Protective Effect of Vaccine Doses and Antibody Titers Against SARS-CoV-2 Infection in Kidney Transplant Recipients.

Patients undergoing kidney transplantation have a poor response to vaccination and a higher risk of disease progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of vaccine doses and antibody titer tests against the mutant variant in these patients remains unclear. We retrospectively analyzed the risk of SARS-CoV-2 infection in a single medical center according to vaccine doses and immune responses before the outbreak. Among 622 kidney transplant patients, there were 77 patients without vaccination, 26 with one dose, 74 with two doses, 357 with three, and 88 with four doses. The vaccination status and infection rate proportion were similar to the general population. Patients undergoing more than three vaccinations had a lower risk of infection (odds ratio = 0.6527, 95% CI = 0.4324-0.9937) and hospitalization (odds ratio = 0.3161, 95% CI = 0.1311-0.7464). Antibody and cellular responses were measured in 181 patients after vaccination. Anti-spike protein antibody titer of more than 1,689.3 BAU/mL is protective against SARS-CoV-2 infection (odds ratio = 0.4136, 95% CI = 0.1800-0.9043). A cellular response by interferon-γ release assay was not correlated with the disease (odds ratio = 1.001, 95% CI = 0.9995-1.002). In conclusion, despite mutant strain, more than three doses of the first-generation vaccine and high antibody titers provided better protection against the omicron variant for a kidney transplant recipient.

Cost-Benefit Analysis of Involving Pharmacist for Medication Therapy Management in a Heart Transplant Clinic.

BACKGROUND: Drug-related problems (DRPs) are common in recipients of solid organ transplants. Pharmacist-led medication therapy management (MTM) has cost benefits in kidney and liver transplants; however, whether MTM is also beneficial in heart transplants remains unclear. This study explored the cost benefits of involving pharmacists in the heart transplant clinic. METHODS: This retrospective study evaluated DRPs for 1 year after implementation of pharmacist-led MTM in a heart transplant clinic. The DRPs were compared between patients receiving transplantation for <1 and >1 year. The risk matrix method was used to assess each DRP in terms of the estimated probability and severity of consequent adverse drug events (ADEs). For cost analysis, both estimated cost savings and avoidance were calculated. RESULTS: During the 1-year MTM, 372 DRPs were identified by the pharmacist, among which 169 (45%) and 203 (55%) were from patients at <1-year and ≥1-year post-transplant periods, respectively. The 2 post-transplant periods (<1 year and ≥1 year) exhibited significant differences in the distribution of the dosage or frequency problems (30% vs 18%, P = .005) and the suggestion of more appropriate medication (4% vs 10%, P = .024). In all, 92 (29%) DRPs had an ADE probability of >10%; and 63 (17%) DRPs were estimated to cause ADEs with moderate severity or higher. The estimated cost savings and cost avoidance were US $4902 and US $4519, which equaled a cost-benefit ratio of 2.39. CONCLUSION: Integration of pharmacists into heart transplant clinics could help address DRPs and may have cost benefits.

Immunogenicity and safety of two-dose SARS-CoV-2 vaccination via different platforms in kidney transplantation recipients.

After kidney transplantation, patients exhibit a poor response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, the efficacy and adverse effects of vaccines based on different platforms in these patients remain unclear. We prospectively analyzed both anti-spike protein antibody and cellular responses 1 month after the first and second doses of SARS-CoV-2 vaccines in 171 kidney transplant patients. Four vaccines, including one viral vector (ChAdOx1 nCov-19, n = 30), two mRNA (mRNA1273, n = 81 and BNT162b2, n = 38), and one protein subunit (MVC-COV1901, n = 22) vaccines were administered. Among the four vaccines, mRNA1273 elicited the strongest humoral response and induced the highest interferon-γ levels in patients with a positive cellular response against the spike protein. Antiproliferative agents were negatively associated with both the antibody and cellular responses. A transient elevation in creatinine levels was noted in approximately half of the patients after the first dose of mRNA1273 or ChadOx1, and only one of them presented with borderline cellular rejection without definite causality to vaccination. In conclusion, mRNA1273 had better immunogenicity than the other vaccines. Further, renal function needs to be carefully monitored after vaccination, and vaccination strategies should be tailored according to the transplant status and vaccine characteristics.

