Clinical characteristics of acute kidney injury in patients with glyphosate surfactant herbicide poisoning.

BACKGROUND: In this study, we investigated the clinical characteristics of acute kidney injury (AKI) in patients with glyphosate surfactant herbicide (GSH) poisoning. METHODS: This study was performed between 2008 and 2021 and included 184 patients categorized into the AKI (n = 82) and nonAKI (n = 102) groups. The incidence, clinical characteristics, and severity of AKI were compared between the groups based on the Risk of renal dysfunction, Injury to the kidney, Failure or Loss of kidney function, and End-stage kidney disease (RIFLE) classification. RESULTS: The incidence of AKI was 44.5%, of which 25.0%, 6.5%, and 13.0% of patients were classified into the Risk, Injury, and Failure categories, respectively. Patients in the AKI group were older (63.3 ± 16.2 years vs. 57.4 ± 17.5 years, p = 0.02) than those in the non-AKI group. The length of hospitalization was longer (10.7 ± 12.1 days vs. 6.5 ± 8.1 days, p = 0.004) and hypotensive episodes occurred more frequently in the AKI group (45.1% vs. 8.8%, p < 0.001). Electrocardiographic (ECG) abnormalities on admission were more frequently observed in the AKI group than in the non-AKI group (80.5% vs. 47.1%, p < 0.001). Patients in the AKI group had poorer renal function (estimated glomerular filtration rate at the time of admission, 62.2 ± 22.9 mL/min/1.73 m2 vs. 88.9 ± 26.1 mL/min/1.73 m2 , p < 0.001) on admission. The mortality rate was higher in the AKI group than in the non-AKI group (18.3% vs. 1.0%, p < 0.001). Multiple logistic regression analysis showed that hypotension and ECG abnormalities upon admission were significant predictors of AKI in patients with GSH poisoning. CONCLUSION: The presence of hypotension on admission may be a useful predictor of AKI in patients with GSH intoxication.

Mosloflavone-Resveratrol Hybrid TMS-HDMF-5z Exhibits Potent In Vitro and In Vivo Anti-Inflammatory Effects Through NF-κB, AP-1, and JAK/STAT Inactivation.

TMS-HDMF-5z is a hybrid of the natural products mosloflavone and resveratrol. It was discovered to show potent inhibitory effects against lipopolysaccharide (LPS)-induced production of inflammatory mediators in RAW 264.7 macrophages. However, its mechanism of action is unknown. Hence this study aimed to demonstrate and explore in vitro and in vivo anti-inflammatory effects of TMS-HDMF-5z and its mechanism of action employing RAW 264.7 macrophages and carrageenan-induced hind paw edema. This work revealed that TMS-HDMF-5z suppressed the LPS-induced inducible nitric-oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein, mRNA, and promoter binding levels and tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6, and interferon-ß (IFN-ß) at the mRNA expression in RAW 264.7 macrophages. The results showed that TMS-HDMF-5z reduced the transcription and DNA binding activities of nuclear factor-κB (NF-κB) through inhibiting nuclear translocation of p65 and phosphorylation of κB inhibitor α (IκBα), IκB kinase (IKK), and TGF-ß activated kinase 1 (TAK1). Additionally, TMS-HDMF-5z attenuated the LPS-induced transcriptional and DNA binding activities of activator protein-1 (AP-1) by suppressing nuclear translocation of phosphorylated c-Fos, c-Jun, and activating transcription factor 2 (ATF2). TMS-HDMF-5z also reduced the LPS-induced phosphorylation of Janus kinase 1/2 (JAK1/2), signal transducers and activators of transcription 1/3 (STAT1/3), p38 mitogen-activated protein kinase (MAPK), and MAPK-activated protein kinase 2 (MK2). In rats, TMS-HDMF-5z alleviated carrageenan-induced hind paw edema through the suppressing iNOS and COX-2 via NF-κB, AP-1, and STAT1/3 inactivation. Collectively, the TMS-HDMF-5z-mediated inhibition of NF-κB, AP-1, and STAT1/3 offer an opportunity for the development of a potential treatment for inflammatory diseases.

