support for Hydraulic Fracturing.

With the rapid growth of unconventional oil and natural gas development transforming the U.S. economic and physical landscape, social scientists have increasingly explored the spatial dynamics of public support for this issue-that is, whether people closer to unconventional oil and gas development are more supportive or more opposed. While theoretical frameworks like construal-level theory and the "Not in My Backyard" (or NIMBY) moniker provide insight into these spatial dynamics, case studies in specific locations experiencing energy development reveal substantial variation in community responses. Larger-scale studies exploring the link between proximity and support have been hampered by data quality and availability. We draw on a unique data set that includes geo-coded data from national surveys (nine waves; n = 19,098) and high-resolution well location data to explore the relationship between proximity and both familiarity with and support for hydraulic fracturing. We use two different measures of proximity-respondent distance to the nearest well and the density of wells within a certain radius of the respondent's location. We find that both types of proximity to new development are linked to more familiarity with hydraulic fracturing, even after controlling for various individual and contextual factors, but only distance-based proximity is linked to more support for the practice. When significant, these relationships are similar to or exceed the effects of race, income, gender, and age. We discuss the implications of these findings for effective risk communication as well as the importance of incorporating spatial analysis into public opinion research on perceptions of energy development.

Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Protects Against Adriamycin and Cyclophosphamide Chemotherapy-Induced Bone Marrow Damage in Female Rats.

Although bone marrow and bone toxicities have been reported in breast cancer survivors, preventative strategies are yet to be developed. Clinical studies suggest consumption of long chain omega-3 polyunsaturated fatty acids (LCn3PUFA) can attenuate age-related bone loss, and recent animal studies also revealed benefits of LCn3PUFA in alleviating bone marrow and bone toxicities associated with methotrexate chemotherapy. Using a female rat model for one of the most commonly used anthracycline-containing breast cancer chemotherapy regimens (adriamycin + cyclophosphamide) (AC) chemotherapy, this study investigated potential effects of daily LCn3PUFA consumption in preserving bone marrow and bone microenvironment during chemotherapy. AC treatment for four cycles significantly reduced bone marrow cellularity and increased marrow adipocyte contents. It increased trabecular bone separation but no obvious changes in bone volume or bone cell densities. LCn3PUFA supplementation (375 mg/100 g/day) attenuated AC-induced bone marrow cell depletion and marrow adiposity. It also partially attenuated AC-induced increases in trabecular bone separation and the cell sizes and nuclear numbers of osteoclasts formed ex vivo from bone marrow cells isolated from AC-treated rats. This study suggests that LCn3PUFA supplementation may have beneficial effects in preventing bone marrow damage and partially protecting the bone during AC cancer chemotherapy.

Combination breast cancer chemotherapy with doxorubicin and cyclophosphamide damages bone and bone marrow in a female rat model.

PURPOSE: Anthracyclines (including doxorubicin) are still the backbone of commonly used breast cancer chemotherapy regimens. Despite increasing use of doxorubicin and cyclophosphamide (AC) combinations for treating breast cancer, their potential to cause adverse skeletal effects remains unclear. METHODS: This study examined the effects of treatments with the AC regimen on bone and bone marrow in adult female rats. RESULTS: AC treatment for four cycles (weekly intravenous injection of 2 mg/kg doxorubicin and 20 mg/kg cyclophosphamide) resulted in a reduced volume of trabecular bone at the metaphysis, which was associated with reduced serum levels of 25-hydroxy vitamin D3 and alkaline phosphatase. Reductions in densities of osteocytes and bone lining cells were also observed. In addition, bone marrow was severely damaged, including a severe reduction in bone marrow cellularity and an increase in marrow adipocyte content. Accompanying these changes, there were increases in mRNA expression of adipogenesis regulatory genes (PPARγ and FABP4) and an inflammatory cytokine (TNFα) in metaphysis bone and bone marrow. CONCLUSIONS: This study indicates that AC chemotherapy may induce some bone loss, due to reduced bone formation, and bone marrow damage, due to increased marrow adiposity. Preventive strategies for preserving the bone and bone marrow microenvironment during anthracycline chemotherapy warrant further investigation.

Cerebrovascular and cognitive benefits of high-oleic peanut consumption in healthy overweight middle-aged adults.

