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Backgrounds: Remdesivir (RDV) is an antiviral agent approved for the treatment of coronavirus disease 2019 (COVID-19); however, is not recommended for patients with renal impairment. Due to limitations associated with prospective clinical trials, real-world data on the safety and efficacy of RDV in patients with renal impairment are necessary. Methods: Propensity score-matched (PSM) retrospective analysis was conducted between March 2020 and September 2022 in COVID-19 patients with an eGFR < 30 mL/min in four Korean hospitals. The RDV treatment group was matched to the untreated control group. The safety and clinical outcomes in patients who received RDV were analyzed. Results: A total of 564 patients were enrolled; 229 patients received RDV either for treatment or prophylaxis. On day 5, no difference in nephrotoxicity was observed between the two groups, and liver enzyme levels were within the normal range. In multivariate analysis for new dialysis, RDV treatment was not a risk factor for new dialysis. Among the 564 patients, 417 were indicated for a 5-day course of RDV treatment and 211 patients were treated with RDV. After PSM, no differences in the clinical outcomes were observed between the two groups. Conclusion: RDV use in COVID-19 patients with renal impairment did not result in significant nephrotoxicity or hepatotoxicity. [ABSTRACT FROM AUTHOR]

Glycopeptide antibiotics (vancomycin and teicoplanin) are usually used for the treatment of Staphylococcus epidermidis infections owing to their increased oxacillin resistance. However, S. epidermidis strains with decreased susceptibility to teicoplanin have become increasingly incident in recent years. We aimed to identify the characteristics of teicoplanin-non-susceptible (Teico-NS) S. epidermidis isolated at our hospital and analyze its relationship with teicoplanin usage. We retrospectively evaluated 328 S. epidermidis strains isolated from clinical isolates between January 2016 and December 2021. All strains were susceptible to vancomycin (minimal inhibitory concentration (MIC) ≤ 4 mg/L). The annual incidence for S. epidermidis strains with an elevated teicoplanin MIC of 8 mg/L ranged from 22.2 to 28.9%. In addition, in 2021, the number of S. epidermidis strains with teicoplanin MIC ≥ 16 mg/L rapidly increased (n = 13, 32.5%). Furthermore, teicoplanin use increased annually until 2019; however, in 2020, it decreased abruptly due to the COVID 19 pandemic. Thus, we could not confirm the existence of a clear correlation between teicoplanin usage and increased incidence of S. epidermidis with reduced teicoplanin-susceptibility. We showed the increased incidence of Teico-NS S. epidermidis in recent years. Further studies are needed to identify the mechanisms and risk factors for teicoplanin-resistance in S. epidermidis. [ABSTRACT FROM AUTHOR]

Research on inequality in higher education (HE) is often dominated by class‐based assumptions about traditional and non‐traditional students. This binary distinction emphasising students' socio‐economic status tends to oversimply the complexity of educational inequality, neglecting crucial factors which affect the perception of social position. Therefore, this study aims to investigate the understanding of inequalities in HE with new data on the meaning of locality, using evidence from comparative studies of institutions. Locality is interpreted as an inclusive concept capturing place identity as well as local attachments based on language, culture and the natural environment. The qualitative and quantitative data were collected from 192 participants in three distinctly different HE institutions, which were deliberately selected according to their socio‐economic, cultural, and institutional status. This mixed methods research confirms the importance of different types of belonging at institutional, local and national levels, and their different effects on student groups. The study captures to what extent geographical mobility is associated with social class, by examining students' sense of belonging and their interpretation of locality in universities across Wales. It challenges the notion of disadvantaged background, and poses a critical question about cultural and geographical familiarity. This study therefore enriches the current debates about the impact of social inequality alongside social class on students' belonging, success and retention in HE. [ABSTRACT FROM AUTHOR]

This study aims to explore the main aspects of sense of belonging, including academic and social engagement, life satisfaction, thoughts of leaving university, demographic characteristics and socio-economic status by applying quantitative measurement. Having considered the concepts of disadvantaged or non-traditional groups deployed in previous studies, a survey questionnaire was designed to investigate how certain factors are related to students' belonging. Statistical analysis of data from 380 participants reveals that students' sense of belonging and retention are crucially influenced by both academic engagement and social engagement, but independently. This study also addresses a lack of research about how the critical factors for disadvantage operate to determine belonging and retention in higher education. The findings should prompt a re-evaluation what we consider to be the sources of 'disadvantage', such as social class, age and ethnicity. [ABSTRACT FROM AUTHOR]

