Observation of Coulomb-Assisted Nuclear Bound State of Ξ

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

Decreased Incidence of Acute Cellular Rejection in Low-Muscle-Mass Recipients After Living-donor Liver Transplantation.

BACKGROUND: Sarcopenia has recently been studied as a potential risk factor for mortality and complications after liver transplantation. We investigated the impact of low muscle mass on postoperative outcomes after living-donor liver transplantation. METHODS: Our study population consisted of 100 adult recipients who underwent living-donor liver transplantation in our department between 2005 and 2017. Recipients were divided into a low-muscle-mass group (L group) and a normal-muscle-mass group (N group) based on skeletal muscle index (SMI) values, and postoperative outcomes were compared between the groups. Regarding factors that were significantly different between the groups, multivariate analyses were performed to identify predictive factors. RESULTS: Based on the SMI definition, 47 and 53 of the recipients were categorized as having low muscle mass (L group) and normal muscle mass (N group), respectively. Comparison between the groups revealed a significantly reduced incidence of rejection (10.6% in L group vs 30.2% in N group, P = .017) and increased incidences of bacterial infection (61.7% in L group vs 37.7% in N group, P = .017) in the L group compared with the N group. The survival rate did not differ significantly between the groups. Multivariate analyses indicated that muscle mass was a significant predictive factor for both rejection and bacterial infection. CONCLUSION: It is important to recognize that muscle mass has an impact not only on bacterial infection but also on rejection in recipients with low muscle mass in the postoperative course of living-donor liver transplantation.

In vitro single-unit recordings reveal increased peripheral nerve conduction velocity by focused pulsed ultrasound.

Ultrasound that is widely used in medical diagnosis has drawn growing interests as a noninvasive means of neuromodulation. Focused pulsed ultrasound (FPUS) effectively modulates neural encoding and transmission in the peripheral nervous system (PNS) with unclear mechanism of action, which is further confounded by contradictory experimental outcomes from recordings of compound action potentials (CAP). To address that, we developed a novel in vitro set up to achieve simultaneous single-unit recordings from individual mouse sciatic nerve axon and systematically studied the neuromodulation effects of FPUS on individual axon. Unlike previous CAP recordings, our single-unit recordings afford superior spatial and temporal resolution to reveal the subtle but consistent effects of ultrasonic neuromodulation. Our results indicate that, 1) FPUS did not evoke action potentials directly in mouse sciatic nerve at all the tested intensities (spatial peak temporal average intensity, ISPTA of 0.91 to 28.2 W/cm2); 2) FPUS increases the nerve conduction velocity (CV) in both fast-conducting A- and slow-conducting C- type axons with effects more pronounced at increased stimulus duration and intensity; and 3) effects of increased CV is reversible and cannot be attributed to the change of local temperature. Our results support existing theories of non-thermal mechanisms underlying ultrasonic neuromodulation with low-intensity FPUS, including NICE, flexoelectricity, and solition models. This work also provides a solid experimental basis to further advance our mechanistic understandings of ultrasonic neuromodulation in the PNS.

Impact of Donor Age on Outcome of Intestinal Transplantation in Japan.

BACKGROUND: Donor age for intestinal transplantation (ITx) is somewhat younger than that for other solid organs. Clear criteria for adequate donors have not been established. There is a donor scarcity for ITx in Japan due to the shortage of young donors. METHODS: We reviewed outcomes associated with ITx in Japan based on donor age for cadaveric and living donation. RESULTS: Standardized report forms were sent to all known ITx programs, asking for information on ITxs performed between 1996 and 2016. All programs responded. Patient and graft survival estimates were obtained using the Kaplan-Meier method. Five institutions provided data on 27 grafts in 24 patients. There were 14 cadaveric and 13 living donor transplants. Median donor age for ITxs was 40 (range, 17-60) years. Graft survival at 5 years was 66% for patients >40 years old (n = 18) and 47% for those <40 years old (n = 9), not a statistically significant difference (P = .49). Graft survival at 5 years was 60% in those >50 years old (n = 5) and 57% for those <50 years old (n = 22), again not a significant difference (P = .27). CONCLUSION: There is no difference in survival between for those with donor age <40 vs >40 years. Donor age for ITx can be extended from >40 to up to 50 years, which may help to mitigate the donor shortage. It will be necessary to clarify the donor criteria for ITx through accumulation of further data on ITx.

