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Background Inflammatory responses play key roles in the development and progression of many pathological conditions, including neurodegenerative diseases. Accurate quantification of inflammatory factors in saliva would be highly advantageous, given its convenience and non-invasive nature, especially in elderly populations. Methods In this study, we measured levels of 10 cytokines, and the pro-inflammatory factor, YKL-40, in plasma and saliva samples from a cohort of nondemented older adults (n = 71; 62% female; 70.3 ± 6.4 years) using sensitive electrochemiluminescence-based immunoassays. Results We found that the mean levels of all cytokines were higher in saliva compared to plasma and that strong sex differences were observed for both saliva and plasma cytokines in this population. Comparing each cytokine between the two biofluids, we found that levels of interferon-gamma (IFNγ), interleukin (IL)-6 and tumor necrosis factor-alpha (TNFα) in blood were significantly correlated with their respective levels in saliva. We further observed that levels of these cytokines in blood were significantly correlated with additional cytokines in saliva, including IL-1β, IL-10, IL-8, IL12p70 and IL-13. Conclusions These findings show that inflammatory markers in saliva are associated with those found in circulation, suggesting shared inflammatory mechanisms between these two fluids. The higher levels of cytokines measured in saliva suggest that it might represent a better peripheral fluid to gauge inflammatory processes. Finally, our findings of robust sex differences in several salivary cytokines could have important implications for their potential use as disease biomarkers in the elderly and might be related to sex differences in the prevalence of age-related conditions.

For practical implementation, numerous attempts have been made to improve the mechanical durability and response rate of temperature-responsive hydrogels. In this study, the introduction of a cocontinuous structure with polydimethylsiloxane (PDMS), which successfully improved both the properties, was found to reverse the temperature dependence of release behavior. The cocontinuous composites of poly(N-isopropylacrylamide) (PNIPAm) and PDMS were prepared via directional melt crystallization and subsequent infiltration of PDMS. The compressive moduli of composites were more than 30 times higher than those of PNIPAm. Further, the existence of soft hydrophobic PDMS walls against the PNIPAm phases accelerated the deswelling process, and thus, it was more than 2,000 times faster than that of PNIPAm. The deswelling rate increased as the size of PDMS phases increased. The release rate accelerated above the lower critical solution temperature (LCST) and slowed below the LCST, reversibly, thereby opposing the behavior of PNIPAm. Therefore, the fast volume shrinkage of PNIPAm phases confined between PDMS phases is responsible for the unique release behavior of the composites, and not the molecular diffusion processes through hydrogel mesh structures. Collectively, these findings highlight a versatile tool for engineering the release behavior of smart drug carriers based on temperature-responsive hydrogels.

Mnemonic discrimination, a cognitive process that relies on hippocampal pattern separation, is one of the first memory domains to decline in aging and preclinical Alzheimer's disease. We tested whether functional connectivity (FC) within the entorhinal–hippocampal circuit, measured with high-resolution resting state fMRI, is associated with mnemonic discrimination and amyloid-β (Aβ) pathology in a sample of 64 cognitively normal human older adults (mean age, 71.3 ± 6.4 years; 67% female). FC was measured between entorhinal–hippocampal circuit nodes with known anatomical connectivity, as well as within cortical memory networks. Aβ pathology was measured with18F-florbetapir-PET, and neurodegeneration was assessed with subregional volume from structural MRI. Participants performed both object and spatial versions of a mnemonic discrimination task outside of the scanner and were classified into low-performing and high-performing groups on each task using a median split. Low object mnemonic discrimination performance was specifically associated with increased FC between anterolateral entorhinal cortex (alEC) and dentate gyrus (DG)/CA3, supporting the importance of this connection to object memory. This hyperconnectivity between alEC and DG/CA3 was related to Aβ pathology and decreased entorhinal cortex volume. In contrast, spatial mnemonic discrimination was not associated with altered FC. Aβ was further associated with dysfunction within hippocampal subfields, particularly with decreased FC between CA1 and subiculum as well as reduced volume in these regions. Our findings suggest that Aβ may indirectly lead to memory impairment through entorhinal–hippocampal circuit dysfunction and neurodegeneration and provide a mechanism for increased vulnerability of object mnemonic discrimination.SIGNIFICANCE STATEMENTMnemonic discrimination is a critical episodic memory process that is performed in the dentate gyrus (DG) and CA3 subfield of the hippocampus, relying on input from entorhinal cortex. Mnemonic discrimination is particularly vulnerable to decline in older adults; however, the mechanisms behind this vulnerability are still unknown. We demonstrate that object mnemonic discrimination impairment is related to hyperconnectivity between the anterolateral entorhinal cortex and DG/CA3. This hyperconnectivity was associated with amyloid-β pathology and neurodegeneration in entorhinal cortex, suggesting aberrantly increased network activity is a pathological process. Our findings provide a mechanistic explanation of the vulnerability of object compared to spatial mnemonic discrimination in older adults and has translational implications for choice of outcome measures in clinical trials for Alzheimer's disease.

