Survival benefits of interventional radiology and surgical teams collaboration during primary trauma surveys: a single-centre retrospective cohort study.

BACKGROUND: A team approach is essential for effective trauma management. Close collaboration between interventional radiologists and surgeons during the initial management of trauma patients is important for prompt and accurate trauma care. This study aimed to determine whether trauma patients benefit from close collaboration between interventional radiology (IR) and surgical teams during the primary trauma survey. METHODS: A retrospective observational study was conducted between 2014 and 2021 at a single institution. Patients were assigned to an embolization group (EG), a surgery group (SG), or a combination group (CG) according to their treatment. The primary and secondary outcomes were survival at hospital discharge compared with the probability of survival (Ps) and the time course of treatment. RESULTS: The analysis included 197 patients, consisting of 135 men and 62 women, with a median age of 56 [IQR, 38-72] years and an injury severity score of 20 [10-29]. The EG, SG, and CG included 114, 48, and 35 patients, respectively. Differences in organ injury patterns were observed between the three groups. In-hospital survival rates in all three groups were higher than the Ps. In particular, the survival rate in the CG was 15.5% higher than the Ps (95% CI: 7.5-23.6%; p < 0.001). In the CG, the median time for starting the initial procedure was 53 [37-79] min and the procedure times for IR and surgery were 48 [29-72] min and 63 [35-94] min, respectively. Those times were significantly shorter among three groups. CONCLUSION: Close collaboration between IR and surgical teams, including the primary survey, improves the survival of severe trauma patients who require both IR procedures and surgeries by improving appropriate treatment selection and reducing the time process.

Transcatheter Arterial Embolization for Blunt Splenic Injury With Resuscitative Endovascular Balloon Occlusion of the Aorta: The Significance of Early Involvement of Radiologists.

Splenectomy is a common procedure for managing splenic injury in patients with unstable vital signs. Transcatheter arterial embolization (TAE) has emerged as a limited alternative to splenectomy, although the role of TAE can be expanded upon the stabilization of vital signs. The current case report discusses a man in his 50s, in shock after a motor vehicle accident, who was successfully stabilized using resuscitative endovascular balloon occlusion of the aorta (REBOA), followed by splenic artery embolization (SAE) instead of splenectomy, with early involvement of diagnostic and interventional radiologists from the initial stage of care. We also discuss the difficulties of SAE under REBOA and the significance of the early involvement of radiologists in trauma care.

Bortezomib Increased Vascular Permeability by Decreasing Cell-Cell Junction Molecules in Human Pulmonary Microvascular Endothelial Cells.

Bortezomib (BTZ), a chemotherapeutic drug used to treat multiple myeloma, induces life-threatening side effects, including severe pulmonary toxicity. However, the mechanisms underlying these effects remain unclear. The objectives of this study were to (1) investigate whether BTZ influences vascular permeability and (2) clarify the effect of BTZ on the expression of molecules associated with cell-cell junctions using human pulmonary microvascular endothelial cells in vitro. Clinically relevant concentrations of BTZ induced limited cytotoxicity and increased the permeability of human pulmonary microvascular endothelial cell monolayers. BTZ decreased the protein expression of claudin-5, occludin, and VE-cadherin but not that of ZO-1 and ß-catenin. Additionally, BTZ decreased the mRNA expression of claudin-5, occludin, ZO-1, VE-cadherin, and ß-catenin. Our results suggest that BTZ increases the vascular permeability of the pulmonary microvascular endothelium by downregulating cell-cell junction molecules, particularly claudin-5, occludin, and VE-cadherin.

Effect of Early Rehabilitation on Walking Independence and Health-Related Quality of Life in Patients With Chronic Foot Wounds: A Multicenter Randomized Clinical Trial.

