Experiences Pertaining to Successful Aging in Middle-Aged Women in South Korea.

This study aimed to analyze and gain an in-depth understanding of the experiences pertaining to successful aging in middle-aged women in South Korea. A sample of 12 middle-aged women, capable of sharing their lived experiences, was divided into three age-based groups: those in their 40s, those in their 50s, and those aged 60-65 years. The collected data were analyzed using Colaizzi's phenomenological method. Five theme clusters and ten themes emerged. The experiences of successful aging among middle-aged women were categorized as: "Coping with changes in the mind and body", "Financially stable life", "Undergoing the aging process with a healthy family", "Preparations for dying well", and "Pursuing a meaningful, harmonious life". These findings highlight the need for programs that prepare middle-aged women to positively accept and enjoy older adulthood by identifying and addressing the factors essential for successful aging and reducing any negative emotions attached to aging and older adulthood.

Paraspinal muscles atrophy on both sides and at multiple levels after unilateral lumbar partial discectomy.

To identify the changes in cross-sectional areas (CSAs) and fatty infiltration of both sides of the paravertebral muscles and their associations with prognostic factors in patients who underwent unilateral lumbar discectomy. We retrospectively reviewed 27 patients who underwent magnetic resonance imaging before and after 1- or 2-level lumbar discectomy. The CSAs and functional cross-sectional areas of the paraspinal muscles were bilaterally measured from L1 to L2 to L5 to S1 based on T2-weighted axial images. These parameters were compared pre-and postoperatively. CSAs and functional cross-sectional areas decreased also in non-operative, non-surgical levels, not only in operated levels after discectomy. In the correlation analysis, the CSA of psoas major muscle at L1 to L2 was significantly decreased in patients with lower preoperative lordosis (r = 0.598, P = .040). The postoperative CSA of psoas major muscle at L4 to L5 was lower in those with the higher Pfirrmann grade (r = -0.590, P = .002); however, the CSA of quadratus lumborum muscle at L1 to L2 showed the opposite result (r = 0.526, P = .036). Similar results were also observed in the partial correlation adjusted for age and postoperative duration. Patients who underwent discectomy experienced overall paraspinal muscle atrophy in the lumbar region, including surgical and non-surgical sites. Such atrophic changes emphasized the need for core strengthening and lumbar rehabilitation from the early period after partial discectomy.

Aromatherapy Massage for Relief of Pruritus and Stress in Older Women.

Context: Pruritus is a common skin disease among older adults. With aging, there is a decrease in skin elasticity and thickness, and vascular changes occur that decrease the skin's ability to retain moisture. Objective: To investigate the effects of aromatherapy massage on pruritis and stress levels in older women. Design: This was a nonequivalence, pre-post, quasi-experimental study. To enhance the appropriateness and accuracy of the intervention, a pilot study was conducted before the main study. Setting: The participants were recruited from six senior citizens' centers in Changwon City, Gyeongnam, South Korea. Participants: The participants were 64 women ≥65 years of age with an average age of 80.7 years and 79.7 years in the intervention and the control groups, respectively. Intervention: The intervention comprised aromatherapy massage with a blend of three essential oils: 1 mL of lavender, 0.25 mL of Roman chamomile, and 0.25 mL of sandalwood diluted to 1.5% with a sweet-almond carrier oil. The control group received massages with 0.25% sandalwood oil. Outcome Measures: The symptom score table of the Pruritus Score Scale was used to measure the degree, area, and frequency of pruritus and its impact on everyday life. The study also measured skin hydration levels using moisture-measuring module sensor, skin pH using the Howskin device, and stress using the Perceived Stress Scale. Results: Of the 64 initial participants, 5 dropped out of the study, resulting in 59 being included in the analysis. A significant difference was found between the intervention and control groups regarding relief of pruritus (U = 302.5, P = .039) and stress levels (U = -6.36, P < .001). No adverse effects were observed. Conclusions: Aromatherapy massage can be an effective intervention to decrease pruritus and stress in older women. Further studies with larger samples that also include men are required to confirm the generalizability of these results.

