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Because of the lack of guidelines and standardized protocols for end-of-life nursing care in intensive care units in Korea, many nurses have reported facing difficulties when providing care for patients. This study attempted to develop a standardized end-of-life nursing protocol for use in intensive care units. A draft of the end-of-life nursing care protocol was developed after a literature review. A Delphi survey was carried out twice with 30 experts, and the content validity ratio of the items was investigated. The draft end-of-life nursing care protocol was divided into 3 separate stages with 24 items: 8 initial end-of-life care assessment items, 5 ongoing end-of-life care items, and 11 post-end-of-life care items. The content validity ratios of the first and second rounds were 0.33 or greater in each category, demonstrating the validity of the proposed draft as a standardized protocol. Furthermore, at the suggestion of the experts, an extra item was added in the last stage, resulting in 25 items. The results of this study are expected to help leading hospitals in South Korea outline the roles and range of tasks for end-of-life care in an intensive care unit and thereby resolve difficulties for nurses. Furthermore, this will improve the medical services that family members receive during end-of-life care.

This study empirically analyzes the effects of exploitation and exploration on the innovation performance of emerging companies. We assumed that R&D expenditures or outsourcing production are positively associated with the level of innovation of the firm. The study conducted an analysis based on World Bank data collected from 2008 to 2009 for 1,555 companies in 11 emerging countries. As a result, firms in many emerging economies with insufficient resources and in low-tech manufacturing industries have shown that exploratory innovation activities, represented by investments in R&D expenditure, are still critical to achieving superior performance in new product production. On the other hand, exploitative activities through outsourcing did not have a significant impact on firms’ innovation performance. Through the results of this analysis, this study suggests that exploratory activities are meaningful in emerging countries to increase their innovation performance.

This study aimed to evaluate the effect of hyaluronan-selected/physiological intracytoplasmic sperm injection (PICSI) on fertilization and quality of cleavage-stage embryos in infertile couples with ≤1% of spermatozoa with normal strict morphology (severe teratozoospermia). Seventy-seven couples underwent PICSI between October 2017 and December 2018 (PICSI group), while 75 couples underwent conventional intracytoplasmic sperm injection (ICSI) between January 2016 and September 2017 (ICSI group). Good quality embryos (GQEs) were evaluated based on morphology. Patient and cycle characteristics were comparable between the PICSI and ICSI groups, except for age and anti-Müllerian hormone (AMH) level (38.4 ± 3.9 years vs. 36.3 ± 4.3 years, p = .002 and 2.06 ± 1.99 ng/mL vs. 2.97 ± 3.25 ng/mL, p = .040). The fertilization rate per oocyte inseminated and GQE rate were significantly higher in the PICSI group than in the ICSI group (82.7% vs. 71.7%, p ˂ .001 and 52.8% vs. 34.0%, p ˂ .001). Furthermore, the absence of GQEs was found to be lower in the PICSI group (13.0% vs. 30.7%, p = .008). Multivariate analysis adjusted for age and AMH level identified PICSI as an unfavorable and independent factor for the absence of GQEs (adjusted odds ratio, 0.333; 95% confidence interval, 0.125–0.890). PICSI seems to be superior to ICSI in terms of fertilization and embryo quality in couples with severe teratozoospermia.

Silicon particles in combination with the dynamic nuclear polarization (DNP) method have recently attracted attention as promising biomedical platforms for drug delivery and medical diagnostics in ...

The southern elephant seal Mirounga leonina is the largest member of the phocid seals and is a highly sexually dimorphic predator at circumpolar regions. In this study, we generated the first high-quality de novo assembly of the blood transcriptome of M. leonina using the Illumina MiSeq platform. A total of 40.5 million raw reads were obtained and assembled using the Oases assembly platform, resulting in 46,445 contigs with an N50 value of 634 bp. We performed functional gene annotations through pathway analyses of the Gene Ontology (GO), Eukaryotic Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Ortholog comparison revealed that a high proportion of the M. leonina blood transcriptome had significant sequence homology within pinnipeds. M. leonine, a deep and long-diving seal, is routinely exposed to progressive hypoxia during dives. KEGG analyses detected an intact hypoxia-inducible factor-1 (HIF-1) signaling pathway, which is a key metabolism pathway in the adaptive homeostatic responses to hypoxia. In the blood transcriptome, many essential genes involved in innate immunity were detected, which suggests that the blood serves as a host defense modulator against exogenous infections in M. leonina. This genomic resource will be useful for understanding adaptive metabolism upon repeated breath-hold dives and determining the health status of southern elephant seals without the need to sacrifice them in experiments.

