Because of considerable between-study heterogeneity and variable quality of ApoE assay, our meta-analysis should be interpreted with caution. In fact, studies included in our meta- analysis varied widely with respect to ApoE assay, which may affect the consistency of outcomes between laboratories. However, there was no standardization of sample handing protocols in ApoE measurement. The differences in the assay procedure may cause variation of ApoE levels measured in different studies. The V.B.Gupta 2011 study  reported highest mean values of ApoE levels, which is almost 5 fold higher than the Arijen J.C. 1998 study . Therefore, all studies in our meta-analysis used plasma or serum to measure ApoE levels, however, no studies used exactly the same assay method, further contributing to subject heteroge- neity. Publication bias also seemed to influence our present results supporting the lower ApoE levelsin AD. Asymmetrical missing data on the right side of the funnel plot suggested that studies failing to find the association between lower ApoE levels and AD Figure 2. Forest plots for ApoE levelsin AD and healthy controls in included studies. AD, Alzheimer’s disease; SD, standard deviation; CI, confidence interval.
Diagnostic biomarkers, also called predictive biomarkers (targets for diagnostic intervention), are identified by characterizing key mutations and molecular pathways involved in tumor development and proliferation. They help optimize therapy decisions by providing information about the likelihood of a response to a chemotherapeutic intervention . Prognostic biomarkers are assigned to a specific tumor type by determining the occurring polymorphism, mutation or the change in DNA methylation or gene expression, or by detecting the presence of specific miRNA molecules or CTCs in the peripheralblood. They enable the monitoring of the advances in anti-cancer therapy, the assessment of the stage of the tumor and its potential malignancy, as well as the prognosis ofdisease remission in every case individually . Treatment and prevention biomarkers are subgroups that require more accurate molecular analysis to guide individual therapy by identifying patients with different outcome risks (such as recurrence of the disease) .
AD, HC and MCI criteria used to recruit subjects in this study have been described in our previous works[20,21]. Cognitive assessment was performed according to the routines of the Memory Clinic of Fundació ACE as described elsewhere. Briefly, MCI subjects fulfilled the Petersen’s diagnostic criteria including subjective memory complaint, normal general cognition, preserved performance in activities of daily living, absence of dementia and a measurable impairment in memory function, with or without deficit in other cognitive domains. All MCI subjects had a CDR rating of 0.5. Based on the Wechsler Memory Scale-III (WMS-III) of NBACE battery an impaired delayed verbal recall for which recognition testing did not improve performance, classified MCI amnesic subjects as having an “Encoding/Storage” pattern of memory loss. Diagnosis of AD individuals followed NINCDS-ADRDA criteria[39,40], a CDR of 1 point or more and a Mini-Mental State Examination (MMSE) below 24 points. Healthy controls were cognitively normal when evaluated in the Fundació ACE, had MMSE scores of at least 26 (considering that the MMSE cut-off has been demonstrated to be <25 in the Spanish population ) , and also had a normal neuroimaging MRI profile.
Three experimental methods were identified to measure global DNA methylation levelsin the present meta-analysis: Three studies used %5-mC; seven studies used LINE-1 with pyrose- quencing (6 studies) and a modified version of the combined bisulfite restriction analysisof the LINE retrotransposable element 1(LRE1) sequence (1 study); one study analyzed the methyl acceptance capacity of DNA using [3H-methyl] S-adenosylmethi- onine. Subgroup analysisin % 5-mC method was homogeneous. However, LINE-1 method and bladder cancer, which was the only cancer type that was analyzed in more than 3 studies, remained significantly heterogeneous. Many analytical methods have been developed to determine DNA methylation levels [48–51]. Methyl acceptance assay is based on the capacity of radio-labeled methyl incorporation into DNA, thus high methyl group incorporation indicates lower levelsof DNA methylation. However, high day-to- day variation and inaccurate DNA concentration due to the difficulty of mixing genomic DNA solution homogenously have been observed . The direct measurement of percentages of 5- methylcytosine was used in many epidemiological studies to estimate global DNA methylation contents using reversed-phase high-performance liquid chromatography (HPLC), liquid chro- matography (LC)-mass spectrometry, or high-performance capil- lary electrophoresis (HPCE). These methods are highly quantita- tive and reproducible, but they are not suitable for epidemiological studies with large sample size and high amount of DNA are required to yield reliable results. Introduction of sodium bisulfite conversion of genomic DNA has revolutionized the analytical methods in methylation analysis . In addition, pyrosequencing which is a high-throughput and accurate method is currently available . Repetitive sequences comprise large portions of the human genome and are CpG-rich [53,54]. Repetitive genomic regions such as LINE-1 and Alu are usually methylated in somatic tissues . Therefore, pyrosequencing with bisulfite-treated DNA
Previous researches have shown that the presence of the e4 allele of Apo E is strongly associated with the risk of atherosclerosis  and Alzheimer’s disease . Our present meta-analysis indicates that Apo e4 allele is a risk factor for the development of gallstones. Due to different affinity to its receptors, Apo E can eventually influence hepatic cholesterol processing by enhancing cholesteryl ester hydrolysis , thus increasing cellular free cholesterol availibity for biliary secretion. There’s also evidence that Apo e4 leads to more intracellular release of free cholesterol from internalized triglyceride-rich particle cholesteryl ester than does e3 . Our meta-analysis give us a clear conclusion that e4 allele is a risk factor of gallbladder stone disease, especially in elder people and Chinese people. In Chinese studies, the result that e4 is a risk factor seems more obvious, although this result is not supported by every Chinese study. We noticed that 7 of 16 qualified studies are published in Chinese in this meta-analysis. Thus, ethnic diversity may affect the process of gallstone formation. To insure the validity of the overall conclusions, we divided the studies into Chinese and non-Chinese. There’s no significant change for the association of e4 allelic model and e4 dominant model, though the magnitude was strengthened for Chinese. Due to the limitation of the number of studies published, our analysis would not be able to include all ethnicities so far. However, we could not exclude the possibility that some negative Figure 2. Pooled random-effects-based odds ratio of developing GSD for e2 versus e3.