A Rare Case of Spinal Epidural Abscess Following Urinary Tract Infection Caused by Escherichia coli in a Patient with Pre-existing Stress Fractures of the Lumbar Spine.

Spinal epidural abscess (SEA) caused by Escherichia coli is an uncommon condition. It usually occurs secondary to urinary tract infection (UTI), following hematogenous propagation. Disruption of spinal anatomic barriers increases susceptibility to SEA. Although rarely, such disruption can take the form of lumbar spine stress fractures, which can result from even innocuous activity. Here, we describe a case of SEA secondary to UTI in a patient with pre-existing stress fractures of the lumbar spine, following use of an automated massage chair. Successful treatment of SEA consisted of surgical debridement and a six-month course of antibiotic therapy.

Strain-Specific Identification and In Vivo Immunomodulatory Activity of Heat-Killed Latilactobacillus sakei K040706.

We previously reported that the immunostimulatory activity of heat-killed Latilactobacillus sakei K040706 in macrophages and cyclophosphamide (CTX)-treated mice. However, identification of heat-killed L. sakei K040706 (heat-killed LS06) using a validated method is not yet reported. Further, the underlying molecular mechanisms for its immunostimulatory effects in CTX-induced immunosuppressed mice remain unknown. In this study, we developed strain-specific genetic markers to detect heat-killed L. sakei LS06. The lower detection limit of the validated primer set was 2.1 × 105 colony forming units (CFU)/mL for the heat-killed LS06 assay. Moreover, oral administration of heat-killed LS06 (108 or 109 CFU/day, p.o.) effectively improved the body loss, thymus index, natural killer cell activity, granzyme B production, and T and B cell proliferation in CTX-treated mice. In addition, heat-killed LS06 enhanced CTX-reduced immune-related cytokine (interferon-γ, interleukin (IL)-2, and IL-12) production and mRNA expression. Heat-killed LS06 also recovered CTX-altered microbiota composition, including the phylum levels of Bacteroidetes, Firmicutes, and Proteobacteria and the family levels of Muribaculaceae, Prevotellaceae, Tannerellaceae, Christensenellaceae, Gracilibacteraceae, and Hungateiclostridiaceae. In conclusion, since heat-killed L. sakei K040706 ameliorated CTX-induced immunosuppression and modulated gut microbiota composition, they have the potential to be used in functional foods for immune regulation.

A Pharmacokinetic Study of Ephedrine and Pseudoephedrine after Oral Administration of Ojeok-San by Validated LC-MS/MS Method in Human Plasma.

A sensitive and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was developed and fully validated for the simultaneous determination of ephedrine and pseudoephedrine in human plasma after oral administration of the herbal prescription Ojeok-san (OJS); 2-phenylethylamine was used as the internal standard (IS). Both compounds presented a linear calibration curve (r2 ≥ 0.99) over a concentration range of 0.2-50 ng/mL. The developed method was fully validated in terms of selectivity, lower limit of quantitation, precision, accuracy, recovery, matrix effect, and stability, according to the regulatory guidelines from the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. This validated method was successfully applied for the pharmacokinetic assessment of ephedrine and pseudoephedrine in 20 healthy Korean volunteers administered OJS.

Clinical significance of hypoalbuminemia in patients with scrub typhus complicated by acute kidney injury.

BACKGROUND: This study aimed to investigate the clinical significance of hypoalbuminemia (HA) in patients with scrub typhus complicated by acute kidney injury (AKI). METHODS: From 2009 to 2018, 611 patients were diagnosed with scrub typhus. We divided the patients into two groups [normoalbuminemia (NA) vs. HA] based on the serum albumin level of 3.0 g/dL and compared the incidence, clinical characteristics, and severity of AKI based on the RIFLE classification between the two groups. RESULTS: Of the total 611 patients, 78 (12.8%) were categorized into the HA group. Compared to patients in the NA group, patients in the HA group were older (73 ± 9 vs. 62 ± 14 years, P<0.001). The HA group had a significantly longer hospital stay (9.6 ± 6.2 vs 6.2 ± 3.1 days, p<0.001) and a higher incidence of complications in respiratory and cardiovascular systems. Furthermore, AKI developed significantly more in patients in the HA group (58% vs. 18%, p<0.001) as compared to the NA group. The overall incidence of AKI was 23.1%; of which, 14.9%, 7.0%, and 1.2% of cases were classified as Risk, Injury, and Failure, respectively. The serum albumin level correlated with AKI severity (3.4 ± 0.5 vs 3.0 ± 0.5 vs 2.6 ± 0.3, p<0.05). In a multivariate logistic regression analysis for predicting AKI, age, presence of co-morbidities such as chronic kidney disease, total bilirubin, leukocytosis, and hypoalbuminemia were significant predictors for AKI. CONCLUSION: Serum albumin level is helpful to predict the development and severity of scrub typhus-associated AKI.