Rehabilitation is usually provided to patients with chronic foot wounds (CFWs) after surgery. This study aimed to assess whether early postoperative rehabilitation could maintain walking independence in hospitalized patients with CFWs. This single-blind, randomized clinical trial was performed between September 10, 2018 and March 2019, involving 60 patients who underwent both surgical procedures and rehabilitation. Participants were randomly allocated into the early rehabilitation (EG, n = 30) or the control (CG, n = 30) groups. EG received early rehabilitation immediately after surgery, while CG received late rehabilitation after wound closure. Both groups received rehabilitation sessions 5 times per week until discharge. The primary outcome was walking independence, measured via Functional Independence Measure (FIM)-gait scores. Secondary outcomes included health-related quality of life (HRQoL) using EuroQol 5 dimensions 5-level (EQ-5D-5L) and the presence of rehabilitation-related adverse events, including dehiscence of wounds and falls. Differences in intervention timing effects were analyzed using nonparametric split-plot factorial design analysis, including Fisher's exact test, Mann-Whitney U test, and Wilcoxon signed-rank test (P < .05). Out of the 60 participants, 53 patients completed the discharge follow up. Three participants (10.0%) from the EG and 4 (13.3%) from the CG dropped out due to postoperative complications unrelated to rehabilitation intervention. No rehabilitation-related adverse events were found. Participants in the EG maintained greater FIM-gait scores during hospitalization than the CG (difference, -1; P = .0001), with a difference of 0 (P = .109) at discharge. EQ-5D-5L significantly improved in both groups (EG: difference, 0.13 [P = .014], CG: difference, 0.17 [P = .0074]). The EG intervention was associated more with maintaining walking independence at discharge than CG intervention. Postoperative rehabilitation improved HRQoL without adverse events, indicating that clinicians should recommend early rehabilitation for patients with CFW to enhance walking independence.

Association of T cell infiltration and morphological change of thymus gland with the aggravation of pulmonary emphysema in testosterone deficiency.

Chronic obstructive pulmonary disease is an inflammatory lung disease characterized by chronic bronchitis and emphysema. Our previous study revealed that testosterone depletion induced T cell infiltration in the lungs and aggravated pulmonary emphysema in orchiectomized (ORX) mice exposed to porcine pancreatic elastase (PPE). However, the association between T cell infiltration and emphysema remains unclear. The aim of this study was to determine whether thymus and T cells are involved in the exacerbation of PPE-induced emphysema in ORX mice. The weight of thymus gland in ORX mice was significantly greater than that of sham mice. The pretreatment of anti-CD3 antibody suppressed PPE-induced thymic enlargement and T cell infiltration in the lungs in ORX mice, resulting in improved expansion of the alveolar diameter, a marker of emphysema exacerbation. These results suggest that increased thymic function due to testosterone deficiency and the associated increased pulmonary infiltration of T cells may trigger the development of emphysema.

Improvement in salt-tolerance of Aspergillus oryzae γ-glutamyl transpeptidase via protein chimerization with Aspergillus sydowii homolog.

γ-Glutamyl transpeptidase is one of the key enzymes involved in glutamate production during high-salt fermentation of soy sauce and miso by koji mold, Aspergillus oryzae. However, the activity of γ-glutamyl transpeptidase from A. oryzae (AOggtA) is markedly reduced in the presence of NaCl, thus classifying it as a non-salt-tolerant enzyme. In contrast, the homologous protein from the xerophilic mold, A. sydowii (ASggtA) maintains its activity under high-salt conditions. Therefore, in this study, a chimeric enzyme, ASAOggtA, was designed and engineered to improve salt-tolerance in AOggtA by swapping the N-terminal region, based on sequence and structure comparisons between salt-tolerant ASggtA and non-salt-tolerant AOggtA. The parental AOggtA and ASggtA and their chimera, ASAOggtA, were heterologously expressed in A. oryzae and purified. The chimeric enzyme inherited the superior activity and stability from each of the two parent enzymes. ASAOggtA showed > 2-fold greater tolerance than AOggtA in the presence of 18% NaCl. In addition, the chimera showed a broader range of pH stability and greater thermostability than ASggtA. AOggtA and ASAOggtA were sy over the range pH 3.0 to pH 10.5. Thermal stability was found to be in the order AOggtA (57.5 °C, t1/2 = 32.5 min) > ASAOggtA (55 °C, t1/2 = 20.5 min) > ASggtA (50 °C, t1/2 = 12.5 min). The catalytic and structural characteristics indicated that non-salt-tolerant AOggtA would not undergo irreversible structural changes in the presence of NaCl, but rather a temporary conformational change, which might result in reducing the substrate binding and catalytic activity, on the basis of kinetic properties. In addition, the chimeric enzyme showed hydrolytic activity toward L-glutamine that was as high as that of AOggtA. The newly-designed chimeric ASAOggtA might have potential applications in high-salt fermentation, such as miso and shoyu, to increase the content of the umami-flavor amino acid, L-glutamate.

