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C-terminal tensin-like (CTEN) is a tensin family protein typically localized to the cytoplasmic side of focal adhesions, and primarily contributes to cell adhesion and migration. Elevated expression and nuclear accumulation of CTEN have been reported in several types of cancers and found to be associated with malignant behaviors. However, the function of nuclear CTEN remains elusive. In this study, we report for the first time that nuclear CTEN associates with chromatin DNA and occupies the region proximal to the transcription start site in several genes. The mRNA expression level of CTEN positively correlates with that of one of its putative target genes, cell division cycle protein 27 (CDC27), in a clinical colorectal cancer dataset, suggesting that CTEN may play a role in the regulation of CDC27 gene expression. Furthermore, we demonstrated that CTEN is recruited to the promoter region of the CDC27 gene and that the mRNA expression and promoter activity of CDC27 are both reduced when CTEN is downregulated. In addition, we found that enhanced nuclear accumulation of CTEN in HCT116 cells by overexpression of CTEN fused with nuclear localization signals increases CDC27 transcript levels and promoter activity. The increased nuclear-localized CTEN also significantly promotes cell migration, and the migratory ability is suppressed when CDC27 is knocked down. These results demonstrate that nuclear CTEN regulates CDC27 expression transcriptionally and promotes cell migration through CDC27. Our findings provide new insights into CTEN moonlighting in the nucleus as a DNA-associated protein and transcriptional regulator involved in modulating cancer cell migration.

RATIONALE: Obesity induces cardiomyopathy characterized by hypertrophy and diastolic dysfunction. Whereas mitophagy mediated through an Atg7-dependent mechanism serves as an essential mechanism to maintain mitochondrial quality during the initial development of obesity cardiomyopathy, Rab9-dependent alternative mitophagy takes over the role during the chronic phase. Although it has been postulated that DRP1 (dynamin-related protein 1)-mediated mitochondrial fission and consequent separation of the damaged portions of mitochondria are essential for mitophagy, the involvement of DRP1 in mitophagy remains controversial. OBJECTIVE: We investigated whether endogenous DRP1 is essential in mediating the 2 forms of mitophagy during high-fat diet (HFD)–induced obesity cardiomyopathy and, if so, what the underlying mechanisms are. METHODS AND RESULTS: Mice were fed either a normal diet or an HFD (60 kcal %fat). Mitophagy, evaluated with Mito-Keima, was increased after 3 weeks of HFD consumption. The induction of mitophagy by HFD consumption was completely abolished in tamoxifen-inducible cardiac-specific Drp1 knockout ( Drp1 MCM) mouse hearts, in which both diastolic and systolic dysfunction were exacerbated. The increase in LC3-dependent general autophagy and colocalization between LC3 and mitochondrial proteins was abolished in Drp1 MCM mice. Activation of alternative mitophagy was also completely abolished in Drp1 MCM mice during the chronic phase of HFD consumption. DRP1 was phosphorylated at Ser616, localized at the mitochondria-associated membranes, and associated with Rab9 and Fis1 only during the chronic, but not acute, phase of HFD consumption. CONCLUSIONS: DRP1 is an essential factor in mitochondrial quality control during obesity cardiomyopathy that controls multiple forms of mitophagy. Although DRP1 regulates conventional mitophagy through a mitochondria-associated membrane–independent mechanism during the acute phase, it acts as a component of the mitophagy machinery at the mitochondria-associated membranes in alternative mitophagy during the chronic phase of HFD consumption.

Cardiac paragangliomas are exceedingly rare. Herein, we describe a patient with a large dopaminesecreting cardiac paraganglioma who had a history of pheochromocytoma after right adrenalectomy. The cardiac surgery was uneventful and without blood pressure fluctuations.The measurement of plasma-free metanephrines or urinary fractionated metanephrines is used as an initial screening test for pheochromocytoma or paraganglioma detection. However, these results must be combined with those of a plasma 3-methoxytyramine test to accurately establish the rare dopaminergic phenotype of pheochromocytomas or paragangliomas, if suspected. F-FDOPA (6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine)-based positron emission tomography (PET) and PET-computed tomography are relatively sensitive and specific; therefore, these techniques are recommended for patients with pheochromocytomas or paragangliomas before operation or during postoperative follow-up.

