A retrospective review of 10-year trends in general anesthesia for cesarean delivery at a university hospital: the impact of a newly launched team on obstetric anesthesia practice.

BACKGROUND: The indications for general anesthesia (GA) in obstetric settings, which are determined in consideration of maternal and fetal outcome, could be affected by local patterns of clinical practice grounded in unique situations and circumstances that vary among medical institutions. Although the use of GA for cesarean delivery has become less common with more frequent adoption of neuraxial anesthesia, GA was previously chosen for pregnancy with placenta previa at our institution in case of unexpected massive hemorrhage. However, the situation has been gradually changing since formation of a team dedicated to obstetric anesthesia practice. Here, we report the results of a review of all cesarean deliveries performed under GA, and assess the impact of our newly launched team on trends in clinical obstetric anesthesia practice at our institution. METHODS: Our original database for obstetric GA during the period of 2010 to 2019 was analyzed. The medical records of all parturients who received GA for cesarean delivery were reviewed to collect detailed information. Interrupted time series analysis was used to evaluate the impact of the launch of our obstetric anesthesia team. RESULTS: As recently as 2014, more than 10% of cesarean deliveries were performed under GA, with placenta previa accounting for the main indication in elective and emergent cases. Our obstetric anesthesia team was formed in 2015 to serve as a communication bridge between the department of anesthesiology and the department of obstetrics. Since then, there has been a steady decline in the percentage of cesarean deliveries performed under GA, decreasing to a low of less than 5% in the latest 2 years. Interrupted time series analysis revealed a significant reduction in obstetric GA after 2015 (P = 0.04), which was associated with decreased use of GA for pregnancy with placenta previa. On the other hand, every year has seen a number of urgent cesarean deliveries requiring GA. CONCLUSIONS: There has been a trend towards fewer obstetric GA since 2015. The optimized use of GA for cesarean delivery was made possible mainly through strengthened partnerships between anesthesiologists and obstetricians with the support of our obstetric anesthesia team.

Parity As a Protective Biomarker Against Silent Brain Infarction in Community-Dwelling Older Adults: The Sefuri Study.

BACKGROUND: Although several studies have reported an association between parity and increased risk of stroke, this relationship remains controversial. AIMS: The present study aimed to determine whether parity is associated with silent brain infarction (SBI), independent of other confounders. METHODS: We analyzed the brain magnetic resonance imaging findings in 576 of community-dwelling older adults with a mean age of 72.1 years. All female participants were asked to provide information regarding the total number of live births, their age at the last parity, and their age at menopause. RESULTS: The prevalence of SBI and the number of infarcts per participant were higher in men than in women. Although all women who had given birth (0, 1-2, 3-4, or 5+ times) exhibited lower age-adjusted odds ratios (ORs) for SBI than men, a significant difference was observed between women with ≧5 births and men after adjustment for common vascular risk factors (OR: .348, 95% confidence interval [95% CI]: .123-.986). Among women who had given birth, the relationship between fertility and SBI was attenuated, but was enhanced after adjustment for age at the last parity (OR: .300, 95% CI: .102-.886). CONCLUSIONS: Our findings indicate that fertile women may be protected against SBI or cerebral small vessel disease via the biological effects associated with reproductive activity, and that high fertility may be a marker of protection against SBI. However, late childbearing may blunt protective effects of fertility against SBI.

Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease, 2017.

BACKGROUND: Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as "allied disorders of Hirschsprung's disease" and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. METHODS: These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis-microcolon-intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo-obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese- and English-language articles in PubMed and Ichu-Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. RESULTS: We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full-thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. CONCLUSIONS: Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies.

Identification of highly selective and potent orexin receptor 1 antagonists derived from a dual orexin receptor 1/2 antagonist based on the structural framework of pyrazoylethylbenzamide.

The design, synthesis, and structure activity relationships of the novel class of pyrazolylethylbenzamide orexin receptor 1-selective antagonists are described. Further derivatization of the prototype dual orexin receptor 1/2 antagonist lead (1) by installing a (S)-methyl group into the ethyl linker moiety between the pyrazole ring and benzamide resulted in an increase of the antagonist potency against orexin receptor 1/2 receptors. Optimization of the benzamide and pyrazole parts of compounds 2 and 9b led to the identification of N-ethyl-5-fluoro-N-{(2S)-1-[5-(4-fluorophenyl)-2H-tetrazol-2-yl]propan-2-yl}-2-(pyrimidin-2-yl)benzamide (24), which exhibited excellent antagonistic activity against orexin receptor 1 with an IC50 of 2.01nM and a 265-fold selectivity for orexin receptor 1 over orexin receptor 2.