Background: Robust evidenced treatment strategy for Coronavirus disease 2019 (COVID-19) has not been established yet. Early, targeted, comprehensive management approach can be essential.Methods: A lopinavir/ritonavir (LPV/r)-based antiviral treatment was administered to the patients with computed tomography (CT)-documented pneumonia. Medical records of patients with COVID-19, previously discharged or hospitalized for ≥ 21 days at the Seoul Medical Center from January 29 to April 15, 2020 were reviewed to analyze clinical and virological outcomes. Patients were divided into two groups (PCR-Negative conversion group vs. Non-negative conversion group and requiring oxygen group vs. Non-requiring oxygen group).Results: In total, 136 patients with a mean age of 41.8 ± 18.2 years were included with median 3-day delay of hospitalization after illness. Thirteen (9.56%) were initially asymptomatic, and 5 (3.67%) were persistently asymptomatic. Eighty-five (62.5%) had CT-documented pneumonia, 94% of whom received LPV/r treatments. A total of 53 patients (38.97%) had negative polymerase chain reaction (PCR) results within 28 days. Eight (9.4%) out of 85 pneumonic patients received oxygen supplementation. Patients with initial lower respiratory symptoms showed significant delay in PCR negative conversion (> 28 days) (odds ratio [OR] 0.166; 95% confidence interval [CI] 0.067-0.477; P < 0.001). However, antiviral treatment for pneumonic patients was significantly related with early conversion within 28 days (OR 3.049; 95% CI 1.128-8.243; P = 0.028). Increasing age increased the likelihood of oxygen supplementation requirement in the pneumonic patient group (OR 1.108; 95% CI 1.021-1.202; P = 0.014).Conclusions: Early, pneumonia targeted LPV/r-based antiviral therapy resulted in a significantly higher probability of negative conversion of PCR within 28 days compared to symptomatic treatment. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) is associated with acute respiratory distress syndrome, and corticosteroids have been considered as possible therapeutic agents for this disease. However, there is limited literature on the appropriate timing of corticosteroid administration to obtain the best possible patient outcomes.Methods: This was a retrospective cohort study including patients with severe COVID-19 who received corticosteroid treatment from March 2 to June 30, 2020 in seven tertiary hospitals in South Korea. We analyzed the patient demographics, characteristics, and clinical outcomes according to the timing of steroid use. Twenty-two patients with severe COVID-19 were enrolled, and they were all treated with corticosteroids.Results: Of the 22 patients who received corticosteroids, 12 patients (55%) were treated within 10 days from diagnosis. There was no significant difference in the baseline characteristics. The initial PaO2/FiO2 ratio was 168.75. The overall case fatality rate was 25%. The mean time from diagnosis to steroid use was 4.08 days and the treatment duration was 14 days in the early use group, while those in the late use group were 12.80 days and 18.50 days, respectively. The PaO2/FiO2 ratio, C-reactive protein level, and cycle threshold value improved over time in both groups. In the early use group, the time from onset of symptoms to discharge (32.4 days vs. 60.0 days, P = 0.030), time from diagnosis to discharge (27.8 days vs. 57.4 days, P = 0.024), and hospital stay (26.0 days vs. 53.9 days, P = 0.033) were shortened.Conclusions: Among patients with severe COVID-19, early use of corticosteroids showed favorable clinical outcomes which were related to a reduction in the length of hospital stay. [ABSTRACT FROM AUTHOR]

