Sensitivity analyses of probabilistic and deterministic DTI tractography methodologies for studying arm muscle architecture.

PURPOSE: To determine the sensitivity profiles of probabilistic and deterministic DTI tractography methods in estimating geometric properties in arm muscle anatomy. METHODS: Spin-echo diffusion-weighted MR images were acquired in the dominant arm of 10 participants. Both deterministic and probabilistic tractography were performed in two different muscle architectures of the parallel-structured biceps brachii (and the pennate-structured flexor carpi ulnaris. Muscle fascicle geometry estimates and number of fascicles were evaluated with respect to tractography turning angle, polynomial fitting order, and SNR. The DTI tractography estimated fascicle lengths were compared with measurements obtained from conventional cadaveric dissection and ultrasound modalities. RESULTS: The probabilistic method generally estimated fascicle lengths closer to ranges reported by conventional methods than the deterministic method, most evident in the biceps brachii (p > 0.05), consisting of longer, arc-like fascicles. For both methods, a wide turning angle (50º-90°) generated fascicle lengths that were in close agreement with conventional methods, most evident in the flexor carpi ulnaris (p > 0.05), consisting of shorter, feather-like fascicles. The probabilistic approach produced at least two times more fascicles than the deterministic approach. For both approaches, second-order fitting yielded about double the complete tracts as third-order fitting. In both muscles, as SNR decreased, deterministic tractography produced less fascicles but consistent geometry (p > 0.05), whereas probabilistic tractography produced a consistent number but altered geometry of fascicles (p < 0.001). CONCLUSION: Findings from this study provide best practice recommendations for implementing DTI tractography in skeletal muscle and will inform future in vivo studies of healthy and pathological muscle structure.

Respiratory microbiome profiles are associated with distinct inflammatory phenotype and lung function in children with asthma.

BACKGROUND: Respiratory microbiome studies have fostered our understanding of various phenotypes and endotypes of heterogeneous asthma. However, the relationship between the respiratory microbiome and clinical phenotypes in children with asthma remains unclear. We aimed to identify microbiome-driven clusters reflecting the clinical features of asthma and their dominant microbiotas in children with asthma. METHODS: Induced sputum was collected from children with asthma, and microbiome profiles were generated via sequencing of the V3-V4 region of the 16S rRNA gene. Cluster analysis was performed using the partitioning around medoid clustering method. The dominant microbiota in each cluster was determined using the Linear Discriminant Effect Size analysis. Each cluster was analyzed for association among the dominant microbiota, clinical phenotype, and inflammatory cytokine. RESULTS: Eighty-three children diagnosed with asthma were evaluated. Among four clusters reflecting the clinical characteristics of asthma, cluster 1, dominated by Haemophilus and Neisseria, demonstrated lower post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) than that in the other clusters and more mixed granulocytic asthma. Neisseria negatively correlated with pre-BD and post-BD FEV1/FVC. Haemophilus and Neisseria positively correlated with programmed death-ligand (PD-L)1. CONCLUSION: To our knowledge, this study is the first to analyze the relationship between an unbiased microbiome-driven cluster and clinical phenotype in children with asthma. The cluster dominated by Haemophilus and Neisseria showed fixed airflow obstruction and mixed granulocytic asthma, which correlated with PD-L1 levels. Thus, microbiome-driven unbiased clustering can help identify new asthma phenotypes related to endotypes in childhood asthma.

Stretch reflex gain scaling at the shoulder varies with synergistic muscle activity.

The unique anatomy of the shoulder allows for expansive mobility but also sometimes precarious stability. It has long been suggested that stretch-sensitive reflexes contribute to maintaining joint stability through feedback control, but little is known about how stretch-sensitive reflexes are coordinated between the muscles of the shoulder. The purpose of this study was to investigate the coordination of stretch reflexes in shoulder muscles elicited by rotations of the glenohumeral joint. We hypothesized that stretch reflexes are sensitive to not only a given muscle's background activity but also the aggregate activity of all muscles crossing the shoulder based on the different groupings of muscles required to actuate the shoulder in three rotational degrees of freedom. We examined the relationship between a muscle's background activity and its reflex response in eight shoulder muscles by applying rotational perturbations while participants produced voluntary isometric torques. We found that this relationship, defined as gain scaling, differed at both short and long latencies based on the direction of voluntary torque generated by the participant. Therefore, gain scaling differed based on the aggregate of muscles that were active, not just the background activity in the muscle within which the reflex was measured. Across all muscles, the consideration of torque-dependent gain scaling improved model fits (ΔR2) by 0.17 ± 0.12. Modulation was most evident when volitional torques and perturbation directions were aligned along the same measurement axis, suggesting a functional role in resisting perturbations among synergists while maintaining task performance.NEW & NOTEWORTHY Careful coordination of muscles crossing the shoulder is needed to maintain the delicate balance between the joint's mobility and stability. We provide experimental evidence that stretch reflexes within shoulder muscles are modulated based on the aggregate activity of muscles crossing the joint, not just the activity of the muscle in which the reflex is elicited. Our results reflect coordination through neural coupling that may help maintain shoulder stability during encounters with environmental perturbations.

