Detailed dynamical features of the slow hydration water in the vicinity of poly(ethylene oxide) chains.

Poly(ethylene oxide) (PEO) is a well-known biocompatible polymer and has widely been used for medical applications. Recently, we have investigated the dynamic behavior of hydration water in the vicinity of PEO chains at physiological temperature and shown the presence of slow water with diffusion coefficient one order of magnitude less than that of bulk water. This could be evidence for the intermediate water that is critical for biocompatibility; however, its detailed dynamical features were not established. In this article, we analyze the quasi-elastic neutron scattering from hydration water through mode distribution analysis and present a microscopic picture of hydration water as well as its relation to cold crystallization.

Dynamics of side chains in poly(quinoxaline-2,3-diyl)s studied via quasielastic neutron scattering.

The side chain dynamics of poly(quinoxaline-2,3-diyl)s (PQXs) are expected to influence their conformation. To investigate these dynamics experimentally, quasielastic neutron scattering (QENS) was performed for PQXs in deuterated tetrahydrofuran (THF-d8) and deuterated 1,1,2-trichloroethane/THF (1,1,2-TCE-d3/THF-d8), in which they formed right-handed and left-handed helical structures, respectively. The mean-square displacement of the PQX side chains in 1,1,2-TCE-d3/THF-d8 was lower than that in THF-d8. Furthermore, QENS complementary studies and molecular dynamics simulations unraveled a coupling between the main-chain and side chain dynamics of PQXs, suggesting the possibility of controlling the main-chain helical chirality through the dynamics of chiral side chains. These insights present a novel strategy for the design of synthetic helical macromolecules with precise chirality control.

Feasibility of laparoscopic-assisted transanal pelvic exenteration in locally advanced rectal cancer with anterior invasion.

BACKGROUND: Transanal (Ta) pelvic exenteration is a promising, minimally invasive method for treating locally advanced colorectal cancer. However, since it is technically difficult to perform, Ta pelvic exenteration is rarely reported in locally advanced T4 rectal cancer cases. The aim of this study was to evaluate the feasibility of transabdominal laparoscopy-assisted Ta pelvic exenteration. METHODS: Six patients (4 males and 2 females) had laparoscopy-assisted Ta total or posterior pelvic exenteration for locally advanced or recurrent colorectal cancer cases at the Nagasaki University Hospital between September 2018 and August 2019. Clinical and pathological outcomes were measured and analyzed. RESULTS: The median operation time and intraoperative blood loss were 481 (range 456-709) minutes and 352.5 (range 257-1660) ml, respectively. R0 resection was achieved in all cases, and no patient required open surgery. Two patients had grade 3 complications (Clavien-Dindo) or higher. There was no mortality, and no reoperation was required. CONCLUSIONS: The results suggest that laparoscopic-assisted Ta pelvic exenteration is an acceptable procedure, may help overcome the current technical difficulties, and may improve outcomes in patients with locally advanced rectal cancer.

Evidence for an Fulde-Ferrell-Larkin-Ovchinnikov State with Segmented Vortices in the BCS-BEC-Crossover Superconductor FeSe.

We present resistivity and thermal-conductivity measurements of superconducting FeSe in intense magnetic fields up to 35 T applied parallel to the ab plane. At low temperatures, the upper critical field µ_{0}H_{c2}^{ab} shows an anomalous upturn, while thermal conductivity exhibits a discontinuous jump at µ_{0}H^{*}≈24 T well below µ_{0}H_{c2}^{ab}, indicating a first-order phase transition in the superconducting state. This demonstrates the emergence of a distinct field-induced superconducting phase. Moreover, the broad resistive transition at high temperatures abruptly becomes sharp upon entering the high-field phase, indicating a dramatic change of the magnetic-flux properties. We attribute the high-field phase to the Fulde-Ferrel-Larkin-Ovchinnikov (FFLO) state, where the formation of planar nodes gives rise to a segmentation of the flux-line lattice. We point out that strongly orbital-dependent pairing as well as spin-orbit interactions, the multiband nature, and the extremely small Fermi energy are important for the formation of the FFLO state in FeSe.

