Inhalation of hydrogen gas mitigates sevoflurane-induced neuronal apoptosis in the neonatal cortex and is associated with changes in protein phosphorylation.

Inhalation of hydrogen (H2) gas is therapeutically effective for cerebrovascular diseases, neurodegenerative disorders, and neonatal brain disorders including pathologies induced by anesthetic gases. To understand the mechanisms underlying the protective effects of H2 on the brain, we investigated the molecular signals affected by H2 in sevoflurane-induced neuronal cell death. We confirmed that neural progenitor cells are susceptible to sevoflurane and undergo apoptosis in the retrosplenial cortex of neonatal mice. Co-administration of 1-8% H2 gas for 3 h to sevoflurane-exposed pups suppressed elevated caspase-3-mediated apoptotic cell death and concomitantly decreased c-Jun phosphorylation and activation of the c-Jun pathway, all of which are induced by oxidative stress. Anesthesia-induced increases in lipid peroxidation and oxidative DNA damage were alleviated by H2 inhalation. Phosphoproteome analysis revealed enriched clusters of differentially phosphorylated proteins in the sevoflurane-exposed neonatal brain that included proteins involved in neuronal development and synaptic signaling. H2 inhalation modified cellular transport pathways that depend on hyperphosphorylated proteins including microtubule-associated protein family. These modifications may be involved in the protective mechanisms of H2 against sevoflurane-induced neuronal cell death.

Thermally stable, highly efficient, ultraflexible organic photovoltaics.

Flexible photovoltaics with extreme mechanical compliance present appealing possibilities to power Internet of Things (IoT) sensors and wearable electronic devices. Although improvement in thermal stability is essential, simultaneous achievement of high power conversion efficiency (PCE) and thermal stability in flexible organic photovoltaics (OPVs) remains challenging due to the difficulties in maintaining an optimal microstructure of the active layer under thermal stress. The insufficient thermal capability of a plastic substrate and the environmental influences cannot be fully expelled by ultrathin barrier coatings. Here, we have successfully fabricated ultraflexible OPVs with initial efficiencies of up to 10% that can endure temperatures of over 100 °C, maintaining 80% of the initial efficiency under accelerated testing conditions for over 500 hours in air. Particularly, we introduce a low-bandgap poly(benzodithiophene-cothieno[3,4-b]thiophene) (PBDTTT) donor polymer that forms a sturdy microstructure when blended with a fullerene acceptor. We demonstrate a feasible way to adhere ultraflexible OPVs onto textiles through a hot-melt process without causing severe performance degradation.

Danaparoid reduces transplant-related mortality in stem cell transplantation for children.

In SCT, death from transplant-related complications is the major obstacle hindering improvement of transplant outcomes, and proper supportive care is essential to reduce TRM. The transplant outcomes of 210 pediatric patients with malignant and non-malignant disorders who consecutively underwent SCT in our institution from 2000 to 2013 were analyzed. The transplant years were divided into three periods: A (2000-2004), B (2005-2008), and C (2009-2013), and an improvement in 5-year OS and a decrease in 5-year TRM were observed over these time periods; that is, OS was 61.5%, 60.3%, and 79.5% (P = .062), and TRM was 19.9%, 7.9%, and 0.0% (P < .001) in periods A, B, and C, respectively. On multivariate analysis, the prognostic factor for TRM for all patients was administration of danaparoid (HR = 0.109, 95% CI = 0.033-0.363, P < .001), and for patients with hematological malignancies in allogeneic SCT, the prognostic factors were danaparoid (HR = 0.046, 95% CI = 0.006-0.326, P = .002) and advanced disease at SCT (HR = 4.802, 95% CI = 1.734-13.30, P = .003). A reduction in TRM after SCT was observed over the time periods, and supportive care with danaparoid was found to be significantly effective in reducing TRM in SCT for children.

