Bio-inspired asymmetric aldehyde arylations catalyzed by rhodium-cyclodextrin self-inclusion complexes.

Transition-metal catalysts are powerful tools for carbon-carbon bond-forming reactions that are difficult to achieve using native enzymes. Enzymes that exhibit inherent selectivities and reactivities through host-guest interactions have inspired widespread interest in incorporating enzymatic behavior into transition-metal catalytic systems that highly efficiently produce enantiopure compounds. Nevertheless, bio-inspired transition-metal catalysts that are highly enantioselective and reactive have rarely been reported. In this study, we applied γ-cyclodextrin-imidazolium salts to the rhodium-catalyzed asymmetric arylations of aldehydes. The method exhibits wide substrate scope and the corresponding arylcarbinols are obtained in excellent yields under optimized conditions, with enantiomeric excesses of up to 96% observed. Kinetic and competition experiments revealed that self-inclusion of the Rh complex contributes to the high enantioselectivity and reactivity achieved by this catalytic system. Thus, this bio-inspired self-inclusion strategy is promising for the development of highly enantioselective and reactive transition-metal catalysts for asymmetric carbon-carbon bond formation.

Magnetic anchor-guided endoscopic submucosal dissection for colorectal tumors (with video).

BACKGROUND: The feasibility of magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD) using a neodymium magnet for colorectal tumors has not been evaluated. The aim of this study was to clarify the feasibility of MAG-ESD for colorectal tumors. METHODS: This prospective trial was conducted at Yamashita Hospital. MAG-ESD was performed for 49 colorectal tumors. The magnetic anchor comprised an internal magnet attached to an endoclip with 3-0 silk. Both external and internal magnets were made using neodymium magnets. The feasibility of traction achieved using MAG-ESD, en bloc resection rate, complete en bloc resection rate, time required for preparation and attachment of the magnetic anchor, procedure time, rate of retrieval of magnetic anchors, and adverse events were evaluated. RESULTS: MAG-ESDs were successfully performed for 48 colorectal tumors except for a rectal case in which the internal magnet stuck to the endoscope. En bloc resections and complete en bloc resections were achieved in all cases. Attaching the magnetic anchor required a median of 8 min (range 3-37 min). Median procedure time was 76 min (range 28-283 min) and the magnetic anchors were retrieved in all cases without adverse events. CONCLUSION: MAG-ESD is feasible and safe in the colon and may facilitate the treatment of all difficult lesions. (UMIN000024100).

α1D-Adrenoceptor blockade increases voiding efficiency by improving external urethral sphincter activity in rats with spinal cord injury.

Ideal therapy for lower urinary tract dysfunction in patients with spinal cord injury (SCI) should decrease detrusor overactivity, thereby promoting urine storage at low intravesical pressure and promoting efficient voiding at low pressure by decreasing detrusor-sphincter dyssynergia. Here we investigated blockade of various α-adrenoceptors to determine the subtype that was principally responsible for improving the voiding dysfunction. The effects of the intravenous α-blocker naftopidil, the α-blocker BMY 7378, and the α-blocker silodosin were evaluated using cystometrography and external urethral sphincter-electromyography (EMG) in decerebrated, unanesthetized female Sprague-Dawley rats with chronic SCI following transection at Th8. Parameters measured included the voided volume, residual volume, voiding efficiency, and burst and silent periods on EMG. Compared with values in decerebrated non-SCI rats, EMG of decerebrated SCI rats revealed more prominent tonic activity, significantly shorter periods of bursting activity, and a reduced ratio of the silent to active period during bursting. Compared with the value before drug administration (control), the voiding efficiency was significantly increased by naftopidil (1 and 3 mg/kg) (<0.05 each), and the burst (<0.01 and <0.05, respectively) and silent periods (<0.01 each) on EMG were significantly lengthened. BMY 7378 (1 mg/kg) significantly increased voiding efficiency and lengthened the burst periods (<0.05 each). Silodosin did not affect any parameters. These results suggest that α-blockade reduces the urethral resistance associated with detrusor-sphincter dyssynergia, thus improving voiding efficiency in SCI rats.

