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1.
Pediatr Res ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31499515

RESUMO

BACKGROUND: Adolescents with single ventricle heart disease (SVHD) who have undergone the Fontan procedure show cognitive/memory deficits. Mammillary bodies are key brain sites that regulate memory; however, their integrity in SVHD is unclear. We evaluated mammillary body (MB) volumes and their associations with cognitive/memory scores in SVHD and controls. METHODS: Brain MRI data were collected from 63 adolescents (25 SVHD; 38 controls) using a 3.0-Tesla MRI scanner. Cognition and memory were assessed using Montreal Cognitive Assessment (MoCA) and Wide Range Assessment of Memory and Learning 2. MB volumes were calculated and compared between groups (ANCOVA, covariates: age, sex, and total brain volume [TBV]). Partial correlations and linear regression were performed to examine associations between volumes and cognitive scores (covariates: age, sex, and TBV). RESULTS: SVHD group showed significantly lower MoCA and WRAML2 scores over controls. MB volumes were significantly reduced in SVHD over controls. After controlling for age, sex, and TBV, MB volumes correlated with MoCA and delayed memory recall scores in SVHD and controls. CONCLUSION: Adolescents with SVHD show reduced MB volumes associated with cognitive/memory deficits. Potential mechanisms of volume losses may include developmental and/or hypoxic/ischemic-induced processes. Providers should screen for cognitive deficits and explore possible interventions to improve memory.

2.
Sci Total Environ ; 699: 134358, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31522047

RESUMO

In India, air pollution has been acknowledged as the fifth most imperative cause of mortality due to high emissions from burning of fossil fuels in industries (brick kilns and thermal power plants), biomass burning, agricultural residue burning and transportation. The emissions of black carbon (BC) with the other air pollutants (CO2, CH4, N2O, HFC, PFC, and SF6), is taking considerable attention in the world because of its ability to effect air quality and weather. The Indo-Gangetic Plains (IGP) region has been considered as one of the greatest source of emissions in India. The short lived climate pollutants (SLCPs) like BC, methane, tropospheric ozone and hydrofluorocarbons have been considered as a climate forcing agent along with CO2. These pollutants have shorter lifetime in atmosphere compared to CO2 and account for the 40-45% of global warming. Among them, BC has a great global warming ability and can increase the Earth's temperature much quicker than carbon dioxide. After CO2, the second highest donors to global warming are CH4 and BC. Recognising the importance of these pollutants, daily concentrations of BC, PM2.5 and PM10 were monitored in three district of IGP during January 2015 to December 2016. The GAINS model was used for assessment of pollution effects, emissions of SLCPs, GHGs and identifying appropriate control actions. The outcomes of modelling advocate that low carbon strategies are more competent to reduce emissions as compared to other control strategies. But, application of low carbon strategies would be restricted by the accessibility of clean fuels. In some cases, finance will be needed to support monitoring of air pollution and other supportive technologies.

4.
Mol Genet Genomic Med ; : e910, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31490001

RESUMO

BACKGROUND: Inducing apoptosis in cancer cells is an important step for the successful treatment of cancer patients. Bcl-2 is an antiapoptotic protein which determines apoptosis by interacting with proapoptotic members of the Bcl-2 family. Exome sequencing has identified Bcl-2 and Bax missense mutations in more than 40 cancer types. However, a little information is available about the functional impact of each Bcl-2 and Bax mutation on the pathogenesis of cancer. METHODS: The mutational data from cancer tissues and cell lines were retrieved from the cBioPortal web resource. The 13 mutated Bcl-2 and wild-type Bax complexes with experimentally verified binding were identified from previous studies wherein, binding for all complexes was reportedly disrupted except one. Several protein-protein docking methods such as ClusPro, HDOCK, PatchDock, FireDock, InterEVDock2 and several mutation prediction methods such as PolyPhen-2, SIFT, and OncoKB have been used to predict the effect of mutation to disrupt the binding between Bcl-2 and Bax. The result obtained was compared with the known experimental data. RESULTS: The protein-protein docking method, ClusPro, employed in the present study confirmed that the binding affinity of 11 out of 13 complexes decreases. Similarly, binding affinity computed for all the 10 wild-type Bcl-2 and mutated Bax complexes agreed with experimentally verified results. CONCLUSION: Several methods like PolyPhen-2, SIFT, and OncoKB have been developed to predict cancer-associated or deleterious mutations, but no method is available to predict apoptosis-inducing mutations. Thus, in this study, we have examined the mutations in Bcl-2 and Bax proteins that disrupt their binding, which is crucial for inducing apoptosis to eradicate cancer. This study suggests that protein-protein docking methods can play a significant role in the identification of hotspot mutations in Bcl-2 or Bax that can disrupt their binding with wild-type partner to induce apoptosis in cancer cells.

