Assessing Feasibility and Safety of Using Ultrasonic Bone Aspirator for Revision Endoscopic Sinus Surgery

Background and Objectives This study introduced and evaluated the efficacy of an ultrasonic bony aspirator (UBA) in revision endoscopic sinus surgery and compared the outcomes to those of the traditional cold instrument approach. Methods This retrospective study enrolled 57 patients who underwent revision endoscopic sinus surgery between June 2010 and December 2017, 17 patients with a UBA approach and 40 patients with traditional instruments. Results Median Lund–Kennedy scores showed a statistically significant difference between the two groups at 3 months (p=0.004). Synechiae occurred in 17.6% and 35% of cases in the UBA and traditional groups, respectively. The mean operative time was significantly shorter in the traditional group (p=0.001). Conclusion The use of a UBA in revision endoscopic sinus surgery was safe and effective

TRAIL sensitize MDR cells to MDR-related drugs by down-regulation of P-glycoprotein through inhibition of DNA-PKcs/Akt/GSK-3β pathway and activation of caspases

<p>Abstract</p> <p>Background</p> <p>The development of new modulator possessing high efficacy, low toxicity and high selectivity is a pivotal approach to overcome P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in cancer treatment. In this study, we suggest a new molecular mechanism that TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) down-regulates P-glycoprotein (P-gp) through inhibition of DNA-PKcs/Akt/GSK-3β pathway and activation of caspases and thereby sensitize MDR cells to MDR-related drugs.</p> <p>Results</p> <p>MDR variants, CEM/VLB_10-2, CEM/VLB_55-8and CEM/VLB₁₀₀cells, with gradually increased levels of P-gp derived from human lymphoblastic leukemia CEM cells, were gradually more susceptible to TRAIL-induced apoptosis and cytotoxicity than parental CEM cells. The P-gp level of MDR variants was positively correlated with the levels of DNA-PKcs, pAkt, pGSK-3β and c-Myc as well as DR5 and negatively correlated with the level of c-FLIPs. Hypersensitivity of CEM/VLB₁₀₀cells to TRAIL was accompanied by the activation of mitochondrial apoptotic pathway as well as the activation of initiator caspases. In addition, TRAIL-induced down-regulation of DNA-PKcs/Akt/GSK-3β pathway and c-FLIP and up-regulation of cell surface expression of death receptors were associated with the increased susceptibility to TRAIL of MDR cells. Moreover, TRAIL inhibited P-gp efflux function via caspase-3-dependent degradation of P-gp as well as DNA-PKcs and subsequently sensitized MDR cells to MDR-related drugs such as vinblastine and doxorubicin. We also found that suppression of DNA-PKcs by siRNA enhanced the susceptibility of MDR cells to vincristine as well as TRAIL via down-regulation of c-FLIP and P-gp expression and up-regulation of DR5.</p> <p>Conclusion</p> <p>This study showed for the first time that the MDR variant of CEM cells was hypersensitive to TRAIL due to up-regulation of DR5 and concomitant down-regulation of c-FLIP, and degradation of P-gp and DNA-PKcs by activation of caspase-3 might be important determinants of TRAIL-induced sensitization of MDR cells to MDR-related drugs. Therefore, combination of TRAIL and chemotherapeutic drugs may be a good strategy for treatment of cancer with multidrug resistance.</p

Precise Synthesis of Bottlebrush Block Copolymers from ω-End-Norbornyl Polystyrene and Poly(4-tert-butoxystyrene) via Living Anionic Polymerization and Ring-Opening Metathesis Polymerization

A facile and efficient synthetic grafting-through strategy for preparing well-defined bottlebrush block copolymers (BBCPs) was developed through a combination of living anionic polymerization (LAP) and ring-opening metathesis polymerization (ROMP). ω-End-norbornyl polystyrene (NPSt) and poly(4-tert-butoxystyrene) (NPtBOS) were synthesized by LAP using terminator of chlorine moiety containing silane-protecting amine and coupled with a subsequent amidation using norbornyl activated ester. Bottlebrush homopolymers of NPSt were obtained by ROMP with ultrahigh molecular weights (MWs, M_w = 2928 kDa) and narrow molecular weight distributions (MWDs, Đ = 1.07) at high degree of polymerizations (DP_w = 1084). Well-defined BBCPs with ultrahigh MWs (M_w ∼ 3055 kDa) and narrow MWDs (Đ ∼ 1.13) were synthesized through sequential ROMP of NPSt with NPtBOS. The effect of ultrahigh MWs was investigated by self-assembly of the BBCPs in which the phase-separated BBCPs presented periodic lamellar structures and exhibited structural colors from blue to pink

