Variations in the anatomical and branching pattern of the left coronary artery: a cadaveric study

Background: Coronary arteries are the branch of ascending aorta and it is the main arterial supply of the myocardium of the heart. Left coronary artery (LCA) usually arises from left posterior aortic sinus. The site of manifestation of myocardial infarction depends on the occlusion of an artery or its branches involved in atherosclerosis. To know the site of lesion and occlusion of the particular artery, detailed anatomy of its course, branches and variations to be studied in detail.Methods: Study was conducted on 55 heart specimens in Department of Anatomy at Sri Siddhartha Medical College (SSMC), Sri Siddhartha Academy of Higher Education (SSAHE). The left coronary artery was dissected carefully, and it was traced from its origin. Any variation in the course and branching pattern was recorded and photographed.Results: No variation was found in the origin of LCA. In the present study, the most frequent division pattern of the left coronary artery was observed as the bifurcation in 30 specimens (54.54%) followed by trifurcation in 23 specimens (41.82%). Tetrafurcation and pentafurcation of LCA were observed in one specimen each (1.82%).Conclusions: Our study tries to focus on branching pattern of LCA for the better knowledge of accurate diagnosis and therapeutic intervention in the management of coronary artery diseases

Structure and dynamics of the active Gs-coupled human secretin receptor

The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding of SecR binding and activation is important for its therapeutic exploitation. We combined cryo-electron microscopy, molecular dynamics, and biochemical cross-linking to determine a 2.3 Å structure, and interrogate dynamics, of secretin bound to the SecR:Gs complex. SecR exhibited a unique organization of its extracellular domain (ECD) relative to its 7-transmembrane (TM) core, forming more extended interactions than other family members. Numerous polar interactions formed between secretin and the receptor extracellular loops (ECLs) and TM helices. Cysteine-cross-linking, cryo-electron microscopy multivariate analysis and molecular dynamics simulations revealed that interactions between peptide and receptor were dynamic, and suggested a model for initial peptide engagement where early interactions between the far N-terminus of the peptide and SecR ECL2 likely occur following initial binding of the peptide C-terminus to the ECD

Thalassemias in South Asia:clinical lessons learnt from Bangladesh

Abstract Thalassemias are emerging as a global public health concern. Due to remarkable success in the reduction of childhood mortality by controlling infectious diseases in developing countries, thalassemias are likely to be a major public health concern in the coming decades in South Asia. Despite the fact that Bangladesh lies in the world’s thalassemia belt, the information on different aspects (epidemiology, clinical course, mortality, complications and treatment outcomes) of thalassemias is lacking. In this comprehensive review, the aim is to to depict the epidemiological aspects of thalassemias, mutation profile and current treatment and management practices in the country by sharing the experience of dealing with 1178 cases over 2009–2014 time periods in a specialized thalassemia treatment centre. We have also discussed the preventative strategies of thalassemias from the context of Bangladesh which could be effective for other developing countries

A novel fluorescein-bisphosphonate based diagnostic tool for the detection of hydroxyapatite in both cell and tissue models

Abstract A rapid and efficient method for the detection of hydroxyapatite (HAP) has been developed which shows superiority to existing well-established methods. This fluorescein-bisphosphonate probe is highly selective for HAP over other calcium minerals and is capable of detecting lower levels of calcification in cellular models than either hydrochloric acid-based calcium leaching assays or the Alizarin S stain. The probe has been shown to be effective in both in vitro vascular calcification models and in vitro bone calcification models. Moreover we have demonstrated binding of this probe to vascular calcification in rat aorta and to areas of microcalcification, in human vascular tissue, beyond the resolution of computed tomography in human atherosclerotic plaques. Fluorescein-BP is therefore a highly sensitive and specific imaging probe for the detection of vascular calcification, with the potential to improve not only ex vivo assessments of HAP deposition but also the detection of vascular microcalcification in humans

Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategy

Background Nephronophthisis associated ciliopathies (NPHP-AC) comprise a group of autosomal recessive cystic kidney diseases that includes nephronophthisis (NPHP), Senior-Loken syndrome (SLS), Joubert syndrome (JBTS), and Meckel-Gruber syndrome (MKS). To date, causative mutations in NPHP-AC have been described for 18 different genes, rendering mutation analysis tedious and expensive. To overcome the broad genetic locus heterogeneity, a strategy of DNA pooling with consecutive massively parallel resequencing (MPR) was devised.Methods In 120 patients with severe NPHP-AC phenotypes, five pools of genomic DNA with 24 patients each were prepared which were used as templates in order to PCR amplify all 376 exons of 18 NPHP-AC genes (NPHP1, INVS, NPHP3, NPHP4, IQCB1, CEP290, GLIS2, RPGRIP1L, NEK8, TMEM67, INPP5E, TMEM216, AHI1, ARL13B, CC2D2A, TTC21B, MKS1, and XPNPEP3). PCR products were then subjected to MPR on an Illumina Genome-Analyser and mutations were subsequently assigned to their respective mutation carrier via CEL I endonuclease based heteroduplex screening and confirmed by Sanger sequencing.Results For proof of principle, DNA from patients with known mutations was used and detection of 22 out of 24 different alleles (92% sensitivity) was demonstrated. MPR led to the molecular diagnosis in 30/120 patients (25%) and 54 pathogenic mutations (27 novel) were identified in seven different NPHP-AC genes. Additionally, in 24 patients only single heterozygous variants of unknown significance were found.Conclusions The combined approach of DNA pooling followed by MPR strongly facilitates mutation analysis in broadly heterogeneous single gene disorders. The lack of mutations in 75% of patients in this cohort indicates further extensive heterogeneity in NPHP-AC

An efficient method to prepare magnetic hydroxyapatite-functionalized multi-walled carbon nanotubes nanocomposite for bone defects

Hydroxyapatite-functionalized multi-walled carbon nanotube (HA-fMWCNT) magnetic nanocomposite was successfully prepared using a novel slurry-compounding method. The prepared HA-fMWCNT nanocomposite with the addition of small amount (0.5 wt%) of fMWCNT exhibited much greater improvement in mechanical properties due to strong interfacial adhesion between acid-treated MWCNTs fillers and HA matrix, thus efficient stress transfer to nanotubes from the matrix. The nanocomposite exhibited excellent haemocompatibility. Fractographic analysis was performed in order to understand the fracture behavior and toughening mechanisms. The fracture mechanisms and micro-deformation were examined by studying the microstructure of arrested crack tips using field emission scanning electron microscopy (FESEM). The origination and formation of microcracks are the dominant fracture mechanisms and micro-deformation in the HA-fMWCNTs nanocomposite. The developed new method enables to the fabrication of magnetic HA-fMWCNTs nanocomposite with superior mechanical performance may be potential for application as high load-bearing bone implants in the biomedical field

Multifunctional hierarchical graphene-carbon fiber hybrid aerogels for strain sensing and energy storage

Graphene oxide nanosheets can be assembled into multifunctional graphene aerogels for sensing and energy storage applications. However, due to strong van der Waals forces, reduced graphene oxide nanosheets often stack together, significantly compromising their performance. Here, we demonstrate high-performance multifunctional hybrid carbon aerogels by hybridizing graphene oxide nanosheets with functionalized carbon fibers using a hydrothermal assembly method followed by two-step freezing, natural drying, and annealing. We compared the difference between carbon microfibers and carbon nanofibers. Our results show that flexible carbon nanofibers can enable more bindings with graphene nanosheets, creating stabler three-dimensional structures and enabling more efficient electron transfer. The resulting hybrid graphene aerogels have a high compressive strength of 56.7 kPa at 50% strain, an electrical conductivity of 3.072 S m−1, and a strain-responsive electrical response sensitivity of 11.3 k Pa−1 in a low-pressure range of 0–0.15 kPa. These hybrid carbon aerogels were applied in strain sensors to detect various human bio-signals. Furthermore, they were used as free-standing electrodes in flexible supercapacitors, demonstrating satisfactory energy storage performances. Overall, we show that three-dimensional graphene-carbon nanofiber hybrid aerogels have excellent multifunctional properties for applications in flexible electronics and energy storage devices. Graphical abstract: [Figure not available: see fulltext.]