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.

Fate of the micropenis and constitutional small penis: do they grow to normalcy in puberty?

INTRODUCTION: Penile length is an important indicator of male sexual development. Scarce data were reported on penile length measurements in children comparing changes between prepuberty and puberty for the small penile issue with long-term follow-up. OBJECTIVE: The purpose of this study was to investigate the possibility of catch-up growth of the penile length of boys with a small penis in the long-term follow-up. STUDY DESIGN: From April 2001 to December 2016, 27 boys who visited the outpatient clinic owing to a small penis, without any chromosomal anomalies and other genital disorder, were investigated retrospectively. Micropenis is defined as 2.5 standard deviations less than the mean stretched penile length (SPL) of age. Periodic penile length, testicular volume, hormonal levels (serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH)), and bone age were measured. Pubertal development was recorded by using the Tanner scale. The effect of hormonal therapy and the factors attributable to the increment of the penile length were evaluated. RESULTS: The mean age at the first visit was 9.8 years (5-12 years) and that at puberty was 12.6 years (10-16 years). The length of the penis at the initial visit was 4.0 ± 0.8 cm (2.5-6.0) and at puberty, 7.3 ± 1.8 cm (4.0-12.0). Nine patients diagnosed with micropenis no longer had a micropenis in puberty. The less the age-matched SPL, the more the increment of SPL that was observed (rho = - 0.548, P = 0.003). The mean increment of SPL in the hormonal therapy group (11 boys) and the non-hormonal therapy group (16 boys) was not statistically different (43.5 ± 22. 9% vs 41.5 ± 21.6%, respectively, P = 0.497). DISCUSSION: This study explains how much the growth of a small penis catches up in puberty. From the point of view of the increment of SPL, the increment was higher in boys who belonged to the smaller penis group. Hormonal therapy does not attribute to an increase in the length after long-term follow-up. Limitations of this study were its retrospective origin with a small number of patients in a single center. CONCLUSION: Catch-up growth of the small penis at puberty was accomplished in most children with a small penis before puberty. Hormonal treatment was not significantly correlated with the penile length increment in the long-term follow-up.

Comorbidities Can Predict Mortality of Kidney Transplant Recipients: Comparison With the Charlson Comorbidity Index.

BACKGROUND: Comorbid conditions are important in the survival of kidney transplant recipients. The weights assigned to comorbidities to predict survival may vary based on the type of index disease and advances in the management of comorbidities. We aimed to develop a modified Charlson comorbidity index (CCI) in renal allograft recipients (mCCI-KT), thereby improving risk stratification for mortality. METHODS: A total of 3765 recipients in a multicenter cohort were included to develop a comorbidity score. The weights of the comorbidities, per the CCI, were recalibrated using a Cox proportional hazards model. RESULTS: Peripheral vascular disease, liver disease, myocardial infarction, and diabetes in the CCI were selected from the Cox proportional hazards model. Thus, the mCCI-KT included 4 comorbidities with recalibrated severity weights. Whereas the CCI did not discriminate for survival, the mCCI-KT provided significant discrimination for survival using the Kaplan-Meier method and Cox regression analysis. The mCCI-KT showed modest increases in c-statistics (0.54 vs 0.52, P = .001) and improved net mortality risk reclassification by 16.3% (95% confidence interval, 3.2-29.4; P = .015) relative to the CCI. CONCLUSION: The mCCI-KT stratifies the risk for mortality in renal allograft recipients better than the CCI, suggesting that it may be a preferred index for use in clinical practice.

A semiconductor photon-sorter.

Obtaining substantial nonlinear effects at the single-photon level is a considerable challenge that holds great potential for quantum optical measurements and information processing. Of the progress that has been made in recent years one of the most promising methods is to scatter coherent light from quantum emitters, imprinting quantum correlations onto the photons. We report effective interactions between photons, controlled by a single semiconductor quantum dot that is weakly coupled to a monolithic cavity. We show that the nonlinearity of a transition modifies the counting statistics of a Poissonian beam, sorting the photons in number. This is used to create strong correlations between detection events and to create polarization-correlated photons from an uncorrelated stream using a single spin. These results pave the way for semiconductor optical switches operated by single quanta of light.

