Tolerability and adequate therapeutic dosage of oral clomipramine for the treatment of premature ejaculation: A randomized, double-blind, placebo-controlled, fixed-dose, parallel-grouped clinical study

Kim, Sae Woong,Choi, Jin Bong,Kim, Su Jin,Kim, Kyung Soo,Kim, Churl Min,Lee, Dong Hyeon,Choi, Whan Seok Nature Publishing Group UK 2018 International journal of impotence research Vol.30 No.2

<P>To evaluate the adequate therapeutic dosage of clomipramine 15 mg/day and clomipramine 30 mg/day in male patients with premature ejaculation (PE), this study enrolled men aged 20-65 years who met diagnostic criteria for PE including Intravaginal Ejaculation Latency Time (IELT) less than 2 min for at least 75% of their sexual intercourses. Subjects received placebo, clomipramine 15 mg, or clomipramine 30 mg prn (2 similar to 6 h before intercourse) for 4 weeks. Efficacy was assessed using fold change, percentile change, and mean change of IELT, as well as Drug Coitus Interval Time (DCIT). A total of 101 patients were randomized into the placebo group, clomipramine 15 mg group, and clomipramine 30 mg group. Analyses of fold changes of IELT in each group revealed that the IELT of both the clomipramine 15 mg group and clomipramine 30 mg group was significantly increased 4 weeks after administration than the placebo group. Adverse events were reported by 11.76, 32.35, and 57.57% of patients in the placebo group, clomipramine 15 mg group, and clomipramine 30 mg group, respectively. Most common adverse events in the clomipramine treatment groups were gastrointestinal disorders and psychiatric disorders of mild to moderate severity. On-demand regimen of clomipramine 15 mg resulted in a significant improvement in IELT and was superior to a regimen of clomipramine 30 mg in terms of risk-to-benefit ratio.</P>

Adjuvant role of macrophages in stem cell-induced cardiac repair in rats

Lim, Soo yeon,Cho, Dong Im,Jeong, Hye-yun,Kang, Hye-jin,Kim, Mi Ra,Cho, Meeyoung,Kim, Yong Sook,Ahn, Youngkeun Nature Publishing Group UK 2018 Experimental and molecular medicine Vol.50 No.11

<▼1><P>Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair.</P></▼1><▼2><P><B>Heart attacks: mixed cell therapy for heart regeneration</B></P><P>A tailored technique involving stem cells and anti-inflammatory immune cells shows promise for repairing heart tissue damage. Immune cells called anti-inflammatory macrophages are vital for healing of the heart following a heart attack. Youngkeun Ahn, Yong Sook Kim and co-workers at Chonnam National University Hospital in Gwangju, South Korea trialed a novel stem cell therapy on rats to improve cardiac repair. They took bone marrow-derived macrophages and stem cells from each rat and incubated the two cell types together to create individualized treatments. Following induced heart attacks, they injected one group of rats with both cell types, and another group with stem cells only. While heart function improved in both groups, the group treated with both cell types showed significant improvements with a greater reduction in cardiac fibrosis and increased the reparative activity of macrophages.</P></▼2>

Predicting cumulative incidence of adverse events in older patients with cancer undergoing first-line palliative chemotherapy: Korean Cancer Study Group (KCSG) multicentre prospective study

Kim, Jin Won,Lee, Yun-Gyoo,Hwang, In Gyu,Song, Hong Suk,Koh, Su Jin,Ko, Yoon Ho,Shin, Seong Hoon,Woo, In Sook,Hong, Soojung,Kim, Tae-Yong,Kim, Sun Young,Nam, Byung-Ho,Kim, Hyun Jung,Kim, Hyo Jung,Lee, Nature Publishing Group UK 2018 The British journal of cancer Vol.118 No.9

