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.

Posterior Occipitocervical Fixation and Intrathecal Baclofen Therapy for the Treatment of Basilar Invagination with Klippel-Feil Syndrome: A Case Report.

Klippel-Feil syndrome (KFS) is characterized by the congenital fusion of the cervical vertebrae and is sometimes accompanied by anomalies in the craniocervical junction. In basilar invagination (BI), which is a dislocation of the dens in an upper direction, compression of the brainstem and cervical cord results in neurological defects and surgery is required. A 16-year-old boy diagnosed with KFS and severe BI presented with spastic tetraplegia, opisthotonus and dyspnea. CT scans showed basilar impression, occipitalization of C1 and fusion of C2/C3. MRI showed ventral compression of the medullocervical junction. Posterior occipitocervical reduction and fusion along with decompression were performed. Paralysis gradually improved postoperatively over 3 weeks. However, severe spasticity and opisthotonus persisted and intrathecal baclofen (ITB) therapy was initiated. Following this, opisthotonus disappeared and spasticity of the extremities improved. Rehabilitation therapy continued by controlling the dose of ITB. Five years after the surgery, self-propelled wheelchair driving was achieved and activities of daily life improved. The treatment strategy for patients with BI and congenital anomalies remains controversial. Posterior reduction and internal fixation using instrumentation were effective techniques in this case. Spasticity control achieved through a combination of surgery and ITB treatment enabled the amelioration of therapeutic efficacy of rehabilitation and the improvement of ADL.

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.

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.

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.

Sputum colour: An indicator of Legionella pneumophila pneumonia.

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

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.

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.

Risk factors for severe immune-related pneumonitis after nivolumab plus ipilimumab therapy for non-small cell lung cancer.

BACKGROUND: The efficacy of anti-CTLA-4 antibody (ipilimumab) plus anti-programmed cell death 1 antibody (nivolumab) in treating advanced non-small cell lung cancer (NSCLC) is impeded by an elevated risk of severe immune-related adverse events. However, our understanding of associations among pre-existing fibrosis, emphysematous changes, and objective indicators as predictive factors is limited for severe pneumonitis in NSCLC patients receiving this combination therapy. Thus, we retrospectively investigated these associations, including overall tumor burden, before treatment initiation in the Japanese population. METHODS: We focused on patients (n = 76) with pre-existing interstitial lung disease (ILD) to identify predictors of severe pneumonitis. Variables included age, sex, smoking status, programmed cell death ligand 1 expression, overall tumor burden, chest computed tomography-confirmed fibrosis, serum markers, and respiratory function test results. RESULTS: Severe pneumonitis was more frequent in patients with squamous cell carcinoma, fibrosis, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP-D) level. Notably, squamous cell carcinoma, baseline %DLCO, and SP-D level were significant risk factors. Our findings revealed the nonsignificance of tumor burden (≥85 mm) in predicting severe pneumonitis, emphasizing the importance of pre-existing ILD. Conversely, in cases without pre-existing fibrosis, severe pneumonitis was not associated with %DLCO or SP-D level (93.2% vs. 91.9%, and 63.3 vs. 40.9 ng/mL, respectively) and was more common in patients with a large overall tumor burden (97.5 vs. 70.0 mm). CONCLUSION: Vigilant monitoring and early intervention are crucial for patients with squamous cell carcinoma, high SP-D level, or low %DLCO undergoing ipilimumab plus nivolumab therapy.

Tubular surgery with the assistance of endoscopic surgery via midline approach for lumbar spinal canal stenosis: a technical note.

PURPOSE: We devised a tubular surgery with the assistance of endoscopic surgery via midline approach to the spinal canal to preserve the bilateral facet joints and the paravertebral muscles when treating lumbar spinal canal stenosis. We report details of this operative procedure. METHODS: A 2-cm incision is made in the skin in the midline of the intervertebral level to be decompressed. The spinous process on the cranial side is partially excised, and incisions along the ligament fiber are made in the midline of the supraspinous and interspinous ligaments to expose the ligamentum flavum. After the lamina and the inferior parts of the bilateral facet joints are adequately excised, the microendoscopic discectomy system is inserted. With this procedure, no muscular tissue is seen in the surgical site. The portal approach is small, but if full advantage is taken of the spinal microendoscope's merits, the bilateral facet joints are preserved and wide decompression of deep parts is possible. The microendoscope is positioned above the spinal canal to provide a good symmetrical field of view to enable easy anatomical orientation. RESULTS: Bilateral intervertebral joints were satisfactorily preserved in ten patients who received this surgery. All became ambulatory on the day after surgery and the clinical results remained favorable 3 years after the operation. CONCLUSION: Tubular surgery with the assistance of endoscopic surgery via a midline approach is a minimally invasive surgical procedure with favorable results that enables preservation of paravertebral muscles and bilateral facet joints.

