Combined Treatment of Mori folium and Mori Cortex Radicis Ameliorate Obesity in Mice via UCP-1 in Brown Adipocytes.

Mori Folium (Morus alba leaf, MF) and Mori Cortex Radicis (Morus alba root cortex, MR) have been studied for their anti-obesity effects by enhancing the browning process and inhibiting adipogenesis. However, important aspects of their protective mechanisms have not been thoroughly investigated, which could aid in developing functional food. Thus, this study aims to determine the synergistic effects of MF and MR against obesity and its associated mechanisms. In an in vitro cell culture model of brown adipocytes, a 1:1 mixture of MF and MR showed a synergistic effect on the expression of brown adipocyte-specific genes, including Ucp-1, Ppargc1a, Cbp/p300-interacting transactivator (Cited), Prdm16, Tbx1, and Fgf21 compared with either MF- or MR-treated conditions. Moreover, they demonstrated the involvement of cAMP and Ca2+ in induction of brown adipocyte-specific genes. In an in vivo model using HFD-fed mice, MF/MR significantly inhibited weight gain, plasma cholesterol, LDL, TG content, fat mass, and adipocyte size. Furthermore, MF/MR inhibited morphological alteration and the expressions of fatty acid synthesis genes such as Srebp1 and Fasn in the white adipose tissue. Thermogenesis genes were recovered in the brown adipose tissue with MF/MR supplementation, indicating that MF/MR regulated adipocytic dysmetabolism where AMPK signaling is involved. In conclusion, these results suggested that MF/MR regulates brown and beige adipocyte processes, providing one of the preventive functional food/herbal medicines against obesity and its associated metabolic diseases.

Efficacy of azilsartan on left ventricular diastolic dysfunction compared with candesartan: J-TASTE randomized controlled trial.

Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, azilsartan may improve the left ventricular (LV) diastolic function in patients with hypertension and either HFpEF or HF with mildly reduced ejection fraction (HFmrEF) more than candesartan. In this randomized, open-label trial, we randomly assigned 193 hypertensive patients with HF and LV ejection fraction ≥ 45% to 20 mg of azilsartan (n = 95) or 8 mg of candesartan (n = 98), once daily for 48 weeks. After the initiation of treatment, changes in the doses of the study drugs were permitted based on the patient's conditions, including blood pressure (median dose at 48 weeks: azilsartan 20.0 mg/day, candesartan 8.0 mg/day). The primary endpoint was the baseline-adjusted change in the ratio of peak early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e') (E/e'). Adjusted least-squares mean (LSM) change in E/e' was - 0.8 (95% confidence interval [CI] - 1.49 to - 0.04) in the azilsartan group and 0.2 (95% CI - 0.49 to 0.94) in the candesartan group, providing the LSM differences of - 1.0 (95% CI - 2.01 to 0.03, P = 0.057). The median change in left atrial volume index was - 2.7 mL/m2 with azilsartan vs 1.4 mL/m2 with candesartan (P = 0.091). The frequency of adverse events related to hypotension and hyperkalemia did not differ between the groups. The current study did not provide strong evidence that azilsartan improves LV diastolic dysfunction, and further confirmatory study is required.

Combination of Panax ginseng and Diospyros kaki Leaf Inhibits White Adipocyte Differentiation and Browning Process through AMP-Activated Protein Kinase (AMPK) Activation In Vitro and In Vivo.

Activating brown adipose tissue (BAT) and stimulating white adipose tissue (WAT) browning is a prospective obesity treatment method. Dietary components derived from plants are the most effective approach to activate BAT and promote WAT browning in rodents. This study investigated the synergistic effects of Panax ginseng (PG) and Diospyros kaki leaf (DKL) extract on adipocyte differentiation and browning, as well as the molecular mechanism underlying their beneficial effects. The administration of PG and DKL to HFD-induced obese mice significantly decreased body weight and epididymal and abdominal adipose tissue mass. In in vitro, PG inhibited the adipogenesis of 3T3-L1 adipocytes by regulating the expression of key adipogenic regulators, such as peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)-α. In contrast, DKL negligibly influenced the adipogenesis of 3T3-L1 adipocytes but greatly increased the protein expression of UCP-1, PGC-1α, and PPARα in BAT and/or WAT. Moreover, PG and DKL inhibited adipogenesis synergistically and activated white adipocyte browning via AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) pathways. These results suggest that a combination of PG and DKL regulates adipogenesis in white adipocytes and browning in brown adipocytes by activating AMPK/SIRT1 axis. The potential use of PG and DKL may represent an important strategy in obesity management that will be safer and more effective.