LRPPRC, TCEA1). From those, PRPF4B, a pre-mRNA processing factor, NAP1L1, a nucleo- some assembly protein, and TCEA1, a transcription elongation factor, are involved in nucleic acid metabolism. Two of the genes identified were also altered in PD patients upon Deep Brain Stimulation (DBS) . One of the genes, LRRC8C, is a component of the volume-regulated anion channel and was also identified in an exon array study in PD leukocytes  and in mouse models of the disease . The other, HNRPDL, belongs to the family of heterogeneous nuclear ribonuclearproteins and is involved in RNA processing. From 10 genes found deregu- lated in the prefrontal cortex of PD patients, 2 were also differentially deregulated between slow and rapid progression patients . These were RNF138, an E3 ubiquitin protein ligase, and SEC24B, involved in vesicle trafficking. Another important vesicular trafficking gene, VAMP1, was also deregulated in our dataset and in the susbtantia nigra of PD patients . A meta-analysis study on gene sets that combined data from several expression studies in periph- eral and brain cells, revealed a major involvement of mitochondrial genes and bioenergetics changes in PD pathology . Although PPARGC1A, suggested as a potential therapeutic tar- get in PD, was not detected as differentially expressed in this study, our analysis revealed enrichment in genes involved in mitochondrial processes. Remarkably, we identified 42 genes (S7 Table) that were also deregulated in brain tissue from MPTP-treated mice, an established model of PD . The common genes were mostly involved in nucleic acid processing, immune response, mitochondria, and metal ion transport. Additionally, a microarray study using SH-SY5Y cells treated with MPP + reported strong deregulation genes involved in tran- scription . Therefore, genes controlling nucleic acid metabolism, immune response and mitochondrial processes may be detrimental in dopaminergic cell death and disease progression.
1. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, et al. ACC/AHA Guidelines for the Management of Patients with Peripheral Arterial Disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society for Vascular Medicine and Biology, and the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arteril Disease). J Am Coll Cardiol. 2006;47(6):1239-312.
Regarding the third objective, the results in this current work show, for the first time, the expression of the Aβ-scavengers TTR, GLS and NEP in the human CP. Transthyretin (TTR) mRNA expression levels were significantly upregulated between control group and Braak stage II (p< 0.0001). TTR is one of the main enzymes secreted by CP where its main function is to transport thyroid hormones, and also possesses high ability to bind Aβ peptides in the CSF and, therefore, to decrease the levelsof Aβ in the brain (Schwarzmen et al., 1996; Ciccone et al., 2016). TTR expression levels also showed statistical difference between Braak stage I and Braak stage II (p< 0.0001), and also between the Braak stage II and Braak stages III and IV/V (p< 0.0001). TTR results showed a subtle upregulation between control group and Braak stage I, although not statistically different, followed by an abrupt increase in mRNA levelsin Braak stage II. The sudden decrease of TTR expression in the stage III, relative to stage II, corresponding to the mild cognitive impairment (MCI) clinical phase, is in agreement with a suggestion of previous authors that in late onset AD patients it occurs a decrease in TTR levelsin the CSF resulting in an increase in the Aβ plaque formation (Alshehri et al., 2015). The same behavior occurs in stage IV/V, corresponding to an advanced AD stage. Further analysisof TTR protein levels is needed to verify if they are as increased as its mRNA levels.