Comparison of Donor Sources in Hematopoietic Stem Cell Transplantation for Childhood Acute Leukemia: A Nationwide Retrospective Study.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best therapeutic option for childhood high-risk acute leukemia. However, which donor source is optimal for children lacking an identical sibling remains unclear. To evaluate the clinical impact of donor source on allo-HSCT in childhood acute leukemia, we analyzed data from 577 children who underwent allo-HSCT after a myeloablative regimen during first or second complete remission from 2005 to 2012, using registry data of the Japan Society for Hematopoietic Cell Transplantation, and we compared outcomes of 7/8 to 8/8 HLA allelic-matched unrelated bone marrow transplantation (UR-BMT, n = 218) and 4/6 to 6/6 HLA allelic-matched unrelated cord blood transplantation (UR-CBT, n = 200) to those of HLA-identical related bone marrow transplantation (ID-BMT, n = 159). The median follow-up of survivors was 40.0 months. Three-year overall survival (OS) and leukemia-free survival (LFS) rates for ID-BMT, UR-BMT, and UR-CBT were 74.8% and 69.0%, 75.0% and 69.6%, and 71.8% and 63.8%, respectively. The multivariate analysis demonstrated that OS and LFS for the 3 groups are comparable, although UR-CBT carries a greater risk of nonrelapse mortality (hazard ratio, 2.20; P = .03, compared to ID-BMT) in the myeloablative setting for childhood high-risk acute leukemia.

Types of skin afferent fibers and spinal opioid receptors that contribute to touch-induced inhibition of heart rate changes evoked by noxious cutaneous heat stimulation.

BACKGROUND: In anesthetized rats and conscious humans, a gentle touch using a soft disc covered with microcones (with a texture similar to that of a finger), but not with a flat disc, inhibits nociceptive somatocardiac reflexes. Such an inhibitory effect is most reliably evoked when touch is applied to the skin ipsilateral and closest to nociceptive inputs. However, the mechanism of this inhibition is not completely elucidated. We aimed to clarify the types of cutaneous afferent fibers and spinal opioid receptors that contribute to antinociceptive effects of microcone touch. RESULTS: The present study comprised two experiments with urethane-anesthetized rats. In the first experiment, unitary activity of skin afferent fibers was recorded from the saphenous nerve, and responses to a 10-min touch using a microcone disc and a flat disc (control) were compared. Greater discharge rate during microcone touch was observed in low-threshold mechanoreceptive Aδ and C afferent units, whereas many Aß afferents responded similarly to the two types of touch. In the second experiment, the effect of an intrathecal injection of opioid receptor antagonists on the inhibitory effects of microcone touch on heart rate responses to noxious heat stimulation was examined. The magnitude of the heart rate response was significantly reduced by microcone touch in rats that received saline or naltrindole (δ-opioid receptor antagonist) injections. However, such an inhibition was not observed in rats that received naloxone (non-selective opioid receptor antagonist) or Phe-Cys-Tyr-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; µ-opioid receptor antagonist) injections. CONCLUSIONS: Microcone touch induced greater responses of low-threshold mechanoreceptive Aδ and C afferent units than control touch. The antinociceptive effect of microcone touch was abolished by intrathecal injection of µ-opioid receptor antagonist. These results suggest that excitation of low-threshold mechanoreceptive Aδ and C afferents produces the release of endogenous µ-opioid ligands in the spinal cord, resulting in the inhibition of nociceptive transmission that contributes to somatocardiac reflexes.

Excimer laser coronary atherectomy with distal protection for neoatherosclerosis rupture: a case report.

