NAIL: An evolutionarily conserved lncRNA essential for licensing coordinated activation of p38 and NFκB in colitis

Akıncılar SC, Wu L, NG QF, et al., NAIL: an evolutionarily conserved lncRNA essential for licensing coordinated activation of p38 and NFκB in colitis. Gut Published Online First: 25 November 2020. doi: 10.1136/gutjnl-2020-32298

Efeitos do tratamento com captopril e losartan em ratos Wistar e ratos espontaneamente hipertensos submetidos a hipertensão arterial pulmonar com monocrotalina

A hipertensão arterial pulmonar (HAP) é uma doença que se inicia com o aumento da resistência das arteríolas pulmonares. Após a sua instalação, sucedem-se várias alterações sobre os sistemas cardiovascular, respiratório e autonômico. Apesar dos trabalhos disponíveis na literatura, o desenvolvimento desta doença em modelos experimentais de hipertensão arterial sistêmica permanece ainda por ser estudado, bem como os efeitos terapêuticos de bloqueadores do sistema renina-angiotensina na reversão desta doença. Os objetivos deste estudo foram avaliar os efeitos cardiovasculares, autonômicos e respiratórios promovidos pela HAP induzida pela monocrotalina (MCT) em ratos Wistar e SHR e os efeitos terapêuticos do tratamento crônico com captopril e losartan na reversão da HAP. Para tanto, foram utilizados ratos Wistar (150-180g) e SHR (150-180g), divididos nos seguintes grupos: Wistar controle tratado com salina ou MCT (WIS-CON-SAL e WIS-CON-MCT, respectivamente), SHR controle tratado com salina ou MCT (SHR-CON-SAL e SHR-CON-MCT, respectivamente), Wistar tratados com Captopril + salina ou MCT (WIS-CPT-SAL e WIS-CPT-MCT, respectivamente), SHR tratados com Captopril + salina ou MCT (SHR-CPT-SAL e SHR-MCT-CPT, respectivamente), Wistar tratados com Losartan + salina ou MCT (WIS-LOS-SAL e WIS-LOS-MCT, respectivamente), SHR tratados com Losartan + salina ou MCT (SHR-LOS-SAL e SHR-LOS-MCT, respectivamente). Os animais tratados com MCT receberam uma única injeção subcutânea (60 mg/Kg SC) e os controles receberam o mesmo volume de salina (~0,8 mL). Ao término da 3ª senama, quando os animais MCTs controle apresentaram HAP, foi feito o tratamento com captopril (100 mg/Kg/mL) ou losartan (30 mg/Kg/mL) na água de beber por 2 semanas no volume diário de 30 mL. Após o tratamento com captopril ou losartan, foram realizados os registros cardiovasculares, respiratórios, gasométricos e a histologia pulmonar. Os resultados mostraram um significativo aumento do Índice Pulmonar nos animais controles tratados com MCT (Wistar e SHR) quando comparados com seus respectivos controles. As pressões ventriculares (PSmáx, PDI e PDF) também foram significativamente aumentadas nos grupos MCTs, bem como os valores de pressão arterial sistólica and diastólica, frequência cardíaca, pressão de pulso e labilidade da pressão arterial média. O tratamento com captopril normalizou todos os parâmetros estudados, no entanto, o losartan se mostrou ineficiente em normalizar os parâmetros hemodinâmicos. As análises morfométricas mostraram um espessamento da camada média dos dos ramos distais da artéria pulmonar e uma diminuição do lúmen nos grupos tratados com MCT. O tratamento com captopril e losartan normalizou estes parâmetros, embora o grupo tratado com losartan tenha sido menos eficaz que o captopril, pois os tratamentos mostraram diferenças significativas entre si. Quanto a avaliação autonômica, os animais MCT mostraram aumento do tônus simpático cardíaco e redução do tônus parassimpático cardíaco. Novamente, o tratamento com captopril normalizou estes parâmetros, enquanto que o losartan foi ineficaz em normalizá-los. Quanto aos parâmetros respiratórios, observamos aumentos no volume corrente, na frequência respiratória, na ventilação minuto e na ventilação alveolar dos animais controles tratados com MCT. Apenas o tratamento com captopril normalizou estes parâmetros. A avaliação gasométrica mostrou que os grupos controles tratados com MCT apresentaram redução da pressão parcial de O2 (hipóxia), aumento da pressão parcial de CO2 (hipercapnia), queda da porcentagem de saturação da hemoglobina (% Hb), aumento do bicarbonato (HCO3-) e acidose. O tratamento com captopril normalizou todos os parâmetros gasométricos, enquanto que o mesmo não foi observado com o losartan para os animais SHR submetidos a HAP. Nossos resultados mostraram que a MCT induziu ao quadro de HAP nos animais Wistar e SHR, bem como importantes alterações cardiovasculares, autonômicas, respiratórias, gasométricas e morfológicas pulmonares. Os tratamentos com captopril e losartan foram capazes de reverter a HAP em animais Wistar e SHR, porém, o captopril se mostrou mais eficiente em normalizar esses parâmetros quando comparados ao losartan. Estes resultados sugerem que o uso de bloqueadores do sistema renina angiotensina pode ser uma opção terapêutica para o tratamento da HAP. Palavras chave: hipertensão arterial pulmonar; monocrotalina; SHR; captopril; losartan

Preliminary studies on the feasibility of addition of vertex view to conventional brain SPECT imaging.