Background: Abdominal aortic stent graft infection (AAGI) is a severe complication. The optimal management of AAGI remains unclear. This study provides updated results of bilateral axillofemoral bypasses (AFBs) for patients with AAGI. Patients and Methods: In total, 31 patients (25 men; mean age, 67.1 years) with AAGI treated using AFB between January 2006 and April 2020 were included. Overall, the mean follow-up duration was 24 months (range, 1-72). In the 23 patients who survived the post-operative period, the mean follow-up duration was 32 months (range, 12-72). Results: Thirty-day and in-hospital mortality rates was 16% and 26%, respectively. The 12-month primary and secondary patency rates for the AFB graft were both 91%. In total, seven (30%) patients received re-interventions such as thrombectomy and balloon angioplasty. No amputation was required during follow-up. Culture results were positive in 87% of pre-operative cultures and 84% of intra-operative cultures. Staphylococcus aureus was the most prevalent pathogen, with four cases of methicillin-resistant Staphylococcus aureus and one each of vancomycin-resistant enterococci, carbapenem-resistant Klebsiella pneumoniae, and carbapenem-resistant Enterobacteriaceae. In-hospital mortality rate was 57% in patients with drug-resistant pathogens. Conclusions: Reconstruction with bilateral AFB and stent graft removal in patients with AAGI is a feasible treatment modality and provided an acceptable patency rate and low amputation rate. Additional studies investigating long-term results and the optimal treatment of AAGI are required.

Background To continuously improve medical quality and provide clinicians with more accurate blood test reports, this study collected blood quality control data in 2017 from a medical examination laboratory in a teaching level hospital located in Taoyuan City, Taiwan. Material and Methods The quality control data were arranged and analyzed from daily complete blood count (CBC), including white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), and platelets (PLT) recorded by a laboratory blood analyzer. Using the empirical Bayesian method, we estimated the variation of concentrations of the last and current batches to establish a novel control chart with adjusted upper and lower limits for the current batch, and then compared results with the traditional Shewhart method. The average run length (ARL) and sensitivity of the empirical Bayesian method were explored. Results The study found that ARL showed a qualified capability for the four blood routine tests when using the empirical Bayesian method. Compared to the Levey-Jennings control chart, the novel control chart presents an alert earlier when a deviation occurs and shows a fake alert later when there is no deviation. Conclusion The parallel tests showed that the longer the time is, the better the test's proficiency. We concluded that the empirical Bayesian method could be applied effectively to improve the capability of daily control in CBC laboratory tests.

Background/Purpose Occult HBV infection (OBI) could have serious clinical consequences in patients receiving immunosuppressive therapy. We aimed to investigate the prevalence of OBI in Chinese patients with autoimmune hepatitis (AIH) and to analyze its clinical and virological features. Methods 103 AIH cases were enrolled. Hepatitis B virus (HBV) serological markers were screened by chemiluminescence. HBV-DNA were detected by nest-PCR and real-time PCR. HBV genotyping and mutation analysis were performed by Sanger sequencing. Results Twenty-four out of 103 (23.30%) AIH patients had OBI as evidenced by positive HBV-DNA and negative hepatitis B surface antigen (HBsAg). HBV genotype C is the predominant genotype (57.89%), which had more amino acid (AA) substitutions in S region than that of B-genotype group (P = 0.001). The distribution of AA substitution in the ‘α’ determinant region between genotype C and B were significantly different (P = 0.042). In addition to those already reported OBI-associated AA substitutions (e.g., sG145R and sV184A), some new OBI-associated AA substitutions (e.g., sV106A, sC137* and sL176P) were found in AIH patients in our study. Three out of 24 (12.50%) OBI patients were diagnosed as decompensated cirrhosis, one patient with S deletion mutation and two patients with HBV extensive AA substitutions. Conclusions There was a higher proportion of AIH patients with OBI than the general population in China, which can be either seropositive or seronegative-OBI in AIH patients is associated with some specific AA substitutions. The presence of deletion mutations and the extent of AA substitutions in the HBV S region may have predictive clinical implications.

To compare the outcomes of using iliac branch devices (IBD) and the crossover chimney (COCh) technique for preserving the internal iliac artery (IIA) during endovascular aortic repair in patients with common iliac aneurysm (CIA). From February 2010 to July 2016, we recruited 61 consecutive and elective patients. Thirty of them received the IBD, and the remaining 31 received the COCh. Their medical chart was reviewed retrospectively, and computed tomographic angiography was performed at 3, 6, and 12 months postoperatively and then yearly as a follow-up. The median follow-up time was 19.72 ± 5.45 months. The technical success rate reached 100% in both groups. The 12-month and 24-month primary IIA patency rates between IBD and COCh group were 90.00% versus 93.54% (p = 0.67) and 83.33% versus 93.54% (p = 0.25). The numbers of stents were 1.00 ± 0.00 and 1.93 ± 0.24 in the IBD and COCh group (p 0.99) and type 2 endoleak (IBD/COCh = 13.33%/12.90%, p > 0.99) between two groups. Neither type 1b or type 3 endoleak nor delayed aortic rupture appeared in our series. The postoperative complication rates did not exhibit significant differences either. Free from reintervention was also similar in both groups (IBD/COCh = 22.50 ± 4.62/23.00 ± 3.87 months, p = 0.64). The IBD and COCh techniques exhibited similar success rates and IIA patency rates at the 24-month follow-up. Both these techniques are feasible for the preservation of IIA in patients with CIA.