White matter hyperintensities are a marker of small vessel cerebrovascular disease that are strongly related to cognition in older adults. Similarly, medial temporal lobe atrophy is well-documented in aging and Alzheimer’s disease and is associated with memory decline. Here, we assessed the relationship between lobar white matter hyperintensities, medial temporal lobe subregional volumes, and hippocampal memory in older adults.We collected MRI scans in a sample of 139 older adults without dementia (88 females, mean age (SD) = 76.95 (10.61)). Participants were administered the Rey Auditory Verbal Learning Test (RAVLT). Regression analyses tested for associations among medial temporal lobe subregional volumes, regional white matter hyperintensities and memory, while adjusting for age, sex, and education and correcting for multiple comparisons.Increased occipital white matter hyperintensities were related to worse RAVLT delayed recall performance, and to reduced CA1, dentate gyrus, perirhinal cortex (Brodmann area 36), and parahippocampal cortex volumes. These medial temporal lobe subregional volumes were related to delayed recall performance. The association of occipital white matter hyperintensities with delayed recall performance was fully mediated statistically only by perirhinal cortex volume.These results suggest that white matter hyperintensities may be associated with memory decline through their impact on medial temporal lobe atrophy. These findings provide new insights into the role of vascular pathologies in memory loss in older adults and suggest that future studies should further examine the neural mechanisms of these relationships in longitudinal samples.

Inflammatory responses play key roles in the development and progression of many pathological conditions, including neurodegenerative conditions. Accurate quantification of inflammatory factors in saliva would be highly advantageous, given its convenience and non-invasive nature, enabling use as biomarkers for disease processes especially in older adults. However, few studies have attempted to validate salivary assays by directly comparing cytokine levels in blood and saliva samples the same individuals. In this study, we measured levels of 10 cytokines, interferon gamma (IFNg), interleukin (IL)-1 beta (IL-1b), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13 and tumor necrosis factor alpha (TNFa), as well as the inflammatory glycoprotein, YKL-40, in blood and saliva samples from a cohort of nondemented older adults (n = 71; 62% female; mean age 70.3 +/- 6.4 yrs; ) using sensitive electrochemiluminescence-based immunoassays. We found that the mean levels of all cytokines were higher in saliva compared to plasma, and specifically that levels of IL-1b, IL-2, IL-4, IL-12p70 and IL-13 in plasma were below the instrument detection limit for more than 50% of the subjects. We found strong sex differences in both saliva and plasma cytokines, with levels of several salivary cytokines, as well as YKL-40, showing higher concentrations in males compared to females. Comparing each cytokine between the two biofluids, we found that levels of IFNg, IL-6 and TNFa in blood were significantly correlated with their respective levels in saliva. We further observed that levels of these cytokines in blood were significantly correlated with additional cytokines in saliva, including IL-1b, IL-10, IL-8, IL12p70 and IL-13. These findings show that inflammatory markers in saliva are associated with those found in circulation, suggesting that inflammatory mechanisms between these two fluids are, at least to some extent, related. Consistent with prior work, several salivary markers were more likely to surpass the detection threshold than plasma markers, suggesting that salivary assays may, at least in some cases, be more useful for detecting physiological changes. Further our findings of robust sex differences in several salivary cytokines could have important implications for their potential use as health or disease biomarkers.

Hydrogels in nature seldom form a single phase, more often forming structured phases with other soft phases, allowing nature to develop responsive and adaptive strategies. Based on knowledge of how hydrogels are utilized in nature, we developed novel 3D cocontinuous composites from soft materials with extremely different properties, a hydrogel and a silicone. These were successfully prepared by infiltrating liquid polydimethylsiloxane (PDMS) into poly(N-isopropylacrylamide) (PNIPAm) frameworks of aligned pores prepared by directional melt crystallization. The composites had outstanding modulus and swelling ratio compared to other mechanically strong hydrogels. More interestingly, the deswelling kinetics were dramatically accelerated (by a factor of 1000), possibly due to the aligned microchannels and the hydrophobic nature of PDMS. As a result, an actuator movement mimicking flowering could be completed in less than 20 s. This novel and versatile cocontinuous composite strategy could overcome the current ...

