ADC Level is Related to DWI Reversal in Patients Undergoing Mechanical Thrombectomy: A Retrospective Cohort Study.

BACKGROUND AND PURPOSE: In patients with ischemic stroke, DWI lesions can occasionally be reversed by reperfusion therapy. This study aimed to ascertain the relationship between ADC levels and DWI reversal in patients with acute ischemic stroke who underwent recanalization treatment. MATERIALS AND METHODS: We conducted a retrospective cohort study in patients with acute ischemic stroke who underwent endovascular mechanical thrombectomy with successful recanalization between April 2017 and March 2021. DWI reversal was assessed through follow-up MR imaging approximately 24 hours after treatment. RESULTS: In total, 118 patients were included. DWI reversal was confirmed in 42 patients. The ADC level in patients with reversal was significantly higher than that in patients without reversal. Eighty-three percent of patients with DWI reversal areas had mean ADC levels of ≥520 × 10-6 mm2/s, and 71% of patients without DWI reversal areas had mean ADC levels of <520 × 10-6 mm2/s. The mean ADC threshold was 520 × 10-6 mm2/s with a sensitivity and specificity of 71% and 83%, respectively. In multivariate analysis, the mean ADC level (OR, 1.023; 95% CI, 1.013-1.033; P < .0001) was independently associated with DWI reversal. Patients with DWI reversal areas had earlier neurologic improvement (NIHSS at 7 days) than patients without reversal areas (P < .0001). CONCLUSIONS: In acute ischemic stroke, the ADC value is independently associated with DWI reversal. Lesions with a mean ADC of ≥520 × 10-6 mm2/s are salvageable by mechanical thrombectomy, and DWI reversal areas regain neurologic function. The ADC value is easily assessed and is a useful tool to predict viable lesions.

Topological metastability supported by thermal fluctuation upon formation of chiral soliton lattice in [Formula: see text].

Topological magnetic structure possesses topological stability characteristics that make it robust against disturbances which are a big advantage for data processing or storage devices of spintronics; nonetheless, such characteristics have been rarely clarified. This paper focused on the formation of chiral soliton lattice (CSL), a one-dimensional topological magnetic structure, and provides a discussion of its topological stability and influence of thermal fluctuation. Herein, CSL responses against change of temperature and applied magnetic field were investigated via small-angle resonant soft X-ray scattering in chromium niobium sulfide ([Formula: see text]). CSL transformation relative to the applied magnetic field demonstrated a clear agreement with the theoretical prediction of the sine-Gordon model. Further, there were apparent differences in the process of chiral soliton creation and annihilation, discussed from the viewpoint of competing between thermal fluctuation and the topological metastability.

Mood Status and Quality of Life in Kidney Recipients After Transplantation.

BACKGROUND: Kidney transplantation is performed as a useful treatment to improve the quality of life (QOL) of patients with end-stage renal failure; however, the correlation between mood status and QOL among recipients post-kidney transplantation have yet to be clarified. METHODS: Sixty-eight post-kidney transplantation patients who visited our institution between March and December 2016 were enrolled in this study. The QOL of the participants as measured by the Short Form-36 Health Survey Version 2 (SF-36v2) questionnaire was compared to results gathered from hemodialysis patients in a previous study. To identify the factors associated with QOL, a multiple regression analysis was performed, including some physical, mental, and socioeconomic characteristics as well as the Profile of Mood States as independent variables. RESULTS: The QOL of the transplantation group was significantly higher for all 8 subscales of SF-36v2 compared to the hemodialysis group. Among the factors, greater age and higher Confusion levels were related to lower physical QOL. In addition, higher Vigor and lower Fatigue levels were related to higher mental QOL, while the condition of having an occupation was related to higher role/social QOL. CONCLUSION: The QOL of recipients after kidney transplantation was better than that of hemodialysis patients. It is important to pay attention to mood status, especially confusion and fatigue, in order to maintain and improve the QOL of the recipient after kidney transplantation. Kidney transplantation can be a beneficial treatment not only physically but also psychologically and socially.

Comparison of ultrasonographic joint and tendon findings in hands between early, treatment-naïve patients with systemic lupus erythematosus and rheumatoid arthritis.