EcoSun Pass: A tool to evaluate the ecofriendliness of UV filters used in sunscreen products.

OBJECTIVE: Sunscreens play a major role in the EU sun protection strategy in order to prevent humans from UV light-induced skin damage. In recent years, the demand for high-quality sunscreen products including aspects of broad range and photostability of the UV protection, showing good spreadability onto human skin and excellent sensorial properties during and after application has increased. Environmental aspects are considered. Sunscreens are complex compositions, with UV filters being the key element in the formulations reaching up to about 30% in content in the final product. Some of these ingredients, however, may be regarded as hazardous for the aquatic environment. Nevertheless, the aquatic ecosystem represents only a single environmental compartment, which may be impacted by UV filters. Therefore, the EcoSun Pass (ESP) tool was developed in order to assess the overall environmental impact of UV filters in combination with its efficacy (Sun Protection Factor, SPF and UVA Protection Factor, UVA-PF). METHODS: For that purpose, at first 24 of the EU-approved UV filters for sunscreen applications were evaluated for their environmental hazard profiles. Nine example UV filter compositions representing both SPF 30 and 50 were evaluated for ecofriendliness using the ESP tool. RESULTS: The results revealed that two out of four SPF 30 compositions are considered as ecofriendly. Likewise, from the SPF 50 two out of five did meet the criteria for ecofriendliness. Furthermore, the results showed that most ecofriendly example formulations have also the lowest overall UV filter content in the product, based on the use of highly innovative and least hazardous UV filters. CONCLUSION: These results demonstrate that the tool is applicable to various formulations being present on the market and thus allows for a selection of most ecofriendly and efficient UV filters to be used in sunscreens.

OBJECTIF: les écrans solaires jouent un rôle majeur dans la stratégie de protection solaire de l'UE, afin de protéger les êtres humains contre les lésions cutanées causées par les rayons ultraviolets. Au cours des dernières années, la demande pour des écrans solaires de haute qualité a augmenté, notamment ceux ayant une bonne capacité d'étalement sur la peau humaine, d'excellentes propriétés sensorielles pendant et après l'application, une plage large et démontrant la photostabilité de la protection anti-UV. Les aspects environnementaux sont pris en compte. Les écrans solaires ont des compositions complexes, les filtres UV étant l'élément clé des formulations, avec une présence jusqu'à près de 30 % dans le contenu du produit final. Toutefois, certains de ces ingrédients peuvent être considérés comme dangereux pour l'environnement aquatique. Néanmoins, l'écosystème aquatique ne représente qu'un seul compartiment environnemental pouvant être affecté par les filtres UV. Par conséquent, l'outil EcoSun Pass (ESP) a été développé afin d'évaluer l'impact environnemental global des filtres UV, ainsi que leur efficacité (facteur de protection solaire, FPS et facteur de protection UV-A, UVAPF). MÉTHODES: dans ce but, les profils de risque environnemental de 24 des filtres UV approuvés dans l'UE, pour les applications d'écran solaire, ont d'abord été évalués. Le respect de l'environnement de neuf exemples de compositions de filtres UV, représentant les FPS 30 et 50, a été évalué à l'aide de l'outil ESP. RÉSULTATS: les résultats ont révélé que deux des quatre compositions de FPS 30 sont considérées comme écologiques. De même, deux écrans solaires sur cinq ayant un indice FPS 50 répondaient aux critères de respect de l'environnement. De plus, les résultats ont montré que la plupart des exemples de formulations écologiques contiennent également la plus faible teneur globale en filtres UV ; elles sont basées sur l'utilisation de filtres UV hautement innovants et les moins dangereux. CONCLUSION: ces résultats démontrent que l'outil est applicable à diverses formulations présentes sur le marché, et qu'il permet donc d'utiliser une sélection des filtres UV les plus écologiques et efficaces dans les écrans solaires.

