Demographic review of aesthetic surgery for patients with facial palsy.

BACKGROUND: This study analyzed the demographic characteristics of patients with facial palsy who were treated using either dynamic or static procedures. This study aimed to compare the frequency of procedure implementation and age distribution between the two groups. METHODS: This study retrospectively analyzed the medical records of patients treated for facial palsy at a single institution from 2014 to 2022. Among cases included in our study, dynamic procedures involved cross-facial nerve graft and latissimus dorsi or gracilis muscle flap transfer. Static procedures included gold weight insertion, canthopexy, browlift, and thread lift/static slings. RESULTS: Among the 31 patients included in our study, eight (25.8%) incorporated dynamic techniques, and the average age of patients was 44.75 years (range, 24-68 years) with a male to female ratio of 1:4. The remaining 23 patients (74.2%) underwent a static procedure, of which the average age was 59.17 years (range, 23-81 years) which was statistically significantly higher than the average age of 44.75 of dynamic patients (p= 0.013). Regarding the timing of treatment after diagnosis, no patient underwent dynamic procedures more than 20 years after initial diagnosis. A greater diversity in the timing of treatment was observed in the static group. All patients who underwent dynamic procedures were treated using static procedures during the study period. CONCLUSION: Because aesthetics-based static techniques are typically quick outpatient procedures that can be performed under local anesthesia, our study shows that these are often preferred treatments for all age groups, especially for debilitated or older patients. Further research is required to investigate the long-term functional outcomes of these surgical techniques in a wider population of patients.

Complete mitochondrial genome of little ringed plover Charadrius dubius (Charadriiformes, Charadriidae).

This study encoded the complete mitochondrial genomic sequence of the little ringed plover Charadrius dubius. The mitochondrial genome has a total length of 16,864 bp, consisting of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and a control region. The nucleotide composition was 23.8% T, 31.6% A, 30.8% C, and 13.8% G. This study provides the basic information on the mitogenome of C. dubius and supports the understanding of mitogenomic information and its phylogenetic relationship within Charadriiformes.

Preclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models.

Human granulocyte colony-stimulating factor (G-CSF, this study used Fc-fused recombinant G-CSF; GX-G3) is an important glycoprotein that stimulates the proliferation of granulocytes and white blood cells. Thus, G-CSF treatment has been considered as a crucial regimen to accelerate recovery from chemotherapy-induced neutropenia in cancer patients suffering from non-myeloid malignancy or acute myeloid leukemia. Despite the therapeutic advantages of G-CSF treatment, an assessment of its immunogenicity must be performed to determine whether the production of anti-G-CSF antibodies causes immune-related disorders. We optimized and validated analytical tools by adopting validation parameters for immunogenicity assessment. Using these validated tools, we analyzed serum samples from rats and monkeys injected subcutaneously with GX-G3 (1, 3 or 10 mg/kg once a week for 4 weeks followed by a 4-week recovery period) to determine immunogenicity response and toxicokinetic parameters with serum concentration of GX-G3. Several rats and monkeys were determined to be positive for anti-GX-G3 antibodies. Moreover, the immunogenicity response of GX-G3 was lower in monkeys than in rats, which was relevant to show less inhibition of toxicokinetic profiles in monkeys, at least 1 mg/kg administrated group, compared to rats. These results suggested the establishment and validation for analyzing anti-GX-G3 antibodies and measurement of serum levels of GX-G3 and anti-GX-G3 antibodies, which was related with toxicokinetic profiles. Taken together, this study provides immunogenicity assessment which is closely implicated with toxicokinetic study of GX-G3 in 4-week repeated administrated toxicological studies.

A Risk Prediction Model for Operative Mortality after Heart Valve Surgery in a Korean Cohort.

