Double difunctionalization of vinyl ether tethered nucleophile with electron-deficient alkene in two-molecule photoredox system.

Double difunctionalization of a vinyl ether tethered hydroxy or carbamoyl group with electron-deficient alkenes such as acrylonitrile or acrylic esters was achieved by visible-light irradiation in a two-molecule photoredox system. Use of anhydrous acetonitrile solution as a solvent promoted both dimerization of the radical cation of electron-rich alkene with electron-rich alkene and intramolecular nucleophilic addition to generate an electron-rich radical that was added to electron-deficient alkene to furnish the double difunctionalized product. A variety of electronically differentiated rich and deficient alkenes were used in the photoreaction; a simple construction of a complex carbon framework containing acetal from simple alkenes was successful under mild conditions.

Successful Treatment of Mucus Plug Due to Allergic Bronchopulmonary Aspergillosis Using Dupilumab.

Allergic bronchopulmonary aspergillosis (ABPA) often necessitates treatment with systemic steroids and antifungals, which are associated with relapses and side effects. We report an 82-year-old woman with eosinophilic asthma, experiencing sputum production and dyspnea, who was diagnosed with ABPA based on her chest CT, pulmonary function tests, and elevated blood eosinophils and immunoglobulin E. Due to the presence of osteoporosis and diabetes, standard steroid therapy was considered a high risk. Instead, we administered dupilumab, an interleukin 4 receptor alpha (IL4-Rα) antibody targeting Th2 cytokine signaling. Remarkable improvements were observed within two weeks, including reduced sputum and dyspnea. After 12 weeks, significant enhancements in asthma control and lung function, along with decreased fractional exhaled nitric oxide (FeNO) levels were noted, with chest CT showing resolution of most of the mucus plugs. This case demonstrates dupilumab's potential as a viable ABPA treatment alternative, particularly for patients who are unsuitable for systemic steroids. More research on the long-term effectiveness and safety of such biologics is needed.

Sputum colour: An indicator of Legionella pneumophila pneumonia.

The sputum colour in patients with severe pneumonia needs to be considered during diagnosis.

One-Leg Robotic-Assisted Gait Training Efficiently Improves Gait Independence for Acute Stroke Hemiplegic Patients: A Prospective Pilot Study.

ABSTRACT: Welwalk is a one-leg robotic-assisted gait system for stroke hemiplegic patients. This study examined the feasibility and efficacy of gait training using Welwalk (Welwalk training) for hemiplegic patients in the early phase after stroke onset, via cooperation between acute care and rehabilitation hospitals. Seven acute stroke patients (mean number of days from onset = 7.9) with severe lower extremity paralysis participated. Patients underwent Welwalk training for 40 min/d, 5 d/wk in an acute care hospital, then 7 d/wk in a rehabilitation hospital with a seamless transition. Functional Independence Measure scores for walking were assessed weekly. The endpoint was reaching Functional Independence Measure walk score of 5 (supervision level). The primary outcome was improvement efficiency of Functional Independence Measure walk, which was the increase in Functional Independence Measure walk score divided by the number of weeks required. Functional Independence Measure walk score for all patients improved from 1.1 to 5 ( P = 0.01, r = 0.96). The mean number of weeks to achieve Functional Independence Measure walk score of 5 was 5 wks, and the improvement efficiency of Functional Independence Measure walk had a mean value of 0.9. No adverse events were reported during Welwalk training. Hemiparetic patients' gait independence may be safely and rapidly improved by starting Welwalk training in the early phase after stroke onset.

Transbronchial cryobiopsy for small peripheral pulmonary lesions using endobronchial ultrasonography and an ultrathin bronchoscope.

