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Species in the genus Trametes (Basidiomycota, Polyporales) have been used in natural medicine for a long time. Many studies reported that mycelia or fruiting bodies of Trametes spp. exhibited effects of antioxidant, anti-inflammatory, anticancer, and antimicrobial activities. However, comparative analysis in this genus is scarce due to limitation of morphological identification and the sample number. In this study, the 19 strains of seven Trametes species were chosen to generate a five-gene-based phylogeny with the 31 global references. In addition, 39 culture extracts were prepared for 13 strains to test for anticancer and antibacterial activities. Strong anticancer activities were found in several extracts from T. hirsuta and T. suaveolens. Anticancer activities of T. suaveolens, T. cf. junipericola and T. trogii were first described here. The antibacterial ability of T. versicolor and T. hirsuta extracts has been confirmed. The antibacterial activities of T. suaveolens have been reported at the first time in this study. These results suggest an efficient application of the genus Trametes as the drug resources especially for anticancer agents. [ABSTRACT FROM AUTHOR]

Expansion of the GGGGCC hexanucleotide repeat in the chromosome 9 open reading frame 72 (C9orf72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS). As in other forms of ALS, selective hyperexcitability of the motor cortex has been implicated as a cause of the motor neuron death in C9orf72-associated ALS. Here, we show that proline-arginine (PR) poly-dipeptides generated from C9orf72 repeat expansions increase the intrinsic excitability in pyramidal neurons of the motor cortex but not in the principal neurons of the visual cortex, somatosensory cortex, or hippocampus. We further show that this effect is attributable to PR-induced enhancement of the persistent sodium current primarily through an Nav1.2-β1-β4 complex. Reconstitution assays reveal that an auxiliary subunit, β4, plays a crucial role in the PR-mediated modulation of human Nav1.2 channel activity. Moreover, compared with the visual cortex, binding of PR poly-dipeptide to Nav1.2 is stronger in the motor cortex, where β4 is highly expressed. Taken together, these studies suggest a cellular mechanism underlying cortical hyperexcitability in C9orf72 ALS by providing evidence that PR poly-dipeptides induce hyperexcitability in cortical motor neurons by modulating the Nav1.2 channel complex. [ABSTRACT FROM AUTHOR]

Purpose: This study sought to compare needle fenestration with a corticosteroid injection for the treatment of chronic plantar fasciitis. We hypothesized that needle fenestration would be as effective as a corticosteroid injection while avoiding the potential adverse effects of the corticosteroid. Materials and Methods: Forty female patients with unilateral chronic plantar fasciitis who did not respond to a minimum of 6 months of various conservative treatments were prospectively randomized to receive either a corticosteroid injection or needle fenestration. Visual analogue scale and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score were used for all patients before treatment and at 3-, 6-, and 12-month following treatment. Results: The corticosteroid injection group had a before-treatment average AOFAS Ankle-Hindfoot score of 56.4, which increased to 87.3 at 3 months and 78.2 at 6 months after treatment but decreased to 62.4 at 12 months. The needle fenestration group had a before treatment average AOFAS ankle-hindfoot score of 49.5, which increased to 77.8 at 3 months and 92.1 at 6 months after treatment and remained at a high score of 89.4 at 12 months. There were no complications in either group. Conclusion: In the treatment of chronic plantar fasciitis, needle fenestration is as effective at 3- and 6-month post-treatment as a corticosteroid injection. Also, unlike a corticosteroid, its effect remains until 12 months post-treatment. [ABSTRACT FROM AUTHOR]

Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell line leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles. However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV), and release very little hepatitis B surface antigen (HBsAg) following cHBV infection in comparison to differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles. Here we investigated whether NTCP could explain the different behaviors between the two cell types. Endogenous NTCP protein from differentiated HepaRG cells was unglycosylated despite wild-type coding sequence. HepaRG cells stably transfected with epitope-tagged NTCP expression construct displayed higher sHBV but not cHBV susceptibility than cells transfected with the null mutant. Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation. Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells. In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV vs. sHBV infection and different HBsAg/HBeAg ratios following cHBV infection. The responsible host factor(s) remain to be identified. IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor. However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV. We found differentiated HepaRG cells expressed nonglycosylated NTCP despite a wild-type coding sequence. NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV. Overexpressing NTCP in HepRG cells did not increase infection by cell culture-derived HBV or distort the ratio between the two viral antigens. These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV. [ABSTRACT FROM AUTHOR]

