The usefulness of proximal anchor balloon technique during implantation of a cardiac resynchronization therapy device in a patient with complex coronary venous anatomy: a case report.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an accepted device treatment in stable heart failure (HF) patients. In recent years increased awareness of coronary anatomy and implantation techniques have significantly impacted this evolving therapy. CASE PRESENTATION: In this article, we present a case describing the usefulness of the proximal balloon anchoring technique to enable initial coronary sinus (CS) cannulization and left ventricular (LV) lead placement in the tortuous coronary sinus during CRT implantation. CONCLUSIONS: The proximal anchor balloon technique can easily enable coronary sinus cannulization and left ventricular lead placement in patients with complex venous anatomy.

Effects of nickle, nickle-cobalt and nickle-cobalt-phosphorus nanocatalysts for enhancing biohydrogen production in microbial electrolysis cells using paper industry wastewater.

Paper industries are water-intensive industries that produce large amount of wastewater containing dyes, toxicity and high nutrient content. These industries require sustainable technology for their waste disposal and MEC could be one of them. However, effective MEC operation at neutral pH and ambient temperature requires economical and efficient cathodes that are capable to treat indusial wastewater along with recovery of energy/biohydrogen. Co-deposits of Nickel, Nickel-Cobalt and Nickel-Cobalt-Phosphorous on the surface of SS and Cu base metals distinctly were used as cathodes in MEC for the concurrent treatment of real paper industry wastewater and biohydrogen production. MECs were utilized in batch mode at neutral pH, applied voltage of 0.6 V and 30 ± 2 °C temperature with paper industry wastewater and activated sludge as microbial sources. The fabricated Nickel-Cobalt-Phosphorous gives the higher hydrogen production rate of 0.16 ± 0.002 m3(H2) m-3d-1 and 0.14 ± 0.002 m3(H2) m -3d -1 respectively, with ~33-42 % treatment efficiency for a 500 ml wastewater in 7-day batch cycle in both the cases; while it is lowest in the case of the control cathodes (SS1 (0.07 ± 0.002 m3(H2) m-3d-1) & Cu1 (0.06 ± 0.004 m3(H2) m-3d-1)). It was also found that fabricated cathodes have the capability to treat industrial wastewater at ambient conditions efficiently with higher energy recovery. Prepared cathodes show enhanced hydrogen production and treatment efficiency as well as are competitive to some reported literature.

Nonselective Beta-Blockers Do Not Affect Survival in Cirrhotic Patients with Ascites.

BACKGROUND: The role of nonselective beta-blockers in cirrhotic patients with ascites has been recently questioned; however, definitive evidence in this regard is still lacking. AIMS: To analyze published data on the influence of nonselective beta-blockers as compared to control group on survival of cirrhotic patients with ascites. METHODS: Computerized bibliographic search on the main databases was performed. Hazard ratios from Kaplan-Meier curves were extracted in order to perform an unbiased comparison of survival estimates. Secondary outcomes were mortality in patients with refractory ascites, pooled rate of nonselective beta-blockers interruption, spontaneous bacterial peritonitis and hepato-renal syndrome incidence. RESULTS: Three randomized controlled trials and 13 observational studies with 8279 patients were included. Overall survival was comparable between the two groups (hazard ratio = 0.86, 0.71-1.03, p = 0.11). Study design resulted as the main source of heterogeneity in sensitivity analysis and meta-regression. Mortality in refractory ascites patients was similar in the two groups (odds ratio = 0.90, 0.45-1.79; p = 0.76). No difference in spontaneous bacterial peritonitis (odds ratio = 0.78, 0.47-1.29, p = 0.33) and hepato-renal syndrome incidence (odds ratio = 1.22, 0.48-3.09; p = 0.67) was observed. Pooled rate of nonselective beta-blockers interruption was 18.6% (5.2-32.1%). CONCLUSIONS: Based on our findings, nonselective beta-blockers should not be routinely withheld in patients with cirrhosis and ascites, even if refractory.