Aging decreases docosahexaenoic acid transport across the blood-brain barrier in C57BL/6J mice.

Nutrients are actively taken up by the brain via various transporters at the blood-brain barrier (BBB). A lack of specific nutrients in the aged brain, including decreased levels of docosahexaenoic acid (DHA), is associated with memory and cognitive dysfunction. To compensate for decreased brain DHA, orally supplied DHA must be transported from the circulating blood to the brain across the BBB through transport carriers, including major facilitator superfamily domain-containing protein 2a (MFSD2A) and fatty acid-binding protein 5 (FABP5) that transport esterified and non-esterified DHA, respectively. Although it is known that the integrity of the BBB is altered during aging, the impact of aging on DHA transport across the BBB has not been fully elucidated. We used 2-, 8-, 12-, and 24-month-old male C57BL/6 mice to evaluate brain uptake of [14C]DHA, as the non-esterified form, using an in situ transcardiac brain perfusion technique. Primary culture of rat brain endothelial cells (RBECs) was used to evaluate the effect of siRNA-mediated MFSD2A knockdown on cellular uptake of [14C]DHA. We observed that the 12- and 24-month-old mice exhibited significant reductions in brain uptake of [14C]DHA and decreased MFSD2A protein expression in the brain microvasculature compared with that of the 2-month-old mice; nevertheless, FABP5 protein expression was up-regulated with age. Brain uptake of [14C]DHA was inhibited by excess unlabeled DHA in 2-month-old mice. Transfection of MFSD2A siRNA into RBECs decreased the MFSD2A protein expression levels by 30% and reduced cellular uptake of [14C]DHA by 20%. These results suggest that MFSD2A is involved in non-esterified DHA transport at the BBB. Therefore, the decreased DHA transport across the BBB that occurs with aging could be due to age-related down-regulation of MFSD2A rather than FABP5.

Senescence in brain pericytes attenuates blood-brain barrier function in vitro: A comparison of serially passaged and isolated pericytes from aged rat brains.

Aging is associated with the dysfunction of the blood-brain barrier (BBB), which comprises brain microvessel endothelial cells (BMECs), astrocytes, and pericytes. Pericytes are present at intervals along the walls of the brain capillaries and play a key role in maintaining BBB integrity. Accumulation of senescent cells and the senescence-associated secretory phenotype (SASP) in the brain facilitate the development of age-related neurodegenerative diseases with BBB dysfunction. However, the ability of pericytes to support BBB integrity and their correlation with cellular senescence or aging remain unknown. Here, we investigated cellular senescence in pericytes focusing on its impact on BBB function using BBB models comprising intact BMECs co-cultured with senescent pericytes, which were obtained through a serial passage or isolated from 18-month-old rats. To assess BBB function, transendothelial electrical resistance (TEER) and permeability of sodium fluorescein (Na-F) were studied. Both serially passaged pericytes (in passage 4, 7, and 10) and aged pericytes isolated from 18-month-old rats showed decreased TEER and enhanced permeability of BMECs to Na-F compared to that of normal pericytes (passage 2 or young). Furthermore, serially passaged and aged pericytes showed characteristic features of cellular senescence, including increased ß-galactosidase activity, cell cycle arrest, enhanced expression of mRNA, and SASP factors. However, the senescence-induced mRNA expression profile of pericyte markers varied between serially passaged and aged pericytes. Hence, in vitro serial passages and isolation from naturally aged rodents differently influenced genetic and biochemical features of senescent brain pericytes. We conclude that senescent brain pericytes can induce BBB dysfunction and those isolated from aged rodents retain the senescence-specific properties. Our findings provide an alternative tool to investigate the senescence in brain pericytes in vitro.

