A sustained high-temperature fusion plasma regime facilitated by fast ions.

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

Suicide associated with COVID-19 infection: an immunological point of view.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a pandemic and leading cause of death. Beyond the deaths directly caused by the virus and the suicides related to the psychological response to the dramatic changes as socioeconomic related to the pandemic, there might also be suicides related to the inflammatory responses of the infection. Infection induces inflammation as a cytokine storm, and there is an increasing number of studies that report a relationship between infection and suicide. MATERIALS AND METHODS: We searched the World Health Organization status report and the PubMed database for keywords (COVID-19, suicide, infection, inflammation, cytokines), and reviewed five cytokine pathways between suicide and inflammation using two meta-analyses and two observational studies starting from November 31, 2020, focusing on the relationship between suicide and inflammation by infection. First, we discussed existing evidence explaining the relationship between suicidal behaviors and inflammation. Second, we summarized the inflammatory features found in COVID-19 patients. Finally, we highlight the potential for these factors to affect the risk of suicide in COVID-19 patients. RESULTS: Patients infected with COVID-19 have high amounts of IL-1ß, IFN-γ, IP10, and MCP1, which may lead to Th1 cell response activation. Also, Th2 cytokines (e.g., IL-4 and IL-10) were increased in COVID-19 infection. In COVID-19 patients, neurological conditions, like headache, dizziness, ataxia, seizures, and others have been observed. CONCLUSIONS: COVID-19 pandemic can serve as a significant environmental factor contributing directly to increased suicide risk; the role of inflammation by an infection should not be overlooked.

Interventions to improve hand hygiene compliance in emergency departments: a systematic review.

The emergency department (ED) is where hand hygiene problems are significant as the procedures in the ED are often high risk and invasive. To date, there have been no comprehensive reviews on hand hygiene in EDs. The aim of this study was to investigate hand hygiene compliance (HHC) rate, factors affecting the HHC rate, and intervention strategies to improve HHC in EDs. Electronic databases were used to search for research published from 1948 to January 2018. The databases included ovidMEDLINE, ovidEMBASE, the Cochrane Library, CINAHL, Koreamed, and Kmbase. All study designs were included. Two reviewers independently extracted the data and assessed the bias risk using reliable and validated tools. A narrative synthesis was performed. Twenty-four studies, including 12 cross-sectional surveys and 12 interventional studies, were included. Of the 12 interventional studies reviewed, only 33% (N = 4) reported HHC rates of more than 50%. Factors that influenced HHC included types of healthcare worker, hand hygiene indication, ED crowding, positive attitudes towards HHC, patient location, auditing hand hygiene, and type of shift. Almost all of the studies (83.3%) applied multimodal or dual interventions to improve HHC. A range of strategies, including education, monitoring and providing feedback, campaigns, and cues, effectively improved HHC. The review findings indicate that there is a room for improvement in HHC in EDs. Future randomized controlled trials are necessary to determine which intervention modalities are most effective and sustainable for HHC improvement.

Penile neurovascular structure revisited: immunohistochemical studies with three-dimensional reconstruction.

Penile erection is a neurovascular phenomenon that requires well coordinated and functional interaction between penile vascular and nervous systems. In order to provide a useful tool to examine pathologic changes in the erectile tissue, mainly focusing on penile neurovascular dysfunction, we established the technique to determine the differential distribution of endothelial cells, smooth muscle cells, pericytes, and nerve fibers in the mouse penis using immunohistochemical staining with three-dimensional reconstruction. Immunofluorescent staining of penile tissue was performed with antibodies against CD31 (an endothelial cell marker), smooth muscle α -actin (SMA, a smooth muscle cell marker), NG2 (a pericyte marker), or ßIII-tubulin (a neuronal marker). We reconstructed three-dimensional images of penile vascular or neurovascular system from stacks of two-dimensional images, which allows volume rendering and provides reliable anatomic information. CD31-positive endothelial cells, SMA-positive smooth muscle cells, and NG2-positive pericytes were evenly distributed and composed sinusoidal or venous wall. However, the endothelial layer of the cavernous artery or dorsal artery was mainly covered with smooth muscle cells and rarely associated with pericytes. The reconstructed three-dimensional images clearly visualized typical wavy appearance of nerve fibers that evenly innervate to cavernous sinusoids, cavernous artery, dorsal vein, and dorsal artery. We observed a significant decrease in CD31-positive endothelial cells, NG2-positive pericytes, and ßIII-tubulin-positive nerve fibers in the penis of diabetic mice compared with those in normal condition. Our protocol for immunofluorescent staining with three-dimensional reconstruction will allow a better understanding of the penile neurovascular anatomy and may constitute a standard technique to determine the efficacy of candidate therapeutics targeting therapeutic angiogenesis or neural regeneration.