This research proposes a gaze pointer-based user interface to provide user-oriented interaction suitable for the virtual reality environment on mobile platforms. For this purpose, a mobile platform-based three-dimensional interactive content is produced to test whether the proposed gaze pointer-based interface increases user satisfaction through the interactions in a virtual reality environment based on mobile platforms. The gaze pointer-based interface--the most common input method for mobile virtual reality content--is designed by considering four types: the visual field range, the feedback system, multi-dimensional information transfer, and background colors. The performance of the proposed gaze pointer-based interface is analyzed by conducting experiments on whether or not it offers motives for user interest, effects of enhanced immersion, provision of new experience, and convenience in operating content. In addition, it is verified whether any negative psychological factors, such as VR sickness, fatigue, difficulty of control, and discomfort in using contents are caused. Finally, through the survey experiment, this study confirmed that it is possible to design different ideal gaze pointer-based interface in mobile VR environment according to presence and convenience. [ABSTRACT FROM AUTHOR]

This study analyzes walking interaction to enhance the immersion and minimize virtual reality (VR) sickness of users by conducting experiments. In this study, the walking interaction is composed of three steps using input devices with a simple structure that can be easily used by anyone. The first step consists of a gamepad control method, which is the most popular but has low presence. The second step consists of a hand-based walking control interface, which is mainly used for interaction in VR applications. The last step consists of a march-in-place detection simulator that interacts with the legs-the key body parts for walking. Four experiments were conducted to determine the degree of direct expression of intention by users in the course of walking interactions that can improve immersion, presence, and prevent VR sickness in VR applications. With regard to the experiments in this study, survey experiments were conducted for general users using the Wilcoxon test, a presence questionnaire, and simulator sickness questionnaire (SSQ). In addition, the technical performance of the VR scenes used in the experiment was analyzed. The experimental results showed that higher immersion was achieved when interactions that felt closer to real walking were provided in VR. Furthermore, it was found that even control methods with a simple structure could be used for walking interactions with minimal VR sickness. Finally, a satisfactory presence was found in VR if the user was able interact using his or her own legs. [ABSTRACT FROM AUTHOR]

We developed a fully automated portable 2-dimensional (2-D) gas chromatography (GC x GC) device, which had a dimension of 60 cm X 50 cm X 10 cm and weight less than 5 kg. The device incorporated a micropreconcentrator/injector, commercial columns, micro-Deans switches, microthermal injectors, microphotoionization detectors, data acquisition cards, and power supplies, as well as computer control and user interface. It employed multiple channels (4 channels) in the second dimension (²D) to increase the ²D separation time (up to 32 s) and hence ²D peak capacity. In addition, a nondestructive flow-through vapor detector was installed at the end of the ¹D column to monitor the eluent from ¹D and assist in reconstructing ¹D elution peaks. With the information obtained jointly from the ¹D and ²D detectors, ¹D elution peaks could be reconstructed with significantly improved ¹D resolution. In this Article, we first discuss the details of the system operating principle and the algorithm to reconstruct ¹D elution peaks, followed by the description and characterization of each component. Finally, 2-D separation of 50 analytes, including alkane (C6-C12), alkene, alcohol, aldehyde, ketone, cycloalkane, and aromatic hydrocarbon, in 14 min is demonstrated, showing the peak capacity of 430--530 and the peak capacity production of 40--80/min. [ABSTRACT FROM AUTHOR]

Purpose: Diagnosis of narcolepsy in childhood is challenging because of ambiguous expression of symptoms and various clinical presentations. The purpose of this study is to delineate the clinical and polysomnographic characteristics of childhood narcolepsy. Methods: This study included 78 patients who were diagnosed with narcolepsy by clinical history and polysomnography (PSG) between February 2002 and June 2015 at Samsung Medical Center. Their medical records were reviewed retrospectively and analyzed between two groups; age of symptom onset and the presence of cataplexy. Results: The age at diagnosis and symptom onset was 15.51±2.73 years and 13.03± 2.79 years. Forty-one patients (52.6%) were diagnosed with narcolepsy with cataplexy. All exhibited excessive daytime sleepiness as the first symptom. In the multiple sleep latency test (MSLT), short sleep latency and more than 3 episodes of mean sleep onset of rapid eye movement were observed. The coexisting sleep disorders varied according to age of onset. There was no significant difference in sleep parameters between the two age groups. The patients with cataplexy had higher scores on the Epworth Sleepiness Scale and shorter mean sleep latencies in the MSLT than those without cataplexy (P<0.05). Conclusion: Pediatric narcolepsy presents with excessive daytime sleepiness and has different co-existing sleep disorders according to age of onset. The degree of sleepiness is higher in the patients with cataplexy. Narcolepsy may be suspected in children with excessive daytime sleepiness even if they do not have cataplexy. This should be confirmed using appropriate sleep questionnaires and PSG with MSLT. [ABSTRACT FROM AUTHOR]

