Exploring Indicators of Subcutaneous Tissue Fluid Accumulation in Breast Cancer-Related Lymphedema Patients Using Fractal Analysis with Virtual Volume.

Background: Breast cancer treatment sometimes causes a chronic swelling of the arm called breast cancer-related lymphedema (BCRL). Its progression is believed to be irreversible and is accompanied by tissue fibrosis and lipidosis, so preventing lymphedema from progressing by appropriate intervention at the site of fluid accumulation at an early stage is crucial. The tissue structure can be evaluated in real time by ultrasonography, and this study aims at assessing the ability of fractal analysis using virtual volume in detecting fluid accumulation within BCRL subcutaneous tissue via ultrasound imaging. Methods and Results: We worked with 21 women who developed BCRL (International Society of Lymphology stage II) after unilateral breast cancer treatment. Their subcutaneous tissues were scanned with an ultrasound system (Sonosite Edge II; Sonosite, Inc., FUJIFILM) using a 6- to 15-MHz linear transducer. Then, a 3-Tesla MR system was used to confirm fluid accumulation in the corresponding area of the ultrasound system. Significant differences in both H + 2 and complexity were observed among the three groups (with hyperintense area, without hyperintense area, and unaffected side) (p < 0.05). Post hoc analysis (Mann-Whitney U test; Bonferroni correction p < 0.0167) revealed a significant difference for "complexity." The evaluation of the distribution in Euclidean space showed that the variation of the distribution decreased in the order of unaffected, without hyperintense area, and with hyperintense area. Conclusion: The "complexity" of the fractal using virtual volume seems to be an effective indicator of the presence or absence of subcutaneous tissue fluid accumulation in BCRL.

Use of Renal Near-Infrared Spectroscopy and Urinary Neutrophil Gelatinase-Associated Lipocalin Monitoring as Indicators of Acute Kidney Injury in Pediatric Cardiac Surgery.

Acute kidney injury (AKI) is a common complication following cardiac surgery under cardiopulmonary bypass (CPB) in children. A prospective study for examining urinary neutrophil gelatinase-associated lipocalin (NGAL) and renal near-infrared spectroscopy (NIRS) trends during AKI was conducted among pediatric patients undergoing cardiac surgery with CPB. Urinary NGAL showed a significant difference between intensive care unit admission (0 h) and 2 h post-admission (p < 0.001) and remained significant up to 4 h (p < 0.05). The renal NIRS in the AKI group showed a significant rate of decrease and lower values during the intraoperative period (p < 0.05). The cumulative median saturation of renal regional saturation of oxygen (rSO2) during CPB was 1637.5% min in the AKI group and 943.0% min in the non-AKI group. The median renal rSO2 scores at a reduction of 20% and 25% were significantly higher (p < 0.001) in the AKI group. Our results suggest that monitoring renal rSO2 scores and limiting their decline might be useful in preventing AKI. The combination of NGAL, renal rSO2, and renal rSO2 scores might be useful in the early diagnosis of AKI during pediatric cardiac surgery.

A Pilot Study of Determining the Reliability of a New Three-Dimensional Scanning System for Measuring Truncal Thickness After Breast Cancer Surgery.

Background: Lymphedema often affects the trunk after breast cancer surgery. Measuring volume baseline can help detect lymphedema-related changes early, thereby allowing for early intervention efforts. However, there is no quantitative method for detecting truncal lymphedema. As a preliminary investigation into the development of a new method for measuring truncal lymphedema, this study aimed to investigate the reliability and define the minimal detectable change (MDC) in posterior truncal thickness using a three-dimensional (3D) scanning system. Methods and Results: This observational study included 21 women who had undergone a mastectomy for breast cancer. The 3D images of every subject's trunk were captured by a handheld 3D scanner at two time points. The acquired 3D images were used to calculate the differences in thickness between the affected and unaffected sides at eight points on the trunk. The reliability was determined by checking for agreement between the trials (intraclass correlation coefficient) and by investigating the presence of systematic bias between the measurement error and true value (Bland-Altman analysis). Then, the MDC was calculated. For 14 of the 21 participants, 3D images without missing data at both time points were obtained. Analysis indicated that there was no systematic bias regarding the mean value at the seven body points. Fair-to-excellent reliability was shown at the five points in the middle of the trunk (MDC: 4.14-9.79 mm). The other three points (at the top and bottom of the trunk) had limited reliability. Conclusions: The 3D scanning system effectively measured the differences in thickness between the affected and unaffected sides of participants' posterior trunks, with fair-to-excellent reliability in the middle of the trunk.