Chronic Kidney Disease and Subclinical Brain Infarction Increase the Risk of Vascular Cognitive Impairment: The Sefuri Study.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the complex associations among chronic kidney disease (CKD), subclinical brain infarction (SBI), and cognitive impairment. METHODS: We used structural equation modeling (SEM) to examine the complex relationships among CKD, SBI, and cognitive function with Mini-Mental State Examination (MMSE; global function) and modified Stroop test (executive function) in a population-based cohort of 560 non-demented elderly subjects. RESULTS: Path analysis based on SEM revealed that the direct paths from estimated glomerular filtration rate (eGFR) to SBI and from SBI to executive function were significant (ß = -.10, P = .027, and ß = .16, P < .001, respectively). Furthermore, the direct path from eGFR to executive function was also significant (ß = -.12, P = .006), indicating that the effects of CKD on executive function are independent of SBI. The direct paths from age and education to global cognitive function were highly significant (ß = -.17 and .22, respectively, P < .001), whereas the direct path from eGFR to MMSE was not significant. CONCLUSIONS: Our findings indicate that CKD confers a risk of vascular cognitive impairment or executive dysfunction through mechanisms dependent and independent of SBI. Treating CKD may be a potential strategy to protect against vascular cognitive impairment or executive dysfunction in healthy elderly subjects.

[Work-Related Issues of Adolescent and Young Adult(AYA)Cancer Survivors - Tips for Supporting Them in and out of Hospitals].

Recent advances in cancer treatment have steadily improved the overall survival rate, and enhancing the quality of life of cancer survivors is the challenge faced at present. One of the major topics in studies on cancer survivors is work-related issues, and the government has been focusing on improving the circumstances of the working population and children. In 2015, the Cancer Control Accelerating Plan set adolescent and young adult(AYA)cancer survivors as the top priority for this plan. Work-related issues of AYA cancer survivors are highly individualized and complicated, mainly because of three characteristics: 1 ) Cancer treatments and/or outpatient follow-ups are accompanied by major life-stage transitions, 2 ) Treatments are prone to be nonstandardized in "rare cancers" or "advanced-stage cancers" and 3 ) Achieving economic independence is difficult because of high medical costs. This article provides some tips for medical professionals working in hospitals on how to support AYA cancer survivors along with their main responsibilities. It also provides an overview of online and offline resources available for supporting this population.

Marriage and fertility in long-term survivors of childhood, adolescent and young adult (AYA) high-grade sarcoma.

PURPOSE: We investigated the marital status and the presence or absence of children in survivors of childhood, adolescent and young adult (AYA) high-grade sarcoma and examined the influence of these factors on the quality of life (QOL) of these survivors. METHODS: Thirty-eight survivors of childhood and AYA high-grade sarcoma (18 males, 20 females) participated in a questionnaire survey on marital status and presence or absence of children, as well as on the health-related QOL (HR-QOL), using the Short Form 36 Health Survey. Diagnoses among these survivors were osteosarcoma (28 participants), Ewing's sarcoma (4 participants), synovial sarcoma (4 participants) and others (2 participants). RESULTS: Of the 18 males who participated in the survey, eight (44.4 %) were married, of whom five (62.5 %) had children. Fifteen (75.0 %) of the 20 females were married, of whom 14 (93.3 %) had children. The proportions of surviving male patients who were married and who had children, respectively, were lower than those of surviving female patients. The proportion of ifosfamide-treated men with children was significantly lower than that of non-ifosfamide-treated men (p = 0.018). With respect to the relationship between marital status and HR-QOL, the scores for the vitality and mental health domains of the SF-36 of survivors who were married were significantly higher than those of unmarried survivors. CONCLUSIONS: The results of our questionnaire survey reveal that among the male survivors of high-grade sarcoma, the proportions of those who were married and of those with children were lower than those of female survivors, suggesting that strategies providing support for marriage and child-rearing may be necessary for the male survivor group. In the married group, mental QOL was high.

