The mechanics of cephalic furrow formation in the Drosophila embryo.

Cephalic furrow formation (CFF) is a major morphogenetic movement during gastrulation in Drosophila melanogaster embryos that gives rise to a deep, transitory epithelial invagination. Recent studies have identified the individual cell shape changes that drive the initiation and progression phases of CFF; however, the underlying mechanics are not yet well understood. During the progression phase, the furrow deepens as columnar cells from both the anterior and posterior directions fold inwards rotating by 90°. To analyze the mechanics of this process, we have developed an advanced two-dimensional lateral vertex model that includes multinode representation of cellular membranes and allows us to capture the membrane curvature associated with pressure variation. Our investigations reveal some key potential mechanical features of CFF, as follows. When cells begin to roll over the cephalic furrow cleft, they become wedge shaped as their apical cortices and overlying membranes expand, lateral cortices and overlying membranes release tension, internal pressures drop, and basal cortices and membranes contract. Then, cells reverse this process by shortening apical cortices and membranes, increasing lateral tension, and causing internal pressures to rise. Since the basal membranes expand, the cells recover their rotated columnar shape once in the furrow. Interestingly, our findings indicate that the basal membranes may be passively reactive throughout the progression phase. We also find that the smooth rolling of cells over the cephalic furrow cleft necessitates that internalized cells provide a solid base through high levels of membrane tension and internal pressure, which allows the transmission of tensile force that pulls new cells into the furrow. These results lead us to suggest that CFF helps to establish a baseline tension across the apical surface of the embryo to facilitate cellular coordination of other morphogenetic movements via mechanical stress feedback mechanisms.

Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes.

BACKGROUND: Endogenous estrogen is cardio-protective in healthy premenopausal women. Despite this favorable action of estrogen, animal models depict a detrimental effect of estradiol on vascular function in the presence of diabetes. The present study sought to determine the role of endogenous estradiol on endothelial function in women with type 1 diabetes. METHOD: 32 women with type 1 diabetes (HbA1c = 8.6 ± 1.7%) and 25 apparently healthy women (HbA1c = 5.2 ± 0.3%) participated. Flow-mediated dilation (FMD), a bioassay of nitric-oxide bioavailability and endothelial function was performed during menses (M) and the late follicular (LF) phase of the menstrual cycle to represent low and high concentrations of estrogen, respectively. In addition, a venous blood sample was collected at each visit to determine circulating concentrations of estradiol, thiobarbituric acid reactive substances (TBARS), and nitrate/nitrite (NOx), biomarkers of oxidative stress and nitric oxide, respectively. Data were collected in (1) 9 additional women with type 1 diabetes using oral hormonal birth control (HBC) (HbA1c = 8.3 ± 2.1%) during the placebo pill week and second active pill week, and (2) a subgroup of 9 demographically matched women with type 1 diabetes not using HBC (HbA1c = 8.9 ± 2.1%). RESULTS: Overall, estradiol was significantly increased during the LF phase compared to M in both type 1 diabetes (Δestradiol = 75 ± 86 pg/mL) and controls (Δestradiol = 71 ± 76 pg/mL); however, an increase in TBARS was only observed in patients with type 1 diabetes (ΔTBARS = 3 ± 13 µM) compared to controls (ΔTBARS = 0 ± 4 µM). FMD was similar (p = 0.406) between groups at M. In addition, FMD increased significantly from M to the LF phase in controls (p = 0.024), whereas a decrease was observed in type 1 diabetes. FMD was greater (p = 0.015) in patients using HBC compared to those not on HBC, independent of menstrual cycle phase. CONCLUSION: Endogenous estradiol increases oxidative stress and contributes to endothelial dysfunction in women with diabetes. Additionally, HBC use appears to be beneficial to endothelial function in type 1 diabetes.

Immune response, phenotyping and molecular graft surveillance in kidney transplant recipients following severe acute respiratory syndrome coronavirus 2 vaccination.

