Unprecedented fire activity above the Arctic Circle linked to rising temperatures.

Arctic fires can release large amounts of carbon from permafrost peatlands. Satellite observations reveal that fires burned ~4.7 million hectares in 2019 and 2020, accounting for 44% of the total burned area in the Siberian Arctic for the entire 1982-2020 period. The summer of 2020 was the warmest in four decades, with fires burning an unprecedentedly large area of carbon-rich soils. We show that factors of fire associated with temperature have increased in recent decades and identified a near-exponential relationship between these factors and annual burned area. Large fires in the Arctic are likely to recur with climatic warming before mid-century, because the temperature trend is reaching a threshold in which small increases in temperature are associated with exponential increases in the area burned.

A scoping review on the health effects of smoke haze from vegetation and peatland fires in Southeast Asia: Issues with study approaches and interpretation.

Smoke haze due to vegetation and peatland fires in Southeast Asia is a serious public health concern. Several approaches have been applied in previous studies; however, the concepts and interpretations of these approaches are poorly understood. In this scoping review, we addressed issues related to the application of epidemiology (EPI), health burden estimation (HBE), and health risk assessment (HRA) approaches, and discussed the interpretation of findings, and current research gaps. Most studies reported an air quality index exceeding the 'unhealthy' level, especially during smoke haze periods. Although smoke haze is a regional issue in Southeast Asia, studies on its related health effects have only been reported from several countries in the region. Each approach revealed increased health effects in a distinct manner: EPI studies reported excess mortality and morbidity during smoke haze compared to non-smoke haze periods; HBE studies estimated approximately 100,000 deaths attributable to smoke haze in the entire Southeast Asia considering all-cause mortality and all age groups, which ranged from 1,064-260,000 for specified mortality cause, age group, study area, and study period; HRA studies quantified potential lifetime cancer and non-cancer risks due to exposure to smoke-related chemicals. Currently, there is a lack of interconnection between these three approaches. The EPI approach requires extensive effort to investigate lifetime health effects, whereas the HRA approach needs to clarify the assumptions in exposure assessments to estimate lifetime health risks. The HBE approach allows the presentation of health impact in different scenarios, however, the risk functions used are derived from EPI studies from other regions. Two recent studies applied a combination of the EPI and HBE approaches to address uncertainty issues due to the selection of risk functions. In conclusion, all approaches revealed potential health risks due to smoke haze. Nonetheless, future studies should consider comparable exposure assessments to allow the integration of the three approaches.

IgG4-related Disease Involving the Cardiovascular System: An Intracardiac Mass and a Mass Lesion Surrounding a Coronary Artery.

A 61-year-old Japanese man with IgG4-related autoimmune pancreatitis developed a mass in the right atrium (RA) and a mass lesion surrounding the left anterior descending coronary artery. We performed an intracardiac echo catheter-guided percutaneous biopsy of the RA mass, and histologically diagnosed it as IgG4-related disease. Oral corticosteroid therapy gradually downsized the mass lesions. We encountered a very rare case with mass lesions in the cardiovascular system of the IgG4-related disease that were able to be diagnosed using an intracardiac echo-guided biopsy.

"Pseudo aortoiliac bifurcation" leading to significant plaque shifting in the endovascular treatment of an aortoiliac bifurcation lesion: a case report.

