RhoA rescues cardiac senescence by regulating Parkin-mediated mitophagy.

Heart failure is one of the leading causes of death worldwide. RhoA, a small GTPase, governs actin dynamics in various tissue and cell types, including cardiomyocytes; however, its involvement in cardiac function has not been fully elucidated. Here, we generated cardiomyocyte-specific RhoA conditional knockout (cKO) mice, which demonstrated a significantly shorter lifespan with left ventricular dilation and severely impaired ejection fraction. We found that the cardiac tissues of the cKO mice exhibited structural disorganization with fibrosis and also exhibited enhanced senescence compared with control mice. In addition, we show that cardiomyocyte mitochondria were structurally abnormal in the aged cKO hearts. Clearance of damaged mitochondria by mitophagy was remarkably inhibited in both cKO cardiomyocytes and RhoA-knockdown HL-1 cultured cardiomyocytes. In RhoA-depleted cardiomyocytes, we reveal that the expression of Parkin, an E3 ubiquitin ligase that plays a crucial role in mitophagy, was reduced, and expression of N-Myc, a negative regulator of Parkin, was increased. We further reveal that the RhoA-Rho kinase axis induced N-Myc phosphorylation, which led to N-Myc degradation and Parkin upregulation. Re-expression of Parkin in RhoA-depleted cardiomyocytes restored mitophagy, reduced mitochondrial damage, attenuated cardiomyocyte senescence, and rescued cardiac function both in vitro and in vivo. Finally, we found that patients with idiopathic dilated cardiomyopathy without causal mutations for dilated cardiomyopathy showed reduced cardiac expression of RhoA and Parkin. These results suggest that RhoA promotes Parkin-mediated mitophagy as an indispensable mechanism contributing to cardioprotection in the aging heart.

Does abdominal protrusion in pregnant women affect abdominal injury severity in motor vehicle collisions? A nationwide database study.

AIMS: Some pregnant women avoid vehicle driving owing to the risk of contact between their protruding abdomen and steering wheel. This study was performed to determine whether abdominal protrusion in late-term pregnant car users affects the occurrence and severity of abdominal injuries in motor vehicle collisions using a national crash database. METHODS: The National Automotive Sampling System/Crashworthiness Data System was used to analyse maternal background, collision characteristics, outcome and Abbreviated Injury Scale (AIS) scores for the body regions of all persons involved in the collision. RESULTS: Comparison of pregnant and non-pregnant women in the driver's seat showed no significant differences in the rate of AIS scores of ≥2 (2+) for abdominal injuries and female outcomes. Comparison of use of the driver's seat and front passenger's seat by pregnant women showed no significant difference in rate of AIS 2+ injuries or in maternal and fetal outcomes. Comparison of pregnant women with a gestational age of ≤27 and >27 weeks in the driver's seat showed no significant differences in rate of AIS 2+ injuries or in maternal and fetal outcomes. CONCLUSIONS: Based on the data from relatively low-speed frontal collisions, obstetrician/gynaecologists should advise pregnant women that they do not need to change their preferred car seat from the driver's seat to another seat because of fear of contact between their protruding abdomen and the vehicle interior.

HIV/AIDS knowledge level, awareness of public health centers and related factors: a cross-sectional study among Brazilians in Japan.