BACKGROUND: Understanding immunogenicity and alloimmune risk following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in kidney transplant recipients is imperative to understanding the correlates of protection and to inform clinical guidelines. METHODS: We studied 50 kidney transplant recipients following SARS-CoV-2 vaccination and quantified their anti-spike protein antibody, donor-derived cell-free DNA (dd-cfDNA), gene expression profiling (GEP), and alloantibody formation. RESULTS: Participants were stratified using nucleocapsid testing as either SARS-CoV-2-naïve or experienced prior to vaccination. One of 34 (3%) SARS-CoV-2 naïve participants developed anti-spike protein antibodies. In contrast, the odds ratio for the association of a prior history of SARS-CoV-2 infection with vaccine response was 18.3 (95% confidence interval 3.2, 105.0, p < 0.01). Pre- and post-vaccination levels did not change for median dd-cfDNA (0.23% vs. 0.21% respectively, p = 0.13), GEP scores (9.85 vs. 10.4 respectively, p = 0.45), calculated panel reactive antibody, de-novo donor specific antibody status, or estimated glomerular filtration rate. CONCLUSIONS: SARS-CoV-2 vaccines do not appear to trigger alloimmunity in kidney transplant recipients. The degree of vaccine immunogenicity was associated most strongly with a prior history of SARS-CoV-2 infection.

Impact of the COVID-19 pandemic on army families: Household finances, familial experiences, and soldiers' behavioral health.

The Coronavirus Disease 2019 (COVID-19) pandemic has significantly impacted employment and finances, childcare, and behavioral health across the United States. The Behavioral Health Advisory Team assessed the pandemic's impact on the behavioral health of U.S. Army soldiers and their families. Over 20,000 soldiers at three large installation groups headquartered in the northwestern continental U.S., Republic of Korea, and Germany participated in the cross-sectional survey. Multivariable logistic regression models indicated that key demographics (gender, rank), severity of household financial impact, changes in work situation due to childcare issues, and family members' difficulty coping (both self and spouse/partner and/or child) were independently and consistently associated with greater odds of screening positive for probable clinical depression and generalized anxiety, respectively. These findings highlight how Army families were impacted similarly by the pandemic as their civilian counterparts. Army leadership may action these findings with targeted support for soldiers and their families to ensure they are utilizing supportive services available to them, and that military services continually evolve to meet soldier and family needs during times of crisis and beyond.

Dual endothelin receptor antagonism increases resting energy expenditure in people with increased adiposity.

Increased adiposity is associated with dysregulation of the endothelin system, both of which increase the risk of cardiovascular disease (CVD). Preclinical data indicate that endothelin dysregulation also reduces resting energy expenditure (REE). The objective was to test the hypothesis that endothelin receptor antagonism will increase REE in people with obesity compared with healthy weight individuals. Using a double blind, placebo-controlled, crossover design, 32 participants [healthy weight (HW): n = 16, BMI: 21.3 ± 2.8 kg/m2, age: 26 ± 7 yr and overweight/obese (OB): n = 16, BMI: 33.5 ± 9.5 kg/m2, age: 31 ± 6 yr] were randomized to receive either 125 mg of bosentan (ETA/B antagonism) or placebo twice per day for 3 days. Breath-by-breath gas exchange data were collected and REE was assessed by indirect calorimetry. Venous blood samples were analyzed for concentrations of endothelin-1 (ET-1). Treatment with bosentan increased plasma ET-1 in both OB and HW groups. Within the OB group, the changes in absolute REE (PLA: -77.6 ± 127.6 vs. BOS: 72.2 ± 146.6 kcal/day; P = 0.046). The change in REE was not different following either treatment in the HW group. Overall, absolute plasma concentrations of ET-1 following treatment with bosentan were significantly associated with kcal/day of fat (r = 0.488, P = 0.005), percentage of fat utilization (r = 0.415, P = 0.020), and inversely associated with the percentage of carbohydrates (r = -0.419, P = 0.019), and respiratory exchange ratio (r = -0.407, P = 0.023). Taken together, these results suggest that modulation of the endothelin system may represent a novel therapeutic approach to increase both resting metabolism and caloric expenditure, and reduce CVD risk in people with increased adiposity.NEW & NOTEWORTHY Findings from our current translational investigation demonstrate that dual endothelin A/B receptor antagonism increases total REE in overweight/obese individuals. These results suggest that modulation of the endothelin system may represent a novel therapeutic target to increase both resting metabolism and caloric expenditure, enhance weight loss, and reduce CVD risk in seemingly healthy individuals with elevated adiposity.

