Search

Background: Infections due to drug-resistant herpes simplex viruses (HSV) represent an important clinical concern, especially in immunocompromised patients. The present study was aimed at detecting acyclovir (ACV) susceptibility in HSV clinical samples., Methods: A total of 13 HSV-positive clinical samples (5 HSV-1 and 8 HSV-2) recovered from patients (1 immunocompromised and 12 of unknown immune status) were included in the study. The genotypic analysis involved an initial UL23 (thymidine kinase) gene sequencing, followed by a confirmatory phenotypic assay using plaque reduction technique., Results: Two novel amino acid changes, A37V and H283N, were detected in HSV-1 positive clinical samples, which were found to be susceptible to acyclovir (half maximal effective concentration = 1.5 µM) by plaque reduction assay., Conclusions: These two novel amino acid changes could be therefore considered as natural polymorphisms, a phenomenon widely associated with the HSV-UL23 gene.

Meningioma, a common primary brain tumor in adults, is graded based on World Health Organization criteria that rely on histology alone. This approach is unable to determine conclusively which tumors, especially benign or atypical, will recur. Molecular characterization of meningioma has identified genetic biomarkers that can predict tumor behavior. Only a few genetic changes are known to classify >85% of all meningioma and clinical trials using targeted therapy to genetic subtypes of meningioma are under way. Immunotherapy is also being trialed in treating high-grade and recurrent meningioma. This review summarizes recent developments characterizing meningioma using genetic and immunologic biomarkers and how these molecular tools may be integrated into existing care together with current World Health Organization grading to improve diagnosis, prognosis, and therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

[This corrects the article DOI: 10.1371/journal.pone.0199949.].

In Australia, turnip weed has been rapidly emerging as one of the major weeds in conservation agricultural systems. Germination and emergence of turnip weed were examined for two populations collected from Gatton and St George regions of Australia; two locations with high and low rainfall, respectively. The seeds of turnip weed germinated at all the tested temperatures, but germination was the lowest at 15/5°C, intermediate at 20/10°C and highest at 25/15°C and 30/20°C. The results indicated a high adaptability of turnip weed to warm environmental conditions, although it is a major problem in the winter season. Germination was higher in dark than light/dark regimes except at 30/20°C. Three was a concomitant reduction in germination as the osmotic potential values decreased from 0 to -1.0 MPa. There was 2 and 4% germination at -0.8 MPa for Gatton and St George populations, respectively, and no germination occurred at an osmotic potential of -1.0 MPa. There was a reduction in germination when the sodium chloride (NaCl) concentration was increased from 0 to 150 mM, and no germination was observed at 200 and 250 mM of NaCl. Turnip weed germinated over a broad range of pH (4 to 10). Seedling emergence was higher at 1 cm depth compared to 0.5 cm or at the soil surface. There was 28 and 33% emergence at the surface for the Gatton and St George populations, respectively, compared to 48 and 56% emergence from 1 cm depth for the Gatton and St George populations, respectively and no emergence was observed from 6 cm depth. The results indicated that tillage leading to shallow burial would promote the emergence of turnip weed; on the contrary, tillage that could bury seeds deep into the soil profile might minimise the emergence. Under ideal conditions and lack of integrated weed management programmes, this weed will emerge, set seeds and enrich the soil seed bank and thereby continue to be a problem in the northern grain region of Australia., Competing Interests: The authors have declared that no competing interests exist.

