The measurements were made at a 6 ha field cropped with forage maize under no-tillage after sowing and located in Northwestern Spain. The objective was to use data from ECa for improving the estimation of soil PR. First, data of ECa were used to determine the optimized sampling scheme of the soil PR in 40 points. Then, correlation analysis showed a significant negative relationship between soil PR and ECa, ranging from −0.36 to −0.70 for the studied soil layers. The spatial dependence of soil PR was best described by spherical models in most soil layers. However, below 0.50 m the spatial pattern of soil PR showed pure nugget effect, which could be due to the limited number of PR data used in these layers as the values of this parameter often were above the range measured by our equipment (5.5 MPa). The use of ECa as secondary variable slightly improved the estimation of PR by universal cokriging, when compared with kriging.This study presents a combined application of an EM38DD for assessing soil apparent electrical conductivity (EC Soil physical properties play an important role on crop growth, if not the most important . On the The use of farm machinery in agricultural production systems disturbs the soil structure and often may generate soil compacted layers that affect soil aeration and infiltration capacity. Different soil management systems produce different levels of soil compaction, depending on water content, type of soil, and agricultural machinery operations.Soil penetration resistance has been found to be well correlated with root growth, and these two variables are inversely proportional. When soil water content decreases, soil mechanical resistance increases, because of the diminution of cohesion within the solid fraction of soil –5. SeverHill and Meza-Montalvo  concludeMost farmers consider the soil as uniform for its management, but soil properties are variable in space and time. As a result of these variations, the use of the average value of a soil property could lead to wrong management decisions. This notwithstanding, conventional agriculture has been based on soil sampling with few samples .a) is a measure of the bulk electrical conductivity of the soil and is influenced by various factors such as soil porosity, concentration of dissolved electrolytes, texture, quantity and composition of colloids, organic matter, and water content in the soil [a) can be used to define specific management zones.The electrical conductivity (EC) is the property that has a material to transmit or conduct electrical current –14. The the soil . Recent a, which makes the interpretation of ECa data difficult. This is because the water content varies with depth, even if the soil is uniform, which may cause strong ECa variations as a function of depth. Moreover, temperature also affects the soil ECa [a are texture, soil water content, and salinity [a [Rhoades et al.  and Nadlsoil ECa , 15. Thisoil ECa . Summarisalinity , 17–19; inity [a .a), measured by EM38, first to generate optimal soil sampling designs and then to improve the spatial estimation of soil resistance to penetration (PR) on the studied field.The aim of this study was to use apparent soil electrical conductivity data  was measured with an induction electromagnetic device, namely, EM38-DD (Geonics Limited). The EM38-DD is constructed by mechanically and electrically integrating two standard EM38 ground conductivity meters. The bottom instrument's transmitter-receiver dipoles are oriented parallel to the earth in horizontal dipole (ECa-H), while for the top instrument, which controls the digital output of the whole instrument, the dipoles are oriented perpendicular to the earth surface in vertical dipole (ECa-V). In the ECa-V mode, the primary magnetic field can effectively penetrate to a depth of 1.5 m, while the ECa-H mode is effective for shallower investigation (0.75 m) [a data.The apparent soil electrical conductivity (EC(0.75 m) . The data data, together with the software ESAP-RSSD 2.35 [veris) was sensed immediately above the penetrometer tip. The penetrometer tip itself was electrically insulated from the penetrometer shaft with a thin dielectric ring. Electrical contact with the tip was by means of a small steel rod inside and insulated from the hollow shaft.The ECSSD 2.35 , were usSSD 2.35 . An onbo0.0-0.1), 0.1-0.2 m (PR0.1-0.2), 0.2-0.3 m (PR0.2-0.3), 0.3-0.4 m (PR0.3-0.4), 0.4-0.5 m (PR0.4-0.5), 0.5-0.6 m (PR0.5-0.6), 0.6-0.7 m (PR0.6-0.7), 0.7-0.8 m (PR0.7-0.8), and 0.8-0.9 m (PR0.8-0.9)  . In each Figures .a values with the soil water content. Pearson's coefficients of correlation and significance levels were calculated between the data using pairs with the package “hmisc” [Gravimetric soil water content was measured at these sampling points: 4, 11, 14, 27, and 40 , in orde “hmisc” .The geostatistical analysis included preliminary statistical analysis, Kolmogorov-Smirnov normality test, analysis of trend, variogram modeling, and estimating values for unsampled locations using the kriging interpolation technique. Initial analysis showed that some variables had a trend; in this case the residual ordinary kriging was used.Using geostatistics, there are two options to solve the problem created by the existence of a drift within the neighborhood search. On the one hand, it can be assumed that the drift is an equation with constant coefficients for the entire study area, which leads to residual kriging. On the other hand it can be assumed that coefficients of the drift equation vary by location of the study area, which results in universal kriging or kriging with trend model; this procedure simultaneously solves drift while kriging equations are solved. In this research the residual ordinary kriging was used . The resSome of the variables with a trend were interpolated by universal cokriging , insteada) measured with EM38-DD and soil resistance to penetration (PR) and electrical conductivity (ECveris) measured with penetrometer Veris P3000  were expected since the number of measurements was much lower (maximum 140), compared to ECa-V and ECa-H data measured with the EM38-DD device  showed an increase with increasing depth, which is in accordance with results presented by Johnson et al. [veris [The average values of the electrical conductivity measured with Veris penetrometer  amount of stones [a were correlated with soil compaction and clay content in the soil profile, thereby enabling to relate ECa with PR.In graph %, . Thus, Ef stones . Motavalf stones  studied veris for the locations where soil water content was measured. It is apparent that there is no good correlation between ECveris and gravimetric soil water for the selected points; to assess dependence between these two variables, more soil water content measurements would be needed.Sudduth et al.  comparinveris and PR data can detect changes in soil density and water content due to compaction, in addition to natural variations in soil texture.Summarizing, we showed that the joint use of ECGossypium hirsutum, Sesamum indicum, Cyamopsis tetragonolobus, Sesbania exaltata, Phaseolus aureus, Vigna sinensis var. Chinese Red, and Sorghum vulgare var. Sumac sorghum) with different tillage systems, these authors describe that values from 2.8 MPa began to restrict the root growth. Ehlers et al. [Avena sativa L.) in the 0–0.25 m layer and found that root growth ceased when PR reached values between 3.6 and 4.9 MPa. Letey [Several authors provided different soil PR threshold values, regarding limitations for crop production. For example, Taylor and Gardner  reporteds et al.  studied a. Letey  and Buena. Letey  noted thaverage  0.0–0.4) in this study was about 2.12 MPa. This value was close to the 2 MPa threshold, commonly cited as restrictive for crop growth. PRaverage  0.4–0.9 was 3.40 MPa, exceeding the value of 2 MPa. However, the average soil water content of this layer is more stable over the study field, as shown in Bennie  stated tBueno  and Amiaa data EM38-DD and ECveris, but the correlation s was not significant below 0.6 m depth. Probably, the lack of correlation at the deepest soil layers is related to the small number of sampling points in these layers obtained with the penetrometer Veris; in turn this is the result of the high content of gravel with depth.a and PR show highly significant negative relationships. This is because ECa is very dependent on the soil water content [a measured with EM38, and they concluded that EM38 survey can be used to detect subplots with an extreme compaction or noncompaction state. According to Ehlers et al. [a and PR. According to Drummond et al. [veris would allow to characterize the soil not only along the landscape but also in depth. This could contribute not only to the understanding of the spatial distribution of PR and ECa, but also to assessing density, texture, and water content in the soil.Pearson's correlations between EC content , 12, 14; content  found gos et al.  PR is mud et al.  althoughveris  0.0-0.1, ECveris  0.1-0.2, ECveris  0.2-0.3, ECveris  0.3-0.4, ECveris  0.4-0.5, ECveris  0.5-0.6, ECveris  0.5-0.6, ECveris  0.7-0.8, ECveris  0.8-0.9, ECveris  average  0.0–0.4  PR0.5-0.6, PR0.6-0.7, PR0.7-0.8, and PR0.8-0.9 showed pure nugget effect. This might indicate that the spacing used between samples was not adequate to detect the spatial variability but may also reflect the small number of points used in the analysis process. The values of the degree of spatial dependence showed that all variables studied had a high value of this parameter, following the accredited criteria of Cambardella et al. [a-V, ECa-H, ECveris  average  0.4–0.9, PR0.0-0.1, PR0.1-0.2, PR0.2-0.3, PR0.3-0.4, PR0.4-0.5, PRaverage  0.0–0.4, and PRaverage  0.4–0.9). The lower range value (a) corresponds to Log ECveris  average  0.4–0.9 (50 m), whereas the highest value was found for Log PRaverage  0-0.4 (130 m). Jabro et al. [a (mS m−1) and PR (MPa) with the Veris penetrometer described values of range for both parameters of 161 m; the values of range in this study were for Veris penetrometer approximately 50 m for ECveris  average  0.4–0.9 and 130 m and 70 m for the PR0.0–0.4 and PRaverage  0.4–0.9, respectively. Figures a-V, ECa-H, ECveris  average  0.4–0.9, and PR .a et al. . Spherico et al.  studied veris  average  0.4–0.9  [The map of the EC 0.4–0.9  has a sind ECa-H , exhibitncreased , 19, 47.r, etc.)  and the r, etc.) , Sudduthr, etc.) , and Jaba-V and ECa-H) with EC measured with the penetrometer Veris  (a.The matrix of linear correlation between the measured data with the EM38-DD equipment (EC0.4–0.9)  confirms0.1-0.2, PR0.2-0.3, PR0.3-0.4, PR0.4-0.5, PRaverage  0.0–0.4, and PRaverage  0.4–0.9). Maps of PR show the opposite behavior to ECveris  average  0.4–0.9 confirming the negative correlation    indicatiaverage  0.0–0.4 × Log ECa-V, Log PRaverage  0.0–0.4 × Log ECa-H, Log PRaverage  0.4–0.9 × Log ECa-V, and Log PRaverage  0.4–0.9 × Log ECa-H, since these were the only attributes that showed an improvement in the coefficient of correlation between the measured and estimated values obtained using kriging and cokriging , except for PR at 0.0-0.1 m layer that has a high value of CV (60.30%). The spherical model was fitted to the data of soil resistance penetration  at the top soil layers. The presence of pure nugget effect for soil penetration resistance at the bottom  may be caused by the limited number of data available for these layers, since the recorded PR values were often not useful, as they were higher than the maximum value measured by the penetrometer (5.5 MPa). Apparent soil electrical conductivity data (ECa) were used to determine the optimized sampling scheme where PR was measured, and this methodology has proved to be efficient and capable for representing the spatial pattern of PR. ECa and PR data show significant negative correlation coefficients, once both properties are related to the soil water content. The use of ECa as secondary variable improved slightly the estimation of PR using universal cokriging with respect to kriging.The data sets EC


