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Yojiro Umezaki,1 Motoko Watanabe,2 Yukiko Shinohara,2 Shiori Sugawara,2 Kaoru Kawasaki,2 Trang TH Tu,2 Takeshi Watanabe,2 Takayuki Suga,2 Anna Miura,2 Miho Takenoshita,2 Yusuke Sato,3 Ichiro Minami,4 Jun Oyama,5 Akira Toriihara,5 Tatsuya Yoshikawa,2 Toru Naito,1 Haruhiko Motomura,2 Akira Toyofuku2 1Section of Geriatric Dentistry, Department of General Dentistry, Fukuoka Dental College, Fukuoka 814-0193, Japan; 2Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, Japan; 3Department of Gerontology and Gerodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, Japan; 4Department of Removable Partial Prosthodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, Japan; 5Department of Diagnostic Radiology and Nuclear Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, JapanCorrespondence: Akira ToyofukuDepartment of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8548, JapanTel/Fax +81- 3-5803-5909Email toyoompm@tmd.ac.jpBackground: Phantom bite syndrome (PBS) is characterized by an uncomfortable sensation during occlusion without any evident abnormality. A recent case–control study with single-photon emission computed tomography (SPECT) using 99mTc-ethyl cysteinate dimer could not find the specific features of regional cerebral blood flow (rCBF), which might be due to the heterogeneity of PBS. We analyzed the brain images of PBS corresponding to the clinical features by studying PBS subgroups.Methods: This study contributes to elucidating the pathophysiology of PBS by evaluating regional brain perfusion on SPECT and its clinical features. We performed SPECT using 99mTc-ethyl cysteinate dimer in 44 patients with PBS. The SPECT images were analyzed qualitatively and quantitatively.Results: Asymmetrical rCBF patterns were detected, corresponding to symptom laterality. Patients with PBS with right-side symptoms showed right-side-predominant rCBF asymmetry in the parietal region and left-side-predominant rCBF asymmetry in the thalamus, and vice versa. Moreover, the analysis of the association between rCBF and patient behaviors revealed that patients who blamed their dentists for their symptoms tended to have a symmetrical rCBF pattern.Conclusion: Patients with PBS showed blood flow imbalance in the thalamus and parietal region corresponding to symptom laterality. There are two types of symmetrical and asymmetrical rCBF patterns in the pathophysiology of PBS despite similar clinical manifestations.Keywords: phantom bite syndrome, cerebral blood flow, single-photon emission computed tomography

The findings of brain perfusion single-photon emission computed tomography (SPECT), which detects abnormalities often before changes manifest in morphological imaging, mainly reflect neurodegeneration and contribute to dementia evaluation. A major shift is about to occur in dementia practice to the approach of diagnosing based on biomarkers and treating with disease-modifying drugs. Accordingly, brain perfusion SPECT will be required to serve as a biomarker of neurodegeneration. Hypoperfusion in Alzheimer's disease (AD) is typically seen in the posterior cingulate cortex and precuneus early in the disease, followed by the temporoparietal cortices. On the other hand, atypical presentations of AD such as the posterior variant, logopenic variant, frontal variant, and corticobasal syndrome exhibit hypoperfusion in areas related to symptoms. Additionally, hypoperfusion especially in the precuneus and parietal association cortex can serve as a predictor of progression from mild cognitive impairment to AD. In dementia with Lewy bodies (DLB), the differentiating feature is the presence of hypoperfusion in the occipital lobes in addition to that observed in AD. Hypoperfusion of the occipital lobe is not a remarkable finding, as it is assumed to reflect functional loss due to impairment of the cholinergic and dopaminergic systems rather than degeneration per se. Moreover, the cingulate island sign reflects the degree of AD pathology comorbid in DLB. Frontotemporal dementia is characterized by regional hypoperfusion according to the three clinical types, and the background pathology is diverse. Idiopathic normal pressure hydrocephalus shows apparent hypoperfusion around the Sylvian fissure and corpus callosum and apparent hyperperfusion in high-convexity areas. The cortex or striatum with diffusion restriction on magnetic resonance imaging in prion diseases reflects spongiform degeneration and brain perfusion SPECT reveals hypoperfusion in the same areas. Brain perfusion SPECT findings in dementia should be carefully interpreted considering background pathology., (© 2024. The Author(s).)

We present a 76-year-old man with cryptogenic new-onset refractory status epilepticus (C-NORSE) with an initial abnormal signal in the nucleus accumbens and a remarkable hyperintense signal on T1-weighted magnetic resonance imaging in the bilateral basal ganglia (BG). His status epilepticus did not respond to most anti-epileptic therapies or immunotherapies, and he died of sepsis. An autopsy revealed severe neuronal loss and hypertrophic astrocytes in the BG and limbic system, with no signs of inflammation or malignancy. This case suggests that lesions in the BG may reflect secondary degeneration and predict poor outcomes in C-NORSE.

