The influence of mechanical Circulatory support on post-transplant outcomes in pediatric patients: A multicenter study from the International Society for Heart and Lung Transplantation (ISHLT) Registry.

BACKGROUND: Mechanical circulatory support (MCS) is increasingly being used as a bridge to transplant in pediatric patients. We compare outcomes in pediatric patients bridged to transplant with MCS from an international cohort. METHODS: This retrospective cohort study of heart-transplant patients reported to the International Society for Heart and Lung Transplantation (ISHLT) registry from 2005-2017 includes 5,095 patients <18 years. Pretransplant MCS exposure and anatomic diagnosis were derived. Outcomes included mortality, renal failure, and stroke. RESULTS: 26% of patients received MCS prior to transplant: 240 (4.7%) on extracorporeal membrane oxygenation (ECMO), 1,030 (20.2%) on ventricular assist device (VAD), and 54 (1%) both. 29% of patients were <1 year, and 43.8% had congenital heart disease (CHD). After adjusting for clinical characteristics, compared to no-MCS and VAD, ECMO had higher mortality during their transplant hospitalization [OR 3.97 & 2.55; 95% CI 2.43-6.49 & 1.42-4.60] while VAD mortality was similar [OR 1.55; CI 0.99-2.45]. Outcomes of ECMO+VAD were similar to ECMO alone, including increased mortality during transplant hospitalization compared to no-MCS [OR 4.74; CI 1.81-12.36]. Patients with CHD on ECMO had increased 1 year, and 10 year mortality [HR 2.36; CI 1.65-3.39], [HR 1.82; CI 1.33-2.49]; there was no difference in survival in dilated cardiomyopathy (DCM) patients based on pretransplant MCS status. CONCLUSION: Survival in CHD and DCM is similar in patients with no MCS or VAD prior to transplant, while pretransplant ECMO use is strongly associated with mortality after transplant particularly in children with CHD. In children with DCM, long term survival was equivalent regardless of MCS status.

Photoinduced antibacterial activity of NRC03 peptide-conjugated dopamine/nano-reduced graphene oxide against Staphylococcus aureus.

In recent years, several drugs have become relatively easy to obtain with the rapid development of the economy and improvement in people's living standards. However, pathogenic bacteria have evolved strains that are resistant to certain drugs, such as antibiotics. Peptides are generally considered to be safe, have high tolerance to drugs, and are easy to manufacture. However, peptides are easily decomposed in complex biological environments. To solve this problem, many studies have modified peptides on the surface of nanomaterials to increase their functionality, biocompatibility, and stability. Meanwhile, nanomaterials have exhibited good absorption of near-infrared (NIR) light. When the NIR laser is focused on nanomaterials, photons are absorbed and the energy of the photons is converted into heat. Low-toxicity NRC03 peptide-conjugated dopamine/nano-reduced-graphene oxide (NRC03-DA/nRGO) nanomaterials are synthesized in this study for antibacterial testing using photothermal technology. The strains used in this study were Gram-positive Staphylococcus aureus (S. aureus). Our results indicated that the synthesized NRC03-DA/nRGO exhibits good absorption of NIR light and high photothermal conversion efficiency. Moreover, the synthesized NRC03-DA/nRGO inhibits the growth and survival of S. aureus. When the NRC03 peptide is modified on the surface of DA/nRGO, its biological stability is improved and the photothermal effect generated by NIR light produces additive effects, thereby indicating potential antibacterial applications.

Millimeter-wave system-on-chip advancement for fusion plasma diagnostics.

Recent advances in radio-frequency system-on-chip technology have provided mm-wave fusion plasma diagnostics with the capability to overcome major challenges such as space inefficiency, inflexible installation, sensitivity, susceptibility to EMI, and prohibitively high cost of conventional discrete component assemblies as higher imaging resolution and data accuracy are achieved by increasing the number of channels. Nowadays, shrinking transistor gate lengths on fabrication techniques have enabled hundreds of GHz operation, which is suitable for millimeter-wave diagnostics on current and future tokamaks. The Davis Millimeter Wave Research Center (DMRC) has successfully developed V-band (55-75 GHz) transmitter and receiver chips for Microwave Imaging Reflectometer (MIR) instruments. The transmitter can illuminate 8 different frequencies simultaneously within 55-75 GHz. Moreover, the receiver has the capability to amplify the reflected signal (>30 dB) while offering 10-30× reduction in noise temperature compared to current MIR instruments. Plasma diagnostics requires ultra-wideband (more than 20 GHz) operation which is approximately nine times wider bandwidth than the recent commercial impetus for communication systems. Current efforts are underway for gallium-arsenide monolithic microwave integrated circuit receiver chips at W-band (75-110 GHz) and F-band (90-140 GHz) permitting measurements at higher toroidal magnetic fields.