Background: This study protocol evaluates the effectiveness of adjuvant electroacupuncture (EA) for urinary retention in poststroke patients undergoing conventional treatments, in comparison with that of a sham control.Methods/design: A multicenter, blinded, randomized controlled trial will be conducted in three hospitals in the Republic of Korea. We are recruiting 54 stroke survivors (aged >19 years), who were diagnosed with urinary retention based on the results of two consecutive post-void residual (PVR) tests, and dividing them randomly into two arms: the EA and Park-sham control groups. They will receive ten sessions of EA or sham treatment for 2 weeks. The participants will be blinded with non-penetrating needles and fake sounds of EA stimulators. The daily PVR ratio will be primarily measured at baseline and at the end of the study to statistically test the effectiveness of EA for poststroke urinary retention. Then, the Korean version of the Qualiveen Questionnaire, the Korean version of the International Prostate Symptom Score, and the blinding index will be assessed. After each EA session or sham EA, adverse events will be reported to evaluate the safety of EA. Results will be analyzed by using the independent t-test or Mann-Whitney U test, based on both intention-to-treat and per-protocol principles.Discussion: The findings will provide clinical evidence for the effectiveness of EA treatment to improve urinary retention in stroke survivors.Trial Registration: This study protocol was registered in ClinicalTrials.gov (NCT02472288) on 10 June 2015. [ABSTRACT FROM AUTHOR]

Background: Hes6 is a transcriptional regulator that induces transcriptional activation by binding to transcription repressor Hes1 and suppressing its activity. Hes6 is controlled by the ubiquitin-proteosome-mediated degradation system. Here we investigated the sumoylation of Hes6 and its functional role in its rhythmic expression. Methods: Hes6, SUMO, and ubiquitin were transfected into HeLa cells and the expression pattern was observed by Western blot and immunoprecipitation. To confirm the effect of sumoylation on the rhythmic expression of Hes6, we generated mouse Hes6 promoter-driven GFP-Hes6 fusion constructs and expressed these constructs in NIH 3T3 cells. Results: Overexpression of SUMO led to sumoylation of Hes6 at both lysine 27 and 30. Protein stability of Hes6 was decreased by sumoylation. Moreover, expression of a Hes6 sumoylation-defective mutant, the 2KR (K27/30R) mutant, or co-expression of SUMO protease SUSP1 with native Hes6, strongly reduced ubiquitination. In addition, sumoylation was associated with both the rhythmic expression and transcriptional regulation of Hes6. Wild type Hes6 showed oscillatory expression with about 2-hour periodicity, whereas the 2KR mutant displayed a longer period. Furthermore, sumoylation of Hes6 derepressed Hes1-induced transcriptional repression. Conclusion: Hes6 sumoylation plays an important role in the regulation of its stability and Hes1-mediated transcription. These results suggest that sumoylation may be crucial for rhythmic expression of Hes6 and downstream target genes. [ABSTRACT FROM AUTHOR]

The article presents a case study of 17-year-old tuberous sclerosis patient diagnosed with chordoid meningioma. The patient underwent magnetic resonance imaging (MRI) showing tumor in the lateral ventricle and prepontine mass and postinitial operation for 23 months. Results of the patient's follow-up MRI show no symptom of tumor recurrence and decrease in her prepontine enhancing mass.

Anesthetic management of pediatric liver transplantation in a patient with osteogenesis imperfecta (OI) requires tough decisions and comprehensive considerations of the cascade of effects that may arise and the required monitoring. Total intravenous anesthesia (TIVA) with propofol and remifentanil was chosen as the main anesthetic strategy. Malignant hyperthermia (MH), skeletal fragility, anhepatic phase during liver transplantation, uncertainties of TIVA in children, and propofol infusion syndrome were considered and monitored. There were no adverse events during the operation. Despite meticulous precautions with regard to the risk of MH, there was an episode of high fever (40°C) in the ICU a few hours after the operation, which was initially feared as MH. Fortunately, MH was ruled out as the fever subsided soon after hydration and antipyretics were given. Although the delivery of supportive care and the administration of dantrolene are the core principles in the management of MH, perioperative fever does not always mean a MH in patients at risk for MH, and other common causes of fever should also be considered. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy is the most common cause of end-stage renal disease. Polymorphism in the tissue inhibitor of metalloproteinase-3 (TIMP3) gene, and the ECM-bound inhibitor of matrix metalloproteinases (MMPs), has been linked to diabetic nephropathy in humans. To elucidate the mechanism, we generated double mutant mice in which the TIMP3 gene was deleted in the genetic diabetic Akita mouse background. The aggravation of diabetic injury occurred in the absence of worsening of hypertension or hyperglycemia. In fact, myocardial TIMP3 levels were not affected in Akita hearts, and cardiac diastolic and systolic function remained unchanged in the double mutant mice. However, TIMP3 levels increased in Akita kidneys and deletion of TIMP3 exacerbated the diabetic renal injury in the Akita mouse, characterized by increased albuminuria, mesangial matrix expansion, and kidney hypertrophy. The progression of diabetic renal injury was accompanied by the upregulation of fibrotic and inflammatory markers, increased production of reactive oxygen species and NADPH oxidase activity, and elevated activity of TNF-α-converting enzyme (TACE) in the TIMP3-/-/Akita kidneys. Moreover, while the elevated phospho-Akt (S473 and T308) and phospho-ERK1/2 in the Akita mice was not detected in the TIMP3-/-/Akita kidneys, PKCβ1 (but not PKCα) was markedly elevated in the double mutant kidneys. Our data provide definitive evidence for a critical and selective role of TIMP3 in diabetic renal injury consistent with gene expression findings from human diabetic kidneys. [ABSTRACT FROM AUTHOR]