Although autophagy is generally protective, uncontrolled or excessive activation of autophagy can be detrimental. However, it is often difficult to distinguish death by autophagy from death with autophagy, and whether autophagy contributes to death in cardiomyocytes (CMs) is still controversial. Excessive activation of autophagy induces a morphologically and biochemically defined form of cell death termed autosis. Whether autosis is involved in tissue injury induced under pathologically relevant conditions is poorly understood. In the present study, myocardial ischemia/reperfusion (I/R) induced autosis in CMs, as evidenced by cell death with numerous vacuoles and perinuclear spaces, and depleted intracellular membranes. Autosis was observed frequently after 6 hours of reperfusion, accompanied by upregulation of Rubicon, attenuation of autophagic flux, and marked accumulation of autophagosomes. Genetic downregulation of Rubicon inhibited autosis and reduced I/R injury, whereas stimulation of autosis during the late phase of I/R with Tat–Beclin 1 exacerbated injury. Suppression of autosis by ouabain, a cardiac glycoside, in humanized Na(+),K(+)-ATPase–knockin mice reduced I/R injury. Taken together, these results demonstrate that autosis is significantly involved in I/R injury in the heart and triggered by dysregulated accumulation of autophagosomes due to upregulation of Rubicon.

Fibrosis is a hallmark of heart disease independent of etiology and is thought to contribute to impaired cardiac dysfunction and development of heart failure. However, the underlying mechanisms that regulate the differentiation of fibroblasts to myofibroblasts and fibrotic responses remain incompletely defined. As a result, effective treatments to mitigate excessive fibrosis are lacking. We recently demonstrated that the Hippo pathway effector Yes-associated protein (YAP) is an important mediator of myofibroblast differentiation and fibrosis in the infarcted heart. Yet, whether YAP activation in cardiac fibroblasts is sufficient to drive fibrosis, and how fibroblast YAP affects myocardial inflammation, a significant component of adverse cardiac remodeling, are largely unknown. In this study, we leveraged adeno-associated virus (AAV) to target cardiac fibroblasts and demonstrate that chronic YAP expression upregulated indices of fibrosis and inflammation in the absence of additional stress. YAP occupied the Ccl2 gene and promoted Ccl2 expression, which was associated with increased macrophage infiltration, pro-inflammatory cytokine expression, collagen deposition, and cardiac dysfunction in mice with cardiac fibroblast-targeted YAP overexpression. These results are consistent with other recent reports and extend our understanding of YAP function in modulating fibrotic and inflammatory responses in the heart.

Rationale: Diabetic cardiomyopathy is accompanied by increased production of NADH, predominantly through oxidation of fatty acids and consequent increases in oxidative stress. The role of Nampt (nicotinamide phosphoribosyltransferase), the rate-limiting enzyme of the salvage pathway of nicotinamide adenine dinucleotide synthesis, in the development of diabetic cardiomyopathy is poorly understood. Objective: We investigated the role of endogenous and exogenous Nampt during the development of diabetic cardiomyopathy in response to high-fat diet (HFD) consumption and in the context of oxidative stress. Methods and Results: HFD consumption upregulated endogenous Nampt, and HFD-induced cardiac diastolic dysfunction, fibrosis, apoptosis, and proinflammatory signaling were alleviated in transgenic mice with cardiac-specific overexpression of Nampt. The alleviation of diastolic dysfunction observed in these mice was abolished by inhibition of NADP(H) production via NADK (NAD kinase) inhibition. Nampt overexpression decreased oxidation of GSH (glutathione) and Trx1 (thioredoxin 1) targets, dityrosine, and the accumulation of toxic lipids, including ceramides and diglycerides, in the presence of HFD consumption. Nampt overexpression upregulated not only NAD + (nicotinamide adenine dinucleotide) but also NADP + (nicotinamide adenine dinucleotide phosphate) and NADPH in the heart and in cultured cardiomyocytes, which, in turn, stimulated the glutathione and Trx1 systems and alleviated oxidative stress in the heart induced by HFD consumption. In cultured cardiomyocytes, Nampt-induced upregulation of NADPH was abolished in the presence of NADK knockdown, whereas that of NAD + was not. Nampt overexpression attenuated H 2 O 2 -induced oxidative inhibition of Prdx1 (peroxiredoxin 1) and mTOR (mammalian target of rapamycin) in an NADK-dependent manner in cultured cardiomyocytes. Nampt overexpression also attenuated H 2 O 2 -induced cell death, an effect that was partly abolished by inhibition of NADK, Trx1, or glutathione synthesis. In contrast, oxidative stress and the development of diabetic cardiomyopathy in response to HFD consumption were exacerbated in Nampt heterozygous knockout (Nampt +/− ) mice. Conclusions: Nampt-mediated production of NAD + protects against oxidative stress, in part, through the NADPH-dependent reducing system, thereby alleviating the development of diabetic cardiomyopathy in response to HFD consumption.

