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The roasting process of sesame oil is expected to alter its internal composition and stability under oxidation condition. Presumably, the effect of roasting may differ with oxidation conditions (i.e., thermal and photo-oxidation), but such studies have not been undertaken. To further evaluate this notion, several type of sesame oils (raw and refined as unroasted oil, and roasted oil) and rapeseed oils as comparison were subjected to thermal oxidation (120℃) and photo-oxidation (50,000 lx) for 5 and 10 hours. The result revealed that the roasting sesame oil exhibited good stability under thermal oxidation, possibly due to the change on antioxidant agents such as sesamol and Maillard products during the roasting process. In contrast, the refined sesame oil (unroasted) demonstrated high stability under photo-oxidation, indicating that the refining process has a more significant impact on the oxidative stability in sesame oil compared to the alterations in its components caused by the roasting process. Taken together, this study is the first to show that the roasting and refining processes of sesame oil alter its internal composition and show different variations in sesame oils' oxidative stability under thermal and photo-oxidation, which holds significance considering its global consumption.

Heteroatom-bridged planar triphenylboranes, in which the three phenyl groups are bridged at the ortho positions by heteroatoms, are attracting growing attention as one of the heteroatom-containing π-conjugated molecules. Herein, we developed the synthetic method of planar triphenylboranes bridged by two oxygen atoms and one nitrogen atom, and the substituent on the nitrogen atom is derived into various aryl and alkyl groups. A key intermediate bearing an imino group (-NH-) was synthesized from a bis-triflate precursor bridged by two oxo groups via a nucleophilic aromatic substitution reaction of benzyl amine and following debenzylation. The X-ray crystallographic analysis revealed that the compound exhibits a planar molecular structure which can form a one-dimensionally π-stacked structure. The photophysical and density functional theory studies revealed that their highest occupied molecular orbitals and lowest unoccupied molecular orbitals (LUMOs) are originated from the triphenylborane moiety, while introducing strong electron-withdrawing groups such as the 4-cyanophenyl group on the nitrogen atom can induce the localization of the LUMO at the aryl groups instead of the triphenylborane moiety.

Objective: We investigated the impact of using a companion robot on the mental state of a community-dwelling older adult who was receiving home-visit rehabilitation services during the state of emergency for coronavirus disease 2019 (COVID-19)., Methods: This case involved an 80-year-old woman with compression fractures of lumbar vertebrae 1 and 2. Her medical history included hypothyroidism, hypertension, dyslipidemia, and depression. The companion robot used was Smibi ® , a healing baby robot that responds in various ways depending on how the user interacts with it. The patient interacted (e.g., hugging, conversing) with Smibi ® for 30 minutes per day for 1 month, from April 2020 (immediately before the declaration of a state of emergency in Japan) to May 2020. The patient was evaluated with the Self-Rating Depression Scale (SDS) before and after using Smibi ® ., Results: The SDS score decreased from 37 points to 26 points after the use of Smibi ® . The items related to diurnal variation, sleep, despair about the future, and dissatisfaction decreased by 2-3 points., Conclusion: Our findings suggest that interacting with Smibi ® may improve depression in older adults who have been forced to refrain from going out due to the spread of COVID-19. Future studies with long-term follow-up and large sample sizes are required to confirm the effectiveness of companion robots in improving depression among community-dwelling older adults., Competing Interests: The authors have no conflicts of interest to declare.

Introduction: A spinner knob attached to the steering wheel enables one-handed driving. However, changes in steering performance and muscle activity of the upper extremity based on the differences in the position of the knob are unknown., Aim: To quantify changes in steering performance and their muscle activity according to the position of the knob., Method: Twenty right-handed healthy men with a mean age of 30.9 years participated in the study. Steering operation (reaction time, accuracy, right-left balance and adaptability) as assessed by steering with both hands and left one-handed driving with the spinner knob at three positions (8, 10, and 12 o'clock) were evaluated using a driving simulator. Muscle activities of the left anterior deltoid, biceps brachii and long head of the triceps brachii during the simulated tasks were also recorded using a wireless surface electromyography., Results: Muscle activity while steering with the knob at 8 o'clock was significantly lower than with the knob at 10 or 12 o'clock, and was equivalent to the steering performance and muscle activity when driving with both hands. On the other hand, muscle activity while driving with the knob at 10 o'clock was significantly higher than with the knob in the other positions., Conclusion: The present study provides basic data for determining the position of the spinner knob attached to the steering wheel when driving one-handed with the non-dominant left hand. Positioning of the knob at 8 o'clock can be recommended on the basis of steering performance and lower muscle activities.IMPLICATIONS FOR REHABILITATIONThe safe driving of an automobile requires the driver to have an adequate range of motion and advanced voluntary motor control of the upper and lower extremities.When steering with the bilateral hands becomes difficult and driving with one-hand is required, it is necessary to attach a spinner knob on the steering wheel.This study provides objective and valuable information for clinicians and therapists to determine the optimum position of the spinner knob.