Conventional Humeral Retroversion Measurements Using Computed Tomography Slices or Ultrasound Images Are Not Correlated With the 3-Dimensional Humeral Retroversion Angle.

BACKGROUND: Humeral retroversion angles determined by previous techniques are varied and/or biased by morphologic variations of the proximal and distal humerus, and their validity should be revisited. To overcome the limitations of previous studies associated with 2-dimensional (2D) images and the reference axes, a 3-dimensional (3D) measurement of humeral retroversion is required. However, comparisons of 2D imaging methods with the 3D computed tomography (CT) measurement as a reference standard have not been heretofore performed. PURPOSE: To determine whether the 3D CT humeral retroversion angle in baseball players is correlated with conventional humeral retroversion measurements. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: A total of 28 humeri from 14 male baseball players were used for measuring humeral retroversion. Participants underwent CT scans, and geometric bone models were created for measuring the 3D CT humeral retroversion angle. Using CT slices, the 2D CT humeral retroversion angle was also determined. Bicipital forearm angle was assessed using the indirect ultrasound technique. Linear regressions and Bland-Altman plots were used to determine whether there were agreements among 3 variables: the 3D CT retroversion, 2D CT retroversion, and bicipital forearm angles. RESULTS: In linear regression analyses, the 3D humeral retroversion angle was not predicted by the 2D CT retroversion (R = 0.167, R (2) = 0.028, P = .395) or the bicipital forearm angle (R = 0.049, R (2) = 0.002, P = .805). The bias of these 2 methods was 20.9° and -15.3°, respectively. Regression analysis demonstrated that the bicipital forearm angle was a significant predictor of the 2D CT retroversion angle (R = 0.632, R (2) = 0.400, P < .001). CONCLUSION: The 3D CT humeral retroversion angle was found to be underestimated by the 2D CT retroversion angle and overestimated by the bicipital forearm angle obtained by the indirect ultrasound, although a previously observed relationship between the 2D CT retroversion and bicipital forearm angles was confirmed. CLINICAL RELEVANCE: Precise measurement of humeral retroversion angle is important because retroversion has been linked to upper extremity disorders, including throwing-related shoulder and elbow disorders in baseball players.

Scapular Kinematics During Late Cocking of a Simulated Throwing Activity in Baseball Players With Shoulder Injury: A Cross-Sectional Study Using a 3D-to-2D Registration Technique.

CONTEXT: Abnormal scapular kinematics during throwing motion in baseball players with shoulder disorders has not yet been clarified, although altered scapular position has been suggested to be associated with shoulder disorder. OBJECTIVE: To determine if the shoulders of baseball players with throwing disorders demonstrate abnormal scapular kinematics during the simulated arm-cocking phase of throwing activity. DESIGN: Cross-sectional study. SETTING: Laboratory. PARTICIPANTS: Eleven baseball players (age 21.1 ± 1.2 y) with a unilateral shoulder disorder volunteered to participate, including 9 players at the college level and 2 at the adult level. The mean playing experience was 12.1 ± 2.7 y. MAIN OUTCOME MEASURES: Scapular upward/downward rotation, anteroposterior tilting, and external/internal rotation during simulated arm-cocking motion were analyzed using a 3-to-2-dimensional registration technique. RESULTS: Scapular external rotation in the throwing shoulder was significantly smaller by 2.0-6.0° than that of the contralateral shoulder. There were no detectable differences in scapular upward/downward rotation or anteroposterior tilting between the throwing and contralateral shoulders. CONCLUSIONS: Compared with that in the contralateral shoulder, scapular external rotation was smaller in the throwing shoulder, which would increase glenohumeral horizontal abduction during the arm-cocking phase and be related to the throwing-shoulder disorder.

Reliability and validity in measurement of true humeral retroversion by a three-dimensional cylinder fitting method.