BACKGROUND: Accurate information is essential so that HIV infection can be detected in time for initiation of HIV/AIDS treatment. Immigrants are at high risk for delayed HIV testing and diagnosis, but foreign residents in Japan also seem to face barriers to accessing HIV/AIDS care. We aimed to assess their knowledge level of HIV/AIDS and awareness of public health centers in Japan (PHCs), and to explore factors related to these items. METHODS: We conducted a cross-sectional study of Brazilians, the largest group of foreigners living in Shiga, using an anonymous, self-administered questionnaire survey in Brazilian Portuguese and Japanese via the Internet and mail. A multiple logistic regression analysis was used to examine the factors related to "Knowledge of HIV/AIDS" and "Awareness of PHCs". RESULTS: A total 182 Brazilians responded. More than half of them were beginners in Japanese. Most respondents were familiar with HIV/AIDS, but only 58% knew the existence of PHCs, and only 25% knew that HIV testing is available at PHCs free of charge and anonymously. A multiple logistic regression analysis showed that PHCs were less recognized by those with intermediate (odds ratio: 5.70, 95% confidence interval: 1.53-21.23) and beginner (odds ratio: 6.81, 95% confidence interval: 1.98-23.45) Japanese proficiency than by those with advanced. CONCLUSIONS: This survey revealed the knowledge level of HIV/AIDS and awareness of PHC among Brazilians in Shiga. Their lack of awareness of PHCs due to language barriers may lead to delays in HIV testing among them. Therefore, it is important for PHCs to disseminate information about medical services related to HIV/AIDS in Portuguese and plain Japanese to facilitate their access to HIV testing. However, PHC efforts alone are not enough. Medical interpreters who are familiar with Brazilian culture and customs, and the clinics that employ them, could help the Brazilian community and PHCs to overcome the language barrier and provide efficient and appropriate medical care to Brazilians. This would be one way to eliminate delays in HIV testing for Brazilians in Shiga.

Factors predicting oral and maxillofacial fractures after falling and factors predicting the duration of treatment.

BACKGROUND/AIM: The first objective of this study was to identify predictive factors for oral and maxillofacial fractures at the initial response to the patient. The second objective was to determine the factors influencing the incidence of treatment duration of more than 1 month using the information shown in the medical record. MATERIALS AND METHODS: Hospital records from 2011 to 2019 were reviewed to identify patients who had sustained oral and maxillofacial injuries by falling or falling from a height. Patterns and types of oral and maxillofacial injury, injury severity, and background of the injury were collected from the hospital records. The variables independently associated with a treatment duration of more than 1 month were determined by logistic regression analysis. RESULTS: In total, 282 patients (150 men, 132 women; median age, 17.5 years) were selected for analysis. Maxillofacial fractures were observed in 20.9% of patients (59/282); among these, mandibular fractures were the most common (47/59). Logistic regression analysis showed that age (odds ratio [OR], 1.026), nighttime occurrence (OR, 2.192), and upper face injury (OR, 20.704) were independent predictive factors for having a maxillofacial fracture. Additionally, the number of injured teeth (OR, 1.515) and the use of intermaxillary fixation (OR, 16.091) were independent predictors of treatment duration of more than 1 month. CONCLUSIONS: These results may be useful in the initial management of maxillofacial injuries in terms of better-informing patients injured by falling their expected treatment duration and managing the psychological impacts of a long treatment duration.

Dysmenorrhea due to undiagnosed obstructed hemi-vagina and ipsilateral renal anomaly syndrome can become a cause of suicide.

BACKGROUND: A Japanese woman in her early twenties had committed suicide, jumped from a 25-meter high bridge into a lake. She had been suffering from severe dysmenorrhea and general fatigue monthly. RESULTS: A forensic autopsy revealed indications of a bicorporeal uterus, obstructed hemi-vagina, and ipsilateral renal agenesis, which lead to a diagnosis of obstructed hemi-vagina and ipsilateral renal anomaly (OHVIRA) syndrome. On the right side of the uterus, an enclosed cavity composed of black clots was observed. Histological findings suggested that her endometrium was in the early proliferative phase, implying that she was in the menstrual phase just before her death. She may have been suffering from severe lower abdominal pain from the increased pressure of the closed uterus cavity. CONCLUSIONS: This case indicates that dysmenorrhea from undiagnosed OHVIRA syndrome can possibly lead to a suicide attempt. In Japan, because suicide was the leading cause of death for people aged 15 to 39 in 2019, preventive measures for suicide should be promoted. The present case also suggests that intervention for dysmenorrhea may prevent this in adolescent woman.

Identification of transmembrane protein 168 mutation in familial Brugada syndrome.