Rapid access to polycyclic N-heteroarenes from unactivated, simple azines via a base-promoted Minisci-type annulation.

Conventional synthetic methods to yield polycyclic heteroarenes have largely relied on metal-mediated arylation reactions requiring pre-functionalised substrates. However, the functionalisation of unactivated azines has been restricted because of their intrinsic low reactivity. Herein, we report a transition-metal-free, radical relay π-extension approach to produce N-doped polycyclic aromatic compounds directly from simple azines and cyclic iodonium salts. Mechanistic and electron paramagnetic resonance studies provide evidence for the in situ generation of organic electron donors, while chemical trapping and electrochemical experiments implicate an iodanyl radical intermediate serving as a formal biaryl radical equivalent. This intermediate, formed by one-electron reduction of the cyclic iodonium salt, acts as the key intermediate driving the Minisci-type arylation reaction. The synthetic utility of this radical-based annulative π-extension method is highlighted by the preparation of an N-doped heptacyclic nanographene fragment through fourfold C-H arylation.

Effect of Cognition Recovery by Repetitive Transcranial Magnetic Stimulation on Ipsilesional Dorsolateral Prefrontal Cortex in Subacute Stroke Patients.

OBJECTIVE: To demonstrate the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the ipsilesional dorsolateral prefrontal cortex (DLPFC) on neurological recovery in patients with subacute phase stroke. METHODS: Patients with supratentorial hemispheric stroke who were hospitalized for intensive rehabilitation in the subacute phase were enrolled for this retrospective analysis. Two groups of patients were selected: the rTMS group who received high-frequency (20 Hz) rTMS ≥ 5 times over the ipsilesional DLPFC, and a control group who did not receive any rTMS. The patients were further divided into groups with right- or left-side brain lesions. Functional measurements for cognitive ability, mood, speech, and activities of daily living, which were assessed at baseline and at the 1-month follow-up as a routine clinical practice, were used for analyses. RESULTS: Among 270 patients with available clinical data, 133 (women, 51; age, 61.0 ± 13.8 years) met the inclusion criteria and were enrolled for analysis. There were no differences in demographic data and functional scores at baseline between the rTMS (n = 49) and control (n = 84) groups. The rTMS group showed a higher gain in the mini-mental status examination (MMSE) total score and subscores of all domains, forward digit span, and FIM-cognition than the control group (P < 0.05). Among the patients with left hemispheric lesions (n = 57), the rTMS group showed better outcomes in cognition and depression through scores of total and "attention and concentration" subscores of MMSE, FIM-cognition, and the geriatric depression scale (P < 0.05). Among the patients with right hemispheric lesions (n = 76), the rTMS group showed better outcomes in cognition through the MMSE total score and subscores of "attention and concentration," "registration," and "recall," and scores of both forward and backward digit spans (P < 0.05). CONCLUSION: High-frequency rTMS over the ipsilesional DLPFC has beneficial effects on the recovery of cognition on both sides as well as mood in patients with left-sided hemispheric lesions.

Formation and Growth of Intermetallic Compounds during Reactions between Liquid Gallium and Solid Nickel.

Liquid metals, such as Ga and eutectic Ga-In, have been extensively studied for various applications, including flexible and wearable devices. For applying liquid metal to electronic devices, interconnection with the various metal electrodes currently in use, and verifying their mechanical reliability are essential. Here, detailed investigations of the formation and growth of intermetallic compounds (IMCs) during the reactions between liquid Ga and solid nickel were conducted. Ga and Ni were reacted at 250, 300, and 350 °C for 10-240 min. The IMC double layer observed after the reactions contained a Ga7Ni3 bottom layer formed during the reactions, and a GaxNi top layer (with 89-95 at.% of Ga) precipitated during cooling. Numerous empty channels exist between the rod-type Ga7Ni3 IMCs. Ga7Ni3 growth occurred only in the vertical direction, without lateral coarsening and merging between the rods. The time exponents were measured at 1.1-1.5, implying that the reaction kinetics were near-interface reaction-controlled. The activation energy for Ga7Ni3 growth was determined as 49.1 kJ/mol. The experimental results of the Ga-Ni reaction study are expected to provide important information for incorporating liquid metals into electronic devices in the future.

