Source Analysis and Effective Control of a COVID-19 Outbreak in a University Teaching Hospital during a Period of Increasing Community Prevalence of COVID-19.

BACKGROUND: South Korea has been experiencing a third wave of coronavirus disease 2019 (COVID-19) since mid-November 2020. Our hospital in Gwangju metropolitan city experienced a healthcare-associated COVID-19 outbreak early in the third wave. The first confirmed COVID-19 patient was a symptomatic neurosurgery resident with high mobility throughout the hospital. We analyzed the transmission routes of nosocomial COVID-19 and discussed infection control strategies. METHODS: We retrospectively analyzed the severe acute respiratory syndrome coronavirus 2 reverse transcription-polymerase chain reaction (RT-PCR) testing results according to time point and evaluated transmission routes. RESULTS: Since COVID-19 was first confirmed in a healthcare worker (HCW) on 11/13/2020, we performed RT-PCR tests for all patients and caregivers and four complete enumeration surveys for all HCWs. We detected three clusters of nosocomial spread and several sporadic cases. The first cluster originated from the community outbreak spot, where an asymptomatic HCW visited, which led to a total of 22 cases. The second cluster, which included patient-to-patient transmission, originated from a COVID-19 positive caregiver before diagnosis and the third cluster involved a radiologist and a banker. We took measures to isolate Building 1 of the hospital for 17 days and controlled the outbreak during a period of increasing community COVID-19 prevalence. Universal screening of all inpatients upon admission and resident caregivers was made mandatory and hospital-related employees are now screened monthly. CONCLUSION: Infection control strategies to prevent the nosocomial transmission of emerging infectious diseases must correspond with community disease prevalence. Our data reinforce the importance of multi-time point surveillance of asymptomatic HCWs and routine surveillance of patients and caregivers during an epidemic.

Comparison of volume-controlled ventilation mode and pressure-controlled ventilation with volume-guaranteed mode in the prone position during lumbar spine surgery.

BACKGROUND: During lumbar spine surgery, patients are placed in the prone position for surgical access. The prone position has various effects on cardiac and pulmonary function, including a decreased cardiac index (CI), decreased dynamic lung compliance (Cdyn), and increased peak inspiratory pressure (Ppeak). In this study, we compared the volume-controlled ventilation mode (VCV) and pressure-controlled ventilation with volume guaranteed mode (PCV-VG) based on hemodynamic and pulmonary variables in the prone position during lumbar spine surgery. METHODS: Thirty-six patients scheduled for lumbar spine surgery in the prone position were enrolled in this prospective, randomized clinical trial. The patients were randomly assigned to receive VCV or PCV-VG. Hemodynamic variables, respiratory variables, and arterial blood gases were measured in the supine position 15 min after the induction of anesthesia, 15 min after placement in the prone position, 30 min after placement in the prone position, and 15 min after placement in the supine position at the end of anesthesia. RESULTS: The hemodynamic variables and arterial blood gas results did not differ significantly between the two groups. Lower Ppeak values were observed in the PCV-VG group than in the VCV group (p = 0.045). The Cdyn values in the VCV group were lower than those in the PCV-VG group (p = 0.040). CONCLUSION: PCV-VG led to lower Ppeak and improved Cdyn values compared with VCV, showing that it may be a favorable alternative mode of mechanical ventilation for patients in the prone position during lumbar spine surgery. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov (NCT03571854). The initial registration date was 6/18/2018.

Selective targeting of dipeptidyl-peptidase 4 (DPP-4) positive senescent chondrocyte ameliorates osteoarthritis progression.