Metabolic syndrome (MS) comprises a set of conditions that are risk factors for cardiovascular diseases and diabetes. Numerous epidemiological studies on MS have been conducted, but there has not been a systematic analysis of the prevalence of MS in the Chinese population. Therefore, the aim of this study was to estimate the pooled prevalence of MS among subjects in Mainland China.We performed a systematic review by searching both English and Chinese literature databases. Random or fixed effects models were used to summarize the prevalence of MS according to statistical tests for heterogeneity. Subgroup, sensitivity, and meta-regression analyses were performed to address heterogeneity. Publication bias was evaluated using Egger’s test.Thirty-five papers were included in the meta-analysis, with a total population of 226,653 Chinese subjects. Among subjects aged 15 years and older, the pooled prevalence was 24.5 % (95 % CI: 22.0–26.9 %). By sex, the prevalences were 19.2 % (95 % CI: 16.9–21.6 %) in males and 27.0 % (95 % CI: 23.5–30.5 %) in females. The pooled prevalence of MS increased with age . Individuals living in urban areas  were more likely to suffer from MS than those living in rural areas . Hypertension was the most prevalent component of MS in males (52.8 %), while the most prevalent component of MS for females was central obesity (46.1 %).Our systematic review suggested a high prevalence of MS among subjects in Mainland China, indicating that MS is a serious public health problem. Therefore, more attention should be paid to the prevention and control of MS.The online version of this article (doi:10.1186/s12889-016-2870-y) contains supplementary material, which is available to authorized users. Metabolic syndrome (MS) is characterized by a cluster of metabolic disorders, such as high blood pressure, hyperglycaemia, central adiposity, and dyslipidemia , 2. MS iChina is the world’s largest developing country and is experiencing an epidemic of MS . The NanWe searched for epidemiological studies on MS from the several electronic databases, including Medline, Embase, the China National Knowledge Infrastructure (CNKI), and the Wanfang and Chongqing VIP. The following search strategy was used: (‘Metabolic syndrome’ OR ‘MS’ OR ‘MetSyn’) AND  AND (‘Chinese’ OR ‘China’ OR ‘Mainland’). All studies published from January 1, 2005 to April 30, 2015 were searched. Unpublished studies were not retrieved. The search language was limited to English and Chinese.To satisfy the analysis requirements and reduce selection deviation, the selected studies were required to meet the following criteria: 1) a population-based study conducted in Mainland China; 2) a cross-sectional study or data; 3) sufficient information of sample size and crude prevalence of MS; 4) a sample size > 500; 5) participants aged 15 years and older; and 6) the use MS diagnostic criteria proposed by the International Diabetes Federation (IDF) in 2005 . AccordiAll searched articles from different electronic databases were combined in Endnote, and duplicates were removed. Two researchers independently screened the titles and abstracts and reviewed the full text of the eligible citations. If they were in disagreement, a third reviewer made the final decision. For each included study, two researchers independently extracted the following information: general information ; study characteristics ; and all possible participant information cholesterol). Two researchers independently assessed the quality of each included study using observational study criteria that were recommended by the Agency of Healthcare Research and Quality . Only wh2 statistic, which shows the percentage of variation across studies  [2 < 50 %), a fixed-effect model was used; otherwise, a random-effect model was used. Subgroup analyses by geographic region, age, sex, and the year of screening were performed to address heterogeneity. Additionally, a meta-regression was conducted to explore potential sources of heterogeneity. Variables such as the year of publication, year of screening, response rate, geographic area , sex ratio , sample size, age range, and quality score were used to perform the meta-regression. Additionally, sensitivity analysis  was performed to assess the influence of any particular study on the pooled estimate.We used a systematic analysis approach to calculate the pooled prevalence of MS from all eligible studies. A random or fixed effects model was selected to summarize the prevalence of MS, using statistical tests for heterogeneity. Heterogeneity among studies was assessed using Cochran’s Q test and Ictively) , 16. If P value of less than 0.05. All statistical analyses were performed using Stata version 12.0  and SPSS version 20.0 .Publication bias was evaluated using Egger’s Test, and independent t-tests were performed as appropriate. The significance level was set at a n = 94,241) and 32 studies reported data on females . Sixteen and 17 studies were conducted on the populations of south and north China, respectively, and two nationwide studies were conducted. Table A total of 1405 citations were searched. Of these, 510 duplicates were removed, and 358 citations were excluded after reading the titles and abstracts. Five hundred thirty-seven articles were further excluded after reviewing the full texts. In total, 35 eligible studies were included in the meta-analysis, which involved a total of 226,653 subjects. The flow diagram of the search process is shown in Fig. I2 = 99.5 %, P < 0.0001). Table P = 0.002). The prevalences of MS in the populations of north and south China were similar . The pooled prevalence of MS in the population living in rural areas  was lower than was observed in urban areas . The pooled prevalence of MS increased with time. The pooled prevalence was 23.8 % (95 % CI: 17.7–29.9 %) during 2000–2005, increasing to 22.3 % (95 % CI: 20.3–24.3 %) during 2005–2010 and 27.0 % (95 % CI: 22.2–31.8 %) during 2010–2015. Additionally, the summarized prevalence of MS increased with age. The pooled prevalences of MS for specific age ranges were 13.9 % (95 % CI: 9.5–18.2 %) for subjects aged 15–39 years, 26.4 % (95 % CI: 20.5–32.3 %) for subjects aged 40–59 years, and 32.4 % (95 % CI: 26.1–38.8 %) for subjects aged ≥ 60 years. The prevalence of MS increased with age in males, peaking in the 40–59 year age group and decreasing thereafter. The prevalence of MS also increased with age in females, peaking in the ≥ 60 years group.The pooled prevalence of MS among Chinese subjects was 24.5 % (95 % CI: 22.0–26.9 %), with a high-level between-study heterogeneity (P = 0.049). Table In terms of the different components of MS, the pooled prevalence estimates of central obesity, hypertension, high fasting plasma glucose, hypertriglyceridaemia, and low HDL cholesterol in males were 33.4, 52.8, 31.5, 32.9, and 27.4 %, respectively. For females, these estimates were 46.1, 40.1, 26.3, 27.7, and 40.4 %, respectively. The prevalence of hypertension in males was significantly higher than in females (P = 0.072) suggested no significant publication bias.Seven citations had a quality score of 6, the lowest among the included studies. In the sensitivity analysis, we noticed a slight change in the pooled MS prevalence estimate (from 24.5 to 25.4 %) when we omitted these seven studies. Egger’s linear regression test . We performed a meta-regression to take this heterogeneity into account. In the univariate meta-regression and multivariable analyses, only the variable of age was significantly associated with heterogeneity  (Table A high level of heterogeneity between studies and subgroups was observed (y) Table .Table 4ROur systematic review of observational studies conducted in the last decade included 35 studies that involved a total of 226,653 participants in Mainland China and covered most regions of the country. The definitions of IDF and the US National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) are widely used in China . The IDFOur meta-analysis revealed that the pooled estimate of MS prevalence among subjects in Mainland China was 24.5 %. This estimate was higher than the prevalence of 16.5 % observed in China in 2000 and approached the worldwide prevalence of 20–25 % . The preOur systematic review showed that MS was more common in females than in males 27.0 vs. 19.2 %), a result that is in line with previous findings .2 %, a r. MenopauThere is an emerging MS epidemic in Mainland China, and it has become a serious public health problem. MS increases the risk for morbidity and mortality of cardiovascular disease and is associated with an increased risk of diabetes . StudiesThe overall quality of the studies included in our systematic review was good; therefore, the sensitivity analysis did not show major differences in the meta-analysis results when studies with the lowest quality scores were omitted. Our meta-analysis included 35 published studies with a large sample size. Nevertheless, our study had some limitations. First, we used the IDF criteria as our diagnosis criteria, and studies based on other diagnosis criteria were not included in our meta-analysis. Second, although most of the included studies had a large sample size that could generate an accurate estimation, the overall analysis revealed a high heterogeneity. Additionally, meta-regression and subgroup analyses did not indicate enough factors to explain the observed heterogeneity. We propose that other factors, such as cigarette smoking, alcohol consumption, stress, and physical inactivity may influence MS heterogeneity. Because of the limited information on these aspects, we could not perform further analyses. Third, the distribution of healthcare resources in Mainland China is unbalanced, with more economically developed areas having better access to health care facilities. This factor may have contributed to more diagnoses and, therefore, a higher reported prevalence in certain studies of different regions in Mainland China.To the best of our knowledge, this was the first systematic review to estimate the pooled prevalence of MS among subjects in Mainland China. Our systematic review indicates a high prevalence of MS among subjects in Mainland China. Information on how MS and its components are distributed could provide a great deal of insight into MS and assist in the planning and implementation of future prevention and control programmes.