Clinical outcomes in Asian elderly kidney transplant recipients: a multicenter cohort study.

BACKGROUND: The kidney transplantation rate in elderly patients is increasing rapidly. However, the clinical outcomes of kidney transplantation in elderly patients have not yet been thoroughly evaluated. METHODS: This multicenter cohort study included adult kidney transplant recipients (KTRs) admitted to five major tertiary hospitals in Korea between 1997 and 2012. A total of 3,565 adult participants were enrolled. Patient survival, allograft survival, and biopsy-proven acute rejection (BPAR) of 242 elderly recipients (≥ 60 years) were assessed and compared with those of a younger population. RESULTS: Patients were divided into five groups according to age at time of transplantation. The proportion of elderly patients was 6.7 % (mean age, 63.1 ± 2.7 years; n = 242). The numbers of male patients (69.4%), those with diabetes mellitus history (36.3%), and those with pretransplantation ischemic heart disease history (17.7%) were significantly higher in the elderly group than in the younger age groups. Elderly patients were more likely to receive a cadaveric kidney, and overall mortality rates were significantly higher in the elderly patients (1-year survival 93.3%, 5-year survival 91.3%). However, death-censored allograft survival rate and BPAR were not affected by patient age (P = .104 and .501, respectively). Among the elderly, BPAR and female donors were independent risk factors for allograft loss. CONCLUSION: The overall survival rate of the elderly KTRs was significantly lower than that of younger KTRs. However, the death-censored allograft survival rate did not differ between groups. Kidney transplantation should not be stagnated especially in elderly patients with end-stage renal disease.

Renal outcomes after liver transplantation in fulminant hepatitis A with acute kidney injury: comparison with hepatorenal syndrome.

BACKGROUND: Liver transplantation (LT) is the treatment of choice for hepatorenal syndrome (HRS). Recently, acute kidney injury (AKI) due to acute hepatitis A (HA) is increasing, but the outcome of LT is not well established. We investigated the outcomes of LT in patients with AKI due to acute HA compared with those of patients with HRS due to other causes. METHODS: We investigated the outcomes of LT in 20 patients with AKI associated with acute HA (HAV group) compared with 76 patients with hepatorenal syndrome (HRS) due to other causes (HRS group) at 3 Korea centers. RESULTS: Preoperative mean prothrombin time and serum creatinine level were higher in the HAV group than in the HRS group. But mean total bilirubin level was lower in the HAV group. There was no difference in Model for End-Stage Liver Disease scores. Post-transplantation patient and graft survival rates were similar between the 2 groups. More patients in the HAV group needed post-transplantation hemodialysis than in the HRS group (65.0% vs 38.2%; P = .043). However, post-transplantation estimated glomerular filtration rate was significantly higher in the HAV group after post-transplantation month 2 (P < .05). CONCLUSIONS: Peri-transplantation kidney function of the HAV group was poorer than that of HRS group. However, post-transplantation long-term renal outcome could be better in the HAV group.

MiR-29b controls fetal mouse neurogenesis by regulating ICAT-mediated Wnt/ß-catenin signaling.

ß-Catenin has been widely implicated in the regulation of mammalian development and cellular homeostasis. However, the mechanisms by which Wnt/ß-catenin signaling components regulate physiological events during brain development remain undetermined. Inactivation of glycogen synthase kinase (GSK)-3ß leads to ß-catenin accumulation in the nucleus, where it couples with T-cell factor (TCF), an association that is disrupted by ICAT (inhibitor of ß-catenin and T cell factor). In this study, we sought to determine whether regulation of ICAT by members of the microRNA-29 family plays a role during neurogenesis and whether deregulation of ICAT results in defective neurogenesis due to impaired ß-catenin-mediated signaling. We found that miR-29b, but not miR-29a or 29c, is significantly upregulated in three-dimensionally cultured neural stem cells (NSCs), whereas ICAT is reduced as aged. Treatment with a miR-29b reduced the reporter activity of a luciferase-ICAT 3'-UTR construct whereas a control (scrambled) miRNA oligonucleotide did not, indicating that miR-29b directly targets the 3'-UTR of ICAT. We also found that treatment with miR-29b diminished NSC self-renewal and proliferation, and controlled their fate, directing their differentiation along certain cell lineages. Furthermore, our in vivo results showed that inhibition of miR-29b by in utero electroporation induced a profound defect in corticogenesis during mouse development. Taken together, our results demonstrate that miR-29b plays a pivotal role in fetal mouse neurogenesis by regulating ICAT-mediated Wnt/ß-catenin signaling.