The transcription factor CLOCK-BMAL1 is a core component of the molecular clock machinery that drives circadian gene expression and physiology in mammals. Recently, we reported that this heterodimeric transcription factor functions as a signaling molecule in response to the resetting stimuli via the Ca2+-dependent protein kinase C pathway. Here, we demonstrate that the CREB-binding protein (CBP) plays a key role in rapid activation of the CLOCK-BMAL1 heterodimer that leads to phase resetting of the circadian clock. Under physiological conditions, a bimolecular fluorescence complementation (BiFC) assay revealed that CLOCK and BMAL1 dimerize in the cytoplasm and subsequently translocate into the nucleus in response to serum stimuli (mean time duration was 29.2 minutes and mean velocity 0.7 mm/minute). Concomitantly, BMAL1 rapidly recruited CBP on Per1 promoter E-box, but not p300 (a functional analog of CBP), in the discrete nuclear foci. However, recruitment of CBP by cAMP/Ca2+ response element-binding (CREB) protein on CRE was not markedly increased upon delivery of the resetting stimuli. Furthermore, overexpression of CBP greatly potentiated the CLOCK-BMAL1-mediated Per1 transcription, and this effect was completely abolished by site-directed mutation of E-box elements, but not by the mutation of CRE in the Per1 promoter. Furthermore, molecular knockdown of CBP severely dampened circadian oscillation of clock gene expression triggered by the resetting stimuli. These findings suggest that CBP recruitment by BMAL1 mediates acute transactivation of CLOCK-BMAL1, thereby inducing immediate-early Per1 transcription and phase resetting of the circadian clock. [ABSTRACT FROM AUTHOR]

The article presents a science experiment teaching students on the concept of total internal reflection through refraction. Topics include steps for the experiment which involves drawing pictures on a magic film and cutting. Also presented are the materials needed in the experiment including overhead projector film, paper, and laminating film.

Malignant carcinomatous change is a rare complication in an enteric duplication cyst, and papillary adenocarcinoma is especially unusual. We describe a papillary adenocarcinoma, arising from a duplication of the colon, seen as a cyst with an enhancing papillary projection nodule located adjacent to the wall of the ascending colon and cecum on computed tomography. [ABSTRACT FROM AUTHOR]

In order to establish a sustainable stormwater management system, research has focused on Low Impact Development (LID) facilities. This study analyzed the runoff reduction efficiency and pollutant removal efficiency in Bioretention facilities. The results of the study were analyzed using long-term monitoring data over three years, and experiments were carried out using real rainfall and artificial rainfall to simulate various rainfall conditions. The Event Mean Concentration (EMC) is a pollutant concentration value for rainfall events. Based on the analysis of inflow and outflow EMC, TSS was found to have the largest reduction. The reduction ratio for efficiency about pollutant and run-off(%) was monitored for 3 years and more. The itemized data was plotted on chart annually. Based on the annual average pollutant removal efficiency values, all the pollutant removal efficiency values, except the runoff reduction efficiency, showed a decrease in efficiency over time. Based on the results of the study, the necessity for proper maintenance was confirmed. The results of this study are expected to inform further research on non-point pollution reduction facilities. • This experiment was conducted over three years to utilize long-term data. • Monitoring was performed under various rainfall conditions. • The average pollutant removal efficiency for all parameters was greater than 80%. • Efficiency of TN and TP inorganic substances that promote eutrophication was also high. • Efficiency for each year, all formed a trend line of decreasing efficiency. [ABSTRACT FROM AUTHOR]

Mass spectrometry (MS) has emerged as a powerful tool within the growing field of immunoproteomics, which aims to understand antibody-mediated immunity at the molecular-level based on the direct determination of serological antibody repertoire. To date, these methods have relied on the use of high-resolution bottom-up proteomic strategies that require effective sampling and characterization of low abundance peptides derived from the antigen-binding domains of polyclonal antibody mixtures. Herein, we describe a method that uses restricted Lys-C enzymatic digestion to increase the average mass of proteolytic IgG peptides (=4.5 kDa) and produce peptides which uniquely derive from single antibody species. This enhances the capacity to discriminate between very similar antibodies present within polyclonal mixtures. Furthermore, our use of 193-nm ultraviolet photodissociation (UVPD) improves spectral coverage of the antibody sequence relative to conventional collision- and electron-based fragmentation methods. We apply these methods to both a monoclonal and an antibody mixture. By identifying from a database search of approximately 15?000 antibody sequences those which compose the mixture, we demonstrate the analytical potential of middle-down UVPD for MS-based serological repertoire analysis. [ABSTRACT FROM AUTHOR]

An abstract of the article regarding the study on the role of the CLOCK/Brain and muscle Arnt-like protein-1 (BMAL1) circadian complex in transcriptional regulation is presented.

