ABSTRACT
Pressure-based membrane processes represent excellent water resource recovery prospects from industrial waste streams. In contrast with conventional pretreatment technologies, studies have shown that membrane pretreatment applications, such as microfiltration (MF), are more cost-effective and improve the results of the overall treatment processes. Hence, enhancing rejection efficiency of MF will enhance the performance of any downstream treatment processes. In this study, 0.45 µm cellulose acetate (CA) microfiltration membranes were modified by vacuum filtration-assisted layer-by-layer deposition of bilayers composed of negatively charged graphene oxide (GO) and positively charged polyethyleneimine (PEI). The performance of 1-, 2-, and 4-bilayer GO-PEI-modified membranes were investigated for their dye-rejection of anionic eriochrome black T (EBT) dye and cationic methylene blue (MB) dye in a cross-flow membrane module. As the number of bilayers on the membrane increased, the membrane thicknesses increased, and the deionized (DI) water flux through the membranes decreased from 4877 LMH/bar for the control (no bilayer) membrane to 2890 LMH/bar for the 4-bilayer membrane. Conversely, the dye-rejection performance of the modified membranes increased as increasing bilayers of GO-PEI deposited on the membranes. The anionic EBT dye saw superior rejection (~90% rejection) compared to the cationic MB dye (~80% rejection), which can be attributable to the electrostatic repulsion between the negatively charged GO surface and anionic EBT dye. After 50% recovery of the saline and dye-laden feed water, there was an observed drop in DI water fluxes of ~40-41% and 36%, respectively. There was also a slight increase in EBT dye-rejection during the composite feed-water experiments, attributed to the precipitation of salts on the membrane feed side or pore spaces, which subsequently reduce the membrane pore sizes.
ABSTRACT
The present study was conducted on Hardhenu and Sahiwal cows to evaluate the genetic diversity and the effect of candidate K232A mutation of diacylglycerol O-acyltransferase (DGAT1) gene on performance traits. PCR product of 413 bp size targeting K232A mutation of DGAT 1 gene was genotyped by Eae1 restriction enzyme and further confirmed by sequencing. The PCR-RFLP analysis for K232A showed that the frequencies of alleles K and A were 0.80 and 0.20 in Hardhenu and 0.98 and 0.02 in Sahiwal cattle, respectively. The frequencies of genotypes for KK and KA genotype were estimated as 0.60 and 0.40 in Hardhenu and 0.96 and 0.04 in Sahiwal cattle, respectively. Chi-square test showed that K232A SNP did not meet with the Hardy-Weinberg equilibrium (p < .01) in Hardhenu cattle. Association analysis revealed that KA genotype was significantly associated with total milk yield (p < .01) and 305 days milk yield (p < .01)in Hardhenu cattle. Hardhenu cows having KA genotype comparatively revealed favorable mean values for AFS (880.31 ± 26.65), AFC (1166.36 ± 19.94), SP (157.46 ± 22.80), CI (441.41 ± 44.28) and AI/Conception (1.80 ± 0.17), indicating that KA genotype can be used as a candidate marker for simultaneous improvement of both production and reproduction traits.
Subject(s)
Diacylglycerol O-Acyltransferase , Polymorphism, Genetic , Female , Cattle/genetics , Animals , Diacylglycerol O-Acyltransferase/genetics , Milk , Mutation , Genotype , Reproduction/genetics , Lactation/geneticsABSTRACT
Growth hormone (GH) is a major regulator of postnatal growth and metabolism in mammals and plays a critical role in growth, production and fertility in cattle. The present study was conducted in dairy cattle to find the association of g.48769565 C > T mutation with growth, production and reproduction traits in Sahiwal and Hardhenu cattle. PCR-RFLP was performed to genotype g.48769565 C > T mutation using the MspI restriction enzyme in our resource cattle population. In Hardhenu cattle, the frequencies of C and T alleles were 0.59 and 0.41, respectively, while genotypic frequencies were 0.33, 0.53 and 0.14 for CC, CT and TT respectively. The frequencies of the C and T alleles were 0.24 and 0.76, respectively, in Sahiwal cattle and it was observed that the highest frequency was for the TT genotype (0.58) and the lowest was for the CC genotype (0.06). Chi-square analysis showed that g.48769565C>T SNP loci meet with the Hardy-Weinberg equilibrium in Sahiwal and Hardhenu cattle. From the least-squares analysis, it was observed that CC genotype was significantly associated with total milk yield (TMY), 300 days milk yield (300D MY), lactation length (LL), dry period (DP) and artificial insemination (AI)/conception (p < .05). We also observed a significant association (p < .05) of genotype CT with 3-month calves body weight. Cows with TT genotype revealed comparatively favourable service period (SP) and calving interval (CI) in our resource population. These observed differences in their allelic and genotypic frequencies in association with the traits underlying production and fertility can be utilized for genetic improvement in dairy cattle.
