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Antimicrobial resistance (AMR) is a threat to patient health. However, data to optimize antimicrobial use are limited. Furthermore, reducing antibiotic use raises concerns regarding patient safety. The effectiveness of antibiotics in reducing the prevalence of AMR is controversial. Researchers at the Japanese Red Cross Ishinomaki Hospital (JRCIH), the only tertiary care hospital in the medical zone, along with local medical and pharmacy associations and public health centers have been leading the AMR control program since 2018. The program involves lectures aimed at optimizing antimicrobial use, regular publication of surveillance data of drug-resistant strains at the JRCIH, and presentation of first-line treatments for community-acquired infections. The delivery of oral antimicrobial agents across the region in 2020 was 28.7% lower than that in 2013, with delivery of cephalosporins, quinolones, and macrolides decreasing by 34.8%, 46.8%, and 56.0%, respectively. Despite these reductions, there has been no associated increase in the number of patients with severe infectious diseases admitted to the JRCIH. The rates of representative drug-resistant bacterial strains, such as extended-spectrum beta-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus, decreased by half. Herein, we demonstrated the potential of collaborative efforts to optimize antimicrobial agent use and reduce the AMR prevalence without compromising patient safety.

A concern has been raised that the persistent COVID-19 infection in an immunocompromised host can be the source of the SARS-CoV-2 variants. This is the case of a 61-year-old man in complete remission of a follicular lymphoma after six cycles of rituximab and bendamustine with additional two cycles of rituximab completed eight months prior to the episode of COVID-19 pneumonia. The patient's respiratory failure was long-lasting, and required mechanical ventilation until day 75. Acquired immunity tested negative throughout the observational period. The viral RNA was detectable until day 100 while the infectious virus was isolated until day 79. Seven haplotypes were identified and the non-synonymous mutations accumulated in the spike gene which included E484Q and S494P. In the management of COVID-19 cases with suppressed immune statuses, initial evaluation of existing immunity and monitoring for infectiousness throughout the clinical course including the convalescent stage may be necessary.

Introduction/Aims Due to muscular weakness and cardiopulmonary dysfunction, patients with muscular dystrophy (MD) have an increased risk of serious complications from coronavirus disease 2019 (COVID-19). Although vaccination is recommended, COVID-19 vaccination safety and immunogenicity in these patients are unknown. We investigated reaction frequency, post-vaccine antibody titers after two mRNA COVID-19 vaccine doses, and clinical predictors of antibody response among patients with MD.We recruited 171 inpatients with MD receiving two BNT162b2 mRNA COVID-19 vaccine doses from seven hospitals. Blood samples were obtained from 53 inpatients before the first dose and 28-30 days after the second dose, and antibody titers were measured.Overall, 104 (60.8%) and 115 (67.6%) patients experienced side effects after the first and second doses, respectively. These were generally mild and self-limited. Multiple logistic regression analysis showed that a bedridden state was associated with reduced side effects (OR: 0.29, 95% CI: 0.12-0.71). The antibody titers of all participants changed from negative to positive after two vaccine doses. The geometric mean titer (GMT) of the inpatients was 239 (95% CI: 159.3-358.7). Older age (RR=0.97, 95% CI: 0.95-0.99) and bedridden state (RR=0.27, 95% CI: 0.14-0.51) were associated with a lower antibody titer. Patients with myotonic dystrophy type 1 (DM1) had a lower GMT than patients with other MDs (RR=0.42, 95% CI: 0.21-0.85).COVID-19 vaccination is safe and immunogenic in inpatients with MD. Patients with DM1 appear to have a poorer COVID-19 antibody response than those with other MDs. This article is protected by copyright. All rights reserved.

Heat shock protein family B member 8, encoded by HSPB8, is an essential component of the chaperone-assisted selective autophagy complex, which maintains muscle function by degrading damaged proteins in the cells. Mutations in HSPB8 have been reported to cause Charcot-Marie-Tooth type 2L, distal hereditary motor neuropathy IIa, and rimmed vacuolar myopathies (RVM). In this study, we identified a novel heterozygous frameshift variant c.525_529del in HSPB8 in a large Japanese family with RVM, using whole exome sequencing. Three affected individuals had severe respiratory failure, which has not been addressed by previous studies. Muscle atrophy in the paraspinal muscles was also a clinical feature of the individuals affected with RVM in this study. The frameshift mutation was located in the last coding exon, and the mutated protein was predicted to harbor an isoleucine-leucine-valine (ILV) sequence, which corresponds to the IXI/V (isoleucine, X amino acids, and isoleucine or valine) motif. The IXI/V motif is essential for assembly into larger oligomers in other small heat shock proteins and all frameshift mutants of HSPB8 were predicted to share the ILV sequence in the C-terminal extension. The in silico prediction tools showed low protein solubility and increased aggregation propensity for the region around the ILV sequence. The IXI/V motif might be associated with the pathogenesis of HSPB8-related RVM.