Effects of the Polarity and Bulkiness of End-Functionalized Side Chains on the Charge Transport of Dicyanovinyl-End-Capped Diketopyrrolopyrrole-Based n-Type Small Molecules.

When designing organic semiconductors, side-chain engineering is as important as modifying the conjugated backbone, which has a significant impact on molecular ordering, morphology, and thus electronic device performance. We have developed three dicyanovinyl-end-capped donor-acceptor diketopyrrolopyrrole-based n-type small molecules (C2C9CN, SiC4CN, and EH4PCN) bearing an identical length of alkyl spacer yet different end-functionalized side chains (i.e., alkyl-, siloxane-, and phosphonate-end pendants). The effects of the end-functionalized side chains on the intrinsic molecular properties, microstructure, and charge transport of the small-molecule series were investigated. In comparison with the alkyl-end side chains, incorporating siloxane-end side chains into the backbone facilitates 2D edge-on oriented high intergrain connectivity/crystallinity and compatibility with the substrate surface, whereas the phosphonate-end analogues have an adverse effect on the film-forming quality due to high polarity. Thereby, an organic field-effect transistor fabricated by SiC4CN shows the best electron mobility up to 1.59 × 10-1 cm2 V-1 s-1 along with a high current on/off ratio >105. This study contributes to our understanding of the role of the end-functionalized side chains (e.g., the effects of polarity and bulkiness of the end groups) for the development of high-performance semiconductors.

Cytoplasmic TDP-43 is involved in cell fate during stress recovery.

Transactive response DNA binding protein 43 (TDP-43) is an RNA processing protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Nuclear TDP-43 mislocalizes in patients to the cytoplasm, where it forms ubiquitin-positive inclusions in affected neurons and glia. Physiologically, cytoplasmic TDP-43 is associated with stress granules (SGs). Here, we explored TDP-43 cytoplasmic accumulation and stress granule formation following osmotic and oxidative stress. We show that sorbitol drives TDP-43 redistribution to the cytoplasm, while arsenite induces the recruitment of cytoplasmic TDP-43 to TIA-1 positive SGs. We demonstrate that inducing acute oxidative stress after TDP-43 cytoplasmic relocalization by osmotic shock induces poly (ADP-ribose) polymerase (PARP) cleavage, which triggers cellular toxicity. Recruitment of cytoplasmic TDP-43 to polyribosomes occurs in an SH-SY5Y cellular stress model and is observed in FTD brain lysate. Moreover, the processing body (P-body) marker DCP1a is detected in TDP-43 granules during recovery from stress. Overall, this study supports a central role for cytoplasmic TDP-43 in controlling protein translation in stressed cells.

Tactile Avatar: Tactile Sensing System Mimicking Human Tactile Cognition.

As a surrogate for human tactile cognition, an artificial tactile perception and cognition system are proposed to produce smooth/soft and rough tactile sensations by its user's tactile feeling; and named this system as "tactile avatar". A piezoelectric tactile sensor is developed to record dynamically various physical information such as pressure, temperature, hardness, sliding velocity, and surface topography. For artificial tactile cognition, the tactile feeling of humans to various tactile materials ranging from smooth/soft to rough are assessed and found variation among participants. Because tactile responses vary among humans, a deep learning structure is designed to allow personalization through training based on individualized histograms of human tactile cognition and recording physical tactile information. The decision error in each avatar system is less than 2% when 42 materials are used to measure the tactile data with 100 trials for each material under 1.2N of contact force with 4cm s-1 of sliding velocity. As a tactile avatar, the machine categorizes newly experienced materials based on the tactile knowledge obtained from training data. The tactile sensation showed a high correlation with the specific user's tendency. This approach can be applied to electronic devices with tactile emotional exchange capabilities, as well as advanced digital experiences.