BACKGROUND: This study aimed to develop a new risk prediction model for operative mortality in a Korean cohort undergoing heart valve surgery using the Korea Heart Valve Surgery Registry (KHVSR) database. METHODS: We analyzed data from 4,742 patients registered in the KHVSR who underwent heart valve surgery at 9 institutions between 2017 and 2018. A risk prediction model was developed for operative mortality, defined as death within 30 days after surgery or during the same hospitalization. A statistical model was generated with a scoring system by multiple logistic regression analyses. The performance of the model was evaluated by its discrimination and calibration abilities. RESULTS: Operative mortality occurred in 142 patients. The final regression models identified 13 risk variables. The risk prediction model showed good discrimination, with a c-statistic of 0.805 and calibration with Hosmer-Lemeshow goodness-of-fit p-value of 0.630. The risk scores ranged from -1 to 15, and were associated with an increase in predicted mortality. The predicted mortality across the risk scores ranged from 0.3% to 80.6%. CONCLUSION: This risk prediction model using a scoring system specific to heart valve surgery was developed from the KHVSR database. The risk prediction model showed that operative mortality could be predicted well in a Korean cohort.

6-month-olds are sensitive to English morphology.

Each language has its unique way to mark grammatical information such as gender, number and tense. For example, English marks number and tense/aspect information with morphological suffixes (e.g., -s or -ed). These morphological suffixes are crucial for language acquisition as they are the basic building blocks of syntax, encode relationships, and convey meaning. Previous research shows that English-learning infants recognize morphological suffixes attached to nonce words by the end of the first year, although even 8-month-olds recognize them when they are attached to known words. These results support an acquisition trajectory where discovery of meaning guides infants' acquisition of morphological suffixes. In this paper, we re-evaluated English-learning infants' knowledge of morphological suffixes in the first year of life. We found that 6-month-olds successfully segmented nonce words suffixed with -s, -ing, -ed and a pseudo-morpheme -sh. Additionally, they related nonce words suffixed with -s, but not -ing, -ed or a pseudo-morpheme -sh and stems. By 8-months, infants were also able to relate nonce words suffixed with -ing and stems. Our results show that infants demonstrate knowledge of morphological relatedness from the earliest stages of acquisition. They do so even in the absence of access to meaning. Based on these results, we argue for a developmental timeline where the acquisition of morphology is, at least, concurrent with the acquisition of phonology and meaning.

Stem similarity modulates infants' acquisition of phonological alternations.

Phonemes have variant pronunciations depending on context. For instance, in American English, the [t] in pat [pæt] and the [d] in pad [pæd] are both realized with a tap [ɾ] when the -ing suffix is attached, [pæɾɪŋ]. We show that despite greater distributional and acoustic support for the [t]-tap alternation, 12-month-olds successfully relate taps to stems with a perceptually-similar final [d], not the dissimilar final-[t]. Thus, distributional learning of phonological alternations is constrained by infants' preference for the alternation of perceptually-similar segments. Further, the ability to relate variant surface forms emerges between 8- and 12-months. Our findings of biased learning provide further empirical support for a role for perceptual similarity in the acquisition of linguistically-relevant categories. We discuss the implications of our findings for phonological theory, language acquisition and models of the mental lexicon.

Pattern and Impact of Off-label Underdosing of Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation Who are Indicated for Standard Dosing.

With safety concerns about increasing bleeding, off-label underdosing of non-vitamin K antagonist anticoagulants (NOACs) is common in East Asian patients with atrial fibrillation (AF). We tried to investigate the pattern of NOAC underdosing and associated clinical outcomes in patients with AF who are indicated for standard dosing. Using the Korean National Health Insurance Service database, we evaluated 16,568 patients with a new prescription of NOAC who are indicated for standard NOAC dosing and compared 4,536 patients with warfarin with respect to thromboembolic events (ischemic stroke or systemic embolization), all-cause mortality and major bleeding. Of the 16,568 patients indicated for standard NOAC dosing, 8,549 (51.9%) received off-label underdosing (50.6% rivaroxaban, 53.0% apixaban). During a median follow up of 15.0 months, as compared with warfarin, underdosing of rivaroxaban was associated with lower risks of major thromboembolic events (hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.41 to 0.69) and all-cause mortality (HR 0.57, 95% CI: 0.41 to 0.82), and a similar risk of major bleeding (HR 1.10, 95% CI: 0.82 to 1.46). However, underdosing of apixaban was associated with similar risks of major thromboembolic events (HR: 0.90; 95% CI: 0.70 to 1.16), all-cause mortality (HR 0.94, 95 CI: 0.71 to 1.24) and major bleeding (HR 0.84, 95% CI: 0.61 to 1.17). In conclusion, in this Korean population with AF who are indicated for standard NOAC dosing, off-label underdosing is common and its clinical benefit over warfarin was inconsistent according to types of NOAC. Notably, apixaban underdosing provides no benefit in effectiveness compared with warfarin.

