Perfusion imaging heterogeneity during NO inhalation distinguishes pulmonary arterial hypertension (PAH) from healthy subjects and has potential as an imaging biomarker.

BACKGROUND: Without aggressive treatment, pulmonary arterial hypertension (PAH) has a 5-year mortality of approximately 40%. A patient's response to vasodilators at diagnosis impacts the therapeutic options and prognosis. We hypothesized that analyzing perfusion images acquired before and during vasodilation could identify characteristic differences between PAH and control subjects. METHODS: We studied 5 controls and 4 subjects with PAH using HRCT and 13NN PET imaging of pulmonary perfusion and ventilation. The total spatial heterogeneity of perfusion (CV2Qtotal) and its components in the vertical (CV2Qvgrad) and cranio-caudal (CV2Qzgrad) directions, and the residual heterogeneity (CV2Qr), were assessed at baseline and while breathing oxygen and nitric oxide (O2 + iNO). The length scale spectrum of CV2Qr was determined from 10 to 110 mm, and the response of regional perfusion to O2 + iNO was calculated as the mean of absolute differences. Vertical gradients in perfusion (Qvgrad) were derived from perfusion images, and ventilation-perfusion distributions from images of 13NN washout kinetics. RESULTS: O2 + iNO significantly enhanced perfusion distribution differences between PAH and controls, allowing differentiation of PAH subjects from controls. During O2 + iNO, CV2Qvgrad was significantly higher in controls than in PAH (0.08 (0.055-0.10) vs. 6.7 × 10-3 (2 × 10-4-0.02), p < 0.001) with a considerable gap between groups. Qvgrad and CV2Qtotal showed smaller differences: - 7.3 vs. - 2.5, p = 0.002, and 0.12 vs. 0.06, p = 0.01. CV2Qvgrad had the largest effect size among the primary parameters during O2 + iNO. CV2Qr, and its length scale spectrum were similar in PAH and controls. Ventilation-perfusion distributions showed a trend towards a difference between PAH and controls at baseline, but it was not statistically significant. CONCLUSIONS: Perfusion imaging during O2 + iNO showed a significant difference in the heterogeneity associated with the vertical gradient in perfusion, distinguishing in this small cohort study PAH subjects from controls.

Optimization and use of near infrared imaging to guide lymph node collection in rhesus macaques (Macaca mulatta).

BACKGROUND: Identification of lymph nodes (LNs) draining a specific site or in obese macaques can be challenging. METHODS: Indocyanine Green (ICG) was administered intradermal (ID), intramuscular, in the oral mucosa, or subserosal in the colon followed by Near Infrared (NIR) imaging. RESULTS: After optimization to maximize LN identification, intradermal ICG was successful in identifying 50-100% of the axillary/inguinal LN at a site. Using NIR, collection of peripheral and mesenteric LNs in obese macaques was 100% successful after traditional methods failed. Additionally, guided collection of LNs draining the site of intraepithelial or intramuscular immunization demonstrated significantly increased numbers of T follicular helper (Tfh) cells in germinal centers of draining compared to nondraining LNs. CONCLUSION: These imaging techniques optimize our ability to evaluate immune changes within LNs over time, even in obese macaques. This approach allows for targeted serial biopsies that permit confidence that draining LNs are being harvested throughout the study.

PET Imaging Reveals Early Pulmonary Perfusion Abnormalities in HIV Infection Similar to Smoking.

Chronic obstructive pulmonary disease (COPD) is the most common noninfectious pulmonary disease among people living with HIV, independent of smoking. However, the cause for this enhanced susceptibility remains unclear, and the effects of HIV on pulmonary perfusion and ventilation are unknown. Methods: We used PET/CT in 46 smokers and nonsmokers, 23 of whom had documented HIV infection. Emphysema was assessed by CT and perfusion by 13N (13NN) PET scans. After removal of image noise, vertical and axial gradients in perfusion were calculated. We tested for differences in the total spatial heterogeneity of perfusion (CV2Qtotal) and its components (CV2Qtotal = CV2Qvgrad [vertical gradient] + CV2Qzgrad [axial gradient] + CV2Qr [residual heterogeneity]) among groups. Results: There were no significant differences in demographic parameters among groups, and all subjects had minimal radiographic evidence of emphysema. Compared with controls, nonsmokers living with HIV had a significantly greater CV2Qr/CV2Qtotal (0.48 vs. 0.36, P = 0.05) and reduced CV2Qvgrad/CV2Qtotal (0.46 vs. 0.65, P = 0.038). Smokers also had a reduced CV2Qvgrad/CV2Qtotal, however, there was no significant difference in CV2Qvgrad/CV2Qtotal between smokers living with and without HIV (0.39 vs. 0.34, P = 0.58), despite a decreased vertical perfusion gradient (Qvgrad) in smokers living with HIV. Conclusion: In nonsmokers living with well-controlled HIV and minimal radiographic emphysema, HIV infection contributes to pulmonary perfusion abnormalities similar to smokers. These data indicate the onset of subclinical pulmonary perfusion abnormalities that could herald the development of significant lung disease in these susceptible individuals.