CLOCK and BMAL1 are bHLH-PAS-containing transcription factors that bind to E-box elements and are indispensable for expression of core circadian clock components such as the Per and Cry genes. A key step in expression is the heterodimerization of CLOCK and BMAL1 and their accumulation in the nucleus with an approximately 24-h periodicity. We show here that nucleocytoplasmic shuttling of BMAL1 is essential for transactivation and for degradation of the CLOCK/BMAL1 heterodimer. Using serial deletions and point mutants, we identified a functional nuclear localization signal and Crm1-dependent nuclear export signals in BMAL1. Transient-transfection experiments revealed that heterodimerization of CLOCK and BMAL1 accelerates their turnover, as well as E-box-dependent clock gene transcription. Moreover, in embryonic mouse fibroblasts, robust transcription of Per2 is tightly associated with massive degradation of the CLOCK/BMAL1 heterodimer. CRY proteins suppressed this process during the transcription-negative phase and led to nuclear accumulation of the CLOCK/BMAL1 heterodimer. Thus, these findings suggest that the decrease of BMAL1 abundance during the circadian cycle reflects robust transcriptional activation of clock genes rather than inhibition of BMAL1 synthesis. [ABSTRACT FROM AUTHOR]

This paper presents the design, fabrication, and characterization of a microhelium dielectric barrier discharge photoionization detector (µHDBD-PID) on chip with dimensions of only ~15 mm ? ~10 mm ? ~0.7 mm and weight of only ~0.25 g. It offers low power consumption (<400 mW), low helium consumption (5.8 mL/min), rapid response (up to ~60 ms at a flow rate of 1.5 mL/min), quick warm-up time (~5 min), an excellent detection limit (a few picograms), a large linear dynamic range (>4 orders of magnitude), and maintenance-free operation. Furthermore, the µHDBD-PID can be driven with a miniaturized (~5 cm ? ~2.5 cm ? ~2.5 cm), light (22 g), and low cost (~$2) power supply with only 1.5 VDC input. The dependence of the µHDBD-PID performance on bias voltage, auxiliary helium flow rate, carrier gas flow rate, and temperature was also systematically investigated. Finally, the µHDBD-PID was employed to detect permanent gases and a sublist of the EPA 8260 standard reagents that include 51 analytes. The µHDBD-PID developed here can have a broad range of applications in portable and microgas chromatography systems for in situ, real-time, and sensitive gas analysis. [ABSTRACT FROM AUTHOR]

The roles of neutrophils in renal inflammation are currently unclear. On examining these cells in the unilateral ureteral obstruction murine model of chronic kidney disease, we found that the injured kidney bore a large and rapidly expanding population of neutrophils that expressed the eosinophil marker Siglec-F. We first verified that these cells were neutrophils. Siglec-F+ neutrophils were recently detected in several studies in other disease contexts. We then showed that a) these cells were derived from conventional neutrophils in the renal vasculature by TGF-β1 and GM-CSF; b) they differed from their parent cells by more frequent hypersegmentation, higher expression of profibrotic inflammatory cytokines, and notably, expression of collagen 1; and c) their depletion reduced collagen deposition and disease progression, but adoptive transfer increased renal fibrosis. These findings have thus unveiled a subtype of neutrophils that participate in renal fibrosis and a potentially new therapeutic target in chronic kidney disease. [ABSTRACT FROM AUTHOR]

Tolosa-Hunt Syndrome (THS) is characterized by painful ophthalmoplegia caused by nonspecific granulomatous inflammation in the cavernous sinus. It shows a prompt response to steroids. However, there is a lack of data regarding the recurrence of THS and no guidelines yet exist for the optimal duration of steroid therapy, especially in children. A 6-year-old boy with headache, ptosis, and oculomotor palsy visited the pediatric emergency room with no other evidence which could account for the etiology of disease in terms of clinical symptoms or laboratory data. Upon brain magnetic resonance imaging (MRI), multiple small-sized enhancing nodules were observed around the left cavernous sinus. He improved with prednisolone treatment. Six months later, his painful ophthalmoplegia relapsed; however, no progressive lesion was visible on the brain MRI, and the symptoms were relieved by repeated steroid therapy. Herein, we report a case of recurrent pediatric Tolosa-Hunt syndrome, which is rare in Korea. [ABSTRACT FROM AUTHOR]