Background: There are cases of superficial siderosis (SS) with spinal ventral fluid-filled collection in the spinal canal. In our previous study, the balanced steady-state free precession sequence magnetic resonance imaging is useful in identifying the location of dural defects. However, because of its narrow scan area and long scan time, it cannot easily detect the defect location in some patients with small dural defect. In this study, we applied 4-dimensional (4D) dynamic computed tomography (CT) imaging, including time-axis imaging, to myelography using the latest CT imaging equipment, which can perform short-time continuous imaging, to identify the dural defect site., Methods: Twenty SS patients with ventral fluid-filled collection in the spinal canal (9 males, 11 females; mean age 61.6 years) underwent 4D dynamic CT myelography. A 192-row helical CT (SOMATOM Force, SIEMENS, Munich, Germany) with high-speed scanning capability was used to obtain 9-11 scans per minute at low dose while passing contrast medium into the subarachnoid space. Then, contrast leakage sites were identified., Results: The contrast leakage sites could be identified in all 20 cases: C7/Th1, 2 cases; Th1/2, 5 cases; Th2/3, 9 cases; Th3/4, 1 case; Th5/6, 1 case; Th7/8, 1 case; and Th8/9, 1 case. Eighteen cases underwent surgical operation, and actual dural defects were confirmed at the contrast leakage sites. The mean ± standard deviation of leakage time from contrast agent injection was 19.0 ± 9.2 s., Conclusions: The 4D dynamic CT myelography can be used to reliably identify the location of spinal fluid leakage. In SS cases, dural defects could be visualized in an average of 19 seconds., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: T-cell acute lymphoblastic leukemia (T-ALL) tends to involve central nervous system (CNS) infiltration at diagnosis. However, cases of residual CNS lesions detected at the end of induction and post early intensification have not been recorded in patients with T-ALL. Also, the ratio and prognosis of patients with residual intracranial lesions have not been defined., Case Presentation: A 9-year-old boy with T-ALL had multiple intracranial tumors, which were still detected post early intensification. To investigate residual CNS lesions, we used 11 C-methionine (MET)-positron emission tomography. Negative MET uptake in CNS lesions and excellent MRD status in bone marrow allowed continuing therapies without hematopoietic cell transplantation., Conclusions: In cases with residual lesions on imaging studies, treatment strategies should be considered by the systemic response, direct assessment of spinal fluid, along with further development of noninvasive imaging methods in CNS. Further retrospective or prospective studies are required to determine the prognosis and frequency of cases with residual intracranial lesions after induction therapy., (© 2024. The Author(s).)

Background: Recent studies have found that atrial fibrillation (AF) is a risk factor for cognitive impairment. Brain hypoperfusion is hypothesized as an underlying mechanism of cognitive decline in AF patients., Objectives: This study sought to assess changes in cerebral blood flow (CBF) and brain volume after catheter ablation of AF., Methods: Patients undergoing catheter ablation of AF were enrolled in this prospective study. AF patients being treated with pharmaceuticals alone served as a control group. Brain magnetic resonance imaging was performed before and 6 months after catheter ablation. CBF was assessed by 2-dimensional phase-contrast magnetic resonance angiography. Brain volume and bilateral hippocampal volume were measured using FreeSurfer software., Results: Of the 57 study patients (age 64 ± 11 years; 45 men; paroxysmal AF: n = 22; nonparoxysmal AF: n = 35), 48 patients were freed from tachyarrhythmia recurrence beyond a 3-month blanking period. Changes in CBF and brain perfusion over 6 months were significantly greater in the study patients than control (CBF: 39.26 vs -34.86 mL; P = 0.01, ANCOVA; brain perfusion: 3.78 vs -3.02 mL/100 mL/min; P = 0.009, ANCOVA), while changes in total brain volume and bilateral hippocampal volume were similar between 2 groups (total brain volume: 2.57 vs -2.15 mL; P = 0.32, ANCOVA; bilateral hippocampal volume: 0.03 vs 0.04 mL; P = 0.8, ANCOVA). Nonparoxysmal AF at baseline was an independent predictor of an increase in CBF of >32.6 mL/min., Conclusions: Catheter ablation of AF has favorable effects on CBF, particularly in nonparoxysmal AF. Our results may partially explain the association between cognitive decline and AF., Competing Interests: Funding Support and Author Disclosures Drs Takahashi and Takigawa have received research grants from Medtronic Japan, Boston Scientific, Japan Lifeline, and WIN International. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. All rights reserved.)

