Anisotropic Fully Gapped Superconductivity Possibly Mediated by Charge Fluctuations in a Nondimeric Organic Complex.

We investigate low-temperature electronic properties of the nondimeric organic superconductor ß^{''}-(ET)_{4}[(H_{3}O)Ga(C_{2}O_{4})_{3}]PhNO_{2}. By examining ultrasonic properties, charge disproportionation (CD) without magnetic field dependence is detected below T_{CD}∼8 K just above the superconducting critical temperature T_{c}∼6 K. From quantum oscillations in high fields, we find variation in the Fermi surface and mass enhancement induced by the CD. Heat capacity studies elucidate that the superconducting gap function is fully gapped in the Fermi surface, but anisotropic with fourfold symmetry. We point out that the pairing mechanism of the superconductivity is possibly dominated by charge fluctuations.

An XPA gene splicing mutation resulting in trace protein expression in an elderly patient with xeroderma pigmentosum group A without neurological abnormalities.

A certain relationship between XPA gene mutations and the severity of symptoms has been observed in patients with xeroderma pigmentosum group A (XP-A). Patients with mutations within the DNA-binding domain usually exhibit severe symptoms, whereas splicing mutations in the same domain sometimes cause very mild symptoms. This inconsistency can be explained by a small amount of functional XPA protein produced from normally spliced transcripts. We herein report the case of an adult Japanese patient with XP-A with unusually mild symptoms. We identified a homozygous c.529G>A mutation in exon 4 of the XPA gene, which resulted in aberrant splicing with a 29-bp deletion in exon 4 causing a frameshift. Intact mRNA was observable, but a Western blot analysis failed to detect any normal XPA protein. We therefore evaluated the DNA repair capacity in normal cells in which the XPA expression was artificially diminished. The repair capacity was still present in cells with trace levels of the XPA protein. The repair capacity of the cells derived from our patient with mild symptoms was poor by comparison, but still significant compared with that of the cells derived from a patient with XP-A with severe symptoms. These results provide strong evidence that a trace level of XPA protein can still exert a relatively strong repair capacity, resulting in only a mild phenotype.

Increase in the Magnetic Ordering Temperature (Tc) as a Function of the Applied Pressure for A2Mn[Mn(CN)6] (A = K, Rb, Cs) Prussian Blue Analogues.

Magnetization measurements under pressure reveal that the external hydrostatic pressure significantly increases in the ferrimagnetic transition temperature, Tc, for A2Mn[Mn(CN)6] (A = K, Rb, Cs). In the case of monoclinic A = K and Rb, dTc/dp values are 21.2 and 14.6 K GPa-1, respectively, and Tc increases by 53 and 39%, respectively, from ambient pressure to 1.0 GPa. The cubic A = Cs compound also shows a monotonous increase with an initial rate of 4.22 K GPa-1 and about 11.4 K GPa-1 above 0.6 GPa, and an overall Tc increase by 26% at 1.0 GPa. The increase in Tc is attributed to deformation of the structure such that the MnII-N≡C angle decreases with increasing pressure. The smaller the alkali cation, the greater the decrease in the MnII-N≡C angle induced by pressure and the larger the increase of dTc/dp. This is in accordance with the ambient-pressure structures for A2Mn[Mn(CN)6] (A = K, Rb, Cs), which have decreasing MnII-N≡C angles that correlate to the observed increasing Tcs as K > Rb > Cs. The large increase in Tc for the A = K compound is the highest class among several cyano-bridged metal complexes. The tuning of the transition temperature by such a weak pressure may lead to additional applications such as switching devices.

Viral load and ganciclovir (GCV) concentration in cerebrospinal fluid of patients successfully treated with GCV or valGCV for human herpesvirus 6 encephalitis/myelitis following umbilical cord blood transplantation.

We describe successful treatment of 3 cases of human herpesvirus 6 (HHV-6) encephalitis/myelitis following cord blood transplantation (CBT). Ganciclovir (GCV) (10 mg/kg/day) reduced HHV-6 load to undetectable levels in cerebrospinal fluid (CSF). Early dose reduction in the presence of HHV-6 detectable in CSF resulted in an increased HHV-6 load. GCV was capably shifted to valganciclovir (VGCV) with an almost equivalent concentration. GCV/VGCV may be effective for HHV-6 encephalitis/myelitis after CBT, although HHV-6 load in CSF should be monitored.