Urinary Exosomal microRNA-21 as a Marker for Scrub Typhus-Associated Acute Kidney Injury.

Background: Urinary microRNA (miRNA)-21 is a biomarker for acute kidney injury (AKI). We conducted this study to determine if a urinary exosomal analysis for this biomarker could serve as a novel diagnostic approach for detecting kidney disease. Materials and Methods: We investigated the clinical significance of urinary exosomal miRNA-21 levels for AKI in scrub typhus patients. We collected 138 urine samples from scrub typhus patients at the time of admission. Urinary exosomal miRNA-21 was assessed in 25 age- and sex-matched scrub typhus patients with and without AKI. Results: The total leukocyte count was higher in AKI patients than in non-AKI patients (10.40 × 103/mL vs. 6.40 × 103/mL, p < 0.01). Urinary exosomal miRNA-21 levels were higher in the AKI group than in the non-AKI group (20.1 ± 1.2 vs. 17.8 ± 1.8 ΔCt value of miRNA-21, p < 0.01). Additionally, the miRNA-21 levels correlated directly with the total leukocyte counts and inversely with the estimated glomerular filtration rate. A receiver operating characteristic curve analysis demonstrated good discriminative power for the diagnosis of scrub typhus-associated AKI, with an area under the curve value of 0.907. Conclusion: Urinary exosomal miRNA-21 could be a surrogate marker for scrub typhus-associated AKI diagnosis.

Oral Intake of Hydrangea serrata (Thunb.) Ser. Leaves Extract Improves Wrinkles, Hydration, Elasticity, Texture, and Roughness in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study.

Previously, we reported that the hot water extract of Hydrangea serrata leaves (WHS) and its active component, hydrangenol, possess in vitro and in vivo effects on skin wrinkles and moisturization. We conducted a randomized, double-blind, placebo-controlled trial to clinically evaluate the effect of WHS on human skin. Participants (n = 151) were randomly assigned to receive either WHS 300 mg, WHS 600 mg, or placebo, once daily for 12 weeks. Skin wrinkle, hydration, elasticity, texture, and roughness parameters were assessed at baseline and after 4, 8, and 12 weeks. Compared to the placebo, skin wrinkles were significantly reduced in both WHS groups after 8 and 12 weeks. In both WHS groups, five parameters (R1-R5) of skin wrinkles significantly improved and skin hydration was significantly enhanced when compared to the placebo group after 12 weeks. Compared with the placebo, three parameters of skin elasticity, including overall elasticity (R2), net elasticity (R5), and ratio of elastic recovery to total deformation (R7), improved after 12 weeks of oral WHS (600 mg) administration. Changes in skin texture and roughness were significantly reduced in both WHS groups. No WHS-related adverse reactions were reported. Hence, WHS could be used as a health supplement for skin anti-aging.

Clinical significance of abnormal chest radiographic findings for acute kidney injury in patients with scrub typhus.

