Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.

CRISPR-based genetic control strategies for insect pests

Genetic control strategies such as the sterile insect technique have successfully fought insect pests worldwide. The CRISPR(clustered regularly interspaced short palindromic repeats) technology, together with high-quality genomic resources obtained in more and more species, greatly facilitates the development of novel genetic control insect strains that can be used in area-wide and species-specific pest control programs. Here, we review the research progress towards state-of-art CRISPR-based genetic control strategies, including gene drive, sex ratio distortion, CRISPRengineered genetic sexing strains, and precision-guided sterile insect technique. These strategies’ working mechanisms,potential resistance development mechanisms, and regulations are illustrated and discussed. In addition, recent developments such as stacked and conditional systems are introduced. We envision that the advances in genetic technology will continue to be one of the driving forces for developing the next generation of pest control strategies.

Heat stress in pigs and broilers:role of gut dysbiosis in the impairment of the gut-liver axis and restoration of these effects by probiotics,prebiotics and synbiotics

Heat stress is one of the most challenging stressors for animal production due to high economic losses resulting from impaired animal’s productivity,health and welfare.Despite the fact that all farm animal species are susceptible to heat stress,birds and pigs are particularly sensitive to heat stress due to either lacking or non-functional sweat glands.Con-vincing evidence in the literature exists that gut dysbiosis,a term used to describe a perturbation of commensal gut microbiota,develops in broilers and pigs under heat stress.Owing to the protective role of commensal bacteria for the gut barrier,gut dysbiosis causes a disruption of the gut barrier leading to endotoxemia,which contributes to the typical characteristics of heat stressed broilers and growing and growing-finishing pigs,such as reduced feed intake,decreased growth and reduced lean carcass weight.A substantial number of studies have shown that feeding of probiotics,prebiotics and synbiotics is an efficacious strategy to protect broilers from heat stress-induced gut barrier disruption through altering the gut microbiota and promoting all decisive structural,biochemical,and immunologi-cal elements of the intestinal barrier.In most of the available studies in heat stressed broilers,the alterations of gut microbiota and improvements of gut barrier function induced by feeding of either probiotics,prebiotics or synbiot-ics were accompanied by an improved productivity,health and/or welfare when compared to non-supplemented broilers exposed to heat stress.These findings indicate that the restoration of gut homeostasis and function is a key target for dietary interventions aiming to provide at least partial protection of broilers from the detrimental impact of heat stress conditions.Despite the fact that the number of studies dealing with the same feeding strategy in heat stressed pigs is limited,the available few studies suggest that feeding of probiotics might also be a suitable approach to enhance productivity,health and welfare in pigs kept under heat stress conditions.

锡林河流域地表水和浅层地下水的稳定同位素研究

2006年4—9月,在从锡林河源头沿河流进行地表水和地下水同位素样品采集和分析的基础上,利用全球降水同位素监测网(GNIP)包头站的大气降水稳定同位素资料,结合锡林河流域的气象和水文资料,对锡林河流域大气降水、地表水和地下水稳定同位素进行了研究.结果表明:地下水中δ18O和δD值分别集中在-11.7‰～-14.9‰和-80‰～-89.5‰范围内,δ18O沿地下水流向有增加的趋势,大部分地下水中δ18O的季节波动性不大;河流干流δ18O和δD的年算术平均值从源区的-12.8‰和-94.5‰到入锡林河水库处的-10.0‰和-79.3‰,差值分别约为3‰和15‰.河水中的δ18O值沿流程增加而增大的现象可归结为受含有较高δ18O值的地下水补给作用和河水的蒸发作用的共同影响,其中对δ18O蒸发富集的研究显示,蒸发引起δ18O富集值为1‰.通过地下水线(GWL)和地表水线(SWL)及区域大气降水线(LMWL)的对比分析发现,在径流季节,降水对地表水的贡献小,地下水是地表水主要的补给源,地表径流基本是地下水的排泄.