A Hippocampus-Inspired Dual-Gated Organic Artificial Synapse for Simultaneous Sensing of a Neurotransmitter and Light.

Organic neuromorphic devices and sensors that mimic the functions of chemical synapses and sensory perception in humans have received much attention for next-generation computing and integrated logic circuits. Despite recent advances, organic artificial synapses capable of detecting both neurotransmitters in liquid environments and light are not reported. Herein, inspired by hippocampal synapses, a dual-gate organic synaptic transistor platform with a photoconductive polymer semiconductor, a ferroelectric insulator of P(VDF-TrFE), and an extended-gate electrode functionalized with boronic acid is developed to simultaneously detect the neurotransmitter dopamine and light. The developed synaptic transistor enables memory consolidation upon repetitive exposure to dopamine and polychromatic light, exhibiting effectively modulated postsynaptic currents. This proof-of-concept hippocampal-synapse-mimetic organic neuromorphic system combining a chemical sensor and a photosensor opens new possibilities for developing low-power organic artificial synaptic multisensors and light-induced memory consolidative artificial synapses, and can also contribute to the development of human-machine interfaces.

Eye Fixation-Related Potentials during Visual Search on Acquaintance and Newly-Learned Faces.

Searching familiar faces in the crowd may involve stimulus-driven attention by emotional significance, together with goal-directed attention due to task-relevant needs. The present study investigated the effect of familiarity on attentional processes by exploring eye fixation-related potentials (EFRPs) and eye gazes when humans searched for, among other distracting faces, either an acquaintance's face or a newly-learned face. Task performance and gaze behavior were indistinguishable for identifying either faces. However, from the EFRP analysis, after a P300 component for successful search of target faces, we found greater deflections of right parietal late positive potentials in response to newly-learned faces than acquaintance's faces, indicating more involvement of goal-directed attention in processing newly-learned faces. In addition, we found greater occipital negativity elicited by acquaintance's faces, reflecting emotional responses to significant stimuli. These results may suggest that finding a familiar face in the crowd would involve lower goal-directed attention and elicit more emotional responses.

Descriptive and functional characterization of epidermal growth factor­like domain 8 in mouse cortical thymic epithelial cells by integrated analysis of gene expression signatures and networks.

Epidermal growth factor­like domain 8 (EGFL8), a newly identified member of the EGFL family, and plays negative regulatory roles in mouse thymic epithelial cells (TECs) and thymocytes. However, the role of EGFL8 in these cells remains poorly understood. In the present study, in order to characterize the function of EGFL8, genome­wide expression profiles in EGFL8­overexpressing or ­silenced mouse cortical TECs (cTECs) were analyzed. Microarray analysis revealed that 458 genes exhibited a >2­fold change in expression levels in the EGFL8­overexpressing vs. the EGFL8­silenced cTECs. Several genes involved in a number of cellular processes, such as the cell cycle, proliferation, growth, migration and differentiation, as well as in apoptosis, reactive oxygen species generation, chemotaxis and immune responses, were differentially expressed in the EGFL8­overexpressing or ­silenced cTECs. WST­1 analysis revealed that that the overexpression of EGFL8 inhibited cTEC proliferation. To investigate the underlying mechanisms of EGFL8 in the regulation of cTEC function, genes related to essential cellular functions were selected. Reverse transcription­polymerase chain reaction analysis revealed that EGFL8 knockdown upregulated the expression of cluster differentiation 74 (CD74), Fas ligand (FasL), C­X­C motif chemokine ligand 5 (CXCL5), CXCL10, CXCL16, C­C motif chemokine ligand 20 (CCL20), vascular endothelial growth factor­A (VEGF­A), interferon regulatory factor 7 (Irf7), insulin­like growth factor binding protein­4 (IGFBP­4), thrombospondin 1 (Thbs1) and nuclear factor κB subunit 2 (NF­κB2) genes, and downregulated the expression of angiopoietin­like 1 (Angptl1), and neuropilin­1 (Nrp1) genes. Additionally, EGFL8 silencing enhanced the expression of anti­apoptotic molecules, such as B­cell lymphoma­2 (Bcl­2) and Bcl­extra large (Bcl­xL), and that of cell cycle­regulating molecules, such as cyclin­dependent kinase 1 (CDK1), CDK4, CDK6 and cyclin D1. Moreover, gene network analysis revealed that EGFL8 exerted negative effects on VEGF­A gene expression. Hence, the altered expression of several genes associated with EGFL8 expression in cTECs highlights the important physiological processes in which EGFL8 is involved, and provides insight into its biological functions.

