Expeditious Access to the B3NO2 Heterocycle Enabling Modular Derivatization.

DATB (1,3-dioxa-5-aza-2,4,6-triborinane) is a unique six-membered heterocycle exhibiting proficient catalytic activity in direct dehydrative amidation. Reported herein is an improved synthetic protocol for DATB derivatives featuring a concise two-step chromatography-free process. Suzuki-Miyaura coupling assembled 2,6-dibromoaniline derivatives and 1,2-phenylenediboronic acid to afford dimeric B-spiroborate salts. Acidic untying of the spiroborates gave rise to the DATB ring system with various substituents.

Azo-tagged C4N4 fluorophores: unusual overcrowded structures and their application to fluorescent imaging.

The C4N4 fluorophore is an intense fluorescence emitter featuring a 2,5-diaminopyrimidine core comprising four carbon and four nitrogen atoms. A series of C4N4 derivatives was photochemically dimerized at the 5-amino group, furnishing overcrowded ortho-tetraaryl-substituted diaryl azo compounds with a characteristic skewed structure revealed by X-ray crystallography. The photoquenched azo-C4N4s are useful for fluorescently visualizing cells under hypoxic conditions.

Risk Factors for Cage Migration Following Lateral Lumbar Interbody Fusion Combined With Posterior Instrumentation: A Multicenter Retrospective Study of 983 Cases.

STUDY DESIGN: A multicenter retrospective study. OBJECTIVE: This study aimed to elucidate the incidence and risk factors of lateral cage migration (LCM) after lateral lumbar interbody fusion (LLIF) combined with posterior instrumentation. SUMMARY OF BACKGROUND DATA: LLIF has recently become a widely accepted procedure for the treatment of lumbar degenerative diseases. Although LLIF complications include vascular, nerve, and abdominal organ injuries, few studies have identified specific risk factors for LCM after LLIF. MATERIALS AND METHODS: Between January 2015 and December 2020, 983 patients with lumbar degenerative diseases or osteoporotic vertebral fractures underwent LLIF combined with posterior instrumentation. The fusion sites were located within the lumbosacral lesions. LCM was defined as a change of >3 mm in the movement of the radiopaque marker on radiographs. The patients were classified into LCM and non-LCM groups. Medical records and preoperative radiographs were also reviewed. The 1:5 nearest-neighbor propensity score matching technique was used to compare both groups, and radiologic parameters, including preoperative disk height (DH), preoperative sagittal disk angle, disk geometry, height variance (cage height minus DH), and endplate injury, were analyzed to identify the factors influencing LCM incidence. RESULTS: There were 16 patients (1.6%) with LCM (10 men and 6 women; mean age 70.1 yr). The Cochran-Armitage trend test showed a linear trend toward an increased rating of LCM with an increasing number of fused segments ( P =0.003), and LCM occurred at the terminal cage-inserted disk level in all patients in the LCM group. After propensity-matched analysis, we identified high DH ( P <0.001), large sagittal disk angle ( P =0.009), round-type disk ( P =0.008), and undersized cage selection ( P <0.001) as risk factors for LCM. CONCLUSION: We identified risk factors for LCM after LLIF combined with posterior instrumentation. To avoid this complication, it is important to select the appropriate cage sizes and enhance posterior fixation for at-risk patients.

Reoperation for Misplaced Pedicle Screws: A Multicenter Retrospective Study.

STUDY DESIGN: A multicenter retrospective analysis. OBJECTIVE: This study aims to investigate reoperation of misplaced pedicle screws (MPSs) after posterior spinal fusion (PSF), focusing on neurological complications. SUMMARY OF BACKGROUND DATA: The management strategy for MPSs and the clinical results after reoperation are poorly defined. MATERIALS AND METHODS: Subjects were 10,754 patients (73,777 pedicle screws) who underwent PSF at 11 hospitals over 15 years. The total number of reoperations for MPS and patient clinical data were obtained from medical records at each hospital. RESULTS: The rate of reoperation for screw misplacement per screw was 0.17%. A total of 69 patients (mean age, 67.4±16.5 yr) underwent reoperation because of 82 MPS. Reasons for reoperation were neurological symptoms (58 patients), contact with vessels (5), suboptimal bone purchase (4), and misplacement recognized during operation (2). Neurological symptoms were the major reason for reoperation in cervical (5/5 screws, 100%) and lumbo-sacral (60/67 screws, 89.6%) regions. Contact with vessels was the major reason for reoperation in the thoracic spine (6/10 screws, 60.0%). We further evaluated 60 MPSs in the lumbo-sacrum necessitating reoperation because of neurological symptoms. The majority of MPSs necessitating reoperation were placed in the lower lumbar spine (43/60 screws, 71.7%). The mean pedicle breach tended to be larger in the incomplete recovery group than in the complete recovery group (6.8±2.4 vs . 5.9±2.2 mm, P =0.146), and the cutoff value resulting in incomplete resolution was 5.0 mm. Multivariate analysis revealed that medial-caudal breaches ( vs . medial breach, odds ratio: 25.8, 95% confidence interval: 2.58-258, P =0.0057) and sensory and motor disturbances ( vs . sensory only, odds ratio: 8.57, 95% confidence interval: 1.30-56.6, P =0.026) were significant factors for incomplete resolution of neurological symptoms. CONCLUSIONS: After reoperation, 70.1% of the patients achieved complete resolution of neurological symptoms. Factors associated with residual neurological symptoms included sensory and motor disturbance, medial-caudal breach, and larger pedicle breach (>5 mm).