Background Context: Its rare prevalence and subtle radiological changes often lead to difficulties in diagnosing cervical ossification of the posterior longitudinal ligament (OPLL) on plain radiographs. However, OPLL progression may lead to trauma-induced spinal cord injury, resulting in severe paralysis. To address the difficulties in diagnosis, a deep learning approach using a convolutional neural network (CNN) was applied., Purpose: The aim of our research was to evaluate the performance of a CNN model for diagnosing cervical OPLL., Study Design and Setting: Diagnostic image study., Patient Sample: This study included 50 patients with cervical OPLL, and 50 control patients with plain radiographs., Outcome Measures: For the CNN model performance evaluation, we calculated the area under the receiver operating characteristic curve (AUC). We also compared the sensitivity, specificity, and accuracy of the diagnosis by the CNN with those of general orthopedic surgeons and spine specialists., Methods: Computed tomography was used as the gold standard for diagnosis. Radiographs of the cervical spine in neutral, flexion, and extension positions were used for training and validation of the CNN model. We used the deep learning PyTorch framework to construct the CNN architecture., Results: The accuracy of the CNN model was 90% (18/20), with a sensitivity and specificity of 80% and 100%, respectively. In contrast, the mean accuracy of orthopedic surgeons was 70%, with a sensitivity and specificity of 73% (SD: 0.12) and 67% (SD: 0.17), respectively. The mean accuracy of the spine surgeons was 75%, with a sensitivity and specificity of 80% (SD: 0.08) and 70% (SD: 0.08), respectively. The AUC of the CNN model based on the radiographs was 0.924., Conclusions: The CNN model had successful diagnostic accuracy and sufficient specificity in the diagnosis of OPLL., Competing Interests: Declaration of competing interests Support for this study was provided by Japan Agency for Medical Research and Development (JP21ek1126633)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Leishmaniasis affects millions of people worldwide, and available treatments have severe limitations. Natural and derivative products are significant sources of innovative therapeutic agents. Naphthoquinones are natural or synthetic chemical compounds with broad biological activity. This systematic review aimed to evaluate the potential anti-Leishmania activity of bioactive compounds derived from naphthoquinones in animal models. Conducted in accordance with PRISMA guidelines, two blocks of MeSH terms were assembled: group I, Leishmania OR Leishmaniasis; group II, Atovaquone OR Lapachol OR Beta lapachone OR Naphthoquinones. The search was performed on PubMed, Web of Science, SCOPUS, EMBASE, and Lilacs databases. Twenty-four articles were retrieved and submitted for quality assessment using the SYRCLE critical appraisal tool. The in vivo anti-Leishmania potential of naphthoquinones was evaluated in visceral and cutaneous leishmaniasis using several measurement parameters. Analyzed compounds varied in structure, association with reference drugs, and encapsulation using a drug delivery system. The study design, including treatment protocol, differed between studies. The findings of the studies in this systematic review indicate the anti-Leishmania potential of naphthoquinones in vivo, with different treatment regimens directed against different Leishmania species. The employed drug delivery systems improve the results concerning selectivity, distribution, and required therapeutic dose. The immunomodulatory action was shown to be beneficial to the host, favoring an adequate immune response against infection by Leishmania parasites since it favored Th 1 responses. All studies presented a moderate to high risk of bias. These findings suggest that more studies are needed to assess the overall effectiveness and safety of these treatments., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Branch-like enhancement (BLE) on contrast-enhanced (CE) magnetic resonance imaging (MRI) was found to be effective in differentiating primary central nervous system lymphoma (PCNSL) from high-grade glioma (HGG) in the cerebellum. However, whether it can be applied to assessments of secondary central nervous system lymphoma (SCNSL), or other cerebellar lesions is unknown. Hence, we retrospectively reviewed cerebellar masses to investigate the use of BLE in differentiating cerebellar lymphoma (CL), both primary and secondary, from other lesions. Two reviewers qualitatively evaluated the presence and degree of BLE on CE-T1 weighted imaging (T1WI). If multiple views were available, we determined the view in which BLE was the most visible. Seventy-five patients with the following pathologies were identified:17 patients with CL, 30 patients with metastasis, 12 patients with hemangioblastoma, 9 patients with HGG, and 7 patients with others. Twelve patients presented with PCNSL and five with SCNSL. Of 17 patients with CL, 15 (88%) had BLE, whereas three (5%) out of 58 patients in the non-CL group showed BLE. In patients who underwent three-dimensional-CE-T1WI, BLE was the most visible on the sagittal image. In conclusion, BLE is a highly specific finding for CL and the sagittal image is important in evaluating this finding., (© 2022. The Author(s).)