Senescent cells increase in many tissues with age and induce age-related pathologies, including osteoarthritis (OA). Senescent chondrocytes (SnCs) are found in OA cartilage, and the clearance of those chondrocytes prevents OA progression. However, targeting SnCs is challenging due to the absence of a senescent chondrocyte-specific marker. Therefore, we used flow cytometry to screen and select senescent chondrocyte surface markers and cross-validated with published transcriptomic data. Chondrocytes expressing dipeptidyl peptidase-4 (DPP-4), the selected senescent chondrocyte-specific marker, had multiple senescence phenotypes, such as increased senescence-associated-galactosidase, p16, p21, and senescence-associated secretory phenotype expression, and showed OA chondrocyte phenotypes. To examine the effects of DPP-4 inhibition on DPP-4+ SnCs, sitagliptin, a DPP-4 inhibitor, was treated in vitro. As a result, DPP-4 inhibition selectively eliminates DPP-4+ SnCs without affecting DPP-4- chondrocytes. To assess in vivo therapeutic efficacy of targeting DPP-4+ SnCs, three known senolytics (ABT263, 17DMAG, and metformin) and sitagliptin were comparatively verified in a DMM-induced rat OA model. Sitagliptin treatment specifically and effectively eliminated DPP-4+ SnCs, compared to the other three senolytics. Furthermore, Intra-articular sitagliptin injection to the rat OA model increased collagen type II and proteoglycan expression and physical functions and decreased cartilage destruction, subchondral bone plate thickness and MMP13 expression, leading to the amelioration of OA phenotypes. Collectively, OARSI score was lowest in the sitagliptin treatment group. Taken together, we verified DPP-4 as a surface marker for SnCs and suggested that the selective targeting of DPP-4+ chondrocytes could be a promising strategy to prevent OA progression.

Rhamnetin attenuates melanogenesis by suppressing oxidative stress and pro-inflammatory mediators.

Rhamnetin is a naturally occurring polyphenolic compound. In this report, experimental evidence is presented on the suppression of melanogenesis by rhamnetin using B16 murine melanoma cells (B16 cells). To document the underlying anti-melanogenic action of rhamnetin, several key biochemical mediators were quantified: superoxide (O2(•-)), nitric oxide (·NO) and peroxynitrite (ONOO(-)) in vitro, and total reactive species (RS) generation, O2(•-), ·NO and ONOO(-), reduced glutathione (GSH)/GSH-to-oxidized glutathione (GSSG) ratio, prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) in B16 cells. Results revealed that rhamnetin inhibited murine tyrosinase activity, suppressed melanin content and oxidative stress, reducing O2(•-),·NO and ONOO(-) in vitro and total RS generation, O2(•-), ·NO and ONOO(-) in B16 cells, while maintaining a well-balanced GSH/GSSG ratio in B16 cells. Results further revealed that rhamnetin suppressed key pro-inflammatory mediators such as PGE2 and TXB2. Thus, these results strongly indicate that rhamnetin has powerful anti-melanogenic properties through its anti-oxidative and anti-inflammatory actions.

Modulation of oxidative stress by proanthocyanidin in H2O2-exposed human diploid fibroblast cells.

Proanthocyanidin (a persimmon-peel extract) is known to have potent antioxidative effects, but its protective action specifically against cellular damage has not been fully explored. In this work, we investigated the protective property of proanthocyanidin against cellular oxidative stress with an experimental model, H2O2-exposed human diploid fibroblasts (HDFs). To investigate the proposed underlying beneficial actions of proanthocyanidin as to cellular injury induced by H2O2, several major biochemical parameters were determined, including estimation of total reactive species (RS) generation, antioxidant enzyme activities, reduced glutathione (GSH)/oxidized glulathione (GSSG) ratio, and mitochondrial membrane potential. The results indicate that proanthocyanidin reduced total RS generation while enhancing the activities of catalase and glutathione reductase and the GSH/GSSG ratio. Additionally, proanthocyanidin was found to protect against mitochondrial membrane damage in HDFs treated H2O2. Based on these results, we conclude that proanthocyanidin has strong protective effects against cellular damage to several key cellular functions by suppressing oxidative stress in H2O2-treated HDFs.

High-glutathione mesenchymal stem cells isolated using the FreSHtracer probe enhance cartilage regeneration in a rabbit chondral defect model.