Three-Year Prospective Follow-up of Potential Pediatric Candidate for Intestinal Transplantation.

Intestinal transplantation (ITx) is a treatment for refractory intestinal failure (IF). However, the indications for and timing of ITx are still controversial because the course of IF is unknown. We performed a prospective multi-institutional cohort study to identify the prognostic factors for referral to an ITx facility. Patients under 18 years of age in Japan who suffered from IF and had received parenteral nutrition for longer than 6 months were enrolled in this study. They were followed up for 3 years. Seventy-two patients were followed. The mean age at the beginning of the study was 7.0 years. Diagnoses were short gut syndrome (n = 25), motility disorder (n = 45), and other (n = 2). The overall 3-year survival rate was 95%. The 3-year survival rate was 86% in patients with intestinal-failure-associated liver disease (IFALD) (n = 6) compared to 97% in those without IFALD (n = 66) (P = .0003). Furthermore, the 3-year survival rates of patients who did and did not meet the criteria for ITx were 82% (n = 11) and 97% (n = 62), respectively (P = .034). Six (44%) of 14 patients whose performance status (PS) was ≥3 at enrollment were dead or still had a PS ≥ 3 at 3 years. This study indicates that IFALD is a poor prognostic factor in pediatric patients with IF. Our indication for ITx, namely the presence of IFALD or loss of more than 2 parenteral nutrition access sites, seems to be applicable.

Phylogenetic and phylodynamic analyses of hepatitis C virus subtype 1a in Okinawa, Japan.

Okinawa Island, located in Southern Japan, has a higher prevalence rate of hepatitis C virus subtype 1a (HCV-1a) infection than that in mainland Japan. Okinawa has a history of US military occupation after World War II. To elucidate the transmission history of HCV-1a in Okinawa, 26 whole-genome sequences were obtained from 29 patients during 2011-2016. Phylogenetic trees were reconstructed to identify the origin and characteristics of HCV-1a in Okinawa with epidemiological information. A phylogenetic tree based on whole-genome sequencing revealed that all of the samples were located below the US branches. Additionally, we identified one cluster comprised of 17 strains (Okinawa, n = 16; United States, n = 1). The majority of the patients in this cluster were people who inject drugs (PWID), indicating the presence of a people who inject drugs (PWID) cluster. Subsequently, Bayesian analyses were employed to reveal viral population dynamics. Intriguingly, a phylodynamic analysis uncovered a substantial increase in effective population size of HCV-1a from 1965 to 1980 and a slight increase in mid-2000, which were associated with an increase in illicit drug use in Okinawa. The estimated divergence time of the PWID cluster was 1967.6 (1964.2-1971.1). These findings suggest that HCV-1a was introduced into Okinawa from the United States in the late 1960s, coincident with the Vietnam War. Subsequently, HCV-1a might have spread among the Japanese population with the spread of injecting drug use. Our study provides an understanding of HCV transmission dynamics in Okinawa, as well as the key role of PWID in HCV transmission.

Incidence of elevated procalcitonin and presepsin levels after severe trauma: a pilot cohort study.

Procalcitonin (PCT) and presepsin (PSEP) are useful biomarkers for diagnosing sepsis; however, elevated PCT and PSEP levels may be observed in conditions other than sepsis. We hypothesised that PCT and PSEP levels could increase after severe traumatic injuries. Trauma patients with an Injury Severity Score of ≥16 from October 2013 to September 2015 were enrolled in our study. We examined PCT and PSEP levels and their positive rates on days 0 and 1. PCT and PSEP levels on days 0 and 1 were compared. Risk factors for increasing sepsis biomarker levels were identified by multivariate logistic regression analyses. In this study, 75 patients were included. PCT levels on days 0 and 1 were 0.1±0.4 and 1.8±6.3 ng/ml, respectively (P=0.02). PSEP levels on days 0 and 1 were 221±261 and 222±207 pg/ml, respectively (P=0.98). As per multivariate logistic regression analyses, packed red blood cell (PRBC) transfusion was the only independent risk factor for higher PCT levels on day 1 (P=0.04). Using PCT to diagnose sepsis in trauma patients on day 1 requires caution. PRBC transfusion was found to be a risk factor for increasing PCT levels. On the other hand, PSEP levels were not affected by trauma during the early phases.

