Gluing blood into gel by electrostatic interaction using a water-soluble polymer as an embolic agent.

Liquid embolic agents are widely used for the endovascular embolization of vascular conditions. However, embolization based on phase transition is limited by the adhesion of the microcatheter to the embolic agent, use of an organic solvent, unintentional catheter retention, and other complications. By mimicking thrombus formation, a water-soluble polymer that rapidly glues blood into a gel without triggering coagulation was developed. The polymer, which consists of cationic and aromatic residues with adjacent sequences, shows electrostatic adhesion with negatively charged blood substances in a physiological environment, while common polycations cannot. Aqueous polymer solutions are injectable through clinical microcatheters and needles. The formed blood gel neither adhered to the catheter nor blocked the port. Postoperative computed tomography imaging showed that the polymer can block the rat femoral artery in vivo and remain at the injection site without nontarget embolization. This study provides an alternative for the development of waterborne embolic agents.

Poly(ADP-ribose) Polymerase (PARP) is Critically Involved in Liver Ischemia/Reperfusion-injury.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) is a DNA-repairing enzyme activated by extreme genomic stress, and therefore is potently activated in the remnant liver suffering from ischemia after surgical resection. However, the impact of PARP on post-ischemic liver injury has not been elucidated yet. MATERIALS AND METHODS: We investigated the impact of PARP on murine hepatocyte/liver injury induced by hypoxia/ischemia, respectively. RESULTS: PJ34, a specific inhibitor of PARP, markedly protected against hypoxia/reoxygenation (H/R)-induced cell death, though z-VAD-fmk, a pan-caspase inhibitor similarly showed the protective effect. PJ34 did not affect H/R-induced caspase activity or caspase-mediated cell death. z-VAD-fmk also did not affect the production of PAR (i.e., PARP activity). Therefore, PARP- and caspase-mediated cell death occurred in a mechanism independent of each other in H/R. H/R immediately induced activation of PARP and cell death afterwards, both of which were suppressed by PJ34 or Trolox, an antioxidant. This suggests that H/R-induced cell death occurred redox-dependently through PARP activation. H/R and OS induced nuclear translocation of apoptosis inducing factor (AIF, a marker of parthanatos) and RIP1-RIP3 interaction (a marker of necroptosis), both of which were suppressed by PJ34. H/R induced PARP-mediated parthanatos and necroptosis redox-dependently. In mouse experiments, PJ34 significantly reduced serum levels of AST, ALT & LDH and areas of hepatic necrosis after liver ischemia/reperfusion, similar to z-VAD-fmk or Trolox. CONCLUSION: PARP, activated by ischemic damage and/or oxidative stress, may play a critical role in post-ischemic liver injury by inducing programmed necrosis (parthanatos and necroptosis). PARP inhibition may be one of the promising strategies against post-ischemic liver injury.

Generation gaps in medical education: An exploratory qualitative study.

This qualitative study aimed to explore medical students' experience of generation gap in their interactions with senior teachers (aged >55) in Japan. Focus group interviews were conducted with 28 medical students (20 to 30 years, mean age 22 ±2 years, classified as millennials, with only one year of studies since starting specialised courses for medicine. The participants were interviewed in groups of four, with each interview lasting 60 minutes. Topics covered included generation gap experienced in daily life and during their studies, and work-life balance issues. The discussions were recorded and transcribed, and content analysis was applied. Four specific influential generation-gap categories were identified - distinctive sociocultural backgrounds, more recent educational media tools and faster information dissemination speed, new-era values, and challenges in communication - that were consistent with findings from previous studies. More senior personnel involved in medical education need to consider these categories to enhance effectiveness of teaching.

Postmortem contrast-enhanced computed tomography via direct large-vessel puncture.

The aim of this study was to assess the usefulness of postmortem contrast-enhanced CT (PMeCT) performed via direct large-vessel puncture when routine postmortem CT suggests a vascular lesion as the cause of death. PMeCT was performed in 9 cases (4 male, 5 female) with a mean age of 76 years (range 52-92) at the time of death. The mean time elapsed since death was 29.1 h (12.0-72.0). The location of the target vessel for puncture was determined based on the CT table position and a grid placed on the body surface. An 18-G spinal needle was advanced to the puncture site, and the needle tip was confirmed to have reached the intended blood vessel. Using negative pressure with a 20-ml syringe, the needle tip was advanced until reverse bleeding was confirmed. Diluted contrast medium was injected slowly to ensure its dispersion within the blood vessels. Following confirmation of no extravasation, additional doses of diluted contrast agent were injected in 3-4 divided doses, with CT scans obtained at each step to track the distribution of contrast agent over time. PMeCT was successful in all cases, revealing cardiac tamponade in 7 (ascending aortic dissection, n = 6; cardiac rupture, n = 1), thoracic aortic aneurysm rupture, n = 1, and iliac artery aneurysm rupture, n = 1. There were no cases of procedure-related extravasation (pseudo-lesions). When postmortem CT reveals pericardial hematoma or bleeding in the thoracic or abdominal cavity, PMeCT can identify the source of bleeding.