BACKGROUND: Plaque shifting is a serious complication of endovascular treatment (EVT) for aortoiliac bifurcation lesions. It is challenging to predict the occurrence of unfavorable plaque shifting correctly. CASE PRESENTATION: We report the case of an 88-year-old Japanese woman who experienced constant pain at rest in her left leg. The ankle-brachial pressure index of her left leg was 0.57. Computed tomography (CT) angiography revealed severe stenosis of the left common iliac artery (CIA) and total occlusion of the left external iliac artery (EIA). We diagnosed the patient with acute exacerbation of a chronic limb ischemia and administered endovascular treatment (EVT) to treat the left CIA and EIA. The results of initial angiography agreed with those of CT angiography. After placing a self-expandable stent for the left CIA lesion, significant unfavorable plaque shifting occurred. From a comparison between pre- and post-stenting angiography, we realized that the plaque protrusion into the terminal aorta had formed a "pseudo aortoiliac bifurcation" that was situated more proximally compared to the true bifurcation. We had incorrectly assessed the height of the aortoiliac bifurcation and exact plaque position and had underestimated the risk of plaque shifting because of this misunderstanding. The patient ultimately developed fatal cholesterol embolization after EVT. CONCLUSIONS: Plaque protrusion into the terminal aorta can form a "pseudo aortoiliac bifurcation", causing the wrong estimation of the height of the aortoiliac bifurcation; "angiographically", the highest point is not always the true bifurcation. Careful assessment of initial angiography to detect the true aortoiliac bifurcation and exact plaque position is essential to avoid unfavorable plaque shifting.

Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular smooth muscle cells and exacerbates abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC-/-) mice subjected to periaortic application of CaCl2 developed AAAs. Six weeks after CaCl2 treatment, internal and external aortic diameters were significantly increased in MURC-/- AAAs compared with WT AAAs, which were accompanied by advanced fibrosis in the tunica media of MURC-/- AAAs. The activity of JNK and matrix metalloproteinase (MMP) -2 and -9 were increased in MURC-/- AAAs compared with WT AAAs at 5 days after CaCl2 treatment. At 6 weeks after CaCl2 treatment, MURC-/- AAAs exhibited attenuated JNK activity compared with WT AAAs. There was no difference in the activity of MMP-2 or -9 between saline and CaCl2 treatments. In MURC/Cavin-4-knockdown VSMCs, TNFα-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Furthermore, WT, MURC-/-, apolipoprotein E-/- (ApoE-/-), and MURC/Cavin-4 and ApoE double-knockout (MURC-/-ApoE-/-) mice were subjected to angiotensin II (Ang II) infusion. In both ApoE-/- and MURC-/-ApoE-/- mice infused for 4 weeks with Ang II, AAAs were promoted. The internal aortic diameter was significantly increased in Ang II-infused MURC-/-ApoE-/- mice compared with Ang II-infused ApoE-/- mice. In MURC/Cavin-4-knockdown VSMCs, Ang II-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Our results suggest that MURC/Cavin-4 in VSMCs modulates AAA progression at the early stage via the activation of JNK and MMP-9. MURC/Cavin-4 is a potential therapeutic target against AAA progression.

PTRF/Cavin-1 Deficiency Causes Cardiac Dysfunction Accompanied by Cardiomyocyte Hypertrophy and Cardiac Fibrosis.

Mutations in the PTRF/Cavin-1 gene cause congenital generalized lipodystrophy type 4 (CGL4) associated with myopathy. Additionally, long-QT syndrome and fatal cardiac arrhythmia are observed in patients with CGL4 who have homozygous PTRF/Cavin-1 mutations. PTRF/Cavin-1 deficiency shows reductions of caveolae and caveolin-3 (Cav3) protein expression in skeletal muscle, and Cav3 deficiency in the heart causes cardiac hypertrophy with loss of caveolae. However, it remains unknown how loss of PTRF/Cavin-1 affects cardiac morphology and function. Here, we present a characterization of the hearts of PTRF/Cavin-1-null (PTRF-/-) mice. Electron microscopy revealed the reduction of caveolae in cardiomyocytes of PTRF-/- mice. PTRF-/- mice at 16 weeks of age developed a progressive cardiomyopathic phenotype with wall thickening of left ventricles and reduced fractional shortening evaluated by echocardiography. Electrocardiography revealed that PTRF-/- mice at 24 weeks of age had low voltages and wide QRS complexes in limb leads. Histological analysis showed cardiomyocyte hypertrophy accompanied by progressive interstitial/perivascular fibrosis. Hypertrophy-related fetal gene expression was also induced in PTRF-/- hearts. Western blotting analysis and quantitative RT-PCR revealed that Cav3 expression was suppressed in PTRF-/- hearts compared with that in wild-type (WT) ones. ERK1/2 was activated in PTRF-/- hearts compared with that in WT ones. These results suggest that loss of PTRF/Cavin-1 protein expression is sufficient to induce a molecular program leading to cardiomyocyte hypertrophy and cardiomyopathy, which is partly attributable to Cav3 reduction in the heart.

