Sex hormones are known to regulate some responses during exercise. Evaluation of the differences in exercise response with regard to menstrual cycle will help understand the menstrual cycle phase specific adaptations to exercise and athletic performance.We investigated the effects of menstrual cycle phase and carbohydrate (CHO) ingestion on immune response during endurance exercise at 30°C. Six healthy women completed 4 trials comprising 90 min of cycling at 50% peak aerobic power 3) in the luteal phase was significantly higher than that in the follicular phase (12.9 × 103). The rise in leukocyte concentration was attenuated upon CHO ingestion, and the difference between menstrual cycle phases disappeared. A significant positive correlation was found between leukocyte concentration and serum free fatty acid concentrations. Interleukin-6, calprotectin, and myeloperoxidase concentrations significantly increased at POST in all trials, but no significant differences were observed between menstrual cycle phase or beverage type. Concentrations of other cytokines did not change during exercise in any of the 4 trials. Menstrual cycle phase and beverage type had no significant effect on the POST outcome. Thus, differences in leukocyte mobilization between menstrual cycle phases could result from the effect of sex hormones on substrate utilization.Although the thermoregulatory responses differed between the menstrual cycle phases, the cardiorespiratory responses were not different. After placebo ingestion, leukocyte concentration (cells/μL) at POST (15.9 × 10The menstrual cycle affected circulating leukocyte concentrations during endurance exercise with POST when a placebo was ingested. Therefore, we recommend ingesting CHO beverages to attenuate immune disturbances, especially in the luteal phase, even though they are unlikely to enhance test performance. With an increase in the number of women participating in sports for recreation, health, fitness, weight management, social interaction, competition, and/or personal accomplishment, the influence of menstrual cycle phase on physiologic response to exercise has received much attention, not only for athletes but also women in general. Sex hormones are known to regulate substrate utilization , muscle A number of studies involving male subjects have reported that exercise causes disturbances in circulating leukocyte concentrations and function and that these effects are dependent on the intensity of exercise and the associated release of stress hormones . FurtherIn women with a normal menstrual cycle, core temperature (Tc) rises by 0.3°–0.5°C in the luteal phase compared to the follicular phase . TherefoSeveral studies have investigated the effect of menstrual cycle phase on endurance exercise performance, but consistent results have not been obtained ,11. One A number of previous studies involving male subjects reported that CHO ingestion during exercise could suppress the mobilization of leukocytes into the circulation -15 and sIt is known that ovarian hormones can exert metabolic actions affecting substrate utilization. For example, administration of estradiol and progesterone in rats has been reported to decrease gluconeogenesis from alanine and to increase hepatic storage , and varThe first purpose of our study was to examine the effect of menstrual cycle phase on immune response to exercise in a hot condition, with a progesterone concentration threshold for luteal phase verification. To our knowledge, the interaction between exercise in a hot condition and menstrual cycle phase with progesterone limitation on immune response has not been systematically studied because the exercise conditions in previous studies were not defined. The second purpose of our study was to investigate the effect of CHO ingestion on immune response. We hypothesized that menstrual cycle may affect immune responses and that CHO ingestion attenuates these effects.Six healthy young women volunteered to take part in this study. All subjects maintained a regular menstrual cycle and were not taking any oral contraceptives before testing. Their mean characteristics were as follows: age, 23  years; weight, 48.7  kg; height, 156.2  cm; and peak aerobic power This study comprised 4 separate experimental trials. Subjects exercised in the condition  during follicular and luteal phases of their menstrual cycle. During the exercise, subjects either consumed a CHO beverage containing 3.8% CHO (2.1% glucose and 1.7% fructose) or a placebo sweetened with an artificial sweetener  that tasted like the CHO beverage. We used a hypotonic CHO beverage , which was reported to attenuate some inflammatory responses to exercise . The comTo estimate menstrual cycle phase, all subjects recorded their oral temperature upon waking every day for at least 2 months and the day of menstruation for 3 months before commencement of the trial. Additionally, blood samples taken before commencement of the exercise were analyzed for estradiol and progesterone concentrations to determine the menstrual phase.rg Scale .All subjects completed four separate experimental trials, with each trial occurring at a specific time during the menstrual cycle, previously determined for each subject by her basal body temperature. For the 2 CHO and 2 placebo trials, 1 trial each occurred in the follicular phase , and 1 trial each in the luteal phase . To avoid a confounding phase and beverage effect with trial order, subjects were randomly assigned trial orders, with 3 subjects commencing in the follicular phase and 3 in the luteal phase. Each experimental trial was performed on a separate day at least 1 week apart. Subjects were asked to only drink water after 21:00 h on the day before the experimental trial, and they ate a standardized breakfast  at 06:00 h, i.e. 6–7 h before each trial. Thereafter, foods and beverages, except for water, were not allowed.In all 4 trials, subjects cycled at 50% Following the 90-min exercise, subjects completed POST that lasted approximately 10 min in the same condition. Subjects were required to complete a set amount of work  as fast as possible. The total amount of work to be performed was calculated using the following formula : Total wg for 10 min. Serum and plasma were then removed and stored at -80°C for future analysis. Serum free fatty acid and plasma glucose concentrations, leukocyte concentrations, hemoglobin, and hematocrit were analyzed by BML, Inc. . Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure plasma concentrations of the cytokines interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, tumor necrosis factor (TNF)-α , IL-8, IL-10, and IL-12p40 , and the neutrophil activation markers myeloperoxidase (MPO) and calprotectin . ELISA measurements were performed according to the instructions for each ELISA kit using a microplate reader . Plasma concentrations of all these variables were adjusted for changes in plasma volume [Venous blood samples were collected by venipuncture from an antecubital vein before exercise (PRE); at the 30-min, 60-min, and 90-min time points during the exercise; and at POST. Blood samples were collected into serum separation tubes or vacutainers containing ethylenediaminetetraacetic acid (EDTA). A fraction of whole blood was used to measure hemoglobin, hematocrit, and full blood cell count. Serum separation tubes were left to allow blood to clot at room temperature for 30 min, while vacutainers containing EDTA for plasma separation were immediately centrifuged at 1,000 × a volume .P = 0.05. Relationships between dependent variables and leukocyte concentration were assessed with Pearson product correlations. The level of statistical significance was set at P < 0.05.All data were checked for normal distribution using the Kolmogorov-Smirnov statistic. Data for rectal temperature, HR, VE, RER, blood glucose, serum free fatty acid, leukocyte concentrations, and performance test result were normally distributed. Data for serum sex hormones, IL-8, IL-12p40, and MPO concentrations were normally distributed after log transformation. Data for serum IL-1β, IL-1ra, IL-6, IL-10, calprotectin, and TNF-α concentrations were not normally distributed. Normally distributed data  repeated analysis of variance (ANOVA). For other normally distributed data , a 4 × 8 factor  repeated ANOVA was used to determine trial effects, time effects, and trial × time interactions. For other normally distributed data , a 4 × 5 factor  repeated ANOVA was used to determine trial effects, time effects, and trial × time interactions. When significant trial effects, time effects, or trial × time interactions were evident, Bonferroni posthoc multiple comparisons were used. Data for serum IL-1β, IL-1ra, IL-6, IL-10, calprotectin, and TNF-α were analyzed using nonparametric Friedman’s ANOVA on ranks test to determine time effects. Kruskal-Wallis’ one-way ANOVA was used to assess differences between trials at specific time points. Data were analyzed using SPSS version 19 for Windows  with the threshold for statistical significance set at P < 0.01), but not of the beverage, on both hormones was observed. Serum estradiol and progesterone concentrations were significantly higher in the luteal phase than in the follicular phase [Table ar phase . We usedar phase ,33.Rectal temperature data during exercise is shown in Figure P < 0.05). Although there was a significant difference within a trial, there was no significant difference between the trials. Rectal temperature was significantly increased over time during exercise (P < 0.01).The results show that menstrual cycle phase and beverage type had significant effect on rectal temperature during exercise (P < 0.01). RER significantly changed over time during exercise (P < 0.01). Furthermore, there was no significant effect of menstrual cycle phase or beverage type on RPE data (data not shown).The total amount of CHO consumed in the CHO trials (FC and LC) was 40 g. Plasma glucose and free fatty acid data are shown in Figure Table P < 0.05) and time (P < 0.01). Blood glucose at 90 min in the LA was significantly lower than that in the LC (P < 0.05), and a lower trend compared with that in the FC (P < 0.068).There was no trial × time interaction with respect to change in glucose; however, there was a main effect in trial (P < 0.05), a main effect in time (P < 0.01), and a trend in trial (P = 0.082) in serum free fatty acid. The concentration at POST in the LA was significantly higher compared with that in the FC (P < 0.01).There was a trial × time interaction , and a main effect in