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Αλέξανδρος Γ. Σφακιανάκης

Sunday, November 29, 2020

Antibacterial Activity of Sodium Hypochlorite Gel versus Different Types of Root Canal Medicaments Using Agar Diffusion Test: An In Vitro Comparative Study

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Aim. This study aimed to evaluate the antibacterial effect of sodium hypochlorite gel and four types of intracanal medicaments. Materials and Methods. The agar diffusion method was used to evaluate the antibacterial effect of five medicaments (sodium hypochlorite gel (NaOCl), chlorhexidine gel (CHX), calcium hydroxide paste (CH), Ledermix, and Diapex plus) against Enterococcus faecalis (E. faecalis), Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli). The zone of inhibition around each medicament was measured in millimeters, after 48 hours of incubation at 37°C. The antibacterial effects of medicaments against each microbial strain and the sensitivity of microorganisms towards each medicament were compared using the one-way ANOVA and Games–Howell post hoc tests. The level of significance was set to .Results. All medicaments showed variable inhibition zones for all bacterial strains except Diapex Plus which showed no antibacterial activity. NaOCl gel exhibited the most significant inhibition zones for all bacterial strains followed by CHX gel, Ledermix, and CH. However, the effect of CHX and CH paste against S. aureus was statistically similar, while the effect of CH against E. faecalis was significantly higher than the Ledermix. Conclusion. Sodium hypochlorite gel displayed the highest antibacterial activity among tested medicaments and can be recommended as a potent intracanal medicament. Chlorhexidine gel showed a significantly higher antibacterial effect when compared with Ledermix and calcium hydroxide. Calcium hydroxide demonstrated stronger antibacterial activity against E. faecalis than Ledermix. Diapex Plus exhibited no antibacterial effect.
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Glycogen Synthase Kinase 3β Promotes Postoperative Cognitive Dysfunction by Inducing the M1 Polarization and Migration of Microglia

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Postoperative cognitive dysfunction (POCD) is a common postoperative central nervous system complication, especially in the elderly. It has been consistently reported that the pathological process of this clinical syndrome is related to neuroinflammation and microglial proliferation. Glycogen synthase kinase 3β (GSK-3β) is a widely expressed kinase with distinct functions in different types of cells. The role of GSK-3β in regulating innate immune activation has been well documented, but as far as we know, its role in POCD has not been fully elucidated. Lithium chloride (LiCl) is a widely used inhibitor of GSK-3β, and it is also the main drug for the treatment of bipolar disorder. Prophylactic administration of lithium chloride (2 mM/kg) can inhibit the expression of proinflammatory mediators in the hippoca mpus, reduce the hippocampal expression of NF-κB, and increase both the downregulation of M1 microglial-related genes (inducible nitric oxide synthase and CD86) and upregulation of M2 microglial-related genes (IL-10 and CD206), to alleviate the cognitive impairment caused by orthopedic surgery. In vitro, LiCl reversed LPS-induced production of proinflammatory mediators and M1 polarization of microglia. To sum up these results, GSK-3β is a key contributor to POCD and a potential target of neuroprotective strategies.
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Urinary Dysfunction Is Associated with Nigrostriatal Dopaminergic Degeneration in Early and Untreated Patients with Parkinson’s Disease

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The aim of the present study was to determine the relation between urinary dysfunction and nigrostriatal dopaminergic degeneration in early and untreated Parkinson's disease (PD). The data were obtained from Parkinson's Progression Markers Initiative database. Two hundred and seventy-five patients and 149 healthy controls were included in our analysis. Urinary symptoms were evaluated with the Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT). We performed correlation analyses between 123I-FP-CIT SPECT imaging data and severity of urinary symptoms in patients with PD and healthy controls. Early and untreated patients with PD exhibited worse urinary symptoms when compared with healthy controls. The severity of urinary symptoms significantly correlated with dopamine transporter binding levels in the caudate and the putamen. After controlling for age and sex, the severity of storage symptoms significantly correlated with dopamine transporter binding levels in the less affected side of the putamen (r = −0.172, ). The correlation was observed in both male (r = −0.152, ) and female patients (r = −0.217, ). No correlations were found between dopamine transporter binding levels and voiding symptoms in male or female patients, or any urinary symptoms in healthy controls. Worse storage symptoms reflect greater nigrostriatal dopaminergic loss in early and untreated PD.
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Acute and Subchronic Oral Safety Profiles

