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1.
Ann Gastroenterol Surg ; 8(5): 877-887, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39229557

ABSTRACT

Aim: The coronavirus disease 2019 (COVID-19) pandemic greatly impacted medical resources such as cancer screening, diagnosis, and treatment given to people for various diseases. We surveyed the impacts of the pandemic on the incidence of complications and mortality following pancreaticoduodenectomy for pancreatic cancer in Japan. Methods: Data on patients who underwent pancreaticoduodenectomy for pancreatic cancer were extracted from the Japanese National Clinical Database (NCD) between 2018 and 2021. The number of the pancreaticoduodenectomy for pancreatic cancer were obtained and then the morbidity and mortality rates were evaluated using a standardized morbidity/mortality ratio (SMR), which is the ratio of the observed number of incidences to the expected number of incidences calculated by the risk calculator previously developed by the NCD. Results: This study included 22 255 cases. The number of pancreaticoduodenectomies exhibited an increasing trend even during the COVID-19 pandemic. The mean observed incidence rates of Grade C pancreatic fistula and Clavien-Dindo grade ≥4 complications, and the 30-day mortality and surgical mortality rates were 0.8%, 1.8%, 0.8% and 0.9%, respectively. The standardized morbidity ratios did not increase during the COVID-19 pandemic. The standardized mortality ratios remained within the range of variations observed before the COVID-19 pandemic. Conclusion: The increasing trend in the number of pancreaticoduodenectomies and favorable short-term outcomes even in the COVID-19 pandemic suggest the medical care for pancreatic cancer in Japan functioned well during the pandemic.

2.
Ann Gastroenterol Surg ; 8(5): 795-806, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39229559

ABSTRACT

Aim: To examine the potential negative effects of the COVID-19 pandemic on short-term postoperative outcomes of emergency surgery for gastroduodenal perforation in Japan. Methods: A total of 7973 cases of gastroduodenal perforation from 2019 to 2021 were retrieved from the National Clinical Database (NCD), which includes >95% of surgical cases in Japan. Data were analyzed nationally and in subgroups for subjects in areas with high infection levels (HILs). Postoperative 30-d mortality, surgical mortality, and complications (Clavien-Dindo (CD) grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. Results: Nationally, data from 2019 vs 2020 and 2021 showed 30-d mortality of 175 (6.7%) vs 398 (7.4%), surgical mortality of 250 (9.5%) vs 537 (10.1%), and complications (CD ≥3) of 558 (21.2%) vs 1163 (21.8%). Among these data, the only significantly high SMR was found for complications in July 2020 (1.36 [95% CI: 1.001-1.80]). In areas with HILs, data from 2019 vs 2020 and 2021 indicated 30-d mortality of 91 (6.3%) vs 215 (7.3%), surgical mortality of 135 (9.4%) vs 294 (10.0%), and complications (CD ≥3) of 304 (21.1%) vs (23.1%). In these data, no month had a significantly high SMR. Conclusion: The COVID-19 pandemic had few negative effects on outcomes after surgery for gastroduodenal perforation. These findings suggest that the emergency system for gastroduodenal perforation in Japan was generally maintained during the pandemic.

3.
Brain Dev ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39242349

ABSTRACT

BACKGROUND: Quantitative EEG is frequently used to monitor children affected by acute encephalopathy (AE), with the expectation of providing comprehensive insights into continuous EEG monitoring. However, the potential of quantitative EEG for estimating outcomes in this context remains unclear. We sought reliable prognostic markers within the color density spectral array (CDSA) of the continuous EEG for AE-affected children undergoing therapeutic hypothermia (TH). METHODS: This retrospective study analyzed CDSA data from eight scalp electrodes of 15 AE-affected children undergoing TH. Two CDSA features were investigated-high-frequency lines (HFLs) and periodic elevation in the low frequency band (PLFB)-along with the corresponding EEG characteristics. The inter-rater reliability for CDSA was assessed by four pediatric neurologists. Outcomes were grouped into either no/mild or severe decline in motor and cognitive functions, then compared with CDSA features. RESULTS: The median EEG recording time was 114 (81-151) h per child. While at least 41 % of HFLs corresponded to typical sleep spindles, 94 % of PLFB aligned with cyclic changes in the amplitude of delta/theta waves on the raw EEG. Inter-rater reliability was higher for HFLs than for PLFB (kappa values: 0.69 vs. 0.46). HFLs were significantly more prevalent in children with no/mild decline than in children with severe decline (p = 0.017), whereas PLFB did not differ significantly (p = 0.33). CONCLUSIONS: This study provides preliminary evidence that reduced HFLs on CDSA predict unfavorable outcomes in AE-affected children undergoing TH. This suggests that maintaining high-frequency waves is critical for optimal brain function.