Subject(s)
Lactation , Milk , Animals , Cattle/genetics , Female , Fertility/genetics , Genotype , Lactation/genetics , Mammals , Reproduction/geneticsABSTRACT
An investigation was conducted to identify polymorphism in mannose-binding lectin 1 (MBL1) gene and its effect on udder health and performance traits in dairy cattle and buffalo of India. Candidate single-nucleotide polymorphism (SNP) c.2534G > A of MBL1 gene was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). All the possible genotypes for SNP c.2534G > A (GG, AG, and AA) were observed in the studied population. However, Sahiwal cows revealed dimorphic pattern (AG and GG). The effect of targeted SNP on incidence of mastitis was evaluated and found to be significant. Animals with GG genotype were less susceptible to clinical mastitis and had comparatively lower somatic cell score (SCS) in Hardhenu cattle (P < 0.01) and Murrah buffalo (P < 0.05). Animals having GG genotype also exhibited significantly (P < 0.05) lower age at first calving (AFC). AG genotyped Murrah buffalo animals revealed significantly higher second lactation milk yield (P < 0.01). GG genotype with SCS and AFC could therefore be exploited as a promising candidate marker for the genetic improvement of udder health and AFC in dairy animals.
Subject(s)
Cattle Diseases , Mannose-Binding Lectin/genetics , Mastitis, Bovine , Animals , Buffaloes/genetics , Cattle/genetics , Cattle Diseases/epidemiology , Cattle Diseases/genetics , Female , Genotype , Lactation , Mammary Glands, Animal , Mastitis, Bovine/epidemiology , Mastitis, Bovine/genetics , Milk , Polymorphism, Single NucleotideABSTRACT
Advanced computing techniques have been used by animal researchers to understand the intricate data structures for deriving the most reliable allusions of populations in order to conserve genetically superior animals. The present attempt was made to evaluate the potential of two advanced techniques, artificial neural networks (ANN) and Bayesian technique (BT), for predicting breeding values (BV) of weaning weight (WWT) using data of 498 lambs born to 41 sires and 173 dams in Harnali sheep for the period from 2014 to 2019. The estimated BV for WWT was initially obtained using univariate animal model under restricted maximum likelihood procedure. ANN using multilayer perceptron with two hidden layers was fitted to training set (75%) of estimated BV to predict BV for test set (25%). Similarly, BT using Markov chain Monte Carlo (MCMC) method was also fitted to similar datasets. The high accuracy of prediction, i.e., correlation between BV and predicted BV, was observed as 0.89 and 0.90 under ANN and BT, respectively. Further, similar ranges of goodness of fit criteria, viz., R2, root mean square error (RMSE), mean absolute error (MAE), and bias, indicated that both ANN and BT had similar prediction ability, which was also confirmed by 10-fold cross-validation. The present study indicated high capability and analogous model adequacy for both techniques that can be exploited in selection programs.
Subject(s)
Neural Networks, Computer , Animals , Bayes Theorem , Body Weight , Monte Carlo Method , Sheep , WeaningABSTRACT
The purpose of the present study was to obtain estimates of variance components and genetic parameters for direct and maternal effects on various growth traits in Beetal goat by fitting four animal models, attempting to separate direct genetic, maternal genetic and maternal permanent environmental effects under restricted maximum likelihood procedure. The data of 3,308 growth trait records of Beetal kids born during the period from 2004 to 2019 were used in the present study. Based on best fitted models, the direct additive h2 estimates were 0.06, 0.27, 0.37, 0.17 and 0.10 for birth weight (BWT), weight at 3 (WT3), 6 (WT6), 9 (WT9) and 12 (WT12) months of age, respectively. Maternal permanent environmental effects significantly contributed for 10% and 7% of total variance for BWT and WWT, respectively, which reduced direct heritability by 40 and 10% for respective traits from the models without these effects. For average daily gain (ADG1) and Kleiber ratios (KR1) up to weaning period (3 months) traits, maternal permanent environmental effects accounted for 7% and 8% of phenotypic variance, respectively, and resulted in a reduction of 6.6% and 5.4% in direct h2 of respective traits. For post-weaning traits, the maternal effects were non-significant (p > .05) which indicates diminishing influence of mothering ability for these traits. High and positive genetic correlations were obtained among WT3-WT6, WT6-WT9 and WT9-WT12 with correlations of 0.96 ± 0.25, 0.84 ± 0.23 and 0.90 ± 0.13, respectively. Thus, early selection at weaning age can be practised taking into consideration maternal variation for effective response to selection in Beetal goat.