Introduction: Chikungunya virus was detected in cases of acute chikungunya fever in renal tissue. However, chikungunya virus-related kidney injury still lacks characterization, and it is unknown whether the kidneys are reservoirs for the virus. We sought to detect histopathological changes and viral antigens in renal tissue, and to evaluate kidney injury markers in different phases of chikungunya fever., Methods: Two groups were evaluated in this exploratory study: patients with biopsy-proven kidney injury established after chikungunya fever, and patients with post-chikungunya fever chronic joint manifestations without known kidney injury, in whom we actively searched for kidney injury markers., Results: In the first group, 15 patients had kidney injury 0.5-24 months after chikungunya fever. The most frequent histopathological diagnoses were glomerular lesions. No viral antigens were detected in renal tissue. High-risk genotypes were detected in patients with atypical hemolytic uremic syndrome and focal and segmental glomerulosclerosis. In the second group, 114 patients had post-chikungunya fever joint manifestations on average for 35.6 months. Mean creatinine and proteinuria were 0.9 mg/dl and 71.5 mg/day, respectively. One patient had isolated hematuria. There was no indication for renal biopsy in this group., Conclusions: Several histopathological features were found after chikungunya fever, without virus detection in renal tissue. These findings suggest that chikungunya virus may trigger kidney lesions with varying degrees of severity at different stages of infection. However, the probability that this virus replicates in the renal tissue seems unlikely., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

We report here the first successful synthesis of planar triphenylborane 1 with the phenyl groups bridged by oxygen and nitrogen atoms via double nucleophilic aromatic substitution reaction. The hetero atom-bridged 1 has excellent planarity. Its structural and photophysical properties are tunable by altering the bridging atoms.

Lewis acid behavior of an oxygen-bridged triphenylborane (1) to amines and the properties of Lewis acid-base adducts of 1 with amines have been investigated. UV-vis titration and 11B NMR experiments showed the formation of Lewis acid-base adducts of 1 with pyridine, DMAP, quinuclidine, and DABCO, respectively (1·amine). X-ray crystallographic analysis revealed that the planar shape of 1 was converted to a bowl shape by the formation of 1·amine. Interestingly, 1·quinuclidine, 12·DABCO, and 1·DABCO exhibited dual emissions. Excitation spectra and photoluminescence decay time measurements suggest that the dual emissions were ascribed to two excited species, i.e., [1·amine]* and [1]* generated by photodissociation in the excited states.

Background/aim: The aim of this study was to develop a method for sequentially collecting cerebrospinal fluid (CSF) from an unanesthetized microminipig, which shares many physiological and anatomical similarities with humans, such as diurnality, and investigate the diurnal variation of melatonin concentration in the CSF., Materials and Methods: A catheter was placed percutaneously into the subarachnoid space of an anesthetized animal, and the tip of the catheter was placed into the cisterna magna under X-ray. We then sequentially collected CSF at light-on and -off times from the unanesthetized animal for several weeks. After catheter placement, a period of one week or more was necessary to relieve the contamination of RBCs in the CSF., Results: A higher melatonin level in the CSF was noted during lights-off time, and the level was higher than that in the serum., Conclusion: This model of sequential collection of CSF will contribute to research in brain functions., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The discovery of a novel series of β-methyltryptophan (β MeTrp) derivatives as selective and orally active non-peptide somatostatin receptor 2 (SSTR2) agonists for the treatment of Type 2 diabetes is described. In our previous research, Compound A, β-MeTrp derivative with highly potent and selective SSTR2 agonistic activity IC 50 (SSTR2/SSTR5)=0.3/>100 (nM), was identified asa drug candidate for treatment of Type 2 diabetes which lowers significantly plasma glucose level in Wistar fatty rats in its oral administrations. However, as serious increase in AUC and phospholipidosis (PLsis) were observed in its toxicological studies in rats, follow-up compounds were searched to avoid risk of PLsis with reference to their in vitro PLsis potentials evaluated on the basis of accumulation of phospholipids in HepG2 cells exposed to the compounds. It has been found that introduction of a carbonyl group onto the piperidine and piperazine or aniline moiety of compounds A and B reduced markedly the in vitro PLsis potentials. And further modification of the compounds and their evaluation led to a discovery of compounds 3k with lower in vitro PLsis potentials exhibiting lowering effect of hypoglycemia-induced glucagon secretion in SD rats (ED 50 =1.1mg/kg) and glucose excursion in meal tolerance test in Wistar fatty diabetic rats (MED=3.0mg/kg) in oral administrations. Compound 3k was selected asa new drug candidate of selective and orally active non-peptide SSTR2 agonists for treatment of Type 2 diabetes with low in vivo PLsis potential., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We report a design strategy to obtain potent DPP-4 inhibitors by incorporating salt bridge formation with Lys554 in the S1' pocket. By applying the strategy to the previously identified templates, quinoline 4 and pyridines 16a, 16b, and 17 have been identified as subnanomolar or nanomolar inhibitors of human DPP-4. Docking studies suggested that a hydrophobic interaction with Tyr547 as well as the salt bridge interaction is important for the extremely high potency. The design strategy would be useful to explore a novel design for DPP-4 inhibitors having a distinct structure with a unique binding mode., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

An oxygen-bridged planarized triphenylborane has been successfully synthesized. X-ray crystallographic analysis revealed that the molecule has a complete planarized structure and the shortest C-B bonds among the triarylboranes synthesized to date.

Object: The goal of this study is to evaluate whether an "ideal shunt" exists., Methods: This is a retrospective analysis based on original papers in the field of Hydrocephalus and Shunts. Patients of all age groups, who had hydrocephalus, and underwent some form of CSF diversion were included. The study has been divided into four stages: from 1900 to 1949, 1950 to 1974, 1975 to 1999, and from 2000 to 2010., Results: In stage 1 (historical era): Saphenous vein grafts, rubber conduits, and other materials were used in CSF diversions. In 1949, the first implantable shunt tube was developed by Nulsen. In stage 2 (experimental stage): the Holter valve was developed. Newer innovations were developed in relation to the ventriculo-atrial shunt, which was the preferred CSF diversion. In stage 3 (developmental stage), a large number of different design shunt systems were developed, with the aim of reducing complications. The ventriculo-peritoneal shunt had become the preferred CSF diversion. Also, the programmable valve was born. In stage 4 (era of programmable valve, there is a preference for the use of programmable shunt systems. However, shunt failure rate at 1 year being around 25 to 40%, and shunt survival at 1 and 2 years are 50-70 and 47-53% in most series., Conclusion: Every shunt is an ideal shunt provided the choice of the shunt used should be made by the matching performance of the shunt system to the altered profile of CSF dynamics of a given patient. The most important factor being the opening pressure.