OBJECTIVE Discovery of a novel antibody would enable diagnosis and early treatment of autoimmune encephalitis. The aim was to discover a novel antibody targeting a synaptic receptor and characterize the pathogenic mechanism. METHOD We screened for unknown antibodies in serum and cerebrospinal fluid samples from autoimmune encephalitis patients. Samples with reactivity to rat brain sections and no reactivity to conventional antibody tests underwent further processing for antibody discovery, using immunoprecipitation to primary neuronal cells, mass-spectrometry analysis, an antigen-binding assay on an antigen-overexpressing cell line, and an electrophysiological assay with cultured hippocampal neurons. RESULTS Two patients had a novel antibody against CaV α2δ (voltage-gated calcium channel alpha-2/delta subunit). The patient samples stained neuropils of the hippocampus, basal ganglia, and cortex in rat brain sections and bound to a CaV α2δ-overexpressing cell line. Knockdown of CaV α2δ expression in cultured neurons turned off the immunoreactivity of the antibody from the patients to the neurons. The patients were associated with preceding meningitis or neuroendocrine carcinoma and responded to immunotherapy. In cultured neurons, the antibody reduced neurotransmitter release from presynaptic nerve terminals by interfering with tight coupling of calcium channels and exocytosis. INTERPRETATION Here, we discovered a novel autoimmune encephalitis associated with anti-CaV α2δ antibody. Further analysis of the antibody in autoimmune encephalitis might promote early diagnosis and treatment. ANN NEUROL 2021;89:740-752.

Measuring the boundary shape of a deformed liquid microjet is of great importance for using it as an optical resonator for various applications. However, there have been technical challenges due to transparency and uncertainty in the refractive index of the liquid. In this study, we have developed a spectroscopic technique that enables simultaneous determination of the boundary shape and the refractive index of a liquid deformed microjet. A detailed procedure of the technique based on imposition of one-to-one correspondence between experimentally observed resonances and numerically calculated ones are presented along with the measurement results including the refractive index of ethanol between a wavelength of 550 nm and 670 nm.

Arabidopsis thaliana genome encodes ten DUF640 (short for domain of unknown function 640)/ALOG (short for Arabidopsis LSH1 and Oryza G1) proteins, also known as light-dependent short hypocotyl (LSH) proteins. While some of the LSH genes regulate organ boundary determination and shade avoidance response, the function of most of these genes remains largely unknown. In this study, we aimed to characterize the function of AtLSH1 and AtLSH2 in Arabidopsis. We overexpressed AtLSH1 and AtLSH2 (with or without the FLAG tag) in Arabidopsis Col-0 plants under the control of the 35S promoter. We also generated knockout or knockdown lines of these genes by miRNA-induced gene silencing (MIGS). We conducted intensive phenotypic analysis of these transgenic lines, and finally performed RNA-seq analysis of two AtLSH2 overexpression (OX) lines. Although AtLSH1 and AtLSH2 amino acid sequences showed high similarly, AtLSH2-OX lines showed much higher levels of their transcripts than those of AtLSH1-OX lines. Additionally, overexpression of AtLSH1 and AtLSH2 greatly inhibited hypocotyl elongation in a light-independent manner, and reduced both vegetative and reproductive growth. However, knockout or knockdown of both these AtLSH genes did not affect plant phenotype. Gene Ontology (GO) analysis of differentially expressed genes (DEGs) identified by RNA-seq revealed enrichment of the GO term ‘response to stimulus’, included phytohormone-responsive genes; however, genes responsible for the abnormal phenotypes of AtLSH2-OX lines could not be identified. Although our data revealed no close association between light and phytohormone signaling components, overexpression of AtLSH1 and AtLSH2 greatly reduced vegetative and reproductive growth of Arabidopsis plants. This property could be used to generate new plants by regulating expression of AtLSH1 and AtLSH2.

Anthocyanins are generally accumulated within a few layers, including the epidermal cells of leaves and stems in plants. Solanum tuberosum cv. ‘Jayoung’ (hereafter, JY) is known to accumulate anthocyanin both in inner tissues and skins. We discovered that anthocyanin accumulation in the inner tissues of JY was almost diminished (more than 95% was decreased) in tuber induction condition. To investigate the transcriptomic mechanism of anthocyanin accumulation in JY flesh, which can be modulated by growth condition, we performed mRNA sequencing with white-colored flesh tissue of Solanum tuberosum cv. ‘Atlantic’ (hereafter, ‘Daeseo’, DS) grown under canonical growth conditions, a JY flesh sample grown under canonical growth conditions, and a JY flesh sample grown under tuber induction conditions. We could identify 36 common DEGs (differentially expressed genes) in JY flesh from canonical growth conditions that showed JY-specifically increased or decreased expression level. These genes were enriched with flavonoid biosynthetic process terms in GO analysis, as well as gene set enrichment analysis (GSEA) analysis. Further in silico analysis on expression levels of anthocyanin biosynthetic genes including rate-limiting genes such as StCHS and StCHI followed by RT-PCR and qRT-PCR analysis showed a strong positive correlation with the observed phenotypes. Finally, we identified StWRKY44 from 36 common DEGs as a possible regulator of anthocyanin accumulation, which was further supported by network analysis. In conclusion, we identified StWRKY44 as a putative regulator of tuber-induction-dependent anthocyanin accumulation.