trial (P < 0.01) and time in leukocyte concentration (P < 0.01). Leukocyte concentration at 90 min in the LA was significantly higher than that in the FC (P < 0.01), and that at POST in the LA were significantly higher than those in the FA (P < 0.05), LC (P < 0.01), and FC (P < 0.01). Leukocyte concentrations at 90 min in the LA was higher than those in the FA (P = 0.073) and LC (P = 0.098). Moreover, leukocyte concentrations at POST in the FA were significantly higher than those in the FC (P < 0.01). Pearson’s correlation coefficient between serum free fatty acid concentration and leukocyte concentration was determined, and a significant positive correlation was found .Serum cytokine concentration data are shown in Table There was a trial × time interaction ( P = 0.07 and LC (P < 0.05) and POST (P < 0.01) from PRE in 3 trials . Moreover, the concentrations at POST in these 3 trials were significantly higher (P < 0.01) than those at 30 min. In the FC trial, the concentration at POST was significantly higher compared with that at PRE and 30 min. However, there were no significant differences between the trials at any time point. Serum MPO concentrations were highest at POST in all trials. There was a main effect in time (P < 0.01), but no trial × time interaction or main effect in trial. Serum calprotectin concentrations were significantly higher (P < 0.01) at POST from PRE in all 4 trials. The concentrations at POST in the FC (P < 0.05), LA (P < 0.01), and LC (P < 0.05) were higher than those at 30 min. Moreover, the concentrations at 90 min in the FC (P < 0.01), LA (P < 0.01), and LC (P < 0.05) were significantly higher than those at PRE.Serum IL-6 concentrations were significantly higher at 90 min  required to complete POST was 675  in the FA, 681  in the LA, 692  in the FC, and 678  in the LC, respectively. There were no significant differences between trials. Subjects indicated an RPE of 20 for all trials at POST.The first purpose of the present study was to investigate the effect of menstrual cycle phase on immune response to exercise. The results showed that menstrual cycle phase affected leukocyte concentrations in response to prolonged exercise; leukocyte mobilization in the luteal phase was larger compared to that in the follicular phase at 90 min of cycling and at POST while ingesting a placebo beverage. However, there was no significant effect of menstrual cycle phase on serum cytokine concentrations. Thus, these results partially supported our hypothesis.The second purpose of this study was to investigate whether CHO ingestion has an effect on immune response to prolonged exercise. The results showed that ingesting a CHO beverage attenuated leukocyte mobilization and eliminated the differences between menstrual cycle phases observed in the placebo beverage trials. However, there was no effect of CHO ingestion on serum cytokine concentrations, which partially supported our hypothesis.A previous study showed that there was no significant difference in total leukocyte concentration between menstrual cycle phases after 90 min of cycling exercise . HoweverIt is well known that there is a substantial increase in leukocyte concentration (mainly neutrophils) during endurance exercise, and this increase depends on the intensity and duration of exercise . It has Some studies have found that menstrual cycle phase does indeed affect hormonal and metabolic responses to exercise ,37, partPrevious studies on male subjects have consistently reported that ingesting CHO during exercise suppresses the rise in circulating neutrophils, most likely by reducing the secretion of stress hormones that regulate neutrophil mobilization by maintaining high blood glucose -15. The Muscle-derived IL-6 appears to be at least partly responsible for the elevated secretion of cortisol during endurance exercise. Infusion of recombinant human IL-6 into resting humans to mimic the exercise-induced plasma concentrations of IL-6 has been shown to increase plasma cortisol in a similar manner ,39. In tMost ,17,21,40Elevated serum MPO concentration after exercise likely reflects neutrophil degranulation because MPO is contained in azurophilic granules within neutrophils. MPO is an important contributor to neutrophil microbicidal activity. Serum MPO concentration depends on exercise intensity  and tempCalprotectin is secreted from monocytes and neutrophils in response to a variety of inflammatory conditions . In the One of the limitations of this study is the absence of cortisol, growth hormone, catecholamine, and muscle glycogen measurements during exercise, which would have allowed a better understanding of the relationships among hormone concentrations, glucose availability, and differential leukocyte concentrations. Even though we found that menstrual cycle phase significantly affected leukocyte concentration, we cannot rule out the possibility that the small cohort of subjects used in this study might have had a negative impact on some of the other measurements, rendering them non-significant. The small number of subjects may not have provided adequate statistical power to detect real, but relatively small, differences in some of the measured variables.Menstrual cycle phase affected circulating leukocyte concentrations during endurance exercise while ingesting a placebo. The degree of leukocyte mobilization was greater in the luteal phase compared with the follicular phase. Ingestion of the CHO beverage eliminated the effect of menstrual cycle phase on leukocyte concentration, which may be explained by the effect of sex hormones on substrate utilization. However, there was no effect of menstrual cycle phase on cytokines during exercise.The results of this study demonstrate that menstrual cycle changes do alter leukocyte concentration during exercise when subjects consume CHO beverage. Indeed, as the placebo trials progressed, differences became more pronounced, indicating that as endogenous CHO reserves were depleted the effect of menstrual cycle changes become more evident. This was further supported by the absences of difference in immune response between the FC and LC trials.In women undergoing endurance training for recreational purposes, prolonged exercise in the luteal phase may lead to larger immune disturbances compared to the follicular phase if they ingest water alone during the duration of the exercise. Therefore, we recommend ingesting carbohydrate beverages to attenuate immune disturbances especially in the luteal phase, even though they are unlikely to enhance test performance. However, the total subject number is small and does not constitute a representative sample, and the results need further validation using larger cohorts.CHO: Carbohydrate; POST: high intensity time trial performance test; Tc: core temperature; RER: Respiratory exchange rate; HR: Heart rate; RPE: Rating of perceived exertion; FA: Follicular phase placebo trial; FC: Follicular phase carbohydrate trial; LA: Luteal phase placebo trial; LC: Luteal phase carbohydrate trial; PRE: Before exercise.At the time of writing this article, one of the authors was employed at Asahi Soft Drinks Company, which manufactured and supplied the beverage for this study.HH, TI, KS, and MH conceived and designed the study. HH, TI, and HH performed the experiments. KS performed blood sampling. HH, TI, and HH carried out immunoassay. HH analyzed the data and wrote the manuscript. All authors read and approved the final manuscript.


TW‐37 (T), are senolytic. Like D and Q, N is senolytic in some, but not all types of senescent cells: N reduced viability of senescent human umbilical vein epithelial cells (HUVECs), IMR90 human lung fibroblasts, and murine embryonic fibroblasts (MEFs), but not human primary preadipocytes, consistent with our previous finding that Bcl‐xl siRNA is senolytic in HUVECs, but not preadipocytes. In contrast, T had little senolytic activity. N targets Bcl‐2, Bcl‐xl, and Bcl‐w, while T targets Bcl‐2, Bcl‐xl, and Mcl‐1. The combination of Bcl‐2, Bcl‐xl, and Bcl‐w siRNAs was senolytic in HUVECs and IMR90 cells, while combination of Bcl‐2, Bcl‐xl, and Mcl‐1 siRNAs was not. Susceptibility to N correlated with patterns of Bcl‐2 family member proteins in different types of human senescent cells, as has been found in predicting response of cancers to N. Thus, N is senolytic and acts in a potentially predictable cell type‐restricted manner. The hypothesis‐driven, bioinformatics‐based approach we used to discover that dasatinib (D) and quercetin (Q) are senolytic can be extended to increase the repertoire of senolytic drugs, including additional cell type‐specific senolytic agents.Clearing senescent cells extends healthspan in mice. Using a hypothesis‐driven bioinformatics‐based approach, we recently identified pro‐survival pathways in human senescent cells that contribute to their resistance to apoptosis. This led to identification of dasatinib (D) and quercetin (Q) as senolytics, agents that target some of these pathways and induce apoptosis preferentially in senescent cells. Among other pro‐survival regulators identified was Bcl‐xl. Here, we tested whether the Bcl‐2 family inhibitors, navitoclax (N) and  MEFs were induced to become senescent by passaging under high oxygen (20%) conditions as in  activity was assayed as previously described . Cells were transduced with siRNA using Lipofectamine and harvested 24 h after transduction. RT–PCR methods are in our publications  and one of our publications , DK50456 (JLK: Adipocyte Subcore), AG043376 (PDR&LJN), the Noaber, Ellison, the Ted Nash and Glenn Foundations, the American Federation for Aging Research, the Connor Group, and the Natural Science Foundation of China (HMD: grant 81572948).YZ, TT, TP, NG, LJN, PDR, and JLK have potential financial interest in this research. The research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic and the Scripps Research Institute (TSRI) conflict of interest policies.Fig. S1 Representative TUNEL assay photographs in senescent and nonsenescent HUVECs and IMR90 cells.Fig. S2 Confirmation of siRNA‐induced decreases in target mRNAs by RT–PCR.Fig. S3 Bcl‐2 family member proteins in senescent vs. nonsenescent Ercc1‐deficient MEFs.Fig. S4–6 Densitometric analyses of Bcl‐2 family member proteins in senescent vs. nonsenescent in HUVECs, IMR90 cells, and primary human preadipocytes, respectively.Click here for additional data file.Table S1 siRNAs and primers.Click here for additional data file.Data S1 Experimental procedures.Click here for additional data file. Click here for additional data file.