We report a patient with myelodysplastic syndrome (MDS) and hepatitis C virus (HCV) infection who was successfully treated with a combination of peginterferon and ribavirin therapy. A 65-year-old man was referred to our hospital for treatment of chronic hepatitis C and close examination of pancytopenia. MDS of "refractory cytopenia with multilineage dysplasia" was diagnosed on the basis of bone marrow findings. Although the patient was not a good candidate for interferon (IFN) therapy because of his pancytopenia, we decided to proceed with IFN therapy for the following reasons: his elevated transaminases could not be controlled; he had a high possibility of recovery from chronic hepatitis C in consideration of his HCV genotype 2a and relatively low RNA titer; and his pancytopenia was expected to worsen in the future. After combination peginterferon/ribavirin therapy, the patient achieved sustained viral response, and the bone marrow findings showed neutrophils with normal granulation and megakaryocytes with normal morphological features. Additionally, the normal 46, XY karyotype converted from 45, X0 which was found before IFN therapy. This suggested that the patient's MDS was completely resolved., (© 2013 The Japan Society of Hepatology.)

The synthesis and characterisation of a series of new Rh and Au complexes bearing 1,2,4-triazol-3-ylidenes with a N-2,4-dinitrophenyl (N-DNP) substituent are described. IR, NMR, single-crystal X-ray diffraction and computational analyses of the Rh complexes revealed that the N-heterocyclic carbenes (NHCs) behaved as strong π acceptors and weak σ donors. In particular, a natural bond orbital (NBO) analysis revealed that the contributions of the Rh→Ccarbene π backbonding interaction energies (ΔEbb ) to the bond dissociation energies (BDE) of the RhCcarbene bond for [RhCl(NHC)(cod)] (cod=1,5-cyclooctadiene) reached up to 63 %. The Au complex exhibited superior catalytic activity in the intermolecular hydroalkoxylation of cyclohexene with 2-methoxyethanol. The NBO analysis suggested that the high catalytic activity of the Au(I) complex resulted from the enhanced π acidity of the Au atom., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Object: Analysis of the safety and morbidity of neuroendoscopic biopsies (NEBs), as well as the reliability in obtaining an accurate diagnosis, has until now been based on studies with relatively small sample sizes. Through the cooperative efforts of several international medical centers, authors of the present study collected data on a large number of patients to obtain better insight into this issue. When possible, they compared pathology obtained through an NEB with the "gold-standard" pathology obtained in open surgery., Methods: Thirteen randomly chosen medical centers in 9 countries collected data for patients who had undergone NEB, which were then analyzed for universal complications, bleeding, navigation technique, pathology, mismatch between biopsy results and final diagnosis, and a number of other potentially influential factors., Results: Data for 293 patients were analyzed. Sixty percent of the patients were male, and patient ages ranged from 0.1 to 78.7 years (median age 20.4 years). The most common tumor locations were pineal (33.1%), thalamic (16.7%), tectal (13%), and hypothalamic (4.4%). Fifty percent of the tumors were larger than 20 mm, 36% were between 10 and 20 mm, and 14% were smaller than 10 mm. Intraoperative bleeding was seen in 275 patients (94%). The amount of blood was noted as mild in 75%, moderate in 13%, and severe in 6%. Infection occurred in 8 patients (3%). Death occurred in 1 patient (0.3%), which was caused by severe intraoperative bleeding. Biopsies were informative in 265 patients (90.4%). Seventy-eight patients (26.6%) had open surgery following the NEB. For these patients, the pathology results from the NEB were compared with those from the open surgery that followed. In 14 cases (17.9%) there was disagreement on the pathology. Of these cases, a meaningful mismatch, in which the erroneous NEB pathology could have led to an inappropriate management decision, occurred in 9 cases (11.5%). Most of these meaningful mismatches were lesions diagnosed as low-grade or pilocytic astrocytoma on the NEB and later proved to be high-grade astrocytoma (4 cases) and 1 case each of meningioma, cavernoma, primitive neuroectodermal tumor, neurocysticercosis, and pineocytoma., Conclusions: In experienced hands, NEBs can be performed with low morbidity and mortality, providing meaningful pathological data for the majority of patients with a wide range of tumor types, locations, and presentations. These biopsies also offer other advantages, such as the ability to perform concomitant endoscopic third ventriculostomy and septum pellucidotomy. However, due caution must be maintained, since pathology obtained from an NEB, as with stereotactic biopsies, may be subject to sampling errors, especially when the results seem to indicate a low-grade glial tumor.