Background: Neoatherosclerosis, a prominent contributor to in-stent restenosis (ISR), persists as a formidable challenge during percutaneous coronary intervention. Excimer laser coronary atherectomy (ELCA) and embolic protection devices may help reduce coronary flow disturbance from procedure-related distal embolization. Case summary: A 71-year-old man experienced in-stent neoatherosclerosis rupture-related non-ST segment elevation myocardial infarction. Multidisciplinary intracoronary imaging, including intravascular ultrasound and optical coherence tomography (OCT), suggested that the ISR was caused by a neoatherosclerosis rupture that can potentially lead to distal embolization. Excimer laser coronary atherectomy (fluence, 45 mJ/mm2 and frequency, 25 pulse/s) using a 1.7 mm concentric catheter was performed with distal protection using Filtrap (Nipro Corporation, Tokyo, Japan), which significantly reduced the volume of the neoatherosclerosis. However, subsequent ELCA on the highest setting (fluence, 60 mJ/mm2 and frequency, 40 pulse/s) led to a filter no-reflow phenomenon, although OCT revealed a further effective vaporization of the neoatherosclerosis and an apparent reduction of soft tissue compatible with the thrombus. After removing the embolic protection device, drug-coated balloon angioplasty provided optimal results without coronary flow disturbance. Discussion: Excimer laser coronary atherectomy reduces soft plaque and thrombus burden, which can reduce the occurrence of distal embolization in select cases. In the case of this patient, procedure-related distal embolization may have been induced by the heightened photomechanical effects resulting from the use of the highest setting in ELCA under increased intracoronary arterial pressure caused by continuous saline injection during ELCA. Concomitant distal protection during ELCA may be more feasible for preventing coronary flow disturbance in patients with a large amount of neoatherosclerosis.

Identification of adrenergic presynaptic and postsynaptic protein locations at neuromuscular junctions, their decrease during aging, and recovery by nicotinamide mononucleotide administration.

Neuromuscular junctions are innervated by motor and sympathetic nerves. The sympathetic modulation of motor innervation shows functional decline during aging, but the cellular and molecular mechanism of this change is not fully known. This study aimed to evaluate the effect of aging on sympathetic nerves and synaptic proteins at mouse neuromuscular junctions. Sympathetic nerves, presynaptic, and postsynaptic proteins of sympathetic nerves at neuromuscular junctions were visualized using immunohistochemistry, and aging-related changes were compared between adult-, aged-, and nicotinamide mononucleotide (NMN) administered aged mice. Sympathetic nerves were detected by anti-tyrosine hydroxylase antibody, and presynaptic protein vesicular monoamine transporter 2 colocalized with the sympathetic nerves. These two signals surrounded motor nerve terminals and acetylcholine receptor clusters. Postsynaptic neurotransmitter receptor ß2-adrenergic receptors colocalized with motor nerve terminals and resided in reduced density at extrasynaptic sarcolemma. The signal intensity of the sympathetic nerve marker did not show a significant difference at neuromuscular junctions between 8.5-month-old adult mice and 25-month-old aged mice. However, the signal intensity of vesicular monoamine transporter 2 and ß2-adrenergic receptors showed age-related decline at neuromuscular junctions. Interestingly, both age-related declines reverted to the adult level after 1 month of oral administration of NMN by drinking water. In contrast, NMN administration did not alter the expression level of sympathetic marker tyrosine hydroxylase at neuromuscular junctions. The results suggest a functional decline of sympathetic nerves at aged neuromuscular junctions due to decreases in presynaptic and postsynaptic proteins, which can be reverted to the adult level by NMN administration.

Wiskott-Aldrich syndrome presenting with a clinical picture mimicking juvenile myelomonocytic leukaemia.

BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency caused by defects of the WAS protein (WASP) gene. Patients with WAS typically demonstrate micro-thrombocytopenia. PROCEDURES: The report describes seven male infants with WAS that initially presented with leukocytosis, monocytosis, and myeloid and erythroid precursors in the peripheral blood (PB) and dysplasia in the bone marrow (BM), which was initially indistinguishable from juvenile myelomonocytic leukaemia (JMML). RESULTS: The median age of affected patients was 1 month (range, 1-4 months). Splenomegaly was absent in four of these patients, which was unusual for JMML. A mutation analysis of genes in the RAS-signalling pathway did not support a diagnosis of JMML. Non-haematological features, such as eczema (n = 7) and bloody stools (n = 6), ultimately led to the diagnosis of WAS at a median age of 4 months (range, 3-8 months), which was confirmed by absent (n = 6) or reduced (n = 1) WASP expression in lymphocytes by flow cytometry (FCM) and a WASP gene mutation. Interestingly, mean platelet volume (MPV) was normal in three of five patients and six of seven patients demonstrated occasional giant platelets, which was not compatible with WAS. CONCLUSIONS: These data suggest that WAS should be considered in male infants presenting with JMML-like features if no molecular markers of JMML can be detected.

