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.

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.

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.

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.

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.

Serum IgA reactivity against GroEL of Streptococcus sanguinis and human heterogeneous nuclear ribonucleoprotein A2/B1 in patients with Behçet disease.

BACKGROUND: Infectious agents, especially Streptococcus sanguinis and herpes simplex virus, have long been postulated as major triggering factors for Behçet disease (BD). OBJECTIVES: To identify an anti-S. sanguinis antigen reacting with serum IgA antibody in patients with BD. METHODS: We detected a target protein by proteomics analysis and evaluated serum IgA reactivity of 100 patients with BD against the identified streptococcal target protein and human heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1. Homologous epitope sequences between the streptococcal target protein and human hnRNP A2/B1 were also evaluated. RESULTS: Four protein bands were detected by immunoprecipitation, and chaperonin GroEL was identified by a proteomics analysis. Reactivity of serum IgA against recombinant S. sanguinis GroEL was detected in 77 of 100 patients with BD (77%) and in 21 of 70 healthy controls (30%). In addition, reactivity of serum IgA against human recombinant hnRNP A2/B1 was seen in 79 of 100 patients with BD (79%) and in eight of 70 healthy controls (11%). Among the eight distinctive epitopes with significant homology between S. sanguinis GroEL and human hnRNP A2/B1, the serum IgA reactivity of patients with BD was markedly higher with epitope 3 (hnRNP A2/B1 peptide 33-46 and GroEL peptide 57-70) and epitope 6 (hnRNP A2/B1 peptide 177-188 and GroEL peptide 347-358). CONCLUSION: We identified an S. sanguinis GroEL protein as a target of serum anti-S. sanguinis IgA antibody reactivity in patients with BD. In addition, patients with BD exhibited serum IgA reactivity against homologous epitope regions between S. sanguinis GroEL and human hnRNP A2/B1.

Both the sera of patients with Behçet's disease and Streptococcus sanguis stimulate membrane expression of hnRNP A2/B1 in endothelial cells.

OBJECTIVES: Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 has been identified as a target antigen of anti-endothelial cell immunglobulin (Ig)A antibodies in patients with Behçet's disease (BD). The aim was to investigate the effects of the sera from BD patients and Streptococcus sanguis on the subcellular expression of hnRNP A2/B1 in human dermal microvascular endothelial cells (HDMECs). METHOD: The sera of BD patients and healthy controls (HC) as well as cultured S. sanguis were used to stimulate HDMECs. Subcellular fractions were obtained from stimulated HDMECs and were subjected to immunoblot analyses. The distribution of hnRNP A2/B1 was investigated by immunocytochemistry and direct immunofluorescence study was performed in biopsy specimens of mucosal ulcers from BD patients. RESULTS: BD patients' sera increased the membrane expression of hnRNP A2/B1 in HDMECs after 12 and 24 h of incubation compared with HDMECs incubated with endothelial cell culture media and HC sera. S. sanguis also increased hnRNP A2/B1 in the cellular membrane. hnRNP A2/B1 mRNA level was also significantly upregulated in HDMECs incubated with BD patients' sera and S. sanguis. Immunocytochemistry demonstrated marked expression of hnRNP A2/B1 in the cytoplasm and cellular membrane of HDMECs incubated with BD patients' sera or S. sanguis. In addition, direct immunofluorescence experiments revealed the co-localization of serum IgA antibodies and monoclonal antibodies (mAbs) against hnRNP A2/B1 in tissue sections from ulcers of BD patients. CONCLUSIONS: Our data indicate that both the sera of BD patients with active disease and S. sanguis infection are inflammatory stimuli that can induce membranous hnRNP A2/B1 expression in HDMECs.

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.

Behçet's disease in concurrence with psoriasis.

BACKGROUND: Behçet's disease (BD) and psoriasis are chronic inflammatory diseases characterized by multisystemic vasculitis and epidermal hyperplasia respectively. Although it has been found that the pathogenesis of BD and psoriasis share common perspectives, reports of patients who have both diseases in concurrence are rare. OBJECTIVES: To analyse and evaluate the clinical manifestations of BD patients who have psoriasis together. METHODS: Retrospective evaluation of the medical records of nine BD patients who were also diagnosed with psoriasis at the BD Specialty Clinic of Severance Hospital was carried out. We analysed the characteristics of patients and the clinical activity of both diseases, and also the effect of the treatment of one disease against the other. RESULTS: Of the nine BD patients who also had psoriasis, male to female ratio was 1 : 2. Two (22.2%) patients had a complete type of BD and seven (77.8%) patients had an incomplete type of BD. For the psoriatic lesions, all nine (100%) patients were diagnosed as psoriasis vulgaris. Five (55.6%) patients had BD as the preceding disease and four (44.4%) patients had psoriasis as the preceding. All five patients who formerly developed BD followed by psoriasis had an active state of BD, but the activity of psoriasis of all nine patients was minimal to average. CONCLUSION: In this study, we evaluated the clinical manifestations of nine patients who had BD and psoriasis together. Although the exact pathogenesis remains unclear, there might be some influence by each disease to the other between BD and psoriasis.