Neurological severity evaluation using magnetic resonance imaging in acute spontaneous spinal epidural haematomas.

PURPOSE: This study aimed to elucidate the severity of neurological deficits in a large series of patients with acute spontaneous spinal epidural haematoma (SSEH) using magnetic resonance imaging (MRI). METHODS: We included 57 patients treated for acute SSEH at 11 institutions and retrospectively analysed their demographic and MRI data upon admission. We investigated MRI findings, such as the haematoma length and canal occupation ratio (COR). The neurological severity of SSEH was assessed based on the American Spinal Injury Association score on admission. RESULTS: Of the 57 patients, 35 (61%) presented with severe paralysis. The MRI analysis showed that SSEH was often located in the cervical spine, dorsal to the spinal cord, and spread over more than three vertebrae. No differences in age, sex, and aetiology were found between patients with and without severe paralysis. The hypo-intensity layer encircling the haematoma, intra-haematoma heterogeneity, and increased CORs were observed more frequently in the severe paralysis group. Furthermore, pathological examination of a dissected haematoma from one patient with a hypo-intensity layer revealed a collagen layer around the haematoma, and patients with intra-haematoma heterogeneity were more likely to have a bleeding predisposition. CONCLUSIONS: In this large series of patients with SSEH, we identified some MRI features associated with severe paralysis, such as the hypo-intensity layer, intra-haematoma heterogeneity, and increased COR. Accordingly, patients with these MRI characteristics should be considered for early surgical intervention.

Pediatric pathological subtrochanteric fracture treated with an adult proximal humerus polyaxial locking plate: A case report.

Pediatric subtrochanteric fractures are relatively rare. There are some surgical options with various plate techniques. Here, we report the first description of a pediatric pathological subtrochanteric fracture treated with an adult proximal humerus polyaxial locking plate and describe the good clinical outcomes achieved. A 10-year-old boy had a pathological subtrochanteric fracture. A non-contact bridging proximal humerus osteosynthesis plate was used. Although this is designed for the adult proximal humerus, its size and shape were considered to fit the pediatric proximal femur. In addition, this is a polyaxial locking plate with a choice of screw insertion directions. During surgery, it was possible to determine an appropriate plate installation position and screw direction in consideration of the location of pathological lesions, the bone shape, and the femoral neck angle. Twelve months postoperatively, the fracture was healed, and pathological lesion consolidated without obvious growth failure.

Use of Insoluble Dietary Fiber and Probiotics for Bowel Preparation Before Colonoscopy: A Prospective Study.

BACKGROUND: In screening colonoscopy, patients usually have to ingest large amounts of bowel-cleansing agents, including polyethylene glycol (PEG). This is difficult and has various side effects; thus, patients avoid undergoing a colonoscopy. We tested a novel bowel preparation method before colonoscopy using insoluble dietary fiber and probiotics (PB). METHODS: This was a prospective clinical study conducted between October 2018 and March 2019 at a general hospital. Forty participants were randomly assigned to low-volume PEG solution diet (MoviPrep), wheat bran fiber (WBF) and probiotic Bifidobacterium animalis subsp. lactis GCL2505 (PB GCL2505), or standard-volume regimen (1.0 to 1.5 L of MoviPrep) (control group). The patient compliance and the quality of bowel preparation were evaluated. RESULTS: Forty individuals aged 38 to 83 years were randomly assigned to the WBF with PB (n=20) and control (n=20) groups. All participants underwent bowel preparation before colonoscopy according to each protocol. The mean required volume of MoviPrep was significantly lower in the WBF with PB group than in the control group (582.5 vs. 1305 mL, P<0.0001). Successful bowel-cleansing rates were not significantly different between the 2 groups; however, the ratio of the Harefield Cleansing Scale grades C and D was significantly lower in the WBF with PB group than in the control group (P=0.0471). CONCLUSIONS: The intake of WBF and GCL2505 before colonoscopy reduces the required PEG quantities while maintaining bowel-cleansing quality. This novel, minimally invasive pretreatment method makes colonoscopy more accessible contributing to the prevention and early treatment of colorectal cancer.