Unusual association between corrected transposition of great arteries and supracardiac total anomalous pulmonary venous connection: a rare combination never reported before.

We describe the case of a 52-day-old child who was diagnosed with a rare combination of corrected transposition of great vessels - hypoplastic right ventricle with supracardiac total anomalous pulmonary venous connection.

Population diversity and adaptive evolution in keratinization genes: impact of environment in shaping skin phenotypes.

Several studies have demonstrated the role of climatic factors in shaping skin phenotypes, particularly pigmentation. Keratinization is another well-designed feature of human skin, which is involved in modulating transepidermal water loss (TEWL). Although this physiological process is closely linked to climate, presently it is not clear whether genetic diversity is observed in keratinization and whether this process also responds to the environmental pressure. To address this, we adopted a multipronged approach, which involved analysis of 1) copy number variations in diverse Indian and HapMap populations from varied geographical regions; 2) genetic association with geoclimatic parameters in 61 populations of dbCLINE database in a set of 549 genes from four processes namely keratinization, pigmentation, epidermal differentiation, and housekeeping functions; 3) sequence divergence in 4,316 orthologous promoters and corresponding exonic regions of human and chimpanzee with macaque as outgroup, and 4) protein sequence divergence (Ka/Ks) across nine vertebrate classes, which differ in their extent of TEWL. Our analyses demonstrate that keratinization and epidermal differentiation genes are under accelerated evolution in the human lineage, relative to pigmentation and housekeeping genes. We show that this entire pathway may have been driven by environmental selection pressure through concordant functional polymorphisms across several genes involved in skin keratinization. Remarkably, this underappreciated function of skin may be a crucial determinant of adaptation to diverse environmental pressures across world populations.

Transcatheter closure of ruptured sinus of Valsalva type IV with misleading severe aortic regurgitation.

We present an unusual case of ruptured sinus of Valsalva (RSOV) in the right atrium, progressive exertional dyspnea, occasional epigastric heaviness, and palpitations. The examination revealed high-pitch continuous murmur. On transthoracic echocardiography, there was a ~5-6 mm size RSOV of non-coronary sinus into right atrium, continuous turbulent flow, and unusual presentation of severe central aortic regurgitation jet with holodiastolic flow reversal seen in the descending aorta. The sinus of Valsalva aneurysm is a rare pathology, which is generally asymptomatic. In this case it manifested through a rupture into the right atrium and needed to be closed to relieve the symptoms. Transcathter closure of RSOV was done by using Amplatzer duct occluding device, there was no residual shunt, and aortic regurgitation completely disappeared. Learning objective: This is a unique case in which ruptured sinus of Valsalva flow and holodiastolic flow reversal were confused with severe aortic regurgitation. Careful and detailed transthoracic echocardiography played a key role in correct diagnosis and proper management.

Usefulness of Doppler derived end diastolic flow gradient across the patent ductus arteriosus in selecting coils for ductal occlusion.

Transcatheter closure of patent ductus arteriosus (PDA) with coils is accepted as an alternative to surgical ligation. We evaluated whether flow gradient across PDA, obtained by Doppler echocardiography, can aid in selecting coils for percutaneous ductal occlusion. 79 consecutive patients with PDA, who underwent successful percutaneous coil occlusion were retrospectively reviewed. Patients with other structural heart disease and pulmonary hypertension with right-to-left shunt were excluded. Echocardiogram and cardiac catheterization were done in all patients. Gianturco (Occluding Spring Emboli; Cook, Bloomington, IN) non-detachable coils of 0.038 and 0.052-inch core sizes were used for ductal occlusion. Trough diastolic gradient was correlated with the size and the number of coils used. Mean age was 8.6 years (range 1.3 to 27 years); 24 males and 55 females; PDA diameter ranged from 1.3 to 4.5 mm. Number of coils used varied from 1 to 4. Echocardiography measured PDA size was 2.5 ± 0.6 mm and significantly differed from angiographically measured size 2.9 ± 0.6 mm (P = 0.05). End diastolic gradient below 38 mmHg predicted use of multiple coils or coils with larger surface area. End diastolic gradient correlated inversely with total surface area of the coils, which indirectly predicted size and number of coils. Thus, the prediction of the size and the number of coils for PDA occlusion can be assisted by the trough diastolic gradients of PDA.