Mechanical Properties and Bioactivity of Poly(Lactic Acid) Composites Containing Poly(Glycolic Acid) Fiber and Hydroxyapatite Particles.

To enhance the mechanical strength and bioactivity of poly(lactic acid) (PLA) to the level that can be used as a material for spinal implants, poly(glycolic acid) (PGA) fibers and hydroxyapatite (HA) were introduced as fillers to PLA composites. To improve the poor interface between HA and PLA, HA was grafted by PLA to form HA-g-PLA through coupling reactions, and mixed with PLA. The size of the HA particles in the PLA matrix was observed to be reduced from several micrometers to sub-micrometer by grafting PLA onto HA. The tensile and flexural strength of PLA/HA-g-PLA composites were increased compared with those of PLA/HA, apparently due to the better dispersion of HA and stronger interfacial adhesion between the HA and PLA matrix. We also examined the effects of the length and frequency of grafted PLA chains on the tensile strength of the composites. By the addition of unidirectionally aligned PGA fibers, the flexural strength of the composites was greatly improved to a level comparable with human compact bone. In the bioactivity tests, the growth of apatite on the surface was fastest and most uniform in the PLA/PGA fiber/HA-g-PLA composite.

An MG53-IRS1-interaction disruptor ameliorates insulin resistance.

Mitsugumin 53 (MG53) is an E3 ligase that induces insulin receptor substrate-1 (IRS-1) ubiquitination and degradation in skeletal muscle. We previously demonstrated that the pharmaceutical disruption of the MG53-IRS-1 interaction improves insulin sensitivity by abrogating IRS-1 ubiquitination and increasing IRS-1 levels in C2C12 myotubes. Here, we developed a novel MG53-IRS-1 interaction disruptor (MID-00935) that ameliorates insulin resistance in diet-induced obese (DIO) mice. MID-00935 disrupted the molecular interaction of MG53 and IRS-1, abrogated MG53-induced IRS-1 ubiquitination and degradation and improved insulin signaling in C2C12 myotubes. Oral administration of MID-00935 increased insulin-induced IRS-1, Akt, and Erk phosphorylation via increasing IRS-1 levels in the skeletal muscle of DIO mice. In DIO mice, MID-00935 treatment lowered fasting blood glucose levels and improved glucose disposal in glucose and insulin tolerance tests. These results suggest that MID-00935 may be a potential muscle-targeting drug candidate for treating insulin resistance.

Tunneled Mesoporous Carbon Nanofibers with Embedded ZnO Nanoparticles for Ultrafast Lithium Storage.

Carbon and metal oxide composites have received considerable attention as anode materials for Li-ion batteries (LIBs) owing to their excellent cycling stability and high specific capacity based on the chemical and physical stability of carbon and the high theoretical specific capacity of metal oxides. However, efforts to obtain ultrafast cycling stability in carbon and metal oxide composites at high current density for practical applications still face important challenges because of the longer Li-ion diffusion pathway, which leads to poor ultrafast performance during cycling. Here, tunneled mesoporous carbon nanofibers with embedded ZnO nanoparticles (TMCNF/ZnO) are synthesized by electrospinning, carbonization, and postcalcination. The optimized TMCNF/ZnO shows improved electrochemical performance, delivering outstanding ultrafast cycling stability, indicating a higher specific capacity than previously reported ZnO-based anode materials in LIBs. Therefore, the unique architecture of TMCNF/ZnO has potential for use as an anode material in ultrafast LIBs.

