Assessment of Allergen-Responsive Regulatory T Cells in Experimental Asthma Induced in Different Mouse Strains.

BACKGROUND: Regulatory T cells (Tregs) are important in regulating responses to innocuous antigens, such as allergens, by controlling the Th2 response, a mechanism that appears to be compromised in atopic asthmatic individuals. Different isogenic mouse strains also have distinct immunological responses and susceptibility to the experimental protocols used to develop lung allergic inflammation. In this work, we investigated the differences in the frequency of Treg cell subtypes among A/J, BALB/c, and C57BL/6, under normal conditions and following induction of allergic asthma with ovalbumin (OVA). METHODS: Subcutaneous sensitization followed by 4 consecutive intranasal OVA challenges induced asthma characteristic changes such as airway hyperreactivity, inflammation, and production of Th2 cytokines (IL-4, IL-13, IL-5, and IL-33) in the lungs of only A/J and BALB/c but not C57BL/6 strain and evaluated by invasive whole-body plethysmography, flow cytometry, and ELISA, respectively. RESULTS: A/J strain naturally showed a higher frequency of CD4+IL-10+ T cells in the lungs of naïve mice compared to the other strains, accompanied by higher frequencies of CD4+IL-4+ T cells. C57BL/6 mice did not develop lung inflammation and presented higher frequency of CD4+CD25+Foxp3+ Treg cells in the bronchoalveolar lavage fluid (BALF) after the allergen challenge. In in vitro settings, allergen-specific stimulation of mediastinal LN (mLN) cells from OVA-challenged animals induced higher frequency of CD4+IL-10+ Treg cells from A/J strain and CD4+CD25+Foxp3+ from C57BL/6. CONCLUSIONS: The observed differences in the frequencies of Treg cell subtypes associated with the susceptibility of the animals to experimental asthma suggest that CD4+CD25+Foxp3+ and IL-10-producing CD4+ Treg cells may play different roles in asthma control. Similar to asthmatic individuals, the lack of an efficient regulatory response and susceptibility to the development of experimental asthma in A/J mice further suggests that this strain could be preferably chosen in experimental models of allergic asthma.

Optimal sunscreen use, during a sun holiday with a very high ultraviolet index, allows vitamin D synthesis without sunburn.

BACKGROUND: Sunlight contains ultraviolet (UV)A and UVB radiation. UVB is essential for vitamin D synthesis but is the main cause of sunburn and skin cancer. Sunscreen use is advocated to reduce the sun's adverse effects but may compromise vitamin D status. OBJECTIVES: To assess the ability of two intervention sunscreens to inhibit vitamin D synthesis during a week-long sun holiday. METHODS: The impact of sunscreens on vitamin D status was studied during a 1-week sun holiday in Tenerife (28° N). Comparisons were made between two formulations, each with a sun protection factor (SPF) of 15. The UVA-protection factor (PF) was low in one case and high in the other. Healthy Polish volunteers (n = 20 per group) were given the sunscreens and advised on the correct application. Comparisons were also made with discretionary sunscreen use (n = 22) and nonholiday groups (51·8° N, n = 17). Sunscreen use in the intervention groups was measured. Behaviour, UV radiation exposure, clothing cover and sunburn were monitored. Serum 25-hydroxyvitamin D3 [25(OH)D3 ] was assessed by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Use of intervention sunscreens was the same (P = 0·60), and both equally inhibited sunburn, which was present in the discretionary use group. There was an increase (P < 0·001) in mean ± SD 25(OH)D3 (28·0 ± 16·5 nmol L-1 ) in the discretionary use group. The high and low UVA-PF sunscreen groups showed statistically significant increases (P < 0·001) of 19·0 ± 14·2 and 13·0 ± 11·4 nmol L-1 25(OH)D3 , respectively with P = 0·022 for difference between the intervention sunscreens. The nonholiday group showed a fall (P = 0·08) of 2·5 ± 5·6 nmol L-1 25(OH)D3 . CONCLUSIONS: Sunscreens may be used to prevent sunburn yet allow vitamin D synthesis. A high UVA-PF sunscreen enables significantly higher vitamin D synthesis than a low UVA-PF sunscreen because the former, by default, transmits more UVB than the latter. What's already known about this topic? Action spectra (wavelength dependence) for erythema and the cutaneous formation of vitamin D overlap considerably in the ultraviolet (UV)B region. Theoretically, sunscreens that inhibit erythema should also inhibit vitamin D synthesis. To date, studies on the inhibitory effects of sunscreens on vitamin D synthesis have given conflicting results, possibly, in part, because people typically apply sunscreen suboptimally. Many studies have design flaws. What does this study add? Sunscreens (sun protection factor, SPF 15) applied at sufficient thickness to inhibit sunburn during a week-long holiday with a very high UV index still allow a highly significant improvement of serum 25-hydroxyvitamin D3 concentration. An SPF 15 formulation with high UVA protection enables better vitamin D synthesis than a low UVA protection product. The former allows more UVB transmission.

