Effects of noise exposure on stress hormone changes during task performance in young Korean men: quasi-experimental study.

Numerous studies have suggested that noise exposure might be associated with changes in stress hormone levels. However, quantitative evidence for these effects in humans is rare and remains controversial. This study aimed to investigate the acute effects of exposure to noise and its different levels on stress hormone changes in task performance. Quasi-experimental noise exposure environment was established for 90 male university student volunteers in their twenties, and each was exposed to different noise levels during task performance. The stress hormones tested included cortisol, adrenocorticotropic hormone (ACTH), adrenaline, and noradrenaline. A one-way ANOVA was performed to investigate differences in hormone levels measured in the three groups according to the noise exposure levels (35, 45, or 75 dB). Analysis of covariance (ANCOVA) was used to adjust for confounding factors that might affect hormone levels. After adjusting for confounders, significant exposure-dependent differences were found in hormone levels in salivary cortisol, serum cortisol, serum ACTH, and serum adrenaline. The amount of hormonal increase in 75 dB exposure group compared to 35 or 45 dB groups was detected. Similar results were also seen in the rate of change analysis. Our findings indicate that short-term noise exposure during task performance elevates stress hormone levels. Further, the extent of stress hormone alterations varies with noise exposure levels. Changes in hormone levels are an objective measure that may be used to identify health effects and stress responses in various noise environments.

Nontraditional Roles of Magnesium Ions in Modulating Sav2152: Insight from a Haloacid Dehalogenase-like Superfamily Phosphatase from Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infection has rapidly spread through various routes. A genomic analysis of clinical MRSA samples revealed an unknown protein, Sav2152, predicted to be a haloacid dehalogenase (HAD)-like hydrolase, making it a potential candidate for a novel drug target. In this study, we determined the crystal structure of Sav2152, which consists of a C2-type cap domain and a core domain. The core domain contains four motifs involved in phosphatase activity that depend on the presence of Mg2+ ions. Specifically, residues D10, D12, and D233, which closely correspond to key residues in structurally homolog proteins, are responsible for binding to the metal ion and are known to play critical roles in phosphatase activity. Our findings indicate that the Mg2+ ion known to stabilize local regions surrounding it, however, paradoxically, destabilizes the local region. Through mutant screening, we identified D10 and D12 as crucial residues for metal binding and maintaining structural stability via various uncharacterized intra-protein interactions, respectively. Substituting D10 with Ala effectively prevents the interaction with Mg2+ ions. The mutation of D12 disrupts important structural associations mediated by D12, leading to a decrease in the stability of Sav2152 and an enhancement in binding affinity to Mg2+ ions. Additionally, our study revealed that D237 can replace D12 and retain phosphatase activity. In summary, our work uncovers the novel role of metal ions in HAD-like phosphatase activity.

The impact of depression, stress, and self-esteem on quality of life among older adults in South Korea.

Background & Objective: Aging is a global trend, and Korea is also entering an aging society, which threatens the mental health of the elderly due to isolation, etc. In line with the growing domestic and international interest in elderly issues, this study aimed to identify the effects of depression, stress and self-esteem on the lives of the elderly in South Korea and to provide basic data for welfare measures. Methods: Depression, stress, self-esteem, and quality of life were measured in 104 South Korean seniors (32 men, 72 women, average age 72.94 years old). Differences between groups according to gender and residence type were confirmed. Results: There were no significant differences in stress among the elderly by place of residence, but there were significant differences in quality of life, depression, and self-esteem. Quality of life and self-esteem were higher in private housing than in public housing, and depression was higher in public housing than in private housing. In addition, lower depression and higher self-esteem were correlated with higher quality of life among the elderly. Conclusion: With the global trend of an aging society, it is essential to continue to pay attention to assist the lives of elderly and provide them with practical support and policies. The quality of life of the elderly requires continuous attention and efforts to support and policies for mental health and economic support.

Long-term outcomes of preterm infants in the first 6 years of life: a nationwide population-based study in Korea.