同位素技术在流域水文研究中的重要进展

近50 a来,同位素技术在流域水文研究中取得了两个方向上的重要进展:从时间上讲,主要是对水体贮存、运移时间变化的评估,这里重点介绍了对地下水滞留时间估算上的重要进展;从空间上讲,主要是对流域水文过程的评估,从对河流-地下水系统内水体的相互转化、径流分割和生物化学过程3个方面的进展进行评述.同位素技术和方法在流域水文研究中将向着理解大流域水文过程的方向发展,同位素信息用来校正和检验降水-径流模型及在可持续水资源管理的定量化研究等方面的潜在价值有待实现.

Diagnosis and treatment of diabetes mellitus in chronic pancreatitis

Diabetes secondary to pancreatic diseases is commonly referred to as pancreatogenic diabetes or type 3c diabetes mellitus.It is a clinically relevant condition with a prevalence of 5%-10%among all diabetic subjects in Western populations.In nearly 80%of all type 3c diabetes mellitus cases,chronic pancreatitis seems to be the underlying disease.The prevalence and clinical importance of diabetes secondary to chronic pancreatitis has certainly been underestimated and underappreciated so far.In contrast to the management of type 1 or type2 diabetes mellitus,the endocrinopathy in type 3c is very complex.The course of the disease is complicated by additional present comorbidities such as maldigestion and concomitant qualitative malnutrition.General awareness that patients with known and/or clinically overt chronic pancreatitis will develop type 3c diabetes mellitus(up to 90%of all cases)is rather good.However,in a patient first presenting with diabetes mellitus,chronic pancreatitis as a potential causative condition is seldom considered.Thus many patients are misdiagnosed.The failure to correctly diagnose type 3 diabetes mellitus leads to a failure to implement an appropriate medical therapy.In patients with type 3c diabetes mellitus treating exocrine pancreatic insufficiency,preventing or treating a lack of fat-soluble vitamins(especially vitamin D)and restoring impaired fat hydrolysis and incretin secretion are key-features of medical therapy.

Calpain system and its involvement in myocardial ischemia and reperfusion injury

Calpains are ubiquitous non-lysosomal Ca2+-dependent cysteine proteases also present in myocardial cytosol and mitochondria.Numerous experimental studies reveal an essential role of the calpain system in myocardial injury during ischemia,reperfusion and postischemic structural remodelling.The increasing Ca2+-content and Ca2+-overload in myocardial cytosol and mitochondria during ischemia and reperfusion causes an activation of calpains.Upon activation they are able to injure the contractile apparatus and impair the energy production by cleaving structural and functional proteins of myocytes and mitochondria.Besides their causal involvement in acute myocardial dysfunction they are also involved in structural remodelling after myocardial infarction by the generation and release of proapoptotic factors from mitochondria.Calpain inhibition can prevent or attenuate myocardial injury during ischemia,reperfusion,and in later stages of myocardial infarction.

Heme oxygenase-1 as a therapeutic target in inflammatory disorders of the gastrointestinal tract

Heme oxygenase (HO)-1 is the inducible isoform of the first and rate-limiting enzyme of heme degradation. HO-1 not only protects against oxidative stress and apoptosis, but has received a great deal of attention in recent years because ofits potent anti-inflammatory functions. Studies with HO-1 knockout animal models have led to major advances in the understanding of how HO-1 might regulate inflammatory immune responses, although little is known on the underlying mechanisms. Due to its beneficial effects the targeted induction of this enzyme is considered to have major therapeutic po- tential for the treatment ofinflammatory disorders. This review discusses current knowledge on the mechanisms that mediate anti-inflammatory protection by HO-1. More specifically, the article deals with the role of HO-1 in the pathophysiology of viral hepatitis, inflammatorybowel disease, and pancreatitis. The effects of specific HO-1 modulation as a potential therapeutic strategy in experimental cell culture and animal models of these gastrointestinal disorders are summarized. In conclusion, targeted regulation of HO-1 holds major promise for future clinical interventions in inflammatory diseases of the gastrointestinal tract.

