Minor Suture Fusion is Associated With Chiari Malformation in Nonsyndromic Craniosynostosis.

Here, we focused on the association between minor suture fusion and Chiari malformation (CM) occurrence in nonsyndromic craniosynostosis (NSC), and evaluated how the minor suture affects the posterior cranial fossa by measuring the posterior fossa deflection angle (PFA). In this retrospective study, the clinical records of 137 patients who underwent surgery for NSC at Aichi Children's Health and Medical Center between April 2010 and May 2022 were analyzed. Clinical data from Aichi Developmental Disability Center Central Hospital was collected for 23 patients as the external validation set. Among the 137 patients, 123 were diagnosed with NSC and the remaining 14 with syndromic craniosynostosis. Of the 123 NSC patients, 23 patients presented with CM. Multivariate analysis showed that occipito-mastoid fusion was the only significant risk factor for CM ( P =0.0218). Within the NSC group, CM patients had a significantly increased PFA (6.33±8.10 deg) compared with those without CM (2.76±3.29 deg, P =0.0487). Nonsyndromic craniosynostosis patients with occipito-mastoid suture fusion had a significantly increased PFA (6.50±7.60 deg) compared with those without occipito-mastoid fusion (2.60±3.23 deg, P =0.0164). In the validation cohort, occipito-mastoid suture fusion was validated as an independent risk factor for CM in univariate analysis. Minor suture fusion may cause CM associated with NSC. Chiari malformation could develop due to an increased PFA due to minor suture fusion, which causes growth disturbance in the affected side and compensatory dilation in the contralateral side within the posterior cranial fossa.

Total Synthesis of Euonymine and Euonyminol Octaacetate.

Euonymine (1) and euonyminol octaacetate (2) share the core structure of euonyminol (3), the most hydroxylated member of the dihydro-ß-agarofuran family. In 2, eight of the nine hydroxy groups of 3 are acetylated, and 1 has six acetyl groups and a 14-membered bislactone comprising a pyridine dicarboxylic acid with two methyl groups. The different acylation patterns provide distinct biological activities: 1 and 2 display anti-HIV and P-glycoprotein inhibitory effects, respectively. The 11 contiguous stereocenters and 9 oxygen functionalities of the ABC-ring system of 1 and 2 represent a formidable challenge, which is further heightened by the macrocyclic structure of 1. Here we disclose an efficient synthetic strategy for enantioselective total synthesis of 1 and 2. Starting from (R)-glycerol acetonide, we constructed the B-ring by an Et3N-accelerated Diels-Alder reaction, the C-ring by intramolecular iodoetherification, and the A-ring by ring-closing olefin metathesis. The 10 stereocenters were installed through a series of substrate-controlled stereoselective C-C and C-O bond formations by exploiting the three-dimensional structures of judiciously designed substrates. These newly developed reaction sequences led to protected euonyminol 5, which served as a common intermediate for assembling 1 and 2. Global deprotection of 5 and subsequent acetylation produced 2. Alternatively, the discriminative protective groups of 5 allowed for site-selective bis-esterification to generate bislactone. Combining [3 + 2]-cycloaddition and reductive desulfurization introduced the last remaining stereocenters of the two methyl groups on the macrocycle. Finally, deprotection and acetylation gave rise to fully synthetic 1 for the first time.

Lacrimal Gland Amyloidosis in an Elderly Patient.

Localized amyloidosis of the lacrimal gland is a rare disease. We report a case of transthyretin-positive localized amyloidosis of the lacrimal gland in a 74-year-old man with left lacrimal gland swelling. Biopsy of the left lacrimal gland showed extensive deposition of nonstructural eosinophilic material in the secretory gland and ducts, which stained positive with direct fast scarlet. Immunostaining was negative for amyloid A and positive for both globulin light chain (kappa, lambda) and transthyretin. It is necessary to consider the possibility of senile systemic amyloidosis, even if localized amyloidosis of the lacrimal gland is suspected.

A Case of IgG4-Related Bilateral Palpebral Conjunctivitis.

The most common sites of IgG4-related ocular disease are the lacrimal glands, infraorbital nerve, and extraocular muscles. Other ocular adnexal sites are relatively rare. We report a rare case of an 83-year-old man who developed palpebral conjunctivitis following bilateral hypertrophic ectropion of the eyelid. Tissue immunostaining revealed many IgG4-positive plasma cells (67 IgG4/74 IgG cells/high-power field). The serum IgG4 level was 76.9 mg/dL, which was within the normal range. The diagnosis was probable IgG4-related disease. The possibility of IgG4-related disease should be considered in a patient presenting with refractory conjunctivitis and hyperemia or hypertrophy of the lower eyelid.

Synthesis of 3ß-tert-Butyldimethylsiloxy-22-phenylthio-23,24-bisnorchola-5,9(11)-diene and Reductive Nucleophilic Attack on a Branched Aliphatic Aldehyde.

3ß-tert-Butyldimethylsiloxy-22-phenylthio-23,24-bisnorchola-5,9(11)-diene, which has a double bond between C-9 and C-11 and a phenylsulfenyl group on the terminus of the side chain, is a potential synthetic intermediate for steroids with 9,11-unsaturation or 9,11-seco skeletons. We describe here the synthesis of the title compound from 17-ethylenedioxy-3-acetoxyandrosta-3,5-dien-11-one. The introduction of an ethylene unit to 3ß-tert-butyldimethylsiloxyandrosta-5,9(11)-dien-17-one by the action of ethyltriphenylphosphonium bromide under basic conditions resulted in an inseparable mixture of two stereoisomeric products (5 : 1). However, in the subsequent step, only the (Z)-isomer was susceptible to the Lewis acid-catalyzed ene reaction with formaldehyde, giving a stereochemically pure product with the desired configuration. Within three steps, the ene-product was derivatized to the title compound, with a total yield of 53% over seven steps. Reductive terminal anion formation by treatment with lithium di-tert-butylbiphenyl (LiDBB) and subsequent nucleophilic attack on a branched aliphatic aldehyde was demonstrated, with an eye toward the introduction of side chains, especially for steroids with oxygen functionality at C-23.

