Read Mapping for Hi-C Analysis.

Hi-C is a popular ligation-based technique to detect 3D physical chromosome structure within the nucleus using cross-linking and next-generation sequencing. As an unbiased genome-wide assay based on chromosome conformation capture, it provides rich insights into chromosome structure, dynamic chromosome folding and interactions, and the regulatory state of a cell. Bioinformatics analyses of Hi-C data require dedicated protocols as most genome alignment tools assume that both paired-end reads will map to the same chromosome, resulting in large two-dimensional matrices as processed data. Here, we outline the necessary steps to generate high-quality aligned Hi-C data by separately mapping each read while correcting for biases from restriction enzyme digests. We introduce our own custom open-source pipeline, which enables users to select an aligner of their choosing with high accuracy and performance. This enables users to generate high-resolution datasets with fast turnaround and fewer unmapped reads. Finally, we discuss recent innovations in experimental techniques, bioinformatics techniques, and their applications in clinical testing for diagnostics.

Clinical implications of the cardio-ankle vascular index before and after transcatheter aortic valve implantation.

BACKGROUND: Arterial stiffness indices are used to assess the material properties of the arterial wall and are associated with cardiovascular events. Aortic stenosis (AS) is commonly caused by degenerative calcification and can be associated with increased arterial stiffness. However, the clinical implications of arterial stiffness indices in AS patients before and after treatment are unknown. METHODS: This single-center observational study enrolled 150 consecutive patients who underwent transcatheter aortic valve implantation (TAVI) for severe AS. The cardio-ankle vascular index (CAVI) was measured before and after TAVI. The patients were divided into two groups according to the CAVI values before and after TAVI: high CAVI group and low CAVI group. Patient and echocardiographic data and clinical outcomes, including cardiac death and hospitalization for heart failure (HF), were compared. RESULTS: The pre- and postprocedural CAVI was 7.90 (6.75-9.30) and 9.65 (8.90-10.65), respectively. In the analyses with preprocedural CAVI, preprocedural echocardiographic aortic valve peak flow velocity was significantly lower in the high CAVI group. No significant differences between the two groups were observed in the occurrence of cardiac death or hospitalization for HF. In the analyses with postprocedural CAVI, B-type natriuretic peptide levels and E / e ' ratio after TAVI were significantly higher in the high CAVI group. The composite of cardiac death and hospitalization occurrence for HF was significantly higher in the high CAVI group. CONCLUSION: CAVI before TAVI is mainly affected by the AS severity, while CAVI after TAVI is associated with left ventricular diastolic dysfunction and late cardiac events, which may reflect arterial stiffness.

Impact of Albuminuria on the Prognosis After Transcatheter Aortic Valve Implantation.

The impact of preoperative albuminuria on the prognosis after transcatheter aortic valve implantation (TAVI) has not been studied. A total of 228 patients who underwent TAVI for severe aortic stenosis (AS) and for whom preoperative urinary data was available were retrospectively investigated. Patients were divided into two groups according to the urinary albumin-to-creatinine ratio (ACR): high (ACR≥ 30 mg/g) and low (ACR<30 mg/g). The urinary total protein-to-creatinine ratio (PCR) and dipstick proteinuria were also evaluated. The primary outcome was the composite outcome of all-cause death and readmission for heart failure. In total, 117 patients had a high ACR and 111 patients had a low ACR. During the median follow-up period of 467 days, patients with a high ACR had a higher incidence of the primary outcome than those with a low ACR (p<0.001). Patients with a high PCR or positive dipstick proteinuria were also at a higher risk for the primary outcome (p<0.001 and p=0.008, respectively). Multivariable Cox proportional hazards analysis showed a high ACR was independently associated with a primary outcome (hazard ratio, 4.98; 95% confidence interval, 1.84-13.49; p=0.002). In conclusion, preoperative albuminuria is an independent predictor of cardiac events in patients with severe AS undergoing TAVI.

Transcatheter Aortic Valve Replacement for Bicuspid Aortic Stenosis With a Severely Calcified Raphe Using An Under-Sized SAPIEN 3 Valve: Sizing by the Circle Method and Deployment by the Pressure-Regulated Method.

