Ratiometric analysis in hyperpolarized NMR (I): test of the two‐site exchange model and the quantification of reaction rate constants

Conventional methods for the analysis of in vivo hyperpolarized ¹³C NMR data from the lactate dehydrogenase (LDH) reaction usually make assumptions on the stability of rate constants and/or the validity of the two‐site exchange model. In this study, we developed a framework to test the validity of the assumption of stable reaction rate constants and the two‐site exchange model in vivo via ratiometric fitting of the time courses of the signal ratio L(t)/P(t). Our analysis provided evidence that the LDH enzymatic kinetics observed by hyperpolarized NMR are in near‐equilibrium and satisfy the two‐site exchange model for only a specific time window. In addition, we quantified both the forward and reverse exchange rate constants of the LDH reaction for the transgenic and mouse xenograft models of breast cancer using the ratio fitting method developed, which includes only two modeling parameters and is less sensitive to the influence of instrument settings/protocols, such as flip angles, degree of polarization and tracer dosage. We further compared the ratio fitting method with a conventional two‐site exchange modeling method, i.e. the differential equation fitting method, using both the experimental and simulated hyperpolarized NMR data. The ratio fitting method appeared to fit better than the differential equation fitting method for the reverse rate constant on the mouse tumor data, with less relative errors on average, whereas the differential equation fitting method also resulted in a negative reverse rate constant for one tumor. The simulation results indicated that the accuracy of both methods depends on the width of the transport function, noise level and rate constant ratio; one method may be more accurate than the other based on the experimental/biological conditions aforementioned. We were able to categorize our tumor models into specific conditions of the computer simulation and to estimate the errors of rate quantification. We also discussed possible approaches to the development of more accurate rate quantification methods for hyperpolarized NMR. Copyright © 2013 John Wiley & Sons, Ltd.     

Total ankle replacement in patients under the age of 50. Should the indications be revised?

BackgroundHigh physical demand and young age are currently considered contraindications for total ankle replacement. This study aimed to compare its results between patients under the age of 50 and those aged 50 or older.Methods103 patients derived from an ongoing prospective multicentric study with a mean follow-up of 41 (range, 24–72) months were included in this study. Clinical status (AOFAS score), range of motion (ROM), complication and survivorship rates were compared between <50 and ≥50 patients.ResultsROM and AOFAS score were significantly higher, as were their increases relatively to pre-operative values in patients <50. Complication and survivorship rates were comparable between both groups.ConclusionsAt medium-term, ankle replacement is at least as effective in patients under the age of 50 as in those with aged 50 or older. Long-term results will allow to assess whether surgical indications for should be revised.     

福建省人体肠道原虫病调查分析

目的 了解福建省人体肠道原虫病流行现状。方法 按全国统一调查方案,以分层整群随机抽样方法,抽取15个调查县(市、区),每个县(市、区)调查5个点,每个调查点调查人数不少于250人。每份标本采用卢戈氏碘液涂片法与生理盐水直接涂片法检查肠道原虫包囊或滋养体。结果 共调查15县(市、区)75个点(村)10 652人,阳性者222人,各种肠道原虫总感染率为2.08%。检出6种肠道原虫,即人芽囊原虫、微小内蜒阿米巴、结肠内阿米巴、哈门氏内阿米巴、波列基内阿米巴及蓝氏贾第鞭毛虫,其感染率分别为0.79%、0.58%、0.41%、0.18%、0.09%与0.02%。男性感染率为0.84%,女性为1.25%,女性高于男性(χ²=8.8126,P<0.05)。感染者最大年龄86岁,最小3岁,以高年龄组(56岁以上)为主,占38.3%。感染者分布于多种职业,其中农民占77.9%,其次为学生占14.4%。调查地区感染率以平潭为最高7.04%,其次为漳浦4.62%与周宁3.92%。浙闽山地丘陵生态功能区感染率为1.52%(83/5469),滇桂粤中部闽南山地丘陵生态功能区为2.68%(139/5183),两者差异具有统计学意义(χ²=17.674,P<0.01)。结论 本次调查的人群原虫总感染率大幅降低,感染虫种明显减少,并以人芽囊原虫为常见的肠道原虫,应列为今后防制重点。     

Pentoxifylline protects against loss of function and renal interstitial fibrosis in chronic experimental partial ureteral obstruction