Purpose To evaluate the effect of renal stent-graft placement on kidney function and size alternation in chronic aortic dissection. Materials and Methods Twenty-five consecutive patients with chronic aortic dissection after thoracic endovascular aortic repair who underwent renal stent-graft placement between January 2015 and December 2016 were retrospectively reviewed. Forty-three patients with chronic aortic dissection who received thoracic endovascular aortic repair in the same period were reviewed as a control group for kidney volume comparison. Results Twenty-five stent-grafts were deployed over 25 renal arteries. Overall renal function was assessed by the slope of the regression line constructed from the plots of creatinine clearance versus time within 2 years after the procedure (–0.2810 vs –0.3146 mL/min–1/mo–1, P = .868), kidney volume at 12 months (129.4 ± 40.9 vs 137.0 ± 44.2 cm2, P = .193) and effective renal plasma flow at 6 months (106.3 ± 46.9 vs 124.4 ± 55.5 mL/min, P = .050) and was not significantly deteriorated. Seven treated patients (87.5%) with a renal artery supplied by a false lumen had a decrease in kidney volume, as did 14 patients (56%) in the control group (P = .206). Three patients with a dissected renal artery (75%) in the stent-graft group had an increase in kidney volume compared with 1 patient (11.1%) in the control group (P = .052). Conclusions Occlusion of the re-entry tear by a stent-graft in the renal artery remains a safe strategy to promote false lumen thrombosis. The stent-graft poses a potential risk of reducing the kidney volume in kidneys supplied by the false lumen but may provide a positive effect in kidney volume with a concomitant dissected renal artery in chronic aortic dissection.

Banding of the ascending aorta has been introduced as a less complex procedure to optimize the proximal landing zone of the stent graft in hybrid aortic arch surgery. However, data about the long-term results and effects of this technique are still limited. We aimed to study the efficacy of banding of the ascending aorta in hybrid aortic arch repair. The study included 11 high-risk patients with dilated ascending aorta (wider than 38 mm in diameter) undergoing ascending aortic banding for hybrid arch repair. Clinical outcomes, including technical success, endoleaks, perioperative mortality and morbidity, and sequential remodeling of the ascending aorta were investigated. The average diameter of the ascending aorta had been reduced (p = 0.02) from 42.1 mm (range = 39.0-46.4) to 37.2 mm (range = 35.6-38.6) after banding procedure. The technical success rate was 100.0%. No type I endoleak occurred, but 2 cases of distal stent graft-induced new entry required re-interventions. The 5-year survival and freedom from aortic events rates both were 81.8%. The ascending aortic diameter remained stable and no proximal migration of the stent graft was observed during the study period. The 5-year results validated the durability of this therapeutic modality, especially in high-risk patients.

Talaromyces (Penicillium) marneffei can cause fatal disseminated infection in immunocompromised hosts. However, therapeutic strategies for the mycosis are limited. Reports of the other fungi suggest that berberine, a component of traditional herb, inhibitors interact with antifungal agents to improve the treatment outcomes. In the study, we evaluated the in vitro efficacy of berberine in combination with conventional antifungal agents against the pathogenic yeast form of T. marneffei. We demonstrate the synergistic effect of combination of berberine with fluconazole (52.38%), itraconazole (66.67%), voriconazole (71.43%), amphotericin B (71.43%) or caspofungin (52.38%) of T. marneffei strains, respectively. Time-kill curves confirmed the synergistic interaction, and no antagonistic was observed in all of the combinations. In conclusion, berberine could enhance the efficacy of conventional antifungal agents against the yeast form of T. marneffei in vitro. The results indicated berberine might have a potential role in combination therapy for talaromycosis.