Transcatheter aortic valve replacement (TAVR) for bicuspid aortic valve stenosis is challenging, and the absence of established methods for sizing the bicuspid aortic valve (BAV) complicates TAVR. We report a case of successful TAVR for bicuspid aortic stenosis with a severely calcified raphe. We used an undersized SAPIEN 3 valve, with three safety measures based on assessment of structural characteristics, sizing by the circle method, and deployment of the valve by the pressure-regulated method.

Multiple giant coronary artery aneurysms with extended coronary ectasia emerging 12 years after previous coronary artery bypass grafting.

A 73-year-old man presented with multiple giant coronary artery aneurysms. Twelve years prior to the presentation, he had undergone coronary artery bypass grafting. At that time, he exhibited small aneurysms (16 mm diameter) in the right coronary artery and a single aneurysm (10 mm diameter) in the left circumflex artery. During follow-up, the aneurysms gradually increased in size (to 45 and 30 mm, respectively, at 12 years after surgery). We resected all of the aneurysms and performed coronary artery bypass grafting of the left circumflex artery through re-sternotomy.

Efficacy of Plasma free Hemoglobin for detecting centrifugal pump thrombosis.

INTRODUCTION: Lactate dehydrogenase (LDH) is widely used as an indicator of pump thrombosis in a centrifugal pump. However, due to the low specificity of LDH, pump thrombosis is difficult to detect in the clinical environment. We measured plasma free hemoglobin (pfHb) with the portable device in ICU. The goal of this investigation is to evaluate its diagnostic ability for pump thrombosis. METHODS: We enrolled 31 consecutive patients who needed Extracorporeal Membrane Oxygenation (ECMO) therapy and pfHb was determined with HemoCue® plasma/Low Hb photometer. Pump thrombosis was analyzed macroscopically at the timing of pump explantation or exchange. Also, we divided the pump thrombosis into a grading scale by the place of thrombosis. RESULTS: The median of peak pfHb was significantly lower in the none thrombus group (0.03 g/dL) than that of in the thrombus group (0.05g/dL) (p = 0.01). In our grading criteria, pfHb was significantly higher when the thrombus is existing near the shaft (p = 0.015). Contrary, no significant difference was found for LDH.The ROC analysis of pfHb revealed an AUC of 0.77 for detecting pump thrombosis with the best statistical cutoff value at 0.05 g/dL (specificity, 78%; sensitivity, 77%). Also, ROC analysis of LDH was performed (AUC, 0.44; cutoff value, 1200 IU/L; specificity, 59%; sensitivity, 54%) and compared with pfHb. AUC was significantly higher in pfHb (p = 0.04). CONCLUSION: Our results showed the efficacy of pfHb for detecting centrifugal pump thrombosis.

Warfarin-induced toxic epidermal necrolysis after mitral valve replacement.

Stevens-Johnson syndrome and toxic epidermal necrolysis are rare diseases that cause acute destruction of the epithelium of the skin and mucous membranes, almost always attributable to drugs. However, warfarin-induced Stevens-Johnson syndrome and toxic epidermal necrolysis is extremely rare. We report the case of 71-year-old woman who died due to destructive erosion all over her skin and mucous membranes. She had received a mitral valve prosthesis, and warfarin was prescribed for antithrombotic therapy. A lymphocyte transformation test for drug hypersensitivity and the clinical history confirmed this phenomenon as warfarin-induced toxic epidermal necrolysis.

[Video Assisted Left Ventricular Pseudoaneurysm Repair].

An 80-year-old male was admitted to our hospital because of subacute myocardial infarction with moderate mitral regurgitation. Though he recovered well and went home within 2 weeks, the transthoracic echocardiography revealed rapid growing aneurysmal changes at the left ventricular posterior wall. We made diagnose of a pseudoaneurysm by the multi detector-row computed tomography, and planed a surgical treatment. Following the cardiac arrest, an endoscope was inserted into the left ventricle, we inspected the relation between the mitral valve and papillary muscles to detect proper suture lines and to avoid the mitral regurgitation. The defect of the left ventricular wall was repaired with 2-layer bovine pericardial patches reinforced with fibrin glue. His postoperative course was uneventful, and he was discharged from hospital on 12th postoperative day. We consider that inspections of intra-ventricle apparatus with the endoscope are useful to prevent the mitral valve insufficiency and keep the optimal left ventricle shape.

Giant biatrial myxoma with two different gross findings.