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Sudarshana powder (SP) is an Ayurvedic preparation, which contains 53 herbal ingredients along with 50% of Andrographis paniculata and is clinically used with bees honey. This study was aimed to determine the safety profile of the SP, and its novel preparation Sudarshana suspension (SS) on male Wistar rats and tolerance studies were conducted for healthy adult volunteers. Acute and subacute toxicity studies of the SS and hot water extract of SP were assessed in Wistar rats by observing the general behavior, analyzing biochemical and haematological parameters, and pathological observation. Healthy consented adult volunteers (n = 35) of either sex were selected, and tolerance studies of SS were tested by measuring the biochemical and haematological parameters. There were no significant () changes observe d in the treated animals with SS and hot water extract of SP compared with control in body weights, food intake, and water consumption as well as the biochemical and haematological parameters. Histopathological studies revealed no significant () changes in the liver, heart, and kidney tissues. The experimental results suggest that novel formulation SS was potentially safe for chronic administration in rats, and no significant differences () were observed in tested parameters on day 3 and day 8 when compared to the day 0 (baseline) values in healthy volunteers. Healthy volunteers did not report any adverse effects or any other complications during the treatment period and the follow-up period. Therefore, it can be concluded that the novel preparation Sudarshana suspension does not cause any significant toxic effects on the blood parameters in animal and human models.
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Pathway Maps of Orphan and Complex Diseases Using an Integrative Computational Approach

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Orphan diseases (ODs) are progressive genetic disorders, which affect a small number of people. The principal fundamental aspects related to these diseases include insufficient knowledge of mechanisms involved in the physiopathology necessary to access correct diagnosis and to develop appropriate healthcare. Unlike ODs, complex diseases (CDs) have been widely studied due to their high incidence and prevalence allowing to understand the underlying mechanisms controlling their physiopathology. Few studies have focused on the relationship between ODs and CDs to identify potential shared pathways and related molecular mechanisms which would allow improving disease diagnosis, prognosis, and treatment. We have performed a computational approach to studying CDs and ODs relationships through (1) connecting disease s to genes based on genes-diseases associations from public databases, (2) connecting ODs and CDs through binary associations based on common associated genes, and (3) linking ODs and CDs to common enriched pathways. Among the most shared significant pathways between ODs and CDs, we found pathways in cancer, p53 signaling, mismatch repair, mTOR signaling, B cell receptor signaling, and apoptosis pathways. Our findings represent a reliable resource that will contribute to identify the relationships between drugs and disease-pathway networks, enabling to optimise patient diagnosis and disease treatment.
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Different Dose Regimens of Intravenous Tranexamic Acid in Adolescent Spinal Deformity Surgery: A Systematic Review and Meta-Analysis

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Objective. To evaluate the efficacy and safety of different dose regimens of intravenous (IV) tranexamic acid (TXA) in adolescent spinal deformity surgery. Methods. Two researchers independently searched multiple databases, including PubMed, Embase, Cochrane Library, and Web of Science to find studies that met the inclusion criteria. A meta-analysis was performed based on the guidelines of the Cochrane Reviewer's Handbook. Results. Six randomized controlled trials (RCTs) and eleven non-RCTs were identified, including 1148 patients. According to different dose regimens of IV TXA, the included studies were divided into the high-dose group and the low-dose group. Compared with placebo, both groups had less total blood loss (TBL) (high dose: , 95% CI: (-2247.16, -1227.94), ,; low dose: , 95% CI: (-666.06, -391.28), ,), intraoperative blood loss (IBL) (high dose: , 95% CI: (-524.3, -78.66), ,; low dose: , 95% CI: (-967.21, -535.08), ,), and blood transfusion rates (high dose: , 95 % CI: (0.1, 0.37), ,; low dose: , 95% CI: (0.18, 0.91), ,). High-dose IV TXA use was associated with more vertebral fusion segments (, 95% CI: (0.23, 0.82), ,). Low-dose IV TXA use was associated with shorter operative time (, 95% CI: (-26.68, -10.17), ,).Conclusion. High-dose and low-dose IV TXA were effective in reducing TBL, IBL, and blood transfusion rates without increasing complications in adolescent patients undergoing spinal deformity surgery. Low-dose IV TXA was effective in reducing the operative time. Both the high-dose and low-dose groups had similar preoperative and postoperative Hb levels compared to the control group.
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Pantoprazole (PPZ) Inhibits RANKL-Induced Osteoclast Formation and Function In Vitro and Prevents Lipopolysaccharide- (LPS-) Induced Inflammatory Calvarial Bone Loss In Vivo