5.
ISA Trans ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31472936

RESUMO

This paper proposes an Externally Recurrent Neural Network (ERNN) for approximating the unknown dynamics of complex nonlinear systems and time series prediction. The proposed model utilizes the present as well as delayed values of the system outputs as well as of the external input. The weight update equations are tested for their boundedness by applying the Lyapunov stability method. Further, the error convergence proof is also given. The proposed model is put to test by considering various nonlinear examples and its performance is also compared with other state of the art methods. The results obtained in the present study indicate that the method is efficient and has provided accurate results.

6.
Eur J Med Chem ; 182: 111602, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31421629

RESUMO

Drug discovery and development are long and financially taxing processes. On an average it takes 12-15 years and costs 1.2 billion USD for successful drug discovery and approval for clinical use. Many lead molecules are not developed further and their potential is not tapped to the fullest due to lack of resources or time constraints. In order for a drug to be approved by FDA for clinical use, it must have excellent therapeutic potential in the desired area of target with minimal toxicities as supported by both pre-clinical and clinical studies. The targeted clinical evaluations fail to explore other potential therapeutic applications of the candidate drug. Drug repurposing or repositioning is a fast and relatively cheap alternative to the lengthy and expensive de novo drug discovery and development. Drug repositioning utilizes the already available clinical trials data for toxicity and adverse effects, at the same time explores the drug's therapeutic potential for a different disease. This review addresses recent developments and future scope of drug repositioning strategy.

7.
Elife ; 82019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31453804

RESUMO

Control of pneumonia and diarrhea mortality in India requires understanding of their etiologies. We combined time series analysis of seasonality, climate region, and clinical syndromes from 243,000 verbal autopsies in the nationally representative Million Death Study. Pneumonia mortality at 1 month-14 years was greatest in January (Rate ratio (RR) 1.66, 99% CI 1.51-1.82; versus the April minimum). Higher RRs at 1-11 months suggested respiratory syncytial virus (RSV) etiology. India's humid subtropical region experienced a unique summer pneumonia mortality. Diarrhea mortality peaked in July (RR 1.66, 1.48-1.85) and January (RR 1.37, 1.23-1.48), while deaths with fever and bloody diarrhea (indicating enteroinvasive bacterial etiology) showed little seasonality. Combining mortality at ages 1-59 months with prevalence surveys, we estimate 40,600 pneumonia deaths from Streptococcus pneumoniae, 20,700 from RSV, 12,600 from influenza, and 7200 from Haemophilus influenzae type b and 24,700 diarrheal deaths from rotavirus occurred in 2015. Careful mortality studies can elucidate etiologies and inform vaccine introduction.

9.
Expert Rev Cardiovasc Ther ; 17(8): 605-623, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31389276

RESUMO

Introduction: Atherosclerotic coronary artery disease, in particular acute myocardial infarction (AMI), is a leading cause of morbidity and mortality globally. Percutaneous coronary intervention (PCI) is the mainstay of treatment for obstructive coronary artery disease and AMI through the restoration of TIMI III flow. Despite good macrovascular flow, the myocardium can remain hypoperfusion due to poor microvascular perfusion, and this is referred to as 'no-reflow'. Various treatments have been studied with variable success in both prevention and treatment of no-reflow. Areas covered: This review outlines the cutting-edge diagnostic investigations which have been explored in no-reflow, allowing a deeper understanding of mechanism and microvascular pathological processes involved in its genesis. These include utility of novel MRI techniques and perfusion echo in conjunction with traditional approaches. Detailed review has been undertaken of both pharmacological and non-pharmacological techniques to prevent and manage microvascular dysfunction associated with no-reflow. Particular attention was paid to the evolution and successes of various mechanical protection devices. Expert opinion: Most promising innovations in the diagnosis and management of no-reflow are evaluated, and future outlook is explored. Emerging advances in acute coronary syndrome have their findings applied a role in modifying the pathophysiology of no-reflow.

