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1.
Article in English | MEDLINE | ID: mdl-38817687

ABSTRACT

Objective: A newly launched endoscopy system (EVIS X1, CV-1500; Olympus) is equipped with texture and color enhancement imaging (TXI). We aimed to investigate the efficacy of TXI for the visibility and diagnostic accuracy of non-polypoid colorectal lesions. Methods: We examined 100 non-polypoid lesions in 42 patients from the same position, angle, and distance of the view in three modes: white light imaging (WLI), narrow-band imaging (NBI), and TXI. The primary outcome was to compare polyp visibility in the three modes using subjective polyp visibility score and objective color difference values. The secondary outcome was to compare the diagnostic accuracy without magnification. Results: Overall, the visibility score of TXI was significantly higher than that of WLI (3.7 ± 1.1 vs. 3.6 ± 1.1; p = 0.008) and lower than that of NBI (3.7 ± 1.1 vs. 3.8 ± 1.1; p = 0.013). Color difference values of TXI were higher than those of WLI (11.5 ± 6.9 vs. 9.1 ± 5.4; p < 0.001) and lower than those of NBI (11.5 ± 6.9 vs. 13.1 ± 7.7; p = 0.002). No significant differences in TXI and NBI (visibility score: 3.7 ± 1.0 vs. 3.8 ± 1.1; p = 0.833, color difference values: 11.6 ± 7.1 vs. 12.9 ± 8.3; p = 0.099) were observed for neoplastic lesions. Moreover, the diagnostic accuracy of TXI was significantly higher than that of NBI (65.5% vs. 57.6%, p = 0.012) for neoplastic lesions. Conclusions: TXI demonstrated higher visibility than that of WLI and lower than that of NBI. Further investigations are warranted to validate the performance of the TXI mode comprehensively.

2.
Ann Gastroenterol Surg ; 8(4): 631-638, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38957561

ABSTRACT

Background: This study aimed to evaluate the efficacy of lateral lymph node dissection (LLND) for rectal cancer by comparing the local control in patients with and without pathological lateral lymph node metastasis (LLNM). Methods: We included 189 patients with rectal cancer who underwent total mesorectal excision and LLND at 13 institutions between 2017 and 2019. Patients with and without pathological LLNM were defined as the pLLNM (+) and (-) groups, respectively. Propensity score-matching helped to balance the basic characteristics of both groups. The incidences of local recurrence (LR) and lateral lymph node recurrence (LLNR) were compared between the groups. Results: In the entire cohort, 39 of the 189 patients had pathological LLNM. The 3-year LR and LLNR rates were 18.3% and 4.0% (p = 0.01) and 7.7% and 3.3% (p = 0.22) in the pLLNM (+) and (-) groups, respectively. After propensity score matching, the data from 62 patients were analyzed. No significant differences in LR or LLNR were observed between both groups. The 3-year LR and LLNR rates were 16.4% and 9.8% (p = 0.46) and 9.7% and 9.8% (p = 0.99) in the pLLNM (+) and (-) groups, respectively. Conclusion: LLND would lead to comparable local control in the pLLNM (+) and (-) groups if the clinicopathological characteristics except for LLNM are similar.