Subject(s)
Body Weight/genetics , Goats/growth & development , Goats/genetics , Maternal Inheritance , Animals , Birth Weight/genetics , Breeding , Female , MaleABSTRACT
BACKGROUND: Atrioventricular block requiring permanent pacemaker (PPM) implantation is a common complication of transcatheter aortic valve replacement (TAVR). The mechanism of atrioventricular (AV) block during TAVR is not fully understood, but it may be due to the mechanical stress of TAVR deployment, resulting in possible injury to the nearby compact AV node. Aortic valve calcification (AVC) may worsen this condition and has been associated with an increased risk for post-TAVR PPM implantation. We performed a retrospective analysis to determine if AVC is predictive for long-term right ventricular (RV) pacing in post-TAVR pacemaker patients at 30 days. METHODS: A total of 262 consecutive patients who underwent TAVR with a balloon-expandable valve were analyzed. AVC data were derived from contrast-enhanced computed tomography and characterized by leaflet sector and region. RESULTS: A total of 25 patients (11.1%) required post-TAVR PPM implantation. Seventeen patients did not require RV pacing at 30 days. Nine of these 17 patients had no RV pacing requirement within 10 days. The presence of intra-procedural heart block (P = 0.004) was the only significant difference between patients who did not require PPM and those who required PPM but they were not RV pacing-dependent at 30 days. Non-coronary cusp (NCC) calcium volume was significantly higher in patients who were pacemaker-dependent at 30 days (P = 0.01) and a calcium volume of > 239.2 mm3 in the NCC was strongly predictive of pacemaker dependence at 30 days (area under the curve (AUC) = 0.813). Pre-existing right bundle branch block (RBBB) (odds ratio (OR) 105.4, P = 0.004), bifascicular block (OR 12.5, P = 0.02), QRS duration (OR 70.43, P = 0.007) and intra-procedural complete heart block (OR 12.83, P = 0.03) were also predictive of pacemaker dependence at 30 days. CONCLUSIONS: In patients who required PPM after TAVR, quantification of AVC by non-coronary leaflet calcium volume was found to be a novel predictor for RV pacing dependence at 30 days. The association of NCC calcification and PPM dependence may be related to the proximity of the conduction bundle to the non-coronary leaflet. Further studies are necessary to improve risk prediction for long-term RV pacing requirements following TAVR.
ABSTRACT
BACKGROUND: Despite measures taken to control traditional risk factors like increased rectal disease activity, anorectal stenosis, and, to a lesser extent, obesity, rates of poor outcomes after rectovaginal fistula (RVF) surgery in women with Crohn's disease (CD) are still high and require further elucidation. To bridge the gap, we sought to identify risk factors beyond the aforementioned determinants that may be associated with poor outcomes in these patients. METHODS: We designed a retrospective, unmatched, case-control study to test our hypothesis. The population comprised women with CD who underwent RVF surgery between the years of 2000 and 2013. Cases were defined as surgeries with an unsuccessful outcome at 4 weeks post-surgery, and controls represented those with a successful outcome at 4 weeks post-surgery. With multivariable logistic regression models, we sought to identify pertinent risk factors for poor outcomes after RVF surgery in these women. RESULTS: Of the 108 women with CD who were referred to our institution for evaluation of RVFs between 2000 and 2013, 39 underwent a total of 63 surgeries, of which 16 were cases and 47 were controls. There were no significant differences between them with regard to medications and clinical or mucosal disease severity, but a significantly higher proportion of poor outcomes arose from the group of women who underwent a mucosal flap procedure (88%) compared to those who had a seton placed (13%; P = 0.0004). The final adjusted logistic regression model demonstrated that women who underwent a mucosal flap procedure instead of a seton placement were 17.5 times more likely to have a poor surgical outcome (odds ratio (OR): 17.51; 95% confidence interval (CI): 3.12 - 98.43; P = 0.0012). Moreover, it was seen that women with active colonic mucosal disease, independent of rectal disease activity, were 4.4 times more likely to have a poor outcome (OR: 4.40; 95% CI: 1.06 - 18.26). CONCLUSION: Mucosal flap procedures, representing the second, or definitive, stage in surgical treatment of RVF are associated with much worse outcomes and therefore should be preceded by aggressive medical optimization of the patient.