Tuning Two Interfaces with Fluoroethylene Carbonate Electrolytes for High-Performance Li/LCO Batteries.

Various electrolytes have been reported to enhance the reversibility of Li-metal electrodes. However, for these electrolytes, concurrent and balanced control of Li-metal and positive electrode interfaces is a critical step toward fabrication of high-performance Li-metal batteries. Here, we report the tuning of Li-metal and lithium cobalt oxide (LCO) interfaces with fluoroethylene carbonate (FEC)-containing electrolytes to achieve high cycling stability of Li/LCO batteries. Reversibility of the Li-metal electrode is considerably enhanced for electrolytes with high FEC contents, confirming the positive effect of FEC on the stabilization of the Li-metal electrode. However, for FEC contents of 50 wt % and above, the discharge capacity is significantly reduced because of the formation of a passivation layer on the LCO cathodes. Using balanced tuning of the two interfaces, stable cycling over 350 cycles at 1.5 mA cm-2 is achieved for a Li/LCO cell with the 1 M LiPF6 FEC/DEC = 30/70 electrolyte. The enhanced reversibility of the Li-metal electrode is associated with the formation of LiF and polycarbonate in the FEC-derived solid electrolyte interface (SEI) layer. In addition, electrolytes with high FEC contents lead to lateral Li deposition on the sides of Li deposits and larger dimensions of rodlike Li deposits, suggesting the elastic and ion-conductive nature of the FEC-derived SEI layer.

Preclinical evaluation of a biobetter candidate: Pharmacokinetics and pharmacodynamics of GX-G3 in healthy and neutropenia-induced rats.

Neutropenia is a condition of an abnormally low number of neutrophils which render patients more susceptible to infections, especially to bacterial infections, as the condition may become life threatening and deadly without prompt medical attention. Various factors such as, anticancer drugs, radiotherapy, infectious diseases, congenital defects, or vitamin B12/B9 deficiency can trigger neutropenia. GX-G3, a human hybrid (hy) Fc-fused granulocyte colony stimulating factor (G-CSF), was developed as next-generation G-CSF for the treatment of cancer therapy-induced neutropenia. In this study, with the aim of investigating this promising potential next-generation G-CSF, comparative pharmacokinetic and pharmacodynamic studies were conducted in healthy and neutropenia-induced rats. It was found that t1/2 of GX-G3 is longer than same mass injection of filgrastim and pegfilgrastim and AUEClast (area under theeffect-time curve from time zero to the last measurable ANC level) of absolute neutrophil count showed a significant increase after GX-G3 injection compared with filgrastim and pegfilgrastim in healthy rats. Besides, in duration of neutropenia after the same mass injection GX-G3 showed about 3.3 days of reduction effect compared with that of filgrastim, and 1.3 days of reduction effect compared with that of pegfilgrastim in neutropenia-induced rats. These results demonstrate that the half-life of GX-G3 is longer than pegfilgrastim and GX-G3 is more effective than filgrastim and pegfilgrastim in neutropenia-induced rats.

Safety and Effectiveness of Contemporary P2Y12 Inhibitors in an East Asian Population With Acute Coronary Syndrome: A Nationwide Population-Based Cohort Study.