Effects of gentle mechanical skin stimulation on subjective symptoms and joint range of motions in people with chronic neck and shoulder discomfort.

This study aimed to examine the efficacy of a 2-week self-administered gentle mechanical skin stimulation on chronic neck and shoulder discomfort. In participants (n = 12) with chronic neck and shoulder discomfort, subjective measures of pain sensation, discomfort, and difficulty in moving using a visual analog scale (VAS, 0-10) and objective measures of 12 different joint range of motions (ROMs) for the cervical and shoulder regions, using a digital goniometer, were collected before and after self-care with contact acupuncture, called microcones. The self-care for 2 weeks significantly (p < 0.001) decreased all VAS scores to 2.2-2.3 from baseline values of 6.0-7.4. Of the 12 ROMs tested, 8 were significantly increased (p < 0.013). This open-label study suggests the use of self-care with microcones in improving subjective symptoms and joint ROMs in people suffering from chronic neck and shoulder discomfort. However, a randomized, double-blind, controlled clinical trial is needed to further investigate the efficacy and safety of microcones.

Sympathetic modulation of hindlimb muscle contractility is altered in aged rats.

It has recently been demonstrated that reflex excitation of muscle sympathetic nerves triggered by muscle contraction contributes to the maintenance of tetanic force (TF) in rat hindlimb muscles. We hypothesized that this feedback mechanism between the contraction of hindlimb muscles and the lumbar sympathetic nerves declines during aging. In this study, we examined the contribution of sympathetic nerves on skeletal muscle contractility in young adult (4-9 months old, n = 11) and aged (32-36 months old, n = 11) male and female rats. The tibial nerve was electrically stimulated to measure the TF of the triceps surae muscles resulting from motor nerve activation before and after cutting or stimulating (at 5-20 Hz) the lumbar sympathetic trunk (LST). The TF amplitude decreased by cutting the LST in the young and aged groups; however, the magnitude of the decrease in TF following transection of the LST in the aged rats (6.2%) was significantly (P = 0.02) smaller compared with that in the young rats (12.9%). The TF amplitude was increased by LST stimulation at ≥ 5 Hz in the young and ≥ 10 Hz in the aged groups. The overall TF response to LST stimulation was not significantly different between the two groups; however, an increase in muscle tonus resulting from LST stimulation, independent of motor nerve stimulation, was significantly (P = 0.03) greater in aged compared with young rats. The sympathetic contribution to support motor nerve-induced muscle contraction declined, whereas sympathetic-mediated muscle tonus, independent of motor nerve activity, was augmented in aged rats. These changes in sympathetic modulation of hindlimb muscle contractility may underlie the reduction of skeletal muscle strength during voluntary contraction and rigidity of motion during senescence.

Insulin resistance induces earlier initiation of cognitive dysfunction mediated by cholinergic deregulation in a mouse model of Alzheimer's disease.

Although insulin resistance increases the risk of Alzheimer's disease (AD), the mechanisms remain unclear, partly because no animal model exhibits the insulin-resistant phenotype without persistent hyperglycemia. Here we established an AD model with whole-body insulin resistance without persistent hyperglycemia (APP/IR-dKI mice) by crossbreeding constitutive knock-in mice with P1195L-mutated insulin receptor (IR-KI mice) and those with mutated amyloid precursor protein (AppNL-G-F mice: APP-KI mice). APP/IR-dKI mice exhibited cognitive impairment at an earlier age than APP-KI mice. Since cholinergic dysfunction is a major characteristic of AD, pharmacological interventions on the cholinergic system were performed to investigate the mechanism. Antagonism to a nicotinic acetylcholine receptor α7 (nAChRα7) suppressed cognitive function and cortical blood flow (CBF) response to cholinergic-regulated peripheral stimulation in APP-KI mice but not APP/IR-dKI mice. Cortical expression of Chrna7, encoding nAChRα7, was downregulated in APP/IR-dKI mice compared with APP-KI. Amyloid ß burden did not differ between APP-KI and APP/IR-dKI mice. Therefore, insulin resistance, not persistent hyperglycemia, induces the earlier onset of cognitive dysfunction and CBF deregulation mediated by nAChRα7 downregulation. Our mouse model will help clarify the association between type 2 diabetes mellitus and AD.