3.
Mol Med Rep ; 30(3)2024 Sep.
Article in English | MEDLINE | ID: mdl-38963029

ABSTRACT

Viral infections in the respiratory tract are common, and, in recent years, severe acute respiratory syndrome coronavirus 2 outbreaks have highlighted the effect of viral infections on antiviral innate immune and inflammatory reactions. Specific treatments for numerous viral respiratory infections have not yet been established and they are mainly treated symptomatically. Therefore, understanding the details of the innate immune system underlying the airway epithelium is crucial for the development of new therapies. The present study aimed to investigate the function and expression of interferon (IFN)­stimulated gene (ISG)60 in non­cancerous bronchial epithelial BEAS­2B cells exposed to a Toll­like receptor 3 agonist. BEAS­2B cells were treated with a synthetic TLR3 ligand, polyinosinic­polycytidylic acid (poly IC). The mRNA and protein expression levels of ISG60 were analyzed using reverse transcription­quantitative PCR and western blotting, respectively. The levels of C­X­C motif chemokine ligand 10 (CXCL10) were examined using an enzyme­linked immunosorbent assay, and the effects of knockdown of IFN­ß, ISG60 and ISG56 were examined using specific small interfering RNAs. Notably, ISG60 expression was increased in proportion to poly IC concentration, and recombinant human IFN­ß also induced ISG60 expression. By contrast, knockdown of IFN­ß and ISG56 decreased ISG60 expression, and ISG60 knockdown reduced CXCL10 and ISG56 expression. These findings suggested that ISG60 is partly implicated in CXCL10 expression and that ISG60 may serve a role in the innate immune response of bronchial epithelial cells. The present study highlights ISG60 as a potential target for new therapeutic strategies against viral infections in the airway.


Subject(s)
Bronchi , Chemokine CXCL10 , Epithelial Cells , Poly I-C , Signal Transduction , Toll-Like Receptor 3 , Humans , Toll-Like Receptor 3/metabolism , Toll-Like Receptor 3/genetics , Chemokine CXCL10/metabolism , Chemokine CXCL10/genetics , Epithelial Cells/metabolism , Epithelial Cells/drug effects , Bronchi/cytology , Bronchi/metabolism , Poly I-C/pharmacology , Signal Transduction/drug effects , Cell Line , Immunity, Innate , Interferon-beta/metabolism , Interferon-beta/genetics , Gene Expression Regulation/drug effects , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , RNA-Binding Proteins , Adaptor Proteins, Signal Transducing , Apoptosis Regulatory Proteins
4.
J Chem Inf Model ; 64(14): 5712-5724, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-38950938

ABSTRACT

Foods possess a range of unexplored functionalities; however, fully identifying these functions through empirical means presents significant challenges. In this study, we have proposed an in silico approach to comprehensively predict the functionalities of foods, encompassing even processed foods. This prediction is accomplished through the utilization of machine learning on biomedical big data. Our focus revolves around disease-related protein pathways, wherein we statistically evaluate how the constituent compounds collaboratively regulate these pathways. The proposed method has been employed across 876 foods and 83 diseases, leading to an extensive revelation of both food functionalities and their underlying operational mechanisms. Additionally, this approach identifies food combinations that potentially affect molecular pathways based on interrelationships between food functions within disease-related pathways. Our proposed method holds potential for advancing preventive healthcare.


Subject(s)
Machine Learning , Humans , Food , Computer Simulation , Big Data
5.
Sci Adv ; 10(28): eadl4913, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38985878

ABSTRACT

The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments. In addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor κΒ ligand (RANKL) in pulmonary lymphocytes, and alveolar type II cells. Anti-RANKL monoclonal antibody treatment suppressed silica-induced osteoclast-like differentiation in the lung and attenuated pulmonary fibrosis. We conclude that silica induces differentiation of pulmonary osteoclast-like cells leading to progressive lung injury, likely due to sustained elaboration of bone-resorbing proteases and hydrochloric acid. Interrupting osteoclast-like differentiation may therefore constitute a promising avenue for moderating lung damage in silicosis.


Subject(s)
Cell Differentiation , Osteoclasts , Pulmonary Fibrosis , Silicon Dioxide , Silicosis , Silicon Dioxide/toxicity , Animals , Humans , Osteoclasts/metabolism , Osteoclasts/drug effects , Osteoclasts/pathology , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/metabolism , Mice , Silicosis/pathology , Silicosis/metabolism , Silicosis/etiology , Cell Differentiation/drug effects , RANK Ligand/metabolism , Disease Models, Animal , Male , Lung/pathology , Lung/metabolism , Lung/drug effects , Macrophages, Alveolar/metabolism , Macrophages, Alveolar/pathology , Macrophages, Alveolar/drug effects , Female
6.
World J Transplant ; 14(2): 92137, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38947967