Order effects in PTSD network analysis: important implications for diagnostic conceptualization, treatment refinement, and research.

BACKGROUND: For decades confirmatory factor analysis (CFA) has been the preeminent method to study the underlying structure of posttraumatic stress disorder (PTSD); however, methodological limitations of CFA have led to the emergence of other analytic approaches. In particular, network analysis has become a gold standard to investigate the structure and relationships between PTSD symptoms. A key methodological limitation, however, which has significant clinical implications, is the lack of data on the potential impact of item order effects on the conclusions reached through network analyses. METHODS: The current study, involving a large sample (N = 5055) of active duty army soldiers following deployment to Iraq, assessed the vulnerability of network analyses and prevalence rate to item order effects. This was done by comparing symptom networks of the DSM-IV PTSD checklist items to these same items distributed in random order. Half of the participants rated their symptoms on traditionally ordered items and half the participants rated the same items, but in random order and interspersed between items from other validated scales. Differences in prevalence rate and network composition were examined. RESULTS: The prevalence rate differed between the ordered and random item samples. Network analyses using the ordered survey closely replicated the conclusions reached in the existing network analyses literature. However, in the random item survey, network composition differed considerably. CONCLUSION: Order effects appear to have a significant impact on conclusions reached from PTSD network analysis. Prevalence rates were also impacted by order effects. These findings have important diagnostic and clinical treatment implications.

Mechanical feedback and robustness of apical constrictions in Drosophila embryo ventral furrow formation.

Formation of the ventral furrow in the Drosophila embryo relies on the apical constriction of cells in the ventral region to produce bending forces that drive tissue invagination. In our recent paper we observed that apical constrictions during the initial phase of ventral furrow formation produce elongated patterns of cellular constriction chains prior to invagination and argued that these are indicative of tensile stress feedback. Here, we quantitatively analyze the constriction patterns preceding ventral furrow formation and find that they are consistent with the predictions of our active-granular-fluid model of a monolayer of mechanically coupled stress-sensitive constricting particles. Our model shows that tensile feedback causes constriction chains to develop along underlying precursor tensile stress chains that gradually strengthen with subsequent cellular constrictions. As seen in both our model and available optogenetic experiments, this mechanism allows constriction chains to penetrate or circumvent zones of reduced cell contractility, thus increasing the robustness of ventral furrow formation to spatial variation of cell contractility by rescuing cellular constrictions in the disrupted regions.

US soldiers and the role of leadership: COVID-19, mental health, and adherence to public health guidelines.

BACKGROUND: Previous studies have documented the impact of domain-specific leadership behaviors on targeted health outcomes in employees. The goal of the present study was to determine the association between specific leadership behaviors addressing COVID-19 and US soldiers' mental health and adherence to COVID-19 public health guidelines. METHODS: An electronic, anonymous survey was administered to US Army soldiers across three major commands (N = 7,829) from December 2020 to January 2021. The primary predictor of interest was soldiers' ratings of their immediate supervisors' behaviors related to COVID-19. The outcomes were soldiers' mental health (i.e., depression and generalized anxiety) and adherence to COVID-19 public health guidelines. Covariates were rank, gender, ratings of immediate supervisors' general leadership, level of COVID-19 concerns, and COVID-19 status (e.g., tested positive, became seriously ill). Logistic regressions were used to model the unique association of COVID-19 leadership behaviors with outcomes after adjusting for covariates. RESULTS: High levels of COVID-19 leadership behaviors were associated with lesser likelihood of soldiers' screening positive for depression (AOR = 0.46; 95% CI [0.39, 0.54]) and anxiety (AOR = 0.54; 95% CI [0.45, 0.64]), and greater likelihood of frequent adherence to preventive health guidelines (AORs = 1.58; 95% CI [1.39, 1.80] to 2.50; 95% CI [2.01, 3.11]). CONCLUSION: Higher levels of COVID-19 leadership behaviors may support soldiers' mental health and encourage their adherence to COVID-19 public health guidelines. Given the link between these leader behaviors and soldier adaptation to the pandemic over and above general leadership, training for supervisors should focus on targeting specific health-promoting behaviors. Results can inform leader training for the military and other high-risk occupations.