To clarify the influence of coronavirus disease-19 (COVID-19) on the care of muscular dystrophy patients, we performed a questionnaire survey that was posted on the internet on May 11, 2020. By the end of July 2020, 542 responses had been collected. Approximately 30% of patients postponed regular consultations, and one-quarter of patients who received consultation more than once a month used telephone consultations. Two of 84 patients with Duchenne muscular dystrophy had reduced their steroid doses. A shortage of ventilator accessories and infection protection equipment occurred following the onset of COVID-19, and this shortage had a serious impact on medical care and infection prevention measures. Reductions in rehabilitation and other services, and avoidance of outings, led to a decrease in exercise and an increase in caregiver burden. Inpatients were restricted from going out and visiting family members. More than 20% of patients reported physical or mental complaints; however, few required treatment. COVID-19 has seriously affected the activities and quality of life of patients with muscular dystrophy. We will continue this survey and analyze the longitudinal changes.

Retropharyngeal hematoma is a potentially life-threatening condition because it can easily lead to airway obstruction. Most of the previously reported cases of retropharyngeal hematoma are caused by predisposing factors such as head and neck trauma, the use of anticoagulants, or the presence of underlying bleeding diathesis. Herein, we report a case of retropharyngeal hematoma in a patient with chronic alcoholism, where we could not confirm any predisposing factors at the time of examination. A 61-year-old man with chronic alcoholism presented to our emergency department with convulsive seizures. He was diagnosed with alcohol withdrawal and transferred to a secondary hospital after the seizure resolved. However, a few hours later, he returned to our department with a persistent cough and complained of pain and swelling in the neck. One hour later, he suddenly developed dyspnea; therefore, emergency intubation was performed. Although initially computed tomography (CT) showed normal findings, contrast-enhanced CT revealed a retropharyngeal hematoma. He was managed conservatively and transferred to a specialty hospital for intensive care. Chronic alcoholism may be a predisposing factor for retropharyngeal hematoma due to the high incidence of head trauma, neck hyperextension by convulsion, and hemostatic disorders. However, taking an accurate patient history is sometimes difficult because of the effects of intoxication or alcohol withdrawal. If a patient with chronic alcoholism presents with symptoms of airway compression, then a retropharyngeal hematoma should be suspected, and emergency intubation should be considered.

We screened anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies among 42 patients who had undiagnosed chronic myopathy from six national hospitals. Anti-SRP and anti-HMGCR antibodies were determined by RNA immuneprecipitation and enzyme-linked immune-sorbent assay (ELISA), respectively. We identified two patients with anti-SRP antibodies (4.7%) and, two with anti-HMGCR antibodies (4.7%). Both of anti-SRP-positive patients showed dysphagia with a high level of creatine kinase. Anti-HMGCR antibodies were associated with mild muscle weakness with a relatively late disease onset. Our study suggests the importance of autoantibody testing among undiagnosed chronic myopathy.

Idiopathic basal ganglia calcification (IBGC) is a rare intractable disease characterized by abnormal mineral deposits, including mostly calcium in the basal ganglia, thalamus, and cerebellum. SLC20A2 is encoding the phosphate transporter PiT-2 and was identified in 2012 as the causative gene of familial IBGC. In this study, we investigated functionally two novel SLC20A2 variants (c.680C > T, c.1487G > A) and two SLC20A2 variants (c.82G > A, c.358G > C) previously reported from patients with IBGC. We evaluated the function of variant PiT-2 using stable cell lines. While inorganic phosphate (Pi) transport activity was abolished in the cells with c.82G > A, c.358G > C, and c.1487G > A variants, activity was maintained at 27.8% of the reference level in cells with the c.680C > T variant. Surprisingly, the c.680C > T variant had been discovered by chance in healthy members of an IBGC family, suggesting that partial preservation of Pi transport activity may avoid the onset of IBGC. In addition, we confirmed that PiT-2 variants could be translocated into the cell membrane to the same extent as PiT-2 wild type. In conclusion, we investigated the PiT-2 dysfunction of four SLC20A2 variants and suggested that a partial reduced Pi transport function of PiT-2 might not be sufficient to induce brain calcification of IBGC.