According to the CSF bulk flow theory, hydrocephalus is caused by an imbalance between CSF formation and absorption, or a block at various locations in the major CSF pathway. New theories, however, have been proposed in which minor CSF pathways may play a significant role in the development of congenital hydrocephalus. The authors review major contributions to the literature and analyze the evolution of theories of CSF dynamics in relation to hydrocephalus, dividing their development into 4 stages on the basis of historical trends. In Stage I (prior to 1950), 2 systems of classifying hydrocephalus were proposed, namely Dandy's classifications of communicating and noncommunicating hydrocephalus and Russell's nonobstructive and obstructive hydrocephalus. In Stage II (1950-1974), based on these theories of major CSF pathway dynamics, treatment focused on ventriculostomy as an alternative to reduction of CSF production by choroid plexus coagulation. In Stage III (1975-1999), some of the specific forms of hydrocephalus, especially in premature infants, were found to be unsuitable for ventriculostomy. In Stage IV (2000-2008), selection of treatment modalities evolved further, with a focus on analysis of the chronological changes in CSF dynamics and the differences in absorption pathways in the developing and mature brains. The authors focus on "minor pathway hydrocephalus" in the immature brain, differentiating it from the conventional classification of obstructive and nonobstructive "major pathway hydrocephalus."

Direct arylation of thiophenes and benzothiophenes with aryltrimethylsilanes was effectively catalyzed by PdCl(2)(MeCN)(2) in the presence of CuCl(2) as an oxidant. The reaction preferentially occurred at the β-position of both thiophenes and benzothiophenes.

An asymmetric allylic substitution of simple allylic ethers with arylboronic acids in the presence of a rhodium(I)/(R)-DTBM-SEGPHOS catalyst has been developed. The reactions proceeded smoothly at room temperature to give the corresponding branch products with excellent regioselectivities and good to excellent enantioselectivities.

Objective: Hydrocephalus is a complex pathophysiology with disturbed cerebrospinal fluid (CSF) circulation. There are numerous numbers of classification trials published focusing on various criteria, such as associated anomalies/underlying lesions, CSF circulation/intracranial pressure patterns, clinical features, and other categories. However, no definitive classification exists comprehensively to cover the variety of these aspects. The new classification of hydrocephalus, "Multi-categorical Hydrocephalus Classification" (Mc HC), was invented and developed to cover the entire aspects of hydrocephalus with all considerable classification items and categories., Materials and Method: Ten categories include "Mc HC" category I: onset (age, phase), II: cause, III: underlying lesion, IV: symptomatology, V: pathophysiology 1-CSF circulation, VI: pathophysiology 2-ICP dynamics, VII: chronology, VII: post-shunt, VIII: post-endoscopic third ventriculostomy, and X: others. From a 100-year search of publication related to the classification of hydrocephalus, 14 representative publications were reviewed and divided into the 10 categories., Results and Discussion: The Baumkuchen classification graph made from the round o'clock classification demonstrated the historical tendency of deviation to the categories in pathophysiology, either CSF or ICP dynamics., Conclusion: In the preliminary clinical application, it was concluded that "Mc HC" is extremely effective in expressing the individual state with various categories in the past and present condition or among the compatible cases of hydrocephalus along with the possible chronological change in the future.

Introduction: Hydrocephalus does not indicate a single clinical entity, but includes a variety of clinicopathological conditions caused by excessive cerebrospinal fluid (CSF) based on the disturbed circulation. Recent progress in prenatal neuroimagings such as MRI and ultrasound echoencephalography on fetus enables to understand clinicopathological conditions of CSF circulation disorder in conjunction with morphological changes in the central nervous system properly. It has been revealed that the CSF dynamics develop in the theory of evolution from the immature brain, as in the animals with the minor CSF pathway predominance, towards matured adult human brain together with the completion of the major CSF pathway: the "Evolution Theory in CSF Dynamics". Now, we can analyze CSF circulation dynamically and also analyze the flow velocity and direction of CSF movement. CENTER OF EXCELLENCE-FETAL HYDROCEPHALUS TOP 10 JAPAN: Along with this technical improvement, the standards of clinicopathological evaluation of hydrocephalus as well as the classification and concept of hydrocephalus shall undergo a major upgrade. Based on such remarkable improvement in the recent practical diagnostic evaluation of fetal hydrocephalus, it is now required to update the guideline for management and treatment of fetal and congenital hydrocephalus, and a nationwide study group; Center of Excellence-Fetal Hydrocephalus Top 10 Japan, was organized in 2008 in Japan. The retrospective analysis of 333 cases of congenital hydrocephalus indicated a fact that 43% of these cases were diagnosed prenatally, and the majority of cases were treated in these top 10 institutes in Japan. Now, congenital hydrocephalus diagnosed immediately after birth is regarded as to be based on embryonic stage; brain disorder in patients with congenital hydrocephalus should be considered in conjunction with neuronal mature process of embryonic stage. The fact is supported by the current trends in hydrocephalus research represented by "Perspective Classification of Congenital Hydrocephalus" and "Multi-categorical Hydrocephalus Classification". The ultimate goal of hydrocephalus treatment remains achieving arrested hydrocephalus by shunt surgeries. In the future, to achieve arrested hydrocephalus, minimum quantity of CSF to be drained should be elucidated. Consideration for accurate operative indication of ETV along with new neuroendoscopic device development and analysis of CSF circulation is expected in the future. The data in this prospective multicenter analysis in this guideline are credited in Oxford Evidence level 2b (Grade II).