In vitro inhibitory effect of aluminum phthalocyanine tetrasulfonate chloride against Leishmania (Viannia) Peruviana and Leishmania (Viannia) Braziliensis. / Efecto inhibitorio in vitro de la ftalocianina de aluminio tetrasulfonada clorada frente a Leishmania (Viannia) peruviana y Leishmania (Viannia) braziliensis.

OBJECTIVES: To evaluate the in vitro photodynamic activity of aluminum phthalocyanine tetrasulfonate chloride (AlPcClS4) on promastigotes and amastigotes of Leishmania (Viannia) peruviana and Leishmania (Viannia) braziliensis. MATERIALS AND METHODS: The activity of photodynamic therapy using AlPcClS4 on Leishmania promastigote and amastigotes was determined by the Methyl Thiazole Tetrazolium (MTT) colorimetric method and quantitative PCR, respectively. RESULTS: Photodynamic treatment showed an inhibitory effect on promastigotes, particularly on Leishmania (V.) peruviana, to a lesser extent on Leishmania (V.) braziliensis and also on intracellular forms of both species. At 24 hours post-radiation, using concentrations of 200 µM and 350 µM, the inhibitory effect on Leishmania (V.) peruviana was 72.9% and 73.9% respectively; at 96 hours the inhibitory effect was of 78.8% and 80.6%, respectively. Regarding intracellular forms, the inhibitory effect on Leishmania (V.) peruviana amastigotes was 57.8% at 72 hours post-treatment, using a concentration of 200 µM. The IC50 was 56.5, 50, 44 and 39.7 µM, at 24, 48, 72 and 96 hours post-radiation, respectively. CONCLUSIONS: Photodynamic therapy using AlPcClS4 against Leishmania species showed encouraging results, mainly on Leishmania (V.) peruviana, suggesting a potential use as an alternative or complement to the usual treatment of tegumentary leishmaniasis. However, new trials are still required to determine the selectivity index for the intracellular form of the parasite, and to develop methods to facilitate the efficient entry of the molecule into the host cell and the parasite.

OBJETIVOS: Evaluar la actividad fotodinámica in vitro de la ftalocianina de aluminio tetrasulfonada clorada (AlPcClS4) sobre promastigotes y amastigotes de Leishmania (Viannia) peruviana y Leishmania (Viannia) braziliensis. MATERIALES Y MÉTODOS: La actividad del tratamiento fotodinámico empleando AlPcClS4 sobre promastigotes y amastigotes de Leishmania fue determinada mediante el método colorimétrico Metil Tiazol Tetrazolium (MTT) y PCR cuantitativo, respectivamente. RESULTADOS: El tratamiento fotodinámico presentó un efecto inhibitorio sobre promastigotes, principalmente sobre Leishmania (V.) peruviana, en menor proporción sobre Leishmania (V.) braziliensis y sobre las formas intracelulares de ambas especies. En Leishmania (V.) peruviana, a las 24 horas posirradiación a 200 µM y 350 µM el efecto inhibitorio fue del 72,9% y 73,9%, respectivamente y a las 96 horas fue del 78,8% y 80,6%, respectivamente. En las formas intracelulares, empleando 200 µM y evaluado a las 72 horas postratamiento, se observó una inhibición del 57,8% de amastigotes de Leishmania (V.) peruviana. El IC50 fue del 56,5; 50; 44; y 39,7 µM, que corresponde a las 24, 48, 72 y 96 horas posirradiación, respectivamente. CONCLUSIONES: El tratamiento fotodinámico empleando AlPcClS4 frente a las especies de Leishmania presentó resultados alentadores principalmente sobre Leishmania (V.) peruviana, lo cual sugiere su potencial uso como alternativa o complemento del tratamiento convencional de la leishmaniasis tegumentaria. Sin embargo, aún se requiere continuar con nuevos ensayos para determinar el índice de selectividad sobre el parásito en su forma intracelular, y desarrollar estrategias que faciliten el ingreso eficiente de la molécula hacia la célula hospedera y al parásito.

Lung parenchymal and airway changes on CT imaging following allergen challenge and bronchoalveolar lavage in atopic and asthmatic subjects.

