From the Cover: Quasiresonant amplification of planetary waves and recent Northern Hemisphere weather extremes

In recent years, the Northern Hemisphere has suffered several devastating regional summer weather extremes, such as the European heat wave in 2003, the Russian heat wave and the Indus river flood in Pakistan in 2010, and the heat wave in the United States in 2011. Here, we propose a common mechanism for the generation of persistent longitudinal planetary-scale high-amplitude patterns of the atmospheric circulation in the Northern Hemisphere midlatitudes. Those patterns—with zonal wave numbers m = 6, 7, or 8—are characteristic of the above extremes. We show that these patterns might result from trapping within midlatitude waveguides of free synoptic waves with zonal wave numbers k ≈ m. Usually, the quasistationary dynamical response with the above wave numbers m to climatological mean thermal and orographic forcing is weak. Such midlatitude waveguides, however, may favor a strong magnification of that response through quasiresonance.     

基于ARIMA乘积季节模型的科室级常规耗材需求量预测研究

目的探讨季节性因素的时间序列分析方法在科室常规耗材库管理中的应用,分析和预测未来一段时间内医用常规耗材的使用需求。方法采用整合移动平均自回归(Autoregressive Integrated Moving Average,ARIMA)乘积季节模型对北京市某医院某科室某品牌注射器2014年1月至2018年12月的逐月使用量进行预测。结果ARIMA(0,1,2)(0,1,1)12模型的平均绝对百分比误差为5.308,在实际业务可接受范围之内,因此模型拟合效果较好,预测结果接近实际产生值。结论ARIMA(0,1,2)(0,1,1)12模型能够准确的进行该类医用常规耗材的短期预测,可应用于医院物资管理信息系统中,实现对医院耗材的合理管控,并为科室制定医用耗材的资金支出预算提供可靠依据。     

Praziquantel treatment of school children from single and mixed infection foci of intestinal and urogenital schistosomiasis along the Senegal River Basin: monitoring treatment success and re-infection patterns

Following major water development schemes in the 1980s, schistosomiasis has become a serious parasitic disease of children living in the Senegal River Basin. Both urogenital (Schistosoma haematobium) and intestinal (Schistosoma mansoni) schistosomiasis can be highly prevalent in school-aged children, with many individuals infected with both parasites. In order to investigate the transmission and re-infection dynamics of both parasite species, single and mixed infection foci at three villages (Nder and Temeye; S. mansoni and S. haematobium foci and Guia; S. haematobium focus) were studied. In each focus infected children were identified and selected for a 12-month study involving two treatments with praziquantel (40 mg/kg) three weeks apart at the beginning of the study and again 6 months into the study. Urine and stool samples were examined for schistosome eggs before and at 6 weeks and 6 months after chemotherapy. Prevalence and intensity of infection were recorded for each child at each time point. Before treatment, in all three villages, the prevalence and intensity of infection was extremely high for both S. mansoni (79–100%) and S. haematobium (81–97%). With the first round of chemotherapy sufficient cure rates (CRs) of both species were achieved in all villages (38–96%) with high egg reduction rates (ERRs) (97–99%). The data show that high and rapid re-infection rates occur, especially for S. mansoni, within a six-month period following treatment. Re-infection must be highly linked to ecological and seasonal factors. The persistence of S. mansoni in Nder could raise concern as levels of infection intensity remain high (geometric mean intensity at baseline 653 epg changed to 705 epg at 12 months) after four rounds of chemotherapy. This phenomenon could be explained by extremely rapid re-infection dynamics or a sub-optimal efficacy of praziquantel against S. mansoni in this village. High intensities in mixed infections may influence disease epidemiology and control warranting further studies. The disease situation in the SRB must be monitored closely and new treatment regimes should be designed and implemented to control schistosomiasis in the school-age population.     