Histomorphological investigation of intrahepatic connective tissue for surgical anatomy based on modern computer imaging analysis.

BACKGROUND/PURPOSE: Computer-assisted tissue imaging and analytical techniques were used to clarify the histomorphological structure of hepatic connective tissue as a practical guide for surgeons. METHODS: Approximately 5000 histological slides were prepared from liver specimens of five autopsied patients. Three-dimensional (3D) reconstruction was performed and subjected to computer imaging analysis. Scanning electron microscopy was also performed on the liver specimens. RESULTS: The 3D reconstructed images revealed the running form of the vasculature and the relationship between the hepatic lobule and connective tissue. The hepatic capsule or portal pedicle was consistently located at the periphery of the hepatic lobules. An artificial intelligence random forest approach clearly segmented hepatic cells, type I collagen (CF), type III collagen (RF), and other cells. The hepatic lobule, portal region, and hepatic capsule were significantly distinguished based on CF and RF occupancy. The capsule directly covering the liver lobule with an RF concentration up to 87% was provisionally named the proper hepatic capsule. The existence of a proper hepatic ligament with distinct occupation rates of CF and RF was also suggested. CONCLUSIONS: The identified proper hepatic capsule and ligament can be important markers for demarcating the dissecting layer during surgical procedures.

Enantioselective Epoxidation of 2,3-Disubstituted Naphthoquinones by a Side Chain Truncated Guanidine-Urea Bifunctional Organocatalyst.

An organocatalytic enantioselective epoxidation of 2,3-disubstituted naphthoquinones with tert-butyl hydroperoxide as an oxidant was developed using a guanidine-urea bifunctional catalyst lacking C2 symmetry, which was designed based upon the insights obtained from the DFT calculation model for our previous C2 symmetric catalyst. The present organocatalytic reaction provides access to a variety of optically active naphthoquinone epoxides bearing aryl and methyl substituents at C2 and C3 in high yields with high enantioselectivities (up to 97:3 er).

Arylation of aryllithiums with S-arylphenothiazinium ions for biaryl synthesis.

Aryllithiums are one of the most common and important aryl nucleophiles; nevertheless, methods for arylation of aryllithums to produce biaryls have been limited. Herein, we report arylation of aryllithiums with S-arylphenothiazinium ions through selective ligand coupling of intermediary sulfuranes. Various unsymmetrical biaryls could be obtained without transition-metal catalysis.

Differential effects of thyrotropin releasing hormone (TRH) on motor execution and motor adaptation process in patients with spinocerebellar degeneration.

BACKGROUND: The cerebellum is known to play a crucial role in sensori-motor adaptation, which includes the prism adaptation. TRH has been widely used as a treatment for cerebellar ataxia in Japan, however effects of TRH on cerebellar adaptation process have not been studied. Here, we studied effects of TRH treatment on the prism adaptation task. METHODS: Eighteen spinocerebellar degeneration (SCD) patients participated in this study. The participants received intravenous injection of 2 mg/day protirelin tartrate once a day for 14 days. In the prism adaptation task, the participants reached to the target on the screen wearing wedge prisms. We compared the Scale for Assessment and Rating of Ataxia (SARA), baseline errors and the aftereffect (AE) of the prism adaptation task between before and after TRH therapy. RESULTS: TRH therapy improved SARA significantly (p = .005). Multiple regression analysis revealed that improvement of SARA score was mainly due to improvement of "Stance" category score. TRH decreased baseline errors of the prism adaptation task (p = .021), while unaffected AEs (p = .252). CONCLUSION: TRH differentially affected clinical cerebellar ataxia including baseline reaching performance in the prism adaptation task, whereas TRH did not affect the learning process of prism adaptation. Different cerebellar functional aspects may underlie the learning process of sensori-motor adaptation and simple motor execution (clinically evaluated cerebellar ataxia).

A Novel Non-Gas Endospray for Applying Fibrin Glue in Laparoscopic Surgery.