BACKGROUND: Computed tomography (CT) imaging findings in the lungs in the setting of an acute allergic response and following bronchoalveolar lavage (BAL) are not well established. Our goals are to characterize the pulmonary CT findings of acute allergic response in both asthmatic and non-asthmatic subjects and, secondarily, to characterize the pulmonary imaging findings following BAL. METHODS: In this prospective observational (cohort) study, we identified atopic, asthmatic (AA) and atopic, non-asthmatic (ANA) subjects. CT of the chest was performed following BAL and instillation of an allergen (AL) and of an inert diluent (DL). Two radiologists analyzed the CT examinations for airway and parenchymal changes. RESULTS: We had a cohort of 20 atopic subjects (AA=10, ANA=10; F=11, M=9; median age: 23.5 years, range: 18-48 years). Compared to diluent instillation and BAL, allergen instillation resulted in more significant bronchial wall thickening (AL=70%, DL=0%, BAL=0%, P<0.01), consolidations (AL=55%, DL=0%, BAL=15%, P<0.05), and septal thickening (AL=35%, DL=0%, BAL=0%, P<0.01). When present, consolidations tended to be more common in asthmatic subjects compared to non-asthmatics following instillation of the allergen, although this did not reach statistical significance (AA=80% vs. ANA=30%; P=0.07). BAL, on the other hand, resulted in more ground-glass opacities (BAL=15/20, 75% vs. AL=2/20, 10%, vs. DL=0/20, 0%; P<0.01). CONCLUSIONS: Acute allergic response in the lungs can result in significant bronchial wall thickening, septal thickening, and consolidations in those with atopy, particularly those with asthma. Localized ground-glass opacities may be expected following BAL, and care should be taken so as to not misinterpret these as significant pathology.

Efecto inhibitorio in vitro de la ftalocianina de aluminio tetrasulfonada clorada frente a Leishmania (Viannia) peruviana y Leishmania (Viannia) braziliensis / In vitro inhibitory effect of aluminum phthalocyanine tetrasulfonate chloride against Leishmania (Viannia) Peruviana and Leishmania (Viannia) Braziliensis

RESUMEN Objetivos: Evaluar la actividad fotodinámica in vitro de la ftalocianina de aluminio tetrasulfonada clorada (AlPcClS4) sobre promastigotes y amastigotes de Leishmania (Viannia) peruviana y Leishmania (Viannia) braziliensis. Materiales y métodos: La actividad del tratamiento fotodinámico empleando AlPcClS4 sobre promastigotes y amastigotes de Leishmania fue determinada mediante el método colorimétrico Metil Tiazol Tetrazolium (MTT) y PCR cuantitativo, respectivamente. Resultados: El tratamiento fotodinámico presentó un efecto inhibitorio sobre promastigotes, principalmente sobre Leishmania (V.) peruviana, en menor proporción sobre Leishmania (V.) braziliensis y sobre las formas intracelulares de ambas especies. En Leishmania (V.) peruviana, a las 24 horas posirradiación a 200 µM y 350 µM el efecto inhibitorio fue del 72,9% y 73,9%, respectivamente y a las 96 horas fue del 78,8% y 80,6%, respectivamente. En las formas intracelulares, empleando 200 µM y evaluado a las 72 horas postratamiento, se observó una inhibición del 57,8% de amastigotes de Leishmania (V.) peruviana. El IC50 fue del 56,5; 50; 44; y 39,7 µM, que corresponde a las 24, 48, 72 y 96 horas posirradiación, respectivamente. Conclusiones: El tratamiento fotodinámico empleando AlPcClS4 frente a las especies de Leishmania presentó resultados alentadores principalmente sobre Leishmania (V.) peruviana, lo cual sugiere su potencial uso como alternativa o complemento del tratamiento convencional de la leishmaniasis tegumentaria. Sin embargo, aún se requiere continuar con nuevos ensayos para determinar el índice de selectividad sobre el parásito en su forma intracelular, y desarrollar estrategias que faciliten el ingreso eficiente de la molécula hacia la célula hospedera y al parásito.

ABSTRACT Objectives: To evaluate the in vitro photodynamic activity of aluminum phthalocyanine tetrasulfonate chloride (AlPcClS4) on promastigotes and amastigotes of Leishmania (Viannia) peruviana and Leishmania (Viannia) braziliensis. Materials and methods: The activity of photodynamic therapy using AlPcClS4 on Leishmania promastigote and amastigotes was determined by the Methyl Thiazole Tetrazolium (MTT) colorimetric method and quantitative PCR, respectively. Results: Photodynamic treatment showed an inhibitory effect on promastigotes, particularly on Leishmania (V.) peruviana, to a lesser extent on Leishmania (V.) braziliensis and also on intracellular forms of both species. At 24 hours post-radiation, using concentrations of 200 μM and 350 μM, the inhibitory effect on Leishmania (V.) peruviana was 72.9% and 73.9% respectively; at 96 hours the inhibitory effect was of 78.8% and 80.6%, respectively. Regarding intracellular forms, the inhibitory effect on Leishmania (V.) peruviana amastigotes was 57.8% at 72 hours post-treatment, using a concentration of 200 μM. The IC50 was 56.5, 50, 44 and 39.7 μM, at 24, 48, 72 and 96 hours post-radiation, respectively. Conclusions: Photodynamic therapy using AlPcClS4 against Leishmania species showed encouraging results, mainly on Leishmania (V.) peruviana, suggesting a potential use as an alternative or complement to the usual treatment of tegumentary leishmaniasis. However, new trials are still required to determine the selectivity index for the intracellular form of the parasite, and to develop methods to facilitate the efficient entry of the molecule into the host cell and the parasite.

Preclinical evaluation of an 111In/225Ac theranostic targeting transformed MUC1 for triple negative breast cancer.