Background: Field cricket (Gryllus bimaculatus) is newly emerged as an edible insect in several countries. Anti-inflammatory effect of glycosaminoglycan derived from this cricket on chronic disease animal model such as diabetic mouse has not been fully investigated yet. Thus, the objective of this study was to determine the anti-oxidative effect of such glycosaminoglycan on diabetic mouse. Methods: To discover potential therapeutic agents, field cricket glycosaminoglycan (GbG) was tested in the present study. Its anti-oxidative activities in diabetic mice were determined based on its abilities to reduce glucose, ALT, AST, ALP, LDL-cholesterol and BUN levels. Dung beetle (C. molossus) glycosaminoglycan (CaG) was used as a positive control. Db mice were intraperitoneally administered for 1 month according to their group assignments: 1) normal (DB-Hetero); 2) control (DB-Homo); 3) 5 mg/kg treatment of CaG (CaG5); 4) 5 mg/kg treatment of GbG (GbG5); and 5) 10 mg/kg treatment of metformin (Metformin 10). Results: Blood glucose level decreased after 1st week of treatment with GbG. LDL-cholesterol and alkaline phosphatase levels were also inhibited by GbG. Markers of oxidative damage, such as protein carbonyl content and levels of hepatocellular biomarkers, were reduced in db mice treated with GbG. Especially anti-oxidative activities of catalase, superoxide dismutase and glutathione peroxidase were significantly increased in GbG treated group compared to those in the control (Db Homo). GbG was composed of heparin disaccharides. Its main N-glycan was identified as Hex9GlcNAc2 (m/z 1905.7) with neutral mono-sugar mainly comprising of hexose and L (+) rhamnose by mass spectroscopy. Conclusions: Sero-biochemical and hepatocellular anti-oxidant assay results in db mice suggest that cricket (G. bimaculatus) glycosaminoglycan might possess anti-oxidative effect in diabetic state. [ABSTRACT FROM AUTHOR]

Purpose: This paper examines the possibility of using sense of belonging as an indicator for social capital. Social capital, from the collective social capital theory perspective, is constructed from three main elements: trust, social network and participation. Social capital is crucial to civil society and well-being, but there is no consensus on how to define and measure it. This paper approaches this problem with the different but related concept of sense of belonging, as belonging overlaps with social capital conceptually, but also is more amenable to measurement. Design/methodology/approach: Qualitative and quantitative data was collected from approximately 800 university students and used to explore the relationship between belonging and social capital both conceptually and empirically in the higher education context. Findings: The mixed methods research analysis in this paper provides strong evidence to show how sense of belonging and social capital are theoretically and empirically intertwined, Conceptually they occupy overlapping spheres and their connections can be clearly traced and measured. This is supported by substantial statistical evidence of their relatedness, despite their independent origins in social research. For these reasons, this paper argues that sense of belonging can be used as a simplified alternative way to measure social capital. Originality/value: This paper explains the advantages of using sense of belonging to understand social capital. It sets out a conceptual framework and provides a statistical demonstration. This paper develops and enriches a current strand of social capital and sense of belonging research in the fields of sociology and higher education policy. [ABSTRACT FROM AUTHOR]

Students' sense of belonging is known to be strongly associated with academic achievement and a successful life at university. To achieve a comprehensive understanding of belonging, this study collected data via the 10 Words Question. Responses from 426 participants were analysed using a sequence of analytic methods including In Vivo coding, systematic coding, clustering, and contingency analysis. The results show that, in addition to academic and social engagement, there are two additional domains of belonging which are often neglected: surroundings and personal space. Surroundings equate to participants' living space, and geographical and cultural location, while personal spaces refer to life satisfaction, life attitudes, identity and personal interests. Both positive and negative data demonstrate the complex and multi-dimensional character of belonging in higher education. The study concludes that policies for student engagement in higher education should reflect all four domains to support the full range of students' experiences. [ABSTRACT FROM AUTHOR]

