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Modulating autophagy and mitophagy, vital cellular quality control systems, offer therapeutic potential for critical illnesses. However, limited drug screening options hinder progress. We present a novel assay using the photoswitchable fluorescent reporter, mito-Kaede, to quantify mitophagy flux. Mito-Kaede's superior UV-induced photoconversion and brightness post-conversion make it ideal for prolonged mitochondrial dynamics tracking. Its specificity in responding to mitophagy, confirmed by parkin-knockout cells, adds value. When coupled with a custom fluid exchange system, enabling efficient medium changes, precise mitophagy observations become feasible. This mitophagy assay, alongside our methodological insights, can decipher mitophagy's role in pathology and supports drug screening efforts.

In the title dinuclear CuII complex, [Cu2(NO3)(C24H46N8)(H2O)](NO3)3·3H2O, the two CuII molecules both have a square-pyramidal geometry, but the ligands in the axial positions are different: a water molecule and a nitrate ion. All nitrate ions, water molecules, and N—H groups are involved in an intermolecular hydrogen-bond network.

Abstract Background Traumatic tension gastrothorax is a rare and potentially fatal condition occurring in patients with congenital or acquired diaphragmatic defects. Traumatic tension gastrothorax leads to acute and severe respiratory distress. Delayed tension gastrothorax that develops late during injury can be more severe. Case presentation An 84-year-old woman was brought to our facility with cardiac arrest and returned to spontaneous circulation after 2 min of cardiopulmonary resuscitation. Computed tomography showed diaphragmatic injury and tension gastrothorax due to trauma because of a fall episode few days earlier. Emergency thoracotomy and laparotomy was performed, because nasogastric tube insertion failed. There was a partially necrotic stomach in the chest cavity. The stomach was retracted from the thoracic cavity into the abdominal cavity and placed in its proper position. There was a 5 cm tear of the diaphragm. The tear was sutured and closed and then the necrotic area of the stomach was resected. Although the surgery relieved the intrathoracic compression, it resulted in re-expansion pulmonary edema immediately after surgery and hypoxemia. The patient was unable to overcome the hypoxemic state and eventually died. Conclusions Delayed tension gastrothorax can lead not only to obstructive shock due to intrathoracic compression but also to more severe organ ischemia and re-expansion pulmonary edema due to insufflation.

Abstract The kidney plays a central role in body fluid homeostasis. Cells in the glomeruli and juxtaglomerular apparatus sense mechanical forces and modulate glomerular filtration and renin release. However, details of mechanosensory systems in these cells are unclear. Piezo2 is a recently identified mechanically activated ion channel found in various tissues, especially sensory neurons. Herein, we examined Piezo2 expression and regulation in mouse kidneys. RNAscope in situ hybridization revealed that Piezo2 expression was highly localized in mesangial cells and juxtaglomerular renin-producing cells. Immunofluorescence assays detected GFP signals in mesangial cells and juxtaglomerular renin-producing cells of Piezo2 GFP reporter mice. Piezo2 transcripts were observed in the Foxd1-positive stromal progenitor cells of the metanephric mesenchyme in the developing mouse kidney, which are precursors of mesangial cells and renin-producing cells. In a mouse model of dehydration, Piezo2 expression was downregulated in mesangial cells and upregulated in juxtaglomerular renin-producing cells, along with the overproduction of renin and enlargement of the area of renin-producing cells. Furthermore, the expression of the renin coding gene Ren1 was reduced by Piezo2 knockdown in cultured juxtaglomerular As4.1 cells under static and stretched conditions. These data suggest pivotal roles for Piezo2 in the regulation of glomerular filtration and body fluid balance.