Utility of QuantiFERON-TB assay for prediction of tuberculosis development in kidney transplant patients in an intermediate-tuberculosis-burden country: lack of evidence for enhanced prediction for short-term tuberculosis development.

INTRODUCTION: Although a latent tuberculosis (TB) infection is a risk factor for active TB, the diagnosis of latent TB infection is difficult in end-stage renal disease patients. PATIENTS AND METHODS: We retrospectively compared the results of the QuantiFERON-TB (QFT) test and the tuberculin skin test in patients on the waiting list for kidney transplantation (KT), and investigated whether the QFT test can predict TB development in KT recipients in an intermediate-TB-burden country. RESULTS: The incidence of post-KT TB was 283 cases/100,000 patient-years among 1274 KT recipients at the Seoul National University Hospital. The overall standardized incidence ratio of TB was 4.358 compared with the general population. A past history of TB infection, smoking history, myocardial infarction after KT, and pneumocystis infection were significant predictors of subsequent TB development (adjusted odds ratios were 3.618, 2.959, 9.993, and 5.708, respectively). Among the 129 recipients who had the QFT test, 42 patients (32.5%) had positive a QFT. At a median follow-up of 8.4 ± 6.8 months, 1 patient with positive QFT results developed TB after KT, and 1 of the 87 patients with negative QFT results developed TB after KT. In both of these 2 cases, active TB developed despite isoniazid prophylaxis. Among 272 patients on the waiting list for KT, the tuberculin skin test and QFT were positive in 22.8% and 35.3%, respectively. The degree of agreement between the 2 tests was poor (κ = 0.352). CONCLUSIONS: The QFT test did not predict subsequent short-term TB development. Furthermore, a long-term and larger-scale study is needed to confirm our results.

Intrinsic rotation driven by non-Maxwellian equilibria in Tokamak plasmas.

The effect of small deviations from a Maxwellian equilibrium on turbulent momentum transport in tokamak plasmas is considered. These non-Maxwellian features, arising from diamagnetic effects, introduce a strong dependence of the radial flux of cocurrent toroidal angular momentum on collisionality: As the plasma goes from nearly collisionless to weakly collisional, the flux reverses direction from radially inward to outward. This indicates a collisionality-dependent transition from peaked to hollow rotation profiles, consistent with experimental observations of intrinsic rotation.

Identification of the effects of aging-related gene-matrix metalloproteinase on allograft outcomes in kidney transplantation.

BACKGROUND: Aging plays a profound role in the ability of the kidney to function. Aging which varies among individuals, has been associated with the matrix metalloproteinase (MMP) 7 and 20 genes. This study was conducted to analyze correlations between polymorphisms of MMP genes [rs880197 in MMP7 (A>T) and rs1711437 in MMP20 (G>A)] and transplant outcomes in 235 recipients. METHODS: Transplant outcomes were evaluated according to the sum of the A alleles in the recipients and the donors. The group with a high number of A alleles (≥3) was compared with the group with a low number (<3). RESULTS: The group with a high number of MMP7 A alleles showed a lower risk of chronic tubulointerstitial lesion than the group with a low number (P = .009). The group with a high number of MMP20 A alleles had showed better long-term kidney function at 10 years after transplantation than the group with a low number (P = .026). Furthermore, the group with a high number of MMP20 A alleles showed a trend toward better graft survival compared with the group with a low number, especially among recipients followed for >1 year (P = .022). CONCLUSIONS: Polymorphisms of MMP7 and MMP20 genes may be surrogate markers to predict long-term outcomes after kidney transplantation.