抑うつ傾向にある児童生徒は増加しているが、抑うつ状態が放置されると、深刻な社会的不適応・ひきこもり など二次的な問題が生じる危険性もあり、早期に気づく必要がある。しかし、思春期の子どもは自己の内面をなかな か語らないことも多く、不安定な心の状態を捉えにくい。本研究では、臨床場面や学校や家庭で子どもの抑うつ感を 早期にキャッチし対応できる方法を検討したい。そこで、Birleson（1981）の子ども版自己記入式抑うつ尺度（DSRS C）の日本語版（村田ら,1996）を用いて、子どもの抑うつ感を測定し、さらに、動的学校画（KSD）を用いて、子 どもの抑うつ感と描画特徴との関連を検討した。関西圏のA 中学校の1 年生210 名（男子104 名、女子106 名）を 対象に、子ども版自己記入式抑うつ尺度（DSRS C）と動的学校画（KSD）を施行した。その結果、抑うつ感の高 いものは自己像を小さく描くこと、友達の行為について何もしていないなどの友達像を描くこと、悲哀感の高いもの は、自己像と先生像との距離を近くに描き、友達像との距離を近くに描かないこと、全体的に統合性に欠ける絵を描 くことなどが示された。今後は、動的家族画（KFD）なども合わせて用いることで、さらに多様な側面から検討し たいと考えている。, The number of children and adolescents with depression has been increasing. Their secondary symptoms such as serious social maladjustment and hikikomori（social withdrawal）cause the therapeutic difficulty. Thus, to detect and treat depression at early stage is required. The drawing technique is one of the methods to discover the social maladjustment. In this research, we investigated whether the drawing technique was able to reveal depression at early stage among children and adolescents. We studied the correlation between the score of depression by means of a Japanese version of Depression Self Rating Scale for Children （DSRS C）and drawing characteristics analyzed by Kinetic School Drawing technique（KSD）. Totally 210 students（104 boys and 106 girls）in seventh grade in Kansai area were enrolled in this study and 196 valid samples（95 boys and 101 girls）were analyzed. The result demonstrated that the students with higher scores on DSRS C tended to draw themselves in a smaller scale and their classmates in an inactive state. Among the students with sad feeling, while the distance between themselves and their teacher was shorter, the distance between themselves and classmates was longer. Therefore

To clarify the current status of genetic counseling and health monitoring for symptomatic and asymptomatic female carriers of dystrophinopathy (Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD)), we sent out questionnaires to 104 member institutions of The Japan's National Liaison Council for Clinical Sections of Medical Genetics, and responses were received from 51 institutions. Between April 2013 and March 2014, 57 carriers at 21 institutions received genetic counseling, and 37 carriers at 15 institutions underwent genetic screening for DMD/BMD mutations. At the 23 institutions that gave genetic counseling, 20 (87%) informed carriers of possible health problems, 14 (61%) informed carriers of cardiomyopathy and heart failure, and 14 (61%) advised carriers about regular medical checkups. Evidence based on accurate and up-to-date epidemiological studies of female carriers is needed and should be widely shared with the families, medical providers, and society.

The impacts of greenhouse gases (GHG) to vehicles through improvements in fuel efficiency via material substitutions and their historical trends were analyzed to assess if lightweighting actually provides its expected benefits. Data for the weight and fuel efficiency of American and Japanese cars over the past 30 years was used for trend analysis. Also, the impacts of GHG in substituting steel for high strength steel, aluminum, carbon fiber reinforced polymer, and magnesium were analyzed. This study shows that while the amount of low-density materials in a vehicle has increased, the weight itself has increased because of the “rebound of design” reflecting the consumer demands. In lightweighting strategy, the material substitution of steel for high strength steel is the most promising option to reduce GHG emissions. Based on recent historical trends, this analysis shows that the GHG payback miles have increased and will continue to increase unless the reduction in GHG emissions occur at higher rates than that of fuel efficiency improvement from steel-based vehicles. This suggests that the competition over steel will become severer in the future for other materials with low densities. To reverse the result, it is necessary to reduce GHG intensities of materials at higher rates than that of improvement of fuel efficiency.

