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SUMMARY OBJECTIVE Monocyte count to HDL-C Ratio (MHR) and Fibrinogen to Albumin Ratio (FAR) have recently emerged as markers of inflammation in atherosclerotic diseases. Our goal was to investigate the relationships of MHR and FAR with the severity of carotid artery stenosis (CAS) in patients with asymptomatic carotid artery disease. METHODS This retrospective study consisted of 300 patients with asymptomatic CAS. Pre-angiographic MHR, FAR, and high-sensitive C-reactive protein (hsCRP) were measured. Carotid angiography was performed in patients with ≥50% stenosis on carotid ultrasonography. Patients were first split into 2 groups based on the degree of CAS and then tertiles (T) of MHR. RESULTS 96 patients had clinically insignificant CAS (

Currently, the most significant mediators of the systemic inflammatory response (SIR), specific to the development of critical states in sepsis, have the chaotic changes of concentrations in the blood. The solution to the problem is using integral indicators. A scoring scale of the SIR (0–16 points) is proposed based on the determination in the blood plasma of CRP, TNF-α, IL-6, IL-8 and IL-10. The scale was used in the survey of 167 patients with a diagnosis of sepsis (43 patients with sepsis according to definitions of “Sepsis-1 or 2” and 124 patients with sepsis according to the criteria of “Sepsis-3”); septic shock was verified in 31 cases and in 48 cases lethal outcomes were recorded. The association of SIR with critical complications of sepsis was revealed, especially under acute septic shock and in cases of a “second wave” (days 5–7) of critical complications. In contrast, prolonged/ subacute sepsis (more than 14 days) under tertiary peritonitis is characterised by a lesser dependence of the criticality of the state on the severity of SIR. The proposed scale is an open system and allows you to modify the range of used particular indicators that are compatible by pathogenetic and diagnostic significance. © 2020, Slovak Academy of Sciences. All rights reserved. The work was carried out within the framework of the IIP UrB RAS theme No АААА-А18-118020590108-7.

Recent studies have shown that increased circulating concentrations of fibroblast growth factor 21 (FGF21) are associated with obesity, metabolic disorder, and atherosclerosis. However the relationship between FGF21 and coronary artery disease (CAD) is controversial This study was planned to investigate the role of FGF21 in CAD development and CAD severity.Seventy-eight patients with stable angina pectoris (SAP) (lesion positive) and 40 control patients (lesion negative) with similar cardiovascular risk factors were included in the study. Serum FGF21 levels were measured by ELISA method. CAD severity was evaluated by using SYNTAX and GENSINI risk scores.FGF21 concentrations were found significantly higher in the SAP group than in the control group. [101.18 ± 141.62 vs. 47.93 ± 58.74 pg/mL; p = 0.03], no correlation was found between the SYNTAX (r = 0.146 and p = 0.134) and GENSINI (r = 0.211 and p = 0.084) scores with serum FGF21 levels. There was a negative relationship between serum FGF21 and serum HDL-C levels in correlation analysis (r = - 0.272; p = 0.026).The serum FGF21 levels are different between SAP and control patients. FGF21 is a marker for CAD diagnosis, but not for the evaluation of CAD severity.Poslednja istraživanja su pokazala da je pove}anje koncentracija u cirkulaciji fibroblastnog faktora rasta 21 (FGF21) praćeno sa gojaznošću, metaboličkim poremećajem i aterosklerzom. Međutim, odnos između FGF21 i koro narnog arterijskog oboljenja (KAO) je kontraverzan. U ovom izučavanju je planirano da se ispita uloga FGF21 u razvoju KAO kao i težina samog oboljenja.U izučavanje je uključeno sedamdeset osam pacijenata sa stabilnom anginom pektoris (SAP) (pozitivna lezija) i 40 kontrolnih pacijenata (lezija negativna) sa sličnim faktorima rizika. Nivoi serumskog FGF21 mereni su ELISA me todom. Težina KAO procenjivana je SYNTAX i GENSI faktorima rizika.Koncentracije FGF21 bile su značajno vi{e u grupi sa SAP nego u kontrolnoj grupi. [101,18 ± 141,62 vs. 47,93 ± 58,74 pg/mL; p = 0,03]. Nije utvrđena korelacija između SYNTAX (r = 0,146 i p = 0,134) i GENSI (r = 0,211 i p = 9,084) skorova sa nivoima serumskog FGF21. Nađen je negativan odnos između serumskog FGF21 i nivoa HDL-C u serumu primenom korelacione analize (r = - 0,272; p = 0,026).Nivoi FGF21 u serumu su različiti kod SAP i kontrolnih pacijenata. FGF21 je marker za dijagnostikovanje KAO, ali ne i za procenu težine KAO.

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PubMed Yılı: 2019 The relationship between sarcoidosis and malignancy is not clear yet. We retrospectively evaluated 131 sarcoidosis patients followed-up at the single Rheumatology center. The incidence of malignancies was investigated in this cohort. A total of 6 (4.6%) patients with malignancy were identified in our cohort of 131 patients with sarcoidosis. Hodgkin lymphoma (HL) was detected in three patients, followed by one patient with breast cancer, one patient with thyroid cancer and one patient with testicular cancer. All patients had chronic sarcoidosis with pulmonary involvement, and only 1 patient had acute sarcoidosis with Löfgren's syndrome. HL developed concomitantly with sarcoidosis in one patient while other two patients developed disease before and after sarcoidosis diagnosis. Two patients with solid tumors developed malignancy years before sarcoidosis diagnosis, while one patient developed thyroid cancer during sarcoidosis follow-up. All 6 sarcoidosis–malignancy patients survived after six year years follow up. We found low incidence of malignancy in patients with sarcoidosis in our small cohort. The sarcoidosis–malignancy relationship can only be a coincidence and/or can be explained by a common pathogenesis. New prospective studies involving large patients series are needed in this regard. © 2019 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología WOS:000608393600010 31153889

Stunting, defined as height-for-age Z score equal to or lower than -2, is associated with increased childhood mortality, cognitive impairment, and chronic diseases. The aim of the study was to investigate the relationship between linear growth, intestinal damage, and systemic inflammation in infants at risk of stunting. We followed up 78 infants aged 5-12 months living in rural areas of Peru for 6 months. Blood samples for biomarkers of intestinal damage (intestinal fatty-acid-binding protein [I-FABP] and zonulin) and systemic inflammation (interleukin-1beta, interleukin-6, tumor necrosis factor alpha [TNF-alpha], soluble CD14, and lipopolysaccharide-binding protein [LBP]) and fecal samples for microbiome analysis were collected at baseline and closure of the study. The children's growth and health status were monitored through biweekly home visits by trained staff. Twenty-one percent of the children became stunted: compared with non-stunted children, they had worse nutritional parameters and higher levels of serum I-FABP at baseline. The likelihood of becoming stunted was strongly associated with an increase in sCD14 over time; LBP and TNF-alpha showed a trend toward increase in stunted children but not in controls. The fecal microbiota composition of stunted children had an increased beta diversity compared with that of healthy controls throughout the study. The relative abundance of Ruminococcus 1 and 2, Clostridium sensu stricto, and Collinsella increased in children becoming stunted but not in controls, whereas Providencia abundance decreased. In conclusion, stunting in our population was preceded by an increase in markers of enterocyte turnover and differences in the fecal microbiota and was associated with increasing levels of systemic inflammation markers.

Purpose: Secreted frizzled-related protein 4 (SFRP4) is an adipokine involving in apoptotic process during ovulation and energy metabolism. Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder associated with insulin resistance and impaired oocyte maturation as well as apoptotic dysfunctions through oocyte development. Our aim was to determine whether there was an alteration in levels of SFRP4 and if there was an association between metabolic or hormonal parameters and SFRP4 in women with PCOS. Methods: We enrolled 80 subjects with PCOS and 80 age- and body mass index (BMI)-matched subjects with normal menstrual cycle into current case–control study. Metabolic and hormonal parameters of enrolled subjects were determined. Circulating SFRP4 levels were measured with ELISA method. Results: We found that circulating SFRP4 levels were elevated in women with PCOS with respect to controls (5.87 ± 1.91 vs. 3.72 ± 1.29 ng/ml, P < 0.001). We also found a positive association between SFRP4 and insulin resistance, androgens, ovarian follicular number or ovarian volume in women with PCOS. Binary logistic regression analysis revealed that subjects with the highest tertile of SFPR4 levels displayed increased possibility of having PCOS risk compared to those subjects with the lowest tertile of SFRP4 levels. Conclusions: Increased SFRP4 levels were not only associated with higher possibility of having PCOS but also related to insulin resistance, hyperandrogenism, ovarian follicular number and ovarian volume, suggesting that SFPR4 could be a player in different pathophysiologic pathways of PCOS. © 2019, Italian Society of Endocrinology (SIE).