4.
J Am Soc Mass Spectrom ; 35(9): 2118-2127, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39136275

ABSTRACT

Capillary electrophoresis coupled with tandem mass spectrometry (CE-MS/MS) offers advantages in peak capacity and sensitivity for metabolic profiling owing to the electroosmotic flow-based separation. However, the utilization of data-independent MS/MS acquisition (DIA) is restricted due to the absence of an optimal procedure for analytical chemistry and its related informatics framework. We assessed the mass spectral quality using two DIA techniques, namely, all-ion fragmentation (AIF) and variable DIA (vDIA), to isolate 60-800 Da precursor ions with respect to annotation rates. Our findings indicate that vDIA, coupled with the updated MS-DIAL chromatogram deconvolution algorithm, yields higher spectral matching scores and annotation rates compared to AIF. Additionally, we evaluated a linear migration time (MT) correction method using internal standards to accurately align chromatographic peaks in a data set. Postcorrection, the data set exhibited less than 0.1 min MT drifts, a difference mostly equivalent to that of conventional reverse-phase liquid chromatography techniques. Moreover, we conducted MT prediction for metabolites recorded in mass spectral libraries and metabolite structure databases containing a total of 469,870 compounds, achieving an accuracy of less than 1.5 min root mean squares. Our platform provides a peak annotation platform utilizing MT information, accurate precursor m/z, and the MS/MS spectrum recommended by the metabolomics standards initiative. Applying this procedure, we investigated metabolic alterations in lipopolysaccharide (LPS)-induced macrophages, characterizing 170 metabolites. Furthermore, we assigned metabolite information to unannotated peaks using an in silico structure elucidation tool, MS-FINDER. The results were integrated into the nodes in the molecular spectrum network based on the MS/MS similarity score. Consequently, we identified significantly altered metabolites in the LPS-administration group, where glycinamide ribonucleotide, not present in any spectral libraries, was newly characterized. Additionally, we retrieved metabolites of false-negative hits during the initial spectral annotation procedure. Overall, our study underscores the potential of CE-MS/MS with DIA and computational mass spectrometry techniques for metabolic profiling.


Subject(s)
Electrophoresis, Capillary , Metabolomics , Tandem Mass Spectrometry , Metabolomics/methods , Electrophoresis, Capillary/methods , Tandem Mass Spectrometry/methods , Animals , Mice , Algorithms , Metabolome/physiology , RAW 264.7 Cells
5.
Esophagus ; 21(4): 411-418, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39158676

ABSTRACT

Esophagectomy for esophageal cancer is a highly invasive gastrointestinal surgical procedure. The National Clinical Database (NCD) of Japan, initiated in 2011, has compiled real-world data on esophagectomy, one of nine major gastroenterological surgeries. This review examines outcomes after esophagectomy analyzed using the Japanese big databases. Certification systems by the Japanese Society of Gastroenterological Surgery (JSGS) and the Japan Esophageal Society (JES) have shown that institutional certification has a greater impact on short-term surgical outcomes than surgeon certification. Minimally invasive esophagectomy has emerged as a viable alternative to open esophagectomy, although careful patient selection is crucial, especially for elderly patients with advanced tumors. The NCD has significantly contributed to the assessment and enhancement of surgical quality and short-term outcomes, while studies based on Comprehensive Registry of Esophageal Cancer in Japan (CRECJ) have provided data on patient characteristics, treatments, and long-term outcomes. The JES has conducted various questionnaire-based retrospective clinical reviews in collaboration with authorized institutions certified by JES. The Diagnosis Procedure Combination (DPC) database provides administrative claims data including itemized prices for surgical, pharmaceutical, laboratory, and other inpatient services. Analyzing these nationwide databases can offer precise insights into surgical quality for esophageal cancer, potentially leading to improved treatment outcomes.