Levetiracetam Suppresses the Infiltration of Neutrophils and Monocytes and Downregulates Many Inflammatory Cytokines during Epileptogenesis in Pilocarpine-Induced Status Epilepticus Mice.

Acute brain inflammation after status epilepticus (SE) is involved in blood-brain barrier (BBB) dysfunction and brain edema, which cause the development of post-SE symptomatic epilepsy. Using pilocarpine-induced SE mice, we previously reported that treatment with levetiracetam (LEV) after SE suppresses increased expression levels of proinflammatory mediators during epileptogenesis and prevents the development of spontaneous recurrent seizures. However, it remains unclear how LEV suppresses neuroinflammation after SE. In this study, we demonstrated that LEV suppressed the infiltration of CD11b+CD45high cells into the brain after SE. CD11b+CD45high cells appeared in the hippocampus between 1 and 4 days after SE and contained Ly6G+Ly6C+ and Ly6G-Ly6C+ cells. Ly6G+Ly6C+ cells expressed higher levels of proinflammatory cytokines such as IL-1ß and TNFα suggesting that these cells were inflammatory neutrophils. Depletion of peripheral Ly6G+Ly6C+ cells prior to SE by anti-Ly6G antibody (NIMP-R14) treatment completely suppressed the infiltration of Ly6G+Ly6C+ cells into the brain. Proteome analysis revealed the downregulation of a variety of inflammatory cytokines, which exhibited increased expression in the post-SE hippocampus. These results suggest that Ly6G+Ly6C+ neutrophils are involved in the induction of acute brain inflammation after SE. The proteome expression profile of the hippocampus treated with LEV after SE was similar to that after NIMP-R14 treatment. Therefore, LEV may prevent acute brain inflammation after SE by suppressing inflammatory neutrophil infiltration.

Percutaneous sclerotherapy using a 4 F pigtail catheter and 40 milliliters of 5% ethanolamine oleate for symptomatic large hepatic cysts.

PURPOSE We retrospectively evaluated the efficacy of percutaneous sclerotherapy using a 4 F catheter and 40 mL of 5% ethanolamine oleate (EO) for symptomatic large hepatic cysts. METHODS Twenty-four patients, including 10 with polycystic liver disease (PLD), were eligible. The mean long- and short-axis diameters of the cyst on computed tomography (CT) were 145.0 ± 35.5 mm (range, 72-216 mm) and 110.5 ± 21.4 mm (range, 63-150 mm), respectively. After aspiration of the fluid contents using a 4 F pigtail catheter, 40 mL of 5% EO was injected into the cyst for 30 min. Then, the catheter was withdrawn after EO removal. Symptomatic relief and complications were evaluated. The percentage reductions at the early (1-3 months later) and late (at the final follow-up) responses were evaluated using an estimated cyst volume calculated by using the following formula: volume = π/6 × long-axis diameter × (short-axis diameter)2 on the maximum cross-section image on CT. Spearman's rank correlation coefficient (ρ) was used to evaluate the correlation between the pretreatment estimated cyst volume and percentage reduction of early and late responses and between the percentage reduction of the late response and length of the follow-up period after sclerotherapy. RESULTS The symptoms disappeared in 23 patients and improved in 1 patient with PLD. The mean aspirated fluid volume was 1337.8 ± 845.4 mL (range, 140-3200 mL). In 1 patient, EO injection was postponed until the second procedure was performed 40 days later due to intraperitoneal leakage of contrast material. In another patient, the EO volume was reduced to 20 mL because of a small cyst size. The mean early and late percentage reductions of the treated cyst were 52.3% ± 23.8% and 87.5% ± 20.4% (mean follow-up period: 48.0 ± 42.4 months), respectively. The symptom recurred in 2 patients with PLD and 1 underwent additional sclerotherapy 14 months later due to re-enlargement of the treated cyst. Another patient underwent transarterial embolization 5 years and 4 months later for other enlarged cysts, although the treated cyst markedly shrank. There were significant negative correlations between the pretreatment estimated cyst volume and percentage reduction of early (P = .027, ρ = - 0.46) and late (P= .007, ρ = - 0.52) responses. However, there were no significant correlations between the percentage reduction and length of the follow-up period (P = .19, ρ = 0.31). Transient pain developed in 1 patient and low-grade fever in 3. CONCLUSION Sclerotherapy using a 4 F catheter and 40 mL of 5% EO is safe and effective for symptomatic large hepatic cysts.