Background/Aim: Extracellular S100b effects are mediated by the receptor for advanced glycation end products (RAGE), which is the S100b membrane receptor. RAGE belongs to the immunoglobulin superfamily of cell surface molecules and serves as a multiligand receptor and is expressed in high abundance by alveolar type I (AT-I) cells in adult pulmonary tissue. This study aimed to provide an insight into the association between the severity of COVID- 19 disease and serum S100b levels during admission to the emergency department (ED). Patients and Methods: A total of 64 patients (34 mild cases; 30 severe cases) were diagnosed with COVID-19 pneumonia and 30 healthy volunteers were admitted to study. Serum S100b levels were measured by using enzymle linked immunoassay method from blood serum samples. Results: Serum S100b levels showed a significantly higher mean value in mild and severe disease cohorts than in healthy controls (p=0.036 and p=0.028 respectively). Receiver operating characteristic (ROC) analysis indicated greater area under the curve (AUC) for serum S100b levels of the COVID-19 patients (AUC=0.663, 95% CI=0.541-0.785; p=0.014). In addition, serum S100b concentration was measured as 151.7 ng/ml at 79.3% sensitivity and 51.7% specificity (p=0.014). Serum S100b protein levels can serve as a valuable clinical marker in establishing diagnosis of patients. Though not useful in identifying different stages of COVID-19 infection, serum S100b concentration along with other known markers can be utilized to reliably predict clinical severity along with other clinical parameters. © 2021 International Institute of Anticancer Research. All rights reserved.

There is an accumulation in studies which strive to reveal zonulin's potential role in mental disorders. To date, one cross-sectional recent study examined zonulin in patients with bipolar disorders (BDs); however, its role still remains vague due to high fluctuation. Our aims are to determine plasma zonulin levels in exacerbation and treatment response periods, and to examine the associations between zonulin and symptom severity in BD. 30 patients with BD type I and 29 healthy controls participated in the current study. Socio-demographic form, Young Mania Rating Scale (YMRS), and Hamilton Depression Rating Scale (HAM-D) were administered. Enzyme-linked immune assay (ELISA) method was used to measure the plasma zonulin levels of the participants. The groups did not differ in plasma zonulin-level comparisons. Plasma zonulin did not alter between the exacerbation and treatment response periods of the patients. Besides, no associations were found between plasma zonulin-level and disease symptoms. Intestinal barrier integrity was not found to be altered among patients with BD type I. The lack of alterations in plasma zonulin level between different periods may be attributable to several factors. One possible factor might be the ELISA method which can detect other proteins (e.g., properdin) rather than zonulin. Therefore, it might fail to indicate direct observation of intestinal permeability. However, future study designs with more accurate estimation of zonulin in a larger sample may provide a different perspective on intestinal permeability's possible role in BD etiology. Celal Bayar Üniversitesi (2018-225)

Background/Aim: A novel human coronavirus, named SARS-COV-2, has recently caused thousands of deaths all around the world. Endoplasmic reticulum (ER) stress plays an important role in the development of diseases. Patients and Methods: We aimed to to investigate the relationship between ER stress markers in patients infected with SARS-COV-2 and patients with pneumonia. A total of 9 patients (4 patients diagnosed with pneumonia and 5 patients diagnosed with SARS-COV-2 infection) who admitted to the emergency Department with symptoms of pneumonia and SARS-COV-2 were included in the study. A total of 18 healthy individuals without any known chronic or acute disease and drug use were included as the healthy control group. Serum human glucose regulated protein 78 (GRP78), serum human C/EBP homologous protein (CHOP) and serum human phospho extracellular signal regulated kinase (PERK) levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: GRP78 levels were found to be significantly higher in SARS-COV-2 positive cases compared to individuals in other groups. Serum GRP- 78 level median value was statistically significantly higher in SARS-COV-2-positive group compared to the other groups (p=0.0003). Serum PERK level was statistically significantly higher in SARS-COV-2-positive pneumonia cases (p=0.046). Conclusion: An association was shown between GRP78 and SARS-COV-2 infection. Although a small number of patients was investigated, these results will be important and guide future treatments of SARS-COV-2. © 2020 International Institute of Anticancer Research. All rights reserved.

The blood hormone erythropoietin (EPO), upon binding to its receptor (EpoR), modulates high-fat diet-induced (HFD-induced) obesity in mice, improves glucose tolerance, and prevents white adipose tissue inflammation. Transgenic mice with constitutive overexpression of human EPO solely in the brain (Tg21) were used to assess the neuroendocrine EPO effect without increasing the hematocrit. Male Tg21 mice resisted HFD-induced weight gain; showed lower serum adrenocorticotropic hormone, corticosterone, and C-reactive protein levels; and prevented myeloid cell recruitment to the hypothalamus compared with WT male mice. HFD-induced hypothalamic inflammation (HI) and microglial activation were higher in male mice, and Tg21 male mice exhibited a lower increase in HI than WT male mice. Physiological EPO function in the brain also showed sexual dimorphism in regulating HFD response. Female estrogen production blocked reduced weight gain and HI. Targeted deletion of EpoR gene expression in neuronal cells worsened HFD-induced glucose intolerance in both male and female mice but increased weight gain and HI in the hypothalamus in male mice only. Both male and female Tg21 mice kept on normal chow and HFD showed significantly improved glycemic control. Our data indicate that cerebral EPO regulates weight gain and HI in a sex-dependent response, distinct from EPO regulation of glycemic control, and independent of erythropoietic EPO response.

Pancreatic cancer decreases survival time and quality of life because of drug resistance and peripheral neuropathy during conventional treatment. This study was undertaken to investigate whether alpha v beta 3 integrin receptor antagonist compounds NDAT and XT199 can suppress the development of cisplatin resistance and cisplatin-induced peripheral neuropathy in an orthotopic pancreatic SUIT2-luc cancer cell mouse model. Anticancer effects of these compounds and their combination with cisplatin were assessed in this tumor mouse model with bioluminescent signaling and histopathology, and a cytokine assay was used to examine expression of inflammatory cytokines IL-1 beta, IL-6, IL-10, and TNF-alpha from plasma samples. To determine the neuroprotective effects of the compounds on cisplatin-induced peripheral neuropathy, behavioral hind-limb posture of the mice was evaluated. The combination therapy of NDAT or XT199 with cisplatin elicited greater inhibition of tumor growth and increased tumor necrosis compared to cisplatin alone. NDAT and XT199 in combination with cisplatin significantly decreased expression of pro-inflammatory cytokines IL-1 beta, IL-6, and TNF-alpha and significantly increased expression of anti-inflammatory cytokine IL-10 in comparison to cisplatin alone. Cisplatin-treated groups showed stocking-glove hind-limb posture, whereas NDAT and XT199 with cisplatin-treated groups displayed normal hind-limb posture. Results clearly suggest that NDAT and XT199 treatment with cisplatin that inactivates NF-kappa B may contribute to increased antitumor and anti-inflammatory efficacy as well as alleviate cisplatin-mediated loss of motor function in this pancreatic tumor mouse model. Pharmaceutical Research Institute at Albany College of Pharmacy Health and Sciences

WOS: 000525972500001 PubMed: 32220120 … Scientific Research Projects Foundation of Pamukkale UniversityPamukkale University [2009TPF013] This study was financially supported by grant number 2009TPF013 from the Scientific Research Projects Foundation of Pamukkale University.