Increased Prehospital Emergency Medical Service Time Interval and Nontransport Rate of Patients With Fever Using Emergency Medical Services Before and After COVID-19 in Busan, Korea.

BACKGROUND: In Korea, patients with fever have been preemptively isolated to isolation beds in the emergency department (ED) since the coronavirus disease 2019 (COVID-19) pandemic began. However, isolation beds were not always available, and transport delays or failure (nontransport), especially for infants, were reported in the media. Few studies have focused on delays and failure in transporting fever patients to the ED. Therefore, this study aimed to examine and compare the emergency medical service (EMS) time interval and nontransport rate of patients with fever using EMSs before and after COVID-19. METHODS: This retrospective observational study analyzed the prehospital EMS time interval and nontransport rate of fever patients who contacted EMSs in Busan, South Korea, from March 1, 2019 to February 28, 2022, using emergency dispatch reports. All fever patients (≥ 37.5°C) who contacted EMSs during this study were included. The EMS time interval was defined as the time between the patient's EMS call and ED arrival time. Nontransport was defined as a case recorded as not being transported in the emergency dispatch reports. The study population of 2019 was compared to the population of 2020 and 2021 with the independent t-test, Mann-Whitney U test, and χ² test. As a subgroup, the EMS time intervals and nontransport rates of infants with fever were compared before and after COVID-19. RESULTS: A total of 554,186 patients accessed the EMS during the study period, and 46,253 patients with fever were included. The EMS time interval (mean ± standard deviation, minutes) of fever patients was 30.9 ± 29.9 in 2019, 46.8 ± 127.8 in 2020 (P < 0.001) and 45.9 ± 34.0 in 2021 (P < 0.001). The nontransport rate (%) was 4.4 in 2019, 20.6 in 2020 (P < 0.001), and 19.5 in 2021 (P < 0.001). For infants with fever, the EMS time interval was 27.6 ± 10.8 in 2019, 35.1 ± 15.4 in 2020 (P < 0.001), and 42.3 ± 20.5 in 2021 (P < 0.001), and the nontransport rate (%) was 2.6 in 2019, 25.0 in 2020, and 19.7 in 2021. CONCLUSION: After the emergence of COVID-19, in Busan, the EMS time interval of fever patients was delayed, and approximately 20% of fever patients were not transported. However, infants with fever had shorter EMS time intervals and higher nontransport rates than the overall study population. A comprehensive approach, including prehospital and hospital ED flow improvements, is required beyond increasing the number of isolation beds.

Early Clinical Outcomes of Manipulation under Anesthesia for Refractory Adhesive Capsulitis: Comparison with Arthroscopic Capsular Release.

BACKGROUD: The purpose of this study was to compare early clinical outcomes of manipulation under anesthesia (MUA) and arthroscopic capsular release (ACR) in patients with refractory adhesive capsulitis (AC). METHODS: Thirty AC patients who underwent MUA (MUA group) were included. As a control group, thirty AC patients who underwent ACR (ACR group) were matched for age and sex with the MUA group. Visual analog scale (VAS) pain score, American shoulder and Elbow Surgeons (ASES) score, and range of motion (ROM) were evaluated preoperatively and at 3, 6, and 12 months after procedure. RESULTS: Both groups had significant improvements in the VAS pain score, ASES score, and ROM at 12 months after procedure. VAS pain score and ASES score were significantly better in the MUA group than in the ACR group at 3 months after procedure. Mean forward flexion was significantly greater in the MUA group than in the ACR group at 3 months after procedure. Mean external rotation and internal rotation were significantly greater in the MUA group than in the ACR group at 3, 6, and 12 months after procedure. Two patients required additional steroid injections at 3 and 6 months after MUA because of recurrent stiffness with pain. CONCLUSIONS: Compared with ACR, MUA provided equivalent clinical outcomes in the early period after procedure. Our study suggests that MUA is a useful option to be considered as treatment for refractory AC before choosing ACR.

Definition, Diagnosis, Treatment, and Prognosis of Frozen Shoulder: A Consensus Survey of Shoulder Specialists.