BACKGROUND: Manually-assisted coughing and mechanical insufflation-exsufflation (MI-E) are commonly used in patients with Duchenne muscular dystrophy (DMD). Few studies have compared cough peak flow (CPF) with manually-assisted coughing to other methods, such as MI-E + manually-assisted coughing. In addition, few studies have reported the reliability of the measured CPF values. This study aimed to compare CPF with different cough-assistance methods and to examine the reliability of CPF data. METHODS: The study included 12 subjects with DMD (mean age, 34 ± 8 y). CPF, CPF + manually-assisted coughing (assisted CPF), maximum insufflation capacity (MIC) + CPF (MIC-CPF), MIC + manually-assisted coughing (MIC+assisted CPF), MI-E (MI-E–CPF), and MI-E + assisted CPF were measured. A spirometer was used to compare CPF measurements obtained with each of the cough-assist techniques. The reliability of the measured CPF values was analyzed using Bland-Altman analysis. RESULTS: CPF was 59 ± 34 L/min, assisted CPF was 113 ± 32 L/min, MIC-CPF was 170 ± 30 L/min, MIC+assisted CPF was 224 ± 62 L/min, MI-E–CPF was 199 ± 40 L/min, and MI-E + assisted CPF was 240 ± 38 L/min. A fixed and proportional bias was found in the CPF measurements made with the peak flow meter and the spirometer. The average 95% CI in the difference between peak flow meter, MI-E, and CPF obtained using the spirometer were −7.45 to −1.95 and −1.45 to 4.95, respectively. Test for correlation was r = 0.54 (P CONCLUSION: MI-E + assisted CPF was the highest. The CPF measured with the peak flow meter suggested underestimation.

Objective This study attempted to clarify the current status of female dystrophinopathy carriers, including the numbers of patients, the status of genetic screening, the status of counseling, physicians' understanding, and barriers to registration. Methods We sent out questionnaires to 402 physicians registered in the Remudy dystrophinopathy registry. The total number of responses received was 130 (response rate: 32%). Result In total, 1,212 cases of Duchenne muscular dystrophy, 365 cases of Becker muscular dystrophy, and 132 cases of female dystrophinopathy with a confirmed genetic mutation were encountered, and genetic testing was performed in the mother in 137, 23, and 12 cases, respectively. With respect to the risk of the onset of health problems, 25% of physicians always explained, 29% usually explained, 29% sometimes explained, and 13% never explained the risk to the mothers and female siblings of dystrophinopathy patients. The most common reason for not explaining the risk was a lack of knowledge/information. Thirty-five percent were familiar with the guidelines for testing the heart function of carriers. Conclusion Fewer mothers of dystrophinopathy patients have undergone genetic testing in Japan than in other countries. A significant portion of doctors did not explain the risks of health problems due to a lack of knowledge. We hope this survey will lead to an increased discussion of female dystrophinopathy patients.

Regular health checkups for mothers of patients with Duchenne muscular dystrophy have been performed at National Hospital Organization Tokushima Hospital since 1994. Among 43 mothers participated in this study, 28 dystrophinopathy carriers were identified. Skeletal and cardiac muscle functions of these subjects were examined. High serum creatine kinase was found in 23 subjects (82.1%). Obvious muscle weakness was present in 5 (17.8%) and had progressed from 1994 to 2015. Cardiomyopathy was observed in 15 subjects (60.0%), including dilated cardiomyopathy-like damage that was more common in the left ventricular (LV) posterior wall. Late gadolinium enhancement on cardiac MRI was found in 5 of 6 subjects, suggesting fibrotic cardiac muscle. In speckle tracking echocardiography performed seven years later, global longitudinal strain was decreased in these subjects, indicating LV myocardial contractile abnormality. These results suggest that female dystrophinopathy carriers should receive regular checkups for detection and treatment of cardiomyopathy, even if they have no cardiac symptoms.