HYPOTHESIS AND BACKGROUND: Humeral retroversion is defined as the orientation of the humeral head relative to the distal humerus. Because none of the previous methods used to measure humeral retroversion strictly follow this definition, values obtained by these techniques vary and may be biased by morphologic variations of the humerus. The purpose of this study was 2-fold: to validate a method to define the axis of the distal humerus with a virtual cylinder and to establish the reliability of 3-dimensional (3D) measurement of humeral retroversion by this cylinder fitting method. METHODS: Humeral retroversion in 14 baseball players (28 humeri) was measured by the 3D cylinder fitting method. The root mean square error was calculated to compare values obtained by a single tester and by 2 different testers using the embedded coordinate system. To establish the reliability, intraclass correlation coefficient (ICC) and precision (standard error of measurement [SEM]) were calculated. RESULTS: The root mean square errors for the humeral coordinate system were <1.0 mm/1.0° for comparison of all translations/rotations obtained by a single tester and <1.0 mm/2.0° for comparison obtained by 2 different testers. Assessment of reliability and precision of the 3D measurement of retroversion yielded an intratester ICC of 0.99 (SEM, 1.0°) and intertester ICC of 0.96 (SEM, 2.8°). DISCUSSION AND CONCLUSION: The error in measurements obtained by a distal humerus cylinder fitting method was small enough not to affect retroversion measurement. The 3D measurement of retroversion by this method provides excellent intratester and intertester reliability.

Neutron diffraction of ice in hydrogels.

Neutron diffraction patterns for deuterated poly-N,N,-dimethylacrylamide (PDMAA) hydrogels were measured from 10 to 300 K to investigate the structure and properties of water in the gels. Diffraction peaks observed below 250 K indicate the existence of ice in the hydrogels. Some diffraction peaks from the ice are at lower diffraction angles than those in ordinary hexagonal ice (Ih). These shifts in peaks indicate that the lattice constants of the a and c axes in the ice are about 0.29 and 0.3% higher than those in ice Ih, respectively. The results show that bulk low-density ice can exist in PDMAA hydrogels. The distortions in the lattice structure of ice imply significant interactions between water molecules and the surrounding polymer chains, which play an important role in the chemical and mechanical properties of the hydrogel.

Age-related requisite concentration of sevoflurane for adequate sedation with combined epidural-general anesthesia.

BACKGROUND: The requisite anesthetic concentration of sevoflurane required to obtain adequate sedation when sufficient analgesics are supplied has not been determined. The purpose of this study was to determine the requisite age-associated concentration of sevoflurane to obtain an adequate level of anesthesia during combined epidural-general anesthesia by bispectral index (BIS) monitoring. METHODS: Twenty-seven elective abdominal surgery patients (American Society of Anesthesiologists physical status I-II) were enrolled. The patients were divided into two groups of more or less than 60 years of age. We investigated the concentration of sevoflurane required to obtain an adequate sedation level during combined epidural-general anesthesia, maintaining the BIS value between 40 and 60. RESULTS: The requisite sevoflurane concentration required to keep the BIS value at 40-60 was not stable during surgery. In the younger group, the maximum concentration of sevoflurane needed during surgery was 1.95 ± 0.14 (95% confidence interval: 1.87-2.10) vol%, while it was 1.54 ± 0.44 (95% confidence interval: 1.27-1.80) vol% in the older group (P < 0.01). CONCLUSIONS: The requisite concentration of sevoflurane required with combined epidural-general anesthesia was 2.5 vol% for the younger group and 2.0 vol% for the older group as determined by BIS monitoring. We believe that these percentages are sufficient to avoid awareness during surgery with adequate analgesia.

Antimuscarinics suppress adenosine triphosphate and prostaglandin E2 release from urothelium with potential improvement in detrusor overactivity in rats with cerebral infarction.