Phthalates are used for industrial plasticizers to impart flexibility and durability to polyvinyl chloride. Despite widespread use of phthalates, reported endocrine-disrupting properties raise safety concerns for consumers. Since phthalates are permitted as excipients in controlled-release capsules and enteric coatings, patients taking drugs containing these chemicals may potentially be at some health risk. In this study, 102 distinct pharmaceutical products were analyzed by gas chromatography/mass spectrometry to determine phthalate content and maximal phthalate exposure rate was calculated. In 102 drug samples, di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and diethyl phthalate (DEP) were detected in 9.8, 27.45, and 5.88% of cases, respectively. The highest level of DEP was found in extended-release (ER) capsules with concentrations ranging from 935.5 to 1535.37 ppb. The highest levels of DBP (1.32–7.07 ppb) were detected in tablets, whereas highest level (7.07 ppb) of DEHP was found in suspension preparations. The phthalate hazard index (HI) (human exposure tolerable daily intake) was calculated for each sample, but no sample exhibited an HI value exceeding 1; the minimum value taken to indicate a serious health risk. Thus, no apparent serious health risk from phthalate exposure arises from taking these medications. The low HI values suggest that phthalate contamination in pharmaceuticals may not pose an apparent significant risk to humans. However, the sources of phthalate present in pharmaceutical products still needs to be investigated and verified through on-site inspections in manufacturing processes in order to minimize human exposure. It is recommended that measures be taken to prevent phthalate contamination in pharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: Dung beetle glycosaminoglycan is known to possess anti-aging activities. However, its anti-cancer mechanisms are not fully elucidated yet. The objective of this study was to evaluate the anti-cancer effect of insect-derived polymer dung beetle glycosaminoglycan (GAG) after intraperitoneally injecting it to melanoma mice induced by B16F10 cells.Methods: To determine molecular mechanism involved in the anti-cancer effect of dung beetle GAG, its origin N-glycan under 3KD Dalton was assayed for melanoma cell cytotoxicity. Quantitative comparisons of adhesive molecule on extracellular matrix and activities of tissue inhibitor of metalloprotease 2 (TIMP-2) were also investigated. In vivo anti-cancer effect of dung beetle GAG on solid tumor size, survival time and gene-expression profiles was also assayed using B10F10 melanoma mice model. Mice with induced melanoma were then treated with Catharsius molossus (dung beetle) GAG (CaG) at 5 mg/kg for 8 weeks to investigate its anti-cancer effects compared to bumblebee (Bombus ignitus) queen glycosaminoglycan (IQG) and Huechys sanguinea glycosaminoglycan (HEG).Results: These N-glycans derived from these GAG were composed of many linear heparinoid polysaccharides, polymers with hexose and N-acetylhexose. Adminstration with these GAGs increased survival time and decreased melanoma sizes in mice, in accordance with their inhibitory effects on cell growth ratio of melanoma B16F10. In addition, treatment with N-glycans derived from theses glycosaminoglycan increased activities of TIMP-2 in HMVEC cells pretreated with TNF-alpha and in melanoma cells, suggesting that they had anti-inflammatory and anticancer activities. In DNA microarray results, compared to control, CaG treated mouse group showed upregulation of 192 genes including collagen,typeI,alpha1 (Col1a1), consistent with the highly increased in vitro extracellular matrix (ECM) adhesion on collagen 1 and up-regulation of heparanase (Hpse). After treatment with CaG, a total of 152 genes were down-regulated, including nuclear RNA export factor (Nxf3) and hyaluronan proteoglycan link protein1 (Hapln1).Conclusions: Glycosaminoglycan, CaG can strengthen ECM by increasing activity of TIMP-2 and adhesion activity on collagen known to inhibit changes of ECM, leading to tumor cell invasion and progression. [ABSTRACT FROM AUTHOR]

Objective: The discovery of two main coreceptors for human immunodeficiency virus (HIV), C‐C chemokine receptor type 5 (CCR5), and C‐X‐C chemokine receptor type 4 has led to a better understanding of the interaction between HIV envelope and host cells, and development of new therapeutic approaches. The purpose of this study was to estimate the prevalence of CCR5 tropism among HIV‐1–infected Koreans and identify the predictors for CCR5 tropism. Methods: We enrolled 250 HIV‐1–infected subjects from four medical centers of three different cities in South Korea between April 2013 and May 2014. Genotypic assay for identifying coreceptor tropism of HIV‐1 was performed with HIV RNA or HIV DNA. Nested polymerase chain reaction and population‐based sequencing for the V3 region (HXB2 position 6225‐7758) of the envelope were performed with HIV RNA or proviral DNA. Proviral DNA was used if the viral load of the subject was below 2000 copies/mL. Genotypic tropism was determined by a web‐based bioinformatics tool ( http://coreceptor.bioinf.mpi‐inf.mpg.de/). Results: Among 250 individuals enrolled, only 143 subjects could be analyzed for genotypic tropism assay with HIV RNA or proviral DNA. The prevalence of CCR5 tropism was 69.2% (N = 99). We could not identify any significant clinical or epidemiological predictors for CCR5 tropism among enrolled subjects. Conclusions: The prevalence of CCR5 tropism in HIV‐1–infected Korean individuals was 69.2%. Since we cannot predict coreceptor tropism by clinical factors, tropism assay should be performed before treatment with the CCR5 antagonist. [ABSTRACT FROM AUTHOR]