Subject(s)
Cell Transformation, Neoplastic/drug effects , Histone-Lysine N-Methyltransferase/antagonists & inhibitors , Leukemia, Biphenotypic, Acute/drug therapy , Myeloid-Lymphoid Leukemia Protein/antagonists & inhibitors , Myeloid-Lymphoid Leukemia Protein/physiology , Oncogene Proteins, Fusion/physiology , Proto-Oncogene Proteins/antagonists & inhibitors , Animals , Cell Line, Tumor , Humans , Leukemia, Biphenotypic, Acute/pathology , MiceSubject(s)
Anemia, Aplastic/genetics , Exons , Polymorphism, Single Nucleotide , Proteins/genetics , Adolescent , Adult , Alleles , Anemia, Aplastic/ethnology , Anemia, Aplastic/pathology , Child , Child, Preschool , Chromosomes, Human, Pair 7/chemistry , Female , Gene Frequency , Heterozygote , Humans , India , Introns , Male , Telomere/chemistry , Telomere Homeostasis , White PeopleABSTRACT
Although the mechanism of Aß action in the pathogenesis of Alzheimer's disease (AD) has remained elusive, it is known to increase the expression of the antagonist of canonical wnt signalling, Dickkopf-1 (Dkk1), whereas the silencing of Dkk1 blocks Aß neurotoxicity. We asked if clusterin, known to be regulated by wnt, is part of an Aß/Dkk1 neurotoxic pathway. Knockdown of clusterin in primary neurons reduced Aß toxicity and DKK1 upregulation and, conversely, Aß increased intracellular clusterin and decreased clusterin protein secretion, resulting in the p53-dependent induction of DKK1. To further elucidate how the clusterin-dependent induction of Dkk1 by Aß mediates neurotoxicity, we measured the effects of Aß and Dkk1 protein on whole-genome expression in primary neurons, finding a common pathway suggestive of activation of wnt-planar cell polarity (PCP)-c-Jun N-terminal kinase (JNK) signalling leading to the induction of genes including EGR1 (early growth response-1), NAB2 (Ngfi-A-binding protein-2) and KLF10 (Krüppel-like factor-10) that, when individually silenced, protected against Aß neurotoxicity and/or tau phosphorylation. Neuronal overexpression of Dkk1 in transgenic mice mimicked this Aß-induced pathway and resulted in age-dependent increases in tau phosphorylation in hippocampus and cognitive impairment. Furthermore, we show that this Dkk1/wnt-PCP-JNK pathway is active in an Aß-based mouse model of AD and in AD brain, but not in a tau-based mouse model or in frontotemporal dementia brain. Thus, we have identified a pathway whereby Aß induces a clusterin/p53/Dkk1/wnt-PCP-JNK pathway, which drives the upregulation of several genes that mediate the development of AD-like neuropathologies, thereby providing new mechanistic insights into the action of Aß in neurodegenerative diseases.
