Power spectral density-based nearinfrared sub-band detection for noninvasive blood glucose prediction in both in-vitro and in-vivo studies

Diabetes is a widespread and serious disease and noninvasive measurement has been in high demand.To address this problem,a power spectral density-based method was offered for determining glucose sensitive sub-bands in the nearinfrared(NIR)spectrum.The experiments were conducted using phantoms of different optical properties in-vitro conditions.The optical bands 1200–1300 nm and 2100–2200 nm were found feasible for measuring blood glucose.After that,a photoplethysmography(PPG)-based low cost and portable optical system was designed.It has six di®erent NIR wavelength LEDs for illumination and an InGaAs photodiode for detection.Optical density values were calculated through the system and used as independent variables for multiple linear regression analysis.The results of blood glucose levels for 24 known healthy subjects showed that the optical system prediction was nearly 80%in the A zone and 20%in the B zone according to the Clarke Error Grid analysis.It was shown that a promising easyuse,continuous,and compact optical system had been designed.

Investigation of Methylation Profiles of TP53, Caspase 9, Caspase 8, Caspase 3 Genes Treated with DNA Methyl Transferase Inhibitor (DNMTi) Zebularine (ZEB) and Caffeic Acid Phenethyl Ester (CAPE) on MCF-7 and MDA-MB-231 Breast Cancer Cell Lines

Purpose: MCF-7 (ER+, WTP53) and MDA-MB-231 (ER Met, Mutant P53) Caffeic Acid Phenethyl Ester (CAPE) and DNA Methyl Transferase Inhibitor (DNMTi) in breast cancer cell lines of Zebularine (ZEB) single and combined application of TP53, caspase-9, caspase 8 and caspase-3 genes as a result of the use of single and combined drug methylation profiles are aimed to be evaluated by specific PCR method. Material-Metods: In the MCF-7 and MDA-MB-231 breast cancer cell lines, MTT test and survival analysis were performed as a result of single and combined application of CAPE and Zebularine and Methylation Specific PCR was performed to examine the methylation of caspase-3, caspase-8, caspase-9 and TP53 genes. Results: According to the results of 24-hour drug administration, the IC50 for the MCF-7 cell line was determined as 200 μM, for CAPE 40 μM and for the combined values of 50 μM ZEB + 5 μM CAPE. The effects of caspase-3, caspase-8, caspase-9 and TP53 genes on the methylation level of ZEB, CAPE and ZEB + CAPE drug combination were determined by using bisulfite modified DNAs in MCF-7 and MDA-MB-231 cell lines. Discussion: In the MCF-7 cell line, the 120 μM ZEB viability rate was 51%, and the viability of 80 μM ZEB MDA-MB-231 breast cancer cells decreased by 59.7%. After 20 μM CAPE, viability in MCF-7 cells decreased by 31% in 120 μM CAPE and MDA-MB-231 cells decreased by 41%. The viability with 40 μM CAPE decreased by 19% in MDA-MB-231 cells. It was found that 20 μM CAPE concentration was associated with TP53 methylation in MCF-7 cell lines. The 80 μM ZEB concentration was found to be closely related to the unmethylated status of the TP53 gene. These results obtained with 50 μM ZEB + 5 μM CAPE application were found to be related to the methylated-unmetylated status of the TP53 gene in half (50%). For the caspase-9 gene of MDA-MB-231 cells, 80 μM ZEB concentration was found to be associated with unmetylated status. The effective use of drugs with low concentrations of the drug dose provides a more appropriate approach in terms of treatment.

