The reaction of 2,5-cyclohexadienones with methylene-tethered allenylsilane in the presence of Lewis or Brønsted acids leads to a cascade of intramolecular cyclization, yielding stereoselective tricyclic fused 6-5-4 carbocycles featuring a silyl-methylenecyclobutane ring. This transformation is notable for the diastereoselective asymmetric desymmetrization of prochiral dienones, attributed to the axial chirality of allene.
BACKGROUND AND OBJECTIVES: A threshold fluence for melanosome disruption has the potential to provide a robust numerical indicator for establishing clinical endpoints for pigmented lesion treatment using a picosecond laser. Although the thresholds for a 755-nm picosecond laser were previously reported, the wavelength dependence has not been investigated. In this study, wavelength-dependent threshold fluences for melanosome disruption were determined. Using a mathematical model based on the thresholds, irradiation parameters for 532-, 730-, 755-, 785-, and 1064-nm picosecond laser treatments were evaluated quantitatively. STUDY DESIGN/MATERIALS AND METHODS: A suspension of melanosomes extracted from porcine eyes was irradiated using picosecond lasers with varying fluence. The mean particle size of the irradiated melanosomes was measured by dynamic light scattering, and their disruption was observed by scanning electron microscopy to determine the disruption thresholds. A mathematical model was developed, combined with the threshold obtained and Monte Carlo light transport to calculate irradiation parameters required to disrupt melanosomes within the skin tissue. RESULTS: The threshold fluences were determined to be 0.95, 2.25, 2.75, and 6.50 J/cm² for 532-, 730-, 785-, and 1064-nm picosecond lasers, respectively. The numerical results quantitatively revealed the relationship between irradiation wavelength, incident fluence, and spot size required to disrupt melanosomes distributed at different depths in the skin tissue. The calculated irradiation parameters were consistent with clinical parameters that showed high efficacy with a low incidence of complications. CONCLUSION: The wavelength-dependent thresholds for melanosome disruption were determined. The results of the evaluation of irradiation parameters from the threshold-based analysis provided numerical indicators for setting the clinical endpoints for 532-, 730-, 755-, 785-, and 1064-nm picosecond lasers.
Lasers, Solid-State , Melanosomes , Animals , Swine , Melanosomes/radiation effects , Lasers , Skin/radiation effects , Lasers, Solid-State/therapeutic use , Treatment Outcome
Background: If asymptomatic acetabular dysplasia (AD) is incidentally identified in adolescence, it is difficult to determine the appropriate follow-up or treatment strategy because the acetabulum is still developing. We investigated the rate of AD normalization at the end of acetabular growth. Methods: This cross-sectional study involved 653 patients (1306 hips) aged 10-14 years with scoliosis or suspected scoliosis. All patients underwent plain standing whole-spine radiography (with the pelvis included) at the first visit. We measured the lateral center-edge angle, Sharp angle, Tönnis angle, and acetabular head index on radiographs. The criterion for AD was a lateral center-edge angle of < 20°. We extracted the data of patients aged < 12 (10-11) years and ≥ 12 (12-14) years with AD. Furthermore, we analyzed the radiographic follow-up data at 15 years of age to identify the AD normalization rate. Results: AD was diagnosed in 19 hips from patients aged < 12 years and in 36 hips from patients aged ≥ 12 years. The AD normalization rate at 15 years of age was 31.6% in those diagnosed at < 12 years of age and 5.6% in those diagnosed at ≥ 12 years of age. Conclusion: AD in adolescence was predictive of AD at the end of growth in 95% of cases diagnosed at ≥ 12 years of age compared with approximately 70% of cases diagnosed at < 12 years of age. Surgical treatment before completion of acetabular growth is beneficial for acetabular remodeling, but the decision to operate should be carefully evaluated in patients aged < 12 years. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-023-01065-4.