Spin-Orbital-Angular-Momentum Coupled Bose-Einstein Condensates.

We demonstrate coupling between the atomic spin- and orbital-angular momentum (OAM) of the atom's center-of-mass motion in a Bose-Einstein condensate (BEC). The coupling is induced by Raman-dressing lasers with a Laguerre-Gaussian beam and creates coreless vortices in an F=1 ^{87}Rb spinor BEC. We observe correlations between spin and OAM in the dressed state and characterize the spin texture; the result is in good agreement with the theory. In the presence of the Raman field, our dressed state is stable for 0.1 s or longer, and it decays due to collision-induced relaxation. As we turn off the Raman beams, the vortex cores in the bare spin |m_{F}=1⟩ and |-1⟩ split. These spin-OAM coupled systems with the Raman-dressing approach have great potential for exploring new topological textures and quantum states.

High-quality thulium iron garnet films with tunable perpendicular magnetic anisotropy by off-axis sputtering - correlation between magnetic properties and film strain.

Thulium iron garnet (TmIG) films with perpendicular magnetic anisotropy (PMA) were grown on gadolinium gallium garnet (GGG) (111) substrates by off-axis sputtering. High-resolution synchrotron radiation X-ray diffraction studies and spherical aberration-corrected scanning transmission electron microscope (Cs-corrected STEM) images showed the excellent crystallinity of the films and their sharp interface with GGG. Damping constant of TmIG thin film was determined to be 0.0133 by frequency-dependent ferromagnetic resonance (FMR) measurements. The saturation magnetization (Ms) and the coercive field (Hc) were obtained systematically as a function of the longitudinal distance (L) between the sputtering target and the substrate. A 170% enhancement of PMA field (H⊥) was achieved by tuning the film composition to increase the tensile strain. Moreover, current-induced magnetization switching on a Pt/TmIG structure was demonstrated with an ultra-low critical current density (jc) of 2.5 × 106 A/cm2, an order of magnitude smaller than the previously reported value. We were able to tune Ms, Hc and H⊥ to obtain an ultra-low jc of switching the magnetization, showing the great potential of sputtered TmIG films for spintronics.

How deep is the inflammation in chronic rhinosinusitis? Sinus wall thickness and blood eosinophilia.

Various factors have been proposed to be related to refractory chronic rhinosinusitis (CRS). Treatment for refractory CRS is challenging for ear, nose, and throat (ENT) surgeons. The aim of the study was to determine the clinical features associated with the severity of CRS that may necessitate revision surgery by eliminating the bias of the surgeons technique using standardizing surgical procedures. Sinus wall thickness and blood eosinophilia, which may represent the depth of inflammation in CRS, are associated with the need for revision surgery. We found that, when the thickness of the postero-lateral maxillary sinus wall is more than 3.03 mm, there is an increased probability for a need for revision surgery. CRS patients with thickened sinus walls were found to have poorer outcomes. Further research is needed in order to justify this type of surgical procedure for CRS.

[Utility of hemoglobin A1c for diagnosing metabolic syndrome in Chinese subjects over 50 years old].