The physiology and toxicology of acute inhalation phosphine poisoning in conscious male rats

Phosphine (PH₃) is a toxidrome-spanning chemical that is widely used as an insecticide and rodenticide. Exposure to PH₃ causes a host of target organ and systemic effects, including oxidative stress, cardiopulmonary toxicity, seizure-like activity and overall metabolic disturbance. A custom dynamic inhalation gas exposure system was designed for the whole-body exposure of conscious male Sprague-Dawley rats (250–350?g) to PH₃. An integrated plethysmography system was used to collect respiratory parameters in real-time before, during and after PH₃ exposure. At several time points post-exposure, rats were euthanized, and various organs were removed and analyzed to assess organ and systemic effects. The 24?h post-exposure LCt₅₀, determined by probit analysis, was 23,270?ppm?×?min (32,345?mg?×?min/m³). PH₃ exposure affects both pulmonary and cardiac function. Unlike typical pulmonary toxicants, PH₃ induced net increases in respiration during exposure. Gross observations of the heart and lungs of exposed rats suggested pulmonary and cardiac tissue damage, but histopathological examination showed little to no observable pathologic changes in those organs. Gene expression studies indicated alterations in inflammatory processes, metabolic function and cell signaling, with particular focus in cardiac tissue. Transmission electron microscopy examination of cardiac tissue revealed ultrastructural damage to both tissue and mitochondria. Altogether, these data reveal that in untreated, un-anesthetized rats, PH₃ inhalation induces acute cardiorespiratory toxicity and injury, leading to death and that it is characterized by a steep dose-response curve. Continued use of our interdisciplinary approach will permit more effective identification of therapeutic windows and development of rational medical countermeasures and countermeasure strategies.     

Reliability of center of pressure measures for assessing the development of sitting postural control through the stages of sitting

Cerebral palsy (CP) impairs an individual’s ability to move and control one’s posture. Unfortunately, the signs and symptoms of CP may not be apparent before age two. Evaluating sitting posture is a potential way to assess the developing mechanisms that contribute to CP. The purpose of this project was to determine the reliability of linear and nonlinear measures, including inter- and intrastage reliability, when used to analyze the center of pressure (COP) time series during the stages of sitting development in children with typical development (TD) and with/at-risk for cerebral palsy (CP). We hypothesized that nonlinear tools would be more reliable than linear tools in assessing childrens’ sitting development, and reliability would increase with development. COP data was recorded for three trials at eight sessions. Linear parameters used were root mean square, range of sway for the anterior-posterior (AP) and medial-lateral (ML) directions, and sway path. Nonlinear parameters used were Approximate Entropy, the largest Lyapunov Exponent, and Correlation Dimension for the AP and ML direction. Participants consisted of 33 children with TD and 26 children with/at-risk for CP. Our results determined that COP is a moderately reliable method for assessing the development of sitting postural control in stages in both groups. Thus, clinicians may be able to use measures from COP data across stages to assess the efficacy of therapeutic interventions that are intended to improve sitting postural abilities in children with/at-risk for CP.     

SARIMA-GRNN组合模型和SARIMA模型在流行性腮腺炎发病率预测中的应用

目的 探讨SARIMA-GRNN组合模型和SARIMA模型在流行性腮腺炎发病率预测中的应用,并对他们的预测效果进行比较。 方法 选取2004—2016年上海市流行性腮腺炎逐月发病率资料,基于2004年1月—2016年6月的数据建立SARIMA模型。利用2004—2015年流行性腮腺炎的SARIMA模型拟合值与实际值、时间因子训练SARIMA-GRNN组合模型,并运用2016年1—6月数据进行验证,筛选模型最优平滑因子(spread)。采用2016年7—12月数据进行回代验证模型的外推预测效果。评价指标包括平均绝对误差百分比(MAPE)、平均误差率(MER)、均方误差(MSE)和平均绝对误差(MAE)。 结果 SARIMA(0,0,2)(0,1,1)₁₂为最优SARIMA模型。SARIMA-GRNN组合模型spread 值为0.0037。SARIMA模型、SARIMA-GRNN组合模型拟合的MAPE、MER、MSE和MAE依次分别为16.19%、15.18%、0.14、0.25;2.93%、2.28%、0.01、0.04。SARIMA模型、SARIMA-GRNN组合模型预测的MAPE、MER、MSE和MAE依次分别为17.40%、17.26%、0.03、0.16;15.24%、15.50%、0.02、0.14。 结论 SARIMA-GRNN组合模型拟合及预测效果均优于SARIMA模型,但预测精度有待进一步提高。     