Gender-Specific Determinants of eHealth Literacy: Results from an Adolescent Internet Behavior Survey in Taiwan.

Adolescents' Internet health information usage has rarely been investigated. Adolescents seek all kinds of information from the Internet, including health information, which affects their Health Literacy that eHealth Literacy (eHL). This study is a retrospective observational study, we have total of 500 questionnaires were distributed, 87% of which were recovered, and we explored the channels that adolescents use to search for health information, their ability to identify false information, and factors affecting the type and content of health information queried. Adolescents believe that the Internet is a good means to seek health information because of its instant accessibility, frequent updating, convenience, and lack of time limits. More boys use the Internet to seek health information than girls in junior high schools (p = 0.009). The Internet is an important source of health information for adolescents but contains extensive misinformation that adolescents cannot identify. Additionally, adolescent boys and girls are interested in different health issues. Therefore, the government should implement measures to minimize misinformation on the Internet and create a healthy, educational online environment to promote Adolescents' eHealth Literacy (eHL).

In-Situ Synchrotron SAXS and WAXS Investigation on the Deformation of Single and Coaxial Electrospun P(VDF-TrFE)-Based Nanofibers.

Coaxial core/shell electrospun nanofibers consisting of ferroelectric P(VDF-TrFE) and relaxor ferroelectric P(VDF-TrFE-CTFE) are tailor-made with hierarchical structures to modulate their mechanical properties with respect to their constituents. Compared with two single and the other coaxial membranes prepared in the research, the core/shell-TrFE/CTFE membrane shows a more prominent mechanical anisotropy between revolving direction (RD) and cross direction (CD) associated with improved resistance to tensile stress for the crystallite phase stability and good strength-ductility balance. This is due to the better degree of core/shell-TrFE-CTFE nanofiber alignment and the crystalline/amorphous ratio. The coupling between terpolymer P(VDF-TrFE-CTFE) and copolymer P(VDF-TrFE) is responsible for phase stabilization, comparing the core/shell-TrFE/CTFE with the pristine terpolymer. Moreover, an impressive collective deformation mechanism of a two-length scale in the core/shell composite structure is found. We apply in-situ synchrotron X-ray to resolve the two-length scale simultaneously by using the small-angle X-ray scattering to characterize the nanofibers and the wide-angle X-ray diffraction to identify the phase transformations. Our findings may serve as guidelines for the fabrication of the electrospun nanofibers used as membranes-based electroactive polymers.

Microstructure and Biological Properties of Electrospun In Situ Polymerization of Polycaprolactone-Graft-Polyacrylic Acid Nanofibers and Its Composite Nanofiber Dressings.

In this study, polycaprolactone (PCL)- and poly(acrylic acid) (PAA)-based electrospun nanofibers were prepared for the carriers of antimicrobials and designed composite nanofiber mats for chronic wound care. The PCL- and PAA-based electrospun nanofibers were prepared through in situ polymerization starting from PCL and acrylic acid (AA). Different amounts of AA were introduced to improve the hydrophilicity of the PCL electrospun nanofibers. A compatibilizer and a photoinitiator were then added to the electrospinning solution to form a grafted structure composed of PCL and PAA (PCL-g-PAA). The grafted PAA was mainly located on the surface of a PCL nanofiber. The optimization of the composition of PCL, AA, compatibilizer, and photoinitiator was studied, and the PCL-g-PAA electrospun nanofibers were characterized through scanning electron microscopy and 1H-NMR spectroscopy. Results showed that the addition of AA to PCL improved the hydrophilicity of the electrospun PCL nanofibers, and a PCL/AA ratio of 80/20 presented the best composition and had smooth nanofiber morphology. Moreover, poly[2 -(tert-butylaminoethyl) methacrylate]-grafted graphene oxide nanosheets (GO-g-PTA) functioned as an antimicrobial agent and was used as filler for PCL-g-PAA nanofibers in the preparation of composite nanofiber mats, which exerted synergistic effects promoted by the antibacterial properties of GO-g-PTA and the hydrophilicity of PCL-g-PAA electrospun nanofibers. Thus, the composite nanofiber mats had antibacterial properties and absorbed body fluids in the wound healing process, thereby promoting cell proliferation. The biodegradation of the PCL-g-PAA electrospun nanofibers also demonstrated an encouraging result of three-fold weight reduction compared to the neat PCL nanofiber. Our findings may serve as guidelines for the fabrication of electrospun nanofiber composites that can be used mats for chronic wound care.