Improvement of androgenetic alopecia with topical Sophora flavescens Aiton extract, and identification of the two active compounds in the extract that stimulate proliferation of human hair keratinocytes.

BACKGROUND: Androgenetic alopecia (AGA) is a hair loss disorder that commonly affects middle-aged men. To date, the properties of a number of natural or synthetic substances have been investigated for their ability to improve the condition. AIM: To evaluate the hair growth-promoting activities of an extract from the root of Sophora flavescens Aiton. METHODS: We used a human hair keratinocyte proliferation assay and ex vivo organ cultures of human hair follicle to examine the potential of the extract to stimulate hair growth via anagen elongation. We isolated the compounds promoting the growth of epithelial cells, and determined their chemical structures. A randomized, double-blinded, placebo-controlled clinical study for S. flavescens extract was carried out for 6 months with patients with AGA. RESULTS: The extract stimulated the proliferation of hair keratinocytes at a concentration of 0.1 ng/mL, while 100 ng/mL of the extract had a marked effect on hair shaft elongation in an organ culture of human hair follicle. Cell proliferation assay-directed fractionation led to the identification of two pterocarpan derivatives, L-maackiain and medicarpin, as active compounds that promote the proliferation of human hair keratinocytes. Studies in human subjects showed that improvement in the inspected alopecia scores in the lotion plus extract group were significant over a period of 6 months (P < 0.01). CONCLUSIONS: S. flavescens root extract is effective for the treatment of AGA. The isolated two pterocarpans might have important role in this effect.

Subcutaneous abscess due to the basidiomycete Phellinus mori in a patient with chronic granulomatous disease.

Chronic granulomatous disease (CGD), a primary immunodeficiency caused by impaired phagocyte killing of intracellular pathogens, is characterized by recurrent, life-threatening, bacterial and fungal infections. As a result of improvements in microbiologic culture and identification techniques, a number of unique filamentous fungi have been reported as significant pathogens in patients with CGD. We report a case of subcutaneous basidiomycete Phellinus mori infection in a patient with CGD. To the best of our knowledge, this is the first reported case of human infection by this fungus. The causative fungus was identified on the basis of its morphological characteristics and nucleotide sequence on the internal transcribed spacer region of the ribosomal RNA gene. This is the fifth case report of filamentous basidiomycetes infecting a patient with CGD; all of these cases have been caused by Phellinus species. We highlight the importance of recognizing filamentous basidiomycetes Phellinus species as possible agents of non-Aspergillus fungal infections in patients with CGD.

Topical adenosine increases thick hair ratio in Japanese men with androgenetic alopecia.

OBJECTIVE: Hair thickness is more important than hair density in the appearance of baldness in male with androgenetic alopecia (AGA). Adenosine improves hair loss by stimulating hair growth and by thickening hair shafts in women. The objective of this study was to evaluate the hair growth efficacy and safety of topical adenosine in men with AGA. METHODS: A lotion containing either adenosine or niacinamide was administered to the scalps of 102 Japanese men twice daily for 6 months in a double-blind, randomized study. Efficacy was evaluated by dermatologists who assessed the quality of the hair and by calculating the percentages of vellus-like and thick hairs among the vertex hairs, as well as hair density. RESULTS: Adenosine was significantly (P < 0.05) superior to niacinamide in terms of global improvement of AGA, increase in the percentage of thick hairs (at least 60 µm) and self-assessment of hair thickness by the study participants. No causal adverse event due to the adenosine lotion was observed. CONCLUSION: These data indicate that adenosine increases thick hair ratio in Japanese men with AGA, and this compound is useful for the improvement of AGA.

Contribution of hair density and hair diameter to the appearance and progression of androgenetic alopecia in Japanese men.