Chloris truncata is a significant weed in summer crops in the subtropical region of Australia. A study was conducted to evaluate the effect of environmental factors on germination and emergence of two populations of C. truncata. Overall, germination was not affected by the populations. Seeds germinated at a wide range of alternating day/night temperatures, suggesting that seeds can germinate throughout the spring, winter and autumn seasons. Seed germination was stimulated by the presence of light; however, 51 to 71% of these seeds still germinated in the dark. The sodium chloride concentration and osmotic potential required to inhibit germination of 50% of the population were 179 mM and -0.52 MPa, respectively. A high proportion of seeds germinated over a wide pH range (4 to 10). Seeds placed on the soil surface had greatest germination (67%) and a burial depth of 3 cm resulted in complete inhibition of emergence. The sorghum residue amount required to reduce emergence by 50% was 1.8 t ha-1. The results suggest that, although this weed will be favored in no-till systems, residue retention on the soil surface will help in reducing its infestation. Seed bank buildup can be managed by burying seeds below the depth of emergence., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Long noncoding RNAs (lncRNA) are a type of noncoding RNA that comprise of longer than 200 nucleotides sequences. They can regulate chromosome structure, gene expression and play an essential role in the pathophysiology of human diseases, especially in tumorigenesis and progression. Nowadays, they are being targeted as potential biomarkers for various cancer types. And many research studies have proven that lncRNAs might bring a new era to cancer diagnosis and support treatment management. The purpose of this review was to inspect the molecular mechanism and clinical significance of long non-coding RNA- differentiation antagonizing nonprotein coding RNA(DANCR) in various types of human cancers., Materials and Methods: In this review, we summarize and figure out recent research studies concerning the expression and biological mechanisms of lncRNA-DANCR in tumour development. The related studies were obtained through a systematic search of PubMed, Embase and Cochrane Library., Results: Long non-coding RNAs-DANCR is a valuable cancer-related lncRNA that its dysregulated expression was found in a variety of malignancies, including hepatocellular carcinoma, breast cancer, glioma, colorectal cancer, gastric cancer, and lung cancer. The aberrant expressions of DANCR have been shown to contribute to proliferation, migration and invasion of cancer cells., Conclusions: Long non-coding RNAs-DANCR likely serves as a useful disease biomarker or therapeutic cancer target., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

The application of genomics in crops has the ability to significantly improve genetic gain for agriculture. Many marker-dense tools have been developed, but few have seen broad adoption in plant genomics due to issues of significant variations of genome size, levels of ploidy, single nucleotide polymorphism (SNP) frequency and reproductive habit. When combined with limited breeding activities, small research communities and scant sequence resources, the suitability of popular systems is often suboptimal and routinely fails to effectively balance cost-effectiveness and sample throughput. Genotyping-by-sequencing (GBS) encompasses a range of protocols including resequencing of the transcriptome. This study describes a skim GBS-transcriptomics (GBS-t) approach developed to be broadly applicable, cost-effective and high-throughput while still assaying a significant number of SNP loci. A range of crop species with differing levels of ploidy and degree of inbreeding/outbreeding were chosen, including perennial ryegrass, a diploid outbreeding forage grass; phalaris, a putative segmental allotetraploid outbreeding forage grass; lentil, a diploid inbreeding grain legume; and canola, an allotetraploid partially outbreeding oilseed. GBS-t was validated as a simple and largely automated, cost-effective method which generates sufficient SNPs (from 89 738 to 231 977) with acceptable levels of missing data and even genome coverage from c. 3 million sequence reads per sample. GBS-t is therefore a broadly applicable system suitable for many crops, offering advantages over other systems. The correct choice of subsequent sequence analysis software is important, and the bioinformatics process should be iterative and tailored to the specific challenges posed by ploidy variation and extent of heterozygosity., (© 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Background: Bilateral superficial cervical plexus block (BSCPB) provides good postoperative analgesia, but its effect on anesthetic consumption is unknown. This study evaluated the effects of BSCPB on sevoflurane consumption during thyroid surgery., Methods: Fifty patients were randomly allocated into groups A and B of 25 each in this prospective double-blind study. Group A received BSCPB with 20 ml 0.25% bupivacaine, whereas group B received 20 ml saline immediately before entropy-guided general anesthesia. Intraoperative hemodynamic parameters, end-tidal sevoflurane concentration, minimum alveolar concentration, and sevoflurane consumption were recorded. Postoperative pain was assessed using a visual analog scale, and the time of the first request for analgesia was noted. All side effects were recorded., Results: Demographics were comparable. Mean sevoflurane consumption [for 30 min: group A = 7.2 (1.1) ml, group B = 8.8 (2.0) ml, P = 0.001; for 60 min: group A = 13.5 (1.7) ml, group B = 16.5 (3.9) ml, P = 0.002] and mean end-tidal sevoflurane concentration [for 30 min: group A = 1.2% (0.2%), group B = 1.4% (0.2%), P = 0.008; for 60 min: group A = 1.2% (0.1%), group B = 1.4% (0.2%), P = 0.010] were significantly lower in group A. Patients in group A had a longer duration of analgesia [361.6 (79.5) min vs. 151.0 (60.2) min, P < 0.001] compared to those in group B., Conclusions: Preinduction BSCPB during thyroid surgery significantly reduced sevoflurane consumption and increased the duration of postoperative analgesia.