BACKGROUND: The objective of this study was to identify a consensus on definition, diagnosis, treatment, and prognosis of frozen shoulder (FS) among shoulder specialists. METHODS: A questionnaire composed of 18 questions about FS-definition, classification, utilization of diagnostic modalities, the propriety of treatment at each stage, and prognosis-was sent to 95 shoulder specialists in Korea. Most questions (15 questions) required an answer on a 5-point analog scale (1, strongly disagree; 5, strongly agree); three questions about the propriety of treatment were binary. RESULTS: We received 71 responses (74.7%). Of the 71 respondents, 84.5% agreed with the proposed definition of FS, and 88.8% agreed that FS should be divided into primary and secondary types according to the proposed definition. Only 43.7% of the respondents agreed that FS in patients with systemic disease should be classified as secondary FS. For the diagnosis of FS, 71.9% agreed that plain radiography should be used and 64.8% agreed ultrasonography should be used. There was a high consensus on proper treatment of FS: 97.2% agreed on education, 94.4%, on the use of nonsteroidal anti-inflammatory drugs; 76.1%, on intra-articular steroid injections; and 97.2%, on stretching exercise. Among all respondents, 22.5% answered that more than 10% of the patients with FS do not respond to conservative treatment. CONCLUSIONS: The survey revealed a general consensus among shoulder specialists on the definition and treatment of FS. However, classification of FS was found controversial.

Acute Displaced Fracture of Lateral Acromion after Reverse Shoulder Arthroplasty: A Case Report and Surgical Technique.

Acromial fractures are well-documented complications subsequent to reverse shoulder arthroplasty (RSA), and most appear as stress fractures with no history of single trauma. To date, no study has reported the occurrence of acute displaced acromial fracture due to sudden strong deltoid contraction during heavy work. Displacement of the fracture results in a challenging surgery since it is difficult to obtain adequate fixation in thin and osteoporotic bones. We report a rare case of acute displaced acromial fracture after successful RSA treatment, using a novel technique of open reduction and internal fixation, applying two 4.5 mm cannulated screws and lateral clavicle pre-contoured plate.

Rationale and Design of the Multicenter Trial on Japan Working Group on the Effects of Angiotensin Receptor Blockers Selection (Azilsartan vs. Candesartan) on Diastolic Function in the Patients Suffering from Heart Failure with Preserved Ejection Fraction: J-TASTE Trial.

BACKGROUND: Previous studies suggest that the pathophysiology of heart failure with preserved ejection fraction (HFpEF) is characterized not only by high ventricular stiffness, but also by vascular stiffness. Azilsartan has higher vascular affinity compared with other angiotensin II receptor blockers (ARBs), which were proven to have no beneficial effects on clinical outcomes in patients with HFpEF in earlier clinical trials. We aimed to test the hypothesis that azilsartan may improve left ventricular diastolic function in HFpEF patients with hypertension in this trial. METHODS: The Effects of Angiotensin Receptor Blockers on Diastolic Function in Patients Suffering from Heart Failure with Preserved Ejection Fraction: J-TASTE trial is a multicenter, randomized, open-labeled, and assessor(s)-blinded, active controlled using candesartan, parallel-group clinical trial, to compare changes in left ventricular (LV) diastolic dysfunction between HFpEF patients with hypertension who have received candesartan or azilsartan for 48 weeks. The primary endpoint is the change in early diastolic wave height/early diastolic mitral annulus velocity (E/e') assessed by echocardiography from the baseline to the end of the study (48 weeks). A total of 190 patients will be recruited into the study. CONCLUSIONS: The design of the J-TASTE trial will provide data on whether differences between the effects of the two tested drugs on LV diastolic function exist in HFpEF patients with hypertension and will improve understanding of the pathophysiological role of vascular stiffness on diastolic function.

False negative rate of syndesmotic injury in pronation-external rotation stage IV ankle fractures.

BACKGROUND: To investigate false negative rate in the diagnosis of diastasis on initial static anteroposterior radiograph and reliability of intraoperative external rotational stress test for detection of concealed disruption of syndesmosis in pronation external rotation (PER) stage IV (Lauge-Hansen) ankle fractures. MATERIALS AND METHODS: We prospectively studied 34 PER stage IV ankle fractures between September 2001 and September 2008. Twenty (59%) patients show syndesmotic injury on initial anteroposterior radiographs. We performed an intraoperative external rotation stress test in other 14 patients with suspicious PER stage IV ankle fractures, which showed no defined syndesmotic injury on anteroposterior radiographs inspite of a medial malleolar fracture, an oblique fibular fracture above the syndesmosis and fracture of the posterior tubercle of the tibia. RESULTS: All 14 fractures showed different degrees of tibiofibular clear space (TFCS) and tibiofibular overlapping (TFO) on the external rotation stress test radiograph compared to the initial plain anteroposterior radiograph. It is important to understand the fracture pattern characterstic of PER stage IV ankle fractures even though it appears normal on anteroposterior radiographs, it is to be confirmed for the concealed syndesmotic injury through a routine intraoperative external rotational stress radiograph.

