Wavily Curved Perylene Diimides: Synthesis, Characterization, and Photovoltaic Properties.

Solubility enhancement is a key issue for developing the perylene diimide-based functional materials. Introduction of curved structure proved an effective solubilizing method without employing steric repulsion. In this work, wavily curved perylene diimides were developed as a new family of highly soluble curved perylene diimides. Moreover, their conformational dynamics, aggregating properties, electronic properties, and photovoltaic performances were thoroughly examined in comparison to the previously reported isomer exhibiting an arched curvature. The waved isomer demonstrated heightened rigidity and a greater propensity for aggregation compared to the arched isomer, likely attributed to its more planar structure. Each benzoxepin unit played a role in cancelling out the curvature on the opposite side. While the difference in the molecular curvature did not cause significant alterations in the photophysical and electron-accepting properties, we identified that the modulation of the curved structure is effective in controlling the morphology of the photoelectric conversion layer.

Switching from zonisamide to perampanel improved the frequency of seizures caused by hyperthermia in Dravet syndrome: a case report.

BACKGROUND: Dravet syndrome is a severe epilepsy disorder characterized by drug-resistant seizures and cognitive dysfunction, often caused by SCN1A gene mutations. It leads to neurodevelopmental delays and motor, behavioral, and cognitive impairments, with a high mortality rate. Treatment options include sodium valproate, clobazam, and newer agents such as cannabidiol and fenfluramine. Zonisamide, which is used in some cases, can cause hyperthermia and oligohydrosis. Herein, we present a case of a patient with Dravet syndrome whose seizures were controlled by treating infections and switching from zonisamide to perampanel. CASE PRESENTATION: A 24-year-old Japanese man with Dravet syndrome presented to our department with aspiration pneumonia. The patient had been treated with valproate, sodium bromide, and zonisamide for a long time. His seizures were triggered by hyperthermia. The patient was experiencing a sustained pattern of hyperthermia caused by infection, zonisamide, and persistent convulsions, which caused a vicious cycle of further seizures. In this case, the control of infection and switching from zonisamide to perampanel improved seizure frequency. CONCLUSION: Dravet syndrome usually begins with generalized clonic seizures in its infancy because of fever and progresses to various seizure types, often triggered by fever or seizure-induced heat due to mutations in the SCN1A gene that increases neuronal excitability. Seizures usually diminish with age, but the heat sensitivity remains. In this case, seizures were increased by repeated infections, and hyperthermia was induced by zonisamide, resulting in status epilepticus. Perampanel, an aminomethylphosphonic acid receptor antagonist, decreased seizures but caused psychiatric symptoms. It was effective in suppressing seizures of Dravet syndrome in this patient.

Investigating hydrophobic environment in alkyl-group-functionalized silica particle with various chain lengths using absorption microspectroscopy.

A well-known solvatochromic dye, Reichardt's dye (R-dye), was used to evaluate the hydrophobicity of alkyl-group-functionalized silica particles (ASPs) with different chain lengths. The absorption spectra of R-dye were measured in a single ASP in a mixed solution of water and an organic solvent (methanol (MeOH), ethanol (EtOH), acetonitrile (ACN), tetrahydrofuran (THF), or N,N-dimethylformamide (DMF)) using absorption microspectroscopy. The polarity parameter in the ASPs (ET), determined by the absorption maximum, was observed to be smaller than those in bulk solutions, indicating that R-dye was present in a more hydrophobic environment. In EtOH, THF, and DMF, R-dye was distributed within the alkyl chain layer including the organic solvent. An increase in the organic solvent content of the bulk solution led to a higher organic solvent concentration in the alkyl chain layer, resulting in a decrease in ET. In MeOH and ACN, the R-dye was distributed within the alkyl chain layer and concentrated phase. Moreover, with the increase in the organic molecule content, the distribution of R-dye in the concentrated phase became dominant in MeOH and ACN system, leading to an increase in the ET value. The findings presented in this paper are expected to attract the attention of a wide range of researchers in chromatography.