However, recent research has shown that the rate at which people visually search through a display is also affected by cognitive strategies. In this study, we investigated the role of choice in visual search, by asking whether giving people a choice alters both preference for a cognitively neutral task and search behavior. Two visual search conditions were examined: one in which participants were given a choice of visual search task (the choice condition), and one in which participants did not have a choice (the no-choice condition). The results showed that the participants in the choice condition rated the task as both more enjoyable and likeable than did the participants in the no-choice condition. However, despite their preferences, actual search performance was slower and less efficient in the choice condition than in the no-choice condition (Exp. 1). Experiment 2 showed that the difference in search performance between the choice and no-choice conditions disappeared when central executive processes became occupied with a task-switching task. These data concur with a  Search efficiency is determined by the RT × Set Size function, which measures how RTs increase with the number of items (set size), to give the Recent work, however, has suggested that cognitive strategies may also influence how people search a display. For example, Smilek, Enns, Eastwood, and Merikle  found thMuch research has shown that the role of choice has a strong influence on people’s preferences and motivation . In this study, we tested whether having a choice in itself is inherently valuable, by using a cognitively neutral task of little personal value to the participant. Here we gave participants a visual search task, asking them to search for an affectively neutral target (the letter T) among affectively neutral distractors (letter Ls). We used these stimuli to ensure that nothing was inherent in the task for people to either like or dislike . Two conditions were tested: a “choice” condition, in which we gave people a choice of which visual search task they could take part in , and a “no-choice” condition, in which people were assigned to a predetermined visual search task. Importantly, unbeknownst to participants in the choice condition, all three visual search tasks were exactly the same (search for a T among Ls). Following Experiment 1, participants were asked to rate how much they enjoyed the task, how much they liked the task, and how difficult they found the task overall.choice-neutral hypothesis. In contrast, giving people a choice could lead them to have increased motivation in the task and to adopt a more active role when searching. It is well-documented that people engage and persist more in a task if they have chosen it  took part in Experiment 1, and 20 participants took part in Experiment 2Displays were generated and responses recorded using Blitz 3-D programs. The distractors were L shapes presented randomly in one of four orientations  on a black background. In Experiment 1, the target was a T, rotated 90° or 270° with equal probabilities, and in Experiment 2, the target was a T, rotated 0° or 180° with equal probabilities. Each L contained a small offset (~0.5°) at the line junction to make search more difficult. All stimuli subtended 1.7° × 1.7°, at a distance of 57.4 cm. Each display had a set size of 4, 8, or 12 items, with individual stimuli positioned within a 6 × 6 invisible matrix. Each display was uniquely generated, and therefore displays were not repeated across the experiment. In Experiment 1, all of the stimuli were white. In Experiment 2, on half of the trials all stimuli were red, and on the other half all stimuli were green.Participants completed an experimental block of 90 trials (30 for each set size). On each trial, a fixation dot was presented for 500 ms, followed by the distractors and target letter. The stimuli were presented on the screen until participants made a response. If participants had not responded in 10,000 ms, the display timed out and the next trial was presented. Participants were asked to respond as quickly and as accurately as possible, and completed a short practice session before each block. Example displays are shown in Fig. not at all) to 7 (very much).In the choice conditions, participants were asked to choose which experimental block they would like to complete. Their choice options were that they could complete either “Condition A,” “Condition B,” or “Condition C.” No other information about the blocks was given to participants. Once participants had chosen, they were given the corresponding condition. However, unknown to the participants, all conditions were the same in every way but their name. In the no-choice conditions, participants were told they had been assigned to one of the conditions and were not given a choice. In Experiment 1, participants were asked to rate how much they enjoyed the task, how much they liked the task, and how difficult they found the task. Responses were collected using three Likert scale questions ranging from 1  = 7.2, p < .01, ηp2 = .068, in which RTs in the choice condition  were slower than those in the no-choice condition , and a main effect of set size, F = 449.2, p < .01, ηp2 = .821, in which RTs increased with set size. The Choice × Set Size interaction was also significant, F = 9.0, p < .01, ηp2 = .084. RTs increased more with set size, showing less efficient search, in the choice condition (80.7 ms/item) than in the no-choice condition (61.2 ms/item).In Experiment 1, RTs less than 200 ms and greater than 4,000 ms were removed as outliers. This led to the removal of 1.4 % and 1.7 % of the data from the choice and no-choice conditions, respectively. RTs less than 200 ms were also removed from Experiment 2 (0 % of the data); however, because the task was more difficult, no upper outlier boundary was applied.F = 25.7, p < .01, ηp2 = .588, and of set size, F = 112.4, p < .01, ηp2 = .862. RTs for target-present trials were faster than target-absent ones, and RTs increased with set size. However, we found no main effect of task switch (F < 1), nor a main effect of choice (F < 1). A significant Target Presence × Set Size interaction was apparent, F = 3.2, p = .05, ηp2 = .151, in which RTs increased more with set size for target-absent than for target-present trials, as well as a significant Task Switch × Set Size interaction, F = 3.8, p < .05, ηp2 = .174, in which RTs increased more with set size for no-task-switch than for task-switch trials. The four-way Target Presence × Task Switch × Set Size × Choice interaction was also significant, F = 3.2, p = .05, ηp2 = .150. None of the other interactions were significant. Error rates are shown in Table F = 8.6, p = .01, ηp2 = .309, in which more errors occurred on target-present trials (4.04 %) than on target-absent trials (4.02 %), and a main effect of set size, in which errors increased with set size, F = 4.0, p < .05, ηp2 = .181. However, none of the other main effects or interactions in either experiments were significant.However, this difference disappeared in Experiment 2, with the engagement of executive processes in the task-switching task. Here, a mixed-design 2 (choice vs. no choice) × 3  × 2 (task switch vs. no task switch) × 2 (present vs. absent) ANOVA on correct participant mean RTs was conducted, with the within-participants factors Set Size, Task Switch, and Target Presence, and the between-participants factor Choice. We observed main effects of target presence, U tests showed that participants in the choice condition rated the visual search task to be more enjoyable than did participants in the no-choice task . Furthermore, participants in the choice task showed a more positive rating when asked how much they liked the task, as compared with participants in the no-choice task . However, no differences emerged in ratings of how difficult participants found the task across the choice and no-choice groups .Figure Previous work has shown that people prefer options that give them a choice . Furthermore, response speed in the choice condition was impaired relative to the no-choice condition. These results cannot be explained by a speed–accuracy trade-off, since error rates were low and there were no differences in errors for choice across conditions. Instead, the data are consistent with the n as on trial n–1  in Experiment 2 were similar to those in Experiment 1, and therefore should have been affected by choice. However, crucially, in Experiment 2 participants were required to maintain the task instructions in working memory throughout the experiment . Therefore, because executive processes were being utilized on all trial types, they would not be available to affect search in the choice condition. The ideas of executive control and automatic mechanisms could be considered similar to people’s dual processing system, commonly known in the field of decision making as System 1 and System 2. System 1 refers to automatic procedures that are quick, effortless, and occur in parallel, whereas System 2 requires much more detailed, controlled, and complex cognitive resources (Kahneman, Previous research has shown that if participants adopt an active search strategy, they show less efficient search than do those who use a more passive strategy (Smilek et al., The present data show that although presenting people with a choice led to greater enjoyment, it did so at the price of impairing search performance. It is generally considered that having a choice is beneficial (Patall et al.,


Plasmodium knowlesi is now recognized as the fifth species of Plasmodium that can cause human malaria. Like the region II of the Duffy binding protein of P. vivax (PvDBPII), the region II of the P. knowlesi Duffy binding protein (PkDBPαII) plays an essential role in the parasite’s invasion into the host’s erythrocyte. Numerous polymorphism studies have been carried out on PvDBPII, but none has been reported on PkDBPαII. In this study, the genetic diversity, haplotyes and allele groups of PkDBPαII of P. knowlesi clinical isolates from Peninsular Malaysia were investigated.The monkey malaria parasite Macaca fascicularis) were used. These samples were collected between 2010 and 2012. The PkDBPαII region of the isolates was amplified by PCR, cloned into Escherichia coli, and sequenced. The genetic diversity, natural selection and haplotypes of PkDBPαII were analysed using MEGA5 and DnaSP ver. 5.10.00 programmes.Blood samples from 20 knowlesi malaria patients and 2 wild monkeys  selection. At the amino acid level, 36 different PkDBPαII haplotypes were identified. Twelve of the 20 human and 1 monkey blood samples had mixed haplotype infections. These haplotypes were clustered into 2 distinct allele groups. The majority of the haplotypes clustered into the large dominant group.Fifty-three PkDBPαII sequences from human infections and 6 from monkeys were obtained. Comparison at the nucleotide level against P. knowlesi from Borneo, which hitherto has recorded the highest number of human knowlesi malaria.Our present study is the first to report the genetic diversity and natural selection of PkDBPαII. Hence, the haplotypes described in this report can be considered as novel. Although a high level of genetic diversity was observed, the PkDBPαII appeared to be under purifying selection. The distribution of the haplotypes was skewed, with one dominant major and one minor group. Future study should investigate PkDBPαII of  Plasmodium. Historically, four species of Plasmodium are known to cause human malaria: Plasmodium falciparum, P. vivax, P. malariae, and P. ovale. However, about a decade ago, P. knowlesi, a malaria parasite of macaque monkeys, was reported to cause a large number of human infections in Sarawak, Borneo Island ).Human blood samples used in this study were collected from 20 patients who were infected with P. knowlesi was extracted from each blood sample using the QIAGEN Blood DNA Extraction kit . In each extraction, 100 μl of blood was used. The extracted DNA was suspended in water to a final volume of 50 μl.Total DNA of the The PkDBPαII was amplified by nested PCR using oligonucleotide primers Pkα-DBP-F1: 5′-CGCATTTTGAAGGAATCCAC-3′ and Pkα-DBP-R1: 5′-TGCTAGACTTACCTTCACCT-3′ for nest 1. The primers for the nest 2 reaction were Pkα-DBP-F: 5′-TCCTCAAAAGGCGGTGACCATCC-3′ and Pkα-DBP-R: 5′-ACTGGCTGCCTTAGATTCAACACCA-3′. Cycling conditions for nest 1 were as follows: 95°C for 4 mins, 30 cycles at 95°C for 30 secs, 48°C for 30 secs, and 72°C for 90 secs, followed by a 10 min extension at 72°C. The amplification for nest 2 was performed using the following cycling profile: 95°C for 4 mins, 30 cycles at 95°C for 30 secs, 56°C for 30 secs, and 72°C for 90 secs, followed by a 10 min extension at 72°C. The PCR product with an expected size of 1053 bp was analyzed on a 1% agarose gel.