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Bone remodeling is a process delicately balanced between osteoclastic bone resorption and osteoblastic bone formation. Osteoclasts (OCs) are multinucleated giant cells formed through the fusion of monocytic precursors of the hematopoietic stem cells lineage. OCs are the exclusive cells responsible for the resorption and degradation of the mineralized bone matrix. Pantoprazole (PPZ), a proton pump inhibitor (PPI), is commonly prescribed to reduce excess gastric acid production for conditions such as gastroesophageal reflux disease and peptic ulcer disease. Studies have found contradictory effects of PPI therapy on bone metabolism due to the lack of understanding of the exact underlying mechanism. In this study, we found that PPZ inhibits receptor activator of nuclear factor-κB (NF-κB) ligand- (RANKL-) induced osteoclastogenesis from bone marrow monocytic/macrophage (BMMs) precursors and the bone-resorbing activity of mature OCs. Correspondingly, the expression of OC marker gen es was also attenuated. At the molecular level, PPZ treatment was associated with reduced activation of the ERK MAPK signaling pathways crucial to OC differentiation. Additionally, the in vivo administration of PPZ protected mice against lipopolysaccharide- (LPS-) induced inflammatory calvarial bone erosion, as a result of the reduced number and activity of OCs on the calvarial bone surface. Although PPI use is associated with increased risk of osteoporosis and bone fractures, our study provides evidence for the direct inhibitory effect of PPZ on OC formation and bone resorption in vitro and in vivo, suggesting a potential therapeutic use of PPZ in the treatment of osteolytic disease with localized bone destruction.
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Clinical Characteristics and Spermatogenesis in Patients with Congenital Hypogonadotropic Hypogonadism Caused by FGFR1 Mutations

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Objective. The aim of this study was to investigate the clinical characteristics of patients diagnosed with congenital hypogonadotropic hypogonadism (CHH) caused by FGFR1 (fibroblast growth factor receptor 1) gene mutations and to evaluate the effect of gonadotropin or pulsatile gonadotropin-releasing hormone (GnRH) therapy on spermatogenesis. Methods. A retrospective study was conducted on CHH patients admitted to Peking Union Medical College Hospital from January 2012 to March 2020. Clinical features and laboratory results were recorded. Testicular volume and sperm count responding to gonadotropin and pulsatile GnRH therapy were compared between the FGFR1 mutation group and the mutation-negative group. Results. (1) FGFR1 mutation group included 14 patients who received sperm-induction therapy, and the mutat ion-negative group enrolled 25 CHH patients. (2) The incidence of cryptorchidism was 50.0% (7/14) and 12.0% (3/25) in the FGFR1 group and the mutation-negative group, respectively (). The baseline testicular volume of the FGFR1 mutation group was smaller than that of the mutation-negative group, 1.6 (0.5–2.0) mL vs. 2 (1.75–4) mL (). The baseline luteinizing hormone (LH), Follicle-stimulating hormone (FSH), and testosterone levels were similar between the two groups. (3) Using the Kaplan–Meier and log-rank tests for the analysis of spermatogenesis, it was found that there was no significant difference in the first sperm appearance between the FGFR1 mutation group and the mutation-negative group (χ2 = 1.974, ). The median time of spermatogenesis in the FGFR1 mutation group was longer than that in the mutation-negative group, 16 months vs. 10 months, respectively. The cumulative spermatogenesis success rate at 12 months in the FGFR1 mutation group (35.71%) was lower than th at in the mutation-negative group (68.75%) (). The sperm concentration in the mutation-negative group was more easily achieved for different thresholds compared with that in the FGFR1 mutation group, but no significant difference was observed () between the two groups. The last follow-up examination showed that the testicular volume was 7.00 (4.75–12.00) mL and 10.56 ± 4.82 mL (), the ejaculate volume of sperm was 2.20 (1.40–2.26) mL and 3.06 ± 1.42 mL (), and the sperm concentration was 7.19 (1.00–9.91) million/mL and 18.80 (4.58–53.62) million/mL () in the FGFR1 mutation and mutation-negative groups, respectively, while the sperm motility (A%, A + B%, and A + B + C%) was similar for the two groups (, 0.909, and 0.759, respectively). The testosterone level during treatment was 366.02 ± 167.03 ng/dL and 362.27 ± 212.86 ng/dL in the FGFR1 mutation and mutation-negative groups, respectively ().Conclusion. Patients with FGFR1 mutations ha ve a higher prevalence of cryptorchidism and smaller testicular volume. Although patients with FGFR1 mutations have a similar rate of success for spermatogenesis compared to that of the mutation-negative patients, a longer treatment period was required and a lower sperm concentration was achieved.
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Reversed Septal Curvature Is Associated with Elevated Troponin Level in Hypertrophic Cardiomyopathy