A Report on the Positive Response to an Outdoor Nature Challenge of a Snow Camp for Young Liver Transplant Patients.

OBJECTIVES: More than two decades have passed since the first living donor liver transplantation was performed in Japan in 1989. There are many reports about problems in adherence to taking medication and medical follow-ups in children who received liver transplants, because there is no transition strategy for those children and parents or guardians. The objective of this study is to measure the effect of nature and outdoor activity to improve children's medical adherence. METHODS: We recruited participants from 9-year-old children who are attending the outpatient liver transplant clinic in a stable condition (no event such as rejection or surgical procedure within 6 months). We took participants to a snow camp and measured its effect by using the IKIRU CHIKARA (IKR) tool, which contain 28 items divided into 3 categories: psychosocial ability, moral fitness, and physical ability. Children were tested on three occasions, before, just after, and 1 month after the camp. RESULTS: Eight patients participated in the snow camp and 7 patients were eligible for the study. The average age was 12.6 with a range 10 to 17 years. There were 3 girls and 4 boys. The average IKR scores before, just after, and 1 month after the camp were 127.9, 131.5, and 126.6, respectively. CONCLUSION: An outdoor activity such as a snow camp can be safely conducted, and it is an acceptable option to incorporate within a pediatric liver transplant program. There were no significant changes in IKR scores during this short observation. Longer observation is needed to measure the effect of nature and outdoor activities.

Adipocytokine, progranulin, augments acetylcholine-induced nitric oxide-mediated relaxation through the increases of cGMP production in rat isolated mesenteric artery.

AIM: Progranulin (PGRN) is a novel adipocytokine with anti-inflammatory effects in vascular cells. The aim of this study was to clarify the effects of PGRN on reactivity of isolated blood vessel. METHODS: Isometric contraction of rat isolated superior mesenteric artery was measured. RESULTS: Pre-treatment with PGRN (10-100 ng mL-1 , 30 min) had no effect on noradrenaline- or 5-hydroxytriptamine-induced contraction. On the other hand, pre-treatment with PGRN (100 ng mL-1 ) augmented acetylcholine (ACh; 30 nm)-induced endothelium-dependent relaxation. Pre-treatment with PGRN (100 ng mL-1 ) augmented ACh (10 µm)-induced nitric oxide (NO)-mediated relaxation in the presence of indomethacin (10 µm), a cyclooxygenase inhibitor, and tetraethyl ammonium (10 mm), a non-selective potassium channel blocker. In contrast, pre-treatment with PGRN (100 ng mL-1 ) had no effect on ACh-induced endothelium-derived hyperpolarizing factor-mediated relaxation. Pre-treatment with PGRN (100 ng mL-1 ) had no effect on ACh (10 µm, 1 min)-induced endothelial NO synthase phosphorylation (at Ser1177) as determined by Western blotting. Pre-treatment with PGRN (100 ng mL-1 ) augmented an NO donor, sodium nitroprusside (SNP; 30 nm-1 µm)- but not a membrane-permeable cGMP analogue, 8-bromo-cGMP-induced relaxation. In the presence of 3-isobutyl-1-methylxanthine (100 µm), a phosphodiesterase inhibitor, pre-treatment with PGRN (100 ng mL-1 ) increased SNP (30 nm, 5 min)-induced cGMP production as determined by enzyme immunoassay. CONCLUSION: We for the first time demonstrate that PGRN augments ACh-induced NO-mediated relaxation through the increases of cGMP production in smooth muscle. These results indicate PGRN as a possible pharmacotherapeutic target against cardiovascular diseases including obesity-related hypertension.

Impact of Portal Hemodynamic Changes in Partial Liver Grafts on Short-Term Graft Regeneration in Living Donor Liver Transplantation.