Objective: To evaluate glycated hemoglobing A1c (HbA1c) in diagnosing metabolic syndrome (MS) in Chinese subjects aged over 50 years. Methods: A community-based cross-sectional survey was conducted between October 2010 and January 2011 in Shipai community, Guangzhou. A total of 1 494 subjects aged over 50 years were investigated. Questionnaire survey and physical examination were performed among all participants. Fasting blood samples were obtained to measure plasma glucose (FPG), blood lipids and HbA1c. MS was defined by the criteria of International Diabetes Federation (IDF), National Cholesterol Education Program-Adult Treatment Panel Ⅲ (ATP Ⅲ)(2005) and Chinese Diabetes Society (CDS), respectively. Receiver operating characteristic (ROC) curves were plotted to explore the accuracy of HbA1c for diagnosing MS. Results: After excluding subjects with missing data, the remaining 1 473 subjects had a median age of 61 years (55-68 years). An HbA1c threshold of 6.1% yielded the highest combination of sensitivity (52.1%) and specificity (84.3%) for diagnosing MS. Using HbA1c≥5.7% as definition of dysglycemia, the prevalence of MS (IDF), MS (ATP Ⅲ) and MS (CDS) were 48.7%, 57.1% and 50.8%, respectively. The κ coefficients were 0.853, 0.768 and 0.730, respectively. Using HbA1c≥6.1% as definition of dysglycemia, the prevalences of MS (IDF), MS (ATP Ⅲ) and MS (CDS) were 41.2%, 45.8% and 39.1%, respectively. The κ coefficients were 0.923, 0.880 and 0.881, respectively. The optimal HbA1c threshold with the highest level of agreement according to IDF, ATP Ⅲ and CDS criteria were 6.1%, 6.3% and 6.3%, respectively. Conclusions: An HbA1c threshold of 6.1% showed a high specificity for diagnosing MS in Chinese subjects aged over 50 years in community-based setting. The optimal HbA1c threshold may vary according to different criteria and populations.

Exercise interventions for patients with gynaecological cancer: a systematic review and meta-analysis.

BACKGROUND: People with gynaecological cancer commonly suffer from physical and psychological symptoms related to their cancer and cancer treatment. OBJECTIVE: To evaluate and synthesise the evidence examining the effect of interventions with an exercise component for females with gynaecological cancer. DATA SOURCES: Medline, CINAHL, EMBASE, PubMed, PEDro, PsycINFO and Cochrane Library were searched systematically in September 2014. STUDY SELECTION: Randomised controlled trials were included if they investigated the effects of interventions with an exercise component in patients with gynaecological cancer. STUDY APPRAISAL: Two reviewers independently assessed the risk of bias of studies using the PEDro scale. RESULTS: Seven randomised controlled trials on five patient groups involving 221 participants were included. The mean PEDro score was 5.3 (standard deviation 1.5) out of 10. Compared with control groups, the intervention groups showed significantly greater improvements in physical activity levels and body mass index. No significant effects were found for fatigue, depression and health-related quality of life. A meta-analysis of functional exercise capacity and muscle strength was not possible due to insufficient data in the included trials. LIMITATIONS: The majority of studies provided exercise as part of multicomponent intervention programmes. CONCLUSIONS: Interventions with an exercise component appear to be effective at improving physical activity levels and body mass index among patients with gynaecological cancer. Further research is required to examine the effects of exercise interventions alone in this population. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42014014019.

Systematic review: effect of psychiatric symptoms on return to work after occupational injury.

BACKGROUND: Although post-traumatic stress disorder (PTSD) and depression are commonly observed following injury, few studies have focused on the effect of psychiatric symptoms on return to work (RTW) following occupational injury. AIMS: To determine the impact of psychiatric symptoms on RTW after occupational injury. METHODS: PubMed (1980-2014), MEDLINE (1980-2014) and PsycINFO (1980-2014) databases were examined with linked fields of research in February 2015. Reference lists of eligible articles were also searched. Cohort, case-control, cross-sectional studies and intervention studies were selected according to predefined criteria. Evidence was synthesized qualitatively according to the Downs and Black and Crombie checklist. The standard checklist was used to assess the methodological quality of each study by two reviewers. RESULTS: Five of the 56 records met the inclusion and exclusion criteria. After occupational injury, the rates of RTW after the injuries varied widely, ranging from 31 to 63%. PTSD symptoms and depressive symptoms appeared to be negatively associated with RTW. CONCLUSIONS: Currently, the evidence is insufficient to draw conclusions about the effects of psychiatric symptoms on RTW after occupational injury and more studies are needed. Future studies with large sample sizes are warranted to determine the prevalence of RTW and to detect the psychiatric factors.

Genome-wide screen identified let-7c/miR-99a/miR-125b regulating tumor progression and stem-like properties in cholangiocarcinoma.