BACKGROUND: Mesenchymal stem cells (MSCs) are a promising cell source for cartilage regeneration. However, the function of MSC can vary according to cell culture conditions, donor age, and heterogeneity of the MSC population, resulting in unregulated MSC quality control. To overcome these limitations, we previously developed a fluorescent real-time thiol tracer (FreSHtracer) that monitors cellular levels of glutathione (GSH), which are known to be closely associated with stem cell function. In this study, we investigated whether using FreSHtracer could selectively separate high-functioning MSCs based on GSH levels and evaluated the chondrogenic potential of MSCs with high GSH levels to repair cartilage defects in vivo. METHODS: Flow cytometry was conducted on FreSHtracer-loaded MSCs to select cells according to their GSH levels. To determine the function of FreSHtracer-isolated MSCs, mRNA expression, migration, and CFU assays were conducted. The MSCs underwent chondrogenic differentiation, followed by analysis of chondrogenic-related gene expression. For in vivo assessment, MSCs with different cellular GSH levels or cell culture densities were injected in a rabbit chondral defect model, followed by histological analysis of cartilage-regenerated defect sites. RESULTS: FreSHtracer successfully isolated MSCs according to GSH levels. MSCs with high cellular GSH levels showed enhanced MSC function, including stem cell marker mRNA expression, migration, CFU, and oxidant resistance. Regardless of the stem cell tissue source, FreSHtracer selectively isolated MSCs with high GSH levels and high functionality. The in vitro chondrogenic potential was the highest in pellets generated by MSCs with high GSH levels, with increased ECM formation and chondrogenic marker expression. Furthermore, the MSCs' function was dependent on cell culture conditions, with relatively higher cell culture densities resulting in higher GSH levels. In vivo, improved cartilage repair was achieved by articular injection of MSCs with high levels of cellular GSH and MSCs cultured under high-density conditions, as confirmed by Collagen type 2 IHC, Safranin-O staining and O'Driscoll scores showing that more hyaline cartilage was formed on the defects. CONCLUSION: FreSHtracer selectively isolates highly functional MSCs that have enhanced in vitro chondrogenesis and in vivo hyaline cartilage regeneration, which can ultimately overcome the current limitations of MSC therapy.

Hyperin and quercetin modulate oxidative stress-induced melanogenesis.

Hyperin and quercetin are phenolic compounds present in fruits and vegetables that have been reported to possess strong anti-oxidative properties. Although increasing evidence strongly suggests that antioxidants suppress the melanin synthesis that is causally associated with oxidative stress, the protective actions of hyperin and quercetin against oxidative stress-induced melanogenesis have not been fully explored. To elucidate the suppressive effects of hyperin and quercetin on oxidative stress and melanin synthesis, peroxynitrite (ONOO(-)) scavenging activity was measured in vitro as were quantifications of melanin content, intracellular total RS, ONOO(-), superoxide ((•)O(2)), nitric oxide (NO(•)), catalase activity and the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. Results showed that in vitro, hyperin and quercetin reduced ONOO(-). Additionally, hyperin and quercetin suppressed total RS, ONOO(-), (•)O(2), and NO(•), catalase activity, and melanin synthesis, while they boosted the GSH/GSSG ratio in B16F10 melanoma cells (B16 cells). Therefore, I propose that hyperin and quercetin have a powerful capacity to modulate oxidative stress-induced melanogenesis.

Comparison of the C-MAC D-blade video laryngoscope and the McCoy laryngoscope for double-lumen endotracheal tube intubation: A prospective randomized controlled study.