Background: HIV-associated neurocognitive disorder (HAND) can occur in patients without prior AIDS defining illness and can be debilitating. This study aimed to evaluate the difference in the patterns of intrinsic brain activity between patients with or without HAND for deepening our understanding of HAND. Methods: We evaluated 24 HIV-infected individuals, 12 with previously diagnosed HAND and 12 previously diagnosed without HAND, and 11 seronegative individuals. These individuals then underwent repeat NP testing and a functional brain MRI scan. For functional MRI analysis, seed-based analysis with bilateral precuneus cortex seed was applied. Results: Among the 12 individuals with previously diagnosed HAND, 3 showed improvement of their neurocognitive function and 1 was excluded for worsening liver disease. Among the 12 patients who previously had normal neurocognitive function, 2 showed neurocognitive impairment. Overall, the HAND group, who had impaired cognitive function at the time of MRI scan, showed significant decrease of resting status functional connectivity between bilateral precuneus and prefrontal cortex (PFC) compared with nonHAND group, those who had normal neurocognitive function (Corrected P<0.05). The functional connectivity with the right inferior frontal operculum and right superior frontal gyrus was positively correlated with memory and learning ability. Conclusions: This cross-sectional study found a significant difference in fMRI patterns between patients with and without HAND. Decreased functional connectivity between precuneus and PFC could be possible functional substrate for cognitive dysfunction in HIV patients, which should be characterized in a longitudinal study. [ABSTRACT FROM AUTHOR]

The cellular source of HIV RNA circulating in blood plasma remains unclear. Here, we investigated whether sequence analysis of HIV RNA populations circulating before combination antiretroviral therapy (cART) and HIV DNA populations in cellular subsets (CS) after cART could identify the cellular sources of circulating HIV RNA. Blood was collected from five subjects at cART initiation and again 6 months later. Naïve CD4+ T cells, resting central memory and effector memory CD4+ T cells, activated CD4+ T cells, monocytes, and natural killer cells were sorted using a fluorescence-activated cell sorter. HIV-1 env C2V3 sequences from HIV RNA in blood plasma and HIV DNA in CSs were generated using single genome sequencing. Sequences were evaluated for viral compartmentalization (Fst test) and migration events (MEs; Slatkin Maddison and cladistic measures) between blood plasma and each CS. Viral compartmentalization was observed in 88% of all cellular subset comparisons (range: 77-100% for each subject). Most observed MEs were directed from blood plasma to CSs (52 MEs, 85.2%). In particular, there was only viral movement from plasma to NK cells (15 MEs), monocytes (seven MEs), and naïve cells (five ME). We observed a total of nine MEs from activated CD4 cells (2/9 MEs), central memory T cells (3/9 MEs), and effector memory T cells (4/9 MEs) to blood plasma. Our results revealed that the HIV RNA population in blood plasma plays an important role in seeding various cellular reservoirs and that the cellular source of the HIV RNA population is activated central memory and effector memory T cells. J. Med. Virol. 88:606-613, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The CopA3 dimer peptide is a coprisin analog that has an anticancer effect against human cancer cells in vitro. In this study, we investigated the anticancer activity of the enantiomeric CopA3 dimer peptide in human gastric cancer cell lines as well as in an in vivo tumor xenograft model. Enantiomeric CopA3 reduced gastric cancer cell viability and exhibited cytotoxicity against cancer cells. Enantiomeric CopA3-induced cell death was mediated by specific interactions with phosphatidylserine and phosphatidylcholine, membrane components that are enriched in cancer cells, in a calcein leakage assay. Moreover, acridine orange/ethidium bromide staining, flow cytometric analysis, and Western blot analysis showed that enantiomeric CopA3 induced apoptotic and necrotic gastric cancer cell death. The antitumor effect was also observed in a mouse tumor xenograft model in which intratumoral inoculation of the peptide resulted in a significant decrease in the SNU-668 gastric cancer tumor volume. In addition, periodic acid-Schiff and hematoxylin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed apoptotic and necrotic cell death in tumor masses treated with greater than 150 μg CopA3. Collectively, these results indicate that the enantiomeric CopA3 dimer peptide induces apoptosis and necrosis of gastric cancer cells in vitro and in vivo, indicating that the peptide is a potential candidate for the treatment of gastric cancer, which is a common cause of cancer and cancer deaths worldwide. [ABSTRACT FROM AUTHOR]