Cholangiocarcinoma (CCA), which is a poor prognosis malignancy that arises from the malignant transformation of cholangiocytes, is associated with chronic inflammation of the biliary epithelium. Thus far, the molecular mechanisms of the origin and neoplastic processes of CCA that are promoted by inflammation are still unclear and need to be fully elucidated. Here using small RNA sequencing to determine the microRNA (miRNA) expression profiles in CCA, we found that let-7c, miR-99a and miR-125b, which are three miRNAs of the same cluster, were downregulated in CCA and targeted interleukin 6 (IL-6), IL-6R and type 1 insulin-like growth factor, which are important cytokines and receptors of the IL-6/signal transducer and activator 3 (STAT3) pathway and have key roles in inflammation and CCA initiation. We also found that enforced expression of let-7c, miR-99a or miR-125b could reduce the activity of STAT3 and further suppress CCA tumorigenicity in vivo and inhibit the migration and invasion of CCA cells in vitro. Surprisingly, let-7c/miR-99a/miR-125b cluster also significantly decreased the ability of CCA cells for cancer stem cell-like mammosphere generation by downregulating CD133 and CD44, which suggests the pivotal roles of let-7c, miR-99a and miR-125b in CCA by regulating both inflammation and stem-like properties. Our findings showed potential links between miRNAs and inflammation, and provide a potential treatment strategy for developing an miRNA-based therapy via IL-6/STAT3 targeting for CCA.

YM155 down-regulates survivin and XIAP, modulates autophagy and induces autophagy-dependent DNA damage in breast cancer cells.

BACKGROUND AND PURPOSE: The aim of this study was to determine the potency and molecular mechanism of action of YM155, a first-in-class survivin inhibitor that is currently under phase I/II clinical investigations, in various drug-resistant breast cancers including the oestrogen receptor positive (ER(+) ) tamoxifen-resistant breast cancer and the caspase-3-deficient breast cancer. EXPERIMENTAL APPROACH: The potency of YM155 in SK-BR-3, MDA-MB-231, MCF7 and its tamoxifen-resistant sublines, TamR6, TamR7, TamR8, TamC3 and TamC6, were determined by MTT assay. Western blot analysis, flow cytometric analysis, reverse transcription-PCR, fluorescent microscopy and comet assay were used to determine the molecular mechanism of action of YM155 in different breast cancer cell lines. KEY RESULTS: YM155 was equally potent towards the parental ER(+) /caspase-3-deficient MCF7 breast cancer cells and its tamoxifen-resistant sublines in vitro. The ER(-) /HER2(+) SK-BR-3 breast cancer cells and the triple-negative/caspase-3-expressing metastatic aggressive MDA-MB-231 breast cancer cells were also sensitive to YM155 with IC50 values in the low nanomolar range. Targeting survivin by YM155 modulated autophagy, induced autophagy-dependent caspase-7 activation and autophagy-dependent DNA damage in breast cancer cells. Interestingly, YM155 also induced XIAP degradation and the degradation of XIAP might play an important role in YM155-induced autophagy in breast cancer cells. CONCLUSIONS AND IMPLICATIONS: YM155 is a potent survivin inhibitor that has potential for the management of various breast cancer subtypes regardless of the expression of ER, HER2 and caspase-3. Importantly, this study provides new insights into YM155's molecular mechanism of action and therapeutic potential in the treatment of tamoxifen-resistant breast cancer.

MicroRNA-149 targets GIT1 to suppress integrin signaling and breast cancer metastasis.

Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5ß1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5ß1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.

MiR-100 regulates cell differentiation and survival by targeting RBSP3, a phosphatase-like tumor suppressor in acute myeloid leukemia.

Acute myeloblastic leukemia (AML) is characterized by the accumulation of abnormal myeloblasts (mainly granulocyte or monocyte precursors) in the bone marrow and blood. Though great progress has been made for improvement in clinical treatment during the past decades, only minority with AML achieve long-term survival. Therefore, further understanding mechanisms of leukemogenesis and exploring novel therapeutic strategies are still crucial for improving disease outcome. MicroRNA-100 (miR-100), a small non-coding RNA molecule, has been reported as a frequent event aberrantly expressed in patients with AML; however, the molecular basis for this phenotype and the statuses of its downstream targets have not yet been elucidated. In the present study, we found that the expression level of miR-100 in vivo was related to the stage of the maturation block underlying the subtypes of myeloid leukemia. In vitro experiments further demonstrated that miR-100 was required to promote the cell proliferation of promyelocytic blasts and arrest them differentiated to granulocyte/monocyte lineages. Significantly, we identified RBSP3, a phosphatase-like tumor suppressor, as a bona fide target of miR-100 and validated that RBSP3 was involved in cell differentiation and survival in AML. Moreover, we revealed a new pathway that miR-100 regulates G1/S transition and S-phase entry and blocks the terminal differentiation by targeting RBSP3, which partly in turn modulates the cell cycle effectors pRB/E2F1 in AML. These events promoted cell proliferation and blocked granulocyte/monocyte differentiation. Our data highlight an important role of miR-100 in the molecular etiology of AML, and implicate the potential application of miR-100 in cancer therapy.