In this study, we demonstrate an acoustofluidic device that enables single-file focusing of submicron particles and bacteria using a two-dimensional (2D) acoustic standing wave. The device consists of a 100 µm ✕ 100 µm square channel that supports 2D particle focusing in the channel center at an actuation frequency of 7.39 MHz. This higher actuation frequency compared with conventional bulk acoustic systems enables radiation-force-dominant motion of submicron particles and overcome the classical size limitation (≈ 2 µm) of acoustic focusing. We present acoustic radiation force-based focusing of particles with diameters less than 0.5 µm at a flow rate of 12 µL min-1, and 1.33 µm particles at flow rates up to 80 µL min-1. The device focused 0.25 µm particles by the 2D acoustic radiation force while undergoing a channel cross-section centered, single-vortex acoustic streaming. A suspension of bacteria was also investigated to evaluate the biological relevance of the device, which demonstrated the alignment of bacteria in the channel at a flow rate of up to 20 µL min-1. The developed acoustofluidic device can align submicron particles within a narrow flow stream in a highly robust manner, validating its use as a flow-through focusing chamber to perform high-throughput and accurate flow cytometry of submicron objects.

Red radish (Raphanus sativus L.) cultivars are a rich source of health-promoting anthocyanins and are considered a potential source of natural colorants used in the cosmetic industry. However, the development of red radish cultivars via conventional breeding is very difficult, given the unusual inheritance of the anthocyanin accumulation trait in radishes. Therefore, molecular markers linked with radish color are needed to facilitate radish breeding. Here, we characterized the RsTT8 gene isolated from four radish genotypes with different skin and flesh colors. Sequence analysis of RsTT8 revealed a large number of polymorphisms, including insertion/deletions (InDels), single nucleotide polymorphisms (SNPs), and simple sequence repeats (SSRs), between the red-fleshed and white-fleshed radish cultivars. To develop molecular markers on the basis of these polymorphisms for discriminating between radish genotypes with different colored flesh tissues, we designed four primer sets specific to the RsTT8 promoter, InDel, SSR, and WD40/acidic domain (WD/AD), and tested these primers on a diverse collection of radish lines. Except for the SSR-specific primer set, all primer sets successfully discriminated between red-fleshed and white-fleshed radish lines. Thus, we developed three molecular markers that can be efficiently used for breeding red-fleshed radish cultivars.

Objective To assess the effect of safety claims and warnings on perceptions of consumer chemical products. Background Manufacturers have two contradictory objectives: to increase sales by emphasizing the positive aspects of a product and to protect consumers from hazards of the product. One of the strategies that some manufactures have devised to achieve these goals is to use anti-warnings. Safety claims placed on consumer chemical products were examined to determine if anti-warnings influenced product perceptions. Method Two experiments were conducted. In Experiment 1, three consumer chemical products with manipulated safety claims were presented to 300 participants, who completed a survey to rate their perceptions of the products. In Experiment 2, the same products with the safety claims and added warnings were presented to 600 participants and were rated using the same measurements as Experiment 1. Results Safety claims on product labels decreased perceived hazards compared to no safety claims on products in both Experiments 1 and 2. In Experiment 2, added warnings raised the perceived hazards. Conclusion The use of safety claims on consumer chemical products had an effect on product perceptions by decreasing hazard perceptions. The addition of strong warnings on product labels mitigated this effect. Application This research provides empirical evidence suggesting that the use of safety claims decreased hazard perceptions of potentially hazardous consumer chemical products and can serve as a possible form of anti-warnings.

Overexpression of the naturally occurring intron-retained (IR) forms of radish RsMYB1 and RsTT8 transcripts in Arabidopsis causes a substantial increase in anthocyanin accumulation. The production of anthocyanins in plants is tightly controlled by the MYB–bHLH–WD40 (MBW) complex. In this study, analysis of four radish (Raphanus sativus L.) inbred lines with different colored taproots revealed that regulatory genes of anthocyanin biosynthesis, RsMYB1 and RsTT8, produce three transcripts, one completely spliced and two intron retention (IR1 and IR2) forms. Transcripts RsMYB1-IR1 and RsMYB1-IR2 retained the 1st (380 nt) and 2nd (149 nt) introns, respectively; RsTT8-IR1 retained the 4th intron (113 nt); RsTT8-IR2 retained both the 3rd (128 nt) and 4th introns. Levels of most IR forms were substantially low in radish samples, but the RsTT8-IR2 level was higher than RsTT8 in red skin/red flesh (RsRf) root. Since all IR forms contained a stop codon within the intron, they were predicted to encode truncated proteins with defective interaction domains, resulting in the inability to form the MBW complex in vivo. However, tobacco leaves transiently co-expressing RsMYB1-IRs and RsTT8-IRs showed substantially higher anthocyanin accumulation than those co-expressing their spliced forms. Consistently, co-expression of constructs encoding truncated proteins with spliced or IR forms of their interaction partner in tobacco leaves did not result in anthocyanin accumulation. Compared with RsMYB1, the overexpression of RsMYB1-IRs in Arabidopsis pap1 mutant increased anthocyanin accumulation by > sevenfold and upregulated the expression of Arabidopsis flavonoid biosynthesis genes including AtTT8. Our results suggest that the stable co-expression of RsMYB1-IRs in fruit trees and vegetable crops could be used to increase their anthocyanin contents.