Background: Metastasis of infradiaphragmatic tumors to the left supraclavicular lymph node is reported to be rare. When metastasis is detected in the left supraclavicular node in patients with head and neck carcinoma, locating the primary cancer remains a difficult and time-consuming challenge despite the dramatic development of screening technologies and treatment methods., Case Presentation: We report three cases of malignant infradiaphragmatic tumor diagnosed following an initial finding of left supraclavicular node metastasis after surgery for tongue squamous cell carcinoma (follow-up period, range 18-62 months). In these cases, adenocarcinoma was diagnosed based on left supraclavicular node biopsies, and a second primary tumor was found, in a 78-year-old Japanese woman with a diagnosis of cholangiocarcinoma, a 64-year-old Japanese man with a diagnosis of bladder carcinoma, and a 61-year-old Japanese man with a diagnosis of prostate carcinoma. In the cholangiocarcinoma case, carbohydrate antigen 19-9 and alpha-fetoprotein levels helped to diagnose cholangiocarcinoma. Palliative care only was given, with survival for 11 months after diagnosis of lymph node metastasis. In the bladder carcinoma case, pathological analysis of fine-needle aspiration biopsy specimen of the metastatic cervical lymph node showed atypical cells with slight squamous differentiation. Hematoxylin-eosin staining of the bladder lesion did not identify a clear glandular or squamous component, and we could not make a definitive diagnosis of whether the lesion was poorly differentiated squamous cell carcinoma, adenocarcinoma, or high-grade urothelial carcinoma. GATA3 staining aided in the diagnosis of urothelial bladder cancer with left supraclavicular node metastasis. He survived for 2 months after diagnosis of left supraclavicular lymph node metastasis. In the prostate carcinoma case, 18 F-fluorodeoxyglucose uptake was weak. Prostate-specific antigen levels and magnetic resonance imaging findings aided the diagnostic process. This patient underwent bilateral orchiectomy and adjuvant hormonal therapy and survived for 47 months after diagnosis of left supraclavicular node metastasis., Conclusions: Pathological diagnosis on the basis of immunohistochemistry and specific diagnosis methods such as radiological and serological assessments are important for providing rapid diagnosis and appropriate treatment., (© 2022. The Author(s).)

Deep learning (DL) has become a remarkably powerful tool for image processing recently. However, the usefulness of DL in positron emission tomography (PET)/computed tomography (CT) for breast cancer (BC) has been insufficiently studied. This study investigated whether a DL model using images with multiple degrees of PET maximum-intensity projection (MIP) images contributes to increase diagnostic accuracy for PET/CT image classification in BC. We retrospectively gathered 400 images of 200 BC and 200 non-BC patients for training data. For each image, we obtained PET MIP images with four different degrees (0°, 30°, 60°, 90°) and made two DL models using Xception. One DL model diagnosed BC with only 0-degree MIP and the other used four different degrees. After training phases, our DL models analyzed test data including 50 BC and 50 non-BC patients. Five radiologists interpreted these test data. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. Our 4-degree model, 0-degree model, and radiologists had a sensitivity of 96%, 82%, and 80-98% and a specificity of 80%, 88%, and 76-92%, respectively. Our 4-degree model had equal or better diagnostic performance compared with that of the radiologists (AUC = 0.936 and 0.872-0.967, p = 0.036-0.405). A DL model similar to our 4-degree model may lead to help radiologists in their diagnostic work in the future.

Background and Purpose: Bilateral T2 hyperintensities in the medial part of the globus pallidus (GP) are sometimes incidentally observed in patients without a known history of diseases that present with such lesions. The purpose of this study was to evaluate the frequency of this finding and the association between this finding and age, lifestyle diseases and GP calcification., Methods: We retrospectively investigated the brain magnetic resonance imaging (MRI) of 742 patients, which included between 104 and 108 consecutive patients from each decade of life between the 20s and 80s. The signal intensity ratio of the medial part to the lateral part of the GP in T2-weighted images (T2 medial/lateral ratio) was evaluated. For cases in which brain computed tomography images were available ( N =437), GP calcifications were also evaluated. The associations between the T2 medial/lateral ratio and age, sex, history of lifestyle diseases and GP calcification were investigated., Results: Bilateral T2 medial/lateral ratios >1.10, 1.30 and 1.50 were observed in 29.8%, 7.1% and 1.8% of all cases, respectively. A high bilateral T2 medial/lateral ratio was observed less frequently in young patients ( p <0.01), more frequently in elderly patients and those with hypertension or dyslipidaemia ( p <0.05) and more frequently in patients with a calcified GP ( p <0.01)., Conclusion: Incidental bilateral T2 hyperintensities in the medial part of the GP on brain MRI are most likely an age-related physiological finding.

Purpose: Synthetic MRI reconstructs multiple sequences in a single acquisition. In the present study, we aimed to compare the image quality and utility of synthetic MRI with that of conventional MRI in the breast., Methods: We retrospectively collected the imaging data of 37 women (mean age: 55.1 years; range: 20-78 years) who had undergone both synthetic and conventional MRI of T2-weighted, T1-weighted, and fat-suppressed (FS)-T2-weighted images. Two independent breast radiologists evaluated the overall image quality, anatomical sharpness, contrast between tissues, image homogeneity, and presence of artifacts of synthetic and conventional MRI on a 5-point scale (5 = very good to 1 = very poor). The interobserver agreement between the radiologists was evaluated using weighted kappa., Results: For synthetic MRI, the acquisition time was 3 min 28 s. On the 5-point scale evaluation of overall image quality, although the scores of synthetic FS-T2-weighted images (4.01 ± 0.56) were lower than that of conventional images (4.95 ± 0.23; P < 0.001), the scores of synthetic T1- and T2-weighted images (4.95 ± 0.23 and 4.97 ± 0.16) were comparable with those of conventional images (4.92 ± 0.27 and 4.97 ± 0.16; P = 0.484 and 1.000, respectively). The kappa coefficient of conventional MRI was fair (0.53; P < 0.001), and that of conventional MRI was fair (0.46; P < 0.001)., Conclusion: The image quality of synthetic T1- and T2-weighted images was similar to that of conventional images and diagnostically acceptable, whereas the quality of synthetic T2-weighted FS images was inferior to conventional images. Although synthetic MRI images of the breast have the potential to provide efficient image diagnosis, further validation and improvement are required for clinical application.