Coprescription of opioid and naloxone in office-based practice and emergency department settings in the United States.

OBJECTIVES: The objective of the study was to estimate the national rates of naloxone coprescribing with opioids in office-based practice and emergency department (ED) settings in the United States (US). STUDY DESIGN: This study is a cross-sectional study. METHODS: We used the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) datasets to estimate the national rates of naloxone coprescribing with opioids for the period 2014-2016. The analysis was stratified into office-based practice and ED settings. In ED settings, opioid and naloxone could be given to patients while they were in ED or as a prescription at discharge. Patients of all ages were considered for the analysis and sampling weights were applied to estimate national rates. RESULTS: In office-based settings, 7918 sample visits included one or more opioid prescriptions (10.67 per 100 office visits). Of those, one included naloxone as a coprescription. In ED settings, the opioid prescription was given at discharge in 6124 sample visits (9.68 per 100 ED visits). Of those, two included naloxone as a coprescription. On the other hand, opioid was given to patients in the ED in 8811 sample visits (13.57 per 100 ED visits). Of those, 30 included naloxone as a coprescription. CONCLUSIONS: The rates of naloxone coprescribing with opioids were extremely low in office-based and ED settings in the US. Expanding access to naloxone is a key component of the public health response to the opioid crisis. Based on our study findings, promoting the coprescription of naloxone with opioids may provide greater access to naloxone for those who are at risk of opioid overdose.

Activated leucocyte cell adhesion molecule (ALCAM/CD166) regulates T cell responses in a murine model of food allergy.

Food allergy is a major public health problem. Studies have shown that long-term interactions between activated leucocyte cell adhesion molecule (ALCAM/CD166) on the surface of antigen-presenting cells, and CD6, a co-stimulatory molecule, influence immune responses. However, there are currently no studies on the functions of ALCAM in food allergy. Therefore, we aimed to identify the functions of ALCAM in ovalbumin (OVA)-induced food allergy using ALCAM-deficient mice. Wild-type (WT) and ALCAM-deficient (ALCAM-/- ) mice were sensitized intraperitoneally and with orally fed OVA. The mice were killed, and parameters related to food allergy and T helper type 2 (Th2) immune responses were analysed. ALCAM serum levels increased and mRNA expression decreased in OVA-challenged WT mice. Serum immunoglobulin (Ig)E levels, Th2 cytokine mRNA and histological injuries were higher in OVA-challenged WT mice than in control mice, and these were attenuated in ALCAM-/- mice. T cell proliferation of total cells, CD3+ CD4+ T cells and activated T cells in immune tissues were diminished in OVA-challenged ALCAM-/- mice. Proliferation of co-cultured T cells and dendritic cells (DCs) was decreased by the anti-CD6 antibody. In addition, WT mice sensitized by adoptive transfer of OVA-pulsed ALCAM-/- BM-derived DCs showed reduced immune responses. Lastly, serum ALCAM levels were higher in children with food allergy than in control subjects. In this study, serum levels of ALCAM were elevated in food allergy-induced WT mice and children with food allergy. Moreover, immune responses and T cell activation were attenuated in OVA-challenged ALCAM-/- mice. These results indicate that ALCAM regulates food allergy by affecting T cell activation.

Chitotriosidase inhibits allergic asthmatic airways via regulation of TGF-ß expression and Foxp3+ Treg cells.

BACKGROUND: Chitotriosidase (chitinase 1, Chit1), a major true chitinase in humans, is induced in childhood asthma and has been implicated in the pathogenesis of a variety of inflammatory and tissue remodeling responses. However, the role and the mechanisms that underlie these contributions to the diseases have not been defined. We hypothesized that Chit1 plays a significant role in the pathogenesis of allergic asthma. METHODS: Wild-type and Chit1-deficient mice and cells in culture were used to define the roles of Chit1 in models of allergic adaptive Th2 inflammation. In addition, the levels of sputum Chit1 were evaluated in pediatric asthma patients and compared to control. RESULTS: The levels of sputum Chit1 were significantly increased in the patients with childhood asthma. Mice with Chit1 null mutation demonstrated enhanced allergic Th2 inflammatory and cytokine and IgE responses to OVA or house dust mite allergen sensitization and challenge. However, the expression levels of TGF-ß1 were significantly decreased with a diminished number of Foxp3+ regulatory T cells (Treg) in the lungs of Chit1-/- mice compared to WT controls. In vitro, the absence of Chit1 significantly reduced TGF-ß-stimulated conversion of CD4+ CD25- naïve T cells to CD4+ Foxp3+ Treg cells, suggesting Chit1 is required for optimal effect of TGF-ß1 in Treg cell differentiation. CONCLUSION: Chit1 plays a protective role in the pathogenesis of allergic inflammation and asthmatic airway responses via regulation of TGF-ß expression and Foxp3+ Treg cells.