Sirt1 during childhood is associated with microvascular function later in life.

Microvascular dysfunction often precedes other age-related macrovascular conditions and predicts future cardiovascular risk. Sirtuin 1 (Sirt1) has recently emerged as a protein that protects the vasculature and reduces the risk of cardiovascular diseases. We tested the hypothesis that lower Sirt1 during childhood is associated with a reduced microvascular function during adulthood. Thirty-four adults (34 ± 3 yr) from the Augusta Heart Study returned to participate in the present clinical observational study. Sirt1 was assessed in samples collected during both adulthood and participants' childhood (16 ± 3 yr), and data were divided based on childhood Sirt1 concentrations: <3 ng/dL (LowCS; n = 16) and ≥3 ng/dL (HighCS; n = 18). MVF was evaluated in all of the adults using laser-Doppler flowmetry coupled with three vascular reactivity tests: 1) local thermal hyperemia (LTH), 2) post-occlusive reactive hyperemia (PORH), and 3) iontophoresis of acetylcholine (ACh). The hyperemic response to LTH was significantly (P ≤ 0.044) lower in the LowCS than in the HighCS group. Similarly, the LowCS also exhibited an ameliorated (P ≤ 0.045) response to the PORH test and lower (P ≤ 0.008) vasodilation in response to iontophoresis of ACh when compared with the HighCS. Positive relationships were identified between childhood Sirt1 and all MVF reactivity tests (r≥0.367, P ≤ 0.004). Novel observations suggest that lower Sirt1 during childhood is associated with premature microvascular dysfunction in adulthood. These findings provide evidence that Sirt1 may play a critical role in microvascular function and have therapeutic potential for the prevention of age-associated vascular dysfunction in humans.NEW & NOTEWORTHY With a longitudinal cohort, novel observations from the present study demonstrate that individuals who had lower Sirt1 early in life exhibit premature microvascular dysfunction during adulthood and may be at higher risk to develop CVD. These results provide experimental evidence that Sirt1 may play an important role in microvascular function with age and represent a potential therapeutic target to prevent premature vascular dysfunction.

Open Source Energy System Modeling Using Break-Even Costs to Inform State-Level Policy: A North Carolina Case Study.

Rigorous model-based analysis can help inform state-level energy and climate policy. In this study, we utilize an open-source energy system optimization model and publicly available data sets to examine future electricity generation, CO2 emissions, and CO2 abatement costs for the North Carolina electric power sector through 2050. Model scenarios include uncertainty in future fuel prices, a hypothetical CO2 cap, and an extended renewable portfolio standard. Across the modeled scenarios, solar photovoltaics represent the most cost-effective low-carbon technology, while trade-offs among carbon constrained scenarios largely involve natural gas and renewables. We also develop a new method to calculate break-even costs, which indicate the capital costs at which specific technologies become cost-effective within the model. Significant variation in break-even costs are observed across different technologies and scenarios. We illustrate how break-even costs can be used to inform the development of an extended renewable portfolio standard in North Carolina. Utilizing the break-even costs to calibrate a tax credit for onshore wind, we find that the resultant wind deployment displaces other renewables, and thus has a negligible effect on CO2 emissions. Such insights can provide crucial guidance to policymakers weighing different policy options. This study provides an analytical framework to conduct similar analyses in other states using an open source model and freely available data sets.

Point-of-Care Ultrasound for Pediatric Endotracheal Tube Placement Confirmation by Advanced Practice Transport Nurses.