PURPOSE: Antimuscarinics improve detrusor overactivity. We evaluated the effects and action mechanisms of imidafenacin (Kyorin Pharmaceutical, Tokyo, Japan), a novel therapeutic agent for overactive bladder with antimuscarinic activity, on mediator release from urothelium and detrusor overactivity induced by cerebral infarction. MATERIALS AND METHODS: Bladder hydrodistention was achieved by intravesical infusion of Krebs solution. Bladder adenosine triphosphate and prostaglandin E(2) were measured in the presence and absence of anticholinergics using luciferin-luciferase assay and enzyme-linked immunoassay, respectively. Cerebral infarction was induced in rats by occluding the left middle cerebral artery. The effects of intravenous imidafenacin on bladder function were examined using cystometry in rats with cerebral infarction and in those pretreated with resiniferatoxin. RESULTS: Increased intravesical adenosine triphosphate and prostaglandin E(2) were shown by induced distention of isolated rat bladders. Imidafenacin and darifenacin (Kemprotec, Middlesbrough, United Kingdom) significantly suppressed the increases in adenosine triphosphate and prostaglandin E(2). Decreased bladder capacity was observed in rats with cerebral infarction. Detrusor overactivity was suppressed with a minimum intravenous dose of 0.001 mg/kg imidafenacin. The effects of imidafenacin were not noted in rats pretreated with resiniferatoxin. CONCLUSIONS: Results support the hypothesis or suggest that imidafenacin improves cerebral infarction induced detrusor overactivity by suppressing peripheral C-fibers. This effect is thought to be associated with suppression of the release of adenosine triphosphate and prostaglandin E(2) from the urothelium.

Urethral Sensations are Related to the Development of Detrusor Overactivity.

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. Clinical findings have led to the assumption that bladder outlet obstruction (BOO) caused by benign prostatic enlargement (BPE) induces storage symptoms and detrusor overactivity. Presumably, BOO by BPE accounts for urgency; however, urgency is not always caused by BOO. Sensory nerves in the wall of the urethra fire in response to urethral fluid flow, and this activity initiates bladder contractions in the quiescent bladder and augments ongoing contractions in the active bladder. In humans, prostatic urethral anesthesia results in significant increases in bladder capacity among BPH patients without neurological diseases, therefore sensory stimuli from an anatomically altered prostatic urethra has the possibility to induce urgency and detrusor overactivity. Studies in animals demonstrate the basis for an excitatory urethra to bladder reflex. Urethral stimulation by prostaglandin E2 induces an excitatory effect on micturition reflex by activation of C-fiber afferent nerves. α1A -adrenoceptor blocker has an inhibitory effect on the micturition reflex, suggesting excitatory urethra to bladder reflex is mediated by α1A -adrenoceptor. Even if there is no obstruction, increase in urethral sensory due to BPE may induce the development of the detrusor overactivity.

Intrinsic microwave dielectric loss of lanthanum aluminate.

The intrinsic dielectric properties of LaAlO3 were investigated to understand the microwave properties of several materials containing LaAlO3. In this study, LaAlO3 single crystals were prepared by the Czochralski method. The temperature dependence of the dielectric properties and neutron inelastic scattering of the single crystals were measured. From these data, the intrinsic dielectric properties were evaluated and it was found that the dielectric loss of the LaAlO3 includes two types of dielectric loss. One is a phonon absorption-related loss and the other is a component of the loss arising from Debye- type orientation polarization. The latter affects the room temperature dielectric loss in materials containing LaAlO3. The present study suggests that avoiding this polarization loss is an important goal in decreasing the total dielectric loss.

[Preparation before anesthesia for patients with myasthenia gravis].

Myasthenia gravis (MG) is an autoimmune disease resulting from the production of antibodies against the acetylcholine receptors of the neuromuscular synapse, and is the disease characterized by weakness and fatigability of the skeletal muscle, with improvement following rest. Adequate preoperative evaluation of the MG patients must be carried out. Especially, the preoperative evaluation of respiratory muscle strength is very important. Although several general anesthetic techniques have been proposed, none has been proven to be superior to the others. It is necessary to evaluate anesthetic management of MG patients according to the severity of the individual patient. But the use of regional anesthesia seems to be warranted whenever possible. Based on the preoperative severity, operative procedure and perioperative management, extubation should be carried out carefully in all MG patients. MG is a disease with many pitfalls in the safe administration of anesthesia.

[Anesthesia preoperative preparation of muscular dystrophy].