Although both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) may lead to joint deformity, SLE arthritis is typically non-erosive and often accompanied by Jaccoud's deformity. Therefore, we examined characteristics of joint and tendon lesions in patients with SLE and RA by ultrasonography. Fifteen treatment-naïve SLE patients and 40 treatment-naïve RA patients with joint symptoms were included in this study. The hand joints and related tendons were ultrasonographically examined using grey-scale (GS) and power Doppler (PD). Joint involvement was comparably observed in patients with SLE and RA (80% versus 95%, p = 0.119). However, tendon involvement was more frequent in SLE than in RA (93% versus 65%, p = 0.045), especially in the wrist joints (73% versus 40%, p = 0.037). When we investigated the intensity of US findings, the joint synovitis score (GS + PD) per affected joint was lower in SLE than RA (2.0 versus 2.6, p = 0.019), while tendon inflammation score was not significantly different (2.1 versus 2.2, p = 0.738). Finally, the examination of concordance between joint and tendon involvement in the same finger revealed that joint lesion appeared in only 49% of fingers having tendon involvement in the SLE group, which was significantly less than 74% in the RA group ( p = 0.010). Thus, as compared with RA, SLE arthropathy is characterized by the predominance of tenosynovitis/periextensor tendon inflammation, which is likely to develop independently from joint synovitis.

A Novel Xenogeneic Graft-Versus-Host Disease Model for Investigating the Pathological Role of Human CD4+ or CD8+ T Cells Using Immunodeficient NOG Mice.

Graft-versus-host disease (GVHD) is a major complication of allogenic bone marrow transplantation and involves the infiltration of donor CD4+ and/or CD8+ T cells into various organs of the recipient. The pathological role of human CD4+ and CD8+ T cells in GVHD remains controversial. In this study, we established two novel xenogeneic (xeno)-GVHD models. Human CD4+ or CD8+ T cells were purified from peripheral blood and were transplanted into immunodeficient NOD/Shi-scid IL2rgnull (NOG) mice. Human CD8+ T cells did not induce major GVHD symptoms in conventional NOG mice. However, CD8+ T cells immediately proliferated and induced severe GVHD when transferred into NOG mice together with at least 0.5 × 106 CD4+ T cells or into NOG human interleukin (IL)-2 transgenic mice. Human CD4+ T cell-transplanted NOG mice developed skin inflammations including alopecia, epidermal hyperplasia, and neutrophilia. Pathogenic T helper (Th)17 cells accumulated in the skin of CD4+ T cell-transplanted NOG mice. Further, an anti-human IL-17 antibody (secukinumab) significantly suppressed these skin pathologies. These results indicate that pathogenic human Th17 cells induce cutaneous GVHD via IL-17-dependent pathways. This study provides fundamental insights into the pathogenesis of xeno-GVHD, and these humanized mouse models may be useful as preclinical tools for the prevention of GVHD.

The Associations of Malnutrition and Aging with Fluid Volume Imbalance between Intra- and Extracellular Water in Patients with Chronic Kidney Disease.

OBJECTIVES: Fluid imbalance due to sodium retention and malnutrition can be characterized by the ratio of extracellular water (ECW) to intracellular water (ICW). We investigated whether the ECW/ICW ratio is a risk factor for adverse outcomes. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: 149 patients with chronic kidney disease from 2005 to 2009, who were followed until August 2013. MEASUREMENTS: Body fluid composition was measured by bioelectrical impedance analysis. Patients were categorized according to the ECW/ICW ratio tertile. Daily nutrient intake was estimated from 24-h dietary recall and analyzed using standard food composition tables. The main outcomes were adverse renal outcomes, as defined by a decline of 50% or more from the baseline glomerular filtration rate or initiation of renal replacement therapy, cardiovascular events, and all-cause mortality. RESULTS: The ECW/ICW ratio increased with downward ICW slope with age and renal dysfunction besides ECW excess with massive proteinuria. Sodium intake, protein intake, and calorie intake were negatively correlated with the ECW/ICW ratios due to the steeper decreasing ICW content with the decreased dietary intake than the decreasing ECW content. During a median 4.9-year follow up, patients in the highest tertile had the worst adverse renal outcomes (15.9 vs. 5.1 per 100 patient-years, P < 0.001), cardiovascular events (4.1 vs. 0.3 per 100 patient-years, P = 0.002), and mortality (11.2 vs. 1.3 per 100 patient-years, P < 0.001). The adjusted hazard ratio (95% confidence intervals) for adverse renal outcomes, cardiovascular events, and mortality were 1.15 (1.03 - 1.26), 1.12 (0.93 - 1.31), and 1.29 (1.11 - 1.50), respectively. CONCLUSIONS: Fluid imbalance between ICW and ECW occurring in malnourished and elderly patients with chronic kidney disease may explain the reserve capacity for volume overload and is associated with adverse renal outcomes and all-cause mortality.