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The aim of study was to compare patients with hypertrophic cardiomyopathy divided according to septal configuration assessed in a 4-chamber apical window. The study group consisted of 56 consecutive patients. Reversed septal curvature (RSC) and non-RSC were diagnosed in 17 (30.4%) and 39 (69.6%) patients, respectively. Both RSC and non-RSC groups were compared in terms of the level of high-sensitivity troponin I (hs-TnI), NT-proBNP (absolute value), NT-proBNP/ULN (value normalized for sex and age), and echocardiographic parameters, including left ventricular outflow tract gradient (LVOTG). A higher level of hs-TnI was observed in RSC patients as compared to the non-RSC group (102 (29.2-214.7) vs. 8.7 (5.3-18) (ng/l), ). A trend toward increased NT-proBNP value was reported in RSC patients (1279 (367.3-1186) vs. 551.7 (273-969) (pg/ml), ). However, no difference in the NT-proBNP/ULN level between both groups was observed. Provocable LVOTG was higher in RSC as compared to non-RSC patients (51 (9.5-105) vs. 13.6 (7.5-31) (mmHg), ). Furthermore, more patients with RSC had prognostically unfavourable increased septal thickness to left LV diameter at the end diastole ratio. Patients with RSC were associated with an increased level of hs-TnI, and the only trend observed in this group was for the higher NT-proBNP levels. RSC seems to be an alerting factor for the risk of ischemic events. Not resting but only provocable LVOTG was higher in RSC as compared to non-RSC patients.
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Hepcidin Is a Reliable Marker of Iron Deficiency Anemia in Newly Diagnosed Patients with Inflammatory Bowel Disease

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Background and Aim. Differentiating iron deficiency anemia (IDA) from anemia of chronic disease (ACD) in patients with inflammatory bowel disease (IBD) represents a clinical challenge. Hepcidin is a polypeptide synthetized in the liver, and iron levels or inflammation mostly regulate hepcidin production. Our aim was to determine serum hepcidin levels in patients with inflammatory bowel disease (IBD) as well to investigate whether hepcidin levels correlate with disease activity. Material and Methods. A case-control study was preformed among newly diagnosed IBD patients and same number age- and sex-matched healthy controls. All patients underwent a total ileocolonoscopy. Complete blood count was obtained in addition to inflammatory markers (CRP, erythrocyte sedimentation rate-ESR). Serum levels of hepcidin were de termined with commercially available enzyme-linked immunosorbent assay (DRG Instruments Marburg, Germany). Serum iron, TIBC, and UIBC were assessed with an electrochemiluminesence immunoassay, and soluble transferrin receptor (sTfR) was assessed using an immunoturbidimetric method. Mayo score and CDAI, respectively, were calculated for each patient. Statistical analyses were performed using the SPSS software version 20.0 for Windows. Results. There was a high statistically significant difference between IBD patients and controls in levels of hepcidin (). Namely, serum hepcidin levels were significantly higher in the control group. There was no statistically significant correlation of serum hepcidin with CRP, Mayo score, or CDAI, respectively (). However, we have found a statistically significant negative correlation of sTfR and TIBC with hepcidin ().Conclusion. Results of our study suggest that hepcidin is a reliable marker of IDA in patients with IBD, and it could be used in routin e clinical practice when determining adequate therapy in these patients.
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Identification of Featured Metabolism-Related Genes in Patients with Acute Myocardial Infarction

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Objective. A growing body of emerging evidence indicates that metabolic processes play a pivotal role in the biological processes underlying acute myocardial infarction (AMI). The aim of the current study was to identify featured metabolism-related genes in patients with AMI using a support vector machine (SVM) and to further explore the value of these genes in the diagnosis of AMI. Methods. Gene microarray expression data related to AMI were downloaded from the GSE66360 dataset in the Gene Expression Omnibus (GEO) database. This data set consisted of 50 AMI samples and 49 normal controls that were randomly classified into a discovery cohort (21 AMI samples and 22 normal controls) and a validation cohort (28 AMI and 28 normal controls). We applied a machine learning method that combined SVM with recursive featur e elimination (RFE) to discriminate AMI patients from normal controls. Based on this, an SVM classifier was constructed. Receiver operating characteristic (ROC) analysis was used to investigate the predictive value for the early diagnosis of AMI in the two cohorts and was then further verified in an independent external cohort. Results. Three metabolism-related genes were identified based on SVM-RFE (AKR1C3, GLUL, and PDE4B). The SVM classifier based on the three genes allowed for excellent discrimination between AMI and healthy samples in both the discovery cohort () and the validation cohort (), and this was further confirmed in the GSE68060 dataset (). Additionally, the SVM classifier allowed for perfect discrimination between recurrent AMI events and nonrecurrent events in the GSE68060 cohort (). GO and KEGG pathway enrichment analysis of the identified featured genes revealed significant enrichment of specific metabolic pathways. Conclusion. The identified metabolism-related ge nes may play important roles in the development of AMI and may represent diagnostic and therapeutic biomarkers of AMI.
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