OBJECTIVE: Peanuts contain bioactive nutrients beneficial for vascular function. This study investigated whether consumption of unsalted peanuts (with skins) would enhance cerebrovascular perfusion and cognitive performance. METHOD: In a randomized crossover trial, 61 volunteers (29 males/32 females, 65 ± 7 years, BMI 31 ± 4 kg/m2) consumed their habitual diet ± high-oleic peanuts (56-84 g/day), each for 12 weeks. Nutrient intakes, vascular and cognitive function were assessed at baseline and at the end of each 12-week phase. Differences between the ends of each phase were compared by general linear repeated measures ANOVA controlling for baseline. Pearson's correlation analyses determined relationships between differences in cerebrovascular reactivity (CVR) and cognitive function. RESULTS: Intakes of bioactive nutrients increased during the peanut phase. CVR was 5% greater in the left middle cerebral artery (MCA) and 7% greater in the right MCA. Small artery elasticity was 10% greater after peanut consumption; large artery elasticity and blood pressure did not differ between phases. Measures of short-term memory, verbal fluency, and processing speed were also higher following the peanut phase; other cognitive measures did not change. Differences in CVR in the left MCA correlated with differences in delayed memory and recognition. DISCUSSION: Regular peanut consumption improved cerebrovascular and cognitive function; increased intakes of bioactive nutrients may have mediated these improvements. This clinical trial was registered with the Australian Clinical Trials Registry (ACTRN 12612000192886).

A qualitative exploration of anesthesia trainees' experiences during transition to a children's hospital.

BACKGROUND: The stresses of starting a new job can make anyone feel tired and inefficient. In health care, this may impair the ability to learn at a time when there is most to learn, and increase the risk of error in a context where errors may lead to patient harm. AIM: The aim of this study was to understand issues which influence anesthesia trainees' transition to a pediatric setting. METHODS: This qualitative study utilized in-depth semi-structured interviews to gather data from 31 anesthesia trainees who had commenced work at a tertiary children's hospital between 4 and 6 weeks previously. Data were examined using thematic analysis. RESULTS: Two key themes were identified: feeling ineffective, which appeared to have both a cognitive component (feeling disoriented) and an emotional component (feeling useless), and feeling anxious or afraid. Trainees found the pediatric environment highly unfamiliar, which made them feel disoriented, inefficient, and at times incompetent. Many experienced difficulty identifying a useful role in a highly specialized area of practice, leading to loss of identity as an expert clinician. Many described an ever-present fear of making an anesthetic error or being unable to manage a rapidly evolving clinical situation. Some trainees developed a negative mindset, which was reinforced by subsequent perceived failures. Overall, these experiences impeded trainees' ability to concentrate and learn. CONCLUSIONS: The impact of disorientation and anxiety on anesthesia trainees as they adapt to a highly specialized clinical environment such as a children's hospital should not be underestimated. Study findings illustrate the importance of helping new trainees to feel less afraid, more useful, and more realistic in assessing their own performance during the transition period.

Selective diffusion spectroscopy using excitation sculpting.

Diffusion spectroscopy NMR provides a sensitive and fast way of determining diffusion coefficient. The coefficient is measured by fitting attenuation of resonance intensities to the Stejskal-Tanner equation, but, because it is an exponential equation, this fitting is quite sensitive to experimental artefacts. Intense resonances in NMR spectra, such as solvent signals, are a particular problem because small fractions of intensity of the intense resonances can significantly change the intensities of minor resonances and distort their calculated diffusion coefficients. This problem can be overcome by selective excitation of only the minor resonances, and the method of choice for this is excitation sculpting. This paper shows that the conventional excitation sculpting pulse sequence can be used directly for DOSY spectroscopy with minimal modification. The sequence suppresses intense resonances very effectively, allowing the reproducible measurement of diffusion coefficients of minor solutes in a solvent containing five separate resonances. It is sensitive and robust to convection. Excitation sculpting will allow the application of diffusion spectroscopy to samples which include multiple intense resonances, such as polymeric solvents. Copyright © 2015 John Wiley & Sons, Ltd.

Assessment of cerebral blood flow in adult patients with aortic coarctation.

BACKGROUND: Survival into adult life in patients with aortic coarctation is typical following surgical and catheter-based techniques to relieve obstruction. Late sequelae are recognised, including stroke, hypertension, and intracerebral aneurysm formation, with the underlying mechanisms being unclear. We hypothesised that patients with a history of aortic coarctation may have abnormalities of cerebral blood flow compared with controls. METHODS: Patients with a history of aortic coarctation underwent assessment of cerebral vascular function. Vascular responsiveness of intracranial vessels to hypercapnia and degree of cerebral artery stiffness using Doppler-derived pulsatility indices were used. Response to photic stimuli was used to assess neurovascular coupling, which reflects endothelial function in response to neuronal activation. Patient results were compared with age- and sex-matched controls. RESULTS: A total of 13 adult patients (males=10; 77%) along with 13 controls underwent evaluation. The mean age was 36.1±3.7 years in the patient group. Patients with a background of aortic coarctation were noted to have increased pulse pressure on blood pressure assessment at baseline with increased intracranial artery stiffness compared with controls. Patients with a history of aortic coarctation had less reactive cerebral vasculature to hypercapnic stimuli and impaired neurovascular coupling compared with controls. RESULTS: Adult patients with aortic coarctation had increased intracranial artery stiffness compared with controls, in addition to cerebral vasculature showing less responsiveness to hypercapnic and photic stimuli. Further studies are required to assess the aetiology and consequences of these documented abnormalities in cerebral blood flow in terms of stroke risk, cerebral aneurysm formation, and cognitive dysfunction.