Femtosecond high-power spontaneous mode-locked operation in vertical-external cavity surface-emitting laser with gigahertz oscillation.

We realize a femtosecond high-power spontaneous mode-locked operation with gigahertz oscillation in a vertical-external cavity surface-emitting laser under the condition of eliminating the internal and external unwanted reflection. We find that the reflectivity of the output coupler has a significant influence not only on the output power but also on the output pulse duration. With an incident pump power of 20 W, we have achieved 2.35 W of average output power with 778 fs pulse duration at a repetition rate of 2.17 GHz. The shortest pulse duration was 654 fs at an average output power of 0.45 W.

Precise measurement of group refractive indices and temperature dependence of refractive index for Nd-doped yttrium orthovanadate by intracavity spontaneous mode locking.

We report on a novel method based on intracavity spontaneous mode locking to precisely measure the group refractive indices and temperature dependence of refractive index of Nd:YVO(4) crystal at the wavelength of 1064 nm. All the experimental results are found to agree very well with the most recent measured values. We also confirm that the developed method is applicable to measuring the group refractive indices and the temperature dependence of the refractive indices of other vanadate crystals, as well as nonlinear crystals.

Simulation and quantification of the natural decay of a typical endocrine disrupting chemical Atrazine in an aquatic system.

The degradation of Atrazine (ATZ) in an outdoor environment was investigated by varying the ATZ concentration and pH levels and then cross-checked with temperature and sunlight information. The overall decay rate constant of ATZ in outdoor is slower in neutral pH and faster at extreme pH levels, while parallel tests show that higher ATZ concentration leads to slower decay rate constant. Two abiotic mechanisms including direct photolysis and hydrolysis were identified and studied in the laboratory as a comparison. Hydrolysis was found to be a slow process but it is a continuous process, which is critical as the sunlight intensity is weak. Effect of temperature on the hydrolysis was also studied. A model incorporating ATZ decay rate constants, pH levels and temperatures was proposed. Photolysis, though, is a non-continuous process in the environment. It is a fast and dominant process, which contributes 82-45% (depending on pH levels) of overall ATZ decay at outdoor. In natural environment, humic acid can act as photosensitizer and enhance photolysis of ATZ at low concentration (<10mg/L); while at high concentration of humic acid, retardation of ATZ decay was observed likely due to the scavenging of radicals and light attenuation.

Alterations of myelin proteins in inflammatory demyelination of BALB/c mice caused by Angiostrongylus cantonensis.

Angiostrongylus cantonensis causes eosinophilic meningitis or meningoencephalitis, yet little is known about demyelination caused by this parasite. To define the course of demyelination caused by A. cantonensis, we analyzed the expression of myelin proteins including myelin-associated glycoprotein (MAG), myelin basic protein (MBP), myelin-associated oligodendrocytic basic protein (MOBP), and proteolipid protein (PLP) in brain and cerebrospinal fluid (CSF)-like fluid of infected and uninfected BALB/c mice. In A. cantonensis-infected mice, the expression of MAG, MBP, MOBP, and PLP mRNAs in brain tissue was decreased, while expression of the corresponding proteins was significantly increased in CSF-like fluid. Light microscopy revealed perivascular infiltrates in the brain during meningoencephalitis, suggesting that the cause of demyelination in angiostrongyliasis was immune system attack on the oligodendrocytic myelin sheath and subsequent release of myelin proteins into the CSF. Thus, intracerebral myelin breakdown in angiostrongyliasis may be a response to inflammatory mediators and the cause of increased myelin proteins in the CSF-like fluid.