<P><B>Background</B></P><P>Older patients have increased risk of toxicity from chemotherapy. Current prediction tools do not provide information on cumulative risk.</P><P><B>Methods</B></P><P>Patients aged ≥ 70 years with solid cancer were prospectively enrolled. A prediction model was developed for adverse events (AEs) ≥ Grade 3 (G3), based on geriatric assessment (GA), laboratory, and clinical variables.</P><P><B>Results</B></P><P>301 patients were enrolled (median age, 75 years). Median number of chemotherapy cycles was 4. During first-line chemotherapy, 53.8% of patients experienced AEs ≥ G3. Serum protein < 6.7 g/dL, initial full-dose chemotherapy, psychological stress or acute disease in the past 3 months, water consumption < 3 cups/day, unable to obey a simple command, and self-perception of poor health were significantly related with AEs ≥ G3. A predicting model with these six variables ranging 0–8 points was selected with the highest discriminatory ability (c-statistic= 0.646), which could classify patients into four risk groups. Predicted cumulative incidence of AEs ≥ G3 was discriminated according to risk groups.</P><P><B>Conclusions</B></P><P>This prediction tool could identify the risk of AEs ≥ G3 after chemotherapy and provide information on the cumulative incidence of AEs in each cycle.</P><P><B>Clinical Trial Id</B></P><P>WHO ICTRP number, KCT0001071</P>

Enrichment of molecular antenna triplets amplifies upconverting nanoparticle emission

Garfield, David J.,Borys, Nicholas J.,Hamed, Samia M.,Torquato, Nicole A.,Tajon, Cheryl A.,Tian, Bining,Shevitski, Brian,Barnard, Edward S.,Suh, Yung Doug,Aloni, Shaul,Neaton, Jeffrey B.,Chan, Emory M Nature Publishing Group UK 2018 Nature photonics Vol.12 No.7

<P>Efficient photon upconversion at low light intensities promises major advances in technologies spanning solar energy harvesting to deep-tissue biophotonics. Here, we discover the critical mechanisms that enable near-infrared dye antennas to significantly enhance performance in lanthanide-doped upconverting nanoparticle (UCNP) systems, and leverage these findings to design dye-UCNP hybrids with a 33,000-fold increase in brightness and a 100-fold increase in efficiency over bare UCNPs. We show that increasing the lanthanide content in the UCNPs shifts the primary energy donor from the dye singlet to its triplet, and the resultant triplet states then mediate energy transfer into the nanocrystals. Time-gated phosphorescence, density functional theory, singlet lifetimes and triplet-quenching experiments support these findings. This interplay between the excited-state populations in organic antennas and the composition of UCNPs presents new design rules that overcome the limitations of previous upconverting materials, enabling performances now relevant for photovoltaics, biophotonics and infrared detection.</P>

Publisher Correction: Direct imaging of the electron liquid at oxide interfaces

Song, Kyung,Ryu, Sangwoo,Lee, Hyungwoo,Paudel, Tula R.,Koch, Christoph T.,Park, Bumsu,Lee, Ja Kyung,Choi, Si-Young,Kim, Young-Min,Kim, Jong Chan,Jeong, Hu Young,Rzchowski, Mark S.,Tsymbal, Evgeny Y.,E Nature Publishing Group UK 2018 Nature nanotechnology Vol.13 No.7

In the version of this Letter originally published, in two instances in Fig. 1 the layers in the cross-sectional view of the (001) interface were incorrectly labelled: in Fig. 1b SrO<SUP>+</SUP> should have read SrO<SUP>0</SUP>; in Fig. 1c LaO<SUP>+</SUP>, AlO<SUB>2</SUB><SUP>–</SUP>, LaO<SUP>+</SUP>, TiO<SUB>2</SUB><SUP>0</SUP>, SrO<SUP>+</SUP>, TiO<SUB>2</SUB><SUP>0</SUP> should have read LaO<SUB>3</SUB><SUP>3–</SUP>, Al<SUP>3+</SUP>, LaO<SUB>3</SUB><SUP>3–</SUP>, Ti<SUP>4+</SUP>, SrO<SUB>3</SUB><SUP>4–</SUP>, Ti<SUP>4+</SUP>. In Fig. 3c the upper-right equation read –σ<SUB>s</SUB> = –e/2a<SUP>2</SUP> but should have read –σ<SUB>s</SUB> = e/2a<SUP>2</SUP> and in Fig. 3f the lower-right equation read –σ<SUB>s</SUB> = –e/2√3a<SUP>2</SUP> but should have read σ<SUB>s</SUB> = –e/2√3a<SUP>2</SUP>. These errors have now been corrected in the online version of the Letter.