[A Case of an EXIT (Ex-utero Intrapartum Treatment) Procedure for a Fetal Giant Oronasopharyngeal Tumor.]

We report successful anesthetic management of an EXIT (ex-utero intrapartum treatment) procedure for fetal giant oronasopharyngeal tumor. A 34-year-old nul- liparous woman was diagnosed as having a fetus with giant oronasopharyngeal tumor and scheduled for an EXIT procedure at 34 weeks of pregnancy. After induction of general anesthesia and tracheal intubation, 6% desflurane and a moderate dose of remifentanil infusion were started to provide anesthesia for both the mother and the fetus. To achieve sufficient uterine relaxation during an EXIT procedure, desflurane was gradually increased up to 10% and nitroglycerin infu- sion was added just before uterine incision. Maternal blood pressure was maintained with continuous infu- sion of phenylephrine. Fetal monitoring during an EXIT procedure was performed with an electrocar- diogram using needle electrodes in addition to trans- thoracic echocardiography. No additional anesthetics were necessary for fetal immobilization. After the completion of tracheostomy followed by the separation of the fetus, nitroglycerin and desflurane were discon- tinued and adequate uterine tone was soon obtained. Maintenance of anesthesia was achieved with propofol and remifentanil for the remaining of the operation. The postoperative course was uneventful. The impor- tance of preoperative detailed simulation and discussion about the procedure among multidisciplinary team members was reconfirmed.

Discovery and in vitro and in vivo profiles of N-ethyl-N-[2-[3-(5-fluoro-2-pyridinyl)-1H-pyrazol-1-yl]ethyl]-2-(2H-1,2,3-triazol-2-yl)-benzamide as a novel class of dual orexin receptor antagonist.

Orexins play an important role in sleep/wake regulation, and orexin receptor antagonists are a focus of novel therapy for the treatment of insomnia. We identified 27e (TASP0428980) as a potent dual orexin receptor antagonist through the systematic modification of our original designed lead A. We demonstrated the potent sleep-promoting effects of 27e at ip dose of 3mg/kg in a rat polysomnogram study. 27e exhibited relatively short half-life profiles in rats and dogs. Furthermore, accumulating evidence regarding ADME profiles indicates that the predicted human half-life of 27e should be 1.2-1.4h. These data indicated that 27e has a short-acting hypnotic property, suggesting that 27e might be useful for treating primary insomnia while exhibiting a low risk of next-day residual somnolence. Thus, 27e and its related compounds should be further evaluated to enable advancement to clinical trials.

Leisure-Time Physical Inactivity Associated with Vascular Depression or Apathy in Community-Dwelling Elderly Subjects: The Sefuri Study.

BACKGROUND: Although physical inactivity is a major public health problem, the causative factors for physical inactivity per se are poorly understood. To address this issue, we investigated the relationship between deep white matter lesions (DWMLs) on magnetic resonance imaging, apathy, and physical activities using structural equation modeling (SEM). METHODS: We examined 317 community-dwelling elderly subjects (137 men and 180 women with a mean age of 64.5 years) without dementia or clinically apparent depression. Physical activity was assessed with a questionnaire consisting of 3 components (leisure-time, work, and sport activities). RESULTS: The mean score from the apathy scale (a visual analogue version of Starkstein's apathy scale) of the Grades 2-3 DWML group was 420 (95% confidence interval [CI] 379-461), which was lower (more apathetic) than the Grade 0 DWML group score of 478 (95% CI 463-492) after adjustment for education as a covariate. SEM showed that the direct paths from DWMLs or education to apathy were significant, and the direct path from apathy to leisure-time activity was highly significant (ß = .25, P < .001). The degree of apathetic behavior was negatively associated with sport activity in female subjects and positively associated with TV watching in male subjects. CONCLUSIONS: The results of the study show that DWMLs are one of the major factors that cause apathetic behavior and that apathy has significant negative effects on leisure-time physical activity in community-dwelling elderly subjects. Even a minor level of apathy without major depression would have a significant impact on activities of daily living and quality of life.

[A Case of Epidural Hematoma Associated with Epidural Anesthesia].

