Efficacy and safety of newly developed ganirelix acetate in infertile women for assisted reproductive technology: a prospective, randomised, controlled study.

This study aimed to investigate the efficacy of Ganilever pre-filled syringe (PFS), a newly developed ganirelix acetate, for the inhibition of premature luteinising hormone (LH) surge in in vitro fertilisation (IVF). A prospective randomised controlled study was conducted (NCT03051087). A total of 236 women (Ganilever group: 114, Orgalutran group: 122) were finally analysed. The patients with LH of >10 mIU/mL on the day of human chorionic gonadotropin (hCG) injection were 0 (0.0%) and 3 (2.5%) in the Ganilever and Orgalutran groups, respectively (p= .25). The number of retrieved oocytes from two groups did not show any significant difference (12.0 ± 6.4 vs. 11.8 ± 6.3, p= .73). Furthermore, the two groups did not show significant differences in the number of good-quality oocytes and embryo, and the rate of fertilisation. Similar safety profiles were also observed. In conclusion, Ganilever PFS showed comparable IVF outcomes and safety profile in IVF, as compared to the Orgalutran. Impact StatementWhat is already known on this subject? Premature LH surge during controlled ovarian stimulation results in the induction of luteinisation of the immature follicles. Thus, gonadotrophin-releasing hormone (GnRH) antagonist protocol was suggested as an option for suppression of premature LH surge. Currently, one of GnRH antagonists being widely used is ganirelix acetate (Orgalutran®; Organon, Oss, The Netherlands). Ganilever pre-filled syringe (PFS) is a newly developed GnRH antagonist containing ganirelix acetate as an active ingredient.What do the results of this study add? Our study demonstrated that Ganilever PFS showed comparable IVF outcomes and patient safety profile in infertile women undergoing in IVF-ET, as compared to the Orgalutran.What are the implications of these findings for clinical practice and/or further research? The results of our study will provide another available GnRH antagonist to be used in patients with IVF.

Survival impact of additional chemotherapy after adjuvant concurrent chemoradiation in patients with early cervical cancer who underwent radical hysterectomy.

BACKGROUND: To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH). METHODS: We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB-IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group). RESULTS: A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P < 0.001). The presence of pathologic risk factors was similar, except for lymph node metastasis, which was more frequent in the study group (72.1% vs. 46.0%; P = 0.001). In survival analyses, no differences in the disease-free survival (DFS; P = 0.539) and overall survival (OS; P = 0.121) were observed between the groups. Multivariate analyses adjusting for surgical approach and other factors revealed that additional chemotherapy was not associated with DFS (adjusted HR, 1.149; 95% CI, 0.552-2.391; P = 0.710) and OS (adjusted HR, 1.877; 95% CI, 0.621-5.673; P = 0.264). The recurrence patterns did not differ with additional chemotherapy. Consistent results were observed in a subset of high-risk patients (n = 139). CONCLUSIONS: Additional chemotherapy after CCRT might not improve survival outcomes in patients with early cervical cancer who undergo RH.

Aggregation induced emission of diketopyrrolopyrrole (DPP) derivatives for highly fluorescent red films.

A large number of diketopyrrolopyrrole (DPP) compounds showing aggregation induced emission (AIE) have been reported in the past few years. However, although DPP compounds exhibited AIE and excellent luminescence properties, their luminescence properties in solid or film states were not much focused on. Here we synthesized and characterized a series of DPP compounds with triphenylamine (TPA) moieties to investigate the AIE properties in the solid film state depending on the functional groups (TPA, BTPA, and MTPA) attached to the TPA moieties. T2 and D2 thin films showed excellent fluorescence quantum yields of 31% and 26%, respectively, compared to an M2 thin film (9%). The restriction of an intramolecular rotation process could inhibit the aggregation induced quenching process and play a key role in achieving highly fluorescent molecules in the solid state.