Poecilocoris lewisi (Korean name: 'Kwangdaenolinjae') is a red-striped gold stink bug (insect) which has been used as a crude drug in traditional medicine of East Asia and Korea. In this study, ethanol extract and glycosaminoglycan from P. lewisi (Pl GAG), as an active substance among its components, were investigated for their potential anti-inflammatory actions. They were found to be a potent inducer of nitric oxide (NO) production from calf pulmonary artery endothelial (CPAE) cells and a stimulator of endothelial nitric oxide synthase in a dose-dependent manner. The anti-inflammatory activities were also evaluated by determining the level of adhesion molecules related to atherogenesis and pro-inflammatory cytokines, such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), secretory phospholipase A, and prostaglandin E, stimulated by tumor necrosis factor (TNF)-α in human umbilical vein endothelial cells (HUVEC). They also showed inhibitory effects on vascular endothelial growth factor (VEGF) production in HUVECs. Matrix metalloproteinases (MMP-2 and 9) were also inhibited by treatment with this extract or glycosaminoglycan. Furthermore, this GAG showed cytotoxicity against CT-26 colon cancer cells whereas having no cytotoxicity in CHO normal cells. Monosaccharide (amino, acidic, neutral monosaccharides) composition of used GAG was characterized by trimethylsilylated GC-MS analysis method. [ABSTRACT FROM AUTHOR]

Anti-inflammatory effects of glycosaminoglycan (GAG) derived from cricket (Gryllus bimaculatus, Gb) were investigated in a complete Freund’s adjuvant (CFA)-treated chronic arthritic rat model. This GAG produced a significant anti-edema effect as evidenced by inhibition of C-reactive protein (CRP) and rheumatoid factor, and interfered with atherogenesis by reducing proinflammatory cytokine levels of (1) vascular endothelial growth factor (VEGF) production in human umbilical vein endothelial cells (HUVEC), (2) interleukin-6, (3) prostaglandin E2-stimulated lipopolysaccharide in RAW 264.7 cells, and (4) tumor necrosis factor (TNF)-α production in normal splenocytes, in a dose-dependent manner. This GAG was also found to induce nitric oxide (NO) production in HUVEC cells and elevated endothelial nitric oxide synthase (eNOS) activity levels. Histological findings demonstrated the fifth lumbar vertebrae (LV) dorsal root ganglion, which was linked to the paw treated with Gb GAG, was repaired against CFA-induced cartilage destruction. Further, combined indomethacin (5 mg/kg)–Gb GAG (10 mg/kg) inhibited more effectively CFA-induced paw edema at 3 h and 2 or 3 d after treatment to levels comparable to only the anti-inflammatory drug indomethacin. Ultraviolet (UV)-irritated skin inflammation also downregulated nuclear factor κB (NFκB) activity in transfected HaCaT cells. Data suggest that the anti-inflammatory effects of GAG obtained from cricket (Gb) may be useful for treatment of inflammatory diseases including chronic arthritis. [ABSTRACT FROM PUBLISHER]

The antihypertensive effects of both extracts and glycosaminoglycan derived fromIsaria sinclairii(IS) were investigated in a spontaneously hypertensive rat (SHR) model. Groups of rats were treated orally with 30 mg/kg each of: (1) saline control or extracts of (2) water-IS (3) methanol-IS, (4) butanol-IS, (5) ethyl acetate-IS, or (6) captopril as positive control. The 30-mg/kg dose was administered with a standard diet every day for a period of 2 wk. The antihypertensive effects of the individual extracts were in the following order: methanol > water > ethyl acetate > butanol. Glycosaminoglycan (GAG) obtained from IS as a water-soluble alcohol precipitation fraction produced an antihypertensive effect. One month following administration of GAG derived from IS to SHR animals there was a marked decrease in systolic blood pressure from 183 to 105 mm Hg and reduced diastolic blood pressure from 148 to 80 mm Hg compared to untreated control SHR rats. It was found that GAG produced an antihypertensive effect, which was more effective than the positive control captopril. In the SHR animal model a fall of 19% in body weight was observed in the group that received GAG. Data thus indicate that GAG derived fromI. sinclairiimay be a potent, naturally occurring antihypertensive agent. SHR (Spontaneously Hypertensive Rat); WKY (Wistar Kyoto Rat); glycosaminoglycan (GAG);I. sinclairii(IS); ISMC30:I. sinclairiimethanol extract 30 mg/kg; ISG2:I. sinclairiiglycosaminoglycan 2 mg/kg; IS GAG:I. sinclairiiglycosaminoglycan.This study was supported by the Rural Development Administration, Basic research project Pj006642 (2009–2012). [ABSTRACT FROM AUTHOR]