Bobble-head doll syndrome (BHDS) is a rare pediatric movement disorder presenting with involuntary 2- to 3-Hz head movements. Common signs and symptoms also found on presentation include macrocephaly, ataxia, developmental delay, optic disc pallor or atrophy, hyperreflexia, tremor, obesity, endocrinopathy, visual disturbance or impairment, headache, and vomiting, among others. The syndrome is associated with suprasellar cysts, third ventricular cysts, or aqueductal obstruction, along with a few other less common conditions. The cause of involuntary head motions is not understood. Treatment is surgical. The authors present 2 cases of BHDS. The first is a 14-year-old boy with BHDS associated with aqueductal obstruction and triventricular hydrocephalus secondary to a tectal tumor. He was successfully treated by endoscopic third ventriculostomy, and all symptoms resolved immediately in the recovery room. This case is unusual in its late age of symptom onset, the primacy of lateral ("no-no") involuntary head rotations, and the associated tectal tumor. The second case is a 7.5-year-old girl with BHDS associated with a suprasellar cyst. She was successfully treated with an endoscopic fenestration but preexisting endocrinopathy persisted, and the patient was diagnosed with autism spectrum disorder at age 12 years. This second case is more typical of BHDS. A comprehensive and up-to-date review of the literature of BHDS and video documentation of the phenomenon are presented.

The current Illumina HiSeq and MiSeq platforms can generate paired-end reads of up to 2 x 250 bp and 2 x 300 bp in length, respectively. These read lengths may be substantially longer than genomic regions of interest when a DNA sequencing library is prepared through a target enrichment-based approach. A sequencing library preparation method has been developed based on the homology-based enzymatic DNA fragment assembly scheme to allow processing of multiple PCR products within a single read. Target sequences were amplified using locus-specific PCR primers with 8 bp tags, and using the tags, homology-based enzymatic DNA assembly was performed with DNA polymerase, T7 exonuclease and T4 DNA ligase. Short PCR amplicons can hence be assembled into a single molecule, along with sequencing adapters specific to the Illumina platforms. As a proof-of-concept experiment, short PCR amplicons (57-66 bp in length) derived from genomic DNA templates of field pea and containing variable nucleotide locations were assembled and sequenced on the MiSeq platform. The results were validated with other genotyping methods. When 5 PCR amplicons were assembled, 4.3 targeted sequences (single-nucleotide polymorphisms) on average were successfully identified within each read. The utility of this for sequencing of short fragments has consequently been demonstrated., (© The Author(s) 2018. Published by Oxford University Press.)

Star-PAP, a nuclear phosphatidylinositol (PI) signal-regulated poly(A) polymerase (PAP), couples with type I PI phosphate kinase α (PIPKIα) and controls gene expression. We show that Star-PAP and PIPKIα together regulate 3'-end processing and expression of pre-mRNAs encoding key anti-invasive factors ( KISS1R , CDH1 , NME1 , CDH13 , FEZ1 , and WIF1 ) in breast cancer. Consistently, the endogenous Star-PAP level is negatively correlated with the cellular invasiveness of breast cancer cells. While silencing Star-PAP or PIPKIα increases cellular invasiveness in low-invasiveness MCF7 cells, Star-PAP overexpression decreases invasiveness in highly invasive MDA-MB-231 cells in a cellular Star-PAP level-dependent manner. However, expression of the PIPKIα-noninteracting Star-PAP mutant or the phosphodeficient Star-PAP (S6A mutant) has no effect on cellular invasiveness. These results strongly indicate that PIPKIα interaction and Star-PAP S6 phosphorylation are required for Star-PAP-mediated regulation of cancer cell invasion and give specificity to target anti-invasive gene expression. Our study establishes Star-PAP-PIPKIα-mediated 3'-end processing as a key anti-invasive mechanism in breast cancer., (Copyright © 2018 A.P. and Laishram.)