Rationale: Transformed MUC1 (tMUC1) is a cancer-associated antigen that is overexpressed in >90% of triple-negative breast cancers (TNBC), a highly metastatic and aggressive subtype of breast cancer. TAB004, a murine antibody targeting tMUC1, has shown efficacy for the targeted delivery of therapeutics to cancer cells. Our aim was to evaluate humanized TAB004 (hTAB004) as a potential theranostic for TNBC. Methods: The internalization of hTAB004 in tMUC1 expressing HCC70 cells was assessed via fluorescent microscopy. hTAB004 was DOTA-conjugated and radiolabeled with Indium-111 or Actinium-225 and tested for stability and tMUC1 binding (ELISA, flow cytometry). Lastly, in vivo biodistribution (SPECT-CT), dosimetry, and efficacy of hTAB004 were evaluated using a TNBC orthotopic mouse model. Results: hTAB004 was shown to bind and internalize into tMUC1-expressing cells. A production method of 225Ac-DOTA-hTAB004 (yield>97%, RCP>97% SA=5 kBq/µg) and 111In-DOTA-hTAB004 (yield>70%, RCP>99%, SA=884 kBq/µg) was developed. The labeled molecules retained their affinity to tMUC1 and were stable in formulation and mouse serum. In NSG female mice bearing orthotopic HCC70 xenografts, the in vivo tumor concentration of 111In-DOTA-hTAB004 was 65 ± 15 %ID/g (120 h post injection). A single 225Ac-DOTA-hTAB004 dose (18.5 kBq) caused a significant reduction in tumor volume (P<0.001, day 22) and increased survival compared to controls (P<0.007). The human dosimetry results were comparable to other clinically used agents. Conclusion: The results obtained with hTAB004 suggest that the 111In/225Ac-DOTA-hTAB004 combination has significant potential as a theranostic strategy in TNBC and merits further development toward clinical translation.

Elevation in lung volume and preventing catastrophic airway closure in asthmatics during bronchoconstriction.

BACKGROUND: Asthma exacerbations cause lung hyperinflation, elevation in load to inspiratory muscles, and decreased breathing capacity that, in severe cases, may lead to inspiratory muscle fatigue and respiratory failure. Hyperinflation has been attributed to a passive mechanical origin; a respiratory system time-constant too long for full exhalation. However, because the increase in volume is also concurrent with activation of inspiratory muscles during exhalation it is unclear whether hyperinflation in broncho-constriction is a passive phenomenon or is actively controlled to avoid airway closure. METHODS: Using CT scanning, we measured the distensibility of individual segmental airways relative to that of their surrounding parenchyma in seven subjects with asthma and nine healthy controls. With this data we tested whether the elevation of lung volume measured after methacholine (MCh) provocation was associated with airway narrowing, or to the volume required to preventing airway closure. We also tested whether the reduction in FVC post-MCh could be attributed to gas trapped behind closed segmental airways. FINDINGS: The changes in lung volume by MCh in subjects with and without asthma were inversely associated with their reduction in average airway lumen. This finding would be inconsistent with hyperinflation by passive elevation of airway resistance. In contrast, the change in volume of each subject was associated with the lung volume estimated to cause the closure of the least stable segmental airway of his/her lungs. In addition, the measured drop in FVC post MCh was associated with the estimated volume of gas trapped behind closed segmental airways at RV. CONCLUSIONS: Our data supports the concept that hyperinflation caused by MCh-induced bronchoconstriction is the result of an actively controlled process where parenchymal distending forces on airways are increased to counteract their closure. To our knowledge, this is the first imaging-based study that associates inter-subject differences in whole lung behavior with the interdependence between individual airways and their surrounding parenchyma.

Hypoxic Pulmonary Vasoconstriction Does Not Explain All Regional Perfusion Redistribution in Asthma.

RATIONALE: Regional hypoventilation in bronchoconstricted patients with asthma is spatially associated with reduced perfusion, which is proposed to result from hypoxic pulmonary vasoconstriction (HPV). OBJECTIVES: To determine the role of HPV in the regional perfusion redistribution in bronchoconstricted patients with asthma. METHODS: Eight patients with asthma completed positron emission tomographic/computed tomographic lung imaging at baseline and after bronchoconstriction, breathing either room air or 80% oxygen (80% O2) on separate days. Relative perfusion, specific ventilation (sV), and gas fraction (Fgas) in the 25% of the lung with the lowest specific ventilation (sVlow) and the remaining lung (sVhigh) were quantified and compared. MEASUREMENTS AND MAIN RESULTS: In the sVlow region, bronchoconstriction caused a significant decrease in sV under both room air and 80% O2 conditions (baseline vs. bronchoconstriction, mean ± SD, 1.02 ± 0.20 vs. 0.35 ± 0.19 and 1.03 ± 0.20 vs. 0.32 ± 0.16, respectively; P < 0.05). In the sVlow region, relative perfusion decreased after bronchoconstriction under room air conditions and also, to a lesser degree, under 80% O2 conditions (1.02 ± 0.19 vs. 0.72 ± 0.08 [P < 0.001] and 1.08 ± 0.19 vs. 0.91 ± 0.12 [P < 0.05], respectively). The Fgas increased after bronchoconstriction under room air conditions only (0.99 ± 0.04 vs. 1.00 ± 0.02; P < 0.05). The sVlow subregion analysis indicated that some of the reduction in relative perfusion after bronchoconstriction under 80% O2 conditions occurred as a result of the presence of regional hypoxia. However, relative perfusion was also significantly reduced in sVlow subregions that were hyperoxic under 80% O2 conditions. CONCLUSIONS: HPV is not the only mechanism that contributes to perfusion redistribution in bronchoconstricted patients with asthma, suggesting that another nonhypoxia mechanism also contributes. We propose that this nonhypoxia mechanism may be either direct mechanical interactions and/or unidentified intercellular signaling between constricted airways, the parenchyma, and the surrounding vasculature.