Therapeutic administration of bone marrow-derived mesenchymal stromal cells reduces airway inflammation without up-regulating Tregs in experimental asthma.

BACKGROUND: Prophylactic administration of mesenchymal stromal cells (MSCs) derived from adipose (AD-MSC) and bone marrow tissue (BM-MSC) in ovalbumin-induced asthma hinders inflammation in a Treg-dependent manner. It is uncertain whether MSCs act through Tregs when inflammation is already established in asthma induced by a clinically relevant allergen. OBJECTIVE: Evaluate the effect of therapeutic administration of MSCs on inflammation and Treg cells in house dust mite (HDM)-induced asthma. METHODS: BM-MSCs and AD-MSCs were administered intratracheally to C57BL/6 mice 1 day after the last HDM challenge. Lung function, remodelling and parenchymal inflammation were assayed 3 or 7 days after MSCs treatment, through invasive plethysmography and histology, respectively. Bronchoalveolar lavage fluid (BALF) and mediastinal lymph nodes (mLNs) were assessed regarding the inflammatory profile by flow cytometry, ELISA and qRT-PCR. MSCs were studied regarding their potential to induce Treg cells from primed and unprimed lymphocytes in vitro. RESULTS: BM-MSCs, but not AD-MSCs, reduced lung influx of eosinophils and B cells and increased IL-10 levels in HDM-challenged mice. Neither BM-MSCs nor AD-MSCs reduced lung parenchymal inflammation, airway hyperresponsiveness or mucus hypersecretion. BM-MSCs and AD-MSCs did not up-regulate Treg cell counts within the airways and mLNs, but BM-MSCs decreased the pro-inflammatory profile of alveolar macrophages. Co-culture of BM-MSCs and AD-MSCs with allergen-stimulated lymphocytes reduced Treg cell counts in a cell-to-cell contact-independent manner, although co-culture of both MSCs with unprimed lymphocytes up-regulated Treg cell counts. CONCLUSIONS: MSCs therapeutically administered exert anti-inflammatory effects in the airway of HDM-challenged mice, but do not ameliorate lung function or remodelling. Although MSC pre-treatment can increase Treg cell numbers, it is highly unlikely that the MSCs will induce Treg cell expansion when lymphocytes are allergenically primed in an established lung inflammation.

Children sustain high levels of skin DNA photodamage, with a modest increase of serum 25-hydroxyvitamin D3 , after a summer holiday in Northern Europe.

BACKGROUND: Childhood solar ultraviolet radiation (UVR) exposure increases the risk of skin cancer in adulthood, which is associated with mutations caused by UVR-induced cyclobutane pyrimidine dimers (CPD). Solar UVR is also the main source of vitamin D, essential for healthy bone development in children. OBJECTIVES: To assess the impact of a 12-day Baltic Sea (54° N) beach holiday on serum 25-hydroxyvitamin D3 [25(OH)D3 ] and CPD in 32 healthy Polish children (skin types I-IV). METHODS: Blood and urine were collected before and after the holiday and assessed for 25(OH)D3 and excreted CPD, respectively, and personal UVR exposure was measured. Diaries were used to record sunbathing, sunburn and sunscreen use. Before- and after-holiday skin redness and pigmentation were measured by reflectance spectroscopy. RESULTS: The average ± SD daily exposure UVR dose was 2·4 ± 1·5 standard erythema doses (SEDs), which is borderline erythemal. The mean concentration of 25(OH)D3 increased (× 1·24 ± 0·19) from 64·7 ± 13·3 to 79·3 ± 18·7 nmol L-1 (P < 0·001). Mean CPD increased 12·6 ± 10·0-fold from 26·9 ± 17·9 to 248·9 ± 113·4 fmol µmol-1 creatinine (P < 0·001). Increased 25(OH)D3 was accompanied by a very much greater increase in DNA damage associated with carcinogenic potential. Overall, skin type had no significant effects on behavioural, clinical or analytical outcomes, but skin types I/II had more CPD (unadjusted P = 0·0496) than skin types III/IV at the end of the holiday. CONCLUSIONS: Careful consideration must be given to the health outcomes of childhood solar exposure, and a much better understanding of the risk-benefit relationships of such exposure is required. Rigorous photoprotection is necessary for children, even in Northern Europe.