Tunable Mechanical and Electrical Properties of Coaxial Electrospun Composite Nanofibers of P(VDF-TrFE) and P(VDF-TrFE-CTFE).

The coaxial core/shell composite electrospun nanofibers consisting of relaxor ferroelectric P(VDF-TrFE-CTFE) and ferroelectric P(VDF-TrFE) polymers are successfully tailored towards superior structural, mechanical, and electrical properties over the individual polymers. The core/shell-TrFE/CTFE membrane discloses a more prominent mechanical anisotropy between the revolving direction (RD) and cross direction (CD) associated with a higher tensile modulus of 26.9 MPa and good strength-ductility balance, beneficial from a better degree of nanofiber alignment, the increased density, and C-F bonding. The interfacial coupling between the terpolymer P(VDF-TrFE-CTFE) and copolymer P(VDF-TrFE) is responsible for comparable full-frequency dielectric responses between the core/shell-TrFE/CTFE and pristine terpolymer. Moreover, an impressive piezoelectric coefficient up to 50.5 pm/V is achieved in the core/shell-TrFE/CTFE composite structure. Our findings corroborate the promising approach of coaxial electrospinning in efficiently tuning mechanical and electrical performances of the electrospun core/shell composite nanofiber membranes-based electroactive polymers (EAPs) actuators as artificial muscle implants.

Association Between Statin Use and Exacerbation of Chronic Obstructive Pulmonary Disease Among Patients Receiving Corticosteroids.

PURPOSE: The role of statins as anti-inflammatory drugs in chronic obstructive pulmonary disease (COPD) is controversial. This study aimed to determine the efficacy of statins used with or without corticosteroids in COPD patients. PATIENTS AND METHODS: This was a retrospective cohort study and used the two million outpatients and inpatients in Taiwan's Longitudinal Health Insurance Database covering 2000 to 2015. A total of 92,460 patients were identified in this study. We divided COPD patients into four groups by auditing each patient's medication (statins used or not; corticosteroids used or not) and used Cox regression to analyze and compare the effects of statins in COPD patients with or without corticosteroids. RESULTS: In terms of all COPD patients, our findings were consistent with previous studies showing that statins decreased COPD-related hospitalization and mortality rates. However, the beneficial effects were only observed in younger patients or those not taking corticosteroids in further analysis. Statins significantly decreased hospitalization and mortality rates in the non-corticosteroids groups. The hazard ratios increased with age and were not statistically significant for patients > 70 years old. Statins did not significantly decrease ED visits, hospitalization, and mortality in corticosteroids groups. CONCLUSION: Statins decreased hospitalization and mortality rates in COPD patients not taking corticosteroids but were not efficacious in patients on corticosteroids therapy. Furthermore, the beneficial effects of statins gradually decreased with patient age. Based on the findings, statins used in COPD patients may need to consider the patient age and corticosteroids used or not.

A panel of anti-influenza virus nucleoprotein antibodies selected from phage-displayed synthetic antibody libraries with rapid diagnostic capability to distinguish diverse influenza virus subtypes.