Brugada syndrome (BrS) is an inherited channelopathy responsible for almost 20% of sudden cardiac deaths in patients with nonstructural cardiac diseases. Approximately 70% of BrS patients, the causative gene mutation(s) remains unknown. In this study, we used whole exome sequencing to investigate candidate mutations in a family clinically diagnosed with BrS. A heterozygous 1616G>A substitution (R539Q mutation) was identified in the transmembrane protein 168 (TMEM168) gene of symptomatic individuals. Similar to endogenous TMEM168, both TMEM168 wild-type (WT) and mutant proteins that were ectopically induced in HL-1 cells showed nuclear membrane localization. A significant decrease in Na+ current and Nav 1.5 protein expression was observed in HL-1 cardiomyocytes expressing mutant TMEM168. Ventricular tachyarrhythmias and conduction disorders were induced in the heterozygous Tmem168 1616G>A knock-in mice by pharmacological stimulation, but not in WT mice. Na+ current was reduced in ventricular cardiomyocytes isolated from the Tmem168 knock-in heart, and Nav 1.5 expression was also impaired. This impairment was dependent on increased Nedd4-2 binding to Nav 1.5 and subsequent ubiquitination. Collectively, our results show an association between the TMEM168 1616G>A mutation and arrhythmogenesis in a family with BrS.

Tightening legal restrictions for drivers with epilepsy in Japan.

Epilepsy is a highly prevalent condition around the world, and many countries impose restrictions on drivers with epilepsy. After toughening the law in Japan, the number of refused driving license applications for patients with epilepsy increased markedly. However, the number of collisions caused by drivers with epilepsy did not decrease.

Visual texture agnosia caused by bilateral posterior cerebral artery stroke: a case study.

A 57-year-old man presented with a bilateral posterior cerebral artery attack and was visually impaired. He had a hard time identifying familiar faces and shades. He also felt that the familiar building looked different, and complained that it was not possible to tell from visual information alone whether the food was cooked or the kimono fabric was soft.We assessed the patient's visual function using real materials and material images and was diagnosed with visual texture agnosia. There are few reports of visual texture agnosia, detailed evaluation is considered important because perceiving texture is important for activities of daily living.

Maxillofacial Injuries in Cyclists: A Biomechanical Approach for the Analysis of Mechanisms of Mandible Fractures.

PURPOSE: The investigators characterized the occurrence of maxillofacial injuries in cyclists and biomechanically analyzed the mechanisms of mandible fractures. METHODS: We retrospectively analyzed injury data and performed biomechanical analyses with finite element models. Hospital records from 2011 through 2019 were reviewed to identify patients who had sustained oral and maxillofacial injuries while riding a bicycle. Patients with maxillofacial fractures were compared to those without. Logistic regression analysis was performed to identify which variables were independently associated with the occurrence of maxillofacial fractures. To reconstruct the injury scenario (one in which a person falls from a bicycle and contacts the road surface with their face), computer simulations using The Total Human Model for Safety model were performed. RESULTS: The hospital records of 94 patients (62 men, 32 women; 26.1 ± 17.3 years of age) who sustained oral and maxillofacial injuries while riding a bicycle were reviewed. Twenty patients (21.3%) sustained maxillofacial fractures; mandible fractures were most common (16 patients). Patients with maxillofacial fractures were significantly older and had higher severity injuries; however, logistic regression analysis showed that only age was an independent predictor of the occurrence of maxillofacial fracture (odds ratio, 1.03; P = .025). In simulations, higher von Mises stresses were found in the mandible when the cyclist fell with the neck extended and the body horizontal, and consequently, the center of mandibular body strikes the road surface. Contact forces were approximately 8 kN. High tensile stresses occurred laterally and high compressive stresses occurred medially in the mandibular ramus, which indicated that the mandibular ramus deformed in the transverse plane. CONCLUSION: Biomechanical analyses show that mandible fractures can occur when a cyclist falls from a bicycle and their lower face strikes the road's surface.

Factors influencing the long-term hospitalization of bicyclists and motorcyclists with oral and maxillofacial injuries.