Calorie restriction reverses age-related alteration of cavernous neurovascular structure in the rat.

Calorie restriction (CR) refers to a reduction of calorie intake without compromising essential nutrients to avoid malnutrition. CR has been established as a non-genetic method of altering longevity and attenuating biological changes associated with aging. Aging is also an important risk factor for erectile dysfunction. The aim of this study was to examine whether CR diet can reverse the age-related alterations of erectile tissue in the aged rat. Four groups of rats were used: young rats (7 months) + ad libitum, aged rats (22 months) + ad libitum, young rats + CR diet, and aged rats + CR diet. The ad libitum group had free access to both food and water, and CR groups were fed 60% of the food intake of their ad libitum littermates, starting from 6 weeks before sacrifice. The penis was harvested and stained with antibodies to von Willebrand factor, smooth muscle α-actin, platelet-derived growth factor receptor-ß, phospho-eNOS, nNOS, and neurofilament. We also performed Masson trichrome staining and TUNEL assay. The blood samples were collected for the measurement of serum total testosterone level. The contents of endothelial cells, smooth muscle cells, pericytes, and neuronal cells as well as serum testosterone levels were significantly lower in the penis of aged rats than in their young littermates. CR significantly restored cavernous endothelial cells, smooth muscle cells, pericytes, and neuronal cell contents and decreased cavernous endothelial cell apoptosis and fibrosis in both young and aged rats. CR also increased serum testosterone level in aged rats, but not in young rats. CR successfully improved age-related derangements in penile neurovascular structures and hormonal disturbance. Along with a variety of lifestyle modifications, our study gave us a scientific rationale for CR as a non-pharmaceutical strategy to reprogram damaged erectile tissue toward neurovascular repair in aged men.

Post calibration of the two-dimensional electron cyclotron emission imaging instrument with electron temperature characteristics of the magnetohydrodynamic instabilities.

The electron cyclotron emission imaging (ECEI) instrument is widely used to study the local electron temperature (Te) fluctuations by measuring the ECE intensity IECE ∝ Te in tokamak plasmas. The ECEI measurement is often processed in a normalized fluctuation quantity against the time averaged value due to complication in absolute calibration. In this paper, the ECEI channels are relatively calibrated using the flat Te assumption of the sawtooth crash or the tearing mode island and a proper extrapolation. The 2-D relatively calibrated electron temperature (Te,rel) images are reconstructed and the displacement amplitude of the magnetohydrodynamic modes can be measured for the accurate quantitative growth analysis.

Clinical significance of serum YKL-40 in Behçet disease.