Background Prior reports indicate that the effect of P2Y12 inhibitors may be different in East Asian patients ("East Asian paradox"); therefore, understanding the outcomes associated with potent P2Y12 inhibitors in different populations is clinically important. Methods and Results In this observational cohort study using administrative healthcare data sets, we compared safety and effectiveness of contemporary P2Y12 inhibitors in patients with acute coronary syndrome. The primary safety outcomes were major and any bleeding, and the primary effectiveness outcomes were major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) and all-cause mortality. Among 70 715 patients with acute coronary syndrome, 56 216 (79.5%) used clopidogrel, 11 402 (16.1%) used ticagrelor, and 3097 (4.4%) used prasugrel. The median follow-up period was 18.0 months (interquartile range: 9.6-26.4 months). In a propensity-matched cohort, compared with clopidogrel, ticagrelor was associated with a higher risk of any bleeding (hazard ratio: 1.23; 95% CI, 1.14-1.33) but a lower risk of mortality (hazard ratio: 0.76; 95% CI, 0.63-0.91). Prasugrel, compared with clopidogrel, was associated with higher risks of any bleeding (hazard ratio: 1.23; 95% CI, 1.06-1.43) and major bleeding (hazard ratio: 1.50; 95% CI, 1.01-2.21) but a similar risk of effectiveness outcomes. No significant difference was noted between ticagrelor and prasugrel with respect to key safety or effectiveness outcomes. Several sensitivity analyses showed similar results. Conclusions In East Asian patients with acute coronary syndrome, compared with clopidogrel, ticagrelor was associated with an increased risk of bleeding but a decreased risk of mortality. Prasugrel was associated with an increase of any bleeding without difference in effectiveness outcomes. The risks of bleeding and ischemic events were similar between ticagrelor and prasugrel.

Budget Impact Analysis of the Change in Peritoneal Dialysis Use Rate in Korea.

Background:While the number of peritoneal dialysis (PD) patients has decreased by 14.4% from 2006 to 2016, the number of hemodialysis (HD) patients has sharply increased, by 237.2%, in the same period, leading to an increase in the total medical cost. We analyzed the effects of the changes in PD use rates for dialysis patients in Korea on the healthcare budget using budget impact analysis (BIA).Methods:The analysis modeled the influence of the increase in dialysis for the target population, changes in modality use rate, and/or changes in costs per patient-year on total medical cost for patients on dialysis, using the National Health Insurance Service (NHI) claims data. We developed 8 scenarios according to the changing PD use rate.Results:In scenarios 1 - 4 (increase in PD patients by 6%, 13%, 20%, and 50% of non-diabetic prevalent HD patients under 65), 5-year budget savings ranged from $47 million to $394 million (0.9% - 7.3% of the end-stage renal disease [ESRD] budget). In scenarios 5 - 8 (increase in incident PD patients by 20%, 50%, 70%, and 100% of non-diabetic patients under 65), 5-year savings ranged from $25 million to $74 million (0.5% - 1.4% of the ESRD budget). In all scenarios, budget savings were higher as PD patients increased, showing a gradually growing trend.Conclusion:In all scenarios from the payer's perspective, savings could be achieved through an increase in PD use. Selecting PD for ESRD patients without different expected clinical outcomes between HD and PD would be beneficial to the NHI budget.

Rational Design of Highly Packed, Crack-Free Sulfur Electrodes by Scaffold-Supported Drying for Ultrahigh-Sulfur-Loaded Lithium-Sulfur Batteries.

Despite the notable progress in the development of rechargeable lithium-sulfur batteries over the last decade, achieving high performance with high-sulfur-loaded sulfur cathodes remains a key challenge on the path to the commercialization of practical lithium-sulfur batteries. This paper presents a novel method by which to fabricate a crack-free sulfur electrode with an ultrahigh sulfur loading (16 mg cm-2) and a high sulfur content (64%). By introducing a porous scaffold on the top of a cast of sulfur cathode slurry, the formation of cracks during the drying of the cast can be prevented due to the lower volume shrinkage of the skin. The scaffold-supported sulfur cathode delivers a notably high capacities of 10.3 mAh cm-2 and 473 mAh cm-3 after a prolonged cycle, demonstrating that the crack-free structure renders more uniform redox reactions at such high sulfur loading. The highly packed, crack-free feature of the sulfur cathode is advantageous, given that it reduces the electrolyte uptake to as low as an E/S ratio of 4 µL mg-1, which additionally contributes to the high energy density. Therefore, the scaffold-supported drying fabrication method as presented here provides an effective route by which to design practically viable, energy-dense lithium-sulfur batteries.