Purpose This study aimed to clarify whether differences in ablation devices used in the knee joint during partial debridement of the proximal end of the femoral attachment of the anterior cruciate ligament (ACL) affect the mechanical properties of the femur-ACL-tibia complex. Methods Electrothermal ablation was generated from Vulcan for the left knees, and radiofrequency ablation was generated from Werewolf Flow 50 Wand for the right knees. The probes were set to the default setting of 120 W and 150 W for Vulcan and Werewolf Flow 50 Wand, respectively. To mimic partial debridement in remnant tissue-preserving (RTP) ACL reconstruction, the bipolar ablation mode and serpentine movements were employed while in contact with the femoral fan-like extension fibers of the ACL. To simulate the arthroscopic environment, the model was immersed in a saline solution. The probes were applied for 60 s, and their biomechanical properties were evaluated. Results A significant difference was observed in the upper yield load between the two groups (Vulcan group, 107.1 ± 93.4 N; Werewolf group, 177.9 ± 108.8 N; P = 0.045). However, no significant differences were noted in linear stiffness (Vulcan group, 47.6 ± 30.9 N/mm; Werewolf group, 50.1 ± 30.5 N/mm; P = 0.85), maximum load (Vulcan group, 276.2 ± 171.8 N; Werewolf group, 397.7 ± 150.8 N; P = 0.26), or elongation at failure (Vulcan group, 6.1 ± 0.9 mm; Werewolf group, 11.6 ± 10.4 mm; P = 0.20) between the two groups. Conclusion The mechanical properties of the ACL after partial ACL femoral attachment debridement for RTP-ACL reconstruction were better when an electrolyte plasmalization device was used. When performing RTP-ACL reconstruction, surgeons must consider that the device used for partial femoral ACL stump debridement may affect the mechanical properties of the ACL remnant tissue. Clinical relevance When performing RTP-ACL reconstruction, surgeons must consider that the device used for partial femoral ACL stump debridement may affect the mechanical properties of the ACL remnant tissue.
This study presents a depth map estimation of fluorescent objects in turbid media, such as biological tissue based on fluorescence observation by two-wavelength excitation and deep learning-based processing. A U-Net-based convolutional neural network is adapted for fluorophore depth maps from the ratiometric information of the two-wavelength excitation fluorescence. The proposed method offers depth map estimation from wide-field fluorescence images with rapid processing. The feasibility of the proposed method was demonstrated experimentally by estimating the depth map of protoporphyrin IX, a recognized cancer biomarker, at different depths within an optical phantom.
Enantioselective addition of an imide N-H bond to alkenes was realized by use of a cationic iridium catalyst. Bulky diphosphine ligands such as DTBM-segphos, DTBM-MeO-biphep, and DTBM-binap were indispensable for the reaction. A variety of styrene derivatives, allylsilanes, and norbornene were good substrates to give the corresponding chiral adducts with high enantioselectivity.
INTRODUCTION: Non-technical skills are essential for surgical patient safety and are implemented in clinical practice. However, training for non-technical skills has not been thoroughly investigated. This study aimed to evaluate the learning curve for non-technical skill-based education in herniorrhaphy. METHODS: Quality improvement initiatives, including non-technical skill-based intervention, were performed in the department of surgery. The intervention included declaring the patient safety policy, briefing and debriefing, and criterion for the switching of places of the trainee and instructor as defined by the department. Patients who underwent herniorrhaphy from April 2014 to September 2017 were included. RESULTS: A total of 14 trainees and nine instructors in the pre-intervention period and 14 trainees and seven instructors in the intervention period were included in this study. The median experience of each trainee was 28 and 15 cases in the pre-intervention and intervention groups, respectively. A total of 749 patients were included: 473 in the pre-intervention period and 328 in the intervention period. Demographics and hernia types were mostly similar between groups, and morbidity was not statistically different between the two groups (3.4 vs. 1.2%, p = 0.054). The nonlinear regression model showed an early decline and deep plateau phase of the learning curve in the intervention group. A significant difference was observed in the plateau operation time (61 min in the pre-intervention group and 52 min in the intervention group). CONCLUSION: This study demonstrated the effectiveness of non-technical skill-based intervention for surgical training. An early decline and deep plateau of the learning curve can be achieved with well-implemented quality improvement initiatives. Nonetheless, further studies are needed to establish a training program for non-technical skill-based learning.