Background and Aims: Unanticipated difficult intubation or the failed intubation in operating room and in emergency department is an imperative source of anesthesia-related patient's mortality. The aim of this study is to compare the predictive value of upper lip bite test (ULBT) and ratio of height to thyromental distance (RHTMD) with other commonly used preoperative airway assessment tests for predicting difficult intubation in Indian population., Materials and Methods: In this prospective, single-blinded observational study, 260 adult patients of either sex, belonging to American Society of Anesthesiologists physical Status I and II undergoing elective surgical procedure under general anesthesia were included in the study. ULBT, RHTMD, inter-incisor gap, modified Mallampati grade, horizontal length of the mandible, head and neck movements, sternomental distance, and TMD were assessed preoperatively and correlated with Cormack and Lehane's grading during laryngoscopy under anesthesia. Statistical analysis was done by Chi-square and Fisher's exact test., Results: ULBT and RHTMD had highest sensitivity (66.7% and 63.3%), specificity (99.1% and 89.6%), positive predictive value (90.9% and 44.2%), and negative predictive value (96.9% and 95.0%), respectively, when compared to other parameters in predicting difficult airway., Conclusion: ULBT and RHTMD may be used as a simple bedside airway assessment tools for prediction of difficult intubation., Competing Interests: There are no conflicts of interest.

Introduction: Co-administration of phenylephrine prevents oxytocin-induced hypotension during caesarean section under spinal anaesthesia (SA), but higher doses cause reflex bradycardia. This study compares the effects of co-administration of two different doses of phenylephrine on oxytocin-induced hypotension during caesarean section under SA., Methods: In this prospective, double-blind study, 90 parturients belonging to the American Society of Anesthesiologists' physical status 1 or 2, undergoing caesarean section under SA were randomised into Group A: oxytocin 3U and phenylephrine 50 μg, Group B: oxytocin 3U and phenylephrine 75 μg, Group C: oxytocin 3U and normal saline, administered intravenously over 5 min after baby extraction. The incidence of hypotension (the primary outcome), rescue vasopressor requirement and side effects were recorded. Statistical analyses were with analysis of variance, Kruskal-Wallis, chi-square and Fisher's exact tests., Results: Demographic parameters such as age, height, weight, level of sensory block at 20 min and duration of surgery were comparable in all the groups. The incidence of hypotension (Group A - 90%, Group B - 10%, Group C - 98%, P = 0.001), magnitude of fall in mean arterial pressure (Group A-15.03 ± 6.12 mm of Hg, Group B - 6.63 ± 4.49 mm of Hg and Group C-13.03 ± 3.39 mm of Hg, P < 0.001) and rescue vasopressor requirement (Group A-45 ± 15.25 mg, Group B-5 ± 15.25, Group C-91.66 ± 26.53, P < 0.001) were significantly lower in Group B compared to A and C., Conclusion: Co-administration of phenylephrine 75 μg with oxytocin 3U reduces the incidence of oxytocin-induced hypotension compared to phenylephrine 50 μg with oxytocin 3U during caesarean section under spinal anaesthesia., Competing Interests: There are no conflicts of interest.