Preexisting antibodies to endemic coronaviruses (CoV) that cross-react with SARS-CoV-2 have the potential to influence the antibody response to COVID-19 vaccination and infection for better or worse. In this observational study of mucosal and systemic humoral immunity in acutely infected, convalescent, and vaccinated subjects, we tested for cross-reactivity against endemic CoV spike (S) protein at subdomain resolution. Elevated responses, particularly to the β-CoV OC43, were observed in all natural infection cohorts tested and were correlated with the response to SARS-CoV-2. The kinetics of this response and isotypes involved suggest that infection boosts preexisting antibody lineages raised against prior endemic CoV exposure that cross-react. While further research is needed to discern whether this recalled response is desirable or detrimental, the boosted antibodies principally targeted the better-conserved S2 subdomain of the viral spike and were not associated with neutralization activity. In contrast, vaccination with a stabilized spike mRNA vaccine did not robustly boost cross-reactive antibodies, suggesting differing antigenicity and immunogenicity. In sum, this study provides evidence that antibodies targeting endemic CoV are robustly boosted in response to SARS-CoV-2 infection but not to vaccination with stabilized S, and that depending on conformation or other factors, the S2 subdomain of the spike protein triggers a rapidly recalled, IgG-dominated response that lacks neutralization activity. [ABSTRACT FROM AUTHOR]

Background: Mutuelles is a community-based health insurance program, established since 1999 by the Government of Rwanda as a key component of the national health strategy on providing universal health care. The objective of the study was to evaluate the impact of Mutuelles on achieving universal coverage of medical services and financial risk protection in its first eight years of implementation. Methods and Findings: We conducted a quantitative impact evaluation of Mutuelles between 2000 and 2008 using nationally-representative surveys. At the national and provincial levels, we traced the evolution of Mutuelles coverage and its impact on child and maternal care coverage from 2000 to 2008, as well as household catastrophic health payments from 2000 to 2006. At the individual level, we investigated the impact of Mutuelles' coverage on enrollees' medical care utilization using logistic regression. We focused on three target populations: the general population, under-five children, and women with delivery. At the household level, we used logistic regression to study the relationship between Mutuelles coverage and the probability of incurring catastrophic health spending. The main limitation was that due to insufficient data, we are not able to study the impact of Mutuelles on health outcomes, such as child and maternal mortalities, directly. The findings show that Mutuelles improved medical care utilization and protected households from catastrophic health spending. Among Mutuelles enrollees, those in the poorest expenditure quintile had a significantly lower rate of utilization and higher rate of catastrophic health spending. The findings are robust to various estimation methods and datasets. Conclusions: Rwanda's experience suggests that community-based health insurance schemes can be effective tools for achieving universal health coverage even in the poorest settings. We suggest a future study on how eliminating Mutuelles copayments for the poorest will improve their healthcare utilization, lower their catastrophic health spending, and affect the finances of health care providers. [ABSTRACT FROM AUTHOR]

Fibroblasts comprise the largest cell population in the myocardium. In heart disease, the number of fibroblasts is increased either by replication of the resident myocardial fibroblasts, migration and transformation of circulating bone marrow cells, or by transformation of endothelial/epithelial cells into fibroblasts and myofibroblasts. The primary function of fibroblasts is to produce structural proteins that comprise the extracellular matrix (ECM). This can be a constructive process; however, hyperactivity of cardiac fibroblasts can result in excess production and deposition of ECM proteins in the myocardium, known as fibrosis, with adverse effects on cardiac structure and function. In addition to being the primary source of ECM proteins, fibroblasts produce a number of cytokines, peptides, and enzymes among which matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), directly impact the ECM turnover and homeostasis. Function of fibroblasts can also in turn be regulated by MMPs and TIMPs. In this review article, we will focus on the function of cardiac fibroblasts in the context of ECM formation, homeostasis and remodeling in the heart. We will discuss the origins and multiple roles of cardiac fibroblasts in myocardial remodeling in different types of heart disease in patients and in animal models. We will further provide an overview of what we have learned from experimental animal models and genetically modified mice with altered expression of ECM regulatory proteins, MMPs and TIMPs. [ABSTRACT FROM AUTHOR]

The dopamine D2 receptor (D2R) plays a crucial role in the regulation of diverse key physiological functions, including motor control, reward, learning, and memory. This receptor is present in vivo in two isoforms, D2L and D2S, generated from the same gene by alternative pre-mRNA splicing. Each isoform has a specific role in vivo, underlining the importance of a strict control of its synthesis, yet the molecular mechanism modulating alternative D2R pre-mRNA splicing has not been completely elucidatd. Here, we identify heterogeneous nuclear ribonucleo- protein M (hnRNP M) as a key molecule controlling D2R splicing. We show that binding of hnRNP M to exon 6 inhibited the inclusion of this exon in the mRNA. Importantly, the splicing factor Nova-1 counteracted hnRNP M effects on D2R pre- mRNA splicing. Indeed, mutations of the putative Nova-1-binding site on exon 6 disrupted Nova-1 RNA assembly and diminished the inhibitory effect of Nova-1 on hnRNP M-dependent exon 6 exclusion. These results identify Nova-1 and hnRNP M as D2R prc-mRNA-binding proteins and show their antagonistic role in the alternative splicing of D2R pre-mRNA. [ABSTRACT FROM AUTHOR]