Subject(s)
Databases, Factual , Esophageal Neoplasms , Esophagectomy , Esophagectomy/statistics & numerical data , Esophagectomy/methods , Humans , Japan/epidemiology , Esophageal Neoplasms/surgery , Certification , Registries , Outcome Assessment, Health Care , Treatment Outcome , Minimally Invasive Surgical Procedures/statistics & numerical data , Minimally Invasive Surgical Procedures/methods , Male , Aged , Female
6.
J Phys Ther Sci ; 36(8): 435-440, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39092410

ABSTRACT

[Purpose] We investigated the utility of wearable inertial and magnetic sensing modules for analyzing neck and trunk movements during the rolling over movement. [Participants and Methods] The participants were instructed to roll over from the supine to the side-lying position with three sensor units attached to their forehead, xiphoid process of the sternum, and abdomen. Experiments were conducted on two prescribed patterns: one emphasizing hip joint flexion and adduction, and the other focusing on scapular protraction and horizontal shoulder joint adduction in two healthy participants (one male and one female). The flexion and rotation angles of the neck and trunk were calculated using conventional spreadsheet software with data obtained from the sensors. The obtained values were compared for agreement with those derived from a three-dimensional (3D) motion analysis device. [Results] The cross-correlation coefficient for the flexion and rotation angles of the neck and trunk between the two measurement methods was approximately 0.85, and the root mean square (RMS) angle difference was approximately 5.0°. [Conclusion] Wearable inertial and magnetic sensors can be used to quantitatively evaluate neck and trunk movements during the rolling over movement.

7.
Circ Cardiovasc Qual Outcomes ; 17(8): e010642, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39167767

ABSTRACT

BACKGROUND: The increasing prevalence of frailty has gained considerable attention due to its profound influence on clinical outcomes. However, our understanding of the progression of frailty and long-term clinical outcomes in older individuals with atrial fibrillation remains scarce. METHODS: Using data from 2012 to 2018 from a comprehensive claims database incorporating primary and hospital care records in Shizuoka, Japan, we selected patients aged ≥65 years with atrial fibrillation who initiated oral anticoagulant therapy. The trajectory of frailty was plotted using Sankey plots, illustrating the annual changes in their frailty according to the electronic frailty index during a 3-year follow-up after oral anticoagulant initiation, along with the incidence of clinical adverse outcomes. For deceased patients, we assessed their frailty status in the year preceding their death. RESULTS: Of 6247 eligible patients (45.1% women; mean age, 79.3±8.0 years) at oral anticoagulant initiation, 7.7% were categorized as fit (electronic frailty index, 0-0.12), 30.1% as mildly frail (>0.12-0.24), 35.4% as moderately frail (>0.24-0.36), and 25.9% as severely frail (>0.36). Over the 3-year follow-up, 10.4% of initially fit patients transitioned to moderately frail or severely frail. Conversely, 12.5% of severely frail patients improved to fit or mildly frail. Death, stroke, and major bleeding occurred in 23.4%, 4.1%, and 2.2% of patients, respectively. Among the mortality cases, 74.8% (N=1183) and 3.5% (N=55) had experienced moderately or severely frail and either a stroke or major bleeding in the year preceding their death, respectively. CONCLUSIONS: In a contemporary era of atrial fibrillation management, a minor fraction of older patients on oral anticoagulants died following a stroke or major bleeding. However, their frailty demonstrated a dynamic trajectory, and a substantial proportion of death was observed after transitioning to a moderately or severely frail state.


