Nitric oxide donors offer protection to RBC from storage lesion

BackgroundRed blood cell (RBC), which is the most commonly transfused blood component, due to its ability to save a life in absence of any other blood components, can be stored up to maximum 6 weeks by following standard preservation procedure. During storage, RBC undergoes various biophysical and biochemical changes (commonly known as storage lesion) for which blood transfusion with “old RBC” shows a lot of clinical problems especially relevant to critically ill patients. Recent research on S-nitrosylation of haemoglobin to improve oxygen delivery of banked blood revealed the important role of nitric oxide (NO) in protecting storage lesion.Materials and methodsIn the present study, we used various “NO donating” chemicals with different NO release dynamics and chemistries in RBC storage cocktails to test the effects of NO on storage lesion. Changes in different storage markers were evaluated after 7 days storage of pre-treated RBC.ResultsAll the NO donors have shown protection against hemolysis. However, S-nitroso glutathione (GSNO) ranks first in shielding RBCs from storage lesion and additionally, it helps in elevating the value of 2, 3-di phosphoglycerate (2, 3-DPG), improving the RBC membrane fluidity and decreasing the adhesion towards endothelial monolayer.DiscussionPresent study reveals that NO released from NO donors confers protection against storage lesions of the RBC. Further, the study confirms that pre-treatment with GSNO, a NO donor and a nitrosylating agent, ensures the best protection to RBC during low temperature storage, when compared to other NO donor treatments.     

中药配方精油——一种中药入药新形式的思考

饮片是中医临床用药的主体,随着中医用药现代化,中药配方颗粒逐步发展并初具规模。虽有中药注射剂、口服液等的加工形式,但只占中药市场的少部分,并以内服为主。而脂溶性成分口服时,溶出受限,吸收相对较少,且具有刺激胃肠道的副作用,造成患者耐受性低。虽有水提、醇提等加工制成的外用制剂,但多为粗制剂,且剂量随意,在一定程度上造成了脂溶性成分的浪费。而中药的脂溶性成分大多具有较好的生物活性,如五味子乙素、丹参酮、绿原酸甲酯等,但却没有合适的药用形式。若想"药"尽其用,就必须对中药的脂溶性成分进行系统研究,在提取、分离和收集工艺均相当成熟的基础上,研发以脂溶性成分为主的,药理药效确切的,又利于其吸收的药用形式。中药精油具有抗衰老、抗痴呆、抗氧化等多种活性,已广泛应用于临床、药妆、保健品等领域。但单方精油作用有限,配伍既可增强药效、降低毒性,也可扩大精油应用范围。因此,可将中药配方精油作为中药入药新形式,并以外用为主、内服为辅,以弥补中药外用多为粗制剂、剂量随意的不足和内服吸收少、刺激胃肠道的劣势,满足临床用药需求,更快、更准、更好、更强地发挥脂溶性成分的药效。     

三种智慧放疗计划预测模型的性能评价

目的比较三种智慧放疗计划预测模型的精度与泛化鲁棒性,为模型选择提供依据。方法收集45例前列腺癌和25例鼻咽癌临床放疗计划,运用Z、L、S模型预测前列腺癌中膀胱和直肠、鼻咽癌中左右腮腺的剂量体积直方图(DVH)。应用预测DVH与临床DVH曲线下面积的差别(|DVH预测-DVH临床|)评价预测误差,误差越小则预测精度越高。在单个危及器官(OAR)上比较3种预测模型的精度,并在不同OAR中计算各模型预测精度的标准差以评价和比较模型的泛化鲁棒性。结果对于膀胱和直肠,L模型的预测误差(0.114和0.163)显著大于Z和S模型(≤0.071,P<0.05);对于左腮腺,S模型的预测误差(0.033)与Z和L模型相近(≤0.025,P>0.05);对于右腮腺,S模型的预测误差(0.033)显著大于Z和L模型(≤0.028,P<0.05)。在不同OAR上,S模型的预测精度标准差比Z、L模型小(分别为0.016、0.018和0.060)。结论在前列腺癌膀胱和直肠的DVH预测中Z和S模型的精度较高,而在鼻咽癌左右腮腺中Z和L模型较高,在不同OAR上S模型的泛化鲁棒性相对较好。     