Background/purpose: Elucidating the transmission mechanism of pain signals from the orofacial area and the corresponding modification mechanism will not only aid in the understanding of pain mechanisms but also provide useful information regarding the development of pain mitigation methods. In this study, the involvement of the pain suppression system in the trigeminal area was investigated through an analysis of the activation status over time in the prefrontal cortex using functional near-infrared spectroscopy (fNIRS). Materials and methods: In 28 healthy, right-handed male volunteers (average age, 30.1 ± 4.2 years) as subjects, a mild, intermittent, acute pain stimulus was administered through the implementation of pocket probing of the gingiva surrounding the right maxillary central incisor. In the prefrontal cortex, the levels of hemoglobin (Hb) were measured using the fNIRS measurement system. Average values of both oxy-Hb and deoxy-Hb were calculated at four stages: rest stage, 20 s prior to the pain stimulus application, and three stages at 20-s intervals within 1 min of stimulation. One-way analysis of variance and multiple comparisons were used to compare representative values to investigate the changes due to pain. Results: Oxy-Hb levels decreased the most during the 20 s stage directly after stimulus application. This change was seen mainly on the contralateral side, after which it returned to the resting baseline level before the stimulus application. Conclusion: Our data demonstrate that in healthy males, a mechanism exists to mitigate pain involving the pain suppression system in the 20 s after feeling mild pain to the gingiva.

Background: Current guidelines recommend that any patient who has experienced anaphylaxis should be prescribed one or more epinephrine autoinjectors (EAI) for immediate self-treatment. However, the etiology of anaphylaxis and prescription patterns of EAI have not been widely examined in Japan. Methods: This was a retrospective cohort study using a large Japanese claims database (JMDC, Tokyo, Japan). We included patients with severe anaphylaxis who received epinephrine in a hospital or outpatient clinic from 2011 to 2016. We extracted patients who were prescribed EAIs and examined the annual trend of EAI prescription rates and refill patterns. Results: We identified 1255 eligible patients. Among them, 361 patients (28.8%) were prescribed EAIs within 30 days after their initial severe anaphylactic episode. In patients who were prescribed EAIs, 65.9% were prescribed EAIs from the same facility in which initial treatment was given for severe anaphylaxis. The prescription rates of EAI significantly increased from 11.1% in 2011 to 30.9% in 2016. Among patients with initial EAI prescriptions, 97.3% refilled their EAI prescriptions at least once and 40.5% refilled their prescriptions annually during the 3 year follow up period. Conclusions: EAI prescription rates were relatively low in patients who experienced severe anaphylaxis in Japan. Physicians should prescribe EAIs to all patients who were treated for anaphylaxis under their care and avoid delegating the responsibility of prescribing EAIs to other facilities. Initial prescription of EAIs can result in improved regular refill and dissemination practices.

Background: Massive anterior mediastinal hematoma due to chest compression during cardiopulmonary resuscitation is often caused by internal mammary artery injury. However, critical massive anterior mediastinal hematoma without damage to major blood vessels is extremely rare. We report a case of life-threatening anterior mediastinal hematoma without internal mammary artery injury during extracorporeal cardiopulmonary resuscitation. Case presentation: A 70-year-old man was transferred to our emergency department because of ventricular fibrillation arrest. Manual chest compressions and venoarterial extracorporeal membrane oxygenation were applied in the angiography room. Acute myocardial infarction was diagnosed, and percutaneous coronary intervention with stent placement was performed. Despite the establishment of venoarterial extracorporeal membrane oxygenation flow, the hemodynamics were unstable. Computed tomography revealed a massive anterior mediastinal hematoma compressing the right heart system and causing obstructive shock. Although local incision and anterior mediastinal hematoma drainage were tried for resolving obstructive shock, the patient's anemia did not improve, and there was still continuous hemorrhaging from the drainage tube. A median thoracotomy was then performed. There was no injury of the main trunk of the internal mammary artery but only hemorrhaging from the sternal fracture site. The patient's hemodynamics and anemia improved after hemostasis and gauze packing. Re-thoracotomy for gauze removal and sternal closure was performed three days post-hospitalization. Conclusions: It is important to consider hemorrhaging and unstable hemodynamics in patients who receive extracorporeal cardiopulmonary resuscitation. Therefore, a thoracotomy may take precedence over intravascular treatment for restoring hemostasis when there is no information regarding the bleeding site, such as the presence of extravasation.