Irinotecan (CPT-11), commonly used in the treatment of many cancer types, may have several side effects that limit the use of CPT-11 in specific tissues such as the heart. In the current study, positive effects of curcumin (CRC) was determined in terms of antioxidant and anti-inflammatory properties against heart damage, caused by CPT-11, in rats. Rats were divided randomly into four equal groups (Control, CPT-11, CRC, and CPT-11 + CRC). CPT-11 10 mg/kg/day was administered intraperitoneally and CRC 100 mg/kg -1 was given orally. Blood and tissue samples were collected from all groups at day 30 for the detection of oxidative stress, histological changes, and cytokine levels. Results showed that CPT-11 caused dramatic changes in heart tissue for oxidative stress parameters (TBARS, SOD, CAT, GSH, and GPx levels), histological tissue damage, and cytokine levels (TNF and IL-4). CRC therapy reversed the elevated oxidative stress, histological tissue damages, and immunological changes and protected cardiac tissue against CPT-11 toxicity when given together with CPT-11. In conclusion, CPT-11 caused adverse effects on cytokine levels, histological alterations, and oxidative stress in rats. However, CRC treatment eliminated these toxic effects with its antioxidant and anti-inflammatory properties. Thus, these results suggest that CRC may play a protective role against CPT-11 toxicity in heart tissue of rats. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Background: We previously identified a Leishmania (L.) major large RAB GTPase (LmlRAB), a new atypical RAB GTPase protein. It is highly conserved in Leishmania species while displaying low level of homology with mammalian homologues. Leishmania small RAB GTPases proteins have been involved in regulation of exocytic and endocytic pathways whereas the role of large RAB GTPases proteins has not been characterized yet. We report here the immunogenicity of both recombinant rLmlRAB and rLmlRABC, in individuals with immunity against L. major or L. infantum.Methods: PBMC were isolated from individuals cured of L. major (CCLm) or from healthy individuals. The latter were subdivided into high or low IFN-γ responders. Healthy high IFN-γ responders, considered as asymptomatics, were living in an endemic area for L. major (HHRLm) or L. infantum (HHRLi). Healthy low IFN-γ responders (HLR) were considered as naïve controls. Cells from all volunteers were stimulated with rLmlRAB or rLmlRABC. Cytokines were analysed by CBA and ELISA and phenotypes of IFN-γ-producing cells were analysed by flow cytometry.Results: Both rLmlRAB and rLmlRABC induced high significant levels of IFN-γ in CCLm, HHRLm and HHRLi groups. Phenotype analysis of rLmlRAB and rLmlRABC-stimulated T cells in CCLm individuals showed a significant increase in the percentage of specific IFN-γ-producing CD4+ and CD8+ T cells. rLmlRAB induced significant granzyme B levels in CCLm and HHRLm. Low but significant granzyme B levels were detected in naïve group. IL-10 was detected in immune and naïve individuals.Conclusion: We showed that rLmlRAB protein and its divergent carboxy-terminal part induced a predominant Th1 response in individuals immune to L. major or L. infantum. Our results suggest that rLmlRAB and rLmlRABC proteins are potential cross-species vaccine candidates against cutaneous and visceral leishmaniasis.

Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1’s effects on liver by comparing wild-type controls, heterozygous igf1+/−, and heterozygous mice treated with IGF-1 for 10 days. Histology, microarray for mRNA gene expression, RT-qPCR, and lipid peroxidation were assessed. Microarray analyses revealed significant underexpression of igf1 in heterozygous mice compared to control mice, restoring normal liver expression after treatment, which then normalized its circulating levels. IGF-1 receptor mRNA was overexpressed in Hz mice liver, while treated mice displayed a similar expression to that of the controls. Heterozygous mice showed overexpression of several genes encoding proteins related to inflammatory and acute-phase proteins and underexpression or overexpression of genes which coded for extracellular matrix, cytoskeleton, and cell junction components. Histology revealed an altered hepatic architecture. In addition, liver oxidative damage was found increased in the heterozygous group. The mere IGF-1 partial deficiency is associated with relevant alterations of the hepatic architecture and expression of genes involved in cytoskeleton, hepatocyte polarity, cell junctions, and extracellular matrix proteins. Moreover, it induces hepatic expression of the IGF-1 receptor and elevated acute-phase and inflammation mediators, which all resulted in liver oxidative damage. Electronic supplementary material The online version of this article (doi:10.1007/s13105-016-0545-x) contains supplementary material, which is available to authorized users.

Background/Aims: Kefir is a kind of fermented probiotic dairy product. The objective of the present study was to investigate the effects of kefir consumption on the fecal microflora and symptoms of patients with inflammatory bowel disease (IBD). Materials and Methods: Kefir was serially diluted and inoculated into de Man, Rogosa, and Sharpe agar and incubated at 37 degrees C for 48 to 72 h under anaerobic conditions. This was a single-center, prospective, open-label randomized controlled trial. Forty-five patients with IBD were classified into two groups: 25 for treatment and 20 for control. A 400 mL/day kefir was administered to the patients for 4 weeks day and night. Their stool Lactobacillus, Lactobacillus kefiri, content was quantitated by real-time quantitative polymerase chain reaction before and after consumption. Abdominal pain, bloating, stool frequency, stool consistency, and feeling good scores were recorded in diaries daily by the patients. Results: A 5x10(7) CFU/mL count of lactic acid bacteria colony forming units was found in a kefir sample as the total average count. Lactobacillus bacterial load of feces of all subjects in the treatment group was between 10(4) and 10(9) CFU/g, and the first and last measurements were statistically significant (p=0.001 in ulcerative colitis and p=0.005 in Crohn's disease (CD)). The L. kefiri bacterial load in the stool of 17 subjects was measured as between 10(4) and 10(6) CFU/g. For patients with CD, there was a significant decrease in erythrocyte sedimentation rate and C-reactive protein, whereas hemoglobin increased, and for the last 2 weeks, bloating scores were significantly reduced (p=0.012), and feeling good scores increased (p=0.032). Conclusion: According to our data, kefir consumption may modulate gut microbiota, and regular consumption of kefir may improve the patient's quality of life in the short term.

Background/Aim: Endoplasmic reticulum (ER) stress plays a critical role in the development of cardiac hypertrophy and heart failure. Heart failure is a crucial health problem that affects 23 million people worldwide, causes approximately 2.4 million people to be hospitalized every year in the USA, and leads to the death of more than 300,000 people. In this study, we aimed to investigate the clinical significance of ER stress markers and the predictive value of acute decompensated heart failure in patients with low ejection fraction heart failure (ADHF). Patients and Methods: This is a prospective case control study. The data included laboratory parameters pertaining to patients with ADHF in the emergency service and lipid parameters obtained during their admission to the hospital. In addition, the same parameters obtained from the control group patients with chronic heart failure (CHF) during their routine polyclinic control were recorded in the data set. Admission time to the hospital and length of hospital stay were included in the data. The levels of glucose regulated protein (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and C/EBP homologous protein (CHOP) in peripheral blood serum obtained from the patients and the control group were measured using the ELISA method. Results: Serum GRP78 concentration was lower in the HF group (p=0.003) compared to the control. The median value of serum PERK concentration in the HF group was higher than that of the control group (573 pg/ml, IQR=477.5-650 vs. 495.5 pg/ml, IQR=294-648, respectively) (p=0.001). However, there were no statistically significant differences in GRP78 and PERK serum concentrations between ADHF and CHF subgroups. Receiver operating characteristic (ROC) curve analysis showed greater area under the curve (AUC) for the serum GRP78 levels of the healthy individuals (AUC=0.748, 95% CI=0.681-0.814, p=0.0003). The serum GRP78 level was found to be 80% sensitive and 70% specific at 147.5 pg/ml (p=0.0003) for distinguishing healthy individuals from HF patients. In the ADHF subgroup, there was a moderate correlation between hospitalization time and serum CHOP concentrations (Spearman rho=0.586 and p=0.001). Conclusion: High GRP78 serum concentration may protect the patient from ER stress. In addition, the serum PERK level is high in patients with HF, whereas it is insufficient in predicting acute decompensation. CHOP may be useful in predicting the length of hospital stay in patients with ADHF. © 2019 International Institute of Anticancer Research. All rights reserved.