Return-to-work intervention during cancer treatment - The providers' experiences.

To explore in-depth understanding of providers' experiences when involved in a return-to-work (RTW) intervention offered during cancer treatment. Semi-structured individual interviews and participant observations at a hospital department and two municipal job centers were carried out, including ten providers (physicians, nurses and social workers). A phenomenological-hermeneutic approach was applied, involving coding, identification of themes and interpretation of findings. Three major themes were identified: Treatment first, Work as an integrated component in cancer rehabilitation, and Challenges in bringing up work issues. Differences in providers' experiences of the RTW intervention offered to cancer patients were found: in the hospital setting RTW was a second priority, whereas in the municipality job centers it was an integrated component. Further studies are needed to investigate how and when occupational rehabilitation services can be implemented across sectors to support cancer patients' RTW. In the future, work issues ought to be systematically presented by providers across sectors as early as possible to support cancer patients' RTW. Cancer patients' individual needs and thoughts about RTW are to be identified by both health care providers during treatment and social workers at the municipality level and shared across sectors.

Evaluation of three-dimensional SonoAVC ultrasound for antral follicle count in infertile women: its agreement with conventional two-dimensional ultrasound and serum levels of anti-Müllerian hormone.

BACKGROUND: Several studies have reported a correlation between antral follicle count by conventional 2D transvaginal sonography and serum anti-Müllerian hormone levels. However, few studies have investigated the effectiveness of 3D SonoAVC transvaginal ultrasound technology, particularly in infertile women. Therefore, this study aims to evaluate the usefulness of three-dimensional (3D) SonoAVC transvaginal ultrasound technology for antral follicle count and its correlation to conventional two-dimensional (2D) transvaginal ultrasound and serum levels of anti-Müllerian hormone in infertile women. METHODS: This cross-sectional study included 42 infertile women with age lower than 40 years that underwent treatment at a private fertility clinic between June and December 2015. Patient data included age, body mass index and cause of infertility. On cycle day 3 the following hormone levels were measured: serum levels of anti-Müllerian hormone, follicle-stimulating hormone, cancer antigen 125, prolactin, thyroid-stimulating hormone and oestradiol; the number of antral follicles was counted as well. The scanning were performed through 2D and 3D technology transvaginal ultrasound. RESULTS: Using a Bland-Altman test we demonstrated that both technologies are quite equivalent. However, antral follicle count is higher using 3D ultrasound technology compared to 2D technology (p < 0.001; Wilcoxon test), this finding is mainly remarkable in ovaries with more than 20 antral follicles. Moreover, the mean time required for manual 2D ultrasound and 3D SonoAVC measurements were 275 ± 109 and 103 ± 57 s, respectively (p < 0.001). Serum AMH concentration correlated to the total number of early antral follicles (correlation coefficients = 0.678 and 0.612; p < 0.001 by 2D ultrasound and 3D SonoAVC, respectively; Spearman's correlation test). CONCLUSIONS: Antral follicle count is better estimated using 3D ultrasound compared to 2D technology. A great advantage of 3D SonoAVC was less time required for an examination and the visual advantage when it need to count more than 20 follicles. TRIAL REGISTRATION: CAAE: 35141114.4.0000.5327 . Registered 10 June 2015.

Focused cardiac ultrasound is feasible in parturients; a prospective observational study.