Aim For infection control in burn patients, it is essential to understand the epidemiology of bloodstream infection (BSI) and the local microbiological situation. There are few studies on blood and swab culture results among burn patients in Japan. The purpose of this study was to investigate the epidemiology of BSI and swab cultures in burn patients. Methods Data from 355 burn patients over 13 years from 2008 were analyzed retrospectively. Bloodstream infection was defined as the isolation of bacteria or fungi from two or more blood cultures. The characteristics of burn patients and microorganisms detected from various cultures were analyzed. Results The mortality rate among burn patients with BSI was 37.8%, which was more than twice that among burn patients without BSI. The univariate analysis showed that inhalation injury, total burn surface area (TBSA), and mortality were associated with BSI. The multivariate logistic analysis indicated that TBSA was an independent risk factor for BSI. The most frequently isolated organism from blood and swab cultures were Candida species and Pseudomonas aeruginosa, respectively. Seventy‐five percent of the microorganisms isolated from blood were detected previously in swab cultures performed within 1 week from blood cultures. Conclusions The prognosis of burn patients with BSI was poor, and TBSA was an independent risk factor for BSI. The predominant organisms isolated from blood and swab cultures were Candida species and P. aeruginosa, respectively. Surveillance wound swab cultures could be utilized for monitoring the local microbiological situation in burn patients.

Abstract Resuscitative endovascular balloon occlusion of the aorta is useful as a troubleshooting response to hemorrhage and a temporary method for maintaining patient hemodynamics.

Abstract Background Vitamin C is a well-documented antioxidant that reduces oxidative stress and fluid infusion in high doses; however, the association between high-dose vitamin C and reduced mortality remains unclear. This study evaluates the effect of high-dose vitamin C in severe burn patients under two varying thresholds. Methods We enrolled adult patients with severe burns (burn index ≥ 15) who were registered in the Japanese Diagnosis Procedure Combination national inpatient database from 2010 to 2016. Propensity score matching was performed between patients who received high-dose vitamin C within 1 day of admission (vitamin C group) and those who did not (control group). High-dose vitamin C was defined as a dosage in excess of 10 g or 24 g within 2 days of admission. The primary outcome was in-hospital mortality. Results Eligible patients (n = 2713) were categorized into the vitamin C group (n = 157) or control group (n = 2556). After 1:4 propensity score matching, we compared 157 and 628 patients who were administered high-dose vitamin C (> 10-g threshold) and controls, respectively. Under this particular threshold, high-dose vitamin C therapy was associated with reduced in-hospital mortality (risk ratio, 0.79; 95% confidence interval, 0.66–0.95; p = 0.006). In contrast, in-hospital mortality did not differ between the control and high-dose vitamin C group under the > 24-g threshold (risk ratio, 0.83; 95% confidence interval, 0.68–1.02; p = 0.068). Conclusions High-dose vitamin C therapy was associated with reduced mortality in patients with severe burns when used under a minimum threshold of 10 g within the first 2 days of admission. While “high-dose” vitamin C therapy lacks a universal definition, the present study reveals that different “high-dose” regimens may yield improved outcomes.

Aim To investigate disaster‐related carbon monoxide (CO) poisoning after the Great East Japan Earthquake using a nationwide inpatient database in Japan. Methods This was a retrospective cohort study. We identified adult patients with CO poisoning who were registered in the Japanese Diagnosis Procedure Combination inpatient database from 2010 to 2017. We evaluated trends in the numbers of patients with CO poisoning each month from disaster (Tohoku region) and non‐disaster areas. In the disaster area, we compared the numbers of patients with CO poisoning during pre‐ and post‐earthquake periods. We also compared the numbers of CO poisonings after the earthquake (

Introduction: The purpose of this study was to evaluate whether cryopreserved (frozen) adipose-derived regenerative cells (ADRCs) have a therapeutic effect on burn wound healing as well as freshly isolated (fresh) ADRCs. Methods: Full thickness burns were created on dorsum of nude mice and burn wound was excised. The wound was covered by artificial dermis with; (i) fresh ADRCs, (ii) frozen ADRCs, and (iii) PBS (control). The assessment for wound healing was performed by morphological, histopathological and immunohistochemical analyses. Results: In vivo analyses exhibited the significant therapeutic effect of frozen ADRCs on burn wound healing up to the similar or higher level of fresh ADRCs. There were significant differences of wound closure, epithelized tissue thickness, and neovascularization between the treatment groups and control group. Although there was no significant difference of therapeutic efficacy between fresh ADRC group and frozen ADRC group, frozen ADRCs improved burn wound healing process in dermal regeneration with increased great type I collagen synthesis compared with fresh ADRCs. Conclusions: These findings indicate that frozen ADRCs allow us to apply not only quickly but also for multiple times, and the cryopreserved ADRCs could therefore be useful for the treatment of burn wounds in clinical settings. Keywords: Burn, Stem cells, Wound healing