Introduction: Mechanically assisted coughing (MAC) is an airway clearance method in which the thorax and/or the abdomen are compressed in synchronization with mechanical insufflation-exsufflation (MI-E). Aims: The purpose of this study was to examine the effects of four MAC procedures on pulmonary function in different conditions of patients with neuromuscular disease (NMD). Methods: Twenty-seven patients (mean age, 54.3 ± 18.8 years) with NMD (PMD=15, ALS=6, other=6) who underwent MI-E were divided into an air stacking group, a no air stacking group, and a tracheostomy positive pressure ventilation(TPPV) group. MAC procedures were divided into the following four groups according to the position of manual assistance: MI-E alone, upper thoracic MAC (UT-MAC), lower thoracic MAC (LT-MAC), and upper thoracic/abdominal MAC (UT/A-MAC). Pulmonary function was evaluated by cough peak flow (CPF) and the value at 75% of the forced vital capacity (V75). Results: In the air stacking group, CPF with MI-E alone was significantly lower than CPF with UT-MAC, LT-MAC, and UT/A-MAC (p Conclusions: In the air stacking group, a higher CPF was achieved with MAC compared with MI-E. However, the effect of MAC was influenced by the position of manual assistance and the presence of scoliosis. MAC did not increase CPF in NMD patients with TPPV.

Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by a loss-of-function mutation of DNAX-activation protein 12 (DAP12) or triggering receptor expressed on myeloid cells 2 (TREM2). TREM2 and DAP12 constitute a receptor/adaptor complex on myeloid cells. The post-receptor signals are transmitted via rapid phosphorylation of the immunoreceptor tyrosine-based activating motif (ITAM) of DAP12, mediated by Src protein tyrosine kinases, followed by binding of phosphorylated ITAM to Src homology 2 (SH2) domains of spleen tyrosine kinase (Syk), resulting in autophosphorylation of the activation loop of Syk. To elucidate the molecular mechanism underlying the pathogenesis of NHD, we investigated Syk expression and activation in the frontal cortex and the hippocampus of three NHD and eight control brains by immunohistochemistry. In NHD brains, the majority of neurons expressed intense immunoreactivities for Syk and Y525/Y526-phosphorylated Syk (pSyk) chiefly located in the cytoplasm, while more limited populations of neurons expressed Src. The levels of pSyk expression were elevated significantly in NHD brains compared with control brains. In both NHD and control brains, substantial populations of microglia and macrophages expressed pSyk, while the great majority of reactive astrocytes and myelinating oligodendrocytes did not express pSyk, Syk or Src. These observations indicate that neuronal expression of pSyk was greatly enhanced in the cerebral cortex and the hippocampus of NHD brains, possibly via non-TREM2/DAP12 signaling pathways involved in Syk activation.

The bisazo dye Ponceau SS forms an acute oblique (V-type) dimer in dilute aqueous solution. In concentrated aqueous solution, these V-type dimers are considered to stack to form V-type blocks of chromonic liquid-crystalline (LC) columns. The weak interactions among these LC columnar V-type blocks have been spectroscopically investigated. On increasing the concentration of Ponceau SS at 25 °C, the V-type LC columnar blocks form a rhombus-type LC columnar block at 2 wt% concentration. These rhombus-type LC columnar blocks are further aligned at an acute angle at 5 and 10 wt% concentrations. The rapidly cooled 10 wt% LC sample shows an unusually sharp J-band-like peak in the electronic absorption spectrum. The emergence of this J-band-like peak has been analyzed from the viewpoint of an exciton model, suggesting that many nearest neighbor unique molecules belonging to many different rhombus-type LC columnar blocks are aligned in a head-to-tail manner to give a giant quasi-linear head-to-tail-type exciton.

Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by genetic mutations of DNAX-activation protein 12 (DAP12) or triggering receptor expressed on myeloid cells 2 (TREM2). TREM2 and DAP12 constitute a receptor/adapter signaling complex expressed on osteoclasts, dendritic cells (DC), macrophages and microglia. Previous studies using knockout mice and mouse brain cell cultures suggest that a loss-of-function of DAP12/TREM2 in microglia plays a central role in the neuropathological manifestation of NHD. However, there exist no immunohistochemical studies that focus attention on microglia in NHD brains. To elucidate a role of microglia in the pathogenesis of NHD, we searched NHD-specific biomarkers and characterized their expression on microglia in NHD brains. Here, we identified allograft inflammatory factor 1 (AIF1, Iba1) and sialic acid binding Ig-like lectin 1 (SIGLEC1) as putative NHD-specific biomarkers by bioinformatics analysis of microarray data of NHD DC. We studied three NHD and eight control brains by immunohistochemistry with a panel of 16 antibodies, including those against Iba1 and SIGLEC1. We verified the absence of DAP12 expression in NHD brains and the expression of DAP12 immunoreactivity on ramified microglia in control brains. Unexpectedly, TREM2 was not expressed on microglia but expressed on a small subset of intravascular monocytes/macrophages in control and NHD brains. In the cortex of NHD brains, we identified accumulation of numerous Iba1-positive microglia to an extent similar to control brains, while SIGLEC1 was undetectable on microglia in all the brains examined. These observations indicate that human microglia in brain tissues do not express TREM2 and DAP12-deficient microglia are preserved in NHD brains, suggesting that the loss of DAP2/TREM2 function in microglia might not be primarily responsible for the neuropathological phenotype of NHD.

Direct numerical simulation (DNS) of a feedback-controlled turbulent channel flow at Reτ = 640 is carried out. As an idealized feedback control, we selectively damp either the small scale wall-normal velocity fluctuations (defined as those with the spanwise wavelength smaller than 300 wall units) or the large scale fluctuations (the spanwise wavelength larger than 300 wall units). The present DNS reveals that the control of small scale fluctuations leads to more drag reduction than that of large scale fluctuations. When the small scale fluctuation is damped, the friction drag is reduced by the amount corresponding to the absence of small scale fluctuation. In contrast, when the large scale fluctuation is damped, the friction drag reduction is much less than that expected from the absence of large scale fluctuation. In the latter case, the contribution from the small scale fluctuation to the friction drag is found to be drastically increased due to the reduction of pressure fluctuation and destruction of Reynolds shear stress.

We report a case of gastrointestinal manifestation of hereditary angioedema. Computed tomography (CT) revealed wall thickening of the gastric antrum, duodenum, and jejunum. Dilatation of the third part of the duodenum, thickening of the small bowel mesentery and omentum, and retroperitoneal edema were present. The importance of considering this condition in patients presenting such CT findings correlated with the appropriate history is discussed.

Tris(8-quinolinolato)aluminum(III) (Alq3) shows electronic absorption bands at 378, 360 (in a 1:1 mixed solvent of methanol and ethanol (ME) at 77 K), 334, 316, 300, 263, 255.8, and 233 nm in ethanol at room temperature. According to the polarized fluorescence excitation spectrum together with MO calculations, for instance, the 360 nm band is assigned to an LL CT transition (an intramolecular charge transfer transition between two ligands), and the 378 nm band to an LM/ML CT one (an intramolecular charge transfer transition between ligand and metal). Alq3 shows a broad fluorescence band peaking at around 478 nm in the ME matrix at 77 K. The emission spectrum measured with a phosphoroscope has two emission bands at 567 and 478 nm. The 567 nm band accompanies vibronic bands at 578 and 605 nm, being safely assigned to a phosphorescence of Alq3. The lifetimes of the 478 and 567 nm bands are both 5.4 ms. The lifetime of the 478 nm band together with the band position and its band shape indicate that this band can be assigned to a delayed fluorescence.

Background Sepsis is an arginine-deficient state and is associated with overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). It has been indicated that low plasma levels of arginine are related to high mortality rates in sepsis. Arginine, however, is also known to be a precursor of NO. Therefore, administration of arginine in septic patients remains controversial. We examined the effects of co-administration of arginine and aminoguanidine, a selective iNOS inhibitor, on sepsis, using rat models. Method Sepsis was induced in rats by cecal ligation and puncture (CLP). Effects of separate and combined administration of arginine and aminoguanidine were investigated by comparing plasma levels of arginine, expressions of heme oxygenase (HO)-1 and HO-2 in liver and lung, and nitrite + nitrate (NOx) excretion in urine, as well as neuroendocrine responses in urine in the early phase of sepsis. Seven-day survival rates were also examined. Results A combination of arginine and aminoguanidine recovered the plasma level of arginine at 6 h post-CLP, decreased expression of HO-1 in liver and lung at 24 h post-CLP, decreased urinary excretion of epinephrine, norepinephrine, dopamine, and 17-hydroxycorticosteroid in the first 24 h post-CLP, and increased 7-d survival. Conclusion It is demonstrated that administration of arginine together with the selective iNOS inhibitor in the early phase of sepsis restores plasma arginine, reduces oxidative stress by probably maintaining NO derived from constitutive NOS, and attenuates neuroendocrine stress responses. This co-administration may be a beneficial treatment approach against sepsis.