®  and transformed into Escherichia coli TOP10F’. Plasmids of recombinant clones harbouring the PkDBPαII fragment were sent to a commercial laboratory for DNA sequencing. To detect the possibility of multiple haplotypes infecting a patient or monkey, plasmids from 4–6 recombinant clones from each transformation mixture were sequenced.PCR products were purified by QIAquick PCR purification Kit  following the manufacturer’s instructions. The purified PCR products were then ligated into cloning vector pGEM-Thttp://www.ebi.ac.uk/Tools/msa/clustalo). Both nucleotide and the deduced amino acid sequences were aligned and analysed. Phylogenetic tree was constructed using the Neighbour Joining method described in MEGA5  were performed using CLUSTAL-Omega programme which was available on-line (in MEGA5 . In consKs) and non-synonymous (Kn) substitutions were estimated and compared by the Z-test (P < 0.05) in MEGA5 using the Nei and Gojobori’s method [Kn will be less than Ks (Kn/Ks < 1). However, in positive selection, non-synonymous mutations can be advantageous and Kn will exceed Ks (Kn/Ks > 1). For testing the neutral theory of evolution, Tajima’s D [P. vivax PvDBPII (GenBank Accession No. M90466) was used as outgroup.DnaSP ver. 5.10.00  was useds method  with thejima’s D  and Fu ajima’s D  tests waet al. [Nested PCR amplification on the human and monkey blood samples isolates produced DNA fragments of 1053 base pairs. The sequence of each fragment was trimmed to 921 bp, based on the PkDBPαII region identified by Singh et al. . This trDNA sequence analyses were conducted to determine nucleotide diversity and genetic differentiation. The average number of pairwise nucleotide differences (K) for the PkDBPαII was 11.736. The overall haplotype diversity (Hd) and nucleotide diversity (π) for the 60 PkDBPαII sequences were 0.986 ± 0.008 and 0.013 ± 0.002, respectively. Detailed analysis of π, with a sliding window plot , revealed diversity ranged from 0.003 to 0.034. The highest peak of nucleotide diversity was within nucleotide positions 600–750, whereas the most conserved region was within nucleotide positions 260–360  to synonymous mutations (Ks) was estimated. Kn (0.00952) was found lower than Ks (0.00278) and the Kn/Ks ratio was 0.347, suggesting that purifying (negative) selection may be occurring in the PkDBPαII. Similarly, the Z test  also indicated purifying selection on PkDBPαII. In the tests of departure of neutrality of selection, the Tajima’s D statistics was -2.085 (P < 0.05), indicating expansion in population size and/or purifying selection. This is further supported by the Fu and Li’s D and F tests statistics .Analysis and comparison at the nucleotide level against Comparison at the amino acid level revealed high polymorphism across the entire PkDBPαII of the isolates Figure . Among tP. vivax and P. knowlesi play an essential role in erythrocyte invasion of the parasites by mediating irreversible binding with its corresponding receptor, the Duffy protein receptor for chemokines (DARC) on the surface of erythrocytes [P. vivax PvDBP has been observed to have a high degree of genetic polymorphism, and most of the polymorphism is located in region II. Although the cysteine and some hydrophobic amino acid residues in PvDBPII are conserved in P. vivax populations from different geographic regions, but the remaining amino acid residues are highly polymorphic [P. knowlesi as a human pathogen, no study has thus far been carried out on PkDBPαII. Our present study is the first to report the diversity and natural selection of PkDBPαII.The DBP of hrocytes . The DBPhrocytes ,20. The ymorphic -11,21-24et al. [The PkDBPαII analysed in this study is based on the region defined by Singh et al.  using stet al. . Again, P. vivax PvDBPII in some neighbour countries, such as Myanmar , Korea  and Sri Lanka  [P. knowlesi, P. cynomolgi, P. inui and P. fieldi) showed evidence for negative selection, which was not found in two human malarial parasites  [P. knowlesi, as evident by the Tajima’s D statistics. In Peninsular Malaysia, deforestation in many areas has increased monkey and forest dwelling Anopheles vector contact to human. The expansion of monkey and vector populations and their ecological niches into human habitation may therefore result in the population expansion of P. knowlesi[The PkDBPαII  in Peninsular Malaysia seemed to be more diverse than 0.00982) . General0.00982) . Positiv0.00982) . On the  knowlesi.P. vivax isolates based on PvDBPII revealed the occurrence of multiple haplotypes in a geographical location, and these haplotypes could be categorized into several allele groups. For example, 25 haplotypes from Thailand were organized into 5 groups [P. knowlesi infection [Phylogenetic studies on 5 groups . In Papu5 groups , whereas5 groups . Our stunfection , was alsP. knowlesi from Borneo, which hitherto has recorded the highest number of human knowlesi malaria.Our present study is the first to report the genetic diversity and natural selection of PkDBPαII. Hence, the haplotypes described in this report can be considered as novel. Although a high level of genetic diversity was observed, the PkDBPαII appeared to be under purifying (negative) selection. Two allele groups of haplotype were obtained. However, the distribution was skewed, in which majority of the haplotypes clustered in a large dominant group. Our study was carried out on Peninsular Malaysia isolates only. Therefore, future study should investigate PkDBPαII of The authors declare that they have no competing interests.MYF and YLL designed the study and supervised the study process. PYC performed all the experiments and analysed the sequence data. MYF and CNA performed sequence and phylogenetic analyses. MYF, YLL and CNA wrote the manuscript. All authors read and approved the final manuscript.Full amino acid sequence alignment of PkDBPαII. Amino acid residues identical to those of the reference sequence (strain H), are indicated by dots. The twelve conserved cysteine (C) residues are marked in yellow. The conserved Y94, N95, K96, R103, L168 and I175 residues required for recognition of DARC on human erythrocytes are highlighted in green.Click here for file


P < 0.001) and 11% (P = 0.001) at every workload, respectively, accompanied by a 16% reduction in lactate concentration in plasma (P < 0.001), although all remained unchanged in the CNT trial (P > 0.2). All of the reductions were significantly greater in the ALA+SFC than the CNT trial (P < 0.05). Furthermore, the training days, impulse, and time at fast walking were 42% (P = 0.028), 102% (P = 0.027), and 69% (P = 0.039) higher during the ALA+SFC than the CNT intake period, respectively. Thus ALA+SFC supplementation augmented exercise efficiency and thereby improved IWT achievement in older women.A reduction in exercise efficiency with aging limits daily living activities. We examined whether 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) increased exercise efficiency and voluntary achievement of interval walking training (IWT) in older women. Ten women [65 ± 3(SD) yr] who had performed IWT for >12 mo and were currently performing IWT participated in this study. The study was conducted in a placebo-controlled, double-blind crossover design. All subjects underwent two trials for 7 days each in which they performed IWT with ALA+SFC  or placebo supplement intake (CNT), intermittently with a 2-wk washout period. Before and after each trial, subjects underwent a graded cycling test at 27.0°C atmospheric temperature and 50% relative humidity, and oxygen consumption rate, carbon dioxide production rate, and lactate concentration in plasma were measured. Furthermore, for the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. We found that, in the ALA+SFC trial, oxygen consumption rate and carbon dioxide production rate during graded cycling decreased by 12% ( ALA is an amino acid that can be found in many foods and is the sole initial material of heme biosynthesis in vivo , 37, 39.in vitro . However2 utilization efficiency in muscle mitochondria, it would increase the exercise efficiency and thereby improve the training achievement in older human subjects. To examine this hypothesis, we conducted a randomized, placebo-controlled, double-blind crossover study in older women.Based on these facts, we hypothesized that, if the oral ingestion of ALA accelerated the OThis study was approved by the Review Board on Human Experiments, Shinshu University School of Medicine, and conformed to the standards set by the Declaration of Helsinki. To minimize the effects of subject selection and the levels of training readiness, the subjects were recruited from the 547 participants in the “Jukunen Taiikudaigaku Project,” which is a health promotion program for middle-aged and older people in Matsumoto City, Japan. The participants had performed the interval walking training (IWT) program for more than 12 mo before this study; therefore, they were familiar with the exercise testing procedures used in the present study. Moreover, their exercise efficiency had likely reached the steady state and would thus enable us to detect only the effects of ALA intake on their exercise efficiency without accounting for the acute effects of exercise training.o2 peak). All subjects were nonsmokers and had no overt history of hepatic, thyroid, renal, metabolic, cardiovascular, or pulmonary disease, or orthopedic limitations in the exercise tests. Moreover, no subjects showed symptoms of iron deficiency anemia, as confirmed in the health examination before participating in the study. In the examination, the hemoglobin concentration ([Hb]), mean corpuscular volume, and mean corpuscular [Hb] were 14.1 ± 0.7 g/dl (mean ± SD), 90.5 ± 2.2 fl, and 33.8 ± 0.7 g/dl, respectively. Their physical characteristics were similar to those observed in our laboratory's previous study  gave written, informed consent before participating in this study. Each subject gave a complete medical history and underwent examinations of physical characteristics, resting blood pressure (BP), and peak aerobic capacity (V̇us study  and are days 1–7). Before and after the supplement intake period (days 0 and 8), subjects underwent a graded cycling test, during which the cardiorespiratory responses and lactate concentration in plasma ([Lac−]p) were measured. During the supplement intake period (days 1–6), except for the day before the graded cycling test (day 7), the training days, intensity, and time were recorded with a triaxial accelerometer   , 34, 52.o2) was increased. Therefore, we thought that a higher dose would be needed to improve mitochondrial function, if it occurred. Regarding dose safety, there is no legal dose limit in Japan because ALA phosphate has been approved as a food ingredient by the Pharmaceutical and Food Safety Bureau, the Ministry of Health, Labour and Welfare. Additionally, because the present study had a placebo-controlled crossover design, we could not test several doses of ALA+SFC.The composition of supplements  is shown in SFC, as a source of the iron ion, was contained in the supplements to enhance the final step of heme biosynthesis by ABCB6 transporter and ferrochelatase in mitochondria and to prevent the accumulation of heme biosynthesis intermediates, such as protoporphyrin IX, which might cause photodamage to the skin during outdoor exercise . AlthougP > 0.2). Moreover, the values generally met the recommended dietary allowance (RDA) for Japanese active older women . The results are shown in er women , and theer women , was verer women .P > 0.4). Subjects were asked to eat the standardized breakfast and lunch at normal time and to finish the standardized dinner by 2100. Additionally, subjects were asked to refrain from ingesting alcohol and caffeine during the day.On the day before the graded cycling test, which occurred four times : the total calories was 1,816 ± 16 kcal, the total protein was 66.6 ± 0.3 g, the total fat was 33.3 ± 0.1 g, and the total carbohydrate was 307 ± 4 g, with no significant differences observed before and after the supplement intake periods or between the CNT and ALA+SFC trials  atmospheric temperature and 50 ± 1% relative humidity. An 18-gauge Teflon catheter was then placed in the left antecubital vein for blood sampling. The catheter was connected to a 20-ml syringe that contained heparinized saline solution through an extension tube 2.0 ml in volume with a three-way stopcock.On the day of testing, subjects reported to the laboratory at 0900; they were normally hydrated but had not eaten any food for more than 12 h before the experiment. To ensure that they were well hydrated, they were instructed to drink 500 ml of tap water 2 h before the visit. Furthermore, they were instructed to ingest a supplement 2 h before the visit on e) every 15 s  to determine the V̇o2 and carbon dioxide production rate (V̇co2)  , Table 4o2 peak were a respiratory exchange ratio of >1.1, V̇o2 leveling off, despite increasing exercise intensity, and HR reaching the age-predicted maximal value. V̇o2 peak was determined by averaging the three largest consecutive values at the end of exercise. We also determined the gas exchange threshold during graded cycling according to the standard method   . Additioo2 and respiratory exchange ratio values during the last minute of each workload were averaged and used to calculate energy expenditure at a given workload. Under these conditions, efficiency was calculated based on the steady-state assumption that energy requirements are met by V̇o2 (1) V̇o2 during the last minute of each workload was relatively constant; and 2) when the values were plotted against workload, there was a linear relationship between them in each subject of each condition . Efficiency was then determined  represents V̇o2 at any time (t); V̇o2 BSLN is the baseline V̇o2 calculated as an average over 5 min before the onset of exercise; ΔV̇o2 is the steady-state increase in V̇o2 above the baseline V̇o2; τ represents the time constant defined as the time required to attain 63% of the ΔV̇o2; and TD represents the mathematically determined time delay for V̇o2 to start to increase after the onset of exercise. Briefly, after abandoning