This study examined the relationship between gestational age and long-term outcomes up to 6 years of age using population-based big data from the National Health Insurance Service in Korea. This retrospective observational cohort study used data from the National Health Information Database (2011-2017). All children born in Korea during 2011 (January 1-December 31) were eligible and were followed up until 2017. Gestational age groups were divided into extremely preterm (< 28 weeks), very preterm (28-31 weeks), moderate-to-late preterm (32-36 weeks), and full-term (37-41 weeks). The survival rate, neurodevelopmental diseases, hearing or visual impairment, and respiratory morbidities were compared for each gestational age group. In total, 370,301 children were included in the analysis. The total survival rate increased with increasing gestational age. Furthermore, the risk of neurodevelopmental diseases (i.e., epilepsy, cerebral palsy, delayed development, mental retardation, language disorder, developmental coordination disorder, autism spectrum disorder), hearing or visual impairment, and asthma-related inhaler prescription increased with decreasing gestational age, despite adjustment for covariates. CONCLUSION: Lower gestational age was associated with an increase in a wide spectrum of adverse neurodevelopmental and respiratory outcomes in the first 6 years of life. Although morbidities were highest at the earliest gestational ages, moderate-to-late preterm children were significantly associated with increased adverse outcomes compared with full-term children. Our findings prove this under-recognized group's long-term follow-up and policy support. WHAT IS KNOWN: • Infants born preterm are at high risk for neurodevelopmental and various medical health problems. • Nationwide research on long-term outcomes for moderate-to-late preterm birth is sparse. WHAT IS NEW: • In this nationwide cohort study, lower gestational age at birth was inversely associated with increased adverse neurodevelopmental and respiratory outcomes in the first 6 years of life. • Long-term follow-up and policy support are required for moderate-to-late preterm children who are at risk of increased adverse outcomes compared with full-term births.

Shift to a Younger Age and Regional Differences in Inflammatory Bowel Disease in Korea: Using Healthcare Administrative Data.

BACKGROUND: Research using healthcare administrative data with a validated algorithm can reveal the real-world data of rare diseases. AIMS: We investigated an accurate algorithm for detecting incident cases of inflammatory bowel disease (IBD) from healthcare data and analyzed the nationwide population-based epidemiological features in Korea. METHODS: Healthcare data from Songpa-Kangdong districts in Seoul were extracted from the National Health Insurance Service and analyzed to identify the best algorithm reflecting the cohort data. The most accurate criterion was applied to the entire database for further analysis. RESULTS: With the selected working criteria, 37,555 incident cases of IBD (Crohn's Disease [CD], 13,130; ulcerative colitis [UC], 24,425) were identified from 2005 to 2016. The male-to-female ratio was 2.5:1 for CD and 1.4:1 for UC. Over 12 years, the annual standardized incidence rate (SIR) per 100,000 people increased from 1.6 to 2.7 and 3.8 to 4.3 for CD and UC, respectively. The peak age at diagnosis of UC shifted from 55-59 years to 20-24 years, whereas that of CD shifted from 19 to 17 years. The SIR of CD was higher in metropolitan areas than in non-metropolitan areas. CONCLUSIONS: This nationwide population-based epidemiologic study of Korean IBD revealed a gradual increase in the incidence rates and a notable shift toward younger age at diagnosis. Males were predominant in both CD and UC. There was an urban-rural difference in the SIR of CD.

The association of plasma cytokines including VEGF with recurrent wheezing in allergic patients.

BACKGROUND: Various cytokines have been studied to determine their functions in the pathogenesis of allergic diseases and their potential as therapeutic targets, but the roles and clinical applicability of many of these cytokines still remain unclear. OBJECTIVE: We aimed to measure the plasma levels of eight cytokines known to be relevant to allergic diseases, and to determine their association with the diagnostic characteristics of allergic patients. METHODS: The levels of a panel of eight cytokines (IL-5, IL-10, IL12p70, Leptin, CXCL5/ENA-78, CCL2/MCP-1, PDGFBB, and VEGF) were measured in plasma obtained from 83 allergic patients. We investigated whether the cytokine levels differed between children and adults. Statistical analyses were then performed to examine their association with the diagnostic characteristics of allergic patients. RESULTS: The levels of leptin, CCL2/MCP-1, PDGFBB, and VEGF were significantly higher in adult patients with allergic rhinitis than in children. Among patients with asthma, the levels of leptin and PDGFBB were elevated in adults. PDGFBB and VEGF levels were significantly associated with asthma. Interestingly, there was a significant association between VEGF level and recurrent wheezing regardless of the analyzed conditions. The levels of VEGF and PDGFBB or CCL2/MCP-1 showed a significant increase together in the presence of recurrent wheezing in child patients. CONCLUSIONS: The plasma levels of four cytokines, particularly VEGF, showed significant associations with some diagnostic characteristics in allergic patients. We suggested that plasma VEGF, which performs pleiotropic functions in allergic responses, could serve as a serological marker relevant to recurrent wheezing in allergic patients.