We report a case of epidural hematoma in an elderly patient with normal coagulability and without difficulty in epidural catheterization. A 76-year-old man with a history of cervical myelopathy was scheduled for gastrojejunostomy under combined epidural and general anesthesia. He had normal bleeding time, coagulation test results, and platelet count. He underwent an epidural catheterization without difficulty. On the first postoperative day, he noticed that could not move his legs with analgesia. After stopping continuous epidural perfusion, he could move legs slightly, but paraplegia remained. On the second postoperative day, MRI of the spine demonstrated a hematoma-like lesion, and severe thoracic and lumbar spinal canal stenosis. Severe vertebral deformation, especially in cases of the elderly, is a potential risk for epidural hematoma after epidural catheterization, because a small hematoma may compress the spinal cord. A careful preoperative evaluation whether to perform epidural catheterization and postoperative observation are required for elderly patients with severe vertebral deformation.

Effects of preoperatively administered carbamazepine and phenytoin on rocuronium-induced neuromuscular block under sevoflurane anesthesia: a retrospective clinical study.

We examined the effects of preoperatively administered phenytoin and carbamazepine on rocuronium-induced neuromuscular block under sevoflurane anesthesia in this retrospective clinical study. When compared to patients without anticonvulsant therapy (n = 16), the recovery index (i.e., the time required from 25% of spontaneous return of T1 to 75% of spontaneous return of T1) was significantly lower in patients with anticonvulsant therapy using carbamazepine and/ or phenytoin (n = 17); however, no significant dose-dependent effects of carbamazepine as well as phenytoin on the recovery index were detected. Further studies are required to elucidate the mechanisms underlying the modifying effects of carbamazepine and phenytoin on pharmacokinetics and pharmacodynamics of rocuronium.

Gene and cytokine profile analysis of macrolide-resistant Mycoplasma pneumoniae infection in Fukuoka, Japan.

BACKGROUND: Recent epidemiologic data suggest that the prevalence of macrolide resistant Mycoplasma pneumoniae (MR-M. pneumoniae) is increasing rapidly worldwide. This study assessed the present status of M. pneumoniae infection in Japan and clinical end-points to distinguish children with MR-M. pneumoniae. METHODS: During an outbreak of M. pneumoniae infections in Fukuoka, Japan in 2010-11, a total of 105 children with clinically suspected M. pneumoniae infection were enrolled. M. pneumoniae was analyzed for macrolide resistance in domain V of the 23S rRNA gene. Sixty -five patients with PCR positive for M. pneumoniae were analyzed with regard to clinical symptoms, efficacy of several antimicrobial agents and several laboratory data. RESULTS: Causative pathogens were detected in 81.0% (85 of 105) and M. pneumoniae was identified 61.9% (65 of 105). The resistance rate of M. pneumoniae was 89.2% (58 of 65) in this general pediatric outpatient setting. Patients infected with MR-M. pneumoniae showed longer times to resolution of fever and required frequent changes of the initially prescribed macrolide to another antimicrobial agent. We observed three different genotypes of M. pneumoniae including the rarely reported A2063T mutation (A2063G: 31 strains, A2063T: 27 strains, no mutation: 7 strains). Drug susceptibility testing showed different antimicrobial susceptibility profiles for each genotype. Serum IFN-gamma, IL-6 and IP-10 levels were higher in patients with MR-genotypes than in those infected with no-mutation strains (p < 0.001). CONCLUSIONS: Macrolide resistance is more common than previously thought and a small epidemic of rarely reported A2063T mutation was observed in Fukuoka, Japan. Furthermore our results reveal the possibility that levels of certain inflammatory cytokines may be a candidate to predict MR-M.pneumoniae infection.

Glucose use in fasted rats under sevoflurane anesthesia and propofol anesthesia.