The muscular dystrophies are inherited myogenic disorders characterized by progressive muscle wasting and weakness of variable distribution and severity. They can be subdivided into several groups, including congenital forms, in accordance with the distribution of predominant muscle weakness: Duchenne/Becker; limb-girdle; Fukuyama type congenital muscular dystrophy; Emery-Dreifus; facioscapulohumeral; oculopharyngeal; myotonic dystrophy, et al. Muscular dystrophies are susceptible to perioperative respiratory, cardiac and other complications, such as rhabdomyolysis. Halogenated inhalational anesthetic agents have been implicated as a cause of acute rhabdomyolysis that resembles malignant hyperthermia. Depolarizing neuromuscular blocking drugs that cause rhabdomyolysis are contraindicated in these patients. Recommendations are proposed for the safe anesthetic management of these patients.

Urinary prostaglandin E2 was increased in patients with suprapontine brain diseases, and associated with overactive bladder syndrome.

OBJECTIVE: To investigate the association between the urinary levels of prostaglandins (PGE(2) and PGF(2α)), nerve growth factor (NGF) and substance P, and overactive bladder (OAB) symptoms in patients with suprapontine brain diseases. MATERIALS AND METHODS: The subjects were 114 patients in the chronic phase of a brain disease and 27 healthy controls with no brain disease or lower urinary tract symptoms (LUTS). The OAB symptoms were assessed with the OAB symptom score and the subjects were then classified into 5 groups: healthy control, patients without LUTS, increased bladder sensation (IBS), OAB dry, and OAB wet. Urinary mediator concentrations were measured using enzyme-linked immunosorbent assay and normalized to the urinary creatinine concentration, and then compared among the 5 groups. RESULTS: The urinary PGE(2) level was significantly higher in patients with brain diseases than in healthy controls, even in the patients without any OAB symptoms, and compared with patients without LUTS, a significant increase in the urinary PGE(2) was observed in patients with OAB dry or wet (P = .004 or .015, respectively). The PGF(2α) level showed a significant increase in OAB wet compared with patients without LUTS (P = .001). The urinary levels of NGF and substance P were not significantly associated with OAB as a result of this type of brain disease. CONCLUSION: The urinary PGE(2) level was putatively elevated in patients with suprapontine brain diseases and associated with the presence of OAB. The PGF(2α) level may also be associated with OAB.

Observation of hydrogen in deuterated methane hydrate by maximum entropy method with neutron powder diffraction.

The crystal structure of deuterated methane hydrate (structure I, space group: Pm(-)3n) was investigated by neutron powder diffraction at temperatures of 7.7-185 K. The scattering amplitude density distribution was examined by a combination of Rietveld method and maximum entropy method (MEM). The distribution of the D atoms in both D(2)O and CD(4) molecules was clarified from three-dimensional graphic images of the scattering amplitude density. The MEM results showed that there were low-density sites for the D atom of D(2)O in a particular location within the D(2)O cage at low temperatures. The MEM provided more reasonable results because of the decrease in the R factor that is attainable by this method. Accordingly, the low-density sites for the D atom of D(2)O probably exist within the D(2)O cage. This suggests that a spatial disorder of the D atom of D(2)O occurs at these sites and that hydrogen bonds between D(2)O molecules become partially weakened. With regard to the CD(4) molecules, there were high-density sites for the D atom of CD(4), and the density distribution of the C and D atoms was observed separately in the scattering amplitude density image. Consequently, the C-D bonds of CD(4) were not observed clearly because the CD(4) molecules had an orientational disorder. The D atoms of CD(4) were displaced from the line between the C and O atoms, and were located near the face center of the polygon in the cage. Accordingly, the D atoms of CD(4) were not bonded to specific O atoms. This result is consistent with the hydrophobicity of the CD(4) molecule. We also report the difference between the small and the large cages in the density distribution map and the temperature dependence of the scattering amplitude density.

[A case of primary urothelial carcinoma of the prostate].

A 42-year-old male diagnosed with primary urothelial carcinoma of the prostate (T4NOM0) underwent pelvic exenteration, and lymph node dissection. Two courses of systemic chemotherapy (gemcitabine and carboplatin) were performed. This patient is alive without any evidence of tumor recurrence at 6 months after surgery.