Immunoassays based on sandwich immuno-complexes of capture and detection antibodies simultaneously binding to the target analytes have been powerful technologies in molecular analyses. Recent developments in single molecule detection technologies enable the detection limit of the sandwich immunoassays approaching femtomolar (10-15 M), driving the needs of developing sensitive and specific antibodies for ever-increasingly broad applications in detecting and quantifying biomarkers. The key components underlying the sandwich immunoassays are antibody-based affinity reagents, for which the conventional sources are mono- or poly-clonal antibodies from immunized animals. The downsides of the animal-based antibodies as affinity reagents arise from the requirement of months of development timespan and limited choices of antibody candidates due to immunodominance of humoral immune responses in animals. Hence, developing animal antibodies capable of distinguishing highly related antigens could be challenging. To overcome the limitation imposed by the animal immune systems, we developed an in vitro methodology based on phage-displayed synthetic antibody libraries for diverse antibodies as affinity reagents against closely related influenza virus nucleoprotein (NP) subtypes, aiming to differentiating avian influenza virus (H5N1) from seasonal influenza viruses (H1N1 and H3N2), for which the NPs are closely related by 90-94% in terms of pairwise amino acid sequence identity. We applied the methodology to attain, within four weeks, a panel of IgGs with distinguishable specificities against a group of representative NPs with pairwise amino acid sequence identities up to more than 90%, and the antibodies derived from the antibody libraries without further affinity refinement had comparable affinity of mouse antibodies to the NPs with the detection limit less than 1 nM of viral NP from lysed virus with sandwich ELISA. The panel of IgGs were capable of rapidly distinguishing infections due to virulent avian influenza virus from infections of seasonal flu, in responding to a probable emergency scenario where avian influenza virus would be transmissible among humans overlapping with the seasonal influenza infections. The results indicate that the in vitro antibody development methodology enables developing diagnostic antibodies that would not otherwise be available from animal-based antibody technologies.

Anserine Reverses Exercise-Induced Oxidative Stress and Preserves Cellular Homeostasis in Healthy Men.

The study tested whether anserine (beta-alanyl-3-methyl-l-histidine), the active ingredient of chicken essence affects exercise-induced oxidative stress, cell integrity, and haematology biomarkers. In a randomized placebo-controlled repeated-measures design, ten healthy men ingested anserine in either a low dose (ANS-LD) 15 mg.kg-1.bw-1, high dose (ANS-HD) 30 mg.kg-1.bw-1, or placebo (PLA), following an exercise challenge (time to exhaustion), on three separate occasions. Anserine supplementation increased superoxide dismutase (SOD) by 50% (p < 0.001, effect size d = 0.8 for both ANS-LD and ANS-HD), and preserved catalase (CAT) activity suggesting an improved antioxidant activity. However, both ANS-LD and ANS-HD elevated glutathione disulfide (GSSG), (both p < 0.001, main treatment effect), and consequently lowered the glutathione to glutathione disulfide (GSH/GSSG) ratio compared with PLA (p < 0.01, main treatment effect), without significant effects on thiobarbituric acid active reactive substances (TBARS). Exercise-induced cell damage biomarkers of glutamic-oxaloacetic transaminase (GOT) and myoglobin were unaffected by anserine. There were slight but significant elevations in glutamate pyruvate transaminase (GPT) and creatine kinase isoenzyme (CKMB), especially in ANS-HD (p < 0.05) compared with ANS-LD or PLA. Haematological biomarkers were largely unaffected by anserine, its dose, and without interaction with post exercise time-course. However, compared with ANS-LD and PLA, ANS-HD increased the mean cell volume (MCV), and decreased the mean corpuscular haemoglobin concentration (MCHC) (p < 0.001). Anserine preserves cellular homoeostasis through enhanced antioxidant activity and protects cell integrity in healthy men, which is important for chronic disease prevention. However, anserine temporal elevated exercise-induced cell-damage, together with enhanced antioxidant activity and haematological responses suggest an augmented exercise-induced adaptative response and recovery.

Intensive measures of luminescence in GaN/InGaN heterostructures.