BACKGROUND: Androgenetic alopecia (AGA) is the most common type of baldness in men. The balding process is associated with the gradual miniaturization of hair follicles and successive hair loss. However, the relative contributions of hair density and diameter to AGA are still unclear. OBJECTIVES: Hair density and hair diameter were investigated in Japanese men with or without AGA to elucidate the importance of these factors in the balding process. METHODS: Male Japanese subjects with or without AGA (n = 369) were included in this study. Hair appearance at the vertex was evaluated by comparison with a series of standard photographs. Hair density was measured using a phototrichogram-based videomicroscopy technique, and hair diameter was assessed by comparison with a series of calibrated threads on the phototrichogram image. RESULTS: All subjects with AGA were ≥ 25 years of age. The mean percentage of thick hairs (> 80 µm) in all subjects with AGA was significantly lower than that in subjects without AGA aged ≥ 25 years (P < 0·01), but the mean percentage of vellus hairs (< 40 µm) in subjects with AGA was significantly higher (P < 0·001). By contrast, the mean density of the hair in all patients with AGA did not significantly differ from the density of those without AGA aged ≥ 25 years. However, the mean density of the hair in subjects without AGA aged < 25 years was significantly higher than that of both subjects without AGA aged ≥ 25 years (P < 0·001) and all subjects with AGA. CONCLUSIONS: Hair loss in men with AGA results mainly from the miniaturization of hair follicles rather than the loss of hair (shedding), at least for individuals who are ≥ 25 years of age and present with AGA.

Safety, tolerability, and feasibility of antifungal prophylaxis with micafungin at 2 mg/kg daily in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Micafungin (MCFG) is used for the prophylaxis of invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (HSCT). However, the safety, efficacy, or optimal dosage/blood levels as prophylaxis is uncertain in pediatric HSCT-patients. METHODS: We prophylactically administered MCFG at 2 mg/kg once daily to 38 children and adolescents undergoing allogeneic HSCT. RESULTS: During MCFG prophylaxis, infusion reactions or adverse events (grades 2-5) related to MCFG use were not found in all the patients. Thus, MCFG prophylaxis was not discontinued and other antifungal agents were not added except for 2 patients in whom probable or possible IFDs developed (completion rate, 94.7 %). To elucidate the influence of HSCT-related complications/drugs on blood concentration of MCFG, we determined the plasma trough and peak levels in 13 and 10 among 38 patients, respectively. The mean trough and peak levels were 3.04 ± 1.21 µg/mL (569 samples) and 9.63 ± 3.62 µg/mL (44 samples), respectively. The peak levels were moderately correlated to the trough levels (R (2) = 0.466). In a patient, the trough level of MCFG transiently increased up to 10.21 µg/mL during hepatic dysfunction due to acute graft-versus-host disease. The MCFG trough levels strongly correlated with T-Bil value (R (2) = 0.894). There was no relationship between the trough levels of MCFG and the circulating concentrations of tacrolimus (R (2) = 0.040). Additionally, MCFG levels were not influenced by treatment with cyclophosphamide or corticosteroids. CONCLUSIONS: Prophylaxis with MCFG at 2 mg/kg once daily may be safe, tolerable, and feasible in pediatric HSCT-patients.

Successful ganciclovir therapy in a patient with human herpesvirus-6 encephalitis after unrelated cord blood transplantation: usefulness of longitudinal measurements of viral load in cerebrospinal fluid.

BACKGROUND: There have been no reports of human herpesvirus-6 (HHV-6) encephalitis treatment based on both HHV-6 DNA load and the antiviral agent's concentration in the cerebrospinal fluid (CSF). PATIENT: A 20-year-old male with a hematological malignancy developed HHV-6 encephalitis 15 days after unrelated cord blood transplantation (UCBT). He had fever, chest pain, memory impairment, and insomnia. His CSF showed no increased cell counts, but the amount of HHV-6 DNA was elevated to 2.0 × 10(6) copies/ìgDNA. Magnetic resonance imaging (MRI) of the head revealed abnormal high-intensity signals in the left limbic system on T2-weighted and diffusion-weighted images. Intravenous administration of ganciclovir (GCV) was initiated at 5 mg/kg every 12 h on day 18, and was continued until day 137. The amount of HHV-6 DNA in the plasma became undetectable on day 25. The HHV-6 load in the CSF decreased to 1.5 × 10(3) copies/ìgDNA on day 32, and reached undetectable levels on day 53. The mean concentration of GCV 1 h after an infusion of 5 mg/kg was 4.12 mg/mL in plasma and 0.7 mg/mL in CSF. The chest pain and insomnia disappeared on days 35 and 47, respectively. Memory defects recovered up to day 85. CONCLUSION: Serial quantification of HHV-6 DNA in CSF may be useful for successful treatment with GCV in post-transplant HHV-6 encephalitis.

Temporary auxiliary partial orthotopic liver transplantation using a small graft for familial amyloid polyneuropathy.