Thus obtained residual data can be used for regression model- ing. However, a question arises if these data contain important information or they are simply a random noise. In the second case the modeling would be certainly unsuccessful. To answer this question some statistical tests can be applied. One of them is the non-parametric runs-test that verifies a randomness hypothesis for a binary-valued data sequence; in case of time-series, the signs of the residual values of the time-series. Another test as- sumes, that if the residual component is of random nature then it is characterized by a low autocorrelation coefficient. In particular, the autocorrelation of the first order is tested (i.e. for time lag equal to 1), using the Durbin-Watson test. The description of the both tests can be found in ).
CSDH mainly occurs in the elderly. The incidence rate in the population over 65 years of age is 7-13/10 million, and the rate in people over 70 years of age is 17-58/10 million (26). However, the CSDH incidence in the general popula- tion is only approximately 1-3/10 million (26,27). Aging can lead to a reduction in the number of EPCs in circulation and a weakening of their function (28-30). Thus, we can infer that there are both lower numbers of EPCs and related dysfunction in the peripheralbloodof CSDH patients. In this study, we measured the peripheralbloodlevelsof EPCs in 30 CSDH patients and in 30 healthy controls. The results showed that the level ofperipheralblood EPCs in CSDH patients was significantly lower compared to the control group. Meanwhile, we found that the change in the levelsof EPCs in recurrent patients between postoperation and preoperation was significantly lower than the level in non- recurrent patients. These data indicate that a higher consumption of EPCs in CSDH patients and decreased EPC levels may lead to a reduced capacity to repair the endothelium, increasing the risks associated with the occurrence and recurrence of CSDH. Thus, we propose that a pharmacological means of increasing the number of circulating EPCs could help to reduce the recurrence rate of CSDH.
Abstract. It has been established that the frequency of polymorphic variants of GSTM1 "+" genes was 43.70 % and the frequency of polymorphic variants of GSTM1 "-"genes made up 56.30 % correspondingly in all newborns in the region, without division into ecological zones. Speaking about GSTT1genes the frequencies of polymorphic variants of GST 1«+» and GST 1«-» were 80.67 % and 19.33 % correspondingly. Positive micro-nucleus test was found in none of the carriers of GST 1«-» polymorphic variant. GSTT1«+» allelic variant was found in all newborns with negative micro-nucleus test. 78.38 % predominance in associations of GSTM1«+»/GSTT1 genotypes is characteristic of newborns with negative micro-nucleus test. Our studies have shown the diagnostic value of molecular-genetic testing in conjunction with the micro-nucleus testing for predictin g newborns‟ genome sensitivity to total exposure of environmental factorsй
smaller prevalence of cardiovascular diseases, and a smaller proportion of cardiovascular deaths showed no significant association of cTn with cardiovascular mortality. cTn is specific for identifying myocardial cell injury. The elevation of cTn in CKD patients may result from microembolization (54), non-ischemic cardiomyopathy or left ventricular hyper- trophy (55-57). Therefore, cTn elevation was found to be strongly associated with increased cardiovascular mortality in CKD patients. The association of cTn elevation with increased all-cause mortality might be the result of a large proportion of cardiovascular deaths in CKD patients. (3) In the population with fewer cardiovascular risk factors, as we found in the subgroup analysis, cTn elevation might not be a predictor. One possible explanation is the decreased renal clearance or degradation of cTn in CKD patients, but more mechanisms should be explored. According to the present results, screening for cardiovascular diseases and performing more active treatment may improve patient outcomes is suggested when serum levelsof cTn are elevated in patients with CKD.
he same cannot be said about lactate from peripheral puncture. he reason why Lper does not relect systemic perfusion as well as Lcen does is possibly related to interference from regional perfusion of the upper limb where the collection took place. Attention was paid to timely collec- tion of this material, and a tourniquet was used in the upper limb for up to two minutes. As expected, the median value of Lper (16.2 mg/dl) was higher than the median lactate value collected from the other sites (Lcen and Lart, 14.0 and 14.0, respectively), since the circulation in situations of septic status is deviated towards the critical organs. Moreover, larger limits of agreement between Lart and Lper were seen in the subgroup of patients with septic shock, thus suggesting that peripheral vasocon- striction due to vasopressors can further impair the relationship between Lper and the overall perfusion. It is worth noting that even in this sce- nario, Lcen performed well. In the control group, which was composed of healthy volunteers, the correlation between the Lart and Lper values was higher, possibly because of the normal conditions of tissue perfusion and homogeneity present in healthy individuals. Unfortunately, it was not possible to evaluate the relationship with Lcen among the healthy controls because of the absence of a central venous catheter.