Differences in the mode of presentation for acute coronary syndrome by pre-hospitalization medication, in relation to coronary risk factors, East-Osaka acute coronary syndrome (EACS) registry.

BACKGROUND: Pre-hospitalization medication such as aspirin and nitrates has been shown to affect the mode of presentation in acute coronary syndrome (ACS). However, it is not formally assessed whether other cardiovascular medications may be contributed to the differences in the mode of presentation, especially in relation to coronary risk factors. METHODS AND RESULTS: We conducted a registration study of patients (M/F 850/323) with either ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA), and examined the differences in the mode of presentation, pre-hospitalization medication, and coronary risk factors. The ratio of the incidence of STEMI and NSTEMI/UA was significantly reduced in patients having pre-hospitalization medication with aspirin, nitrates or statins, but not with other medications such as beta-blockers in multivariate analysis. Pre-hospitalization medication with aspirin and nitrates was significantly associated with the same reduction of the ratio in patients with male gender, hypertension, diabetes mellitus and a history of coronary artery disease. However, in patients who smoked, were obese and hypercholesterolemic, pre-hospitalization medication with nitrates was significantly associated with the reduced ratio. The ratio was significantly low in patients with males and hypercholesterolemia treated with statins before admission. CONCLUSION: Depending on their coronary risk factors, pre-hospitalization medication with aspirin, nitrates or statins was associated with a different presentation and evolution of ACS.

Admission with metabolic disorder is a useful predictor of the 1-year prognosis for patients with unstable angina, but not for patients with acute myocardial infarction: east-Osaka acute coronary syndrome registry.

BACKGROUND: For patients with acute myocardial infarction (AMI), several studies have examined the relationship between the metabolic syndrome and prognostic outcome. However, few studies have revealed an association between the metabolic syndrome and clinical outcomes in patients with unstable angina (UA). This study compared the differences in the usefulness of recognizing metabolic disorders for the prediction of a 1-year prognosis in patients with UA and AMI. METHODS: The study cohort consisted of 1173 patients with a mean age of 67 years. The focus was on general prognostic factors and five metabolic disorders (body mass index; hypertension; blood glucose/diabetes mellitus; and, serum concentrations of triglycerides and high-density lipoprotein cholesterol) at the time of admission. RESULTS: According to multivariate logistic regression analysis, metabolic scores on admission positively related to 1-year mortality or major adverse cardiovascular events (MACE) for patients with UA, but not for those with AMI, with an increase in either all-causes mortality or MACE being associated with the degree of metabolic dysfunction. No other general prognostic factors were related to either 1-year mortality or MACE in patients with UA. By contrast, general prognostic factors such as age and the Killip classification had a positive effect on 1-year mortality or on MACE for the patients with AMI. CONCLUSION: Accumulation of the effects of each metabolic disorder may affect mortality and MACE for patients with UA.

Echocardiographic progression of a subepicardial aneurysm after inferior myocardial infarction.

A 62-year-old man presented to hospital with chest oppression. Coronary angiography revealed total occlusion of the right coronary artery and inferior myocardial infarction was diagnosed. He was treated by percutaneous coronary intervention with stenting for myocardial infarction. After four months, echocardiography revealed a huge aneurysm protruding below the inferior surface of the left ventricle. It was considered to be a pseudoaneurysm from the echocardiographic findings. The patient had no symptoms and he refused surgery, so progression of the aneurysm was monitored carefully. At seven months after revascularization, the aneurysm showed a marked increase in size, with a maximal diameter of 48 mm and orifice diameter of 22 mm. Accordingly, the patient agreed to undergo surgical excision. The aneurysm was resected and the defect was closed with a pericardial patch. Pathological examination revealed all of the myocardial elements in the aneurysm wall and thrombus in its lumen. In conclusion, this was a rare case of ventricular subepicardial aneurysm.

Elevation of the ratio of transmitral E velocity to early diastolic mitral annular velocity continues even after recovery from acute stage in patients with diastolic heart failure.

BACKGROUND: Clinical features of diastolic heart failure (DHF) have not been well characterized, leading to an inaccuracy in the diagnosis of DHF. Recently, the ratio of transmitral E velocity to early diastolic mitral annular velocity (E/E') has been shown to be useful to assess LV filling pressure. PURPOSE: We tested the hypothesis that persistent elevation of E/E' ratio is one of the characteristics of patients with DHF. METHODS: Candidates of this study were 89 patients who presented to the emergency department because of acute pulmonary congestion. Those with an ejection fraction of >45% on admission comprised the DHF group (n=18). A control group consisted of consecutive 30 hypertensive patients with an ejection fraction of >45%. Doppler echocardiographic data were obtained with plasma BNP measure in the chronic stage >6 months after the emergent admission. RESULTS: The E/E' ratio was higher in the DHF group than in the control group (16.7±2.8 vs. 9.4±3.3, p<0.01). BNP level was also elevated in the DHF group. CONCLUSION: A persistent elevation of E/E' ratio may be an indicator of patients with or at risk of DHF among subjects with preserved systolic function independent of LV hypertrophy.