Enhancing biohydrogen production from sugar industry wastewater using Ni, Ni-Co and Ni-Co-P electrodeposits as cathodes in microbial electrolysis cells.

Microbial electrolysis cell (MEC) can be utilized for the simultaneous treatment of actual industry wastewater and biohydrogen production. However, efficient and cost-effective cathode, working at ambient conditions and neutral pH, are required to make the MEC as a sustainable technology. In this study, MEC with electrodeposited cathodes (co-deposits of Ni, Ni-Co and Ni-Co-P) were utilized to evaluate the treatment efficiency and hydrogen recovery of sugar industry wastewater. MECs operation was carried out at 30 ± 2 °C temperature in batch mode at an applied voltage of 0.6 V in neutral pH with sugar industry effluent (COD 4850 ± 50 mg L-1, BOD 1950 ± 20 mg L-1) and activated sludge as a source of microorganism. The Ni-Co-P electrodeposit on both cases achieved the maximum H2 production rate of 0.24 ± 0.005 m3(H2) m-3 d-1 and 0.21 ± 0.005 m3(H2) m-3 d-1 with ~50 % treatment efficiency for a 500 ml effluent in 7 days' batch cycles. It was also found that fabricated cathodes can treat real wastewater efficiently with considerable energy recovery than previously reported literature. This study showed the potentiality of the real-time industrial effluents treatment and biohydrogen production near to ambient atmospheric conditions that emphasizes the waste to energy bio-electrochemical system.

Premature coronary artery disease, risk factors, clinical presentation, angiography and interventions: Hospital based registry.

BACKGROUND & AIMS: Premature coronary artery disease (CAD) is endemic in India. We performed a study to identify risk factors, clinical presentation, angiographic findings and interventions in premature CAD. METHODS: Successive patients who underwent percutaneous intervention (PCI) were enrolled from January 2018 to June 2021. Premature CAD was defined as women 45-59 y and men 40-54 y and very premature as women <45 y and men <40 y. Descriptive statistics are presented. Univariate odds ratio (OR) and 95% confidence intervals (95%CI) were calculated to identify differences in various groups. RESULTS: 4672 patients (women 936, men 3736) were enrolled. Premature CAD was in 1238 (26.5%; women 31.9%; men 25.1%) and very premature in 212 (4.5%; women 6.5%, men 4.0%). In premature and very premature vs non-premature CAD, OR (95%CI) for high cholesterol ≥200 mg/dl [women 1.52(1.03-2.25) and 1.59(0.79-3.20); men 1.73(1.38-2.17) and 1.92(1.22-3.03)], non-HDL cholesterol ≥130 mg/dl [women 1.84(1.35-2.52) and 1.32(0.72-2.42); men 1.69(1.43-1.90) and 1.67(1.17-2.34)], LDL cholesterol [men 1.10(0.95-1.25) and 1.04(0.77-1.41)], and tobacco [women 1.40(0.84-2.35) and 2.14(0.95-4.82); men 1.63(1.34-1.98) and 1.27(0.81-1.97)] were higher while hypertension, diabetes and chronic kidney disease were more in non-premature(p < 0.05). Presentation as STEMI was marginally more in women with premature [1.13(0.85-1.51)] and very premature [1.29(0.75-2.22)] CAD and was significantly higher in men [1.35(1.16-1.56) and 1.79(1.29-2.49)]. Location and extent of CAD were not different. CONCLUSIONS: In India, a third of CAD patients presenting for coronary intervention have premature disease. Important risk factors are high total and non-HDL cholesterol and tobacco (men) with greater presentation as STEMI. Extent and type of CAD are similar to non-premature CAD indicating severe disease.

Genetic heterogeneity in Van der Woude syndrome: identification of NOL4 and IRF6 haplotype from the noncoding region as candidates in two families.