Integrated model for COVID-19 diagnosis based on computed tomography artificial intelligence, and clinical features: a multicenter cohort study.

Background: We developed and validated a machine learning diagnostic model for the novel coronavirus (COVID-19) disease, integrating artificial-intelligence-based computed tomography (CT) imaging and clinical features. Methods: We conducted a retrospective cohort study in 11 Japanese tertiary care facilities that treated COVID-19 patients. Participants were tested using both real-time reverse transcription polymerase chain reaction (RT-PCR) and chest CTs between January 1 and May 30, 2020. We chronologically split the dataset in each hospital into training and test sets, containing patients in a 7:3 ratio. A Light Gradient Boosting Machine model was used for the analysis. Results: A total of 703 patients were included, and two models-the full model and the A-blood model-were developed for their diagnosis. The A-blood model included eight variables (the Ali-M3 confidence, along with seven clinical features of blood counts and biochemistry markers). The areas under the receiver-operator curve of both models [0.91, 95% confidence interval (CI): 0.86 to 0.95 for the full model and 0.90, 95% CI: 0.86 to 0.94 for the A-blood model] were better than that of the Ali-M3 confidence (0.78, 95% CI: 0.71 to 0.83) in the test set. Conclusions: The A-blood model, a COVID-19 diagnostic model developed in this study, combines machine-learning and CT evaluation with blood test data and performs better than the Ali-M3 framework existing for this purpose. This would significantly aid physicians in making a quicker diagnosis of COVID-19.

A low albumin level as a risk factor for transient severe motion artifact induced by gadoxetate disodium administration: A retrospective observational study with free-breathing dynamic MRI and an experimental study in rats.

OBJECTIVES: In the arterial phase of gadoxetate disodium administration for dynamic MRI, transient severe motion (TSM) sometimes occurs, making image evaluation difficult. This study was to identify risk factors for TSM in a clinical study, and confirm them and investigate the cause in an animal study. METHODS: A retrospective, single-center, observational study included patients who underwent dynamic MRI using gadoxetate disodium for the first time from April 2016 to September 2019 and free-breathing MRI was performed. Differences in clinical characteristics and laboratory tests between the presence and absence of TSM were examined. Animal experiments were conducted in 50 rats; gadoxetate disodium was injected into three sites (distal inferior vena cava (IVC), ascending aorta, and descending aorta) to identify the organ which triggers respiratory irregularities. Phosphate-buffered saline and gadopentetate dimeglumine were also injected into the distal IVC. In addition, to evaluate the effect of albumin, gadoxetate disodium was diluted with phosphate-buffered saline or 5% human serum albumin and injected into the ascending aorta. The time course of the respiratory rate was monitored and evaluated. RESULTS: 20 of 51 (39.2%) patients showed TSM. On multivariable analysis, a low albumin level was an independent risk factor (P = .035). Gadoxetate disodium administration caused significant tachypnea compared to gadopentetate dimeglumine or PBS (an elevation of 16.6 vs 3.0 or 4.3 breaths/min; both P < .001) in rats. The starting time of tachypnea was earlier with injection into the ascending aorta than into the descending aorta (10.3 vs 17.9 sec; P < .001) and the distal IVC (vs 15.6 sec; P < .001). With dilution with albumin instead of phosphate-buffered saline, tachypnea was delayed and suppressed (9.9 vs 13.0 sec; P < .001, 24.1 vs 17.0 breaths/min; P = .031). CONCLUSIONS: A low albumin level is a risk factor for TSM, which could be caused by the effect of gadoxetate disodium on the head and neck region.