Antithrombin III (AT III) in cerebrospinal fluid (CSF) has been suggested to have high specificity and sensitivity in separating primary central nervous system (CNS) lymphoma from other neurological conditions. We measured with ELISA CSF and serum AT III and albumin levels in 12 lymphoma patients with CNS involvement, 30 lymphoma patients without CNS involvement, and 41 patients with non-neoplastic neurological diseases. AT III immunostaining was also carried out, in lymphoma patients. Both CSF AT III and albumin levels were higher in lymphoma patients with CNS involvement. AT III/albumin ratio in CSF was the most sensitive and specific measure for diagnosis. Lowest it was in patients with known CNS lymphoma. Serum AT III levels were lower both in CNS lymphoma and systemic lymphoma. CSF AT III levels were shown to be higher in lymphoma patients with CNS involvement, when AT III/albumin ratios were lower. This was probably a result of lowered serum AT III levels, indicating that high levels of AT III in CSF might reflect only leakage of the blood–brain barrier. Thus, AT III fails to be a specific marker for diagnosis of lymphoma CNS involvement. About 2 % of all systemic lymphomas are primary central nervous system (CNS) lymphomas (PCNSLs). These are rapidly progressing diseases with often fatal outcome despite the use of high-dose methotrexate-containing treatment regimens . UsuallyIn addition to the above, lymphomas presenting primarily as systemic disease may recur in the CNS. The prognosis in cases of CNS relapse is dismal. At least 5 % of patients with diffuse large B cell lymphoma (DLBCL) will develop CNS involvement if appropriate prophylactic therapy is not given . Early CAntithrombin III (AT III) is a protein produced by hepatocytes, and its physiological role is to play a part in the normal anticoagulation system –6. AT IIIt was suggested in a paper by Roy et al. that AT III in CSF is a specific biomarker of PCNSL, and more accurate in identification of CNS lymphoma than CSF cytology , 8. The The aim of the present study was to evaluate whether or not CSF AT III is an independent biomarker of lymphoma CNS lesions or a marker of blood–brain barrier leakage, and whether it could be used to find patients with systemic lymphoma and subclinical CNS disease. The biology of AT III was also explored to see if it is present in endothelial and/or lymphoma cells, to discover the possible origin of CSF AT III.The lymphoma study samples were taken from patients treated at Oulu University Hospital during 2009–2012 after receiving written informed consent in each case. All patients suffered from histologically confirmed lymphoma. The clinical data was collected carefully from hospital records. The principles of Declaration of Helsinki were followed in this study. Ethical resolution was applied from the Local Ethics Committee of the Northern Ostrobothnia Hospital District and from National Supervisory Authority for Welfare and Health . Valvira permission number was 6622/05.01.00.06/2010.Patient details are presented in Table As a control group, 42 CSF samples were collected from patients with non-neoplastic neurological diseases . These were 19 cases with clinically, genetically, or autopsy-confirmed Alzheimer’s disease, 6 patients with multiple sclerosis (MS) diagnosed according to McDonald’s 2005 criteria  and alsoAntithrombin III concentrations in CSF were detected by using an ELISA. Commercial assay kits  were used. The principles of this assay have been described previously [× g for 10 min. AT III concentrations were measured by ELISA  according to the manufacturer’s instructions. In this assay, standards and samples are competed with a biotinylated AT III sandwiched by the immobilized antibody and streptavidin-peroxidase conjugate.Blood was collected in siliconized 3.5-ml glass containers containing one part serum gel solution. Serum was prepared from blood by centrifugation at 1500 n = 38; brain, n = 3; ventricle, n = 1). All tissue samples had been surgically removed from patients during normal diagnostic procedures and used for the study later. Immunostaining was performed as described previously [For immunohistochemical analyses, 42 tissue samples were available. Most of them were lymph node biopsy samples, but brain and ventricle biopsy samples were also present . Continuous variables with normal distributions were compared by using independent samples The median age of the patients with lymphoma  was 62.5. The non-lymphoma patients  were somewhat younger (median age 52).p = 0.002, in Mann–Whitney U test). The median albumin concentration in the CSF of patients with lymphoma was 243 mg/l (52.5–9727), and it was 193 mg/l (105.5–1099) in the non-lymphoma group. This difference was not statistically significant (p = 0.219). Concentrations of CSF AT III were also compared in different patient groups . Concentrations of CSF AT III were also compared in patients with CNS lymphoma (including PCNSL patients and patients with CNS-relapsed systemic lymphoma) versus those with non-neoplastic neurological diseases. In this comparison, in patients with CNS lymphoma, CSF AT III concentrations remained still higher (p = 0.009), as seen in Fig. p = 0.006). We compared CSF AT III concentrations in patients with MS disease with those in lymphoma patients with CNS involvement (both primary and secondary), and the concentrations were rather similar (p = 0.167). When comparing CSF AT III concentrations between groups of lymphoma patients with CNS involvement (both primary and secondary) versus lymphoma patients with systemic disease only, no differences were found (p = 0.126).The median CSF AT III concentration was found to be 1.47 μg/ml (range 0.49–6.91) in the lymphoma patients, and it was 1.08 μg/ml (0.50–4.05) in the group of patients with non-neoplastic neurological disorders Table . The difups Fig. . When cop < 0.001).The AT III/ albumin ratio was calculated as reported previously . When cop < 0.001). The mean serum albumin level was 40.94 g/l (26–49) in patients with lymphoma and 44.55 g/l (37–49) in the non-lymphoma group. This difference was also statistically significant (p = 0.029).Antithrombin III and albumin concentrations were also assayed in serum, as shown in Table p = 0.036 and p = 0.037, Fig. The amount of immunoreactive protein staining was analyzed in three separate groups; tumor cytoplasm, tumor nuclear membrane, and tumor vasculature. In Fig. p = 0.009), CSF AT III alone had AUC 0.791 (p = 0.002), and CSF albumin had AUC 0.839 (p < 0.001)  curves of CNS lymphoma patients, including both primary and secondary CNS lymphomas, versus patients with non-neoplastic neurological disorders. All diagnostic tests yielded somewhat similar results: CSF AT III/albumin ratio had area under curve (AUC) 0.250 (p = 0.167). Taken together, these findings indicate that CSF AT III might reflect only a blood–brain barrier leakage, and it may not be an independent marker of CNS lymphoma.In the present study, we found that CSF AT III concentrations were higher in patients with CNS lymphoma compared with patients with non-neoplastic neurological diseases. However, the values overlapped with each other, indicating that the specificity of CSF AT III measurement for CNS lymphoma is not valid for clinical use. Moreover, high CSF albumin levels had better specificity for CNS lymphoma than did CSF AT III levels. The most specific test to separate groups with lymphoma CNS involvement from other patient groups was the CSF AT III/ albumin ratio. Surprisingly, low ratios predicted the existence of primary or secondary CNS lymphoma. To study further the reason for these low ratio levels, we also measured the serum AT III concentrations. We found low serum AT III levels in lymphoma patients, which might explain the low CSF AT III/ albumin ratio in these patients. In MS in which the blood–brain barrier is probably leaking , the conAntithrombin III is a physiological anticoagulative protein produced by hepatocytes . It is iThere have been several studies on cancer patients in which changes in serum AT III levels have been investigated, with variable results , 18, 19.In our study, we detected lowered serum AT III concentrations in lymphoma patients, which may be caused by either increased use or decreased production . We alsop = 0.006). It has been previously suggested that CSF AT III concentrations could allow differentiation of CNS lymphoma from other malignant CNS conditions [p = 0.002) and albumin  was not clear, indicating that AT III is not a novel biomarker that could be used to select patients with lymphoma from those with other diseases.In a previous study by Roy et al., a mean CSF AT III level of 3.1 μg/ml was reported in CNS lymphoma patients and a mean value of 0.53 μg/ml in control patients without lymphoma . In the nditions . This clThe patients in this study were treated with CNS prophylactic therapy due to a high risk of CNS relapse, and there was also a possibility that some of them primarily had subclinical CNS disease. This might have influenced the results concerning AT III concentrations in the CSF. The median age of the patients was also higher than in the non-lymphoma patients, which might have had an effect on the results. There was no evaluation of neurodegenerative diseases in the lymphoma patients. Serum samples were not available from the patients with neurological conditions, but it is not likely that this would have had an impact on the results.The difference between the present study and the previous ones , 8 is thIn summary, in the present study, we found that elevated CSF AT III levels in patients with CNS involvement of lymphoma reflect the magnitude of blood–brain barrier disruption and AT III is not an independent biomarker of lymphoma CNS involvement.