ABSTRACT

BACKGROUND: Lung transplantation is a well-established treatment of end-stage lung disease. A rodent model is an inexpensive way to collect biological data from a living model after lung transplantation. However, mastering the surgical technique takes time owing to the small organ size. AIM: To conduct rat lung transplantation using a shunt cannula (SC) or modified cannula (MC) and assess their efficacy. METHODS: Rat lung transplantation was performed in 11 animals in the SC group and 12 in the MC group. We devised a method of rat lung transplantation using a coronary SC for coronary artery bypass surgery as an anastomosis of pulmonary arteriovenous vessels and bronchioles. The same surgeon performed all surgical procedures in the donor and recipient rats without using a magnifying glass. The success rate of lung transplantation, operating time, and PaO2 values were compared after 2-h reperfusion after transplantation. RESULTS: Ten and 12 lungs were successfully transplanted in the SC and MC groups, respectively. In the SC group, one animal had cardiac arrest within 1 h after reperfusion owing to bleeding during pulmonary vein anastomosis. The operating time for the removal of the heart-lung block from the donor and preparation of the left lung graft was 26.8 ± 2.3 and 25.7 ± 1.3 min in the SC and MC groups, respectively (P = 0.21). The time required for left lung transplantation in the recipients was 37.5 ± 2.8 min and 35.9 ± 1.4 min in the SC and MC groups, respectively (P = 0.12). PaO2 values at 2 h after reperfusion were 456.2 ± 25.5 and 461.2 ± 21.5 mmHg in the SC and MC groups, respectively (P = 0.63), without difference between the groups. CONCLUSION: A hyperacute rat lung transplantation model using a coronary SC was created using a simple technique. The MC was inexpensive, easy to prepare, and simple to operate.

7.
Arch Gynecol Obstet ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940845

ABSTRACT

BACKGROUND: Dense adhesion due to severe endometriosis between the posterior cervical peritoneum and the anterior sigmoid or rectum obliterates the cul-de-sac and distorts normal anatomic landmarks. Surgery for endometriosis is associated with severe complications, including ureteral and rectal injuries, as well as voiding dysfunction. It is important to develop the retroperitoneal avascular space based on precise anatomical landmarks to minimize the risk of ureteral, rectal, and hypogastric nerve injuries. We herein report the anatomical highlights and standardized and reproducible surgical steps of total laparoscopic hysterectomy for posterior cul-de-sac obliteration. OPERATIVE TECHNIQUE: We approach the patient with posterior cul-de-sac obliteration using the following five steps. Step 1: Preparation (Mobilization of the sigmoid colon and bladder separation from the uterus). Step 2: Development of the lateral pararectal space and identification of the ureter. Step 3: Isolation of the ureter. Step 4: Development of the medial pararectal space and separation of the hypogastric nerve plane. Step 5: Reopening of the pouch of Douglas. CONCLUSION: Surgeons should recognize the importance of developing the retroperitoneal avascular space based on precise anatomical landmarks, and each surgical step must be reproducible.

8.
Thorac Cancer ; 15(20): 1572-1581, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38828610

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Ipilimumab , Lung Neoplasms , Nivolumab , Pneumonia , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/complications , Male , Nivolumab/adverse effects , Nivolumab/therapeutic use , Nivolumab/administration & dosage , Female , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Ipilimumab/adverse effects , Ipilimumab/therapeutic use , Ipilimumab/administration & dosage , Aged , Risk Factors , Pneumonia/chemically induced , Pneumonia/pathology , Retrospective Studies , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aged, 80 and over
9.
Mol Pharm ; 21(7): 3459-3470, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38809159