BACKGROUND: Abnormal chest radiographs are frequently encountered in patients with scrub typhus. This study aimed to investigate whether chest radiography on admission is significant as a predictive factor for acute kidney injury (AKI) in patients with scrub typhus. METHODS: From 2010 to 2016, 467 patients were diagnosed with scrub typhus in our hospital. We divided the patients into two groups: normal chest radiograph (NCR) and abnormal chest radiograph (AbNCR), based on chest radiography findings. The incidence, clinical characteristics, and severity of AKI were compared between AKI and non-AKI groups according to the RIFLE classification. RESULTS: Of the 467 patients, 96 (20.6%) constituted the AbNCR group. Compared with NCR patients, AbNCR patients were older (71 ± 11 vs. 62 ± 13 years, P < 0.001) and had higher total leukocyte counts (9.43 × 103/mL vs. 6.98 × 103/mL, P < 0.001). The AbNCR group had significantly longer duration of hospital stay (8.9 ± 5.5 vs. 6.3 ± 2.8 days, P < 0.001) and higher incidence of AKI (46.9% vs. 15.1%, P < 0.001). The common abnormal chest radiographic findings were pulmonary abnormalities, such as pulmonary congestion and pleural effusion. The overall AKI incidence was 21.6%, of which 12.4%, 7.9%, and 1.3% cases were classified as risk, injury, and failure, respectively. In a multivariable logistic regression analysis for association with AKI, old age, presence of chronic kidney disease or hypertension, leukocytosis, hypoalbuminemia, and chest radiographic abnormalities on admission were significant predictors of AKI. CONCLUSION: Chest radiographic abnormalities on admission were independently associated with AKI in patients with scrub typhus.

Transplantation of a kidney from a donor with vancomycin-resistant Enterococci.

The colonization of vancomycin-resistant Enterococci before and after solid organ transplantation is associated with an increased risk of its infection. The prevalence of these bacterial colonies in renal transplant recipients are as high as that in intensive care unit patients. However, it is unclear whether donors with vancomycin-resistant Enterococci colonization can be considered in renal transplantation. Herein, we report a case wherein a kidney was transplanted from a deceased donor with vancomycin-resistant Enterococci colonies in urine and rectal swab. After transplant, the recipient had no vancomycin-resistant Enterococci infection and maintained relatively good renal function.

Efficacy and Safety of CKD-11101 (Proposed Biosimilar of Darbepoetin-Alfa) Compared with Darbepoetin-Alfa in Patients on Hemodialysis: A Randomized, Double-Blinded, Parallel-Group Phase III Study.

BACKGROUND: Darbepoetin-alfa is an erythropoiesis-stimulating agent (ESA) with a long elimination half-life that achieves better hemoglobin (Hb) stability than short-acting ESAs. OBJECTIVE: We aimed to evaluate the efficacy and safety of intravenous CKD-11101 (a biosimilar of darbepoetin-alfa) compared with those of darbepoetin-alfa in hemodialysis patients. METHODS: The study was performed in 24 centers in Korea between June 2015 and June 2017. The study subjects were randomized in a double-blind manner. The follow-up duration was 24 weeks, which consisted of 20 weeks of maintenance and 4 weeks of evaluation period. All patients underwent a stabilization period to achieve a target baseline Hb of 10-12 g/dL before randomization. Following randomization, patients received darbepoetin-alfa or CKD-11101 weekly or biweekly. RESULTS: A total of 403 patients were randomized into two groups, and a total of 325 patients (80.6%) completed the investigation. The differences between the two groups in terms of change in the average Hb level from baseline to evaluation were not significant. The average administered dose of ESA was similar between the groups. There was no difference in the proportion of patients who maintained the target Hb during the evaluation period [60.4% vs. 66.2% in the CKD-11101 and darbepoetin-alfa groups, respectively (p = 0.3038)]. In addition, the safety analysis, consisting of adverse events and adverse drug reactions, showed comparable results between the two groups. CONCLUSION: The changes in the level of Hb, dose of erythropoietin, and achievement rate of the target Hb during the study period were comparable between the groups. CKD-11101 has an equivalent efficacy and safety compared with darbepoetin-alfa in patients undergoing hemodialysis.

Metallic contact induced van der Waals gap in a MoS2 FET.