Temperature is an important abiotic factor that directly influences the physiology of marine fish. The Antarctic bullhead notothen Notothenia coriiceps inhabits water with temperatures ranging from — 1.9 to 2°C at circumpolar regions. Thus, N. coriiceps is useful as a model animal for understanding the effects of temperature stress. To assess the transcriptional response of skin tissue to temperature changes, Antarctic bullhead notothen were exposed to two temperature stresses, 4°C and — 2°C, following acclimatization at 2°C. Twenty-four hours after the temperature change, skin transcriptomes were sequenced using the Illumina Hiseq 2000 platform and analyzed using a series of bioinformatics tools. Functional gene annotations through pathway analyses of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases revealed commonly or distinctively modulated transcriptional changes in skin. Both temperature stressors significantly upregulated the actin cytoskeleton regulation pathway and the skin’s water barrier function, while the stressors downregulated the metabolism involved in muscle contraction, choline receptor regulation, collagen regulation, and immunity. Cold stress caused significant downregulation of the mRNA expression of genes involved in vasopressin-regulated water reabsorption. Neither the heat- nor cold-stressed skin transcriptomes exhibited significant heat shock protein expression. Our results suggest that, as a first barrier for fish, the skin has complex metabolisms with high transcriptional sensitivity against environmental temperature stress. These results will be useful for understanding the skin-specific molecular mechanisms that Antarctic fish use to adapt to temperature fluctuations.

This study provides evidence on how venture capital (VC) investment affects startup firms&rsquo, sustainable growth and performance. Despite the rich and abundant research on the relationship between VC investment and startup performance, there is no clear evidence about the contribution of VC investment on the performance and market value of invested firms. In order to accurately measure the impact of VC investment, this study explored how VC investment at each stage of growth affects a startup&rsquo, s sustainable growth and performance. Based on signaling theory and information asymmetry, this study proposed a positive link between initial-stage VC investment and a startup&rsquo, s growth and performance. Using a sample of 363 firms listed from 2000 to 2007, this study demonstrated that startups are sustained and perform better as they receive their VC investment at the initial stage. The level of potential absorptive capacity positively moderated this association, unlike realized absorptive capacity, which did not show significant moderating effects.

Glutaredoxin (Grx), a major redox regulator, can act as a reductant of methionine sulfoxide reductase A (MsrA). However, the biochemical mechanisms involved in MsrA activity regeneration by Grx remain largely unknown. In this study, we investigated the regeneration mechanism of 1-Cys type Clostridium oremlandii MsrA (cMsrA) lacking a resolving Cys residue in a Grx-dependent assay. Kinetic analysis showed that cMsrA could be reduced by both monothiol and dithiol Grxs as efficiently as by in vitro reductant dithiothreitol. Our data revealed that the catalytic Cys sulfenic acid intermediate is not glutathionylated in the presence of the substrate, and that Grx instead directly formed a complex with cMsrA. Mass spectrometry analysis identified a disulfide bond between the N-terminal catalytic Cys of the active site of Grx and the catalytic Cys of cMsrA. This mixed disulfide bond could be resolved by glutathione. Based on these findings, we propose a model for regeneration of 1-Cys type cMsrA by Grx that involves no glutathionylation on the catalytic Cys of cMsrA. This mechanism contrasts with that of the previously known 1-Cys type MsrB.

Platelet-activating factor receptor (PAFR) plays an important role in bacterial infection and inflammation. We examined the effect of the bacterial cell wall components lipopolysaccharide (LPS) and lipoteichoic acid (LTA) from Lactobacillus plantarum (pLTA) and Staphylococcus aureus (aLTA) on PAFR expression in THP-1, a monocyte-like cell line. LPS and aLTA, but not pLTA, significantly increased PAFR expression, whereas priming with pLTA inhibited LPSmediated or aLTA-mediated PAFR expression. Expression of Toll-like receptor (TLR) 2 and 4, and CD14 increased with LPS and aLTA treatments, but was inhibited by pLTA pretreatment. Neutralizing antibodies against TLR2, TLR4, and CD14 showed that these receptors were important in LPS-mediated or aLTA-mediated PAFR expression. PAFR expression is mainly regulated by the nuclear factor kappa B signaling pathway. Blocking PAF binding to PAFR using a PAFR inhibitor indicated that LPS-mediated or aLTA-mediated PAF expression affected TNF-α production. In the mouse small intestine, pLTA inhibited PAFR, TLR2, and TLR4 expression that was induced by heat-labile toxin. Our data suggested that pLTA has an anti-inflammatory effect by inhibiting the expression of PAFR that was induced by pathogenic ligands.