Botulinum toxin injection into the superior rectus for treatment of strabismus.

Botulinum toxin injected into the superior rectus (SR) has rarely been described in the literature. We conducted a database search to identify all cases of SR toxin from 1982 to 2010 at our institution. Out of a total of 7575 patients in the database, only eight cases of SR toxin were identified, all of which had residual hypertropia following previous ocular surgery. This surgery comprised: retinal surgery (3 patients), strabismus surgery for thyroid eye disease (2), and transposition for VI nerve palsy (2 patients). In seven out of eight cases, a long-lasting mean reduction of 10(Δ) was achieved from between two and three injections. Ptosis occurred in all but one case, but resolved. We conclude that SR toxin injection has very limited indications, but may be considered in residual hypertropia presumed secondary to a tight or overacting SR where the patient can tolerate the temporary iatrogenic ptosis.

Therapeutic effects of stem cells and substrate reduction in juvenile Sandhoff mice.

Sandhoff Disease (SD) involves the CNS accumulation of ganglioside GM2 and asialo-GM2 (GA2) due to inherited defects in the ß-subunit gene of ß-hexosaminidase A and B (Hexb gene). Substrate reduction therapy, utilizing imino sugar N-butyldeoxygalactonojirimycin (NB-DGJ), reduces ganglioside biosynthesis and levels of stored GM2 in SD mice. Intracranial transplantation of Neural Stem Cells (NSCs) can provide enzymatic cross correction, to help reduce ganglioside storage and extend life. Here we tested the effect of NSCs and NB-DGJ, alone and together, on brain ß-hexosaminidase activity, GM2, and GA2 content in juvenile SD mice. The SD mice received either cerebral NSC transplantation at post-natal day 0 (p-0), intraperitoneal injection of NB-DGJ (500 mg/kg/day) from p-9 to p-15, or received dual treatments. The brains were analyzed at p-15. ß-galactosidase staining confirmed engraftment of lacZ-expressing NSCs in the cerebral cortex. Compared to untreated and sham-treated SD controls, NSC treatment alone provided a slight increase in Hex activity and significantly decreased GA2 content. However, NSCs had no effect on GM2 content when analyzed at p-15. NB-DGJ alone had no effect on Hex activity, but significantly reduced GM2 and GA2 content. Hex activity was slightly elevated in the NSC + drug-treated mice. GM2 and GA2 content in the dual treated mice were similar to that of the NB-DGJ treated mice. These data indicate that NB-DGJ alone was more effective in targeting storage in juvenile SD mice than were NSCs alone. No additive or synergistic effect between NSC and drug was found in these juvenile SD mice.

Evaluation of methods to estimate glomerular filtration rate versus actual drug clearance in patients with chronic spinal cord injury.

STUDY DESIGN: A retrospective chart review. OBJECTIVES: To evaluate different methods of estimating renal function compared with patient-specific vancomycin and aminoglycoside (AG) clearance (CL(DRUG)) in patients with spinal cord injury (SCI), and to develop a new equation to more accurately estimate glomerular filtration rate (GFR) in SCI patients in order to optimize dosing for vancomycin and AG. SETTING: Veterans Affairs medical center in California, United States of America, tertiary care facility with the largest inpatient SCI center in the VA system. METHODS: Retrospective data collection from patient records. Pharmacokinetic analysis was performed to obtain actual CL(DRUG,) which is compared with different methods of estimating GFR.A total of 310 patients were initially assessed; however, only 141 patients met the inclusion criteria, had a diagnosis of chronic SCI, and received vancomycin or AG with at least one drug level at steady state from January to December of 2008. RESULTS: All four equations evaluated to estimate GFR significantly overestimated CL(DRUG): the Modification of Diet in Renal Disease equation by 141%, Cockcroft-Gault equation by 83%, Chronic Kidney Disease Epidemiology Collaboration equation by 82% and 24-h endogenous creatinine clearance by 71% (P<0.001). The modified Cockcroft-Gault equation (CL(M)) showed improvement, however, still overestimated CL(DRUG) by 39% (P<0.001). Thus, a new equation for SCI (CL(SCI)) was developed which underestimated CL(DRUG) by <5% (P=0.16). CONCLUSION: Compared with different methods of estimating GFR, CL(SCI)=2.3 × x (0.7) (x equals CL(M) in ml min(-1)) more accurately estimates CL(DRUG) in chronic SCI patients.