BACKGROUND: In pregnancy, the major causes of morbidity and mortality include diseases that affect circulation profoundly and restoration of normal circulation is a key objective. Focused cardiac ultrasound provides information on the individual determinants of circulation and has a significant impact on patient management. This study aimed to determine the feasibility of focused cardiac ultrasound in term parturients. METHODS: Forty parturients underwent focused cardiac ultrasound. Parasternal long-axis, parasternal short-axis, 4-chamber and subcostal views were performed in the left-lateral position and the supine position by a novice operator. All images were graded on the following scale: 1 = no image; 2 = poor and insufficient image; 3 = sufficient image quality; 4 = good image quality; 5 = perfect image quality. A cut-off grade of three signified images sufficient for clinical decision-making. RESULTS: Images sufficient for clinical decision-making were obtained in all patients when including all imaging views. 37/40 (93 %) patients presented images of grade ≥ 4, whereas 10/40 (25%) patients had images of grade 5. Image grades were higher in the left lateral position (all P < 0.001). Parturients with a body mass index ≤ 30 kg/m2 did not present different image grades than parturients with a higher body mass index (P = 0.753). Subcostal views could not be obtained. CONCLUSION: Focused cardiac ultrasound is feasible in the obstetric population and images of sufficient quality for clinical decision-making were obtained in all parturients by an operator with limited experience.

Ultrasound-guidance outperforms the palpation technique for peripheral venous catheterisation in anaesthetised toddlers: a randomised study.

BACKGROUND: Traditional palpation technique for peripheral venous catheter (PVC) placement can be challenging. We aimed to compare the Dynamic Needle Tip Positioning (DNTP) ultrasound technique with the palpation technique for PVC placement in anaesthetised toddlers undergoing elective, low-risk procedures. METHODS: The study was a randomised, controlled, crossover study. Five operators applied both techniques for PVC on 50 children < 4 years. The primary endpoint was first attempt success rate. The secondary endpoints were: (1) overall success rate, (2) number of skin perforations, (3) number of needle redirections, (4) number of catheters used, (5) total time, (6) needle manipulation time, (7) distance to the nearest flexion crease, (8) anatomical region of catheterisation, (9) size of the catheters and (10) the effects of visibility, and palpability of the veins. RESULTS: The first attempt success rate and the overall success rate were significantly higher in the DNTP group (42/50 vs. 30/50, P = 0.029), (50/50 vs. 42/50, P = 0.008). Furthermore, a lower number of skin perforations (60 vs. 84, P = 0.013) and needle redirections (14 vs. 131, P < 0.001) and increased distance to the nearest flexion crease (P < 0.001) were seen in the DNTP group. There were no significant differences in number of catheters used (60 vs. 75 P = 0.050) or total time (P = 0.073), however, the needle manipulation time was longer in the DNTP group (P = 0.011). The success rate decreased with less visible and palpable veins in the palpation group (p = 0.006). CONCLUSION: Ultrasound-guidance outperforms the traditional palpation technique for peripheral venous catheterisation in anaesthetised toddlers undergoing elective, low-risk procedures.

Asphyxia causes ultrasonographic D-shaping of the left ventricle--an experimental porcine study.

INTRODUCTION: In critical care, early diagnosis and correct treatment are of the utmost importance. Focused ultrasonography has gained acceptance as a pivotal tool for this by elucidating the underlying pathology. For example, massive pulmonary embolism is characterised by right ventricular dilatation. However, theoretically these characteristics might also be generated by asphyxia and the consequent hypoxia. We aimed to evaluate the ultrasonographic characteristics of asphyxia in a porcine model. METHODS: Nineteen (13 intervention, 6 control) piglets were subjected to asphyxia until cardiac arrest, by disconnecting the ventilator tube. Ultrasonographic short-axis cine loops of the left ventricle were obtained every 30 seconds. The left ventricular (LV) eccentricity index (index of LV D-shaping) was quantified along with LV end-diastolic/end-systolic areas. Invasive pressures were measured throughout. RESULTS: The LV eccentricity index increased from 1.14 (1.10-1.31) to 1.86 (1.48-2.38), (P = 0.002), after 1.5 min, receded thereafter to baseline levels followed by a second increase after 5.5 min. LV end-diastolic area decreased from 11.6 cm(2) (11.1-13.2) to 6.3 cm(2) (3.3 -11.0) after 2.0 min (P = 0.009). Subsequently, values returned to the baseline level. DISCUSSION: The early and transient acute dilatation of the RV, coinciding with D-shaping of the LV and decrease in LV end-diastolic area seen in our study represent a combination of ultrasonographic characteristics normally attributed to pulmonary embolism. Early changes in ventricular chamber sizes and shape with septal flattening related to asphyxia can occur, but appear to be transient and disappear as circulatory collapse progresses, in an animal model. Despite this, asphyxia may represent a cause of ultrasonographic misinterpretation.