There is now compelling evidence for a link between enteric microbiota and brain function. The ingestion of probiotics modulates the processing of information that is strongly linked to anxiety and depression, and influences the neuroendocrine stress response. We have recently demonstrated that prebiotics (soluble fibres that augment the growth of indigenous microbiota) have significant neurobiological effects in rats, but their action in humans has not been reported.The present study explored the effects of two prebiotics on the secretion of the stress hormone, cortisol and emotional processing in healthy volunteers.Forty-five healthy volunteers received one of two prebiotics  or a placebo  daily for 3 weeks. The salivary cortisol awakening response was sampled before and after prebiotic/placebo administration. On the final day of treatment, participants completed a computerised task battery assessing the processing of emotionally salient information.The salivary cortisol awakening response was significantly lower after B-GOS intake compared with placebo. Participants also showed decreased attentional vigilance to negative versus positive information in a dot-probe task after B-GOS compared to placebo intake. No effects were found after the administration of FOS.The suppression of the neuroendocrine stress response and the increase in the processing of positive versus negative attentional vigilance in subjects supplemented with B-GOS are consistent with previous findings of endocrine and anxiolytic effects of microbiota proliferation. Further studies are therefore needed to test the utility of B-GOS supplementation in the treatment of stress-related disorders. Lactobacilli and Bifidobacteria—also have neurotropic effects . Raised levels of circulating corticosterone in germ-free rodents  on the processing of emotional information and hypothalamic-pituitary-adrenal (HPA) axis activity in healthy human volunteers.Forty-five volunteers  recruited through online and poster adverts completed the study. Inclusion criteria were aged 18–45 years, fluent English speaker and BMI range 18–25. Exclusion criteria were previous or current neurological, psychiatric, gastrointestinal or endocrine disorders, or other relevant medical history; current or recent (<3 months) regular medication use; previous or current substance/alcohol dependence or abuse within the last 3 months; regular tobacco use (>5 cigarettes/day); and participation in research studies involving medication intake (within 3 months) or prior completion of the Emotional Test Battery (ETB). To ensure that the enteric environment was consistent in all volunteers, additional exclusion criteria were: no antibiotic use 3 months prior to the study, no regular use of pre- and probiotics (and within 3 months prior to the study) and no vegan diets. Finally, participants were asked to adhere to their regular diets and avoid supplements or special diets. No significant dietary variations were noted.Participants were assessed with the Structured Clinical Interview for DSM-IV  or a placebo . The use of maltodextrin as a placebo compound in prebiotic trials is well established  and on the final day of prebiotic/placebo administration (day 21), using the salivary cortisol awakening response , participants completed a validated computerised test battery assessing the processing of emotional stimuli . Participants were instructed to indicate the number of stars as quickly and accurately as possible using two labelled keys. A key press terminated the probe presentation and trial. There were 180 trials in total , and emotional words were presented at the top and the bottom location with equal frequency. Masked and unmasked trials were presented in random order. Reaction time and accuracy scores were recorded, and attentional vigilance scores were calculated for each participant by subtracting the reaction time from trials when probes appeared in the same position as the emotional word  from those trials when probes appeared in the opposite position to the emotional word .In the facial expression recognition task (FERT), the perception of six basic emotions  or a neutral expression  or agreeable (N = 30) personality characteristics  were square root transformed and analysed in a mixed design ANOVA with time point of sampling  and day of sampling (pre- vs. post-treatment) as repeated-measures variables and prebiotic treatment group  as a between-subjects variable. Raw cortisol values are presented for clarity. The behavioural outcome variables of the ETB were also analysed with mixed design ANOVAs, with prebiotic treatment group as between-subjects factor and emotion and task condition as within-subjects factors. Significant interactions were followed up using main effects analyses. Greenhouse-Geisser corrections were used where assumptions of sphericity were not met.There were no significant differences between groups for age, trait measures of anxiety, stress reactivity, neuroticism or cognitive status as assessed by digit span .Of the 23 female participants, 13 used hormonal methods of contraception. Menstrual cycle phase was reported by 16 females, and an additional two female participants reported no or very infrequent menses due to hormonal contraceptive use—these were coded as a separate group. Cycle phase was analysed according to the following phases . The effect of hormonal contraceptive on the first sample of salivary cortisol after waking showed a trend for lower levels in females taking contraceptives compared to those who were not (mean (SD) = 8.20 (3.42) vs. mean (SD) = 10.65 (4.37), F = 3.74, p = 0.07); however, this difference was stable across days of testing and treatment groups . The effect of hormonal contraceptives on cortisol AUC-g was not significant  = 3.01, p > 0.1), and there were no significant interactions with testing day or treatment group .There was no significant difference in the number of females who took hormonal contraceptives between the groups . Due to insufficient power, the effects of menstrual phase on cortisol or attention were not tested with ANOVAs.The number of participants who were in a particular cycle phase at the time of testing did not differ between the groups  = 1.08, n.s.; day 21: main effect of group F = 4.20, p < 0.05, followed up with Sidak-corrected contrasts: placebo vs. GOS, p = 0.02, all others p > 0.1). Main effects analyses of the day × group × time ANOVA confirmed that cortisol levels were increased post-waking 15, 30, 45 and 60 min after waking  = 58.61, p < 0.001, planned follow-up contrasts all significant at p < 0.001). The main effects of day of sampling and treatment group were not significant (p > 0.1). Gender was not entered as a factor of interest due to insufficient power.Salivary cortisol did not differ significantly between groups at baseline but was significantly lower following B-GOS compared with placebo Fig. . This waF = 3.52, p = 0.039], followed up with separate group ANOVAs for pre/day 0  and post/day 21 ).The lowered CAR in the B-GOS compared to the placebo group on day 21 of supplement administration was also confirmed when analysing area under the curve with respect to ground  = 3.14, p = 0.05]). As can be seen in Fig. F = 4.29, p = 0.02; masked: F = 0.85, p > 0.1). Follow-up analyses with separate ANOVAs for prebiotic group compared with placebo in the unmasked condition confirmed this effect as driven by increased positive versus negative vigilance after B-GOS compared to placebo, while the FOS group did not perform differently to placebo  = 6.94, p = 0.014, FOS vs. placebo: valence × group F = 3.20, n.s.).There was a significant group × emotion × masking condition interaction in the visual dot-probe task  = 1.71, n.s., emotion × group interaction F = 0.67, n.s.). Analysis of reaction time data revealed no significant interaction between group and emotion  = 0.53, n.s.; emotion × group interaction F = 1.10, n.s.).There were no significant effects of prebiotic treatment on measures of accuracy  = 12.82, p < 0.01) and in the emotional word recognition task  = 23.34, p < 0.001); however, there was no significant main effect of prebiotic treatment group  = 0.80, p > 0.1) and the relative speeding for positive words did not differ between groups  = 0.35, p > 0.1). Positive words were also remembered more often than negative words in both the surprise recall task , negative = 5.70 (2.29); F = 16.16, p < 0.001) and in the recognition task , negative words = 22.36 (SD = 3.88); F = 53.54, p < 0.001), but these effect did not differ between groups (p > 0.1).Participants responded faster to positive  compared to negative  self-referential personality words in the emotional categorisation task .To test the hypothesis that cortisol levels were associated with changes in attentional dot-probe performance in the B-GOS group, we correlated difference scores of positive versus negative reaction times in the unmasked condition with absolute cortisol levels upon waking on the day of testing and with the difference in pre- versus post-prebiotics cortisol values (day 0–day 21). There were no associations of cortisol with attentional performance , we were unable to confirm a moderating effect of cortisol reactivity on behaviour. Although there is strong evidence for a role of the gut microbiota in the regulation of the HPA axis (see Dinan and Cryan While initial results of the B-GOS prebiotic on the cortisol awakening response are promising, we had insufficient power to investigate gender effects, which have previously been reported (Pruessner et al. We found a selective modulation of attention to emotional stimuli and HPA axis reactivity following B-GOS prebiotic supplement in healthy participants, supporting a key role for gut microbiota in the regulation of affective function. This, to our knowledge, is the first study extending findings of the central effects of probiotics to behavioural effects of prebiotics in humans.


We used plasma metabolite analysis to estimate variation in fattening rate in four neotropical migratory songbirds utilising riparian habitat at a dam-impacted stopover in British Columbia, Canada. Our study suggests that although hydroelectric dam operations influence water levels this does not significantly impact fattening rates of birds using these habitats. Riparian habitat makes up a small fraction of the landscape but provides important stopover habitat for migratory birds. Hydroelectric dam operations cause fluctuations in water levels that can change the amount or quality of riparian habitat, which in turn might affect potential fattening rates of migrant birds. Here we used plasma metabolite analysis to estimate variation in fattening rate in relationship to variable water levels associated with reservoir management in four species of neotropical migratory songbirds using riparian habitat at a dam-impacted stopover site in Revelstoke, British Columbia, Canada. Residual plasma triglyceride, our measure of estimated fattening rate, varied systematically with time of day and Julian date and varied consistently among species, but did not vary with age or sex. Controlling for potentially confounding variables, we found no inter-annual variation in estimated fattening rate, even though there were marked differences in water levels among years. Likewise, there was no relationship between daily variation in water levels and estimated fattening rate. Data on feather isotopes (δD), indicative of migratory origin, did not add explanatory power to our models. There was inter-annual variation in plasma glycerol and β-hydroxybutyrate levels and significant, though weak, relationships between these metabolites and water level (higher metabolite levels when drier) that might indicate effects on ‘body condition’ independent of fattening rate. Our study suggests that, at present, although hydroelectric dam operations influence water levels in the Arrows Lake Reservoir and adjacent riparian habitats, this does not significantly impact fattening rates of