The management of patients with thyroid eye disease after bilateral orbital 3 wall decompression.

INTRODUCTION: Thyroid eye disease is the most common cause of unilateral and bilateral proptosis in adults. Orbital decompression surgery may cause and/or worsen a pre-existing ocular motility disorder. METHODS: A retrospective review was carried out of all bilateral 3 wall orbital decompressions for severe thyroid eye disease performed between January 2002 and December 2004 by one surgeon. Subsequent surgeries were recorded. RESULTS: Seventy-four patients were identified, 59 (80%) females and 15 (20%) males. Mean age at the time of decompression was 46 years. Fifteen (20%) patients complained of diplopia due to strabismus prior to decompression surgery and 20 (27%) developed new diplopia postsurgery. Twenty patients (27%) required no further intervention following decompression surgery; the remainder underwent an average of 2.5 procedures. Strabismus surgery was performed in 32 (43%) patients. The mean time from the decompression to first strabismus surgery was 12 months. Forty-three (58%) patients underwent lid surgery. The mean time from decompression to first lid surgery was 16 months. CONCLUSION: This study demonstrates how this group of complex patients required multiple surgical procedures within an extended timescale, therefore requiring several in- and outpatient visits.

Inhibition of insulin degrading enzyme by racecadotril in the brain of Wistar rats.

Racecadotril is an enkephalinase inhibitor used to treat abdominal discomfort in the clinic. The blood-glucose lowering action of racecadotril has been observed in rats; however, the mechanisms remain obscure. 8-week-old Wistar rats were intravenously injected with racecadotril and the levels of insulin in the brain were measured. Additionally, brain homogenates were co-incubated with racecadotril or thiorphan to evaluate insulin degrading enzyme (IDE) activity. Otherwise, rats were pretreated by intracerebroventricular (i. c. v.) injection of insulin antibody or glibenclamide at a dose sufficient to inhibit K (ATP) channels prior to injection of racecadotril. Moreover, rats were vagotomized to evaluate the role of the cholinergic nerve. Racecadotril significantly decreased the plasma glucose in rats; this action of racecadotril was abolished by i. c. v. pretreatment with insulin antibody or glibenclamide. Also, i. c. v. injection of thiorphan, the active form of racecadotril, lowered blood glucose, but this effect disappeared in the presence of the insulin antibody. In rat brain homogenates, racecadotril and thiorphan inhibited IDE activity and increased the cerebral insulin level. The blood-glucose lowering action of racecadotril or thiorphan was diminished in vagotomized rats. Our results suggest that racecadotril lowers blood glucose mainly through inhibition of IDE activity and increases endogenous insulin in the brain. Subsequently, the increased insulin might activate insulin receptor, which opens the K (ATP) channel and induces peripheral insulin release through the vagal nerve. Thus, we provide the new finding that racecadotril has the ability to inhibit IDE in rat brain.

Successfully treated multicentric Castleman's disease with renal thrombotic microangiopathy using rituximab and corticosteroid.

Thrombotic microangiopathy (TMA) is a rare renal complication accompanied with Castleman's disease. We report the first case of TMA combined plasma cell type multicentric Castleman's disease (MCD) which was successfully treated with rituximab and corticosteroid. A previously healthy 60-year-old Korean man was admitted due to acute renal failure, thrombocytopenia, and multiple lymphadenopathies. The result of lymph node biopsy was plasma cell type Castleman's disease and TMA was revealed by kidney biopsy. After treatment with rituximab, prednisolone and temporary hemodialysis, complete remission was achieved. The combination of corticosteroid and rituximab was associated with improvement for this patient.