Time- and Dose-Dependent Association of Statin Use With Risk of Clinically Relevant New-Onset Diabetes Mellitus in Primary Prevention: A Nationwide Observational Cohort Study.

Background Given that statins are increasingly being used for primary-prevention, the public concerns regarding the risk of new-onset diabetes mellitus associated with statin use may be an issue. Methods and Results Using healthcare data from the national health insurance examinees, our study comprised a cohort of adults aged ≥40 years with hypercholesterolemia who would be eligible for statin therapy for primary prevention from 2005 to 2012. The primary outcome was the occurrence of clinically relevant new-onset diabetes mellitus requiring medical therapy. Among 2 162 119 adults with hypercholesterolemia who might be eligible for statin therapy, 638 625 (29.5%) ever used statins and 1 523 494 (70.5%) never used statins. In the propensity-matched cohort of 518 491 pairs, during mean follow-up of 3.9 years, being an ever-user of statin was significantly associated with diabetes mellitus risk compared with being a never-user of statin (13.4 versus 6.9 per 1000 person-years; adjusted hazard ratio [ HR ], 1.88; 95% CI , 1.85-1.93). With increasing duration of statin use, the risk of diabetes mellitus was proportionally increased ( HR 1.25 <1 year, HR 2.22 for 1-2 years, and HR 2.62 >2 years). An excess risk of diabetes mellitus was also associated with a higher intensity ( HR 1.75 for low-to-moderate potency and HR 2.31 for high potency) and a cumulative dosing of statin ( HR 1.06 for low-tertile, HR 1.74 for middle-tertile, and HR 2.52 for high-tertile of defined-daily-disease). Conclusions In patients receiving statin therapy for primary prevention, there was a time- and dose-dependent association of statin use with an increasing risk of new-onset diabetes mellitus.

Achieving three-dimensional lithium sulfide growth in lithium-sulfur batteries using high-donor-number anions.

Uncontrolled growth of insulating lithium sulfide leads to passivation of sulfur cathodes, which limits high sulfur utilization in lithium-sulfur batteries. Sulfur utilization can be augmented in electrolytes based on solvents with high Gutmann Donor Number; however, violent lithium metal corrosion is a drawback. Here we report that particulate lithium sulfide growth can be achieved using a salt anion with a high donor number, such as bromide or triflate. The use of bromide leads to ~95 % sulfur utilization by suppressing electrode passivation. More importantly, the electrolytes with high-donor-number salt anions are notably compatible with lithium metal electrodes. The approach enables a high sulfur-loaded cell with areal capacity higher than 4 mA h cm-2 and high sulfur utilization ( > 90 %). This work offers a simple but practical strategy to modulate lithium sulfide growth, while conserving stability for high-performance lithium-sulfur batteries.

Oleic acid enhances keratinocytes differentiation via the upregulation of miR-203 in human epidermal keratinocytes.

BACKGROUND: Oleic acid (OA) is an unsaturated free fatty acid (FFA) constituent of sebum. FFAs modulate keratinocyte differentiation. In this study, we determined whether OA affects keratinocyte differentiation in neonatal human epidermal keratinocytes (HEKn). METHODS: HEKn was grown in EpiLife medium. The cells were treated with various concentrations of OA. The expression levels of keratin 10 and involucrin were determined using Western blotting (for the proteins) and quantitative real time polymerase chain reaction (qRT-PCR) (for the mRNAs). Cytoskeletal changes were investigated by immunofluorescent staining. The levels of microRNA (miR)-203 were determined by stem-loop qRT-PCR. The effect of miR-203 on keratinocyte differentiation was evaluated using anti-miR-203. RESULTS: Treatment with OA promoted the expression of keratin 10 and involucrin, which are markers of spinous and granular layer keratinocytes, respectively. Treatment with OA also induced cell stratification and cytoskeletal changes such as the concentric ring organization of actin, a loss of planar polarity, and increased localization of epithelial cadherin (E-cadherin) at cell-cell contacts. OA increased the expression of miR-203, which is associated with keratinocyte differentiation, and reduced the expression of p63, a target of miR-203, in HEKn. Furthermore, transfection with anti-miR-203 suppressed the OA-induced expression of involucrin. CONCLUSIONS: Oleic acid accelerates keratinocyte differentiation via the upregulation of miR-203 in HEKn under sub-confluent conditions.