Purpose– The purpose of this paper is to examine the relationships among satisfaction with food-related life (SWFL), perceived foodservice quality, and quality of life for older adults.Design/methodology/approach– A survey done using face-to-face interviews of older adults residing in long-term care facilities. A total of 238 older adults participated in this study.Findings– The results showed that perceived foodservice quality had a strong association with SWFL; SWFL had a significant positive association with quality of life; perceived foodservice quality positively related to quality of life. Increased SWFL would improve quality of older adults.Research limitations/implications– This study has limitations related to convenience sample. Different sampling could help with generalization of results.Practical implications– Foodservice managers in long-term care facilitates should try to maximize food and service qualities for residents because improving food and service quality improves their quality of life. For example, offering a variety of menus to allow older adults to enjoy food and improve their SWFL.Originality/value– This study emphasized that food was important to older adults and helped determine quality of life for them. SWFL was rarely empirically examined in the previous research.

The chinstrap (Pygoscelis antarcticus) and gentoo (P. papua) penguins are distributed throughout Antarctica and the sub-Antarctic islands. In this study, high-quality de novo assemblies of blood transcriptomes from these penguins were generated using the Illumina MiSeq platform. A total of 22.2 and 21.8 raw reads were obtained from chinstrap and gentoo penguins, respectively. These reads were assembled using the Oases assembly platform and resulted in 26,036 and 21,854 contigs with N50 values of 929 and 933 base pairs, respectively. Functional gene annotations through pathway analyses of the Gene Ontology, EuKaryotic Orthologous Groups, and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were performed for each blood transcriptome, resulting in a similar compositional order between the two transcriptomes. Ortholog comparisons with previously published transcriptomes from the Adélie (P. adeliae) and emperor (Aptenodytes forsteri) penguins revealed that a high proportion of the four penguins’ transcriptomes had significant sequence homology. Because blood and tissues of penguins have been used to monitor pollution in Antarctica, immune parameters in blood could be important indicators for understanding the health status of penguins and other Antarctic animals. In the blood transcriptomes, KEGG analyses detected many essential genes involved in the major innate immunity pathways, which are key metabolic pathways for maintaining homeostasis against exogenous infections or toxins. Blood transcriptome studies such as this may be useful for checking the immune and health status of penguins without sacrifice.

Nm23-H1/NDPK-A, a tumour metastasis suppressor, is a multifunctional housekeeping enzyme with nucleoside diphosphate kinase activity. Hexameric Nm23-H1 is required for suppression of tumour metastasis and it is dissociated into dimers under oxidative conditions. Here, the crystal structure of oxidized Nm23-H1 is presented. It reveals the formation of an intramolecular disulfide bond between Cys4 and Cys145 that triggers a large conformational change that destabilizes the hexameric state. The dependence of the dissociation dynamics on the H2O2 concentration was determined using hydrogen/deuterium-exchange experiments. The quaternary conformational change provides a suitable environment for the oxidation of Cys109 to sulfonic acid, as demonstrated by peptide sequencing using nanoUPLC-ESI-q-TOF tandem MS. From these and other data, it is proposed that the molecular and cellular functions of Nm23-H1 are regulated by a series of oxidative modifications coupled to its oligomeric states and that the modified cysteines are resolvable by NADPH-dependent reduction systems. These findings broaden the understanding of the complicated enzyme-regulatory mechanisms that operate under oxidative conditions.

Reactive oxygen species (ROS) are key molecules regulating various cellular processes. However, what the cellular targets of ROS are and how their functions are regulated is unclear. This study explored the cellular proteomic changes in response to oxidative stress using H2O2 in dose- and recovery time-dependent ways. We found discernible changes in 76 proteins appearing as 103 spots on 2D-PAGE. Of these, Prxs, DJ-1, UCH-L3 and Rla0 are readily oxidized in response to mild H2O2 stress, and then degraded and active proteins are newly synthesized during recovery. In studies designed to understand the degradation process, multiple cellular modifications of redox-sensitive proteins were identified by peptide sequencing with nanoUPLC-ESI-q-TOF tandem mass spectrometry and the oxidative structural changes of Prx2 explored employing hydrogen/deuterium exchange-mass spectrometry (HDX-MS). We found that hydrogen/deuterium exchange rate increased in C-terminal region of oxidized Prx2, suggesting the exposure of this region to solvent under oxidation. We also found that Lys191 residue in this exposed C-terminal region of oxidized Prx2 is polyubiquitinated and the ubiquitinated Prx2 is readily degraded in proteasome and autophagy. These findings suggest that oxidation-induced ubiquitination and degradation can be a quality control mechanism of oxidized redox-sensitive proteins including Prxs and DJ-1.