BACKGROUND: Transbronchial biopsy using an ultrathin bronchoscope (UTB) has a high diagnostic yield for peripheral pulmonary lesions (PPLs). When combined with peripheral transbronchial needle aspiration (pTBNA), it improves the diagnostic yield of "adjacent to" radial endobronchial ultrasonography (rEBUS) findings. However, pTBNA is a complicated technique, and the specimen volume is often inadequate for diagnostic and multiplex analyses. Recently, transbronchial cryobiopsy (TBCB) using a 1.1-mm cryoprobe that could be inserted into an UTB has been available. We investigated whether TBCB combined with forceps biopsy using a 1.1-mm cryoprobe with an UTB improved the diagnostic yield of "adjacent to" lesions. METHODS: The data of 66 consecutive patients who underwent TBCB and forceps biopsy using UTB (hemostasis using two-scope method) under rEBUS for small PPLs (≤30 mm) were retrospectively analyzed. The histological diagnosis rate using TBCB and forceps biopsy, TBCB alone, or forceps biopsy alone was compared between cases where the rEBUS probe was "within" and "adjacent to" lesions. RESULTS: The diagnosis rate using TBCB and forceps biopsy was 81.8 % for all lesions ("within" vs. "adjacent to" cases: 88.4 % vs. 69.6 %; p = 0.093). The corresponding rate using TBCB alone was 80.3 % (86.0 % vs. 69.6 %; p = 0.19), and that using forceps biopsy alone was 62.1 % (74.4 % vs. 39.1 %; p = 0.008). Bleeding leading to discontinuation of the examination occurred in four (6.1 %) patients; however, in all cases, bleeding could be controlled endoscopically. CONCLUSION: Forceps biopsy with TBCB during ultrathin bronchoscopy for small PPLs improved the diagnostic yield when the lesions were adjacent to the rEBUS probe.

Molecular Cloning, Expression Analyses, and Physiological Roles of Cathelicidins in the Bursa of Fabricius of the Japanese Quail, Coturnix japonica.

Antimicrobial peptides (AMPs) act directly on pathogens and maintain the anti-inflammatory effects and activation of immunocompetent cells. Therefore, the activation of the immune system in poultry via the elevation of endogenous AMPs has been attempted. In this study, we focused on the host defense mechanisms in the bursa of Fabricius (BF) of Japanese quail, cloned the cDNA of cathelicidin (CATH)-1 to -3, and analyzed their expression sites. In situ hybridization experiments revealed the mRNA expression of the CATHs in the interfollicular epithelium surrounding the lumen of the quail BF, which suggests that each CATH may exert its antimicrobial action directly in the BF. The intravenous injection of bacterial lipoteichoic acid and lipopolysaccharide endotoxins into the quail promoted the mRNA expression of CATH-1 and CATH-3 in the BF. The addition of CATH-1 or CATH-2 at the time of the antigen injection into mice resulted in antiserum with high antibody titers. Ad libitum administration of butyrate, a short-chain fatty acid, in the drinking water induced an increase in CATH-2 mRNA expression in the BF under certain conditions. These results may improve the defense mechanisms of quail by stimulating CATH expression in the BF through their diet.

Preferential formation of specific hexose and heptose in the formose reaction under microwave irradiation.

To realize sustainable societies, the production of organic compounds not based on fossil resources should be developed. Thus, C1 chemistry, utilizing one-carbon compounds as starting materials, has been of increasing importance. In particular, the formose reaction is promising because the reaction produces sugars (monosaccharides) from formaldehyde under basic conditions. On the other hand, since microwave (MW) induces the rotational motion of molecules, MW irradiation often improves the selectivity and efficiency of reactions. In this study, the formose reaction under MW irradiation was thus investigated under various conditions. The formose reaction proceeded very fast using 1.0 mol per kg formaldehyde and 55 mmol per kg calcium hydroxide (Ca(OH)2) as a catalyst at a high set temperature (150 °C) for a short time (1 min) to form preferentially specific hexose and heptose. The major products were isolated by thin layer chromatography and characterized by mass spectroscopy and NMR. These characterization data elucidated that the hexose and heptose were 2-hydroxymethyl-1,2,4,5-tetrahydroxy-3-pentanone (C6*) and 2,4-bis(hydroxymethyl)-1,2,4,5-tetrahydroxy-3-pentanone (C7*), respectively. On the basis of these observations, as well as density functional theory calculations, a plausible reaction pathway was also discussed; once 1,3-dihydroxyacetone is formed, consecutive aldol reactions favorably occur to form C6* and C7*.