10.
Curr Diabetes Rev ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438829

RESUMO

BACKGROUND: Diabetes is a multifactorial disease and a major cause for many microvascular and macrovascular complications. The disease will ultimately lead to high rate mortality if it is not managed properly. Treatment of diabetes without any side effects has always remained a major challenge for the health care practitioners. INTRODUCTION: The current review discusses the various conventional drugs, herbal drugs, combination therapy and the use of nutraceuticals for the effective management of diabetes mellitus. The biotechnological aspects of various antidiabetic drugs are also discussed. METHODS: Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was culminated in terms of various approaches that are used for the treatment of diabetes. RESULTS: More than 170 papers including both, research and review articles, were included in this review in order to produce a comprehensive as well as readily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose, mechanism of action and possible side effects. The article also focuses on combination therapies containing synthetic as well as herbal drugs to treat the disease. The role of pre and probiotics in management of diabetes is also highlighted. CONCLUSION: Oral antihyperglycemics which are used to treat diabetes can cause many adverse effects and if given in combination can lead to drug-drug interactions. The combination of various phytochemicals with synthetic drugs can overcome the challenge faced by the synthetic drug treatment. Herbal and nutraceuticals therapy and the use of probiotics and prebiotics is a more holistic therapy due to its natural origin and traditional use.

11.
Anal Chim Acta ; 1078: 151-160, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31358213

RESUMO

Herein, we report a new signal amplification scheme for quantitative biochemical analysis based on gold nanoparticle (GNPs) catalyzed polymerization of transparent silane solution to milky white and turbid siloxane. Using immunoassay as a proof of concept, GNP labeled immunoprobe was used to bind captured antigen and catalyse the polymerization reaction allowing sensitive biochemical investigation. The polymerization reaction was optimized for standard 96 well polystyrene microtiter plates and we discovered that sodium lactate acts as an enhancer in the polymerization reaction as it reduces detection time to merely 30 min. The sensing strategy was applied to detection and quantification of Salmonella Typhimurium in water and egg samples and the platform showed excellent visibly quantifiable analytical response up to 100 cells mL-1. Furthermore, clinical utility and potential of the method was validated by detecting Vi capsular polysaccharide (Vi antigen) responsible for typhoidal Salmonellosis in human serum in sandwich format with a detection limit of 1 ng mL-1. The method serves as the first report towards nanoparticle triggered polymerization for development of rapid and low cost quantitative biochemical assay.


Assuntos
Ouro/química , Imunoensaio/métodos , Nanopartículas Metálicas/química , Polissacarídeos Bacterianos/sangue , Salmonella typhimurium/isolamento & purificação , Siloxanas/síntese química , Animais , Anticorpos/imunologia , Galinhas , Água Potável/microbiologia , Ovos/microbiologia , Contaminação de Alimentos/análise , Humanos , Limite de Detecção , Tamanho da Partícula , Polimerização , Polissacarídeos Bacterianos/imunologia , Estudo de Prova de Conceito , Salmonella typhimurium/imunologia , Silanos/química , Temperatura Ambiente
12.
J Card Fail ; 25(9): 757-766, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31265919

RESUMO

BACKGROUND: Patients with heart failure (HF) show abnormal autonomic activities, which may stem from altered functional connectivity (FC) between different brain sites. METHODS AND RESULTS: We evaluate insular and cerebellar FC with other brain areas, before, during, and after the Valsalva challenge, with functional magnetic resonance imaging in 35 HF and 35 control subjects. Significant insular FC emerged with striatum, thalamus, and anterior cingulate. While left and right cerebellar cortices showed significant FC with each other constituting the cerebellum network, the insula and cerebellum networks showed significant negative FC with each other at baseline, challenge, and recovery phases. The challenge induced increased FC within the insula and the cerebellum networks in both HF and controls. However, patients with HF showed more increased insular network FC, but less enhanced cerebellar FC. During the recovery phase, the negative FC between the insular network and cerebellum enhanced significantly in controls, but not in HF. Lower left ventricle ejection fraction was correlated with lower insula network FC, and impaired negative FC between cerebellum and the insula network in HF. CONCLUSIONS: Increased insular FC in patients with HF might contribute to exaggerated sympathetic tone. While impaired cerebellar FC and diminished negative interactions between cerebellum and insular systems may indicate impaired parasympathetic functions in HF.