Educational Personnel , Herniorrhaphy , Humans , Educational Status , Learning Curve , Drive
Laser ablation is a minimally invasive therapeutic technique to denature tumors through coagulation and/or vaporization. Computational simulations of laser ablation can evaluate treatment outcomes quantitatively and provide numerical indices to determine treatment conditions, thus accelerating the technique's clinical application. These simulations involve calculations of light transport, thermal diffusion, and the extent of thermal damage. The optical properties of tissue, which govern light transport through the tissue, vary during heating, and this affects the treatment outcomes. Nevertheless, the optical properties in conventional simulations of coagulation and vaporization remain constant. Here, we propose a laser ablation simulation based on Monte Carlo light transport with a dynamic optical properties (DOP) model. The proposed simulation is validated by performing optical properties measurements and laser irradiation experiments on porcine liver tissue. The DOP model showed the replicability of the changes in tissue optical properties during heating. Furthermore, the proposed simulation estimated coagulation areas that were comparable to experimental results at low-power irradiation settings and provided more than 2.5 times higher accuracy when calculating coagulation and vaporization areas than simulations using static optical properties at high-power irradiation settings. Our results demonstrate the proposed simulation's applicability to coagulation and vaporization region calculations in tissue for retrospectively evaluating the treatment effects of laser ablation.
Laser Therapy , Animals , Swine , Retrospective Studies , Blood Coagulation , Computer Simulation , Heating
The standard treatment for platinum-sensitive relapsed ovarian cancer (PSROC) is platinum-based chemotherapy followed by olaparib monotherapy. A retrospective study was conducted to identify factors affecting the survival of patients with PSROC undergoing olaparib monotherapy in real-world clinical settings. The study enrolled 122 patients who received olaparib monotherapy between April 2018 and December 2020 at three national centers in Japan. The study used the Kaplan-Meier method and univariable and multivariable Cox proportional hazards models to evaluate the associations between factors and progression-free survival (PFS). Patients with BRCA1/2 mutations had a significantly longer median PFS than those without these mutations. Both the BRCA1/2 mutation-positive and mutation-negative groups exhibited a prolonged PFS when the platinum-free interval (PFI) was ≥ 12 months. Cancer antigen 125 (CA-125) level within reference values was significantly linked to prolonged PFS, while a high platelet-to-lymphocyte ratio (≥ 210) was significantly associated with poor PFS in the BRCA1/2 mutation-negative group. The study suggests that a PFI of ≥ 12 months may predict survival after olaparib monotherapy in patients with PSROC, regardless of their BRCA1/2 mutation status. Additionally, a CA-125 level within reference values may be associated with extended survival in patients without BRCA1/2 mutations. A larger prospective study should confirm these findings.