The design, synthesis, and structure-activity relationships of a new class of potent and orally active non-peptide dipeptidyl peptidase IV (DPP-4) inhibitors, 3-aminomethyl-1,2-dihydro-4-phenyl-1-isoquinolones, are described. We hypothesized that the 4-phenyl group of the isoquinolone occupies the S1 pocket of the enzyme, the 3-aminomethyl group forms an electrostatic interaction with the S2 pocket, and the introduction of a hydrogen bond donor onto the 6- or 7-substituent provides interaction with the hydrophilic region of the enzyme. Based on this hypothesis, intensive research focused on developing new non-peptide DPP-4 inhibitors has been carried out. Among the compounds designed in this study, we identified 2-[(3-aminomethyl-2-(2-methylpropyl)-1-oxo-4-phenyl-1,2-dihydro-6-isoquinolinyl)oxy]acetamide (35a) as a potent, selective, and orally bioavailable DPP-4 inhibitor, which exhibited in vivo efficacy in diabetic model rats. Finally, X-ray crystallography of 35a in a complex with the enzyme validated our hypothesized binding mode and identified Lys554 as a new target-binding site available for DPP-4 inhibitors., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Dipeptidyl peptidase IV (DPP-4) inhibition is a validated therapeutic option for type 2 diabetes, exhibiting multiple antidiabetic effects with little or no risk of hypoglycemia. In our studies involving non-covalent DPP-4 inhibitors, a novel series of quinoline-based inhibitors were designed based on the co-crystal structure of isoquinolone 2 in complex with DPP-4 to target the side chain of Lys554. Synthesis and evaluation of designed compounds revealed 1-[3-(aminomethyl)-4-(4-methylphenyl)-2-(2-methylpropyl)quinolin-6-yl]piperazine-2,5-dione (1) as a potent, selective, and orally active DPP-4 inhibitor (IC₅₀=1.3 nM) with long-lasting ex vivo activity in dogs and excellent antihyperglycemic effects in rats. A docking study of compound 1 revealed a hydrogen-bonding interaction with the side chain of Lys554, suggesting this residue as a potential target site useful for enhancing DPP-4 inhibition., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: The authors describe the case of a 29-month-old boy who presented with acute non-communicating hydrocephalus caused by a small tumor in the fourth ventricle. He became brain-dead immediately and remained stable in that condition., Materials and Methods: Six months later, despite being in a brain-dead state, a rapid direct tumor extension from the intracranial to extracranial region was observed, and chemoradiotherapy was performed following tumor biopsy. The histopathological diagnosis was large cell medulloblastoma. Although treatment was initially effective, the tumor again aggressively invaded the cervical muscles via the spinal canal. Comparative genomic hybridization (metaphase) analysis revealed a pattern of aberrations predictive of a poor prognosis (+1q, ?17p, +17q, and probable amplification of c-myc gene), and he eventually died 11 months after onset., Results: Direct invasion of medulloblastoma from the intracranial to extracranial region is extremely rare, and, to our knowledge, this is the first report of medulloblastoma exhibiting rapid extension to the extracranial region in brain-dead state., Conclusions: For patients with medulloblastomas, careful observation is needed even in brain-dead state. The etiology of this rare condition as well as the genetic characteristics responsible for aggressive tumor behavior are discussed.

The aim in reporting this case was to discuss the pathophysiology and treatment issues in an infant with a giant syringobulbia associated with a right cerebellopontine angle (CPA) arachnoid cyst causing noncommunicating hydrocephalus. This 7-month-old infant presented to the hospital with a history of delayed milestones and an abnormal increase in head circumference. Magnetic resonance images and CT scans of the brain showed a large CSF cavity involving the entire brainstem and a right CPA arachnoid cyst causing obstruction of the fourth ventricle and dilation of the lateral and third ventricles. Cerebrospinal fluid diversion was performed by direct communication from the syringobulbia cavity to the left lateral ventricle and from the left lateral ventricle through another ventricular catheter; external ventricular drainage was performed temporarily for 5 days. Communication between the syrinx and arachnoid cyst was confirmed. Clinically, there was a reduction in head circumference, and serial MR imaging of the brain showed a decrease in the size of the syrinx cavity and the ventricle along with opening of the normal CSF pathways. The postoperative course was uneventful, and no further intervention was necessary. On follow-up of the child at 3 years, his developmental milestones were normal. Surgical intervention for this condition is mandatory. The appropriate type of surgery should be performed on the basis of the pathophysiology of the developing syringobulbia.

Object: The current, generally accepted optimal management for hydrocephalus related to vestibular schwannomas (VSs) is primary tumor removal, with further treatment reserved only for patients who remain symptomatic. Previous studies have shown, however, that this management can lead to an increase in surgery-related complications. In this study, the authors evaluated their experience with the treatment of such patients, with the aim of identifying the following: 1) the parameters correlating to the need for specific hydrocephalus treatment following VS surgery; and 2) patients at risk for developing hydrocephalus-related complications., Methods: This was a retrospective study of a 400-patient series. The complication rates and outcomes following primary hydrocephalus treatment versus primary VS removal were compared. Patients undergoing primary tumor removal were further subdivided on the basis of the need for subsequent hydrocephalus treatment. The 3 categories of parameters tested for correlation with the need for such subsequent treatment as well as with heightened risk for developing complications were patient-, tumor-, and hydrocephalus-related., Results: Of the entire series, 53 patients presented with hydrocephalus. Forty-eight of 53 patients underwent primary VS surgery, of whom 42 (87.5%) did not require additional hydrocephalus treatment. Of the 6 patients who did require additional hydrocephalus treatment, only 3 ultimately required a VP shunt. Factors correlating to the need of hydrocephalus treatment after VS removal were large tumor size, irregular tumor surface, and severe preoperative hydrocephalus. Patients with a longer symptom duration prior to surgery, those with polycyclic tumors, or with inhomogeneous VS, were at heightened risk for the development of CSF leaks. The general and functional outcome of surgery showed no correlation to the presence of preoperative hydrocephalus., Conclusions: Primary tumor removal is the optimum management of disease in patients with VS with associated hydrocephalus; it leads to resolution of the hydrocephalus in the majority of cases, and the outcome is similar to that of patients without hydrocephalus. Certain factors may aid in identifying patients at risk for developing persistent hydrocephalus as well as those at risk for CSF leaks.

