The evaluation of the colour changes of traditional composites, ceramic blocks and cad/cam composites in different solutions.

AIMS: The aim of this study is to investigate the color changes of three different traditional composites, one ceramic and two resin-based composites CAD/CAM blocks in different solutions. METHODS: The materials used in the study were CAD/CAM block containing lithium disilicate glass ceramic (Ivoclar), Vita Enamic containing resin (VITA), Lava Ultimate Block containing resin (3M ESPE), G-aenial anterior composite (GC,), Filtek™ Ultimate Universal composite (3M ESPE) and Clearfil Majesty Esthetic composite (Kuaray). As colouring solutions, red wine (Buzbaǧ), black tea (Lipton), coffee (Nescafe) and distilled water (EAU distillee) were used. For the preparation of the traditional composite samples to be used in the study, 7 × 7 mm square-shaped plexiglass moulds, 1.2 mm in thickness, were used. The CAD/CAM blocks with ceramic and resin content were cut at the same thickness using a Struers sensitive cutting device. The samples were then randomly separated into grups of 10 and of the 240 samples, groups were separated into 6 different materials and 4 different solutions. The colour measurements of the 240 samples were taken at baseline, 30 days and 120 days with a Lovibond spectrophotometer (Tintometer). RESULTS: A statistically significant difference was determined between the materials in respect of the ΔE values in the 30-day solution groups (P < 0.05). No statistically significant difference was determined in the ΔE values of the different materials in the 30-day and 120-day distilled water groups (P > 0.05). A statistically significant difference was determined between the materials in respect of the ΔE values in the 120-day solution groups (P < 0.05). CONCLUSION: In respect of discolouration, ceramic blocks are more successful. Resin-based blocks and traditional aesthetic composites showed more discolouration. The dietary habits of the patient should be taken into consideration in the selection of the restorative material.

Surgical outcomes of sleeve resections performed for non-small cell lung cancer; A single center experience.

BACKGROUND: Although bronchial sleeve resections were performed instead of pneumonectomy in patients with insufficient pulmonary function initially, it is currently available as an alternative to pneumonectomy even in patients with adequate pulmonary reserve. AIMS: In this study, we aimed to evaluate the sleeve resections performed for lung cancer in terms of technical, postoperative complication mortality, survival rates and survival factors, complication and to compare them with the literature. METHODS: Patients who underwent sleeve lung resection with diagnosis of non-small cell lung cancer at our department between January 2012 and December 2017 were included in the study. Patients' data were analyzed according to tumor size, tumor histopathology, hilar/mediastinal lymph nodes invasion status, postoperative complications, operative mortality, resection type, overall survival and diseases-free survival, tumor location, and length of stay in intensive care unit. RESULTS: A total of 71 patients included the study. Right upper sleeve lobectomy was applied to 40 (56.3%) patients and left upper sleeve lobectomy was performed to 19 (26.8%) patients. The most common histopathological diagnosis was squamous cell carcinoma. The mean tumor diameter was 3.39 (SD: 2.25) cm. There was no nodal invasion in 41 (57.7%) patients and N1 nodal positivity was detected in 18 (25.4%) patients and N2 positivity in 12 (16.9%) patients. Median survival time was 43.6 months (35.4-51.8 months), the 3- and 5-year overall survival were 65.7% and 40.6%, respectively. There was a statistically significant correlation relationship between nodal invasion and recurrence, but this relation was not found in overall survival. CONCLUSION: In our study, no significant correlation was found between mediastinal lymph node invasion and overall survival. Supporting this result with multi-centered and prospective studies may encourage surgeons for sleeve resection in indicated patients had lung cancer with nodal invasion.

Integrase Strand Transfer Inhibitors (INSTIs) Resistance Mutations in HIV-1 Infected Turkish Patients.