Background Elevated levels of fetuin-A are associated with increased risks of metabolic syndrome, type 2 diabetes and nonalcoholic fatty liver disease. This meta-analysis investigated whether exercise interventions can reduce fetuin-A in adults. Methods We searched clinical trials that objectively assessed fetuin-A and included study arms with exercise intervention. The pre-intervention and post-intervention data were used for meta-analysis. The effect sizes were calculated as standardized mean differences or changes in fetuin-A and expressed as Hedges’ g using random-effects models. Results The overall Hedges’ g for fetuin-A in all included interventions was − 0.640 (95%CI − 1.129 to − 0.151; n = 9), but this effect was not observed in obese (g = − 0.096; 95%CI, − 0.328 to 0.135) and type 2 diabetes/dysglycemia (g = − 0.56; 95%CI, − 1.348 to 0.236) individuals. Additionally, the random-effects meta-regression analysis showed that there was not a greater decrease in fetuin-A in individuals who achieved greater body mass index reductions (regression coefficient = 0.065; 95%CI, − 0.185 to 0.315). Conclusion Supervised exercise is associated with reductions in fetuin-A levels in adults and elderly. However, the results of the present meta-analysis should be interpreted with caution because of the variety of type of exercises and individual obesity related-disorders involve. Therefore, additional high-quality randomized controlled trials describing the effect of supervised exercise interventions on fetuin-A in adults are still needed. Electronic supplementary material The online version of this article (10.1186/s12944-019-0962-2) contains supplementary material, which is available to authorized users.

2-s2.0-85099804246 Objective: This study aims to determine the protective effects of apocynin, a NADPH oxidase inhibitor, and melatonin, an endogenous anti-oxidant, in an animal model of ovarian ischemia/reperfusion (I/R) injury. Materials/Methods: Thirty-five female rats were randomly divided into five groups, namely group I (sham), group II (I/R), group III (I/R + 10 mg/kg apocynin), group IV (I/R + 20 mg/kg apocynin), and group V (I/R + 10 mg/kg melatonin). Ovarian tissue and serum superoxide dismutase (SOD) and catalase (CAT) activities and malondialdehyde (MDA) and protein carbonyl (PC) levels were measured. Ovarian histopathology was examined and Bax, caspase 3, and iNOS immunoreactivities were evaluated. Results: Preoperative apocynin and melatonin significantly increased SOD and CAT activities (P < 0.05, P < 0.05, P < 0.01, P < 0.01, P < 0.01, P < 0.05, P < 0.05, and P

The aims of this study were: the identification of proteins differentially represented in the serum proteome of dogs with leishmaniosis after treatment and the verification of one selected protein as a possible biomarker for treatment monitoring. Serum samples from five dogs with leishmaniosis, before and after treatment were pooled into two groups and analysed using 2-dimensional electrophoresis followed by mass spectrometry analysis (MS). The MS analysis allowed the identification of 8 proteins differently expressed. APO-A1 was selected and an immunoturbidimetric assay was validated for its measurement in dogs. Significantly decreased concentrations of APO-A1 in dogs with leishmaniosis and a significant increase after a good response to the treatment were observed, suggesting that APO-A1 could be a potential biomarker of treatment monitoring with the advantages of an automated measurement. Robles Chillida foundation Program for Research Groups of Excellence of the Seneca Foundation - 19894/GERM/15 "Juan de la Cierva" postdoctoral fellowship (Spanish Ministry of Economy and Competitiveness)

Background High blood pressure is still a challenge for emergency physicians to discern the patients that require further analysis to establish the existence of acute hypertensive target organ damage (TOD). The present study aimed to reveal that adropin levels are useful for detecting TOD in patients presenting with high blood pressure. Methods Patients presenting with a blood pressure of more than 180/110 mm Hg were enrolled into the study. After a resting period of 15 minutes, patients' blood pressures were measured thrice at 5-minute intervals while the patients were sitting on a chair, and the average of these measurements was accepted as the baseline value. Blood samples were obtained for either adropin levels or possible TOD during the emergency department admission. Results A total of 119 patients were included in the study. The mean systolic and diastolic blood pressures of study patients were 204.8 ± 23.2 and 108.3 ± 10.3, respectively, and 42% (n = 50) of the patients had TOD. Although the adropin levels were similar between the patients with or without TOD (TOD group = 195 pg/mL, interquartile range [IQR]: 178-201; no-TOD group = 196 pg/mL, IQR: 176-204 [P =.982]), it is significantly higher in normotensive patients (normotensive group = 289 pg/mL, IQR: 193-403) compared with the hypertensive ones (P

Several sources of evidence indicate that exercise during and after breast cancer could positively modulate the tumor microenvironment. This meta-analysis aimed to determine the effects of exercise training on mediators of inflammation in breast cancer survivors. We searched for randomized controlled trials published from January 1990 to March 2014. An inverse variance method of meta-analysis was performed using a random effects model in the presence of statistical heterogeneity. Eight high-quality trials (n = 478) were included. Exercise improved the serum concentrations of IL6 [weighted mean difference (WMD) = −0.55 pg/mL; 95% confidence interval (CI), −1.02 to −0.09], TNFα (WMD = −0.64 pg/mL; 95% CI, −1.21 to −0.06), IL8 (MD = −0.49 pg/mL; 95% CI, −0.89 to −0.09), and IL2 (WMD = 1.03 pg/mL; 95% CI, 0.40 to 1.67). No significant differences were found in the serum concentrations of C-reactive protein (WMD = −0.15; 95% CI, −0.56 to 0.25) or IL10 (WMD = 0.41; 95% CI, −0.18 to 1.02). Exercise training positively modulates chronic low-grade inflammation in women with breast cancer, which may impact upon carcinogenic mechanisms and the tumor microenvironment. These findings align with the other positive effects of exercise for breast cancer survivors, reinforcing the appropriateness of exercise prescription in this population. Cancer Epidemiol Biomarkers Prev; 25(7); 1009–17. ©2016 AACR.

Background/aim: Midkine (MK), a heparin-binding growth factor, has an important role in cancer progression. The aim of this study was to determine MK expression in breast tissue and the preoperative and postoperative serum levels of patients with breast cancer. Materials and methods: Sixty-one patients with breast cancer participated in our study. The MK serum levels were measured pre- and postoperatively for these patients. We also analyzed breast tissues of the 61 patients immunohistochemically. We examined serum midkine levels in 49 healthy volunteers. Results: MK expression was observed in 44 (72.1%) of 61 breast cancer patients. In breast cancer patients the serum MK levels (3.68 ± 2.13 ng/mL (mean ± SD)) were significantly higher than in the control group (1.77 ± 0.38 ng/mL) before tumor removal (P = 0.000). After tumor removal, serum MK levels (2.47 ± 1.00 ng/mL) were significantly (P = 0.000) decreased according to preoperative levels. Increased serum levels of MK were related with tumor stages when clinical parameters were analyzed. Conclusion: We found that increased serum MK levels and protein expressions were associated with the carcinogenesis of breast cancer. MK levels decreased after tumor removal. According to our findings, MK might be a useful tumor marker for patients with breast cancer.

Purpose: Nutritional status and micronutrient levels of end stage renal disease (ESRD) patients may vary depending on the mode of renal replacement therapy (RRT). We aimed to compare the effects of hemodialysis, peritoneal dialysis (PD) and renal transplantation (RT) on micronutrient levels and nutritional status in ESRD patients. Patients and Methods: A total of 77 ESRD patients who had not received RRT were included in this prospective longitudinal study. All ESRD patients underwent a blood serum analysis that assessed the micronutrients such as selenium, copper, zinc, chromium, retinol, thiamine and vitamin B6 as well as a nutritional status assessment. After the baseline assessments and the initiation of RRT was accomplished, all patients were followed for 6 months. Results: The study showed significant improvements in subjective global assessment scores (percentage increases in score A were 26.6 and 36.6; p= 0.039 and p= 0.001; respectively), mid-arm circumference and the skin-fold thicknesses (p < 0.001, p < 0.001; respectively) in the RT and hemodialysis groups. The examinations at sixth month revealed a significant increase in body weight (4.8 kg; p= 0.002) and albumin levels (0.6 g/dL; p < 0.001) in only RT group. Zinc, thiamin and vitamin B6 were the most deficient micronutrients (44.1 %, 24.7 % and 35.1 %; respectively) in ESRD patients. There was a significant increase in selenium and retinol levels (p= 0.020 and p < 0.001; respectively) but a significant decrease in thiamin levels (p= 0.041) in RT patients. A significant increase in retinol levels (p= 0.028) and a significant decrease in thiamin levels (p= 0.022) was observed in the hemodialysis patients. However, no significant change in micronutrient levels was observed in the PD patients. Conclusion: The results support the recommendation that ESRD patients should be supplemented with watersoluble vitamins, especially thiamine and vitamin B6, and trace elements, especially zinc. RT appears to be superior to other modes of RRT when examining SGA score, anthropometric measurements, albumin and micronutrient levels.