Radiological characteristics of skeletal growth in neonates and infants with achondroplasia.

Achondroplasia (ACH) is the most common form of skeletal dysplasia characterized by a rhizomelic short stature. Radiological skeletal findings in pediatric and adult patients with ACH include short long bones, a relatively longer fibula compared to the tibia, a narrow lumbar interpedicular distance, and a hypoplastic iliac wing. Nonetheless, the characteristics of skeletal growth during the neonatal and infantile periods have scarcely been explored. Therefore, this retrospective study aimed to analyze the radiological skeletal growth during the neonatal and infantile periods in 41 Japanese patients with genetically confirmed ACH. The length of long bones in the upper and lower limbs and the lumbar interpedicular distances at L1 and L4 were measured. These parameters showed significant positive correlations with age. The upper segment-to-lower segment ratio in the lower limbs resembled the data of healthy controls from previous reports. The L1/L4 and fibula/tibia ratios increased with age, suggesting that some representative skeletal phenotypes of ACH were less distinct during the neonatal and infantile periods. In conclusion, for the first time, this study radiologically characterized skeletal growth during the neonatal and infantile periods of patients with genetically confirmed ACH.

Comparison between Cases of Total Hip Arthroplasty Followed by Colonna Capsular Arthroplasty and Lorenz Cast Reduction in Patients with Developmental Dysplasia of the Hip.

Most patients with developmental dysplasia of the hip (DDH) now receive closed-reduction treatment within 6 months after birth. The long-term outcomes of patients with late-detection DDH have remained unclear. We reviewed the clinical records of 18 patients who underwent Colonna capsular arthroplasty (n=8) or closed reduction (n=10) for developmental dysplasia of the hip as infants or young children and underwent total hip arthroplasty approximately in midlife. Both the Colonna capsular arthroplasty and closed reduction groups achieved good clinical results after total hip arthroplasty. However, the operating time was longer and the improvements of hip range of motion and clinical score were significantly worse in the Colonna capsular arthroplasty group than in the closed reduction group.

Clinical Application of 18F-THK5351 PET to Identify Inflammatory Lesions Through Imaging Astrogliosis in a Case of Cytomegalovirus Ventriculoencephalitis.

ABSTRACT: 18F-THK5351 PET is used to estimate the degree of astrogliosis. Because inflammatory lesions usually accompany astrogliosis, 18F-THK5351 PET is potentially worthy of clinical application in inflammatory disorders. Here, we report a case of cytomegalovirus ventriculoencephalitis in an immunocompromised 75-year-old woman who underwent 18F-THK5351 PET and conventional neuroimaging modalities, including 11C-methionine, 18F-FDG, and MRI. 18F-THK5351 PET was clearly superior to the other modalities in identifying inflammatory lesions and can therefore be a useful marker for identifying inflammatory lesions through imaging astrogliosis. This feature of 18F-THK5351 may contribute to the early diagnosis of cytomegalovirus ventriculoencephalitis.

Lambert-Eaton Myasthenic Syndrome Complicated by anti-GABAB Receptor Encephalitis.

A 74-year-old man experienced diplopia, generalized muscle weakness, and acute respiratory failure. He was diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) and treated with immunotherapy, but no improvement was observed, and additional symptoms, including central apnea and hallucinations, appeared. Subsequent serum and cerebrospinal fluid (CSF) analyses confirmed the presence of GABAB receptor antibodies, indicating the coexistence of autoimmune encephalitis. Although there were no findings of malignancy, it is highly likely that occult small-cell lung carcinoma was present. When atypical symptoms occur in patients with LEMS, it is important to consider the possibility of concomitant autoimmune encephalitis.

Factors related to fixedness after transbronchial fiducial marker placement for image-guided proton therapy: A retrospective study.