The effect of participation of interventional radiology team in a primary trauma survey on patient outcome.

PURPOSE: The purpose of this study was to examine the survival benefits of a workflow in which an interventional radiology (IR) team participates in a primary trauma survey on patients with hemodynamically unstable trauma. MATERIALS AND METHODS: A retrospective observational study was conducted between 2012 and 2019 at a single institution. Patients who underwent an IR procedure as the initial hemostasis were assigned to the hemodynamically stable group (HSG) or hemodynamically unstable group (HUG). The primary and secondary outcomes were survival at hospital discharge compared with the probability of survival (Ps) and the time course. RESULTS: A total of 160 patients (100 men, 60 women; median age, 57.5 years [interquartile range (IQR): 31.5-72 years]) with an injury severity score of 24 (IQR: 13.75-34) were included. A total of 125 patients were included in the HSG group and 35 patients in the HUG group. The observational survival rate was significantly greater than the Ps rate by 4.9% (95% confidence interval [CI]: 1.6-8.4%; P = 0.005) in HSG and by 24.6% in HUG (95% CI: 16.9-32.3%; P < 0.001). The observational survival rate was significantly greater than Ps in HUG than in HSG (P < 0.001). The median time to initiate IR procedures and the median procedure time in HUG were 54 min [IQR: 45-66 min] and 48 min [IQR: 30-85 min], respectively; both were significantly shorter than those in the HSG. CONCLUSION: A trauma workflow utilizing an IR team in a primary survey is associated with improved survival of patients with hemodynamically unstable trauma when compared with Ps with a shorter time course.

Development and external validation of a deep learning-based computed tomography classification system for COVID-19.

BACKGROUND: We aimed to develop and externally validate a novel machine learning model that can classify CT image findings as positive or negative for SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR). METHODS: We used 2,928 images from a wide variety of case-control type data sources for the development and internal validation of the machine learning model. A total of 633 COVID-19 cases and 2,295 non-COVID-19 cases were included in the study. We randomly divided cases into training and tuning sets at a ratio of 8:2. For external validation, we used 893 images from 740 consecutive patients at 11 acute care hospitals suspected of having COVID-19 at the time of diagnosis. The dataset included 343 COVID-19 patients. The reference standard was RT-PCR. RESULTS: In external validation, the sensitivity and specificity of the model were 0.869 and 0.432, at the low-level cutoff, 0.724 and 0.721, at the high-level cutoff. Area under the receiver operating characteristic was 0.76. CONCLUSIONS: Our machine learning model exhibited a high sensitivity in external validation datasets and may assist physicians to rule out COVID-19 diagnosis in a timely manner at emergency departments. Further studies are warranted to improve model specificity.

Efficacy of Superselective Conventional Transarterial Chemoembolization Using Guidance Software for Hepatocellular Carcinoma within Three Lesions Smaller Than 3 cm.

The indication of transarterial chemoembolization (TACE) has advanced to hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage A when surgical resection (SR), thermal ablation, and bridging to transplantation are contraindicated; however, TACE for small HCC is frequently difficult and ineffective because of less hypervascularity and the presence of tumor portions receiving a dual blood supply. Here, we report outcomes of superselective conventional TACE (cTACE) for 259 patients with HCCs within three lesions smaller than 3 cm using guidance software. Automated tumor feeder detection (AFD) functionality was applied to identify tumor feeders on cone-beam computed tomography during hepatic arteriography (CBCTHA) data. When it failed, the feeder was identified by manual feeder detection functionality and/or selective angiography and CBCTHA. Regarding the technical success in 382 tumors (mean diameter, 17.2 ± 5.9 mm), 310 (81.2%) were completely embolized with a safety margin (5 mm wide for HCC ≤25 mm and 10 mm wide for HCC >25 mm). In 61 (16.0%), the entire tumor was embolized but the safety margin was not uniformly obtained. The entire tumor was not embolized in 11 (2.9%). Regarding the tumor response at 2-3 months after cTACE in 303 tumors excluding those treated with combined radiofrequency ablation (RFA) or SR and lost to follow-up, 287 (94.7%) were classified into complete response, seven (2.3%) into partial response, and nine (3.0%) into stable disease. The mean follow-up period was 44.9 ± 27.6 months (range, 1-109) and the cumulative local tumor progression rates at 1, 3, 5, and 7 years were 17.8, 27.8, 32.0, and 36.0%, respectively. The 1-, 3-, 5-, and 7-year overall and recurrence-free survival rates in 175 patients, excluding those with Child-Pugh C class, who died of other malignancies, or who underwent combined RFA or hepatic resection, were 97.1 and 68.7, 82.8 and 34.9, 64.8 and 20.2, and 45.3 and 17.3%, respectively. Our results indicate the efficacy of superselective cTACE using guidance software for HCC within three lesions smaller than 3 cm.