分化型甲状腺癌患者口服131I后体内活度变化及剂量水平

目的 研究¹³¹I治疗分化型甲状腺癌（DTC）患者体内放射性活度及外部剂量水平的变化规律，分析二者之间的关系，并估算400 MBq患者剂量当量率的修正因子。方法 研究对象为43例甲状腺全切术后，首次行¹³¹I"清甲"治疗的DTC患者，服药量为1 850~3 700 MBq，平均服药量（2 405±777）MBq。分别于口服¹³¹I后2、6、20、22、24、27、30、44、46、48、54、68及72 h，测定患者的体内剩余放射性活度以及患者前部0.3、1及3 m处的剂量当量率。结果 患者服¹³¹I后的体内剩余放射性活度随时间变化函数为A=A₀（1.033 16e^{-0.062 4t}+0.017 17）。可估算出"清甲"治疗的DTC患者有效半减期为12.19 h，体内放射性活度降至400 MBq仅需26.4~38.9 h。患者服用¹³¹I后距其0.3、1及3 m的标准化剂量当量率随时间变化函数分别为：Ḣ_0.3=127.220 7e^{-0.054 8t}+3.765 71、Ḣ₁=30.225 8e^{-0.064 4t}+0.824 67、Ḣ₃=4.161 9e^{-0.061 5t}+0.167 97。患者服¹³¹I后体内剩余放射性活度与1 m处剂量当量率呈正相关（r=0.982，P<0.05），函数为Ḣ₁=0.025A+1.245。DTC患者体内剩余活度分别为1 000、700和400 MBq时，距患者1 m处对应的剂量当量率分为26.2、18.7和11.2 μSv/h。估算活度为400 MBq的患者0.3、1及3 m处剂量当量率的修正因子分别为0.25、0.49及0.70。结论 服用¹³¹I活度在3 700 MBq以下的DTC患者仅需住院2日便可达到出院标准。当DTC患者体内活度降至400 MBq时，其1 m处的剂量当量率远小于25 μSv/h。单纯利用点源公式估算患者周围剂量当量率会造成高估的情况，因此对于公式估算患者周围辐射水平时使用的修正因子还需进一步研究，使模型估算结果更贴合实际情况。     

Safety data from the MenB-FHbp clinical development program in healthy individuals aged 10 years and older

BackgroundThe MenB-FHbp vaccine (Trumenba®) is licensed in various countries for the prevention of meningococcal serogroup B disease in individuals ≥ 10 years of age. The clinical development program included 11 completed trials where, in each trial, MenB-FHbp had an acceptable safety profile after a primary vaccination series was administered to individuals 10–65 years of age. However, the detection of potential rare events was limited because of individual clinical trial size. The current safety analysis evaluates pooled reactogenicity and other adverse events (AEs) reported in these trials to identify new safety signals not detectable in individual trials.MethodsEleven trials contributed safety data, of which 10 recorded local and systemic reactogenicity events; 8 of the trials were controlled, and reactogenicity data were pooled for 7 of these 8 trials. Additional AE evaluations included immediate AEs (IAEs), medically attended AEs (MAEs), serious AEs (SAEs), newly diagnosed chronic medical conditions (NDCMCs), and autoimmune or neuroinflammatory conditions.ResultsLocal and systemic reactions were more frequent in the MenB-FHbp group (n = 15,294) compared with controls (n = 5509), although most reactions were transient and mild to moderate in severity. Frequencies of IAEs, SAEs, MAEs, NDCMCs, and autoimmune or neuroinflammatory conditions were similar between the MenB-FHbp and control groups.ConclusionsMenB-FHbp demonstrated a favorable safety and tolerability profile in the clinical development program of > 15,000 vaccine recipients ≥ 10 years of age. No new safety signals were identified in the pooled analysis compared with data from the individual trials. Continued postmarketing safety surveillance is important for the identification of rare events.Clinicaltrials.gov: NCT01299480; NCT000808028; NCT00879814; NCT00780806; NCT01352845; NCT01352793; NCT01461993; NCT01323270; NCT01830855; NCT01461980; NCT01768117.     

Differing Characteristics of Human-Shaped Visual Stimuli Affect Clinicians’ Dosage of a Spinal Manipulative Thrust on a Low-Fidelity Model: A Cross-Sectional Study

ObjectiveThe purpose of this study was to determine whether chiropractic clinicians modulate spinal manipulation (SM) thrust characteristics based on visual perception of simulated human silhouette attributes.MethodsWe performed a cross-sectional within-participant design with 8 experienced chiropractors. During each trial, participants observed a human-shaped life-sized silhouette of a mock patient and delivered an SM thrust on a low-fidelity thoracic spine model based on their visual perception. Silhouettes varied on the following 3 factors: apparent sex (male or female silhouette), height (short, average, tall), and body mass index (BMI) (underweight, healthy, obese). Each combination was presented 6 times for a total of 108 trials in random order. Outcome measures included peak thrust force, thrust duration, peak preload force, peak acceleration, time to peak acceleration, and rate of force application. A 3-way repeated measures analysis of variance model was used to for each variable, followed by Tukey's honestly significant difference on significant interactions.ResultsPeak thrust force was reduced when apparent sex of the presented silhouette was female (F_1,7 = 5.70, P = .048). Thrust duration was largely invariant, except that a BMI by height interaction revealed a longer duration occurred for healthy tall participants than healthy short participants (F_4,28 = 4.34, P = .007). Compared to an image depicting obese BMI, an image appearing underweight lead to reduced peak acceleration (F_2,5 = 6.756, P = .009). Clinician time to peak acceleration was reduced in short compared to tall silhouettes (t₇ = 2.20, P = .032).ConclusionVisual perception of simulated human silhouette attributes, including apparent sex, height, and BMI, influenced SM dose characteristics through both kinetic and kinematic measures. The results suggest that visual information from mock patients affects the decision-making of chiropractic clinicians delivering SM thrusts.