13.
Environ Sci Pollut Res Int ; 26(25): 26082-26089, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31278642

RESUMO

Proper management of biomedical waste (BMW) is required to avoid environmental and human health risks. The current study evaluated the BWM practices in public and private health care facilities of Fatehgarh Sahib District in Punjab, India. The study was conducted, using a modified World Health Organization (WHO) tool in 120 health care facilities randomly selected from rural and urban areas. At primary health care level, BMW management guidelines were followed in 67.2% of the public sector and 40.4% of the private sector facilities, whereas in secondary health care sectors both private and public sector follows 100% compliance. Health facilities were graded into different categories according to median score, i.e., scores less than < 2.5 was categorized as red (no credible BMW management system in place), scores between 2.5 to 7.5 as yellow (system present but needs major improvement) and scores > 7.5 as green (good system in place for BMW). It was observed that among primary health care facilities, 85% of the public sector and 64% of private sector facilities falls in the red category, whereas for secondary health care facilities only 8% fall in the red category. Logistic regression helped to identify the major factors that affect the performance of the health care facility, and it shows that regular training on BMW and improved infrastructure can improve the BMW management practices. Further, proper management of BMW requires multi-sectoral coordination, which can be better addressed through policies and by providing periodical training to all stakeholders.

14.
Int J Mol Sci ; 20(14)2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31336658

RESUMO

Understanding the gene regulatory network governing cancer initiation and progression is necessary, although it remains largely unexplored. Enhancer elements represent the center of this regulatory circuit. The study aims to identify the gene expression change driven by copy number variation in enhancer elements of pancreatic adenocarcinoma (PAAD). The pancreatic tissue specific enhancer and target gene data were taken from EnhancerAtlas. The gene expression and copy number data were taken from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) and copy number variations (CNVs) were identified between matched tumor-normal samples of PAAD. Significant CNVs were matched onto enhancer coordinates by using genomic intersection functionality from BEDTools. By combining the gene expression and CNV data, we identified 169 genes whose expression shows a positive correlation with the CNV of enhancers. We further identified 16 genes which are regulated by a super enhancer and 15 genes which have high prognostic potential (Z-score > 1.96). Cox proportional hazard analysis of these genes indicates that these are better predictors of survival. Taken together, our integrative analytical approach identifies enhancer CNV-driven gene expression change in PAAD, which could lead to better understanding of PAAD pathogenesis and to the design of enhancer-based cancer treatment strategies.

15.
J Pharm Pharmacol ; 71(9): 1370-1383, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31304982

RESUMO

Objectives Considerable progress has been made in the treatment of Alzheimer's disease (AD), but all available strategies focus on alleviating symptoms rather than curing, which means that AD is viewed as an unresolvable neurodegenerative disease. Nanotechnological applications offer an alternative platform for the treatment of neurodegenerative diseases. This review aims to summarize the recent nanomedicine and nanotechnology developments for the treatment of AD.  Key findings A plethora of nanocarriers and nanoparticle prodrugs have been reported to have negligible cytotoxicity in animal models, and these developments have revealed new opportunities for development of new classes of potent drug formulations for AD. Different nanotechnology-based approaches such as polymers, emulsions, lipo-carriers, solid lipid carriers, carbon nanotubes and metal-based carriers have been developed over the past decade, and they have been focusing on both neuroprotective and neurogenerative techniques to treat AD. Studies also reveal that nanotechnological approaches can aid in early diagnosis of AD and enhance therapeutic efficacy and bioavailability.  Summary  Notably, the drugs used conventionally to target the central nervous system have limitations that include an inability to cross the 'blood-brain barrier' or the 'blood-cerebrospinal fluid barrier' effectively and high drug efflux due to the activity of P-glycoprotein, but these limitations can be successfully overcome when nanocarriers are used for targeted drug delivery in AD.

16.
Dalton Trans ; 48(30): 11469-11479, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31290881

RESUMO

Two rhodium complexes Rh1 and Rh2 with isoquinoline derivatives were synthesized and characterized. Both complexes displayed strong anticancer activity against various cancer cells and low cytotoxicity against non-cancer cells. These complexes triggered apoptosis via mitochondrial dysfunction that increased the levels of ROS and Ca2+ and released cytochrome C which ultimately activated caspases and the apoptosis pathway. The different biological activities of Rh1 and Rh2 could be associated with the presence of methoxy substituents on the ligands. In vivo studies showed that Rh1 effectively inhibited tumor growth in a T-24 xenograft mouse model with a less adverse effect than cisplatin. Overall, Rh1 and Rh2 induced apoptosis via mitochondrial pathways and could be developed as effective anticancer agents.