We experienced a giant biatrial myxoma concomitant with hepatocellular carcinoma. Most of myxomas originate from the left atrium, and biatrial myxomas are extremely rare. Excision of the giant cardiac tumor was performed to avoid risks of life-threatening complications. The resected mass was grossly composed of two parts with the border of interatrial septum and with the shape of peanut shell. Although microscopic examinations revealed enlarged vessels, hemorrhages and hemosiderosis in the left part and high cellularity with chronic inflammation in the right part, spindle-shaped cells in a loose myxoid stroma were observed in both parts of the tumor, consistent with the diagnosis of myxoma. His second operation for hepatic cancer was successfully performed following 1 month after the first operation. Surgical treatment should be considered for giant atrium tumor which has risk of life-threatening complications even if patients have another cancer.

[Aortoesophageal Fistula due to Aortic Aneurysm;Report of a Case].

A 77-year-old woman presented with general fatigue, was found to have anemia, and was referred to our hospital. Upper gastrointestinal endoscopy revealed a submucosal elevated lesion with a bleeding site and debris at the middle thoracic esophagus. Enhanced computed tomography demonstrated a thoracic aortic aneurysm compressing the esophagus. She was diagnosed with an aorto-esophageal fistula due to the thoracic aortic aneurysm. Graft replacement was performed under partial extracorporeal circulation. Because the perforation of the esophagus was small, omental flap transposition was performed without esophagectomy. Her post-operative course was uneventful, and she has been doing well without any infective episodes over 3 years after surgery.

[Corrected Transposition of the Great Arteries, Ventricular Septal Defect, Tricuspid Regurgitation and Pulmonary Hypertension Operated at Middle Age: Report of a Case].

A 45-year-old male with corrected transposition of great arteries and the ventricular septal defect (VSD) was considered to have no indication for the total repair because of severe pulmonary hypertension in his young age. He was suffered from heart failure with absence at the age of 44. Detail examinations revealed the severe tricuspid valve regurgitation with VSD. We reevaluated him for the operative indication by the aspect of pulmonary hypertension. His pulmonary vascular resistance decreased with the administration of 100% oxygen, and no pulmonary vascular obstructions were detected in the lung specimen. As a result, he underwent VSD patch closure and tricuspid valve replacement. His postoperative course was uneventful and he was discharged from our hospital at day 16 postoperatively. Our data suggested that reevaluation including lung biopsy should be important to determine operative indication for adult congenital heart disease.

[Acute type a aortic dissection operated in childhood; report of a case].

A 12-year-old boy without any previous history and risk factors of cardiovascular disease presented to the emergency room with persisting general fatigue, bilateral shoulder pain and facial pallor. He was diagnosed as acute type A aortic dissection with cardiac tamponade by ultrasonic cardiogram (UCG) and computed tomography (CT) imaging, and the emergency surgery was indicated. He underwent hemiarch replacement because his aorta diameter was quite small but grafting as a large vascular prosthesis as possible was necessary in consideration of the growth. His postoperative course was uneventful and good, and he was discharged from our hospital in day 21 postoperatively. Acute aortic dissection in childhood is very rare but life-threatening. We should consider the particularity of children and make early diagnosis and treatment appropriately.

[Left atrial posterior wall flap method for II a type of the isolated total anomalous pulmonary venous drainage].

We address the left atrial posterior wall flap (LAPF) method for the isolated total anomalous pulmonary venous drainage( TAPVD) II a. The postoperative pulmonary venous obstruction( PVO) is a serious complication and is not rare after repair of the isolated TAPVD II a by the conventional surgical techniques. The LAPF method contains superiorities to prevent PVO to the conventional surgical techniques by wider left atrium(LA) - pulmonary vein(PV) communication, less risk of turbulence and no need of a prosthetic patch or an autologous pericardial patch. Furthermore, from a hemodynamic point of view, it makes LA-PV communication a functional preloading chamber which leads the postoperative hemodynamics stable. So, we think that the LAPF method is able to be a standard operative technique for the isolated TAPVD II a.

[A case with Stanford type A acute aortic dissection that presented with consciousness disturbance and hemiparesis].