migratory passerines using these habitats. Conservation of migratory birds requires research across the entire avian annual cycle to inform potential management and habitat conservation . RipariaHydroelectric development has contributed to the loss of riparian habitat in the Pacific Northwest; 16 major dams have created a reservoir system that has led to the loss of >87% of the riparian habitat within the Canadian portion of the Columbia River Basin . HydroelSeveral recent studies have investigated the impact dams might have on local and migrant avifauna using the riparian habitats in the drawdown zones . Green eHere we take a physiological approach, estimating the fattening rates of neotropical migrants at a stopover site using plasma metabolite analysis. Plasma metabolite analysis uses residual plasma triglyceride levels (controlling for body mass and other covariates) to estimate rates of fattening or refuelling; high levels of plasma triglyceride represent high fattening rates  and freeGeothlypis trichas (COYE); Orange-crowned Warbler, Oreothlypis celata (OCWA); Wilson's Warbler, Cardellina pusilla (WIWA); and Yellow Warbler, Setophaga petechia (YWAR)] using riparian habitat at a dam-impacted stopover site in Revelstoke, British Columbia. The specific goals of this study were as follows: (i) to quantify water levels at our study site and to demonstrate marked variation in water levels, both among and within years, associated with reservoir operations; (ii) to confirm systematic relationships between residual plasma triglyceride, time of day and Julian date consistent with this, providing an index of estimated fattening rate; (iii) to determine whether residual plasma triglyceride (estimated fattening rate) and glycerol or β-hydroxybutyrate  vary annually, reflective of inter-annual variation in water levels, and with feather stable-hydrogen-isotope values, reflecting the geographical origin (breeding latitude) of migratory birds  toPopulus spp.) with a diverse understory, surrounded by willow scrub, surrounded by shrub-savannah, grasslands, wetlands and the Columbia river  from 15 July to 30 September 2008, 2009 and 2010. Machete Island is a semi-wooded riparian habitat of about 30 ha, composed of deciduous forest dominated by cottonwood . Birds were blood sampled from the left brachial artery with a 26.5 gauge needle, and blood was collected into heparinized micro-capillary tubes (50–100 μl). All birds were sampled within 30 min of extraction from the mist nets. The mean handling time between extraction from the net and blood sampling was 21.6 ± 10.7 min . After bleeding was complete, birds were banded with aluminum USFW bands, age and sex were identified  but did vary with Julian date , indicating that the number of birds increased as migration proceeded.We captured and blood sampled 107 COYE, 76 YWAR, 62 OCWA and 51 WIWA in 2008; 165 COYE, 87 YWAR, 102 OCWA and 43 WIWA in 2009; and 74 COYE, 56 YWAR, 50 OCWA and 71 WIWA in 2010. All birds were captured using passive mist netting . All assays were run in 400 μl, flat-bottom 96-weIl microplates  and read with a microplate spectrophotometer (Biotec 340EL or Powerwave X 340), as previously described (e.g. n = 13 assays), 6.8% (n = 15) and 5.2% (n = 7) in 2008, 2009 and 2010, respectively. The overall coefficient of variation for all years was 6.7%, but there was some evidence of systematic variation in our standard curve among years. Therefore, in order to compare plasma triglyceride values across years we standardized data for 2008 and 2009 against the slope of the standard curve relating absorbance to concentration for 2010.Blood samples were stored at 4°C for up to 2 h before being centrifuged for 6 min at 10 0002O, TEA buffer, NAD+/INT, Diaphorase suspension), and the plate was read at 2 min to obtain a baseline reading. After adding 2 μl of the active reagent (3-hydroxybutyrate dehydrogenase suspension), subsequent readings were taken every 30 s for 30 min. The rate of change in β-hydroxybutyrate was calculated as the difference in absorbance between 2 and 15 min, and concentrations were determined from a standard curve. The intra-year coefficient of variation for 2008 was 12.2% (n = 9), for 2009 15.8% (n = 4) and for 2010 5.2% (n = 11). The inter-year coefficient of variation for β-hydroxybutyrate assays was 5.8% across all three years (with no evidence of systematic bias among years for β-hydroxybutyrate).β-hydroxybutyrate was measured using a D-3-Hydroxybutyric acid kit .Feathers were washed in 2:1 chloroform:methanol solution for 24 h, drained, and then air-dried in a fume hood for an additional 24 h to remove excess solvent. Feather samples (0.3–0.5 mg) were placed in small silver capsules  and sent to the University of California Davis Stable Isotope Facility in California, USA. Samples were analysed using a Hekatech HT Oxygen Analyzer interfaced to a PDZ Europa 20:20 isotope ratio mass spectrometer after allowing the samples to equilibrate with laboratory standards for at least 96 h, as described by Statistical analyses were all performed in SAS statistical software . In general, we analysed each species separately as an independent test of each hypothesis, due to concerns about comparing plasma metabolite levels among species . EstimatP > 0.05 in all cases), glycerol  or β-hydroxybutyrate  in any species. We therefore pooled data by age and sex, and included all individuals of unknown age and sex, in all subsequent analyses.Our primary interest was to determine whether plasma metabolites varied among years, potentially reflecting variation in water levels (see Results), and whether feather δD values (reflecting the breeding latitude of birds) influenced this relationship. Firstly, we compared variation in plasma triglyceride, glycerol and β-hydroxybutyrate by age and sex classes within each species, pooling all data and controlling for year as a main effect and mass, handling time, time of day, Julian date and bird density as covariates. There was no significant effect of age, sex or the age × sex interaction for plasma triglyceride , with plasma triglyceride, glycerol and β-hydroxybutyrate as the dependent variables, year as a main effect, and feather δD values, body mass, handling time, time of day, Julian date and bird density as covariates, for each species separately.Thirdly, we repeated the multivariate analysis after combining the data from all four species in order to assess whether plasma metabolite levels varied across species, including year, species and year × species as main effects, and the same covariates.Finally, we conducted three multivariate analyses, with plasma triglyceride, glycerol and β-hydroxybutyrate as the dependent variables, water level as the main effect, species as a factor, and body mass, handling time, time of day, Julian date and bird density as covariates.P > 0.05), and we report statistics for the final reduced model. We calculated water level for the day of capture [water level = elevation of the banding station (438.7 m) minus current reservoir elevation] such that positive values indicate that the site is inundated by water. When the water reached this elevation, the lowest mist-net lines were flooded, so we used this value as the elevation of the banding station. Reservoir water elevation data are collected at Fauquier, Arrow Lake .For each analysis, we initially ran the full model but then eliminated non-significant terms (10 (+1) values corrected for mass, unless otherwise noted.All values are expressed as the lsmean ± SE, unless otherwise noted. Given values for triglyceride, glycerol and β-hydroxybutyrate concentration are residual logThere was marked annual and seasonal variation in water levels during the study period Fig. . Water la priori that there were species differences in body mass, so we analysed inter-annual variation in body mass for each species separately. There was a significant effect of year on body mass in WIWA  and YWAR , although the patterns differed in the two species. In WIWA, birds were heavier (P < 0.01) in 2008 (7.82 ± 0.14 g) compared with 2009 (7.55 ± 0.16 g) and 2010 (7.65 ± 0.11 g). In YWAR, birds were lighter in 2010 (9.08 ± 0.14 g) compared with 2008 (9.36 ± 0.13 g) and 2009 (9.25 ± 0.12 g). In contrast, mean body mass did not differ among years in COYE  or OCWA .We knew P < 0.025 in all cases), but not in COYE . Body mass increased with Julian date in OCWA  and WIWA , but not in COYE or YWAR (P > 0.05 in both cases). Additionally, there was no effect of year or a time × year interaction for any species , and time of day explained only 5.0, 15 and 5% of the total variation in body mass in OCWA, WIWA and YWAR, respectively. There was no effect of year or a Julian date × year interaction for OCWA, WIWA and YWAR (P > 0.20). In COYE, there was a significant Julian date × year interaction ; mass varied with date in 2008 , but not in 2009 or 2010 (P > 0.20).Body mass increased with time of day in OCWA, WIWA and YWAR (10 + 1 lsmeans ± SE) for each species in 2008–2010, controlling for feather δD value, body mass, handling time, time of day, Julian date and bird density , are given in Table r = −0.19, n = 621, P < 0.001), but plasma triglyceride was not correlated with plasma glycerol .Mean residual plasma metabolite concentrations . Julian date and time of day were the only covariates retained in all models for plasma triglyceride ; plasma triglyceride increased with time of day , i.e. the seasonal increase in plasma triglyceride was similar in all years. Body mass was retained in the model for WIWA only . Feather δD value, handling time and bird density were not significant in any models (P > 0.15) for any species. The lack of effect of feather δD was not due to lack of variation in isotope signatures, which was in fact large, i.e. mean δD for COYE, −154.7 , OCWA −162.9 , WIWA, −143.9  and YWAR, −158.3 . Feather δD varied with Julian date in all four species (P < 0.025). However, the slope and strength of the relationship varied among species; feather δD increased with date in COYE  and, more markedly, in WIWA , but decreased with date in OCWA  and YWAR .Plasma triglyceride was independent of year in reduced models for all four species  in all four species, whereas plasma β-hydroxybutyrate was higher in 2009 compared with both 2008 and 2010  and OCWA (P < 0.05), but not for WIWA or YWAR, or for β-hydroxybutyrate in any species. Time of day and handling time were significant for plasma glycerol in YWAR only , and time of day was significant for plasma β-hydroxybutyrate in WIWA only (P < 0.001); Julian day was significant in the model for β-hydroxybutyrate in OCWA only (P < 0.001).For both plasma glycerol and β-hydroxybutyrate, there was a highly significant effect of year , being higher in WIWA compared with all other species  and Julian date (P < 0.001). There was also an effect of species on plasma glycerol , but here glycerol was higher in COYE than in all other species . In contrast, there was no difference in plasma β-hydroxybutyrate levels among species .Estimated fattening rate varied among species  and there was no species × water level interaction (P > 0.70). There was an effect of species . In contrast, plasma glycerol varied with water level  and species , but there was no species × water level interaction (P > 0.60). Finally, for β-hydroxybutyrate there was an effect of water level , no effect of species , but there was a species × water level interaction . Water level affected β-hydroxybutyrate in COYE, OCWA and YWAR , but not in WIWA (P > 0.90). In both cases, residual plasma metabolites levels increased with decreasing water levels (i.e. with drier conditions), and this relationship was stronger for glycerol  whether plasma triglyceride levels, as a measure of estimated fattening rate, varied among years with very different patterns of variation in water levels, or with daily variation in water levels, in reservoir-impacted riparian habitat; and (ii) whether feather δD values [reflecting variation in the geographical origin (breeding latitude) of migratory birds] influenced this relationship. We confirmed that: (i) plasma triglyceride varied systematically with time of day and Julian date; (ii) estimated fattening rate varied among species; but (iii) estimated fattening rate did not vary with age or sex, all of which confirms results of previous studies (see below) and supports the idea that plasma triglyceride does provide an index of fattening rate. However, we found no inter-annual variation in estimated fattening rate, even though there were marked differences in water levels among years. Likewise, there was no relationship between daily water levels and estimated fattening rate. Furthermore, data on feather δD values did not add to the explanatory power of models in any of our analyses. Finally, we did find inter-annual variation in plasma glycerol and β-hydroxybutyrate levels and significant, though weak, relationships between these metabolites and water level (higher metabolite levels when drier).