ABSTRACT

The aim of this study is to establish and test an in vitro digestion-in situ absorption model that can mimic in vivo drug flux by employing a physiologically relevant value of the membrane surface area (S)/volume (V) ratio for accurate prediction of oral drug absorption from lipid-based formulations (LBFs). Three different types of LBFs (Type IIIA-MC, Type IIIA-LC, and Type IV) loaded with cinnarizine (CNZ), a lipophilic weak base with borderline permeability, and a control suspension were prepared. Subsequently, a simultaneous in vitro digestion-permeation experiment was conducted using a side-by-side diffusion cell with a dialysis membrane having a low S/V value. During digestion, CNZ partially precipitated for Type IV, while it remained solubilized in the aqueous phase for Type IIIA-MC and Type IIIA-LC in the donor compartment. However, in vitro drug fluxes for Type IIIA-MC and Type IIIA-LC were lower than those for Type IV due to the reduced free fraction of CNZ in the donor compartment. In pharmacokinetic studies, a similar improvement in in vivo oral exposure relative to suspension was observed, regardless of the LBFs used. Consequently, a poor correlation was found between in vitro permeation and areas under the plasma concentration-time curve (AUCoral) (R2 = 0.087). A luminal concentration measurement study revealed that this discrepancy was attributed to the extremely high absorption rate of CNZ in the gastrointestinal tract compared to that across a dialysis membrane evaluated by the in vitro digestion-permeation model, i.e., the absorption of CNZ in vivo was completed regardless of the extent of the free fraction, owing to the rapid removal of CNZ from the intestine. Subsequently, we aimed to predict the oral absorption of CNZ from the same formulations using a model that demonstrated high drug flux by employing the physiologically relevant S/V value and rat jejunum segment as an absorption sink (for replicating in vivo intestinal permeability). Predigested formulations were injected into the rat intestinal loop, and AUCloop values were calculated from the plasma concentration-time profiles. A better correlation was found between AUCloop and AUCoral (R2 = 0.72), although AUCloop underestimated AUCoral for Type IV due to the precipitation of CNZ during the predigestion process. However, this result indicated the importance of mimicking the in vivo drug absorption rate in the predictive model. The method presented herein is valuable for the development of LBFs.


Subject(s)
Cinnarizine , Digestion , Intestinal Absorption , Lipids , Permeability , Cinnarizine/pharmacokinetics , Cinnarizine/chemistry , Cinnarizine/administration & dosage , Intestinal Absorption/physiology , Lipids/chemistry , Lipids/pharmacokinetics , Administration, Oral , Digestion/physiology , Animals , Models, Biological , Rats , Drug Compounding/methods , Membranes, Artificial , Chemistry, Pharmaceutical/methods
10.
J Vet Med Sci ; 86(6): 653-655, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38631888

ABSTRACT

The present study analyzed B-cell clonality and bovine leukemia virus (BLV) provirus integration sites in cattle with enzootic bovine leukosis (EBL) having BLV proviral copy numbers less or greater than the number of bovine nucleated cells. EBL cattle with BLV copy numbers less than the number of bovine nucleated cells showed monoclonal and biclonal proliferation of B-cells with one BLV provirus integration site. On the other hand, EBL cattle with BLV copy numbers greater than the number of bovine nucleated cells showed monoclonal proliferation of B-cells with two BLV provirus integration sites. These results suggest that superinfection of BLV can occur in EBL cattle.


Subject(s)
B-Lymphocytes , DNA, Viral , Enzootic Bovine Leukosis , Leukemia Virus, Bovine , Proviruses , Animals , Leukemia Virus, Bovine/genetics , Enzootic Bovine Leukosis/virology , Cattle , Proviruses/genetics , DNA, Viral/genetics , B-Lymphocytes/virology , Virus Integration , Cell Proliferation
11.
Neuromolecular Med ; 26(1): 16, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38668900

ABSTRACT

Toll-like receptor (TLR) 7 plays an important role in recognizing virus-derived nucleic acids. TLR7 signaling in astrocytes and microglia is critical for activating immune responses against neurotrophic viruses. Neurons express TLR7, similar to glial cells; however, the role of neuronal TLR7 has not yet been fully elucidated. This study sought to determine whether resiquimod, the TLR7/8 agonist, induces the expression of inflammatory chemokines in SH-SY5Y human neuroblastoma cells. Immunofluorescence microscopy revealed that TLR7 was constitutively expressed in SH-SY5Y cells. Stimulation with resiquimod induced C-C motif chemokine ligand 2 (CCL2) expression, accompanied by the activation of nuclear factor-kappa B (NF-κB) in SH-SY5Y cells. Resiquimod increased mRNA levels of C-X-C motif chemokine ligand 8 (CXCL8) and CXCL10, while the increase was slight at the protein level. Knockdown of NF-κB p65 eliminated resiquimod-induced CCL2 production. This study provides novel evidence that resiquimod has promising therapeutic potential against central nervous system viral infections through its immunostimulatory effects on neurons.