MURC deficiency in smooth muscle attenuates pulmonary hypertension.

Emerging evidence suggests that caveolin-1 (Cav1) is associated with pulmonary arterial hypertension. MURC (also called Cavin-4) is a member of the cavin family, which regulates caveolar formation and functions together with caveolins. Here, we show that hypoxia increased Murc mRNA expression in the mouse lung, and that Murc-null mice exhibited attenuation of hypoxia-induced pulmonary hypertension (PH) accompanied by reduced ROCK activity in the lung. Conditional knockout mice lacking Murc in smooth muscle also resist hypoxia-induced PH. MURC regulates the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through Rho/ROCK signalling. Cav1 suppresses RhoA activity in PASMCs, which is reversed by MURC. MURC binds to Cav1 and inhibits the association of Cav1 with the active form of Gα13, resulting in the facilitated association of the active form of Gα13 with p115RhoGEF. These results reveal that MURC has a function in the development of PH through modulating Rho/ROCK signalling.

Extensive ischemic ulcers due to limb occlusion after endovascular aneurysm repair: a case report.

INTRODUCTION: Limb occlusion after endovascular aneurysm repair (EVAR) is a well-known complication. However, extensive ischemic ulcers due to limb occlusion are extremely rare. CASE DESCRIPTION: We report a rare case of extensive ischemic ulcers that developed seven months after EVAR in an 85-year-old Japanese man. He had been taking appropriate anticoagulant therapy because of paroxysmal atrial fibrillation. Angiography showed a left limb occlusion and superficial femoral artery (SFA) chronic total occlusion (CTO), and intravascular ultrasound showed limb kinking. Endovascular therapy (EVT) was performed, and stent placement was used to cover a large amount of thrombi and correct the limb kinking, leading to complete recovery of left limb blood flow. After additional EVT was performed for the SFA CTO, outflow improved and the ulcers healed completely. DISCUSSION AND EVALUATION: It seemed that the combination of poor inflow and poor outflow led to limb thrombosis. CONCLUSIONS: Here, we describe an extremely rare case of extensive ischemic ulcers due to limb occlusion after EVAR. Patients should undergo careful follow-up after EVAR to monitor blood flow to the lower extremities. Additionally, the early detection and correction of limb kinking and poor outflow are essential to prevent the development of ischemic ulcers.

The coiled-coil domain of MURC/cavin-4 is involved in membrane trafficking of caveolin-3 in cardiomyocytes.

Muscle-restricted coiled-coil protein (MURC), also referred to as cavin-4, is a member of the cavin family that works cooperatively with caveolins in caveola formation and function. Cavins are cytoplasmic proteins with coiled-coil domains and form heteromeric complexes, which are recruited to caveolae in cells expressing caveolins. Among caveolins, caveolin-3 (Cav3) is exclusively expressed in muscle cells, similar to MURC/cavin-4. In the heart, Cav3 overexpression contributes to cardiac protection, and its deficiency leads to progressive cardiomyopathy. Mutations in the MURC/cavin-4 gene have been identified in patients with dilated cardiomyopathy. In the present study, we show the role of MURC/cavin-4 as a caveolar component in the heart. In H9c2 cells, MURC/cavin-4 was localized at the plasma membrane, whereas a MURC/cavin-4 mutant lacking the coiled-coil domain (ΔCC) was primarily localized to the cytoplasm. ΔCC bound to Cav3 and impaired membrane localization of Cav3 in cardiomyocytes. Additionally, although ΔCC did not alter Cav3 mRNA expression, ΔCC decreased the Cav3 protein level. MURC/cavin-4 and ΔCC similarly induced cardiomyocyte hypertrophy; however, ΔCC showed higher hypertrophy-related fetal gene expression than MURC/cavin-4. ΔCC induced ERK activation in cardiomyocytes. Transgenic mice expressing ΔCC in the heart (ΔCC-Tg mice) showed impaired cardiac function accompanied by cardiomyocyte hypertrophy and marked interstitial fibrosis. Hearts from ΔCC-Tg mice showed a reduction of the Cav3 protein level and activation of ERK. These results suggest that MURC/cavin-4 requires its coiled-coil domain to target the plasma membrane and to stabilize Cav3 at the plasma membrane of cardiomyocytes and that MURC/cavin-4 functions as a crucial caveolar component to regulate cardiac function.

