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2.
J Card Surg ; 34(8): 714-716, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31376176

RESUMO

The pooled estimate of a recent meta-analysis concluded that rate of reoperation at 1 year was significantly higher in Aortic valve repair (8.82% vs 3.70%) as compared with aortic valve replacement in patients with aortic regurgitation (odds ratio = 2.67, 95% confidence interval [1.08, 3.62], P = .03). We performed a trial sequential analysis using the published data of the meta-analysis and found the evidence is not strong enough for the conclusion.

5.
Biosens Bioelectron ; 142: 111526, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31362203

RESUMO

Efficient manipulation of micro biological cells has always been a very important task in healthcare sector for which a Micro Electro Mechanical System (MEMS) based impedance flow cytometry has been proven to be a promising technique. This technique utilise the advantage of dielectrophoresis (DEP) force which is generated by non-uniform electric field in a microfluidic channel using an appropriate external AC supply at certain frequency range. The DEP forces generated in micro-channel depend upon various biological and physical parameters of cell and suspending medium. Apart from that design parameters of microfluidic channel and dimension of electrodes used for generating DEP action also plays major role in micro cell/bead manipulation. This article give remarks on the operating parameters which affects the cell manipulation and interrogates the currently accepted various electrode orientations in microfluidic MEMS flow cytometer technologies for effective manipulation of micro entities like healthy human cells (T-lymphocytes, B- lymphocytes, Monocytes, Leukocytes erythrocytes and human kidney cells HEK293), animal cells (neuroblastoma N115 and sheep red blood cells), cancer cells (MCF-7, MDA-435 and CD34+), yeast cells (saccharomyces cerevisiae, listeria innocua and E. coli) and micro particles (polystyrene beads) based on their dielectric properties using DEP action. Article focuses on the key electrode orientations for generation of non-uniform electric field in microfluidic flow cytometer like tapered electrodes, trapezoidal electrode arrays, Interdigitated electrodes, curved microelectrode and 3D electrode orientations and give remarks on their advantages and limitations. The cell manipulation with current MEMS impedance flow cytometry orientations targeting possibilities of implementation of the lab-on-chip devices has been discussed.

6.
Sci Rep ; 9(1): 9825, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285443

RESUMO

Microbial pattern recognition critically contributes to innate response, both at extracellular and intracellular cytosolic surveillance pathway (CSP) interface. However, the role of pattern recognition by host innate receptors in CSP is poorly understood in Leishmania donovani infection. Here, we have demonstrated that cytosolic targeting of L.donovani DNA (Ld-DNA) inhibits macrophage responsiveness to IFNÉ£, through decreased MHC-II expression and lowered pSTAT1 (Y701) levels, involving host three-prime repair exonuclease-1 (TREX-1). The Ld-DNA potently induced type-1 IFNs, i.e. significant over-production of IFNß through activation of the IRF pathway. Interestingly, knockdown of TRIF or MyD88 expression in macrophages had no effect on cytosolic Ld-DNA transfection-mediated IFN-ß production, indicating involvement of a TLR independent pathway. Contrastingly, Ld-DNA failed to induce IFNß in both TBK-1 and IRF3KO knockout macrophages. Although IFNß was not induced by Ld-DNA in STING- knockout macrophages, STING alone was not enough for the induction. Evidently, besides STING, Ld-DNA recognition for induction of IFNß critically required cytosolic cyclic GMP-AMP synthase (cGAS). Furthermore, the cGAS dependent targeting of Ld-DNA induced IFNß over-production that contributed to antimony resistance in L.donovani infection. We provide the first evidence that enhanced cytosolic sensing of Ld-DNA in infection by antimony resistant (SBR-LD), but not antimony sensitive L.donovani strains (SBS-LD), was critically regulated by host MDRs, multi drug resistant associated protein 1 (MRP 1) and permeability glycoprotein (P-gp) in macrophages. Collectively, our results disclose Ld-DNA as a vital pathogen associated molecular pattern (PAMP) driving host Type-I IFN responses and antimony resistance. The findings may help in future development of policies for novel anti-leishmanial therapeutics.

7.
Pediatr Blood Cancer ; : e27929, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31339233

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation, often associated with genetic defects of lymphocyte cytotoxicity. Though a distinctive constellation of features has been described for HLH, diagnosis remains challenging as patients have diverse presentations associated with a variety of triggers. We propose two concepts to clarify how HLH is diagnosed and treated: within the broader syndrome of HLH, "HLH disease" should be distinguished from "HLH disease mimics" and HLH subtypes should be categorized by specific etiologic associations, not the ambiguous dichotomy of "primary" and "secondary." We provide expert-based advice regarding the diagnosis and initiation of treatment for patients with HLH, rooted in improved understanding of its pathophysiology.