Subject(s)
Chemokine CCL2 , Chemokine CXCL10 , Imidazoles , Interleukin-8 , Toll-Like Receptor 7 , Transcription Factor RelA , Humans , Cell Line, Tumor , Chemokine CCL2/genetics , Chemokine CCL2/biosynthesis , Chemokine CXCL10/genetics , Chemokine CXCL10/biosynthesis , Imidazoles/pharmacology , Interleukin-8/genetics , Interleukin-8/biosynthesis , Neuroblastoma , Neurons/drug effects , Neurons/metabolism , NF-kappa B/metabolism , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Signal Transduction/drug effects , Toll-Like Receptor 7/agonists , Toll-Like Receptor 7/genetics , Toll-Like Receptor 8/agonists , Toll-Like Receptor 8/genetics , Transcription Factor RelA/metabolism , Transcription Factor RelA/genetics
12.
Clin Transl Sci ; 17(4): e13803, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38651283

ABSTRACT

Drug safety communications (DSCs) are essential tools for communicating important postmarket serious drug safety information to healthcare professionals and patients. Previous studies characterized DSCs issued by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA); however, knowledge about the activities of the Pharmaceuticals and Medical Devices Agency (PMDA)/the Ministry of Health, Labor and Welfare (MHLW) is limited. This study characterized DSCs by the PMDA/MHLW in comparison with previously reported DSCs by the FDA and the EMA. We retrospectively analyzed 37 DSCs of 41 adverse drug reactions (ADRs) for 33 drugs in Japan from 1997 to 2022. Most DSCs were related to non-oncology drugs (30/37, 81.1%), and the median (interquartile range) time from approval to DSC issuance was 19 (10-51) months. Notably, the regulatory review reports and the latest labels before DSC issuance did not describe 16/28 (57.1%) and 12/37 (32.4%) of the ADRs related to DSCs, respectively. Most DSCs resulted in label revisions (36/37, 97.3%) and seven drugs were eventually withdrawn. Some DSC characteristics are similar among the PMDA/MHLW, the FDA, and the EMA; however, the number, contents, and range of new safety issues addressed by DSCs differ among the three jurisdictions. Our study emphasized the importance of continuous efforts to gather postmarket drug safety information because substantial ADRs that led to DSCs were recognized after approval and were associated with critical label revisions and withdrawals. Future studies are required to address global challenges for regulatory harmonization of safety-related regulatory actions.


Subject(s)
Drug Approval , Drug-Related Side Effects and Adverse Reactions , Product Surveillance, Postmarketing , Japan , Humans , Product Surveillance, Postmarketing/statistics & numerical data , Retrospective Studies , Drug-Related Side Effects and Adverse Reactions/epidemiology , United States Food and Drug Administration/standards , Drug Labeling/standards , United States , Adverse Drug Reaction Reporting Systems/statistics & numerical data
13.
Surg Endosc ; 38(5): 2834-2841, 2024 May.
Article in English | MEDLINE | ID: mdl-38605169