We genetically screened patients with ataxia with ocular motor apraxia type 1 (AOA1)/early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), with a Japanese variant form of Friedreich’s ataxia. Three patients were found to have a homozygous insertion mutation of the aprataxin gene (689insT). An elder sister of a patient in this series died of cerebral hemorrhage at the age of 45, and underwent autopsy. In her cerebellar cortex, the mean density of Purkinje cells in the flocculus had predominantly decreased to 6.7% of normal controls, whereas the Purkinje cells in the other areas of the cerebellar hemisphere had decreased to 78.2%. This suggests that the cerebellar flocculus is the primary affected lesion in AOA1/EAOH, which should be associated with ocular motor apraxia.

Mice infected with Schistosoma mansoni develop hepatic fibrosis associated with enhanced collagen synthesis that out-paces induced collagenase activity. Administration of one dose of concanavalin A [Con A (200 micrograms)] by i.p. injection to mice at 5 or 6 weeks after infection with 50 S. mansoni cercariae decreased liver collagen content by 50% compared to levels in control-infected mice injected with either homologous immunoglobulin (200 micrograms) or phosphate-buffered saline; additional doses of Con A had no further effect. The decrease in collagen content could not be attributed to either decreased egg deposition in the liver or inhibition of liver collagen synthesis, but was coincident with a greater solubility of granulomas. Collagen contents of skin and tail were unaffected. The relative solubilities of liver collagen in 8 M urea: 10 mM dithiothreitol were greater in treated animals as compared to controls. However, the amounts of collagen solubilized were similar in both sets of animals, since the total collagen content of treated mice was 50% of the controls. A possible explanation for these results is that much of the synthesized collagen does not accumulate in treated animals, whereas it does accumulate in controls. Peak collagenase and neutral protease activities occurred at 7 weeks postinfection in treated animals, and were 2-fold greater than in controls. Similar effects were observed when succinylated Con A was administered. The results suggest that Con A may modulate host-immune responses influencing fibrogenesis in hepatic murine schistosomiasis.

It has been observed for the binary systems of oriented nematic hosts and nonmesomorphic guests (substituted anthraquinones) that the orientational orders of amino-substituted anthraquinones ascend with increasing guest concentrations. A new quantitative and experimental procedure has been proposed for obtaining the host–guest isotropic dispersion, isotropic electrostatic, anisotropic dispersion, and anisotropic electrostatic interaction energies. Among these four host–guest interaction energies, the host–guest isotropic dispersion interaction energy alone is demonstrated to be well correlated with the concentration dependence of the orientational order of the guest. A model is also proposed for the cooperative and isotropic host–guest interaction.

Oxygen-derived free radicals play important roles in pathophysiological processes in critically ill patients, but the data characterizing relationships between radicals and neuroendocrine system response are sparse. To search the cue to reduce the oxidative cellular damage from the point of view of neuroendocrine system response, we studied the indicators of neuroendocrine and inflammatory responses excreted in urine in 14 burn patients (42.3 +/- 31.4 years old, and 32.3 +/- 27.6% burn of total body surface area [%TBSA]) during the first seven days post burn. The daily mean amounts of urinary excretion of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a marker of oxidative cellular damage, were above the upper limit of the standard value during the studied period. The total amount of urinary excretion of 8-OHdG in the first day post burn correlated with burn severity indices: %TBSA (r = 0.63, p = 0.021) and burn index (r = 0.70, p = 0.008). The daily urinary excretion of 8-OHdG correlated with the daily urinary excretion of norepinephrine and nitrite plus nitrate (NOx) during the studied period except day 2 post burn, and correlated with the daily urinary excretion of 17-hydroxycorticosteriod (17-OHCS) in days 2, 3, and 7 post burn. These data suggest that oxidative cellular damage correlates with burn severity and neuroendocrine system response modulates inflammation and oxidative cellular damage. Modulation of neuroendocrine system response and inflammation in the treatment in the early phase of burn may be useful to reduce the oxidative cellular damage and to prevent multiple organ failures in patients with extensive burn.