Changes in Soil C and N Contents and Mineralization Across a Cultivation Chronosequence of Paddy Fields in Subtropical China

Dynamics of soil organic matter in a cultivation chronosequence of paddy fields were studied in subtropical China.Mineralization of soil organic matter was determined by measuring CO2 evolution from soil during 20 days of laboratoryincubation. In the first 30 years of cultivation, soil organic C and N contents increased rapidly. After 30 years, 0-10 cmsoil contained 19.6 g kg-1 organic C and 1.62 g kg-1 total N, with the corresponding values of 18.1 g kg-1 and 1.50g kg-1 for 10-20 cm, and then remained stable even after 80 years of rice cultivation. During 20 days incubation themineralization rates of organic C and N in surface soil (0-10 cm) ranged from 2.2% to 3.3% and from 2.8% to 6.7%,respectively, of organic C and total N contents. Biologically active C size generally increased with increasing soil organicC and N contents. Soil dissolved organic C decreased after cultivation of wasteland to 10 years paddy field and thenincreased. Soil microbial biomass C increased with number of years under cultivation, while soil microbial biomass Nincreased during the first 30 years of cultivation and then stabilized. After 30 years of cultivation surface soil (0-10 cm)contained 332.8 mg kg-1 of microbial biomass C and 23.85 mg kg-1 of microbial biomass N, which were 111% and 47%higher than those in soil cultivated for 3 years. It was suggested that surface soil with 30 years of rice cultivation insubtropical China would have attained a steady state of organic C content, being about 19 g kg-1.

Innovative immunohistochemistry identifies MMP-9 expressing macrophages at the invasive front of murine HCC

AIM:To investigate the proteolytic contribution of tumor-associated macrophages(TAM)in tumor invasion,we analyzed whether TAM at the invasive front of small HCC in Abcb4-/--mice show an enhanced expression of MMP-9. METHODS:Liver cryosections of the hepatocellular carcinoma(HCC)invasive front from 12 mo old Abcb4-/--mice were stained for collagen typeⅠand MMP-9 using Alexa488 and Alexa568 labeled secondary antibodies.Afterwards,the Alexa568 dye was bleached and the macrophage marker F4/80 was visualized using Alexa568 labeled secondary antibodies.Finally, photographs of the invasive tumor front were digitally overlaid and analyzed. RESULTS:After complete bleaching of the primary dye,specific fluorescence staining of a third antigen, here F4/80,was successfully performed on the same histological section.With this method,we were able to identify conglomerates of matrix metalloproteinase (MMP-9)expressing macrophages within the tumor capsule of HCC. CONCLUSION:MMP-9 expressing macrophages are involved in matrix remodelling at the invasive tumor front of HCC.The described staining protocol provides a simple yet powerful extension of conventional immuno-histochemistry,facilitating visualization of at least three different antigens plus nuclei in one single histological section.

Effects of supplementation of green tea extract on the milk performance of peripartal dairy cows and the expression of stress response genes in the liver