Outcomes After Use of Standard- and Low-Dose Non-Vitamin K Oral Anticoagulants in Asian Patients With Atrial Fibrillation.

Background and Purpose- Limited data are available describing the relative effectiveness, safety, and optimal dosing of non-vitamin K antagonist oral anticoagulants (NOACs) for treatment of nonvalvular atrial fibrillation in East Asian patients. We tried to compare effectiveness and safety outcomes of standard- and low-dose NOACs and warfarin in this population. Methods- Using nationwide administrative claims-based datasets from the Korean National Health Insurance Service Database (July 1, 2015, to December 31, 2016), this study comprised 56 504 anticoagulation-naive nonvalvular atrial fibrillation patients with high thromboembolic risk (CHA2DS2-VASc score, ≥2) treated with oral anticoagulants. Main study outcomes included thromboembolic events (ischemic stroke or systemic embolism), major bleeding, and mortality. Results- Among the study patients, 10 409 (18.4%) received warfarin and 46 095 (81.6%) were treated with NOACs: dabigatran (n=12 593; 22.3%), rivaroxaban (n=21 000; 37.2%), and apixaban (n=12 502; 22.1%). Low-dose NOAC (75.1% dabigatran, 59.7% rivaroxaban, and 62.7% apixaban) was more frequently used than standard-dose NOAC. During median follow-up of 15.0 months, each NOAC was associated with significantly lower risk of thromboembolic events (hazard ratio [HR], 0.76; 95% CI, 0.75-0.81 for dabigatran; HR, 0.74; 95% CI, 0.65-0.83 for rivaroxaban; and HR, 0.68; 95% CI, 0.59-0.78 for apixaban). Regarding safety outcomes, dabigatran (HR, 0.81; CI, 0.69-0.95) and apixaban (HR, 0.67; CI, 0.56-0.79) were associated with lower risk of major bleeding but not with rivaroxaban (HR, 0.96; CI, 0.84-1.11). Among adults <75 years of age without chronic kidney disease, use of low-dose apixaban did not demonstrate clinical benefit over warfarin with respect to thromboembolic events (HR, 0.99; CI, 0.76-1.28) and mortality (HR, 0.85; CI, 0.62-1.16). Conclusions- In this cohort of East Asian patients with nonvalvular atrial fibrillation, NOACs were associated with better effectiveness and safety outcomes versus warfarin. Lower NOAC doses were more often used, but an unjustified underdosing of apixaban seems to result in lower clinical benefit.

Inhaled bronchodilators and acute myocardial infarction: a nested case-control study.

We investigated the association between the use of inhaled bronchodilators and the risk of AMI. A nested case-control study using the nationwide insurance claims database was conducted. Overall, 11,054 AMI cases and 47,815 matched (up to 1:5) controls were identified from 1,036,119 subjects without acute major cardiovascular events in the past year. Long-acting and short-acting ß-agonists (LABAs and SABAs) were associated with increase in the risk of AMI, although an inhaled corticosteroid combined with a long-acting ß-agonist was not. Long-acting muscarinic antagonists (LAMAs) in a dry powder inhaler (DPI) were significantly associated with reduced risk of AMI, while LAMAs in a soft mist inhaler (SMI) didn't decrease the risk of it. In hypertensive or diabetic patients, LAMAs in a DPI were associated with reduced risk of AMI, but LABAs were associated with increased risk. Among the ß-blocker users, the reduction of AMI risk by LAMAs was the most significant. In conclusions, inhaled ß-agonists were associated with increase in the risk of AMI, while LABAs accompanied by ICSs were not associated with increase in the risk of AMI. LAMAs in a DPI use were associated with lower risk of AMI.

