Epidermoid cyst in intrapancreatic accessory spleen: A systematic review

Background/Objectives

Due to its rarity, epidermoid cyst in intrapancreatic accessory spleen (ECIPAS) is still a diagnostic dilemma during clinical practice. The aim of this review was to summarize the epidemiologic features and management of ECIPAS.

No Apparent Correlation of kp with Steric Hindrance for Branched Acrylates

The Arrhenius parameters of the propagation rate coefficient, k_p, are determined via the pulsed laser polymerization—size exclusion chromatography (PLP‐SEC) method for five branched acrylates (tert‐butyl (tBA), isobornyl (iBoA), benzyl (BnA), 2‐ethylhexyl (EHA), and 2‐propylheptyl acrylate (PHA)) in 1 m solution in butyl acetate (BuAc) to complete the series, published by Haehnel et al. in 2014, of branched acrylates (isononyl (INA‐A), tridecyl (TDA‐A and TDN‐A), heptadecyl (C17A), and henicosyl acrylate (C21A)) in solution that do not show a trend in k_p. Furthermore, the propagation rate coefficients of the branched acrylates in 1 m solution are critically compared with the branched acrylates in bulk as well as branched methacrylates. A summary of the trends and family‐type behavior for the linear and branched (meth)acrylates as well as methacrylates with cyclic ester side chains is provided. For the branched acrylates in 1 m solution, no clear trends of the propagation rate coefficients, k_p, or Arrhenius parameters A and E_A are detectable and—in contrast to the corresponding methacrylates—there is no family‐type behavior observed in solution as well as in bulk.

     

Improved quantification of protein in vaccines containing aluminum hydroxide by simple modification of the Lowry method

Aluminum (Al) components in vaccines are known to act as adsorbents that interfere with accurate protein quantification by the Lowry method. Therefore, certain modifications based on the characteristics and compositions of the vaccine are required for determination of protein contents.We investigated the effects of an additional centrifugal separation and found that protein contents were overestimated by up to 238% without centrifugation through a collaborative study performed with hepatitis B vaccines containing Al. However, addition of a centrifugation step yielded protein concentrations that were similar to the actual values, with small coefficients of variation (CVs). Proficiency testing performed in 11 laboratories showed that four laboratories did not have satisfactory results for vaccines containing aluminum hydroxide, although all laboratories were proficient in protein analysis when samples did not contain aluminum hydroxide. Incomplete resuspension of aluminum hydroxide solution with alkaline copper solution was the major cause of insufficient proficiency in these laboratories.     

Efficient statistical tests to compare Youden index: accounting for contingency correlation

Youden index is widely utilized in studies evaluating accuracy of diagnostic tests and performance of predictive, prognostic, or risk models. However, both one and two independent sample tests on Youden index have been derived ignoring the dependence (association) between sensitivity and specificity, resulting in potentially misleading findings. Besides, paired sample test on Youden index is currently unavailable. This article develops efficient statistical inference procedures for one sample, independent, and paired sample tests on Youden index by accounting for contingency correlation, namely associations between sensitivity and specificity and paired samples typically represented in contingency tables. For one and two independent sample tests, the variances are estimated by Delta method, and the statistical inference is based on the central limit theory, which are then verified by bootstrap estimates. For paired samples test, we show that the estimated covariance of the two sensitivities and specificities can be represented as a function of kappa statistic so the test can be readily carried out. We then show the remarkable accuracy of the estimated variance using a constrained optimization approach. Simulation is performed to evaluate the statistical properties of the derived tests. The proposed approaches yield more stable type I errors at the nominal level and substantially higher power (efficiency) than does the original Youden's approach. Therefore, the simple explicit large sample solution performs very well. Because we can readily implement the asymptotic and exact bootstrap computation with common software like R, the method is broadly applicable to the evaluation of diagnostic tests and model performance. Copyright © 2015 John Wiley & Sons, Ltd.     