Donor shortage is a major issue in liver transplantation. We have successfully performed temporary auxiliary partial orthotopic liver transplantation (APOLT) using a small volume graft procured from a living donor for recipients with familial amyloid polyneuropathy (FAP). The aim of this study was to evaluate this procedure by comparing it with standard living donor liver transplantation (LDLT). We compared 13 recipients undergoing this procedure with 23 recipients undergoing a standard LDLT for the treatment of FAP. The estimated donor graft volume and the graft volume/recipient's standard liver volume ratio were significantly smaller in the temporary APOLT group than in the standard LDLT group. Postoperative complications were comparable, although the hospital stay was longer in the temporary APOLT group. All the patients safely underwent a remnant native liver resection about 2 months after their first operation in the temporary APOLT group. No symptoms related to FAP developed before the remnant liver resection, and no significant differences in graft and patient survival were observed between the two groups. We successfully performed temporary APOLT using a small volume liver graft without postoperative liver failure for FAP. Temporary APOLT for FAP might be a useful alternative procedure for expanding the donor pool for LDLT.

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.

The palliative care knowledge test: reliability and validity of an instrument to measure palliative care knowledge among health professionals.

Development of palliative care educational programmes continues in Japan. An instrument to evaluate a wider range of palliative care knowledge among general physicians and nurses is needed. However, such an instrument does not currently exist. The aim of this study was to develop an assessment to measure the efficacy of palliative care educational programmes. The questionnaire survey was validated with a group of 940 nurses at two facilities. The response rate was 85 % (n = 797). This study used psychometric methods such as item response theory and intraclass correlation coefficients. Ultimately, 20 items in 5 domains including 'philosophy', 'pain', 'dyspnoea', 'psychiatric problems' and 'gastrointestinal problems' were selected. For these items, the intraclass correlation was 0.88 overall and 0.61-0.82 in each domain; the Kuder-Richardson formula 20 in internal consistency was 0.81. Validity and reliability of the instrument were established. This tool is designed to evaluate a wider range of palliative care knowledge than currently available assessments and can be used for general physicians and nurses. The evaluation of educational programmes and the clarification of actual knowledge acquired are possible using this instrument.

Spin ordering and enhancement of electronic heat capacity in an organic system of (DI-DCNQI)(2)(Ag(1-x)Cu(x)).

Thermodynamic measurements on the organic system of (DI-DCNQI)(2)(Ag(1-x)Cu(x)) (x = 0,0.05, 0.71, 0.90) were performed to study the change from the charge-ordered (CO) insulating state to the π-d hybridized metallic state. A thermal anomaly associated with the antiferromagnetic transition that occurred in the charge-ordered lattice was observed at 6.2 K from the temperature dependence of the heat capacity of (DI-DCNQI)(2)Ag. We have found that the magnetic entropy around the peak is only 1.5% of Rln2, corresponding to the full entropy expected for the formula unit of (DI-DCNQI)(2)Ag. This anomaly is suppressed down to about 3 K in the x = 0.05 sample owing to the disorders induced in the CO lattice. In the metallic concentration of x = 0.90, the low-temperature electronic heat capacity coefficient, γ was found to be enhanced by up to about 63.6 mJ K(-2) mol(-1) probably owing to the cooperative effect of π-d hybridization and intersite Coulomb interaction (V).

Cooperative interaction between ETS1 and GFI1 transcription factors in the repression of Bax gene expression.

The proto-oncoproteins ETS1 and growth factor independent-1 (GFI1) are implicated in cell growth and differentiation in various types of cells, and their deregulated expression is involved in malignant transformation. Here, we report that ETS1 and GFI1 interact and affect gene expression through their cross-talk. Co-immunoprecipitation analyses and glutathione-S-transferase pull-down assays revealed that ETS1 bound directly to GFI1 via its Ets domain, and GFI1 bound to ETS1 via its zinc-finger domain. Luciferase (Luc) assays using artificial reporters showed that GFI1 repressed ETS1-mediated transcriptional activation and ETS1 repressed GFI1-mediated transcriptional activation, in a dose-dependent manner. However, in the Bax promoter where the Ets- and Gfi-binding sites (EBS and GBS) are adjacent, ETS1 and GFI1 cooperatively reduced activation. Site-directed mutagenesis on the EBS and GBS of the Bax promoter showed that both binding sites were necessary for full repression. Chromatin immunoprecipitation analyses confirmed that an ETS1-GFI1 complex formed on the Bax promoter even when either EBS or GBS was mutated. Introduction of small interfering RNA against ETS1 and/or GFI1 enhanced endogenous Bax gene expression. Our results suggest that the interaction between ETS1 and GFI1 facilitates their binding to specific sites on the Bax promoter and represses Bax expression in vivo.