Brinquedo terapêutico no procedimento de punção venosa: estratégia para reduzir alterações comportamentais / Juguete terapéutico durante el procedimiento de punción venosa: estrategia para reducir alteraciones de comportamiento / Therapeutic toy during the procedure of venipuncture: a strategy to reduce behavioral changes

Introdução: A enfermagem pediátrica deve estar atenta aos subsídios da assistência que tornem possível um melhor manejo da dor e da ansiedade oriundas da hospitalização infantil, geralmente, causadas pela realização de procedimentos invasivos como a punção venosa. O uso do Brinquedo Terapêutico Instrucional (BTI) pode representar uma intervenção eficaz para lidar com os efeitos negativos da hospitalização. Objetivo: Comparar as reações manifestadas pela criança frente ao preparo para punção venosa antes e após o uso do BTI. Materiais e Métodos: A pesquisa é analítica, exploratória e de abordagem quantitativa. Para análise dos dados foi utilizado o teste de McNemar. A amostra consistiu de 21 crianças hospitalizadas, pré-escolares e escolares, a coleta deu-se entre junho e agosto de 2012, em unidade de internação pediátrica do Crato, CE (Brasil). Resultados e Discussão: Após o uso do BTI, observou-se uma redução na frequência de variáveis comportamentais que indicam menor adaptação ao procedimento, com significância estatística em especial para: “Solicita a presença Materna” e “Evita olhar para o Profissional” (p<0,001). A realização das sessões também potencializou a frequência de, praticamente, todos os comportamentos associados a uma melhor aceitação ao preparo ou realização da punção venosa, com destaque para “Observa o Profissional” (p<0,001) e “Sorri” (p<0,005). Conclusões: O BTI constitui relevante intervenção para a enfermagem pediátrica, sendo necessário, para sua aplicação sistematizada, articular ações que visem uma maior sensibilização dos órgãos gestores dos serviços de pediatria, maior capacitação dos profissionais envolvidos e melhor abordagem do ensino do brinquedo terapêutico nos cursos de graduação de enfermagem.

Introducción: La enfermería pediátrica debe conocer los recursos de asistencia que permitan mejor manejo del dolor y la ansiedad ocasionada de una hospitalización infantil, generalmente, causadas por realización de procedimientos invasivos, como la punción venosa. El uso del Juego Terapéutico Instruccional (JTI) puede representar una intervención eficaz para hacer frente a efectos negativos de la hospitalización. Objetivo: Comparar las reacciones manifestadas por el niño sometido a punción venosa antes y después del uso del JTI. Materiales y Métodos: El estudio es analítico, exploratorio y cuantitativo. Para el análisis de datos se empleó el test de McNemar. La muestra consistió en 21 niños hospitalizados, pre-escolares y escolares, la recolección de datos ocurrió entre junio y agosto de 2012 en unidad pediátrica de Crato, CE (Brasil). Resultados y Discusión: Después del uso del JTI, se observó una reducción en la frecuencia de las variables de comportamiento que indican una adaptación menor al procedimiento de punción venosa, estadísticamente significativo: “Solicita la presencia Materna” y “Evita mirar el Profesional” (p <0,001). La realización de las sesiones también potencializó la frecuencia de prácticamente todos los comportamientos asociados a una mejor aceptación a la preparación o realización de la punción venosa: “Observa el Profesional” (p <0,001) y “Sonríe” (p <0,005). Conclusiones: El JTI constituye una intervención relevante para la enfermería pediátrica, siendo necesario para su aplicación, articular acciones destinadas a aumentar la sensibilización entre los administradores de los servicios de pediatría, mayor capacitación de los profesionales y un mejor abordaje en la educación del juguete terapéutico en los pregrados de enfermería.