融水小型猪剖检程序以及主要脏器自发性病变组织学观察

目的掌握融水小型猪主要器官解剖学及组织学数据。方法选择6月龄F1代小型猪雌雄各两头,麻醉后测体重,进行大体解剖,颈动脉取血测定全身血量、血浆量,记录脊柱数量和恒齿齿式,取出主要脏器进行拍照、称重及测量,切取脏器的部分组织,用福尔马林固定后做组织切片,在显微镜下观察并拍照。结果获得了融水小型猪的主要脏器形态图片、组织学显微图片、主要脏器重量、脏器系数及其他基础数据。结论初步掌握了融水小型猪的器官解剖学和组织学基础数据。     

ADC值和标化 ADC值诊断前列腺癌恶性程度价值的比较

目的：比较表观扩散系数（ADC）值和标化ADC值在诊断前列腺癌恶性程度中的价值。方法回顾性分析经病理证实的34例前列腺癌的弥散加权成像（DWI）扫描结果。测量患者49个癌灶及外周带正常区域的ADC值,计算癌灶标化 ADC值。根据病理Gleason评分,49个癌灶分为：≤6分（低危组）、7分（中危组）、≥8分（高危组）共3组。对各组ADC值之间和标化ADC值之间的差别及ADC值和标化ADC值与Gleason评分之间的相关性进行统计学分析。结果前列腺癌 ADC值及标化ADC值3组整体差异均有统计学意义（P＜0．01）,但两两比较ADC值在中危组与高危组之间差异无统计学意义（P＞0．05）,而标化ADC值在各组间差异均有统计学意义（ P＜0．05）。ADC值（ r＝－0．546,P＝0．000）和标化 ADC 值（ r＝－0．575,P＝0．000）与Gleason评分均呈负相关。在比较前列腺癌各组的ROC曲线下面积时,标化ADC值与ADC值之间的差异无统计学意义（P＞0．05）,但当特异性调整至100％时,标化ADC值在区别低危组与中危组、低危组与高危组时较ADC值具有更高的灵敏性（47．5％ vs ．5．6％、78．2％ vs ．50．9％）。结论 ADC值和标化ADC值与Gleason评分均呈负相关,但标化ADC值在诊断前列腺癌恶性程度方面可能具有更高的效能。     

Validity and Reliability of Outcome Measures Assessing Dexterity,Coordination, and Upper Limb Strength in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

Objective

To document in adults affected by autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) the intra- and interrater reliability, standard error of measurement, agreement, minimal detectable change, and construct validity of the 9-Hole Peg Test (NHPT), the Standardized Finger-to-Nose Test (SFNT), and grip strength.

住院病人空间分布函数研究

目的:研究住院病人空间分布以及住院病人距离衰减系数,了解居民医疗服务获得的地理可及性现状,为区域卫生规划提供决策依据。方法:随机抽取23家医疗机构住院病人,利用地理信息系统计算病人到就诊医疗机构的距离以及相应的住院病人概率,进行多种曲线模型拟合,根据决定系数和模拟图形选择适宜的模型,得出相应的距离衰减系数。结果:指数曲线模型在二级医疗机构中拟合效果较好,乘幂曲线模型在三级医疗机构中拟合效果较好。指数曲线模型中二级综合医疗机构、二级专科医疗机构住院病人距离衰减系数均值分别为0.51、0.50。乘幂曲线模型中三级综合医疗机构、三级专科医疗机构住院病人距离衰减系数均值分别为0.84、0.53。结论:二级医疗机构住院病人概率随距离衰减的趋势快于三级医疗机构,综合医疗机构住院病人概率随距离衰减的趋势快于专科医疗机构。在区域卫生规划中计算卫生资源配置水平时,对于不同级别、类别的医疗机构应采用不同的距离衰减系数。     

Correlations Between the Incidence of National Notifiable Infectious Diseases and Public Open Data,Including Meteorological Factors and Medical Facility Resources

Objectives:

This study was performed to investigate the relationship between the incidence of national notifiable infectious diseases (NNIDs) and meteorological factors, air pollution levels, and hospital resources in Korea.

Methods:

We collected and stored 660 000 pieces of publicly available data associated with infectious diseases from public data portals and the Diseases Web Statistics System of Korea. We analyzed correlations between the monthly incidence of these diseases and monthly average temperatures and monthly average relative humidity, as well as vaccination rates, number of hospitals, and number of hospital beds by district in Seoul.

Results:

Of the 34 NNIDs, malaria showed the most significant correlation with temperature (r=0.949, p<0.01) and concentration of nitrogen dioxide (r=-0.884, p<0.01). We also found a strong correlation between the incidence of NNIDs and the number of hospital beds in 25 districts in Seoul (r=0.606, p<0.01). In particular, Geumcheon-gu was found to have the lowest incidence rate of NNIDs and the highest number of hospital beds per patient.