BACKGROUND: The usefulness of transbronchially inserted gold fiducial markers has been reported in radiation therapy and proton therapy for mobile lesions, such as lung tumors. However, there is occasional dropout of inserted markers. This retrospective study investigated the factors related to dropout of markers inserted for image-guided proton therapy (IGPT). METHODS: Between June 2013 and October 2021, 535 markers were inserted in 171 patients with lung tumors. We investigated whether marker dropout was affected by the location of marker insertion, distance between the marker and the chest wall (DMC), and difference in forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). Marker dropout from the time of planning computed tomography (CT) to follow-up CT was also evaluated. RESULTS: Of the 535 inserted markers, 417 were confirmed on planning CT and 356 on follow-up CT after IGPT. Multivariate analysis revealed that marker insertion into the upper lobe and FEV1/FVC ≥70% were factors associated with total marker dropout. Marker dropout between planning CT and follow-up CT was associated with DMC, FEV1/FVC ≥70%, and planning CT performed within 4 days of marker insertion. CONCLUSIONS: Marker dropout can be minimized by inserting markers more peripherally, by considering the planned insertion location, and FEV1/FVC. Additionally, planning CT should be scheduled at least 5 days after marker insertion.

Atypical posterior reversible encephalopathy syndrome associated with Sjögren'|s syndrome: a case report.

Sjögren'|s syndrome (SJS) is a common autoimmune disease. Generally, posterior reversible encephalopathy syndrome (PRES) is often concomitant with autoimmune disease; however, PRES rarely complicates SJS. Thus, the detailed clinical course of cases with SJS and PRES remains unknown. We present the case of a 71-year-old female patient with primary SJS, whose magnetic resonance (MR) images showed bilateral vasogenic edema in the basal ganglia, brainstem, and cerebellum. Cerebrospinal fluid (CSF) examination revealed increased IgG index and higher interleukin-6 and anti-SSA-autoantibody levels. Management of her blood pressure combined with corticosteroid therapy improved her neurological symptoms, including abnormal CSF and MR imaging findings.

Expression of Acetabular Labral Vascular Endothelial Growth Factor and Nerve Growth Factor Is Directly Associated with Hip Osteoarthritis Pain: Investigation by Immunohistochemical Staining.

The acetabular labrum enhances hip joint stability and plays a key role in osteoarthritis (OA) progression. Labral nerve endings contribute to hip OA pain. Moreover, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) are associated with pain. Consequently, we analysed VEGF and NGF expression levels in the labrum and their roles in OA. Labra obtained from OA patients were stained immunohistochemically, and labral cells were cultured and subjected to a reverse transcription (RT)-polymerase chain reaction (PCR) to analyse VEGF and NGF mRNA expression. VEGF and NGF expression were compared in each region of the labrum. Correlations between VEGF and NGF expression and age, body mass index, Kellgren-Lawrence grade, Harris Hip Score, the visual analogue scale (VAS), and Krenn score were analysed, and the RT-PCR confirmed the findings. VEGF and NGF expression were high on the labral articular side, negatively correlated with the Krenn score, and positively correlated with the VAS in early OA. VEGF and NGF mRNA expression increased significantly in patients with severe pain and decreased significantly in severely degenerated labra. In early OA, VEGF and NGF expression in the acetabular labrum was associated with the occurrence of hip pain; therefore, these factors could be effective targets for pain management.

Mechanical stretching induces calcification and cartilage matrix metabolism, causing degeneration of the acetabular labrum.