There is still debate over which method of the surgery is the most appropriate for the treatment of scaphocephalic infants. In addition, change in psychomotor development following these procedures is a very complex issue that has not yet been resolved. In this paper, the authors describe a surgical technique for immediate spontaneous shape correction of infantile scaphocephaly. There were significant differences between pre- and postoperative cephalic index. We also describe an improvement in the developmental quotient following surgery. Therefore, this expantile zigzag craniectomy should be recommended to correct for isolated sagittal craniosynostosis in infants.

Inhibition of dipeptidyl peptidase IV (DPP-4) is an exciting new approach for the treatment of diabetes. To date there has been no DPP-4 chemotype possessing a carboxy group that has progressed into clinical trials. Originating from the discovery of the structurally novel quinoline derivative 1, we designed novel pyridine derivatives containing a carboxy group. In our design, the carboxy group interacted with the targeted amino acid residues around the catalytic region and thereby increased the inhibitory activity. After further optimization, we identified a hydrate of [5-(aminomethyl)-6-(2,2-dimethylpropyl)-2-ethyl-4-(4-methylphenyl)pyridin-3-yl]acetic acid (30c) as a potent and selective DPP-4 inhibitor. The desired interactions with the critical active-site residues, such as a salt-bridge interaction with Arg125, were confirmed by X-ray cocrystal structure analysis. In addition, compound 30c showed a desired preclinical safety profile, and it was encoded as TAK-100.

This report describes the case of a neonate with myeloschisis weighing 599 g that underwent an operation for spinal cord reconstruction resulting in substantial neuronal functional recovery. At 28 weeks of gestation, oligohydramnios was detected and the female fetus was diagnosed with intrauterine growth retardation. At birth by emergency caesarean section, she showed lumbosacral myeloschisis and complete paralysis of the lower extremities. Surgical repair and spinal cord reconstruction was performed 2 days after birth by closing the neural placode. Total blood loss was only 2 ml. Within 3 months of the operation, lower extremity neurologic function gradually improved down to the level of the knee joint. To our knowledge, this case is the lowest recorded body weight for a neonate with myeloschisis repair at birth, and this further suggests the possibility of improvement of lower extremity neurologic function after birth and surgical reconstruction., (Copyright © 2012 S. Karger AG, Basel.)

A 30-year-old woman presented with traumatic carotid-cavernous fistula associated with persistent primitive trigeminal artery (PPTA) manifesting as right conjunctival chemosis, exophthalmos, and diplopia. The lesion was treated successfully by trans-arterial coil embolization using the double catheter method with balloon assist. Injury to the PPTA is relatively rare and the PPTA should be sacrificed together with the fistula during the repair.

We have previously discovered nicotinic acid derivative 1 as a structurally novel dipeptidyl peptidase IV (DPP-4) inhibitor. In this study, we obtained the X-ray co-crystal structure between nicotinic acid derivative 1 and DPP-4. From these X-ray co-crystallography results, to achieve more potent inhibitory activity, we targeted Arg125 as a potential amino acid residue because it was located near the pyridine core, and some known DPP-4 inhibitors were reported to interact with this residue. We hypothesized that the guanidino group of Arg125 could interact with two hydrogen-bond acceptors in a bidentate manner. Therefore, we designed a series of 3-pyridylacetamide derivatives possessing an additional hydrogen-bond acceptor that could have the desired bidentate interaction with Arg125. We discovered the dihydrochloride of 1-{[5-(aminomethyl)-2-methyl-4-(4-methylphenyl)-6-(2-methylpropyl)pyridin-3-yl]acetyl}-l-prolinamide (13j) to be a potent and selective DPP-4 inhibitor that could interact with the guanidino group of Arg125 in a unique bidentate manner., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

We reviewed the clinical prognosis and therapeutic aspects in the management of pediatric moyamoya disease from our data base for the last 8 years since establishment of our institution. We found 99 cerebrovascular disease cases among the total of 1,159 cases, and 20 out of them were moyamoya disease. Only 13 cases were analyzed as the rest were not available for follow up. Nine girls and 4 boys were admitted with an average age of 5 years-old 4 months. Initial symptom were TIA in 5, cerebral infarction in 5, migraine in 2, and epilepsy in one. The type of moyamoya disease was bilateral type in 10 cases, and unilateral type in 3 cases. Clinical condition and investigations, as well as the effect of conservative management, required surgery in 9 cases (8 indirect revascularization and one direct-bypass surgery), and the rest 4 cases were managed conservatively. Only 10 cases were followed-up, 9 operated cases and one conservatively managed case. In 6 of 9 of the operated cases, there was recurrence: cerebral infarction in 3, TIA recurrence in 2 and epileptic seizure in one. On MRA a steno-occlusive lesion of PCA was found in 4 of the 6 recurrence patients, and improvement was achieved by additional surgery in one of them. All of the cases developed good postoperative collateral circulation. The conservatively treated patient did not show neither steno-occlusive lesion of PCA, nor a clinical recurrence for 7 years observation. Therefore, posterior circulation system in moyamoya disease is important as a collateral circulation in addition to the revascularization procedures, and we believe that the progression of the steno-occlusive lesion of PCA is an important indicator, predicting recurrence.

