High-frequency optical coherence tomography predictors of aneurysm occlusion following flow diverter treatment in a preclinical model.

BACKGROUND: High-frequency optical coherence tomography (HF-OCT) is an intravascular imaging method that allows for volumetric imaging of flow diverters in vivo. OBJECTIVE: To examine the hypothesis that a threshold for both volume and area of communicating malapposition can be predictive of early aneurysm occlusion. METHODS: Fifty-two rabbits underwent elastase aneurysm formation, followed by treatment with a flow diverter. At the time of implant, HF-OCT was acquired to study the rate and degree of communicating malapposition. Treated aneurysms were allowed to heal for either 90 or 180 days and euthanized following catheter angiography. Healing was dichotomized into aneurysm remnant or neck remnant/complete occlusion. Communicating malapposition was measured by HF-OCT using a semi-automatic algorithm able to detect any points where the flow diverter was more than 50 µm from the vessel wall. This was then summed across image slices to either a volume or area. Finally, a subsampled population was used to train a statistical classifier for the larger dataset. RESULTS: No difference in occlusion rate was found between device type or follow-up time (p=0.28 and p=0.67, respectively). Both volume and area of malapposition were significantly lower in aneurysms with a good outcome (p<0.001, both). From the statistical model, a volume of less than 0.56 mm3 or a normalized area less than 0.69 as quantified by HF-OCT was predictive of occlusion (p<0.001, each). CONCLUSIONS: HF-OCT allows for measurements of both volume and area of malapposition and, from these measurements, an accurate prediction for early aneurysm occlusion can be made.

The moderating effect of entrepreneurial motivation on the relationship between entrepreneurial intention and behaviour: An extension of the theory of planned behaviour on emerging economy.

Background: The study investigates the influence of antecedents of the theory of planned behaviour (TPB) and personality traits on entrepreneurial intention and behaviour among engineering students in an emerging economy. It employs the extension of the TPB model by focusing on the intention-behaviour gap, an under-researched area in research. Furthermore, it investigates the moderating effect of entrepreneurial motivation on the relationship between intention and behaviour to improve conceptual model predictability. Methods: A structured questionnaire was used to gather data from 1,564 engineering students, and the data were analyzed using structural equation modelling (SEM) with Amos software. Results: The results revealed that subjective norms were the strongest predictor of entrepreneurial intention and behaviour, followed by entrepreneurial alertness, perceived behavioural control, attitude towards entrepreneurship, need for achievement, and risk tolerance. Moreover, the moderation analysis showed that entrepreneurial motivation was crucial in moderating the relationship between intention and behaviour. Conclusions: The present conceptual model contributes to the existing TPB model by improving predictive power to understand the intention-behaviour relationship. The results of the study will assist policymakers, academicians of higher education institutions, and universities in developing policies, strategies, and curricula to engage more students in entrepreneurial activities.

Germplasm variability-assisted near infrared reflectance spectroscopy chemometrics to develop multi-trait robust prediction models in rice.

Rice is a major staple food across the world in which wide variations in nutrient composition are reported. Rice improvement programs need germplasm accessions with extreme values for any nutritional trait. Near infrared reflectance spectroscopy (NIRS) uses electromagnetic radiations in the NIR region to rapidly measure the biochemical composition of food and agricultural products. NIRS prediction models provide a rapid assessment tool but their applicability is limited by the sample diversity, used for developing them. NIRS spectral variability was used to select a diverse sample set of 180 accessions, and reference data were generated using association of analytical chemists and standard methods. Different spectral pre-processing (up to fourth-order derivatization), scatter corrections (SNV-DT, MSC), and regression methods (partial least square, modified partial least square, and principle component regression) were employed for each trait. Best-fit models for total protein, starch, amylose, dietary fiber, and oil content were selected based on high RSQ, RPD with low SEP(C) in external validation. All the prediction models had ratio of prediction to deviation (RPD) > 2 amongst which the best models were obtained for dietary fiber and protein with R 2 = 0.945 and 0.917, SEP(C) = 0.069 and 0.329, and RPD = 3.62 and 3.46. A paired sample t-test at a 95% confidence interval was performed to ensure that the difference in predicted and laboratory values was non-significant.