BACKGROUND: We previously reported the marked differences in the effects of sevoflurane anesthesia and propofol anesthesia on glucose use in fed rats; however, we could not elucidate mechanisms underlying the differences. METHODS: We used fasted rats in this study. After surgical preparation under sevoflurane anesthesia, rats were divided into 3 groups: awake rats, rats under sevoflurane anesthesia, and rats under propofol anesthesia. All rats underwent the IV glucose tolerance test (IVGTT); 0.5 g/kg glucose was administered IV to rats. Just before IVGTT, some rats were pretreated with glibenclamide or diazoxide. We measured glucose, insulin, tumor necrosis factor-α (TNF-α), and high molecular weight adiponectin levels during IVGTT and calculated the quantitative insulin sensitivity check index (QUICKI) using glucose and insulin levels before glucose administration in each rat. RESULTS: Before glucose administration, rats under sevoflurane anesthesia showed similar glucose and insulin levels with significantly higher QUICKI compared with awake rats, while rats under propofol anesthesia showed similar glucose levels and significantly higher insulin levels with significantly lower QUICKI compared with awake rats. After glucose administration, rats under sevoflurane anesthesia showed significantly higher glucose levels and similar insulin levels compared with awake rats, while rats under propofol anesthesia showed similar glucose levels and significantly higher insulin levels compared with awake rats. Before glucose administration, TNF-α levels in rats under sevoflurane anesthesia and rats under propofol anesthesia were similar to those in awake rats. After glucose administration, TNF-α was undetectable in all awake rats and all rats under sevoflurane anesthesia, whereas TNF-α was detectable in all rats under propofol anesthesia; TNF-α levels in rats under propofol anesthesia were significantly higher than those in awake rats. High molecular weight adiponectin levels in rats under sevoflurane anesthesia and rats under propofol anesthesia were similar to those in awake rats throughout the experimental period. In rats under sevoflurane anesthesia, glibenclamide significantly decreased glucose levels and significantly increased insulin levels; however, diazoxide produced no significant effects on glucose and insulin levels. In rats under propofol anesthesia, glibenclamide significantly decreased glucose levels and significantly increased insulin levels, while diazoxide significantly decreased glucose levels without changing insulin levels. CONCLUSIONS: Sevoflurane anesthesia attenuates glucose-induced insulin secretion without affecting basic insulin secretion, while propofol anesthesia enhances insulin secretion. Propofol anesthesia exaggerates insulin-resistive conditions, whereas sevoflurane anesthesia dose not impair insulin sensitivity; there may be a possible association of TNF-α with insulin-resistive conditions under propofol anesthesia.

Characterization of an endo-processive-type xyloglucanase having a ß-1,4-glucan-binding module and an endo-type xyloglucanase from Streptomyces avermitilis.

We cloned two glycoside hydrolase family 74 genes, the sav_1856 gene and the sav_2574 gene, from Streptomyces avermitilis NBRC14893 and characterized the resultant recombinant proteins. The sav_1856 gene product (SaGH74A) consisted of a catalytic domain and a family 2 carbohydrate-binding module at the C terminus, while the sav_2574 gene product (SaGH74B) consisted of only a catalytic domain. SaGH74A and SaGH74B were expressed successfully and had molecular masses of 92 and 78 kDa, respectively. Both recombinant proteins were xyloglucanases. SaGH74A had optimal activity at 60°C and pH 5.5, while SaGH74B had optimal activity at 55°C and pH 6.0. SaGH74A was stable over a broad pH range (pH 4.5 to 9.0), whereas SaGH74B was stable over a relatively narrow pH range (pH 6.0 to 6.5). Analysis of the hydrolysis products of tamarind xyloglucan and xyloglucan-derived oligosaccharides indicated that SaGH74A was endo-processive, while SaGH74B was a typical endo-enzyme. The C terminus of SaGH74A, which was annotated as a carbohydrate-binding module, bound to ß-1,4-linked glucan-containing soluble polysaccharides such as hydroxyethyl cellulose, barley glucan, and xyloglucan.

A New Quantitative Triage System for Hospitalized Neonates to Assist with Decisions of Hospital Evacuation Priorities.