Bioinspired total synthesis of boneratamides A-C.

We disclose the first synthesis of the marine natural product, (+)-boneratamide A, whose structure is composed of a terpene unit linked via an amide bond to a pyroglutamic acid moiety. The key step in this route is a bioinspired Ugi reaction of (+)-axisonitrile-3 with acetone as the carbonyl component and L-glutamic acid. This reaction brings about a remarkably efficient, one-pot assembly of reaction components concomitant with γ-lactam ring formation to produce (+)-boneratamide A in 70% yield. (+)-Boneratamide B and (-)-boneratamide C methyl esters were also synthesized using a similar bioinspired strategy, and the relative stereochemistries at the stereogenic centers in these substances were elucidated using X-ray analysis.

Lifestyle Factors Associated with Metabolic Syndrome in Urban Cambodia.

This study aimed to identify lifestyle factors associated with metabolic syndrome (MetS) in urban Cambodia. In this cross-sectional study, we used existing health checkup data from a private hospital in Phnom Penh, Cambodia. The participants comprised 5459 Cambodians aged ≥20 years who underwent health checkups between 2017 and 2019. The harmonized diagnostic definition was used as the MetS criteria. The prevalence of MetS was 56.6% overall, 60.4% in men and 52.6% in women. The lifestyle factor significantly associated with MetS in both sexes were "eating quicker than others", (men: odds ratio [OR]= 2.25, 95% confidence interval [CI] = 1.68-3.03, women: OR = 1.92, 95%CI = 1.41-2.60), "walking faster than others", (men: OR = 0.78, 95% CI = 0.67-0.92, women: OR = 0.75, 95% CI = 0.62-0.89) and "drinking alcohol" (men: OR = 1.33, 95% CI = 1.10-1.61, women: OR = 1.33, 95% CI = 1.09-1.62). Other significant associations with MetS for men was "eating speed is normal", (OR = 1.73, 95%CI = 1.30-2.31), and, for women, "eating food after dinner at least 3 days a week", (OR = 1.25, 95%CI = 1.01-1.55), "skipping breakfast at least 3 days a week", (OR = 0.83, 95%CI = 0.69-0.99) and "getting enough rest from sleep" (OR = 1.19, 95% CI = 1.01-1.42) were significantly associated with MetS. Lifestyle interventions through health education and guidance may be effective in preventing MetS in Cambodia.

Prevalence of Metabolic Syndrome and Its Components in Urban Cambodia: A Cross-Sectional Study.

BACKGROUND: The incidence of noncommunicable diseases, such as cardiovascular diseases and diabetes mellitus, is increasing in Cambodia. Urbanization and lifestyle changes due to rapid economic development have affected the components of metabolic syndrome (MetS). This study aimed to determine the prevalence of MetS, MetS components, and health status among Cambodians living in urban areas. METHODS: This cross-sectional study enrolled adult Cambodians (age ≥ 20 years) who underwent a health checkup at a Japanese hospital in Phnom Penh. MetS was defined based on the harmonized diagnostic definition from the joint interim statement. RESULTS: Among the 6090 (3174 men and 2916 women) participants who were enrolled in the study, the prevalence of MetS was 60.1% in men and 52.4% in women. The prevalence of elevated blood pressure was 73.2% in men and 65.3% in women, and was the highest MetS component in both men and women. In contrast, the lowest prevalence rates were observed for abdominal obesity (44.8%) in men and for high triglyceride levels (33.5%) in women. The MetS group showed a significantly higher proportion of patients with hypertension, diabetes, dyslipidemia, and obesity compared with the non-MetS group. CONCLUSION: The high prevalence of MetS in this study was attributed to urbanization, as in economically developed countries. It is necessary to explore the lifestyle habits of Cambodians that contribute to MetS and to develop preventive measures to reduce the incidence and prevalence of MetS.