Arterial reconstruction in a case of subintimal dissection of celiac arterial tributaries in living donor liver transplantation: a case report.

BACKGROUND: Hepatic arterial reconstruction is one of the critical issues in living donor liver transplantation (LDLT). Herein we have reported an LDLT case whose celiac arterial trunk tributaries were insufficient as host arteries because of extensive subintimal dissection proceeding to all tributaries of the celiac arterial trunk. PATIENTS AND METHODS: A 45-year-old woman with fulminant hepatic failure underwent LDLT. After reperfusion of the hepatic and portal veins, subintimal dissection of the recipient right and left hepatic arteries was found to extend to all tributaries of the celiac arterial trunk, preventing an anastomosis using the more proximal part of these arteries. Therefore, a jejunal arterial arcade of Roux-en-Y limb mobilized for biliary reconstruction was anastomosed to the donor left hepatic artery in end-to-end fashion. RESULTS: Arterial blood flow to the grafted liver was established successfully, and the patient's postoperative recovery was excellent. Postoperative computed tomography demonstrated sufficient hepatic arterial blood flow. The patient is doing well 4 years after transplantation. CONCLUSION: The method of hepatic graft arterialization described herein is an important option for LDLT recipients when tributaries of the celiac arterial trunk are insufficient as host arteries.

Chromosomal change during 6-mercaptopurine (6-MP) therapy in juvenile myelomonocytic leukemia: the growth of a 6-MP-refractory clone that already exists at onset.

Among 11 JMML children, two had an abnormal karyotype, and nine had a normal karyotype at onset. In one patient with trisomy 8 and four patients with a normal karyotype, a new clone with an aberrant karyotype emerged 1-14 months after 6-mercaptopurine (6-MP) therapy as shown by G-banding analyses. Fluorescence in situ hybridization disclosed that an abnormal clone existed in approximately 3-6% of bone marrow cells at onset or before 6-MP therapy in all the four cases examined, and increased to approximately 12-90% during the treatment. In culture with granulocyte-macrophage colony-stimulating factor, cytogenetically abnormal clones that proliferated during 6-MP therapy possessed significantly less sensitivity to the antimetabolite, compared with cells that decreased in numbers after the therapy. A PTPN11 mutation was detected in all of granulocyte-macrophage colonies irrespective of karyotypic aberration in one patient, whereas approximately 80% of erythroid colonies and 20% of mixed colonies possessed neither a PTPN11 mutation nor chromosomal abnormalities. The appearance of chromosomal aberrations shown by G-banding during 6-MP therapy in some JMML cases may result, in part, from the growth of a 6-MP-refractory clone that already exists at onset. It is possible that treatment with 6-MP promotes progression of the disease.

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.

Significance of chemokine receptor expression in aggressive NK cell leukemia.

Natural killer (NK) cell-type lymphoproliferative diseases of granular lymphocytes can be subdivided into aggressive NK cell leukemia (ANKL) and chronic NK cell lymphocytosis (CNKL). One reason for the poor outcome in ANKL is leukemic infiltration into multiple organs. The mechanisms of cell trafficking associated with the chemokine system have been investigated in NK cells. To clarify the mechanism of systemic migration of leukemic NK cells, we enrolled nine ANKL and six CNKL cases, and analyzed the expression profiles and functions of chemokine receptors by flowcytometry and chemotaxis assay. CXCR1 was detected on NK cells in all groups, and CCR5 was positive in all ANKL cells. Proliferating NK cells were simultaneously positive for CXCR1 and CCR5 in all ANKL patients examined, and NK cells with this phenotype did not expand in CNKL patients or healthy donors. ANKL cells showed enhanced chemotaxis toward the ligands of these receptors. These results indicated that the chemokine system might play an important role in the pathophysiology of ANKL and that chemokine receptor profiling might be a novel tool for discriminating ANKL cells from benign NK cells.