the phase I response of V̇o2 for the first 15 s to exclude the cardiodynamic effect , subjects were instructed to perform IWT, repeating five or more sets of 3 min of low-intensity walking at 40% of V̇o2 peak, followed by 3 min of high-intensity walking above 70% of V̇o2 peak per day for 4 or more days/wk, where training days, intensity, and time were recorded with a portable triaxial accelerometer (JD Mate) and transferred to the computer server at Shinshu University Graduate School of Medicine over the internet , which suggests no effects of weather conditions on the training achievement.Regarding the weather conditions on the first 6 of 7 days of supplement intake in the CNT and ALA+SFC trials, the precipitation from 0500 to 2000 was 1.7 ± 0.7 and 2.6 ± 0.8 mm/day, atmospheric temperature was 15.7 ± 1.1 and 13.9 ± 1.0°C, and relative humidity was 71 ± 1 and 75 ± 1%, respectively, with no significant differences observed between trials , period [the effect of stimulation order was present in CNT-(ALA+SFC) sequence group vs. (ALA+SFC)-CNT sequence group], and supplement effects. For the analysis, data were averaged during the graded cycling test, and changes after supplement intake (after-before) were calculated for each period. The three effects were then determined by the method reported by Chow and Liu . The nulP > 0.1). [Hb] before and after supplement intake was 13.3 ± 0.3 and 13.1 ± 0.3 g/dl in the CNT trial, respectively, and 13.1 ± 0.4 and 12.9 ± 0.4 g/dl in the ALA+SFC trial, respectively, with no significant differences between them . Additionally, V̇o2 peak and peak HR during the graded cycling test remained unchanged after supplement intake in both trials ; however, the peak workload tended to increase (P = 0.081). Furthermore, the time to exhaustion significantly increased by 0.8 min in the ALA+SFC trial (P = 0.022), although not in the CNT trial (P = 0.47) (P = 0.040).As shown in  = 0.47) ; the inco2, V̇co2, and V̇e responses during the graded cycling test. When comparing the responses obtained before and after supplement intake, an increase in V̇o2 after supplement intake was significantly attenuated by 12% for every workload 1 min after the start of exercise in the ALA+SFC trial (P < 0.001), although this did not occur in the CNT trial (P = 0.49). Similarly, an increase in V̇co2 and V̇e was significantly attenuated by 11% for every workload 2 min after the start of exercise in the ALA+SFC trial , although this did not occur in the CNT trial . We confirmed that the reduction in V̇o2 and V̇co2 after supplement intake was significantly greater in the ALA+SFC than in the CNT trial . In addition, there were no significant differences in HR and BP during the graded cycling test before and after supplement intake in either trial .NT trial , but the−]p during the graded cycling test. After supplement intake, the increase in [Lac−]p was significantly attenuated by 16% every workload in the ALA+SFC trial (P < 0.001), although this did not occur in the CNT trial (P = 0.59). We confirmed that the reduction in [Lac−]p after supplement intake was significantly greater in the ALA+SFC than in the CNT trial  vs. the (ALA+SFC)-CNT sequence group (n = 5)  was 0.93 ± 0.32 ml·kg−1·min−1. For the (ALA+SFC)-CNT sequence, the change in V̇o2 after supplement intake was −1.06 ± 0.26 ml·kg−1·min−1 in period 1 and −0.32 ± 0.45 ml·kg−1·min−1 in period 2, and the difference over time (periods 1−2) was −0.74 ± 0.56 ml·kg−1·min−1, which was significantly different from that observed in the CNT-(ALA+SFC) sequence (P = 0.032), thus indicating a significant supplement effect. Similarly, a significant supplement effect was observed in V̇co2 (P = 0.048) and [Lac−]p (P = 0.039), but was not observed in V̇e (P = 0.13). No carryover or period effects were observed in V̇o2, V̇co2, V̇e, or [Lac−]p (P = 0.52–0.97).The changes in respiratory responses to the graded cycling test were also examined by comparing the CNT-(ALA+SFC) sequence group ( (n = 5) , 26. ForP = 0.0086 for gross efficiency, P = 0.039 for net efficiency), although this did not occur in the CNT trial . On the other hand, we found no significant differences in delta efficiency before vs. after supplement intake in the ALA+SFC trial (P = 0.61).o2 responses to exercise, we determined the V̇o2 kinetics parameters at the onset of exercise. As shown in τ after supplement intake was significantly shortened (P = 0.026), and that ΔV̇o2 was significantly decreased (P = 0.0018) in the ALA+SFC trial, although this did not occur in the CNT trial , whereas TD remained unchanged after supplement intake in both trials .To assess the effect of ALA on transient V̇A), training impulse (B), and training time (C) during the supplement intake period (days 1–6). Training days were 42% higher in the ALA+SFC than the CNT trial (P = 0.028). The impulses at total and fast walking were 72% and 102% higher in the ALA+SFC than the CNT trial . The training time at fast walking was 69% higher in the ALA+SFC than the CNT trial (P = 0.039).A), training impulse (B), and training time (C) on each day in the period of supplement intake. The ratio in the ALA+SFC trial tended to increase after the 5th and 6th days, but with no significant differences from that in the CNT trial . Training impulse at fast walking in the ALA+SFC trial increased after the 3rd day, with significant differences from that in the CNT trial (P = 0.028). Similarly, training time at fast walking in the ALA+SFC trial increased after the 3rd day, with significant differences from that in the CNT trial (P = 0.039).o2, V̇co2, and [Lac−]p during the graded cycling test were significantly reduced at every workload with ALA+SFC supplementation, and that all of the reductions were significantly greater in the ALA+SFC trial than in the CNT trial. In addition, training days, training impulse, and training time at fast walking were significantly higher in the ALA+SFC trial than in the CNT trial.Although ALA has been reported to enhance the production of heme and cytochromes in vitro , 39 to ao2 during the graded cycling test was significantly reduced by 12% at every workload in the ALA+SFC trial, but not in the CNT trial, with 12% increases in gross and net efficiencies with significance. Regarding the mechanisms, Ferguson et al.  with age and suggested that the phosphorylative-coupling efficiency (ATP/V̇o2) rather than contractile-coupling efficiency (work/ATP) played a key role in the reduced cycling efficiency with age. In the present study, we first confirmed in the whole body of older human subjects that the oral ingestion of ALA increased the gross and net efficiencies during cycling by 12% at the cadence mentioned above; however, we found no significant increase in delta efficiency, reflecting in part the phosphorylative-coupling efficiency, in the ALA+SFC trial  and ΔV̇o2 is an indicator of an O2 deficit  has been recommended in recent guidelines to increase V̇o2 peak in older people .This study was supported by a grant from the No conflicts of interest, financial or otherwise, are declared by the author(s).Author contributions: S.M., A.M., Y.-i.K., S.I., K.T., T.T., M.N., and H.N. conception and design of research; S.M., A.M., Y.-i.K., S.I., Y.K., Y.O., E.S., and H.N. performed experiments; S.M., A.M., and S.I. analyzed data; S.M., A.M., Y.-i.K., S.I., and H.N. interpreted results of experiments; S.M. and A.M. prepared figures; S.M., A.M., and H.N. drafted manuscript; S.M., M.N., and H.N. edited and revised manuscript; S.M., A.M., Y.-i.K., S.I., Y.K., Y.O., E.S., K.T., T.T., M.N., and H.N. approved final version of manuscript.


Study of plasma and intracellular concentrations of atazanavir, lopinavir, nevirapine, and efavirenz was conducted on 48 patients under short cycles of antiretroviral therapy. Intracellular concentrations (IC) were still measurable for all drugs after 85 h or 110 h drug intake despite the absence of drug in plasma for atazanavir and lopinavir. A linear relationship between plasma and intracellular efavirenz was observed. Further studies to fully understand the impact of IC in the intermittent antiviral treatment are required. Despite new approved anti-HIV drugs and more effective combinations, uninterrupted antiretroviral therapy is still considered to be required to avoid treatment failure. However strict adherence to HIV treatment might be difficult to achieve regarding side effects or personal environment.Leibowitch and coworkers have previously published a pilot study that evaluated the efficacy of intermittent antiviral treatment administered to HIV-infected patients under stepwise reductions in weekly medication . During We undertook a retrospective analysis on both plasma and peripheral blood monoclear cells (PBMCs) which have been collected during the study. Plasma and intracellular concentrations (IC) were investigated for two protease inhibitors (PI), atazanavir (ATV) and lopinavir (LPV), and two nonnucleoside reverse transcriptase inhibitors (NNRTI), efavirenz (EFZ) and nevirapine (NVP).All patients were selected on the basis of both their volunteering to follow an uncharted course of anti-HIV treatment and their adherence to repeated monitoring with the approval of the Raymond Poincaré Hospital Ethics Review Committee on Infectious Diseases. An individualized letter acknowledging the off-label, nonvalidated status of these exploratory prescriptions at their onset was personally addressed to and signed by each individual patient. Baseline characteristics of the patients and virological and immunological outcomes have been reported previously . The maj2O mixture . The number of PBMCs was determined following cell lysis by using a validated biochemical test which relies on an established DNA-based fluorescence signal [6 cells. In order to compare intracellular and plasma concentrations, IC were converted into the amount per volume, based on the approximation that the PBMCs volume is 0.4 pL [ ter-butyl-methyl-ether was carried out using efavirenz-d4 and amprenavir-d4 as internal standards. Calibration curves were linear for all compounds in the 100–10000 ng/mL range. The limits of detection were 0.50 ng/mL for LPV and ATV and 50 ng/mL for NVP and EFZ. Only values in the calibration range were considered for ratio calculation. The intra- and interassay precisions evaluated at 400, 1500, and 8000 ng/mL were all <15% and the intra- and interassay accuracies were in the 93.5–106% range at the three concentrations.All IC were measured by immunoassays we previously developed and PBMCs treated as previously described –5. Briefe signal . The cons 0.4 pL . Plasma Statistical analysis was performed using GraphPad Prism 5.03 computer software .PI and NNRTI target viral enzyme into the infected cells. There is still debate whether intracellular concentrations could be a useful parameter for efficacy or toxicity prediction. However relatively few data are available on intracellular concentrations . Intrace6 cells for 400 mg, 600 mg, and 800 mg, respectively, 13 h after intake. Despite apparent difference in the median values, no statistical difference using one-way ANOVA followed by Tukey-Kramer test was noticed. The median IPC ratios are 0.49, 0.30, and 0.21, respectively. IC are 39.1 and 511.3 fmol per 106 cells for 400 mg and 600 mg, respectively, 85 h after intake. In all cases, the IPC ratio is lower than previously reported [reported . Altoget6 cells for 300 mg 13 h and 85 after intake, respectively. A high IPC ratio (3.04) is observed at 13 h; however no plasma concentration was detected at 85 h despite significant residual IC. So far, no clinical data has been published for ATV IC.For ATV, IC are 1685 and 76.4 fmol per 106 cells for 400 mg 13 h, 60 h, 85 h, and 110 h after intake, respectively. The IPC ratios are 1.40, 1.84, 1.92, and 0.83, respectively. For EFZ 600 mg, IC are 3762, 2064, and 3707 fmol per 106 cells for 600 mg 13 h, 60 h, and 85 h after intake, respectively. The IPC ratios are 1.40, 1.84, 1.92, and 0.83, respectively. As previously noticed [r2 = 0.77, P < 0.0001; for statistical validity only these data (n = 28) were analyzed). A relationship was already observed in another study [For EFZ 400 mg, IC are 3081, 1131, 10250, and 547 fmol per 106 cells for 400 mg 13 h, 85 h, and 110 h after intake, respectively. The IPC ratios are 0.006, 0.064, and 0.049. IC are very low compared to other drugs and in particular EFV, another NNRTI, and there is no intracellular accumulation which is in accordance with previous results [For NVP, IC are 40.4, 69.5, and 7.2 fmol per 10 results . HoweverIt is noteworthy that for all drugs IC are still quantifiable after 85 h or 110 h drug intake even for PI when no plasma concentration was detected which may be due to shorter half-life for PI  thaIn conclusion, this study provides complementary observations about rather limited IC data. A prospective designed clinical trial is needed for further warranty before considering short weekly cycles of antiretroviral medicines as an alternative and these results absolutely do not support that nonstrict adherence may equally be effective as current established treatment. The presence of intracellular drugs after several days of intake is a very interesting observation suggesting quite longer half-life than in plasma and may be one of the parameters explaining such viral control. Understanding of the mechanism of action should take into account intracellular concentrations. A better comprehension of intracellular pharmacology could improve long-term therapy.