Comparison of Ablation Area and Change in Functional Liver Reserve after Radiofrequency Ablation for Hepatocellular Carcinoma Using the arfa® and VIVA® Systems.

Radiofrequency ablation (RFA) is recommended in Japan for patients with hepatocellular carcinomas (HCCs) one to three in number and ≤3 cm in size. The arfa® and VIVA® RFA systems are widely used for patients with HCC and this retrospective observational study aims to compare their performances. The study included 365 patients with HCCs one to three in number and ≤3 cm in size who underwent RFA using the arfa® system (arfa® group) or the VIVA® system (VIVA® group). The total bilirubin (T-Bil) level after RFA was higher in the arfa® group than in the VIVA® group. With a 3-cm electrode needle, the longest diameter (Dmax) and the shortest diameter were analyzed and found to be greater in the arfa® group than in the VIVA® group. Furthermore, Dmax with the 2.5-cm electrode needle was greater in the arfa® group than in the VIVA® group. Statistically significant differences in the ablation area and in the T-Bil value after RFA were observed between the groups; however, these differences are not considered clinical problems because the difference in the ablation area was only slight and the Child-Pugh score was the same between the groups. Thus, hepatologists can use either of the RFA systems based on their preference.

Novel Technique for Tetralogy of Fallot Repair with Transannular Patch Using Pedicled Own Pericardium.

In the surgical repair of the tetralogy of Fallot with a narrow pulmonary valve annulus, the transannular patch method is used for right ventricular outflow tract repair. To prevent pulmonary regurgitation and valve calcification, we created and applied a new transannular patch method using pedicled own pericardium in a 5-month-old boy with tetralogy of Fallot. After closing the ventricular septal defect as usual with a 0.4 mm Gore-Tex sheet, we decided that the pulmonary valve could not be spared, because the pulmonary valve opening size was 6 mm. After removing the right ventricular abnormal myocardium, each edge of the pedicled own pericardium patch was sewn from 5 mm above the pulmonary valve commissures toward the basis of the pulmonary valve ring. The transannular patch was created using a Gore-Tex graft sawn to the right ventricular outflow tract. Echocardiography performed 6 months post surgery showed no pulmonary stenosis and trivial pulmonary insufficiency.

Evidence and Challenges in Left Atrial Appendage Management.

This review aimed to discuss the anatomical properties of the left atrial appendage (LAA), its relationship with atrial fibrillation (AF), effectiveness of LAA occlusion (LAAO), techniques, and new devices used to perform this procedure. An electronic search was performed to identify studies, in the English language, on LAA management. Searches were performed on PubMed Central, Scopus, and Medline from the dates of database inception to February 2020. For the assessed papers, data were extracted from the reviewed text, tables, and figures, by two independent authors. Anticoagulant therapy for patients with AF has proven beneficial and is highly recommended, but it is challenging for many patients to maintain optimal treatment. Surgery is the most cost-effective option; surgical methods include simple LAA resection, thoracoscopic surgery, and catheter treatment. Each procedure has its advantages and disadvantages, and many prospective studies have been conducted to evaluate various treatment methods. In managing the LAA, dissection of the LAA, such as changes in its shape and size due to remodeling during AF, changes in autonomic nerve function, and thrombosis, must be understood anatomically and physiologically. We believe that early treatment intervention for the LAA should be considered particularly in cases of recurrent AF.

Prediction of the Presence of Fluid Accumulation in the Subcutaneous Tissue in BCRL Using Texture Analysis of Ultrasound Images.

