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To quantify physiologic changes in anterior-posterior laxity of the normal knee caused acutely by exercise, we evaluated the exercise level and the duration of exercise needed to cause changes in laxity, the magnitude of changes in laxity, and the time needed for laxity to return to the level before exercise, by continuously applying a fixed exercise load. After a 20-minute run at 7 km/hr, anterior laxity with a displacement force of 133 N increased by about one third, and the compliance increased by one half with anterior drawer between 0 and 67 N. These changes were maintained at a similar level during exercise. The levels before exercise were restored gradually over 1 hour after exercise. As the muscle strength showed no changes during exercise, we consider these changes in laxity are not associated with a decrease in muscle strength. Furthermore, since the changes in knee laxity after triathlon (in which the knee is subjected to prolonged excessive exercise) are similar to those after running at 7 km/hr, we believe that the magnitude of changes in laxity after exercise is fixed, regardless of the level of the exercise load. Moreover, the threshold of exercise that causes the maximum change is low. [ABSTRACT FROM AUTHOR]

Background: Marfan syndrome (MFS) is an inherited disorder caused by mutations in the FBN1 gene encoding fibrillin-1, a matrix component of extracellular microfibrils. The main cause of morbidity and mortality in MFS is thoracic aortic aneurysm and dissection, but the underlying mechanisms remain undetermined., Methods: To elucidate the role of endothelial XOR (xanthine oxidoreductase)-derived reactive oxygen species in aortic aneurysm progression, we inhibited in vivo function of XOR either by endothelial cell (EC)-specific disruption of the Xdh gene or by systemic administration of an XOR inhibitor febuxostat in MFS mice harboring the Fbn1 missense mutation p.(Cys1041Gly). We assessed the aberrant activation of mechanosensitive signaling in the ascending aorta of Fbn1 C1041G/+ mice. Further analysis of human aortic ECs investigated the mechanisms by which mechanical stress upregulates XOR expression., Results: We found a significant increase in reactive oxygen species generation in the ascending aorta of patients with MFS and Fbn1 C1041G/+ mice, which was associated with a significant increase in protein expression and enzymatic activity of XOR protein in aortic ECs. Genetic disruption of Xdh in ECs or treatment with febuxostat significantly suppressed aortic aneurysm progression and improved perivascular infiltration of macrophages. Mechanistically, mechanosensitive signaling involving FAK (focal adhesion kinase)-p38 MAPK (p38 mitogen-activated protein kinase) and Egr-1 (early growth response-1) was aberrantly activated in the ascending aorta of Fbn1 C1041G/+ mice, and mechanical stress on human aortic ECs upregulated XOR expression through Egr-1 upregulation. Consistently, EC-specific knockout of XOR or systemic administration of febuxostat in Fbn1 C1041G/+ mice suppressed reactive oxygen species generation, FAK-p38 MAPK activation, and Egr-1 upregulation., Conclusions: Aberrant activation of mechanosensitive signaling in vascular ECs triggered endothelial XOR activation and reactive oxygen species generation, which contributes to the progression of aortic aneurysms in MFS. These findings highlight a drug repositioning approach using a uric acid-lowering drug febuxostat as a potential therapy for MFS.

Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorder that rarely coexists with infectious thoracoabdominal aortic aneurysms (TAAA) requiring open repair. A 57-year-old patient with MG underwent elective thoracoabdominal aortic replacement. He was diagnosed with MG (Osserman classification II A). Extent IV thoracoabdominal aortic repair was performed under general anesthesia and maintained by total intravenous anesthesia. The patient was withdrawn from the ventilator on postoperative day 5 without spinal cord ischemia and myasthenic crisis. The management of infectious TAAA with myasthenia gravis warrants not only the prevention of complications associated with the crisis but also multidisciplinary treatments for infection control., (@ 2024 The Editorial Committee of Annals of Vascular Diseases.)