The cationic ZnII part of aqua(1,4,7,10-tetraazacyclododecane)zinc(II) bis(perchlorate), [Zn(C8H20N4)(H2O)](ClO4)2, exhibits a slightly distorted square-pyramidal coordination environment with a water molecule in the apical position. In the crystal, the macrocyclic ring alternates between two conformations with equal occupancies. Two of the three perchlorate anions are situated about a twofold rotation axis, and one of them shows disorder of the O atoms with occupancies of 0.62 (7) and 0.38 (7). In the crystal, the complexes are connected by intermolecular hydrogen bonding via the perchlorate anions.

Aim Combination treatment with clindamycin is recommended in patients with invasive group A Streptococcus infection; however, whether the same treatment is effective in invasive group B Streptococcus and S. dysgalactiae subspecies equisimilis infections remains unknown. We aimed to investigate whether clindamycin added to standard of care therapy would be effective in patients with invasive non‐group A β‐hemolytic Streptococcus infections. Methods This was a nationwide retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database focusing on the period between 2010 and 2018. We extracted data on patients diagnosed with sepsis due to non‐group A β‐hemolytic Streptococcus. One‐to‐four propensity score‐matching was undertaken to compare patients who were treated with clindamycin within 2 days of admission (clindamycin group) and those who did not (control group). The primary outcome was in‐hospital mortality. Results We identified 3754 eligible patients during the study period. The patients were divided into the clindamycin (n = 296) and control groups (n = 3458). After one‐to‐four propensity score matching, we compared 289 and 1156 patients with and without clindamycin, respectively. In‐hospital mortality did not significantly differ between the two groups (9.7% versus 10.3%; risk difference 0.3%; 95% confidence interval, –3.5% to 4.2%). Conclusions This nationwide database study showed that combination therapy involving the use of clindamycin was not associated with lower in‐hospital mortality in patients with invasive non‐group A β‐hemolytic Streptococcus.

Aim: The present study aimed to describe the prevalence, prognosis and annual trends of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) patients, using a nationwide inpatient database in Japan. Methods: This was a nationwide retrospective cohort study, using the Japanese Diagnosis Procedure Combination inpatient database. We included OHCA patients registered in the database from July 2010 to March 2017 and analyzed the annual prevalence of OHCA patients who received ECPR. The outcomes included survival to hospital discharge and survival with favorable neurologic outcome at hospital discharge. The annual trends on the outcomes were also analyzed. Results: We identified 217,907 eligible patients. OHCA patients were divided into patients with ECPR (n = 5,612) and conventional CPR (n = 212,295). The prevalence of ECPR performed in OHCA patients was 2.6%. ECPR prevalence significantly increased from 2.1% in 2010 to 3.0% in 2016 (P

OBJECTIVE:Developing an adequate disaster response capacity involves an assessment of available resources in areas that are vulnerable to disaster. Here, we sought to evaluate the gap between predicted damage in a foreseeable major earthquake versus existing municipality-level resources in Tokyo, Japan. METHODS:Our study focused on the 53 municipalities in Tokyo to evaluate the relationships between the predicted number of severe casualties per 1,000 population from a future earthquake, community characteristics, and inpatient bed supply in local hospitals. Correlation analysis and supply-demand balance estimations were carried out at the municipality level, and the results were geographically visualized using choropleth maps. RESULTS:The correlation analysis showed that higher casualties were correlated with municipalities with faster population increase, higher taxable incomes, lower unemployment rates, and higher bed volumes in disaster base hospitals. Under a maximal damage scenario in a future earthquake, we predict a shortage of 2,780 beds for the treatment of severe casualties across Tokyo. Even under a scenario of cooperation among neighboring municipalities, a shortage of 7,107 beds would remain. CONCLUSIONS:Tokyo is located in a zone where major earthquake damage is anticipated. Cooperation between neighboring municipalities may not suffice to address the undersupply of beds during the acute phase of a disaster. Hence, existing disaster preparedness plans require further reinforcement with a focus on local vulnerabilities.

