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Withaferin-A (WA) as an anti-inflammatory and immunomodulatory agent may have clinical utility either as a single agent or in combination for the prevention of aGvHD. Correspondence to: vgota76@gmail.com I Background: i Acute graft versus host disease (aGvHD) is a major complication of allogenic bone marrow transplantation (alloBMT). [Extracted from the article]

Vein of Galen malformation (VGM) is a rare intracranial vascular malformation. High output heart failure is common in infancy and is characterized by dilatation of all the cardiac chambers. We report an unusual case of VGM in a 3‐month‐old infant without dilatation of the right‐sided cardiac chambers. We then demonstrate importance of comprehensive evaluation in detecting rare coexistence of anomalous right superior caval vein connection to the left atrium. [ABSTRACT FROM AUTHOR]

Saline contrast echocardiography is an established imaging modality. Logical interpretation of a carefully performed study is vital to realize its diagnostic potential. In this review, we discuss utility of saline contrast echocardiography in evaluation of various pathologies within and outside the heart other than a patent foramen ovale. [ABSTRACT FROM AUTHOR]

The 5th Congress of Asia Pacific Pediatric Cardiac Society was held in New Delhi from 6-9 March 2014. This article describes the journey of preparing and hosting one of the largest international events in the specialty of Pediatric Cardiac Care ever held in India. A total of 938 delegates, including 400 from outside India, participated. The scientific program was inclusive keeping in mind the diverse background of delegates from the member nations. Large numbers of research papers were presented, mostly by fellows in training. [ABSTRACT FROM AUTHOR]

Aim This study evaluated patient satisfaction and clinical effectiveness of intracoronal bleach in traumatized anterior discolored intact teeth. Assessment of awareness and knowledge of the patient regarding treatment modalities for such cases was also performed. Material and method Forty-one patients were included in the study. Walking bleach was performed using sodium perborate (tetrahydrate) after root canal treatment and proper cervical seal. Patient was recalled after 1 week for evaluation. The bleaching procedure was repeated again till the patient agreed for it. On each recall visit, shade evaluation was performed using the Vita Classic shade guide. On completion of treatment, the patients were questioned as to their satisfaction level. Statistical analysis was carried out using anova. Results 87.8% of the subjects were highly satisfied with the results obtained; 7.32% were satisfied, while 4.9% were not satisfied. Average number of appointments needed for highly satisfied group was 2.75, and average shade change obtained was 11.97. Significantly more number of appointments were needed for the older patients ( P < 0.01) or patients with older trauma ( P < 0.05)/discoloration ( P < 0.05). Severity of discoloration did not affect the number of appointments ( P > 0.05). Most of the participants (97.6%) were not aware of bleaching procedure. The aspect of this treatment, which satisfied them the most, was improvement of the tooth coloration followed by conservation of tooth structure while the most perplexing thing was the unpredictability of final shade achieved and lack of color stability. Conclusions High level of patient satisfaction after non-vital tooth bleach treatment strongly supports this treatment modality to be a conservative treatment alternative for traumatized discolored anterior tooth. [ABSTRACT FROM AUTHOR]

De novo expression of human T-cell leukemia virus type 1 Tax results in cellular genomic instability. We demonstrated previously that Tax associates with the cell cycle check point regulator Chk2 and proposed that the inappropriate activation of Chk2 provides a model for Tax-induced loss of genetic integrity (Haoudi, A., Daniels, R. C., Wong, E., Kupfer, G., and Semmes, O. J. (2003)1. Biol. Chem. 278, 37736–37744). Here we provide an explanation for how Tax induces some Chk2 activities but represses others. We show that Tax interaction with Chk2 generates two activation signals in Chk2, oligomerization and autophosphorylation. However, egress of Chk2 from chromatin, normally observed in response to ionizing radiation, was repressed in Tax-expressing cells. Analysis of chromatin-bound Chk2 from Tax-expressing cells revealed phosphorylation at Thr378, Ser379, Thr383, Thr387, and Thr389. In contrast, chromatin-bound Chk2 in the absence of Tax was phosphorylated at Thr383 and Thr387 in response to ionizing radiation. We further establish that Tax binds to the kinase domain of Chk2. Confocal microscopy revealed a redistribution of Chk2 to colocalize with Tax in Tax speckled structures, which we have shown previously to coincide with interchromatin granules. We propose that Tax binding via the Chk2 kinase domain sequesters phosphorylated Chk2 within chromatin, thus hindering chromatin egress and appropriate response to DNA damage. [ABSTRACT FROM AUTHOR]