BACKGROUND: Serum YKL-40 is an inflammatory biomarker of endothelial dysfunction and may play a role in the inflammatory process of Behçet disease (BD). OBJECTIVES: Serum YKL-40 levels were evaluated in patients with BD in order to identify associations with other inflammatory cytokines and establish laboratory parameters. Serum YKL-40 levels were also compared with BD clinical features and disease activity. METHODS: In total, 112 patients with BD and 45 age- and sex-matched healthy volunteers were included. Disease activity was assessed with BD Current Activity Form score and Electronic Medical Record-based Activity Index (EMRAI) score. RESULTS: Serum YKL-40 levels were significantly higher in patients with BD (median 41·88, range 12·52-171·30 ng mL(-1) ) than in healthy volunteers (median 20·92, range 5·01-64·20 ng mL(-1) ; P < 0·01). The cut-off value for YKL-40 (30·005 ng mL(-1) ) was determined from the receiver operating characteristic curve. EMRAI scores and the proportion of patients in the active phase of BD presenting with two or more major criteria were significantly higher in patients with elevated YKL-40 levels (P = 0·04 and P = 0·04, respectively). A statistically significant elevation in YKL-40 levels was observed in patients with active BD compared with patients with inactive BD (P = 0·05). Serum YKL-40 values were positively correlated with interleukin-6 and EMRAI scores (both P = 0·04), indicating that serum YKL-40 levels are increased in patients with BD and positively correlate with disease activity. CONCLUSIONS: YKL-40 may play a role in the pathophysiology of BD and provide a useful marker for monitoring patients with BD.

hTERT mediates norepinephrine-induced Slug expression and ovarian cancer aggressiveness.

Stress hormones have been implicated in both tumor initiation and progression. Human telomerase reverse transcriptase (hTERT) is overexpressed in cancer cells and associated with malignant tumor progression and poor outcome. We thus sought to determine whether the stress hormone norepinephrine (NE) could induce hTERT expression and subsequently ovarian cancer progression. Unexpectedly, NE induced hTERT transcript and protein expression, and subsequently ovarian cancer cell invasion. Pharmacologic inhibition of ß2-adrenergic receptor 2 and protein kinase A, as well as silencing of hypoxia-inducible factor-1α and c-Myc expression, profoundly attenuated NE-induced hTERT expression. Strikingly, stimulation of the cells with NE or ectopic expression of hTERT induced expression of Slug, ovarian cancer cell epithelial-mesenchymal transition (EMT) and invasion. Silencing of hTERT expression abrogated NE-induced ovarian cancer cell invasion, EMT and Slug expression. In addition, silencing of Slug expression significantly inhibited NE- and hTERT-induced ovarian cancer cell EMT and invasion. Moreover, continuous exposure to NE was sufficient to enhance in vivo hTERT expression and metastasis of ovarian cancer cells to the lung. Finally, we provide evidence that hTERT links Src to Slug expression in NE-induced ovarian cancer EMT and metastasis. We thus demonstrate a novel role of hTERT in stress hormone-induced ovarian cancer aggressiveness through inducing Slug, providing novel biomarkers and potential therapeutic targets for ovarian cancer.

Variant Influenza Associated with Live Animal Markets, Minnesota.

Variant influenza viruses are swine-origin influenza A viruses that cause illness in humans. Surveillance for variant influenza A viruses, including characterization of exposure settings, is important because of the potential emergence of novel influenza viruses with pandemic potential. In Minnesota, we have documented variant influenza A virus infections associated with swine exposure at live animal markets.

Quasi 3D ECE imaging system for study of MHD instabilities in KSTAR.

A second electron cyclotron emission imaging (ECEI) system has been installed on the KSTAR tokamak, toroidally separated by 1/16th of the torus from the first ECEI system. For the first time, the dynamical evolutions of MHD instabilities from the plasma core to the edge have been visualized in quasi-3D for a wide range of the KSTAR operation (B0 = 1.7∼3.5 T). This flexible diagnostic capability has been realized by substantial improvements in large-aperture quasi-optical microwave components including the development of broad-band polarization rotators for imaging of the fundamental ordinary ECE as well as the usual 2nd harmonic extraordinary ECE.

Toroidal mode number estimation of the edge-localized modes using the KSTAR 3-D electron cyclotron emission imaging system.

A new and more accurate technique is presented for determining the toroidal mode number n of edge-localized modes (ELMs) using two independent electron cyclotron emission imaging (ECEI) systems in the Korea Superconducting Tokamak Advanced Research (KSTAR) device. The technique involves the measurement of the poloidal spacing between adjacent ELM filaments, and of the pitch angle α* of filaments at the plasma outboard midplane. Equilibrium reconstruction verifies that α* is nearly constant and thus well-defined at the midplane edge. Estimates of n obtained using two ECEI systems agree well with n measured by the conventional technique employing an array of Mirnov coils.