Objective evaluation of chest findings in infants by postmortem computed tomography.

PURPOSE: The purpose of this study was to review the findings of computed tomography (CT) performed early postmortem on infants and to clarify the postmortem CT lung findings that occur in the absence of abnormal histopathological findings. MATERIALS AND METHODS: From July 2016 to March 2022, 72 infants were autopsied with postmortem CT (41 boys 31 girls, aged 0-36 (mean 8.2) months). Autopsy and postmortem CT lung findings were compared with the causes of death identified by the autopsies, namely sudden infant death syndrome (n = 37), acute circulatory system disease (18), drowning (7), asphyxia (5), and dehydration/undernutrition (5). RESULTS: The %aerated lung volume (-700 HU or less) ranged from 0 % to 33 % (mean 1.5 %, median 0 %), being <1 % in 61 cases (84.7 %) and >3 % in 3/5 (60 %) of the dehydration/undernutrition group. The dehydration/undernutrition group showed significant preservation of lung field air content compared with the other causes of death groups (p < 0.05). Receiver characteristic curve analysis showed a cut off value of 0.8 % and area under the curve of 0.88806. The drowning group had significantly greater pleural cavity fluid retention than the other causes of death groups (p < 0.05). No correlation was found between postmortem interval and pleural cavity fluid retention. However, resuscitation time and pleural cavity fluid retention were correlated. CONCLUSION: Evaluation of CT values on postmortem lung fields of infants usually reveals a marked decrease in air content. When air content exceeds 0.8% on infant postmortem CT, dehydration/undernutrition should be considered in the differential diagnosis.

Objective Evaluation of Oral and Pharyngeal Areas in Autopsy Cases of Obstructive Sleep Apnea Syndrome via Postmortem CT.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) can cause sudden death during sleep. Previous findings have suggested that OSAS development is related to maxillofacial morphology. Evaluation of facial morphology can determine the risk of developing the disease, and establishing an objective method to assess the underlying etiology of OSAS-related death would be advantageous. OBJECTIVE: The objective of this study is to determine the key features of obstructive sleep apnea syndrome (OSAS) using postmortem oral and pharyngeal computed tomography (CT). METHODS: We retrospectively assessed autopsy cases of patients with (n=25) and without (n=25) OSAS-related death. We used oral and pharyngeal CT images to compare the oral and pharyngeal cavity volume (OPCV), oral and pharyngeal soft tissue volume (OPSV), oral and pharyngeal air space volume (OPAV), and OPAV to OPCV ratio (%air). Receiver operating curve (ROC) analysis was used to determine the accuracy of OSAS prediction. We assessed participants with body mass index (BMI) values within the normal range. RESULTS: Among the 50 subjects, we observed significant between-group differences in OPSV, OPAV, and % air, whereas there were significant between-group differences in OPSV and %air among 28 subjects with normal BMI values. Both comparisons suggested that OSAS-related death was associated with low %air and high OPSV values. CONCLUSION: The %air and OPSV are useful for assessing postmortem oropharyngeal CT images. OSAS-related sudden death is likely when %air and OPSV values are ≤20.1% and ≥127.2 ml, respectively. Among those with normal BMI values, % air and OPSV values of ≤22.8% and ≥111.5 ml, respectively, predict OSAS-related sudden death.

Mental workload during endoscopic sinus surgery is associated with surgeons' skill levels.

Introduction: Surgeons' mental workload during endoscopic sinus surgery (ESS) has not been fully evaluated. The assessment was challenging due to the great diversity of each patient's anatomy and the consequence variety of surgical difficulties. In this study, we examined the mental workload of surgeons with various surgical skill levels during ESS under the standardized condition provided by novel-designed 3D sinus models. Materials and methods: Forty-seven participants performed a high-fidelity ESS simulation with 3D-printed sinus models. Surgeons' mental workload was assessed with the national aeronautics and space administration-task load index (NASA-TLX). Associations between the total and subscales score of NASA-TLX and surgical skill index, including the board certification status, the number of experienced ESS cases, and the objective structured assessment of technical skills (OSATS), were analyzed. In addition, 10 registrars repeated the simulation surgery, and their NASA-TLX score was compared before and after the repetitive training. Results: The total NASA-TLX score was significantly associated with OSATS score (p = 0.0001). Primary component analysis classified the surgeons' mental burden into three different categories: (1) the skill-level-dependent factors (temporal demand, effort, and performance), (2) the skill-level-independent factors (mental and physical demand), and (3) frustration. After the repetitive training, the skill-level-dependent factors were alleviated (temporal demand; z = -2.3664, p = 0.0091, effort; z = -2.1704, p = 0.0346, and performance; z = -2.5992, p = 0.0017), the independent factors were increased (mental demand; z = -2.5992, p = 0.0023 and physical demand; z = -2.2509, p = 0.0213), and frustration did not change (p = 0.3625). Conclusion: Some of the mental workload during ESS is associated with surgical skill level and alleviated with repetitive training. However, other aspects remain a burden or could worsen even when surgeons have gained surgical experience. Routine assessment of registrars' mental burdens would be necessary during surgical training to sustain their mental health.