Van der Woude syndrome (VWS) shows an autosomal dominant pattern of inheritance with two known candidate genes, IRF6 and GRHL3. In this study, by employing genome-wide linkage analyses on two VWS affected families, we report the cosegregation of an intronic rare variant in NOL4 in one family, and a haplotype consisting of three variants in the noncoding region of IRF6 (introns 1, 8 and 3'UTR) in the other family. Using mouse, as well as human embryos as a model, we demonstrate the expression of NOL4 in the lip and palate primordia during their development. Luciferase, as well as miRNA-transfection assays show decline in the expression of mutant NOL4 construct due to the creation of a binding site for hsa-miR-4796-5p. In family 2, the noncoding region IRF6 haplotype turns out to be the candidate possibly by diminishing its IRF6 expression to half of its normal activity. Thus, here we report a new candidate gene (NOL4) and a haplotype of IRF6 forVWS, and highlight the genetic heterogeneity of this disorder in the Indian population.

Whole exome sequencing unveils a frameshift mutation in CNGB3 for cone dystrophy: A case report of an Indian family.

RATIONALE: Genetic elucidation of cone-dominated retinal dystrophies in Indian subcontinent is much needed to identify and catalog underlying genetic defects. In this context, the present study recruited a consanguineous Indian family affected with autosomal recessive cone dystrophy (CD). Considering the huge genetic heterogeneity and recessive inheritance of the disease, we chose to dissect out causal variant in this family by whole exome sequencing (WES). PATIENT CONCERNS: In the recruited family, three of the six siblings had complaints of poor visual acuity, photophobia, and disturbed colour vision since early childhood. Fundus examination disclosed vascular attenuation and macular retinal pigment epithelium (RPE) changes in all the affected siblings, signifying degeneration of photoreceptor cells. DIAGNOSIS: Complete clinical investigation and electroretinography studies led to the diagnosis of cone dystrophy in three siblings of the family. INTERVENTIONS: Detailed ophthalmic examination, including family history, visual function testing, and retinal imaging, was performed. We captured and sequenced exomes of 2 affected siblings and their mother using SureSelect Human All Exon V5 Kit on Illumina HiSeq 2000/2500 platform with 100 bp paired-end sequencing method. Candidates after data analysis were screened by segregation analysis and Sanger sequencing. Considering recessive inheritance and consanguinity in the pedigree, we attempted to map large loci homozygous by descent in the genome of patients using exome sequencing variants. Extensive protein modeling was carried out to assess possible consequences of the identified variant on the 3-dimensional structure of the protein. OUTCOMES: WES generated more than 65,000 variants for each individual. Assuming recessive inheritance, 13,026 variants were selected. Further filtering on the basis of their position in gene, class, and minor allele frequency constricted the huge list to 12 rare variants. Finally, we ascertained a single base deletion c.1148delC (p.Thr383fs) in the gene CNGB3 as the causal variant. This is a recurrent frameshift mutation resulting in truncated CNGB3 protein. We mapped a large 15-Mb stretch of homozygous markers spanning the causal variant in the proband. The gene CNGB3 encodes modulatory subunit of cyclic nucleotide-gated channels in cone photoreceptors. Protein modeling reveals loss of 2 transmembrane helices and conserved CAP_ED domain in truncated CNGB3, which eventually is predicted to form nonfunctional channels and hamper phototransduction. LESSONS: We have identified a recurrent mutation c.1148delC (p.Thr383fs) in CNGB3 for autosomal recessive CD. The present report provides the first description of CNGB3 mutation from India. It is also the foremost investigation of familial CD in Indian patients; therefore, it presents the primary genetic etiology of CD in India.

Radial left ventricular dyssynchrony by speckle tracking in apical versus non apical right ventricular pacing- evidence of dyssynchrony on medium term follow up.