BACKGROUND/AIM: Because bicyclists and motorcyclists with oral and maxillofacial injuries often suffer from disabilities requiring long-term treatment, reducing the severity of such injuries is a valuable objective for improving these people's quality of life (QOL). The aims of this study were, first, to present the prevalence and patterns of oral and maxillofacial injuries of bicyclists and motorcyclists and to compare the features of these injuries and, second, to determine the factors contributing to long-term hospitalization for these patients and to propose effective preventive measures. MATERIAL AND METHODS: This was a single-center retrospective analysis. Hospital records from 2011 through 2018 were reviewed for all patients who had sustained oral and maxillofacial injuries in bicycle or motorcycle collisions and had presented at a university hospital which was the only hospital in the region attended 24 hours per day by oral and maxillofacial surgeons. Characteristics of the oral and maxillofacial injuries, injury severity, and factors influencing the length of hospitalization were examined. RESULTS: Records of 130 patients (82 bicyclists and 48 motorcyclists) with a mean age of 28.0 years were analyzed. Thirty-three patients (25.4%) had maxillofacial fractures, with 41 fracture lines while 103 patients (79.2%) had dental injuries and 57 patients (43.8%) had soft-tissue injuries. The distribution and prevalence of oral and maxillofacial injuries were similar for bicyclists and motorcyclists. However, motorcyclists had significantly higher Abbreviated Injury Scale (AIS) scores for facial injuries and the maximum AIS score than did bicyclists. According to a multiple regression analysis, the number of fracture lines and the requirement for intermaxillary fixation were independent factors influencing long-term hospitalization (standard regression coefficients: 6.795 and 6.715, respectively; P < .001). CONCLUSIONS: The number of fracture lines and the use of intermaxillary fixation were independent factors influencing long-term hospitalization of both bicyclists and motorcyclists with oral and maxillofacial injuries.

Hit-and-runs more common with pedestrians lying on the road: Analysis of a nationwide database in Japan.

PURPOSE: To determine the trends with fatally or otherwise injured pedestrians lying on the road and the relationship to hit-and-run incidents in Japan. METHODS: We extracted data for 2012-2016 from the records of the Institute for Traffic Accident Research and Data Analysis, Japan, a nationwide traffic accident database. All the injured and fatally injured pedestrians were selected. We examined the levels of pedestrian injury, vehicle speed immediately before the collision, whether or not the pedestrian was lying on the road, and hit-and-run incidents. Chi-square test was employed to make a statistical comparison between the two groups. RESULTS: The database contained data on 286,383 pedestrian casualties and 7256 fatalities; 8.3% of fatalities (602 persons) and 0.6% of casualties (1827 persons) involved pedestrians lying on the road. The rates of fatalities and severe injuries were significantly higher for pedestrians who were lying on the road than for those who were not. Hit-and-run incidents were evident in 4.0% of casualties and 7.3% of fatalities. The rate of hit-and-run cases was also significantly higher among pedestrians who were lying on the road. Among fatally injured pedestrians not lying on the road, the rates with speeds of ≥30 km/h did not differ significantly between hit-and-run and other cases. However, when the pedestrians were lying on the road, the rate was significantly increased in hit-and-run cases. CONCLUSION: This is the first report to focus on pedestrians lying on the road and being involved in hit-and-run incidents. In addition to preventing hit-and-run incidents, prevention of pedestrians lying on the road could also decrease fatalities.

Factors influencing the length of emergency room stay and hospital stay in non-fatal bicycle accidents: A retrospective analysis.

PURPOSE: Lengthy hospitalization places a burden on patients and healthcare resources. However, the factors affecting the length of hospital stay (LHoS) and length of emergency room stay (LERS) in non-fatal bicycle accidents are currently unclear. We investigated these factors to inform efforts to minimize hospitalization. METHODS: We performed a retrospective analysis of data from non-fatal injured bicyclists admitted to the Emergency and Critical Care Center at Kyoto Medical Center between January 2012 and December 2016. We measured LHoS, LERS, mechanism of injury, head injury prevalence, polytrauma, operations performed, injury severity score (ISS), abbreviated injury scale (AIS) score, maximum AIS score, and trauma and injury severity score probability of survival. We conducted multiple regression analysis to determine predictors of LHoS and LERS. RESULTS: Within the study period, 82 victims met the inclusion and exclusion criteria and were included. Mean age was (46.0 ± 24.7) years. Overall mean LHoS was (16.8 ± 25.2) days, mean LERS was (10.6 ± 14.7) days, median ISS was 9 (interquartile range (IQR): 3-16), median maximum AIS was 3 (IQR: 1-4), and median trauma and injury severity score probability of survival was 98.0% (IQR: 95.5%-99.6%). Age, maximum AIS, ISS, and prevalence of surgery were significantly greater in long LHoS and LERS group compared with short LHoS and LERS group (p < 0.05). Performance of surgery independently explained LHoS (p = 0.0003) and ISS independently explained LERS (p = 0.0009). CONCLUSION: Surgery was associated with long hospital stays and ISS was associated with long emergency room stays. To improve the quality life of the bicyclists, preventive measures for reducing injury severity or avoiding injuries needing operation are required.