Background and Objective: Alexander disease (ALXDRD) is an autosomal dominant neurologic disorder caused by mutations in the glial fibrillary acidic protein ( GFAP ) gene and is pathologically defined by Rosenthal fiber accumulation. Most mutations are exonic missense mutations, and splice site mutations are rare. We report a very-late-onset autopsied case of adult-onset ALXDRD with a novel splice site mutation., Methods: Genetic testing of GFAP was performed by Sanger sequencing. Using autopsied brain tissues, GFAP transcript analysis was performed., Results: The patient presented mild upper motor neuron symptoms in contrast to the severe atrophy of spinal cord and medulla oblongata. The patient had c.619-1G>A mutation, which is located in the canonical splice acceptor site of intron 3. The brain RNA analysis identified the r.619&#95;621del (p.Glu207del) mutation, which is explained by the activation of the cryptic splice acceptor site in the second and third nucleotides from the 5' end of the exon 4., Discussion: GFAP gene expression analysis is necessary to clarify the effects of intronic mutations on splicing, even if they are in canonical splice sites. This case showed a much milder phenotype than those in previous cases with missense mutations at Glu207, thereby expanding the clinical spectrum of ALXDRD with Glu207 mutation., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Primary breast osteosarcoma (PBO) is very rare. This report presents a case of POB that was evaluated by multiple modalities. A woman in her 70s presented with a mass of increasing size in her right breast. A mammogram and an ultrasound visualized a lobulated mass containing coarse calcification in the right breast. Magnetic resonance imaging showed a strong enhancement effect and high signal on diffusion-weighted imaging. Further imaging on 18F-fluorodeoxyglucose positron-emission tomography and computed tomography exhibited a high uptake. A right total mastectomy was performed. Histologic examination revealed abundant periosteal formation, areas of calcification and moderately pleomorphic oval to spindle-shaped stromal cells, leading to the diagnosis of PBO. The presence of calcified breast tumors exhibiting aggressive growth indicates that PBO should be added to the differential diagnosis.

A woman in her 60s presented to our hospital with a left breast mass that was diagnosed as breast cancer. 18F-Fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) revealed intense, hot uptake in the cancerous mass and left axillary lymph node metastasis. After chemotherapy, another PET/CT scan was performed. Although the mass and left axillary lymph nodes shrank and FDG uptake decreased, enlarged lymph nodes with high FDG uptake appeared in the right axilla. The patient had a painful vesicular eruption on the front to the back of the right upper hemithorax, which was diagnosed as active herpes zoster. Active herpes zoster mimics a worsening axillary lymph node metastasis on the PET/CT scan.

Aim: Current treatments for leishmaniases are not satisfactory, thus alternatives are needed. We searched for clinical trials with immunotherapeutic approaches for patients with leishmaniasis. Materials & methods: Out of 205 articles, 24 clinical trials were selected, and eight submitted to meta-analysis. Results: A reduction in healing time was observed in patients with tegumentary leishmaniasis treated with pentavalent antimony plus granulocyte-macrophage colony-stimulating factor, and therapeutic vaccines. Overall meta-analysis indicated that immunotherapy associated with the standard chemotherapy generated a significantly reduced risk of treatment failure than the pentavalent antimony alone (p = 0.03). Conclusion: Our review confirmed the efficacy of immunotherapies for the treatment of cutaneous and visceral leishmaniasis and highlighted the importance of clinical trials using immunotherapies for leishmaniases.

Objectives: The outcomes of tegumentary leishmaniasis (TL) rely on a complex interaction between the host immune system and the parasite. This study assessed the influence of polymorphisms in immune-related genes on TL., Methods: Web of Science, Scopus, PubMed, and Embase databases were searched systemically. The meta-analysis used a retrospective model in examining alleles, heterozygotes, and homozygotes. A quality assessment and an analysis of cumulative evidence were performed., Results: A total of 29 genes (encoding for cytokines, chemokines, and other immune receptors) and 84 polymorphisms were analyzed. The IL-1β&#95;rs16944 (OR = 1.341, p = 0.003), TNF-α&#95;rs1800629 (OR = 3.804, p = 0.004), MIF&#95;rs755622 (OR = 3.357, p = 0.001), and INF- γ&#95;rs243056 (OR = 1.670, p = 0.028) polymorphisms were speculated as risk factor for TL. They decrease the expression of the corresponding genes crucial for TL control. The quality assessment score was approximately 50%, suggesting the need for a clear method and polymorphism characterization for further comparison. The relevant risk of bias and other considerations resulted in low and moderate cumulative evidence confidence., Conclusions: IL-1β&#95;rs16944, TNF-α&#95;rs1800629, MIF&#95;rs755622, and INF-γ&#95;rs2430561 polymorphisms were speculated as risk factor for TL, corroborating that IL-1β, TNF-α, INF-γ, and MIF are involved in the TL pathogenesis.