Teenagers and young adults with cancer in Europe: from national programmes to a European integrated coordinated project.

Over 14 000 patients aged 15-24 are estimated to be diagnosed with cancer in the European Union (EU) each year. Teenagers and young adults (TYA) often fall down gaps between children's and adults cancer services. The specific challenges of providing optimal care to them are described, but we present a summary of recent progress. Progress to overcome these challenges is happening at different rates across Europe. We summarise the European national projects in this field but more recently we have seen the beginnings of European coordination. Within the EU 7th Funding Programme (FP7) European Network for Cancer Research in Children and Adolescents programme (ENCCA), a specific European Network for Teenagers and Young Adults with Cancer has held a series of scientific meetings, including professionals, patients and caregivers. This group has proposed unanswered research questions and agreed key features of a high-quality service that can improve outcomes for TYA with cancer, including the primacy of collaboration between adult and paediatric services to eliminate the gap in the management of TYA with cancer.

Effects of levosimendan in patients with left ventricular hypertrophy undergoing aortic valve replacement.

BACKGROUND: Left ventricular hypertrophy is associated with adverse outcomes, including death, during cardiac surgery. This may be facilitated by an increased oxygen demand and diastolic dysfunction. Levosimendan augments haemodynamics without further oxygen consumption and improves echocardiographic indices of diastolic dysfunction. This study aimed to describe the haemodynamic effects of short-term pre- and intra-operative levosimendan infusion including advanced echocardiographic measures of diastolic and systolic heart function. METHODS: The study was randomised, double-blinded and placebo-controlled performed at a single-centre university hospital. Patients with left ventricular hypertrophy and ejection fraction > 45% scheduled for single procedure aortic valve replacement were included and randomised to infusion of either levosimendan 0.1 µg/kg/min or placebo from 4 h before anaesthesia to the end of surgery. Outcome measures were echocardiographic indices of left ventricular diastolic function: E/e' (primary endpoint), e', e'/a' and indices of systolic function: longitudinal strain, ejection fraction and s'. Patients were followed until 6 months after surgery. In addition, invasive haemodynamic measures were obtained perioperatively. RESULTS: The trial was prematurely terminated due to an overall high incidence of post-operative atrial fibrillation (15/20, P = 0.002) after inclusion of 20 patients. The relative decrease in perioperative cardiac index was lower (P = 0.016) in the levosimendan group. There was no difference in E/e', and similar results were found for all measures of systolic function. CONCLUSION: Short-term levosimendan caused a transient relative increase in cardiac index, but no effect was seen on the first post-operative day and up to 6 months post-operatively with indices of systolic and diastolic heart function.

UVR exposure and vitamin D in a rural population. A study of outdoor working farmers, their spouses and children.

BACKGROUND: Living and working in the countryside may result in excessive UVR exposure, with increased risk of skin cancer. Some sun exposure is, however, recommended, since vitamin D production is UVB-dependent. OBJECTIVES: To examine UVR exposure and vitamin D levels in a rural population of outdoor working male farmers, their indoor working spouses and their children, expected to receive high UVR exposure. METHODS: Prospective, cohort study. During the summer 2009 daily, personal UVR exposure and sun behaviour were recorded by dosimetry and diaries (17 403 days). Vitamin D was measured at the end of summer and the following winter. RESULTS: Risk behaviour (= exposure of shoulders/upper body to the sun), beach days, sunscreen use and sunburns were infrequent. Farmers and boys had the highest daily UVR exposure (both 1.5 SED per day), likewise on work days. On non-work days the UVR exposure was even higher (up to 2.0 SED per day). Farmers, girls and boys had a higher chronic UVR exposure than the spouses, who had more intermittent high UVR exposure. Vitamin D levels did not differ between family members. At the end of summer 16% of the participants were vitamin D insufficient, the following winter, 61%. Some UVR exposure variables correlated positively, but weakly, with vitamin D levels. CONCLUSIONS: UVR exposure was generally high among this study population, however, vitamin D levels still dropped below the recommended level during winter for most participants. Differences in UVR exposure between the groups did not result in differences in vitamin D levels.