Pain after any surgical procedure is inevitable but can be controlled by administration of analgesics in most cases. Postoperative pain after surgical treatment of mandibular fractures can be treated by nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics. The purpose of this study is to critically compare the postoperative analgesic efficacy of small doses of intravenous TRAMADOL (opioid analgesic) versus LORNOXICAM (NSAID) in patients with mandibular trauma undergoing open reduction and internal fixation (ORIF) and to assess the presence of any adverse effects due to NSAID or opioid use. Forty adult ASA grade I-II patients with mandibular trauma, scheduled for ORIF under general anesthesia in the Department of Oral and Maxillofacial Surgery, College of Dental Sciences, Davangere, were selected for the study. The patients were randomly assigned into a tramadol group (Group T) and a lornoxicam group (Group L) and were administered intravenous tramadol 50 mg and intravenous lornoxicam 8 mg, respectively, at specific postoperative intervals. Pain intensity was quantitatively assessed at the 2nd, 4th, 6th, 12th, and 24th postoperative hours using a visual analog scale of 10 cm. Adverse effects of the analgesics were also recorded and compared. Both the drugs resulted in a significant decrease in pain intensity from 2nd to 24th postoperative hours, but better pain control was observed in Group L at 24th postoperative hour. Only two patients experienced nausea and vomiting in Group T and one patient experienced gastric acidity in Group L. The comparative results clearly demonstrate that pain control by intravenous lornoxicam is significantly better than by intravenous tramadol at 24th postoperative hour after ORIF of mandibular trauma. Side effects produced by both the drugs were minor and had no apparent effect on the study results.

Superior Thyroid Artery (STA) usually arises from the ventral surface of the External Carotid Artery (ECA) just below the level of tip of greater cornu of hyoid bone and it runs anteriorly, downwards and medially. Lingual artery arises at the level of tip of greater cornu of hyoid bone and it runs anteriorly, upwards and medially. Rarely, both STA and lingual artery may originate as a common trunk called thyrolingual trunk. But a thyrolingual trunk arising from Common Carotid Artery (CCA) is very rare. We report a case of patient diagnosed to have carcinoma of right lower alveolus with nodal recurrence; with thyrolingual trunk arising from the medial aspect of CCA, which was detected incidentally during neck dissection.

Avena fatua and Avena ludoviciana are closely related grass weed species infesting a large number of crops around the world. These species are widely distributed in diverse agro-ecosystems from temperate to sub-tropical regions due to their unique seed traits, successful germination ecology, high competitive ability, and allelopathic potential. A. fatua is more widespread, adaptable, and problematic than A. ludoviciana. Both these species infest major winter and spring crops, including wheat, oat, barley, canola, maize, alfalfa, and sunflower, causing up to 70% yield losses depending on crop species and weed density. Chemical control has been challenged by large-scale herbicide resistance evolution in these weed species. A. fatua is the most widespread herbicide-resistant weed in the world, infesting about 5 million hectares in 13 countries. The use of alternative herbicides with different modes of action has proved effective. Several cultural practices, including diverse crop rotations, cover crops, improved crop competition (using competitive cultivars, high seed rates, narrow row spacing, altered crop geometry), and allelopathic suppression, have shown promise for controlling A. fatua and A. ludoviciana. The integrated use of these cultural methods can reduce the herbicide dose required, and lower dependency on herbicides to control these grasses. Moreover, integrated management may successfully control herbicide-resistant populations of these weed species. The use of integrated approaches based on the knowledge of biology and ecology of A. fatua and A. ludoviciana may help to manage them sustainably in the future.

Drug abuse (e.g., methamphetamine-Meth or cocaine-Coc) is one of the major risk factors for becoming infected with HIV-1, and studies show that in combination, drug abuse and HIV-1 lead to significantly greater damage to CNS. To overcome these issues, we have developed a novel nanoformulation (NF) for drug-abusing population infected with HIV-1. In this work, a novel approach was developed for the co-encapsulation of Nelfinavir (Nel) and Rimcazole (Rico) using layer-by-layer (LbL) assembled magnetic nanoformulation for the cure of neuroAIDS. Developed NF was evaluated for blood-brain barrier (BBB) transmigration, cell uptake, cytotoxicity and efficacy (p24 assay) in HIV-1 infected primary astrocyte (HA) in presence or absence of Coc and Meth. Developed magnetic nanoformulation (NF) fabricated using the LbL approach exhibited higher amounts of drug loading (Nel and Rico) with 100% release of both the therapeutic agents in a sustained manner for 8 days. NF efficacy studies indicated a dose-dependent decrease in p24 levels in HIV-1-infected HA (~55%) compared to Coc + Meth treated (~50%). The results showed that Rico significantly subdued the effect of drugs of abuse on HIV infectivity. NF successfully transmigrated (38.8 ± 6.5%) across in vitro BBB model on the application of an external magnetic field and showed >90% of cell viability with efficient cell uptake. In conclusion, our proof of concept study revealed that sustained and concurrent release of sigma σ1 antagonist and anti-HIV drug from the developed novel sustained release NF can overcome the exacerbated effects of drugs of abuse in HIV infection and may solve the issue of medication adherence in the drug-abusing HIV-1 infected population.