Chronic progressive neuro-Behçet's disease (CPNBD) is characterized by slowly progressive cognitive decline, cerebellar ataxia, and brainstem atrophy without acute encephalomeningitis. To evaluate the progression of CPNBD during treatment, we conducted a retrospective, longitudinal comparative analysis of the clinical features and brain magnetic resonance imaging (MRI) in patients with CPNBD. We classified participants into three groups: NBD with acute encephalomeningitis alone (Group A, 8 patients with acute neuro-Behçet's disease [ANBD]), primary progressive CPNBD (Group B, 3 patients), and a combination of acute encephalomeningitis, and chronic progression (Group C, 2 patients). Routine laboratory tests and monthly rate of enlargement of the width of the third ventricle (ΔWTVm) and relative value of ΔWTVm to the transverse cerebral diameter (ΔWTVIm) were statistically evaluated. Although higher cell count values and interleukin-6 concentration in the cerebrospinal fluid were observed in ANBD, both ΔWTVm (p = 0.008) and ΔWTVIm (p = 0.008) were significantly larger in CPNBD phase than in the ANBD phase. Effective treatment for CPNBD seemed to reduce ΔWTVm and ΔWTVIm in some patients. Sequential evaluation of WTV in patients with CPNBD is a highly sensitive candidate biomarker of early diagnosis and treatment efficacy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: We aimed to evaluate deep learning approach with convolutional neural networks (CNNs) to discriminate between benign and malignant lesions on maximum intensity projections of dynamic contrast-enhanced breast magnetic resonance imaging (MRI)., Methods: We retrospectively gathered maximum intensity projections of dynamic contrast-enhanced breast MRI of 106 benign (including 22 normal) and 180 malignant cases for training and validation data. CNN models were constructed to calculate the probability of malignancy using CNN architectures (DenseNet121, DenseNet169, InceptionResNetV2, InceptionV3, NasNetMobile, and Xception) with 500 epochs and analyzed that of 25 benign (including 12 normal) and 47 malignant cases for test data. Two human readers also interpreted these test data and scored the probability of malignancy for each case using Breast Imaging Reporting and Data System. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were calculated., Results: The CNN models showed a mean AUC of 0.830 (range, 0.750-0.895). The best model was InceptionResNetV2. This model, Reader 1, and Reader 2 had sensitivities of 74.5%, 72.3%, and 78.7%; specificities of 96.0%, 88.0%, and 80.0%; and AUCs of 0.895, 0.823, and 0.849, respectively. No significant difference arose between the CNN models and human readers (p > 0.125)., Conclusion: Our CNN models showed comparable diagnostic performance in differentiating between benign and malignant lesions to human readers on maximum intensity projection of dynamic contrast-enhanced breast MRI., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Breast cancer is the most frequently diagnosed cancer in women; it poses a serious threat to women's health. Thus, early detection and proper treatment can improve patient prognosis. Breast ultrasound is one of the most commonly used modalities for diagnosing and detecting breast cancer in clinical practice. Deep learning technology has made significant progress in data extraction and analysis for medical images in recent years. Therefore, the use of deep learning for breast ultrasonic imaging in clinical practice is extremely important, as it saves time, reduces radiologist fatigue, and compensates for a lack of experience and skills in some cases. This review article discusses the basic technical knowledge and algorithms of deep learning for breast ultrasound and the application of deep learning technology in image classification, object detection, segmentation, and image synthesis. Finally, we discuss the current issues and future perspectives of deep learning technology in breast ultrasound.

This systematic review investigated the evidence for the therapeutic potential of essential oils (EOs) against Leishmania amazonensis. We searched available scientific publications from 2005 to 2019 in the PubMed and Web of Science electronic databases, according to PRISMA statement. The search strategy utilized descriptors and free terms. The EOs effect of 35 species of plants identified in this systematic review study, 45.7% had half of the maximal inhibitory concentration (IC50) 10 < IC50 ⩽ 50 μg mL-1 and 14.3% had a 10 < IC50μg mL-1 for promastigote forms of L. amazonensis. EOs from Cymbopogon citratus species had the lowest IC50 (1.7 μg mL-1). Among the plant species analyzed for activity against intracellular amastigote forms of L. amazonensis, 39.4% had an IC50 10 < IC50 ⩽ 50 μg mL-1, and 33.3% had an IC50 10 < IC50μg mL-1. Aloysia gratissima EO showed the lowest IC50 (0.16 μg mL-1) for intracellular amastigotes. EOs of Chenopodium ambrosioides, Copaifera martii and Carapa guianensis, administered by the oral route, were effective in reducing parasitic load and lesion volume in L. amazonensis-infected BALB/c mice. EOs of Bixa orellana and C. ambrosioides were effective when administered intraperitoneally. Most of the studies analyzed in vitro and in vivo for the risk of bias showed moderate methodological quality. These results indicate a stimulus for the development of new phytotherapy drugs for leishmaniasis treatment.