OBJECTIVE: This study aimed to identify which point-of-care ultrasound (POCUS) techniques and sonographic signs were reliably acquired and interpreted by transport nurses for the confirmation of endotracheal tube placement in children. METHODS: We developed and assessed a multimodal POCUS training curriculum for transport nurses that evaluated 5 sonographic signs using 3 scanning techniques. RESULTS: Twenty-one transport nurses were enrolled in the curriculum. The mean scores (95% confidence interval [CI]) of the knowledge test were 82% (95% CI, 63%-93%), 88% (95% CI, 68%-95%), and 74% (95% CI, 53%-87%) for tracheal, lung, and hemidiaphragmatic scans, respectively. For the simulation image evaluation, 94% (95% CI, 77%-99%) of tracheal scan images, 97% (95% CI, 81%-99%) of lung scan images, and 88% (95% CI, 69%-96%) of hemidiaphragmatic scan images were determined clinically useful. For the pediatric intensive care unit image evaluation, 100% (95% CI, 86%-100%) of tracheal scan images, 100% (95% CI, 86%-100%) of lung scan images, and 79% (95% CI, 59%-91%) of hemidiaphragmatic scan images were determined clinically useful. A tracheal dilation sign was rarely captured by POCUS. CONCLUSION: Transport nurses can acquire POCUS skills to confirm endotracheal tube placement in children. A combination of a double trachea sign, a lung sliding sign, and a lung pulse sign could be a feasible POCUS approach.

Actomyosin contraction during cellularization is regulated in part by Src64 control of Actin 5C protein levels.

Src64 is required for actomyosin contraction during cellularization of the Drosophila embryonic blastoderm. The mechanism of actomyosin ring constriction is poorly understood even though a number of cytoskeletal regulators have been implicated in the assembly, organization, and contraction of these microfilament rings. How these cytoskeletal processes are regulated during development is even less well understood. To investigate the role of Src64 as an upstream regulator of actomyosin contraction, we conducted a proteomics screen to identify proteins whose expression levels are controlled by src64. Global levels of actin are reduced in src64 mutant embryos. Furthermore, we show that reduction of the actin isoform Actin 5C causes defects in actomyosin contraction during cellularization similar to those caused by src64 mutation, indicating that a relatively high level of Actin 5C is required for normal actomyosin contraction and furrow canal structure. However, reduction of Actin 5C levels only slows down actomyosin ring constriction rather than preventing it, suggesting that src64 acts not only to modulate actin levels, but also to regulate the actomyosin cytoskeleton by other means.

Authorization of tissues from deceased patients for genetic research.

Tissues from deceased donors provide important data for genomic research and Organ Procurement Organizations (OPOs) play a significant role. To understand the decisions of families who donated for transplantation and made decisions about donation to the Genotype-Tissue Expression Project (GTEx), we examined donation decisions of family decision makers (FDMs). 413 families were interviewed by telephone. The OPO staff who made the transplant and research requests completed self-administered surveys; a total of 309 matching surveys from 99 OPO staff were obtained. 76.8% of families donated to the GTEx project. Logistic regression analysis found that FDM consent to GTEx donation was associated with endorsement of policies to promote biobanking (OR = 1.35), positive attitudes about medical research (OR = 1.1), lack of concern regarding a breach of confidentiality (OR = 1.54), comfort with tissue donation (OR = 1.24), and prior authorization to solid organ donation (OR = 3.17). OPO staff characteristics associated with GTEx donation included being female (OR = 3.57), White (OR = 4.97), comfort with hospital staff role in donation (OR = 1.61), and number of topics discussed with families (OR = 57.9). Donor type, FDM attitudes, OPO staff sociodemographics, OPO comfort with the GTEx authorization process, and intensity of discussing research-specific issues were significantly associated with GTEx donation decisions.

Use of a Parabolic Microphone to Detect Hidden Subjects in Search and Rescue.

INTRODUCTION: This study compares a parabolic microphone to unaided hearing in detecting and comprehending hidden callers at ranges of 322 to 2510 m. METHODS: Eight subjects were placed 322 to 2510 m away from a central listening point. The subjects were concealed, and their calling volume was calibrated. In random order, subjects were asked to call the name of a state for 5 minutes. Listeners with parabolic microphones and others with unaided hearing recorded the direction of the call (detection) and name of the state (comprehension). RESULTS: The parabolic microphone was superior to unaided hearing in both detecting subjects and comprehending their calls, with an effect size (Cohen's d) of 1.58 for detection and 1.55 for comprehension. For each of the 8 hidden subjects, there were 24 detection attempts with the parabolic microphone and 54 to 60 attempts by unaided listeners. At the longer distances (1529-2510 m), the parabolic microphone was better at detecting callers (83% vs 51%; P<0.00001 by χ2) and comprehension (57% vs 12%; P<0.00001). At the shorter distances (322-1190 m), the parabolic microphone offered advantages in detection (100% vs 83%; P=0.000023) and comprehension (86% vs 51%; P<0.00001), although not as pronounced as at the longer distances. CONCLUSIONS: Use of a 66-cm (26-inch) parabolic microphone significantly improved detection and comprehension of hidden calling subjects at distances between 322 and 2510 m when compared with unaided hearing. This study supports the use of a parabolic microphone in search and rescue to locate responsive subjects in favorable weather and terrain.