Comorbid diabetes is common in heart failure and associated with increased hospitalization and mortality. Nonetheless, the association between glycemic control and outcomes among patients with heart failure and diabetes remains poorly characterized, particularly among low income and minority patients.We performed a retrospective cohort study of outpatients with heart failure and diabetes in the New York City Health and Hospitals Corporation, the largest municipal health care system in the United States. Cox proportional hazard models were used to measure the association between HbA1c levels and outcomes of all-cause hospitalization, heart failure hospitalization, and mortality.Of 4723 patients with heart failure and diabetes, 42.6 % were black, 30.5 % were Hispanic/Latino, 31.4 % were Medicaid beneficiaries and 22.9 % were uninsured. As compared to patients with an HbA1c of 8.0–8.9 %, patients with an HbA1c of <6.5, 6.5–6.9, 7.0–7.9, and ≥9.0 % had an adjusted hazard ratio (aHR) (95 % CI) for all-cause hospitalization of 1.03 (0.90–1.17), 1.05 (0.91–1.22), 1.03 (0.90–1.17), and 1.13 (1.00–1.28), respectively. An HbA1c ≥ 9.0 % was also associated with an increased risk of heart failure hospitalization  and a non-significant increased risk in mortality  when compared to HbA1c of 8.0–8.9 %.Among a cohort of primarily minority and low income patients with heart failure and diabetes, an increased risk of hospitalization was observed only for an HbA1c greater than 9 %. Heart failure and diabetes are two chronic diseases that commonly coexist. Among patients with heart failure, the prevalence of diabetes is as high as 40 % –3 and isDespite the increased risk of poor outcomes among patients with heart failure and diabetes, the optimal hemoglobin A1c (HbA1c) level for patients with heart failure and diabetes remains uncertain. Due to lack of existing data, heart failure guidelines do not specifically address the intensity of glycemic control among individuals with heart failure , and theThe purpose of this study was to evaluate the association of HbA1c with all-cause hospitalization among patients with heart failure and diabetes in a hospital system serving a diverse, urban, and primarily low-income population. We hypothesized that hospitalization rates would vary with level of HbA1c with a U-shaped relationship, such that moderate glycemic control would be associated with reduced all-cause hospitalization, heart failure hospitalization, and mortality.We performed a non-concurrent cohort study of patients in the New York City Health and Hospitals Corporation (HHC), the largest municipal health care system in the United States. The corporation serves approximately 1.4 million people, of whom nearly 500,000 are uninsured, and includes 11 hospitals, six diagnostic and treatment centers, four long term care centers, and one hundred community health centers . The priWe included patients with heart failure and diabetes who had an outpatient clinic visit in HHC between 1/1/2007 and 12/31/2010. Diagnoses were based on International Classification of Diseases, Clinical Modification (ICD-9-CM) codes of 428 and 250, respectively, in the problem list . AdditioThe primary outcome was all-cause hospitalization. Secondary outcomes were heart failure hospitalization and mortality. Heart failure hospitalization was based on a principal diagnosis of heart failure using standard ICD-9-CM codes , 27.The primary exposure was HbA1c, which was categorized into the following clinically relevant categories: <6.5, 6.5–6.9, 7.0–7.9, 8.0–8.9, and ≥9.0 %. Other patient characteristics included age, gender, race, ethnicity, primary payer, prior utilization, comorbidities, diabetes severity, systolic blood pressure, pulse, creatinine, hemoglobin, active medications, prior utilization, and HHC facility of the clinic visit. Characteristics were assessed at time of clinic visit with the exception of laboratory values which, if unavailable at time of clinical visit, could be included if assessed up to 90 days prior to the clinic visit. In the data warehouse, race was self-reported as a single category and included responses of “Black or African American”, “Hispanic Black”, and “Hispanic or Latino”. From this information, we created a race variable that was categorized as black or other and an ethnicity variable which was categorized as Hispanic/Latino and other. Comorbidities were based on standard algorithms . Diabeten = 117) were censored on their last date of service.Follow up time was defined from time of clinic visit. Patients were followed to the time of death or December 31, 2010; patients who were unable to be accurately matched to mortality data ) plot and statistically using the Schoenfeld residuals. We developed adjusted Cox models incorporating baseline patient characteristics as well as shared-frailty to account for clustering within each HHC site . CovariaStatistical significance was pre-specified with an alpha level of 0.05 (two-tailed). Statistical analyses were performed using Stata 13 .This study was approved by the New York University School of Medicine Institutional Review Board.Of the 4723 patients with heart failure and diabetes included in the study, the median age was 64 years, 42.6 % were black, and 30.5 % were Hispanic or Latino. At the time of clinic visit, 31.4 % of patients were Medicaid beneficiaries and 22.9 % of patients had no insurance.The mean HbA1c (SD) for the cohort was 8.2 (2.4). The distribution of HbA1c categories of <6.5, 6.5–6.9, 7.0–7.9, 8.0–8.9, and ≥9.0 % was: 21.8, 12.7, 22.6, 15.0, and 28.0 %, respectively. Patients with high HbA1c were younger and had high rates of Medicaid insurance when compared to patients with low HbA1c  of 173  days. During follow up, 67.0 % of patients were hospitalized for any cause. Overall rates of hospitalization were similar across HbA1c groups  follow up for mortality was 658  days. Over 30 % of patients with HbA1c < 6.5 % died during the period while mortality rates for higher HbA1c categories ranged from 23.7 to 26.8 %  may be appropriate” for subpopulations such as those with limited life expectancy or significant comorbidity . In suppThis study was approved by the NYU School of Medicine institutional review board, which granted a waiver of consent.Not applicable.Data will not be shared due to restrictions related to patient confidentiality.