Wounds constitute severe problems in public health. Inappropriate manipulation to promote wound healing and indiscriminate use of antibiotics may contribute to failure in wound treatment, leading to bacterial growth and resistance. Appropriate and correct approaches to wound treatment are crucially important. Further, the development of new and effective treatment modalities is important to decrease infection-related mortality and to reduce patient suffering and side effects. Photodynamic therapy (PDT) could be a promising approach to ameliorate this global health problem. We researched articles that used PDT in wound healing in vivo. The systematic review included articles that investigated the effect of PDT on wound healing in animals, published from May 2008 through 2018, in the databases PubMed and Web of Science. The main types of wounds described in the selected articles were burns, abrasions, and excisional wounds. Most of the studies tested PDT in wounds infected by methicillin-resistant Staphylococcus aureus, S. aureus standard strain, or Pseudomonas aeruginosa. The studies demonstrated that PDT contributes in several ways to the wound healing process, such as killing bacterial cells and stimulating the proliferation of fibroblasts and consequently of collagen and elastin. Based on these studies, PDT provided excellent results for the wound healing process, acting in several steps and accelerating tissue repair. PDT has proven to be a promising therapeutic modality, able to inhibit bacterial regrowth or kill bacteria, contributing significantly to accelerate the wound healing process., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We aimed to evaluate an artificial intelligence (AI) system that can detect and diagnose lesions of maximum intensity projection (MIP) in dynamic contrast-enhanced (DCE) breast magnetic resonance imaging (MRI). We retrospectively gathered MIPs of DCE breast MRI for training and validation data from 30 and 7 normal individuals, 49 and 20 benign cases, and 135 and 45 malignant cases, respectively. Breast lesions were indicated with a bounding box and labeled as benign or malignant by a radiologist, while the AI system was trained to detect and calculate possibilities of malignancy using RetinaNet. The AI system was analyzed using test sets of 13 normal, 20 benign, and 52 malignant cases. Four human readers also scored these test data with and without the assistance of the AI system for the possibility of a malignancy in each breast. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were 0.926, 0.828, and 0.925 for the AI system; 0.847, 0.841, and 0.884 for human readers without AI; and 0.889, 0.823, and 0.899 for human readers with AI using a cutoff value of 2%, respectively. The AI system showed better diagnostic performance compared to the human readers ( p = 0.002), and because of the increased performance of human readers with the assistance of the AI system, the AUC of human readers was significantly higher with than without the AI system ( p = 0.039). Our AI system showed a high performance ability in detecting and diagnosing lesions in MIPs of DCE breast MRI and increased the diagnostic performance of human readers.