Background: Breast cancer-related lymphedema (BCRL) is a chronic swelling of the arm due to breast cancer treatment. Lymphedema is diagnosed and staged on the basis of limb circumference measurements and the patient's subjective symptoms, which have poor reproducibility and objectivity: these cannot detect any fluid accumulation in the tissue. Ultrasonography is a feasible noninvasive technique that can be used to evaluate tissue structure in real time. This study aimed to assess the ability of texture features for discriminating the presence of accumulated fluid within the subcutaneous tissue of BCRL using ultrasound (US) imaging. Methods and Results: This study included 20 women who were treated for unilateral breast cancer and who subsequently developed BCRL (International Society of Lymphology stage II). Subcutaneous tissue was scanned through an US system (Sonosite Edge II; Sonosite, Inc., FUJIFILM) using a 6- to 15-MHz linear transducer to assess the ability of texture features for discriminating the presence of accumulated fluid within the subcutaneous tissue of BCRL. Fluid accumulation was observed using a 3-Tesla MR system under double-echo steady-state conditions. There was a significant difference among the three groups (with hyperintense area, without hyperintense area, and unaffected side) in 11 of 14 textural features (p < 0.05). Post hoc analysis (Mann-Whitney U test; Bonferroni correction p < 0.0167) revealed significant differences in seven textural features within the hyperintense area. Conclusions: This study revealed that seven texture features quantified by US imaging data can provide information regarding fluid accumulation in the subcutaneous tissue of lymphedema.

Atrial septal defect and patent ductus arteriosus closure in an 8-month-old patient with Silver-Russell syndrome.

We present a case of an 8-month-old boy with Silver-Russell syndrome who had high pulmonary vascular resistance, atrial septal defect, and patent ductus arteriosus. He underwent cardiac surgery using cardiopulmonary bypass without any complications.

Cerebral oxygen saturation (rSO2) during cardiopulmonary bypass (CPB) measured using the INVOS oximeter closely correlates with baseline rSO2.

Baseline cerebral regional saturation (rSO2) measured using the INVOS 5100C (Medtronic, MN, USA) varies widely among patients with cardiac and/or renal diseases. To identify significant correlates of baseline rSO2 and to investigate intraoperative rSO2 changes, we conducted a retrospective study in 494 patients undergoing on-pump cardiovascular surgery. Correlations between preoperative blood laboratory test variables and baseline rSO2 before anesthesia were examined. Intraoperative rSO2 changes were analyzed. Of all the variables examined, log-transformed B-type natriuretic peptide (BNP) most significantly and negatively correlated with baseline rSO2 (r = - 0.652, p < 0.0001). Intraoperatively, rSO2 showed the lowest value during cardiopulmonary bypass (CPB) (median rSO2: 56.2% during CPB vs. 63.9% at baseline, p < 0.0001). Although rSO2 during CPB correlated positively with hemoglobin concentration and oxygen delivery during CPB (r = 0.192, p < 0.0001; and r = 0.172, p = 0.0001, respectively), it correlated much more closely with baseline rSO2 (r = - 0.589, p < 0.0001). Thus, patients showing low baseline rSO2 primarily associated with preoperatively high BNP continued to show low rSO2 even during CPB independent of hemodynamics artificially controlled by CPB. Our findings suggest that low baseline rSO2 in patients with high BNP due to cardiac and/or renal diseases is more likely to result from tissue edema causing alterations in optical pathlength and thus in calculated rSO2 values, not readily modifiable with CPB, rather than actual cerebral hemodynamic alterations readily modifiable with CPB. These may partly explain why the INVOS oximeter is a trend monitor requiring baseline measures.

Efficacy of Underwater Endoscopic Mucosal Resection for Superficial Non-Ampullary Duodenal Epithelial Tumor.

BACKGROUND/AIMS: Endoscopic resection (ER) for superficial non-ampullary duodenal epithelial tumors (SNADETs) is challenging. Conventional endoscopic mucosal resection (CEMR) is also problematic due to the anatomical features of the duodenum. We compared the safety and efficacy of underwater endoscopic mucosal resection (UEMR) with those of CEMR through a retrospective analysis. METHODS: Altogether, 44 consecutive patients with 46 SNADETs underwent ER (18 CEMR cases and 28 UEMR cases) between January 2016 and October 2019. We investigated the proportions of en bloc resection, R0 resection, complications, resection time, and total procedure time and compared the outcomes of patients from the CEMR group with those of patients from the UEMR group. RESULTS: The median tumor size was 8.0 mm (range, 2.0-20.0 mm). The UEMR group showed a higher proportion of en bloc resection (96.4% vs. 72.2%, p<0.05) and significantly lower median resection time and total procedure time (4 min vs. 9.5 min, p<0.05 and 13 min vs. 19 min, p<0.05; respectively) than the CEMR group. No complications were observed. However, two patients treated with piecemeal resection in the CEMR group had residual tumors. CONCLUSION: UEMR is a feasible therapeutic option for SNADETs. It can be recommended as a standard treatment.