Purpose To report the ophthalmological approach of a patient with Blau syndrome (BS) in Colombia. Observations We describe a 9-year-old Colombian boy with sporadic BS due to a de novo nucleotide-binding oligomerization domain containing 2 (NOD2) mutation, who presented with joint and dermatologic symptoms. He was referred to the uveitis service with a single functional eye, due to retinal detachment in the other eye. Despite treatment with corticosteroids, methotrexate, and adalimumab, the patient continued to exhibit progressive disease. Conclusion BS-related uveitis is characterized by severe ocular morbidity. Appropriate interdisciplinary treatment is necessary for the correct identification and management of the disease, considering the inherent difficulty in its diagnosis due to its diverse clinical manifestations. The severity of BS-related uveitis in this report highlights the need for more effective therapies.

Purpose: To investigate the YKL-40, as a marker of inflammation, in aqueous humor and serum of cataract patients with and without pseudoexfoliation syndrome (PEX). Methods: Aqueous humor and serum samples were obtained from 44 patients who underwent phacoemulsification surgery. All patients were divided into two groups: PEX (n = 24) and control (n = 20). YKL-40 levels were measured with enzyme-linked immunosorbent assay (ELISA). The differences between the groups were assessed by using Chi-square and independent sample t-tests. The Pearson correlation coefficient was used to evaluate the correlation between variables. Results: There was a significant difference between the mean YKL-40 levels in the aqueous humor of PEX group (112.0 ± 35.8 ng/mL) and control subjects (88.2 ± 30.6 ng/mL) (P = 0.025). However, the difference between the mean YKL-40 levels in the serum of PEX group (53.5 ± 29.1 ng/mL) and control subjects (44.6 ± 30.2 ng/mL) was non-significant (P = 0.326). The correlation between aqueous humor and serum YKL-40 concentrations was significant in both the groups (r = 0.833, P < 0.001; r = 0.840, P < 0.001, respectively). Conclusions: Increased aqueous humor levels of YKL-40 demonstrate that it is local, but not a systemic marker for inflammation in patients with PEX. © 2018, The Royal College of Ophthalmologists.

In the general population, metabolic syndrome (MetS) is associated with a 4 times relative risk of developing diabetes and approximately a 2-fold risk of coronary heart disease, stroke, and premature mortality [1]. In patients with schizophrenia the overall rate of MetS is 32.5% [1]. This contributes to having an average mortality rate that is 2-3 times higher than the general population, corresponding to a 10-25 year shortened life expectancy [2]. Antipsychotics are associated with an increased risk for several physical diseases, including obesity, dyslipidemia, diabetes mellitus [2,3]. Use both of classical conventional and modern atypical neuroleptics have been associated with metabolic disturbances; so drug-induced metabolic disturbances are observed in 39.0% of patients taking haloperidol, 44.0% - clozapine, 22.0% - aripiprazole, 33.3% - amisulpride, 34.0% - olanzapine, 35.0% – risperidone [4]. Therefore, an ongoing need exists for reliable predictors of metabolic risks in individual patients indicated for antipsychotic treatment. Apolipoproteins and cholesterol play a critical role in synapse and myelin maintenance as well as integrity and may thus be both appealing candidates in the pathogenesis of schizophrenia and biomarkers of antipsychotic induce side metabolic effects [5]. The aim of this study is to investigate serum apolipoproteins concentration in schizophrenic patients with or without metabolic syndrome and healthy donors. Methods: The study was carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans. After obtaining approval of the study protocol by the local ethical committee, suitable participants were recruited from psychiatric hospitals. We included 53 patients with diagnosis of paranoid schizophrenia verified according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10: F20). Patients have been divided into two groups with and without MetS according to criteria the International Diabetes Federation (2005). All patients received antipsychotic treatment. The control group included 20 mentally and physically healthy subjects. Serum apolipoproteins A1, C3, E, A2 and C2 were measured using xMAP technology (Luminex). Statistical analysis was performed by SPSS version 20.0. Results: We found a significant decrease in the concentration of apolipoprotein A1 in the serum of schizophrenic patients with a MetS (p = 0.002) and no side effects (p = 0.013) compared with the control group. The level of ApoC3 (p = 0.001) and ApoC2 (p = 0.002) were increased in patients with schizophrenia with MetS in comparison with the control group and patients without MetS. No other significant differences were established concerning the other assayed apolipoproteins. Conclusions: Literature date and our results suggest that disturbances in level of Apo A1 play role in pathogenesis of schizophrenia while level of ApoC3 and ApoC2 can reflect the metabolic disbalance and could be a novel biomarker to predict metabolic side effects associated with antipsychotic treatment. Future studies with a larger sample size, a well-defined control group, a longer study time duration could be of great clinical utility, when these can predict antipsychotic-associated metabolic problems in patients that carry a higher cardiovascular risk. Disclosure statement: This work is supported by RSF grant N 18-15-00011

Despite gastric cancer being rare nowadays in Western countries, it remains one of the leading causes of cancer death worldwide. The course of the disease varies, so the individual gastric cancer patient’s prognosis is difficult to determine. The need for new biomarkers is crucial. The aim of this study was to evaluate the prognostic value of serum matrix metalloproteinase-8, serum tissue inhibitor of metalloproteinase-1, and tissue matrix metalloproteinase-8 in patients with gastric cancer. Preoperative serum samples from 233 patients with gastric cancer were retrospectively analyzed. Serum levels of matrix metalloproteinase-8 were analyzed with immunofluorometric assay, and tissue inhibitor of metalloproteinase-1 levels were determined by enzyme-linked immunosorbent assay. We also determined the tissue expression of matrix metalloproteinase-8 in 276 gastric cancer samples by immunohistochemistry. Survival data and death causes came from patient records, the Population Register Center of Finland, and Statistics Finland. Patients with a low (131 ng/mL) serum matrix metalloproteinase-8 level had a considerably unfavorable prognosis (p = 0.002). Those patients with a high (≥170 ng/mL) serum tissue inhibitor of metalloproteinase-1 level also had a poor prognosis (p 0.30) molar ratios predicted a worse prognosis (p = 0.020). Tissue matrix metalloproteinase-8 did not influence prognosis. These results suggest that serum matrix metalloproteinase-8, tissue inhibitor of metalloproteinase-1, and the ratio of matrix metalloproteinase-8/ tissue inhibitor of metalloproteinase-1 may prove useful biomarkers for prediction of prognosis in patients with gastric cancer.

Purpose: The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury. Methods: We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume. Results: Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P = 0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P = 0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P = 0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher VT. Conclusions: Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241). © 2018, The Author(s).

Aim: Patient- and disease-related factors, as well as operation technique, all have the potential to impact on postoperative outcome in Crohn's disease. The available evidence is based on small series and often displays conflicting results. The aim was to investigate the effect of preoperative and intra-operative risk factors on 30-day postoperative outcome in patients undergoing surgery for Crohn's disease. Method: This was an international prospective snapshot audit including consecutive patients undergoing right hemicolectomy or ileocaecal resection. The study analysed a subset of patients who underwent surgery for Crohn's disease. The primary outcome measure was the overall Clavien–Dindo postoperative complication rate. The key secondary outcomes were anastomotic leak, reoperation, surgical site infection and length of stay in hospital. Multivariable binary logistic regression analyses were used to produce odds ratios and 95% confidence intervals. Results: In all, 375 resections in 375 patients were included. The median age was 37 and 57.1% were women. In multivariate analyses, postoperative complications were associated with preoperative parenteral nutrition (OR 2.36, 95% CI 1.10–4.97), urgent/expedited surgical intervention (OR 2.00, 95% CI 1.13–3.55) and unplanned intra-operative adverse events (OR 2.30, 95% CI 1.20–4.45). The postoperative length of stay in hospital was prolonged in patients who received preoperative parenteral nutrition (OR 31, 95% CI 1.08–1.61) and those who had urgent/expedited operations (OR 1.21, 95% CI 1.07–1.37). Conclusion: Preoperative parenteral nutritional support, urgent/expedited operation and unplanned intra-operative adverse events were associated with unfavourable postoperative outcome. Enhanced preoperative optimization and improved planning of operation pathways and timings may improve outcomes for patients. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland

Background: Research over the last two decades has highlighted the critical role of Brain-derived neurotrophic factor (BDNF) in brain neuroplasticity. Studies suggest that physical exercise may have a positive impact on the release of BDNF and therefore, brain plasticity. These results in animal and human studies have potential implications for the recovery from damage to the brain and for interventions that aim to facilitate neuroplasticity and, therefore, the rehabilitation process. Purpose: The aim of this study was to carry out a systematic review of the literature investigating how aerobic exercises and functional task training influence BDNF concentrations post-stroke in humans and animal models. Data Sources: Searches were conducted in PubMed (via National Library of Medicine), SCOPUS (Elsevier), CINAHL with Full Text (EBSCO), MEDLINE 1946-present with daily updates (Ovid) and Cochrane. Study Selection: All of the database searches were limited to the period from January, 2004 to May, 2017. Data Extraction: Two reviewers extracted study details and data. The methodological quality of the studies that used animal models was assessed using the ARRIVE Guidelines, and the study that evaluated human BDNF was assessed using the PEDro Scale. Data Synthesis: Twenty-one articles were included in this review. BDNF measurements were performed systemically (serum/plasma) or locally (central nervous system). Only one study evaluated human BDNF concentrations following physical exercise, while 20 studies were experimental studies using a stroke model in animals. A wide variation was observed in the training protocol between studies, although treadmill walking was the most common type of intervention among the studies. Studies were of variable quality: the studies that used animal models scored from 8/20 to 15/20 according to the ARRIVE Guidelines. The only study that evaluated human subjects scored 5/10 according to the PEDro scale and, which indicates a quality classified as "fair". Conclusions: The results of the current systematic review suggest that aerobic exercise promotes changes in central BDNF concentrations post-stroke. On the other hand, BDNF responses following functional exercises, such as reaching training and Constraint Induced Movement Therapy (CIMT), seem to be still controversial. Given the lack of studies evaluating post-stroke BDNF concentration following physical exercise in humans, these conclusions are based on animal work. © 2018 Alcantara, García-Salazar, Silva-Couto, Santos, Reisman and Russo.

The current study aims to compare the serum brain-derived neurotrophic factor (BDNF), proBDNF and tissue plasminogen activator (tPA) levels in cases that have developed posttraumatic stress disorder (PTSD) in consequence of sexual abuse with those in healthy control subjects. Thirty-one female patients between 8 and 18 years of age who have been diagnosed with PTSD due to sexual abuse and thirty-one healthy female volunteer controls were included in the study. Frequency, intensity and severity of PTSD symptoms were assessed on the basis of Clinician-Administered Post-Traumatic Stress Disorder Scale for Children and Adolescents (CAPS-CA). Serum BDNF, proBDNF and tPA levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. Results of the present study revealed that serum levels of BDNF and proBDNF in PTSD group were significantly lower but tPA level was significantly higher as compared to healthy control subjects. There were no correlations between CAPS-CA scores and BDNF, proBDNF and tPA levels. Decreased levels of BDNF, as suggested to have a role in the etiopathogenesis of PTSD, appear to be a result of the reduction in proBDNF production. The increased tPA levels in such cases, on the other hand, can be a compensatory mechanism serving to increase the BDNF levels. © 2018

Background: Pre-eclampsia (PE) carries an increased risk for maternal and/or fetal mortality or serious morbidity. PE is associated with ischemia and increased oxidative stress in the placenta, which may lead to modification of plasma albumin to ischemia-modified albumin (IMA). The aim of this study was to investigate IMA and hematological parameters in mothers and in premature infants in normal and in pre-eclamptic pregnancies. Methods: Twenty-five pregnant women with PE and their premature newborns were categorized as the PE group, and 25 normotensive pregnant women and their premature newborns as the control group. Preterm infants are classified as small for gestational age (SGA) or non-SGA according to the Fenton preterm growth chart. Serum IMA, complete blood count (CBC), liver function tests (LFT), renal function tests (RFT), albumin, and C-reactive protein were measured in the mothers immediately before birth, and in the cord blood and serum of the newborns at 6 and 24 h after birth. Clinical and demographic data were recorded for both groups. Results: While IMA, LFT and RFT were significantly increased in the PE group compared with the control group, albumin and CBC were significantly lower in the PE group. A total of 40% of PE newborns were SGA, 30% of whom had severe SGA (birthweight

Background: The self-assessment of perceived immune status is important, as this subjective observation is leading for individuals to decide whether or not to seek medical help or adapt their lifestyle. Current assessments of perceived immune status are conducted with 1-item ratings [1]. the Immune Function Questionnaire (IFQ) [2], or various self-composed questionnaires. While a 1-item perceived immune functioning score provides no information about which aspects of immune status may be affected, the disadvantage of multiple item scales is that they are time-consuming to complete. This may be a burden to certain patient populations, and limit their use in clinical practice in which quick and cost-effective assessments are sometimes essential. Aim: The aim of the current studies was to develop a short Immune Status Questionnaire (ISQ). Methods: To develop the ISQ, four studies were conducted. Participants were young adults, aged 18 to 30 years old. In Study 1 (n = 295), an adjusted version of the IFQ was administered, which was complemented with the items shortness of breath, skin problems, muscle and joint pain, and the common cold. A stepwise linear regression analysis was conducted to identify those items that had a predictive validity of at least 85% with regard to the sum score of all items. These items were combined to form the ISQ. In Study 2 (n = 569), the ISQ was compared with the 1-item perceived immune functioning score (Donners et al. 2015). In Study 3 (n = 291), the original item scoring was compared to a new Likert scale scoring. Study 4 (n = 52) was conducted to investigate the test-retest reliability of the ISQ. Results: Analysis of the data from Study 1 revealed seven items that together comprised the ISQ (predictive validity of 85%): common cold, diarrhea, sudden high fever, headache, muscle and joint pain, skin problems and coughing. The items are scored on a 5-point Likert scale ranging from 0 to 4. The overall ISQ score ranges from 0 to 28, with higher scores indicating a poorer immune status. Study 2 revealed that the ISQ correlated significantly with the 1-item perceived immune functioning (r = 0.383, p

The polymorphisms in leptin (LEPG-2548A) and leptin-receptor (LEPRGln223Arg) seem to influence obesity and lipid metabolism among others. The aim of this study was to investigate the effect of these polymorphisms on adiposity, leptin (sLeptin), and leptin-receptor (sLeptin-receptor) serum concentrations as well as inflammation markers. We included 382 adults originally from Western Mexico. They were genotyped by PCR-RFLP. Obese individuals showed higher sLeptin (58.2±31.35 ng/mL) but lower sLeptin-receptor (12.6±3.74 ng/mL) levels than normal weight ones (17.6±14.62 ng/mL,17.4±4.62 ng/mL, resp.),P<0.001. Obese subjects carriers of Arg/Arg genotype had more (P=0.016) sLeptin-receptor (14.7±4.96 ng/mL) and less (P=0.004) sLeptin (44.0±28.12 ng/mL) levels than Gln/Gln genotype (11.0±2.92 ng/mL,80.3±33.24 ng/mL, resp.). Body fat mass was lower (Pfrom 0.003 to 0.045) for A/A (36.5%±6.80) or Arg/Arg (36.8%±6.82) genotypes with respect to G/G (41.3%±5.52) and G/A (41.6%±5.61) or Gln/Gln (43.7%±4.74) and Gln/Arg (41.0%±5.52) genotypes carriers. Our results suggest thatLEP-2548A andLEPR223Arg could be genetic markers of less body fat mass accumulation in obese subjects from Western Mexico.