Mechanism of increased microbial autofluorescence by heat treatment.

The total direct count (TDC) microbial enumeration method is rapid and suitable for analysing environmental samples containing numerous un-culturable micro-organisms. Conventional TDC methods require the addition of a fluorescent stain and are thus unsuitable for automatic monitoring. We unexpectedly found that heated micro-organisms emit strong autofluorescence. This study was conducted to determine how heating enhances the autofluorescence of bacteria and fungi and to evaluate whether the phenomenon could be exploited to develop a new TDC method. Bacterial autofluorescence was augmented by heating cells at 200°C. ELISA results indicated that levels of advanced glycation end products (AGEs) increased in heated microbes. Catechin, an inhibitor of the Maillard reaction, disrupted the intensification of autofluorescence. These results suggest that the enhanced autofluorescence is associated with the formation of AGEs and that the reaction could be utilized as alternative probe in TDC methods. SIGNIFICANCE AND IMPACT OF THE STUDY: Autofluorescence of bacteria and fungi was prominently intensified by heat treatment at 200°C. This phenomenon was associated with advanced glycation end products formed in micro-organisms via the Maillard reaction. The fluorescence signal was strong enough to be utilized as an alternative probe for fluorescent dye in the total direct count method. This phenomenon could be incorporated in an automatic apparatus for microbial enumeration, as it does not require staining.

Prediction of neurological recovery in spontaneous spinal epidural hematoma using apparent diffusion coefficient values.

OBJECTIVE: Magnetic resonance imaging (MRI) is useful in diagnosing spontaneous spinal epidural hematoma (SSEH). The purpose of the present study is to determine whether apparent diffusion coefficient (ADC) values could determine severity of spinal cord damage and predict functional recovery in SSEH. METHODS: The study involved four consecutive patients with SSEH (two men and two women: aged 21-76 years). Using axial slices, ADC values were determined in four separate regions of the spinal cord. These areas were classified into the following three groups based on findings in T2-weighted images: normal T2 intensity; persistent T2 abnormality; and temporary T2 abnormality. ADC values among different groups were compared. The relationship between preoperative ADC values and neurological grades were also evaluated. RESULTS: ADC values in normal T2 areas were 0.89 ± 0.10 × 10(-3) mm(2) s(-1), whereas those for the persistent T2 abnormality group were significantly lower (0.63 ± 0.14 × 10(-3)). In a patient who was Frankel A on admission and in the follow-up, the ADC value was as low as 0.41 × 10(-3). Functional recovery was also limited in the spinal cord segments with lower ADC values. In the temporary T2 abnormality group, ADC values were significantly higher (1.05 ± 0.10 × 10(-3)). CONCLUSIONS: In SSEH, if MRI demonstrated T2-hyperintensity with lower ADC values, patients may suffer from irreversible spinal cord damages. ADC values of the spinal cord can be added as a new factor that reliably indicated the severity of spinal cord damage and predicted functional recovery.

Strong plastic responses in aerenchyma formation in F1 hybrids of Imperata cylindrica under different soil moisture conditions.

Hybrids can express traits plastically, enabling them to occupy environments that differ from parental environments. However, there is insufficient evidence demonstrating how phenotypic plasticity in specific traits mediates hybrid performance. Two parental ecotypes of Imperata cylindrica produce F1 hybrids. The E-type in wet habitats has larger internal aerenchyma than the C-type in dry habitats. This study evaluated relationships between habitat utilisation, aerenchyma plasticity, and growth of I. cylindrica accessions. We hypothesize that plasticity in expressing parental traits explains hybrid establishment in habitats with various soil moisture conditions. Aerenchyma formation was examined in the leaf midribs, rhizomes and roots of two parental ecotypes and their F1 hybrids in their natural habitats. In common garden experiments, we examined plastic aerenchyma formation in leaf midribs, rhizomes and roots of natural and artificial F1 hybrids and parental ecotypes and quantified vegetative growth performance. In the natural habitats where soil moisture content varied widely, the F1 hybrids showed larger variation in aerenchyma formation in rhizomes than their parental ecotypes. In the common garden experiments, F1 hybrids showed high plasticity of aerenchyma formation in rhizomes, and their growth was similar to that of C-type and E-type under drained and flooded conditions, respectively. The results demonstrate that F1 hybrids of I. cylindrica exhibit plasticity in aerenchyma development in response to varying local soil moisture content. This characteristic allows the hybrids to thrive in diverse soil moisture conditions.