Lentil ( Lens culinaris Medik.) is a diploid (2n = 2x = 14), self-pollinating, cool-season, grain legume that is cultivated worldwide and is highly valuable due to its high protein content. However, lentil production is constrained by many factors including biotic stresses, majority of which are fungal diseases such as ascochyta blight (AB), fusarium wilt, rust, stemphylium blight, anthracnose, and botrytis gray mold. Among various diseases, AB is a major -problem in many lentil-producing countries and can significantly reduce crop production. Breeding for AB resistance has been a priority for breeding programs across the globe and consequently, a number of resistance sources have been identified and extensively exploited. In order to increase the efficiency of combining genes from different genetic backgrounds, molecular genetic tools can be integrated with conventional breeding methods. A range of genetic linkage maps have been generated based on DNA-based markers, and quantitative trait loci (QTLs) for AB resistance have been identified. Molecular markers linked to these QTLs may potentially be used for efficient pyramiding of the AB disease resistance genes. Significant genomic resources have been established to identify and characterize resistance genes, including an integrated genetic map, expressed sequence tag libraries, gene based markers, and draft genome sequences. These resources are already being utilized for lentil crop improvement, to more effectively select for disease resistance, as a case study of the Australian breeding program will show. The combination of genomic resources, effective molecular genetic tools and high resolution phenotyping tools will improve the efficiency of selection for ascochyta blight resistance and accelerate varietal development of global lentil breeding programs.

Background: Organophosphorus compound poisoning (OPCP) is a major public health problem in developing countries like India. Atropine and oximes remain the main-stay of management. Magnesium sulfate (MgSO 4 ) has shown benefit in the management of OPCP., Aims: This study was designed to assess the effect of MgSO 4 on outcome in OPCP patients admitted to Intensive Care Unit (ICU)., Settings and Design: Double-blind prospective randomized clinical trial in an ICU of tertiary care institution., Methods: One hundred patients (50 in each group) of OPCP, confirmed by history and syndrome of OPCP with low plasma pseudocholinesterase, aged between 18 and 60 years were studied. Magnesium group (Group M) received 4 g of 20% MgSO 4 infusion over 30 min at admission to ICU, control group (Group C) received normal saline placebo in the same manner. Patients were assessed for the need for intubation, requirement of atropine, duration of mechanical ventilation, duration of ICU stay, and its effect on mortality., Statistical Analysis: Chi-square test and Fisher's exact test for categorical data, independent sample t -test, and paired t -test for nominal data., Results: Demographics and basal serum magnesium levels were comparable. Atropine requirement was higher in Group C (74.82 ± 22.39 mg) compared to Group M (53.11 ± 45.83 mg) ( P < 0.001). A total of 33 patients in Group C and 23 patients in Group M required intubation, respectively ( P = 0.043). The mean duration of mechanical ventilation was 4.51 ± 2 days in Group C compared to 4.13 ± 1.6 days in Group M ( P = 0.45). ICU stay was 5.36 ± 2.018 days in Group C compared to 4.54 ± 1.581 days in Group M ( P = 0.026). There was no significant difference in mortality between the groups., Conclusion: Four grams of MgSO 4 given to OPCP patients within 24 h of admission to ICU, decreases atropine requirement, need for intubation, and ICU stay., Competing Interests: There are no conflicts of interest.