We have investigated the improvement in resolution and sensitivity for brain imaging which would result by the addition of a single stationary vertex view to the tomographic data. This method has the practical advantage of being relatively inexpensive and easy to implement. The uniform Cramer-Rao lower bound was used as a mathematical tool to evaluate the quantitative performance of this new imaging geometry. The uniform bound is a plot of the minimum achievable standard deviation in estimating the pixel intensity as a function of the bias gradient length. Uniform lower bound analysis indicated a gain in performance by adding the vertex data set. For regions of interest at the peripheral of the field of view, improvement is limited to within 7 cm from vertex detector; while for regions of interest close to the center of the field of view, substantial improvement is observed over the useful depth for brain SPECT imaging. Simulation experiments were done with a simple six slice phantom and with the Hoffman brain phantom. Visual inspection of the reconstructed images showed improvement in resolution and noise characteristics over reconstructed images without the vertex data. Improvement degraded as distance from the vertex detector is increased. For a simple six slice phantom and a radially undersampled tomograph, adding the vertex data reduced the standard deviation for a center pixel by a factor of 4 for the top plane, and 15% for the bottom plane. Nonbrain activities inside the FOV of the vertex detector but not the tomograph is jointly estimated by cubic spline fitting in the image reconstruction process. For background activity that increased vertex detector counts by 20%, the standard deviation in pixel intensity estimate was increased by about 15% at the center pixel of the planes. We also investigated the problem of bleed through which is unique to this imaging geometry, and proposed a solution to reduce the problem. Addition of a vertex view to brain SPECT data shows substantial reduction in mean square error for a plane close to the vertex detector. The vertex view should lead to improved cortical imaging, and to moderate improvement for deep structures.Ph.D.Applied SciencesBiomedical engineeringElectrical engineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/130318/2/9722052.pd

Radiation hazards of building materials

published_or_final_versionRadioisotopeMasterMaster of Philosoph

Proton range monitoring using 13N peak for proton therapy applications

The Monte Carlo method is employed in this study to simulate the proton irradiation of a water-gel phantom. Positron-emitting radionuclides such as 11C, 15O, and 13N are scored using the Particle and Heavy Ion Transport Code System Monte Carlo code package. Previously, it was reported that as a result of 16O(p,2p2n)13N nuclear reaction, whose threshold energy is relatively low (5.660 MeV), a 13N peak is formed near the actual Bragg peak. Consideringthe generated 13N peak, we obtain offset distance values between the 13N peak and the actual Bragg peak for various incident proton energies ranging from 45 to 250 MeV, with an energy interval of 5 MeV. The offset distances fluctuate between 1.0 and 2.0 mm. For example, the offset distances between the 13N peak and the Bragg peak are 2.0, 2.0, and 1.0 mm for incident proton energies of 80, 160, and 240 MeV, respectively. These slight fluctuations for different incident proton energies are due to the relatively stable energydependent cross-section data for the 16O(p,2p2n)13N nuclear reaction. Hence, we develop an open-source computer program that performs linear and non-linear interpolations of offset distance data against the incident proton energy, which further reduces the energy interval from 5 to 0.1 MeV. In addition, we perform spectral analysis to reconstruct the 13N Bragg peak, and the results are consistent with those predicted from Monte Carlo computations. Hence, the results are used to generate three-dimensional scatter plots of the 13N radionuclide distribution in the modeled phantom. The obtained results and the developed methodologies will facilitate future investigations into proton range monitoring for therapeutic applications

Factors reducing inappropriate attendances to emergency departments before and during the COVID-19 pandemic: A multicentre study

10.47102/annals-acadmedsg.2021151Annals of the Academy of Medicine, Singapore5011818-826Complete

Quantitative Spatial Characterization of Lymph Node Tumor for N Stage Improvement of Nasopharyngeal Carcinoma Patients

This study aims to investigate the feasibility of improving the prognosis stratification of the N staging system of Nasopharyngeal Carcinoma (NPC) from quantitative spatial characterizations of metastatic lymph node (LN) for NPC in a multi-institutional setting. A total of 194 and 284 NPC patients were included from two local hospitals as the discovery and validation cohort. Spatial relationships between LN and the surrounding organs were quantified by both distance and angle histograms, followed by principal component analysis. Independent prognostic factors were identified and combined with the N stage into a new prognostic index by univariate and multivariate Cox regressions on disease-free survival (DFS). The new three-class risk stratification based on the constructed prognostic index demonstrated superior cross-institutional performance in DFS. The hazard ratios of the high-risk to low-risk group were 9.07 (p p p p = 0.171) of N3 to N1. Our spatial characterizations of lymph node tumor anatomy improved the existing N-stage in NPC prognosis. Our quantitative approach may facilitate the discovery of new anatomical characteristics to improve patient staging in other diseases

Quantitative Spatial Characterization of Lymph Node Tumor for N Stage Improvement of Nasopharyngeal Carcinoma Patients

This study aims to investigate the feasibility of improving the prognosis stratification of the N staging system of Nasopharyngeal Carcinoma (NPC) from quantitative spatial characterizations of metastatic lymph node (LN) for NPC in a multi-institutional setting. A total of 194 and 284 NPC patients were included from two local hospitals as the discovery and validation cohort. Spatial relationships between LN and the surrounding organs were quantified by both distance and angle histograms, followed by principal component analysis. Independent prognostic factors were identified and combined with the N stage into a new prognostic index by univariate and multivariate Cox regressions on disease-free survival (DFS). The new three-class risk stratification based on the constructed prognostic index demonstrated superior cross-institutional performance in DFS. The hazard ratios of the high-risk to low-risk group were 9.07 (p < 0.001) and 4.02 (p < 0.001) on training and validation, respectively, compared with 5.19 (p < 0.001) and 1.82 (p = 0.171) of N3 to N1. Our spatial characterizations of lymph node tumor anatomy improved the existing N-stage in NPC prognosis. Our quantitative approach may facilitate the discovery of new anatomical characteristics to improve patient staging in other diseases