OBJECTIVES: Integrase strand transfer inhibitor (INSTI) is a new class of antiretroviral (ARV) drugs designed to block the action of the integrase viral enzyme, which is responsible for insertation of the HIV-1 genome into the host DNA. The aim of this study was to evaluate for the first time INSTI resistance mutations in Turkish patients. METHODS: This study was conducted in Turkey, between April 2013 and April 2015 using 169 HIV-1-infected patients (78 ARV naive patients and 91 ARV-experienced patients). Laboratory and clinical characteristics of ARV naive and ARV-experienced patients were as follows: gender (M/F): 71/7 and 80/11, median age: 38 and 38.4; median CD4(+) T-cell: 236 and 216 cells/mm(3), median HIV-1 RNA: 4.95+E5 and 1.08E+6 copies/ml. Population-based seqeunces of the reverse transcriptase, protease, and integrase domains of the HIV-1 pol gene were used to detect HIV-1 drug resistance mutations. RESULT: INSTI resistance mutations were not found in recently diagnosed HIV-1-infected patients. However, ARV-experienced patients had major resistance mutations associated with raltegravir and elvitegravir; the following results were generated:F121Y, Y143R, Q148R and E157Q (6/91 - 6.6%). CONCLUSIONS: The prevalence of INSTI resistant mutations in ART-experienced patients suggested that resistance testing must be incorporated as an integral part of HIV management with INSTI therapies.

In vitro and clinical studies on the efficacy of α-cyclodextrin and hydroxytyrosol against SARS-CoV-2 infection.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new coronavirus responsible for the current pandemic of coronavirus disease 2019 (COVID-19). This virus attacks cells of the airway epithelium by binding transmembrane angiotensin-converting enzyme 2 (ACE2). Hydroxytyrosol has anti-viral properties. Alpha-cyclodextrin can deplete sphingolipids and phospholipids from cell membranes. The aim of the present experimental study was to evaluate the efficacy of α-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2 infection in in vitro cell models and humans. PATIENTS AND METHODS: For in vitro experiments on Vero E6 cells, RNA for RT-qPCR analysis was extracted from Caco2 and human fibroblast cell lines. For study in humans, the treatment group consisted of 149 healthy volunteers in Northern Cyprus, considered at higher risk of SARS-CoV-2 infection than the general population. The volunteers used nasal spray containing α-cyclodextrin and hydroxytyrosol for 4 weeks. The control group consisted of 76 healthy volunteers who did not use the spray. RESULTS: RT-qPCR experiments on targeted genes involved in endocytosis showed a reduction in gene expression, whereas cytotoxicity and cytoprotective tests showed that the compounds exerted a protective effect against SARS-CoV-2 infection at non-cytotoxic concentrations. None of the volunteers became positive to SARS-CoV-2 RT-qPCR assay during the 30 days of treatment. CONCLUSIONS: Treatment with α-cyclodextrin and hydroxytyrosol nasal spray improved defenses against SARS-CoV-2 infection and reduced synthesis of viral particles.

Naturally occurring amino-acid substitutions to nucleos(t)ide analogues in treatment naive Turkish patients with chronic hepatitis B.

Naturally occurring amino-acid substitutions in the hepatitis B virus (HBV) polymerase gene may be responsible for resistance to nucleoside/nucleotide (NUCs) analogues. To date, only pre-existing lamivudine resistance has been extensively studied. The aim of the present study was to determine the naturally occurring or pre-existing amino-acid substitutions related to NUCs in treatment naive Turkish patients with chronic hepatitis B (CHB). The investigation involved a total of 88 patients (65 males and 23 females; mean age, 34 years; range, 15-61 years) who were diagnosed with CHB between April 2008 and January 2009. According to HBeAg status, 66 patients were HBeAg-negative and 22 patients were HBeAg positive. Naturally occurring substitutions in the HBV polymerase region were detected by DNA sequencing in 17 (19%) and 30 (34%) patients, based on manual and geno2pheno tool database interpretation, respectively. Each amino-acid substitution appeared alone and included rtA194T, rtV214A, rtQ215S, rtI233V and rtN236T. The median values for viral load, ALT and AST were 3.3 log(10) (2.0-6.0) IU/mL, 36 (12-515) U/L and 27 (13-284) U/L, respectively, but these did not correlate with the observed amino-acid substitutions in the polymerase region. By direct sequencing, genotype D of HBV was found to still be dominant among Turkish patients. In conclusion, every patient who is diagnosed with CHB should be monitored before the start of treatment for more effective management of patient treatment options.