8.
Angiology ; : 3319719865670, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331187
10.
Molecules ; 24(12)2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31213016

RESUMO

Nucleosome Assembly Protein (NAP) is a highly conserved family of histone chaperones present in yeast, animals, and plants. Unlike other organisms, plants possess an additional class of proteins in its NAP family, known as the NAP1-related proteins or NRP. Arabidopsis thaliana possesses two NRP isoforms, namely AtNRP1 and AtNRP2, that share 87% sequence identity. Both AtNRP1 and AtNRP2 get expressed in all the plant tissues. Most works in the past, including structural studies, have focused on AtNRP1. We wanted to do a comparative study of the two proteins to find why the plant would have two very similar proteins and whether there is any difference between the two for their structure and function as histone chaperones. Here we report the crystal structure of AtNRP2 and a comparative analysis of its structural architecture with other NAP family proteins. The crystal structure of AtNRP2 shows it to be a homodimer, with its fold similar to that of other structurally characterized NAP family proteins. Although AtNRP1 and AtNRP2 have a similar fold, upon structural superposition, we find an offset in the dimerization helix of the two proteins. We evaluated the stability, oligomerization status, and histone chaperoning properties of the two proteins, for a comparison. The thermal melting experiments suggest that AtNRP2 is more stable than AtNRP1 at higher temperatures. In addition, electrophoretic mobility shift assay and isothermal titration calorimetry experiments suggest histone binding ability of AtNRP2 is higher than that of AtNRP1. Overall, these results provide insights about the specific function and relevance of AtNRP2 in plants through structural and biophysical studies.

11.
IEEE Trans Cybern ; 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31251204

RESUMO

Visual tracking is a complex problem due to unconstrained appearance variations and a dynamic environment. The extraction of complementary information from the object environment via multiple features and adaption to the target's appearance variations are the key problems of this paper. To this end, we propose a robust object tracking framework based on the unified graph fusion (UGF) of multicue to adapt to the object's appearance. The proposed cross-diffusion of sparse and dense features not only suppresses the individual feature deficiencies but also extracts the complementary information from multicue. This iterative process builds robust unified features which are invariant to object deformations, fast motion, and occlusion. Robustness of the unified feature also enables the random forest classifier to precisely distinguish the foreground from the background, adding resilience to background clutter. In addition, we present a novel kernel-based adaptation strategy using outlier detection and a transductive reliability metric. The adaptation strategy updates the appearance model to accommodate variations in scale, illumination, and rotation. Both qualitative and quantitative analyses on benchmark video sequences from OTB-50, OTB-100, VOT2017/18, and UAV123 show that the proposed UGF tracker performs favorably against 18 other state-of-the-art trackers under various object tracking challenges.

12.
J Infect ; 79(2): 139-152, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31181223

RESUMO

OBJECTIVE: Mycobacterium tuberculosis (M. tb) has a sumptuous repertoire of effector molecules to counter host defenses. Some of these antigens inhibit autophagy but the exact mechanism of this inhibition is poorly understood. METHODS: Purified protein derivative (PPD) was fractionated using 10 (PPD 10, antigenic molecular weight > 10 kDa) and 3 (PPD 3, mol. weight > 3 kDa) kDa cutters. Effect of these fractions on Calcimycin-induced autophagy and intracellular mycobacterial viability was then studied using different experimental approaches. RESULT: We found significant downregulation of autophagy by PPD 3 pre-treatment in Calcimycin-treated dTHP-1 cells compared to PPD 10. This reduction in autophagy also corroborated with the enhanced survival of mycobacteria in macrophages. We demonstrate that recombinant early secreted antigenic target 6 (rESAT-6) is responsible to inhibit Calcimycin-induced autophagy and enhance intracellular survival of mycobacteria. We also show that pre-treatment with rESAT-6 upregulates microRNA (miR)-30a-3p expression and vis-a-vis downregulates miR-30a-5p expression in Calcimycin-treated dTHP-1 cells. Transfection studies with either miR-30a-3p inhibitor or miR-30a-5p mimic clearly elucidated the opposing roles of miR-30a-3p and miR-30a-5p in rESAT-6 mediated mycobacterial survival through autophagy inhibition. CONCLUSION: Taken together, our result evidently highlights that rESAT-6 enhances intracellular survival of mycobacteria by modulating miR-30a-3p and miR-30a-5p expression.

