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    Controlled cross-linking of porcine cholecyst extracellular matrix for preparing tissue engineering scaffold. Biomed Mater Res. part B

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    Treatment with cross‐linking agents for stabilizing biomolecules is an integral step during the preparation of many extracellular matrix‐based tissue engineering scaffolds from mammalian organs. However, excess cross‐linking may cause nonavailability of biomolecules and consequent deterioration of bioinductive properties of the scaffold. The present study considered controlling the extent of cross‐linking in a porcine cholecyst extracellular matrix scaffold prepared by a nonenzymatic and nondetergent method, by ex situ incubation of the source organ in varying concentrations of neutral buffered formaldehyde (10, 4, 1 or 0%; v/v) for in situ cross‐linking of biomolecules. Reduction of the formaldehyde concentration resulted in an increase in the extent of biodegradation and a decrease in the compactness of the mesh‐like surface microarchitecture of the scaffold. Retention of collagen was maximum when treated with 10% neutral buffered formaldehyde without any variation in the content of elastin and sulphated glycosaminoglycans. Although there was a reduction in the quantity of growth factors following the cross‐linking, fibroblasts remained viable on the scaffolds. The retention of major biomolecule was maximum and autodigestion was minimum in the scaffold prepared by the ex situ treatment of cholecyst in 10% neutral buffered formalin and found suitable for preparing the tissue engineering scaffold

    Correlation between pulsatility index (pi) in transcranial doppler (tcd) and cognitive profile of patients with alzheimer’s dementia and vascular dementia

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    The World Health Organization (WHO) predicts that by 2025, about 3/4th of the estimated 1.2 billion people aged >60 years will reside in developing countries1 . 4.6 million new cases of dementia are added every year, and the highest rate of growth is expected in South Asian countries including India. Education attainment is known to protect against dementia. Diet and lifestyle can also influence risk of dementia, and studies suggest that disorders affecting the vascular system, such as hypertension, diabetes mellitus and obesity, increase the risk for dementia, including Alzheimer's disease (AD). There is increasing evidence linking cerebral hypoperfusion and neurodegeneration, specifically in Alzheimer’s disease (AD) and vascular dementia (VaD)2 . In the Rotterdam study3 , cerebral hypoperfusion was demonstrated to be a risk or an aggravating factor in dementia. Hypoperfusion because of microangiopathy, macroangiopathy or cardiac dysfunction can promote or accelerate neurodegeneration, blood-brain barrier disruption and neuroinflammation.4 Diagnostic tools that can provide real-time functional assessment of the cerebrovascular tree can have a significant impact on our understanding of the vascular contribution to neurodegeneration at different stages of cognitive decline. Ultrasound can evaluate the cerebrovascular tree for pathological structure and functional changes contributing to cerebral hypoperfusion. Studies have shown an association between leukoaraiosis and transcranial doppler (TCD) pulsatility index (PI) in several kinds of patients.5 Despite increasing evidence supporting the utility of these methods in detection of microvascular pathology, cerebral hypoperfusion, neurovascular unit dysfunction and disease progression, non-availability for routine use and incomplete standardisation limit their use in daily routine. Studies have evaluated the utility of Middle cerebral artery-Pulsatility index (MCA PI) to differentiate between AD and VaD and have found conflicting results.6 PI has been correlated with severity of cognitive decline in few studies. Studies have also evaluated correlation of PI with decline in cognition. However, correlation of PI with detailed cognitive profile has not been evaluated. In this background, we planned our study to assess whether MCA PI can be used to differentiate between patients with AD and VaD. Also, we propose that increase in PI correlates with severity of cognitive deficit in patients with dementia

    Myocardial t1 mapping: relation of t1 values to myocardial perfusion, early gadolinium enhancement and late gadolinium enhancement in hypertrophic cardiomyopathy

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    Hypertrophic cardiomyopathy (HCM) is a disorder of myocardium with a genetic basis, characterized by an increase in myocardial thickness, non-dilated left ventricle and increased in ejection fraction(1). Incidence is believed to be 1 in 500 people(2) with heterogeneous phenotypic expression. Natural history is variable presenting as sudden cardiac death, heart failure or arrhythmias. HCM is usually a diagnosis of exclusion, while other ethology of LV hypertrophy needs to be ruled out. Most common differential diagnosis are hypertension, valvular heart diseases and infiltrative cardiomyopathies(2). HCM is defined as a wall thickness of > 15 mm either any echocardiography, Computed tomography or cardiac magnetic resonance imaging (CMR), without any identifiable cause(3). Cardiac involvement is usually asymmetric, most commonly involving the basal septum, followed by apical and mid cavity involvement. Echocardiogram is usually the first modality for diagnosis and assessment of HCM. CMR is the established modality for diagnosis, risk stratification, and management of the patients diagnosed with HCM. Myocardial fibrosis has proven to be associated with severe hypertrophy, and an increase in fibrosis reflects onto failing LV function and risk of sudden cardiac death secondary to arrythmias in patients of HCM(4). Myocardial fibrosis determined by Late gadolinium enhancement (LGE) has been established as the maker for future risk of sudden cardiac death(5). Increase in myocardial crypts in phenotype positive HCM is associated with particular gene mutations(6). These crypts can be assessed using Early gadolinium enhancement (EGE) sequence which can predict areas of subtle changes even before fibrosis sets in. Assessment of LGE requires CMR contrast for fibrosis quantification. T1 mapping is a novel technique which can assess the local/diffuse fibrosis without the requirement of an MR contrast agent. Native T1 maps have proven to be a cost-effective method or fibrosis assessment without 10 exposure to gadolinium-based contrast agent(7). Microvascular perfusion defects in HCM patients is an important marker of prognosis and future arrhythmic episodes causing sudden cardiac death(8). This study was aimed at determining the relationship between Early gadolinium enhancement (EGE)/Late gadolinium enhancement (LGE) and native T1 values in patients of hypertrophic cardiomyopathy