International models of investigator-initiated trials: implications for Japan.

BACKGROUND: Academic/institutional investigator-initiated clinical trials benefit individuals and society by supplementing gaps in industry-sponsored clinical trials. MATERIALS: In May 2010, experts from Japan, the Republic of Korea, the UK, and the United States, met at a symposium in Tokyo, Japan, to discuss how policies related to the conduct of clinical trials, which have been shown to be effective, may be applied to other regions of the world. RESULTS: In order to increase the availability of anticancer drugs world-wide, nations including Japan should examine the benefits of increasing the number of investigator-initiated clinical trials. These trials represent one of the most effective ways to translate basic scientific knowledge into clinical practice. These trials should be conducted under GCP guidelines and include Investigational New Drug application submissions with the ultimate goal of future drug approval. CONCLUSIONS: To maximize the effectiveness of these trials, a policy to educate health care professionals, cancer patients and their families, and the public in general on the benefits of clinical trials should be strengthened. Finally, policies that expedite the clinical development of novel cancer drugs which have already been shown to be effective in other countries are needed in many nations including Japan to accelerate drug approval.

Bactericidal activity and oral pathogen inactivation by electromagnetic wave irradiation.

AIMS: The aim of this work was to clarify the effects of electromagnetic wave irradiation (EMWI) on oral bacterial pathogens. METHODS AND RESULTS: A Gram-negative (Porphyromonas gingivalis) or Gram-positive (Streptococcus mutans, S. intermedius, Enterococcus faecalis) bacterial suspension was irradiated by EMW apparatus (500-1000 kHz, 5-15 times, 1 s time(-1) ). Quantification of survival bacteria by CFU counting revealed that EMWI exhibited marked bactericidal activity against all tested bacteria and bactericidal activity at 500 kHz increased in an irradiation number-dependent manner. After EMWI at 500 kHz, scanning electron microscopic observations showed that the chain of S. mutans cells was shortened after 5 irradiations and the outlines of bacterial cells (S. mutans and P. gingivalis) were unclear after 5-10 irradiations. EMWI inhibited the inductive effect of S. mutans on pro-inflammatory cytokine production in human monocytes and this inhibitory effect was comparable with that of heat-killed bacteria. Furthermore, using an enzyme activity assay, EMWI partially inactivated the activities of gingipains from P. gingivalis. CONCLUSIONS: These findings demonstrated that EMWI has inactivation and bactericidal activities against single microbial species among four kinds of oral pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: Electromagnetic wave irradiation may be applicable for medical disinfection and sterilization, such as refractory periapical periodontitis.

Effect of age on bowel management in traumatic central cord syndrome.

STUDY DESIGN: A retrospective multicenter study. OBJECTIVES: To investigate the characteristics of bowel dysfunction in elderly people with traumatic central cord syndrome (TCCS). SETTING: A total of 28 Rosai hospitals in Japan. METHODS: The Rosai Hospital registry included 3006 persons with spinal cord injury during 1997-2007. The study subjects were 186 patients with TCCS (160 men, 26 women; mean age, 61.7±11.6 years, ±s.d.). Patients were divided according to age into the young group (<50 years, n=30), the middle-age group (50-69 years, n=112) and the elderly group (≥70 years, n=44). We assessed the differences in bowel management techniques (spontaneous, rectal medications and manual emptying) and activity of daily living (ADL) with respect to bowel care at discharge among the three groups. RESULTS: Continent spontaneous defecation was the most common bowel management method (50%, 93/186). The percentage of elderly subjects on continent spontaneous defecation (36.4%) was significantly less than that of the young group (66.7%; P<0.05). Furthermore, the percentage of elderly patients who required no bowel care (18.2%) was significantly less than those of the young (53.3%) and middle-age groups (41.1%; P<0.01). However, few differences in bowel care-related ADL were recognized among the three groups in patients who required manual emptying. CONCLUSION: The results identified significantly fewer patients aged ≥70 years with 'continent spontaneous defecation' or 'independent for bowel care' compared with younger patients. The results also highlighted the clinical importance of bowel dysfunction associated with TCCS especially in elderly people.