The intensive measures of luminescence in a GaN/InGaN multiple quantum well system are used to examine the thermodynamics and phenomenological structure. The radiative /nonradiative transitions along with absorbed or emitted phonons that occur between the different quantum states of the electrons and holes associated with these processes make the quantum efficiency of a semiconductor nanosystem in an equilibrium state an extensive property. It has long been recognized that tuning of the indium (In) composition in InGaN interlayers gives the potential to obtain a spectrum in the near-infrared to near-ultraviolet spectral range. The thermodynamic intensive properties, including the Debye temperature, carrier temperature, and junction temperature, are the most appropriate metrics to describe the optical-related interactions inherent in a given heterostructure and so can be used as the state variables for understanding the quantum exchange behaviors. The energetic features of the quantum processes are characterized based on analysis of the intensive parameters as determined by means of electroluminescence (EL) and photoluminescence (PL) spectroscopy and current-voltage measurement and then correlated with the designed InGaN/GaN microstructures. According to the McCumber-Sturge theory, the EL and PL Debye temperatures obtained experimentally signal the strength of the electron-phonon and photon-phonon interaction, respectively, while the EL and PL carrier/junction temperatures correspond to the carrier localization. Higher EL Debye temperatures and lower EL carrier/junction temperatures reflect significantly higher luminescence quantum yields, indicative of electron-phonon coupling in the transfer of thermal energy between the confined electrons and the enhancement by excited phonons of heat-assisted emissions. On the other hand, the observation of low luminescence efficiency, corresponding to the lower PL Debye temperatures and higher PL carrier/junction temperatures, is attributed to photon-phonon coupling. These findings are in good accordance to the dependence of the EL and PL quantum efficiency on the In-content of the InGaN/GaN barriers, suggesting that the characteristic Debye and carrier/junction temperatures are intensive parameters useful for assessing the optical properties of a nano-engineered semiconductor heterostructure.

A randomized, open-label pharmacokinetic trial of tacrolimus extended-release dosing in obese de novo kidney transplant recipients.

PURPOSE: Tacrolimus extended-release (TAC-ER; Astagraf XL® ) is utilized in many immunosuppressive regimens post-renal transplantation. Current dosing recommendation for the TAC-ER in renal transplant is 0.15-0.2 mg/kg/day administered once daily. The purpose of this study was to determine the best method of dosing TAC-ER in obese renal transplant recipients. METHODS: De novo obese kidney transplant recipients were randomized to receive TAC-ER 0.15 mg/kg/day based on either adjusted body weight (aBW) or ideal body weight (IBW). Post-transplant patients underwent three pharmacokinetic assessments over 14 days. The primary endpoint was the difference in TAC-ER exposure (AUC0-24) in obese patients dosed using aBW compared with IBW. RESULTS: A total of 20 obese renal transplant recipients were randomized to participate in the study (10 aBW and 10 IBW). Results of the primary outcome (AUC0-24) on Study Day 1, 7, and 14 were not statistically different between the two groups. There was no difference in the number of days to therapeutic trough concentration between the two dosing weights (aBW = 5.1, IBW = 4.9, days; P = 0.90). CONCLUSION: In a population of obese renal transplant recipients, comparable trough concentrations and overall exposure in both groups indicate that IBW may be preferred, as less initial drug was needed to attain adequate exposure.

High throughput discovery of influenza virus neutralizing antibodies from phage-displayed synthetic antibody libraries.

Pandemic and epidemic outbreaks of influenza A virus (IAV) infection pose severe challenges to human society. Passive immunotherapy with recombinant neutralizing antibodies can potentially mitigate the threats of IAV infection. With a high throughput neutralizing antibody discovery platform, we produced artificial anti-hemagglutinin (HA) IAV-neutralizing IgGs from phage-displayed synthetic scFv libraries without necessitating prior memory of antibody-antigen interactions or relying on affinity maturation essential for in vivo immune systems to generate highly specific neutralizing antibodies. At least two thirds of the epitope groups of the artificial anti-HA antibodies resemble those of natural protective anti-HA antibodies, providing alternatives to neutralizing antibodies from natural antibody repertoires. With continuing advancement in designing and constructing synthetic scFv libraries, this technological platform is useful in mitigating not only the threats of IAV pandemics but also those from other newly emerging viral infections.

Graphene/h-BN Heterostructures for Vertical Architecture of RRAM Design.