−1 for American Redstarts and 0.98% lean body mass h−1 for Wilson's Warblers (−1) and above the estimated 0.24–0.26% lean body mass h−1 required to cover overnight energy use (−1) were within the range reported for refuelling migratory birds in other studies , capture rates are >20 times higher during the peak of the migration period (late August) than at the end of July  related to plasma triglyceride levels in two of four species in our study, and the pattern of variation in body mass among years was not consistent between or within species. Individuals tended to be heavier in 2008 than in subsequent years in WIWA and YWAR, but this did not hold for other species. Likewise, in four species of migrants, fat score and body mass were not related to time of day or date and did not vary consistently with altitudinal differences in estimated fattening rate based on plasma triglyceride analysis  in WIWA compared with the other species in each of the 3 years. r2 = 0.04). Furthermore, we did not find consistent relationships between plasma β-hydroxybutyrate or glycerol and time of day or date factors, which should predict fattening rate  fed a high-protein insect diet had higher plasma β-hydroxybutyrate concentrations than birds fed a low-protein diet, even though diet did not affect short-term mass change. However, these studies did not look at the effect of diet on glycerol. In contrast to our data on plasma triglyceride, we found significant inter-annual variation in mean plasma glycerol and β-hydroxybutyrate levels, and both these metabolites were related to variation in daily water levels, with higher residual metabolite levels in drier conditions, and with glycerol showing stronger relationships. Elevated plasma levels of glycerol and β-hydroxybutyrate are typically considered to be measures of fasting and fat catabolism. However, this is usually associated with extreme fasting (e.g. in large-bodied birds, Finally, in relationship to the primary goal of our study, we found no evidence that estimated fattening rate varied among years with very different patterns of variation in water levels, or with daily variation in water levels, in this reservoir-impacted riparian habitat. Previous studies have shown that there can be consistent differences in plasma triglyceride levels between different habitats, including habitats at migratory stopover sites . Gugliel


Pregnancy associated cardiovascular pathologies have a significant impact on outcome for mother and child. Bioimpedance cardiography may provide additional outcome-relevant information early in pregnancy and may also be used as a predictive instrument for pregnancy-associated diseases.th–13th week of gestation every 5th week as well as at two occasions post partum employing bioimpedance cardiography.We performed a prospective longitudinal cohort trial in an outpatient setting and included 242 pregnant women. Cardiac output and concomitant hemodynamic data were recorded from 11Cardiac output increased during pregnancy and peaked early in the third trimester. A higher heart rate and a decreased systemic vascular resistance were accountable for the observed changes. Women who had a pregnancy-associated disease during a previous pregnancy or developed hypertension or preeclampsia had a significantly increased cardiac output early in pregnancy. Furthermore, an effect of cardiac output on birthweight was found in healthy pregnancies and could be confirmed with multiple linear regression analysis.Cardiovascular adaptation during pregnancy is characterized by distinct pattern described herein. These may be altered in women at risk for preeclampsia or reduced birthweigth. The assessment of cardiac parameters by bioimpedance cardiography could be performed at low costs without additional risks. Hemodynamic adaptations during normal pregnancy enable the female body to comply with increased metabolic demands to fulfill fetal requirements. Blood pressure decreases during pregnancy as a consequence of vascular dilatation, which in turn leads to an increase of cardiac output due to an increased heart rate and a higher stroke volume , 2. Thesth week of gestation, measured on two different occasions and proteinuria [However, this “stress test” may reveal underlying cardiovascular diseases . Furtherteinuria .th–14th week of gestation in women who developed preeclampsia or gestational hypertension later in pregnancy [The assessment of cardiac output and systemic vascular resistance adds significant information to blood pressure and heart rate. As a key finding in prior trials, an increased cardiac output could be detected as early as in the 10regnancy . Thus, tThe gold standard for the assessment of cardiac output is thermodilution using a cardiac catheter . AlthougWe decided to perform a prospective trial in order to establish the applicability of bioimpedance cardiography for the assessment of cardiovascular parameters during pregnancy . Severalwww.medical.philips.com). Two pairs of electrodes were placed on the neck and two pairs were placed on the trunk, respectively. Every measurement was performed in a quiet room after a resting period of 10 min. The automatic assessment and data printout were performed after stable readings could have been achieved. To estimate the hemodynamic influence of a growing fetus compressing the Vena cava in a supine position, every measurement was performed in supine as well as in side position. Cardiac output and not cardiac index was chosen for all analysis hence previous results indicated a low correlation of cardiac output to body surface area during pregnancy [Between 2006 and 2009, 242 pregnant women were included in this prospective cohort study after providing written informed consent. A high number of women were included to evaluate also disease processes not primarily present and occurring throughout the pregnancy. The local ethics committee approved the study protocol EK 619/2006). We measured cardiovascular parameters noninvasively by monitoring the tissue impedance of distinct thoracic regions . An impe/2006. Weth–13th week of gestation. Patients with pre-existing diabetes, cardiac disease  or intravenous drug abuse were not included. Every visit included medical history assessment, a physical examination to diagnose symptoms of preeclampsia and other pregnancy related diseases, an ECG and the measurement of cardiac output, blood pressure, heart rate, systemic vascular resistance and stroke volume. Cardiac output and concomitant data were recorded at the 11th–13th, 14th–17th, 18th–22nd, 23rd–27th, 28th–32nd, 33rd–36th and after the 37th week of gestation as well as six weeks and six months post partum. Every onset of a pregnancy related disease was recorded, evaluated and treated according to current guidelines [th week of gestation [Women were asked to participate in this study at their routine visit for the first ultrasound control at the outpatient department of the obstetrics and gynecology clinic usually performed between the 11n = 28) and thyroid gland disease . Nine patients suffered from gestational diabetes mellitus during a previous pregnancy. Nine patients had a family history of preeclampsia. Due to a low number or heterogonous groups, patients with the aforementioned characteristics were not analyzed as specific group. However, patients with previous pregnancy related hypertension (n = 17), previous preeclampsia (n = 7) or previous HELLP syndrome (n = 6) were grouped (n = 29) and compared to the healthy control group.A flow chart was added to depict final patient groups for the analysis performed in this study Fig. . Pre-exin = 6), new onset of hypertension (n = 5), gestational diabetes mellitus (n = 12) and HELLP syndrome (n = 2). In addition, abnormal Doppler (n = 4) and preterm labor (n = 9) were recorded.During the pregnancy under investigation, patients were diagnosed with preeclampsia (n = 128). However, six women had a twin pregnancy and were, although healthy, not included in the “healthy” group due to changed hemodynamic parameters in twin pregnancies.All women without any previous or current relevant disease described herein were classified as healthy and grouped for analysis  lower than 0.05 were considered statistically significant. Statistical analysis was performed with SPSS 21 . Figures were calculated and drawn by applying the spline function. Single data points were printed for comparisons with a low number of measurements.Data sets were descriptively analyzed and are presented as means ± SD. For comparison of data, sets were tested for normal distribution (Shapiro-Wilk test). To compare outcome parameters between groups of healthy and pathologic pregnancies, an analysis of variance was performed. The Pearson correlation coefficient was calculated to analyze relationships. Time points were compared pair-wise with a Sidak correction for the significance level due to the multiple comparisons applied herein. A multiple linear regression was performed to assess the effect of cardiac output on birthweight including maternal age, body mass index and smoking habit. n = 128) was only present in the 33rd–36th week of gestation. A significant and high correlation of cardiovascular parameters between body positions was present throughout pregnancy  and compared to post-delivery . Heart rate was significantly increased from the 23rd week of gestation compared to 11th–13th week (p < 0.001) and compared to post-delivery (Table p = 0.002). Systolic blood pressure and stroke volume showed no significant difference throughout pregnancy and after delivery (Table th week of gestation compared to 14th – 22nd week of gestation (Table p < 0.02). Furthermore, systemic vascular resistance was significantly lower in the 33rd–36th week of gestation compared to 11th–13th week (p = 0.009) and compared to post-delivery .Cardiac output in the 33ry Table . Howevern = 29). This group had significantly increased cardiac output and heart rate in the first months and a significantly increased blood pressure throughout pregnancy. Eleven patients had a previously diagnosed hypertension, two patients developed preeclampsia, two patients developed HELLP syndrome, two patients had an abnormal Doppler and two patients suffered from preterm delivery.Women with preeclampsia, HELLP syndrome or hypertension in a previous pregnancy were grouped and analyzed Table ; n = 29.p < 0.01). In addition, cardiac output was significantly increased from 5.2 to 6.8 l/min at 11th–13th week of gestation compared to the healthy group due to an increased stroke volume . Cardiac output was no longer increased from the 14th week of gestation, but systemic vascular resistance was significantly increased .Patients with a new onset of pregnancy related hypertension during this pregnancy had a significantly increased cardiac output due to an increased stroke volume compared to the healthy group Fig. . Patientp = 0.014), 0.42 (p = 0.006) and 0.32 (p = 0.058) for the 23rd–27th, 28th–32nd and 33rd–37th week of gestation, respectively. Concordantly, the Pearson correlation coefficient for systemic vascular resistance was −0.41 (p = 0.004), −0.33 (p = 0.033) and −0.31 (p = 0.061) for the 23rd–27th, 28th–32nd and 33rd–37th week of gestation, respectively. A multiple linear regression analysis including cardiac output, maternal age, body mass index and smoking habit revealed cardiac output as the only independent predictor for birthweight . Furthermore, birthweight and gestational age were significantly reduced in hypertensive pregnancies to 2548 ± 903 g at 37 ± 5 weeks compared to 3308 ± 554 g at 39 ± 2 weeks in healthy pregnancies .A correlation analysis of cardiac output and systemic vascular resistance with birthweight in healthy women revealed a positive correlation for cardiac output and a negative correlation for systemic vascular resistance. The Pearson correlation coefficient for cardiac output was 0.32 . Measurements in pathologic groups were not analyzed in relation to the body mass index due to the limited number of observations.In conclusion, cardiovascular adaptation during pregnancy is altered in women at risk for preeclampsia or reduced birthweigth. Distinct hemodynamic pattern were present early in pregnancy and could be assessed by bioimpedance cardiography at low costs without additional risk.ECG, electrocardiogram; HELLP, Hemolysis, Elevated Liver enzymes, Low Platelet count; ICG, impedance cardiography; SD, standard deviation; SPSS, Statistical Package for the Social Sciences