Decarboxylative Side-Chain Functionalization of Aspartic/Glutamic Acids Using Two-Molecule Photoredox Catalysts.

The side-chain functionalization of aspartic/glutamic acid derivatives through photoinduced decarboxylation was achieved by using organic two-molecule photoredox catalysts without racemization under mild conditions. A facile process involving the preparation of substrates and photoinduced decarboxylative radical additions can provide easy access to the linked amino acids with carbohydrates and amino acids at the side chain.

Measurement of the horizontal beam emittance of undulator radiation by tandem-double-slit optical system.

A tandem-double-slit optical system was constructed to evaluate the practical beam emittance of undulator radiation. The optical system was a combination of an upstream slit (S1) and downstream slit (S2) aligned on the optical axis with an appropriate separation. The intensity distribution after the double slits, I(x1, x2), was measured by scanning S1 and S2 in the horizontal direction. Coordinates having 1/\sqrt e intensity were extracted from I(x1, x2), whose contour provided the standard deviation ellipse in the x1-x2 space. I(x1, x2) was converted to the corresponding distribution in the phase space, I(x1, x1'). The horizontal beam emittance was evaluated to be 3.1 nm rad, which was larger than the value of 2.4 nm rad estimated by using ray-tracing. It was found that the increase was mainly due to an increase in beam divergence rather than size.

Comparison of ultrathin bronchoscopy with conventional bronchoscopy for the diagnosis of peripheral lung lesions without virtual bronchial navigation.

BACKGROUND: For the precise management of advanced lung cancers, bronchoscopy with a high diagnostic yield and abundant tumor specimens are required. In recent years, new devices and techniques have been rapidly developed, including the endobronchial ultrasound (EBUS) using a guide sheath, virtual bronchoscopic navigation (VBN), and ultra-thin bronchoscope (UTB), for the diagnosis of peripheral pulmonary lesions (PPLs). These techniques increase the diagnostic yield for PPL, thus requiring fewer biopsy specimens. VBN is generally not available at the city hospitals in Japan. In this study, using fluoroscopy without VBN, we studied whether the histologic diagnostic yield of radial EBUS for PPLs would be higher using a UTB (without guide sheath) or conventional bronchoscope (CB) (with guide sheath). METHODS: We retrospectively reviewed consecutive patients with suspected lung cancer who underwent bronchoscopy at the Hakodate Goryoukaku Hospital from April 2017 to March 2019. We analyzed 168 patients-102 using UTB and 66 using CB. RESULTS: The diagnostic yields for PPL were significantly higher in the UTB group than in the CB group (74.5% vs. 59.1%; P = 0.04). The median examination time was significantly longer in the UTB group than in the CB group (24 vs. 20 min; P = 0.01). There were no statistically significant differences in the complication rate between the UTB and CB groups (3.9% vs. 3.0%; P = 0.69). CONCLUSIONS: UTB had a significantly higher tissue diagnostic yield than CB, without the use of VBN.

Asymptomatic congenital tracheal stenosis.

Congenital tracheal stenosis (CTS) is often identified by characteristic wheezes and cyanosis in childhood. However, an asymptomatic progression to adulthood is rare. Asymptomatic latent CTS cases with a mild degree of stenosis may exist.

Magnetic Resonance Imaging Evaluation of the Effects of Surgical Invasiveness on Paravertebral Muscles After Muscle-preserving Interlaminar Decompression (MILD).