Raising future forensic pathologists (first report): results of a preliminary questionnaire survey.

The shortage of future forensic pathologists is a serious problem both in Japan and overseas. In Japan, however, factors such as government budget cuts and increasing the autopsy rates, make the condition even worse. In an attempt to improve this situation, we implemented a questionnaire survey to investigate the particular features necessary when selecting a career in forensic medicine. As a preliminary study, we sent the questionnaire along with an anonymous answer sheet to all forensic pathologists with a degree in medicine M.D., who were affiliated with universities in Hokkaido and the Tohoku district of Japan as of August 2011. Thirteen physicians in nine universities (response rate 77.8%) returned the answer sheet. Characteristics of participants are listed below: years of experience, board specialty and number of years as board certified specialists, percentage of work effort spent on autopsy practice, the time when they decided to work as a forensic pathologist, the time when to best recommend forensic pathologist as a career, and crucial factors in choosing the specialty of forensic medicine. As a result of this research, we've revealed the importance of undergraduate medical education or the effect on the role models. Furthermore, we've also extracted miscellaneous comments, such as standardization of minimum requirements. In our study, we' ve found some clues to increase future candidates in the field forensic medicine. However, we must collect further samples for our questionnaire survey to validate the study, and, as a future project, we must also address this problem at the congress of forensic medicine.

Raising future forensic pathologists (second report): results of a preliminary interview survey.

Fostering the specialists of forensic pathology has become a worldwide problem. In Japan, factors such as government budget cuts, the introduction of initial postgraduate clinical training system, as well as national policy on increasing autopsy rates, may deter young graduates from entering this specialty. The aim of this study was to look for clues to promote the training of young forensic pathologists. We selected and interviewed five forensic pathologists, with each interview lasting approximately 60 minutes, and picked up common views among them. The interviews topic, based on a prior survey, was: "What do you believe forensic pathologists require to promote the training of their successors." We selected common views on the three themes listed below; 1) standardization of minimum requirements to be independent forensic pathologists, 2) balancing forensic pathologists' time among autopsy practice, research, and education, and 3) preparing positions for younger forensic pathologists. These opinions were the same as those of previous studies conducted overseas and must be discussed at academic conferences in the future, where both junior and senior forensic pathologists participate.

Objective skull fracture evaluation by using the postmortem 3D-CT skull fracture score in fatal falls.

PURPOSE: We evaluated the usefulness of skull fracture analysis using three-dimensional computed tomography skull fracture scores (3DCT-SFs) in cases of fatal falls. MATERIALS AND METHODS: From April 2016 to September 2020, 46 cases of fatal falls from great heights (33 males, 13 females; mean age: 52.7 (range: 18-89) years) were examined using routine postmortem CT. The 3DCT-SFs were determined as the sum of the fracture line lengths measured on a volume rendering image. Skull fracture severity was classified into four stages according to the 3DCT-SFs. These stages were compared by macroscopic evaluation of skull fracture severity (injury level 0: no fracture; injury level I: fracture without deviation; injury level II: fracture with deviation; injury level III: comminuted open skull fracture). The relationship between 3DCT-SFs values, the fall distance, and the hardness of the landing surface was also examined. RESULTS: Skull fractures occurred in 26 cases (56.5%). The mean 3DCT-SFs of the cases that were classified as stages I, Ⅱ, and III were 86.6 (5.0-187.0), 832.0 (235.1-1865.8), and 3582.5 (2171.6-4787.6), respectively. Upon macroscopic evaluation of fracture severity, there were 8, 10, and 8 cases of injury levels I, II, and III, respectively. The 3DCT-SFs-based stages correlated significantly with the macroscopic skull fracture severity levels (R2 = 0.936). Solid-surface fall points resulted in significantly higher 3DCT-SFs than soft surfaces. Comminuted open fracture of the skull (stage III) occurred with fall distances ≥ 24 m. CONCLUSION: The 3DCT-SFs correlate well with macroscopic findings and are useful as an objective skull fracture index.