Treatment outcomes of proton beam therapy combined with retrograde intra-arterial infusion chemotherapy for locally advanced oral cancer in the elderly.

The aim of this study was to evaluate the therapeutic efficacy and safety of proton beam therapy combined with retrograde intra-arterial infusion chemotherapy in elderly patients with locally advanced oral cancer. Between February 2009 and October 2019, 42 oral cancer patients aged ≥75 years were treated with this therapy. Median age was 80 years (range 75-90 years) and the median follow-up duration was 39 months (range 2-106 months). Of the 42 patients, 34 (81%) were diagnosed with stage IV cancer. The 3-year overall survival, local control, progression-free survival, and disease-specific survival rates were 56%, 69%, 32%, and 67%, respectively. Regarding acute toxicities, grade 3 neutropenia was observed in six patients (14%), anaemia in five (12%), acute kidney injury in one (2%), and oral mucositis in 18 (42%). Late toxicities of grade 3 were observed in seven patients: dysphagia in six (14%) and osteonecrosis of the jaw in one (2%). This study showed that proton beam therapy combined with retrograde intra-arterial infusion chemotherapy was effective for elderly patients with oral cancer, and toxicities were tolerable and manageable. The study findings suggest that this therapy is a potential treatment option for elderly oral cancer patients with difficulty in surgery and systemic chemotherapy.

Charge-neutral fermions and magnetic field-driven instability in insulating YbIr3Si7.

Kondo lattice materials, where localized magnetic moments couple to itinerant electrons, provide a very rich backdrop for strong electron correlations. They are known to realize many exotic phenomena, with a dramatic example being recent observations of quantum oscillations and metallic thermal conduction in insulators, implying the emergence of enigmatic charge-neutral fermions. Here, we show that thermal conductivity and specific heat measurements in insulating YbIr3Si7 reveal emergent neutral excitations, whose properties are sensitively changed by a field-driven transition between two antiferromagnetic phases. In the low-field phase, a significant violation of the Wiedemann-Franz law demonstrates that YbIr3Si7 is a charge insulator but a thermal metal. In the high-field phase, thermal conductivity exhibits a sharp drop below 300 mK, indicating a transition from a thermal metal into an insulator/semimetal driven by the magnetic transition. These results suggest that spin degrees of freedom directly couple to the neutral fermions, whose emergent Fermi surface undergoes a field-driven instability at low temperatures.

Incidence of symptomatic autonomic dysreflexia varies according to the bowel and bladder management techniques in patients with spinal cord injury.

STUDY DESIGN: A retrospective, multicenter study. OBJECTIVES: To investigate the relationship between bowel and bladder management methods and symptomatic autonomic dysreflexia (AD) during hospitalization in patients with spinal cord injury (SCI). SETTING: Twenty-eight Rosai hospitals in Japan. METHODS: The study subjects were 571 patients with SCI who had been admitted to 28 Rosai hospitals between April 1997 and March 2007 for rehabilitation therapy and fulfilled the following criteria: (1) SCI at or above sixth thoracic level, (2) discharged from hospital after more than 4 months of admission for initial injury and (3) lack of pressure ulcers, deep venous thrombosis, ureteral and renal stones or heterotopic ossification throughout hospitalization to exclude possible influence of these complications on cardiovascular reflexes. The study subjects were examined for the incidence of symptomatic AD according to age, sex, ASIA Impairment Scale, injury level, bowel and bladder management techniques at discharge. RESULTS: The Rosai Hospital registry included 3006 persons with SCI during 1997-2007, and 571 patients fulfilled the above criteria. The highest incidence of symptomatic AD was diagnosed in subjects using reflex voiding and in those using manual removal of stool. By contrast, the lowest incidence of symptomatic AD was in those on continent spontaneous voiding and continent spontaneous defecation. CONCLUSION: Medical staff should evaluate the presence of AD in patients with SCI at or above the T6 level under bladder and bowel management such as reflex voiding and manual removal of stool.