Synergistic anticancer effect of docosahexaenoic acid and isoliquiritigenin on human colorectal cancer cells through ROS-mediated regulation of the JNK and cytochrome c release.

A large body of research has demonstrated a synergistic anticancer effect between docosahexaenoic acid (DHA) and standard chemotherapy regimens against colorectal cancer (CRC). In this study, we investigated the chemotherapeutic potential of cotreatment with DHA and isoliquiritigenin (ISL) against CRC HCT-116 cells. Apoptosis was confirmed by Annexin V/PI staining and expression of apoptosis-associated proteins. The synergistic effect of DHA and ISL combination on apoptosis was detected using combination index approaches. Flow cytometry was carried out using fluorescent probes to measure the production of reactive oxygen species (ROS). DHA and ISL in combination synergistically enhanced the decrease in cell viability versus the compounds used alone. Moreover, we demonstrated that the synergistic anti-CRC activity of cotreatment with these two compounds was achieved by inducing the apoptosis caspase-dependently mediated through augmented ROS generation followed by increased Fas ligand mRNA expression and cytochrome c release. Our data also demonstrated that cotreating with DHA and ISL strongly upregulated the phosphorylation of ERK and JNK, which are functionally associated with ROS induced by the two compounds in combination. Interestingly, further study revealed that inhibiting ERK phosphorylation strongly enhanced Fas ligand mRNA expression and the combination of the two compounds induced stronger cytotoxicity, whereas inhibiting JNK phosphorylation significantly reduced the apoptotic signals mediated by cotreatment with these two compounds. Excessive ROS-induced JNK activation and cytochrome c release from mitochondria played a key role in the synergistic anticancer activity of CRC cells by cotreating with DHA and ISL.

Adverse Events in Healthcare Workers after the First Dose of ChAdOx1 nCoV-19 or BNT162b2 mRNA COVID-19 Vaccination: a Single Center Experience.

Coronavirus disease 2019 vaccinations for healthcare workers (HCWs) have begun in South Korea. To investigate adverse events (AEs) of the first dose of each vaccine, any symptom was collected daily for seven days after vaccination in a tertiary hospital. We found that 1,301 of 1,403 ChAdOx1 nCoV-19 recipients and 38 of 80 BNT162b2 recipients reported AEs respectively (90.9% vs. 52.5%): injection-site pain (77.7% vs. 51.2%), myalgia (60.5% vs. 11.2%), fatigue (50.7% vs. 7.5%), headache (47.4% vs. 7.5%), and fever (36.1% vs. 5%; P < 0.001 for all). Young HCWs reported more AEs with ChAdOx1 nCoV-19 than with BNT162b2. No incidences of anaphylaxis were observed. Only one serious AE required hospitalization for serious vomiting, and completely recovered. In conclusion, reported AEs were more common in recipients with ChAdOx1 nCoV-19 than in those with BNT162b2. However, most of the reported AEs were mild to moderate in severity. Sufficient explanation and preparation for expected AEs required to promote widespread vaccination.

Can We Estimate Quality of Life in Pediatric Inflammatory Bowel Disease Patients? An Asian Multicenter Study.

OBJECTIVES: Inflammatory bowel disease (IBD) is a chronic lifelong condition and is related to poor quality of life (QoL). The aim of this study was to evaluate the QoL of Asian pediatric patients with IBD and to determine the clinical factors that can influence QoL. METHODS: Children and adolescents aged 9 to 18 years diagnosed with IBD were enrolled from 7 hospitals. The patients completed the IMPACT-III questionnaire, and clinical data were collected. The results of the questionnaire and the correlation with clinical data were analyzed. RESULTS: A total of 208 patients (Crohn disease: n = 166; ulcerative colitis: n = 42) were enrolled. There was no definite QoL difference according to the Paris classification. Female sex (-5.92 ±â€Š2.97, P = 0.0347) and active disease status (-10.79 ±â€Š3.11, P = 0.0006) were significantly associated with poor QoL. Extreme body weight z score and older age at diagnosis were also associated with worse QoL. CONCLUSIONS: Various clinical factors may affect the QoL in patients with IBD, but determining the overall QoL of patients using only these clinical factors is difficult. Therefore, regular direct measurements of QoL are necessary to better understand patients with IBD.