Universal impedance matching and the perfect transmission of white light

Im, Ku,Kang, Ji-Hun,Park, Q-Han Nature Publishing Group UK 2018 Nature photonics Vol.12 No.3

<P>Light is reflected at the interface between heterogeneous media due to the mismatch of impedance(1-3). Removing this mismatch using additional materials, a technique known as anti-reflection, has so far been restricted to specific frequencies and incidence angles(3-7). The anti-reflection of white light, which requires the simultaneous matching of impedance over extremely wide angular and spectral ranges, has until now been considered impossible. Here, we develop a theory of universal impedance matching and introduce a matching layer that enables the perfect transmission of white light. The ability of a matching layer to assist in omnidirectional and frequency-independent anti-reflection has been confirmed analytically and numerically. We explain the feasibility of a universal matching layer using metamaterials, and demonstrate a transmission rate of over 99% for white light in the visible range with a double-layered dielectric metamaterial. This is confirmed experimentally by demonstrating the omnidirectional anti-reflection of microwaves in heterogeneous media.</P>

In vivo transduction of ETV2 improves cardiac function and induces vascular regeneration following myocardial infarction

Lee, Sunghun,Lee, Dong Hun,Park, Bong-Woo,Kim, Riyoun,Hoang, Anh Duc,Woo, Sang-Keun,Xiong, Wenjun,Lee, Yong Jin,Ban, Kiwon,Park, Hun-Jun Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.2

<▼1><P>Vascular regeneration in ischemic hearts has been considered a target for new therapeutic strategies. It has been reported that ETV2 is essential for vascular development, injury-induced neovascularization and direct cell reprogramming of non-endothelial cells into endothelial cells. Thus, the objective of this study was to explore the therapeutic potential of ETV2 in murine models of myocardial infarction in vivo. Direct myocardial delivery of lentiviral ETV2 into rodents undergoing myocardial infarction dramatically upregulated the expression of markers for angiogenesis as well as anti-fibrosis and anti-inflammatory factors in vivo. Consistent with these findings, echocardiography showed significantly improved cardiac function in hearts with induced myocardial infarction upon ETV2 injection compared to that in the control virus-injected group as determined by enhanced ejection fraction and fractional shortening. In addition, ETV2-injected hearts were protected against massive fibrosis with a remarkable increase in capillary density. Interestingly, major fractions of capillaries were stained positive for ETV2. In addition, ECs infected with ETV2 showed enhanced proliferation, suggesting a direct role of ETV2 in vascular regeneration in diseased hearts. Furthermore, culture media from ETV2-overexpressing cardiac fibroblasts promoted endothelial cell migration based on scratch assay. Importantly, intramyocardial injection of the adeno-associated virus form of ETV2 into rat hearts with induced myocardial infarction designed for clinical applicability consistently resulted in significant augmentation of cardiac function. We provide compelling evidence that ETV2 has a robust effect on vascular regeneration and enhanced cardiac repair after myocardial infarction, highlighting a potential therapeutic function of ETV2 as an efficient means to treat failing hearts.</P></▼1><▼2><P><B>Cardiovascular disease: New hope for healing the heart</B></P><P>A gene therapy strategy that stimulates cardiovascular repair could improve recovery for heart attack patients. Heart attacks inflict severe damage on the heart and blood vessels, tissues with limited capacity for self-repair. Researchers led by Kiwon Ban of the City University of Hong Kong and Hun-Jun Park of the Catholic University of Korea, Seoul, have now demonstrated that a gene responsible for cardiovascular development can also efficiently stimulate heart repair. They used viruses to deliver the gene into a mouse model of heart attack, and showed that treated heart tissues exhibited strong recovery relative to untreated controls. The treatment reduced scar tissue formation and promoted proliferation of the cells lining blood vessels and blood vessel formation, measurably improving heart function. This approach could lay the groundwork for treating a common potentially fatal event.</P></▼2>

Holstein polaron in a valley-degenerate two-dimensional semiconductor

Kang, Mingu,Jung, Sung Won,Shin, Woo Jong,Sohn, Yeongsup,Ryu, Sae Hee,Kim, Timur K.,Hoesch, Moritz,Kim, Keun Su Nature Publishing Group UK 2018 NATURE MATERIALS Vol.17 No.8