BACKGROUND: Regeneration of partial liver grafts is critical for successful living donor liver transplantation (LDLT), especially in adult recipients. The purpose of this study was to investigate the intraoperative hemodynamic changes in partial liver grafts and characterize their potential impact on post-transplant liver regeneration in LDLT. METHODS: We examined the portal venous flow (PVF) and hepatic arterial flow (HAF) to partial liver grafts by means of ultrasonic transit time flowmeter of donors immediately before graft retrieval and of the corresponding recipients after vascular reconstruction in 48 LDLT cases. We evaluated post-transplant liver regeneration according to the changes in graft liver volume between the time of transplantation and the 7th post-transplant day. RESULTS: There was a significant increase in PVF to the partial liver grafts in recipients (rPVF) compared with that in donors. In contrast, graft HAF in recipients significantly decreased compared with that in donors. The rPVF inversely correlated with graft weight (GW)-recipient body weight ratio (GRWR), whereas HAF volume showed no significant correlation. The rPVF/GW positively correlated with the rate of liver regeneration (GRR), which inversely correlated with GRWR. The rPVF/GW was significantly higher, and GRR tended to be larger in the small graft group than in the non-small graft group. CONCLUSIONS: Intraoperative portal hemodynamic changes in partial liver grafts strongly affect their post-transplant regeneration. In particular, in small liver grafts, an immediate and remarkable increase in graft PVF may contribute to rapid liver regeneration after LDLT if the increased PVF remains within a safe range.

Experimental Identification of Electric Field Excitation Mechanisms in a Structural Transition of Tokamak Plasmas.

Self-regulation between structure and turbulence, which is a fundamental process in the complex system, has been widely regarded as one of the central issues in modern physics. A typical example of that in magnetically confined plasmas is the Low confinement mode to High confinement mode (L-H) transition, which is intensely studied for more than thirty years since it provides a confinement improvement necessary for the realization of the fusion reactor. An essential issue in the L-H transition physics is the mechanism of the abrupt "radial" electric field generation in toroidal plasmas. To date, several models for the L-H transition have been proposed but the systematic experimental validation is still challenging. Here we report the systematic and quantitative model validations of the radial electric field excitation mechanism for the first time, using a data set of the turbulence and the radial electric field having a high spatiotemporal resolution. Examining time derivative of Poisson's equation, the sum of the loss-cone loss current and the neoclassical bulk viscosity current is found to behave as the experimentally observed radial current that excites the radial electric field within a few factors of magnitude.

Antigen-specific cytotoxic T lymphocytes target airway CD103+ and CD11b+ dendritic cells to suppress allergic inflammation.

Allergic airway inflammation is driven by the recognition of inhaled allergen by T helper type 2 (Th2) cells in the airway and lung. Allergen-specific cytotoxic T lymphocytes (CTLs) can strongly reduce airway inflammation, however, the mechanism of their inhibitory activity is not fully defined. We used mouse models to show that allergen-specific CTLs reduced early cytokine production by Th2 cells in lung, and their subsequent accumulation and production of interleukin (IL)-4 and IL-13. In addition, treatment with specific CTLs also increased the proportion of caspase(+) dendritic cells (DCs) in mediastinal lymph node (MLN), and decreased the numbers of CD103(+) and CD11b(+) DCs in the lung. This decrease required expression of the cytotoxic mediator perforin in CTLs and of the appropriate MHC-antigen ligand on DCs, suggesting that direct CTL-DC contact was necessary. Lastly, lung imaging experiments revealed that in airway-challenged mice XCR1-GFP(+) DCs, corresponding to the CD103(+) DC subset, and XCR1-GFP(-) CD11c(+) cells, which include CD11b(+) DCs and alveolar macrophages, both clustered in the areas surrounding the small airways and were closely associated with allergen-specific CTLs. Thus, allergen-specific CTLs reduce allergic airway inflammation by depleting CD103(+) and CD11b(+) DC populations in the lung, and may constitute a mechanism through which allergic immune responses are regulated.

Impact of intestinal transplantation for intestinal failure in Japan.