Structure-based functional identification of Helicobacter pylori HP0268 as a nuclease with both DNA nicking and RNase activities.

HP0268 is a conserved, uncharacterized protein from Helicobacter pylori. Here, we determined the solution structure of HP0268 using three-dimensional nuclear magnetic resonance (NMR) spectroscopy, revealing that this protein is structurally most similar to a small MutS-related (SMR) domain that exhibits nicking endonuclease activity. We also demonstrated for the first time that HP0268 is a nicking endonuclease and a purine-specific ribonuclease through gel electrophoresis and fluorescence spectroscopy. The nuclease activities for DNA and RNA were maximally increased by Mn(2+) and Mg(2+) ions, respectively, and decreased by Cu(2+) ions. Using NMR chemical shift perturbations, the metal and nucleotide binding sites of HP0268 were determined to be spatially divided but close to each other. The lysine residues (Lys7, Lys11 and Lys43) are clustered and form the nucleotide binding site. Moreover, site-directed mutagenesis was used to define the catalytic active site of HP0268, revealing that this site contains two acidic residues, Asp50 and Glu54, in the metal binding site. The nucleotide binding and active sites are not conserved in the structural homologues of HP0268. This study will contribute to improving our understanding of the structure and functionality of a wide spectrum of nucleases.

Elevated expression of JMJD6 is associated with oral carcinogenesis and maintains cancer stemness properties.

Cancer stem cells (CSCs) are defined as a small subpopulation of cancer cells within a tumor and responsible for initiation and maintenance of tumor growth. Thus, understanding of molecular regulators of CSCs is of paramount importance for the development of effective cancer therapies. Here, we identified jumonji domain-containing protein 6 (JMJD6) as a novel molecular regulator of oral CSCs. JMJD6 is highly expressed in CSC-enriched populations of human oral squamous cell carcinoma (OSCC) cell lines. Moreover, immunohistochemical staining revealed significantly high level of JMJD6 in OSCC tissues compared to normal human oral epithelia, suggesting that expression of JMJD6 positively correlates with oral carcinogenesis. Subsequent functional analysis showed that knockdown of endogenous JMJD6 in OSCC strongly suppressed self-renewal capacity, a key characteristic of CSCs, and anchorage-independent growth. Conversely, ectopic expression of JMJD6 enhanced CSC characteristics including self-renewal, ALDH1 activity, migration/invasion and drug resistance. Expression of CSC-related genes was also markedly affected by modulating JMJD6 expression. Mechanistically, JMJD6 induces interleukin 4 (IL4) transcription by binding to its promoter region. IL4 rescues self-renewal capacity in JMJD6- knocked down OSCC cells, suggesting the importance of JMJD6-IL4 axis in oral CSCs. Our studies identify JMJD6 as a molecular determinant of CSC phenotype, suggesting that inhibition of JMJD6 may offer an effective therapeutic modality against oral cancer.

Orai1 mediates osteogenic differentiation via BMP signaling pathway in bone marrow mesenchymal stem cells.

Orai1 is a pore-subunit of store-operated Ca(2+) release-activated Ca(2+) (CRAC) channel that mediates Ca(2+) influx in most non-excitable cells via store-operated Ca(2+) entry (SOCE) mechanism. We previously demonstrated that Orai1 is involved in mediating osteogenic potential of mesenchymal stem cells (MSCs), but the underlying mechanism of this function remains unknown. Here, we report that Orai1 mediates osteogenic differentiation via bone morphogenic protein (BMP) signaling pathway in bone marrow MSCs (BMSCs). In osteogenic conditions, BMSCs derived from wild-type mice underwent osteoblastic differentiation and induced mineralization as demonstrated by increased alkaline phosphatase activity and alizarin red S staining, respectively. The expression of Runx2, a master regulator of osteoblast differentiation, and osteogenic differentiation markers were markedly increased in wild-type BMSCs under osteogenic conditions. In contrast, osteogenic conditions failed to induce such effects in BMSCs derived from Orai1-deficient (Orai1(-/-)) mice, indicating that Orai1 is, in part, necessary for osteogenic differentiation of MSCs. We also found that BMP2 successfully induced phosphorylation of Smad1/5/8, the immediate effector molecules of BMP signaling, in wild-type BMSCs, but failed to do so in Orai1(-/-) BMSCs. Downstream target genes of BMP signaling pathway were consistently increased by osteogenic conditions in wild-type BMSCs, but not in Orai1(-/-) BMSCs, suggesting a novel molecular link between Orai1 and BMP signaling pathway in the osteogenic differentiation process. Further functional studies demonstrated that activation of BMP signaling rescues osteogenic differentiation capacity of Orai1(-/-) BMSCs. In conclusion, Orai1 regulates osteogenic differentiation through BMP signaling, and the Orai1-BMP signaling may be a possible therapeutic target for treating bone-related diseases.