The patient was a 63-year-old female who had a past history of hypertension. She suddenly complained of agonizing pain and became comatose soon thereafter. Upon admission, she was in a state of shock, with upper airway obstruction and a coma. The pupils were dilated on both sides. The laboratory data showed that D-dimer was >80µg/mL. Brain CT scan and diffusion weighted MRI of the brain showed no abnormality. On brain 2D-CT angiography, the visualization of the right internal carotid artery and the right vertebral artery was poor. She eventually was able to nod her head in response to verbal commands, but her left extremities were completely hemiplegic. Cerebral angiography showed occlusion of the right vertebral artery at the branching point from the brachiocephalic artery, and was visualized in a retrograde fashion through the left vertebral artery. The brachiocephalic artery was severely stenotic in aortography. During angiography, she became able to speak and complained of back pain. Chest CT just after angiography showed a dissection in the aortic arch. Therefore, she was directed to the cardiovascular surgeon for immediate consultation. During the operation, the aortic dissection was revealed to be Stanford type A. Laceration of the intima was found in the ascending aorta and cardiac tamponade was also found. Total arch replacement was performed. The pathological examination showed that the arterial dissection occurred in the layer of elastic fiber, and the minimum arterial thickness of the medial layer was 0.2mm. The patient improved after the operation and her neurological deficits disappeared completely 13 days after operation. Brain and spinal MRI 15 days after the operation showed no abnormality.

Suppression of pleiotropic phenotypes of a Burkholderia multivorans fur mutant by oxyR mutation.

Fur (ferric uptake regulator) is an iron-responsive transcriptional regulator in many bacterial species, and the fur mutant of Burkholderia multivorans ATCC 17616 exhibits pleiotropic phenotypes, such as an inability to efficiently use several carbon sources, as well as high sensitivity to hydrogen peroxide (H(2)O(2)), paraquat (a superoxide-producing compound) and nitric oxide (NO). To gain more insight into the pleiotropic role of the Fur protein of ATCC 17616, spontaneous suppressor mutants of the ATCC 17616 fur mutant that restored tolerance to NO were isolated and characterized in this study. The microarray-based comparative genomic analysis and subsequent sequencing analysis indicated that such suppressor mutants had a 2 bp deletion in the oxyR gene, whose orthologues encode H(2)O(2)-responsive transcriptional regulators in other bacterial species. The suppressor mutants and the reconstructed fur-oxyR double-deletion mutant showed indistinguishable phenotypes in that they were all (i) more resistant than the fur mutant to H(2)O(2), superoxide, NO and streptonigrin (an iron-activated antibiotic) and (ii) able to use carbon sources that cannot efficiently support the growth of the fur mutant. These results clearly indicate that the oxyR mutation suppressed the pleiotropic effect of the B. multivorans fur mutant. The fur-oxyR double mutants were found to overexpress the KatG (catalase/peroxidase) and AhpC1 and AhpD (alkyl hydroperoxide reductase subunits C and D) proteins, and their enzymic activities to remove reactive oxygen and nitrogen species were suggested to be responsible for the suppression of phenotypes caused by the fur mutation.

Pleiotropic roles of iron-responsive transcriptional regulator Fur in Burkholderia multivorans.

The fur (ferric uptake regulator) gene of Burkholderia multivorans ATCC 17616 was identified by transposon mutagenesis analysis. The fur deletion mutant of strain ATCC 17616 (i) constitutively produced siderophores, (ii) was more sensitive to reactive oxygen species (ROS) than the wild-type strain, (iii) showed lower superoxide dismutase and catalase activities than the wild-type strain, (iv) was unable to grow on M9 minimal agar plates containing several substrates that can be used as sole carbon sources by the wild-type strain, and (v) was hypersensitive to nitrite and nitric oxide under microaerobic and aerobic conditions, respectively. These results clearly indicate that the Fur protein in strain ATCC 17616 plays pleiotropic roles in iron homeostasis, removal and/or resistance to ROS and nitrosative stress, and energy metabolism. Furthermore, employment of an in vivo Fur titration assay system led to the isolation from the ATCC 17616 genome of 13 Fur-binding DNA regions, and a subsequent electrophoretic mobility-shift assay confirmed the direct binding of Fur protein to all of these DNA regions. Transcriptional analysis of the genes located just downstream of the Fur-binding sites demonstrated that Fur acts as a repressor for these genes. Nine of the 13 regions were presumed to be involved in the acquisition and utilization of iron.