INTRODUCTION: Hospitalized neonates are vulnerable to natural and man-made disasters because of their persistent requirement for medical resources and may need to be evacuated to safe locations when electricity and medical gas supply become unreliable. In Japan, a triage system for hospitalized neonates, or the Simple Triage and Rapid Treatment for Neonates, Revised (START-Neo-R), has been used to determine whether neonates are in suitable conditions for transportation. However, this scale is not useful to determine the evacuation order of neonates because a considerable number of evacuees are classified into the same categories. STUDY OBJECTIVE: To solve this problem, a novel triage system, Neonatal Extrication Triage (NEXT) was developed. This study tested the validity and reproducibility of both triages and compared them with a standardized prognostic scoring system for hospitalized neonates, the Neonatal Therapeutic Intervention Scoring System (NTISS). METHODS: In this retrospective observational study, physicians and nurses independently assessed each neonate hospitalized at a tertiary neonatal intensive care unit (NICU) twice weekly using NEXT and START-Neo-R. The NEXT system comprises six questionnaires regarding medical resources required during transition and transportation, providing composite scores on a 12-point scale. The START-Neo-R classified neonates into five levels based on the severity of disease and dependence on medical care. Inter-rater reliability of both systems was assessed using Cohen's kappa coefficient, whereas the criterion validity with NTISS was assessed using Spearman's correlation coefficient. RESULTS: Overall, 162 neonates were assessed for 49 days, resulting in triage data for 1,079 accumulated patients. Both NEXT scores and START-Neo-R ranks were well-dispersed across different levels without excessive accumulation in specific categories. Inter-rater reliability of NEXT (kappa coefficient, 0.973; 95% confidence interval, 0.969-0.976) and START-Neo-R (kappa coefficient, 0.952; 95% confidence interval, 0.946-0.957) between physicians and nurses was sufficiently high. The correlation coefficient of NEXT and START-Neo-R scores with NTISS scores were 0.889 (P <.001) and 0.850 (P <.001), respectively. CONCLUSIONS: Both START-Neo-R and NEXT had good reproducibility and correlation with the severity of neonates indicated by NTISS. With its well-dispersed scores across different levels, the NEXT system might be a powerful tool to determine the priority of evacuation objectively.

Near-infrared light scattering and water diffusion in newborn brains.

OBJECTIVE: MRI provides useful information regarding brain maturation and injury in newborn infants. However, MRI studies are generally restricted during acute phase, resulting in uncertainty around upstream clinical events responsible for subtle cerebral injuries. Time-resolved near-infrared spectroscopy non-invasively provides the reduced scattering coefficient ( µ s ' ), which theoretically reflects tissue structural complexity. This study aimed to test whether µ s ' values of the newborn head reflected MRI findings. METHODS: Between June 2009 and January 2015, 77 hospitalised newborn infants (31.7 ± 3.8 weeks gestation) were assessed at 38.8 ± 1.3 weeks post-conceptional age. Associations of µ s ' values with MRI scores, mean diffusivity and fractional anisotropy were assessed. RESULTS: Univariable analysis showed that µ s ' values were associated with gestational week (p = 0.035; regression coefficient [B], 0.065; 95% confidence interval [CI], 0.005-0.125), fractional anisotropy in the cortical grey matter (p = 0.020; B, -5.994; 95%CI, -11.032 to -0.957), average diffusivity in the cortical grey matter (p < 0.001; B, -4.728; 95%CI, -7.063 to -2.394) and subcortical white matter (p = 0.001; B, -2.071; 95%CI, -3.311 to -0.832), subarachnoid space (p < 0.001; B, -0.289; 95%CI, -0.376 to -0.201) and absence of brain abnormality (p = 0.042; B, -0.422; 95%CI, -0.829 to -0.015). The multivariable model to explain µ s ' values comprised average diffusivity in the subcortical white matter (p < 0.001; B, -2.066; 95%CI, -3.200 to -0.932), subarachnoid space (p < 0.001; B, -0.314; 95%CI, -0.412 to -0.216) and absence of brain abnormality (p = 0.021; B, -0.400; 95%CI, -0.739 to -0.061). INTERPRETATION: Light scattering was associated with brain structure indicated by MRI-assessed brain abnormality and diffusion-tensor-imaging-assessed water diffusivity. When serially assessed in a larger population, µ s ' values might help identify covert clinical events responsible for subtle cerebral injury.

Secondary neoplasms after retinoblastoma treatment: retrospective cohort study of 754 patients in Japan.