The Correlation Between Fluid Distribution and Swelling or Subjective Symptoms of the Trunk in Lymphedema Patients: A Preliminary Observational Study.

Background: Manual lymph drainage (MLD) is one of the common treatments for breast cancer-related lymphedema (BCRL). Although the primary goal of MLD is to drain the excessive fluid accumulated in the affected upper limb and trunk to an area of the body that drains usually, the use of MLD is decided based on swelling and subjective symptoms, without assessing whether there is fluid accumulated in the affected region. The purpose of this study was to examine truncal fluid distribution in a sample of BCRL patients and investigate any correlation between such fluid distribution and swelling or subjective symptoms. Methods and Results: An observational study was conducted with 13 women who had unilateral, upper extremity BCRL. Fluid distribution was evaluated by using two magnetic resonance imaging (MRI) sequences: half-Fourier acquisition single-shot turbo spin echo and three-dimensional double-echo steady-state. The presence of swelling was determined by lymphedema therapists, and subjective symptoms were measured by using a visual analog scale. On MRI, no participants had any free water signals in the trunk. However, seven had swelling and all 13 had some kind of subjective symptoms on the affected side of their trunk. Conclusions: These results suggest that swelling and subjective symptoms do not correlate with the presence of truncal fluid. For such cases, a different approach than MLD may be needed to address truncal swelling and related subjective symptoms. Checking for the presence of fluid in the truncal region may help MLD be used more appropriately.

Coronary Revascularization of Giant Aneurysms in Children With Kawasaki Disease: A Report of Two Cases.

In recent years, >100 cases of coronary artery stenotic lesions due to Kawasaki disease were treated with coronary artery bypass grafting (CABG). Surgical indications include stenosis of >75%, myocardial infarction history, electrocardiographic changes, and ischemia, as detected by myocardial scintigraphy and electrocardiography, due to drugs or exercise. Some centers have reported good patency rates, even in infants. The advantages of CABG in younger patients are minimal loss of left ventricular function, early elimination of post-operative ischemia risk, and improved quality of life. However, the disadvantage of performing CABG in younger patients is the small coronary artery diameter and the thin vessel wall, which can lead to post-operative occlusion, especially when performed by inexperienced surgeons. The optimal timing of CABG varies by institution and case, which depends on the presence or absence of complications, such as left ventricular dysfunction or valve regurgitation, and surgeon's experience. Importantly, unlike adult surgery, childhood CABG needs to be kept open for the very longest possible period of time to determine the optimal conditions for surgery. We report two pediatric cases of giant coronary artery aneurysms diagnosed in infancy. During school age, the patients had a mild decline of left ventricular ejection function. In one case, there were no clinical symptoms because of the development of collateral vessels and limitation of exercise. Both patients underwent surgery with good results. The gastric gastroepiploic artery could be anastomosed owing to the development of collateral blood vessels, although it was obstructed. At 1 year after surgery, both patients had a good post-operative course without complications of anastomotic stenosis or myocardial damage due to aneurysm resection. If conditions are favorable, bypass surgery can be postponed to several years until the coronary arteries are sufficiently large to warrant a delay in coronary artery stenosis in cases of infantile Kawasaki disease.

Comparison of serum fibrosis biomarkers for diagnosing significant liver fibrosis in patients with chronic hepatitis B.