Urban versus rural differences in the occurrence of hip fractures in Japan's Kyoto prefecture during 2008-2010: a comparison of femoral neck and trochanteric fractures.

BACKGROUND: To investigate the differences in the characteristics of femoral neck and trochanteric fractures between urban and rural areas of Kyoto Prefecture in Japan. METHODS: Fracture type (neck vs. trochanteric), age, sex, place where fracture occurred (indoors vs. outdoors), and cause of injury were surveyed among patients aged ≥65 years who sustained hip fractures between 2008 and 2010 and who were treated at 1 of 13 participating hospitals (5 urban, 8 rural). The ratio of sick beds to total number of beds at the participating hospitals was 19.6% (2,188/11,158) in the urban area and 34.9% (1,963/5,623) in the rural area. We also investigated the incidence of hip fracture in Tango medical district as a representative rural area. RESULTS: There were 1,346 neck (mean age, 82.4 years) and 1,606 trochanteric fractures (mean age, 85.0 years). The ratio of neck to trochanteric fractures was higher in the urban area than in the rural area in all age groups (65-74, 75-84, and ≥ 85 years). There were no apparent differences in place or cause of injury. The incidence of hip fracture in the women of Tango medical district was lower than the national average. CONCLUSIONS: There was a difference in the ratio of neck to trochanteric fractures between urban and rural areas. This difference is estimated to be caused by the high and low incidence of neck fracture in urban and rural areas, respectively.

Bone marrow-derived cells from the footprint infiltrate into the repaired rotator cuff.

BACKGROUND: Cells from the bone marrow are considered important during the rotator cuff repair process, but the kinetics of bone marrow-derived cells in this process is unknown. PURPOSE: To analyze the kinetics of bone marrow cells during the rotator cuff repair process, to review whether or not they are histologically involved in rotator cuff healing, and to analyze the biomechanics of the repaired tissues. METHODS: Bone marrow chimeric rats that express green fluorescent protein (GFP) only in bone marrow- and circulation-derived cells were created. Bilateral supraspinatus tendons were separated from the greater tuberosity of the humeral head to produce a rotator cuff transection model. Drilling into the bone marrow was performed in the greater tuberosity of the right humerus and the supraspinatus tendon was repaired (drilling group), while the supraspinatus tendon was repaired on the left shoulder without drilling (control group). We examined the histology of the rotator cuff, the ultimate force-to-failure, and the proportion of GFP-positive cells in the repaired rotator cuff at 2, 4 and 8 weeks after surgery. RESULTS: Mesenchymal cells were observed in the repaired rotator cuff at 2 weeks in both groups. There were more GFP-positive cells in the drilling group than the control group at 2, 4 and 8 weeks. The ultimate force-to-failure was significantly higher in the drilling group than the control group at 4 and 8 weeks. CONCLUSION: Bone marrow-derived cells passed through holes drilled in the humerus footprint, infiltrated the repaired rotator cuff and contributed to postsurgical rotator cuff healing.

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*.

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.

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.

Evaluation of lateral instability of the atlanto-axial joint in rheumatoid arthritis using dynamic open-mouth view radiographs.

Upper cervical involvement is common in patients with rheumatoid arthritis (RA). Anterior atlanto-axial subluxation (aAAS) sometimes occurs at an early stage of the disease. We hypothesized that not only antero-posterior instability but lateral instability may occur with atlanto-axial involvement in RA. To prove this hypothesis, we evaluated the lateral instability of the atlanto-axial joint in RA, using dynamic open-mouth view radiographs. Thirty RA patients and a control group of 22 non-RA outpatients were enrolled in this study. The patients underwent lateral view radiographs of the cervical spine during flexion and extension, and antero-posterior (AP) open-mouth views during maximum right and left bending of the neck. The anterior atlanto-dental interval (AADI) was measured to evaluate antero-posterior instability of the atlanto-axial joint, and atlanto-dental lateral shift (ADLS) was defined to evaluate dynamic lateral instability. In the RA group, AADI averaged 3.2 mm in flexion, and in eight patients, it exceeded 3 mm in flexion (aAAS). In the control group, the AADI averaged 1.0 mm in flexion. The ADLS in the RA group averaged 14.8%, and this was significantly greater than in the control group, in which it averaged 6.1%. The ADLS averaged 20.6% in the RA subgroup with aAAS, and 12.7% in the RA subgroup without aAAS. In both subgroups, the ADLS was significantly greater than that of the control group. In this study, dynamic lateral instability of the atlanto-axial joint in RA was demonstrated. The results suggest that an evaluation of the dynamic lateral instability of the atlanto-axial joint can be useful for early diagnosis of atlanto-axial lesions in RA.