Discovery of a novel antibody would enable diagnosis and early treatment of autoimmune encephalitis. The aim was to discover a novel antibody targeting a synaptic receptor and characterize the pathogenic mechanism.We screened for unknown antibodies in serum and cerebrospinal fluid samples from autoimmune encephalitis patients. Samples with reactivity to rat brain sections and no reactivity to conventional antibody tests underwent further processing for antibody discovery, using immunoprecipitation to primary neuronal cells, mass-spectrometry analysis, an antigen-binding assay on an antigen-overexpressing cell line, and an electrophysiological assay with cultured hippocampal neurons.Two patients had a novel antibody against CaHere, we discovered a novel autoimmune encephalitis associated with anti-Ca

Background Vaccine safety surveillance is important because it is related to vaccine hesitancy, which affects vaccination rate. To increase confidence in vaccination, the active monitoring of vaccine adverse events is important. For effective active surveillance, we developed and verified a machine learning-based active surveillance system using national claim data. Methods We used two databases, one from the Korea Disease Control and Prevention Agency, which contains flu vaccination records for the elderly, and another from the National Health Insurance Service, which contains the claim data of vaccinated people. We developed a case-crossover design based machine learning model to predict the health outcome of interest events (anaphylaxis and agranulocytosis) using a random forest. Feature importance values were evaluated to determine candidate associations with each outcome. We investigated the relationship of the features to each event via a literature review, comparison with the Side Effect Resource, and using the Local Interpretable Model-agnostic Explanation method. Results The trained model predicted each health outcome of interest with a high accuracy (approximately 70%). We found literature supporting our results, and most of the important drug-related features were listed in the Side Effect Resource database as inducing the health outcome of interest. For anaphylaxis, flu vaccination ranked high in our feature importance analysis and had a positive association in Local Interpretable Model-Agnostic Explanation analysis. Although the feature importance of vaccination was lower for agranulocytosis, it also had a positive relationship in the Local Interpretable Model-Agnostic Explanation analysis. Conclusion We developed a machine learning-based active surveillance system for detecting possible factors that can induce adverse events using health claim and vaccination databases. The results of the study demonstrated a potentially useful application of two linked national health record databases. Our model can contribute to the establishment of a system for conducting active surveillance on vaccination., Graphical Abstract

We report neuropsychological and neuropathological findings for a patient (A.B.), who developed memory impairment after a cardiac arrest at age 39. A.B. was a clinical psychologist who, although unable to return to work, was an active participant in our neuropsychological studies for 24 y. He exhibited a moderately severe and circumscribed impairment in the formation of long-term, declarative memory (anterograde amnesia), together with temporally graded retrograde amnesia covering ∼5 y prior to the cardiac arrest. More remote memory for both facts and autobiographical events was intact. His neuropathology was extensive and involved the medial temporal lobe, the diencephalon, cerebral cortex, basal ganglia, and cerebellum. In the hippocampal formation, there was substantial cell loss in the CA1 and CA3 fields, the hilus of the dentate gyrus (with sparing of granule cells), and the entorhinal cortex. There was also cell loss in the CA2 field, but some remnants remained. The amygdala demonstrated substantial neuronal loss, particularly in its deep nuclei. In the thalamus, there was damage and atrophy of the anterior nuclear complex, the mediodorsal nucleus, and the pulvinar. There was also loss of cells in the medial and lateral mammillary nuclei in the hypothalamus. We suggest that the neuropathology resulted from two separate factors: the initial cardiac arrest (and respiratory distress) and the recurrent seizures that followed, which led to additional damage characteristic of temporal lobe epilepsy.

In anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, we analysed the efficacy of a combined immunotherapy protocol consisting of teratoma removal, steroid, intravenous immunoglobulin (IVIG), rituximab and tocilizumab (T-SIRT). This cohort study included seventy-eight consecutive patients treated for anti-NMDAR encephalitis between Jan 2014 and Oct 2019 in a national referral hospital. Detailed 2-year disease time course was analysed using Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores at every 2 weeks for 12 weeks from baseline, every month for the next 3 months and then every 3 months. Treatment regimens at each time point were categorized as SI, SIR, or SIRT with/without teratoma removal (T). Adverse events were classified according to the Common Terminology Criteria for Adverse-Events (CTCAE v5.0), where a severe adverse event was defined as an adverse event with CATAE grade 4. In a linear mixed model analysis, using the SIRT regimen was more effective than SIR or SI regimens in lowering CASE scores (P