STUDY DESIGN: This is a retrospective study. OBJECTIVES: The aim of this study was to determine the extent of damage to the paravertebral muscles after muscle-preserving interlaminar decompression (MILD) using magnetic resonance imaging to evaluate changes in the multifidus muscle (MF). SUMMARY OF BACKGROUND DATA: Short-term surgical outcomes of MILD for lumbar spinal canal stenosis (LSCS) are satisfactory; however, the extent of damage to the paravertebral muscles after MILD remains unclear. METHODS: Thirty-four patients (18 men/16 women; mean age: 72.6 y) who had LSCS treated with MILD were retrospectively investigated. A total of 61 decompressed disk levels [L2/3(5); L3/4(21); L4/5(30); L5/S(5)] and 34 nondecompressed levels (L1/2) were assessed. There was 1 decompressed disk level in 12 cases, 2 in 17 cases, and 3 in 5 cases. Magnetic resonance imaging scans were obtained before surgery and at 3 and 12-18 months after surgery, using the same scanner. The rate of paravertebral muscle atrophy was evaluated to compare the area of the MF in the T2-weighted axial plane (intervertebral disk level) preoperatively and postoperatively, using OsiriX Medical Imaging Software. Changes in muscle signal intensity were also recorded. Statistical analysis was performed using 3-way analysis of variance with the post hoc Fisher PSLD test. RESULTS: The rate of MF atrophy was 4.0% at the decompressed levels and 2.1% at the nondecompressed levels. There were no changes of signal intensity in the MF between the preoperative and postoperative periods. In decompressed levels, muscle atrophy and signal intensity were significantly improved from 3 months to 12-18 months after surgery. The number and level of the decompressed disks did not affect the extent of muscle injury. CONCLUSIONS: The extent of paravertebral muscle injury after MILD is satisfactory. The midline interlaminar approach used in this technique may prevent local denervation and irreversible damage to the paravertebral muscles. These results indicate that MILD is useful to treat LSCS less invasively.

Innovative Technique for the Placement of the Drainage Tube for Microendoscopic Spinal Decompression.

STUDY DESIGN: A technical note and retrospective study. OBJECTIVES: The objectives were to describe a new method of drainage tube placement during microendoscopic spinal decompression, and compare the positioning and fluid discharge obtained with this method and the conventional method. SUMMARY OF BACKGROUND DATA: To prevent postoperative epidural hematoma after microendoscopic decompression, a drainage tube must be placed in a suitable location. However, the narrow operative field makes precise control of the position of the tube technically difficult. We developed a method to reliably place the tube in the desired location. MATERIALS AND METHODS: We use a Deschamps aneurysm needle with a slightly curved tip, which we call a drain passer. With the microendoscope in position, the drain passer, with a silk thread passed through the eye at the needle tip, is inserted percutaneously into the endoscopic field of view. The drainage tube is passed through the loop of silk thread protruding from the inside of the tubular retractor, and the thread is pulled to the outside, guiding the end of the drainage tube into the wound. This method was used in 23 cases at 44 intervertebral levels (drain passer group), and the conventional method in 20 cases at 32 intervertebral levels (conventional group). Postoperative plain radiographs were taken, and the amount of fluid discharge at postoperative hour 24 was measured. RESULTS: Drainage tube positioning was favorable at 43 intervertebral levels (97.7%) in the drain passer group and 26 intervertebral levels (81.3%) in the conventional group. Mean fluid discharge was 58.4±32.2 g in the drain passer group and 38.4±23.0 g in the conventional group. Positioning was significantly better and fluid discharge was significantly greater in the drain passer group. CONCLUSION: The results indicate that this method is a useful drainage tube placement technique for preventing postoperative epidural hematoma.

Comparative analysis of medial patellofemoral ligament length change pattern in patients with patellar dislocation using open-MRI.

PURPOSE: Medial patellofemoral ligament (MPFL) reconstruction has become a common form of treatment for recurrent patellar dislocation. This study was performed using open-MRI to compare the length change pattern of MPFL in patients with a history of patellar dislocation to that in healthy subjects. METHODS: The subjects comprised 10 knees of 8 males and 13 knees of 12 females with a history of one or more patellar dislocations. The length of the MPFL was measured using open-MRI in both the leg-extended position and knee-flexed positions to analyse the length change pattern. RESULTS: The average MPFL lengths were 58.6 ± 6.5 mm and 52.0 ± 4.6 mm for males and females in the extended knee position, respectively. The length change pattern of the MPFL showed slight variation up to a flexion angle of 30° and a clear decrease above 30°. This pattern differed from that of normal MPFL. In terms of morphology, the fibre bundle of the damaged MPFL followed a convex course towards the side of the patellofemoral joint surface at a knee flexion angle of 60°, whereas that of the normal MPFL followed a straight course. CONCLUSION: The in vivo damaged MPFL length change pattern was specific and differed distinctly from that of normal MPFL. The results of the present study suggested that MPFL fibres with a history of patellar dislocation lack sufficient tension at knee flexion angles of 0°-60°. However, further studies are needed to obtain a better understanding of cases with a patellar dislocation or postsurgical cases of MPFL reconstruction. LEVEL OF EVIDENCE: III.