Simple, Frequent Indicator for Personal Identification-Postmortem and Antemortem Abdominal Computed Tomography Findings of a Charred Body.

Postmortem personal identification in forensic science is performed using various methods. However, severely burnt bodies are hard to identify using odontological or skeletal features because of carbonization, and sometimes DNA profiling is impracticable because of the unavailability of the relatives. We present a case of a burn victim found after a house fire. Personal identification was attempted, but the body was heavily charred to the bones and the use of physical appearance was impracticable. There were no known relatives or personal belongings of the deceased for comparison of DNA typing. We obtained a series of abdominal computed tomography (CT) scans taken antemortem and found bilateral multiple renal cysts, left renal artery calcification, and a big right inguinal hernia, which matched the deceased's postmortem CT findings and autopsy findings. To date, studies of identification by CT have acted for a rise in precision, but they require complicated calculation or high graphical methods. Calcification of the arteries or renal cysts seen in our case are very common lesions present in many adults with abundant variation; thus, they may be helpful as simple indicators for identification.

Pedaling improves gait ability of hemiparetic patients with stiff-knee gait: fall prevention during gait.

BACKGROUND AND PURPOSE: Stiff-knee gait, which is a gait abnormality observed after stroke, is characterized by decreased knee flexion angles during the swing phase, and it contributes to a decline in gait ability. This study aimed to identify the immediate effects of pedaling exercises on stiff-knee gait from a kinesiophysiological perspective. METHODS: Twenty-one patients with chronic post-stroke hemiparesis and stiff-knee gait were randomly assigned to a pedaling group and a walking group. An ergometer was set at a load of 5 Nm and rotation speed of 40 rpm, and gait was performed at a comfortable speed; both the groups performed the intervention for 10 min. Kinematic and electromyographical data while walking on flat surfaces were immediately measured before and after the intervention. RESULTS: In the pedaling group, activity of the rectus femoris significantly decreased from the pre-swing phase to the early swing phase during gait after the intervention. Flexion angles and flexion angular velocities of the knee and hip joints significantly increased during the same period. The pedaling group showed increased step length on the paralyzed side and gait velocity. CONCLUSIONS: Pedaling increases knee flexion during the swing phase in hemiparetic patients with stiff-knee gait and improves gait ability.

Criminal mercury vapor poisoning using heated tobacco product.

We report an unusual case of mercury vapor poisoning from using a heated tobacco product. The suspect had added grains of mercury into 20 cigarettes in a pack. When a 36-year-old Japanese man inserted one of these cigarettes into the battery powered holder, it was heated to a temperature of 350 °C, and he inhaled vaporized mercury. After using 14 of the cigarettes over 16 h, he noticed he had flu-like symptoms so he visited the hospital. Although no physical abnormalities were revealed, 99 µg/L of mercury was detected in his serum sample. His general condition improved gradually and his whole blood mercury level had decreased to 38 µg/L 5 days later. When the remaining six cigarettes in the pack were examined, many metallic grains weighing a total of 1.57 g were observed. Energy dispersive X-ray fluorescence spectrometry confirmed the grains as elemental mercury. Accordingly, the victim was diagnosed with mercury poisoning. Because the mercury was incorporated into cigarettes, an unusual and novel intoxication occurred through the heating of the tobacco product. Both medical and forensic scientific examination confirmed this event as attempted murder.

Drowning of a patient with epilepsy while showering.