Electrical metal contacts formed with 2D materials strongly affect device performance. Here, we used scanning transmission electron microscopy (STEM) and energy-dispersive spectroscopy (EDS) to characterize the interfacial structure formed and physical damage induced between MoS2 and the most commonly used metals, Ti, Cr, Au, and Pd. We further correlated the electrical performance with physical defects observed at the 2D interfacial structure. The contact resistances were higher in the order of Ti, Au, Pd, and Cr contacts, but all 4-point probe mobilities measured with metals in contact with identical quadrilayer MoS2 were ∼65 cm2 V-1 s-1, confirming the reliability of the devices. According to the STEM and EDS analyses, the Ti contact gave rise to a van der Waals gap between the clean quadrilayer MoS2 and the Ti contact. By contrast, Cr migrated into MoS2 while Mo and S counter-migrated into the SiO2 substrate. Au and Pd formed glassy layers that resulted in the migration of Mo and S into the Au and Pd electrodes. These interfacial structures between MoS2 and contact metals strongly correlated with the electrical performance of 2D MoS2 FETs, providing practical guidelines to form van der Waals contacts.

A Fermi-Level-Pinning-Free 1D Electrical Contact at the Intrinsic 2D MoS2 -Metal Junction.

Currently 2D crystals are being studied intensively for use in future nanoelectronics, as conventional semiconductor devices face challenges in high power consumption and short channel effects when scaled to the quantum limit. Toward this end, achieving barrier-free contact to 2D semiconductors has emerged as a major roadblock. In conventional contacts to bulk metals, the 2D semiconductor Fermi levels become pinned inside the bandgap, deviating from the ideal Schottky-Mott rule and resulting in significant suppression of carrier transport in the device. Here, MoS2 polarity control is realized without extrinsic doping by employing a 1D elemental metal contact scheme. The use of high-work-function palladium (Pd) or gold (Au) enables a high-quality p-type dominant contact to intrinsic MoS2 , realizing Fermi level depinning. Field-effect transistors (FETs) with Pd edge contact and Au edge contact show high performance with the highest hole mobility reaching 330 and 432 cm2 V-1 s-1 at 300 K, respectively. The ideal Fermi level alignment allows creation of p- and n-type FETs on the same intrinsic MoS2 flake using Pd and low-work-function molybdenum (Mo) contacts, respectively. This device acts as an efficient inverter, a basic building block for semiconductor integrated circuits, with gain reaching 15 at VD = 5 V.

Elucidation of an intrinsic parameter for evaluating the electrical quality of graphene flakes.

A test method for evaluating the quality of graphene flakes, such as reduced graphene oxide (rGO) and graphene nanopowder (GNP), was developed in this study. The pelletizer was selected for a sampling tool, which enables us to formulate the flake sample as a measurable sample. Various parameters were measured from the pelletized sample in order to elucidate the best parameter for representing the quality of the graphene flakes in terms of their electrical properties. Based on the analysis of 4-probe measurement data on the pelletized sample, the best intrinsic parameter is volume resistivity (or volume conductivity) rather than resistivity (or conductivity). Additionally, the possible modification of a sample before and after the pressurization was investigated by electron microscopy and Raman spectroscopy. No significant modification was observed. The volume conductivity in the two types of the graphene was different from their individual conductivities by one order of magnitude. Based on the results of X-ray photoelectron spectroscopy and Raman spectroscopy measurements, the volume conductivity of the graphene flake samples was governed by the oxygen content in the sample. Our achievements will promote the effective use of powder-type graphene products for further applications.

Clinical characteristics of sepsis-induced acute kidney injury in patients undergoing continuous renal replacement therapy.