Background: We hypothesised that supplementation of green tea extract(GTE) in dairy cows during the transition period can attenuate proinflammatory conditions and prevent endoplasmic reticulum(ER) stress in the liver of these cows. Thirty Holstein cows with an average parity of 3.06(± 1.31, SD) were divided into a control group and a group that received a daily amount of 10 g of GTE from d 7 before the calving day and a daily amount of 20 g of GTE from the day of calving until d 7 of lactation.Results: Cows supplemented with GTE did not show differences in energy intake or milk yield in weeks 2–7 of lactation. However, these cows had a lower milk fat concentration and a lower energy corrected milk yield than the control cows and showed a trend of improved energy balance. The relative m RNA concentrations of proinflammatory genes, genes involved in the acute phase reaction and antioxidant genes in the liver in weeks 1, 4 and 7 of lactation were not different between the two groups of cows. The concentrations of α-tocopherol and the Trolox equivalent antioxidant capacity in plasma were not different between the two groups. However, the group supplemented with GTE showed significant reductions of some genes of the unfolded protein response(UPR) in week 1 and a trend of lower liver triacylglycerol(TAG) concentrations in the liver compared to the control group.Conclusions: This study shows that supplementation of GTE in dairy cows lowers the fat concentration in the milk but overall has no effect on the expression of inflammatory genes and the antioxidative status in dairy cows during early lactation. The finding of reduced m RNA levels of genes involved in the UPR at week 1, however, supports other results showing that supplementation of polyphenols could prevent the development of ER stress in the liver of cows during early lactation. The finding of a tendency towards a reduced TAG concentration in the liver of cows supplemented with GTE might be due to an improved energy balance in these cows.

Stable Isotopes in Precipitation in Xilin River Basin,Northern China and Their Implications

Under the increasing pressure of water shortage and steppe degradation, information on the hydrological cycle in steppe region in Inner Mongolia, China is urgently needed. An intensive investigation of the temporal varia-tions of δD and δ^18O in precipitation was conducted in 2007-2008 in the Xilin River Basin, Inner Mongolia in the northern China. The 6D and δ^18O values for 54 precipitation samples range from ＋1.1%o to -34.7%0 and -3.0%0 to -269%0, respectively. This wide range indicates that stable isotopes in precipitation are primarily controlled by differ-ent condensation mechanisms as a function of air temperature and varying sources of vapor. The relationship between δD and δ^18O defined a well constrained line given by δD = 7.896180 ＋ 9.5, which is nearly identical to the Meteoric Water Line in the northern China. The temperature effect is clearly displayed in this area. The results of backward tra-jectory of each precipitation day show that the vapor of the precipitation in cold season （October to March） mainly originates from the west while the moisture source is more complicated in warm season （April to September）. A light precipitation amount effect existes at the precipitation event scale in this area. The vapor source of precipitation with higher d-excesses are mainly from the west wind or neighboring inland area and precipitation with lower d-excesses from a monsoon source from the southeastern China.

Spatial variation of stable isotopes in different waters during melt season in the Laohugou Glacial Catchment, Shule River basin

To evaluate isotopic tracers at natural abundances by providing basic isotope data of the hydrological investigations and assessing the impacts of different factors on the water cycle, a total of 197 water samples were collected from the Laohugou Glacial catchment in the Shule River basin northwestern China during the 2013 ablation seasons and analyzed their H- and O-isotope composition. The results showed that the isotopic composition of precipitation in the Qilianshan Station in the Laohugou Glacial catchment was remarkable variability. Correspondingly, a higher slope of δ180-δD diagram, with an average of 8.74, is obtained based on the precipitation samples collected on the Glacier No.la, mainly attributed to the lower temperature on the glacier surface. Because of percolation and elution, the bottom of the firn the isotopic composition at is nearly steady. The 6180 /altitude gradients for precipitation and melt water were -o.37%o/100 m and -o.34%o/100 m, respectively Exposed to the air and influenced by strong ablation and evaporation, the isotopic values and the 6180 vs 6D diagram of the glacial surface ice show no altitudinal effect, indicating that glacier ice has the similar origins with the firn. The variation of isotopic composition in the melt water, varying from -l0.7‰ to -16.9‰ （8180） and from -61.1%o to -122.1%o （6D） indicates the recharging of snowmelt and glacial ice melt water produced at different altitudes. With a mean value of -13.3‰ for 8180 and -89.7‰ for 8D, the isotopic composition of the stream water is much closer to the melt water, indicating that stream water is mainly recharged by the ablation water. Our results of the stable isotopic compositions in natural water in the Laohugou Glacial catchment indicate the fractionations and the smoothing fluctuations of the stable isotopes during evaporation, infiltration and mixture.