    Ultrasound guided parasternal modified intercostal nerve block: role as a preemptive analgesic adjunt in fast tracking for mitigating postoperative sternotomy pain

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    Fear of uncontrolled pain is among the primary concerns of many patients who are about to undergo surgery. Pain affects patients physiological and psychological recovery (1). Adequate postoperative analgesia prevents unnecessary patient discomfort, may decrease morbidity, may decrease postoperative hospital lengths of stay, and thus may decrease costs. So aggressive implementation of well-planned pain management strategy is crucial for decreasing post-sternotomy pain and resultant morbidity and mortality in cardiothoracic surgeries (2)(3). Inadequate analgesia and/or an uninhibited stress response during the postoperative period may increase morbidity by causing adverse hemodynamic, metabolic, immunologic, and hemostatic alterations. Analgesic medication modalities, providing optimal relief from pain-anxiety, can facilitate early tracheal extubation, with minimal compromise on airway-reflexes during post-tracheal extubation period after cardiac surgery. This would result in optimal patient comfort-satisfaction without any post-operative pain (4).Also in the recent years, a multimodal approach utilizing combined regional and systemic analgesics with different mechanisms of action has been found to be promising and beneficial in terms of treating acute pain and preventing chronic pain after cardiac surgery. Pre-emptive analgesia execution assumes a critical role in blunting traumatic or surgical damage induced stimulus modification in both peripheral and central nervous system, and therefore this modality must be considered during the decision making of preoperative analgesic techniques (5)(6)

    Role of quantitative susceptibility weighted imaging in evaluating disease activity of lesions in multiple sclerosis

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    Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system. Majority of the patients start with a relapsing –remitting course, which has clearly defined episode of neurologic disability and recovery. Pathologic hallmark of MS was presence of focal plaques in white and gray matter associated with heavy infiltration of macrophages with myelin debris, lymphocytes, and large reactive multinucleated astrocytes called Creutzfeldt-Peters cells1 . The etiologic mechanism underlying this demyelinating disease is generally believed to be autoimmune inflammation however the intial triggerer and the further development of CNS plaques are not well established1 . Conventional magnetic resonance imaging (MRI) has been used routinely to diagnose and monitor the disease spatially and temporally. The use of conventional MRI to measure the disease activity and assess effects of therapy is now standard in clinical practice and drug trials. T2-weighted imaging (T2WI) is highly sensitive in the detection of hyperintensities in white matter but, hyperintensities on T2WI can correspond to a wide spectrum of pathology, ranging from edema and mild demyelination to lesions in which the neurons and supporting glial cells are replaced by glial scars or liquid necrosis. In MS , gadolinium enhancement on T1-weighted imaging (T1WI) can suggest an acute inflammation, which is a marker of disease activity2,3. It is becoming a consensus among many studies that iron is enriched within oligodendrocytes and myelin in both normal and diseased tissue. One explanation for such findings proposes that iron is associated with the biosynthetic enzymes of myelinogenesis4 . In MS , stages of relapse and remission alternate during disease progression, identification and characterization of active lesions are critical for correct diagnosis and therapy. In clinical practice, current active lesion assessment is based on gadolinium (Gd) enhancement on T1-weighted MR imaging2,3. However, because Gd enhancement reflects leakage of the blood-brain barrier, it is considered as an indirect measure of inflammation that is preceded and outlasted by infiltration of immune cells. The 8 activation of resident innate immune cells may not be captured on T1WI Gd5 . In addition, concerns over repeated Gd exposure have recently been raised, as new data showing long term Gd retention in the brain of patients with normal renal function who have undergone multiple Gd injections is emerging. In patients with MS in whom Gd retention seems also to be associated with secondary progression of the disease. 6,7 Therefore it has become a necessity to identify a ‗Gd-enhancing‘ or ‗active MS‘ lesions without the use of a contrast agent to reduce scan time, cost, Gd accumulation and adverse effects. A non-contrast based imaging modality to detect active lesions also helps in routine follow up / monitoring of MS patients on therapy. It is known that microglia and macrophages in an alternative activation, M2 type macrophages (ferritin poor macrophages) remove myelin debris from MS lesions which usually accumulate in the periphery of the active lesion, 8 whereas the classic pro inflammatory M1 type macrophages (ferritin rich macrophages)- which tend to accumulate iron- was more commonly present in the chronic lesions9 . Both M1 and M2 type macrophage accumulation varies in different types of lesions which may result in change in susceptibility values and iron content in them. Susceptibility weighted imaging (SWI) has been shown to be very sensitive to iron in the form of hemosiderin, ferritin, and deoxyhemoglobin, offering the ability to measure iron on the order of several µg/g of tissue in vivo10,11. SWI is a 3D, high-resolution, fully flow compensated gradient-echo sequence that uses magnitude and phase data both separately and together to enhance information about local tissue susceptibility. In the past, phase images were seldom used because artifacts from the background field destroyed the integrity of small changes seen in pristine tissue. As we know now, phase images contain a wealth of information that may not be observed from the magnitude images. Recently, SWI-filtered phase images were used to map out putative iron content in the brain11,12. Phase images are a direct measure of the sources of local susceptibility changes. MR imaging have demonstrated 9 that, the magnetic susceptibility of an MS lesion changes rapidly as the lesion evolves longitudinally which can be measured by various iron quantification methods. Our study was designed to assess whether Quantitative SWI (Routine SWI) is a viable technique to identify active enhancing MS lesions without Gd injection. In this study, we explore the routine SWI imaging with quantification of phase values and iron content. To best of our knowledge, this is the first study , in which the routinely available SWI sequence was used for quantification of iron content in MS lesions. The goal of this study is to investigate whether the measured phase values and iron content in the lesions will differentiate active lesions from inactive lesions