Subject(s)
Anticoagulants , Atrial Fibrillation , Databases, Factual , Frail Elderly , Frailty , Geriatric Assessment , Humans , Atrial Fibrillation/drug therapy , Atrial Fibrillation/diagnosis , Atrial Fibrillation/mortality , Aged , Female , Male , Frailty/diagnosis , Frailty/mortality , Aged, 80 and over , Anticoagulants/adverse effects , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Japan/epidemiology , Risk Factors , Time Factors , Administration, Oral , Risk Assessment , Age Factors , Treatment Outcome , Stroke/mortality , Stroke/diagnosis , Stroke/epidemiology , Retrospective Studies , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Incidence , Prevalence
8.
JCO Precis Oncol ; 8: e2300425, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39116356

ABSTRACT

PURPOSE: Panel-based comprehensive genomic profiling (CGP) is used in clinical practice worldwide; however, large real-world data (RWD) of patients with advanced small intestine cancer have not been characterized. We investigated differences in the prevalence of clinically relevant alterations across molecularly defined or age-stratified subgroups. PATIENTS AND METHODS: This was a collaborative biomarker study of RWD from CGP testing (Foundation Medicine, Inc). Hybrid capture was conducted on at least 324 cancer-related genes and select introns from up to 31 genes frequently rearranged in cancer. Overall, 1,364 patients with advanced small intestine cancer were available for analyses and were stratified by age (≥40 years/<40 years), microsatellite instability (MSI) status, tumor mutational burden (TMB) status (high ≥10/low <10 Muts/Mb), and select gene alterations. The frequency of alterations was analyzed using a chi-square test with Yate's correction. RESULTS: Genes with frequent alterations included TP53 (59.8%), KRAS (54.8%), APC (27.7%), and CDKN2A (22.4%). Frequent genes with amplifications were MYC (6.7%), MDM2 (5.9%), GATA6 (5.5%), and CCND1 (3.4%). Patients younger than 40 years had significantly lower frequency of APC mutations than those 40 years and older (10.4% v 28.7%; P = .0008). Druggable genomic alterations were detected in 22.3% of patients: BRAF V600E (1.2%), BRCA1 (1.8%), BRCA2 (3.2%), ERBB2 amplification (3.2%), KRAS G12C (3.3%), NTRK1/2/3 fusion (0.07%), MSI-high (7.0%), and TMB-high (12.2%), with no significant differences in the frequency according to age (<40 years v ≥40 years; 22.1% v 22.3%). TMB of 10-20 Mut/Mb was observed in 4.8% of patients, and TMB ≥20 Mut/Mb was seen in 7.3% of the cohort. CONCLUSION: RWD from clinical panel testing revealed the genomic landscape in small intestine cancer by subgroup. These findings provide insights for the future development of treatments in advanced small intestine cancer.


Subject(s)
Intestinal Neoplasms , Intestine, Small , Humans , Male , Female , Middle Aged , Adult , Intestinal Neoplasms/genetics , Aged , Aged, 80 and over , Genomics , Young Adult , Mutation , Microsatellite Instability
9.
Biochem Biophys Rep ; 39: 101789, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39104840

ABSTRACT

The mechanism by which the skin, a non-visual tissue, responds to light remains unknown. To date, opsin expression has been demonstrated in keratinocytes, melanocytes, and fibroblasts, all of which are skin-derived cells. In this study, we examined whether the visual cycle, by which opsin activity is maintained, is present in skin keratinocytes. We also identified the wavelengths of light to which opsin in keratinocytes responds and explored their effects on skin keratinocytes. The fetal rat skin keratinocytes used in this study expressed OPN2, 3, and 5 in addition to enzymes involved in the visual cycle, and all-trans-retinal, which is produced by exposure to light, was reconverted to 11-cis-retinal, resulting in opsin activation. Using the production of all-trans-retinal after light exposure as an indicator, we discovered that keratinocytes responded to light at 450 nm. Furthermore, actin alpha cardiac muscle 1 expression in keratinocytes was enhanced and cell migration was suppressed by exposure to light at these wavelengths. These results indicate that keratinocytes express various opsins and have a visual cycle that keeps opsin active. Moreover, keratinocytes were shown to respond to the blue/UV region of the light spectrum, suggesting that opsin plays a role in the light response of the skin.

