Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model

Background The radiosensitising effect of the poly(ADP-ribose) polymerase inhibitor olaparib on tumours has been reported. However, its effect on normal tissues in combination with radiation has not been well studied. Herein, we investigated the therapeutic index of olaparib combined with hemithoracic radiation in a urethane-induced mouse lung cancer model. Methods To assess tolerability, A/J mice were treated with olaparib plus whole thorax radiation (13 Gy), body weight changes were monitored and normal tissue effects were assessed by histology. In anti-tumour (intervention) studies, A/J mice were injected with urethane to induce lung tumours, and were then treated with olaparib alone, left thorax radiation alone or the combination of olaparib plus left thorax radiation at 8 weeks (early intervention) or 18 weeks (late intervention) after urethane injection. Anti-tumour efficacy and normal tissue effects were assessed by visual inspection, magnetic resonance imaging and histology. Results Enhanced body weight loss and oesophageal toxicity were observed when olaparib was combined with whole thorax but not hemithorax radiation. In both the early and late intervention studies, olaparib increased the anti-tumour effects of hemithoracic irradiation without increasing lung toxicity. Conclusions The addition of olaparib increased the therapeutic index of hemithoracic radiation in a mouse model of lung cancer.

Dulaglutide exerts beneficial anti atherosclerotic effects in ApoE knockout mice with diabetes: the earlier, the better

There has been no report about the mechanism for anti-atherosclerotic effects of dulaglutide (Dula) and/or about the difference of its effectiveness between in an early and a late phase of diabetes. To address such questions, streptozotocin (STZ) was intraperitoneally injected to ApoE knockout mice at 8 weeks of age. Either Dula or vehicle was administered to STZ-induced diabetic ApoE knockout mice from 10 to 18 weeks of age as an early intervention group and from 18 to 26 weeks as a late intervention group. Next, non-diabetic ApoE knockout mice without STZ injection were subcutaneously injected with either Dula or vehicle. In an early intervention group, atherosclerotic lesion in aortic arch and Mac-2 and CD68-positive areas in aortic root were significantly smaller in Dula group. In abdominal aorta, expression levels of some villain factors were lower in Dula group. In a late intervention group, there were no immunohistological differences in aortic root and expression levels of various factors between two groups. Furthermore, even in non-diabetic ApoE knockout mice, expression levels of inflammatory and macrophage markers were reduced by treatment with Dula. Taken together, Dula exerts more beneficial anti-atherosclerotic effects in an early phase of diabetes rather than in a late phase.

Neonatal Pain Assessment From Facial Expression Using Deep Neural Networks

Currently, neonatal pain assessment varies among health professionals, leading to late intervention and flimsy treatment of pain in several occasions. Therefore, it is essential to understand the deficiencies of the current pattern of pain assessment tools in order to develop new ones, less subjective and susceptible to external variable influences. The aim of this paper is to investigate neonatal pain assessment using two models of Deep Learning: Neonatal Convolutional Neural Network trained end-to-end and ResNet trained using Transfer Learning. We used for training two distinct databases (COPE and Unifesp) and our results showed that the use of multi-racial databases might improve the evaluation of automatic models of neonatal pain assessment.

EMDR Group Protocol With Children: A Field Study

The Eye Movement Desensitization and Reprocessing Group Protocol with Children (EMDR-GP/C) was first developed by Korkmazlar following the Marmara earthquake in Turkey in 1999 and can be adapted for different populations. This study focused on EMDR-GP with children who lost their fathers in the mine explosion that occurred in 2014 in Soma, Turkey. The EMDR-GP/C was used with 41 children (7–12 years old) in the early intervention, 3 weeks after the disaster, and used with 25 other children (6–13 years old) in the late intervention, 18 months after the disaster, when posttraumatic stress disorder symptoms had developed. The differences between the early and late implementations of EMDR-GP/C are presented in this article. In the early intervention, children processed the trauma by focusing on the “events” as they saw or heard them; however, 18 months after the disaster, children processed their “emotions” about the event in the desensitization phase. Results show a significant decrease in scores of subjective units of disturbance (SUDs) for both intervention periods. An analysis was also conducted, comparing decreases in SUD scores for younger and older children, with no differences found in their response to treatment. Pre and follow-up data were collected for the late intervention condition, using the Child Report of Posttraumatic Symptoms (CROPS), and showed a significant decrease at 18-month follow-up. Further studies are suggested to determine effectiveness of EMDR-GP/C with other populations.

Avaliação de dor em expressão facial neonatal por meio de redes neurais profundas

Neonatal pain assessment might suffer variation among health professionals, leading to late intervention and flimsy treatment of pain in several occasions. Therefore, it is essential to develop computational tools of pain assessment, less subjective and susceptible to external variable influences. Deep learning models, especially Convolutional Neural Networks, have gained ground in the last decade, due to many successful applications in image analysis, object recognitions and human emotion recognitions. In this context, the general aim this dissertation was analyse quantitatively and qualitatively models of Convolutional Neural Networks in the task neonatal pain classification through a computacional framework based in face images of two distinct databases (an international, named COPE, and other national, named UNIFESP). How specific aims were implemented, evaluated and compared the performance of three existent models used in literature: Neonatal Convolutional Neural Network (N-CNN) and two type of ResNet50 models. The quantitative results showed the excellence of N-CNN to neonatal pain assessment automatic, with average accuracy of 87.2% and 78.7% for the databases COPE and UNIFESP, respectively. However, the quantitative analysis showed that all neural models evaluated, including N-CNN models, can learn artifacts from the imagens and not variation discriminating in faces, thus showed the necessity more studies to apply this models in clinical practice

Combined inhibition of CCR2 and ACE provides added protection against progression of diabetic nephropathy in Nos3-deficient mice

Macrophage-mediated renal injury promotes the development of diabetic nephropathy. Blockade of chemokine (C-C motif) receptor 2 (CCR2) inhibits kidney macrophage accumulation and early glomerular damage in diabetic animals. This study tested early and late interventions with a CCR2 antagonist (CCR2A) in a model of progressive diabetic glomerulosclerosis and determined whether CCR2A provides added benefit over conventional treatment with an angiotensin-converting enzyme inhibitor (ACEi). Diabetes was induced in hypertensive endothelial nitric oxide synthase ( Nos3)-deficient mice by administration of five low-dose streptozotocin (STZ) injections daily. Groups of diabetic Nos3−/− mice received a CCR2A (30 mg·kg−1·day−1 PF-04634817 in chow) as an early intervention ( weeks 2–15 after STZ). The late intervention ( weeks 8–15 after STZ) involved PF-04634817 alone, ACEi (captopril in water 10 mg·kg−1·day−1) alone, or combined ACEi + CCR2A. Control diabetic and nondiabetic Nos3−/− mice received normal chow and water. Early intervention with a CCR2A inhibited kidney inflammation and glomerulosclerosis, albuminuria, podocyte loss, and renal function impairment but not hypertension in diabetic Nos3−/− mice. Late intervention with a CCR2A also inhibited kidney inflammation, glomerulosclerosis, and renal dysfunction but did not affect albuminuria. ACEi alone suppressed hypertension and albuminuria and partially reduced podocyte loss and glomerulosclerosis but did not affect renal dysfunction. Compared with ACEi alone, the combined late intervention with ACEi + CCR2A provided better protection against kidney damage (inflammation, glomerulosclerosis, and renal function impairment) but not albuminuria. In conclusion, this study demonstrates that combining CCR2A and ACEi provides broader and superior renal protection than ACEi alone in a model of established diabetic glomerulosclerosis with hypertension.