PURPOSE: The acetabular labrum plays an important role in joint lubrication, and damage to this structure leads to osteoarthritis. This study aimed to histologically classify the degree of degeneration of the acetabular labrum and to investigate the changes in gene expression induced by mechanical stretching. METHODS: We obtained acetabular labrum cells from patients with hip osteoarthritis during total hip arthroplasty (n = 25). The labrum was stained with safranin O, and images were histologically evaluated using a new parameter, the red/blue (R/B) value. The samples were divided into the degenerated group (D group: n = 18) and the healthy group (H group: n = 7) in accordance with the Kellgren-Lawrence (KL) grade. The cultured acetabular labral cells were subjected to loaded uniaxial cyclic tensile strain (CTS). After CTS, changes in gene expression were examined in both groups. RESULTS: Spearman's correlation analysis revealed that the R/B value was significantly correlated with the KL grade and the Krenn score. The expression levels of genes related to cartilage metabolism, osteogenesis and angiogenesis significantly increased after CTS in the H group, while gene expression in the D group showed weaker changes after CTS than that in the H group compared to the nonstretched control group. CONCLUSIONS: The degree of labral degeneration could be classified histologically using the R/B value and the KL grade. Mechanical stretching caused changes in gene expression that support the pathological features of labral degeneration.

Elevated Expression of CCN3 in Articular Cartilage Induces Osteoarthritis in Hip Joints Irrespective of Age and Weight Bearing.

Osteoarthritis (OA) occurs not only in the knee but also in peripheral joints throughout the whole body. Previously, we have shown that the expression of cellular communication network factor 3 (CCN3), a matricellular protein, increases with age in knee articular cartilage, and the misexpression of CCN3 in cartilage induces senescence-associated secretory phenotype (SASP) factors, indicating that CCN3 promotes cartilage senescence. Here, we investigated the correlation between CCN3 expression and OA degenerative changes, principally in human femoral head cartilage. Human femoral heads obtained from patients who received total hip arthroplasty were categorized into OA and femoral neck fracture (normal) groups without significant age differences. Gene expression analysis of RNA obtained from femoral head cartilage revealed that CCN3 and MMP-13 expression in the non-weight-bearing part was significantly higher in the OA group than in the normal group, whereas the weight-bearing OA parts and normal cartilage showed no significant differences in the expression of these genes. The expression of COL10A1, however, was significantly higher in weight-bearing OA parts compared with normal weight-bearing parts, and was also higher in weight-bearing parts compared with non-weight-bearing parts in the OA group. In contrast, OA primary chondrocytes from weight-bearing parts showed higher expression of CCN3, p16, ADAMTS4, and IL-1ß than chondrocytes from the corresponding normal group, and higher ADAMTS4 and IL-1ß in the non-weight-bearing part compared with the corresponding normal group. Acan expression was significantly lower in the non-weight-bearing group in OA primary chondrocytes than in the corresponding normal chondrocytes. The expression level of CCN3 did not show significant differences between the weight-bearing part and non-weight-bearing part in both OA and normal primary chondrocytes. Immunohistochemical analysis showed accumulated CCN3 and aggrecan neoepitope staining in both the weight-bearing part and non-weight-bearing part in the OA group compared with the normal group. The CCN3 expression level in cartilage had a positive correlation with the Mankin score. X-ray analysis of cartilage-specific CCN3 overexpression mice (Tg) revealed deformation of the femoral and humeral head in the early stage, and immunohistochemical analysis showed accumulated aggrecan neoepitope staining as well as CCN3 staining and the roughening of the joint surface in Tg femoral and humeral heads. Primary chondrocytes from the Tg femoral head showed enhanced expression of Ccn3, Adamts5, p16, Il-6, and Tnfα, and decreased expression of Col2a1 and -an. These findings indicate a correlation between OA degenerative changes and the expression of CCN3, irrespective of age and mechanical loading. Furthermore, the Mankin score indicates that the expression level of Ccn3 correlates with the progression of OA.

A radiological footprint equivalent to liquefactive necrosis observed in the course of disappearing liver metastases in rectal cancer: A case report and review of the literature.