Patients diagnosed of DeBakey type III aortic dissection with partial thrombosis of false lumen (FL) have a higher mortality rate. However, IIIb dissections with full patent FL tend to exhibit a partially thrombosed FL quickly after thoracic endovascular aortic repair (TEVAR); thus, we investigated survival and aortic remodeling in this population.We reviewed computed tomography aortograms (CTAs) of 123 patients with TEVAR-treated IIIb aortic dissections from July 2006 to June 2015; contrast density of CTAs represented intraluminal flow. Patients were selected to fit in 2 groups of FL in term of FL contrast density: low flow (LF) group (non-opacification in the midway of FL) and high flow (HF) group (full patent FL).Surgical mortality was 10.3% in the HF group and 4.5% in the LF group (n = 61; LF = 22; HF = 39). 3 patients in the HF group suffered from lethal aortic rupture in 10 days postoperatively. The HF group showed significant increase in maximal diameter, and had larger thoracic (+4.00 ± 2.68 vs -1.16 ± 3.42 mm, P.001) aortic diameter expansion from preoperation to one week postoperation. Both groups exhibited significant favorable thoracic TL expansion and maximal aortic diameter shrinkage in postoperative one week to one year. However, HF group displayed less thoracic aortic FL regression (-70.9 ± 83.5 vs -113.9 ± 95.0 cmPreoperative HF in the FL has an unfavorable effect on thoracic aortic diameter in one week post-TEVAR. This might increase the risk of aortic rupture.

OBJECTIVES Although commercial iliac branch devices offer a new and valid endovascular approach to treating iliac aneurysm and effectively preserve antegrade flow of the internal iliac artery, their use may not be suited for all types of challenging anatomy, especially isolated common iliac artery aneurysm. Our custom-made iliac bifurcation device has a unique design and excludes both combined and isolated iliac branch aneurysm. This study validated the efficacy and safety of the custom device by comparing clinical outcomes between groups receiving commercial and custom devices. METHODS Data of consecutive patients receiving iliac bifurcation device implantation for iliac aneurysm with or without concomitant endovascular repair for abdominal aortic aneurysm from January 2010 to May 2019 were reviewed. RESULTS Iliac bifurcation device implantation with or without concomitant abdominal aortic aneurysm stent grafting was completed in 46 patients (commercial, n = 35; custom, n = 11). No significant differences were observed regarding postoperative complications, occlusion or endoleak. Comparisons of primary (80.8% vs 85.7%, P = 0.88) and secondary (86.5% vs 85.7%, P = 0.85) patency and freedom from reintervention (88.2% vs 100%, P = 0.33), all-cause mortality (78.6% vs 100%, P = 0.25) and aneurysm-related mortality (100% vs 100%, P = 1.00) also indicated no differences at a 5-year surveillance point. Furthermore, the iliac aneurysms of the groups displayed similar shrinkage 1 year after procedures. CONCLUSIONS For iliac aneurysm, the novel custom-made iliac bifurcation device is an adaptable design not inferior to commercial devices with regard to postoperative complications, bridge occlusion, endoleak and short-term aneurysm remodelling. It provides an alternative for treatment, particularly when certain anatomic challenges are present. Clinical trial registration 2018-07-050BC, 2017-01-023ACF.

Background To continuously improve medical quality and provide clinicians with more accurate blood test reports, this study collected blood quality control data in 2017 from a medical examination laboratory in a teaching level hospital located in Taoyuan City, Taiwan. Material and Methods The quality control data were arranged and analyzed from daily complete blood count (CBC), including white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), and platelets (PLT) recorded by a laboratory blood analyzer. Using the empirical Bayesian method, we estimated the variation of concentrations of the last and current batches to establish a novel control chart with adjusted upper and lower limits for the current batch, and then compared results with the traditional Shewhart method. The average run length (ARL) and sensitivity of the empirical Bayesian method were explored. Results The study found that ARL showed a qualified capability for the four blood routine tests when using the empirical Bayesian method. Compared to the Levey–Jennings control chart, the novel control chart presents an alert earlier when a deviation occurs and shows a fake alert later when there is no deviation. Conclusion The parallel tests showed that the longer the time is, the better the test’s proficiency. We concluded that the empirical Bayesian method could be applied effectively to improve the capability of daily control in CBC laboratory tests.