Preoperative evaluation of the deep cerebral veins using 3-tesla magnetic resonance imaging.

BACKGROUND: Surgical treatment of deep-seated tumors such as supratentorial intraventricular and thalamic-pineal-tectal region tumors carries a risk of postoperative deficits due to possible damage to deep cerebral veins including the internal cerebral vein. It is often difficult to identify whether the vessel encountered during surgery needs to be preserved or not through the small operative field. Therefore, preoperative evaluation of deep venous structures is important. We evaluated the usefulness of 3-Tesla magnetic resonance imaging (3 T MRI) for this purpose. METHODS: First, the ability to detect deep venous structures was compared with both 3-dimensional computed tomographical angiography (3D-CTA) and 3 T MRI in patients without any damage to deep venous structures. Images of 7 consecutive patients suffering from insulo-opercular gliomas who underwent both imaging modes for the identification of lateral striate arteries were reconstructed for evaluation of the deep cerebral veins. Subsequently, surgery for tumors at the supratentorial intraventricular and thalamic-pineal-tectal regions was prospectively performed with preoperative evaluation of deep venous system only using 3 T MRI. RESULTS: Information on the deep venous systems acquired by 3 T MRI was as useful as that acquired by 3D-CTA. Until today, we have treated 8 cases of supratentorial intraventricular and thalamic-pineal-tectal region tumors with preoperative evaluation of the deep venous system using 3 T MRI without any morbidity. CONCLUSION: Information on the deep venous system obtained with 3 T MRI aids the surgery of supratentorial intraventricular and thalamic-pineal-tectal region tumors. As the required sequences of 3 T MRI are same as those necessary for the neuronavigation system, and 3 T MRI can be achieved without the use of iodine-based contrast agents, 3 T MRI can be an alternative for preoperative evaluation of the deep venous systems.

Complications of Endovascular Treatments for Brain Arteriovenous Malformations: A Nationwide Surveillance.

BACKGROUND AND PURPOSE: Embolization is widely performed to treat brain arteriovenous malformations, but little has been reported on factors contributing to complications. We retrospectively reviewed a nationwide surveillance to identify risk factors contributing to complications and short-term clinical outcomes in the endovascular treatment of brain arteriovenous malformations. MATERIALS AND METHODS: Data for endovascular treatment of brain arteriovenous malformations were extracted from the Japanese nationwide surveillance. Patient characteristics, brain arteriovenous malformation features, procedures, angiographic results, complications, and clinical outcomes at 30 days postprocedure were analyzed. RESULTS: A total of 1042 endovascular procedures (788 patients; mean, 1.43 ± 0.85 procedures per patient) performed in 111 institutions from 2010 to 2014 were reviewed. Liquid materials were used in 976 procedures (93.7%): to perform presurgical embolization in 638 procedures (61.2%), preradiosurgical embolization in 160 (15.4%), and as sole endovascular treatment in 231 (22.2%). Complete or near-complete obliteration of brain arteriovenous malformations was obtained in 386 procedures (37.0%). Procedure-related complications occurred in 136 procedures (13.1%), including hemorrhagic complications in 59 (5.7%) and ischemic complications in 57 (5.5%). Univariate analysis identified deep venous drainage, associated aneurysms, infratentorial location, and preradiosurgical embolization as statistically significant risk factors for complications. Multivariate analysis showed that embolization of brain arteriovenous malformations in the infratentorial location was significantly associated with complications. Patients with complications due to endovascular procedures had worse clinical outcomes 30 days after the procedures than those without complications. CONCLUSIONS: Complications arising after endovascular treatment of brain arteriovenous malformations are not negligible even though they may play a role in adjunctive therapy, especially in the management of infratentorial brain arteriovenous malformations.