GRIM19 ameliorates acute graft-versus-host disease (GVHD) by modulating Th17 and Treg cell balance through down-regulation of STAT3 and NF-AT activation.

BACKGROUND: T helper (Th) 17 cells are a subset of T helper cells that express interleukin (IL)-17 and initiate the inflammatory response in autoimmune diseases. Regulatory T cells (Tregs) are a subpopulation of T cells that produce forkhead box P3 (FOXP3) and inhibit the immune response. Graft versus host disease (GVHD) is a complication of allogeneic tissue transplantation, and Th17 cells and their proinflammatory activity play a central role in the pathogenesis of GVHD. Gene associated with retinoid-interferon-induced mortality (GRIM) 19, originally identified as a nuclear protein, is expressed ubiquitously in various human tissues and regulate signal transducer and activator of transcription (STAT)3 activity. METHODS: Splenoytes and bone marrow cells were transplanted into mice with GVHD. The alloresponse of T cells and GVHD clinical score was measured. Realtime-polymerase chain reaction (realtime-PCR) was used to examine mRNA level. Flow cytometry and enzyme linked immunosorbent assay (ELISA) was used to evaluate protein expression. RESULTS: A GRIM19 transgenic cell transplant inhibited Th17 cell differentiation, alloreactive T cell responses, and STAT3 expression in mice with GVHD. On the other hand, the differentiation of Tregs and STAT5 production were enhanced by GRIM19. Overall, the severity of GVHD was decreased in mice that had received GRIM19 transgenic bone marrow and spleen transplants. Transplantation from GRIM19-overexpressing cells downregulated the expression of nuclear factor of activated T cells (NFATc1) but promoted the expression of regulator of calcineurin (RCAN)3 while downregulating NFAT-dependent cytokine gene expression. This complex mechanism underlies the therapeutic effect of GRIM19. CONCLUSIONS: We observed that GRIM19 can reduce Th17 cell differentiation and alloreactive T cell responses in vitro and in vivo. Additionally, GRIM19 suppressed the severity of GVHD by modulating STAT3 activity and controlling Th17 and Treg cell differentiation. These results suggest that GRIM19 attenuates acute GVHD through the inhibition of the excessive inflammatory response mediated by T cell activation.

The clinical implication of single nucleotide polymorphisms in deoxycytidine kinase in chronic hepatitis B patients treated with lamivudine.

Deoxycytidine kinase (dCK) is a critical enzyme involved in intracellular phosphorylation of lamivudine (LAM) to its active triphosphates. We conducted this study to determine dCK polymorphisms in Koreans and to evaluate whether the discovered single nucleotide polymorphisms (SNPs) were associated with treatment outcomes in chronic hepatitis B (CHB) patients treated with LAM. The full-length dCK gene was sequenced from 24 healthy volunteers and 24 patients with CHB. One hundred twenty-seven patients with CHB who were followed-up for at least 24 months after LAM treatment were enrolled. Virological response as determined by undetectable HBV DNA was defined as a good drug response. Primary non-response at 6 months and virological breakthrough within 12 months were defined as a poor drug response. Six novel dCK SNPs were found (-2052C/A, IVS3 - 46G/del, IVS4 + 40G/T, IVS5 + 39T/C, IVS5 - 72A/T, and 966-975T10/T11). In particular, two promoter SNPs, namely -360C/G and -201C/T, were in full linkage disequilibrium. These two SNPs had a higher allele frequency than previously reported in Caucasian, Japanese, and Chinese (26% vs. 2%, 13.1%, and 15.6%, respectively). There was no significant difference between treatment response groups in terms of the distributions of SNP genotypes or allele frequencies. However, there was significant difference in the allele frequency of -360G/-201T between HBeAg seroclearance group and HBeAg non-seroclearance group (P = 0.045). In conclusion, six novel dCK SNPs were discovered. Two promoter SNPs, namely -360C/G and -201C/T, were more frequent in Koreans than other populations. In particular, HBeAg-positive patients with the -360G/-201T haplotype may help HBeAg seroclearance in response to LAM therapy.