Tubulointerstitial fibrosis (TIF) is a hallmark of chronic kidney disease resulting from diverse etiologies and predicts severity and progression of the kidney disease. To investigate the pathogenesis of TIF, complete unilateral ureteral obstruction (UUO) is the most widely used animal model. However, UUO precludes evaluation of renal function. In the present study, we created a rat model of chronic partial ureteral obstruction (PUO), which allowed assessment of renal function at different intervals after obstruction. We examined the effects of pentoxifylline (PTF), a phosphodiesterase inhibitor used clinically to treat peripheral artery disease, on renal function and TIF. Studies were performed in sham-PUO rats and rats with 14-day PUO or 30-day PUO receiving vehicle in drinking water or PTF (400?mg/liter in drinking water). At day-14 PUO, glomerular filtration rate (GFR) was markedly and similarly depressed in rats receiving vehicle or PTF as compared with sham-operated rats. However, at day-30 PUO, GFR in rats receiving PTF was significantly higher than that in rats receiving vehicle, approaching the level seen in the sham-operated rats. At day-30 PUO, histologic studies also revealed a marked reduction of TIF in rats treated with PTF as compared with the rats receiving vehicle in drinking water. Western blot analysis demonstrated that at day-30 the expression of α-smooth muscle actin (an indicator of renal fibrosis) in the medulla was significantly reduced in PUO rats treated with PTF. In conclusion, PTF treatment ameliorated renal fibrosis and helped preserve renal function in a rodent model of PUO.     

人类基础代谢率测量方法的研究进展

基础代谢率对于制定人群每日能量所需，科学指导膳食具有重要意义。目前基础代谢率有3种测量方法， 包括直接测热法、间接测热法和公式估算法。直接测热法难度较大不易实现，仅仅运用于某些特殊人群中；而间接 测热法和公式推测法是目前使用较多的两种方法。间接测热法准确性高，适用于有基础代谢测量需要的个体或公式 推测法的数据收集。公式推测法简便易行，适合大样本人群。     

The efficacy of lapatinib and capecitabine in HER-2 positive breast cancer with brain metastases: A systematic review and pooled analysis

IntroductionBreast cancer (BC) with HER-2/neu overexpression or amplification (HER-2+) is associated with a higher prevalence of brain metastases (BMs) when compared to other subtypes. Among approved drugs for HER-2+ BC, lapatinib (L) is associated with single agent activity toward BMs. We conducted a systematic review to determine the efficacy of L, singly or in combination with capecitabine (C), as a treatment for HER-2+ BMs.Material and methodsWe searched PubMed, EMBASE, The Cochrane Library, SCOPUS, Web of Science, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (ICTRP), and the European Union Clinical Trials Register for studies reporting data on L, singly or in combination with C, for the treatment of HER-2+ BC with BMs. Primary end-points were overall response rate (ORR) and disease control rate (DCR); these were pooled to provide an aggregate value. Progression-free survival (PFS) and overall survival (OS) were secondary end-points. Data were pooled using number of events/number of evaluable patients, according to a fixed or random effect model.ResultsOverall, 12 studies were included in the present meta-analysis, for a total of 799 patients with BMs. The pooled overall response rate (ORR) was 21.4% (95% CI 11.7–35.9). After exclusion of patients that received L alone, ORR reached 29.2% (95% CI 18.5–42.7). The pooled median PFS and OS were 4.1 (95% CI 3.1–6.7) and 11.2 (95% CI 8.9–14.1) months, respectively.ConclusionsDue to its activity on BMs, the L + C combination may be considered for HER-2+ BC that has progressed in the brain, when local therapy has been performed or failed and re-irradiation is not feasible.     

Nickel titanium springs versus stainless steel springs: A randomized clinical trial of two methods of space closure

Objective: To compare the clinical performance of nickel titanium (NiTi) versus stainless steel (SS) springs during orthodontic space closure. Design: Two-centre parallel group randomized clinical trial. Setting: Orthodontic Department University of Manchester Dental Hospital and Orthodontic Department Countess of Chester Hospital, United Kingdom. Subjects and methods: Forty orthodontic patients requiring fixed appliance treatment were enrolled, each being randomly allocated into either NiTi (n?=?19) or SS groups (n?=?21). Study models were constructed at the start of the space closure phase (T₀) and following the completion of space closure (T₁). The rate of space closure achieved for each patient was calculated by taking an average measurement from the tip of the canine to the mesiobuccal groove on the first permanent molar of each quadrant. Results: The study was terminated early due to time constraints. Only 30 patients completed, 15 in each study group. There was no statistically significant difference between the amounts of space closed (mean difference 0.17?mm (95%CI ?0.99 to 1.34; P?=?0.76)). The mean rate of space closure for NiTi coil springs was 0.58?mm/4 weeks (SD 0.24) and 0.85?mm/4 weeks (SD 0.36) for the stainless steel springs. There was a statistically significant difference between the two groups (P?=?0.024), in favour of the stainless steel springs, when the mean values per patient were compared. Conclusions: Our study shows that stainless steel springs are clinically effective; these springs produce as much space closure as their more expensive rivals, the NiTi springs.