Modified Woods-Saxon Potential for Heavy-Ion Fusion Reaction

A modified Woods-Saxon （MWS） potential is proposed for describing nucleus-nucleus interaction based on the Skyrme energy-density functional approach. Fusion barriers for a large number of fusion reactions from light to heavy systems can be described well with this potential. The suitable incident energies for fusion reactions leading to superheavy nuclei are also explored. It seems to us that the MWS potential is useful for selecting the suitable incident energies for fusion reactions for producing super-heavy nuclei.

Neurocode-Tracking Based on Quantitative Fast Dynamic EEG Recording in Combination with Eye-Tracking

Information processing within the brain relies on electro-chemical features. Electric events are accessible by recording of the EEG. These electric oscillations might be regarded as a neuronal code carrying information on important motor, cognitive and emotional events. A new approach of quantitative assessment of very short time epochs of 364 ms has been developed on the base of particularly defined frequency ranges and called “Neurocode-Tracking”. The new method was technically validated by the use of a signal generator and was found to correspond to classical quantitative EEG analysis except for some smudging during the transition from one frequency range to the next. Real data from a subject were obtained during relaxation and performance of three mental tasks. Data were time averaged for 180 s using the classical method and compared to data averaging during 16.4 s. Results were nearly identical with respect to spectral signatures showing the expected midline frontal theta increases during performance of three cognitive tests but not during relaxation. Collection of very short time epochs of 728 ms duration confirmed task dependent frontal theta increases, most prominent during calculation performance test (CPT), less during d2-concentration and memory test, none during relaxation. Finally, the new technique was combined with eye-tracking. Capture of the EEG mapping video of Neurocode-Tracking and synchronization with the gaze overlay video by starting recording with an audio signal (gong) allowed a match of gazes precisely with the corresponding electric events. Use of this technical combination in research will hopefully lead to a new understanding of spectral signatures of electric activity called enkephaloglyphs.

Fibroblast growth factor 21 in dairy cows:current knowledge and potential relevance

Fibroblast growth factor 21(FGF21)has been identified as an important regulator of carbohydrate and lipid metabolism,which plays an important role for metabolic regulation,particularly under conditions of energy deprivation or stress conditions.Dairy cows are subjected to a negative energy balance and various kinds of stress particularly during the periparturient phase and during early lactation.It has been shown that the plasma concentration of FGF21 in dairy cows is dramatically increased at parturition and remains high during the first weeks of lactation.This finding suggests that FGF21 might exert similar functions in dairy cows than in other species,such as mice or humans.However,the role of FGF21 in dairy cows has been less investigated so far.Following a brief summary of the previous findings about the function of FGF21 in humans and mice,the present review aims to present the current state of knowledge about the role of FGF21 in dairy cows.The first part of the review deals with the tissue localization of FGF21 and with conditions leading to an upregulation of FGF21 expression in the liver of dairy cows.In the second part,the influence of nutrition on FGF21 expression and the role of FGF21 for metabolic diseases in dairy cows is addressed.In the third part,findings of exogenous FGF21 application on metabolism in dairy cows are reported.Finally,the potential relevance of FGF21 in dairy cows is discussed.It is concluded that FGF21 might be of great importance for metabolic adaptation to negative energy balance and stress conditions in dairy cows.However,further studies are needed for a better understanding of the functions of FGF21 in dairy cows.