Human tissue-plasminogen activator (t-PA) is a thrombolytic protein that plays an active role in dissolving fibrin clots by fibrinolysis and in activating the transition from plasminogen to plasmin in blood vessels. The recombinant tissue-plasminogen activator (rTPA) produced in plants is a soluble protein derived from human t-PA. In order to produce rTPA protein in plants, a DNA fragment encoding the t-PA protein was cloned into a plant binary plasmid that included the cauliflower mosaic virus 35S promoter, a tobacco etch virus (TEV) leader sequence, an N-terminal signal peptide of the alfala glucose-regulated endoplasmic reticular protein, and an 35S terminator. The insertion of the rTPA gene in genomic DNA of phospinothricin-resistant tobacco plants was confirmed by polymerase chain reaction (PCR). The presence of the rTPA-specific transcript in the total RNAs of transgenic plants leaves was verified by reverse transcription (RT)-PCR. Immunoblot analysis of the transformed tobacco leaves revealed single bands of 68-kDa rTPAs. Enzyme-linked immunosorbent assay experiments demonstrated that the highest level of rTPA expression was 0.0014% of the total soluble protein in tobacco plants. Fibrinolysis of rTPA was confirmed by fibrin plate assay and zymography. These studies demonstrate that plants can be employed as bioreactor systems for the production of an enzymatically active t-PA with properties similar to the recombinant t-PA produced by mammalian cells. [ABSTRACT FROM AUTHOR]

The fine structure of acharan sulfate, a recently discovered glycosaminoglycan isolated from Achatina fulica, was examined. This glycosaminoglycan has a major disaccharide repeating unit of →4)‐α‐d‐GlcNpAc(1→4)‐α‐l‐IdoAp2S(1→ (where GlcNpAc is N‐acetylglucosamine, IdoAp is iduronic acid, and S is sulfate) making it structurally related to both heparin and heparan sulfate. Using heparin lyases prepared from Flavobacterium heparinum and a newly isolated heparinase from Bacteroides stercoris, the controlled enzymatic depolymerization of acharan sulfate was undertaken to prepare a mixture of oligosaccharides. Fractionation of this mixture of oligosaccharides by strong‐anion‐exchange high performance liquid chromatography afforded oligosaccharides that capillary electrophoresis established were sufficiently pure for structural characterization. Electrospray ionization mass spectrometry identified two series of oligosaccharides, one derived from acharan sulfate's major repeating unit and a second minor group of undersulfated oligosaccharides. Proton nuclear magnetic resonance spectroscopy established the structure of these two classes of oligosaccharides to be ΔUAp2S(1→[4)‐α‐d‐GlcNpAc(1→4)‐α‐l‐IdoAp2S(1→]n4)‐ d‐GlcNpAcα,β (where n = 0,1,2,3 and ΔUAp is 4‐deoxy‐α‐l‐threo‐hex‐4‐enopyranosyluronic acid) and ΔUAp(1→[4)‐ α‐d‐GlcNpAc(1→4)‐α‐l‐IdoAp2S(1→]m‐d‐GlcNpAcα,β (where m = 1,2,3). These results suggest the presence of minor sequence variants in acharan sulfate containing unsulfated iduronic acid having the structure →4)‐α‐d‐GlcNpAc(1→4)‐α‐l‐IdoAp(1→. [ABSTRACT FROM PUBLISHER]

Introduction: Multiple comorbidities among HIV‐positive individuals may increase the potential for polypharmacy causing drug‐to‐drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age‐associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age‐associated comorbidities on therapeutic outcomes of cART in HIV‐positive adults in Asian countries. Methods: Patients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those <50 years and those ≥50 years without comorbidities. We analysed 5411 patients with virological failure and 5621 with immunologic failure. Our failure outcomes were defined to be in‐line with the World Health Organization 2016 guidelines. Cox regression analysis was used to analyse time to first virological and immunological failure. Results: The incidence of virologic failure was 7.72/100 person‐years. Virological failure was less likely in patients with better adherence and higher CD4 count at cART initiation. Those acquiring HIV through intravenous drug use were more likely to have virological failure compared to those infected through heterosexual contact. On univariate analysis, patients aged <50 years without comorbidities were more likely to experience virological failure than those aged ≥50 years with comorbidities (hazard ratio 1.75, 95% confidence interval (CI) 1.31 to 2.33, p < 0.001). However, the multivariate model showed that age‐related comorbidities were not significant factors for virological failure (hazard ratio 1.31, 95% CI 0.98 to 1.74, p = 0.07). There were 391 immunological failures, with an incidence of 2.75/100 person‐years. On multivariate analysis, those aged <50 years without comorbidities (p = 0.025) and age <50 years with comorbidities (p = 0.001) were less likely to develop immunological failure compared to those aged ≥50 years with comorbidities. Conclusions: In our Asia regional cohort, age‐associated comorbidities did not affect virologic outcomes of cART. Among those with comorbidities, patients <50 years old showed a better CD4 response. [ABSTRACT FROM AUTHOR]