A 72-year-old female diagnosed with rectal cancer treated with a surgical procedure was reported. As 3 liver metastases (LMs) appeared in multidetector CT, adjuvant chemotherapy using Bevacizumab combined with modified FOLFOX-6 was completed. LMs were changed to cystic lesions during the follow-up period, consistent with liquefactive necrosis. These cystic lesions that appeared in the course of disappearing LMs (DLMs) were identified by CT as homogeneous low signal intensity in hepatocyte specific Gd-enhanced MRI. This might be pathognomonic radiological footprint equivalent to liquefactive necrosis observed in the process of DLM and must be carefully followed in the course of radiological complete response. The radiological changing findings of LMs to cystic changes, high sensitivity of detecting DLM, and limitations of Gd-MRI might be meaningful to clinicians.

Impact of Antibody Cocktail Therapy Combined with Casirivimab and Imdevimab on Clinical Outcome for patients with COVID-19 in A Real-Life Setting: A Single Institute Analysis.

BACKGROUND: Recent data from clinical trials suggest that antibody cocktail therapy, which combined casirivimab and imdevimab, is linked to the reduction of the risk of hospitalization or death among high-risk patients with COVID-19. However, it remains unclear how effective the therapy is in a real-life clinical practice. METHODS: We retrospectively analyzed patients with COVID-19 with high-risk factors who underwent the antibody cocktail therapy, compared with those who were not given the cocktail therapy while being isolated in nonmedical facilities during the same period. RESULTS: Data from 55 patients who received the antibody cocktail therapy and 53 patients with initial isolation in nonmedical facilities were analyzed. A total of 22 (41.5 %) of 53 patients staying in isolation facilities were eventually hospitalized and received medical interventions. By contrast, 13 (23.6 %) of 55 patients who received the antibody cocktail therapy subsequently underwent further medical interventions. In multivariate analysis, the antibody cocktail therapy significantly reduced the need for further medical interventions by 70 % compared with isolation (odds ratio=0.30, 95%CI [0.10-0.87], p=0.027). Patients with percutaneous oxygen saturation 96% or higher were significantly favoured for the therapy and had an advantage. CONCLUSION: The results of this study indicate that the antibody cocktail therapy is associated with reducing burden on hospitals during the COVID-19 pandemic.

Mycobacterium avium complex lung disease in a patient treated with an immune checkpoint inhibitor: A case report.

Immune checkpoint inhibitors (ICIs) are becoming widely used for the treatment of various types of cancer. However, characteristic side effects, which are referred to as immune-related adverse events, may appear, and they have important clinical implications for the management of patients treated with ICIs. The development of mycobacterial infections has also been reported, but they have mostly been seen in cases with tuberculosis, and only a few cases involved non-tuberculous mycobacteriosis. We herein present the case of an 82-year-old man who was treated with nivolumab for gastric cancer. After the 22nd course of the treatment, the patient experienced loss of appetite for 1 week, and infiltration shadows were observed in the lower lobe of the left lung. Treatment for bacterial pneumonia was ineffective, and the lung field shadow gradually worsened. Mycobacterium intracellulare was detected in two consecutive sputum cultures. Thus, the patient was diagnosed with Mycobacterium avium complex (MAC) lung disease, and treatment for MAC infection was thus initiated, with subsequent improvement of the patient's condition and infiltration shadows. At 7 months after the start of treatment, the sputum cultures became negative for acid-fast bacilli. Since MAC lung disease may develop acutely during immunotherapy with ICIs, clinicians should include it in the differential diagnoses for pneumonia during immunotherapy with ICIs.

Lambert-Eaton Myasthenic Syndrome Caused by Atezolizumab in a Patient with Small-cell Lung Cancer.

We herein report a 74-year-old man who developed Lambert-Eaton myasthenic syndrome (LEMS) during atezolizumab treatment for extensive-stage small-cell lung cancer. He was started on maintenance immunotherapy with atezolizumab every three weeks after four cycles of atezolizumab plus carboplatin plus etoposide combination therapy. After 13 cycles of maintenance atezolizumab therapy, he complained of muscular weakness and fatigue. Findings from a nerve conduction study and positive findings for anti-P/Q-type voltage-gated calcium channel antibody resulted in a diagnosis of LEMS. This was a rare case of LEMS as a neurological immune-related adverse event induced by atezolizumab therapy.

