Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are novel anti-diabetic drugs whose glucose-lowering effect and cardiovascular and renal benefits were evidenced in clinical trials. We investigated the real-world efficacy and safety of the combination of SGLT2i and GLP-1RA in patients with type 2 diabetes mellitus in Korea. The medical records of 104 patients who maintained the combination for at least 1 year were retrospectively reviewed. The change in glycosylated hemoglobin (HbA1c) after 6 months and 1 year of treatment was evaluated. The mean age was 51 years, and 41% were female. The mean baseline HbA1c, body mass index, and duration of diabetes were 9.0%, 28.8 kg/m2, and 11.7 years, respectively. Compared with baseline, the HbA1c decreased by 1.5% (95% confidence interval [CI], 1.27 to 1.74; P<0.001) after 6 months and by 1.4% (95% CI, 1.19 to 1.70; P<0.001) after 1 year. Over 1 year, the bodyweight change was -2.8 kg (95% CI, -4.21 to -1.47; P<0.001). The combination of SGLT2i and GLP-1RA is effective and tolerable in type 2 diabetes mellitus patients in real-world practice.

Endosymbiotic Male-Killing Spiroplasma Affects the Physiological and Behavioral Ecology of Macrocheles-Drosophila Interactions.

While many arthropod endosymbionts are vertically transmitted, phylogenetic studies reveal repeated introductions of hemolymph-dwelling Spiroplasma into Drosophila. Introductions are often attributed to horizontal transmission via ectoparasite vectors. Here, we test if mites (Macrocheles subbadius) prefer to infect Spiroplasma poulsonii MSRO (Melanogaster sex ratio organism)-infected flies and if MSRO infection impairs fly resistance against secondary mite attack. First, we tested if mites prefer MSRO+ or MSRO- flies using pairwise choice tests across fly ages. We then tested whether mite preferences are explained by changes in fly physiology, specifically increased metabolic rate (measured as CO2 production). We hypothesize that this preference is due in part to MSRO+ flies expressing higher metabolic rates. However, our results showed mite preference depended on an interaction between fly age and MSRO status: mites avoided 14-day-old MSRO+ flies relative to MSRO- flies (31% infection) but preferred MSRO+ flies (64% infection) among 26-day-old flies. Using flowthrough respirometry, we found 14-day-old MSRO+ flies had higher CO2 emissions than MSRO- flies (32% greater), whereas at 26 days old the CO2 production among MSRO+ flies was 20% lower than that of MSRO- flies. Thus, mite preferences for high-metabolic-rate hosts did not explain the infection biases in this study. To assess changes in susceptibility to infection, we measured fly endurance using geotaxis assays. Older flies had lower endurance consistent with fly senescence, and this effect was magnified among MSRO+ flies. Given the biological importance of male-killing Spiroplasma, potential changes in the interactions of hosts and potential vectors could impact the ecology and evolution of host species. IMPORTANCE Male-killing endosymbionts are transmitted from mother to daughter and kill male offspring. Despite these major ecological effects, how these endosymbionts colonize new host species is not always clear. Mites are sometimes hypothesized to transfer these bacteria between hosts/host species. Here, we test if (i) mites prefer to infect flies that harbor Spiroplasma poulisoni MSRO and (ii) flies infected with MSRO are less able to resist mite infection. Our results show that flies infected with MSRO have weaker anti-mite resistance, but the mite preference/aversion for MSRO+ flies varied with fly age. Given the fitness and population impacts of male-killing Spiroplasma, changes in fly-mite interactions have implications for the ecology and evolution of these symbioses.

Isolation of Skin Leukocytes Uncovers Phagocyte Inflammatory Responses During Induction and Resolution of Cutaneous Inflammation in Fish.

Leukocytes offer a critical layer of protection to the host following skin infections. Delineating the kinetics of cutaneous leukocyte recruitment as well as their anti-microbial and regulatory profiles is challenging since it requires the isolation of adequate cell numbers and maintenance of their functional properties. Herein, we took advantage of a modified procedure to gain insights into the contributions of fish phagocytes through induction and resolution phases of acute cutaneous inflammation in goldfish (Carassius auratus). Our data shows early upregulation of pro-inflammatory cytokines and chemokines, which was paired with neutrophil-dominant leukocyte migration of neutrophils from circulation to the injury site. Recruited neutrophils were associated with high levels of reactive oxygen species (ROS). Following pathogen elimination, a reduction in ROS levels and pro-inflammatory cytokines expression preceded the resolution of inflammation. These results provide a better understanding of the cutaneous immune responses in fish. Moreover, the increased viability and functionality of isolated skin leukocytes opens the door to better understand a range of additional skin diseases.

Creation and control of multi-phonon Fock states in a bulk acoustic-wave resonator.

Quantum states of mechanical motion can be important resources for quantum information, metrology and studies of fundamental physics. Recent demonstrations of superconducting qubits coupled to acoustic resonators have opened up the possibility of performing quantum operations on macroscale motional modes1-3, which can act as long-lived quantum memories or transducers. In addition, they can potentially be used to test decoherence mechanisms in macroscale objects and other modifications to standard quantum theory4,5. Many of these applications call for the ability to create and characterize complex quantum states, such as states with a well defined phonon number, also known as phonon Fock states. Such capabilities require fast quantum operations and long coherence times of the mechanical mode. Here we demonstrate the controlled generation of multi-phonon Fock states in a macroscale bulk acoustic-wave resonator. We also perform Wigner tomography and state reconstruction to highlight the quantum nature of the prepared states6. These demonstrations are made possible by the long coherence times of our acoustic resonator and our ability to selectively couple a superconducting qubit to individual phonon modes. Our work shows that circuit quantum acoustodynamics7 enables sophisticated quantum control of macroscale mechanical objects and opens up the possibility of using acoustic modes as quantum resources.

Traffic accident severity analysis with rain-related factors using structural equation modeling - A case study of Seoul City.

Weather conditions are strongly correlated with traffic accident severity. In particular, rain-related factors are an important cause of traffic accidents due to the poor visibility and reduced friction resulting from slippery road conditions. This paper presents a systematic approach to analyze the extent to which the rainfall intensity and level of water depth are responsible for traffic accidents using Seoul City, Korea, as a case study. The rainfall and traffic accident data over a nine-year period (from 2007 to 2015) for Seoul were analyzed through Structural Equation Modeling to identify the relationships among variables by handling endogenous and exogenous variables simultaneously. In the model, four latent variables, namely those representing the road; traffic, environmental, and human factors; and rain and water depth factors, were defined and the coefficients of the latent, endogenous, and exogenous variables were estimated to obtain the level of accident severity. Furthermore, a statistical goodness of fit index was suggested for model fitting. In conclusion, traffic, environmental, and human factors; rain and water depth factors; and road factors are mutually correlated with the level of accident severity. Compact cars, young drivers, female drivers, heavy rain, deep water, and roads with a long drainage length are more likely to be associated with an increase in the level of accident severity, as are features like a tangent, down slope, right-hand curve, and shorter curve length.