ABSTRACT

BACKGROUND: Stoma prolapse (SP) is a common stoma-related complication, particularly in loop colostomies. This study aimed to investigate potential risk factors for SP development after laparoscopic loop colostomy. METHODS: In total, data from 140 patients who underwent laparoscopic loop colostomy were analyzed between September 2016 and March 2022. Risk factors for SP were investigated retrospectively. RESULTS: The median follow-up duration after colostomy was 12.5 months, and SP occurred in 33 (23.6%) patients. Multivariate analysis showed that being overweight (body mass index ≥ 25; odds ratio [OR], 8.69; 95% confidential interval [CI], 1.61-46.72; p = 0.012) and having a thin rectus abdominis penetration of the stoma (< 8.9 mm; OR, 8.22; 95% CI, 2.50-27.05; p < 0.001) were independent risk factors for SP. Other patient characteristics and surgical factors associated with stoma construction were unrelated to SP development. CONCLUSIONS: Being overweight and the route penetrating the thinner rectus abdominis during stoma construction was associated with a significantly higher incidence of SP after laparoscopic loop colostomy. Selecting a construction site that penetrates the thicker rectus abdominis muscle may be crucial for preventing SP.


Subject(s)
Colostomy , Laparoscopy , Surgical Stomas , Humans , Colostomy/adverse effects , Colostomy/methods , Female , Laparoscopy/methods , Laparoscopy/adverse effects , Male , Risk Factors , Middle Aged , Retrospective Studies , Surgical Stomas/adverse effects , Prolapse , Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Adult , Incidence , Rectus Abdominis , Overweight/epidemiology , Aged, 80 and over
14.
J Equine Sci ; 35(1): 15-19, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38524753

ABSTRACT

Equine testicular arteritis commonly occurs as a consequence of the migration of nematode larvae or equine arteritis virus (EAV) infection. However, testicular arteritis without evidence of these infections has been reported, and the underlying pathogenesis remains unclear. We encountered testicular arteritis without evidence of nematode or EAV infection in a 3-year-old male heavy draft horse with scrotal enlargement. Grossly, the volume of the pampiniform plexus was markedly increased due to edema. Histologically, non-suppurative and necrotizing testicular arteritis, characterized by lymphocyte infiltration and fibrinoid necrosis of the arterial walls, was diffusely observed in the spermatic cord, pampiniform plexus (most severe), testis, and epididymis. We were unable to identify the cause of arteritis, such as a viral infection or autoimmune abnormality.

15.
Mol Biol Rep ; 51(1): 417, 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38483660

ABSTRACT

BACKGROUND: Bronchial epithelial cells are at the front line of viral infections. Toll-like receptor 3 (TLR3) cascade causes the expression of interferon (IFN)-ß and IFN-stimulated genes (ISGs), which in turn induce an antiviral response. Members of the transmembrane protein (TMEM) family are expressed in various cell types. Although the prognostic value of TMEM2 in various cancers has been reported, its association with infectious diseases remains unknown. In this study, we investigated the effects of TMEM2 on antiviral immunity in BEAS-2B bronchial epithelial cells. METHODS AND RESULTS: TMEM2 protein was found in the cytoplasm of normal human bronchial epithelial cells and differed between organs using immunohistochemistry. Cultured BEAS-2B cells were transfected with TMEM2 siRNA, followed by administration of TLR3 ligand polyinosinic-polycytidylic acid (poly IC) or recombinant human (r(h)) IFN-ß. The expression of TMEM2, IFN-ß, ISG56, C-X-C motif chemokine ligand 10 (CXCL10) and hyaluronan were evaluated appropriately by western blotting, quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. TMEM2 expression was not altered by poly IC stimulation. Knockdown of TMEM2 increased poly IC-induced expression of IFN-ß, CXCL10, and ISG56, while IFN-ß-induced expression of ISG56 and CXCL10 were not changed by TMEM2 knockdown. The hyaluronan concentration in the medium was decreased by either TMEM2 knockdown or poly IC, but additive or synergistic effects were not observed. CONCLUSIONS: TMEM2 knockdown enhanced TLR3-mediated IFN-ß, CXCL10, and ISG56 expression in BEAS-2B cells. This implies that TMEM2 suppresses antiviral immune responses and prevents tissue injury in bronchial epithelial cells.


