Neurotrophic factors play an integral role in hippocampal plasticity, and interaction with HPA axis components, especially glucocorticoid receptors (GR), can mediate the structural and functional changes. In the present work, we investigated the long-term effects of combined exercise training (CET) and voluntary physical activity in an enriched environment (EE) in the pre-pubertal period on hippocampal neurotrophic factors and GR. For this purpose, a longitudinal study was designed. After three weeks, all rats were kept in the standard cages without any interventions until adulthood. Western blot analysis revealed a significant increase in hippocampal BDNF and VEGF protein levels in both EE and CET groups (P less then 0.001), along with an increase in GR protein levels. In addition, EE decreased serum corticosterone levels compared to CET (P less then 0.05). Serum insulin-like growth factor-1 (IGF-1) levels did not demonstrate remarkable changes between groups. Training interventions during sensitive developmental periods may produce profound and long-lasting effects on the hippocampus, at least in part by interactive effects of neurotrophic factors cascades and GR.
  Breast cancer patients frequently develop radiation dermatitis (RD) when undergoing post-operative radiation therapy (RT). Traditional RD assessment methods measure clinician-reported outcomes (CROs), but patient-reported outcomes (PROs) have gained recent popularity. The purpose of this prospective analysis was to compare PROs with CROs of breast RD.
 
  Demographic and treatment characteristics were prospectively collected for patients receiving post-operative RT between February 2018 to September 2020. Patients and clinicians completed a skin symptom assessment at baseline, weekly during RT, and at a one- to three-month follow-up visit. Skin treatments used by patients were collected. Concordance between each PRO and CRO was determined using percent concordance and concordance index (C-statistic) by logistic regression analysis.
 
  A total of 777 patients were included in the present study. All skin symptom assessment items were significantly underreported by clinicians in comparison to patients (p<0.0001), with a low to moderate level of concordance (C-statistic range 0.58-0.70; percent concordance range 29-50%). The majority of patients used moisturizing creams as a prophylactic measure (65.1%), as per institutional guidelines.
 
  There were significant discrepancies between PROs and CROs when assessing breast RD. CROs alone are insufficient in measuring RD as they fail to capture the impact on patient quality of life. The study findings highlight the need for improved RD symptom assessment and support the development of a new tool with both patient and clinician components.
 There were significant discrepancies between PROs and CROs when assessing breast RD. CROs alone are insufficient in measuring RD as they fail to capture the impact on patient quality of life. The study findings highlight the need for improved RD symptom assessment and support the development of a new tool with both patient and clinician components.
  A major burden of introducing an online daily adaptive proton therapy (DAPT) workflow is the time and resources needed to correct the daily propagated contours. In this study, we evaluated the dosimetric impact of neglecting the online correction of the propagated contours in a DAPT workflow.
 
  For five NSCLC patients with nine repeated deep-inspiration breath-hold CTs, proton therapy plans were optimised on the planning CT to deliver 60Gy-RBE in 30 fractions. All repeated CTs were registered with six different clinically used deformable image registration (DIR) algorithms to the corresponding planning CT. Structures were propagated rigidly and with each DIR algorithm and reference structures were contoured on each repeated CT. DAPT plans were optimised with the uncorrected, propagated structures (propagated DAPT doses) and on the reference structures (ideal DAPT doses), non-adapted doses were recalculated on all repeated CTs.
 
  Due to anatomical changes occurring during the therapy, the clinical target volume (CTV) coverage of the non-adapted doses reduces on average by 9.7% (V95) compared to an ideal DAPT doses. For the propagated DAPT doses, the CTV coverage was always restored (average differences in the CTV V95<1% compared to the ideal DAPT doses). Hotspots were always reduced with any DAPT approach.
 
  For the patients presented here, a benefit of online DAPT was shown, even if the daily optimisation is based on propagated structures with some residual uncertainties. However, a careful (offline) structure review is necessary and corrections can be included in an offline adaption.
 For the patients presented here, a benefit of online DAPT was shown, even if the daily optimisation is based on propagated structures with some residual uncertainties. However, a careful (offline) structure review is necessary and corrections can be included in an offline adaption.Nitric oxide (NO), a versatile free radical and a signalling molecule, plays an important role in the haematopoiesis, inflammation and infection. Impaired proliferation and differentiation of myeloid cells lead to malignancies and Hematopoietic deficiencies. This study was aimed to define the role of nNOS derived NO in neutrophil differentiation (in-vitro) and granulopoiesis (in-vivo) using multipronged approaches.  https://www.selleckchem.com/products/gsk2830371.html  The results obtained from nNOS over-expressing K562 cells revealed induction in C/EBPα derived neutrophil differentiation as evident by an increase in the expression of neutrophil specific cell surface markers, genes, transcription factors and functionality. nNOS mediated response also involved G-CSFR-STAT-3 axis during differentiation. Consistent increase in NO generation was observed during neutrophil differentiation of mice and human CD34+ HSPCs. Furthermore, granulopoiesis was abrogated in the nNOS inhibitor treated mice, depicting a decrease in the numbers of BM mature and progenitor neutrophils. Likewise, in vitro inhibition of nNOS in human CD34+ HSPCs indicated an indispensable role of nNOS in neutrophil differentiation. Expression of nNOS inhibitory protein, NOSIP was significantly and consistently decreased during the final stage of differentiation and was linked with the augmentation in NO release. Moreover, neutrophils from CML patients had more NOSIP and less NO generation as compared to the PMNs from healthy individuals. The present study thus indicates a critical role of nNOS, and its interaction with NOSIP during neutrophil differentiation. The study also highlights the importance of nNOS in the neutrophil progenitor proliferation and differentiation warranting investigations to assess its role in the haematopoiesis-related disorders.