Model carcinogen adsorption dynamics of DNA gel.

We have derived theoretical equations describing the adsorption of carcinogen to gels in an immersion medium containing carcinogens. The theory was developed for a cylindrical boundary condition under the assumption of a carcinogen diffusion-limited process combined with the "moving boundary picture (Furusawa et al., 2007)". The time course of the adsorbed carcinogen layer thickness and that of the carcinogen concentration in an immersion medium were expressed by a set of scaled variables, and the asymptotic behavior in the initial stage was derived. Experiments based on the theory were performed using a DNA gel sandwiched between a set of coverglasses in a medium containing acridine orange (AO). The boundary between the AO-adsorbed gel layer and AO-nonadsorbed gel layer was traced during the immersion. The time courses of the AO-adsorbed gel layer thickness and the AO concentration in the immersion medium were well explained by the theory, and the number ratio of the total AO molecules to the adsorption sites in the DNA gel was determined.

MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors.

The actions of catecholamines on adrenergic receptors (ARs) induce sympathetic responses, and sustained activation of the sympathetic nervous system results in disrupted circulatory homeostasis. In cardiomyocytes, α1-ARs localize to flask-shaped membrane microdomains known as "caveolae." Caveolae require both caveolin and cavin proteins for their biogenesis and function. However, the functional roles and molecular interactions of caveolar components in cardiomyocytes are poorly understood. Here, we showed that muscle-restricted coiled-coil protein (MURC)/Cavin-4 regulated α1-AR-induced cardiomyocyte hypertrophy through enhancement of ERK1/2 activation in caveolae. MURC/Cavin-4 was expressed in the caveolae and T tubules of cardiomyocytes. MURC/Cavin-4 overexpression distended the caveolae, whereas MURC/Cavin-4 was not essential for their formation. MURC/Cavin-4 deficiency attenuated cardiac hypertrophy induced by α1-AR stimulation in the presence of caveolae. Interestingly, MURC/Cavin-4 bound to α1A- and α1B-ARs as well as ERK1/2 in caveolae, and spatiotemporally modulated MEK/ERK signaling in response to α1-AR stimulation. Thus, MURC/Cavin-4 facilitates ERK1/2 recruitment to caveolae and efficient α1-AR signaling mediated by caveolae in cardiomyocytes, which provides a unique insight into the molecular mechanisms underlying caveola-mediated signaling in cardiac hypertrophy.

Effects of cardiologist experience on outcomes of patients with ST-elevated myocardial infarction treated with primary PCI in a local area in Japan.

Primary percutaneous coronary intervention (PCI) for ST-elevated myocardial infarction (STEMI) results in dramatically improved clinical outcomes when performed in a timely manner. Although guidelines for STEMI patients recommend PCI should be performed by experienced operators with acceptable PCI volume, cardiologists in a local area must perform primary PCI at their own hospitals. This study evaluated the effects of cardiologist experience on outcomes for STEMI patients in a local area in Japan.Between April 2007 and March 2010, 140 consecutive STEMI patients were admitted to our hospital and 121 of these patients received primary PCI. STEMI patients undergoing primary PCI were divided into two groups according to the operator's experience as a cardiologist. We retrospectively analyzed their clinical backgrounds, PCI findings, in-hospital outcomes, and drug administration at discharge.There were no significant differences in any clinical characteristics, angiographic findings, or PCI procedures between the two groups. Clinical outcomes of the two groups were similar, except for the length of hospital stay (21.1 ± 5.8 versus 15.5 ± 9.7; P = 0.0255). The frequency of administration of drugs such as ß-blockers (59.1% versus 34.0%; P = 0.0086), aldosterone blockade (10.4% versus 25.5%; P = 0.0334), and nicorandil (76.1% versus 25.5%; P = < 0.0001) was different between the two groups.The clinical outcomes of STEMI patients in this study were satisfactory and almost equivalent when compared according to the experience of the attending cardiologist. The present findings suggest the important clinical implication that younger cardiologists who have experienced PCI procedures to a certain extent can safely perform primary PCI and contribute to better prognoses of STEMI patients.