Detection of Dentinal Microcracks in Radicular Dentin after Shaping with XP-endo Shaper, Neoendo Flex Files, and Hero Shaper Using Scanning Electron Microscope: An In Vitro Study.

The study aimed to compare the extent of dentinal microcracks in the radicular dentin using hand K files and various types of rotary nickel-titanium (NiTi) file systems. Forty mandibular incisor teeth (human) were grouped for the study. The root apices were closed, and the canals were straight (<5°). The samples were divided into four groups (n = 10). Group 1-Hand K file system (SybronEndo, SA), Group 2-XP-endo Shaper (FKG Dentaire, La Chaux-de-Fonds, Switzerland), Groups 3-Neoendoflex file (Neoendo, Orikam, India), and Group 4-Hero Shaper files (Micro-Mega, Becacon, France). Sectioning was done at 3, 6, and 9 mm from the apex, perpendicular to the long axis using a diamond disc under water coolant. The cut samples were then observed through a scanning electron microscope at ×50 enlargement. The control group showed no microcracks except one sample in the coronal third, which was less significant. The difference in the amount of crack detected on comparing the different groups was significant. In the experimental groups, XP-endo Shaper group showed significantly less number of cracks than the Neoendo flex, and Hero Shaper groups. Within the limitations of this study, all the system, except hand K files, produced remarkable dentinal microcracks. Least cracks were seen in canals instrumented with XP-endo Shaper. It can also be noted that single file system causes less number of microcracks.

Convex Calibrated Surrogates for the Multi-Label F-Measure.

The F-measure is a widely used performance measure for multi-label classification, where multiple labels can be active in an instance simultaneously (e.g. in image tagging, multiple tags can be active in any image). In particular, the F-measure explicitly balances recall (fraction of active labels predicted to be active) and precision (fraction of labels predicted to be active that are actually so), both of which are important in evaluating the overall performance of a multi-label classifier. As with most discrete prediction problems, however, directly optimizing the F-measure is computationally hard. In this paper, we explore the question of designing convex surrogate losses that are calibrated for the F-measure - specifically, that have the property that minimizing the surrogate loss yields (in the limit of sufficient data) a Bayes optimal multi-label classifier for the F-measure. We show that the F-measure for an s-label problem, when viewed as a 2 s × 2 s loss matrix, has rank at most s 2 + 1, and apply a result of Ramaswamy et al. (2014) to design a family of convex calibrated surrogates for the F-measure. The resulting surrogate risk minimization algorithms can be viewed as decomposing the multi-label F-measure learning problem into s 2 + 1 binary class probability estimation problems. We also provide a quantitative regret transfer bound for our surrogates, which allows any regret guarantees for the binary problems to be transferred to regret guarantees for the overall F-measure problem, and discuss a connection with the algorithm of Dembczynski et al. (2013). Our experiments confirm our theoretical findings.

Massively-Parallelized, Deterministic Mechanoporation for Intracellular Delivery.

Microfluidic intracellular delivery approaches based on plasma membrane poration have shown promise for addressing the limitations of conventional cellular engineering techniques in a wide range of applications in biology and medicine. However, the inherent stochasticity of the poration process in many of these approaches often results in a trade-off between delivery efficiency and cellular viability, thus potentially limiting their utility. Herein, we present a novel microfluidic device concept that mitigates this trade-off by providing opportunity for deterministic mechanoporation (DMP) of cells en masse. This is achieved by the impingement of each cell upon a single needle-like penetrator during aspiration-based capture, followed by diffusive influx of exogenous cargo through the resulting membrane pore, once the cells are released by reversal of flow. Massive parallelization enables high throughput operation, while single-site poration allows for delivery of small and large-molecule cargos in difficult-to-transfect cells with efficiencies and viabilities that exceed both conventional and emerging transfection techniques. As such, DMP shows promise for advancing cellular engineering practice in general and engineered cell product manufacturing in particular.