Classification of hydrocephalus is the most crucial but the most complicated academic challenge within the hydrocephalus research field. The major difficulty in this challenge arises from the fact that the classification is based on almost all subjects in hydrocephalus research, i.e., definition and terminology of hydrocephalus, pathophysiology, hydrocephalus chronology, specific forms of hydrocephalus, associated congenital anomalies/syndrome and underlying conditions, diagnostic procedures for hydrocephalus, and treatment modalities in hydrocephalus. The current status of the classification of hydrocephalus in individual subgroups was reviewed and summarized from publications in the last 60 years (1950-2010), and discussed focusing on the variety of characteristics in hydrocephalus, with more and more new aspects recently disclosed not only in fetal and pediatric but also in adult hydrocephalus. A recently-reported classification of hydrocephalus, "Multi-categorical Hydrocephalus Classification" provides comprehensive coverage of the entire aspects of hydrocephalus with current important classification categories and subtypes.

Rh(I) catalyzes the reductive coupling reaction of a wide variety of aldehydes with conjugated dienes in the presence of a stoichiometric amount of triethylborane to provide homoallyl alcohols in a single operation.

Aicardi syndrome is an X-linked dominant disorder characterized by the pathognonomic association of three clinical signs: agenesis of the corpus callosum, infantile spasms, and chorioretinal lacunae. This is a severe syndrome with an estimated survival rate of 76% at 6 years and 40% at 14 years and a maximum developmental level like a 12-month-old baby in 91% of cases. We illustrate a case of Aicardi syndrome with bilateral, small chorioretinal lacunae, infantile spasms with a typical hypsarrhythmia, defects of thoracic vertebra and bilateral absence of the 12th rib associated with an arachnoid cyst of the quadrigeminal cistern, and presence of the corpus callosum with a favorable outcome.

Objective: Various operative procedures have been described for the treatment of pediatric moyamoya disease. However, the majority of invasive or radical procedures proposed have focused primarily on revascularization and few have discussed to maximizing preservation of the already growing neovascular network., Methods: This present procedure describes the supratemporal artery is anastomosed to the inner layer of the dura mater and surrounded by the outer layer as a sandwich with a blunt procedure of dural layer separation., Results: This technique efficiently established an anastomotic connection between the supratemporal artery and the cortical brain, and the dura mater postoperatively with maximally preserving the existing vascular network., Conclusion: IDAS, the modified surgical technique of EDAS, shall be benefit in preserving the already developed collateral circulation, and underlying structure over the brain cortex as much as possible, which is important particularly in pediatric moyamoya patients.

Object: The natural history of asymptomatic spinal lipoma in infancy remains unclear, and the indication for the prophylactic untethering operation is still debatable. To address this question, a multicenter cooperative study for the treatment of spinal lipoma was performed by the 7 most active institutions in neurosurgical care for spina bifida in Japan between 2001 and 2005., Methods: Patients were classified using the embryopathogenetic surgicoanatomical classification. Their neurosurgical postoperative course was analyzed using the Spina Bifida Neurological Scale. Among 261 patients, 159 were asymptomatic and 102 were symptomatic., Results: Of the 136 patients for whom prophylactic surgeries were performed, 135 remained asymptomatic and only 1 (0.4%) of the 261 patients presented with mild sensory disturbance. Mild foot deformity was identified in 1 (4.3%) of 23 conservatively observed patients. Of 100 symptomatic patients, deterioration after surgery was seen in 6%, and improvement in 44%. Complete resolution of symptoms was seen in only 14.2%. Filar types for patients > 3 years old improved in Spina Bifida Neurological Scale scores from 12.3 to 14.0. The mean age of symptomatic patients with lipomyelomeningocele was the youngest of all (1.3 years), which indicates lipomyelomeningocele may deteriorate in early infancy. Improvements from surgery were seen for all types of lipoma except the caudal type, presenting at an older mean age (15 years)., Conclusions: A low rate of postsurgical worsening indicates that surgeries for asymptomatic and symptomatic lipomas are safe. Surgeries done after the onset of symptoms seldom cure the patients. These two results support early untethering for any kind of lipoma; however, further study of the natural history is required.

NY-ESO-1, one of the most immunogenic cancer/testis antigens, provides attractive targets for cancer immunotherapy. NY-ESO-1 has been demonstrated to be expressed in a range of solid tumors via DNA demethylation and/or histone modification; however, it has been rarely expressed in glioma. The reversibility of these epigenetic aberrations is potentially attractive for glioma treatment with DNA-methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi), leading to reactivation of silenced genes. We previously demonstrated de novo induction of NY-ESO-1 in glioma cells by DNMTi. In this study, we show that an anticonvulsant, i.e., valproic acid (VPA), also acting as an HDACi, enhances induction of NY-ESO-1 in synergy with DNMTi. Chromatin assays demonstrated that combination of DNMTi and VPA elicited significant DNA demethylation, histone H3 Lys9 demethylation, and acetylation. These findings not only shed light on an epigenetic immunotherapy, but also suggest that the silencing of NY-ESO-1 is mediated by histone modification.

Nocardia is a bacterial infection primarily originating from organic rich soil, endemic to several international geographic locations. We present the case of a 61-year-old woman previously treated for endometrial carcinoma, who three years later developed metastatic pulmonary disease and received systemic chemotherapy. After five months, she developed a large right posterior lobe lesion, suspicious for metastatic CNS disease. However, following neurosurgical resection of the lesion and infectious disease consultation, a diagnosis of nocardia was made.