Dislodgement and gastrointestinal tract penetration of bone cement used for spinal reconstruction after lumbosacral vertebral tumor excision: A case report.

INTRODUCTION: Polymethylmethacrylate (PMMA) cement is useful for spinal reconstruction, but can cause complications including new vertebral fractures, neurological disorders and pulmonary embolism. We report a case in PMMA cement used for spinal reconstruction after tumor curettage dislodged and penetrated the gastrointestinal tract. DIAGNOSES: The patient was diagnosed with a retroperitoneal extragonadal germ cell tumor at age 27 years. After chemotherapy and tumor resection, the tumor remained. It gradually increased in size and infiltrated lumbosacral vertebrae, causing him to present at age 35 years with increased low back pain. Image findings showed bone destruction in the vertebral bodies accompanied by neoplastic lesions. The left and right common iliac arteries and inferior vena cava were enclosed in the tumor on the anterior side of the vertebral bodies. Lumbosacral bone tumor due to direct extragonadal germ cell tumor infiltration was diagnosed. A 2-step operation was planned; first, fixation of the posterior side of the vertebral bodies, followed by tumor resection using an anterior transperitoneal approach, and spinal reconstruction using PMMA cement. After surgery, the PMMA cement gradually dislodged towards the anterior side and, 2 years 9 months after surgery, it had penetrated the retroperitoneum. The patient subsequently developed nausea and abdominal pain and was readmitted to hospital. The diagnosis was intestinal blockage with dislodged PMMA cement, and an operation was performed to remove the cement present in the small intestine. There was strong intra-abdominal adhesion, the peritoneum between the vertebral bodies and intestine could not be identified, and no additional treatment for vertebral body defects could be performed. After surgery, gastrointestinal symptoms resolved. CONCLUSION: Although this was a rare case, when using bone cement for vertebral body reconstruction, the way of anchoring for the cement must be thoroughly planned to assure no cement dislodgement can occur.

Differences in monthly variation, cause, and place of injury between femoral neck and trochanteric fractures: 6-year survey (2008-2013) in Kyoto prefecture, Japan.

BACKGROUND: The incidence of femoral neck and trochanteric fractures reportedly differ by age and regionality. We investigated differences in monthly variations of the occurrence of femoral neck and trochanteric fractures as well as place and cause of injury in the Kyoto prefecture over a 6-year period. METHODS: Fracture type (neck or trochanteric fracture), age, sex, place of injury, and cause of injury were surveyed among patients aged ≥ 65 years with hip fractures that occurred between 2008 and 2013 who were treated in 1 of 13 participating hospitals (5 in an urban area and 8 in a rural area). The proportion of sick beds in the participating hospitals was 24.7% (4,151/16,781). Monthly variations in the number of patients were investigated in urban and rural areas in addition to the entire Kyoto prefecture. Place of injury was classified as indoors or outdoors, and cause of injury was categorized as simple fall, accident, or uncertain. RESULTS: There were 2,826 patients with neck fractures (mean age, 82.1 years) and 3,305 patients with trochanteric fractures (mean age, 85.0 years). There were similarities in the monthly variation of the number of fractures in addition to the place and cause of injury between neck and trochanteric fractures. Indoors (approximately 74%) and simple falls (approximately 78%) were the primary place and cause of injury, respectively. The place of injury was not significantly different by fracture type with each age group. Significantly more patients with neck fracture had "uncertain" as the cause of injury than trochanteric fracture in all age groups. CONCLUSIONS: Based on the results of the present study, the injury pattern might not have a great effect on the susceptibility difference between neck and trochanteric fractures.