The human T-cell leukemia virus type 1 (HTLV-1) viral protein Tax is a transactivator of transcription driven by the cognate viral long terminal repeat (LTR). Tax exerts its effect through three nonidentical copies of the Tax-responsive element (TxRE), a member of the asymmetric cyclic AMP response element (CRE) family of enhancer sequences. Transactivation is mediated via interaction of Tax with members of the CREB/ATF family bound to TxRE. We have identified a cellular repressor of transcription, activating transcription factor x (ATFx), as a novel Tax-binding protein. In addition to binding directly to Tax we show by electrophoretic mobility shift assay that ATFx binds to the TxRE enhancer element via the bZIP domain. The functional impact of this bridging interaction results in repression of both basal and Tax-induced transcription from the HTLV-1 LTR. ATFx is unique among ATF family of proteins in that it is cell cycle regulated and exerts a tight repressive control over apoptotic signaling. We propose that recruitment of ATFx to the HTLV-1 LTR serves to link viral transcription with critical events in cellular homeostasis. [ABSTRACT FROM AUTHOR]

It inhibits GR in cell-free system and in A549 cells which in turn modulates mitochondrial redox leading to ROS dependent apoptosis in A549 cells. Correspondence to: vikramgota@gmail.com I Background: i The dedicated thioredoxin and glutathione redox systems are the central antioxidant defense mechanisms by which mitochondria neutralize the excess ROS. [Extracted from the article]

In the present work, effect of heat treatment on microstructure and corrosion behaviour of a high Mo containing α + β titanium alloy (Ti-6Al-1 V-4Mo-0.1Si) has been investigated. Heat treatment results in the formation of wide variety of microstructure depending on the heating temperature (below or above the β transus) and cooling conditions. Martensite was observed after oil quenching (OQ), Widmanstatten α (α WS) + β after air cooling (AC) and lamellar α (α L) + β after furnace cooling (FC). The corrosion behaviour of the heat-treated specimens were studied in simulated body fluid (SBF) at 37 °C using open circuit potential-time (OCP), electrochemical impedance spectroscopy (EIS) and potentio-dynamic polarization tests. X-ray photoelectron spectroscopy (XPS) was used to investigate the chemical nature of the corroded surfaces. The study revealed that, in general, OQed samples had increased corrosion resistance than the ACed and FCed samples. XPS confirmed the presence of TiO 2 and Al 2 O 3 on the corroded sample. The alloy's improved corrosion resistance was attributed to stable inert TiO 2 film. Samples heat treated at 950 °C were found to have better corrosion resistance in general. • Martensite, Widmanstannen α, Basketweaven α structure were formed after heat treatments. • All samples exhibited self-passivation behavior in simulated body fluid solution. • XPS analysis confirmed the presence of TiO 2 and Al 2 O 3 layer. • The oxide film consisted of two layers i.e., outer porous layer and inner barrier layer. • Heat treatment in α + β region showed optimum corrosion properties. [ABSTRACT FROM AUTHOR]