Spatiotemporal plant hormone analysis from cryosections using laser microdissection-liquid chromatography-mass spectrometry.

Laser microdissection (LMD) is used for isolating specific regions or single cells from a wide variety of tissue samples under direct microscopic observation. The LMD method enables the harvest of the cells of interest in a region or specific cells for several analyses, such as DNA/RNA analysis, proteomics, metabolomics, and other molecular analyses. Currently, LMD is used to study various biological events at the tissue or cellular level; it has been used in a wide range of research fields. In this report, we describe techniques for isolating different tissues/specific cells from cryosections of incised Arabidopsis flowering stems by LMD for spatiotemporal quantitative plant hormone analysis. The endogenous indole-3-acetic acid levels in the epidermis/cortex, vascular bundles, and pith of Arabidopsis flowering stems were approximately 19.0 pg mm-3, 33.5 pg mm-3, and 3.32 pg mm-3, respectively, and these endogenous levels were altered spatiotemporally after incision. We also analyzed jasmonic acid from LMD-isolated cells and showed that the endogenous levels increased in the range of approximately 200-3,500 pg mm-3 depending on the tissue and region at 1 h after incision and then decreased to less than 100 pg mm-3 or undetectable levels at 24 h after incision. Quantitative analyses of phytohormones, including jasmonic acid-related molecules, gibberellin, abscisic acid, and cytokinins, could also be performed using the same cell samples. These results showed that spatiotemporal changes in plant hormones could be quantitatively and simultaneously analyzed by LMD-isolated cells from cryosections with positional information. The combination of quantitative analysis by liquid chromatography-mass spectrometry (LC-MS) and sampling by the LMD method provides a comprehensive and quantitative understanding of spatiotemporal changes in plant hormones in a region- and tissue-specific manner. Therefore, LMD-LC-MS methods will contribute to our understanding of the physiological events that control the process of plant growth and development.

Evaluation of the labrum on postoperative magnetic resonance images: a predictor of acetabular development in developmental dysplasia of the hip.

INTRODUCTION: Residual acetabular dysplasia of the hip after open reduction can complicate the treatment of developmental dysplasia of the hip (DDH) due to the potential need for corrective surgery. This retrospective study aimed to determine the predictive factors for acetabular development using postoperative radiographs and magnetic resonance imaging (MRI). METHODS: We retrospectively investigated 74 hips of patients with DDH who underwent open reduction after reaching walking age and were followed up radiologically until skeletal maturity. We evaluated the cartilaginous acetabulum and labrum using a new method that measures the cartilaginous and labral landmarks on coronal and axial MR T2*-weighted images in patients aged 5 years. The mean age at the time of surgery was 22 months and that at the final survey was 20 years. Severin classification was determined at the final follow-up. Groups with good (53 hips) and poor (21 hips) outcomes were compared using the postoperative radiographic and MRI parameters recorded at 5 years of age. Factors predicting acetabular development were identified using univariate and multiple logistic analyses. RESULTS: There were no significant differences in the bony-acetabular index (AI) and centre-edge (CE) angle between the good and poor outcome groups. However, the poor outcome group had significantly larger cartilaginous- and labral-AIs but significantly smaller cartilaginous- and labral-CE angles than the good outcome group (both p < 0.05). Multiple logistic regression analysis showed that labral-AI and labral-CE angle were predictors of acetabular development after open reduction for DDH, and their optimal cut-offs were 4° (77% sensitivity, 76% specificity) and 37° (68% sensitivity, 85% specificity), respectively. DISCUSSION: Normal cartilaginous acetabulum development occurs in childhood, and evaluation using only radiographs is difficult. However, labral-AI ⩾4° and labral-CE angle <37° on MRI at 5 years of age offer useful indications for corrective surgery in patients with DDH.