Background: Employees' health conditions are issues for not only employees themselves but also companies and society to keep medical costs low and productivity high., Data and Methods: In this analysis, 15,574 observations from 2,319 employees at four operational sites of a large corporation were used. The dataset contained physical and mental health conditions obtained from annual mandatory medical checkups, the Brief Job Stress Questionnaire (BJSQ), and work record information. Health and other factors related to long-term absenteeism (over three days in a quarter) were analyzed. Data were collected between February 2021 and January 2022, and we converted into quarterly observations. A logit (logistic regression) model was used in the analysis., Results: Age and gender were identified as important basic characteristics. The estimates for these variables were positive and negative and significant at the 1% level. Among the variables obtained from the medical checkups, the estimates for diastolic blood pressure, HbA1c, anamnesis, heart disease history, smoking, increased weight, and frequency of alcohol consumption were positive and significant at the 1% level, further those for taking antihypertensive medications and kidney disease history were positive and significant at the 5% level. In contrast, the estimates for systolic blood pressure and amount of alcohol consumption were negative and significant at the 1% level. The estimate for taking antihyperglycemic medications and health guidelines were negative and significant at the 5% level. Among the variables obtained from the BJSQ, the estimates for amount of work felt, fatigue and support from family and friends were positive and significant at the 1%, and the estimate for irritation was positive and significant at the 5% level. The estimates for controlling job and physical complaints were negative and significant at the 1% level, and those for usage of employee's ability to work and suitability of the work were negative and significant at the 5% level. As all four operational sites were located in the northeastern region of Japan (cold and snowy in winter), the seasonal effects were significant at the 1% level. The effect of year was also significant and significant differences were observed among the sites at the 1% level., Conclusion: Some physical and mental health conditions were strongly associated with long-term absenteeism. By improving these conditions, corporations could reduce the number of employee absence days. As absenteeism was costly for corporations due to replacement employees and their training costs to maintain operations, employers must be concerned about rising healthcare (direct and indirect) costs and implement investments to improve employees' health conditions., Limitations: This study's results were based on only one corporation and the dataset was observatory. The employees were primarily operators working inside the building and most of them are healthy. Therefore, the sample selection biases might exist, and the results cannot be generalized to other types of jobs, working conditions, or companies. As medical checkups and the BJSQ are mandatory for most companies in Japan, the framework of this study can be applied to other companies. Although we used the BJSQ results, better mental measures might exist. Similar analyses for different corporations are necessary., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nawata.)

The house fly is known to be a vector of antibiotic-resistant bacteria (ARB) in animal farms. It is also possible that the house fly contributes to the spread of ARB and antibiotic resistance genes (ARGs) among various environments. We hypothesized that ARB and ARGs present in marine fish and fishery food may gain access to humans via the house fly. We show herein that pAQU1, a marine bacterial ARG-bearing plasmid, persists in the house fly intestine for 5 days after fly ingestion of marine bacteria. In the case of Escherichia coli bearing the same plasmid, the persistence period exceeded 7 days. This interval is sufficient for transmission to human environments, meaning that the house fly is capable of serving as a vector of marine-derived ARGs. Time course monitoring of the house fly intestinal microflora showed that the initial microflora was occupied abundantly with Enterobacteriaceae. Experimentally ingested bacteria dominated the intestinal environment immediately following ingestion; however, after 72 h, the intestinal microflora recovered to resemble that observed at baseline, when diverse genera of Enterobacteriaceae were seen. Given that pAQU1 in marine bacteria and E. coli were detected in fly excrement (defined here as any combination of feces and regurgitated material) at 7 days post-bacterial ingestion, we hypothesize that the house fly may serve as a vector for transmission of ARGs from marine items and fish to humans via contamination with fly excrement., (© 2024. The Author(s).)