Molecular lesions in childhood and adult acute megakaryoblastic leukaemia.

While acute megakaryoblastic leukaemia (AMKL) occurs in children with (DS-AMKL) and without (paediatric non-DS-AMKL) Down syndrome, it can also affect adults without DS (adult non-DS-AMKL). We have analysed these subgroups of patients (11 children with DS-AMKL, 12 children and four adults with non-DS-AMKL) for the presence of molecular lesions, including mutations and chromosomal abnormalities studied by sequencing and single nucleotide polymorphism array-based karyotyping, respectively. In children, AMKL was associated with trisomy 21 (somatic in non-DS-AMKL), while numerical aberrations of chromosome 21 were only rarely associated with adult AMKL. DS-AMKL was also associated with recurrent somatic gains of 1q (4/11 DS-AMKL patients). In contrast to trisomy 21 and gains of 1q, other additional chromosomal lesions were evenly distributed between children and adults with AMKL. A mutational screen found GATA1 mutations in 11/12 DS-AMKL, but mutations were rare in paediatric non-DS-AMKL (1/12) and adult AMKL (0/4). JAK3 (1/11), JAK2 (1/11), and TP53 mutations (1/11) were found only in patients with DS-AMKL. ASXL1, IDH1/2, DNMT3A, RUNX1 and CBL mutations were not found in any of the patient group studied, while NRAS mutation was identified in two patients with paediatric non-DS-AMKL.

Incidence, clinical features, and risk factors of idiopathic pneumonia syndrome following hematopoietic stem cell transplantation in children.

BACKGROUND: Idiopathic pneumonia syndrome (IPS) is a severe complication that can occur after hematopoietic stem cell transplantation (HSCT) and is often associated with a fatal outcome despite intensive supportive care. PROCEDURE: To assess the incidence and risk factors of IPS, we reviewed 251 consecutive patients (median age, 7.0 years) who received HSCT at the Department of Pediatrics, Nagoya University Hospital, between January 1990 and July 2009. RESULTS: Twenty of 251 (cumulative incidence of IPS at 2 years after HSCT, 8.0%; 95% confidence interval (CI), 5.1-12.4%) patients developed IPS. The median duration from HSCT to diagnosis of IPS was 67 days (range, 12-486 days). Patients with IPS had significantly higher 5-year transplant-related mortality compared to patients without IPS (52% (95% CI, 19-77%) vs. 13% (95% CI, 5-25%), P < 0.001), and the probability of 5-year overall survival was significantly worse for patients with IPS (42% (95% CI, 25-64%) vs. 68% (95% CI, 59-76%), P = 0.01). By multivariate analysis, high risk in underlying disease (HR, 2.5; 95% CI, 1.0-6.7; P = 0.05) and a busulfan-containing regimen (HR, 3.5; 95% CI, 1.3-9.9; P < 0.01) were identified as the independent risk factors for developing IPS. CONCLUSION: The prophylactic strategies for IPS in patients with these risk factors were warranted.

Mild thermal stimulation of the buttock skin increases urinary voiding efficiency in anesthetized rats.

In the present study, we examined the effects of mild thermal stimulation of the skin on voiding efficiency using urethane-anesthetized rats with reduced voiding efficiency. Spontaneous urination was induced by infusing saline. For each voiding, the voiding efficiency was calculated from the voided volume and the bladder capacity measured. A Peltier thermode was attached to the buttock skin to apply stimulation: cooling between to 25 °C and 35 °C, every 20 s throughout the saline infusion. The voiding efficiency was 29 ± 9 % (mean ± SD) before stimulation and increased significantly by 10-15 % during stimulation. During thermal stimulation, the maximum vesical pressure during micturition was unchanged, but the urethral relaxation duration was significantly prolonged. Applying local anesthesia to the stimulated skin area abolished the changes in voiding efficiency in response to thermal stimulation. These results suggest that the excitation of cutaneous thermoreceptive afferents modulates urethral function during urination, thereby improving voiding efficiency.