Chronic hepatitis B (CHB) virus continues to be a leading cause of morbidity and mortality worldwide. The diagnosis of liver fibrosis has a key role in selecting patients with CHB for antiviral treatment. However, serum biomarkers demonstrate limited diagnostic utility. The present study aimed to compare the performances of fibrosis biomarkers for diagnosing significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB and to identify the most appropriate biomarker for these patients. The current study included 96 antiviral-naïve patients with CHB who underwent liver biopsy. METAVIR scoring system was used to assess liver fibrosis and necroinflammation. The diagnostic performances were evaluated of the platelet (PLT) count; the levels of hyaluronan, serum 7S domain of type 4 collagen, procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer (M2BPGi) and N-terminal type III collagen propeptide (Pro-C3); the fibrosis index based on four factors; the aspartate aminotransferase-to-platelet ratio index; and enhanced liver fibrosis score for identifying significant liver fibrosis [≥fibrosis stage 2 (F2)]. All fibrosis biomarkers, except the Pro-C3 level, correlated with the fibrosis stage. M2BPGi was better than other biomarkers for diagnosing ≥F2, with the highest area under the curve of 0.902. M2BPGi demonstrated a higher diagnostic accuracy for significant fibrosis than mild/severe fibrosis or cirrhosis. However, no significant correlation was observed between the M2BPGi level and fibrosis stage in patients with CHB having significant liver necroinflammation defined as ≥ necroinflammatory activity 2. The M2BPGi level and PLT count were exclusively correlated with the fibrosis stage in 73 patients without significant liver necroinflammation. M2BPGi demonstrated the highest diagnostic performance for significant fibrosis in patients having significant liver fibrosis with no significant liver necroinflammation. In conclusion, the M2BPGi level can accurately diagnose significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB.

Nursing activities at clinics in rural areas in Japan: gaps between recognition of importance and implementation.

This study determined the level of implementation and the importance placed on various nursing activities at clinics in rural areas of Japan in order to explore the achievement and perceived importance of implementing certain nursing roles and activities at such clinics. To identify these items, a questionnaire was administered to 40 nurses working in rural clinics. The results showed that activities related to "Basic Nursing Practice" and "Community Understanding" were recognized as important and were performed by almost all nurses. Some activities related to "Administration and Operation" and "Cooperation with Local Government" were recognized as important, but were not implemented, thereby hampering the continuum of care across the health system. These activities, which are related to collaboration with hospitals and local governments that support the clinics, included adjustment of staff inside and outside the facilities to guarantee the use of paid holidays, as well as collaboration with acute care, remote medical systems, and local governments during emergencies and for disaster preparation. Additional support for nurses in collaboration between clinics in rural areas, hospitals, and regional administrations that support the clinics remains a challenge to be addressed.

Thyroid-stimulating hormone is an independent risk factor of non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Hypothyroidism might play a crucial role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The association of subclinical hypothyroidism with NAFLD has been inconsistent. The relationship of NAFLD with thyroid function parameters and subclinical hypothyroidism was determined. METHODS: This cross-sectional study included 70 patients with subclinical hypothyroidism and 70 controls with euthyroidism matched according to gender, age, and body mass index (BMI). NAFLD was diagnosed via abdominal ultrasonography. The association between NAFLD and subclinical hypothyroidism was analyzed. RESULTS: The prevalence of NAFLD was significantly higher in patients with subclinical hypothyroidism than in those with euthyroidism. Multivariate analysis showed that subclinical hypothyroidism was an independent risk factor of NAFLD adjusted by metabolic-related factors, such as BMI, triglyceride, high-density lipoprotein-cholesterol, hypertension, and diabetes. Thyroid-stimulating hormone (TSH) was an independent risk factor of NAFLD adjusted by the same metabolic-related factors, but free thyroxine (FT4) was not a risk factor. The FIB-4 index, a noninvasive marker of liver fibrosis was significantly higher in patients with subclinical hypothyroidism than in those with euthyroidism. Compared with patients with euthyroidism, the proportion of the FIB-4 index ≥2.67 was significantly higher, and the proportion of the FIB-4 index <1.30 was lower in patients with subclinical hypothyroidism. CONCLUSIONS: TSH elevation even within the euthyroid range is an independent risk factor of NAFLD and may influence the progression of liver fibrosis, even with a normal FT4 level.

Hydralazine Sensitizes to the Antifibrotic Effect of 5-Aza-2'-deoxycytidine in Hepatic Stellate Cells.