Effect of intracorneal ring segment implantation on corneal asphericity

AIM： To evaluate the visual, refractive and corneal asphericity changes after intrastromal corneal ring segment（ICRS） implantation for visual rehabilitation of keratoconus.METHODS： A total of 42 eyes of 32 patients were included. After creation of intrastromal tunnels of 5.01±0.03 mm inner diameter, 5.71±0.03 mm outer diameter and at 384.21±34.12 μm depth, 1 or 2 ICRS of 150-300 μm thickness and 90°-210° arc length were implanted. Changes in uncorrected distance visual acuity（UDVA）, corrected distance visual acuity（CDVA）, refractive errors, mean simulated keratometry readings SimK_（avg）, anterior and posterior corneal asphericity values（Q_（ant） and Q_（post）, respectively） measured with Scheimpflug topography were evaluated retrospectively. RESULTS： There was a significant improvement in UDVA and CDVA, along with a significant decrease in refractive spherical equivalent（SE）, cylinder and SimK_（avg） postoperatively（P〈0.001 for all）. Mean Qant increased from-1.06±0.48 to-0.57±0.58 postoperatively（P〈0.001）. Change in mean Qpost was insignificant（P=0.92）. Postoperative changes in UDVA and CDVA were not correlated with the postoperative changes in SE and cylinder（P〉0.05 for all）; but were correlated with the preoperative SimK_（avg） and Q_（ant） values（P〈0.001 for all）. CONCLUSION： ICRS implantation seems to approximate the anterior corneal asphericity of ＂advanced prolate＂ shape to ＂optimal prolate＂ shape and an ＂ideal Q value＂ of-0.46; which may have a role in improved UDVA and CDVA postoperatively, besides decreased refractive cylinder values.

Analysis of aggressiveness factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization

AIM To investigate novel predictors of survival in hepatocellular carcinoma(HCC) patients following transarterial chemoembolization(TACE).METHODS One hundred sixty seven patients with un-resectable HCC were retrospectively analyzed to identify factors that might contribute to their HCC biology and aggressiveness. We correlated routine laboratory results(total bilirubin, AST, ALKP, GGTP, albumin etc.) to maximum tumor diameter, number of tumor nodules, portal vein thrombosis and blood alpha-fetoprotein levels. These 4 parameters were previously combined to form an aggressiveness index(AgI). We used The Wilcoxon ranksum(Mann-Whitney), to test the correlation between the AgI categories and liver function parameters. The Cox proportional hazards model was applied to evaluate the categories of AgI associated with overall survival. RESULTS The AgI was strongly correlated with survival in this novel patient population. Three year survival probability for AgI > or < 4 was 42.4% vs 61.8%; P < 0.0863 respectively. Several factors independently correlated with AgI using univariate multiple logistic regression of AgI with 8 laboratory parameters. Lower albumin levels had an OR of 2.56(95%CI: 1.120-5.863 P < 0.026), elevated Alkaline phosphatase and gamma glutamyl transpeptidase(GGTP) had ORs of 1.01(95%CI: 1.003-1.026, P < 0.017) and 0.99(95%CI: 0.99-1.00, P < 0.053) respectively. In a Cox proportional hazard model combining mortality for AgI score and liver function parameters, only GGTP levels and the AgI were independently associated with survival. An AgI > 4 had HR for mortality of 2.18(95%CI: 1.108-4.310, P < 0.024). GGTP's single unit change had a HR for mortality of 1.003(95%CI: 1.001-1.006, P < 0.016). These were considered in the final multivariate model with the total cohort. An AgI > 4 had a HR for mortality of 2.26(95%CI: 1.184-4.327, P < 0.016). GGTP had a HR of 1.003(95%CI: 1.001-1.004, P < 0.001).CONCLUSION Our study validates the AgI in a new population with un-resectable HCC patients undergoing TACE. The analysis establishes a correlation between GGTP and the AgI.

The number of intracorneal ring segments in asymmetric and central cones

Background:To compare the results of single versus double intracorneal ring segment(ICRS)(KeraRing)implantation in keratoconus with respect to different cone locations.Methods:Twenty-two eyes of 18 patients with totally asymmetric cones(20-80%or 0-100%distribution along steep axis)were implanted with single ICRS(Group 1),38 eyes of 32 patients with central or partially asymmetric cones(50-50%or 40-60%distribution along steep axis)were implanted with double ICRS(Group 2),at a depth of 80%of the site of implantation,in channels created with femtosecond laser device.All patients had uncorrected and corrected distance visual acuities(UDVA and CDVA,respectively)of≤0.3 Snellen lines.Results:In both groups,patients had median UDVA and CDVA gain of 3 Snellen lines(P>0.05).Postoperative improvement in indices of vertical asymmetry and height decentration in Group 1;simulated keratometry,corneal astigmatism and anterior corneal asphericity values in Group 2 were greater(P<0.05).A total of 10 eyes(45.5%)in Group 1 were recommended double ring implantation by the manufacturer’s nomogram,but underwent single ICRS implantation and achieved visual,refractive,tomographic outcomes comparable to that in Group 2,although corneal cylindrical correction was less and final topographic astigmatism was greater.Conclusion:Double ICRS implantation seems to be superior in terms of keratometry,corneal astigmatism and anterior corneal asphericity improvement.Single ICRS implantation in totally asymmetric cones seems to provide satisfactory visual,refractive and tomographic results,similar to double ICRS implantation in central and partially asymmetric cones,by inducing central shift of the cone.