Conclusions:

In this study, we conducted a correlational analysis of public data from Korean government portals that can be used as parameters to forecast the spread of outbreaks.     

Role of Components in the Formation of Self-microemulsifying Drug Delivery Systems

Components:In order to formulate a successful SMEDDS for maximum therapeutic effect, due consideration must be given to various factors such as physicochemical properties of the active moiety as well as excipients, potential for drug excipient interaction (in vitro and in vivo) and physiological factors that promote or inhibit the bioavailability. Further, other important factors such as regulatory status, solubilization capacity, miscibility, physical state of the excipients at room temperature, digestibility and compatibility with capsule shell, chemical stability and cost of the materials should also be considered during the formulation[15]. Such a rationale approach not only helps in reducing the time involved in the formulation development but also reduces the cost of its development[11].

Oil/lipid phase:

The function of oil phase in self-microemulsifying system is to solubilize the hydrophobic/lipophilic active moiety in order to improve both drug loading and bioavailability of the hydrophobic active moiety. Selection of oil plays a vital role in the formulation as it determines the amount of drug that can be solubilized in the system[16]. A lipid molecule with a large hydrophobic portion compared to hydrophilic portion is desirable as it maximizes the amount of drug that can be solubilized. Open in a separate windowLIST OF OILS USED IN FORMULATION OF SMEDDS

Long chain triglycerides:

Lipids that have fatty acid chains of 14-20 carbons are categorized as LCTs[17]. Fixed oils i.e., vegetable oils contain a mixture of glyceride esters of unsaturated long chain fatty acids. These are considered safe as they are commonly present in daily food and are easily digestible[15]. Large hydrophobic portion of triglycerides is responsible for their high solvent capacity for lipophilic moieties. Though it is difficult to microemulsify, some marketed formulations such as Neoral^® (composed of olive oil which, has shown superior oral bioavailability) and Topicaine^® gel (composed of Jojoba oil for transdermal application) have been successfully practicing the microemulsification of LCTs[18].

Medium chain triglycerides and related esters:

Lipids that have fatty acid chains of 6-12 carbons are categorized as MCTs[17]. MCTs are the most common choice of oil for SMEDDS as they are resistant to oxidation and possess high solvent capacity compared to LCT because of their high effective concentration of ester group. MCTs produced from the distillation of coconut oil are known as glyceryl tricaprylate and comprises of saturated C8 and C10 fatty acids in the liquid state[15]. Labrafac CM 10, a MCT, has shown superior solubility for fenofibrate and produced wider microemulsion region at all surfactant/co-surfactant combinations than Maisine 35, which, is a LCT[19]. Drug substance should possess minimum solubility of 50 mg/ml in LCTs for lymphatic absorption[20]. Upon digestion, products of short and medium chain triglycerides are directed towards portal vein whereas chylomicrons formed from LCTs triggers the lymphatic transport. Further, highly hydrophobic drug substances are easily soluble in vegetable oils and can easily be formulated as simple oil solutions which are readily emulsified in the gut. However, most conventional hydrophobic drug substances do not exhibit superior solubility in LCT such as vegetable oil[21,22].Moderately hydrophobic drug substances, on the other hand, cannot be formulated into simple oil solutions as their solubility is limited. In such cases, SMEDDS are promising alternative where the drug solubility in the oil will be enhanced due to microemulsification of oil by surfactants. It is well accepted that oils with long hydrocarbon chains (high molecular volume) such as soybean oil, castor oil are difficult to microemulsify compared to MCT (low molecular volume) such as capmul MCM and Miglyol. However, solubilizing capacity of oil for lipophilic moiety increases with chain length (hydrophobic portion) of the oil. Hence the selection of oil is a compromise between the solubilizing potential and ability to facilitate the formation of microemulsion[23]. Malcolmson et al. studied the solubility of testosterone propionate in various oils for the formulation of O/W microemulsion and concluded that oils with larger molecular volume such as triglycerides show superior solubility than the corresponding micellar solution containing only surfactants without oil[24,25]. Enhancement of drug solubility in SMEDDS not only relies on the solubility of the drug in the oil but also on the surfactant(s). For instance, ethyl butyrate, small molecular volume oil, has shown higher solubility for testosterone propionate but its ME formulation has only improved the solubility slightly than the corresponding micellar solution. On the contrary, Miglyol 812 which is a larger molecular volume oil has shown improved solubilization in the ME formulation though the solubility of testosterone propionate is less in the individual components compared to ethyl butyrate[24].