Purpose: Fibrin glue and polyglycolic acid felt are used for tissue repair in various surgical procedures. However, using a spray device to apply fibrin sealant during laparoscopic surgery can increase the intraperitoneal pressure, which can cause complications such as air embolism. We developed a novel non-gas endospray for use in laparoscopic surgery. This study aimed to evaluate the sealing effect of this non-gas endospray in comparison with a conventional gas-spray device and to evaluate the safety of its application in the clinical setting. Materials and Methods: An ex vivo pressure test model was used to assess the sealing effect of the non-gas endospray (method 1) versus conventional gas-spray (method 2). A bottle was sealed with a rabbit skin sample that had been pierced nine times by a 19G needle. Each skin sample was sealed using either method 1 or method 2 (n = 10 for each method). The non-gas endospray was then used in two patients undergoing laparoscopic splenectomy with CO2 pneumoperitoneum. Intra-abdominal pressure was measured throughout the surgery. Results: Bursting pressures were similar in method 1 (246.9 ± 123.2 mmHg) and method 2 (265.5 ± 93.6 mmHg; P = 0.7082). During laparoscopic splenectomy, the non-gas endospray was successfully used to apply fibrin glue without any increase in intra-abdominal pressure. Conclusions: The novel non-gas endospray produced a strong sealing effect similar to that of a conventional gas-spray device and has thus far proved feasible in the clinical setting.

Plasticity induction in the pre-supplementary motor area (pre-SMA) and SMA-proper differentially affects visuomotor sequence learning.

BACKGROUND: Both pre-supplementary motor area (pre-SMA) and SMA-proper (SMA) must play important roles in visuomotor sequence learning. However, functional differences between the pre-SMA and SMA have not been well studied in humans. OBJECTIVE: To elucidate the functional differences between the pre-SMA and SMA in sequence learning in humans. METHODS: To induce LTP/LTD, we administered quadripulse transcranial magnetic stimulation (QPS) with an inter-stimulus interval of 5 or 50 ms (QPS-5/50) over the pre-SMA or SMA in healthy volunteers. The sham stimulation was also done as a control. We studied the effects of LTP/LTD in the pre-SMA/SMA on a new sequence learning and the performance of well-learned sequence by using sequence learning task called the "2 × 10 task". Effects on the simple choice reaction time task were also studied for comparison. RESULTS: QPS-5 over the pre-SMA increased the error rate without any changes in movement speed. When administered over the SMA, QPS-5 decreased, and QPS-50 increased the rate of reaction time reduction across trials without changes in the error rate. QPS over neither the pre-SMA nor SMA affected the performances of a well-learned sequence or a simple choice reaction time task. CONCLUSIONS: Our findings that QPS over the pre-SMA correlated with sequence learning performance and that over the SMA with execution speed are consistent with the previous results in animals and humans. Our results lend further support to the utility of QPS for modulating motor learning in humans.

Effects of L-DOPA on quadripulse magnetic stimulation-induced long-term potentiation in older adults.

Reduced cortical plasticity has been previously reported in older adult as compared with young adults. However, the effects of dopamine on this plasticity reduction remain unknown. Here, we assessed the effects of high-dose (200 mg) and medium-dose (100 mg) L-3,4-dihydroxyphenylalanine (L-DOPA) intake on the long-term potentiation (LTP)-like effect induced by quadripulse magnetic stimulation (QPS) in older adults (aged ∼65 years). The subjects were 32 (200 mg) and 20 (100 mg) healthy older adult volunteers. This study was designed as a double-blind, crossover and placebo-controlled trial on one dose of L-dopa. Two hours after taking L-DOPA or placebo-drug, QPS was applied over the motor cortex. Motor evoked potentials were recorded to evaluate the motor cortical excitability changes. We found that both doses of L-DOPA enhanced LTP after QPS in older adults as one group. We classified subjects into QPS responders and QPS nonresponders. Both L-DOPA doses produced significant LTP enhancement in QPS nonresponders, whereas either of doses did not produce significant LTP enhancement in QPS responders. Collectively, our findings suggest that the neural plasticity reductions observed in older adults could be partly improved by dopamine.

Successful use of flexible silicone mesh for management of prolonged open abdomen.

BACKGROUND: Open abdomen management (OAM) is used not only for trauma but also for treatment of peritonitis. However, the rate of successful fascial closure in patients with OAM remains low. CASE PRESENTATION: The patient was a 38-year-old morbidly obese man who underwent laparoscopic sleeve gastrectomy. Twenty days after surgery, postoperative leakage resulted in panperitonitis. In this case, we undertook drainage by open laparotomy. The patient's status was generally unstable and he was treated with OAM. We used flexible silicone mesh as the dressing material for negative-pressure wound therapy. Open abdominal management continued until status improvement (32 days). Fascial closure was eventually successful because of good granulation growth. CONCLUSION: When combined with negative-pressure wound therapy, silicone mesh prevents wound adhesions and infection after surgery. Silicone mesh is useful for patients with increased risk of infection, such as those with diffuse peritonitis.