15.
Int J Pharm ; 565: 358-366, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31075441

RESUMO

In the current study, the ability to use in-line NIR inside the feed frame of a tablet press to monitor the residence time distribution inside the tablet press was investigated. Pulse-response experiments were performed. In-line measurements inside the feed frame were compared to measurements on the actual produced tablets and the influence of different tableting parameters on the concentration profiles were studied. Turret speed had a major influence on the concentration profiles and RTD parameters. The in-line and off-line concentration profiles did not align with each other as spiking material was still detected in the tablets when no spiking material was observed in the powder blend by the in-line measuring method. The cause of this mismatch between the in-line and off-line curves was the in-line measuring position. By adjusting the position of the NIR probe to the bottom of the feed frame instead of at the top of the feed frame, a perfect alignment between in-line and off-line concentration curves was acquired. In-line measurements at the bottom of the feed frame could, if optimisation to avoid probe fouling is possible, be ideal for real-time measurement and control of the blend concentration during tableting. When probe fouling cannot be avoided, the correlation between the in-line measured concentration at the top of the feed frame and the concentration of the produced tablets should be investigated and modelled to enable real-time measurement and control based on in-line measurements.

16.
Environ Sci Technol ; 53(9): 4765-4774, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31021611

RESUMO

Accurate emission inventories serve as critical inputs for air quality and climate models but are poorly constrained over India. We present a new municipal open waste burning emission inventory from India (OWBEII), at a resolution of 0.1° × 0.1°. Out of the 216 (201-232) Tg y-1 of waste produced in the year 2015, 68 (45-105) Tg y-1 was burned in the open. To determine emissions from waste burning, emission factors of 59 non-methane volatile organic compounds (NMVOCs), CH4, CO2, CO, and NO x were measured from garbage fires in rural and urban sites in India. The NMVOC emissions from open waste burning of 1.4-2 Tg y-1 increase India's total anthropogenic NMVOC budget by 8-12%, while BC emissions (40-110 Ggy-1) increase the total anthropogenic BC emissions by 8-12%. Open waste burning in India emits 3-7 Tg y-1 of CO and 58-130 Tg y-1 of CO2. Emissions increase the total anthropogenic CO and CO2 in the MIX-Asia inventory by 4-11% and 2-6%, respectively. Open waste burning may affect atmospheric OH reactivity and ozone formation rates downwind of urban centers through the emission of other highly reactive compounds such as acetaldehyde (20-320 Gg y-1), propene (50-170 Gg y-1), and ethene (50-190 Gg y-1) and is s source of carcinogenic benzene (30-280 Gg y-1).

17.
Proteomics ; : e1900042, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30950571

RESUMO

Challenges in metabolomics for a given spectrum of disease are more or less comparable, ranging from the accurate measurement of metabolite abundance, compound annotation, identification of unknown constituents, and interpretation of untargeted and analysis of high throughput targeted metabolomics data leading to the identification of biomarkers. However, metabolomics approaches in cancer studies specifically suffer from several additional challenges and require robust ways to sample the cells and tissues in order to tackle the constantly evolving cancer landscape. These constraints include, but are not limited to, discriminating the signals from given cell types and those that are cancer specific, discerning signals that are systemic and confounded, cell culture-based challenges associated with cell line identities and media standardizations, the need to look beyond Warburg effects, citrate cycle, lactate metabolism, and identifying and developing technologies to precisely and effectively sample and profile the heterogeneous tumor environment. This review article discusses some of the current and pertinent hurdles in cancer metabolomics studies. In addition, it addresses some of the most recent and exciting developments in metabolomics that may address some of these issues. The aim of this article is to update the oncometabolomics research community about the challenges and potential solutions to these issues.