Automated registration of optical coherence tomography and dermoscopy in the assessment of sub-clinical spread in basal cell carcinoma.

Optical coherence tomography (OCT) has been shown to be of clinical value in imaging basal cell carcinoma (BCC). A novel dual OCT-video imaging system, providing automated registration of OCT and dermoscopy, has been developed to assess the potential of OCT in measuring the degree of sub-clinical spread of BCC. Seventeen patients selected for Mohs micrographic surgery (MMS) for BCC were recruited to the study. The extent of BCC infiltration beyond a segment of the clinically assessed pre-surgical border was evaluated using OCT. Sufficiently accurate (<0.5 mm) registration of OCT and dermoscopy images was achieved in 9 patients. The location of the OCT-assessed BCC border was also compared with that of the final surgical defect. Infiltration of BCC across the clinical border ranged from 0 mm to >2.5 mm. In addition, the OCT border lay between 0.5 mm and 2.0 mm inside the final MMS defect in those cases where this could be assessed. In one case, where the final MMS defect was over 17 mm from the clinical border, OCT showed >2.5 mm infiltration across the clinical border at the FOV limit. These results provide evidence that OCT allows more accurate assessment of sub-clinical spread of BCC than clinical observation alone. Such a capability may have clinical value in reducing the number of surgical stages in MMS for BCC. There may also be a role for OCT in aiding the selection of patients most suitable for MMS.

Aberrant expression of Wnt family contributes to the pathogenesis of diabetes-induced erectile dysfunction.

Diabetic erectile dysfunction (ED) has multiple causative factors, such as endothelial and smooth muscle dysfunction and cavernous fibrosis. Wnt signalling is essential for normal embryonic development and for tissue homeostasis in adults. Aberrant activation of Wnt family members has been implicated in tissue fibrosis and in angiogenesis. In this study, we investigated the differential expression of Wnts in the penises of mice with streptozotocin-induced diabetic ED. We also examined the effect of transforming growth factor-ß1 (TGF-ß1) on the expression of Wnts in primary cultured fibroblasts isolated from human tunica albuginea. Among the mouse and human Wnts tested, 16 mouse Wnts and 14 human Wnts were detected in the corpus cavernosum tissue of normal mice and in fibroblasts derived from human tunica albuginea respectively. We observed up-regulation of Wnt10b (known to be involved in tissue fibrosis) and down-regulation of Wnt16 (known to be involved in vasculogenesis and hematopoiesis), both in the diabetic condition in vivo and with treatment of fibroblasts with TGF-ß1 in vitro. Wnt10b was mainly expressed in fibroblasts and Wnt16 was colocalized with smooth muscle cells in the corpus cavernosum tissue. Cavernous TGF-ß1 protein expression and the degree of cavernous fibrosis determined by the ratio of collagen to smooth muscle content were significantly higher in diabetic mice than in controls. Cavernous endothelial content was significantly decreased by the diabetic condition. Overexpression of Wnt16 with plasmid vector accelerated tube formation in primary cultured mouse cavernous endothelial cells. However, down-regulation of Wnt10b with small interfering RNA did not decrease the production of extracellular matrix protein in human fibroblasts. This is the first report demonstrating the differential expression of Wnts in diabetic mouse penis. Aberrant Wnt expression might contribute to the pathogenesis of ED.

The effect of CD34+ cell-containing autologous platelet-rich plasma injection on pattern hair loss: a preliminary study.