OBJECTIVE: Little is known about the incidence of secondary neoplasms among survivors of retinoblastoma in Japan. The objective of our study was to analyze the cumulative incidence rate of secondary neoplasms following retinoblastoma and to investigate the risk factors of developing secondary neoplasms. METHODS: We conducted a retrospective cohort study of 754 retinoblastoma patients who visited the National Cancer Center Hospital in Tokyo between 1964 and 2007. The cumulative incidence rate curves were drawn using the competing risk method and compared with the Gray's test. Using competing risk regression analysis, multivariate analysis estimated the subdistribution hazard ratio of factors related to the development of secondary neoplasms. RESULTS: The median length of follow-up was 108 months (0-594 months). Twenty-one (2.8%) patients developed 23 secondary neoplasms in total. The cumulative incidence rates of secondary neoplasms after retinoblastoma treatment were 2.4% at 10 years after diagnosis, 4.3% at 20 years, 6.4% at 30 years and 19.1% at 40 years. Ten patients (1.3%) died and 723 (95.9%) were alive without developing secondary neoplasms. The subdistribution hazard ratios of hereditary retinoblastoma and external beam irradiation were 4.85 (95% confidence interval = 0.74-31.85) and 4.76 (95% confidence interval = 0.69-33.09), respectively. CONCLUSIONS: We demonstrated the cumulative incidence rate of secondary neoplasms following retinoblastoma in Japan. The subdistribution hazards ratios of hereditary retinoblastoma and external beam irradiation were high but not significant because of statistical power. The long-term follow-up of retinoblastoma survivors is warranted to understand secondary neoplasm risk.

Foetal growth, birth transition, enteral nutrition and brain light scattering.

If the brain structure is assessed at neonatal intensive care units, covert clinical events related with subtle brain injury might be identified. The reduced scattering coefficient of near-infrared light (µS') obtained using time-resolved near-infrared spectroscopy from the forehead of infants is associated with gestational age, body weight and Apgar scores, presumably reflecting subtle changes of the brain related to foetal growth and birth transition. One hundred twenty-eight preterm and term infants were studied to test whether µS' obtained from the head at term-equivalent age is associated with foetal growth, birth transition and nutritional status after birth, which are key independent variables of developmental outcomes. As potential independent variables of µS', birth weight, Apgar scores, age at full enteral feeding and post-conceptional age at the study were assessed to represent foetal growth, birth transition and nutritional status after birth. Subsequently, higher µS' values were associated with higher Apgar scores (p = 0.003) and earlier establishment of enteral feeding (p < 0.001). The scattering property of near-infrared light within the neonatal brain might reflect changes associated with birth transition and nutritional status thereafter, which might be used as a non-invasive biomarker to identify covert independent variables of brain injury in preterm infants.

Analysis of exposed cellulose surfaces in pretreated wood biomass using carbohydrate-binding module (CBM)-cyan fluorescent protein (CFP).

In enzymatic saccharification of lignocellulosics, the access of the enzymes to exposed cellulose surfaces is a key initial step in triggering hydrolysis. However, knowledge of the structure-hydrolyzability relationship of the pretreated biomass is still limited. Here we used fluorescent-labeled recombinant carbohydrate-binding modules (CBMs) from Clostridium josui as specific markers for crystalline cellulose (CjCBM3) and non-crystalline cellulose (CjCBM28) to analyze the complex surfaces of wood tissues pretreated with NaOH, NaOH-Na(2)S (kraft pulping), hydrothermolysis, ball-milling, and organosolvolysis. Japanese cedar wood, one of the most recalcitrant softwood species was selected for the analysis. The binding analysis clarified the linear dependency of the exposure of crystalline and non-crystalline cellulose surfaces for enzymatic saccharification yield by the organosolv and kraft delignification processes. Ball-milling for 5-30 min increased saccharification yield up to 77%, but adsorption by the CjCBM-cyan fluorescent proteins (CFPs) was below 5%. Adsorption of CjCBM-CFPs on the hydrothermolysis pulp were less than half of those for organosolvolysis pulp, in coincidence with low saccharification yields. For all the pretreated wood, crystallinity index was not directly correlated with the overall saccharification yield. Fluorescent microscopy revealed that CjCBM3-CFP and CjCBM28-CFP were site-specifically adsorbed on external fibrous structures and ruptured or distorted fiber surfaces. The assay system with CBM-CFPs is a powerful measure to estimate the initiation sites of hydrolysis and saccharification yields from chemically delignified wood pulps.