Damage control surgery in perforated diverticulitis: ongoing peritonitis at second surgery predicts a worse outcome.

PURPOSE: Damage control strategy (DCS) is a two-staged procedure for the treatment of perforated diverticular disease complicated by generalized peritonitis. The aim of this retrospective multicenter cohort study was to evaluate the prognostic impact of an ongoing peritonitis at the time of second surgery. METHODS: Consecutive patients who underwent DCS for perforated diverticular disease of the sigmoid colon with generalized peritonitis at four surgical centers were included. Damage control strategy is a two-stage emergency procedure: limited resection of the diseased colonic segment, closure of oral and aboral colon, and application of a negative pressure assisted abdominal closure system at the initial surgery followed by second laparotomy 48 h later. Therein, decision for definite reconstruction (anastomosis or Hartmann's procedure (HP)) is made. An ongoing peritonitis at second surgery was defined as presence of visible fibrinous, purulent, or fecal peritoneal fluid. Microbiologic findings from peritoneal smear at first surgery were collected and analyzed. RESULTS: Between 5/2011 and 7/2017, 74 patients underwent a DCS for perforated diverticular disease complicated by generalized peritonitis (female: 40, male: 34). At second surgery, 55% presented with ongoing peritonitis (OP). Patients with OP had higher rate of organ failure (32 vs. 9%, p = 0.024), higher Mannheim Peritonitis Index (25.2 vs. 18.9; p = 0.001), and increased operation time (105 vs. 84 min., p = 0.008) at first surgery. An anastomosis was constructed in all patients with no OP (nOP) at second surgery as opposed to 71% in the OP group (p < 0.001). Complication rate (44 vs. 24%, p = 0.092), mortality (12 vs. 0%, p = 0.061), overall number of surgeries (3.4 vs. 2.4, p = 0.017), enterostomy rate (76 vs. 36%, p = 0.001), and length of hospital stay (25 vs. 18.8 days, p = 0.03) were all increased in OP group. OP at second surgery occurred significantly more often in patients with Enterococcus infection (81 vs. 44%, p = 0.005) and with fungal infection (100 vs. 49%, p = 0.007). In a multivariate analysis, Enterococcus infection was associated with increased morbidity (67 vs. 21%, p < 0.001), enterostomy rate (81 vs. 48%, p = 0.017), and anastomotic leakage (29 vs. 6%, p = 0.042), whereas fungal peritonitis was associated with an increased mortality (43 vs. 4%, p = 0.014). CONCLUSION: Ongoing peritonitis after DCS is a predictor of a worse outcome in patients with perforated diverticulitis. Enterococcal and fungal infections have a negative impact on occurrence of OP and overall outcome.

Endopeptidase inhibition attenuates the contraction induced by big endothelin-1 of isolated human penile erectile tissue.

Peptides, such as C-type natriuretic peptide (CNP), vasoactive intestinal polypeptide (VIP) and endothelin 1 (ET-1), are involved in the control of penile erectile tissue (corpus cavernosum = CC). Inhibiting the degradation of CNP and VIP or conversion of Big ET-1 into ET-1 by endopeptidase enzymes should result in an enhancement of CC smooth muscle relaxation. Using the tissue bath technique, responses of isolated CC, challenged by noradrenaline (NA, 1 µm), to increasing concentrations of the endopeptidase inhibitor KC 12615 (1 nm - 10 µm), CNP and VIP (0.1 nm - 1 µm), were investigated. Effects of CNP, VIP and Big ET-1 (0.1 nm - 100 nm) on the tissue tension were also evaluated following pre-exposure to 10 µm of KC 12615. Big ET-1 induced contraction of the CC amounting to a force generation of 1,200 mg. The contraction was attenuated in the presence of KC 12615 by 35% and 50%, respectively. The tension induced by NA was reversed by VIP and CNP to 38.7% ± 15.8% and 61% ± 13%, respectively, of the initial force. The findings might be of significance with regard to future pharmacological treatment options for male ED, where an endothelial dysfunction exists.