Factors Influencing Pleural Effusion after Fontan Operation:an Analysis with 95 Patients

Objective To investigate the association between preoperative,operative,and postoperative factors and persistent pleural effusion after the extracardiac Fontan procedure. Methods Ninety-five consecutive patients diagnosed with univentricular heart underwent extracardiac connection using Gore-Tax conduits at the Department of Children’s Heart Centre,Justus-Liebig-University Giessen in Germany from June 1996 to July 2007. The outcome measures were duration and volume of chest tube drainage after surgical intervention. The investigated factors included age and weight at the time of operation,anatomical diagnosis,preoperative oxygen saturation,mean pulmonary artery pressure,ventricular end-diastolic pressure,fenestration,cardiopulmonary bypass time,conduit size,postoperative pulmonary artery pressure,administration of angiotensin-converting enzyme inhibitors,and postoperative infection. Associations between these factors and persistent pleural effusion after the extracardiac Fontan procedure were analyzed. Results Every patient suffered postoperative effusion. The median duration of postoperative chest tube drainage was 9 days (range,3-69 days),and the median volume was 12 mL·kg-1·d-1 (range,2.0-37.5 mL·kg-1·d-1). Thirty-seven (38.9%) patients had pleural drainage for more than 15 days,and the volume in 35 (36.8%) patients exceeded 25 mL·kg-1·d-1. Nineteen (20%) patients required placement of additional chest tubes for re-accumulation of pleural effusion after removal of previous chest tubes. Fifteen (17.8%) patients were hospitalized again due to pleural effusion after discharge. The median length of hospital stay after the operation was 14 days (range,4-78 days). Multivariate analysis results showed that non-fenestration,low preoperative oxygen saturation,and postoperative infections were independent risk factors for prolonged duration of pleural drainage (P<0.05). Long cardiopulmonary bypass time,non-fenestration,small conduit size,and low preoperative oxygen saturation were independent risk factors for excessive volume of pleural drainage (P<0.05).Conclusions For reduing postoperative duration and volume of pleural drainage following Fontan procedure,it seems to be important to improve the preoperative oxygen saturation,use large size of conduit,shorten cardiopulmonary bypass time,and make fenestration during the operation,as well as avoid postoperative infections.

Neutron Skin Thickness of Nuclei and Effective Nucleon-Nucleon Interactions

The Skyrme energy density functional is applied to study the ground state properties of a series of finite nuclei. The charge rms radii, neutron rms radii, and the neutron skin thickness for some nuclei are calculated and compared with the experimental data. The constraint on the effective interactions, especially, the density dependence of the isospin-dependent. part of Skyrme interactions is extracted by the data of neutron skin thicknesses of ^208Pb and isotopes of Sn.

Psychophysiological Effects of Sideritis and Bacopa Extract and Three Combinations Thereof—A Quantitative EEG Study in Subjects Suffering from Mild Cognitive Impairment (MCI)

Mild cognitive impairment (MCI) is regarded as a transitional stage during the development of Alzheimer’s disease. Diagnosis of MCI can be obtained by the questionnaire “DemTect” in German speaking countries. Quantitative assessment has been successfully performed using psychometric testing concomitantly with quantitative EEG recording. The present investigation aimed at the possible treatment of MCI with two botanicals, namely extracts from Sideritis scardica (500 mg) or Bacopa monnieri (320 mg) and three combinations thereof using this method in order to find a new treatment. The performance of the d2-test, an arithmetic calculation test (CPT) and a memory-test revealed better performance for the d2-test only in the presence of Sideritis extract or the combinations with Bacopa extract. Quantitative EEG assessment during the different experimental conditions showed massive differences between both extracts. Whereas Sideritis extract and its combination with a low amount of Bacopa extract (160 mg) induced increases of spectral power in fronto-temporal brain areas, Bacopa and the combination of Sideritis with high amounts of Bacopa extract produced attenuation of all waves except for delta in fronto-temporal brain areas. These differences were also documented by quantitative EEG maps in comparison to Placebo. A different action of both extracts was confirmed by discriminant analysis, where Sideritis extract and its combination with low Bacopa grouped together quite at distance to Bacopa and the combination of Sideritis with high Bacopa. A combination of Sideritis extract with a low amount of Bacopa should be tested with daily repetitive dosing for at least 4 weeks as a consequence.