Female genital mutilation/cutting (FGM/C) is common across the globe and seen in high income countries that host migrants from high prevalence countries. Management of FGM/C in the host countries can be complicated due its often conflicting social, cultural, ethical, legal, and medical dynamics. Health profession organizations often create policy and position statements that set the tone and direction for the organization and describe desired methods, behaviors and actions applicable to the entire organization and its members. It is unclear whether or what organizational statements exist on FGM/C. We reviewed publicly available statements made by health profession organizations whose members care for women and girls affected by or at risk for, FGM/C, and assessed their content related to medicalization, reinfibulation and vacation cutting. Of a total of 47 organizations, 24 (51%) had any statements. Of 15 physician organizations, only 4 (26%) US-based physician organizations had any statements. 17 had specific statements on clinician involvement, but the tone and instructional nature varied. Re-infibulation was mentioned by 41% organizations with statements. 29% mentioned vacation cutting. Many, but not all, health profession organizations have statements for their members on FGM/C, and those vary in what is covered, and in what recommendations are given. Health profession organizations serve and are the face and voice of their members. As such, they have a responsibility to educate their members, set the tone for the conversation, and make their stand clear to their members and other stakeholders, including patients.

The study was conducted to investigate effects of yeast cell wall product on growth performance, immune responses, and gene expression of tight junction proteins of weaned pigs. A total of 112 weaned pigs (7.98 ± 0.43 kg BW) were randomly assigned to 2 dietary treatments (8 pigs/pen; 7 replicates/treatments) for 4 weeks in a randomized complete block design (block = BW). Dietary treatments were 1) a commercial basal nursery diet (CON) and 2) CON + 0.05% yeast cell wall product (YCW, EasyBio Inc., Seoul, Korea). Blood was collected from one randomly selected pig per pen on d 0, 7, and 14 after weaning. The randomly selected one pig per replicate was euthanized to collect ileum tissue samples at the end of the experimental period. Measurements were growth performance, number of white blood cells (WBC) by an automated hematology analyzer calibrated for porcine blood, cortisol, tumor necrosis factor-α (TNF-α), transforming growth factor-β1, interleukin-1β (IL-1β), and interleukin-6 (IL-6) by the ELISA, and gene expression of tight junction in ileum tissues. Data were analyzed using the PROC GLM procedure of SAS. The statistical model for every measurement included dietary effect and BW as a covariate. Pigs fed YCW had higher (P < 0.10) ADG than those fed CON during overall experimental period. Pigs fed YCW had lower WBC on d 14 (P < 0.10), TNF-α on d 7 (P < 0.10), and decreased IL-1β on d 14 (P < 0.05) than those fed CON. In addition, The YCW increased (P < 0.05) expression of Claudin family, Occludin, Muc1, INF-α, and IL-6, but decreased (P < 0.05) expression of TNF-α genes in the ileum tissues compared with CON. In conclusion, addition of yeast cell wall product in the nursery diet improved growth performance and gut health and modified immune responses of weaned pigs.

Two experiments were conducted to investigate effects of dietary flavor as a feed additive on growth performance of weaned pigs. The flavor used in experiments was a commercial product (Luctarom®, Lucta Guangzhou, China) containing milky cream flavor. In Exp. 1, 72 weaned pigs (initial BW = 6.51 ± 0.21 kg) were randomly assigned to 2 dietary treatments (4 pigs/pen; 9 replicates/treatment): an experimental diet based on corn and soybean meal (CON1) and CON1 supplemented with 0.05% flavor (FLA). In Exp. 2, 72 weaned pigs (initial BW = 6.66 ± 0.32 kg) were randomly assigned to 2 dietary treatments (4 pigs/pen; 9 replicates/treatment): a commercial diet based on corn and soybean meal with spray dried plasma, fish meal, and zinc oxide (CON2) and CON2 supplemented with FLA. Pigs were fed respective dietary treatment for 6 weeks. Growth performance was measured on day 1, 7, 14, 21, and 42 after weaning. Data were analyzed using the PROC GLM procedure of SAS. The statistical model for every measurement included dietary effect and BW as a covariate in a randomized complete block design (block = BW). In Exp. 1, pigs fed FLA tended to increase ADG (0.493 vs. 0.451 kg/d; P < 0.10) during the experimental period compared with those fed CON1. However, there were no differences in ADFI and G:F between CON1 and FLA. In Exp. 2, pigs fed FLA had greater ADG (0.548 vs. 0.463 kg/d; P < 0.05) and tended to increase ADFI (0.870 vs. 0.753 kg/d; P < 0.10) during the experimental period than those fed CON2. However, there was no difference in G:F between CON2 and FLA. In conclusion, the addition of dietary flavor in experimental and commercial nursery diets improved growth performance of weaned pigs.