Nucleoside diphosphate kinase (NDPK) catalyzes transfer of the γ-phosphoryl group from a nucleoside triphosphate (NTP) to a nucleoside diphosphate. The high-energy phosphate for this reaction is usually supplied by ATP. NDPK plays a primary role not only in maintaining cellular pools of all NTPs but also in the regulation of important cellular processes. NDPK-A (or Nm23-H1), one of eight human NDPKs, acts as a metastasis suppressor for some tumour types. A recent study showed that homohexameric human NDPK-A is regulated in response to oxidative stress. The activity of NDPK-A is reduced, with a concomitant increase in the population of dimeric NDPK-A, under oxidative conditions. In this study, human NDPK-A has been crystallized under oxidative conditions and X-ray data have been collected to 2.80 Å resolution using synchrotron radiation. The crystal belonged to the primitive cubic space group P2(1)3, with unit-cell parameters a = b = c = 106.8 Å. There is one NDPK-A dimer in the asymmetric unit. The preliminary electron-density map shows a large conformational change of the C-terminal domain of NDPK-A induced by a novel disulfide bond that is formed under oxidative conditions.

Redox-active cysteine, a highly reactive sulfhydryl, is one of the major targets of ROS. Formation of disulfide bonds and other oxidative derivatives of cysteine including sulfenic, sulfinic, and sulfonic acids, regulates the biological function of various proteins. We identified novel low-abundant cysteine modifications in cellular GAPDH purified on 2-dimensional gel electrophoresis (2D-PAGE) by employing selectively excluded mass screening analysis for nano ultraperformance liquid chromatography-electrospray-quadrupole-time of flight tandem mass spectrometry, in conjunction with MODi and MODmap algorithm. We observed unexpected mass shifts (Δm = −16, −34, +64, +87, and +103 Da) at redox-active cysteine residue in cellular GAPDH purified on 2D-PAGE, in oxidized NDP kinase A, peroxiredoxin 6, and in various mitochondrial proteins. Mass differences of −16, −34, and +64 Da are presumed to reflect the conversion of cysteine to serine, dehydroalanine (DHA), and Cys-SO2-SH respectively. To determine the plausible pathways to the formation of these products, we prepared model compounds and examined the hydrolysis and hydration of thiosulfonate (Cys-S-SO2-Cys) either to DHA (Δm = −34 Da) or serine along with Cys-SO2-SH (Δm = +64 Da). We also detected acrylamide adducts of sulfenic and sulfinic acids (+87 and +103 Da). These findings suggest that oxidations take place at redox-active cysteine residues in cellular proteins, with the formation of thiosulfonate, Cys-SO2-SH, and DHA, and conversion of cysteine to serine, in addition to sulfenic, sulfinic and sulfonic acids of reactive cysteine.

φSG-JL2 is a newly discovered lytic bacteriophage infecting Salmonella enterica serovar Gallinarum biovar Gallinarum but is nonlytic to a rough vaccine strain of serovar Gallinarum biovar Gallinarum (SG-9R), S. enterica serovar Enteritidis, S. enterica serovar Typhimurium, and S. enterica serovar Gallinarum biovar Pullorum. The φSG-JL2 genome is 38,815 bp in length (GC content, 50.9%; 230-bp-long direct terminal repeats), and 55 putative genes may be transcribed from the same strand. Functions were assigned to 30 genes based on high amino acid similarity to known proteins. Most of the expected proteins except tail fiber (31.9%) and the overall organization of the genomes were similar to those of yersiniophage φYeO3-12. φSG-JL2 could be classified as a new T7-like virus and represents the first serovar Gallinarum biovar Gallinarum phage genome to be sequenced. On the basis of intraspecific ratios of nonsynonymous to synonymous nucleotide changes (Pi[a]/Pi[s]), gene 2 encoding the host RNA polymerase inhibitor displayed Darwinian positive selection. Pretreatment of chickens with φSG-JL2 before intratracheal challenge with wild-type serovar Gallinarum biovar Gallinarum protected most birds from fowl typhoid. Therefore, φSG-JL2 may be useful for the differentiation of serovar Gallinarum biovar Gallinarum from other Salmonella serotypes, prophylactic application in fowl typhoid control, and understanding of the vertical evolution of T7-like viruses.