In vitro water resistance testing using SPF simulation based on spectroscopic analysis of rinsed sunscreens.

OBJECTIVE: Water resistance retention (WRR) is the third performance attribute of sunscreens. Today, the standardized method for testing WRR is performed in vivo. For screening purposes, an in vitro method is highly preferable. Up to now, however, available methods have failed in accurately predicting in vivo WRR. In this study, we examine a novel in vitro approach aimed at enhancing in vivo prediction of WRR. METHODS: We investigated two approaches, including a traditional procedure referred to as the 'plate method', which involves measuring in vitro sun-protection factor (SPF) before and after water immersion, and a new approach termed the 'solution method'. The latter employed a computational method to calculate the SPF using UV transmittance measurements of a sunscreen solution, obtained by rinsing the substrate without water immersion and with water immersion. It also had a model function for describing film irregularity. The aim was to avoid the effect of substrate-to-product affinity on the film distribution, which impacts the measured absolute value of the in vitro SPF occurring in the conventional approach. For both methodologies, we assessed two substrates for the sunscreen application based on different polymers, the widely used polymethylmethacrylate (PMMA) and the ethylene methacrylate acid copolymer (EMA). RESULTS: The agreement between in vivo and in vitro WRR values obtained from each of the four test conditions was analysed using different sunscreens. No correlation was found between in vivo and in vitro WRR using the plate method, independently of the plate type. In contrast, the solution method, using EMA plates, revealed a significant correlation between in vivo and in vitro results, with an especially high correlation for in vivo non-water-resistant sunscreens. The results of two operators were comparable. The solution method was unsuitable for PMMA plates. CONCLUSION: Despite the small discrepancy remaining between WRR values obtained from the in vitro solution method and in vivo method, which itself shows variability in results, this work provided a new insight into the in vitro testing of water resistance of sunscreens.

A multicenter study on anaphylaxis caused by peanut, tree nuts, and seeds in children and adolescents.

Peanut (PN) and tree nuts (TNs) are common causes of anaphylaxis in Western countries, but no information is available in Korea. To feature clinical characteristics of anaphylaxis caused by PN, TNs, and seeds, a retrospective medical record review was performed in 14 university hospitals in Korea (2009-2013). One hundred and twenty-six cases were identified, with the mean age of 4.9 years. PN, walnut (WN), and pine nut accounted for 32.5%, 41.3%, and 7.1%, respectively. The median values of specific IgE (sIgE) to PN, WN, and pine nut were 10.50, 8.74, and 4.61 kUA /l, respectively. Among 50 cases managed in the emergency department, 52.0% were treated with epinephrine, 66.0% with steroid, 94.0% with antihistamines, 36.0% with oxygen, and 48.0% with bronchodilator. In conclusion, WN, PN, and pine nut were the three most common triggers of anaphylaxis in Korean children, and anaphylaxis could occur at remarkably low levels of sIgE.

Increased sputum levels of thymus and activation-regulated chemokine in children with asthma not eosinophilic bronchitis.

BACKGROUND: Thymus and activation-regulated chemokine (TARC), a member of the CC chemokine family, plays a crucial role in Th2-specific inflammation. We aimed to determine the concentration of sputum TARC in children with asthma and eosinophilic bronchitis (EB) and its relation with eosinophilic inflammation, pulmonary function, and bronchial hyper-responsiveness. METHODS: In total, 90 children with asthma, 38 with EB, and 45 control subjects were enrolled. TARC levels were measured in sputum supernatants using an ELISA. We performed pulmonary function tests and measured exhaled fractional nitric oxide, eosinophil counts in blood, and sputum and serum levels of total IgE in all children. RESULTS: Sputum TARC levels were significantly higher in children with asthma than in either children with EB (p=0.004) or the control subjects (p=0.014). Among patients with asthma, sputum TARC concentration was higher in children with sputum eosinophilia than in those without sputum eosinophilia (p=0.035). Sputum TARC levels positively correlated with eosinophil counts in sputum, serum total IgE levels, exhaled fractional nitric, and the bronchodilator response. Negative significant correlations were found between sputum TARC and FEV1/FVC (the ratio of forced expiratory volume in one second and forced expiratory vital capacity) or PC20 (the provocative concentration of methacholine causing a 20% decrease in the FEV1). CONCLUSION: Elevated TARC levels in sputum were detected in children with asthma but not in children with EB. Sputum TARC could be a supportive marker for discrimination of asthma from EB in children showing characteristics of eosinophilic airway inflammation.