Review of therapies for intermediate and advanced stage hepatocellular carcinoma, not suitable for curative therapies: a rapidly changing landscape

Recent clinical trials and new agents have permitted greater clarity in the choice of effective agents for that majority of patients with hepatocellular carcinoma who have advanced disease at diagnosis and thus cannot be offered potentially curative resection,ablation or liver transplantation.The main treatment for these patients remains chemoembolization,although evidence for selective internal radiation therapy(SIRT)with SIR-Spheres or Theraphere,is beginning to suggest that the results with this may be comparable with less toxicity.Patients who have failed chemoembolization or SIRT or have metastatic disease at presentation are suitable for the multikinase inhibitor sorafenib(nexavar)or newly-approved lenvatinib(lenvima)as first line therapies.The choice between which of them to use first is not currently clear.Patients who have failed sorafenib can be offered a choice of FDA-approved regorafenib(stivarga)or immune checkpoint inhibitor nivolumab(opdivo)as second line agents.For that considerable percent of patients presenting with macroscopic portal vein thrombosis,the choice appears to be between multikinase inhibitor or SIRT,given the potential toxicity of chemoembolization in this setting.However,considering the potency of both nivolumab and regorafenib and the pipeline of new agents such as atezolizumab(tecentriq)in current clinical trials,including new immune checkpoint inhibitors,this landscape may change within a couple of years,especially if new evidence arises for the superior effectiveness of combinations of any of these agents over single agents.

Wnt/β-catenin signaling in heart regeneration

The ability to repair damaged or lost tissues varies significantly among vertebrates.The regenerative ability of the heart is clinically very relevant,because adult teleost fish and amphibians can regenerate heart tissue,but we mammals cannot.Interestingly,heart regeneration is possible in neonatal mice,but this ability is lost within 7 days after birth.In zebrafish and neonatal mice,lost cardiomyocytes are regenerated via proliferation of spared,differentiated cardiomyocytes.While some cardiomyocyte turnover occurs in adult mammals,the cardiomyocyte production rate is too low in response to injury to regenerate the heart.Instead,mammalian hearts respond to injury by remodeling of spared tissue,which includes cardiomyocyte hypertrophy.Wnt/β-catenin signaling plays important roles during vertebrate heart development,and it is re-activated in response to cardiac injury.In this review,we discuss the known functions of this signaling pathway in injured hearts,its involvement in cardiac fibrosis and hypertrophy,and potential therapeutic approaches that might promote cardiac repair after injury by modifying Wnt/β-catenin signaling.Regulation of cardiac remodeling by this signaling pathway appears to vary depending on the injury model and the exact stages that have been studied.Thus,conflicting data have been published regarding a potential role of Wnt/β-catenin pathway in promotion of fibrosis and cardiomyocyte hypertrophy.In addition,the Wnt inhibitory secreted Frizzled-related proteins(sFrps)appear to have Wnt-dependent and Wnt-independent roles in the injured heart.Thus,while the exact functions of Wnt/β-catenin pathway activity in response to injury still need to be elucidated in the non-regenerating mammalian heart,but also in regenerating lower vertebrates,manipulation of the pathway is essential for creation of therapeutically useful cardiomyocytes from stem cells in culture.Hopefully,a detailed understanding of the in vivo role of Wnt/β-catenin signaling in injured mammalian and non-mammalian hearts will also contribute to the success of current efforts towards developing regenerative therapies.