In Japan, because the most common site of drowning among patients with epilepsy is the bathtub, showering is generally recommended as an alternative to bathing. We herein report a case involving a female patient with epilepsy who drowned while showering. She had been diagnosed with epilepsy approximately 25 years previously, and her condition had progressed to refractory epilepsy. Carbamazepine, levetiracetam, lamotrigine, clobazam, and perampanel were prescribed daily. One day while showering, the patient was found lying with her face immersed in water that had accumulated on the floor of the bathtub. A forensic autopsy revealed water in the stomach, trachea, and proximal regions of both lung bronchi as well as white and red foam on the pharynx and larynx. A total of 1.9 µg/mL of lamotrigine, 0.14 µg/mL of carbamazepine, and 0.069 µg/mL of perampanel were detected in the patient's blood. The patient's cause of death was determined to be drowning due to an epileptic seizure. Although the patient was prescribed five types of antiepileptic medication, only three were detected in her blood. The current case demonstrates that drowning can occur while showering, suggesting that it is unsafe for patients with medication nonadherence. To prevent unintentional deaths in the bathroom, we recommend that patients with epilepsy maintain high adherence to all prescriptions and are supervised by a family member, even when showering. The current case is the first autopsy report of a patient with epilepsy who drowned while showering.

Autopsy Cases of Motorcyclists Dying of Trauma or Disease.

We aimed to provide a better estimation of health-related motorcycle fatalities by comparing the backgrounds, mechanisms of injuries, and injury severity of victims who died of collision versus those who died of disease. We retrospectively analyzed autopsy records of 29 motorcyclists (mean age, 61.0 ± 21.0 years), none of whom had been driving under the influence of alcohol. Altogether, 22 (75.9%) had died of trauma, and 7 had died of disease. The disease-death victims were significantly older and had a significantly higher prevalence of a medical history compared with those with trauma-related death (100% vs 45.5%, P = 0.01), especially of lifestyle diseases (100% vs 13.6%, P < 0.001) and heart or cerebrovascular disease (57.1% vs 13.6%, P = 0.02). All of the victims who were affected by disease and 50% of trauma-death victims had fallen on the road without a vehicle collision (P = 0.02). Mean Injury Severity Score of the trauma-death group was significantly higher than that of the disease-death group (48.1 vs 9.1, P < 0.001). A forensic autopsy should be performed for all motorcyclist fatalities to diagnose a disease-related death during motorcycle riding. To reduce the incidence of these accidents, motorcyclists should maintain a good physical status.

Seatbelt paths of the pregnant women sitting in the rear seat of a motor vehicle.

PURPOSE: Seatbelt use during pregnancy is important to improve maternal and fetal survival after motor vehicle collisions. However, because the rear seatbelt of a motor vehicle tends to make contact with the neck, even if it is adequately used, some pregnant women sitting in the rear seat opt not to fasten the belt. The purpose of this study is to explore seatbelt-neck contact for pregnant women sitting in the rear seat of a motor vehicle. METHODS: We carried out an anthropometric study. Japanese women who were ≥30 weeks pregnant (n = 12) sat in the left side of the rear seat of a typical mid-size passenger sedan and fastened the seatbelt. Seating posture was investigated by measuring the coordinates of the anthropometric data points of the pregnant women (head, shoulder, hip joint, and knee joint). The belt path was analyzed by measuring the clearance between the belt and the sternum or navel. RESULTS: Among the 12 pregnant women at 33.9 week ± 3.3 week gestation, the shoulder belt deviated to the right side and subsequently contacted to the neck in four pregnant women (Contact group). The height of the Contact group was significantly shorter than that of Non-contact group (152.3 cm ± 3.0 cm vs. 159.0 cm ± 3.3 cm, p = 0.008). Regarding the relative position of the seatbelt to the subject's body, the distances from the top of the sternum to the center of the shoulder belt were significantly shorter in Contact group (3.9 cm ± 3.5 cm) than that in the Non-contact group (8.0 cm ± 1.6 cm, p = 0.03). However, no significant difference was found for the distance from the umbilicus to the center of the lap belt. CONCLUSION: Our findings show that because of short height and late term of pregnancy with protrusion of the abdomen, the shoulder belt deviates to the right or left, avoiding the protruded uterus, and subsequently makes contact with the neck. Seatbelt systems for rear seats need to be developed to improve passenger safety, especially for pregnant women.