Inhibiting cytosolic translation and autophagy improves health in mitochondrial disease.

Mitochondrial respiratory chain (RC) disease therapies directed at intra-mitochondrial pathology are largely ineffective. Recognizing that RC dysfunction invokes pronounced extra-mitochondrial transcriptional adaptations, particularly involving dysregulated translation, we hypothesized that translational dysregulation is itself contributing to the pathophysiology of RC disease. Here, we investigated the activities, and effects from direct inhibition, of a central translational regulator (mTORC1) and its downstream biological processes in diverse genetic and pharmacological models of RC disease. Our data identify novel mechanisms underlying the cellular pathogenesis of RC dysfunction, including the combined induction of proteotoxic stress, the ER stress response and autophagy. mTORC1 inhibition with rapamycin partially ameliorated renal disease in B6.Pdss2(kd/kd) mice with complexes I-III/II-III deficiencies, improved viability and mitochondrial physiology in gas-1(fc21) nematodes with complex I deficiency, and rescued viability across a variety of RC-inhibited human cells. Even more effective was probucol, a PPAR-activating anti-lipid drug that we show also inhibits mTORC1. However, directly inhibiting mTORC1-regulated downstream activities yielded the most pronounced and sustained benefit. Partial inhibition of translation by cycloheximide, or of autophagy by lithium chloride, rescued viability, preserved cellular respiratory capacity and induced mitochondrial translation and biogenesis. Cycloheximide also ameliorated proteotoxic stress via a uniquely selective reduction of cytosolic protein translation. RNAseq-based transcriptome profiling of treatment effects in gas-1(fc21) mutants provide further evidence that these therapies effectively restored altered translation and autophagy pathways toward that of wild-type animals. Overall, partially inhibiting cytosolic translation and autophagy offer novel treatment strategies to improve health across the diverse array of human diseases whose pathogenesis involves RC dysfunction.

Inhibition of Cytohesins Protects against Genetic Models of Motor Neuron Disease.

Mutant genes that underlie Mendelian forms of amyotrophic lateral sclerosis (ALS) and biochemical investigations of genetic disease models point to potential driver pathophysiological events involving endoplasmic reticulum (ER) stress and autophagy. Several steps in these cell biological processes are known to be controlled physiologically by small ADP-ribosylation factor (ARF) signaling. Here, we investigated the role of ARF guanine nucleotide exchange factors (GEFs), cytohesins, in models of ALS. Genetic or pharmacological inhibition of cytohesins protects motor neurons in vitro from proteotoxic insults and rescues locomotor defects in a Caenorhabditis elegans model of disease. Cytohesins form a complex with mutant superoxide dismutase 1 (SOD1), a known cause of familial ALS, but this is not associated with a change in GEF activity or ARF activation. ER stress evoked by mutant SOD1 expression is alleviated by antagonism of cytohesin activity. In the setting of mutant SOD1 toxicity, inhibition of cytohesin activity enhances autophagic flux and reduces the burden of misfolded SOD1. These observations suggest that targeting cytohesins may have potential benefits for the treatment of ALS.

Cell shape change and invagination of the cephalic furrow involves reorganization of F-actin.

Invagination of epithelial sheets to form furrows is a fundamental morphogenetic movement and is found in a variety of developmental events including gastrulation and vertebrate neural tube formation. The cephalic furrow is a deep epithelial invagination that forms during Drosophila gastrulation. In the first phase of cephalic furrow formation, the initiator cells that will lead invagination undergo apicobasal shortening and apical constriction in the absence of epithelial invagination. In the second phase of cephalic furrow formation, the epithelium starts to invaginate, accompanied by both basal expansion and continued apicobasal shortening of the initiator cells. The cells adjacent to the initiator cells also adopt wedge shapes, but only after invagination is well underway. Myosin II does not appear to drive apical constriction in cephalic furrow formation. However, cortical F-actin is increased in the apices of the initiator cells and in invaginating cells during both phases of cephalic furrow formation. These findings suggest that a novel mechanism for epithelial invagination is involved in cephalic furrow formation.