Ultrasonography-guided radial artery catheterization is superior compared with the traditional palpation technique: a prospective, randomized, blinded, crossover study.

BACKGROUND: Radial artery catheterization is gaining popularity for diagnostic and interventional procedures. Palpation technique is widely used for the procedure, but ultrasonography has been shown to increase catheterization success. A recently described ultrasonography technique is termed 'dynamic needle tip positioning'. We aimed to compare the traditional palpation technique and dynamic needle tip positioning technique in regard to clinically relevant end points. METHODS: The study was conducted as a randomized, patient-blinded, crossover study. Patients underwent bilateral radial artery catheterization using both techniques. The primary end point of the study was needle manipulation time. Additional end points were (1) the number of skin perforations, (2) the number of attempts targeting the vessel, (3) the number of catheters placed in first attempt and (4) the number of catheters used. RESULTS: Forty patients were analyzed. There was no significant difference in median needle manipulation time [32 s (range 11-96 s) vs. 39 s (range 9-575 s), P = 0.525], although the variance was lower in the dynamic needle tip positioning group (P < 0.001). In the traditional palpation technique group, a higher number of skin perforations (57 vs. 40, P = 0.003), catheters (46 vs. 40, P = 0.025) and attempts targeting the vessel (104 vs. 43, P < 0.001) were necessary compared with the ultrasonography dynamic needle tip positioning group. First attempt success rate was significantly higher in the ultrasonography dynamic needle tip positioning group (23/40 vs. 38/40, P < 0.001). CONCLUSION: Ultrasonography guidance using the dynamic needle tip positioning technique for radial artery catheterization significantly improves clinically relevant aspects of the procedure.

Field-scale Variation in Colloid Dispersibility and Transport: Multiple Linear Regressions to Soil Physico-Chemical and Structural Properties.

Water-dispersible soil colloids (WDC) act as carriers for sorbing chemicals in macroporous soils and hence constitute a significant risk for the aquatic environment. The prediction of WDC readily available for facilitated chemical transport is an unsolved challenge. This study identifies key parameters and predictive indicators for assessing field-scale variation of WDC. Samples representing three measurement scales (1- to 2-mm aggregates, intact 100-cm rings, and intact 6283 cm columns) were retrieved from the topsoil of a 1.69-ha agricultural field in a 15-m by 15-m grid to determine colloid dispersibility, mobilization, and transport. The amount of WDC was determined using (i) a laser diffraction method on 1- to 2-mm aggregates and (ii) an end-over-end shaking method on 100-cm intact rings. The accumulated amount of colloids leached from 20-cm by 20-cm intact columns was determined as a measure of the integrated colloid mobilization and transport. The WDC and the accumulated colloid transport were higher in samples from the northern part of the field. Using multiple linear regression (MLR) analyses, WDC or amount of colloids transported were predicted at the three measurement scales from 24 measured, geo-referenced parameters to identify parameters that could serve as indicator parameters for screening for colloid dispersibility, mobilization, and transport. The MLR analyses were performed at each sample scale using all, only northern, and only southern field locations. Generally, the predictive power of the regression models was best on the smallest 1- to 2-mm aggregate scale. Overall, our results suggest that different drivers controlled colloid dispersibility and transport at the three measurement scales and in the two subareas of the field.

Using a knowledge utilization framework to explore how findings from one study can be applied to other nursing contexts.

AIM: To discuss the complexities of moving research into practice and through a case example, explore how empirical findings from one specific study could be applied to nursing in other contexts. BACKGROUND: The processes of moving research findings into practice are complex and multidimensional. In this paper, an innovative approach to social support, network-focused nursing (NFN), is used as a case example to illustrate these complexities. Social support is associated with better recovery and survival after illness and based on this, a NFN programme was developed in a Danish oncology youth unit. Subsequently, a research study was undertaken to investigate the programme and based on the findings, the concept NFN was developed. METHODS: A knowledge utilization framework is used to explore how empirical findings from the NFN study could be applied to nursing more generally. Aligned with this, the specific considerations for implementing NFN are explicated. DISCUSSION: Strong leadership, education, management support and effective communication are critical factors for research utilization. Moving research into practice requires openness to new ideas. Nursing and healthcare policies therefore need to support environments in which creativity and innovation can flourish. NFN was developed in teenager and young adult cancer care, but its principles may be transferable to other clinical environments. CONCLUSIONS: It is important that nurse managers and policy makers ensure that support and education are available to nurses to facilitate moving research into practice. Moreover, resources need to be considered, particularly in countries where financial and organizational infrastructures may be weak.