Introduction: Pediatric nurses should always be attentive to the care subsidies that make possible a better control of pain and anxiety generated by infant hospitalization. Generally, these adverse feeling in children are caused by the realization of intrusive procedures, such as venipuncture. The use of the Therapeutic Toy Instructional (TTI) may represent an effective intervention to deal with the negatives effects of hospitalization. Objective: To compare the reactions expressed by the child, exposed to venipuncture, before and after the use of TTI. Materials and Methods: The research is analytical, exploratory and quantitative approach. For analysis of the data was employed the McNemar test. The sample consisted of 21 hospitalized children, pre-school and school ages, the process of data was collected between June and August of 2012 in a pediatric unit from Crato, CE (Brazil). Results and Discussion: After using the TTI, there was a reduction in frequency of behavioral variables that indicate less adaptation to the procedure, particularly for “Require the presence of mother" and "Try not to look for the Professional" (p <0.001). The realization of the sessions also increased the frequency of many behaviors associated with better acceptance of the procedure, especially: "Look for the Professional" (p <0.001) and "Smile" (p <0.005). Conclusions: The TTI is a relevant intervention for pediatric nursing; to use it in a systematic way is needed: planning actions aimed at increasing awareness among managers of pediatric services, better training of professionals and the inclusion of teaching of therapeutic toy in nursing courses.

Regional Ventilation and Aerosol Deposition with Helium-Oxygen in Bronchoconstricted Asthmatic Lungs.

BACKGROUND: Theoretical models suggest that He-O2 as carrier gas may lead to more homogeneous ventilation and aerosol deposition than air. However, these effects have not been clinically consistent and it is unclear why subjects may or may not respond to the therapy. Here we present 3D-imaging data of aerosol deposition and ventilation distributions from subjects with asthma inhaling He-O2 as carrier gas. The data are compared with those that we previously obtained from a similar group of subjects inhaling air. METHODS: Subjects with mild-to-moderate asthma were bronchoconstricted with methacholine and imaged with PET-CT while inhaling aerosol carried with He-O2. Mean-normalized-values of lobar specific ventilation sV* and deposition sD* were derived and the factors affecting the distribution of sD* were evaluated along with the effects of breathing frequency (f) and regional expansion (FVOL). RESULTS: Lobar distributions of sD* and sV* with He-O2 were not statistically different from those previously measured with air. However, with He-O2 there was a larger number of lobes having sV* and sD* closer to unity and, in those subjects with uneven deposition distributions, the correlation of sD* with sV* was on average higher (p < 0.05) in He-O2 (0.84 ± 0.8) compared with air (0.55 ± 0.28). In contrast with air, where the frequency of breathing during nebulization was associated with the degree of sD*-sV* correlation, with He-O2 there was no association. Also, the modulation of f on the correlation between FVOL and sD*/sV* in air, was not observed in He-O2. CONCLUSION: There were no differences in the inter-lobar heterogeneity of sD* or sV* in this group of mild asthmatic subjects breathing He-O2 compared with patients previously breathing air. Future studies, using these personalized 3D data sets as input to CFD models, are needed to understand if, and for whom, breathing He-O2 during aerosol inhalation may be beneficial.

What Causes Uneven Aerosol Deposition in the Bronchoconstricted Lung? A Quantitative Imaging Study.

BACKGROUND: A previous PET-CT imaging study of 14 bronchoconstricted asthmatic subjects showed that peripheral aerosol deposition was highly variable among subjects and lobes. The aim of this work was to identify and quantify factors responsible for this variability. METHODS: A theoretical framework was formulated to integrate four factors affecting aerosol deposition: differences in ventilation, in how air vs. aerosol distribute at each bifurcation, in the fraction of aerosol escaping feeding airways, and in the fraction of aerosol reaching the periphery that is exhaled. These factors were quantified in 12 of the subjects using PET-CT measurements of relative specific deposition sD*, relative specific ventilation sV* (measured with dynamic PET or estimated as change in expansion between two static HRCTs), average lobar expansion FVOL, and breathing frequency measured during aerosol inhalation fN. RESULTS: The fraction of the variance of sD* explained by sV* (0.38), by bifurcation effects (0.38), and by differences in deposition along feeding airways (0.31) were similar in magnitude. We could not directly estimate the contribution of aerosol that was exhaled. Differences in expansion did not explain any fraction of the variability in sD* among lobes. The dependence of sD* on sV* was high in subjects breathing with low fN, but weakened among those breathing faster. Finally, sD*/sV* showed positive dependence on FVOL among low fN subjects, while the dependence was negative among high fN subjects. CONCLUSION: The theoretical framework allowed us to analyze experimentally measured aerosol deposition imaging data. When considering bronchoconstricted asthmatic subjects, a dynamic measurement of ventilation is required to evaluate its effect on aerosol transport. The mechanisms behind the identified effects of fN and FVOL on aerosol deposition need further study and may have important implications for aerosol therapy in subjects with heterogeneous ventilation.

A method for mapping regional oxygen and CO2 transfer in the lung.