10.
Int J Urol ; 2024 Aug 18.
Article in English | MEDLINE | ID: mdl-39154336

ABSTRACT

OBJECTIVES: The National Clinical Database (NCD) Urology Division commenced registration in April 2018 in Japan. This is the first report to focus on five surgeries for which detailed information is registered. METHODS: We herein describe annual trends in and the complication grades of the following five surgeries: partial nephrectomy, radical nephrectomy, radical cystectomy, radical prostatectomy, and pyeloplasty, using the NCD. A total of 149 417 patients treated with the five types of surgeries based on NCD data were enrolled in this report. RESULTS: The number of patients was 55 630 for partial/radical nephrectomy from April 2018 to December 2021, 83 653 for radical prostatectomy from April 2018 to December 2021, and 9342 for radical cystectomy from January 2020 to December 2021. In 2021, partial nephrectomy was performed on 7416 cases, radical nephrectomy on 7739 cases, radical prostatectomy on 22 692 cases, radical cystectomy on 4677 cases, and pyeloplasty on 792 cases. CONCLUSIONS: The results obtained showed that a robot-assisted or laparoscopic procedure has replaced open surgery as the common approach for all five surgeries. An analysis of NCD data may be useful for understanding trends in surgical procedures across the major field of urology.

11.
Surg Today ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39190110

ABSTRACT

PURPOSE: We aimed to identify preoperative risk factors for secondary spontaneous pneumothorax surgery. METHODS: The National Clinical Database of Japan, with six annual datasets from 2014 to 2019, was used. All patients who underwent surgery for secondary spontaneous pneumothorax were included, excluding those < 15 years old and those with incomplete data. The effects of preoperative risk factors were analyzed for operative mortality (mortality during hospitalization or within 30 days, regardless of hospitalization status), 30-day mortality, and postoperative respiratory morbidities. RESULTS: Of the 18,309 patients enrolled in the study, operative mortality, 30-day mortality, and postoperative respiratory morbidities were observed in 654 (3.6%), 343 (1.9%), and 2258 (12.3%) patients, respectively. Increasing age, male sex, body mass index < 18.5 or > 30, performance status > 2, emergent surgery, interstitial pneumonia, and diabetes in preoperative co-morbidity, tumors, and other diseases in underlying lung disease were significant risk factors for operative mortality. Those for 30-day mortality included autoimmune disease instead of male sex and diabetes, while those for postoperative respiratory morbidities included lymphangiomyomatosis instead of a body mass index > 30. CONCLUSION: We identified many preoperative risk factors for operative mortality, 30-day mortality, and postoperative respiratory morbidities in secondary spontaneous pneumothorax surgery. These findings will assist in selecting appropriate surgical candidates.

12.
Int J Urol ; 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39105577

ABSTRACT

BACKGROUND: The Japanese National Clinical Database (NCD) is a large-scale, nationwide, web-based data entry system that covers the majority of surgical cases performed in Japan. An NCD specializing in urological surgery was launched based on the NCD system in 2018. METHODS: All urological surgeries performed at more than 1000 institutions were registered from 2018. We herein report the number of surgeries conducted as stipulated in the "Certified Urology Surgeon Training Curriculum" between April 2018 and December 2021. RESULTS: A total of 1 377 677 cases were registered from 1185 facilities nationwide under the initiative of the Japanese Urological Association. We examined the number of procedures performed every year for each of the 10 categories. CONCLUSIONS: The NCD system sustainably provides important information relating to the preoperative status, operational outcome, and best practice for urological surgery in Japan.

14.
Brain Dev ; 46(9): 302-307, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39089917

ABSTRACT

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) develops along with status epilepticus and widespread subcortical white matter edema. We aimed to evaluate the epileptic foci and networks in two patients with epilepsy after AESD using simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI). METHODS: Statistically significant blood oxygen level-dependent (BOLD) responses related to interictal epileptiform discharges (IEDs) were analyzed using an event-related design of hemodynamic response functions with multiple peaks. RESULTS: Patient 1 developed focal seizures at age 10 years, one year after AESD onset. Positive BOLD changes were observed in the bilateral frontotemporal lobes, left parietal lobe, and left insula. BOLD changes were also observed in the subcortical structures. Patient 2 developed epileptic spasms at age two years, one month after AESD onset. Following total corpus callosotomy (CC) at age three years, the epileptic spasms resolved, and neurodevelopmental improvement was observed. Before CC, positive BOLD changes were observed bilaterally in the frontotemporal lobes. BOLD changes were also observed in the subcortical structures. After CC, the positive BOLD changes were localized in the temporal lobe ipsilateral to the IEDs, and the negative BOLD changes were mainly in the cortex and subcortical structures of the hemisphere ipsilateral to IEDs. CONCLUSION: EEG-fMRI revealed multiple epileptic foci and extensive epileptic networks, including subcortical structures in two cases with post-AESD epilepsy. CC may be effective in disconnecting the bilaterally synchronous epileptic networks of epileptic spasms after AESD, and pre-and post-operative changes in EEG-fMRI may reflect improvements in epileptic symptoms.