Simultaneous loss of phospholipase Cδ1 and phospholipase Cδ3 causes cardiomyocyte apoptosis and cardiomyopathy.

Phospholipase C (PLC) is a key enzyme in phosphoinositide turnover. Among 13 PLC isozymes, PLCδ1 and PLCδ3 share high sequence homology and similar tissue distribution, and are expected to have functional redundancy in many tissues. We previously reported that the simultaneous loss of PLCδ1 and PLCδ3 caused embryonic lethality because of excessive apoptosis and impaired vascularization of the placenta. Prenatal death of PLCδ1/PLCδ3 double-knockout mice hampered our investigation of the roles of these genes in adult animals. Here, we generated PLCδ1/PLCδ3 double-knockout mice that expressed PLCδ1 in extra-embryonic tissues (cDKO mice) to escape embryonic lethality. The cDKO mice were born at the expected Mendelian ratio, which indicated that the simultaneous loss of PLCδ1 and PLCδ3 in the embryo proper did not impair embryonic development. However, half of the cDKO mice died prematurely. In addition, the surviving cDKO mice spontaneously showed cardiac abnormalities, such as increased heart weight/tibial length ratios, impaired cardiac function, cardiac fibrosis, dilation, and hypertrophy. Predating these abnormalities, excessive apoptosis of their cardiomyocytes was observed. In addition, siRNA-mediated simultaneous silencing of PLCδ1 and PLCδ3 increased apoptosis in differentiated-H9c2 cardiomyoblasts. Activation of Akt and protein kinase C (PKC) θ was impaired in the hearts of the cDKO mice. siRNA-mediated simultaneous silencing of PLCδ1 and PLCδ3 also decreased activated Akt and PKCθ in differentiated-H9c2 cardiomyoblasts. These results indicate that PLCδ1 and PLCδ3 are required for cardiomyocyte survival and normal cardiac function.

Biochemical and hematologic effects of polyvinylpyrrolidone-wrapped fullerene C60 after oral administration.

The fullerene C60 is used in consumer products such as cosmetics owing to its antioxidative effects and is being developed for nanomedical applications. However, knowledge regarding the safety of fullerene C60, especially after oral administration, is sparse. Here, we examined the safety of fullerene C60 in mice after 7 d of exposure to orally administered polyvinylpyrrolidone (PVP)-wrapped fullerene C60 (PVP-fullerene C60). Mice treated with PVP-fullerene C60 showed few changes in the plasma levels of various markers of kidney and liver injury and experienced no significant hematologic effects. Furthermore, the histology of the colon of PVP-fullerene C60-treated mice was indistinguishable from that of control mice. These results suggest that PVP-fullerene C60 lacks toxicity after high-dose oral administration and indicate that PVP-fullerene C60 can be considered safe for oral medication. These data provide basic information that likely will facilitate the production of safe and effective forms of fullerene C60.

Diverse populations of intrinsic cholinergic interneurons in the mouse olfactory bulb.

Cholinergic activities affect olfactory bulb (OB) information processing and associated learning and memory. However, the presence of intrinsic cholinergic interneurons in the OB remains controversial. As a result, morphological and functional properties of these cells are largely undetermined. We characterized cholinergic interneurons using transgenic mice that selectively mark choline acetyltransferase (ChAT)-expressing cells and immunolabeling. We found a significant number of intrinsic cholinergic interneurons in the OB. These interneurons reside primarily in the glomerular layer (GL) and external plexiform layer (EPL) and exhibit diverse distribution patterns of nerve processes, indicating functional heterogeneity. Further, we found these neurons express ChAT and vesicular acetylcholine transporter (VAChT), but do not immunoreact to glutamatergic, GABAergic or dopaminergic markers and are distinct from calretinin-expressing interneurons. Interestingly, the cholinergic population partially overlaps with the calbindin D28K-expressing interneuron population, revealing the neurotransmitter identity of this sub-population. Additionally, we quantitatively determined the density of VAChT labeled cholinergic nerve fibers in various layers of the OB, as well as the intensity of VAChT immunoreactivity within the GL, suggesting primary sites of cholinergic actions. Taken together, our results provide clear evidence showing the presence of a significant number of cholinergic interneurons and that these morphologically and distributionally diverse interneurons make up complex local cholinergic networks in the OB. Thus, our results suggest that olfactory information processing is modulated by dual cholinergic systems of local interneuron networks and centrifugal projections.