Five ACE inhibitory peptides were purified from the oyster hydrolysate using a multistep chromatographic procedure comprised of ion-exchange, size exclusion, and reversed-phase liquid chromatography. Their sequences were identified as TAY, VK, KY, FYN, and YA, using automated Edman degradation and mass spectrometry. These peptides were synthesized, and their IC50 values were measured to be 16.7, 29.0, 51.5, 68.2, and 93.9 μM, respectively. Toxicity of the peptides on the HepG2 cell line was not detected. The oyster hydrolysate also significantly decreased the systolic blood pressure of spontaneously hypertensive rats (SHR). The antihypertensive effect of the oyster hydrolysate on SHR was rapid and long-lasting, compared to commercially obtained sardine hydrolysate. These results suggest that the oyster hydrolysate could be a source of effective nutraceuticals against hypertension.Following cross-linking by microbial transglutaminase, modified oyster proteins were hydrolyzed to improve inhibitory activity against angiotensin-converting enzyme (ACE) inhibitory activity with the use of a single protease, or a combination of six proteases. The oyster hydrolysate with the lowest 50% ACE inhibitory concentration (IC Hypertension affects about 70 million people in the USA, with an overlap in those suffering from cardiovascular disease , and it Oysters are abundantly maricultured along the seashore of Tongyeong, Korea. The decline in export and consumption of fresh oysters promoted the search for a new application. ACE inhibitory peptides have been isolated and characterized from an oyster protein and from salt-fermented oyster sauce , 18. Newγ-glutamyltransferase, EC 2.3.2.13) catalyzes an acyl-transfer reaction between the γ-carboxamide group of peptide-bound glutamine residues (acyl acceptors) and a variety of primary amines (acyl acceptors), including the ε-amino group of lysine residues in certain proteins [ε-(γ-glutamyl)lysine bond formed through protein cross-linking exhibits high resistance to proteolytic degradation [Transglutaminase , Flavourzyme 500 MG , Protamex 1.5 MG , and Neutrase 0.8 L  were obtained from Biosis Co. . MTGase (103 U/g) was obtained from Ajinomoto Co. . Acetonitrile and methanol were high-performance liquid chromatography (HPLC) grade. All other reagents were reagent grade. HiLoad Q-Sepharose, Superdex peptide, and Source 5RPC ST columns were purchased from GE Healthcare . A Bondclone C18 column was purchased from Daiso Chemical Co. .Oysters were purchased from a local market in October 2011 . ACE enzyme , pepsin , trypsin , N-Hisppuryl-His-Leu hydrate , and Captopril (Sigma C4042) were purchased from Sigma Chemical Co. . Several specific peptides  were synthesized at GL Biochem Ltd. . Sardine hydrolysate was purchased from Chosunmuyak Co. . Alcalase 2.4 L . The minced oyster was suspended in four volumes of distilled water and homogenized with a homogenizer . The suspension was adjusted to pH 6.5–7.0 with 1 M NaOH, after which 1% MTGase (by weight of fresh oyster) was added. The mixture was then incubated at 30°C for 1 h in a 5 L jar fermenter  with stirring at 150 rpm. After the reaction, MTGase was inactivated by immersion in a 95°C–100°C water bath for 1 h. To determine the optimum hydrolysis time and protease, the oyster protein was hydrolyzed with each protease for 1, 2, 3, 4, 5, or 6 h or by two-step hydrolysis using Protamex with the other five proteases, respectively, for 1 h in the same jar fermenter. The ratio of protease to fresh oyster was 1% for Alcalase, Flavourzyme, Neutrase, and Protamex, 0.1% for pepsin, and 0.05% for trypsin. After inactivating the proteases in a 95°C–100°C water bath for 1 h, the mixture was centrifuged , after which the supernatant was ultrafiltered with a 10 kDa membrane using a lab scale TFF system . The material with a molecular size < 10 kDa was lyophilized and stored at −20°C until use. The scheme and hydrolysis conditions for the preparation of oyster hydrolysate are shown in μL) was mixed with 225 μL of ACE solution (0.025 units/mL), which was preincubated at 37°C for 10 min before adding 50 μL HHL . The mixture was then incubated for 30 min at 37°C. The reaction was stopped by adding 75 μL of 1 M HCl, and the mixture was centrifuged at 8,160 g . The amount of hippuric acid (HA) in the supernatant was determined by reversed-phase HPLC  on C18 . The IC50 value was calculated as the inhibitor concentration required for inhibition of 50% of the ACE activity. The percentage of inhibition of the enzyme activity was calculated as follows:ACE inhibitory activities of the oyster hydrolysates prepared with the different enzymatic hydrolysis conditions  were meaOyster hydrolysate prepared at the optimized enzymatic condition was dissolved in 20 mM Tris-Cl, pH 8.0 buffer, and the ACE inhibitory fraction was eluted using a HiLoad Q-Sepharose column (16 × 100 mm). Elution was performed using a linear gradient system from solvent A  to solvent B  over 100 min at a flow rate of 1 mL/min and detected at 254 nm. Every 2 mL fraction was collected, and ACE inhibitory activities were determined. Fractions with high ACE inhibitory activity were pooled and concentrated using an Amicon stirred cell with a 1 kDa membrane. The concentrated fractions (< 1 kDa) were loaded on a Superdex peptide column (10 × 300 mm) and eluted with 20 mM Tris-Cl, pH 7.5 at a flow rate of 0.5 mL/min. Detection was then carried out at 216 nm. Each 1 mL fraction was collected, and ACE inhibitory activities were detected. Fractions with high ACE inhibitory activity were dried completely in a speed vacuum concentrator  and applied to the reversed-phase column for further purification.μL of sample was applied to the column and elution was carried as follows: two column volumes of solvent A, fourteen column volumes of solvent A-B gradient, four column volumes of solvent B, and four column volumes of solvent A. The purified ACE inhibitory peptides were dried in a speed vacuum concentrator for amino acid sequence identification.Active fractions were dissolved in 0.1% TFA in water and fractionated using the AKTA purifier system  with a Source 5RPC ST column (4.6 × 150 mm). Elution was performed using a linear gradient system from solvent A (0.1% TFA in water) to solvent B (0.1% TFA/60% ACN) over 90 min at a flow rate of 1 mL/min and detected at 216 nm. The column was equilibrated with solvent A, after which 50 The sequence of peptides was analyzed by the Edman method using a 491 Protein Sequencer . The molecular mass of the peptides was determined by an AB SCIEX API 3200 QTRAP mass spectrometer . The peptides were subsequently synthesized using the solid-phase method at GL Biochem Co. . The purities of the synthesized peptides were >95.8%, confirmed by reversed-phase HPLC analysis.4 cells per well were incubated at 35°C for 24 h under 95% humidity and 5% CO2. After incubation, the synthetic peptides were added  and cells were incubated under the same conditions for an additional 24 h. Cell growth was assessed with the CellTiter 96 Aqueous One Solution Cell Proliferation Assay kit  and absorbance was determined with a microplate reader  at 490 nm. Cell viability was calculated as the percentage of absorbance of the synthetic peptide-treated groups compared with that of the untreated group (100% viability).The ACE inhibitory activities of the synthetic peptides were measured, and the cell toxicity was evaluated by cell viability testing on the hepatocyte cell line HepG2. HepG2 cells were cultured in MEM medium containing 10% fetal bovine serum. Ninety-six well plates containing 1 × 10n = 3); normal WKR control group (n = 3); oyster hydrolysate-treated SHR group ; sardine hydrolysate-treated SHR group ; and Captopril-treated SHR group . After intragastric administration of the samples using Sonde, SBP of the rats was measured by a Coda noninvasive blood pressure system  using the tail-cuff method after prewarming for 30 min in an environmental chamber of 32°C at 0, 3, 6, 9, 12, and 24 h. Subsequent measurement of blood pressure was expressed as a percentage of that at the initial time.Spontaneously hypertensive rats (SHR) with systolic blood pressure (SBP) between 170 and 190 mmHg and original strain Wistar Kyoto rats (WKR) with SBP between 100 and 125 mmHg were purchased from Harlan, USA . All rats were treated in accordance with Kyung Hee University guidelines for the care and use of laboratory animals. The animals were individually housed in stainless steel cages and adapted to 23 ± 1°C and humidity of 55 ± 5% under a 12 h light-dark cycle. The 12-week-old rats were fed a pelletized commercial chow diet for a period of 1 week after arrival and then randomly divided into five groups: untreated SHR control group (P < 0.05) were considered statistically significant.Data were expressed as the mean with standard deviation of triplicate determinations. Analysis of variance was carried out by the Tukey HSD test using the JMP 10 package . Probability values less than 5%  matched well with the molecular weight of YA, 252.3 Da.To identify the purified peptides, the active fractions  were subjected to automated Edman degradation and mass spectrometry. Manual analysis yielded the peptides sequences as FYN (442.5 Da), TAY (353.4 Da), KY (309.4 Da), VK (245.3 Da), and YA (252.3 Da), respectively. The mass spectra of Frac. 4-2-1 (YA) are shown in 50 values of the synthetic peptides TAY, VK, KY, FYN, and YA were subsequently measured to be 16.7, 29.0, 51.5, 68.2, and 93.9 μM, respectively , which had initial SBP in the range of 62.0 ± 5.6% to 65.5 ± 6.2%. Sardine hydrolysate and Captopril were used as positive controls. The SBP of the SHR was significantly lowered 9 h after administration of the sardine hydrolysate and the antihypertensive activity continued up to 12 h after administration compared to the WKR control (P < 0.05). However, the maximum decrease in SBP by Captopril was observed 12 h after administration, which was 85.3 ± 4.5% of the initial SBP (P = 0.33), which may be due to the small dosage administered [Antihypertensive activities of oyster hydrolysate were evaluated by measuring the SBP of SHR at 0, 3, 6, 9, 12, and 24 h after oral administration . SHR wertial SBP . Captoprnistered . CompareThis study demonstrated that the ACE inhibitory activity of the MTGase-cross-linked oyster protein can be significantly improved by a two-step hydrolysis with Protamex and Neutrase. Five ACE inhibitory peptides were purified and identified from the oyster hydrolysate using ion-exchange, size exclusion, and reversed-phase chromatography. The oyster hydrolysate showed high antihypertension effect in vivo compared to sardine hydrolysate. It is, thus, possible to produce natural and effective antihypertensive products from oyster through enzymatic hydrolysis. Such oyster hydrolysate can be utilized as a nutraceutical or functional food, and the purified ACE inhibitory peptides have the potential for use as lead compounds of an antihypertension drug. Further work, including analysis of the physicochemical properties and quality control parameters for the hydrolysate, is in progress and will be reported.