IL-1 Receptor Blockade Alleviates Graft-versus-Host Disease through Downregulation of an Interleukin-1ß-Dependent Glycolytic Pathway in Th17 Cells.

T helper (Th) 17 cells are a subset of Th cells expressing interleukin- (IL-) 17 and initiating an inflammatory response in autoimmune diseases. Graft-versus-host disease (GVHD) is an immune inflammatory disease caused by interactions between the adaptive immunity of donor and recipient. The Th17 lineage exhibits proinflammatory activity and is believed to be a central player in GVHD. IL-1 performs a key function in immune responses and induces development of Th17 cells. Here, we show that blockade of IL-1 signaling suppresses Th17 cell differentiation and alleviates GVHD severity. We hypothesized that the IL-1 receptor antagonist (IL-1Ra) would suppress Th17 cell differentiation in vitro via inhibition of glycolysis-related genes. Blockade of IL-1 using IL-1Ra downregulated Th17 cell differentiation, an alloreactive T cell response, and expression of genes of the glycolysis pathway. Severity of GVHD was reduced in mice with a transplant of IL-Ra-treated cells, in comparison with control mice. To clarify the mechanisms via which IL-1Ra exerts the therapeutic effect, we demonstrated in vivo that IL-1Ra decreased the proportion of Th17 cells, increased the proportion of FoxP3-expressing T regulatory (Treg) cells, and inhibited expression of glycolysis-related genes and suppressed Th17 cell development and B-cell activation. These results suggest that blockade of IL-1 signaling ameliorates GVHD via suppression of excessive T cell-related inflammation.

Neurofeedback training improves the dual-task performance ability in stroke patients.

Owing to the reduced capacity for information processing following a stroke, patients commonly present with difficulties in performing activities of daily living that combine two or more tasks. To address this problem, in the present study, we investigated the effects of neurofeedback training on the abilities of stroke patients to perform dual motor tasks. We randomly assigned 20 patients who had sustained a stroke within the preceding 6 months to either a pseudo-neurofeedback (n = 10) or neurofeedback (n = 10) group. Both groups participated in a general exercise intervention for 8 weeks, three times a week for 30 min per session, under the same conditions. An electrode was secured to the scalp over the region of the central lobe (Cz), in compliance with the International 10-20 System. The electrode was inactive for the pseudo-training group. Participants in the neurofeedback training group received the 30-min neurofeedback training per session for reinforcing the sensorimotor rhythm. Electroencephalographic activity of the two groups was compared. In addition, selected parameters of gait (velocity, cadence [step/min], stance phase [%], and foot pressure) were analyzed using a 10-m walk test, attention-demanding task, walk task and quantified by the SmartStep system. The neurofeedback group showed significantly improved the regulation of the sensorimotor rhythm (p < 0.001) and ability to execute dual tasks (p < 0.01). Significant improvements on selected gait parameters (velocity and cadence; p < 0.05) were also observed. We thus propose that the neurofeedback training is effective to improve the dual-task performance in stroke patients.

Optical Management Using Monovision and Yoked Prism for Acquired Strabismus and Nystagmus Secondary to a Neurodegenerative Disease.

Acquired involuntary eye movement disorders, including noncomitant strabismus, nystagmus, and saccadic dyskinesia, are common ocular manifestations of many neurodegenerative diseases. These patients may experience visual symptoms, such as blurred vision, diplopia, and oscillopsia, which can significantly impact their use of vision. The goal of the management for these patients is to reduce the visual symptoms using any combination of available management strategies. This case report discusses the effective optical management using the combination of spectacle monovision correction and yoked prism to improve visual symptoms in a patient with olivopontocerebellar atrophy.