Subject(s)
Amyloid beta-Peptides/toxicity , Clusterin/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , MAP Kinase Signaling System/drug effects , Neurons/drug effects , Wnt Proteins/metabolism , Aged , Alzheimer Disease/pathology , Animals , Cells, Cultured , Clusterin/genetics , Embryo, Mammalian , Enzyme Inhibitors/pharmacology , Female , Gene Expression Regulation/drug effects , Humans , Intercellular Signaling Peptides and Proteins/genetics , MAP Kinase Signaling System/genetics , Male , Mice , Mice, Inbred C57BL , Rats , Rats, Sprague-DawleyABSTRACT
The gene encoding the α-amylase from Bacillus licheniformis was cloned, with and without the native signal sequence, and expressed in Escherichia coli, resulting in the production of the recombinant protein in the cytoplasm as insoluble but enzymatically active aggregates. Expression with a low concentration of the inducer at low temperature resulted in the production of the recombinant protein in soluble form in a significantly higher amount. The protein produced with signal sequence was exported to the extracellular medium, whereas there was no export of the protein produced from the gene without the signal sequence. Similarly, the α-amylase activity in the culture medium increased with time after induction in case of the protein produced with signal sequence. Molecular mass determinations by MALDI-TOF mass spectrometry and N-terminal amino acid sequencing of the purified recombinant α-amylase from the extracellular medium revealed that the native signal peptide was cleaved by E. coli signal peptidase between Ala28 and Ala29. It seems possible that the signal peptide of α-amylase from B. licheniformis can be used for the secretion of other recombinant proteins produced using the E. coli expression system.
Subject(s)
Bacillus/enzymology , Bacterial Proteins/metabolism , Escherichia coli/enzymology , Membrane Proteins/metabolism , Serine Endopeptidases/metabolism , alpha-Amylases/metabolism , Bacterial Proteins/genetics , Escherichia coli/genetics , Protein Sorting Signals , alpha-Amylases/geneticsABSTRACT
This study reports for the first time, to our knowledge, descriptive epidemiological data for 188 invasive Candida isolates from Pakistan, including species identification and antifungal susceptibility against fluconazole, itraconazole, voriconazole, caspofungin, micafungin, anidulafungin and amphotericin. Risk factors for invasive candidiasis (IC) were determined for 96 patients from Karachi, Pakistan. In adults and neonates, Candida tropicalis (38 and 36â%, respectively) was the most common species, followed in adults by Candida parapsilosis (17.8â%), Candida glabrata (15.9â%) and Candida albicans (12.3â%). C. albicans (21â%) was the second most common in neonates. In children, C. albicans (31.9â%), C. tropicalis (26.4â%) and C. parapsilosis (19.4â%) were the most common. C. albicans IC was significantly associated with paediatric age [crude odds ratio (COR) 3.46, 95â% confidence interval (CI) 1.63-7.32]. Rare species made up 17.5â% of the total isolates studied. Resistance to fluconazole was seen in C. glabrata (15â.0%) and Candida krusei (100â.0%). Only one isolate (C. glabrata) was resistant to all three echinocandins. Low MICs of fluconazole for 98â% (184/188) of isolates tested support its continued use as an empiric therapy for IC. Non-C. albicans IC was associated with the use of ß-lactam inhibitor combinations (COR 3.16, 95â% CI 1.05-9.57). Use of healthcare devices was documented in 85.4â% of IC patients, whilst 75â.0% had been admitted to special care units. Surprisingly, 66.7â% of patients with IC were not obviously immunosuppressed. The high frequency of modifiable risk factors in this population indicates that candidaemia can be reduced with stringent antibiotic and infection control measures. These data will be useful for empiric selection of antifungals in Karachi, and contribute to global assessments of antifungal resistance.
Subject(s)
Antifungal Agents/pharmacology , Candida , Candidiasis, Invasive/epidemiology , Candidiasis, Invasive/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Candida/classification , Candida/drug effects , Candida/genetics , Candida/isolation & purification , Candidiasis, Invasive/drug therapy , Child , Child, Preschool , Drug Resistance, Fungal , Female , Humans , Infant , Infant, Newborn , Male , Microbial Sensitivity Tests , Middle Aged , Pakistan/epidemiology , Young AdultABSTRACT
A systematic investigation on nonlinear optical properties such as three photon absorption (3PA) wavelength dependent of Kerr type nonlinear refraction in direct and indirect band gap crystals has been reported in the present work. The Z-scan measurements are recorded for both ZnO and CdI(2) with femtosecond laser pulses while the wavelength dependent of the Kerr nonlinearity are in agreement with a two band model. The wavelength dependence of the 3PA is determined by [(3E(photon)/E(g))-1](5/2)[(3E(photon)/E(g))](-9) in the case of direct band gap crystal and [(3E(photon)±âΩ/E(g))-1](5/2)[(3E(photon)±âΩ/E(g))](-9) in the case of indirect band gap crystal. In the present investigation the value of 3PA in the case of indirect band gap crystal is lower than the direct band gap crystal which is due to the phonon assisted transition. The materials of large band gap with optical nonlinearity and fast response speed should be dominating factor for further photonic devices such as optical limiters, optical switches and optical modulators. The higher order nonlinear optical effects have also been determined in the present study.