Evaluation of oral air space volume in obstructive sleep apnea syndrome using clinical and postmortem CT imaging.

OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) induces upper airway occlusion and may cause sudden death during sleep. This study sought to clarify the relationship between oral air space volume and OSAS onset, which is influenced by multiple factors, such as jawbone, dentition morphology, and oral soft-tissue volume. METHODS: (1) 50 subjects from deceased cases were divided into two groups: OSAS (25 subjects) and controls (25 subjects). (2) 28 subjects from clinical cases were divided into two groups: OSAS (9 subjects) and controls (19 subjects). In all cases, the Computed Tomography (CT) images of the facial region were obtained, and four parameters of oral area volume were analyzed in deceased and clinical cases, and comparisons and analyses were performed between OSAS and control cases. In addition, the efficiency of measurement of these parameters was evaluated using Receiver Operating Characteristic (ROC) curves in OSAS. RESULTS: (1) In deceased cases, oral soft-tissue volume (OSV), oral air-space volume (OAV), and the ratio of OAV to OSV (%air) showed a significant correlation. (2) In clinical cases, OAV and %air showed a significant correlation. In both postmortem and clinical images, a small %air value indicates a high risk of developing OSAS and a high probability of OSAS-related sudden death. CONCLUSIONS: It was shown that the %air is an index to evaluate OSAS by CT imaging of the oral region. OSAS may be indicated when the %air value is ≦ 16.0% in deceased cases and ≦ 6.6% in clinical cases.

The usefulness of measuring n-butyric acid concentration as a new indicator of blood decomposition in forensic autopsy.

In forensic medicine, although various alcohols have been reported as indicators of decomposition in collected blood, no studies have examined short-chain fatty acids as indicators. In this study, the blood n-butyric acid concentration was quantified, and the association between n-butyric acid and decomposition was investigated to determine whether the detection of n-butyric acid could be a new indicator of decomposition. Among the forensic autopsies performed from 2016 to 2018 in our laboratory, the cases were divided into decomposed (n = 20) and non-decomposed (n = 20) groups based on macroscopic findings. Blood samples collected at the time of autopsy were derivatized with 3-nitrophenylhydrazine hydrochloride after solid-phase extraction. The n-butyric acid concentration was measured using liquid chromatography-tandem mass spectrometry. In addition, ethanol and n-propanol were measured using a gas chromatography-flame ionization detector. There was a significant difference (p < 0.01) in the concentrations of n-butyric acid between the decomposed and non-decomposed groups (0.343 ± 0.259 [0.030-0.973] and 0.003 ± 0.002 [0.001-0.007] mg/mL, respectively). In the decomposed group, n-butyric acid was detected at high concentrations, even in cases where n-propanol was low. These results suggest that n-butyric acid is more likely to be an indicator of blood decomposition than n-propanol.

Repetitive simulation training with novel 3D-printed sinus models for functional endoscopic sinus surgeries.

Background: The purpose of this study was to find a utility of a newly developed 3D-printed sinus model and to evaluate the educational benefit of simulation training with the models for functional endoscopic sinus surgery (FESS). Material and methods: Forty-seven otolaryngologists were categorized as experts (board-certified physicians with ≥200 experiences of FESS, n = 9), intermediates (board-certified physicians with <200 experiences of FESS, n = 19), and novices (registrars, n = 19). They performed FESS simulation training on 3D-printed models manufactured from DICOM images of computed tomography (CT) scan of real patients. Their surgical performance was assessed with the objective structured assessment of technical skills (OSATS) score and dissection quality evaluated radiologically with a postdissection CT scan. First we evaluated the face, content, and constructive values. Second we evaluated the educational benefit of the training. Ten novices underwent training (training group) and their outcomes were compared to the remaining novices without training (control group). The training group performed cadaveric FESS surgeries before and after the repetitive training. Results: The feedback from experts revealed high face and content value of the 3D-printed models. Experts, intermediates, and novices demonstrated statistical differences in their OSATS scores (74.7 ± 3.6, 58.3 ± 10.1, and 43.1 ± 11.1, respectively, p < .001), and dissection quality (81.1 ± 13.1, 93.7 ± 15.1, and 126.4 ± 25.2, respectively, p < .001). The training group improved their OSATS score (41.1 ± 8.0 to 61.1 ± 6.9, p < .001) and dissection quality (122.1 ± 22.2 to 90.9 ± 10.3, p = .013), while the control group not. After training, 80% of novices with no prior FESS experiences completed surgeries on cadaver sinuses. Conclusion: Repeated training using the models revealed an initial learning curve in novices, which was confirmed in cadaveric mock FESS surgeries. Level of evidence: N/A.