Subject(s)
Hyaluronic Acid , Toll-Like Receptor 3 , Humans , Toll-Like Receptor 3/genetics , Toll-Like Receptor 3/metabolism , Ligands , Poly I-C/pharmacology , Epithelial Cells/metabolism , Cells, Cultured , Chemokine CXCL10/genetics
16.
Acta Trop ; 254: 107185, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38494059

ABSTRACT

Animal African trypanosomosis (AAT) is an important global disease of livestock that causes economic losses of up to 4.5 billion US dollars per year. Thus, eliminating AAT in endemic countries will improve agricultural productivity and economic growth. To prevent AAT, vector control and the development of prophylactic drugs are crucial. Ascofuranone (AF) is a bioactive fungal compound with proven in vitro trypanocidal potency and in vivo treatment efficacy. However, the complex stereoselective synthesis of AF has prevented its cost-effective industrial production. Recently, a genetically modified strain of Acremonium egyptiacum fungus that produces a high yield of AF was developed. Therefore, we hypothesized that the oral administration of the AF-producing fungus itself may be effective against AAT. Hence, this study aimed to evaluate the prophylactic activity of orally administered dry-heat-sterilized A. egyptiacum against Trypanosoma congolense IL3000 infection using a mouse model. The survival rate was significantly prolonged (p = 0.009), and parasitemia was suppressed in all AF-fungus-treated groups (Group 1-9) compared with that in the untreated control group (Group 10). Hence, the trypanocidal activity of AF was retained after dry-heat-sterilization of the AF-producing fungus and that its oral administration effectively prevented AAT. Since AAT is endemic to rural areas with underdeveloped veterinary infrastructure, dry-heat-sterilized A. egyptiacum would be the most cost-effective potential treatment for AAT.


Subject(s)
Acremonium , Disease Models, Animal , Trypanosoma congolense , Trypanosomiasis, African , Animals , Trypanosomiasis, African/prevention & control , Trypanosomiasis, African/drug therapy , Trypanosomiasis, African/veterinary , Trypanosoma congolense/drug effects , Administration, Oral , Mice , Female , Parasitemia/prevention & control , Parasitemia/drug therapy , Mice, Inbred BALB C
17.
Opt Express ; 32(2): 1802-1824, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38297724

ABSTRACT

It has been well established that photonic crystal nanocavities with wavelength sized mode volume enable various integrable photonic devices with extremely small consumption energy and small footprint. In this study, we explore the possibility of non-volatile functionalities employing photonic crystal nanocavities and phase change material, Ge2Sb2Te5 (GST). Recently, non-volatile photonic devices based on GST have attracted significant interest and are expected to enable energy-efficient photonic processing, especially for optical computing. However, the device size and the area of GST in previous studies have been rather large. Here, we propose and fabricate Si photonic crystal nanocavities on which submicron-square GST patterns are selectively loaded. Because of the strong light confinement, extremely small area of GST is sufficient to manipulate the cavity mode. We have succeeded to fabricate 30-nm-thick and several-100nm-square GST blocks patterned at the center of photonic crystal cavity with a high alignment accuracy. We confirmed that the resonant wavelength and Q-factor of cavity modes are controlled by the phase change of GST. Moreover, cavity formation controlled by submicron-sized GST is also demonstrated by GST-loaded photonic-crystal line-defect waveguides. Our approach in which we place sub-micron-sized GST inside a photonic crystal nanocavity is promising for realizing extremely energy-efficient non-volatile integrable photonic devices, such as switches, modulators, memories, and reconfigurable novel devices.