Potential biomarkers of tardive dyskinesia: a multiplex analysis of blood serum A.S. Boiko(1), E.G. Kornetova(2), S.A. Ivanova(1), A.J.M. Loonen(3) (1)Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Laboratory of Molecular Genetics and Biochemistry, Tomsk, Russia (2)Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Department of Endogenous Disorders, Tomsk, Russia (3)University of Groningen, Groningen Research Institute of Pharmacy, Groningen, The Netherlands Long-term antipsychotic treatment of schizophrenia is associated with the emergence of tardive dyskinesia (TD), a motor syndrome consisting of involuntary and hyperkinetic movements [1]. Pathogenesis of this drug-induced movement disorder is not yet fully established, but may be connected to oxidative stress-related indirect pathway neurotoxicity [2]. Dysregulations in immune, hormonal and neurotrophic systems have been postulated to be one of the mechanisms underlying this form of neurotoxicity [3,4]. Principle aims of translational psychiatric research are searching for biomarkers which can be used to diagnose pathological biochemical processes and to identify molecular targets for treatment as well as development of pharmacogenetic approaches to personalize this therapy. The aim is to study potential endocrine, neurotrophic and immunological markers of tardive dyskinesia in the blood serum of patients with schizophrenia with antipsychotic therapy. Methods: After obtaining approval of the study protocol by the local ethical committee, suitable participants were recruited from psychiatric hospitals. All subjects gave informed consent after proper explanation of the study. TD was assessed cross-sectionally by the use of the Abnormal Involuntary Movement Scale (AIMS) [1,5]. The concentrations of cortisol, brain-derived neurotrophic factor (BDNF), prolactin, cytokines (tumor necrosis factor (TNFa), interleukin 1 (IL-1β), interleukin 3 (IL-3), interleukin 6 (IL-6), interferon gamma (INF-γ) and S100β were measured in blood serum using the MILLIPLEX® MAP panels (Merck, Darmstadt, Germany) by the multiplex analyzer MAGPIX (Luminex, USA). Statistical analyses were performed using SPSS software for Windows. Results were expressed as median and quartile intervals (Me [Q1; Q3]) or mean and standard deviation (M ± SD). Differences were considered significant at p ≤ 0.05. Results: In total 180 patients with schizophrenia, 128 males and 52 females (age 39.2 ± 12.1 years), receiving long-term antipsychotic treatment were included. These patients were divided into two groups: 71 patients with tardive dyskinesia and 109 patients without this movement disorder. A significant (p = 0.04) decrease in BDNF concentration was observed in patients with TD (1.9 [1.01; 2.99] ng/ml) in comparison to patients without TD (2.66 [1.29; 3.89] ng/ml). An increase (p = 0.05) of the serum IL-6 level of patients with TD (5.69 [3.55; 7.4] pg/ml) was detected relative to patients without TD (4.69 [2.82; 6.13] pg/ml). In addition, a statistical trend (p = 0.06) of increased serum S100β concentration was found in TD patients (85.29 ± 5.53 ng/L) compared to patients without this side effect (75.14 ± 2.81 ng/L). No other significant differences were established concerning the other assayed biomarkers. Conclusions: The biological processes that might play a role in the development of TD are not confined to the human brain per se. Hormonal and immune systems are also involved, which may be related to these systems being closely interrelated. Furthermore, these parameters may provide information about risk factors of the movement disorder. Identifying markers that can be used as diagnostics or predictors of treatment response in people with tardive dyskinesia will be an important step towards being able to provide personalized treatment. References [1] Loonen, A.J., van Praag, H.M., 2007. Measuring movement disorders in antipsychotic drug trials: the need to define a new standard. J Clin Psychopharmacol 27, 423–430. [2] Loonen, A.J.M., Ivanova, S.A., 2013. New insights into the mechanism of druginduced dyskinesia. CNS Spectrums 18 (01), 15–20. [3] Wu, J.Q., Chen, D.Ch., Tan, Yu.L., Tan, Sh.P., Hui, L., Lv, M.H., Soares, J.C., Zhang, X.Y., 2015. Altered BDNF is correlated to cognition impairment in schizophrenia patients with tardive dyskinesia. Psychopharmacology 232, 223–232. [4] An, H.M., Tan, Y.L., Shi, J., Wang, Z.R., Soars, J.C., Wu, J.Q., Yang, F.D., Huang, X.F., Zhang, X.Y., 2015. Altered IL-2, IL-6 and IL-8 serum levels in schizophrenia patients with tardive dyskinesia. Schizophr Res 162 (1–3), 261–268. [5] Loonen, A.J.M., Doorschot, C.H., van Hemert, D.A., Oostelbos, M.C., Sijben, A.E., 2001. The schedule for the assessment of drug-induced movement disorders (SADIMoD): inter-rater reliability and construct validity. Int J Neuropsychopharmacol 4, 347–360. Keywords: Biological markers Schizophrenia: clinical Neuroleptics & antipsychotics: clinical

The aim of this study was the identification of proteins differentially represented in the serum proteome of seropositive dogs with (Group 1) and without (Group 2) clinical-pathologic signs consistent with ehrlichiosis compared to healthy control dogs. Serum samples were collected from 20 dogs of various breeds with naturally occurring ehrlichiosis (10 dogs belonged to Group 1 and 10 to Group 2) and 10 healthy dogs. Two-dimensional electrophoresis (2DE) of pooled serum for each of the group of dogs were run in triplicate. 2D image analysis showed 39 spots differently expressed between Group 1 and Group 2 compared with healthy ones. Mass spectrometry analysis allowed identification of 6 proteins: albumin, haptoglobin (Hp), alpha-l-antitrypsin (AAT), Retinol Binding Protein 4 (RBP-4), alpha-l-acid glycoprotein (AGP) and vitamin D-binding protein (VDBP). When a confirmatory study was performed for albumin, Hp, AAT and RBP-4 by using different assays, significant differences (P < 0.05) between diseased and healthy groups were observed. It can be concluded that there are significant changes in the serum proteome of dogs with ehrlichiosis with modifications in proteins related with the acute phase response such as Hp, albumin and AGP, with vitamin A transport such as RBP-4, with inhibitors of serine proteases and anti-inflammatory proteins such as AAT, and vitamin D metabolism and actin scavengers such as VDBP. "Ministerio de Economia y Competividad" of Spain Fundacion Seneca - 19894/GERM/15

After the landmark approval of T-VEC, oncolytic viruses are finding their way to the clinics. However, response rates have still room for improvement, and unfortunately there are currently no available markers to predict responses for oncolytic immunotherapy. Interleukin 8 (IL-8) production is upregulated in many cancers and it also connects to several pathways that have been shown to impair the efficacy of adenoviral immunotherapy. We studied the role of IL-8 in 103 cancer patients treated with oncolytic adenoviruses. We found high baseline serum IL-8 concentration to be independently associated with poor prognosis (p

Introduction:Cancer cachexia is one of the most frequent effects of malignancy, is often associated with poor prognosis, and may account for up to 20% of cancer deaths. The aim of our study was to evaluate the relationship of cancer cachexia and serum levels of resistin and leptin in patients with advanced non–small cell lung cancer.Methods:A total of 67 chemotherapy-naïve patients with advanced-stage non–small cell cancer and a control group containing 20 healthy individuals without a known chronic disease were enrolled in this study. All individuals in the control group were age and sex matched. Demographic, anthropometric, laboratory data and serum levels of adipokines were measured for 2 groups. Progression-free survival and overall survival were estimated using the Kaplan-Meier method. Survival among various factors was calculated using the log-rank test.Results:Patients presented significantly higher serum resistin ( P = .0001) and lower serum leptin levels ( P = .025) than the control group. Lower serum levels of leptin were correlated with overall survival ( P = .011).Conclusions:Serum leptin and resistin levels play key role as proinflammatory cytokines in lung cancer and cancer cachexia; however, their use as diagnostic or prognostic markers is not possible yet, and further large-scale studies are required to confirm our findings.

Background Fanconi anemia (FA) is a condition characterized by genetic instability and short stature, which is due to growth hormone (GH) deficiency in most cases. However, no apparent relationships have been identified between FA complementation group genes and GH. In this study, we thereby considered an association between FA and Laron syndrome (LS) (insulin-like growth factor 1 [IGF-1] deficiency). Methods A 21-year-old female Mexican patient with a genetic diagnosis of FA was referred to our research department for an evaluation of her short stature. Upon admission to our facility, her phenotype led to a suspicion of LS; accordingly, serum levels of IGF-1 and IGF binding protein 3 were analyzed and a GH stimulation test was performed. In addition, we used a next-generation sequencing approach for a molecular evaluation of FA disease-causing mutations and genes involved in the GH-IGF signaling pathway. Results Tests revealed low levels of IGF-1 and IGF binding protein 3 that remained within normal ranges, as well as a lack of response to GH stimulation. Sequencing confirmed a defect in the GH receptor signaling pathway. Conclusions To the best of our knowledge, this study is the first to suggest an association between FA and LS. We propose that IGF-1 administration might improve some FA complications and functions based upon IGF-1 beneficial actions observed in animal, cell and indirect clinical models: erythropoiesis modulation, immune function improvement and metabolic regulation.