Backgrounds: Several studies have evaluated the impact of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) combined with antimicrobial stewardship in patients with positive blood cultures; clinical outcomes improved. However, in many hospitals, antimicrobial stewardship is not available because of restricted medical resources. Thus, we investigated the impact of evaluation by MALDI-TOF MS on the clinical outcomes of patients with bacteremia and fungemia treated in a clinical setting lacking an antimicrobial stewardship program (ASP).Methods: We designed a pre-post quasi experimental study and retrospectively reviewed the medical records of patients aged > 18 years old with bacteremia and fungemia during two periods: October-December 2012 and October-December 2013. Conventional methods were used to detect microbial pathogens in 2012, and MALDI-TOF MS was employed in 2013. Clinical outcomes compared between periods were the time to pathogen identification, time to effective therapy, 30-day all-cause mortality, time to microbiological clearance, length of ICU stay, and rate of recurrence of the same bloodstream infection (BSI).Results: A total of 556 patients were enrolled; 302 patients in 2012, and 254 in 2013. The use of MALDI-TOF MS without an ASP reduced the time to pathogen identification (86.4 vs. 63.5 h, P < 0.001) but did not significantly reduce the time to effective therapy (27.4 vs. 23.2 h, P = 0.187). Also, none of the following differed significantly between the two periods: mortality (17.5 vs. 15.7%, P = 0.571), the time to microbiological clearance (3.6 vs. 3.7 days, P = 0.675), the length of ICU stay (16.8 vs. 14.7 days, P = 0.706), and the recurrence rate of the same BSI (5.0 vs. 2.8%, P = 0.183).Conclusions: The use of MALDI-TOF MS alone in a setting lacking an ASP did not afford clinical benefits. An ASP combined with MALDI-TOF MS is necessary to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Bronchiolitis obliterans organizing pneumonia (BOOP) is a type of diffuse interstitial lung disease characterized by the pathology of fibroblastic plugs in the lumens of the respiratory bronchioles, alveolar ducts, and alveoli. The occurrence of BOOP in human immunodeficiency virus (HIV)-infected patients has rarely been described, and there have been no clinical case reports in Korea.Case Presentation: A 24-year-old female who had been diagnosed with HIV ten years prior was admitted due to a 1-year history of cough and sputum production and a 3-day history of fever. She had poor adherence to anti-retroviral therapy (ART) due to gastrointestinal troubles. At the time of admission, her CD4 T-cell count was 5 cells/mm(3). A high resolution computed tomography (CT) scan showed tiny centrilobular nodules with a tree-in-bud pattern in both lungs. Bacterial culture, Pneumocystis jirovecii polymerase chain reaction (PCR), Aspergillus galactomannan antigen (Ag) assay, and respiratory virus PCR were negative. Rapid chest x-ray improvement was seen after a 7-day treatment with anti-tuberculosis medication, ceftriaxone, and clarithromycin. Miliary tuberculosis seemed unlikely considering the rapid radiologic improvement and negative tuberculosis PCR results. Due to the unknown etiology, we performed video-assisted thoracoscopic surgery (VATS) to determine the cause of the diffuse lung infiltration. Pathologic findings were consistent with BOOP, while tissue acid-fast bacilli (AFB) stain and tuberculosis PCR results were negative. Tuberculosis medication and intravenous ceftriaxone were discontinued, while treatment with clarithromycin monotherapy was sustained. Five months after discharge, the patient was asymptomatic with a normal chest x-ray and as her adherence to ART improved, her CD4 T-cell count rose to 181 cells/mm(3). Clarithromycin was discontinued at that time and the patient is currently receiving regular outpatient follow-up.Conclusion: This case suggests that macrolides are a potential treatment option in HIV-infected patients with mild BOOP. In cases that are otherwise unexplained or unresponsive to treatment, BOOP should be taken into consideration and surgical biopsy performed to confirm a diagnosis of BOOP. [ABSTRACT FROM AUTHOR]