Appearance and dynamics of helical flux tubes under electron cyclotron resonance heating in the core of KSTAR plasmas.

Dual (or sometimes multiple) flux tubes (DFTs) have been observed in the core of sawtoothing KSTAR tokamak plasmas with electron cyclotron resonance heating. The time evolution of the flux tubes visualized by a 2D electron cyclotron emission imaging diagnostic typically consists of four distinctive phases: (1) growth of one flux tube out of multiple small flux tubes during the initial buildup period following a sawtooth crash, resulting in a single dominant flux tube along the m/n=1/1 helical magnetic field lines, (2) sudden rapid growth of another flux tube via a fast heat transfer from the first one, resulting in approximately identical DFTs, (3) coalescence of the two flux tubes into a single m/n=1/1 flux tube resembling the internal kink mode in the normal sawteeth, which is explained by a model of two current-carrying wires confined on a flux surface, and (4) fast localized crash of the merged flux tube similar to the standard sawtooth crash. The dynamics of the DFTs implies that the internal kink mode is not a unique prerequisite to the sawtooth crash, providing a new insight on the control of the sawtooth.

Two-dimensional visualization of growth and burst of the edge-localized filaments in KSTAR H-mode plasmas.

The filamentary nature and dynamics of edge-localized modes (ELMs) in the KSTAR high-confinement mode plasmas have been visualized in 2D via electron cyclotron emission imaging. The ELM filaments rotating with a net poloidal velocity are observed to evolve in three distinctive stages: initial linear growth, interim quasisteady state, and final crash. The crash is initiated by a narrow fingerlike perturbation growing radially from a poloidally elongated filament. The filament bursts through this finger, leading to fast and collective heat convection from the edge region into the scrape-off layer, i.e., ELM crash.

Ritonavir-induced acute kidney injury: kidney biopsy findings and review of literature.

Ritonavir therapy is not generally considered nephrotoxic. We report a case of acute kidney injury secondary to ritonavir, with kidney biopsy demonstrating extensive acute tubular injury. This is the first report of a kidney biopsy and pathology in acute kidney injury associated with ritonavir. A review of published medical literature on the topic is also presented.

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.

The effect of high pressure-low temperature treatment on physicochemical properties in milk.

This study was carried out to investigate the effect of high pressure-low temperature (HPLT) treatment on physicochemical properties and nutrients in milk. The milk was treated at 200 MPa and -4 degrees C for 10, 20, and 30 min. Protease and lipase activities of HPLT-treated milk were highly inactivated compared with that of raw milk. Among time treatments, the 30-min treatment showed the lowest activities compared with others. Absorbance of thiobarbituric acid increased with time in HLPT-treated milks; however, no difference was observed between the raw milk and milk treated for 10 min. The concentrations of short-chain fatty acids except C(4) in HPLT-treated milks increased with time. The total free amino acids in HPLT-treated milks were greater than that of the raw milk for the 30-min treatment. L-Ascorbic acid, niacin, and riboflavin in HPLT-treated milks were significantly lower compared with concentrations in raw milk. For color, the L-value of HPLT-treated milks was significantly lower than that of the raw milk; however, there was no difference in the a-value for 10 min and in the b-value at 20 min between the raw milk and the HPLT-treated milks.

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.

Elastic vesicles as topical/transdermal drug delivery systems.

Skin acts a major target as well as a principle barrier for topical/transdermal drug delivery. Despite the many advantages of this system, the major obstacle is the low diffusion rate of drugs across the stratum corneum. Several methods have been assessed to increase the permeation rate of drugs temporarily. One simple and convenient approach is application of drugs in formulation with elastic vesicles or skin enhancers. Elastic vesicles are classified with phospholipid (Transfersomes((R)) and ethosomes) and detergent-based types. Elastic vesicles were more efficient at delivering a low and high molecular weight drug to the skin in terms of quantity and depth. Their effectiveness strongly depends on their physicochemical properties: composition, duration and application volume, and entrapment efficiency and application methods. This review focuses on the effect of elastic liposomes for enhancing the drug penetration and defines the action mechanism of penetration into deeper skin.