BACKGROUND: Mobilized CD34+ cells in peripheral blood have angiogenic potential, which is an important factor in active hair growth. In addition, activated autologous platelet-rich plasma (PRP) has been reported to induce the proliferation of dermal papilla cells. OBJECTIVES: To investigate the clinical efficacy of interfollicular injection of CD34+ cell-containing PRP preparation for pattern hair loss. PATIENTS AND METHODS: CD34+ cell-containing PRP preparation was injected on the scalps of 13 patients with pattern hair loss, and 13 patients were treated with interfollicular placental extract injection as a control. The numbers of platelets in PRP were microscopically counted and CD34+ cells were evaluated with flow cytometry. RESULTS: Three months after the first treatment, the patients presented clinical improvement in the mean number of hairs, 20.5 ± 17.0% (P < 0.0001), mean hair thickness, 31.3 ± 30.1% (P < 0.0001), and mean two-point score, 84.4 ± 51.7% (P < 0.0001) compared with baseline values. At 6 months, the patients presented clinical improvement in mean hair count, 29.2 ± 17.8% (P < 0.0001), mean hair thickness, 46.4 ± 37.5% (P < 0.0001), and mean two-point score, 121.3 ± 66.8% (P < 0.0001) compared with baseline. The MIXED procedure revealed that CD34+ cell-containing PRP treatment presented a higher degree of improvement than placental extract treatment in hair thickness (P = 0.027) and overall clinical improvement (P = 0.023). CONCLUSION: Our data suggest that the interfollicular injection of autologous CD34+ cell-containing PRP preparation has a positive therapeutic effect on male and female pattern hair loss without remarkable major side-effects.

Immunopathogenic characterization of cutaneous inflammation in Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a recurrent multisystemic inflammatory disease characterized by recurrent oral aphthous and genital ulcers, ocular lesions and cutaneous lesions. Although many studies of cytokine levels in sera of BD patients have been conducted, there are only limited number of studies about the cytokine expression and cellular infiltration in the BD-related skin lesions. OBJECTIVES: To investigate the immunophenotypes and cytokine profiles of BD-related skin lesions. METHODS: Twenty patients who fulfilled the diagnostic criteria for BD with BD-related skin lesions were enrolled in this study. We assessed the histopathological features of BD-related skin lesions by immunohistochemical studies with anti-human CD4, CD8, CD68, FoxP3, CD-11b, IFN-γ and IL-4 antibodies. RESULTS: Immunophenotyping of inflammatory infiltrating cells showed that CD68+ macrophages were the most common type of infiltrated cells in erythema nodosum-like lesions, erythema multiforme-like lesions and Sweet's syndrome-like lesions, whereas neutrophils were the main population of inflammatory infiltrating cells in papulopustular lesions. In all of the four types of BD-related skin lesions, the percentage of CD8+ T cells was higher than that of CD4+ T cells (P < 0.05), and IL-4 expression was stronger than IFN-γ expression (P < 0.05). CONCLUSION: In this study, we assessed the infiltrating inflammatory cells and cytokine expression of acute cutaneous lesions in BD through immunohistochemical staining of BD-related skin lesions. Further studies about the disease activity and the molecular biology underlying the cutaneous inflammation are needed to understand the detailed pathogenesis of BD.

Changing clinical expression of Behçet disease in Korea during three decades (1983-2012): chronological analysis of 3674 hospital-based patients.

BACKGROUND: Behçet disease (BD) is a chronic multisystemic vasculitis affecting blood vessels of any calibre or type. Recent evidence suggests that the clinical expression of BD is lessening. OBJECTIVES: To examine the clinical expression of BD in Korea during the past three decades via a large patient registry. METHODS: Initial manifestations of patients with BD seen at a tertiary referral hospital between 1983 and 2012 were reviewed retrospectively, stratifying patients by decade to compare epidemiological data and cardinal symptoms. RESULTS: In total 3674 patients with BD were reviewed. Significant proportional declines occurred with respect to male sex, complete type BD and major presenting features (genital ulcers, ocular involvement and skin lesions), whereas the mean patient age rose progressively, as did the frequencies of joint, gastrointestinal and central nervous system manifestations (all P < 0·0001). CONCLUSIONS: During the past three decades, clinical expression of BD in Korea has changed, resulting in fewer instances of complete type disease, declining male propensity, and shifting patterns of organ involvement.

Distal renal tubular acidosis associated with Sjogren syndrome.