ATP spreads inflammation to other limbs through crosstalk between sensory neurons and interneurons.

Neural circuits between lesions are one mechanism through which local inflammation spreads to remote positions. Here, we show the inflammatory signal on one side of the joint is spread to the other side via sensory neuron-interneuron crosstalk, with ATP at the core. Surgical ablation or pharmacological inhibition of this neural pathway prevented inflammation development on the other side. Mechanistic analysis showed that ATP serves as both a neurotransmitter and an inflammation enhancer, thus acting as an intermediary between the local inflammation and neural pathway that induces inflammation on the other side. These results suggest blockade of this neural pathway, which is named the remote inflammation gateway reflex, may have therapeutic value for inflammatory diseases, particularly those, such as rheumatoid arthritis, in which inflammation spreads to remote positions.

Prognostic factors for outcomes of pediatric patients with refractory or relapsed acute leukemia undergoing allogeneic progenitor cell transplantation.

Allogeneic stem cell transplantation (SCT) is the only curative therapy for patients with refractory or relapsed acute leukemia, although the prognosis remains poor. Few reports have described outcomes of SCT in pediatric patients with refractory acute leukemia. To identify prognostic factors for these patients, we retrospectively evaluated SCT outcomes for advanced acute leukemia in 82 pediatric patients from 3 transplant units in Nagoya City between 1990 and 2008. Median age at transplantation was 8 years (range, 0.5-17 years). Transplantation was performed in the first refractory relapse for 53 patients (64.6%), in the second or subsequent relapse for 16 patients (19.5%), and during primary induction failure for 13 patients (15.9%). Only 4 patients (4.9%) underwent transplantation in the untreated first relapse, and 39 patients (47.6%) received unrelated donor progenitor cells. Of the 82 patients, 61 died (77.9%), with a median survival of 7.1 months (95% confidence interval [CI], 4.2-10.0 months). Median disease-free survival (DFS) was 4.7 months (95% CI, 2.6-6.9 months). In multivariate analysis, peripheral blood blasts, cord blood transplantation, and more than 3 courses of previous salvage chemotherapy were predictive of DFS. These results support the notion that allogeneic SCT offers only a small chance of cure for most pediatric patients with refractory or relapsed acute leukemia, and suggest that reduction of the leukemia burden and earlier optimal timing of transplantation are essential for long-term survival even in patients with refractory acute leukemia.

Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA-identical related donors.

Although some studies have reported that TBI and MEL offer an effective conditioning regimen for autologous SCT in acute leukemia, little has been reported regarding outcomes of allogeneic SCT. We retrospectively evaluated outcomes for 50 pediatric patients who underwent allo-SCT conditioned with intravenous MEL (180-210 mg/m(2) ) and fractionated TBI (12-13.2 Gy) from HLA-identical related donors. Nineteen patients were in CR1, 18 were in CR2, and 13 showed advanced-stage disease (≥ CR3). Patients had received allo-SCT from HLA-identical siblings (n = 45) or phenotypically HLA-identical family donors (n = 5). Median duration of follow-up for all disease-free patients was 61 months (range, 8.8-177 months). At the time of analysis, 12 patients had died. Eleven of those died of relapse, and one died of TRM. DFS rates for all patients, patients with AML (n = 12), and patients with lymphoid malignancy (n = 38) were 61.4% and 82.1%, respectively. DFS rates for CR1, CR2, and ≥CR3 cases were 89.2%, 88.1%, and 23.1%, respectively (p < 0.05). MEL/TBI for pediatric patients with hematological malignancies was associated with lower relapse rates and no increase in toxicity, resulting in better survival.