Cell-based therapy for intracerebral hemorrhage (ICH) has a great therapeutic potential. However, methods to effectively induce direct regeneration of the damaged neural tissue after cell transplantation have not been established, which, if done, would improve the efficacy of cell-based therapy. In this study, we aimed to develop a cell sheet with neurovasculogenic potential and evaluate its usefulness in a canine ICH model. We designed a composite cell sheet made of neural progenitors derived from human olfactory neuroepithelium and vascular progenitors from human adipose tissue-derived stromal cells. We also generated a physiologic canine ICH model by manually injecting and then infusing autologous blood under arterial pressure. We transplanted the sheet cells (cell sheet group) or saline (control group) at the cortex over the hematoma at subacute stages (2 weeks from ICH induction). At 4 weeks from the cell transplantation, cell survival, migration, and differentiation were evaluated. Hemispheric atrophy and neurobehavioral recovery were also compared between the groups. As a result, the cell sheet was rich in extracellular matrices and expressed neurotrophic factors as well as the markers for neuronal development. After transplantation, the cells successfully survived for 4 weeks, and a large portion of those migrated to the perihematomal site and differentiated into neurons and pericytes (20% and 30% of migrated stem cells, respectively). Transplantation of cell sheets alleviated hemorrhage-related hemispheric atrophy ( p = 0.042) and showed tendency for improving functional recovery ( p = 0.062). Therefore, we concluded that the cell sheet transplantation technique might induce direct regeneration of neural tissue and might improve outcomes of intracerebral hemorrhage.

Since the World Health Organization identified interprofessional education (IPE) as an important component in primary health care in the 1980s, medical and health sciences educators have continued to debate factors for implementing effective IPE in the classroom. Although IPE research is widespread internationally, few studies have been done in South Korea. This study explored the current status of IPE and examined factors that influence IPE in South Korea. A total of 30 (70%) out of 41 medical education experts in medical schools participated. Forty-seven percent of the participants reported that they allocated less than 5% of their time implementing IPE in the curriculum of their schools throughout the 4 years of medical school. Although all experts (100%) agreed that IPE is essential for medical students, they expressed practical difficulties in implementing IPE in the current education system. Factors that influence IPE are scheduling and curriculum (e.g., rigid curriculum vs. providing learning environment) and attitudes (e.g., lack of reciprocal respect vs. willingness to change). In addition, participants reported that communication skills and collaborative practice employing clinical practice or role-playing would be appropriate education methods and content for IPE in the future. The findings of this study provide a foundation for the implementation of IPE in South Korea. Future research directions for IPE in medical, nursing, and pharmacy schools are discussed.

The study was conducted to investigate effects of dietary inactivated probiotics on growth performance, nutrient digestibility, and immune responses of weaned pigs. A total of 96 weaned pigs (initial BW = 6.95 ± 0.25 kg) were randomly assigned to 4 dietary treatments with increasing levels of inactive probiotics (4 pigs/replicate; 6 replicates/treatment; 0, 0.1, 0.2, and 0.4%; CON, T1, T2, and T3) in a randomized complete block design (BW and sex as blocks). The inactivated probiotics used in this experiment was a commercial product (CJ CheilJedang Biotechnology Research Institute, Seoul, Korea) containing 1 x 106 CFU/g on stains of Lactobacillus rhamnosus. Pigs were fed respective dietary treatments for 4 weeks. During the last week of the experimental period, pigs were fed their respective dietary treatments containing 0.2% chromic oxide. Fecal samples were collected by rectal palpation daily for the last 3 days after the 4-day adjustment period during the last week of experiment. Blood was collected from randomly selected one pig each pen on d 1, 3, 7, and 14 after weaning. Measurements were growth performance, apparent total tract digestibility (ATTD), TNF-α, TGF-β, CRP, and cortisol by ELISA. Data were analyzed using the MIXED procedure of SAS. The inactivated probiotics increased ADG (471, 501, and 513 vs. 428 g/d; P < 0.05) and G:F (0.65, 0.69, and 0.71 vs. 0.58 g/g; P < 0.05) during overall experimental period compared with CON. The inactivated probiotics increased ATTD of GE (86.87, 87.29, and 88.53 vs. 85.25%; P < 0.05) compared with CON. The inactivated probiotics decreased TNF-α (600, 542, and 523 vs. 849 pg/ml; P < 0.05) and cortisol (5.58, 5.56, and 5.44 vs. 7.25 ng/ml; P < 0.05) on d 7 compared with CON. In conclusion, addition of inactivated probiotics improved growth performance, and nutrient digestibility, and modified immune responses.