It has so far not been possible to fabricate a sol-gel-derived hafnia film with a uniform surface by spin-coating an aqueous hafnia sol on a stainless steel substrate. The reason is that the substrate repulses the sol because of the latter's high surface energy. To improve the wettability and coating properties of the sol on the substrate, the authors degreased the substrate in a strong basic solution with and without the application of a 2-A electric current prior to the spin-coating process. After the surface treatment, it was found by atomic force microscopy and temperature programmed desorption analysis, respectively, that the surface roughness and the amount of water adsorbed on the substrate surface increased. The water and hafnia sol droplet contact angles on the substrate deceased. Thus, the sols were wetted and spread well on the surface-treated substrates during the spin-coating process, resulting in sol-gel-derived hafnia films with uniform and flat surfaces.

Background In the Great East Japan Earthquake, the Japanese Red Cross Ishinomaki Hospital played an important role as a principal referral center within the Ishinomaki region, one of the most severely affected areas in eastern Japan. The present study describes the patient population, clinical characteristics, and time courses of the medical problems observed at this hospital. Methods A retrospective survey of medical logs and records was conducted on the first 2 weeks after the earthquake to characterize orthopedic traumas and related disorders treated during this catastrophe. Patient number, severity of injuries, number of patients secondarily transported to the referral medical centers in the inland area, and the number of surgeries performed during the study period were investigated. Results Totally, 7686 patients visited the hospital. Of which, 1807 patients suffered from exogenous diseases, such as trauma, burns, crush syndrome, deep venous thrombosis, and infectious diseases. Patients who suffered from hypothermia were the most frequently seen within the first 2 weeks after the earthquake. Interestingly, most patients' conditions were not severe and required only simple treatments. Four patients (0.2% of patients with exogenous diseases) were secondarily transported to the referral medical centers in the inland area and only four patients were surgically treated because of a lack of available implants, surgical devices, and electric power supply. Discussion and conclusions The Great East Japan Earthquake and subsequent tsunami, which occurred during an early spring afternoon, resulted in a unique orthopedic patient population, which included few severely injured patients compared with numerous deaths. We believe that each coastal region hospital should develop its own emergency medical care system to address future tsunami events while considering their surrounding environment. The information described in the present study should be important for preparation toward future events involving massive earthquakes followed by tsunami disasters.

Time-resolved transient absorption spectra of photo-irradiated 2,2′-pyridil were measured in PVA films. The broad bands at 552 and ∼455 nm, appearing just after photo-excitation of 2,2′-pyridil, ar...

We report a paraneoplastic neuropathy with severe motor involvement following sensory-ataxic disturbance. Anti-disialosyl immunoglobulin M (IgM) antibody was detected in the course of malignant lymphoma of diffuse large B-cell type, which usually spares the motor system. Onset was subacute, with relapsing and remitting sensory ataxia, muscle weakness, bulbar palsy, respiratory paralysis, and ophthalmoplegia; only neck rotation was retained in the terminal stage. Autopsy showed no lymphoma cells infiltrating the nervous system. Motor neurons survived in the spinal cord, but mean diameter of the ventral spinal nerve roots was reduced considerably. The gracile fasciculus and the sural nerve were more markedly degenerated than proximal portions. Morphometric study showed that most of the proximal motor and sensory axons did not extend distally. This autopsy report provides further definition of a neuropathy associated with malignant lymphoma and IgM antibodies against disialosyl residues.

The first shorter-molecular-axis polarized electronic absorption band of 7-methylxanthone-2-carboxylic acid octadecyl ester shows a surface pressure dependence in Langmuir films, giving rise to a s...

Fluoranthene (FA) forms a 1:1 van der Waals complex with benzene in cyclohexane. The 1H NMR spectrum of this complex shows that the FA moiety in the complex state has five kinds of hydrogen atoms and that the 1H NMR peaks assigned to the protons attached to the naphthalene skeleton are largely shifted to higher magnetic field on complex formation with benzene. These observations indicate that the complex takes the structure of CS symmetry, in which the benzene molecule mainly interacts with the π electronic system localized on the naphthalene moiety of FA. The present ab initio calculations reproduce well the 1H NMR spectral shifts mentioned above and the experimentally predicted CS structure of the complex. According to the PPP calculations for the electronic absorption spectral changes on the complex formation, the FA-benzene complex is considered to take a sandwich type structure.