Background: Over the course of time, new developments associated with the embryogenesis of the murine heart have served to clarify the developmental processes observed in the human heart. This evidence allows for the creation of a developmental framework for many congenital cardiac defects. Aims: We aim to solidify the framework related to the categorization of both solitary and multiple ventricular septal defects. Materials and Methods: Mice having genetic perturbation of the Furin enzyme have demonstrated perimembranous and juxta‐arterial ventricular septal defects, permitting the inference to be made that these defects can co‐exist with defects occurring within the apical muscular septum. Results: Basis of developmental evidence, furthermore, all interventricular communications can be placed into one of three groups, namely those which are perimembranous, juxta‐arterial, and muscular. All of the defects are described based on their borders as seen from the morphologically right ventricle. Our focus here will be on those defects within the muscular ventricular septum, recognizing that such defects can co‐exist with those that are perimembranous. We discuss the differentiation of multiple discrete defects from those referred to as the "Swiss cheese" variant. Conclusions: As we show, appropriate surgical management requires an understanding of the specific terminology, as the surgical approach may differ depending on the combination of the individual defects. Data from the Society for Thoracic Surgeons revealed that both mortality and morbidity were increased in the setting of multiple as opposed to solitary ventricular septal defects. [ABSTRACT FROM AUTHOR]

Aortic atresia with an associated ventricular septal defect and adequate sized left ventricle is extremely rare. We present two cases in which an alternate diagnosis was suggested on echocardiography because the hypoplastic aortic trunk was missed due to its small caliber. The final diagnosis was, however, clinched on dual source computed tomography, which not only showed the thin aortic trunk but also clearly depicted the coronary artery origins from the hypoplastic aortic root. To the best of our knowledge, use of multi-detector computed tomography in aortic atresia with well developed left ventricle has not been reported in literature till date. [ABSTRACT FROM AUTHOR]

Aortopulmonary collaterals (APCs) are occluded either preoperatively or at the time of cardiac surgery in patients with pulmonary atresia and ventricular septal defect (PAVSD). If left untreated, APCs are an important cause of deterioration in the early postoperative period. We present here an unusual case with a large residual APC causing refractory low-output state in the early postoperative period. Usual arterial approach failed due to extensive angulation with ostial narrowing. The large residual APC was successfully closed with an Amplatzer duct occluder (ADO) device delivered through the transvenous route. [ABSTRACT FROM AUTHOR]

Background: Acute rheumatic fever (ARF) and acute rheumatic carditis (ARC) continue to be a major public health problem in developing countries. Objective: To study the characteristics of children with ARC being treated at a tertiary centre. Methods and Results: We studied 126 children (mean age 10.4 ± 2.3 years, range 5–15 years, 60% males) diagnosed with ARC by treating cardiologists. Most had lower socio-economic status. Fifty of 126 (40%) presented with a first episode of ARC. Joint symptoms were present in 29% and fever in 25%. Only 2.4% had subcutaneous nodules and none had erythema marginatum or chorea. Fifty-one percent presented in NYHA class II and 29% in NYHA class III or IV. Tachycardia and heart failure were present in 53% and 21%, respectively. Recent worsening of NYHA class (dyspnoea) was the commonest feature (48%). Laboratory investigations showed raised antistreptolysin O titres (>333 units) in only 36.7% of patients. Raised C-reactive protein (CRP) was present in 70%, while raised erythrocyte sedimentation rate was found in only 37% of patients. On the basis of above findings, the modified Jones criteria (2015) for the diagnosis of ARF were satisfied only in 46% of children. Echocardiography showed mitral valve thickening in 77% and small nodules on the tip of the leaflets in 43% (27 and 8%, respectively for aortic valve). Left ventricular ejection fraction was <50% in only 3 patients. The dominant valve lesion was mitral regurgitation (MR) (present in 95% of patients; severe in 78%, moderate in 15%), while aortic regurgitation was present in 44% (severe in 14%). Conclusions: The criteria are often not satisfied by patients being treated for ARC. Recent unexplained worsening of dyspnoea, young age, significant MR, echocardiographic nodules, and elevated CRP are important indicators. [ABSTRACT FROM AUTHOR]