From April 2018 to February 2021, 150 patients underwent MitraClip implantation for severe functional mitral regurgitation (MR) at our hospital. Two of our patients, an 85-year-old man and an 84-year-old woman, developed a single leaflet device attachment in the acute phase after the implantation and had severe residual MR requiring surgical correction. The recurrent MR was first pointed out on day 5 and day 4, and the duration between MitraClip implantation and surgery was 13 and 55 days, respectively. Due to strong adhesions with the clips and severe valve damage after MitraClip implantation, both cases underwent mitral valve replacement with a good postoperative course. In patients with a high-risk baseline profile, surgical mitral valve replacement after failed MitraClip implantation should be considered at an optimal timing, and a detailed echocardiographic follow-up is required.

Competing Interests: Conflict of interest: None declared

We report the first demonstration of a frequency tunable backward THz-wave parametric oscillator (BW-TPO) centered at a high frequency of 0.87 THz using a slant-stripe-type magnesium oxide-doped periodically poled lithium niobate (PPLN) crystal as the nonlinear medium. Down-converted THz and idler beams generate upon excitation of the PPLN with a sub-nanosecond pulsed source of λ = 1064.44 nm. The resulting first idler has a wavelength of 1067.75 nm, equivalent to an oscillation frequency of 0.872 THz as per the spectral line separation from the pump. We also present angle tuning of the BW-TPO frequency ranging from 0.836-0.905 THz through PPLN rotation. The threshold pump intensity for BW-TPO is determined to be 5.6 GW/cm 2 while obtaining a conversion efficiency as high as 12.3% at a pump energy (intensity) of 15.25 mJ (8.90 GW/cm 2 ). A reduction of the BW-TPO threshold energy and improved pump-to-idler energy conversion efficiency resulted from injection seeding with a CW laser at the same wavelength as the first idler. The THz output is also directly proportional to seed power.

The patient was a 69-year-old man who underwent emergency surgery for acute aortic dissection that developed 5 months after coronary artery bypass grafting. The left internal thoracic artery (LITA) graft anastomosed to the left descending artery was not affected by the aortic dissection, and during the ascending aortic replacement, the artery was not identified for clamping. Although fully sufficient cardioplegia was not achieved due to the patent LITA graft, the patient's postoperative cardiac function was good. The two anastomotic sites of the vein grafts to the ascending aorta were excised along with a remnant of the aortic wall in an island fashion and were reimplanted onto the artificial graft. Based on the site of intimal tear, we speculated that partial clamping during the previous surgery had caused the dissection.

Background: Heart disease (HD), cerebrovascular disease (CBD), and kidney disease (KD) are serious diseases worldwide. These diseases constitute the leading causes of death worldwide and are costly to treat. An analysis of risk factors is necessary to prevent these diseases., Data and Methods: Risk factors were analyzed using data from 2,837,334, 2,864,874, and 2,870,262 medical checkups obtained from the JMDC Claims Database. The side effects of medications used to control hypertension (antihypertensive medications), hyperglycemia (antihyperglycemic medications), and hypercholesterolemia (cholesterol medications), including their interactions, were also evaluated. Logit models were used to calculate the odds ratios and confidence intervals. The sample period was from January 2005 to September 2019., Results: Age and history of diseases were found to be very important factors, and the risk of having diseases could be almost doubled. Urine protein levels and recent large weight changes were also important factors for all three diseases and made the risks 10%-30% higher, except for KD. For KD, the risk was more than double for individuals with high urine protein levels. Negative side effects were observed with antihypertensive, antihyperglycemic, and cholesterol medications. In particular, when antihypertensive medications were used, the risks were almost doubled for HD and CBD. The risk would be triple for KD when individuals were taking antihypertensive medications. If they did not take antihypertensive medications and took other medications, these values were lower (20%-40% for HD, 50%-70% for CBD, and 60%-90% for KD). The interactions between the different types of medications were not very large. When antihypertensive and cholesterol medications were used simultaneously, the risk increased significantly in cases of HD and KD., Conclusion: It is very important for individuals with risk factors to improve their physical condition for the prevention of these diseases. Taking antihypertensive, antihyperglycemic, and cholesterol medications, especially antihypertensive medications, may be serious risk factors. Special care and additional studies are necessary to prescribe these medications, particularly antihypertensive medications., Limitations: No experimental interventions were performed. As the dataset was comprised of the results of health checkups of workers in Japan, individuals aged 76 and above were not included. Since the dataset only contained information obtained in Japan and the Japanese are ethnically homogeneous, potential ethnic effects on the diseases were not evaluated., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Nawata.)