Competing Interests: There are no conflicts of interest

The study was initiated to determine the anticancer activity of a novel compound isolated from the plant Mimosa pudica. The structure of the compound was identified as a derivative of myricetin having alkyl, hydroxy alkyl and methyl substitutions on the basis of spectral evidences (UV-vis, FT-IR, 1 H NMR and Mass spectra). The isolated compound was interpreted as 2-(2',6'-dimethyl-3',4',5'-alkyl or hydroxy alkyl substituted phenyl)-3-oxy-(alkyl or hydoxy alkyl)- 5,7-dihydroxy-chromen-4-one. In vitro evaluation of anticancer activity against human lung adenocarcinoma cell line (A549) and human erythroleukemic cell line (K562) were conducted using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. In vivo anticancer activity was determined against Dalton's Ascites Lymphoma (DAL) in Swiss albino mice. The mice were treated with intraperitoneal administration of the compound at 25mg/kg and 100mg/kg body weight and were compared with the normal, DAL control and standard drug cyclophosphamide treated groups. The histology revealed that the compound could protect the cellular architecture of liver and kidney. The results from the in vitro, in vivo and histological examinations confirmed the ethnopharmacological significance of the isolated compound and could be considered further for the development of an effective drug against cancer., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

RNA-Seq using second-generation sequencing technologies permits generation of a reference unigene set for a given species, in the absence of a well-annotated genome sequence, supporting functional genomics studies, gene characterisation and detailed expression analysis for specific morphophysiological or environmental stress response traits. A reference unigene set for lentil has been developed, consisting of 58,986 contigs and scaffolds with an N50 length of 1719 bp. Comparison to gene complements from related species, reference protein databases, previously published lentil transcriptomes and a draft genome sequence validated the current dataset in terms of degree of completeness and utility. A large proportion (98%) of unigenes were expressed in more than one tissue, at varying levels. Candidate genes associated with mechanisms of tolerance to both boron toxicity and time of flowering were identified, which can eventually be used for the development of gene-based markers. This study has provided a comprehensive, assembled and annotated reference gene set for lentil that can be used for multiple applications, permitting identification of genes for pathway-specific expression analysis, genetic modification approaches, development of resources for genotypic analysis, and assistance in the annotation of a future lentil genome sequence., Competing Interests: The authors declare no conflict of interest.

Lentil ( Lens culinaris Medik.) is a self-pollinating, diploid, annual, cool-season, food legume crop that is cultivated throughout the world. Ascochyta blight (AB), caused by Ascochyta lentis Vassilievsky, is an economically important and widespread disease of lentil. Development of cultivars with high levels of durable resistance provides an environmentally acceptable and economically feasible method for AB control. A detailed understanding of the genetic basis of AB resistance is hence highly desirable, in order to obtain insight into the number and influence of resistance genes. Genetic linkage maps based on single nucleotide polymorphisms (SNP) and simple sequence repeat (SSR) markers have been developed from three recombinant inbred line (RIL) populations. The IH × NF map contained 460 loci across 1461.6 cM, while the IH × DIG map contained 329 loci across 1302.5 cM and the third map, NF × DIG contained 330 loci across 1914.1 cM. Data from these maps were combined with a map from a previously published study through use of bridging markers to generate a consensus linkage map containing 689 loci distributed across seven linkage groups (LGs), with a cumulative length of 2429.61 cM at an average density of one marker per 3.5 cM. Trait dissection of AB resistance was performed for the RIL populations, identifying totals of two and three quantitative trait loci (QTLs) explaining 52 and 69% of phenotypic variation for resistance to infection in the IH × DIG and IH × NF populations, respectively. Presence of common markers in the vicinity of the AB&#95;IH1- and AB&#95;IH2.1/AB&#95;IH2.2-containing regions on both maps supports the inference that a common genomic region is responsible for conferring resistance and is associated with the resistant parent, Indianhead. The third QTL was derived from Northfield. Evaluation of markers associated with AB resistance across a diverse lentil germplasm panel revealed that the identity of alleles associated with AB&#95;IH1 predicted the phenotypic responses with high levels of accuracy (~86%), and therefore have the potential to be widely adopted in lentil breeding programs. The availability of RIL-based maps, a consensus map, and validated markers linked to AB resistance provide important resources for lentil improvement.