BRCA1 Protein , Ovarian Neoplasms , Female , Humans , BRCA2 Protein , Prospective Studies , Retrospective Studies , CA-125 Antigen , Carcinoma, Ovarian Epithelial , Platinum
Significance: Photobleaching of the photosensitizer reduces fluorescence observation time and the intensity of fluorescence emitted for tumor detection during 5-aminolevulinic acid-based photodynamic diagnosis. Aim: This study aims to utilize the concept of fluorescence photoswitching, which uses the fluorescence emission from photosensitizer excitation followed by the simultaneous excitation of the photosensitizer and its photoproduct to increase the fluorescence detection intensity during PDD of deeply located tumors. Approach: The fluorescence photobleaching of protoporphyrin IX (PpIX) and the formation of its photoproduct, photoprotoporhyrin (Ppp), caused by exposure to 505 nm light were investigated in solution, ex vivo, and in vivo, and the fluorescence photoswitching was analyzed. The fluorescence observations of PpIX and Ppp were performed with 505 and 450 or 455 nm excitation, respectively, which is the suited wavelength for the primary excitation of each fluorophore. Results: Fluorescence photoswitching was observed in all forms of PpIX investigated, and the fluorescence photoswitching time, fluorescence intensity relative to the initial PpIX and Ppp intensity, and fluorescence intensity relative to PpIX after photobleaching were obtained. The dependence of the fluorescence photoswitching time and intensity on the irradiation power density was noted. A fluorescence intensity increase between 1.6 and 3.9 times was achieved with simultaneous excitation of PpIX and Ppp after fluorescence photoswitching, compared with the excitation of PpIX alone. Conclusions: We have demonstrated the potential of fluorescence photoswitching for the improvement of the fluorescence observation intensity for the PDD of deeply located tumors.
Neoplasms , Photochemotherapy , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Fluorescence , Aminolevulinic Acid , Protoporphyrins , Neoplasms/diagnostic imaging
Ruthenium-catalysed N-alkylation of anilines with sugar derivatives proceeded via the borrowing hydrogen strategy. Primary carbohydrate alcohols were successfully applied to N-alkylation of aniline derivatives to give the corresponding aminosugars in high yields.
BACKGROUND: Most previous reports of normal acetabular radiographic values focused on adults or elderly people. Recent reports have described premature hip osteoarthritis in adolescents not caused by acetabular dysplasia. In addition, there is a certain failure rate of surgical treatment for young patients with borderline acetabular dysplasia. Accurate indices for treatment of adolescent hips are unclear because standard measurement values of the adolescent acetabulum have not been reported. METHODS: This cross-sectional study involved 552 Japanese adolescents aged 12-18 years who had scoliosis or suspected scoliosis and asymptomatic hips. All persons underwent plain standing anteroposterior whole-spine radiography, and measurements were obtained using the pelvic part of the radiograph. We excluded persons who were unable to correctly perform measurements because of conditions such as pelvic rotation or lateral inclination and persons in whom closure of the triradiate cartilage or closure of the secondary ossification centers of the acetabulum had not yet occurred. In 1101 hips, we measured the lateral center-edge angle (LCEA), Tönnis angle, Sharp angle, acetabular head index (AHI), lateral subluxation (LS), vertical subluxation (VS), and peak-to-edge distance (PED). We evaluated the correlation coefficient and coefficient of determination between each parameter and age, height, body weight, and body mass index (BMI) and assessed the intra- and inter-rater reliability of each radiographic parameter. RESULTS: Among all hips, the mean of each parameter was as follows: LCEA, 27.9° ± 4.8°; Tönnis angle, 5.0° ± 3.7°; Sharp angle, 44.1° ± 3.1°; AHI, 82.1% ± 5.5%; LS, 5.4 ± 1.4 mm; VS, 0.3 ± 1.2 mm; and PED, 14.0 ± 2.3 mm. The correlation between each parameter and age, height, body weight, and BMI was considerably low. Intra- and inter-rater reliability was moderate or good for almost all parameters. CONCLUSIONS: The values for each radiographic parameter of the acetabulum in this study are considered standard for the adolescent acetabulum without age-related changes. Some parameters differ slightly from the normal values for adults or elderly people in previous reports; thus, we suggest careful evaluation of these parameters for adolescents.