Agreement between cardiac outputs by four-dimensional echocardiography and thermodilution method is poor.

OBJECTIVE: The objective of the study was to determine the agreement of cardiac output (CO) measured by four-dimensional echocardiography (4D echo) to simultaneously obtain CO from pulmonary artery catheter (PAC) using thermodilution technique. MATERIALS AND METHODS: Sixty-three comparable readings from 27 patients scheduled for elective coronary artery bypass were included. All echocardiographic measurements were obtained by one experienced echocardiographer. All echo images were analyzed independently and blinded from PAC-obtained measurements. Analysis was primarily done by Bland and Altman plot. The collected data were further controlled for interobserver bias and image quality. RESULTS: Differences in CO measurements increased with higher CO, hence values were logarithmically transformed. On the logaritmic scale, the 4D echo underestimated CO by 0.37 l/min compared with PAC, indicating that PAC measurements were 1.45 times higher than the 4D echo (95% confidence interval 1.32-1.52) and limits of agreement 0.97-2.14). The interobserver bias of 4D echo measurement analysis was 0.29 l/min (95% confidence interval 0.16-0.42) and limits of agreement -0.8-1.38). No difference was seen in image quality between comparisons with good agreement compared with comparisons with poor agreement. CONCLUSION: The agreement between COs by 4D echo and standard PAC thermodilution technique was poor. 4D echo underestimates CO as compared with PAC. This is most likely caused by the analysis software or low frame rate inherent to the technique.

Pleural effusion decreases left ventricular pre-load and causes haemodynamic compromise: an experimental porcine study.

BACKGROUND: Although pleural effusion is a common complication in critically ill patients, detailed knowledge is missing about the haemodynamic impact and the underlining mechanisms. The aim of this study was to evaluate the haemodynamic effect of incremental pleural effusion by means of invasive haemodynamic parameters and transthoracic echocardiography. METHODS: This experimental interventional study was conducted using 22 female piglets (17.5-21.5 kg) randomized for right-side (n = 9) and left-side (n = 9) pleural effusion, or sham operation (n = 4). Pleural effusion was induced by infusing incremental volumes of saline into the pleural cavity. Invasive haemodynamic measurements and echocardiographical images were obtained at baseline, a volume of 45 ml/kg, a volume of 75 ml/kg and 45 min after drainage. RESULTS: No difference (all P > 0.147) was found between right- and left-side pleural effusion, and the groups were thus pooled. At 45 ml/kg cardiac output, mean arterial pressure, stroke volume and mixed venous saturation decreased (all P < 0.003); central venous pressure and pulmonary arterial pressure increased (both P > 0.003) at this point. The changes accelerated at 75 ml/kg. At 45 ml/kg left ventricular pre-load in terms of end-diastolic area decreased significantly (P < 0.001). The effect on haemodynamics and cardiac dimensions changed dramatically at 75 ml/kg. Cardiac output, mean arterial pressure, central venous pressure and left ventricular end-diastolic area returned to normal during a recovery period of 45 min (all P > 0.061). CONCLUSION: Incremental volumes of unilateral pleural effusion induced a significant haemodynamic impact fully reversible after drainage. Pleural effusion causes a significant decrease of left ventricular pre-load in a diverse picture of haemodynamic compromise.

Ultrasound assessment of inferior vena cava collapsibility is not a valid measure of preload changes during triggered positive pressure ventilation: a controlled cross-over study.