Aim. To assess the effects of mydriatics commonly used in clinical practice on choroidal thickness and anterior chamber change. Methods. This was a prospective, randomized, controlled, double-blinded study including a single eye of the participants. The subjects were assigned into 4 groups to receive tropicamide 1%, phenylephrine 2.5%, cyclopentolate 1%, and artificial tears. At the baseline, anterior chamber parameters were assessed using a Pentacam Scheimpflug camera system, and choroidal thickness (CT) was measured using a spectral-domain OCT with Enhanced Depth Imaging (EDI) modality. All measurements were repeated again after drug administration. Results. Increases in pupil diameter, volume, and depth of anterior chamber were found to be significant , while decreases in the choroidal thickness were found to be significant in subjects receiving mydriatics (p < 0.05). Conclusions. The study has shown that while cyclopentolate, tropicamide, and phenylephrine cause a decrease in choroidal thickness, they also lead to an increase in the volume and depth of anterior chamber. However, no correlation was detected between anterior chamber parameters and choroidal changes after drug administration. These findings suggest that the mydriatics may affect the choroidal thickness regardless of anterior chamber parameters. This study was registered with trial registration number 2014/357. Mydriatics have a broad range of applications in ocular examination and treatment to allow for pupil dilatation and/or cycloplegia. In clinical practice, these agents are used to achieve cycloplegia before refraction examination; to achieve pupil dilatation before fundus examination, surgery, and angiography; or to prevent synechia in the management of uveitis. After administration, many changes occur in the iris root, anterior chamber angle, anterior chamber depth, iris thickness, and iris volume as well as pupil dilatation –3.The choroidea is a vascular layer localized in the outer sclera and inner retinal layers. It has many major functions, including oxygenation of inner nuclear layers and retinal pigment epithelium . GreaterIt is possible that the choroidea, a part of uvea like iris, may display certain changes after mydriatic use. There have been a limited number of studies measuring choroidal thickness after mydriatic use. In these studies, conflicting results were reported after measurements with sufficient dilatation in healthy individuals, suggesting no change , 14 or tSubjects: this was designed as a randomized, placebo-controlled, double-blinded study including a single eye of participants. The study followed the tenets of the Declaration of Helsinki and was approved by the Local Ethics Committee of Erciyes University (2014/357). All individuals received both oral information and written information about the study, and each was provided with written and informed consent before participation to the study.All individuals underwent a screening process involving a complete ophthalmologic examination, including visual acuity and refraction, slit-lamp biomicroscopy, fundus examination, and intraocular pressures measured using noncontact tonometry. Axial length was measured using an IOL Master . Anterior chamber parameters were measured using a Pentacam rotating Scheimpflug camera . The retina nerve fiber layer and choroidal thickness measurements were obtained through the Spectralis OCT .All individuals required a best corrected visual acuity of 20/25 or better, with refractive error <5 diopters, 3 diopters of cylinder, and absence of glaucomatous optic disc changes. Exclusion criteria included any retinal diseases, history of ocular injury or surgery, any reasons for poor image quality of OCT such as unstable fixation or severe cataract, and age younger than 18 years.Two hundred and forty eyes of 120 individuals satisfying the inclusion criteria were enrolled in the study between May 2014 and September 2014. Both eyes were enrolled, and one eye of each individual was randomly selected. A double-blinded protocol was used, and those who evaluated the EDI-OCT did not know which drug was administered to each patient.All individuals were randomly assigned into 4 groups based on the application of drops. Subjects who received a drop of tropicamide 1% 3 times at 5 min intervals were referred to as the tropicamide group, while subjects who received a drop of 2.5% phenylephrine 3 times at 5 min intervals were the phenylephrine group. Subjects who received a drop of cyclopentolate 1% 3 times at 5 min intervals were defined as the cyclopentolate group, and subjects who received a drop of artificial tears 3 times at 5 min intervals were defined as the control group.Procedure of image acquisition: the procedure of obtaining EDI-OCT has been previously described . The subOcular biometrics before and after application of drops in each subject were also assessed with the IOL Master. The measures of axial length (AXL), lens thickness, and anterior chamber depth (ACD) along the visual axis were obtained through a single measurement procedure.For each subject, corneal thickness, anterior chamber depth (ACD), corneal volume, anterior chamber angle (ACA), corneal curvature, and anterior chamber volume (ACV) were obtained through Pentacam before and after instillation of drops.Statistical analysis: all data analyses were performed by using the Statistical Package for the Social Sciences (SPSS) for Windows version 22.0 . The Pearson chi-square test was used to assess qualitative variables. Continuous variables were presented as mean ± standard deviation. Correlation coefficient (CC) was calculated for each of the ocular parameters. The measurement reliability of CC was considered “excellent” if the values of CC > 0.75, “good” if the values of CC > 0.4, and “poor” if the values of CC < 0.4.p > 0.05). Homogeneity of variances was tested by using Levene's test. For parametric statistics, data with normal distribution were analyzed using one-way ANOVA test to compare the groups. When a significant result was obtained, the Tukey test was used for post hoc comparisons. Repeated measurements of anterior chamber parameters, choroidal thickness, and intraocular pressure of the groups were compared by a Paired t-test. For nonparametric statistics, data with skewed distribution were analyzed by using Kruskal-Wallis test. When a significant result was obtained, Mann-Whitney U test with Bonferroni's correction was used for post hoc comparisons. A p value < 0.05 was considered statistically significant.For each continuous variable, normality was checked by Kolmogorov-Smirnov test, and it did not depart significantly from a normally distributed sample , the phenylephrine group , the cyclopentolate group , and the control group . The mean spheric equivalent was measured as −0.55 ± 1.49 diopters in the tropicamide group, −0.73 ± 1.60 diopters in the phenylephrine group, 0.01 ± 2.24 diopters in the cyclopentolate group, and −1.0 ± 1.20 diopters in the control group. There were no significant differences in the demographic characteristics and ocular parameters between those who received mydriatics and those who were in the control group. Demographics and ocular parameters in all groups were summarized in p = 0.000), but the extent of pupil diameter was found to be higher in the tropicamide and the cyclopentolate groups than in the phenylephrine group. The anterior chamber depth increased from 2.88 ± 0.33 mm at baseline to 2.96 ± 0.34 mm after drug administration in the tropicamide group, from 3.03 ± 0.32 mm to 3.11 ± 0.34 mm in the phenylephrine group, from 3.09 ± 0.33 mm to 3.22 ± 0.31 in the cyclopentolate group, and from 3.11 ± 0.34 mm to 3.14 ± 0.38 mm in the control group, respectively.Overall, 120 patients  were included in the study. The mean age was 30.9 ± 9.7 years (age range: 18–56 years). All patients were randomly divided into 4 groups. Groups were comprised of the tropicamide group (p = 0.000). When it comes to the anterior chamber volume, the study found that it increased from 154.76 ± 34.99 mm3 at baseline to 171.90 ± 31.52 mm3 after drug administration in the tropicamide group, from 178.28 ± 39.43 mm3 to 193.97 ± 34.69 mm3 in the phenylephrine group, from 187.93 ± 35.38 mm3 to 203.84 ± 30.06 mm3 in the cyclopentolate group, and from 184.66 ± 38.97 mm3 to 185.10 ± 38.94 mm3 in the control group, respectively. These results also show that the anterior chamber volume increased significantly in the subjects who received mydriatics when compared to the control group (p = 0.000).These results demonstrate that the anterior chamber depth increased significantly in the subjects who received mydriatics when compared to the control group , but no significant difference was detected among the tropicamide, phenylephrine, and cyclopentolate groups in terms of choroidal thinning. Moreover, no significant difference was also detected in the central choroidal thickness before and after drug administration in the control group (p = 0.172).The central EDI-OCT measurements before and after drug administration were 328.65 ± 87.88 µ and 291.48 ± 72.80 in the tropicamide group, 324.34 ± 79.36 µ and 305.58 ± 66.94 µ in the phenylephrine group, 291.41 ± 85.32 µ and 280.12 ± 84.30 µ in the cyclopentolate group, and 297.47 ± 68.72 µ and 305.47 ± 67.87 µ in the control group, respectively. Thus, the temporal EDI-OCT measurements saw a significant decrease in the participants who received mydriatics when compared to the participants in the control group (p = 0.000). On the other hand, no significant difference was detected in the central choroidal thickness in the control group (p = 0.072). The nasal EDI-OCT measurements before and after drug administration were 302.10 ± 84.48 µ and 286.03 ± 74.78 in the tropicamide group, 313.45 ± 66.98 µ and 296.86 ± 64.30 µ in the phenylephrine group, 290.34 ± 85.89 µ and 276.87 ± 86.52 µ in the cyclopentolate group, and 305.53 ± 81.13 µ and 300.77 ± 75.79 µ in the control group, respectively. The nasal EDI-OCT measurements significantly decreased in the subjects receiving mydriatics when compared to the control group (p = 0.000). No significant differences were detected in the central choroidal thickness in the control group (p = 0.232). Changes in the anterior chamber parameters, choroidal thickness, and intraocular pressure before and after drug administration in all groups are summarized in The temporal EDI-OCT measurements before and after drug administration were 308.90 ± 79.36 r = −0.136, p = 0.200). The same was also true for anterior chamber volume .No statistical difference in the choroidal thickness was observed for subjects with an increase in anterior chamber depth and subjects with changes in anterior chamber depth were compared  (p = 0.086). No significant difference was found between the subjects with PD > 6.0 mm and with PD < 6.0 mm in the groups receiving tropicamide 1% and phenylephrine 2.5%, but the extent of the choroidal thinning was found to be higher in the subjects with PD > 6.0 mm in the cyclopentolate group. Overall, no significant correlations were detected between the central choroidal thickness and pupil diameter .In general, the mean for the pupil diameter increased from 3.17 ± 0.85 mm at baseline to 5.57 ± 1.59 mm after drug administration, while the means for the central, subfoveal, and choroidal thicknesses decreased from 326.94 ± 78.59 α-agonist with sympathomimetic effects. Generally, sympathomimetic agents have shorter onset and duration of action than antimuscarinic agents. There may be changes in several parameters, such as the iris configuration and angle, the volume and the depth of anterior chamber during pupil dilatation, and cycloplegia induced by mydriatics [Mydriatics induce pupil dilatation or cycloplegia through several mechanisms, including sympathomimetic and antimuscarinic activities. In Turkey, there are three commercially available mydriatic preparations in common use. Of these, cyclopentolate 1% and tropicamide 1% have antimuscarinic (parasympatholytic) effects. The major difference between these antimuscarinic drugs is the duration of action. Phenylephrine 2.5% is an driatics . Length driatics –20. Paradriatics . Both drIn our study, it was found that all mydriatic agents led to significant choroidal thinning. No correlation was demonstrated between choroidal changes and pupil diameter or volume and depth of anterior chamber. In the cyclopentolate group, it was found that the extent of thinning was significantly higher in the subjects with PD > 6,0 mm than those with PD < 6.0 mm. However, no such differences were observed in the tropicamide and phenylephrine groups.Similarly, Kara et al.  found chContrary to our results, it was shown that there was no change in choroidal thickness in 2 studies using mydriatic agents , 14. In Sander et al.  state thIn conclusion results have failed to demonstrate a correlation between the pupil diameter and choroidal changes in the subjects with PD > 6.0 mm receiving tropicamide 1% and phenylephrine. Only in the group that received cyclopentolate was choroidal thinning found to be significantly different in the subjects with PD > 6.0 mm compared to those with PD < 6.0 mm. The most important difference of cyclopentolate, an antimuscarinic agent, is a longer duration of action than the other agents used. Thus, it may have longer effect in tissue. Given the smaller number of subjects with PD < 6.0 mm, we think it appropriate to reevaluate these results in studies with larger sample size, as these results may be completely incidental.To the best of our knowledge, ours is the first study comparing anterior chamber changes and choroidal thickness after mydriatic use to be found in the literature. Our results have demonstrated that mydriatic drug use resulted in choroidal thinning, which was found to be independent from both anterior chamber depth and volume.Although the choroidal effect that resulted from mydriatic use was thinning on average, it was not observed in all participants in the same way. While there was no significant change in some participants, there was an increase in some others. Excluding pupil diameter changes, anterior chamber parameters also displayed individual differences. There was no statistically significant relationship between anterior chamber parameters and choroidal changes. This might lead us to think that there might be some other factors causing changes in individual CT as a result of mydriatic use. This may also explain why there are conflicting findings in the literature. We are in the opinion that this subject should be further analyzed by large-scale works that utilize different types of data.In the studies on choroidal thickness, it is important to indicate whether results are obtained before or after mydriatic use in order to assess study. Based on these results, it appears to be impossible to determine the extent of drug effects on the choroidea through evaluation of anterior chamber data.