Acetabulum , Hip Joint , Adolescent , Humans , Acetabulum/diagnostic imaging , Body Weight , Cross-Sectional Studies , East Asian People , Hip Dislocation , Hip Dislocation, Congenital , Hip Joint/diagnostic imaging , Reproducibility of Results , Retrospective Studies , Scoliosis , Child , Reference Values
A miniaturized endoscopic laser system with laser steering has great potential to expand the application of minimally invasive laser treatment for micro-lesions inside narrow organs. The conventional systems require separate optical paths for endoscopic imaging and laser steering, which limits their application inside narrower organs. Herein, we present a novel endoscopic image-guided laser treatment system with a thin tip that can access inside narrow organs. The system uses a single fiber bundle to simultaneously acquire endoscopic images and modulate the laser-irradiated area. The insertion and operation of the system in a narrow space were demonstrated using an artificial vascular model. Repeated laser steering along set targets demonstrated accurate laser irradiation within a root-mean-square error of 28 [Formula: see text]m, and static repeatability such that the laser irradiation position was controlled within a 12 [Formula: see text]m radius of dispersion about the mean trajectory. Unexpected irradiation on the distal irradiated plane due to fiber bundle crosstalk was reduced by selecting the appropriate laser input diameter. The laser steering trajectory spatially controlled the photothermal effects, vaporization, and coagulation of chicken liver tissue. This novel system achieves minimally invasive endoscopic laser treatment with high lesion-selectivity in narrow organs, such as the peripheral lung and coronary arteries.
Blood Substitutes , Endoscopy , Lasers , Blood Coagulation , Coronary Vessels
The catalytic enantioselective hydroarylation of 1,1-disubstituted alkenes proceeded by using a cationic iridium/(R)-binap complex to give the corresponding adducts in high yields with high enantioselectivity. The reaction of arenes substituted with heteroaromatic directing groups proceeded to give the addition products linear-selectively. Methallylamine derivatives were good acceptors to obtain high enantioselectivities. The adduct bearing maleimide moiety was readily transformed into the ß-chiral amine derivative without loss of the enantiomeric purity.
Alkenes , Iridium , Stereoisomerism , Amines , Catalysis
BACKGROUND AND OBJECTIVES: The clinical use of 532-nm short-pulsed lasers has provided effective treatment of epidermal pigmented lesions. However, the detection of significant differences in treatment effects between picosecond and nanosecond lasers has still varied among clinical studies. For robust evaluation of the differences based on the treatment mechanism, this study presents a nonlinear absorption-based analysis of energy deposition in melanosomes for 532-nm short-pulsed laser treatment. STUDY DESIGN/MATERIALS AND METHODS: Nonlinear absorption by melanin is modeled based on sequential two-photon absorption. Absorption cross-sections and nonradiative lifetimes of melanin, which are necessary for the nonlinear absorption-based analysis, are determined from transmittance measurement. Using the model and parameters, energy deposition in melanosomes was calculated with varying fluence and pulse width settings, including actual clinical parameters. RESULTS: The energy deposition in melanosomes increased with shorter laser pulses, and subnanosecond laser pulses were found to be most efficient. The comparison of energy deposition calculated using clinical parameters demonstrated the differences in treatment effects between picosecond and nanosecond lasers reported in clinical studies. CONCLUSION: The nonlinear absorption-based analysis provides quantitative evidence for the safety and efficacy evaluation of short-pulsed laser treatments, which may lead to the establishment of numerical indices for determining treatment conditions. Future studies considering the effects of the surrounding tissue on energy deposition in melanosomes will be needed.
Melanins , Melanosomes , Lasers , Treatment Outcome , Administration, Cutaneous
Enantioselective direct α-C(sp3)-H alkylation of saturated cyclic amines having N-methylbenzimidazolyl as a directing group was realized by using a cationic iridium/chiral diphosphine catalyst. The alkylation of pyrrolidine derivatives with various terminal alkenes proceeded to give α-alkylated products in high yields with high enantioselectivities. Chiral α,α'-dialkylated pyrrolidine derivatives were also synthesized by using an excess of alkenes or by stepwise alkylation.