Inhibition of microglial and astrocytic inflammatory responses by the immunosuppressant mycophenolate mofetil.

AIMS: Nucleotide depletion induced by the immunosuppressant mycophenolate mofetil (MMF) has been shown to exert neuroprotective effects. It remains unclear whether nucleotide depletion directly counteracts neuronal demise or whether it inhibits microglial or astrocytic activation, thereby resulting in indirect neuroprotection. METHODS: Effects of MMF on isolated microglial cells, astrocyte/microglial cell co-cultures and isolated hippocampal neurones were analysed by immunocytochemistry, quantitative morphometry, and elisa. RESULTS: We found that: (i) MMF suppressed lipopolysaccharide-induced microglial secretion of interleukin-1ß, tumour necrosis factor-α and nitric oxide; (ii) MMF suppressed lipopolysaccharide-induced astrocytic production of tumour necrosis factor-α but not of nitric oxide; (iii) MMF strongly inhibited proliferation of both microglial cells and astrocytes; (iv) MMF did not protect isolated hippocampal neurones from excitotoxic injury; and (v) effects of MMF on glial cells were reversed after treatment with guanosine. CONCLUSIONS: Nucleotide depletion induced by MMF inhibits microglial and astrocytic activation. Microglial and astrocytic proliferation is suppressed by MMF-induced inhibition of the salvage pathway enzyme inosine monophosphate dehydrogenase. The previously observed neuroprotection after MMF treatment seems to be indirectly mediated, making this compound an interesting immunosuppressant in the treatment of acute central nervous system lesions.

An outbreak of oropharyngeal tularaemia linked to natural spring water.

A tularaemia outbreak was investigated involving 188 suspected cases in the Kocaeli region of Turkey between December 2004 and April 2005. A case-control study comprising 135 laboratory-confirmed cases and 55 controls was undertaken to identify risk factors for the development of the outbreak and to evaluate laboratory diagnostic methods. Tularaemia was confirmed by a microagglutination test (MAT) titre of >or=1 : 160 in 90 of the patients. In MAT-negative sera, 23/44 (52 %) were positive by ELISA with Francisella tularensis LPS and 1/9 (11 %) by Western blotting with this antigen. A species-specific PCR was positive in 16/25 (64 %) throat swabs and 8/13 (62 %) lymph node aspirates. Multivariate analysis showed that drinking natural spring water was the leading risk factor for the development of tularaemia (P=0.0001, odds ratio 0.165, 95 % CI 0.790-0.346). The outbreak ceased after abandonment of the suspected natural water springs.

Thy1-Targeted Microbubbles for Ultrasound Molecular Imaging of Pancreatic Ductal Adenocarcinoma.

Purpose: To engineer a dual human and murine Thy1-binding single-chain-antibody ligand (Thy1-scFv) for contrast microbubble-enhanced ultrasound molecular imaging of pancreatic ductal adenocarcinoma (PDAC).Experimental Design: Thy1-scFv were engineered using yeast-surface-display techniques. Binding to soluble human and murine Thy1 and to Thy1-expressing cells was assessed by flow cytometry. Thy1-scFv was then attached to gas-filled microbubbles to create MBThy1-scFv Thy1 binding of MBThy1-scFv to Thy1-expressing cells was evaluated under flow shear stress conditions in flow-chamber experiments. MBscFv-scrambled and MBNon-targeted were used as negative controls. All microbubble types were tested in both orthotopic human PDAC xenografts and transgenic PDAC mice in vivoResults: Thy1-scFv had a KD of 3.4 ± 0.36 nmol/L for human and 9.2 ± 1.7 nmol/L for murine Thy1 and showed binding to both soluble and cellularly expressed Thy1. MBThy1-scFv was attached to Thy1 with high affinity compared with negative control microbubbles (P < 0.01) as assessed by flow cytometry. Similarly, flow-chamber studies showed significantly (P < 0.01) higher binding of MBThy1-scFv (3.0 ± 0.81 MB/cell) to Thy1-expressing cells than MBscFv-scrambled (0.57 ± 0.53) and MBNon-targeted (0.43 ± 0.53). In vivo ultrasound molecular imaging using MBThy1-scFv demonstrated significantly higher signal (P < 0.01) in both orthotopic (5.32 ± 1.59 a.u.) and transgenic PDAC (5.68 ± 2.5 a.u.) mice compared with chronic pancreatitis (0.84 ± 0.6 a.u.) and normal pancreas (0.67 ± 0.71 a.u.). Ex vivo immunofluorescence confirmed significantly (P < 0.01) increased Thy1 expression in PDAC compared with chronic pancreatitis and normal pancreas tissue.Conclusions: A dual human and murine Thy1-binding scFv was designed to generate contrast microbubbles to allow PDAC detection with ultrasound. Clin Cancer Res; 24(7); 1574-85. ©2018 AACR.