BACKGROUND: Inserting a double-lumen endotracheal tube (DLT) poses more challenge than inserting a single-lumen tube. The C-MAC D-blade videolaryngoscope is a useful alternative to the direct laryngoscope. However, no study has compared its performance with that of the McCoy laryngoscope, which has a hyperangulated blade tip similar to that of the C-MAC D-blade. We aimed to compare the performance of the C-MAC D-blade videolaryngoscope with that of the McCoy laryngoscope in DLT intubation. METHODS: In this prospective randomized controlled study, 90 patients requiring DLT intubation were randomly allocated to either the C-MAC D-blade videolaryngoscope group (group C, n = 47) or McCoy laryngoscope group (group M, n = 43). During intubation, the percentage of glottic opening, modified Cormack-Lehane grade, time taken for intubation, malposition of the bronchial lumen, and hemodynamic parameters were recorded. After intubation, we assessed the intubation difficulty scale score and, a postoperative sore throat in the recovery room. RESULTS: The time taken for intubation was 35.85 ±â€…10.77 seconds and 33.18 ±â€…11.97 seconds in groups C and M, respectively (P = .269). The modified Cormack-Lehane grade was significantly lower in group C than in group M (P = .000). Percentage of glottic opening was significantly higher in group C (79.36 ±â€…13.42%) than in group M (53.49 ±â€…29.83%) (P = .000). The intubation difficulty scale score was significantly lower in group C than in group M (P = .030). There were no significant differences between the 2 groups in terms of malposition status, hemodynamic parameters, or visual analog scale score for a postoperative sore throat. CONCLUSION: Although the time taken for intubation was comparable between the 2 intubation devices, the C-MAC D-blade videolaryngoscope facilitated glottis visualization and reduced the intubation difficulty scale better than the McCoy laryngoscope in patients undergoing DLT intubation.

ProbeMatch: rapid alignment of oligonucleotides to genome allowing both gaps and mismatches.

SUMMARY: We have developed a tool, called ProbeMatch, for matching a large set of oligonucleotide sequences against a genome database using gapped alignments. Unlike most of the existing tools such as ELAND which only perform ungapped alignments allowing at most two mismatches, ProbeMatch generates both ungapped and gapped alignments allowing up to three errors including insertion, deletion and mismatch. To speedup sequence alignment, ProbeMatch uses gapped q-grams and q-grams of various patterns to identify target hits to a query sequence. This approach results in fewer initial sequences to examine with no loss in sensitivity. ProbeMatch has been used to align 169,095 Illumina GAII reads against the human genome, which could not be mapped by ELAND, and found alignments for 28,625 reads of the 169,095 reads in less than 3 h. AVAILABILITY: Source code is freely available at (http://www.cs.wisc.edu/~jignesh/probematch/).

Preparation and characterization of Rh catalyst supported on nanoporous alumina for the ethylene hydroformylation.

Nanoporous gamma-aluminas were prepared by a sol-gel method with and without surfactant, and characterized by nitrogen adsorption-desorption, transmission electron microscopy (TEM), X-ray diffraction (XRD) and temperature programmed reduction (TPR). The resulting materials were applied to Rh catalyst supports for the ethylene hydroformylation. The ordered nanoporous alumina (A-1) which was prepared using surfactant, showed well-developed pore structures with high surface area. Rh catalyst supported on A-1 alumina (Rh/A-1) exhibited higher catalytic activity in the ethylene hydroformylation than other Rh catalysts. It is believed that the high catalytic performance of Rh/A-1 resulted from the well-developed pore structure with high surface area of ordered nanoporous A-1 and consequently finely dispersed Rh particle on the surface of gamma-alumina support.

Integrating a Resilience Scorecard and Landscape Performance into a Geodesign Process.

Uncertainty about the impacts of sea level rise make the ability to forecast future spatial conditions a necessary planning/design tool. Geodesign integrates multiple fields of science with change/impact models and planning/design strategies. Proactive planning analyses such as newly developed scorecards allow for plan evaluation; design strategies can now be quantitatively assessed using landscape performance calculators. Neither have been explored as Geodesign tools. A Geodesign process was developed using the resilience scorecard to assess flood vulnerability using projections for the 100 year floodplain with sea level rise by 2100. Projections were used as a guide to develop a resilient master plan for League City, TX, USA. Future impacts of the plan are projected using landscape performance measures.

Cardiac arrest caused by contralateral tension pneumothorax during one-lung ventilation: - A case report.

BACKGROUND: Tension pneumothorax on the contralateral lung during one-lung ventilation (OLV) can be life-threatening if not rapidly diagnosed and managed. However, diagnosis is often delayed because the classic signs of tension pneumothorax are similar to clinical manifestations commonly observed during OLV. CASE: We report a case of contralateral tension pneumothorax in a patient undergoing right upper lobectomy during OLV. The patient suffered from sudden cardiac arrest and was assisted by extra-corporeal membrane oxygenation. CONCLUSIONS: Contralateral pneumothorax during OLV is rare but can occur at any time. Therefore, anesthesiologists should consider this critical complication.