Background: Amplatzer vascular plugs (AVPs) are devices ideally suited to close medium-to-large vascular communications. There is limited published literature regarding the utility of AVPs in congenital cardiovascular malformations (CCVMs). Aims: To describe the use of AVPs in different CCVMs and to evaluate their safety and efficacy. Materials and Methods: All patients who required an AVP for the closure of CCVM were included in this retrospective review of our catheterization laboratory data. The efficacy and safety of AVPs are reported. Results: A total of 39 AVPs were implanted in 31 patients. Thirteen (33%) were AVP type I and 23 (59%) were AVP type II. AVP type III were implanted in two patients and type IV in one patient. The major indications for their use included closure of pulmonary arteriovenous malformation (AVM) (n = 7), aortopulmonary collaterals (n = 7), closure of a patent Blalock-Taussig shunt (n = 5), systemic AVM (n = 5), coronary AVM (n = 4), patent ductus arteriosus (PDA) (n = 3), pulmonary artery aneurysms (n = 3), and venovenous collaterals (n = 2). Deployment of the AVP was done predominantly via the 5--7F Judkin's right coronary guide catheter. Overall 92% of the AVPs could be successfully deployed and resulted in occlusion of the target vessel in all cases, within 10 minutes. No procedure-related or access site complication occurred. Conclusions: AVPs are versatile, easy to use, and effective devices to occlude the vascular communications in a variety of settings. AVP II is especially useful in the closure of tubular structures with a high flow. [ABSTRACT FROM AUTHOR]

The human T-cell leukemia virus type 1 oncoprotein Tax has pleiotropic activities, a subset of which likely leads to immortalization of T cells. Tax is expressed and known to function in both the cell nucleus and the cytoplasm. Tax has defined nuclear localization (NLS) and nuclear export signals that enable shuttling between the two compartments. In this study, we identified a novel region in Tax that targets the protein to discrete nuclear foci that we have previously termed Tax speckled structures (TSS). We demonstrated that the identified region is both necessary and sufficient for directing proteins to TSS. This novel TSS localization signal (TSLS), spanning amino acids 50 to 75, is separable from and adjacent to the NLS of Tax. Coexpression of a Tax NLS mutant and a Tax TSLS mutant rescued the nuclear entry and subnuclear TSS targeting of both proteins, demonstrating that these signals are independent domains. Our analysis also revealed that Tax proteins deficient for dimerization fail to localize to the nucleus. Consequently, when we restored dimerization via induction of a heterologous "dimerizer" domain, nuclear localization was rescued. Thus, we defined additional domains in Tax specific for nuclear localization and subnuclear targeting. Our results reveal a more complex network for regulation of Tax subcellular localization and subsequent function. [ABSTRACT FROM AUTHOR]

Human 1-cell leukemia virus type-1 is the causative agent for adult T-cell leukemia. Previous research has established that the viral oncoprotein Tax mediates the transformation process by impairing cell cycle control and cellular response to DNA damage. We showed previously that Tax sequesters huChk2 within chromatin and impairs the response to ionizing radiation. Here we demonstrate that DNA-dependent protein kinase (DNA-PK) is a member of the TaxChk2 nuclear complex. The catalytic subunit, DNA-PKcs, and the regulatory subunit, Ku70, were present. Tax-containing nuclear extracts showed increased DNA-PK activity, and specific inhibition of DNA-PK prevented Tax-induced activation of Chk2 kinase activity. Expression of Tax induced foci formation and phosphorylation of H2AX. However, Tax-induced constitutive signaling of the DNA-PK pathway impaired cellular response to new damage, as reflected in suppression of ionizing radiation-induced DNA-PK phosphorylation and γH2AX stabilization. Tax co-localized with phospho-DNA-PK into nuclear speckles and a nuclear excluded Tax mutant sequestered endogenous phospho-DNA-PK into the cytoplasm, suggesting that Tax interaction with DNA-PK is an initiating event. We also describe a novel interaction between DNA-PK and Chk2 that requires Tax. We propose that Tax binds to and stabilizes a protein complex with DNA-PK and Chk2, resulting in a saturation of DNA-PK-mediated damage repair response. [ABSTRACT FROM AUTHOR]