The development of RRAM is one of the mainstreams for next generation non-volatile memories to replace the conventional charge-based flash memory. More importantly, the simpler structure of RRAM makes it feasible to be integrated into a passive crossbar array for high-density memory applications. By stacking up the crossbar arrays, the ultra-high density of 3D horizontal RRAM (3D-HRAM) can be realized. However, 3D-HRAM requires critical lithography and other process for every stacked layer, and this fabrication cost overhead increases linearly with the number of stacks. Here, it is demonstrated that the 2D material-based vertical RRAM structure composed of graphene plane electrode/multilayer h-BN insulating dielectric stacked layers, AlOx/TiOx resistive switching layer and ITO pillar electrode exhibits reliable device performance including forming-free, low power consumption (Pset = ~2 µW and Preset = ~0.2 µW), and large memory window (>300). The scanning transmission electron microscopy indicates that the thickness of multilayer h-BN is around 2 nm. Due to the ultrathin-insulating dielectric and naturally high thermal conductivity characteristics of h-BN, the vertical structure combining the graphene plane electrode with multilayer h-BN insulating dielectric can pave the way toward a new area of ultra high-density memory integration in the future.

Dual-functional Memory and Threshold Resistive Switching Based on the Push-Pull Mechanism of Oxygen Ions.

The combination of nonvolatile memory switching and volatile threshold switching functions of transition metal oxides in crossbar memory arrays is of great potential for replacing charge-based flash memory in very-large-scale integration. Here, we show that the resistive switching material structure, (amorphous TiOx)/(Ag nanoparticles)/(polycrystalline TiOx), fabricated on the textured-FTO substrate with ITO as the top electrode exhibits both the memory switching and threshold switching functions. When the device is used for resistive switching, it is forming-free for resistive memory applications with low operation voltage (<± 1 V) and self-compliance to current up to 50 µA. When it is used for threshold switching, the low threshold current is beneficial for improving the device selectivity. The variation of oxygen distribution measured by energy dispersive X-ray spectroscopy and scanning transmission electron microscopy indicates the formation or rupture of conducting filaments in the device at different resistance states. It is therefore suggested that the push and pull actions of oxygen ions in the amorphous TiOx and polycrystalline TiOx films during the voltage sweep account for the memory switching and threshold switching properties in the device.

Iridovirus CARD Protein Inhibits Apoptosis through Intrinsic and Extrinsic Pathways.

Grouper iridovirus (GIV) belongs to the genus Ranavirus of the family Iridoviridae; the genomes of such viruses contain an anti-apoptotic caspase recruitment domain (CARD) gene. The GIV-CARD gene encodes a protein of 91 amino acids with a molecular mass of 10,505 Daltons, and shows high similarity to other viral CARD genes and human ICEBERG. In this study, we used Northern blot to demonstrate that GIV-CARD transcription begins at 4 h post-infection; furthermore, we report that its transcription is completely inhibited by cycloheximide but not by aphidicolin, indicating that GIV-CARD is an early gene. GIV-CARD-EGFP and GIV-CARD-FLAG recombinant proteins were observed to translocate from the cytoplasm into the nucleus, but no obvious nuclear localization sequence was observed within GIV-CARD. RNA interference-mediated knockdown of GIV-CARD in GK cells infected with GIV inhibited expression of GIV-CARD and five other viral genes during the early stages of infection, and also reduced GIV infection ability. Immunostaining was performed to show that apoptosis was effectively inhibited in cells expressing GIV-CARD. HeLa cells irradiated with UV or treated with anti-Fas antibody will undergo apoptosis through the intrinsic and extrinsic pathways, respectively. However, over-expression of recombinant GIV-CARD protein in HeLa cells inhibited apoptosis induced by mitochondrial and death receptor signaling. Finally, we report that expression of GIV-CARD in HeLa cells significantly reduced the activities of caspase-8 and -9 following apoptosis triggered by anti-Fas antibody. Taken together, these results demonstrate that GIV-CARD inhibits apoptosis through both intrinsic and extrinsic pathways.

Recognition of Linear B-Cell Epitope of Betanodavirus Coat Protein by RG-M18 Neutralizing mAB Inhibits Giant Grouper Nervous Necrosis Virus (GGNNV) Infection.