Relationship between sputum clusterin levels and childhood asthma.

BACKGROUND: Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammation-associated diseases. Clusterin levels in childhood asthma have not been evaluated. OBJECTIVES: (1) To evaluate sputum clusterin levels in children with asthma compared to a control group. (2) To assess the relationships between sputum clusterin levels and airway inflammation, pulmonary function, and bronchial hyperresponsiveness. METHODS: This study included 170 children aged 5-18 years with stable asthma (n = 91), asthma exacerbation (n = 29), or no asthma (healthy controls; n = 50). Induced sputum, pulmonary function, and methacholine challenge tests were performed. Stable asthma was classified into two groups according to the severity. Clusterin levels in sputum were measured using an enzyme-linked immunosorbent assay. RESULTS: Children with stable asthma had a higher clusterin level than healthy controls [4540 (3872-5651) pg/mL vs. 3857 (1054-4369) pg/mL, P < 0.001]. The clusterin level was also more elevated in eosinophil-dominant sputum than in non-eosinophilic sputum in stable asthma [5094 (4243-6257) pg/mL vs. 4110 (1871-4839) pg/mL, P = 0.0017]. Clusterin levels were associated with asthma severity. Paradoxically, clusterin levels were lower during asthma exacerbation than in stable asthma [1838 (350-4790] pg/mL vs. 4540 (3872-5651) pg/mL, P < 0.001]. Clusterin levels were strongly correlated with the methacholine concentration that caused a 20% decrease in the forced expiratory volume in 1 s (r = -0.617, P < 0.001); there was no significant correlation between clusterin levels and other pulmonary function parameters. CONCLUSIONS AND CLINICAL RELEVANCE: Clusterin levels were altered in children with stable asthma and asthma exacerbation because of its antioxidant and anti-inflammatory effects. Clusterin may be a marker that reflects airway inflammation and severity of symptoms, and it can be used in the assessment and management of childhood asthma.

Reduction of cardiac and coronary artery doses in irradiation of left-sided breast cancer during inspiration breath hold : A planning study.

BACKGROUND AND PURPOSE: The radiation dose received by the heart during adjuvant left-sided breast irradiation plays a crucial role in development of late toxicity. Although the absolute risk of cardiotoxicity can be reduced with modern irradiation techniques, cardiotoxic chemotherapy increases the risk of late damage. Thus, the radiation dose to the heart should be minimized. This study evaluated the influence of different amplitudes of inspiration breath hold (IBH) during simulated left-sided breast irradiation on cardiac doses compared to free breathing (FB). PATIENTS AND METHODS: CT data of 11 lung cancer patients were retrospectively used as left-sided pseudo-breast cancer cases. Two CT scans were used, one during IBH and one during FB, and two treatment plans were generated. Relevant heart, lung, and left anterior descending artery (LAD) parameters were derived from dose-volume histograms. The normal tissue complication probabilities (NTCPs) for the heart were calculated based on the relative seriality model. Inspiration depth was quantified using chest volume and diameter, and correlated thereafter to a possible sparing of heart tissue. RESULTS: Mean reduction of heart dose for IBH compared to FB was 40 % (1.65 vs. 0.99 Gy; p = 0.007). Maximum dose to the heart and LAD could be decreased by 33 % (p = 0.011) and 43 % (p = 0.024), respectively. The mean anteroposterior shift was 5 mm (range 0.9-9.5 mm). Significant negative correlations between the relative change in LAD mean dose and the mean thoracic diameter and volume change, as well as with the absolute change in thoracic diameter were seen. The NTCP for cardiac mortality could be decreased by about 78 % (p = 0.017). CONCLUSION: For left-sided breast cancer patients, cardiac doses can be significantly decreased with tangential irradiation and IBH.

Effect of stress hyperglycemia and intensive rehabilitation therapy in non-diabetic hemorrhagic stroke: Korean Stroke Cohort for Functioning and Rehabilitation.