OBJECTIVE: The aim of this study was to investigate the clinical characteristics of sepsis-induced acute kidney injury (AKI) in patients undergoing continuous renal replacement therapy (CRRT). METHODS: From 2011 to 2015, we enrolled 340 patients who were treated with CRRT for sepsis at the Presbyterian Medical Center. In all patients, CRRT was performed using the PRISMA platform. We divided these patients into two groups (survivors and non-survivors) according to the 28-day all-cause mortality. We compared clinical characteristics and analyzed the predictors of mortality. RESULTS: The 28-day all-cause mortality was 62%. Survivors were younger than non-survivors and had higher platelet counts (178 ± 101 × 103/mL vs. 134 ± 84 × 103/mL, p < .01) and serum creatinine levels (4.2 ± 2.8 vs. 3.3 ± 2.7, p < .01). However, survivors had lower red blood cell distribution width (RDW) scores (14.9 ± 2.1 vs. 16.1 ± 3.3, p < .01) and APACHE II scores (24.5 ± 5.8 vs. 26.9 ± 5.7, p < .01) than non-survivors. Furthermore, survivors were more likely than non-survivors to have a urine output of >0.05 mL/kg/h (66% vs. 86%, p = .001) in the first day. In a multivariate logistic regression analysis, age, platelet count, RDW score, APACHE II score, serum creatinine level, and a urine output of <0.05 mL/kg/h the first day were prognostic factors for the 28-day all-cause mortality. CONCLUSION: Age, platelet count, APACHE II score, RDW score, serum creatinine level, and urine output the first day are useful predictors for the 28-day all-cause mortality in sepsis patients requiring CRRT.

Clinical significance of NGAL and KIM-1 for acute kidney injury in patients with scrub typhus.

BACKGROUND: The aim of this study is to investigate the clinical significance of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for acute kidney injury (AKI) in patients with scrub typhus. METHODS: From 2014 to 2015, 145 patients were diagnosed with scrub typhus. Of these, we enrolled 138 patients who were followed up until renal recovery or for at least 3 months. We measured serum and urine NGAL and KIM-1 levels and evaluated prognostic factors affecting scrub typhus-associated AKI. RESULTS: Of the 138 patients, 25 had scrub typhus-associated AKI. The incidence of AKI was 18.1%; of which 11.6%, 4.3%, and 2.2% were classified as risk, injury, and failure, respectively, according to RIFLE criteria. Compared with patients in the non-AKI group, patients in the AKI group were older and showed higher total leukocyte counts and hypoalbuminemia or one or more comorbidities such as hypertension (72% vs 33%, p<0.01), diabetes (40% vs 14%, p<0.01), or chronic kidney disease (32% vs 1%, p<0.01). In addition, serum NGAL values (404± 269 vs 116± 78 ng/mL, P<0.001), KIM-1 values (0.80± 0.52 vs 0.33± 0.68 ng/mL, P<0.001), urine NGAL/creatinine values (371± 672 vs 27± 39 ng/mg, P<0.001) and urine KIM-1/creatinine values (4.04± 2.43 vs 2.38± 1.89 ng/mg, P<0.001) were higher in the AKI group than in the non-AKI group. By multivariate logistic regression, serum NGAL and the presence of chronic kidney disease were significant predictors of AKI. CONCLUSION: Serum NGAL might be an additive predictor for scrub typhus-associated AKI.

Comparison of clinical characteristics of patients with acute kidney injury after intravenous versus inhaled colistin therapy.

BACKGROUND: The aim of this study was to investigate the incidence and clinical characteristics of intravenous (IV) or inhaled (IH) colistin-associated acute kidney injury (AKI) using the Risk, Injury, Failure, Loss, End-stage Renal Disease criteria. METHODS: From 2010 to 2014, 160 patients were treated with IV or IH colistin. Of these, we included 126 patients who received colistin for > 72 hours for the treatment of pneumonia and compared the incidence and clinical characteristics of patients in the IV (n = 107) and IH (n = 19) groups. RESULTS: The patients included 104 men and 22 women, with a mean age of 69 years (range, 24-91 years). The mortality rate was 45%, and AKI occurred in 75 (60%) patients. At the end of therapy, the bacteriologic cure rate was 66%. There were no differences in the clinical characteristics between the IV and IH groups except for age. In comparison with patients in the IV group, the patients in the IH group were older (74 ± 8 vs. 68 ± 12 years, P = 0.026). The incidence of AKI was not different between the 2 groups (62 vs. 47%, P = not significant), and there was no difference in the severity of AKI according to the Risk, Injury, Failure, Loss, End-stage Renal Disease criteria. Of the 83 patients with AKI, 6 and 1 patients underwent renal replacement therapy, respectively. CONCLUSION: The incidence of AKI in patients with colistin therapy is 60% in our center. It seems that IH colistin therapy could not be better in safety than IV colistin therapy.