INTRODUCTION: The prognosis of intestinal failure has improved dramatically in the past few decades with the development of parenteral nutrition (PN). However, PN-dependent patients still have numerous complications. Intestinal transplantation can significantly improve their prognosis and quality of life. We report on the impact of intestinal transplantation for intestinal failure in Japan. METHODS: Intestinal transplantations have been performed in Japan since 1996. Standardized forms were sent to all known intestinal transplantation programs, asking for information on intestinal transplantations performed between 1996 and June 31, 2012. All programs responded. Patient and graft survival estimates were obtained using the Kaplan-Meier method and analyzed with the Wilcoxon statistic. RESULTS: Five institutions provided data on 24 grafts in 21 patients. There were 12 cadaveric and 12 living related donor transplants. Causes of intestinal failure included short gut syndrome (n = 9), intestinal motility function disorders (n = 11), retransplantation (n = 3), and other (n = 1). The overall 1- and 5-year patient survival rates were 86% and 68%, respectively. In cases (n = 15) after 2006, the 1-year patient survival rate was 92%, and the 5-year survival rate was 83%. One- and five-year graft survival rates were 87% and 78%, respectively. More than 80% of all current survivors discontinued PN. CONCLUSIONS: Intestinal transplantation has become an effective therapy for patients with intestinal failure who cannot tolerate PN. After 2006, patient and graft survival rates approached rates associated with standard treatment for end-stage intestinal failure. Further improvements are expected with early referral due to suitable donor organ and pretransplant management.

Left-side hepatectomy in living donors: through a reduced upper-midline incision for liver transplantation.

BACKGROUND: We present our attempts at reducing the length of incision in living donor left-side hepatectomy without laparoscopic approach. METHODS: The chief surgeon initially made a 10-cm upper midline incision and performed all procedures through a minilaparotomy without abdominal wall lifting or pneumoperitoneum. For the procedures in the lateral and deep areas, we effectively applied traction to the wound in multiple directions using a wound retraction system so that the chief surgeon could obtain a good direct view. We also placed a fiberscope on the minilaparotomy so that the assistant surgeons could obtain an additional video view via a monitor. Surgeons lengthened the incision at their own discretion if the initial length was thought to be too short for the donor's safety. Since February 2009, we have employed this operation for 19 living donors (12 lateral segmentectomies and 7 left hepatectomies) and compared parameters between the 19 donors and 34 previous donors who underwent the procedure with standard incision (11 lateral segmentectomies and 23 left hepatectomies). RESULTS: The resultant length of incision was significantly reduced in operations with reduced incision length as compared with standard incision. Clinical outcomes such as operation time and length of hospital stay were comparable or significantly reduced with the reduced incision. The resultant incision length remained within 10 and 12 cm in lateral segmentectomy and left hepatectomy cases, respectively, whose body mass index was less than 22. CONCLUSION: It appears to be feasible to reduce the incision length for living donor left-side hepatectomy, especially in nonobese cases.

Spatiotemporal structures of edge limit-cycle oscillation before L-to-H transition in the JFT-2M tokamak.

In this Letter, we report analyses of spatiotemporal dynamics of turbulence and structure in the limit-cycle oscillation (LCO) that precedes an L-to-H transition. Zonal flows are not observed during LCO, and the oscillation is the periodic generations or decays of barrier with edge-localized mean flow. Oscillatory Reynolds stress is found to be too small to accelerate the LCO flow, by considering the dielectric constant in magnetized toroidal plasmas. Propagation of changes of the density gradient and turbulence amplitude into the core is also observed.

A national survey of patients with intestinal motility disorders who are potential candidates for intestinal transplantation in Japan.

Intestinal motility disorders are a major cause of intestinal failure. Severe cases such as idiopathic pseudo-obstruction represent life-threatening illnessed. Intestinal transplantation is a treatment for severe motility disorders with irreversible intestinal failure. However, the prevalence of severe motility disorders is unknown. We performed a national survey to identify patients with intestinal motility disorders who require an intestinal transplant. The national survey of 302 institutions treating intestinal motility disorders identified 147 patients treated from 2006 to 2011 at 46 institutions. The mean patient age was 12.1 years (range, 0.3-77.5). The mean age of onset was 3.0 years (range, 0.0-68.8). Diagnoses included chronic idiopathic intestinal pseudo-obstruction (n = 96), Hirschsprung disease (n = 29), megacystis microcolon intestinal hypoperistalsis syndrome (n = 18), and other (n = 6). There were 126 survivors and 21 patients who died during the last 5 years. The mortality rate was 14.3%. Eighty-five percent of patients required parenteral nutrition for more than 6 months, which was defined as irreversible intestinal failure. Among surviving patients with irreversible intestinal failure, 8 (9.4 %) developed hepatic failure with jaundice and 27 (31.8%) 2 or more central vein thromboses. In all, at least 35 patients (41%) with irreversible failure due to intestinal motility disorders may be candidates for transplantation. The prevalence of severe intestinal motility disorders was elucidated in Japan. Severe cases should be referred to transplant centers.