BACKGROUND AND PURPOSE: We investigated the effect of stress hyperglycemia on the functional outcomes of non-diabetic hemorrhagic stroke. In addition, we investigated the usefulness of intensive rehabilitation for improving functional outcomes in patients with stress hyperglycemia. METHODS: Non-diabetic hemorrhagic stroke patients were recruited and divided into two groups: intracerebral hemorrhage (ICH) (n = 165) and subarachnoid hemorrhage (SAH) (n = 156). Each group was divided into non-diabetics with or without stress hyperglycemia. Functional assessments were performed at 7 days and 3, 6 and 12 months after stroke onset. The non-diabetic with stress hyperglycemia groups were again divided into two groups who either received or did not receive intensive rehabilitation treatment. Serial functional outcome was compared between groups. RESULTS: For the ICH group, patients with stress hyperglycemia had worse modified Rankin Scale, National Institutes of Health Stroke Scale, Functional Ambulatory Category and Korean Mini-Mental State Examination scores than patients without stress hyperglycemia. For the SAH group, patients with stress hyperglycemia had worse scores on all functional assessments than patients without stress hyperglycemia at all time-points. After intensive rehabilitation treatment of patients with stress hyperglycemia, the ICH group had better scores on Functional Ambulatory Category and the SAH group had better scores on all functional assessments than patients without intensive rehabilitation treatment. CONCLUSIONS: Stress hyperglycemia affects the long-term prognosis of non-diabetic hemorrhagic stroke patients. Among stress hyperglycemia patients, intensive rehabilitation can enhance functional improvement after stroke.

Effects of endopeptidase inhibition on the relaxation response of isolated human penile erectile tissue to vasoactive peptides.

Peptides, such as CNP, CGRP and VIP, are involved in the function of male penile erectile tissue. Tissue levels of said peptides are controlled by the endopeptidase enzymes. Theoretically, the inhibition of the degradation of CNP, CGRP and/or VIP should result in an enhancement in penile smooth muscle relaxation. The effects were investigated of CNP or VIP (0.1 nm-1 µm), without and following pre-exposure of the tissue to a threshold concentration of the endopeptidase inhibitor KC 12615 (10 µm, for 20 min), on the reversion of tension induced by means of electrical field stimulation. Drug effects on the production of cyclic AMP/GMP were also evaluated. Neither KC 12615, CNP and VIP nor the combination of CNP plus KC 12615 or VIP plus KC 12615 increased the response of the tissue to EFS. While no effects were observed of a pre-exposure of the tissue to KC 12615 on the production of cyclic AMP in the presence of VIP, an enhancement was registered in the accumulation of cyclic AMP in the presence of CNP plus KC 12615. Further studies are indicated to investigate whether endopeptidase inhibitors might tend to be more effective in tissues affected by a decreased local production of vasoactive peptides.

IgE cross-reactivity of peanut with walnut and soybean in children with food allergy.

BACKGROUND: Peanut allergies are common and can be life-threating for sensitised individuals. Peanut allergens share significant amino acid homology with those of other legumes and tree nuts, but their cross-reactivity still remains unclear. OBJECTIVE: We sought to determine the clinical significance of the cross-reactivity of peanut allergens with those of walnut and soybean. METHODS: Pooled sera from eight subjects with both peanut and walnut specific IgE were investigated in an inhibition test. After the sera were incubated with either peanut or walnut protein extracts, the quantity of IgE antibodies against the peanut and walnut was measured using an immunoCAP test. Likewise, pooled sera from 18 subjects with both peanut and soybean specific IgE antibodies were incubated with either peanut or soybean protein extracts and evaluated with a peanut and soybean immunoCAP test. SDS-PAGE and immunoblotting were also performed with peanut, walnut and soybean protein extracts and relevant sera. RESULTS: Peanut specific IgE was inhibited up to 20% and 26% by walnut and soybean protein extracts, respectively. In reverse, walnut and soybean specific IgE were inhibited up to 21% and 23% by peanut protein extracts, respectively. In the immunoblot analysis, pooled serum from the subjects with peanut specific IgE antibodies reacted with walnut protein extracts significantly. CONCLUSION: Although the clinical significance of the cross-reactivity of peanut specific IgE with walnut and soybean protein extracts has not been established, we believe that individuals who are allergic to peanuts need to be cautious about consuming walnuts and soybeans.

Damage control strategy for the treatment of perforated diverticulitis with generalized peritonitis.