Background. Industrial processing of the pecan nut Carya illinoinensis K. Koch generated a large amount of shells, which have been used to prepare nutritional supplements and medicinal products; however, the safe use of shells requires assessment. This study evaluated the toxic, genotoxic, and mutagenic effects of pecan shell aqueous extract (PSAE) and the possible contribution of phenolic compounds, ellagic and gallic acids, and inorganic elements present in PSAE to induce toxicity. Results. Levels of inorganic elements like K, P, Cl, and Rb quantified using the Particle-Induced X-Ray Emission method were higher in PSAE than in pecan shells, while Mg and Mn levels were higher in shells. Mice showed neurobehavioral toxicity when given high PSAE doses . The LD50 was 1,166.3 mg kg−1. However, PSAE (50–200 mg·kg−1) and the phenolic compounds (10–100 mg·kg−1) did not induce DNA damage or mutagenicity evaluated using the comet assay and micronucleus test. Treatment with ellagic acid (10–100 mg·kg−1) decreased triglyceride and glucose levels, while treatments with PSAE and gallic acid had no effect. Conclusion. Pecan shell toxicity might be associated with high concentrations of inorganic elements such as Mn, Al, Cu, and Fe acting on the central nervous system, besides phytochemical components, suggesting that the definition of the safe dose should take into account the consumption of micronutrients.  Carya illinoinensis (Wangenh.) K. Koch are generated as a byproduct of processing pecan nuts produced on an industrial scale in the southern states of Brazil. Although the shells were initially considered a waste material, their fate began to change with studies showing their nutritional value [ in natura and in nutraceutical products against obesity and hypercholesterolemia. Pecan shells and gallic and ellagic acids have been investigated in the prevention or treatment of human diseases such as metabolic and inflammatory conditions, neurological disorders, gastric ulcers, and cancer [The pecan nut shells fromal value –3. Higheal value . The shed cancer –10. Howed cancer . Carya illinoinensis (Wangenh.) K. Koch by determining the median lethal dose (LD50) and analyzing behavioral, biochemical, genotoxic, and mutagenic parameters in mice. In addition, gallic and ellagic acids were evaluated for these parameters and compared with pecan shells. Inorganic elements present in pecan shells were determined. Thus, the mechanisms of toxicity, genotoxic, and mutagenic effects of shells could be discussed based on their chemical constituents.The present study evaluated the acute toxicity of shells from the pecan speciesPecans (Barton variety) were collected in Cachoeira do Sul, RS, Brazil (coordinates 30°11′39.29′′S and 52°48′1.23′′W). A voucher specimen was deposited at the Herbarium of Lutheran University of Brazil (ULBRA) ; it was recorded under number 4289 and identified by Dr. Sérgio Bordignon at ULBRA. The shells were washed and dried in an oven at 35°C with air circulation for 7 days. The dried shells (450 g) were finely milled and extracted with water by decoction at 100°C for 15 min . After cooling, the filtered extract was frozen and concentrated by lyophilization to obtain a final yield of 143.1 g  pecan shell aqueous extract (PSAE).−6 mbar. A 3 MV Tandetron accelerator was used to irradiate the target with a 2.0 MeV proton beam and an average current of 3.5 nA. The X-rays produced in the samples were detected using a Si (Li) detector with an energy resolution of approximately 160 eV at 5.9 keV. The PIXE spectra were fitted and quantified using the GUPIXWIN software package developed at the University of Guelph  [The elemental composition of the PSAE and pecan shells was determined using the Particle-Induced X-Ray Emission (PIXE) technique. Briefly, the lyophilized extracts and the same finely milled dried shells used in the preparation of PSAE were pressed into thick pellets and placed in the target holder inside the reaction chamber, which was maintained at a pressure of approximately 10 Canada) –14 and t Canada) .Mus musculus) weighing 35–45 g from our breeding colony were used. Animals were housed at 22 ± 2°C, under a 12 h/12 h light/dark cycle, with 60% relative humidity, and received water and food ad libitum. All experimental procedures were performed in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals and were approved by the Ethics Committee on Animal Use (CEUA) at ULBRA (protocol number 201245-P).Ninety-five CF-1 male mice , 500 mg kg−1 PSAE, 1,000 mg kg−1 PSAE, and 2,000 mg kg−1 PSAE; treatments were administered by oral gavage. Signs of toxicity, including lethargy, piloerection, and increased respiratory rate, were observed immediately after PSAE administration in all doses and persisted for 1 h. The survival rates used to calculate the LD50 were 100%, 60%, and 0% at doses of 500, 1,000, and 2,000 mg kg−1, respectively, in the first 24 h. All surviving PSAE-treated animals were euthanized by decapitation. The LD50 was determined using probit regression analysis with a confidence interval of 5% in the StatPlus Professional 2009 software to assess the number of deaths with each dose. Probit analysis indicated an LD50 of 1,166.3 mg kg−1 with a standard error of 304.6.To determine LD50, the selected highest PSAE dose was 200 mg kg−1 daily for three consecutive days , following the recommendation described elsewhere [Based on LDlsewhere , to evaln = 10), PSAE , ellagic acid  , or gallic acid   by oral gavage for three consecutive days. A positive control group treated with cyclophosphamide   was included in the micronucleus test. Hydrogen peroxide (ex vivo treatment: slides from vehicle group treated with H2O2 0.25 mM for 5 min) was used as positive control in the comet assay. The vehicle and PSAE groups (n = 10 per group) were also subjected to open field studies after the first dose. Five animals per group were used to perform the comet assay, micronucleus test, and biochemical analyses.The animals were treated with vehicle  24 h after the first administration to perform the comet assay; the animals were treated for two other consecutive days. Twenty-four hours after the last administration, all mice were euthanized by decapitation and blood samples were collected to perform the comet assay and biochemical analyses. Bone marrow from both femurs was collected to perform the micronucleus test.Peripheral blood was collected from the tail vein . Latency to start the locomotion, crossing of black lines, and rearing times were counted and used as measurements of motivation, locomotion, and exploration, respectively .The habituation test was conducted 24 h after the first exploration; the animals were placed again in the open field box for 5 min and the number of rearing times was counted (test session). Long-term retention of habituation to a novel environment can be considered a type of learning. A decrease in rearing between the first and second exploration sessions was considered to be a measure of habituation .The alkaline comet assay was conducted as previously described . Images The micronucleus test was performed according to international guidelines . To avoiμL of blood was collected from each animal. The samples were centrifuged at 419 ×g for 8 min. The serum obtained was frozen and sent to the Veterinary Hospital of ULBRA for analysis of cholesterol, triglycerides, glucose, and alanine aminotransferase levels using Labtest kits from Labtest Diagnóstica SA . The tests were performed using a semiautomatic biochemical analyzer .The animals were left to fast for 6 h before euthanasia and blood collection for biochemical analysis. Approximately 500  t-test and when necessary the Welch correction. Open field data are expressed as the mean ± standard error of the mean (SEM). These data were examined using a one-way analysis of variance (ANOVA) followed by Duncan's test. The habituation test results are expressed as the mean ± SEM. Comparisons between rearing in training and test sessions within the same group in the habituation experiment were conducted using a paired t-test. All other data are expressed as the mean ± standard deviation (SD) and were analyzed using ANOVA followed by Dunnett's test. In all comparisons, p ≤ 0.05 was considered statistically significant.Analysis of inorganic elements was determined using Student'sThe inorganic components found in PSAE and pecan shells (SHELL) were as follows: sodium (Na), magnesium (Mg), aluminum (Al), silicon (Si), phosphorus (P), sulfur (S), chloride (Cl), potassium (K), calcium (Ca), chromium (Cr), manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), rubidium (Rb), strontium (Sr), and barium (Ba). K, P, Cl, and Rb contents were higher in PSAE than in pecan shells, while Mg and Mn levels were higher in shells .p = 0.469; p = 0.129; p = 0.437; −1 of PSAE , the groups treated with 50 and 100 mg kgactivity , suggestThe results of the comet assay performed in blood samples collected at 24 h and 72 h after treatment showed no genotoxic activities of PSAE and ellagic and gallic acids Tables .The results of the micronucleus tests  showed nThere were no statistically significant differences in any biochemical parameters between the animals treated with different concentrations of gallic acid and PSAE  and the  Carya illinoinensis (Wangenh.) K. Koch have been empirically used to decrease glucose and cholesterol levels in obese, diabetic, and/or hypercholesterolemic patients; however, few studies evaluated toxicological parameters to support their safe use as a nutritional supplement or for medicinal purpose. This study evaluated toxicity and genotoxic activities of an aqueous extract from shells (PSAE) and the involvement of their major organic and inorganic compounds that may elicit toxicological effects. In the determination of LD50  the toxicity and death induced by higher doses of PSAE tested in mice could be due to high concentrations of bioactive compounds, including ellagic and gallic acids. However, no toxicity signs were detected when those phenolic compounds were administered alone at doses up to 100 mg kg−1.Pecan nut shells fromThe inorganic elements present in PSAE and pecan shells were analyzed by Particle-Induced X-Ray Emission (PIXE) . K, P, C−1) did not affect the locomotion and exploratory activity, in comparison to vehicle group (−1 of PSAE showed decreased rearing in comparison to the group treated with 50 mg kg−1 (p < 0.05). This same highest dose impaired the habituation memory  was established by the World Health Organization [−1 for adult men and women, respectively, and 1.2 to 1.5 mg d−1 for children between 1 and 8 years of age [The presence of Cu and Mn in PSAE  is harmful, as shown in recent data that suggest that high levels of Cu and Mn are associated with brain toxicity –27. The s of age . Baccharis sp., when exposed to polluted areas [−1. However, other chemical components might be involved in inducing toxicity. PSAE is a complex mixture of organic and inorganic compounds that interact with one other and might produce synergistic and additive effects.The Cu content of 29.9 ± 14.5 ppm in PSAE is higher than that previously reported in studies of other medicinal plants, fruits, and juices , 31. Cu ed areas . The exced areas . Oxidatied areas , and daied areas . Thus, t−1 of Fe or Cu, respectively, for six days [PSAE, gallic acid, and ellagic acid did not increase micronucleus frequency in the bone marrow of the mice, indicating that they did not induce clastogenicity (chromosome breakage) and aneugenicity (chromosome lagging due to dysfunction of the mitotic apparatus) , which csix days .Treatment with PSAE or gallic acid did not affect any of the biochemical parameters tested . However Carya illinoinensis.The pecan shells analyzed provide a range of essential micronutrients and contain high levels of antioxidants; however, the shells have inorganic elements whose accumulation can be harmful and should be taken into account in the manufacturing of nutraceutical products of