This paper presents a novel approach to visualizing regional lung function, through quantitative three-dimensional maps of O2 and CO2 transfer rates. These maps describe the contribution of anatomical regions to overall gas exchange and demonstrate how transfer rates of the two gas species' differ regionally. An algorithm for generating such maps is presented, and for illustration, regional gas transfer maps were generated using values of ventilation and perfusion imaged by PET/CT for a healthy subject and an asthmatic patient after bronchoprovocation. In a sensitivity analysis, compartment values of gas transfer showed minor sensitivity to imaging noise in the ventilation and perfusion data, and moderate sensitivity to estimation errors in global lung input values, chiefly global alveolar ventilation, followed by cardiac output and arterial-venous O2 content difference. Gas transfer maps offer an intuitive display of physiologically relevant lung function at a regional level, the potential for an improved understanding of pulmonary gas exchange in health and disease, and potentially a presurgical evaluation tool.

Allergic Non-Asthmatic Adults Have Regional Pulmonary Responses to Segmental Allergen Challenge.

BACKGROUND: Allergic non-asthmatic (ANA) adults experience upper airway symptoms of allergic disease such as rhinorrhea, congestion and sneezing without symptoms of asthma. The aim of this study was to utilize PET-CT functional imaging to determine whether allergen challenge elicits a pulmonary response in ANA subjects or whether their allergic disease is truly isolated to the upper airways. METHODS: In 6 ANA subjects, bronchoalveolar lavages (BAL) were performed at baseline and 24h after instillation of an allergen and a diluent in separate lung lobes. After instillation (10h), functional imaging was performed to quantify and compare regional perfusion, ventilation, fractional gas content (Fgas), and glucose uptake rate (Ki) between the baseline, diluent and allergen lobes. BAL cell counts were also compared. RESULTS: In ANA subjects, compared to the baseline and diluent lobes, perfusion and ventilation were significantly lower in the allergen lobe (median [inter-quartile range], baseline vs. diluent vs. allergen: Mean-normalized perfusion; 0.87 [0.85-0.97] vs. 0.90 [0.86-0.98] vs. 0.59 [0.55-0.67]; p<0.05. Mean-normalized ventilation 0.89 [0.88-0.98] vs. 0.95 [0.89-1.02] vs. 0.63 [0.52-0.67], p<0.05). In contrast, no significant differences were found in Fgas between baseline, diluent and allergen lobes or in Ki. Total cell counts, eosinophil and neutrophil cell counts (cells/ml BAL) were significantly greater in the allergen lobe compared to the baseline lobe (all P<0.05). CONCLUSIONS: Despite having no clinical symptoms of a lower airway allergic response (cough and wheeze) allergic non-asthmatic subjects have a pulmonary response to allergen exposure which manifests as reduced ventilation and perfusion.

Analysis of three-dimensional aerosol deposition in pharmacologically relevant terms: beyond black or white ROIs.

BACKGROUND: This article presents a novel methodological approach to evaluate images of aerosol deposition taken with PET-CT cameras. Traditionally, Black-or-White (BW) Regions of Interest (ROIs) are created to cover Anatomical Regions (ARs) segmented from the high-resolution CT. Such ROIs do not usually consider blurring effects due to limited spatial resolution or breathing motion, and do not consider uncertainty in the AR position within the PET image. The new methodology presented here (Grayscale) addresses these issues, allows estimates of aerosol deposition within ARs, and expresses the deposition in terms of Tissue Dosing (in the lung periphery) and Inner Surface Concentration (in the larger airways). METHODS: Imaging data included a PET deposition image acquired during breathing and two CT scans acquired during breath holds at different lung volumes. The lungs were segmented into anatomically consistent ARs to allow unbiased comparisons across subjects and across lobes. The Grayscale method involves defining Voxel Influence Matrices (VIMs) to consider how average activity within each AR influences the measured activity within each voxel. The BW and Grayscale methods were used to analyze aerosol deposition in 14 bronchoconstricted asthmatics. RESULTS: Grayscale resulted in a closer description of the PET image than BW (p<0.0001) and exposed a seven-fold underestimation in measures of specific deposition. The Average Tissue Dosing was 2.11×10(-6) Total Lung Dose/mg. The average Inner Surface Concentration was 45×10(-6) Total Lung Dose/mm(2), with the left lower lobe having a lower ISC than lobes of the right lung (p<0.05). There was a strong lobar heterogeneity in these measures (COV=0.3). CONCLUSION: The Grayscale approach is an improvement over the BW approach and provides a closer description of the PET image. It can be used to characterize heterogeneous concentrations throughout the lung and may be important in translational research and in the evaluation of aerosol delivery systems.