Asli Gorek Dilektasli,1 Ezgi Demirdogen Cetinoglu,1 Esra Uzaslan,1 Ferah Budak,2 Funda Coskun,1 Ahmet Ursavas,1 Ilker Ercan,3 Ercument Ege1 1Department of Pulmonary Disesaes, 2Department of Immunology, 3Department of Biostatistics, Uludag University Faculty of Medicine, Bursa, Turkey Introduction: Chemokine (C-C motif) ligand 18 (CCL-18) has been shown to be elevated in chronic obstructive pulmonary disease (COPD) patients. This study primarily aimed to evaluate whether the serum CCL-18 level differentiates the frequent exacerbator COPD phenotype from infrequent exacerbators. The secondary aim was to investigate whether serum CCL-18 level is a risk factor for exacerbations requiring hospitalization. Materials and methods: Clinically stable COPD patients and participants with smoking history but normal spirometry (NSp) were recruited for the study. Modified Medical Research Council Dyspnea Scale, COPD Assessment Test, spirometry, and 6-min walking test were performed. Serum CCL-18 levels were measured with a commercial ELISA Kit. Results: Sixty COPD patients and 20 NSp patients were recruited. Serum CCL-18 levels were higher in COPD patients than those in NSp patients (169 vs 94 ng/mL,P

Aim: We aimed to evaluate the relationships between monocyte-to-high-density lipoprotein ratio (MHR) and lymphocyte-to-monocyte ratio (LMR) and rheumatic mitral valve stenosis (RMVS). Methodology: A total of 368 patients with mitral stenosis and 80 healthy participants were included. Patients were categorized into two groups in respect to the severity of RMVS as mild-moderate group (mitral valve area ≥1.0 cm2) and severe group (mitral valve area 2). Results: The MHR (10.6 ± 2.3, 11.6 ± 2.6, 13.8 ± 3.1; p < 0.001) and C-reactive protein levels (control group, nonsevere RMVS and severe RMVS groups 3.4 ± 0.7, 4.4 ± 1.1, 5.2 ± 1.4, respectively; p < 0.001) were significantly increased whereas LMR (4.51 ± 1.3, 3.57 ± 1.3, 3.14 ± 1.4; p < 0.001) levels were significantly decreased in parallel to the severity of mitral stenosis. Discussion/conclusion: MHR and LMR can be used to predict severity of RMVS.

Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R). In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides); carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions. © 2017 González-Guerra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Objective: This study aimed to evaluate the correlation between fragmented QRS complex (fQRS), aortic stiffness, and diastolic dysfunction in hemodialysis patients. Subjects and Methods: A sample of 56 patients who received hemodialysis treatment was stratified into 2 groups according to their electrocardiography (ECG) patterns with or without fQRS. Baseline characteristics and laboratory parameters of patients were documented. Conventional echocardiographic and Doppler echocardiographic procedures were performed in all patients. The mean early (Em) diastolic and late (Am) diastolic myocardial velocities were calculated. These tests were performed before dialysis. The Student t test, Mann-Whitney U test, χ2 test, Spearman correlation, and multivariate linear regression analysis were used to analyze parameters where appropriate. Results: Of the 56 patients under hemodialysis, fQRS in ECG was detected in 26 (46.4%). Echocardiographic evaluation showed that deceleration time (237.57 ± 40.10 ms; p = 0.030), isovolumic relaxation time (126.84 ± 15.62 ms; p < 0.001), early (E)/late (A) ventricular filling velocity (E/A) ratio (1.15 ± 0.40; p ≤ 0.001), and aortic stiffness index value (9.62 ± 4.53; p = 0.016) exhibited a statistical increase in hemodialysis patients with fQRS compared to patients without fQRS. E (58.23 ± 19.96 m/s; p = 0.004), and Em (5.96 ± 2.08 cm/s; p = 0.023) velocity levels were significantly lower in hemodialysis patients with fQRS than patients without fQRS. Aortic stiffness closely correlated with diastolic dysfunction (deceleration time r = 0.273, p = 0.042; isovolumic relaxation time r = 0.497, p < 0.001; E/A ratio r = -0.449, p = 0.001). On multivariate linear regression analysis, fQRS and aortic stiffness were independently associated in hemodialysis patients (β = 0.321, p = 0.049). Conclusions: Increased aortic stiffness and left ventricular systolic dysfunction were observed more frequently in hemodialysis patients with fQRS than in patients without fQRS. fQRS is an important determinant of aortic stiffness in hemodialysis patients.

© 2017 International Osteoporosis Foundation and National Osteoporosis Foundation Summary: Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with whole-body bone mineral density (WBMD) in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. Introduction: This study aims to investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during ‘healthy’ ageing. Methods: WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18–30 years; 53% female). Results: WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates (r values ranging from 0.174 to 0.254, all p < 0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD. Conclusion: Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young.

Purpose: Fractional exhaled nitric oxide (FeNO) has emerged as an important biomarker in asthma. Increasing evidence points to atopy as a confounding factor in the interpretation of elevated FeNO. We conducted a longitudinal study to understand the clinical significance of FeNO as an inflammatory biomarker. Methods: We identified 19 children aged 13-15 years at baseline with a significant elevation in FeNO ≥ 80 parts per billion (ppb) and randomly selected a group of children of similar age with a moderate elevation (40-79 ppb) and normal-to-low FeNO (

Background: Congenital leptin deficiency is a recessive genetic disorder associated with severe early-onset obesity. It is caused by mutations in the leptin (LEP) gene, which encodes the protein product leptin. These mutations may cause nonsense-mediated mRNA decay, defective secretion or the phenomenon of biologically inactive leptin, but typically lead to an absence of circulating leptin, resulting in a rare type of monogenic extreme obesity with intense hyperphagia, and serious metabolic abnormalities. Methods: We present two severely obese sisters from Colombia, members of the same lineal consanguinity. Their serum leptin was measured by MicroELISA. DNA sequencing was performed on MiSeq equipment (Illumina) of a next-generation sequencing (NGS) panel involving genes related to severe obesity, including LEP. Results: Direct sequencing of the coding region of LEP gene in the sisters revealed a novel homozygous missense mutation in exon 3 [NM_002303.3], C350G&gt, T [p.C117F]. Detailed information and clinical measurements of these sisters were also collected. Their serum leptin levels were undetectable despite their markedly elevated fat mass. Conclusions: The mutation of LEP, absence of detectable leptin, and the severe obesity found in these sisters provide the first evidence of monogenic leptin deficiency reported in the continents of North and South America.

It is known that adipose tissue mass increases with age, and that a number of hormones, collectively called adipokines, are produced by adipose tissue. For most of them it is not known whether their plasmatic levels change with age. Moreover, it is known that adipose tissue infiltration in skeletal muscle is related to sarcopenia and loss of muscle strength. In this study we investigated the age-related changes of representative adipokines and insulin-like growth factor (IGF)-1 and their effect on muscle strength. We studied the association between circulating levels of adiponectin, leptin, resistin and IGF-1 and muscle strength. This cross-sectional study included 412 subjects of different age (152 subjects aged 18-30 years and 260 subjects aged 69-81 years) recruited within the framework of the European research network project "Myoage". The levels of adiponectin (both in male and female subjects) and leptin (only in males) were significantly higher in old subjects compared to young, while those of IGF-1 were lower in old subjects. In old subjects adiponectin, resistin and the resistin/IGF-1 ratio (but not IGF-1 alone) were inversely associated with quadriceps torque, while only adiponectin was inversely associated with handgrip strength independently from percentage of fat mass, height, age, gender and geographical origin. The ratio of leptin to adiponectin was directly associated with handgrip strength in both young and old subjects. These results suggest that in humans the age-associated loss of strength is associated with the levels of representative adipokines and IGF-1.