Subject(s)
Nonlinear Dynamics , Optical Phenomena , Refractometry/methods , Absorption , Crystallography, X-Ray , Photons , Zinc Oxide/chemistryABSTRACT
ß3 Adrenergic receptor (ß3-AR), is a potential therapeutic target for the treatment of type II diabetes and obesity. We report the identification of novel compounds as ß3-AR agonists by integrating different approaches of energetic analysis, structure based pharmacophore designing and virtual screening. In a step wise filtering protocol, structure based virtual screening of 2, 33, 450 compounds was done. These molecules were docked into the active site of the receptor utilizing three levels of accuracy; ligands passing the HTVS (high throughput virtual screening) step were subsequently analyzed in Glide SP (Standard Precision) and finally in Glide XP (Extra Precision) to estimate the receptor ligand binding affinities. In the second step a total of 300 pharmacophore hypotheses were generated from a set of known and diverse ß3-AR agonists. The best hypothesis showed six features: three hydrogen bond acceptors, one positively charged group, and two aromatic rings. To cross validate, pharmacophore filtering was done on the set of shortlisted compounds from structure based VS (virtual screening). The different screening techniques employed were validated using enrichment factor calculations. The energetic based Pharmacophore performed fairly well at distinguishing active from the inactive compounds and yielded a greater diversity of active molecules whereas the number of actives retrieved in the case of structure based screening was the highest.
Subject(s)
Adrenergic beta-3 Receptor Agonists/chemistry , Adrenergic beta-3 Receptor Agonists/pharmacology , Drug Design , Receptors, Adrenergic, beta-3/metabolism , Diabetes Mellitus, Type 2/drug therapy , Humans , Molecular Docking Simulation , Protein Binding , Quantitative Structure-Activity RelationshipABSTRACT
In this paper, a telemedicine system for managing diabetic patients with better care is presented. The system is an end to end solution which relies on the integration of front end (patient unit) and backend web server. A key feature of the system developed is the very low cost automated approach. The front-end of the system is capable of reading glucose measurements from any glucose meter and sending them automatically via existing networks to the back-end server. The back-end is designed and developed using n-tier web client architecture based on model-view-controller design pattern using open source technology, a cost effective solution. The back-end helps the health-care provider with data analysis; data visualization and decision support, and allows them to send feedback and therapeutic advice to patients from anywhere using a browser enabled device. This system will be evaluated during the trials which will be conducted in collaboration with a local hospital in phased manner.
Subject(s)
Computer Communication Networks , Diabetes Mellitus/diagnosis , Diabetes Mellitus/drug therapy , Medical Informatics Applications , Remote Sensing Technology/methods , Telemedicine/methods , Blood Glucose/analysis , Cost-Benefit Analysis , Diabetes Mellitus/blood , Disease Management , Humans , Insulin/administration & dosage , Remote Sensing Technology/economics , Remote Sensing Technology/instrumentation , Telemedicine/economics , Telemedicine/instrumentation , User-Computer InterfaceABSTRACT
Prostate cancer is a serious molecular disorder that arises because of reduction in tumour suppressors and overexpression of oncogenes. The malignant cells survive within the context of a three-dimensional microenvironment in which they are exposed to mechanical and physical cues. These signals are, nonetheless, deregulated through perturbations to mechanotransduction, from the nanoscale level to the tissue level. Increasingly sophisticated interpretations have uncovered significant contributions of signal transduction cascades in governing prostate cancer progression. To dismantle the major determinants that lie beneath disruption of spatiotemporal patterns of activity, crosstalk between various signalling cascades and their opposing and promoting effects on TRAIL-mediated activities cannot be ruled out. It is important to focus on that molecular multiplicity of cancer cells, various phenotypes reflecting expression of a variety of target oncogenes, reversible to irreversible, exclusive, overlapping or linked, coexist and compete with each other. Comprehensive investigations into TRAIL-mediated mitochondrial dynamics will remain a worthwhile area for underlining causes of tumourigenesis and for unravelling interference options.