18.
Phytomedicine ; 59: 152903, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981188

RESUMO

BACKGROUND: The prevalence of procoagulant state under prolonged hypoxic exposures and the complications and lack of specificity associated with use of existing anti-thrombotic agents have necessitated the search for safer and natural therapeutics. Codonopsis, a widely studied medicinal herb, has been reported to decrease whole blood viscosity but the bioactive ingredients involved, and their mechanism of action therein however remain to be investigated. PURPOSE: The present study aimed at evaluating the efficacy of C. clematidea root extract and mechanism of action of its bioactive constituent flavonoid, Kaempferol, in ameliorating hypobaric hypoxia induced procoagulant state. METHODS: Fingerprinting analysis of methanolic extract of C. clematidea root was performed by RP-HPLC. In vitro toxicity study was conducted using HUVEC cell line and in vivo acute and sub-acute toxicity were done according to OECD guidelines (section-4, number-420 and 407 respectively). Adult male Sprague-Dawley rats weighing 230-250 g were exposed to global hypoxia simulating an altitude of 7600 m (282 mmHg), in animal decompression chamber for 3, 7, 14 and 21 days for in vivo studies. Dose optimisation of the extract was done by quantification of Thromboxane A2 in the serum of hypoxic rats. C. clematidea root extract was also evaluated for its in vitro and in vivo antioxidant properties. Procoagulant changes were studied by biochemical plasma coagulation assays and expression analysis of the signalling molecules of the platelet activation cascade like vWF, platelet activation marker CD41, GpIb-IX-V (CD42), Lyn kinase, p-PI3K, p-ERK and p-PLCγ were conducted to investigate C. clematidea mediated signalling mechanisms. RESULTS: Methanolic extract of C. clematidea root showed improved antioxidant status and improvement in bleeding time and in vitro coagulation assays like pT, aPTT, INR. Decreased concentrations of D-Dimers along with that of platelet activation marker CD41 and serum concentration of Thromboxane A2 were observed in C. clematidea root extract supplemented hypoxic animals. Phosphorylation of Lyn kinase, was reduced despite increase in concentration of activating ligand vWF. CONCLUSION: C. clematidea root extract was effective in preventing hypoxia induced platelet activation and resultant procoagulant state by inhibiting Lyn kinase, a serine threonine kinase effector of vWF signalling cascade.

19.
Blood ; 133(23): 2465-2477, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-30992265

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic T cells. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary (acquired) form is most frequent in adults. Secondary HLH is commonly triggered by infections or malignancies but may also be induced by autoinflammatory/autoimmune disorders, in which case it is called macrophage activation syndrome (MAS; or MAS-HLH). Most information on the diagnosis and treatment of HLH comes from the pediatric literature. Although helpful in some adult cases, this raises several challenges. For example, the HLH-2004 diagnostic criteria developed for children are commonly applied but are not validated for adults. Another challenge in HLH diagnosis is that patients may present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome. Treatment algorithms targeting hyperinflammation are frequently based on pediatric protocols, such as HLH-94 and HLH-2004, which may result in overtreatment and unnecessary toxicity in adults. Therefore, dose reductions, individualized tailoring of treatment duration, and an age-dependent modified diagnostic approach are to be considered. Here, we present expert opinions derived from an interdisciplinary working group on adult HLH, sponsored by the Histiocyte Society, to facilitate knowledge transfer between physicians caring for pediatric and adult patients with HLH, with the aim to improve the outcome for adult patients affected by HLH.

20.
Life Sci ; 225: 79-87, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30946838

RESUMO

The different ailments of heart including myocardial infarction (MI) and ischemic heart diseases are the foremost trigger of high mortality across the world which is instigated by sedentary life style, chronic hyperglycaemia and atherosclerosis. Albeit strenuous exercise itself induces temporary hypoxia which causes myocardial damage and this vitiosus circulus is poorly understood and has been assumed difficult to break. Present investigation targets temporal dynamics of aerobic exercise treatment induced preconditioning against diabetes associated pre- and post- myocardial injury. The persisting high blood sugar level leads to several biochemical alterations at pre- and post-MI phase. Here, we present the assessment of temporal expression of cardiac biomarkers (CKMB, LDH, cTnI and serum nitrite/nitrate), oxidative stress (myocardial TBARS and reduced NBT), inflammatory cytokines (IL-6, TNF-α and IL-10), renal biomarkers (BUN, serum creatinine and microproteinuria) and structural alterations of cardio-renal tissue. Aerobic exercise preconditioning significantly downregulate the pathological events or biomarkers and upsurge the physiological biomarkers at both pre- and post-MI phase. The attenuation or returning of pathological makers to lowest level at different time points endorses the therapeutic management of aerobic exercise against diabetic MI. Furthermore, the temporal expression of various cardio-renal biomarkers pattern elucidates that aerobic exercise preconditioning boost the strength and consolidate the cardiac muscles to work under stress. Despite the presence of traditional knowledge about health benefits of aerobic exercise, it is yet to be brought into the clinical arena. In spite of few impending challenges subjected to additional investigations, aerobic exercise preconditioning shows a high degree of promise.


Assuntos
Biomarcadores/análise , Diabetes Mellitus Experimental/fisiopatologia , Precondicionamento Isquêmico Miocárdico/métodos , Infarto do Miocárdio/complicações , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Condicionamento Físico Animal , Animais , Lipídeos/análise , Estresse Oxidativo , Ratos
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