Electrolyte imbalance after total joint arthroplasty: risk factors and impact on length of hospital stay.

BACKGROUND: Clinical as well as subclinical hyponatremia is frequently seen after orthopedic surgery. The study was aimed to determine the frequency and severity of hyponatremia in a cohort of total joint arthroplasty cases and identify the risk factors and their impact. METHODS: This is a retrospective observational study of 546 consecutive cases of total joint arthroplasty patients from a single institution. Only primary hip and knee replacements were included. The study was approved by the institutional review board. Preoperative and postoperative serum electrolytes were recorded till 45-day review. This was correlated with the age, gender, BMI, drug intake, and comorbidities. RESULTS: We identified 84.9% postsurgical hyponatremia in our cohort. Of these 80% were mild, 16% moderate and 4% severe. Preoperative hyponatremia was a consistent finding in most severe cases. Thaizides, ACE inhibitors, and longer surgeries like bilateral TKRs had more hyponatremia. Hospital stay was not impacted in this study for reasons discussed. There were no deaths in this series during the follow-up period, but two patients were rehospitalized. CONCLUSION: Postsurgical hyponatremia occurs in up to 85% of primary hip and knee arthroplasty patients. The most consistent predictor of severe electrolyte disturbance postsurgery is preoperative hyponatremia. Older age, female gender, longer surgery, and drugs like thiazides and ACE inhibitors seemed contributory.

Does Femoral Notching During Total Knee Arthroplasty Influence Periprosthetic Fracture. A Prospective Study.

BACKGROUND: Notching of the anterior femoral cortex during total knee arthroplasty (TKA) has been attributed to cause supracondylar fractures of the femur. Anatomic variations in the femur bone in different races make notching inevitable when standard designs of prostheses are used. The objective of this study is to determine the prevalence of notching when a PFC Sigma knee was used in an Indian population sample using the anterior referencing system and to assess the frequency of femoral shaft fractures in these cases. METHODS: This is a single-center, prospective study. All patients undergoing TKA were recruited and followed up for a minimum of 2 years. All patients had a PFC Sigma knee (DePuy Synthes), and the anterior referencing system was used for implantation. The Knee Society Score was used for outcome scoring and the Gujarathi's schema for the grading of notching. Radiological outcomes were evaluated by an independent observer. Linear regression analysis assessed the effect of notching on range of motion and final score. RESULTS: Of the 200 cases, 21% had varying degrees of notching. Grade I was seen in 13%, grade II in 6.5%, grade III in 1%, and grade IV in 0.5% in this series. There was no supracondylar fracture in 2 years. Notching had no bearing on the range of movement or outcome scores. CONCLUSION: Although notching is best avoided, this study has shown no correlation between notching and supracondylar fracture of the femur following TKA. It does not appear to have any bearing on the range of movement or final outcome scores.

Environmental enrichment ameliorates chronic immobilisation stress-induced spatial learning deficits and restores the expression of BDNF, VEGF, GFAP and glucocorticoid receptors.

Severe and prolonged stress is the main environmental factor that precipitates depression, anxiety and cognitive dysfunctions. On the other hand, exposure to environmental enrichment (EE) has been shown to induce progressive plasticity in the brain and improve learning and memory in various neurological and psychiatric disorders. It is not known whether exposure to enriched environment could ameliorate chronic immobilisation stress-induced cognitive deficits and altered molecular markers. Hence, in the present study we aimed to evaluate the effect of enriched environment on chronic immobilisation stress (CIS) associated changes in spatial learning and memory, behavioural measures of anxiety, depression and molecular markers as well as structural alterations. Male Wistar rats were subjected to chronic immobilisation stress for 2h/day/10days followed by 2weeks of exposure to EE. CIS resulted in weight loss, anhedonia, increased immobility, spatial learning and memory impairment, enhanced anxiety, and reduced expression of BDNF, VEGF, GFAP and glucocorticoid receptors (GR) in discrete brain regions. Interestingly, stressed rats exposed to enrichment ameliorated behavioural depression, spatial learning and memory impairment and reduced anxiety behaviour. In addition, EE restored BDNF, VEGF, GFAP and GR expression and normalized hypotrophy of dentate gyrus and hippocampus in CIS rats. In contrast, EE did not restore hypertrophy of the amygdalar complex. Thus, EE ameliorates stress-induced cognitive deficits by modulating the neurotrophic factors, astrocytes and glucocorticoid receptors in the hippocampus, frontal cortex and amygdala.