    Black phosphorous, a prospective graphene substitute for biomedical applications

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    2D materials have gained spectacular status across various scientific and technological disciplines owing to their exceptional unique properties. The very recent member of 2D family, Black Phosphorus monolayers, known as Phosphorene have attracted recent scientific attention since its first exfoliation and appreciable rediscovery in 2014. Compared to other 2D materials and graphene analogs, it has outstanding properties like tunable band gap, good carrier mobility, excellent ON-OFF current ratio, potent in vivo biocompatibility and non-toxic biodegradability. Although the outlook of this material seems to be a promising candidate for future biomedical technology, its practical applications are still highly challenging. Unveiling those challenges by proper characterization and functionalization makes this material a mile stone for future theranostic and biomedicine scenario. This review has given precise attention to familiarize with the unique fundamental properties of black phosphorus, which makes it an excellent platform for future biomedical applications. Also underlines various synthesis procedures applicable for BP nanosheets and quantum dot synthesis. Its various biomedical applications including biosensors, cancer therapy, imaging and photothermal/photo acoustic/photodynamic therapy, drug delivery, neuronal regeneration, 3D printing scaffold etc., are subsequently reviewed. Furthermore this review briefly focused on the toxicity of this emerging material

    PEG grafted chitosan scaffold for dual growth factor delivery for enhanced wound healing

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    Application of growth factors at wound site has improved the efficiency and quality of healing. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) induce proliferation of various cells in wound healing. Delivery of growth factor from controlled release systems protect it from degradation and also result in sustained delivery of it at the site of injury. The goal of the study was to develop a Polyethylene glycol (PEG) cross-linked cotton-like chitosan scaffold (CS-PEG-H) by freeze-drying method and chemically conjugate heparin to the scaffold to which the growth factors can be electrostatically bound and evaluate its wound healing properties in vitro and in vivo. The growth factor containing scaffolds induced increased proliferation of HaCaT cells, increased neovascularization and collagen formation seen by H and E and Masson’s trichrome staining. Immunohistochemistry was performed using the Ki67 marker which increased proliferation of cells in growth factor containing scaffold treated group. Frequent dressing changes are a major deterrent to proper wound healing. Our system was found to release both VEGF and bFGF in a continuous manner and attained stability after 7 days. Thus our system can maintain therapeutic levels of growth factor at the wound bed thereby avoiding the need for daily applications and frequent dressing changes. Thus, it can be a promising candidate for wound healing

    Morphological abnormalities in hypertrophic cardiomyopathy - a cardiac mri based study

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    Hypertrophic cardiomyopathy (HCM) has a varied clinical course due to its genotypic and phenotypic heterogeneity. Several autopsy studies have shown abnormalities of the mitral valve in some HCM patients. Cardiovascular magnetic resonance (CMR) has become the imaging modality of choice due to its high spatial resolution, well suited to define the diverse phenotypic expression of this complex disease. HCM has been documented to have various mitral valve abnormalities like an increased length of the leaflets and area, leaflet thickening, impaired mitral leaflet coaptation, and left ventricular outflow tract obstruction (LVOT) due to the systolic anterior motion of the mitral leaflets. Cardiovascular magnetic resonance (CMR) provides an excellent opportunity to assess the papillary muscle (PM) abnormalities like an increased number and mass, bifidity, hypertrophy, antero-apical displacement and LGE of the papillary muscle. Various guidelines recommend surgical myectomy as the preferred modality for patients with left ventricular outflow tract (LVOT) gradient ≥50 mm Hg who fail to respond to medications or who experience side effects. Alcohol septal ablation (ASA) in patients with mitral valve abnormalities results in persistent SAM, gradients, and mitral regurgitation (MR)

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