Nagilactone E, an antifungal agent derived from the root bark of Podocarpus nagi, inhibits 1,3-β glucan synthesis; however, its inhibitory activity is weak. Anethole, the principal component of anise oil, enhances the antifungal activity of nagilactone E. We aimed to determine the combinatorial effect and underlying mechanisms of action of nagilactone E and anethole against the budding yeast Saccharomyces cerevisiae. Analyses using gene-deficient strains showed that the multidrug efflux pump PDR5 is associated with nagilactone E resistance; its transcription was gradually restricted in cells treated with the drug combination for a prolonged duration but not in nagilactone-E-treated cells. Green-fluorescent-protein-tagged Pdr5p was intensively expressed and localized on the plasma membrane of nagilactone-E-treated cells but not in drug-combination-treated cells. Quick-freeze deep-etch electron microscopy revealed the smoothening of intertwined fiber structures on the cell surface of drug-combination-treated cells and spheroplasts, indicating a decline in cell wall components and loss of cell wall strength. Anethole enhanced the antifungal activity of nagilactone E by enabling its retention within cells, thereby accelerating cell wall damage. The combination of nagilactone E and anethole can be employed in clinical settings as an antifungal, as well as a food preservative to restrict food spoilage.

Agrobacterium tumefaciens is a pathogen of various plants which transfers its own DNA (T-DNA) to the host plants. It is used for producing genetically modified plants with this ability. To control T-DNA transfer to the right place, toxin-antitoxin (TA) systems of A. tumefaciens were used to control the target site of transfer without any unintentional targeting. Here, we describe a toxin-antitoxin system, Atu0939 (mazE-at) and Atu0940 (mazF-at), in the chromosome of Agrobacterium tumefaciens. The toxin in the TA system has 33.3% identity and 45.5% similarity with MazF in Escherichia coli. The expression of MazF-at caused cell growth inhibition, while cells with MazF-at co-expressed with MazE-at grew normally. In vivo and in vitro assays revealed that MazF-at inhibited protein synthesis by decreasing the cellular mRNA stability. Moreover, the catalytic residue of MazF-at was determined to be the 24th glutamic acid using site-directed mutagenesis. From the results, we concluded that MazF-at is a type II toxin-antitoxin system and a ribosome-independent endoribonuclease. Here, we characterized a TA system in A. tumefaciens whose understanding might help to find its physiological function and to develop further applications.

Intravascular treatments such as arterial embolization and resuscitative endovascular balloon occlusion of the aorta are being increasingly performed in emergency cases, in addition to the increasing use of arterial access as an intensive care monitoring tool. Thus, arterial access-related complications are being commonly reported. A 40- year-old man with renal artery stenosis underwent renal artery stent placement via the left inguinal puncture approach. After the procedure, his groin was manually compressed to hemostasis for 30 min. He unexpectedly developed shock the following day, and computed tomography revealed a ruptured pseudoaneurysm of the left external iliac artery (EIA) following iatrogenic vascular trauma owing to an inappropriately performed groin puncture. We initially controlled the hemorrhage using endovascular balloon occlusion of the left EIA. Subsequently, the injured EIA was repaired using a direct suture. The postoperative course was uneventful. Herein, we evaluated the causes of iatrogenic complications and the effectiveness of our treatment strategy.

Toxin-antitoxin (TA) systems are widespread among the plasmids and genomes of bacteria and archaea. This work reports the first description of a functional TA system in Streptomyces that is identical in two species routinely used in the laboratory: Streptomyces lividans and S. coelicolor. The described system belongs to the YefM/YoeB family and has a considerable similarity to Escherichia coli YefM/YoeB (about 53% identity and 73% similarity). Lethal effect of the S. lividans putative toxin (YoeBsl) was observed when expressed alone in E. coli SC36 (MG1655 ΔyefM-yoeB). However, no toxicity was obtained when co-expression of the antitoxin and toxin (YefM/YoeBsl) was carried out. The toxic effect was also observed when the yoeBsl was cloned in multicopy in the wild-type S. lividans or in a single copy in a S. lividans mutant, in which this TA system had been deleted. The S. lividans YefM/YoeBsl complex, purified from E. coli, binds with high affinity to its own promoter region but not to other three random selected promoters from Streptomyces. In vivo experiments demonstrated that the expression of yoeBsl in E. coli blocks translation initiation processing mRNA at three bases downstream of the initiation codon after 2 minutes of induction. These results indicate that the mechanism of action is identical to that of YoeB from E. coli.