Renal tubular acidosis is a common cause of normal anion gap metabolic acidosis but these disorders can be easily missed or misdiagnosed. We highlight the approach to assessing renal tubular acidosis by discussing a case study with a temporal data set collected over more than 5 weeks. We highlight the principles and the necessary information required for a diagnosis of classic distal renal tubular acidosis. We also briefly review several aspects of type 1 renal tubular acidosis related to autoimmune disease, drugs and thyroid disorders.

New decontamination method based on caprylic acid in combination with citric acid or vanillin for eliminating Cronobacter sakazakii and Salmonella enterica serovar Typhimurium in reconstituted infant formula.

The antimicrobial effects of natural compounds (caprylic acid, CA; citric acid, CTA; and vanillin, VNL) on the inactivation of Cronobacter sakazakii and Salmonella enterica serovar Typhimurium were examined in reconstituted infant formula. The samples were treated with: 1) CA, CTA, or VNL alone (0, 10, 20, 30, 40, 60, and 80 mM); 2) a combination of CA (10 and 20 mM) and CTA (15 and 30 mM); and 3) a combination of CA (10 and 20 mM) and VNL (15 and 30 mM), at mild feeding temperatures (40 °C and 45 °C), and the bacterial populations were assayed periodically (0, 5, 10, and 30 min). For both bacteria, the combined treatments had marked synergistic antimicrobial effects compared with the sum of the effects of each individual treatment. For example, there was no noticeable reduction (P > 0.05) in the population of C. sakazakii following an individual treatment with 20 mM CA or 30 mM CTA for 5 min at 40 °C, whereas the population was reduced to undetectable levels (reduction > 7.3 log CFU/ml) following treatment with a combination of CA and CTA (20 CA+30 CTA for 5 min at 40 °C). As the temperature increased, the bactericidal effect was stronger at all time points with a synergistic effect. In a validation assay using a low level inoculum (approximately 10³ CFU/ml) of desiccation-stressed bacteria in certain conditions, the combined treatments (e.g., CA 10 mM+CTA 30 mM for 5 min at 45 °C for C. sakazakii, and CA 10mM+VNL 15 mM for 10 min at 45 °C for S. Typhimurium) completely destroyed the bacteria with no recovery of cell viability. Disintegration of the membrane and changes in the cell structure or morphology, such as plasmolysis and membrane disruption, were detected by flow cytometry and electron microscopy, respectively. These methods use antimicrobials that could be applied as food additives in infant formula, which may help to eliminate bacteria.

RAF kinase inhibitor-independent constitutive activation of Yes-associated protein 1 promotes tumor progression in thyroid cancer.

The transcription coactivator Yes-associated protein 1 (YAP1) is regulated by the Hippo tumor suppressor pathway. However, the role of YAP1 in thyroid cancer, which is frequently associated with the BRAF(V600E) mutation, remains unknown. This study aimed to investigate the role of YAP1 in thyroid cancer. YAP1 was overexpressed in papillary (PTC) and anaplastic thyroid cancer, and nuclear YAP1 was more frequently detected in BRAF(V600E) (+) PTC. In the thyroid cancer cell lines TPC-1 and HTH7, which do not have the BRAF(V600E) mutation, YAP1 was cytosolic and inactive at high cell densities. In contrast, YAP1 was retained in the nucleus and its target genes were expressed in the thyroid cancer cells 8505C and K1, which harbor the BRAF(V600E) mutation, regardless of cell density. Furthermore, the nuclear activation of YAP1 in 8505C was not inhibited by RAF or MEK inhibitor. In vitro experiments, YAP1 silencing or overexpression affected migratory capacities of 8505C and TPC-1 cells. YAP1 knockdown resulted in marked decrease of tumor volume, invasion and distant metastasis in orthotopic tumor xenograft mouse models using the 8505C thyroid cancer cell line. Taken together, YAP1 is involved in the tumor progression of thyroid cancer and YAP1-mediated effects might not be affected by the currently used RAF kinase inhibitors.