Nivel de habilidades sociales que poseen los adolescentes de la I.E. Estados Unidos, Comas, Lima-Perú 2013 / Level of social skills of the adolescents at the I.E. Estados Unidos, Comas, Lima-Peru 2013

Las habilidades sociales permiten que los adolescentes mantengan relaciones sociales positivas con los otros y que afronten las demandas de su entorno social. El objetivo general fue determinar el Nivel de Habilidades Sociales que poseen los adolescentes de la I.E. Estados Unidos, Comas. El estudio de investigación es de enfoque cuantitativo, el método es descriptivo de corte transversal y el instrumento utilizado fue una Cuestionario de Habilidades Sociales de Goldstein validada que consta de 50 ítems aplicado a 98 adolescentes de nivel secundario, evidenciando los siguientes resultados: el nivel de habilidades sociales es medio y según sus 06 dimensiones son: las Primeras habilidades sociales se encuentran en un nivel medio, las Habilidades Sociales Avanzadas en un nivel medio, las habilidades relacionadas con los sentimientos en un nivel alto, las habilidades alternativas a la agresión en un nivel medio, las habilidades para hacer frente al estrés en un nivel medio y las habilidades de planificación se encuentran en un nivel alto. Las conclusiones a las que se llegaron es que el nivel de habilidades sociales es medio, y según sus dimensiones hay habilidades que se han desarrollado más que otras; por lo que se puede afirmar que los adolescentes no aplican las habilidades sociales en su interactuar diario con sus pares o que no lo han desarrollado completamente.

Social skills allow teenagers to maintain positive social relationships with others and to counter the demands of their social environment. The overall objective was to determine the level of Social skills possessed by teenagers in the School Estados Unidos, Comas. The research study is a quantitative approach, the method is descriptive cross-sectional and the instrument used was a questionnaire validated Goldstein Social Skills consisting of 50 items applied 98 teenagers to secondary, showing the following results: the level of social skills is medium and according with its 06 dimensions are: First social skills are at an average level, Advanced social Skills in a medium level skills related to feelings at a high level, alternative skills to aggression in intermediate level skills to cope with stress in a medium level and planning skills are at a high level. The conclusions were that the level of social skills is medium, and according to its dimensions, there are skills that have developed less than others, so we can say that teenager's social skills do not apply in their daily interaction with their peers or who have not fully developed.

The effect of omalizumab on ventilation and perfusion in adults with allergic asthma.

Omalizumab promotes clinical improvement in patients with allergic asthma, but its effect on pulmonary function is unclear. One possibility is that omalizumab improves asthma symptoms through effects on the regional distributions of ventilation, perfusion, and ventilation/perfusion matching, metrics which can be assessed with Nitrogen-13-saline Position Emission Tomography (PET). Four adults with moderate to severe uncontrolled allergic asthma underwent symptom assessment, spirometry and functional pulmonary imaging with Nitrogen-13-saline PET before and after 4-5 months of treatment with omalizumab. PET imaging was used to determine ventilation/perfusion ratios, the heterogeneity (coefficient of variation, COV) of ventilation and perfusion, and lung regions with ventilation defects. There were no significant changes in spirometry values after omalizumab treatment, but there was a trend towards an improvement in symptom scores. There was little change in the matching of ventilation and perfusion. The COV of perfusion was similar before and after omalizumab treatment. The COV of ventilation was also similar before (0.57 (0.28)) and after (0.66 (0.13)) treatment, and it was similar to previously published values for healthy subjects. There was a non-significant trend towards an increase in the extent of ventilation defects after omalizumab treatment, from 5 (15)% to 12.8 (14.7)%. Treatment of moderate to severe uncontrolled allergic asthma with omalizumab did not result in a significant improvement in ventilation and perfusion metrics assessed with functional PET imaging. The normal COV of ventilation which was unaffected by treatment supports the hypothesis that omalizumab exerts its clinical effect on lung function during allergen exposure rather than in between exacerbations.

Respiratory system reactance is an independent determinant of asthma control.

The mechanisms underlying not well-controlled (NWC) asthma remain poorly understood, but accumulating evidence points to peripheral airway dysfunction as a key contributor. The present study tests whether our recently described respiratory system reactance (Xrs) assessment of peripheral airway dysfunction reveals insight into poor asthma control. The aim of this study was to investigate the contribution of Xrs to asthma control. In 22 subjects with asthma, we measured Xrs (forced oscillation technique), spirometry, lung volumes, and ventilation heterogeneity (inert-gas washout), before and after bronchodilator administration. The relationship between Xrs and lung volume during a deflation maneuver yielded two parameters: the volume at which Xrs abruptly decreased (closing volume) and Xrs at this volume (Xrscrit). Lowered (more negative) Xrscrit reflects reduced apparent lung compliance at high lung volumes due, for example, to heterogeneous airway narrowing and unresolved airway closure or near closure above the critical lung volume. Asthma control was assessed via the 6-point Asthma Control Questionnaire (ACQ6). NWC asthma was defined as ACQ6 > 1.0. In 10 NWC and 12 well-controlled subjects, ACQ6 was strongly associated with postbronchodilator (post-BD) Xrscrit (R(2) = 0.43, P < 0.001), independent of all measured variables, and was a strong predictor of NWC asthma (receiver operator characteristic area = 0.94, P < 0.001). By contrast, Xrs measures at lower lung volumes were not associated with ACQ6. Xrscrit itself was significantly associated with measures of gas trapping and ventilation heterogeneity, thus confirming the link between Xrs and airway closure and heterogeneity. Residual airway dysfunction at high lung volumes assessed via Xrscrit is an independent contributor to asthma control.