17.
Chem Rev ; 119(16): 9657-9721, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31306015

RESUMO

Calix[n]arenes (n = 4, 5, 6, 8) are "chalicelike" phenol-based macrocycles that are among the most fascinating and highly studied scaffolds in supramolecular chemistry. This stems from the functional and tunable diversity at both their upper and lower rims, their preorganized nonpolar cavities and preorganized ion-binding sites, and their well-defined conformations. Conjugation of calixarene scaffolds with various fluorogenic groups has led to the development of smart fluorescent probes that have been utilized as molecular sensors, in bioimaging, for drug and gene delivery, in self-assembly/aggregation, and as smart materials. The fine-tuning and incorporation of different ligating sites in the calix[4]arene scaffold have produced numerous molecular sensors for cations, anions, and biomolecules. Moreover, the aqueous solubility of p-sulfonatocalix[4]arenes has engendered their potential use in drug/gene delivery and enzymatic assays. In addition, because of their strong optical properties, fluorescent calix[4]arenes have been used to develop smart materials, including gels as well as nonlinear optical, organic light-emitting diode, and multiphoton materials. Finally, significant developments in the utility of fluorescent higher calixarenes have been made for bioapplications. This review critically summarizes the recent advances made in all of these different areas.

19.
J Assoc Physicians India ; 67(4): 52-56, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31309799

RESUMO

Background: Chronic aluminum toxicity (CAT) in end stage kidney disease (ESKD) patients is now a rare clinical disorder, unlike in the past, because of improvements in hemodialysis water purification systems and discontinuation of use of aluminum hydroxide as a phosphate binder. The use of aluminum utensils for cooking could be an unrecognised cause of the CAT. Objective: To assess the association between aluminum kitchen utensils used for cooking meals and chronic aluminum toxicity (CAT) in patients on maintenance hemodialysis (MHD). Material and Methods: In this case control study, a total of 31 (cases n=10; controls n=21) patients on MHD for more than one year were included. Cases were defined as patients with clinical manifestations (including laboratory parameters) of CAT and high (>200 mcg/L) serum aluminum levels. Control group was chosen from the same hemodialysis facilities. Association between use of aluminum utensils for cooking and occurrence of CAT was assessed. Results: The mean age of patients in the cases and the control group was 52.90 and 52.95 years respectively with on significant difference (p=0.99). There was no difference in mean duration of dialysis (p=0.78), serum calcium level (p=0.06), serum phosphate level (p=0.19), serum albumin level (p=0.06), history of hypertension (p=1.00) and history of diabetes (n=0.12) between two groups. Mean haemoglobin (p<0.05) and mean iPTH (p<0.05) was significantly lower in the cases as compared to control group. Thirteen patients had history of use of aluminum utensils [cases 10 (76.90%) and control 3 (23.10%); p<0.05]. All cases i.e. 10 (100%) had exposure to aluminum utensils whereas three (14.3%) patients in the control group had exposure to aluminum utensils whereas 18 (85.7%) patients had no exposure. The relative risk of having CAT because of use of aluminum utensils compared to not using was 28.46 (1.81 to 445.3) and the odd's ratio estimated was 120 (5.45 to 2642). Conclusion: Use of aluminum utensils for cooking meals is associated with CAT. Larger studies are required to confirm these findings.


Assuntos
Alumínio/envenenamento , Culinária/instrumentação , Intoxicação por Metais Pesados/epidemiologia , Falência Renal Crônica/epidemiologia , Diálise Renal , Estudos de Casos e Controles , Humanos
20.
Artigo em Inglês | MEDLINE | ID: mdl-31268345

RESUMO

The aim of present study was to introduce the role of quality by design to produce curcumin crystals with enhanced dissolution rate and bioavailability. The liquid antisolvent method was used to produce crystals. The crystal growth was controlled using the Box-Behnken design. The variables used in the crystallization process included the ratio of pyrocatechol to polyethylene glycol (PEG) 1500, solvent addition rate, stirring time, and stirring speed. Combination of these variables was found to yield curcumin crystals of 2.45 ± 0.56 µm size and 0.321 polydispersity index that exhibited enhanced solubility, dissolution rate, product yield, and compressibility. The optimized curcumin crystals were characterized by Fourier-transform infrared spectrophotometer (FT-IR), nuclear magnetic resonance, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. The dissolution rate and oral bioavailability of optimized curcumin crystals were found to be 2.66- and 7.08-folds higher than its unprocessed form. The optimized crystals were found stable for 6 months under accelerated temperature of 40°C and 75% relative humidity as there was no significant difference observed in the crystal size and dissolution profile.

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