Fourteen month follow-up angioscopic findings of a sirolimus-eluting stent implanted in a 15-year-old saphenous vein graft.

Saphenous vein grafts (SVGs) are common, as is their degeneration and early failure after coronary artery bypass graft surgery (CABG). Percutaneous SVG intervention with drug-eluting stents (DES) was associated with superior short-term clinical outcomes. However, SVG intervention compared with coronary intervention often results in distal embolisation and periprocedural myocardial infarction. In this case, we discuss 9 and 14 month follow-up neointimal coverage of a DES implanted in a 15 year-old SVG and other morphological changes using angioscopy.

Intracoronary nicorandil relieves multiple coronary vasospasm with hemodynamic collapse.

A 49-year-old woman was referred to hospital because of chest discomfort. Coronary angiography revealed subtotal occlusion of the left coronary artery and the right coronary artery, but subsequent hemodynamic collapse occurred. Based on the results of intravascular ultrasound the occlusion was suspected to be caused by coronary vasospasm, which was not relieved by intracoronary injection of isosorbide dinitrate (1 mg), but was alleviated by nicorandil (2 mg), a potassium-channel opener. After discharge from hospital, the patient stopped taking her medication and returned complaining of chest discomfort again. Intravenous verapamil (5 mg) did not improve it, but direct intracoronary administration of nicorandil (2 mg) did bring relief. This case suggests that nicorandil is effective for coronary vasospasm.

Effect of early use of low-dose pravastatin on major adverse cardiac events in patients with acute myocardial infarction: the OACIS-LIPID Study.

BACKGROUND: It is unclear whether early initiation of low-dose pravastatin therapy can reduce the occurrence of major adverse cardiac events after acute myocardial infarction (AMI). METHODS AND RESULTS: The study group comprised 353 patients with AMI who had plasma total cholesterol levels of 200-250 mg/dl and triglyceride levels <300 mg/dl. The patients were randomly assigned to either receive pravastatin (10 mg/daily, n=176) or not (n=177). The primary endpoint was a composite of death, nonfatal myocardial infarction (MI), unstable angina (UA), stroke, revascularization, and rehospitalization because of other cardiovascular disease. The follow-up period was 9 months. The primary endpoint occurred in 31 patients (17.9%) in the pravastatin group and 55 patients (31.4%) in the non-pravastatin group (relative risk, 0.56; 95% confidence interval, 0.36-0.87). There were no significant differences in the risk of death, nonfatal MI, UA, and stroke between the 2 groups, although the pravastatin group had a lower risk of need for revascularization. CONCLUSION: For patients with AMI, early and low-dose pravastatin therapy (10 mg/daily) reduces recurrent major adverse cardiac events, mostly the requirement for revascularization.

Angioscopic findings of delayed healing at sites of sirolimus-eluting stent overlap after 21-month implantation.

Treatment of de novo coronary stenosis with sirolimus-eluting stents is associated with very low rates of target lesion revascularization and other major adverse cardiac events in the short-term after implantation, but a definite frequency of late-stent thrombosis (LST) over a long-term follow-up has become evident. One of the predictors of LST is stent overlap. We reported the angioscopic findings of very delayed healing at sites of sirolimus-eluting stent overlap 21 months post-implantation.

Detecting intimal hyperplasia of subclavian artery stent by multislice computed tomography.

A 62-year-old man was performed stent implantation for right subclavian artery stenosis two years ago. For the evaluation of stent patency, multislice computed tomography (MSCT) was performed. Volume rendering image demonstrated that the stent was patent, but curved multiplanar reformation revealed a relatively low- density area inside the stent, suggesting intimal hyperplasia. Cross-sectional images were converted into Plaque Map display, which color-codes CT densities. Plaque was eccentrically distributed from ten o'clock to four o'clock. The attenuation of the plaque was 250--350 HU, which was less than the attenuation of contrast media (350--500 HU). Invasive aortography demonstrated the stent to be mildly stenosed in the corresponding position. Gray-scale and VH (virtual histology)-intravascular ultrasound demonstrated that eccentric intimal thickening consisted with predominant fibrous plaque. MSCT combined with Plaque Map effectively detected intimal thickening of subclavian artery stent.