Pirfenidone in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease without proven effective therapy. A multicentre, double-blind, placebo-controlled, randomised phase III clinical trial was conducted in Japanese patients with well-defined IPF to determine the efficacy and safety of pirfenidone, a novel antifibrotic oral agent, over 52 weeks. Of 275 patients randomised (high-dose, 1,800 mg x day(-1); low-dose, 1,200 mg x day(-1); or placebo groups in the ratio 2:1:2), 267 patients were evaluated for the efficacy of pirfenidone. Prior to unblinding, the primary end-point was revised; the change in vital capacity (VC) was assessed at week 52. Secondary end-points included the progression-free survival (PFS) time. Significant differences were observed in VC decline (primary end-point) between the placebo group (-0.16 L) and the high-dose group (-0.09 L) (p = 0.0416); differences between the two groups (p = 0.0280) were also observed in the PFS (the secondary end-point). Although photosensitivity, a well-established side-effect of pirfenidone, was the major adverse event in this study, it was mild in severity in most of the patients. Pirfenidone was relatively well tolerated in patients with IPF. Treatment with pirfenidone may decrease the rate of decline in VC and may increase the PFS time over 52 weeks. Additional studies are needed to confirm these findings.

A phase II dose-ranging study of palonosetron in Japanese patients receiving moderately emetogenic chemotherapy, including anthracycline and cyclophosphamide-based chemotherapy.

BACKGROUND: The 5-HT(3) receptor antagonists (RAs) help maintain the standard of care, in various combinations with other agents, for prevention of chemotherapy-induced nausea and vomiting (CINV). Palonosetron is a new generation 5-HT(3) RA with indication not only acute but also delayed nausea and vomiting induced by moderately emetogenic chemotherapy (MEC). This study was carried out to determine the optimal dosage of palonosetron in combination with dexamethasone in patients in Japan. PATIENTS AND METHODS: This study evaluated the efficacy and safety of palonosetron in patients receiving MEC combined with dexamethasone. Patients received single doses of 0.075, 0.25, or 0.75 mg of palonosetron before MEC. Dexamethasone was infused before palonosetron, at 20 mg for the patients receiving paclitaxel (Taxol) and 8 mg for the patients not receiving paclitaxel. The primary end point was complete response (CR: no emetic episodes and no rescue medication) in the acute phase (0-24 h). RESULTS: In total, 204 patients (88 men, 116 women; 96 with paclitaxel, 108 without paclitaxel) were assessable for efficacy. No dose-response relationship was observed regarding the CR rate in the acute phase. CR rates increased dose dependently for delayed (24-120 h) and overall (0-120 h) phases in patients receiving anthracyclines and cyclophosphamide combination (AC/EC, n = 80); however, the difference in CR rates among doses was not statistically significant. The most commonly reported adverse events related to palonosetron were constipation and headache, confirming the class safety profile. CONCLUSION: This study indicates a statistically nonsignificant trend for the dose-response relationship for antiemetic protection in the delayed and overall phases in AC/EC patients (the regimen currently considered to be more emetogenic than MEC).

Effect of individual fat areas on early surgical outcomes after open gastrectomy for gastric cancer.

BACKGROUND: Obesity is generally considered a risk factor for postoperative morbidity following open gastrectomy. Body mass index (BMI) is widely accepted as an indicator of obesity, but does not necessarily reflect the distribution of fat. It is unclear how different types of fat may affect the operative procedure and outcome. METHODS: The relationship between fat area (total, visceral and subcutaneous fat, and BMI) and early surgical outcomes (bleeding, operating time, morbidity, hospital death and hospital stay) was investigated in 135 patients who had a curative gastrectomy at the Cancer Institute Hospital, Tokyo, in 2006. RESULTS: Postoperative intra-abdominal infection, which occurred in 13 patients (9.6 per cent), correlated strongly with visceral (P = 0.023) and total (P = 0.037) fat area. Visceral fat area also correlated with hospital death (P = 0.041) and a longer hospital stay (P = 0.001). Subcutaneous fat area and BMI did not correlate with these early surgical outcomes. CONCLUSION: Patients with a high visceral fat area are more likely to develop an intra-abdominal infection after gastrectomy. Assessment of fat area, in particular visceral fat area, should alert surgeons to increased postoperative risks.