PURPOSE: Respiratory changes in the diameter of the inferior vena cava (IVC) have been validated as a measure of volume status and preload responsiveness during spontaneous breathing and mechanical ventilation. However, many intensive care patients are ventilated with triggered positive pressure ventilation (PPV). In this setting, there is no evidence regarding IVC collapsibility (IVCc) as a surrogate for preload. We aimed to elucidate the effects of increasing levels of triggered PPV and of varying preload conditions on the IVCc. MATERIALS AND METHODS: 10 healthy volunteers were connected to a ventilator through a tight-fitting mask and exposed to 6 different levels of positive end-expiratory pressure (PEEP) and pressure support (PS) after a baseline reading. All ventilator settings were performed at neutral preload (horizontal position), low preload (reverse-Trendelenburg) and high preload (Trendelenburg position with an intravenous fluid bolus). At each ventilator setting, the IVC was imaged throughout at least 1 respiratory cycle using 3 commonly used ultrasound techniques including sagittal M-mode and 2-dimensional echocardiography in both sagittal and transverse views. RESULTS: Increasing PS diminished IVCc (p = 0.01) in the reverse-Trendelenburg position, and increasing PEEP caused a higher IVCc in the Trendelenburg position (p = 0.02). In the horizontal position, no significant effects of increasing PS, PEEP or a combination of the two were seen. Overall ANOVA analysis showed that IVCc was not independent of preload. During PPV, IVCc was highest at neutral preload at most ventilator settings, IVCc was lowest at low preload, while high preload generally facilitated an IVCc between neutral and high preload. In addition, sagittal M-mode and transverse 2-dimensional echocardiography overestimated IVCc as compared to sagittal 2-dimensional echocardiography. CONCLUSION: The compiled results of this study show that IVCc cannot be held as a valid measure of preload status during PPV. This may be explained by systematic alterations in other determinants for IVCc. Comparison of methods encourages the use of sagittal 2-dimensional echocardiography for dynamic imaging of the IVC. Sagittal M-mode and transverse 2-dimensional echocardiography overestimate IVCc as compared to sagittal 2-dimensional echocardiography.

19p13.3 aberrations are associated with dysmorphic features and deviant psychomotor development.

Here, we describe 2 patients with de novo genomic imbalances of 19p13.3. Using high-resolution microarray analysis, we detected a 1.25-Mb deletion in one patient and a 0.81- Mb duplication in another. The resulting phenotypes are quite different; one is a 2-year-old boy with macrocephaly and normal growth, while the other is a 9-year-old boy with microcephaly and growth retardation since birth. Both have dysmorphic features and psychomotor developmental delay. This report gives evidence of the effect of small aberrations of chromosome 19 and describes the phenotypes arising from a duplication and deletion of the same location at 19p13.3.

Lidocaine-derivative JMF2-1 prevents ovalbumin-induced airway inflammation by regulating the function and survival of T cells.

BACKGROUND: Inhalation of the local anaesthetic lidocaine has been suggested to be beneficial for asthmatics, but airway anaesthesia is unpleasant and may exacerbate bronchoconstriction. Our previous study showed that inhalation of the lidocaine analogue JMF2-1 can elicit the anti-inflammatory properties of lidocaine without anaesthesia. This prompted further research on the mechanism of action and putative therapeutic application of JMF2-1. OBJECTIVE: We tested the hypothesis that JMF2-1 would prevent allergen-induced lung inflammation and airway hyperresponsiveness (AHR) by modulating T cell function in vivo and in vitro. Methods Local and systemic changes in leucocyte levels, cytokine production and lung mechanics were examined in a murine model of lung inflammation. JMF2-1 (0.05-2%) or saline was aerosolized twice a day during the ovalbumin (OVA)-provocation period (19-21 days post-sensitization). Analyses were performed 24 h after the final challenge. Primary cultured lymph node cells were used to assess the effects of JMF2-1 (100-600 µm) at the cellular level. RESULTS: OVA challenge resulted in lung recruitment of CD4(+) T cells and eosinophils, increased generation of inflammatory cytokines and AHR to inhaled methacholine within 24 h. These changes were prevented by JMF2-1 nebulization, and occurred in parallel with an increase in the number of apoptotic cells in the lung. JMF2-1 treatment did not alter levels of CD4(+) or CD8(+) T cells in the thymus or lymph nodes of naïve mice, although it inhibited OVA-induced IL-13 production and the lymphocyte proliferative response in vitro. It also induced apoptosis of OVA-activated lymphocytes in a mechanism sensitive to z-VAD, indicating that JMF2-1 mediates caspase-dependent apoptosis. CONCLUSION: Inhalation of JMF2-1 prevents the cardinal features of asthma by reducing T(H) 2 cytokine generation and lung eosinophilic inflammatory infiltrates via local inhibition of T cell function and survival. JMF2-1 may represent a novel therapeutic alternative for asthma control with distinct advantages over local anaesthetics.