Phencyclidine affects firing activity of ventral tegmental area neurons that are related to reward and social behaviors in rats.

Patients with schizophrenia exhibit deficits in motivation and affect, which suggests an impairment in the reward system. The psychotomimetic drug, phencyclidine (PCP), also induces schizophrenia-like negative symptoms, such as reduced motivation, blunted affect, and social withdrawal in both humans and animals. Previous studies have indicated that the dopaminergic neurons in the ventral tegmental area (VTA) play a pivotal role in the development of reward-associated learning and motivation. However, how PCP affects the activity of VTA neurons during performance of a reward-related task and social interaction with others in unanesthetized animals remains unclear. Here, we recorded the unit activity of VTA neurons in freely moving rats before and after systemic administration of PCP in a classical conditioning paradigm, and during social interaction with an unfamiliar partner. In the classical conditioning task, two different tones were sequentially presented, one of which accompanied electrical stimulation of the medial forebrain bundle as an unconditioned stimulus. After identifying the response properties of recorded neurons in the classical conditioning task and social interaction, animals received an intraperitoneal injection of PCP. Our study demonstrated that most VTA neurons responsive to reward-associated stimuli were also activated during social interaction. Such activation of neurons was considerably suppressed by systemic administration of PCP, thus, PCP may affect the firing activity of VTA neurons that are involved in motivation, learning, and social interaction. Disruption of the response of VTA neurons to reward stimuli and socially interactive situations may be involved in PCP-induced impairments similar to the negative symptoms of schizophrenia.

Transverse excitations in liquid Sn.

Transverse acoustic (TA) excitation modes were observed in inelastic x-ray scattering (IXS) spectra of liquid Sn. The excitation energies and widths of the TA modes are in good agreement with results of an ab initio molecular dynamics simulation. By comparing current correlation spectra between the experimental and theoretical results quantitatively, we have concluded that the TA modes can be detected experimentally through the quasi-TA branches in the longitudinal current correlation spectra. The lifetime and propagation length of the TA modes were determined to be ~0.7 ps and 0.8-1.0 nm, respectively, corresponding to the size of cages formed instantaneously in liquid Sn.

Neuroanatomical study on the tecto-suprageniculate-dorsal auditory cortex pathway in the rat.

Previous anatomical and physiological studies suggest that the superior colliculus sends integrated sensory information to the multimodal cortical areas via the thalamic suprageniculate nucleus (SG). However, the detailed distribution of rat tecto-SG axon terminals and SG neurons projecting to the multimodal cortex, as well as synaptic connections between these tectal axons and SG neurons, remains unclear. In this study, the organization of the tecto-thalamo-cortical pathway was investigated via combined injections of anterograde and retrograde tracers followed by light and electron microscopic observations. Injections of a retrograde tracer, cholera toxin B subunit (CTB), into the temporal cortex, area 2, dorsal part (Te2D), and injections of an anterograde tracer, biotinylated dextran amine (BDA), into the deep layers of the superior colliculus produced the following results: (1) Retrogradely CTB-labeled neurons were found throughout SG, predominantly in its rostral part. CTB-labeled neurons were also found in other cortical areas such as the visual cortex, the auditory cortex, the parietal association cortex, and the perirhinal cortex. (2) Anterogradely BDA-labeled axons and their terminals were also observed throughout SG. Dual visualization of BDA and CTB showed that retrogradely labeled SG neurons and anterogradely labeled tectal axon terminal boutons overlapped considerably in the rostral part of SG, and their direct synaptic contacts were also confirmed via electron microscopy. These findings suggest that multimodal information from the superior colliculus can be processed directly in SG neurons projecting to Te2D.