Invasive fungal infections in pediatric patients with hematologic malignancies receiving oral amphotericin B solution and early intravenous administration of fluconazole.

This study aimed to determine the frequency of invasive fungal infection (IFI) in pediatric patients with hematologic malignancy who received amphotericin B oral suspension and early intravenous fluconazole during the neutropenic phase as prophylaxis for IFI. Records of 743 neutropenic episodes induced by cytotoxic chemotherapy between 1997 and 2008 were retrospectively reviewed to determine risk factors for and frequency of IFI. The overall frequency of IFI was 0.8% (n=6) and frequencies of proven, probable, and possible infections were 0.3% (n=2), 0.4% (n=3), and 0.1% (n=1), respectively. During 351 episodes of profound neutropenia (neutrophil count <500/µL for ≥ 14 d), overall incidence of IFI was 1.71% (n=6). Pulmonary aspergillosis was the most common causative agent, and no patients showed candidemia, or hepatosplenic candidiasis. Cytotoxic chemotherapy regimens for acute myelogenous leukemia and profound neutropenia were significantly associated with IFI (P=0.004 and P=0.009, respectively). No IFI-attributable deaths or breakthrough fungal infections occurred. Our results indicate that amphotericin B oral solution and early intravenous fluconazole may be effective in reducing the incidence and mortality of IFI in pediatric patients with hematologic malignancies.

Maintenance of contractile force of the hind limb muscles by the somato-lumbar sympathetic reflexes.

This study aimed to clarify whether the reflex excitation of muscle sympathetic nerves induced by contractions of the skeletal muscles modulates their contractility. In anesthetized rats, isometric tetanic contractions of the triceps surae muscles were induced by electrical stimulation of the intact tibial nerve before and after transection of the lumbar sympathetic trunk (LST), spinal cord, or dorsal roots. The amplitude of the tetanic force (TF) was reduced by approximately 10% at 20 min after transection of the LST, spinal cord, or dorsal roots. The recorded postganglionic sympathetic nerve activity from the lumbar gray ramus revealed that both spinal and supraspinal reflexes were induced in response to the contractions. Repetitive electrical stimulation of the cut peripheral end of the LST increased the TF amplitude. Our results indicated that the spinal and supraspinal somato-sympathetic nerve reflexes induced by contractions of the skeletal muscles contribute to the maintenance of their own contractile force.

Influence of Intragastric Administration of Traditional Japanese Medicine, Ninjin'Yoeito, on Cerebral Blood Flow via Muscarinic Acetylcholine Receptors.

Ninjin'yoeito (NYT) is a traditional medicine that has been used for mitigating physical frailty, such as fatigue and anorexia, as well as for cognitive dysfunction. Maintenance of adequate cerebral blood flow (CBF) is important for preventing cognitive dysfunction. The present study aimed to examine the effect of NYT on CBF. Male C57BL/6 J mice were anesthetized with urethane and were artificially ventilated. We measured CBF in the neocortex with laser-speckle contrast imaging for 10 min before administration and 60 min after administration. We administered NYT solution (0.25, 0.5, 1, and 2 g/kg) or vehicle (distilled water; DW) over 5 min via an intragastric catheter. We surgically transected the vagus nerve to investigate its contribution as a neural pathway and intraperitoneally injected atropine to block muscarinic acetylcholine receptors. Finally, we tested the CBF response to cutaneous brushing stimulation applied to the left hind paw (30 sec). CBF decreased after DW administration, starting from 30 min onward, whereas CBF did not change after NYT. The averaged CBF change following DW administration differed from that following NYT (1 g/kg) but not from those following the other doses of NYT. Arterial pressure was not affected by either solution. CBF after NYT (1 g/kg) was not affected by vagotomy but was lower following additional atropine. In response to brushing stimulation, CBF in the right (contralateral) parietal cortex increased. The magnitude of CBF increase following NYT was greater than that following DW. These results suggest that NYT prevents CBF decrease via cholinergic activation independent of vagal activity and enhances the CBF response to somatosensory stimulation.