An Experimental Study to Evaluate the Effect of Memantine in Animal Models of Anxiety in Swiss Albino Mice.

BACKGROUND: Due to the adverse effects produced by the present conventional medicines for anxiety disorders, research for newer drugs is still desirable. From the literature it is evident that NMDA receptors play a key role in animal models of anxiety. AIM: The present study is done to evaluate the antianxiety effect of memantine in swiss albino mice. MATERIALS AND METHODS: The experimental study was conducted from November 2014 to January 2015. Animals were divided into four groups. Twelve mice were randomly allotted in each group. Animals in the first group received normal saline as a control 10ml/kg, lorazepam 0.5mg/kg was administered to second group, memantine 3mg/kg as a test drug was given to the third group and memantine 3mg/kg + lorazepam 0.5mg/kg was administered to the fourth group. All the drugs were given for 7 consecutive days by intraperitoneal route. RESULTS: Results were analyzed by one-way ANOVA followed by Post-hoc Tukey's test. On the 1(st) day, memantine treated group did not show statistical significant anxiolytic effect in both the behavioural paradigms when compared to control group. On the 8(th) day, the animals showed significant decrease p<0.001 in step down latency period in shock free zone (185.4±3.87 Vs 278.3±5.49), significant increase p<0.001 in step down errors (6.8±0.78 Vs 1.4±0.19) and significant increase p<0.001 in total time spent in shock zone (32.1±2.22 Vs 5.6±0.6). In open field test, on 8(th) day the animals treated with memantine when compared to control group, showed significant increase p<0.001 in number of squares crossed (112.7± 2.69 Vs 83.2±2.96), time spent in central square (11.5±1.26 Vs 3.4±0.65), no. of rearings (32.4±2.61 Vs 17±1.81) and significant decrease p<0.001 in freezing time (15.2±1.12 Vs 20.2±2.29). Memantine showed synergistic antianxiety effect when combined with lorazepam. CONCLUSION: Memantine showed significant anxiolytic effect in open field and passive avoidance response tests which are commonly used experimental models to assess anxiety states in animals.

Genetic Diversity and Population Structure in Aromatic and Quality Rice (Oryza sativa L.) Landraces from North-Eastern India.

The North-eastern (NE) India, comprising of Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland, Sikkim and Tripura, possess diverse array of locally adapted non-Basmati aromatic germplasm. The germplasm collections from this region could serve as valuable resources in breeding for abiotic stress tolerance, grain yield and cooking/eating quality. To utilize such collections, however, breeders need information about the extent and distribution of genetic diversity present within collections. In this study, we report the result of population genetic analysis of 107 aromatic and quality rice accessions collected from different parts of NE India, as well as classified these accessions in the context of a set of structured global rice cultivars. A total of 322 alleles were amplified by 40 simple sequence repeat (SSR) markers with an average of 8.03 alleles per locus. Average gene diversity was 0.67. Population structure analysis revealed that NE Indian aromatic rice can be subdivided into three genetically distinct population clusters: P1, joha rice accessions from Assam, tai rices from Mizoram and those from Sikkim; P2, aromatic rice accessions from Nagaland; and P3, chakhao rice germplasm from Manipur [corrected]. Pair-wise FST between three groups varied from 0.223 (P1 vs P2) to 0.453 (P2 vs P3). With reference to the global classification of rice cultivars, two major groups (Indica and Japonica) were identified in NE Indian germplasm. The aromatic accessions from Assam, Manipur and Sikkim were assigned to the Indica group, while the accessions from Nagaland exhibited close association with Japonica. The tai accessions of Mizoram along with few chakhao accessions collected from the hill districts of Manipur were identified as admixed. The results highlight the importance of regional genetic studies for understanding diversification of aromatic rice in India. The data also suggest that there is scope for exploiting the genetic diversity of aromatic and quality rice germplasm of NE India for rice improvement.