Cannabinoid 1 receptor (CB1R) inverse agonists reduce body weight and improve several parameters of glucose homeostasis. However, these drugs have also been associated with deleterious side effects. CB1R expression is widespread in the brain and in peripheral tissues, but whether specific sites of expression can mediate the beneficial metabolic effects of CB1R drugs, while avoiding the untoward side effects, remains unclear. Evidence suggests inverse agonists may act on key sites within the central nervous system to improve metabolism. The ventromedial hypothalamus (VMH) is a critical node regulating energy balance and glucose homeostasis. To determine the contributions of CB1Rs expressed in VMH neurons in regulating metabolic homeostasis, we generated mice lacking CB1Rs in the VMH. We found that the deletion of CB1Rs in the VMH did not affect body weight in chow- and high-fat diet-fed male and female mice. We also found that deletion of CB1Rs in the VMH did not alter weight loss responses induced by the CB1R inverse agonist SR141716. However, we did find that CB1Rs of the VMH regulate parameters of glucose homeostasis independent of body weight in diet-induced obese male mice. [ABSTRACT FROM AUTHOR]

The article discusses that immune receptors play essential roles in adaptive immunity, and enumerating and identifying these sequences are key to understanding responses to infection or vaccination, for discovering therapeutic antibodies, and for engineering T cells; and mentions that reverse transcription xenopolymerase (RTX) is exceptionally resistant to the presence of very high concentrations of eukaryotic cell lysates.

Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here, we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice (Uhrf1ΔLimb/ΔLimb) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation and proliferation. RNA-seq performed on primary cultured chondrocytes obtained from Uhrf1ΔLimb/ΔLimb mice showed abnormal chondrocyte differentiation. In addition, integrative analyses using RNA-seq and MBD-seq revealed that Uhrf1 deficiency decreased genome-wide DNA methylation and increased gene expression through reducedDNA methylation in the promoter regions of 28 genes, including Hspb1, which is reported to be an IL1-related gene and to affect chondrocyte differentiation. Hspb1 knockdown in cKO chondrocytes can normalize abnormal expression of genes involved in chondrocyte differentiation, such as Mmp13. These results indicate that Uhrf1 governs cell type-specific transcriptional regulation by controlling the genome-wide DNA methylation status and regulating consequent cell differentiation and skeletal maturation. [ABSTRACT FROM AUTHOR]

Background: Head fixation can induce hemodynamic instability. Remifentanil is commonly used with propofol for total intravenous anesthesia (TIVA) during neurosurgery. This study investigated the 90% effective concentration (EC90) of remifentanil for blunting of cardiovascular responses to head fixation during neurosurgery via bispectral index (BIS) monitoring. Methods: Fifty patients undergoing neurosurgery requiring head fixation were enrolled. This study was performed using the biased coin up-and-down design sequential method (BCD). After tracheal intubation, the effect-site target concentration (Ce) of remifentanil was adjusted to achieve hemodynamic stability and reset to the level preoperatively assigned to each patient, according to the BCD method, approximately 10 min before head fixation. Baseline hemodynamic values were recorded before head fixation. An ineffective response was defined as a case with a > 20% increase in hemodynamic values from baseline. Otherwise, the response was determined to be effective. The EC90 of remifentanil was calculated as a modified isotonic estimator. Results: Forty-three patients completed this study. The EC90 of remifentanil for blunting cardiovascular responses to head fixation was estimated to be 6.48 ng/mL (95% CI, 5.94-6.83 ng/mL). Conclusions: Adjustment of the Ce of remifentanil to approximately 6.5 ng/mL before head fixation could prevent noxious cardiovascular responses in 90% of neurosurgical ASA I-II patients aged 20 to 65 years old during propofol target-controlled infusion titrated to maintain BIS between 40 and 50. Trial registration: ClinicalTrials.gov Identifier NCT01489137, retrospectively registered 5 December 2011. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined ambulatory cardiovascular physiological parameters of taxi drivers while driving in relation to their occupational hazards. This study aims to investigate and quantify the impact of worksite physical hazards as a whole on ambulatory heart rate of professional taxi drivers while driving without their typical worksite psychosocial stressors. Methods: Ambulatory heart rate (HRdriving) of 13 non-smoking male taxi drivers (24 to 67 years old) while driving was continuously assessed on their 6-hour experimental on-road driving in Los Angeles. Percent maximum HR range (PMHRdriving) of the drivers while driving was estimated based on the individual HRdriving values and US adult population resting HR (HRrest) reference data. For analyses, the HRdriving and PMHRdriving data were split and averaged into 5-min segments. Five physical hazards inside taxi cabs were also monitored while driving. Work stress and work hours on typical work days were self-reported. Results: The means of the ambulatory 5-min HRdriving and PMHRdriving values of the 13 drivers were 80.5 bpm (11. 2 bpm higher than their mean HRrest) and 10.7 % (range, 5.7 to 19.9 %), respectively. The means were lower than the upper limits of ambulatory HR and PMHR for a sustainable 8-hour work (35 bpm above HRrest and 30 % PMHR), although 15–27 % of the 5-min HRdriving and PMHRdriving values of one driver were higher than the limits. The levels of the five physical hazards among the drivers were modest: temperature (26.4 ± 3.0 °C), relative humidity (40.7 ± 10.4 %), PM2.5 (21.5 ± 7.9 μg/m3), CO2 (1,267.1 ± 580.0 ppm) and noise (69.7 ± 3.0 dBA). The drivers worked, on average, 72 h per week and more than half of them reported that their job were often stressful. Conclusions: The impact of physical worksite hazards alone on ambulatory HR of professional taxi drivers in Los Angeles generally appeared to be minor. Future ambulatory heart rate studies including both physical and psychosocial hazards of professional taxi drivers are warranted. [ABSTRACT FROM AUTHOR]