Synthesis of enantiomerically enriched drug precursors and an insect pheromone via reduction of ketones using commercially available carbonyl reductase screening kit "Chiralscreen® OH".

Commercially available "Chiralscreen® OH" starter kit containing five types of carbonyl reductases (E001, E007, E031, E039, and E078) was used for the reduction of several aromatic and aliphatic ketones to obtain enantiomerically enriched drug precursors and an insect pheromone. Almost stereochemically pure secondary alcohols, used in the synthesis of drugs such as (R)-rasagiline mesylate, (S)-rivastigmine, (R)-chlorphenesin carbamate, and (R)-mexiletine, and the insect pheromone (4S,5R)-sitophilure, were conveniently obtained. The enzymes worked well with ketones containing at least one non-bulky substituent at the carbonyl group. The diverse stereochemical preference of the above five carbonyl reductases was clarified.

Installation of a Neuromate Robot for Stereotactic Surgery: Efforts to Conform to Japanese Specifications and an Approach for Clinical Use-Technical Notes.

The neuromate is a commercially available, image-guided robotic system for use in stereotactic surgery and is employed in Europe and North America. In June 2015, this device was approved in accordance with the Pharmaceutical Affairs Law in Japan. The neuromate can be specified to a wide range of stereotactic procedures in Japan. The stereotactic X-ray system, developed by a Japanese manufacturer, is normally attached to the operating table that provides lateral and anteroposterior images to verify the positions of the recording electrodes. The neuromate is designed to be used with the patient in the supine position on a flat operating table. In Japan, deep brain stimulation surgery is widely performed with the patient's head positioned upward so as to minimize cerebrospinal fluid leakage. The robot base where the patient's head is fixed has an adaptation for a tilted head position (by 25 degrees) to accommodate the operating table at proper angle to hold the patient's upper body. After these modifications, the accuracy of neuromate localization was examined on a computed tomography phantom preparation, showing that the root mean square error was 0.12 ± 0.10 mm. In our hospital, robotic surgeries, such as those using the Da Vinci system or neuromate, require operative guidelines directed by the Medical Risk Management Office and Biomedical Research and Innovation Office. These guidelines include directions for use, procedural manuals, and training courses.

[Mood States in outpatients with lesional epilepsy at the neurosurgical clinic and improvement in mood States after lamotrigine addiction].

People with epilepsy have a high incidence of mood disorders that may affect their quality of life. Lamotrigine(LTG)is one of the antiepileptic drugs that are commercially available in Japan these days and its mood-stabilizing qualities were well known. First, 66 outpatients with epilepsy were evaluated for changes in mood states by the Profile of Mood States(POMS)and the Japanese-edition Beck Depression Inventory-Second Edition(BDI-II)on self report. The POMS questionnaire includes 30 items that address six components of mood. At baseline, one third of the outpatients with epilepsy had mood problems compared by POMS health reference. The mean BDI-II baseline score was 14.9±10.1, and one third of these epilepsy patients exhibited moderate or severe depression. Second, in the twelve patients with epilepsy, LTG was added to other antiepileptic drugs, and the POMS and BDI-II were administered at baseline and after addiction to LTG. 4 out of 8(50%)patients with simple partial seizure and 5 out of 8(62.5%)patients after the adjunctive therapy experienced at least a 50% reduction in the number of seizures compared with the self-reported baseline before the adjunctive therapy. The component scores of Depression-Dejection, Anger-Hostility and Confusion-Bewilderment in POMS were statistically improved in these patients completing adjunctive LTG(pared t-test, p<0.05). In these patients, the mean BDI-II baseline score was 25.8±13.1. Following administration of LTG, there was a significant decrease in the mean BDI-II scores(15.0±6.6)between baseline and the end of adjunctive LTG. This study suggests that, in addition to seizure control, LTG may have a mood-stabilizing effect and improve the quality of life in patients with epilepsy.

Preoperative regional cerebral blood flow and postoperative clinical improvement in patients with Parkinson's disease undergoing subthalamic nucleus deep brain stimulation.

Preoperative regional cerebral blood flow (rCBF) was measured in 92 patients with Parkinson's disease (PD) by iodine-123 N-isopropyl-p-iodoamphetamine single-photon emission computed tomography. Quantitative mapping of rCBF was performed using the stereotactic extraction estimation method. The clinical features of the patients were assessed according to the Unified Parkinson Disease Rating Scale (UPDRS). The correlation between rCBF and improvement in the UPDRS score following surgery was examined. rCBF in the fusiform gyrus, superior and inferior parietal gyri, middle occipital gyrus, superior frontal gyrus, and middle temporal gyrus of the Talairach Daemon Level 3 was significantly correlated with UPDRS part II (off stage) and III (on stage) scores (p < 0.05). rCBF in the middle temporal gyrus (p = 0.00147), medial frontal gyrus (p = 0.00713), and cerebellum (p = 0.048) of the Talairach Daemon Level 3 was significantly greater in 47 patients with >60% improvement of UPDRS part III (off stage) score than in 37 patients with 40-60% improvement. The cutoff value of rCBF, which indicated that >40% improvement in the surgical outcome could be expected, was 38.8 ± 6.2 ml/100 g/min in the frontal lobe. This study indicated that rCBF in patients with PD might be related to their clinical features, suggesting that quantitative mapping of rCBF may be useful for predicting surgical outcome.