Inhibition of PMA-induced, LFA-1-dependent lymphocyte aggregation by ADP ribosylation of the small molecular weight GTP binding protein, rho.

Botulinum C3 exoenzyme specifically ADP-ribosylates a group of ras-related small molecular weight GTP-binding proteins, rho, and inhibits their biological activity. Using this enzyme, we examined the function of rho in PMA-induced activation of lymphocyte function-associated antigen-1 (LFA-1) in a B lymphoblastoid cell line, JY. Northern blot analysis revealed that among the three rho genes, rhoA mRNA was predominantly expressed in JY cells. Consistently, only one [32P]ADP-ribosylated band was found when the lysate of the cells was subjected to ADP ribosylation by C3 exoenzyme. When the cells were cultured with C3 exoenzyme, this substrate was ADP-ribosylated in situ in a time- and concentration-dependent manner. Concomitant with this ADP ribosylation, PMA-induced LFA-1/intercellular adhesion molecule (ICAM)-1-dependent aggregation of JY cells was inhibited. This inhibition was blocked by prior treatment of the enzyme with an anti-C3 monoclonal antibody, and overcome by stimulation with higher concentrations of PMA. The C3 exoenzyme-induced inhibition was not affected by shaking of the cell suspension, while inhibition of aggregation by cytochalasin B was abolished by this procedure, suggesting that the inhibitory effect of the C3 exoenzyme treatment was not due to decrease in cell motility. The C3 exoenzyme treatment affected neither protein phosphorylation in JY cells before and after PMA stimulation, nor affected surface expression of LFA-1 and ICAM-1. These results suggest that rhoA protein works downstream of protein kinase C activation linking PMA stimulation to LFA-1 activation and aggregation in JY cells.

Entorhinal-hippocampal interactions revealed by real-time imaging.

The entorhinal cortex provides the major cortical input to the hippocampus, and both structures have been implicated in memory processes. The dynamics of neuronal circuits in the entorhinal-hippocampal system were studied in slices by optical imaging with high spatial and temporal resolution. Reverberation of neural activity was detected in the entorhinal cortex and was more prominent when the inhibition due to gamma-aminobutyric acid was slightly suppressed. Neural activity was transferred in a frequency-dependent way from the entorhinal cortex to the hippocampus. The entorhinal neuronal circuit could contribute to memory processes by holding information and selectively gating the entry of information into the hippocampus.

Clinicopathological study of prognostic factors in patients with pituitary adenomas and Ki-67 labeling index of more than 3%.

BACKGROUND: Pituitary adenoma is generally indolent, but an aggressive subtype including atypical adenoma has uncertain prognosis, and an unclear relationship between prognosis and morphology. AIM: To investigate the prognostic factors of adenomas with Ki-67 labeling index of more than 3%. SUBJECTS AND METHODS: Patients with surgically treated pituitary adenomas with Ki-67 labeling index of more than 3% were retrospectively identified as 13 males and 20 females aged from 15 to 73 yr (mean 47.2 yr) among 527 patients with pituitary adenoma treated at the Department of Neurosurgery, Tohoku University and Department of Neurosurgery, Kohnan Hospital between January 2001 and December 2007. RESULTS: The tumors included 12 cases of gross totally removed pituitary adenomas, and 21 non-totally removed adenomas. Statistical analysis found significant differences in recurrence between gross total and non-total removal (log-rank test, p<0.001), and giant adenomas had higher risk of recurrence or re-growth (log-rank test, p<0.01); 71.4% of re-growth was detected within 12 months if the patients had tumor remnants after the operation. Both immunohistochemical types of tumor and invasion of the surrounding tissue had no statistical correlation with tumor regrowth, and high Ki-67 and p53 labeling index had no relationship with duration of stable disease among these patients independently. CONCLUSIONS: Gross total removal is the most important prognostic factor in patients with adenoma with Ki-67 labeling index of more than 3%. In contrast, giant adenoma carries higher risk of recurrence and/or re-growth. If gross total removal is not achieved immediate adjuvant therapy should be performed.