Subject(s)
Electroencephalography , Magnetic Resonance Imaging , Seizures , Humans , Electroencephalography/methods , Child , Magnetic Resonance Imaging/methods , Male , Seizures/physiopathology , Seizures/etiology , Seizures/diagnostic imaging , Female , Epilepsy/physiopathology , Epilepsy/diagnostic imaging , Child, Preschool , Brain/diagnostic imaging , Brain/physiopathology , Brain Diseases/physiopathology , Brain Diseases/etiology , Brain Diseases/diagnostic imaging
16.
Surg Endosc ; 38(8): 4306-4315, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38872022

ABSTRACT

BACKGROUND: Little is known about prognostic factors for patients 85 years or older undergoing endoscopic submucosal dissection for early gastric cancer. Therefore, this study aimed to identify such prognostic factors. METHODS: We retrospectively evaluated the long-term outcomes and prognostic factors of 143 patients 85 years or older undergoing endoscopic submucosal dissection for early gastric cancer at a single-center between October 2005 and September 2020. Using the Kaplan-Meier method and a Cox proportional hazards regression model, we examined the relationships of patient characteristics and endoscopic curability (additional gastrectomy recommended [eCuraC-2] or not recommended) with overall survival. RESULTS: The median age of the patients was 86 years, and most patients were men (65%). The eCuraC-2 rate was 14.7%. During the follow-up period, 55 patients died; however, only two patients died due to gastric cancer. The 3-year and 5-year overall survival rates were 91.5% and 74.7%, respectively. Male sex (hazard ratio, 2.23; 95% confidence interval, 1.16-4.30), American Society of Anesthesiologists Physical Status of 3 (hazard ratio, 2.57; 95% confidence interval, 1.32-4.99), body mass index < 18.9 kg/m2 (hazard ratio, 2.21; 95% confidence interval, 1.11-4.40), and eCuraC-2 (hazard ratio, 3.04; 95% confidence interval, 1.37-6.75) were identified as independent prognostic factors. Moreover, patients with eCuraC-2 had significantly more poor prognostic factors than those who did not. CONCLUSIONS: The decision to perform endoscopic submucosal dissection for patients with the aforementioned prognostic factors should be carefully considered because follow-up without endoscopic submucosal dissection is possible.


Subject(s)
Endoscopic Mucosal Resection , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Male , Female , Endoscopic Mucosal Resection/methods , Retrospective Studies , Aged, 80 and over , Prognosis , Survival Rate , Gastrectomy/methods , Age Factors
17.
J Biotechnol ; 391: 57-63, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38851397

ABSTRACT

Antigen-presenting cells (APCs) play an important role in virus infection control by bridging innate and adaptive immune responses. Macrophages and dendritic cells (DCs) possess various surface receptors to recognize/internalize antigens, and antibody binding can enhance pathogen-opsonizing uptake by these APCs via interaction of antibody fragment crystallizable (Fc) domains with Fc receptors, evoking profound pathogen control in certain settings. Here, we examined phagocytosis-enhancing potential of Fc domains directly oriented on a retroviral virion/virus-like particle (VLP) surface. We generated an expression vector coding a murine Fc fragment fused to the transmembrane region (TM) of a retroviral envelope protein, deriving expression of the Fc-TM fusion protein on the transfected cell surface and production of virions incorporating the chimeric Fc upon co-transfection. Incubation of Fc-displaying simian immunodeficiency virus (SIV) with murine J774 macrophages and bone marrow-derived DCs derived Fc receptor-dependent enhanced uptake, being visualized by imaging cytometry. Alternative preparation of a murine leukemia virus (MLV) backbone-based Fc-displaying VLP loading an influenza virus hemagglutinin (HA) antigen resulted in enhanced HA internalization by macrophages, stating antigen compatibility of the design. Results show that the Fc-TM fusion molecule can be displayed on certain viruses/VLPs and may be utilized as a molecular adjuvant to facilitate APC antigen uptake.