Large skull base meningiomas frequently encase the major cerebral vessels and cranial nerves, and receive blood supply from the branches of the internal carotid artery. One-stage resection of these tumors is difficult due to the long time needed for surgery and profuse bleeding from the tumor. We report herein a case of large sphenoid ridge atypical meningioma that was successfully resected using a combination of two-stage surgery and irradiation. A 56-year-old man was referred to us with mild left hemiparesis and visual deterioration. Computed tomography and magnetic resonance imaging showed a large sphenoid ridge meningioma. Angiography showed blood supply from the branches of both external and internal carotid arteries, and pial blood supply from the middle cerebral artery. In the first surgery after embolization of feeder vessels from the external carotid artery, the tumor was still hemorrhagic and was partially resected with 2,374 ml of blood loss. Symptoms were improved after the first surgery. Pathological diagnosis was atypical meningioma. In the second surgery after 40 Gy of irradiation, the remnant tumor was no longer hemorrhagic and was totally resected. Staged surgery with irradiation is one treatment option for large vascular skull base meningiomas, particularly for atypical meningiomas.

Objectives: The aims of this study were to describe and analyze the technique of neuroendoscopic foraminal plasty of foramen of Monro (NEFPFMO) in the treatment of isolated unilateral hydrocephalus (IUH) due to membranous occlusion, to evaluate its efficacy and safety, and to define the benefits of neuronavigational guidance of the procedure., Materials and Methods: Two symptomatic neonates with IUH, as a result of congenital atresia of foramen of Monro, underwent NEFPFMO plus neuroendoscopic septostomy in the first case and neuronavigational guidance in the second one. Clinical results were excellent in both neonates. The postoperative ventricular size decreased and the progressive IUH changed to the state of arrested hydrocephalus. The neuronavigation was precise., Conclusion: NEFPFMO should be the primary treatment option in patients with IUH due to membranous occlusion of foramen of Monro. It reestablishes natural anatomical communication and provides real physiological cerebrospinal fluid flow. Neuronavigation is a useful adjunct of NEFPFMO.

The treatment of hydrocephalus nowadays is still a challenge for neurosurgery. Neuroendoscopy is a valuable alternative of the CSF shunts in hydrocephalus management. Because of the complicated and always changeable pathophysiology of hydrocephalus, the history of the endoscopic treatment of hydrocephalus is also a history of severe frustrations, great expectations, and significant achievements. The historical milestones and state of the art of neuroendoscopic treatment of hydrocephalus are reviewed for each of its surgical techniques: choroid plexus coagulation, third ventriculostomy, aqueductoplasty, septostomy, foraminal plasty of the foramen of Monro, and foraminal plasty of the foramen of Magendie. The future trends of neuroendoscopic treatment of hydrocephalus such as robotics, image-guided neuroendoscopic surgical techniques, treatment "in utero", application of stem cell therapy, implementation of new technological solutions, and so on are discussed in the light of the approaching end of the century of neuroendoscopy.

Objects: To characterize the anatomical features of the ventricular regions in patients with myeloschisis and related to successful performance of endoscopic third ventriculostomy (ETV)., Methods: Radiological and endoscopic findings of 21 myeloschisis patients were retrospectively reviewed. Radiological features that could interfere with endoscopic procedures were (1) a huge massa intermedia (12/19), (2) sloping of the third ventricular floor (3/10), (3) narrow anteroposterior length of the third ventricular floor (2/10), and (4) narrow prepontine cistern (8/21). Endoscopic findings were (a) a narrow foramen of Monro (0/3), (b) hypertrophy of the anterior commissure (1/3), (c) sloping of the third ventricle floor (1/3), (d) a huge massa intermedia (3/3), and (e) opaque third ventricular floor (3/3). These endoscopic findings did not interfere with endoscopic procedures by using the Oi-HandyPro neuroendoscope without the above-mentioned radiological features 3 or 4., Conclusion: Narrow anteroposterior length of the third ventricular floor and narrow prepontine cistern are not infrequently observed. Preoperative evaluation and intraoperative inspection of these findings are very important in successful performance of ETV.

The study population included 193 patients with prenatally diagnosed (fetal) hydrocephalus and 181 with postnatally (12 or less than 12 months after birth) diagnosed (infantile) hydrocephalus identified by a nationwide questionnaire survey of congenital hydrocephalus performed in 2000. Of 180 patients with fetal, 101 (56.1%) were diagnosed before week 32 of gestation and 18 (10%) were diagnosed week 37 and later of gestation. In patients with fetal hydrocephalus, US was used in more than 80% of the cases, whereas in patients with infantile hydrocephalus, CT was used in more than half of the cases. For diagnosis of fetal hydrocephalus, either US or MRI had become dominantly utilized and CT had gone out of use in 1996-2000. The adoption ratio of cesarean delivery to transvaginal delivery was around 7 to 3 in patients with fetal hydrocephalus, and 2 to 7 in patients with infantile hydrocephalus, respectively, with significant difference between fetal hydrocephalus and infantile hydrocephalus groups (p < 0.001). Clinical outcomes in patients with fetal hydrocephalus was better in those delivered transvaginally than in those by cesarean delivery, although without no statistical significance (p = 0.124) and those in patients with infantile hydrocephalus showed almost no difference between transvaginal and cesarean delivery groups. There was a tendency for the Apgar score at 5 min to be lower in smaller birth weight infants with a body weight of less than 2000g. This score could be useful as an index for predicting immediate postnatal death in patients with fetal hydrocephalus.