The emergence and spread of cryptococcosis caused by the Cryptococcus gattii species complex has become a major public concern worldwide. C. deuterogattii (VGIIa) outbreaks in the Pacific Northwest region demonstrate the expansion of this fungal infection to temperate climate regions. However, infections due to the C. gattii species complex in China have rarely been reported. In this study, we studied eleven clinical strains of the C. gattii species complex isolated from Guangxi, southern China. The genetic identity and variability of these isolates were analyzed via multi-locus sequence typing (MLST), and the phylogenetic relationships among these isolates and global isolates were evaluated. The mating type, physiological features and antifungal susceptibilities of these isolates were also characterized. Among the eleven isolates, six belonged to C. deuterogattii, while five belonged to C. gattii sensu stricto. The C. deuterogattii strains from Guangxi, southern China were genetically variable and clustered with different clinical isolates from Brazil. All strains were MATα, and three C. deuterogattii isolates (GX0104, GX0105 and GX0147) were able to undergo sexual reproduction. Moreover, most strains had capsule and were capable of melanin production when compared to the outbreak strain from Canada. Most isolates were susceptible to antifungal drugs; yet one of eleven immunocompetent patients died of cryptococcal meningitis caused by C. deuterogattii (GX0147). Our study indicated that the highly pathogenic C. deuterogattii may be emerging in southern China, and effective nationwide surveillance of C. gattii species complex infection is necessary., Author summary Cryptococcosis is a fatal systemic fungal disease caused by Cryptococcus neoformans/gattii species complexes. As a former member of the C. neoformans, C. gattii had been easily neglected before being elevated to species level. Human C. gattii species complex infection was previously confined to the tropical and subtropical regions worldwide. However, in 1999, an outbreak of C. gattii species complex occurred on Vancouver Island in Canada then expanded to the Pacific Northwest in the USA, causing over 200 infections. The highly virulent, highly pathogenic and more resistant to antifungal drugs of this species have become a therapeutic problem. To initiate a better understanding of the infection characteristics and pathogenicity of C. gattii species complex in Guangxi, southern China, the current study aimed to characterize the C. gattii species complex isolates genetically and phenotypically. The ISHAM consensus MLST scheme was utilized to investigate the genetic structure of C. gattii species complex and to correlate their geographic origin, clinical source, virulence factors and antifungal susceptibility. The authors expect that this work can support surveillance and encourage more research and public health initiatives to prevent and control the cryptococcosis cause by C. gattii species complex.

More than half of diabetic patients develop diastolic heart failure. Nampt is a rate-limiting enzyme for NAD synthesis. Phosphorylation of NAD by NAD kinase (NADK) generates NAD phosphate (NADP), which is in turn converted to NADPH and provides the GSH and thioredoxin (Trx) systems with a reducing power. Whether Nampt is protective against diabetic cardiomyopathy (DCM) and, if so, whether NADK mediates the salutary function of Nampt are unknown. We employed mice with cardiac-specific Nampt overexpression (Nampt-cTG) and a mouse model of DCM induced by high fat diet (HFD) consumption. HFD-induced diastolic dysfunction, indicated by an elevated end-diastolic pressure-volume relationship (EDPVR), was ameliorated in Nampt-cTG mice (EDPVR: wild-type mice (WT) Normal Diet (ND): 0.045; WT HFD (1 month): 0.136; Nampt-cTG: 0.042: Nampt-cTG HFD: 0.055*, p2 O 2 -induced oxidation of Trx1 substrates in an NADK-dependent manner in cardiomyocytes. Nampt overexpression inhibited H 2 O 2 -induced cell death, an effect that was attenuated in the presence of NADK inhibition. Systemic Nampt heterozygous knockout promoted HFD-induced diastolic dysfunction and oxidative stress in the heart in vivo . These results suggest that Nampt protects the heart against diastolic dysfunction through upregulation of the reducing system, which occurs through NADK-dependent upregulation of the reducing equivalent, namely NADPH.

Regulation of mitochondrial energetics is key to maintain cardiac function. Perm1 ( P GC-1 and E RR- r egulator, m uscle 1 ) was previously shown to enhance exercise endurance in skeletal muscle through increasing mitochondrial bioenergetics. Despite the significant expression levels of Perm1 in the heart, its role in the healthy and diseased hearts has never been investigated. We found that cardiac Perm1 was downregulated in the mouse failing heart subjected to pressure overload for 4 weeks (24.4 ± 5.9 % of sham operated, p

Thioredoxin 1 (Trx1) is an oxidoreductase that reduces proteins with disulfide bonds. Trx1 also functions as a transnitrosylase, but this occurs only when Trx1 is oxidized at Cys32 and Cys35. In cultured cardiomyocytes (CMs), glucose deprivation (GD) induces oxidation of Trx1 and Trx1 is transnitrosylated. Thus, we hypothesized that Trx1 promotes GD-induced autophagy through its function as a transnitrosylase rather than as an oxidoreductase. GD-induced autophagy, evaluated by counting GFP-LC3 puncta, was inhibited in the presence of the transnitrosylation-defective Trx1C73S mutant (GFP-LC3 puncta per cell under GD; control: 38; Trx1 knockdown: 2*; Trx1C73S: 17*; p