Ultrafast Lithium Storage Using Antimony-Doped Tin Oxide Nanoparticles Sandwiched between Carbon Nanofibers and a Carbon Skin.

Metal oxides as anode materials for Li-ion batteries (LIBs) are of significant interest to many potential technologies because of their high theoretical capacity value, low price, and environmentally friendly features. In spite of these considerable benefits and ongoing progress in the field, momentous challenges exist, related with structural disintegration due to volume expansion of electrode materials. This leads to rapid capacity decline and must be resolved in order to progress for realistic utilization of LIBs with ultrafast cycling stability. This article proposes a novel architecture of Sb-doped SnO2 nanoparticles sandwiched between carbon nanofiber and carbon skin (CNF/ATO/C) using electrospinning and hydrothermal methods. The CNF/ATO/C exhibits superb electrochemical behavior such as high specific capacity and outstanding cycling stability (705 mA h g-1 after 100 cycles), outstanding high-rate performance (411 mA h g-1 at 2000 mA g-1), and ultrafast cycling stability (347 mA h g-1 at 2000 mA g-1 after 100 cycles), which is high compared to any reported value using SnO2-based anode materials. Thus, this unique architecture furnishes profitable effects, including electroactive sites, structural stability, and electrical conductivity, which can potentially be realizes for ultrafast LIBs.

Carbon-Encapsulated Hollow Porous Vanadium-Oxide Nanofibers for Improved Lithium Storage Properties.

Carbon-encapsulated hollow porous vanadium-oxide (C/HPV2O5) nanofibers have been fabricated using electrospinning and postcalcination. By optimized postcalcination of vanadium-nitride and carbon-nanofiber composites at 400 °C for 30 min, we synthesized a unique architecture electrode with interior void spaces and well-defined pores as well as a uniform carbon layer on the V2O5 nanofiber surface. The optimized C/HPV2O5 electrode postcalcined at 400 °C for 30 min showed improved lithium storage properties with high specific discharge capacities, excellent cycling durability (241 mA h g(-1) at 100 cycles), and improved high-rate performance (155 mA h g(-1) at 1000 mA g(-1)), which is the highest performance in comparison with previously reported V2O5-based cathode materials. The improved electrochemical feature is due to the attractive properties of the carbon-encapsulated hollow porous structure: (I) excellent cycling durability with high specific capacity relative to the adoption of carbon encapsulation as a physical buffer layer and the effective accommodation of volume changes due to the hollow porous structure, (II) improved high-rate performance because of a shorter Li-ion diffusion pathway resulting from interior void spaces and well-defined pores at the surface. This unique electrode structure can potentially provide new cathode materials for high-performance lithium-ion batteries.

Evaluation of TV commercials using neurophysiological responses.