Objectives: This study aims to discuss the midterm results of thoracic endovascular aortic repair (TEVAR) with reentry closure for chronic type B aortic dissection (CTBAD). Materials and Methods: This retrospective study analyzed 13 patients with CTBAD who underwent TEVAR with reentry closure between July 2014 and December 2020. We evaluated the false lumen (FL) cross-sectional area using computed tomography images of the descending aorta at the level of the bronchial bifurcation, Valsalva sinus, celiac artery, and infrarenal abdominal aorta pre- and postoperation. The study endpoints were technical and clinical success rates, freedom from additional aortic reintervention or surgery, and survival. Results: Technical success was obtained in 12 patients (92.3%) with no hospital mortality and neurological complications. The postoperative observation period was 49.2±21.5 months. The clinical success rate was 76.9% (10 cases), and a postoperative reduction of the FL cross-sectional area was obtained in 53.8% of patients. The 5-year overall survival rate was 64.8% with no aortic-related deaths while the 5-year freedom from additional aortic surgery rate was 66.7%. Conclusions: TEVAR with reentry closure suggests preventing FL dilatation or rupture in CTBAD, but the revision of our devices and further research with more patients and longer follow-up periods are required., Competing Interests: Disclosure StatementAll authors have no conflicts of interest to declare., (© 2022 The Editorial Committee of Annals of Vascular Diseases.)

Congenital abdominal aortic aneurysm (AAA) with coarctation has been considered an extremely rare condition. In this study, we present a 3-year-old boy, who was diagnosed by chance with congenital AAA at first operation. We replaced the AAA+coarctation with a 6-mm polytetrafluoroethylene (PTFE) graft. Histological examination of the aortic wall revealed no particular abnormalities. Collateral vessels were noted to develop over 14 years of followup. Good blood flow to both lower limbs and no intermittent claudication were observed. After growth, at the age 17, he underwent extra-anatomical bypass using a 12-mm PTFE graft. This is the first report of successful treatment of congenital AAA+coarctation with longterm followup., Competing Interests: Disclosure StatementHiroshi Nishimaki serves as a consultant to the Dantex Corporation. The other authors have no conflicts of interest to declare., (© 2022 The Editorial Committee of Annals of Vascular Diseases.)

Muscle mass is an important factor for surviving an illness. Ultrasound has gained increased attention as a muscle mass assessment method because of its noninvasiveness and portability. However, data on the frequency of ultrasound-based muscle mass assessment are limited, and there are some barriers to its implementation. Hence, a web-based cross-sectional survey was conducted on healthcare providers in Japan, which comprised four parts: 1) participant characteristics; 2) general muscle mass assessment; 3) ultrasound-based muscle mass assessment; and 4) the necessity of, interest in, and barriers to its implementation. Necessity and interest were assessed using an 11-point Likert scale, whereas barriers were assessed using a 5-point Likert scale, in which "Strongly agree" and "Agree" were counted for the analysis. Of the 1,058 responders, 1,026 participants, comprising 282 physicians, 489 physical therapists, 84 occupational therapists, 120 nurses, and 51 dieticians, were included in the analysis. In total, 93% of the participants were familiar with general muscle mass assessment, and 64% had conducted it. Ultrasound-based muscle mass assessment was performed by 21% of the participants. Necessity and interest scored 7 (6-8) and 8 (7-10), respectively for ultrasound-based muscle mass assessment. The barriers to its implementation included lack of relevant education (84%), limited staff (61%), and absence of fixed protocol (61%). Regardless of the necessity of and interest in ultrasound-based muscle mass assessment, it was only conducted by one-fifth of the healthcare providers, and the most important barrier to its implementation was lack of education., Competing Interests: The authors have declared that no competing interests exist.