When Is Ligand p Ka a Good Descriptor for Catalyst Energetics? In Search of Optimal CO2 Hydration Catalysts.

We present a detailed study of nearly 70 Zn molecular catalysts for CO2 hydration from four diverse ligand classes ranging from well-studied carbonic anhydrase mimics (e.g., cyclen) to new structures we obtain by leveraging diverse hits from large organic libraries. Using microkinetic analysis and establishing linear free energy relationships, we confirm that turnover is sensitive to the relative thermodynamic stability of reactive hydroxyl and bound bicarbonate moieties. We observe a wide range of thermodynamic stabilities for these intermediates, showing up to 6 kcal/mol improvement over well-studied cyclen catalysts. We observe a good correlation between the p Ka of the Zn-OH2 moiety and the resulting relative stability of hydroxyl moieties over bicarbonate, which may be rationalized by the dominant effect of the difference in higher Zn-OH bond order in comparison to weaker bonding in bicarbonate and water. A direct relationship is identified between isolated organic ligand p Ka and the p Ka of a bound water molecule on the catalyst. Thus, organic ligand p Ka, which is intuitive, easy to compute or tabulate, and much less sensitive to electronic structure method choice than whole-catalyst properties, is a good quantitative descriptor for predicting the effect of through-bond electronic effects on relative CO2 hydration energetics. We expect this to be applicable to other reactions where is it essential to stabilize turnover-determining hydroxyl species with respect to more weakly bound moieties. Finally, we note exceptions for rigid ligands (e.g., porphyrins) that are observed to preferentially stabilize hydroxyl over bicarbonate without reducing p Ka values as substantially. We expect the strategy outlined here, to (i) curate diverse ligands from large organic libraries and (ii) identify when ligand-only properties can determine catalyst energetics, to be broadly useful for both experimental and computational catalyst design.

Simple modification of basic dyes with bulky &symmetric WCAs for improving their solubilities in organic solvents without color change.

A simple and easy solubility enhancement of basic dyes was performed with bulky and symmetric weakly coordinating anions (WCAs). The WCAs decreased the ionic character of the dyes by broadening the partial charge distribution and causing a screening effect on the ionic bonding. This new modification with WCAs has advantages in that it has no influence on the optical properties of the dyes. The solubilities of unmodified and modified dyes were tested in several organic solvents. X-ray powder diffraction patterns of the dyes were measured. Color films were prepared with the dyes and their color loci were analyzed to evaluate the optical properties. By the modification with WCAs, commercial basic dyes showed sufficient solubilities for be applied to various applications while preserving their superior optical properties.

Optimization of the Thermoelectric Figure of Merit in Crystalline C60 with Intercalation Chemistry.

Crystalline C60 is an appealing candidate material for thermoelectric (TE) applications due to its extremely low thermal conductivity and potentially high electrical conductivity with metal atom intercalation. We investigate the TE properties of crystalline C60 intercalated with alkali and alkaline earth metals using both classical and quantum mechanical calculations. For the electronic structure, our results show that variation of intercalated metal atoms has a large impact on energy dispersions, which leads to broad tunability of the power factor. For the thermal transport, we show that dopants introduce strong phonon scattering into crystalline C60, leading to considerably lower thermal conductivity. Taking both into account, our calculations suggest that appropriate choice of metal atom intercalation in crystalline C60 could yield figures of merit near 1 at room temperature.

High-efficiency thermoelectrics with functionalized graphene.

Graphene superlattices made with chemical functionalization offer the possibility of tuning both the thermal and electronic properties via nanopatterning of the graphene surface. Using classical and quantum mechanical calculations, we predict that suitable chemical functionalization of graphene can introduce peaks in the density of states at the band edge that result in a large enhancement in the Seebeck coefficient, leading to an increase in the room-temperature power factor of a factor of 2 compared to pristine graphene, despite the degraded electrical conductivity. Furthermore, the presence of patterns on graphene reduces the thermal conductivity, which when taken together leads to an increase in the figure of merit for functionalized graphene by up to 2 orders of magnitude over that of pristine graphene, reaching its maximum ZT ∼ 3 at room temperature according to our calculations. These results suggest that appropriate chemical functionalization could lead to efficient graphene-based thermoelectric materials.