INTRODUCTION: To study effects of various sites of right ventricular pacing lead implantation on left ventricular function by 2-dimensional (2D) speckle tracking for radial strain and LV dyssynchrony. METHODS: This was retrospective prospective study. Fifteen patients each with right ventricular (RV) apical (RV apex and apical septum) and non-apical (mid septal and low right ventricular outflow tract [RVOT]) were programmed to obtain 100% ventricular pacing for evaluation by echo. Location and orientation of lead tip was noted and archived by fluoroscopy. Electrocardiography (ECG) was archived and 2D echo radial dyssynchrony was calculated. RESULTS: The baseline data was similar between two groups. Intraventricular dyssynchrony was significantly more in apical location as compared to non-apical location (radial dyssynchrony: 108.2 ± 50.2 vs. 50.5 ± 24, P < 0.001; septal to posterior wall delay [SLWD] 63.5 ± 27.5 vs. 34 ± 10.7, P < 0.001, SPWD 112.5 ± 58.1 vs. 62.7 ± 12.1, P = 0.003). The left ventricular ejection fraction was decreased more in apical location than non apical location. Interventricular dyssynchrony was more in apical group but was not statistically significant. The QRS duration, QTc and lead thresholds were higher in apical group but not statistically significant. CONCLUSION: Pacing in non apical location (RV mid septum or low RVOT) is associated with less dyssynchrony by specific measures like 2D radial strain and correlates with better ventricular function in long term.

Mitral Stenosis, LV Aneurysm, Myocardial Bridge, and Myocardial Infarction: The Mystery Demystified.

Coronary embolisation, spontaneous coronary artery dissection, and myocardial bridges are rare causes of Myocardial Infarction (MI) in the youth. Here, we report a young male who developed myocardial infarction at the age of 19. Investigations revealed that he had mitral stenosis, myocardial bridge, and angiographic features of healed coronary dissection.

Cardiac rhabdomyoma in familial tuberous sclerosis.

Cardiac rhabdomyomas are often associated with tuberous sclerosis in infants. We report a 5 month old child presented with a tumor in the right ventricle and echocardiography features of rhabdomyoma. Both the child and her father had cutaneous features of tuberous sclerosis. In the absence of features of congestive heart failure, surgery is rarely required.

Neovascularization in left atrial myxoma.

ABSTRACT: We report a case with a left atrial mass who underwent coronary angiography to rule out coronary artery disease. Coronary angiography revealed an anomalous tortuous vascular structure originating from the left circumflex coronary artery to the left atrial tumor suggestive of neovascularization. Preoperative coronary angiography is useful for coronary artery evaluation and also provides additional information regarding the feeding vessel supplying the mass.

Clinical profile of patients hospitalized with heart failure in Bharatpur, Nepal.

INTRODUCTION: Heart failure (HF) is a common cardiovascular condition whose incidence and prevalence are increasing. Being a common reason for urgent hospital admission, it is a major cause of morbidity and mortality for the patients. In the developed countries coronary artery disease remains the leading cause of HF, whereas, in the underdeveloped countries, rheumatic heart disease leading to valvular lesion still remains the commonest causes of HF admission.The current study was designed to evaluate the clinical profile and medications prescribed reflecting the extent to which evidence based medicine is being practiced at our community. METHODS: Clinical profile and prescribed medications of patients with diagnosis of HF who were admitted in the cardiology department of College of Medical Sciences & Teaching Hospital (CMS-TH), Bharatpur, Nepal, April 2010 to May 2012, were analyzed. A total of 255 patients presented with HF during the studied period were included. RESULTS: Coronary artery disease, rheumatic heart disease, dilated cardiomyopathy, hypertensive heart failure, cor-pulmonale, and congenital heart disease leading to HF were found in 93 (36.5%), 65 (25.5%), 37 (14.5%), 22 (8.6%), 31 (12.2%),and 7 (2.7%) patients respectively. The commonest presenting symptom was shortness of breath (81%) and the commonest sign was bilateral basal crepitations (68%). From all patients, 89%, 64%, 51%, 16%, 48%, and 32% received loop diuretics, angiotensin-converting enzyme inhibitor, digoxin, angiotensin receptor blocker, spironolactone, and beta-blocking agents respectively. CONCLUSION: Coronary artery disease leading to HF was the commonest cause of HF admission in our centre. Despite current guidelines suggesting the use of beta-blocking agent in patients with HF, only 32% of our patients received this class of medications. Thus, many patients were not being managed fully in accordance with the evidence-based guidelines.