The evolution of surgical treatment for gastrointestinal cancers.

INTRODUCTION: According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. MATERIALS AND METHODS, AND RESULTS: Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. CONCLUSION: We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival.

Increased facilitation of the primary motor cortex in de novo Parkinson's disease.

INTRODUCTION: Paired-pulse transcranial magnetic stimulation (TMS) is useful to estimate the balance between inhibitory and facilitatory circuits of the primary motor cortex (M1) in Parkinson's disease (PD). Results of earlier studies are, however, incongruent: some reports describe normal short-interval intracortical inhibition (SICI), but others describe reduced SICI. We hypothesize that exaggerated intracortical facilitation masks normal inhibition, and that a triple-pulse method can reveal masked inhibition in PD. METHODS: Ten PD patients who had not been exposed to dopaminergic medications were enrolled. Results were compared with those obtained from 10 age-matched healthy volunteers. We measured TMS-elicited motor evoked potential (MEP) as an index of M1 excitability. We tested SICI, intracortical facilitation (ICF), and short-interval intracortical facilitation (SICF), which has three distinct facilitatory peaks, using the paired-pulse TMS paradigm. A triple-pulse protocol, SICI + SICF, was investigated as described in our earlier study. This protocol examined SICF in the presence of SICI, thereby allowing our test of true inhibitory influence on a specific component of MEP-generating mechanism known as I3 wave. RESULTS: In PD patients, SICI estimated using the conventional method was decreased, whereas SICF was enhanced around its second peak out of the three. Results for SICI + SICF were comparable between PD patients and healthy controls, suggesting normal inhibition of I3 waves in PD patients. CONCLUSION: We confirmed the SICF enhancement in drug naïve PD patients. We propose that I3 wave inhibition by a subthreshold pulse shown by SICI paradigm is unaffected in PD. The triple-pulse method can reveal masked inhibition.

Efficacy of Novel Multispectral Imaging Device to Determine Anastomosis for Esophagogastrostomy.

BACKGROUND: Biomedical imaging devices that utilize the optical characteristics of hemoglobin (Hb) have become widespread. In the field of gastroenterology, there is a strong demand for devices that can apply this technique to surgical navigation. We aimed to introduce our novel multispectral device capable of intraoperatively performing quantitative imaging of the oxygen (O2) saturation and Hb amount of tissues noninvasively and in real time, and to examine its application for deciding the appropriate anastomosis point after subtotal or total esophagectomy. MATERIALS AND METHODS: A total of 39 patients with esophageal cancer were studied. Tissue O2 saturation and Hb amount of the gastric tube just before esophagogastric anastomosis were evaluated using a multispectral tissue quantitative imaging device. The anastomosis point was decided depending on the quantitative values and patterns of both the tissue O2 saturation and Hb amount. RESULTS: The device can instantaneously and noninvasively quantify and visualize the tissue O2 saturation and Hb amount using reflected light. The tissue Hb status could be classified into the following four types: good circulation type, congestion type, ischemia type, and mixed type of congestion and ischemia. Postoperative anastomotic failure occurred in 2 cases, and both were mixed cases. CONCLUSIONS: The method of quantitatively imaging the tissue O2 saturation and Hb level in real time and noninvasively using a multispectral device allows instantaneous determination of the anastomosis and related organ conditions, thereby contributing to determining the appropriate treatment direction.

Catalysis Based on C-I⋠⋠⋠π Halogen Bonds: Electrophilic Activation of 2-Alkenylindoles by Cationic Halogen-Bond Donors for [4+2] Cycloadditions.

Homo- and cross-[4+2] cycloadditions of 2-alkenylindoles, catalyzed by cationic halogen-bond donors, were developed. Under mild reaction conditions, 3-indolyl-substituted tetrahydrocarbazole derivatives were obtained in good to excellent yields. Experimental and quantum calculation studies revealed that the electrophilic activation of 2-alkenylindoles was achieved by C-I⋅⋅⋅π halogen bonds.

Diastereoselective Synthesis of CF3-Substituted Spiroisochromans by [1,5]-Hydride Shift/Cyclization/Intramolecular Friedel-Crafts Reaction Sequence.

Developed herein is a diastereoselective synthesis of CF3-substituted spiroisochromans via C(sp3)-H bond functionalization involving sequential transformations ([1,5]-hydride shift/cyclization/elimination of MeOH/intramolecular Friedel-Crafts reaction).