Ultrasound Molecular Imaging of the Breast Cancer Neovasculature using Engineered Fibronectin Scaffold Ligands: A Novel Class of Targeted Contrast Ultrasound Agent.

Molecularly-targeted microbubbles (MBs) are increasingly being recognized as promising contrast agents for oncological molecular imaging with ultrasound. With the detection and validation of new molecular imaging targets, novel binding ligands are needed that bind to molecular imaging targets with high affinity and specificity. In this study we assessed a novel class of potentially clinically translatable MBs using an engineered 10(th) type III domain of human-fibronectin (MB-FN3VEGFR2) scaffold-ligand to image VEGFR2 on the neovasculature of cancer. The in vitro binding of MB-FN3VEGFR2 to a soluble VEGFR2 was assessed by flow-cytometry (FACS) and binding to VEGFR2-expressing cells was assessed by flow-chamber cell attachment studies under flow shear stress conditions. In vivo binding of MB-FN3VEGFR2 was tested in a transgenic mouse model (FVB/N Tg(MMTV/PyMT634Mul) of breast cancer and control litter mates with normal mammary glands. In vitro FACS and flow-chamber cell attachment studies showed significantly (P<0.01) higher binding to VEGFR2 using MB-FN3VEGFR2 than control agents. In vivo ultrasound molecular imaging (USMI) studies using MB-FN3VEGFR2 demonstrated specific binding to VEGFR2 and was significantly higher (P<0.01) in breast cancer compared to normal breast tissue. Ex vivo immunofluorescence-analysis showed significantly (P<0.01) increased VEGFR2-expression in breast cancer compared to normal mammary tissue. Our results suggest that MBs coupled to FN3-scaffolds can be designed and used for USMI of breast cancer neoangiogenesis. Due to their small size, stability, solubility, the lack of glycosylation and disulfide bonds, FN3-scaffolds can be recombinantly produced with the advantage of generating small, high affinity ligands in a cost efficient way for USMI.

A case report: antiviral triple therapy with telaprevir in a haemodialysed HCV patient in Turkey.

A 49-year-old woman was diagnosed with chronic hepatitis C 7 years ago. She began haemodialysis at the same time. She was on the waiting list for kidney transplantation (KTx). The real-time PCR technique revealed an HCV RNA viral load of 212,000 IU/ml, genotype 1a, IL28B the rs12979860 minor allele heterozygous CT (rs8099917 TT homozygous). She had a history of first antiviral treatment for 48 weeks of PEG-IFN-alpha 2a, 135 µg/week in 2011, but the HCV infection relapsed. Considering her relatively young age, candidacy for renal transplant, and the heterozygous pattern of IL28B, we decided to proceed with a second (and last) antiviral treatment using triple therapy with telaprevir at the regular dose of 750 mg every 8 hours+PEG-IFN-alpha 2a 135 µg/week sc+200 mg RBV three times a week. At the end of 6-month therapy, HCV RNA was found to be negative at months 3, 5, and 6.The patient has reached the sustained virological response (SVR) and is ready for KTx. All renal transplant candidates (dialysis-dependent, or not) with HCV should be assessed for antiviral treatment given the increased risk of progressive liver disease due to immunosuppressive therapy, increased life expectancy compared to other HCV-positive patients on dialysis, and the inability to receive interferon after transplantation.