Thermal transport in functionalized graphene.

We investigate the effects of two-dimensional (2D) periodic patterns of functional groups on the thermal transport in a graphene monolayer by employing molecular and lattice dynamics simulations. Our calculations show that the use of patterned 2D shapes on graphene reduces the room temperature thermal conductivity, by as much as 40 times lower than that of the pristine monolayer, due to a combination of boundary and clamping effects. Lattice dynamics calculations elucidate the correlation between this large reduction in thermal conductivity and two dynamical properties of the main heat carrying phonon modes: (1) decreased phonon lifetimes by an order of magnitude due to scattering, and (2) direction-dependent group velocities arising from phonon confinement. Taken together, these results suggest that patterned graphene nanoroads provide a method for tuning the thermal conductivity of graphene without the introduction of defects in the lattice, opening an important possibility for thermoelectric applications.

Two cases of Plasmodium vivax Malaria with the clinical picture resembling toxic shock.

Fatal complications of Plasmodium falciparum malaria have been reported. However, complicated P. vivax malaria is rare. We observed two unusual cases of P. vivax malaria who presented with clinical pictures of toxic shock. Both showed disseminated intravascular coagulation with marked thrombocytopenia, oliguric renal failure, and pulmonary edema. Examination of initial blood smears showed a P. vivax parasitemia of 2,352/microL and 12,376/microL, respectively. The patients were treated with hydroxychloroquine and primaquine without an antibacterial agent. These cases emphasize the importance of considering the possibility of P. vivax malarial infection in patients with a clinical picture resembling toxic shock if they have a travel history to malaria-endemic areas.

Continuous fabrication of biocatalyst immobilized microparticles using photopolymerization and immiscible liquids in microfluidic systems.

We report a novel technique for manufacturing polymeric microparticles containing biocatalysts by the behavior of immiscible liquids in microfluidic systems and in situ photopolymerization. The approach utilizes a UV-polymerizable hydrogel/enzyme solution and an immiscible oil solution. The oil and hydrogel solutions form emulsions in pressure-driven flow in microchannels at high values of the dimensionless capillary number (Ca). The resultant hydrogel droplets are then polymerized in situ via exposure to 365 nm UV light. This technique allows for the generation of monodisperse particles whose size can be controlled by the regulation of flow rates. In addition, both manufacturing microparticles and immobilizing biocatalysts can be performed simultaneously and continuously.

Inhibitory effect of mast cell-mediated acute and chronic allergic reactions by Dodutang.

Dodutang has been used for treatment of various allergic inflammation diseases in Korea. However, it is still unclear how Dodutang prevents these diseases in experimental animal models. Mast cells play an important roles in allergic and other inflammatory reactions by producing a spectrum of powerful mediators including preformed and de novo synthesized cytokines. In this study, we investigated the effect of Dodutang on mast cell-mediated allergic and inflammatory reactions. Dodutang (0.001-5 g/L) significantly inhibited the histamine release from rat peritoneal mast cells activated by compound 48/80. Dodutang (0.001-5 g/kg) dose-dependantly inhibited the passive cutaneous anaphylaxis reaction activated by anti-dinitrophenyl (DNP) IgE in a rat model, especially, by 78.96% at the concentration of 5 g/kg. In addition, Dodutang potently inhibited the secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated human mast cells. However, IL-6 secretion was enhanced at the same conditions. Dodutang also inhibited the main inflammatory cytokine TNF-alpha protein expression in human mast cells. These results provide evidences that Dodutang may be beneficial in the treatment of acute and chronic allergic diseases.