This study was conducted to evaluate effects of dietary multi-carbohydrases (MCS) in a lactating sow diet on productive performance and immune responses of sows and their piglets. A total of 12 sows (218.37 ± 5.5 kg BW; 2 parity) were randomly assigned to 2 dietary treatments: a diet based on corn-soybean meal (CON) and CON with 0.01% MCS. The MCS contained xylanase (2,700 units/g), β-glucanase (700 units/g), and cellulase (800 units/g). Sows were fed the dietary treatments for 28 days (weaning) after farrowing. Blood samples were collected from sows on d 0, 3, and 7 after farrowing and randomly selected 2 nursing piglets in each sow on d 3, 7, and 14 after birth. Measurements were productive performance of sows, frequency of diarrhea of piglets, and immune responses of sows and their piglets. Sows fed MCS had lower (p < 0.05) their body weight change than those fed CON. Piglets from sows fed MCS had higher (p < 0.05) average weight gain and body weight at weaning day and lower (p < 0.10) frequency of diarrhea than those from sows fed CON. Sows fed MCS had lower number of white blood cells (WBC) on d 3 (p < 0.05) and TGF-β1 on d 7 (p < 0.10) during lactation than those fed CON. Similarly, piglets from sows fed MCS had also lower (p < 0.05) number of WBC on d 3 and d 7 and TGF-β1 and C-reactive protein on d 7 during lactation than those from sows fed CON. In addition, piglets from sows fed MCS had higher (p < 0.10) immunoglobulin G and M on d 7 during lactation those from sows fed CON. In conclusion, addition of dietary MCS in the lactating sow diet based on corn and soybean meal improved productive performance of sows and their litters and modulated their immune responses.

We administered map-reading tasks in which participants navigated an array of marks on the floor by following paths on hand-held maps that made up to nine turns. The burden on memory was minimal because the map was always available. Nevertheless, because the map was held in a fixed position in relation to the body, spatial computations were continually needed to transform map coordinates into geographical coordinates as participants followed the maps. Patients with lesions limited to the hippocampus (n = 5) performed similar to controls at all path lengths (experiment 1). They were also intact at executing single moves to an adjacent location, even when trials began by facing in a direction that put the map coordinates and geographical coordinates into conflict (experiment 2). By contrast, one patient with large medial temporal lobe (MTL) lesions performed poorly overall in experiment 1 and poorly in experiment 2 when trials began by facing in the direction that placed the map coordinates and geographical coordinates in maximal conflict. Directly after testing, all patients were impaired at remembering factual details about the task. The findings suggest that the hippocampus is not needed to carry out the spatial computations needed for map reading and navigating from maps. The impairment in map reading associated with large MTL lesions may depend on damage in or near the parahippocampal cortex.

The psychosocial environment is one of the major contributors of social stress. Family members or caregivers who consistently communicate with individuals with brain disorders are considered at risk for physical and mental health deterioration, possibly leading to mental disorders. However, the underlying neural mechanisms of this phenomenon remain poorly understood. To address this, we developed a social stress paradigm in which a mouse model of epilepsy or depression was housed long-term (>4weeks) with normal conspecifics. We characterized the behavioral phenotypes and electrophysiologically investigated the neural activity of conspecific cagemate mice. The cagemates exhibited deficits in behavioral tasks assessing anxiety, locomotion, learning/memory, and depression-like behavior. Furthermore, they showed severe social impairment in social behavioral tasks involving social interaction or aggression. Strikingly, behavioral dysfunction remained in the cagemates 4weeks following co-housing cessation with the mouse models. In an electrophysiological study, the cagemates showed an increased number of spikes in medial prefrontal cortex (mPFC) neurons. Our results demonstrate that conspecifics co-housed with mouse models of brain disorders develop chronic behavioral dysfunctions, and suggest a possible association between abnormal mPFC neural activity and their behavioral pathogenesis. These findings contribute to the understanding of the psychosocial and psychiatric symptoms frequently present in families or caregivers of patients with brain disorders.

Optimal models are needed to understand the pathophysiology of human cerebral aneurysms (CA). We investigated the development of experimental CA by decreasing the activity of lysyl oxidases by dietary copper deficiency from the time of gestation and then augmenting vascular stress by angiotensin II infusion in adulthood. Rats were fed copper-free, low-copper, or normal diets at different time periods from gestation to adulthood. The incidences of CAs were evaluated and autopsies performed to determine the coexistence of cardiovascular diseases. A copper-free diet from gestation was associated with high mortality rates (79.1%) resulting from rupture of ascending aorta aneurysms; a low-copper diet led to acceptable mortality rates (13.6%) and produced CAs and subarachnoid hemorrhage in 46.4% and 3.6% of animals, respectively. Higher proportions of CAs (up to 33.3%) in the rats primed for copper deficiency from gestation ruptured following angiotensin II infusion from adulthood. Gene expression array analyses of the CAs indicated that genes involving extracellular matrix and vascular remodeling were altered in this model. This model enables future research to understand the entire pathogenetic basis of CA development and rupture in association with systemic vasculopathies.