A 60-year-old woman presented to our department with severe tongue pain. On initial examination, the mucosal surface of the tongue was intact but a hard submucosal mass on the dorsum of the tongue was detected on palpation. Magnetic resonance imaging demonstrated an ill-defined tumor in the intrinsic tongue muscles. Sequential whole-body positron emission tomography/computed tomography revealed a tumor of the pancreas apart from the tongue lesion, and upper gastrointestinal endoscopy revealed gastric mucosa ulceration. On biopsy, the tongue lesion was confirmed to be metastatic gastric adenocarcinoma, and the gastric ulcer was simultaneously diagnosed as poorly differentiated gastric adenocarcinoma. The definitive diagnosis was thus gastric adenocarcinoma and synchronous pancreatic cancer, with gastric carcinoma metastases to the tongue. We administered FOLFIRINOX treatment for pancreatic cancer and FLTAX treatment for gastric cancer. Because of difficulty with oral intake due to the growth of the tongue lesion, we administered palliative radiation therapy at a dose of 30 Gy in 10 fractions following which the patient was able to resume oral intake and was satisfied with this outcome. She died 8 months after her first visit to our department., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Olivary hypertrophy (OH) is the secondary degeneration of the inferior olivary nucleus (ION). It is observed one month after the onset of a primary lesion within the dento-rubro-olivary pathway and is usually associated with oculopalatal tremors. Here, we report two unique cases with rare autoimmune diseases leading to OH development with progressive cerebellar ataxia, both of which improved with steroid treatment. The first patient was a 59-year-old man with slowly progressive dysarthria and ataxic gait without palatal tremor. Anti-N-methyl-d-aspartate (NMDA) receptor antibody was positive in the CSF, supporting a diagnosis of anti-NMDA receptor encephalitis. The second patient was a 56-year-old man who developed dysarthria, ataxia, gait disturbance, and palatal tremor. He was diagnosed with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), based on presence of a punctate contrast-enhancing lesion in the middle cerebellar peduncle, pons, and cerebellum on magnetic resonance imaging (MRI). Brain MRI in both patients demonstrated high signal intensity regions in the bilateral IONs. Semi-quantitative volume analysis of MRI revealed significant reduction in ION volume after steroid treatment and accordingly cerebellar ataxia was improved in both cases. Clinical and radiological features of the two cases were unique, indicating potential novel etiologies in the pathophysiology of OH associated with cerebellar ataxia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: 2-Cl-C.OXT-A (COA-Cl) is a novel synthesized adenosine analog that activates Sphingosine-1-phosphate 1 receptor (S1P1R) and combines with the adenosine A1 receptor (A1R) in G proteins and was shown to enhance angiogenesis and improve the brain function in rat stroke models. However, the role of COA-Cl in hearts remains unclear. COA-Cl, which has a similar structure to xanthine derivatives, has the potential to suppress phosphodiesterase (PDE), which is an important factor involved in the beating of heart muscle., Methods and Results: Cardiac organoids with fibroblasts, human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs), and hiPSC-derived endothelial cells (hiPSC-ECs) were cultured until they started beating. The beating and contraction of organoids were observed before and after the application of COA-Cl. COA-Cl significantly increased the beating rate and fractional area change in organoids. To elucidate the mechanism underlying these effects of COA-Cl on cardiac myocytes, pure hiPSC-CM spheroids were evaluated in the presence/absence of Suramin (antagonist of A1R). The effects of COA-Cl, SEW2871 (direct stimulator of S1P1R), two positive inotropes (Isoproterenol [ISO] and Forskolin [FSK]), and negative inotrope (Propranolol [PRP]) on spheroids were assessed based on the beating rates and cAMP levels. COA-Cl stimulated the beating rates about 1.5-fold compared with ISO and FSK, while PRP suppressed the beating rate. However, no marked changes were observed with SEW2871. COA-Cl, ISO, and FSK increased the cAMP level. In contrast, the level of cAMP did not change with PRP or SEW2871 treatment. The results were the same in the presence of Suramin as absence. Furthermore, an enzyme analysis showed that COA-Cl suppressed the PDE activity by half., Conclusions: COA-Cl, which has neovascularization effects, suppressed PDE and increased the contraction of cardiac organoids, independent of S1P1R and A1R. These findings suggest that COA-Cl may be useful as an inotropic agent for promoting angiogenesis in the future., Competing Interests: The authors have declared that no competing interests exist.

Lymphocytic myocarditis is an inflammatory disease of the heart that may present in a myriad of fashions ranging from mild febrile illness to florid myocarditis and cardiogenic shock. Given its nonspecific clinical presentation, the diagnosis of lymphocytic myocarditis is often challenging. The authors describe four cases of lymphocytic myocarditis in young women who presented with cardiogenic shock. Two patients survived and two died. This presentation has not been seen previously in Hawai'i and the public awareness of this condition is critical. Early diagnosis and the prompt initiation of biventricular mechanical circulatory support appear to have been critical in improving patient survival., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Leishmaniasis is a neglected disease and drugs approved for its treatment often lead to abandonment, failure of therapy and even death. Photodynamic therapy (PDT) has been shown to be a promising, non-invasive and selective for a target region without requiring high-cost technology. Usually, it is employed a photosensitizing agent (PS) incorporated into nanoparticles (NP). Pluronics ® P-123 and F-127 micelles are very interesting aqueous NP promoting efficient and selective delivery and less adverse effects. This study aimed to detect the activity of Pluronics ® P-123 and F-127 themselves since there is a scarcity of data on these NP activities without drugs incorporation. This study evaluated, in vitro, the activity of Pluronics ® against promastigotes and amastigotes of Leishmania amazonensis and also their cytotoxicities. Additionally, the determination of the mitochondria membrane potential in promastigotes, internalization of these Pluronics ® in the parasite membrane and macrophages and its stability in the culture medium was evaluated. Results showed that Pluronics ® did not cause significant damage to human red cells and promastigotes. The P-123 and F-127 inhibited the survival rate of L. amazonensis amastigotes, and also presented loss of mitochondrial membrane potential on promastigotes. The Pluronics ® showed low cytotoxic activity on J774A.1 macrophages, while only P-123 showed moderate cytotoxicity for BALB/c macrophages. The stability of P-123 and F-127 in culture medium was maintained for ten days. In conclusion, the NP studied can be used for incorporating potent leishmanicidal chemotherapy, due to their selectivity towards macrophages, being a promising system for the treatment of cutaneous leishmaniasis., (Copyright © 2019 Elsevier B.V. All rights reserved.)