Accuracy of deep learning-based computed tomography diagnostic system for COVID-19: A consecutive sampling external validation cohort study.

Ali-M3, an artificial intelligence program, analyzes chest computed tomography (CT) and detects the likelihood of coronavirus disease (COVID-19) based on scores ranging from 0 to 1. However, Ali-M3 has not been externally validated. Our aim was to evaluate the accuracy of Ali-M3 for detecting COVID-19 and discuss its clinical value. We evaluated the external validity of Ali-M3 using sequential Japanese sampling data. In this retrospective cohort study, COVID-19 infection probabilities for 617 symptomatic patients were determined using Ali-M3. In 11 Japanese tertiary care facilities, these patients underwent reverse transcription-polymerase chain reaction (RT-PCR) testing. They also underwent chest CT to confirm a diagnosis of COVID-19. Of the 617 patients, 289 (46.8%) were RT-PCR-positive. The area under the curve (AUC) of Ali-M3 for predicting a COVID-19 diagnosis was 0.797 (95% confidence interval: 0.762‒0.833) and the goodness-of-fit was P = 0.156. With a cut-off probability of a diagnosis of COVID-19 by Ali-M3 set at 0.5, the sensitivity and specificity were 80.6% and 68.3%, respectively. A cut-off of 0.2 yielded a sensitivity and specificity of 89.2% and 43.2%, respectively. Among the 223 patients who required oxygen, the AUC was 0.825. Sensitivity at a cut-off of 0.5% and 0.2% was 88.7% and 97.9%, respectively. Although the sensitivity was lower when the days from symptom onset were fewer, the sensitivity increased for both cut-off values after 5 days. We evaluated Ali-M3 using external validation with symptomatic patient data from Japanese tertiary care facilities. As Ali-M3 showed sufficient sensitivity performance, despite a lower specificity performance, Ali-M3 could be useful in excluding a diagnosis of COVID-19.

Predicting intestinal viability by consecutive photoacoustic monitoring of oxygenation recovery after reperfusion in acute mesenteric ischemia in rats.

The purpose was to assess whether consecutive monitoring of oxygenation by photoacoustic imaging (PAI) can objectively predict intestinal viability during surgery for acute mesenteric ischemia (AMI). PAI uses laser light to detect relative amounts of oxygenated and deoxygenated hemoglobin in intestinal tissue. In 30 rats, AMI was induced by clamping the mesenteric and marginal vessels of the ileum for 0 min in the control group, 30 min in the mild group, and 180 min in the severe group (10 rats per group). After 60 min of reperfusion, intestinal damage was evaluated pathologically. Oxygenation of the intestine was monitored throughout the procedure in real time by a commercially available PAI system and compared among the groups. All rats showed irreversible (i.e. transmucosal or transmural infarction) damage in the severe group. After reperfusion, the oxygenation in the mild group recovered immediately and was significantly higher than in the severe group at 1, 5, 10, 30, and 60 min (P = .011, 002, < .001, 001, and 001, respectively). Oxygenation showed a significant strong negative correlation with pathological severity (rs = - 0.7783, - 0.7806, - 0.7422, - 0.7728, and - 0.7704, respectively). In conclusion, PAI could objectively predict irreversible ischemic damage immediately after reperfusion, which potentially prevents inadequate surgery.