Hepatocyte growth factor/c-met promotes proliferation, suppresses apoptosis, and improves matrix metabolism in rabbit nucleus pulposus cells in vitro.

The etiology of intervertebral disc (IVD) degeneration is closely related to apoptosis and extracellular matrix degradation in nucleus pulposus (NP) cells. These defects in NP cells are induced by excessive external stressors such as reactive oxygen species (ROS) and inflammatory cytokines. Recently, hepatocyte growth factor (HGF) has been shown to repair damage in various diseases through anti-apoptotic and anti-inflammatory activity. In this study, we investigated the effects of HGF on NP cell abnormality caused by ROS and inflammatory cytokines by using primary NP cells isolated from rabbit IVD. HGF significantly enhanced the proliferation of NP cells. Apoptosis of NP cells induced by H2 O2 or TNF-α was significantly inhibited by HGF. Induction of mRNA expression of the inflammation mediators cyclooxygenase-2 and matrix metalloproteinase-3 and -9 by TNF-α was significantly suppressed by HGF treatment. Expression of c-Met, a specific receptor for HGF, was confirmed in NP cells and was increased by TNF-α, suggesting that inflammatory cytokines increase sensitivity to HGF. These findings demonstrate that activation of HGF/c-Met signaling suppresses damage caused by ROS and inflammation in NP cells through multiple pathways. We further suggest the clinical potential of HGF for counteracting IVD degradation involved in NP cell abnormalities.

Outcomes in cases of lumbar degenerative spondylolisthesis more than 5 years after treatment with minimally invasive decompression: examination of pre- and postoperative slippage, intervertebral disc changes, and clinical results.

OBJECT: There are reports that fusion is the standard treatment of choice for cases of lumbar degenerative spondylolisthesis (LDS) associated with lumbar spinal canal stenosis with a large degree of slippage. The reasons why, however, have not been clarified. On the other hand, it is known that the progress of slippage decreases and restabilization occurs over the natural course of LDS. Therefore, if minimally invasive decompression could be performed, there would be little possibility of it influencing the natural course of LDS, so it would not be necessary to include preoperative percentage slip in the criteria for the selection of fusion. This study examined the course of LDS cases more than 5 years after treatment with minimally invasive decompression to determine whether pre- and postoperative slippage and disc changes influence the clinical results. METHODS: A total of 51 intervertebral segments in 51 cases with the chief complaint of radicular or cauda equina symptoms due to lumbar spinal canal stenosis were examined after prospective treatment with minimally invasive decompression for LDS. The mean age of the patients at the time of surgery was 66.7 years and the mean follow-up period was 7 years 4 months. Minimally invasive decompression was performed regardless of the degree of low-back pain or percentage slip. The outcome variables were clinical results and changes in imaging findings. RESULTS: Over the follow-up period, postoperative percentage slip increased and disc height decreased, but the Japanese Orthopaedic Association score improved. Regardless of the preoperative percentage slip, disc height, or degree of intervertebral disc degeneration or segmental instability, the clinical results were favorable. In the high preoperative percentage slip group, low disc height group, and progressive disc degeneration group, there was little postoperative progress of slippage. In the group with a postoperative slippage increase of more than 5%, slippage increased significantly at postoperative year 2, but no significant difference was observed at the final follow-up. CONCLUSIONS: When minimally invasive decompression was performed to treat LDS, the postoperative change in slippage was no different from that during the natural course. Furthermore, regardless of the degree of preoperative slippage or intervertebral disc degeneration, the clinical results were favorable. Also, the higher the preoperative percentage slip and the more that disc degeneration progressed, the more the progress of postoperative slippage decreased. Because the postoperative progress of slippage decreased, it is believed that even after minimally invasive decompression, restabilization occurs as it would during the natural course. If minimally invasive decompression can be performed to treat LDS, it is believed that preoperative percentage slip and intervertebral disc degeneration do not have to be included in the appropriateness criteria for fusion.