BACKGROUND: The best surgical strategy for the management of perforated diverticulitis with generalized peritonitis of the sigmoid colon is not clearly defined. The aim of this retrospective cohort study was to evaluate the value of a damage control strategy. METHODS: All patients who underwent emergency laparotomy for perforated diverticular disease of the sigmoid colon with generalized peritonitis between 2010 and 2015 were included. The damage control strategy (study group), included a two- stage procedure: limited resection of the diseased colonic segment, closure of proximal colon and distal stump, and application of an abdominal vacuum at the initial surgery followed by second-look laparotomy 24-48 h later At this point a choice was made between anastomosis and Hartmann's procedure. The control group consisted of patients receiving definitive reconstruction (anastomosis or Hartmann's procedure) at the initial operation. RESULTS: Thirty-seven patients were included in the study. Damage control strategy was applied in 19 patients and the control group consisted of 18 patients. Both groups were comparable in terms of demographics, severity of peritonitis, and comorbidities. The overall postoperative mortality was 11 % (n = 4). There were no statistically significant differences between both groups regarding postoperative morbidity and mortality; however, a significantly higher proportion of patients in the control group had a stoma after the initial hospital stay (83 vs. 47 %, p = 0.038). This difference was still significant after adjustment for sex, age, Mannheim Peritonitis Index, American Society of Anesthesiologists class and presence of septic shock at presentation. At the end of the follow-up period, 15 of 17 survivors in the study group and 13 of 16 survivors in the control group had their intestinal continuity restored (p = 0.66). CONCLUSIONS: Damage control strategy in patients with generalized peritonitis due to perforated diverticulitis leads to a significantly reduced stoma rate after the initial hospital stay without an increased risk of postoperative morbidity.

Does financial compensation for living kidney donation change willingness to donate?

The potential use of financial compensation to increase living kidney donation rates remains controversial in potentially introducing undue inducement of vulnerable populations to donate. This cross-sectional study assessed amounts of financial compensation that would generate motivation and an undue inducement to donate to family/friends or strangers. Individuals leaving six Departments of Motor Vehicles were surveyed. Of the 210 participants who provided verbal consent (94% participation rate), respondents' willingness to donate would not change (70%), or would increase (29%) with compensation. Median lowest amounts of financial compensation for which participants would begin to consider donating a kidney were $5000 for family/friends, and $10,000 for strangers; respondents reporting $0 for family/friends (52%) or strangers (26%) were excluded from analysis. Median lowest amounts of financial compensation for which participants could no longer decline (perceive an undue inducement) were $50,000 for family/friends, and $100,000 for strangers; respondents reporting $0 for family/friends (44%) or strangers (23%) were excluded from analysis. The two most preferred forms of compensation included: direct payment of money (61%) and paid leave (21%). The two most preferred uses of compensation included: paying off debt (38%) and paying nonmedical expenses associated with the transplant (29%). Findings suggest tolerance for, but little practical impact of, financial compensation. Certain compensation amounts could motivate the public to donate without being perceived as an undue inducement.

Pandemic influenza virus, pH1N1, induces asthmatic symptoms via activation of innate lymphoid cells.

BACKGROUND: The pandemic strain of the influenza A virus (pH1N1) in 2009 caused many complications in patients. In this study, we introduce asthmatic symptoms as a complication of pH1N1 infection in children, not having a relationship with asthma history. The aim of this study was to quantify asthmatic symptoms in pH1N1-infected children and elucidate the underlying mechanisms of airway hyper-responsiveness (AHR) induced in a murine model of pH1N1 infection. METHODS: As a retrospective study, pH1N1-infected children who were hospitalized with moderate to severe acute asthmatic symptoms were enrolled and administered a methacholine challenge test (MCT) at 3 months post-discharge. Additionally, the induction of AHR by pH1N1 infection was measured by MCT in wild-type and Rag1(-/-) mice. The effect of the innate immune response on the development of AHR following pH1N1 infection was investigated. RESULTS: More than 70% of the pH1N1-infected children without a pre-infection diagnosis of asthma had a negative response on the MCT. None of these children had recurrent wheezing or asthma during the 3 years following pH1N1 infection. The development of AHR in pH1N1-infected mice was associated with an elevation in IL-33 and innate lymphoid cells 2 (ILC2). CONCLUSIONS: This study demonstrates that pH1N1 infection directly induces transient asthmatic symptoms in patients regardless of their medical history. pH1N1 infection was shown to stimulate the rapid development of AHR and Th2-type cytokine secretion in mice via the activation of ILC2; it may be activated independently of adaptive immunity.