Inhibitory effects of 6-(3-hydroxyphenyl)-2-naphthol on tyrosinase activity and melanin synthesis.

As a part of an ongoing project searching for new skin-lightening agents, the inhibitory property of 6-(3-Hydroxyphenyl)-2-naphthol (HPN) on melanogenesis was investigated. The inhibitory action of HPN (IC(50)=15.2 muM) on mushroom tyrosinase was revealed. To further explore the action of HPN on melanogenesis, the inhibition of tyrosinase and melanin levels were measured in B16 melanoma cells (B16 cells). Results show that HPN inhibited tyrosinase activity and reduced melanin in B16 cells. Therefore, our data indicate HPN as a new candidate for depigmentation reagents.

Preparation and characterization of a PtSn nanocatalyst for use in ethanol electro-oxidation.

A PtSn nanocatalyst supported on carbon (PtSn) was prepared with the enhancement of the extent of alloy degree of Pt with Sn by the heat treatment at 300 degrees C in a nitrogen atmosphere (PtSn/C-HT). The PtSn and PtSn/C-HT catalysts prepared were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and electrochemical methods, and were tested as an electro-catalyst in ethanol electro-oxidation. Results showed that the average particle size of the PtSn/C-HT was increased by the heat treatment, compared to that of PtSn. The catalytic activity of PtSn/C-HT, however, was superior in ethanol electro-oxidation. The enhanced catalytic activity of PtSn/C-HT was attributed to both the high degree of alloying in the PtSn structure and the extended Pt lattice, which promote catalytic activities in ethanol electro-oxidation and removal of intermediate CO species.

The anti-melanogenic effect of pycnogenol by its anti-oxidative actions.

Pycnogenol is a natural plant extract from pine bark that contains compounds that have anti-oxidative, free-radical scavenging properties. In this work, utilizing cultured B16 melanoma cells (B16 cells), pycnogenol was investigated for its ability to inhibit tyrosinase activity and melanin biosynthesis. We also examined the anti-oxidative power of pycnogenol by measuring its suppressive effect against peroxynitrite (ONOO-), superoxide (.O2), nitric oxide (NO.), and hydroxyl radical (.OH)-scavenging activities using an electron spin resonance spectrometer. Results show that pycnogenol had a strong anti-tyrosinase activity and suppressed melanin biosynthesis. Further, our results showed that through its anti-oxidative properties, pycnogenol suppressed .O2) NO., ONOO-, and .OH in in vitro assays, and reactive species, ONOO-, .O2, and NO., while up-regulating the reduced glutathione/oxidized glutathione ratio in B16 cells. Based on the findings, we propose that pycnogenol exerts anti-melanogenic activity via its anti-oxidative actions.

Molecular analysis of endogenous avian leukosis/sarcoma virus genomes in Korean chicken embryos.

Since the status of endogenous avian leucosis/sarcoma virus (ALSV) infections in Korean broiler chickens is unclear, this study examined embryonated eggs obtained from broiler farms and Korean native chicken breeds in Korea using PCR with the primer sets specific for endogenous ALSVs. The PCR assays detected the genomes of EAV, ev, ev/J and ART-CH belonging to the endogenous ALSV from all embryos tested. Phylogenetically, the Korean EAV genomes were more closely related to the prototype EAV-0 than to the other prototype, E51. The Korean ART-CH elements clustered together but were distinct from the prototype ART-CH clones, 5 and 14. Although there was comparatively little divergence in the nucleotide and amino acid sequences of the Korean ev and ev/J genomes compared with the other known ev and ev/J genomes, the Korean genomes had phylogenetically distinct branches. From these results, endogenous genomes are quite prevalent in Korean broiler chickens. In addition, the endogenous genomes circulating in Korean broiler chickens are genetically different from the other known endogenous genomes. These results are expected to provide useful information for the control and establishment of a surveillance system for endogenous ALSVs in Korea.