Effective surgical treatment for controlling the acute heart failure induced by acutely progressed mitral regurgitation with nonbacterial thrombotic endocarditis.

A 45-year-old woman complaining of consciousness disturbance demonstrated multiple brain infarctions. Echocardiogram showed vegetation on the posterior mitral leaflet. Infectious endocarditis was initially suspected and we started empirical antibiotics. However, mitral vegetation grew rapidly and caused severe mitral regurgitation. Acute heart failure was so poorly controlled by conservative treatment that we concluded cardiac surgery was indicated. Mitral valve replacement was safely performed, and there was no sign of heart failure or recurrent thromboembolism during the postoperative course. Thereafter, multiple hepatic masses and a solid lesion in the pancreatic head were detected by computed tomography. The patient finally died of multiple organ failure that presumably resulted from malignancy in the terminal stage. The clinical course of this case can be explained by the pathology of nonbacterial thrombotic endocarditis (NBTE). The standard treatment for NBTE consists of systemic anticoagulation as well as controlling the underlying malignancy. However, we could not diagnose this case as NBTE before surgery. Although mitral valve replacement was finally effective to control acute heart failure in this case, NBTE should be exactly diagnosed as quickly as possible and the treatment policy should be deliberated.

Subacutely progressed extensive aortic dissection complicated with catheter-induced dissection in left main coronary artery.

A 64-year-old man complaining of resting angina underwent emergent coronary angiogram and significant stenosis in the mid-left anterior descending artery was discovered. Although deployment of the drug-eluting Cypher stent relieved the stenosis, the guiding catheter accidentally induced coronary dissection in the left main coronary artery (LMCA). Then, deployment of another Cypher stent at the lesion successfully managed the complication. 20 days later, although asymptomatic, extensive aortic dissection was detected from the coronary sinus of Valsalva to the femoral artery. 64-Row multidetector computed tomography demonstrated that the dissection originated from the LMCA and retrogradely expanded to the aorta. This type of dissection is a rare complication related to coronary intervention and even in such a clinical setting, asymptomatic delayed progression of retrograde aortic dissection has not previously been reported to our knowledge.

Fatal splenic laceration in a young woman caused by idiopathic isolated splenic vein thrombosis.

A 38-year-old woman died of hemorrhagic shock caused by idiopathic bleeding in the abdominal cavity. At autopsy, more than 5,000 mL hemoperitoneum was detected. There was no remarkable bleeding site except for a small tear in the surface of the spleen. Microscopic examination suggested that isolated splenic vein thrombosis induced coagulative necrosis of the spleen and subsequently caused splenic laceration. Whenever a case of hemoperitoneum is encountered, splenic rupture should be included in the differential diagnosis; it is imperative to manage such cases as promptly as possible.

Chronic pericardial constriction induced severe ischemic hepatitis manifesting as hypoglycemic attack.

Ischemic hepatitis, otherwise known as "shock liver", is characterized by a massive, but transient increase in serum transaminase levels, usually associated with cardiac failure. A patient who did not have a predisposition to hypoglycemia was discovered at home with disturbed consciousness caused by hypoglycemia. She had been diagnosed as having constrictive pericarditis several years earlier and had developed ischemic hepatitis. Though the high serum transaminase levels were rapidly normalized, severe jaundice gradually developed and the patient finally died of multiple organ failure. Hypoglycemia, which is considered secondary to reduced gluconeogenesis in the exhausted liver, is a rare complication of constrictive pericarditis.