Blocking activator protein 1 activity in donor cells reduces severity of acute graft-versus-host disease through reciprocal regulation of IL-17-producing T cells/regulatory T cells.

Acute graft-versus-host disease (aGVHD) is a major cause of mortality in allogeneic bone marrow transplantation. Here, the diminishing effect of activator protein 1 (AP-1) blocking with a synthetic retinoid (SR11302) on the severity of aGVHD in a murine model was investigated. MHC-mismatched strain combinations were used in vivo: C57BL/6 (H-2k(b)) donors into lethally irradiated BALB/c (H-2k(d)) recipients. SR11302 inhibited alloreactive T cell response in a dose-dependent manner and negatively regulated signal transducer and activator of transcription 3 (STAT3) activation. AP-1 blocking in T cells inhibited the differentiation of Th1 and Th17. Conversely, Foxp3(+) regulatory T cells (Treg) population dramatically expanded. Transfer of SR11302-treated donor splenocytes into lethally irradiated recipients diminished the lethality and clinical severity of aGVHD. In line with these results, AP-1 blocking in donor splenocytes exhibited reduced Th17/Th1 population and enhanced in vivo Treg population. Beneficial Treg expanding property of SR11302 was associated with the induction of Foxp3 and STAT5 transcription factor, where the inhibiting property of Th17 was achieved by suppressing the phosphorylated form of STAT3 and enhancing SOCS3. In conclusion, the preventive potential of AP-1 inhibitor in aGVHD may be accomplished by altering CD4(+) T cell differentiation through modulating transcription factors.

Visual Guidance for User Placement in Avatar-Mediated Telepresence between Dissimilar Spaces.

Rapid advances in technology gradually realize immersive mixed-reality (MR) telepresence between distant spaces. This paper presents a novel visual guidance system for avatar-mediated telepresence, directing users to optimal placements that facilitate the clear transfer of gaze and pointing contexts through remote avatars in dissimilar spaces, where the spatial relationship between the remote avatar and the interaction targets may differ from that of the local user. Representing the spatial relationship between the user/avatar and interaction targets with angle-based interaction features, we assign recommendation scores of sampled local placements as their maximum feature similarity with remote placements. These scores are visualized as color-coded 2D sectors to inform the users of better placements for interaction with selected targets. In addition, virtual objects of the remote space are overlapped with the local space for the user to better understand the recommendations. We examine whether the proposed score measure agrees with the actual user perception of the partner's interaction context and find a score threshold for recommendation through user experiments in virtual reality (VR). A subsequent user study in VR investigates the effectiveness and perceptual overload of different combinations of visualizations. Finally, we conduct a user study in an MR telepresence scenario to evaluate the effectiveness of our method in real-world applications.

ABCB1 c.2677G>T variation is associated with adverse reactions of OROS-methylphenidate in children and adolescents with ADHD.

OBJECTIVES: Osmotic-release oral system (OROS)-methylphenidate (MPH) is a safe and well-tolerated drug. Some patients cannot continue this regimen with adverse drug reactions (ADRs). As drug efflux transporters of the central nervous system, ABCB1 plays an important role in the clearance of psychotropic drugs and their metabolites from brain tissues. We hypothesized that genetic variations in the ABCB1 gene may affect ADRs to OROS-MPH. METHODS: We analyzed ADRs of OROS-MPH in 134 children and adolescents with attention-deficit hyperactivity disorder who completed a 4-week trial of OROS-MPH. The ADRs of OROS-MPH were evaluated by administering the Barkley Stimulant Side Effects Rating Scale. RESULTS: Our study proved that MPH is a substrate for ABCB1 by using membrane vesicle assay. We analyzed the influence of ABCB1 polymorphisms on ADRs to OROS-MPH. From the association study between ABCB1 polymorphisms and ADRs of OROS-MPH, c.2677G>T (p.Ala893Ser, rs2032582) showed a strong association with OROS-MPH-related ADRs (P = 0.008; odds ratio, 5.72). Furthermore, logistic regression analysis indicated that the TT genotype at the ABCB1 2677 locus is an independent determinant of ADRs attributed to OROS-MPH. In a functional study, the 893Ser variant markedly reduced MPH transport across the cell membrane. CONCLUSIONS: This is the first study to demonstrate that the TT genotype at position 2677 in the ABCB1 gene is associated with ADRs to OROS-MPH.