Precise Synthesis of Bottlebrush Block Copolymers from ω-End-Norbornyl Polystyrene and Poly(4-tert-butoxystyrene) via Living Anionic Polymerization and Ring-Opening Metathesis Polymerization

A facile and efficient synthetic grafting-through strategy for preparing well-defined bottlebrush block copolymers (BBCPs) was developed through a combination of living anionic polymerization (LAP) and ring-opening metathesis polymerization (ROMP). ω-End-norbornyl polystyrene (NPSt) and poly(4-tert-butoxystyrene) (NPtBOS) were synthesized by LAP using terminator of chlorine moiety containing silane-protecting amine and coupled with a subsequent amidation using norbornyl activated ester. Bottlebrush homopolymers of NPSt were obtained by ROMP with ultrahigh molecular weights (MWs, M_w = 2928 kDa) and narrow molecular weight distributions (MWDs, Đ = 1.07) at high degree of polymerizations (DP_w = 1084). Well-defined BBCPs with ultrahigh MWs (M_w ∼ 3055 kDa) and narrow MWDs (Đ ∼ 1.13) were synthesized through sequential ROMP of NPSt with NPtBOS. The effect of ultrahigh MWs was investigated by self-assembly of the BBCPs in which the phase-separated BBCPs presented periodic lamellar structures and exhibited structural colors from blue to pink

Experimental Formulation of Photonic Crystal Properties for Hierarchically Self-Assembled POSS–Bottlebrush Block Copolymers

Rodlike “POSS–bottlebrush block copolymers” (POSSBBCPs) containing crystalline polyhedral oligomeric silsesquioxane (POSS) pendants in A block and amorphous polymeric grafts in B block were utilized to create one-dimensional (1D) photonic crystals (PCs). 3-(12-(cis-5-Norbornene-exo-2,3-dicarboximido)dodecanoylamino)propylheptaisobutyl POSS (NB-A16-POSS, MA) and exo-5-norbornene-2-carbonyl-end poly(benzyl methacrylate) (NBPBzMA, MB) were employed in sequential ring-opening metathesis polymerization to afford poly[3-(12-(cis-5-norbornene-exo-2,3-dicarboximido)dodecanoylamino)propylheptaisobutyl POSS]-block-poly(exo-5-norbornene-2-carbonylate-graft-benzyl methacrylate)s, P(NB-A16-POSS)-b-P(NB-g-BzMA)s, with well-modulated block compositions (fA = 34, 50, and 67 wt %) and overall degrees of polymerization (DP = 323–939). The P(NB-A16-POSS)-b-P(NB-g-BzMA)s hierarchically self-assembled to form highly ordered 1D PC films with periodic lamellar arrays that can reflect visible light with particular wavelengths. Their reflectance bandwidths, reflectivities, and ranges of peak reflectance wavelnegth (λ_(peak)) were largely dependent on the block composition. The 1D PC films based on lamellar P(NB-A16-POSS)-b-P(NB-g-BzMA)s demonstrated the capability of formaulation of λ_(peak) as linear functions of initial polymerization parameter ([M]_0/[I]_0)

The comparison of the impact of arterial stiffness and central pressure on left ventricular geometry and diastolic function