<P>Two-dimensional (2D) crystals have emerged as a class of materials with tunable carrier density(1). Carrier doping to 2D semiconductors can be used to modulate many-body interactions(2) and to explore novel composite particles. The Holstein polaron is a small composite particle of an electron that carries a cloud of self-induced lattice deformation (or phonons)(3-5), which has been proposed to play a key role in high-temperature superconductivity(6) and carrier mobility in devices(7). Here we report the discovery of Holstein polarons in a surfacedoped layered semiconductor, MoS2, in which a puzzling 2D superconducting dome with the critical temperature of 12 K was found recently(8-11). Using a high-resolution band mapping of charge carriers, we found strong band renormalizations collectively identified as a hitherto unobserved spectral function of Holstein polarons(12-18). The short-range nature of electronphonon(e-ph) coupling in MoS2 can be explained by its valley degeneracy, which enables strong intervalley coupling mediated by acoustic phonons. The coupling strength is found to increase gradually along the superconducting dome up to the intermediate regime, which suggests a bipolaronic pairing in the 2D superconductivity.</P>

Reconstruction of antibody dynamics and infection histories to evaluate dengue risk

Salje, Henrik,Cummings, Derek A. T.,Rodriguez-Barraquer, Isabel,Katzelnick, Leah C.,Lessler, Justin,Klungthong, Chonticha,Thaisomboonsuk, Butsaya,Nisalak, Ananda,Weg, Alden,Ellison, Damon,Macareo, Lou Nature Publishing Group UK 2018 Nature Vol.557 No.7707

<P>As with many pathogens, most dengue infections are subclinical and therefore unobserved(1). Coupled with limited understanding of the dynamic behaviour of potential serological markers of infection, this observational problem has wide-ranging implications, including hampering our understanding of individual-and population-level correlates of infection and disease risk and how these change over time, between assay interpretations and with cohort design. Here we develop a framework that simultaneously characterizes antibody dynamics and identifies subclinical infections via Bayesian augmentation from detailed cohort data (3,451 individuals with blood draws every 91 days, 143,548 haemagglutination inhibition assay titre measurements)(2,3). We identify 1,149 infections (95% confidence interval, 1,135-1,163) that were not detected by active surveillance and estimate that 65% of infections are subclinical. After infection, individuals develop a stable set point antibody load after one year that places them within or outside a risk window. Individuals with pre-existing titres of <= 1: 40 develop haemorrhagic fever 7.4 (95% confidence interval, 2.5-8.2) times more often than naive individuals compared to 0.0 times for individuals with titres > 1: 40 (95% confidence interval: 0.0-1.3). Plaque reduction neutralization test titres <= 1: 100 were similarly associated with severe disease. Across the population, variability in the size of epidemics results in large-scale temporal changes in infection and disease risk that correlate poorly with age.</P>

Inverse relationship between present-day tropical precipitation and its sensitivity to greenhouse warming

Ham, Yoo-Geun,Kug, Jong-Seong,Choi, Jun-Young,Jin, Fei-Fei,Watanabe, Masahiro Nature Publishing Group UK 2018 Nature climate change Vol.8 No.1

<P>Future changes in rainfall have serious impacts on human adaptation to climate change, but quantification of these changes is subject to large uncertainties in climate model projections. To narrow these uncertainties, significant efforts have been made to understand the intermodel differences in future rainfall changes. Here, we show a strong inverse relationship between present-day precipitation and its future change to possibly calibrate future precipitation change by removing the present-day bias in climate models. The results of the models with less tropical (40 degrees S-40 degrees N) present-day precipitation are closely linked to the dryness over the equatorial central-eastern Pacific, and project weaker regional precipitation increase due to the anthropogenic greenhouse forcing(1-6) with stronger zonal Walker circulation. This induces Indo-western Pacific warming through Bjerknes feedback, which reduces relative humidity by the enhanced atmospheric boundary-layer mixing in the future projection. This increases the air-sea humidity difference to enhance tropical evaporation and the resultant precipitation. Our estimation of the sensitivity of the tropical precipitation per 1 K warming, after removing a common bias in the present-day simulation, is about 50% greater than the original future multi-model projection.</P>