Drug solubility in lipid:

Oil component alters the solubility of the drug in SMEDDS by penetrating into the hydrophobic portion of the surfactant monolayer. Extent of oil penetration varies and depends on the molecular volume, polarity, size and shape of the oil molecule. Overall drug solubility in SMEDDS is always higher than the solubility of drug in individual excipients that combine to form SMEDDS. However, such higher solubility considerably depends on the solubility of drug in oil phase, interfacial locus of the drug and drug-surfactant interactions at the interface[26]. In light scattering experiments, it was observed that oils with small molecular volume act like co-surfactants and penetrate into the surfactant monolayer. This forms thinner polyoxyethylene chains near the hydrophobic core of the micelle disrupting the main locus of the drug solubilization due to which, a higher solubility of drug is not observed. Large molecular volume oils, however, forms a distinct core and do not penetrate effectively into the surfactant monolayer. The locus of drug solubilization was found to be effected by the microstructure and solubility of the drug in the excipients. The locus of drug solubilization was found to be at the interface of micelle for phytosterols whereas the same for cholesterol was found to be between the hydrophobic head groups of surfactant molecules. This is attributed to altered side chain flexibility of phytosterol due to the additional substitution of alkyl side chain compared to cholesterol[27].In addition to molecular volume and polarity of the oil, drug solubility in oil is affected by physicochemical properties of drug molecule itself. Consideration of BCS classification and Lipinski''s rule of 5 for the selection of drug is only useful during initial screening stages. As per BCS classification, some of the acidic drugs are listed in Class II despite having good absorption and disposition as they do not satisfy the requirement of higher solubility at low pH values. Lipinski''s rule of 5, on the other hand, holds good only when the drug is not a substrate for the active transporter[4]. This suggests that aqueous solubility and log P alone are not sufficient to predict the solubility of drug in the oil. This further indicates that the solubility of any two drugs with similar log P would not be the same due to their different physicochemical properties.To demonstrate this, a study was conducted in our laboratory with two antihypertensive drugs having close partition coefficient (log P) values, different aqueous solubility and varying physicochemical properties. Candesartan cilexetil is hydrophobic and has log P value of 7.3, molecular weight 610.66 g/mol with a polar surface area 135.77 whereas, valsartan is slightly soluble in aqueous phase with log P value of 5.3, molecular weight 434.53 g/mol with a polar surface area 103.48 (clogP and polar surface area were calculated using chembiodraw ultra 11.0). Unlike candesartan cilexetil, valsartan exhibits pH dependent solubility[28].If only log P and aqueous solubility of these two drugs are considered, it is only natural to assume that candesartan cilexetil would be highly soluble in lipid phase whereas valsartan would be less soluble. A specific and sensitive HPLC-UV method was developed and validated to measure the super saturation solubility of these two drugs in various oils and the results showed a completely different solubility profiles. Solubility profile of these two drugs in different oil phase is given in fig. 2.Open in a separate windowFig. 2Solubility of active ingredients in various oils. Valsartan, candesartan cilexetil.Although log P and polar surface area of valsartan and candesartan cilexetil are closer, their solubility with triacetin, castor oil and capmul MCM C8 differs significantly. This may be attributed to the hydrogen bonding capacity and electrostatic interaction of both the scaffold with the oils. Nevertheless, valsartan is having aliphatic carboxylic group which is expected to be involved in hydrogen bond interaction with the hydrogen acceptor functionality of the triacetin as well as castor oil. We assume that the branched chain aliphatic ester moiety of triacetin, capmul MCM C8 and castor oil gets involved in the electrostatic repulsion with cilexetil part of candesartan. In case of valsartan, such electrostatic interactions are not possible. Furthermore, aliphatic ester chain of triacetin and castor oil may solvate the lipophilic chain of valsartan more favorably than candesartan in the absence of any electrostatic repulsion (proposed interaction is shown in fig. 3). However, significant difference was not observed with other oils such as olive oil, peanut oil, corn oil, miglyol 810, sunflower oil and soybean oil (data not shown).Open in a separate windowFig. 3Proposed interactions of valsartan and candesartan cilexetil with triacetin.