BACKGROUND: Hepatic stellate cell (HSC) activation is essential for the development of liver fibrosis. Epigenetic machinery, such as DNA methylation, is largely involved in the regulation of gene expression during HSC activation. Although the pharmacological DNA demethylation of HSC using 5-aza-2'-deoxycytidine (5-aza-dC) yielded an antifibrotic effect, this drug has been reported to induce excessive cytotoxicity at a high dose. Hydralazine (HDZ), an antihypertensive agent, also exhibits non-nucleoside demethylating activity. However, the effect of HDZ on HSC activation remains unclear. In this study, we performed a combined treatment with 5-aza-dC and HDZ to obtain an enhanced antifibrotic effect with lower cytotoxicity. METHODS: HSC-T6 cells were used as a rat HSC cell line in this study. The cells were cultivated together with 1 µM 5-Aza-dC and/or 10 µg/mL of HDZ, which were refreshed every 24 h until the 96 h treatment ended. Cell proliferation was measured using the WST-1 assay. The mRNA expression levels of peptidylprolyl isomerase A (Ppia), an internal control gene, collagen type I alpha 1 (Cola1), RAS protein activator like 1 (Rasal1), and phosphatase and tensin homolog deleted from chromosome 10 (Pten) were analyzed using quantitative reverse transcription polymerase chain reaction. RESULTS: The percentage cell viability with 5-aza-dC, HDZ, and combined treatment vs. the vehicle-only control was 101.4 ± 2.5, 95.2 ± 5.7, and 79.2 ± 0.7 (p < 0.01 for 5-aza-dC and p < 0.01 for HDZ), respectively, in the 48 h treatment, and 52.4 ± 5.6, 65.9 ± 3.4, and 29.9 ± 1.3 (p < 0.01 for 5-aza-dC and p < 0.01 for HDZ), respectively, in the 96 h treatment. 5-Aza-dC and the combined treatment markedly decreased Cola1 mRNA levels. Accordingly, the expression levels of Rasal1 and Pten, which are antifibrotic genes, were increased by treatment after the 5-aza-dC and combined treatments. Moreover, single treatment with HDZ did not affect the expression levels of Cola1, Rasal1, or Pten. These results suggest that HDZ sensitizes to the antifibrotic effect of 5-aza-dC in HSC-T6 cells. The molecular mechanism underlying the sensitization to the antifibrotic effect of 5-aza-dC by HDZ remains to be elucidated. The expression levels of rat equilibrative nucleoside transporter genes (rEnt1, rEnt2, and rEnt3) were not affected by HDZ in this study. CONCLUSIONS: Further confirmation using primary HSCs and in vivo animal models is desirable, but combined treatment with 5-aza-dC and HDZ may be an effective therapy for liver fibrosis without severe adverse effects.

Exercise echocardiography demonstrates potential myocardial damage in patients with repaired tetralogy of Fallot using layer-specific strain analysis.

INTRODUCTION: Exercise stress echocardiography and layer-specific strains are emerging as important tools for cardiac assessment. This study was aimed to evaluate layer-specific strains and torsion parameters during exercise in order to investigate the characteristics of cardiac dysfunction in patients with repaired tetralogy of Fallot and to detect subclinical left ventricular dysfunction. MATERIALS AND METHODS: Thirteen patients with repaired tetralogy of Fallot (median age, 17.3 [interquartile range, 14.5-22.9] years; 6 males) and 13 controls (median age, 28.5 [interquartile range, 27.6-31.6] years; 13 males) underwent echocardiography at rest and during supine exercise. Layer-specific longitudinal strain and circumferential strain of three myocardial layers (endocardium, midmyocardium, and epicardium), torsion, and untwisting rate were measured using two-dimensional speckle-tracking echocardiography. RESULTS: Peak endocardial papillary circumferential strain (-21.1 ± 2.6% vs. -25.8 ± 3.8%, p = 0.007), midmyocardial apical circumferential strain (-11.1 ± 4.0% vs. -15.6 ± 3.2%, p = 0.001), epicardial apical circumferential strain (-11.1 ± 4.0% vs. -15.6 ± 3.2%, p = 0.021), and torsion (8.9 ± 6.0 vs. 14.9 ± 4.8 degree, p = 0.021) were significantly lower in the repaired tetralogy of Fallot group than in the control group during exercise, though no significant difference was found between patients and controls at rest. CONCLUSIONS: Analysis of layer-specific strains and torsion parameters during exercise could detect subclinical left ventricular dysfunction in patients with repaired tetralogy of Fallot, which might reflect potential myocardial damage, at a stage where these parameters have normal values at rest. This finding provides new insight into the mechanisms of cardiac dysfunction in patients with repaired tetralogy of Fallot.