Seasonal Variation of Phyto-Constituents of Tea Leaves Affects Antiproliferative Potential

Objective: Tea (Camellia sinensis Linn.; family: Theaceae) is popular as a stimulant beverage across the globe and is also utilized as a functional antioxidant in alternative medicine. This study has evaluated the impact of seasonal variation on phyto-constituents of tea.

Method: The antiproliferative potential of methanolic extracts of tea leaves collected in the rainy season (MECR) was compared with the extract of tea leaves collected in the autumn season (MECA) of the same mother plant. Evaluation of in vivo antitumor activity was carried out in adult female Swiss albino mice groups inoculated with Ehrlich ascites carcinoma (EAC) cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to compare efficacy of MECR with that of MECA in the EAC cell line. Both qualitative and quantitative tests for phytochemical constituents present in MECA and MECR were performed. Antitumor efficacy of both the extracts was determined by evaluating different tumor markers showing dose-dependent cytotoxicity.

Results: Statistically significant reduction in EAC-induced tumor was observed in MECR treated mice compared to MECA treated ones. Cell decimation was significantly higher with MECR treatment, where restoration of different parameters including tissue structures returned to normal. Moreover, gas chromatography–mass spectrometry (GC-MS) study revealed the presence of cyclobarbital and benzazulene derivative in MECR, which is thought to be a novel source of these chemicals.

Conclusions: To our knowledge, there is no report that has attempted to reveal nutritional changes in terms of efficacy and variation in anticancer constituents in tea leaves, plucked in two seasons. This study revealed a novel source of barbital and benzazulene derivative. The unique presence of cyclobarbital and benzazulene, as revealed from GC-MS data, in methanolic extract of tea leaves collected during the rainy season (MECR) may have contributed to its enhanced in vitro (adopting MTT assay) and in vivo (on EAC-infected Swiss albino mice) cytotoxicity vis-à-vis antiproliferative properties compared to methanolic extract of tea leaves collected during the autumn season (MECA). The nature of plucking leaves in the two selected seasons is different.     

Computational studies on horseshoe shape pocket of human orexin receptor type 2 and boat conformation of suvorexant by molecular dynamics simulations

The FDA approved drug suvorexant binds to the horseshoe shape pocket of OX₂R with the boat conformation. The horseshoe shape pocket plays an important role on the biological activity of OX₂R in the cell membrane. To study the binding mechanism between the horseshoe shape pocket of OX₂R and boat conformation of suvorexant, the crystal structures of wild type and N324A mutant of OX₂R in complex with antagonist suvorexant are chosen to perform molecular dynamics (MD) simulations, QM/MM, and MMGBSA calculations. By comparison with the wild type of OX₂R, the results show the 1,2,3‐triazole and p‐toluamide groups of suvorexant are changed in the N324A mutant of OX₂R during 200 ns MD simulations. The QM/MM and weak interaction analysis are employed to calculate the non‐covalent bonds interaction between suvorexant and key residues in the wild type and N324A mutant of OX₂R. The MMGBSA calculations indicate the entropy energy is an important influence factor for suvorexant affinity in the distorted horseshoe shape pocket of OX₂R. Our results not only show the horseshoe shape pocket of OX₂R is the necessary conformation for the binding of antagonist suvorexant, but also give the important sites and structural features for antagonist design of OX₂R.