BACKGROUND: In recent years, neuroscientific knowledge has been applied to marketing as a novel and efficient means to comprehend the cognitive and behavioral aspects of consumers. A number of studies have attempted to evaluate media contents, especially TV commercials using various neuroimaging techniques such as electroencephalography (EEG). Yet neurophysiological examination of detailed cognitive and affective responses in viewers is still required to provide practical information to marketers. Here, this study develops a method to analyze temporal patterns of EEG data and extract affective and cognitive indices such as happiness, surprise, and attention for TV commercial evaluation. METHODS: Twenty participants participated in the study. We developed the neurophysiological indices for TV commercial evaluation using classification model. Specifically, these model-based indices were customized using individual EEG features. We used a video game for developing the index of attention and four video clips for developing indices of happiness and surprise. Statistical processes including one-way analyses of variance (ANOVA) and the cross validation scheme were used to select EEG features for each index. The EEG features were composed of the combinations of spectral power at selected channels from the cross validation for each individual. The Fisher's linear discriminant classifier (FLDA) was used to estimate each neurophysiological index during viewing four different TV commercials. Post hoc behavioral responses of preference, short-term memory, and recall were measured. RESULTS: Behavioral results showed significant differences for all preference, short-term memory rates, and recall rates between commercials, leading to a 'high-ranked' commercial group and a 'low-ranked' group (P < 0.05). Neural estimation of happiness results revealed a significant difference between the high-ranked and the low-ranked commercials in happiness index (P < 0.01). The order of rankings based on happiness and attention matched well with the order of behavioral response rankings. In the elapsed-time analysis of the highest-ranked commercial, we could point to visual and auditory semantic structures of the commercial that induced increases in the happiness index. CONCLUSIONS: Our results demonstrated that the neurophysiological indices developed in this study may provide a useful tool for evaluating TV commercials.

Rapid immuno-analytical system physically integrated with lens-free CMOS image sensor for food-borne pathogens.

To realize an inexpensive, pocket-sized immunosensor system, a rapid test devise based on cross-flow immuno-chromatography was physically combined with a lens-free CMOS image sensor (CIS), which was then applied to the detection of the food-borne pathogen, Salmonella typhimurium (S. typhimurium). Two CISs, each retaining 1.3 mega pixel array, were mounted on a printed circuit board to fabricate a disposable sensing module, being connectable with a signal detection system. For the bacterial analysis, a cellulose membrane-based immunosensing platform, ELISA-on-a-chip (EOC), was employed, being integrated with the CIS module, and the antigen-antibody reaction sites were aligned with the respective sensor. In such sensor construction, the chemiluminescent signals produced from the EOC are transferred directly into the sensors and are converted to electric signals on the detector. The EOC-CIS integrated sensor was capable of detecting a traceable amount of the bacterium (4.22 × 10(3)CFU/mL), nearly comparable to that adopting a sophisticated detector such as cooled-charge-coupled device, while having greatly reduced dimensions and cost. Upon coupling with immuno-magnetic separation, the sensor showed an additional 67-fold enhancement in the detection limit. Furthermore, a real sample test was carried out for fish muscles inoculated with a sample of 3.3CFU S. typhimurium per 10 g, which was able to be detected earlier than 6h after the onset of pre-enrichment by culture.

Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encoding a novel human factor VIII variant.

Recombinant adeno-associated virus (rAAV) vectors encoding human factor VIII (hFVIII) were systematically evaluated for hemophilia A (HA) gene therapy. A 5.7-kb rAAV-expression cassette (rAAV-HLP-codop-hFVIII-N6) containing a codon-optimized hFVIII cDNA in which a 226 amino acid (aa) B-domain spacer replaced the entire B domain and a hybrid liver-specific promoter (HLP) mediated 10-fold higher hFVIII levels in mice compared with non-codon-optimized variants. A further twofold improvement in potency was achieved by replacing the 226-aa N6 spacer with a novel 17-aa peptide (V3) in which 6 glycosylation triplets from the B domain were juxtaposed. The resulting 5.2-kb rAAV-HLP-codop-hFVIII-V3 cassette was more efficiently packaged within AAV virions and mediated supraphysiologic hFVIII expression (732 ± 162% of normal) in HA knock-out mice following administration of 2 × 10(12) vector genomes/kg, a vector dose shown to be safe in subjects with hemophilia B. Stable hFVIII expression at 15 ± 4% of normal was observed at this dose in a nonhuman primate. hFVIII expression above 100% was observed in 3 macaques that received a higher dose of either this vector or the N6 variant. These animals developed neutralizing anti-FVIII antibodies that were abrogated with transient immunosuppression. Therefore, rAAV-HLP-codop-hFVIII-V3 substantially improves the prospects of effective HA gene therapy.