Subject(s)
Antigen-Presenting Cells , Dendritic Cells , Immunoglobulin Fc Fragments , Virion , Animals , Mice , Immunoglobulin Fc Fragments/genetics , Immunoglobulin Fc Fragments/metabolism , Immunoglobulin Fc Fragments/immunology , Antigen-Presenting Cells/immunology , Antigen-Presenting Cells/metabolism , Virion/metabolism , Virion/genetics , Dendritic Cells/immunology , Dendritic Cells/metabolism , Macrophages/metabolism , Macrophages/immunology , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Recombinant Fusion Proteins/immunology , Simian Immunodeficiency Virus/immunology , Simian Immunodeficiency Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Cell Line , Leukemia Virus, Murine/genetics , Phagocytosis , Humans
19.
Heliyon ; 10(11): e32197, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38868059

ABSTRACT

Background: Myocardial infarction-related left ventricular pseudoaneurysm (LVP), covered by the adjacent pericardial or scar tissue, is a fatal sequela of left ventricular rupture. Whereas hypertrophic cardiomyopathy (HCM) may cause left ventricular true aneurysm. Differentiating LVP from left ventricular true aneurysm is crucial because their natural histories and treatment strategies are distinct. However, the incidence and management of HCM-related LVP remain unknown. Case presentation: An 88-year-old man was admitted to our hospital with sudden-onset chest pain. Upon initial examination, vital signs were stable, and a grade 4/6 systolic murmur was noted. An electrocardiogram revealed atrial fibrillation and poor R-wave progression without ST-T changes or negative T-waves. An echocardiography showed mild left ventricular hypertrophy, mid-ventricular obstruction with a significant intraventricular pressure gradient, left ventricular outflow tract obstruction, and a small left ventricular apical outpouching. Cardiac computed tomography angiography (CCTA) assisted in the diagnosis of LVP, and an accompanying pericardial effusion suggested impending cardiac rupture. Because the patient initially refused our proposed urgent surgery, medication was initiated with continuous hemodynamic monitoring in the intensive care unit; however, the patient's condition did not improve. During a semi-urgent surgical repair of the aneurysmal wall, LVP was observed and confirmed by pathology. Myocardial tissue adjacent to the pseudoaneurysm was consistent with that of HCM. Subsequently, a final diagnosis of HCM-related LVP was made. The postoperative course was notable for transient profound hypotension. Thereafter, the patient died of non-occlusive mesenteric ischemia on day 6. Conclusions: To our knowledge, this is the first reported case of HCM-related LVP mimicking impending cardiac rupture. Our case highlights the importance of considering HCM-related LVP in patients with left ventricular outpouching and CCTA in the LVP diagnosis. In further research, data on the appropriate management of HCM-related LVP should be accumulated.

20.
Evol Appl ; 17(6): e13727, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38894981

ABSTRACT

For endemic benthos inhabiting hydrothermal vent fields, larval recruitment is critical for population maintenance and colonization via migration among separated sites. The vent-endemic limpet, Lepetodrilus nux, is abundant at deep-sea hydrothermal vents in the Okinawa Trough, a back-arc basin in the northwestern Pacific; nonetheless, it is endangered due to deep-sea mining. This species is associated with many other vent species and is an important successor in these vent ecosystems. However, limpet genetic diversity and connectivity among local populations have not yet been examined. We conducted a population genetics study of L. nux at five hydrothermal vent fields (maximum geographic distance, ~545 km; depths ~700 m to ~1650 m) using 14 polymorphic microsatellite loci previously developed. Genetic diversity has been maintained among these populations. Meanwhile, fine population genetic structure was detected between distant populations, even within this back-arc basin, reflecting geographic distances between vent fields. There was a significant, positive correlation between genetic differentiation and geographic distance, but no correlation with depth. Contrary to dispersal patterns predicted by an ocean circulation model, genetic migration is not necessarily unidirectional, based on relative migration rates. While ocean circulation contributes to dispersal of L. nux among vent fields in the Okinawa Trough, genetic connectivity may be maintained by complex, bidirectional dispersal processes over multiple generations.

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