18.
Gynecol Oncol Rep ; 52: 101346, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38404911

ABSTRACT

Lymphatic ascites is a postoperative complication of lymph node dissection. Most symptomatic cases improve with conservative treatments. However, optimal management strategies for intractable lymphatic ascites remain controversial, and clinicians sometimes encounter intractable lymphatic ascites that does not respond to conservative management. We herein report a case of postoperative intractable lymphatic ascites that was successfully treated with intranodal lymphangiography (LG) from inguinal lymph nodes under microsurgery. A 56-year-old woman was diagnosed with stage II endometrial cancer and underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomies. On postoperative day (POD) 13, the patient presented with abdominal distention, and lymphatic ascites was diagnosed. Although the patient was treated with conservative management and lymphaticovenular anastomosis, her lymphatic ascites did not resolve. Finally, intranodal LG from the inguinal region was performed under microsurgery. A 2-cm incision was made on each side of the inguinal region. Once the lymph nodes were identified, a 23-gauge needle was inserted into the lymph node and lipiodol was injected. Extravasation of lipiodol into the abdomen from the left side of the lower pelvic region was confirmed. The postoperative course was uneventful. The ascites gradually decreased and disappeared within two weeks after LG.

19.
Echocardiography ; 41(1): e15735, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38284671

ABSTRACT

OBJECTIVES: We previously reported a higher left atrial volume index (LAVI) was independently associated with left atrial (LA) appendage (LAA) thrombus formation in 737 patients with non-valvular atrial fibrillation (NVAF) receiving appropriate oral anticoagulation therapy. Since our previous study was a retrospective single-center study, we designed and conducted a prospective multi-center study to verify our findings for LAVI as a predictor of LAA thrombus in patients with NVAF receiving appropriate oral anticoagulation therapy. METHODS: This prospective multi-center study comprised 746 consecutive patients with NVAF recruited between December 2021 and March 2023 from eight institutions in Japan, who were receiving appropriate oral anticoagulation therapy, had undergone transthoracic echocardiography and transesophageal echocardiography (TEE). RESULTS: LAA thrombi were observed in 21 patients (2.8%). The prevalence of LAA thrombus formation in patients with paroxysmal AF (PAF) was significantly lower than that in patients with non-PAF (0.7% vs. 4.1%, p = .006). LAA thrombus formation was detected in none (0/171) of the patients with normal size LA (LAVI ≤ 34 mL/m2 ). The prevalence of LAA thrombus formation in patients with mildly dilated LA (LAVI: 34-49.9 mL/m2 ) was 2.1% (6/283), but that in PAF patients was low at 1.0% (1/104). Furthermore, this prevalence in patients with severely dilated LA (LAVI ≥ 50 mL/m2 ) was high at 5.1% (15/292). CONCLUSIONS: The findings of this prospective multi-center study are consistent with those of our previous study. Thus, the need for TEE prior to catheter ablation or electrical cardioversion can be determined by the level of LAVI.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Heart Diseases , Thrombosis , Humans , Atrial Appendage/diagnostic imaging , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Retrospective Studies , Prospective Studies , Heart Atria/diagnostic imaging , Echocardiography, Transesophageal , Thrombosis/complications , Anticoagulants/therapeutic use
20.
Biosens Bioelectron ; 249: 116006, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38199081

ABSTRACT

The rapid identification of pathogenic bacteria is crucial across various industries, including food or beverage manufacturing. Bacterial microcolony image-based classification has emerged as a promising approach to expedite identification, automate inspections, and reduce costs. However, conventional imaging methods have significant practical limitations, namely low throughput caused by the limited imaging range and slow imaging speed. To address these challenges, we developed an imaging system based on a line image sensor for rapid and wide-field imaging compared to existing colony imaging methods. This system can image a standard Petri dish (92 mm in diameter) completely within 22 s, successfully acquiring bacterial microcolony images. This process yielded a set of discrimination parameters termed as colony fingerprints, which were employed for machine learning. We demonstrated the performance of our system by identifying Staphylococcus aureus in food products using a machine learning model trained on a colony fingerprint dataset of 15 species from 9 genera, including foodborne pathogens. While conventional mass spectrometry-based methods require 24 h of incubation, our colony fingerprinting approach achieved 96% accuracy in just 10 h of incubation. Line image sensor offer high imaging speeds and scalability, allowing for swift and straightforward microbiological testing, eliminating the need for specialized expertise and overcoming the limitations of conventional methods. This innovation marks a transformative shift in industrial applications.


Subject(s)
Biosensing Techniques , Bacteria , Machine Learning
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