Evidence of microvascular dysfunction in patients with cystic fibrosis.

Cystic fibrosis (CF) is a genetic, multisystemic disorder with broad clinical manifestations apart from the well-characterized pulmonary dysfunction. Recent findings have described impairment in conduit vessel function in patients with CF; however, whether microvascular function is affected in this population has yet to be elucidated. Using laser-Doppler imaging, we evaluated microvascular function through postocclusive reactive hyperemia (PORH), local thermal hyperemia (LTH), and iontophoresis with acetylcholine (ACh). PORH [518 ± 174% (CF) and 801 ± 125% (control), P = 0.039], LTH [1,338 ± 436% (CF) and 1,574 ± 620% (control), P = 0.045], and iontophoresis with ACh [416 ± 140% (CF) and 617 ± 143% (control), P = 0.032] were significantly lower in patients with CF than control subjects. In addition, the ratio of PORH to LTH was significantly (P = 0.043) lower in patients with CF (55.3 ± 5.1%) than control subjects (68.8 ± 3.1%). Significant positive correlations between LTH and forced expiratory volume in 1 s (%predicted) (r = 0.441, P = 0.013) and between the PORH-to-LTH ratio and exercise capacity (r = 0.350, P = 0.049) were observed. These data provide evidence of microvascular dysfunction in patients with CF compared with control subjects. In addition, our data demonstrate a complex relationship between microvascular function and classical markers of disease severity (i.e., pulmonary function and exercise capacity) in CF.

Longitudinal determinants of mental health treatment-seeking by US soldiers.

BACKGROUND: Studies with members of the armed forces have found a gap between reports of mental health symptoms and treatment-seeking. AIMS: To assess the impact of attitudes on treatment-seeking behaviours in soldiers returning from a combat deployment. METHOD: A sample of 529 US soldiers were surveyed 4 months (time 1) and 12 months (time 2) post-deployment. Mental health symptoms and treatment-seeking attitudes were assessed at time 1; reported mental healthcare visits were assessed at time 2. RESULTS: Factor analysis of the total time 1 sample revealed four attitude factors: professional concerns, practical barriers, preference for self-management and positive attitudes about treatment. For the subset of 160 soldiers reporting a mental health problem at time 1, and controlling for mental health symptom severity, self-management inversely predicted treatment-seeking; positive attitudes were positively related. CONCLUSIONS: Results demonstrate the importance of broadening the conceptualisation of barriers and facilitators of mental healthcare beyond stigma. Techniques and delivery models emphasising self-care may help increase soldiers' interest in using mental health services.

Mental health outcomes in US and UK military personnel returning from Iraq.

BACKGROUND: Research of military personnel who deployed to the conflicts in Iraq or Afghanistan has suggested that there are differences in mental health outcomes between UK and US military personnel. AIMS: To compare the prevalence of post-traumatic stress disorder (PTSD), hazardous alcohol consumption, aggressive behaviour and multiple physical symptoms in US and UK military personnel deployed to Iraq. METHOD: Data were from one US (n = 1560) and one UK (n = 313) study of post-deployment military health of army personnel who had deployed to Iraq during 2007-2008. Analyses were stratified by high- and low-combat exposure. RESULTS: Significant differences in combat exposure and sociodemographics were observed between US and UK personnel; controlling for these variables accounted for the difference in prevalence of PTSD, but not in the total symptom level scores. Levels of hazardous alcohol consumption (low-combat exposure: odds ratio (OR) = 0.13, 95% CI 0.07-0.21; high-combat exposure: OR = 0.23, 95% CI 0.14-0.39) and aggression (low-combat exposure: OR = 0.36, 95% CI 0.19-0.68) were significantly lower in US compared with UK personnel. There was no difference in multiple physical symptoms. CONCLUSIONS: Differences in self-reported combat exposures explain most of the differences in reported prevalence of PTSD. Adjusting for self-reported combat exposures and sociodemographics did not explain differences in hazardous alcohol consumption or aggression.