Betanodavirus is a causative agent of viral nervous necrosis syndrome in many important aquaculture marine fish larvae, resulting in high global mortality. The coat protein of Betanodavirus is the sole structural protein, and it can assemble the virion particle by itself. In this study, we used a high-titer neutralizing mAB, RG-M18, to identify the linear B-cell epitope on the viral coat protein. By mapping a series of recombinant proteins generated using the E. coli PET expression system, we demonstrated that the linear epitope recognized by RG-M18 is located at the C-terminus of the coat protein, between amino acid residues 195 and 338. To define the minimal epitope region, a set of overlapping peptides were synthesized and evaluated for RG-M18 binding. Such analysis identified the 195VNVSVLCR202 motif as the minimal epitope. Comparative analysis of Alanine scanning mutagenesis with dot-blotting and ELISA revealed that Valine197, Valine199, and Cysteine201 are critical for antibody binding. Substitution of Leucine200 in the RGNNV, BFNNV, and TPNNV genotypes with Methionine200 (thereby simulating the SJNNV genotype) did not affect binding affinity, implying that RG-M18 can recognize all genotypes of Betanodaviruses. In competition experiments, synthetic multiple antigen peptides of this epitope dramatically suppressed giant grouper nervous necrosis virus (GGNNV) propagation in grouper brain cells. The data provide new insights into the protective mechanism of this neutralizing mAB, with broader implications for Betanodavirus vaccinology and antiviral peptide drug development.

Effects of signal sequence on phage-displayed disulfide-stabilized single chain antibody variable fragment (sc-dsFv) libraries.

Phage-displayed single chain variable fragment (scFv) libraries are powerful tools in antibody engineering. Disulfide-stabilized scFv (sc-dsFv) with an interface disulfide bond is structure-wise more stable than the corresponding scFv. A set of recently discovered signal sequences replacing the wild type (pelB) signal peptidase cleavage site in the c-region has been shown to be effective in rescuing the expression of sc-dsFv libraries on the phage surface. However, the effects of the other regions of the signal sequence on the expression of the sc-dsFv libraries and on the formation of the interface disulfide bond in the phage-displayed sc-dsFv have not been clear. In this work, selected novel signal sequence variants in the h-region were shown to be equally effective in promoting sc-dsFv library expression on the phage surface; the expression level and complexity of the sc-dsFv libraries were comparable to the corresponding scFv libraries produced with the wild-type (pelB) signal sequence. The interface disulfide bond in the phage-displayed sc-dsFv was proven to form to a large extent in the library variant ensemble generated with signal sequence variants in both the h-region and the c-region. The sc-dsFv engineering platform established in this work can be applied to many of the known scFv molecules which are in need of a more stable version for the applications under harsh conditions or for longer shelf-life.

[Loneliness: a concept analysis].

Loneliness is a kind of mood that most people have experienced at one time or another. Individual experiences with loneliness as joyful or painful saturation are highly personal and can be defined only in such a context. Loneliness has differing effects on the long-term health of individuals. Although loneliness impacts greatly on individual health, there is little in the literature related to concept analyses of loneliness. The purpose of this article was to use Walker and Avant's (2005) concept analysis methodology to review conceptual definitions of loneliness, characteristics, antecedents and consequences; construct examples and establish empirical measurements. Results indicate that defining attributes of loneliness included an individual's subjective mood, descriptions of aloneness, depression, desolation or empty feelings, and the perception of the spirit isolated from others. It is hoped that nursing staffs may better understand loneliness through this article, provide an assessment of client loneliness as early as possible, and enhance client health condition.

The genetic background difference between diabetic patients with and without nephropathy in a Taiwanese population by linkage disequilibrium mapping using 382 autosomal STR markers.

The genome-wide linkage disequilibrium screening for loci associated with genetic difference between diabetic patients with and without nephropathy was conducted employing 382 autosomal STR markers involving 185 diabetic subjects. Among them, 25 STR markers showed evidence for nominal association with a difference between the two diabetic groups. To investigate the reliability of the association result, the E2a/Pbx1-activated gene in pre-B cells 1 (EB-1) gene was selected from 267 diabetic subjects for single-nucleotide polymorphism genotyping because its genomic region encircles the significant STR marker D12S346. It is clear that some single-nucleotide polymorphisms and haplotypes of the EB-1 gene are associated with genetic difference between diabetic patients with and without nephropathy. This study further indicates that diabetic nephropathy is indeed a genetically heterogeneous group of diseases with similar clinical phenotypes.