IGVBrowser--a genomic variation resource from diverse Indian populations.

The Indian Genome Variation Consortium (IGVC) project, an initiative of the Council for Scientific and Industrial Research, has been the first large-scale comprehensive study of the Indian population. One of the major aims of the project is to study and catalog the variations in nearly thousand candidate genes related to diseases and drug response for predictive marker discovery, founder identification and also to address questions related to ethnic diversity, migrations, extent and relatedness with other world population. The Phase I of the project aimed at providing a set of reference populations that would represent the entire genetic spectrum of India in terms of language, ethnicity and geography and Phase II in providing variation data on candidate genes and genome wide neutral markers on these reference set of populations. We report here development of the IGVBrowser that provides allele and genotype frequency data generated in the IGVC project. The database harbors 4229 SNPs from more than 900 candidate genes in contrasting Indian populations. Analysis shows that most of the markers are from genic regions. Further, a large fraction of genes are implicated in cardiovascular, metabolic, cancer and immune system-related diseases. Thus, the IGVC data provide a basal level variation data in Indian population to study genetic diseases and pharmacology. Additionally, it also houses data on ∼50,000 (Affy 50 K array) genome wide neutral markers in these reference populations. In IGVBrowser one can analyze and compare genomic variations in Indian population with those reported in HapMap along with annotation information from various primary data sources. Database URL: http://igvbrowser.igib.res.in.

Mapping human genetic diversity in Asia.

Asia harbors substantial cultural and linguistic diversity, but the geographic structure of genetic variation across the continent remains enigmatic. Here we report a large-scale survey of autosomal variation from a broad geographic sample of Asian human populations. Our results show that genetic ancestry is strongly correlated with linguistic affiliations as well as geography. Most populations show relatedness within ethnic/linguistic groups, despite prevalent gene flow among populations. More than 90% of East Asian (EA) haplotypes could be found in either Southeast Asian (SEA) or Central-South Asian (CSA) populations and show clinal structure with haplotype diversity decreasing from south to north. Furthermore, 50% of EA haplotypes were found in SEA only and 5% were found in CSA only, indicating that SEA was a major geographic source of EA populations.

Non-random genomic divergence in repetitive sequences of human and chimpanzee in genes of different functional categories.

Sequencing of the human and chimpanzee genomes has revealed approximately 99% similarity in the coding sequence between both the species, which in no way parallels the observable phenotypic differences. Contribution of the non-coding sequences which comprise a bulk of the genome, in functional divergence between human and chimpanzee, is largely understudied. In this context, we have compared extents of divergence in the non-coding repetitive DNA in a data set of well-classified neuronal and housekeeping genes between human and chimpanzee. The coding regions of these genes have earlier been extensively compared between the two species. It was revealed that the neurodevelopmental genes show accelerated evolution compared to neurophysiology and housekeeping genes in human. In this study, comparative analysis in terms of repeat spectrum, divergence in dinucleotide content density, JC divergence and its partitioning in repeats versus unique regions and transcription factor binding sites indicate different extents of functional constraints associated with the non-coding repeat regions. The constraints are also different when the upstream and downstream genic regions are compared across the functional categories. The neurodevelopmental genes seem to diverge more in the genic regions, whereas the neurophysiology genes show higher divergence in the upstream 2 kb region. Most of the divergence observed in the housekeeping genes is contributed by repeats. We also observe an accumulation of function-specific transcription factor profiles in the human lineage. Interestingly, a major fraction of the regulatory sites in these regions is differently partitioned in the repetitive sequences which in turn is dependant upon the relative distribution of the repeats across the functional categories. Thus, differential distribution of repeats across the various functional categories could have substantial effects on genome wide regulation and structure. The insights obtained from this study further add a new facet to the contribution of non-coding factors especially repeats in divergence of human and chimpanzee.