MRI as an alternative to serum ferritin for diagnosis of iron overload in children in the context of immune response after stem cell transplantation

Multiple blood cell transfusions may cause iron overload or even liver fibrosis, requiring early diagnosis and intervention. SF is the standard for estimating iron levels in the body, but it also increases with inflammation. We hypothesized that T₂* magnetic resonance (MR) relaxometry is a more accurate alternative for follow‐up in pediatric patients before and after allogenic SCT. Twenty‐three children (mean age 10.2 years, 10 female, 13 male) were evaluated prospectively before SCT as well as at least 1 year after SCT with T₂* relaxometry on a 1.5 T MR‐scanner to estimate liver iron concentrations from the T₂* values (“MR‐Fe”). The results were compared with SF, while also considering CRP, and correlated with the number of transfusions. Overall, 24.3 transfusions were administered in average, mainly within 100 days of SCT (mean 10.5 units). Both MR‐Fe and SF increased after SCT and decreased in the absence of new transfusions 1 year later without chelate therapy. This suggests regeneration of LP and iron loss, although the original states were not reached. Additionally, simultaneous peaks of CRP and SF were observed directly after SCT. MR‐Fe did neither reveal these peaks nor was it associated with CRP (P = .39). We postulate that these early CRP and SF peaks after SCT are probably related to inflammatory reactions and not to iron overload. Thus, SF is not reliable for iron overload diagnosis after SCT in every condition. Beside this interaction, SF and MR‐Fe revealed similar accuracy. MRI, however, has practical and economical disadvantages in routine estimation of iron.     

siRNA沉默HLA-A2基因表达对人脐带间充质干细胞诱导成骨的影响

目的探讨RNAi技术下调人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,hUCMSCs)HLA-A2基因表达后,对HLA-A2基因诱导成骨的影响。方法利用HLA-A2靶向小分子干扰RNA(small interfering RNA,siRNA)转染hUCMSCs,实验组为转染的细胞,对照组为未转染细胞。免疫细胞化学染色、Western Blot法检测两组细胞HLA-A2的表达;用诱导剂(0.1μmol/L地塞米松、10mmol/Lβ-甘油磷酸钠、50mg/L维生素C)行成骨诱导分化,茜素红矿化结节染色计数;碱性磷酸酶(ALP)染色以及比色法检测ALP活性。结果免疫细胞化学染色显示,实验组HLA-A2表达为弱阳性,对照组HLA-A2表达为阳性;Western Blot法检测HLA-A2蛋白的表达量对照组明显高于实验组。茜素红矿化结节染色显示:两组细胞均出现红色结节的阳性染色,但无差异(P0.05);两组ALP染色细胞胞浆均呈蓝色阳性反应,ALP活性检测结果显示两组无差异(P0.05)。结论应用RNAi技术下调HLA-A2基因表达后,不影响人脐带间充质干细胞的成骨诱导。     

Fostering graduate nurse practice readiness in context

BackgroundThe healthcare environment is highly pressured, dynamic and demanding of staff. Existing research indicates that when graduate nurses begin work, they are not practice ready and struggle to adapt and manage their responsibilities as registered nurses.AimAs part of a larger study, this paper examines the impact of the healthcare environment on graduate nurses’ practice readiness and the factors that assist them to become practice ready.MethodMultiple case study design with 67 participants from four different professional groups employed in four healthcare institutions in one state in Australia. Grounded theory methods of data analysis, document review, and cross case analysis were utilised in this study.FindingsThe healthcare system, workplace environment and quality of workplace interactions impact on actual and perceived graduate nurse performance. Graduate nurses develop practice readiness progressively along a transition continuum and attaining practice readiness is reliant on factors present in both the education and workplace environments.DiscussionEducation and workplace factors collectively create the right environment for graduate nurses to flourish. Education and practice sectors need to work together to ensure graduate readiness over a four-year timeline from the commencement of nursing studies through to the end of the graduate year to ensure practice readiness.ConclusionCreating positive workplace environments that support nursing students and graduate nurses to develop practice readiness can enhance the quality of care they provide, promote their retention in the health workforce and contribute to improved healthcare practice and outcomes.     

Preclinical hyperpolarized 129Xe MRI: ventilation and T2* mapping in mouse lungs at 7 T using multi‐echo flyback UTE

Fast apparent transverse relaxation (short T₂*) is a common obstacle when attempting to perform quantitative ¹H MRI of the lungs. While T₂* times are longer for pulmonary hyperpolarized (HP) gas functional imaging (in particular for gaseous ¹²⁹Xe), T₂* can still lead to quantitative inaccuracies for sequences requiring longer echo times (such as diffusion weighted images) or longer readout duration (such as spiral sequences). This is especially true in preclinical studies, where high magnetic fields lead to shorter relaxation times than are typically seen in human studies. However, the T₂* of HP ¹²⁹Xe in the most common animal model of human disease (mice) has not been reported. Herein, we present a multi‐echo radial flyback imaging sequence and use it to measure HP ¹²⁹Xe T₂* at 7 T under a variety of respiratory conditions. This sequence mitigates the impact of T₁ relaxation outside the animal by using multiple gradient‐refocused echoes to acquire images at a number of effective echo times for each RF excitation. After validating the sequence using a phantom containing water doped with superparamagnetic iron oxide nanoparticles, we measured the ¹²⁹Xe T₂* in vivo for 10 healthy C57Bl/6 J mice and found T₂* ~ 5 ms in the lung airspaces. Interestingly, T₂* was relatively constant over all experimental conditions, and varied significantly with sex, but not age, mass, or the O₂ content of the inhaled gas mixture. These results are discussed in the context of T₂* relaxation within porous media.     

Intestinal Permeability to Mannitol and Lactulose in Children with Type 1 Diabetes with the HLA-DQB1*02 Allele

Food antigens and enteroviruses are possible triggers of type 1 diabetes. Because permeability of the intestinal epithelium may facilitate contact of these antigens with the mucosal immune system, we set out to study intestinal permeability in patients with type 1 diabetes. Children with type 1 diabetes (n = 26, mean age 12 years, mean duration of disease 4 years) and 24 healthy age-matched control children were given mannitol and lactulose orally, and their intestinal permeability was measured as a percentage of this dose recovered in urine. Patients with type 1 diabetes did not differ in their permeability to lactulose, nor was their lactulose/mannitol ratio any different from that of controls. However, patients with type 1 diabetes who had the HLA-DQB1 &#72 02 allele and, therefore, a higher risk for celiac disease (CD) absorbed significantly more mannitol (mean+95% CI): 17.7% (15.2-20.2) than did those negative for this allele: 12.3% (8.2-16.4), p = 0.04. Their lactulose permeability was also higher: 0.30 (0.16-0.44) and 0.09% (0-0.18), respectively, p = 0.02. Although the differences in permeability reach statistical significance, there was still much overlap between the two groups in terms of actual laboratory values. The higher permeability of patients with the HLA-DQB1 &#72 02 allele suggests that these patients may be more prone to develop abnormal immune responses to food antigens.