Blood-Brain Barrier Dysfunction Amplifies the Development of Neuroinflammation: Understanding of Cellular Events in Brain Microvascular Endothelial Cells for Prevention and Treatment of BBB Dysfunction.

Neuroinflammation is involved in the onset or progression of various neurodegenerative diseases. Initiation of neuroinflammation is triggered by endogenous substances (damage-associated molecular patterns) and/or exogenous pathogens. Activation of glial cells (microglia and astrocytes) is widely recognized as a hallmark of neuroinflammation and triggers the release of proinflammatory cytokines, leading to neurotoxicity and neuronal dysfunction. Another feature associated with neuroinflammatory diseases is impairment of the blood-brain barrier (BBB). The BBB, which is composed of brain endothelial cells connected by tight junctions, maintains brain homeostasis and protects neurons. Impairment of this barrier allows trafficking of immune cells or plasma proteins into the brain parenchyma and subsequent inflammatory processes in the brain. Besides neurons, activated glial cells also affect BBB integrity. Therefore, BBB dysfunction can amplify neuroinflammation and act as a key process in the development of neuroinflammation. BBB integrity is determined by the integration of multiple signaling pathways within brain endothelial cells through intercellular communication between brain endothelial cells and brain perivascular cells (pericytes, astrocytes, microglia, and oligodendrocytes). For prevention of BBB disruption, both cellular components, such as signaling molecules in brain endothelial cells, and non-cellular components, such as inflammatory mediators released by perivascular cells, should be considered. Thus, understanding of intracellular signaling pathways that disrupt the BBB can provide novel treatments for neurological diseases associated with neuroinflammation. In this review, we discuss current knowledge regarding the underlying mechanisms involved in BBB impairment by inflammatory mediators released by perivascular cells.

Testosterone deficiency promotes the development of pulmonary emphysema in orchiectomized mice exposed to elastase.

Testosterone deficiency is commonly observed in male patients with chronic obstructive pulmonary disease (COPD), which is characterized by chronic inflammation of the airways and pulmonary emphysema. Although clinical trials have indicated that testosterone replacement therapy can improve respiratory function in patients with COPD, the role of testosterone in the pathogenesis of COPD remains unclear. The aim of this study was to explore the effect of testosterone deficiency on the development of pulmonary emphysema in orchiectomized (ORX) mice exposed to porcine pancreatic elastase (PPE). ORX mice developed more severe emphysematous changes 21 d after PPE inhalation than non-ORX mice. Testosterone propionate supplementation significantly reduced PPE-induced emphysematous changes in ORX mice. PPE exposure also increased the number of neutrophils and T cells in bronchoalveolar lavage fluid (BALF) of mice that had undergone ORX and sham surgery. T cell counts were significantly higher in the BALF of ORX mice than of sham mice. Testosterone supplementation reduced the infiltration of T cells into BALF and alleviated emphysematous changes in the lungs of ORX mice. Our findings suggest that testosterone, a male-specific hormone, may suppress the development of pulmonary emphysema through the regulation of T cell-mediated immunity.

Cardiac-specific loss of mitoNEET expression is linked with age-related heart failure.

Heart failure (HF) occurs frequently among older individuals, and dysfunction of cardiac mitochondria is often observed. We here show the cardiac-specific downregulation of a certain mitochondrial component during the chronological aging of mice, which is detrimental to the heart. MitoNEET is a mitochondrial outer membrane protein, encoded by CDGSH iron sulfur domain 1 (CISD1). Expression of mitoNEET was specifically downregulated in the heart and kidney of chronologically aged mice. Mice with a constitutive cardiac-specific deletion of CISD1 on the C57BL/6J background showed cardiac dysfunction only after 12 months of age and developed HF after 16 months; whereas irregular morphology and higher levels of reactive oxygen species in their cardiac mitochondria were observed at earlier time points. Our results suggest a possible mechanism by which cardiac mitochondria may gradually lose their integrity during natural aging, and shed light on an uncharted molecular basis closely related to age-associated HF.