Background: Heart diseases (HD) are the leading cause of deaths in the world. Many studies have been done on the relationships among hypertension, HD and antihypertensive medications. Most of the studies find that hypertension is a significant risk factor of HD, but there are some studies in which hypertension is not a risk factor. As antihypertensive medications are routinely prescribed to prevent HD, it is necessary to evaluate the effects of these and other risk factors of HD., Data and Methods: The relationship between hypertension and HD was analyzed using 6,773,464 medical checkups obtained from the JMDC Claims Database obtained from January 2005 to September 2019. Factors potentially affecting HD, including blood pressures (BP) and usage of antihypertensive medications, were evaluated using 2,861,769 observations. To avoid the causality problem, probit models were used to analyze the probability of an individual who had no history of HD at year t developing HD by year t + 1., Results: A positive relation between systolic blood pressure (SBP) and HD was found in the equation without any other covariates. However, the significant relation between HD and BP disappeared when the models contained various other factors as covariates. When a 10-year age or longer interval was used in the model, a positive relation between the two variables was found, suggesting that SBP works as a proxy variable. Taking antihypertensive medications greatly increases the probability of developing HD in the next year. Higher levels of cholesterols decrease the probability of developing HD., Conclusion: Unlike many previous studies, no significant relationship between HD and hypertension was found in the models containing multiple covariates. The accepted relation might actually be spurious, and it is important to select covariates carefully. Taking antihypertensive medications appears to increase the probability of developing HD in the next year, suggesting the need for further research and greater caution in the use of antihypertensive medications., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nawata.)

Introduction: According to the 2017 data, occupational accidents are more common in social welfare facilities compared with other industries; in particular, the number of occupational accidents resulting in four or more days of absence from work due to low back pain (LBP) or falls has increased and is considered problematic. Although physical therapy has been demonstrated to be effective in preventing LBP and falls in older adults living in the community, no randomised controlled trials have examined whether individual online physical therapy can prevent LBP and falls in nursing care workers (NCW)., Methods and Analysis: A total of 120 NCW aged 20 years or older will be randomly assigned to an online individualised therapy group (ITG) or usual group (UG) after obtaining informed consent. We defined an NCW as a person who assists disabled and elderly persons with eating, bathing and toileting activities in social welfare facilities. We will follow-up the participants 12 months after the start of the intervention and compare the results at 3, 6 and 12 months. The primary endpoint will be the Oswestry Disability Index (ODI); ITG participants will receive professional advice on LBP and musculoskeletal problems from a physical therapist via online interview and email as often as they wish over a 6-month period; UG participants will only have access to brochures and video feeds related to LBP and fall prevention. Owing to the nature of the study, blinding the participants and interventionists is not possible; however, the outcomes will be assessed via a web-based questionnaire to prevent detection bias. The null hypothesis is that there is no clinically important difference in the primary outcome between the two treatment groups and that a decrease in the ODI score of at least 20% is clinically meaningful., Ethics and Dissemination: The Ethics Committee of the Japanese Society of Occupational Medicine approved the protocol of this study. The results of this study will be disseminated through peer-reviewed journals and conference presentations., Trial Registration Number: jRCT1070210128., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Tissue fibrosis and organ dysfunction are hallmarks of age-related diseases including heart failure, but it remains elusive whether there is a common pathway to induce both events. Through single-cell RNA-seq, spatial transcriptomics, and genetic perturbation, we elucidate that high-temperature requirement A serine peptidase 3 (Htra3) is a critical regulator of cardiac fibrosis and heart failure by maintaining the identity of quiescent cardiac fibroblasts through degrading transforming growth factor-β (TGF-β). Pressure overload downregulates expression of Htra3 in cardiac fibroblasts and activated TGF-β signaling, which induces not only cardiac fibrosis but also heart failure through DNA damage accumulation and secretory phenotype induction in failing cardiomyocytes. Overexpression of Htra3 in the heart inhibits TGF-β signaling and ameliorates cardiac dysfunction after pressure overload. Htra3-regulated induction of spatio-temporal cardiac fibrosis and cardiomyocyte secretory phenotype are observed specifically in infarct regions after myocardial infarction. Integrative analyses of single-cardiomyocyte transcriptome and plasma proteome in human reveal that IGFBP7, which is a cytokine downstream of TGF-β and secreted from failing cardiomyocytes, is the most predictable marker of advanced heart failure. These findings highlight the roles of cardiac fibroblasts in regulating cardiomyocyte homeostasis and cardiac fibrosis through the Htra3-TGF-β-IGFBP7 pathway, which would be a therapeutic target for heart failure., (© 2022. The Author(s).)