To compare the outcomes of using iliac branch devices (IBD) and the crossover chimney (COCh) technique for preserving the internal iliac artery (IIA) during endovascular aortic repair in patients with common iliac aneurysm (CIA).From February 2010 to July 2016, we recruited 61 consecutive and elective patients. Thirty of them received the IBD, and the remaining 31 received the COCh. Their medical chart was reviewed retrospectively, and computed tomographic angiography was performed at 3, 6, and 12 months postoperatively and then yearly as a follow-up.The median follow-up time was 19.72 ± 5.45 months. The technical success rate reached 100% in both groups. The 12-month and 24-month primary IIA patency rates between IBD and COCh group were 90.00% versus 93.54% (p = 0.67) and 83.33% versus 93.54% (p = 0.25). The numbers of stents were 1.00 ± 0.00 and 1.93 ± 0.24 in the IBD and COCh group (p 0.001). No significant difference was observed for the incidence of type 1a (IBD/COCh = 3.33%/6.45%, p 0.99) and type 2 endoleak (IBD/COCh = 13.33%/12.90%, p 0.99) between two groups. Neither type 1b or type 3 endoleak nor delayed aortic rupture appeared in our series. The postoperative complication rates did not exhibit significant differences either. Free from reintervention was also similar in both groups (IBD/COCh = 22.50 ± 4.62/23.00 ± 3.87 months, p = 0.64).The IBD and COCh techniques exhibited similar success rates and IIA patency rates at the 24-month follow-up. Both these techniques are feasible for the preservation of IIA in patients with CIA.

OBJECTIVE. The purpose of this study was to compare the volume alteration and effective renal plasma flow of kidneys supplied by false lumens (FLs) with those of kidneys supplied by true lumens (TLs), to show the discrepancy in perfusion between the two lumens. We sought to corroborate malperfusion of FL-supplied kidneys with imaging characteristics observed on CT angiography. MATERIALS AND METHODS. A retrospective analysis was conducted using prospectively collected data for 87 patients with a diagnosis of residual chronic aortic dissection between 2005 and 2013 who had one kidney perfused by a TL and the other kidney perfused by a FL. RESULTS. Overall, at follow-up, FL-supplied kidneys had a mean (± SD) effective renal plasma flow (117.5 ± 42.6 vs 146.6 ± 41.0 mL/min; p = 0.004) and volume (131.1 ± 37.1 vs 146.5 ± 33.3 cm3; p = 0.004) that were lower than those of TL-supplied kidneys. Multivariate analysis revealed the presence of a proximal major inlet (odds ratio, 0.306; 95% CI, 0.103-0.910; p = 0.033) and large FL area (odds ratio, 0.104; CI, 0.012-0.880; p = 0.038) as factors protecting against malperfusion of FL-supplied kidneys. In patients with dissected renal arteries, the FL-supplied kidney had low effective renal plasma flow (mean, 88.5 ± 26.8 vs 149.6 ± 43.5 mL/min; p = 0.004) and diminished volume (mean, 120.4 ± 30.4 vs 152.3 ± 24.6 cm3; p = 0.001). CONCLUSION. In the present study, kidneys perfused by FLs showed decreased volume and reduced effective renal plasma flow during follow-up, particularly those kidneys with dissected renal arteries, a small FL area at the renal level, and lack of a proximal major inlet. Further studies are warranted to identify the clinical relevance of malperfusion in FL-supplied kidneys.

The proliferation of advanced analytics and artificial intelligence has been driven by huge volumes of data that are mostly generated at the edge. Simultaneously, there is a rising demand to perform analytics on edge platforms (i.e., near-sensor data analytics). However, conventional architectures of such platforms may not execute the targeted applications in an energy-efficient manner. Emerging near and in-memory computing paradigms can increase the energy efficiency of edge platforms by relying on emerging logic and memory devices. More importantly, these paradigms enable the possibility of performing computations on unconventional platforms, namely flexible computing systems. In this paper, we explore the benefits of in-memory computing at the edge on a flexible substrate enabled by thin-film transistors (TFTs) and resistive RAM (RRAM). As a case study, we consider bio-signal processing application workloads, i.e., compressive sensing and anomaly detection. We model the device, circuit, and architecture of our targeted platform and evaluate the corresponding system-level performance. Preliminary results indicate that in-memory computing enabled by flexible electronic devices enables a new class of edge platforms with lower power consumption, compared to that of rigid TFT devices.