In silico study of peptide inhibitors against BACE 1.

Peptides are increasingly used as inhibitors of various disease specific targets. Several naturally occurring and synthetically developed peptides are undergoing clinical trials. Our work explores the possibility of reusing the non-expressing DNA sequences to predict potential drug-target specific peptides. Recently, we experimentally demonstrated the artificial synthesis of novel proteins from non-coding regions of Escherichia coli genome. In this study, a library of synthetic peptides (Synpeps) was constructed from 2500 intergenic E. coli sequences and screened against Beta-secretase 1 protein, a known drug target for Alzheimer's disease (AD). Secondary and tertiary protein structure predictions followed by protein-protein docking studies were performed to identify the most promising enzyme inhibitors. Interacting residues and favorable binding poses of lead peptide inhibitors were studied. Though initial results are encouraging, experimental validation is required in future to develop efficient target specific inhibitors against AD.

Mapping of yellow mosaic virus (YMV) resistance in soybean (Glycine max L. Merr.) through association mapping approach.

Yellow Mosaic Virus (YMV) is a serious disease of soybean. Resistance to YMV was mapped in 180 soybean genotypes through association mapping approach using 121 simple sequence repeats (SSR) and four resistance gene analogue (RGA)-based markers. The association mapping population (AMP) (96 genotypes) and confirmation population (CP) (84 genotypes) was tested for resistance to YMV at hot-spot consecutively for 3 years (2007-2009). The genotypes exhibited significant variability for YMV resistance (P < 0.01). Molecular genotyping and population structure analysis with 'admixture' co-ancestry model detected seven optimal sub-populations in the AMP. Linkage disequilibrium (LD) between the markers extended up to 35 and 10 cM with r2 > 0.15, and >0.25, respectively. The 4 RGA-based markers showed no association with YMV resistance. Two SSR markers, Satt301 and GMHSP179 on chromosome 17 were found to be in significant LD with YMV resistance. Contingency Chi-square test confirmed the association (P < 0.01) and the utility of the markers was validated in the CP. It would pave the way for marker assisted selection for YMV resistance in soybean. This is the first report of its kind in soybean.

Comparative efficacy of storage bags, storability and damage potential of bruchid beetle.

Groundnut during storage is attacked by number of stored grain pests and management of these insect pests particularly bruchid beetle, Caryedon serratus (Oliver) is of prime importance as they directly damage the pod and kernels. In this regard different storage bags that could be used and duration up to which we can store groundnut has been studied. Super grain bag recorded minimum number of eggs laid and less damage and minimum weight loss in pods and kernels in comparison to other storage bags. Analysis of variance for multiple regression models were found to be significant in all bags for variables viz, number of eggs laid, damage in pods and kernels, weight loss in pods and kernels throughout the season. Multiple comparison results showed that there was a high probability of eggs laid and pod damage in lino bag, fertilizer bag and gunny bag, whereas super grain bag was found to be more effective in managing the C. serratus owing to very low air circulation.

Efficacy and insecticidal properties of some essential oils against Caryedon serratus (Oliver)-a storage pest of groundnut.

During storage groundnut is attacked by number of stored grain pest and management of these insect pests particularly bruchid beetle, Caryedon serratus (Oliver) is of prime importance as they directly damage the pod and kernels. Hence, some essential oils were tested for their insecticidal and fungicidal properties. Highest total bruchid mortality was recorded with the application of neem oil and pongamia oil at 10% (v/w) concentration and lowest in eucalyptus oil at 5% (v/w). Number of eggs laid was recorded 2.3 in neem oil 10% (v/w) which was lowest and significantly superior over untreated control and was at par with castor oil 10% (v/w) which recorded 2.5 eggs per 100 g of groundnut pods. There was no adult emergence in the groundnut pods treated with castor oil, eucalyptus oil, neem oil and pongamia oil at 10% (v/w) concentration. Groundnut pods treated with castor oil, eucalyptus oil, neem oil and pongamia oil at 10% (v/w) and neem oil at 5% (v/w) concentrations recorded no damage to pods and kernels and also zero per cent weight loss. These oils effectively influenced groundnut bruchid establishment and reduce damage besides reduction in aflatoxin contamination.

Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study.

INTRODUCTION: The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients. METHODS: Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0-2. Patients took vorinostat 400 mg PO daily days 1-14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40 % of patients being free of progression at that time point. This study followed a two-stage minimax design. RESULTS: Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1-6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8 %). Median PFS was 1.5 months, 3m-PFS rate 11.1 %, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy. CONCLUSIONS: Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients.

Mitochondrial function in human brains is affected by pre- and post mortem factors.

AIM: Mitochondrial function and the ensuing ATP synthesis are central to the functioning of the brain and contribute to neuronal physiology. Most studies on neurodegenerative diseases have highlighted that mitochondrial dysfunction is an important event contributing to pathology. However, studies on the human brain mitochondria in various neurodegenerative disorders heavily rely on post mortem samples. As post mortem tissues are influenced by pre- and post mortem factors, we investigated the effect of these variables on mitochondrial function. METHODS: We examined whether the mitochondrial function (represented by mitochondrial enzymes and antioxidant activities) in post mortem human brains (n=45) was affected by increased storage time (11.8-104.1 months), age of the donor (2 days to 80 years), post mortem interval (2.5-26 h), gender difference and agonal state [based on Glasgow Coma Scale: range=3-15] in the frontal cortex, as a prototype. RESULTS: We observed that the activities of citrate synthase, succinate dehydrogenase and mitochondrial reductase (MTT) were significantly affected only by gender difference (citrate synthase: P=0.005; succinate dehydrogenase: P=0.01; mitochondrial reductase: P=0.006), being higher in females, but not by any other factor. Mitochondrial complex I activity was significantly inhibited by increasing age (r=-0.40; P=0.05). On the other hand, the mitochondrial antioxidant enzyme glutathione reductase decreased with severe agonal state (P=0.003), while the activity of glutathione-S-transferase declined with increased storage time (P=0.005) and severe agonal state (P=0.02). CONCLUSION: Our data highlight the influence of pre- and post mortem factors on preservation of mitochondrial function with implications for studies on brain pathology employing stored human samples.

Cytotoxic and pro-apoptotic effects of Abrus precatorius L. on human metastatic breast cancer cell line, MDA-MB-231.

Abrus precatorius is highly regarded as a universal panacea in the herbal medicine with diverse pharmacological activity spectra. This experimental study on the mechanism of the anticancer activity of A. precatorius leaf extracts, may offer new evidence for A. precatorius in the treatment of breast cancer in clinical practice. Cell death was determined by using MTT assay. Further analyses were carried out by doing DNA laddering, PARP cleavage, FACS, semi-quantitative RT-PCR and detection of cellular reactive oxygen species (ROS) by DCFDA assay. A. precatorius showed very striking inhibition on MDA-MB-231 cells. MTT assay showed more than 75 % inhibition of the cells and treated cells indicated visible laddering pattern with thick compact band. PARP cleavage produced 89 kDa cleavage product which was associated with apoptosis. Flow cytometer exhibited a sub-G0/G1 peak as an indicative of apoptosis. mRNA expression level of apoptosis-related genes p21 and p53 was markedly increased in cells treated with the extract as compared to control. The up-regulation of p21 and p53 may be the molecular mechanisms by which A. precatorius extract which induces apoptosis. An increase in the concentration of A. precatorius extract does not generate ROS, instead it reduces ROS formation in MDA-MB-231 cells, as evident from the shift in fluorescence below untreated control. This is the first report showing that A. precatorius leaf extract exhibits a growth inhibitory effect by induction of apoptosis in MDA-MB-231 cells. Our results contribute towards validation of the A. precatorius extract as a potentially effective chemopreventive or therapeutic agent against breast cancer.