Locally advanced or metastatic disease accounts for two thirds of total patients with pancreatic cancer. Patients with pancreatic cancer are assessed as resectable, potentially resectable (borderline) or unresectable according to pre-operative examinations. The chances of resectability may be enhanced by using neoadjuvant systemic chemotherapy, radiotherapy or both. This case report presents a locally advanced pancreatic adenocarcinoma that was identified to be unresectable during surgical exploration. After receiving concurrent chemoradiotherapy, the patient was re-evaluated, identified as unresectable and received gemcitabine maintenance chemotherapy. Herein, we report the case of a patient with unresectable locally advanced pancreatic adenocarcinoma who achieved a complete response lasting for more than 32 months after receiving concurrent chmoradiotherapy followed by gemcitabine maintenance chemotherapy. [ABSTRACT FROM AUTHOR]

Improvement of the stability of blue phosphorescent dopant material is one of the key factors for real application of organic light-emitting diodes (OLEDs). In this study, we found that the intramolecular hydrogen bonding in an ancillary ligand from a heteroleptic Ir(III) complex can play an important role in the stability of blue phosphorescence. To rationalize the role of intramolecular hydrogen bonding, a series of Ir(III) complexes is designed and prepared: Ir(dfppy)2(pic-OH) (1a), Ir(dfppy)2(pic-OMe) (1b), Ir(ppy)2(pic-OH) (2a), and Ir(ppy)2(pic-OMe) (2b). The emission lifetime of Ir(dfppy)2(pic-OH) (1a) (τem = 3.19 μs) in dichloromethane solution was found to be significantly longer than that of Ir(dfppy)2(pic-OMe) (1b) (τem = 0.94 μs), because of a substantial difference in the nonradiative decay rate (knr = 0.28 × 105 s-1 for (1a) vs 2.99 × 105 s-1 for (1b)). These results were attributed to the intramolecular OH···OC hydrogen bond of the 3-hydroxy-picolinato ligand. Finally, device lifetime was significantly improved when 1a was used as the dopant compared to FIrpic, a well-known blue dopant. Device III (1a as dopant) achieved an operational lifetime of 34.3 h for an initial luminance of 400 nits compared to that of device IV (FIrpic as dopant), a value of 20.1 h, indicating that the intramolecular hydrogen bond in ancillary ligand is playing an important role in device stability. [ABSTRACT FROM AUTHOR]

The beneficial influence of incorporation of acid-treated and rutile TiO2 (r-TiO2)-modified multi-wall carbon nanotubes (MWNTs) in TiO2 films on photocurrent–voltage characteristics of dye-sensitized solar cells (DSSCs) was studied. Two different routes were adopted for the modification of acid-treated MWNTs (a-MWNTs) with r-TiO2. The films and MWNTs were characterized by electron microscopy, energy dispersive X-ray spectroscopy, XRD and Raman spectroscopy. In the case of incorporation of a-MWNTs with r-TiO2 modification, short-circuit photocurrent ( J sc) of the pertinent DSSC increased by 35% compared with that of a cell with bare TiO2 film. The open-circuit voltage remained almost the same for all cases. The enhanced J sc is explained by the increased surface area of the film, enhanced cluster formation of TiO2 particles around a-MWNTs, and improved interconnectivity of TiO2 particles in the presence of a-MWNTs. [ABSTRACT FROM AUTHOR]