Subject(s)
Apoptosis , Hedgehog Proteins/metabolism , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , TNF-Related Apoptosis-Inducing Ligand/metabolism , Wnt Proteins/metabolism , Animals , Hedgehog Proteins/biosynthesis , Hedgehog Proteins/genetics , Humans , Male , Proteome , Wnt Proteins/biosynthesis , Wnt Proteins/genetics , Wnt Signaling Pathway/drug effectsABSTRACT
In developing countries, oral immunization is more readily accepted than parenteral, as it accompanies the ease and safety of administration and induces the desired mucosal immune response against highly infectious pathogen transmitted through mucosal routes. Despite the obvious need and apparent merits, the success in the field of oral vaccination is limited due to factors including harsh gastric environment, enzymatic barrier, intestinal epithelium barrier and the fear of oral tolerance reported in case of mucosal vaccination. The number of strategies has been focused at conquering the mucosal barrier for maximization of the intestinal uptake and stabilization of the biological at all stages before they reach their target. Although, considerable success has been attained using these strategies but none of these have achieved commercial status. Therefore a rationally designed oral vaccine should be successfully delivered to the intestinal mucosal immune cells, and induce both humoral and cellular counterparts of immunity along with the mucosal immune response. The aim of this review article is to describe the recent development in the understanding of the molecular mechanism and implication of gastrointestinal epithelium and cytokines interplay in the induction of immunity and tolerance. The review has been elaborated to discuss the rationale of design of suitable carrier in conjunction with the peculiar necessities of gastrointestinal tract for induction of well balanced immune response.
Subject(s)
Drug Design , Gastrointestinal Diseases/immunology , Gastrointestinal Diseases/therapy , Gastrointestinal Tract/immunology , Vaccines/therapeutic use , Administration, Oral , Animals , HumansABSTRACT
BACKGROUND: Patients with inflammatory bowel disease (IBD) often do not take their medications as prescribed. OBJECTIVE: To examine self-reported adherence rates in IBD patients at the Stollery Children's Hospital (Edmonton, Alberta) and to determine predictors of medication adherence. METHODS: A survey was mailed to 212 pediatric IBD patients of the Stollery Children's Hospital. A chart review was completed for those who returned the survey. RESULTS: A total of 119 patients completed the survey. The nonresponders were significantly older than responders (14.5 years versus 13.2 years; P=0.032). The overall adherence rate was 80%. Nonadherence was associated with older age (14.6 years versus 13.0 years; P=0.04), longer disease duration (5.0 years versus 3.1 years; P=0.004) and reported use of herbal medications (40.0% versus 13.6%; P=0.029). The most common reasons reported for missing medications were forgetfulness, feeling better and too many medications. In addition, patients reported being more likely to take anti-inflammatory medications and less likely to take herbal medicines. CONCLUSION: Identified predictors of nonadherence such as age, disease duration and use of herbal treatments may enable the development of specific strategies to improve adherence in adolescents with IBD.
Subject(s)
Inflammatory Bowel Diseases/drug therapy , Medication Adherence , Phytotherapy , Adolescent , Age Factors , Alberta , Anti-Inflammatory Agents/therapeutic use , Child , Cross-Sectional Studies , Data Collection , Female , Hospitals, Pediatric , Humans , Male , Time FactorsABSTRACT
BACKGROUND AND PURPOSE: Many patients with non-cancer diagnoses utilize palliative services. There is little data on the palliative care needs of patients with neurologic and neurosurgical disorders. METHODS: Retrospective chart review. Log sheets which contain all patients seen between January 2004 and 2007 by palliative medicine (PM) were reviewed. Patients with neurologic or neurosurgical disorders were identified and their in-patient charts and electronic records reviewed. Patients with cancer were excluded. RESULTS: A total of 1429 cancer patients were seen by PM. Neurologic or neurosurgical diseases were the second most common in patients seen by the PM service, in 177 cases. Forty-seven patients were excluded. Complete data was collected on 129 patients. Mean age was 70. Seventy-one (55%) were female. The most common neurologic diagnosis was ischemic stroke in 33 (26%). Seventy-five (58%) had symptoms recorded. Reasons for PM consultation included 'comfort measures' in 40 (39%) and 'hospice candidacy' in 38 (37%). The most common recommendation made by the PM service was morphine in 44 (42%). Sixty-three (49%) were deemed hospice appropriate. CONCLUSIONS: Our findings support the need for PM services for patients with various neurologic and neurosurgical disorders. Understanding these needs will allow for the tailoring of palliative care services to such patients.