Metformin can activate imidazoline I-2 receptors to lower plasma glucose in type 1-like diabetic rats.

Metformin is widely used in clinic for handling the diabetic disorders. However, action mechanisms of metformin remain obscure. It has recently been indicated that guanidinium derivatives are ligands to activate type-2 imidazoline receptors (I-2 receptors) that can improve diabetes through increment in skeletal muscle glucose uptake. Also, activation of I-2 receptors can increase the release of ß-endorphin in diabetic animals. Because metformin is a guanidinium derivative, we were interested in the effect of metformin on I-2 receptors. In the present study, the marked blood glucose-lowering action of metformin in streptozotocin-induced type-1 like diabetes rats was blocked by specific I-2 receptor antagonist, BU224, in a dose-dependent manner. Also, the increase of ß-endorphin release by metformin was blocked by BU224 in same manner. A specific competition between metformin and BU224 was observed in isolated adrenal medulla. Otherwise, amiloride at the dose sufficient to block I-2A receptor abolished the metformin-induced ß-endorphin release, but only the blood glucose-lowering action of metformin was markedly reduced. In addition, the blood glucose-lowering action of metformin in bilateral adrenalectomized rats was diminished by amiloride at higher doses. These results suggest that metformin might activate imidazoline I-2 receptors while I-2A receptors link the increase of ß-endorphin release and I-2B receptors couple to the other actions for lowering of blood glucose in type-1 like diabetic rats.

'Smoking': use of cigarettes, cigars and blunts among Southeast Asian American youth and young adults.

Increased use of cigars has been noted among youth, as well as use of blunts (hollowed-out cigars filled with marijuana). Three types of relationships have been previously hypothesized between use of tobacco and marijuana in substance use progression. We aimed to assess these relationships for Southeast Asian American youth and adults in an urban population. We conducted in-person interviews with 164 Southeast Asians, smokers and non-smokers, in two low-income urban communities in Northern California, collecting both quantitative and qualitative data. Analysis of the quantitative data indicated distinct use patterns for blunts, cigars and other forms of marijuana in terms of associations with generation in the United States. The use of these items was also found to be related: ever having smoked cigarettes or blunts increased the risk of ever having smoked the other three items. Qualitative data found indications of all three hypothesized relationships between tobacco and marijuana for youths but not for older adults. For youths in the study, 'smoking' was found to constitute a social construct within which use of cigarettes, cigars and blunts were somewhat interchangeable. Youths in similar settings may initiate into and progress through smoking as an activity domain rather than any one of these items.

Residual symptomatic superior oblique palsy.

PURPOSE: To determine the outcome of patients treated for residual symptomatic hyperdeviations, in a tertiary referral centre, following a previous weakening procedure of the ipsilateral Inferior Oblique (IO) muscle in Superior Oblique (SO) palsy. METHODS: A retrospective review of 37 patients seen over 6 years at one institution who had remained symptomatic from a SO palsy despite having had an initial weakening procedure to their ipsilateral IO (myectomy or recession). Median age was 19 years (range 3 to 56 years). Information recorded included pre- and postoperative deviation and ocular motility findings, preoperative symptoms, findings at the time of surgery, and outcome. RESULTS: Nine patients underwent repeat weakening surgery (disinsertion) on the ipsilateral IO only. Thirteen patients underwent strengthening surgery on the ipsilateral SO only. Nine patients had surgery on both the ipsilateral IO and SO. Six patients had surgery on the ipsilateral IO with either horizontal or vertical rectus surgery. Nine (24%) patients remained symptomatic after their initial procedure and are regarded as initial failures. Four of these patients had masked bilateral IO weakness. Five patients required additional surgery. At final outcome, 84% were discharged with resolution of their symptoms. CONCLUSIONS: In the light of these findings we suggest an approach for the management of these patients. This should always include exploring a previously operated ipsilateral IO. Despite this, patients should be warned that they have a 1 in 4 chance of needing further surgery to achieve adequate ocular motility.