P < 0.05). Gait velocity was significantly slower in cataract patients compared with controls before surgery, but no longer different after surgery. In simulated patients, mean velocity was 87.0 ± 11.4% of normal vision with a 3° visual field and 92.4 ± 12.3% of normal when counting fingers. Initial velocity was 89.1 ± 14.6% of normal vision with a 3° visual field and 92.7 ± 11.6% of normal when counting fingers. There was a significant difference between normal and impaired visual function (P < 0.05). The results demonstrate the close relationship between visual function and gait in cataract patients and simulated patients.The aim of the present study was to measure gait velocity in cataract and simulated patients. The study was performed on 239 cataract patients, 115 age-matched subjects, and 11 simulated patients. We measured gait velocity and analyzed gait using a three-dimensional motion analysis system. Mean gait velocity before and 2 and 7 months after cataract surgery was 0.91 ± 0.19, 1.04 ± 0.21, and 1.06 ± 0.21 m/s, respectively, for males and 0.84 ± 0.22, 0.91 ± 0.24, and 0.92 ± 0.25 m/s, respectively, for females. The increase after surgery was significant in both groups at 7 months ( As such, a clinical study into preoperative motor function decline and postoperative improvement in cataract patients could be of considerable benefit to public health. Ophthalmological interventions and experimental simulation of vision loss using eyewear could provide more useful information regarding the contribution of vision to motor function than conventional methods. In the present study we analyzed 239 cataract patients to explore correlations between gait velocity and ocular and systemic parameters. Gait velocity has been proposed as a relevant clinical indicator of well being in older adults and has been shown to predict survivalThe Institutional Review Board and Ethics Committee of Keio University School of Medicine approved this study and the methods were carried out in accordance with the approved guidelines. All cataract and simulated patients provided written informed consent before taking part in the study. Subjects were recruited to the study from cataract patients and individuals with normal vision visiting eye clinics at the National Hospital Organization Saitama Hospital  and International Health and Welfare University Mita Hospital  between May 2011 and April 2013. Simulated patients were recruited from Keio University Hospital  between September 2013 and February 2014.The mean (±SD) age of the 239 cataract patients  was 74.5 ± 8.0 years. Patients were undergoing phacoemulsification and intra-ocular lens (IOL) implantation. Cataract patients were enrolled consecutively from the eye clinic and not biased. All surgeries were performed under topical anesthesia and a soft acrylic IOL  was inserted by experienced surgeons. Best corrected visual acuity was converted to logarithm of minimal angle of resolution (LogMAR) units, and cataract opacity in the optical axis accounting for visual disturbance was classified as posterior subcapsular cataract, nuclear sclerosis (greater than Grade 2 on Emery–Little classification), or central cortical opacity. Some patients had mixed-type opacity. All patients completed the Japanese versionThe control group consisted of 115 subjects with normal vision visiting the eye clinic for non-vision-related problems, including an eye health check, vitreous floaters, and ocular discomfort. Inclusion criteria for the control group were age between 64 and 84 years, not using a cane or walking aid, and normal vision . Exclusion criteria were vision-affecting eye disease, diabetes, brain infarction, and orthopedic and/or neurological complications, including paralysis, Parkinson’s disease, and a history of orthopedic surgery. Subjects were asked to walk at their preferred velocity in the examination room in the eye clinic, and 4-m gait velocity was measured once by a trained technician using a digital stopwatch.®; Qualysis, Gothenburg, Sweden)32Eleven healthy male volunteers  were recruited as simulated patients. Gait was evaluated in these subjects at the Gait Laboratory of the Department of Orthopedic Surgery using skin markers attached over the sacrum as part of a three-dimensional motion capture system  and SPSS version 21 . P < 0.05 was considered significant.Where appropriate, data are given as the mean ± SD. Data were analyzed using ANOVA and P < 0.05, paired t-test). Mean gait velocity in male  and female  controls with normal vision was 0.92 ± 0.21 and 0.95 ± 0.17 m/s, respectively. The difference in gait velocity between cataract patients and controls was significant before surgery , but not 2 months after surgery, in both gender groups.Demographics and gait velocity for cataract patients are given in P < 0.01, Pearson’s product moment correlation), age (P < 0.001), height (P < 0.001), visual acuity in the worse eye (P < 0.05), and VFQ-25 score (P < 0.001) adjusted for age and sex (P < 0.05) and the presence of posterior subcapsular cataract adjusted for age and sex (P < 0.01). Graphic representation revealed a strong correlation between age and gait velocity  and 2 months after  surgery demonstrate an increase in gait speed after surgery.Stepwise multiple regression analysis of gait velocity and related parameters revealed that preoperative velocity was significantly correlated with sex  with a visual acuity of 20/600, 81.8 ± 23.6% (P < 0.05) when counting fingers, and 79.8 ± 15.4% (P < 0.01) with a visual field of 3° (P < 0.01). Initial velocity in simulated patients was 90.5 ± 8.8% of normal (P < 0.05) with a visual acuity of 20/600, 82.5 ± 13.8% (P < 0.05) when counting fingers, and 84.3 ± 9.7% (P < 0.05) with a visual field of 3° (P < 0.05).Simulated patients exhibited significantly reduced gait velocity when visual function was impaired compared with normal-vision conditions . Mean veThe results of the present study demonstrate that gait velocity increases 2 months after cataract surgery and further increases at 7 months, despite the fact that these elderly patients are also 7 months older. To the best of our knowledge, the present study is the largest clinical case series of gait velocity in patients undergoing cataract surgery. The improvement in gait velocity was not dependent on age, sex, or height, indicating that sensory, neural, or psychological robustness may be more important than musculoskeletal components for achieving and maintaining a healthy gait in older people. Therefore, age-related declines in gait may be due not only to physical frailty as a consequence of aging, but also to a fear of falling as a result of low visual recognition exacerbated by eye disease. It was interesting that, prior to surgery, the cataract patients in the present study had significantly slower gait velocity than age-matched subjects with normal vision without cataract but, after surgery, cataract patients walked faster than the control subjects even through some of them had diabetes and other comorbidities that could possibly suppress gait. Our clinical impression was that the cataract patients decided to undergo surgery only when they were mentally and physically robust enough to tolerate the procedure. According to recent reports, postoperative improvements in sleep quality or mental status are no longer evident in some cases 1 year after surgery3536Most previous studies of gait speed were performed as part of a health check for a large population, so very simple methods (in terms of efficacy and safety) were used to determine gait speed, such as measurements made over a short distance using a stopwatch. In the present study, we chose to measure walking velocity over a distance of 4 m because the reproducibility and standardization of this technique have been established in many studieset al.In the present study, visual acuity in the worse eye was correlated with preoperative gait velocity and postoperative improvement, which accords with the study of Matsuo With regard to the type of cataract opacity, patients with posterior subcapsular cataract exhibited a greater increase in gait velocity compared with patients with other types of opacities. These findings support those of previous studies that posterior subcapsular cataract is a significant prognostic determinant of cataract surgery for quality of life and sleep31Three-dimensional motion capture is a modern technology for analyzing motion under normal and pathological conditions. It is commonly used in orthopedic evaluation by capturing the motion of each joint and bone32391718192021222324412425363743The limitations of the present study include the type of control subjects for old cataract patients, simulated patients, and the learning curve of participants. There are many systemic conditions that can potentially affect gait velocity and most older adults may have age-related disabilities and comorbidities. Physicians and nurses observed the gait and sitting and standing posture of subjects with normal vision to confirm that they were eligible to be enrolled in the study as normal controls. It was not ethical to ask older participants to walk while wearing simulation goggles because of safety concerns. However, we believe the healthy simulated patients in the present study successfully served as a relevant experimental model and contributed to reasonable results. With regard to the possible learning curve of participants, gait velocity measurements were performed only once using a very simple method that required no skill or practice. Measurements after surgery were performed 2 and 7 months after the initial measurement and, after this time, the patients may not remember how they walked in the initial assessment. Although graders were not masked as to subject characteristics, we do not believe this resulted in bias because the graders used the same simple method for all subjects.In conclusion, we found that the gait velocity of cataract patients increased over 7 months after surgery and exceeded that of age-matched controls with normal vision. Three-dimensional motion analysis of simulated patients also demonstrated a significant correlation between visual function and gait velocity. The results of the present study confirm motor function benefits after visual restoration by cataract surgery.How to cite this article: Ayaki, M. et al. Motor function benefits of visual restoration measured in age-related cataract and simulated patients: Case-control and clinical experimental studies. Sci. Rep.5, 14595; doi: 10.1038/srep14595 (2015).