The clinical examination included anthropometric measurements. Body mass index, determined by the weight (kilograms) divided by the square of the height (meters); waist circumference was measured at the umbilicus level. Blood pressure was taken after 5 min- utes rest in the sitting position, with an automatic device (Omron model HEM-712C, Omron Health Care, Inc, USA). The mean of the last 2 measurements was used to express systolic and diastolic blood pres- sure values. Fasting blood samples were taken for several tests. Non-diabetic and self-reported diabetic subjects with fasting capillary glucose <200 mg/dL, screened with glucose-oxidase strips, were submitted to a 75-gram oral glucose tolerance test.
Optimisation of the turbine mixer’s performance during the preparations of the sand mix still remains an important issue as this mixer type is now in widespread use. Monitoring techniques of the system sand mixing include the analysisof electric power demand by the mixer’s drive based on measurements of power components. This study shows the operating characteristics of turbine mixers as the function of electric power demand by the drive system.
In conclusion, the combined predictive value of differentially expressed genes inperipheralblood correlates with the extent of coronary atherosclerosis. Importantly, the expression pattern of the same genes is also correlated with the extent ofdiseasein atherosclerotic aortas. While these findings need prospective validation in further populations, our findings also suggest that gene expression profiles might represent a novel and promising non-invasive test to assess the presence and extent of coronary artery disease. Although the extent of angiographic disease is a strong predictor of clinical outcome, further studies in larger and unselected populations will also be needed to examine the Figure 2. Partial least squares plot per cohort. Results of the partial least squares regression analysis with 160 genes applied separately to each of the three cohorts (A) ‘‘Matched Men’’ (B) ‘‘Unmatched Men’’ and (C) ‘‘‘Unmatched Women’’. Models were each time constructed in two cohorts and then tested in the third cohort. Individual patients are ordered by their CAD-Index. Labels represent the individual CAD-Index. Controls (full line) have all CAD-Index 0, and the CAD-Index of cases (dotted line) increases from 23 up to 100. While the controls remain quite stable in the range of -2 standard deviations, the t1-scores increase with increasing CAD-Index (t1 indicates the t1 score vector result from the PLS analysis).
On the other hand there is no foundation for the supposi- tion that, in our casuistic, the motor features of PD, which fre- quently affect the daily activities, could have caused an impact on the Pfeffer questionnaire scores increasing the diagnosis of dementia, since this questionnaire was not a fundamental ele- ment in this diagnosis.
cytofluorimetric assay. Obtained data processing was conducted with the use of parametric and non-parametric methods of biostatistics by programs EXEL-2003 ® and Biostatistics 4.03. Results and discussion. The data obtained indicates the disbalance in their system, which above all is characterized by a considerable level increase of pro-inflammatory IL-6 up to 134,09 ± 22,72 pg/ml (control level 11,83 ± 1,64 pg/ml) and Тn relatТon to moderate growth oflevelsof IL-2 а TNF-α at subacute myocarditis. Such increase in level of IL-6 can take place due to the change of pro-inflammatory effect to anti- inflammatory in a remote period. In a complex with IL-10 IL-6 limits the secretion of TNF-α. For tСТs reason, Тts level remains high at chronic herpesvirus myocarditis and exceeds the level of the control group by over 8 times. In addition, there is an increase oflevelsof anti-
This was a cross-sectional descriptive study approved by the Ethics Committee of the Federal University of Minas Gerais under record CAAE-0399.0.203.000 11. We studied 20 consecutive adult patients, of both genders, with a diagnosis of schistosomiasis that were referred to undergo surgical treatment of SPH. All patients were diagnosed with hepatosplenic schistosomiasis confirmed by parasitological examination of stool and rectal biopsy positive for Schistosoma mansoni eggs, abdominal ultrasound and liver biopsy during surgery, which revealed Symmers-Bogliolo fibrosis 1,19 .
The celiac disease is an autoimmune gastrointestinal disorder caused by gluten from wheat, rye or barley. In genetically predisposed persons, gluten induces the immune-mediated inflammation of small intestinal mucosa. Histological lesions include intraepithelial lymphocytosis, crypt hypertrophy and villous atrophy, resulting in malabsorption of micro- and macronutrients. The only treatment for celiac patients is a permanent gluten-free diet (GFD). Reactive oxygen species (ROS) and oxidative stress are strongly associated with the celiac disease. Glutathione (GSH) is a main detoxifier of endogenous and exogenous ROS in the intestine. In order to explain the role of glutathione redox cycle in celiac patients, we examined the activities of GSH- related antioxidant (AO) enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the concentration of GSH in small intestinal biopsies and peripheralbloodof children affected by the celiac disease. The concentration of lipid hydroperoxides (LOOH) as markers of oxidative damage was measured in the same samples. The results clearly demonstrate a significant malfunction of GSH redox cycle with a concomitant decrease in the capacity to regenerate GSH and detoxify LOOH in celiac patients, even after several years of GFD. The oral administration of GSH and a diet rich in natural antioxidants, as well as appropriate dietary supplements, could be of great benefit to the patients.