Background This study was performed to compare the associations of brachial-ankle pulse wave velocity (baPWV) and central blood pressure (CBP) measurements with left ventricular (LV) geometry and diastolic function. Methods A total of 77 subjects (64.5 ± 10.8 years, 67.5% females) without documented cardiovascular disease were prospectively recruited. All subjects underwent transthoracic echocardiography, baPWV and noninvasive measurement of CBP on the same day. Results In simple linear correlation analyses, neither baPWV nor CBP was associated with LV mass index or relative wall thickness (P > 0.05 for each). Although baPWV significantly correlated with septal e´ velocity in simple linear correlation analyses (r = 0.258, P = 0.025), the significance was lost after controlling for potential confounder (P = 0.881). In simple linear correlation analyses, central systolic blood pressure (CSBP) and central pulse pressure (CPP) significantly correlated with both septal e´ velocity or E/e´ (P  0.05 for each). After controlling for confounders, including age, sex and body mass index, CSBP correlated with septal e´ velocity (β = − 0.258, P = 0.025), but not with E/e´ (P = 0.074). CPP correlated with both septal e´ velocity (β = − 0.300, P = 0.014) and E/e´ (β = 0.428, P = 0.002) in the same multivariable model. Conclusions In subjects without documented cardiovascular disease, CSBP and CPP may be more strongly associated with LV diastolic function than baPWV. Further studies with a larger sample size are needed to confirm our results.This study was supported by a research grant from the Korean Society of Hypertension

Evaluation of changes in random blood glucose and body mass index during and after completion of chemotherapy in children with acute lymphoblastic leukemia

PurposeImproved survival of patients with childhood acute lymphoblastic leukemia (ALL) has drawn attention to the potential for late consequences of previous treatments among survivors, including metabolic syndrome. In this study, we evaluated changes in 3 parameters, namely, random blood glucose, body mass index (BMI), and Z score for BMI (Z-BMI), in children with ALL during chemotherapy and after completion of treatment.MethodsPatients newly diagnosed with ALL from January, 2005 to December, 2008 at Saint Mary's Hospital, The Catholic University of Korea, who completed treatment with chemotherapy only were included (n=107). Random glucose, BMI, and Z-BMI were recorded at 5 intervals: at diagnosis, before maintenance treatment, at completion of maintenance treatment, and 6 and 12 months after completion of maintenance treatment. Similar analyses were conducted on 2 subcohorts based on ALL risk groups.ResultsFor random glucose, a paired comparison showed significantly lower levels at 12 months post-treatment compared to those at initial diagnosis (P<0.001) and before maintenance (P<0.001). The Z-BMI score was significantly higher before maintenance than at diagnosis (P<0.001), but decreased significantly at the end of treatment (P<0.001) and remained low at 6 months (P<0.001) and 12 months (P<0.001) post-treatment. Similar results were obtained upon analysis of risk group-based subcohorts.ConclusionFor a cohort of ALL patients treated without allogeneic transplantation or cranial irradiation, decrease in random glucose and Z-BMI after completion of chemotherapy does not indicate future glucose intolerance or obesity

Arterial stiffness and its associations with left ventricular diastolic function according to heart failure types

Background Little is known about the characteristics of arterial stiffness in heart failure (HF). This study was performed to compare the degree of arterial stiffness and its association with left ventricular (LV) diastolic function among three groups: control subjects, patients with HF with reduced ejection fraction (HFrEF), and patients with HF with preserved ejection fraction (HFpEF). Methods A total of 83 patients with HFrEF, 68 patients with HFpEF, and 84 control subjects were analyzed. All HF patients had a history of hospitalization for HF treatment. Brachial-ankle pulse wave velocity (baPWV) measurement and transthoracic echocardiography were performed at the same day in a stable condition. Results The baPWV was significantly higher in patients with both HFrEF and HFpEF compared to control subjects (1,661 ± 390, 1,909 ± 466, and 1,477 ± 296cm/sec, respectively; P < 0.05 for each). After adjustment of age, baPWV values were similar between patients with HFrEF and HFpEF (P = 0.948). In the multiple linear regression analysis, baPWV was significantly associated with both septal e′ velocity (β = –0.360, P = 0.001) and E/e′ (β = 0.344, P = 0.001). However, baPWV was not associated with either of the diastolic indices in HFrEF group. The baPWV was associated only with septal e′ velocity (β = –0.429, P = 0.002) but not with E/e′ in the HFpEF group in the same multivariable analysis. Conclusions Although arterial stiffness was increased, its association with LV diastolic function was attenuated in HF patients compared to control subjects. The degree of arterial stiffening was similar between HFrEF and HFpEF.This study was supported by a research grant funded by the Korean Society of Hypertension (No. KSH-R-2020–01)