Purpose: To report a retrospective analysis of risk factors for edge restenosis after Viabahn stent-graft treatment of superficial femoral artery (SFA) occlusive disease and determine any protective effect of drug-coated balloons (DCBs) used at the time of stent-graft implantation. Methods: Between October 2011 and July 2016, 110 patients (mean age 73.3±7.6 years; 78 men) were treated with the Viabahn stent-graft for long SFA occlusions. Thirty-eight (34.5%) patients had DCB reinforcement at the distal edge of the stent-graft. For analysis, the population was divided into groups of no edge stenosis patients (n=88; mean lesion length 22.4±4.2 cm) and edge stenosis patients (n=22; mean lesion length 23.5±5.7 cm). The clinical outcomes, ankle-brachial indices, computed tomography angiography findings, and patency were compared at a minimum of 12 months. Logistic regression analysis was employed to determine risk factors for edge stenosis; the results are presented as the odds ratio (OR) and 95% confidence interval. Results: No differences in clinical or procedural characteristics were identified except the higher incidence of diabetes (p=0.008) and greater need for retrograde access (p=0.033) in the edge stenosis group. DCB reinforcement reduced the incidence of edge stenosis (p=0.021) and target lesion revascularization (TLR; p=0.010) and resulted in a significantly higher 1-year primary patency rate (92.1% vs 76.4%, p=0.042). However, multivariate analysis revealed only poor distal runoff (OR 0.31, 95% CI 0.11 to 0.83, p=0.020) as a predictor of edge stenosis. Conclusion: The risk of edge stenosis after Viabahn implantation was higher in patients with poor distal runoff. DCB reinforcement over the distal edge reduced edge stenosis, decreased 1-year TLR, and improved 1-year primary patency.

Background In chronic type B aortic dissection, late distal stent graft–induced new entry (SINE) has a possible negative role in long-term aortic remodeling. This study aimed to investigate the impact of SINE occurrence on survival by evaluating true and false lumen remodeling in thoracic and abdominal segments at midterm surveillance. Methods This study enrolled 65 patients with chronic type B aortic dissection (DeBakey type IIIb), who had received hybrid thoracic endovascular aortic repair (TEVAR) and had completed surveillance for at least 3 years. The 3-year survival rate was 84.7%. The patients were classified into non-SINE (n = 47) and SINE (n = 18) groups. Serial computed tomography scans were used to analyze volumetric change, true and false lumens, and thrombus volume from arch to aortic bifurcation level. Results The SINE event occurred at a median of 22.5 months. In the SINE group, there was a significant interruption of the abdominal true lumen expansion in the second year (median 0.01 [interquartile range (IQR), –0.03 to 0.12] in the non-SINE group versus median –0.04 [IQR, –0.12 to 0.04] in the SINE group; p = 0.014). There was a significantly worse thoracic false lumen remodeling in the SINE group compared with the non-SINE group in the third year after the SINE event occurred (median 0 [IQR, –0.09 to 0.05] in the non-SINE group versus median 0.06 [IQR, 0 to 0.13] in the SINE group; p = 0.038). Conclusions For chronic aortic dissection, late occurrence of distal SINE could influence abdominal true lumen expansion and thoracic false lumen shrinkage. Early reintervention for distal SINE could improve aortic remodeling in chronic aortic dissection.

Background: Aggressive and early thrombus removal strategy has been widely used as a treatment for iliofemoral deep vein thrombosis (DVT). We compared the long-tem venous outcome, including postthrombotic syndrome (PTS), in patients undergoing catheter-directed thrombolysis (CDT) and pharmacomechanical thrombectomy (PMT). Methods: From January 2009 to December 2013, 61 patients with acute proximal DVT were enrolled in this prospective study. Thirty-one patients underwent CDT and 30 patients underwent PMT, and each patient was followed for at least 2 years after treatment. Observations included venous outflow resistance, venous insufficiency, thrombus score (TS), severity of PTS, and surgical complications. Results: Venous outflow obstruction was similar in the CDT and PMT groups (32.3% vs. 30.0%, p = 0.695), and venous insufficiency of each group was 38.7% and 30.0% (p = 0.774), respectively. The TS at 24 months of each group showed no significant difference (0.90 vs. 0.70, p = 0.526). The mean Villalta scale scores of the CDT and PMT groups were 3.13 and 1.87, respectively (p = 0.042). Patients without PTS had significantly lower TS since 1 week postoperatively (1.59 vs. 4.60, p