BACKGROUND: Antimicrobial photodynamic therapy (aPDT) using aminolaevulinic acid (ALA) is a promising alternative to antibiotic therapy. ALA administration induces protoporphyrin IX (PpIX) accumulation in bacteria, and light excitation of the accumulated PpIX generates singlet oxygen to bacterial toxicity. Several factors, including drug administration and light irradiation conditions, contribute to the antibiotic effect. Such multiple parameters should be determined moderately for effective aPDT in clinical practice. METHODS: A mathematical model to predict bacterial dynamics in ALA-aPDT following clinical conditions was constructed. Applying a pharmacokineticspharmacodynamics (PK-PD) approach, which is widely used in antimicrobial drug evaluation, viable bacteria count by defining the bactericidal rate as the concentration of singlet oxygen produced when PpIX in bacteria is irradiated by light. RESULTS: The in vitro experimental results of ALA-aPDT for Pseudomonas aeruginosa demonstrated the PK-PD model validity. The killing rate has an upper limit, and the lower power density for a long irradiation time can suppress the viable bacteria number when the light dosages are the same. CONCLUSIONS: This study proposed a model of bacterial viability change in ALA-aPDT based on the PK-PD model and confirmed, by in vitro experiments using PA, that the variation of bacterial viability with light-sensitive substance concentration and light irradiation power densities could be expressed. Further validation of the PK-PD model with other gram negative and gram positive strains will be needed.
Photochemotherapy , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Singlet Oxygen , Aminolevulinic Acid/pharmacology , Protoporphyrins/pharmacology , Anti-Bacterial Agents , Models, Theoretical
Iridium-catalyzed asymmetric C-H addition of an N-methyl group on 3-trifluoromethyl-2-(N-methylamino)pyridine to cyclic alkenes was realized by using a phosphine-olefin ligand. Indene and its 7-substituted derivatives, acenaphthylene, and some bicyclic alkenes underwent the addition to give the corresponding products in good yields with high enantioselectivity.
BACKGROUND: Manual operations of the hydraulic jack device can become ergonomic stressors for the musculoskeletal system because of the required operational forces, muscle activities, or working postures. However, the usability of the hydraulic jack has not been fully explored for non-professional personnel. OBJECTIVES: To evaluate the musculoskeletal loads during manual operations of a hydraulic jack based on the ergonomic postural analysis and electromyographyMETHODS:Nine men operated the lever of a hydraulic jack with three positions: parallel to and near (P-N), parallel to and far from (P-F), and orthogonal to the jack lever (O). Postural loads were evaluated by Loading on the Upper Body Assessment (LUBA), an ergonomic observational method, and were classified into action categories. The surface electromyogram of eight muscles and the subjective sense of burden were also measured. RESULTS: The initial force for lever pushing reached 40-80 N and exceeded the recommended forces for the unusual postures. The overall assessment of LUBA showed that 31% of working postures observed in O position require immediate consideration and corrective action and the maximum holding time estimated was <â1 minute. The postural load increased due to the shoulder joint abduction in the P-F and O positions and due to the trunk rotation in O position. CONCLUSIONS: The results suggest that operating the hydraulic jack cause considerable postural loads and manual forces insufficient for several minutes of manual task. Therefore, improving working methods and tool designs are needed to improve usability and decrease the risk of musculoskeletal disorders during jack operations.
Musculoskeletal System , Workload , Electromyography , Ergonomics , Humans , Male , Posture/physiology
Iridium-catalyzed sp3 C-H alkylation of an N-methyl group with 1,5- and 1,6-dienes proceeded to give five- and six-membered carbocyclic compounds, respectively, in high yields. The reaction involves intermolecular alkylation of the N-methyl group with a vinyl moiety and subsequent intramolecular cyclization at the ß-position of the initially formed alkylated intermediate. The reaction using a chiral bidentate phosphine ligand enabled the asymmetric synthesis of the cyclic compounds.
Iridium , Polyenes , Alkylation , Catalysis , Cyclization