Ameliorative effects of proanthocyanidin on oxidative stress and inflammation in streptozotocin-induced diabetic rats.

Recent evidence strongly suggests that oxidative stress due to redox imbalance is causally associated with inflammatory processes and various diseases including diabetes. We examined the effects of proanthocyanidin from persimmon peel, using both oligomers and polymers, against oxidative stress with elucidation of the underlying mechanisms in streptozotocin-induced diabetic rats. The elevation of lipid peroxidation in the kidney and serum under the diabetic condition was decreased by the administration of proanthocyanidin. The suppression of reactive oxygen species generation and elevation of the reduced glutathione/oxidized glutathione ratio were observed in the groups administered proanthocyanidin. These results support the protective role of proanthocyanidin from oxidative stress induced by diabetes. Moreover, proanthocyanidin, especially its oligomeric form, affected the inflammatory process with regulation of related protein expression, inducible nitric oxide synthase, cyclooxygenase-2, and upstream regulators, nuclear factor kappaB, and inhibitor-binding protein kappaB-alpha. Proanthocyanidin ameliorated the diabetic condition by decreases of serum glucose, glycosylated protein, serum urea nitrogen, urinary protein, and renal advanced glycation endproducts. In particular, oligomeric proanthocyanidin exerted a stronger protective activity than the polymeric form. This suggests that the polymerization of proanthocyanidin has an effect on its protective effect against diabetes. The present study supports the beneficial effect of proanthocyanidin against diabetes and oxidative stress-related inflammatory processes.

miBLAST: scalable evaluation of a batch of nucleotide sequence queries with BLAST.

A common task in many modern bioinformatics applications is to match a set of nucleotide query sequences against a large sequence dataset. Existing tools, such as BLAST, are designed to evaluate a single query at a time and can be unacceptably slow when the number of sequences in the query set is large. In this paper, we present a new algorithm, called miBLAST, that evaluates such batch workloads efficiently. At the core, miBLAST employs a q-gram filtering and an index join for efficiently detecting similarity between the query sequences and database sequences. This set-oriented technique, which indexes both the query and the database sets, results in substantial performance improvements over existing methods. Our results show that miBLAST is significantly faster than BLAST in many cases. For example, miBLAST aligned 247 965 oligonucleotide sequences in the Affymetrix probe set against the Human UniGene in 1.26 days, compared with 27.27 days with BLAST (an improvement by a factor of 22). The relative performance of miBLAST increases for larger word sizes; however, it decreases for longer queries. miBLAST employs the familiar BLAST statistical model and output format, guaranteeing the same accuracy as BLAST and facilitating a seamless transition for existing BLAST users.

Antioxidative and anti-inflammatory actions of docosahexaenoic acid and eicosapentaenoic acid in renal epithelial cells and macrophages.

Oxidative stress due to excessive reactive species (RS) and weakened antioxidant defenses is causally associated with inflammation and inflammatory mediators. To investigate the effects of the major fish oil ingredients, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on oxidative stress-related inflammatory status, we conducted in vitro experiments utilizing rat renal epithelial cells (NRK-52E) and murine macrophages (RAW 264.7) by assessing their effects on the generation of cyclooxygenase (COX)-2-derived and xanthine oxidase (XOD)-derived RS, reduced glutathione (GSH) levels, and antioxidative enzyme activities. Additionally, 6-keto-prostaglandin (PG) F1alpha, PGE2, and nitrite levels were measured in lipopolysaccharide-stimulated RAW 264.7 macrophages. Results showed that the generation of RS from arachidonic acid through the COX-2 and XOD pathways was effectively suppressed by DHA and EPA, while GSH levels and antioxidative enzyme activities were significantly enhanced by DHA and EPA. Furthermore, levels of inflammatory mediators (thromboxane B2, PGE2, and 6-keto-PGF1alpha) and nitrite were effectively down-regulated by DHA and EPA. These results strongly indicate that DHA and EPA exert antioxidative and anti-inflammatory actions by reducing the cellular levels of RS, pro-inflammatory mediators, and nitrite levels and by maintaining higher GSH levels and antioxidative enzyme activities.