This report describes a rare case of brachial artery dissection associated with closed elbow dislocation caused by a snowboarding injury. After peripheral ischaemic findings in the right upper extremity were confirmed, urgent duplex-sonography was performed to diagnose the brachial artery injury. Urgent revascularisation surgery was promptly performed, and arterial dissection was diagnosed by intraoperative findings, in which the adventitia of the brachial artery was intact and the intima was disrupted. In this case, because there was no golden time window before undertaking urgent revascularisation surgery, duplex-sonography was very useful for making an emergency diagnosis. To diagnose arterial dissection, because the adventitia of the brachial artery is intact, it is necessary to perform arteriotomy to identify intimal disruption in the brachial artery. When diagnosing traumatic elbow dislocation, it is important to suspect arterial dissection., Competing Interests: The authors declare no conflict of interest., (©2022 Tottori University Medical Press.)

Using a nonlinear optical mixing known as a frequency up-conversion process, we demonstrate an optical cross-correlation technique for the detection and characterization of sub-nanosecond (sub-ns) terahertz (THz)-wave pulses. A monochromatic THz-wave pulse from an injection-seeded THz-wave parametric generator (is-TPG) was mixed with a near-infrared (NIR) pump pulse to generate a NIR idler pulse in a trapezoidal-prism-shaped MgO-doped lithium niobate crystal under the noncollinear phase-matching condition. By measuring pump-energy and crystal-length dependencies, we show that the frequency up-conversion of sub-ns THz-wave pulses with and without subsequent parametric amplification can be used for sensitive detection and intensity cross-correlation characterization, respectively. Using this cross-correlation technique, we reveal that the temporal profile of THz-wave pulses from the is-TPG driven by a 351-ps 1064-nm pump laser has slightly-frequency-dependent pulse width in the range of 150-190 ps at full width at half-maximum in the tunable range of 0.95-2.00 THz.

Objective: To examine whether there is an association between prehospital transfer distance and surgical mortality in emergency thoracic aortic surgery., Methods: A retrospective cohort study using a national clinical database in Japan was conducted. Patients who underwent emergency thoracic aortic surgery from January 1, 2014, to December 31, 2016, were included. Patients with type B dissection were excluded. A multilevel logistic regression analysis was performed to examine the association between prehospital transfer distance and surgical mortality. In addition, an instrumental variable analysis was performed to address unmeasured confounding., Results: A total of 12,004 patients underwent emergency thoracic aortic surgeries at 495 hospitals. Surgical mortality was 13.8%. The risk-adjusted mortality odds ratio for standardized distance (mean 12.8 km, standard deviation 15.2 km) was 0.94 (95% confidence interval, 0.87-1.01; P = .09). Instrumental variable analysis did not reveal a significant association between transfer distance and surgical mortality as well., Conclusions: No significant association was found between surgical mortality and prehospital transfer distance in emergency thoracic aortic surgery cases. Suspected cases of acute thoracic aortic syndrome may be transferred safely to distant high-volume hospitals., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)