Mutation of the cyclic di-GMP phosphodiesterase gene in Burkholderia lata SK875 attenuates virulence and enhances biofilm formation.

Burkholderia sp. is a gram-negative bacterium that commonly exists in the environment, and can cause diseases in plants, animals, and humans. Here, a transposon mutant library of a Burkholderia lata isolate from a pig with swine respiratory disease in Korea was screened for strains showing attenuated virulence in Caenorhabditis elegans. One such mutant was obtained, and the Tn5 insertion junction was mapped to rpfR, a gene encoding a cyclic di-GMP phosphodiesterase that functions as a receptor. Mutation of rpfR caused a reduction in growth on CPG agar and swimming motility as well as a rough colony morphology on Congo red agar. TLC analysis showed reduced AHL secretion, which was in agreement with the results from plate-based and bioluminescence assays. The mutant strain produced significantly more biofilm detected by crystal violet staining than the parent strain. SEM of the mutant strain clearly showed that the overproduced biofilm contained a filamentous structure. These results suggest that the cyclic di-GMP phosphodiesterase RpfR plays an important role in quorum sensing modulation of the bacterial virulence and biofilm formation.

Enhancing the Cycling Stability of Sodium Metal Electrodes by Building an Inorganic-Organic Composite Protective Layer.

Owing to the natural abundance of sodium resources and their low price, next-generation batteries employing an Na metal anode, such as Na-O2 and Na-S systems, have attracted a great deal of interest. However, the poor reversibility of an Na metal electrode during repeated electrochemical plating and stripping is a major obstacle to realizing rechargeable sodium metal batteries. It mainly originates from Na dendrite formation and exhaustive electrolyte decomposition due to the high reactivity of Na metal. Herein, we report a free-standing composite protective layer (FCPL) for enhancing the reversibility of an Na metal electrode by mechanically suppressing Na dendritic growth and mitigating the electrolyte decomposition. A systematic variation of the liquid electrolyte uptake of FCPL verifies the existence of a critical shear modulus for suppressing Na dendrite growth, being in good agreement with a linear elastic theory, and emphasizes the importance of the ionic conductivity of FCPL for attaining uniform Na plating and stripping. The Na-Na symmetric cell with an optimized FCPL exhibits a cycle life two times longer than that of a bare Na electrode.

Association between metformin use and mortality in patients with type 2 diabetes mellitus and localized resectable pancreatic cancer: a nationwide population-based study in korea.

BACKGROUND: Preclinical studies support an antitumor effect of metformin. However, clinical studies have conflicting results and metformin's effect remains controversial. The aim of this study was to evaluate metformin's effect on clinical outcomes in diabetic patients with pancreatic cancer treated with curative resection. RESULTS: A total of 764 patients underwent curative resection, met none of the exclusion criteria, and were prescribed oral hypoglycemic agents. The cancer-specific survival (5-year, 31.9% vs. 22.2%, p < 0.001) was significantly higher in the 530 metformin users than in the 234 diabetic metformin non-users. After multivariable adjustments, metformin users had significantly lower cancer-specific mortality as compared with metformin non-users (hazard ratio, 0.727; 95% confidence interval, 0.611-0.868). Cubic spline regression analysis demonstrated significantly decreased cancer-specific mortality with increasing dose of metformin (p = 0.0047). MATERIALS AND METHODS: Data were provided from the Korea Central Cancer Registry and the National Health Insurance Service in the Republic of Korea. The study cohort consisted of 28,862 patients newly diagnosed with pancreatic cancer between 2005 and 2011. Metformin exposure was determined from prescription information from 6 months before the first diagnosis of pancreatic cancer to last follow-up. The main outcome was cancer-specific survival. CONCLUSIONS: This large study indicates that metformin might decrease cancer-specific mortality rates in localized resectable pancreatic cancer patients with pre-existing diabetes, independently of other factors, with a dose-response relationship.