Interplay between lncRNAs and mRNAs is rapidly emerging as a key epigenetic mechanism in controlling various cell functions. HIV can actively infect and/or can persist latently for years by manipulating host epigenetics; however, its molecular essence remains undiscovered in entirety. Here for the first time, we delineate the influence of HIV on global lncRNAs expression in monocytic cells lines. Our analysis revealed the expression modulation of nearly 1060 such lncRNAs which are associated with differentially expressed mRNAs in active and latent infection. This suggests a greater role of lncRNAs in regulating transcriptional and post-transcriptional gene expression during HIV infection. The differentially expressed mRNAs were involved in several different biological pathways where immunological networks were most enriched. Importantly, we discovered that HIV induces expression reversal of more than 150 lncRNAs between its active and latent infection. Also, hundreds of unique lncRNAs were identified in both infection conditions. The pathology specific "gene-expression reversal" and "on-and-off" switching of lncRNAs and associated mRNAs may lead to establish the relationship between active and HIV infection.

There are no clearly defined guidelines for when an open or closed treatment is indicated for treatment of mandibular condylar fractures. The aim of the study is to analyze the mandibular function after nonsurgical treatment of unilateral subcondylar fractures, in a prospective study. A prospective study was conducted on 30 patients with unilateral mandibular subcondylar fracture undergoing nonsurgical treatment. Clinical and radiographic examinations were done prior to treatment and at 12-month follow-up. Pain, perceived occlusion, mouth opening, protrusion, and horizontal movements of the mandible were evaluated by clinical examination. Radiologic evaluation was done using Panoramic and Reverse Towne's radiographs. At 12-month follow-up, there was minimal pain in the temporomandibular joint region, there was an improvement in the perceived occlusion, and mouth opening did not reduce. There was insignificant absolute difference between left and right lateral mandibular movements. The amount of increase in the protrusion of mandible was insignificant. On radiographic evaluation, the degree of coronal and sagittal displacement was insignificant at follow-up. Mean ramus height pretreatment and 12 months posttreatment were 0.98 ± 0.50 and 0.87 ± 0.47, respectively. Based on this study, patients had adequate mandibular function and minimal pain after nonsurgical treatment. Unilateral subcondylar fractures of the mandible can be treated nonsurgically in patients with minimal occlusal discrepancies, adequate mouth opening, minimal displacement of condyle, and minimal ramus height shortening.

Although the introduction of antiretroviral therapy has reduced the prevalence of severe forms of neurocognitive disorders, human immunodeficiency virus (HIV)-1-associated neurocognitive disorders were observed in 50% of HIV-infected patients globally. The blood-brain barrier is known to be impermeable to most of antiretroviral drugs. Successful delivery of antiretroviral drugs into the brain may induce an inflammatory response, which may further induce neurotoxicity. Therefore, alternate options to antiretroviral drugs for decreasing the HIV infection and neurotoxicity may help in reducing neurocognitive impairments observed in HIV-infected patients. In this study, we explored the role of magnetic nanoparticle (MNP)-bound tissue inhibitor of metalloproteinase-1 (TIMP1) protein in reducing HIV infection levels, oxidative stress, and recovering spine density in HIV-infected SK-N-MC neuroblastoma cells. We did not observe any neuronal cytotoxicity with either the free TIMP1 or MNP-bound TIMP1 used in our study. We observed significantly reduced HIV infection in both solution phase and in MNP-bound TIMP1-exposed neuronal cells. Furthermore, we also observed significantly reduced reactive oxygen species production in both the test groups compared to the neuronal cells infected with HIV alone. To observe the effect of both soluble-phase TIMP1 and MNP-bound TIMP1 on spine density in HIV-infected neuronal cells, confocal microscopy was used. We observed significant recovery of spine density in both the test groups when compared to the cells infected with HIV alone, indicting the neuroprotective effect of TIMP1. Therefore, our results suggest that the MNP-bound TIMP1 delivery method across the blood-brain barrier can be used for reducing HIV infectivity in brain tissue and neuronal toxicity in HIV-infected patients.

The present paper reviews current knowledge on how changes of plant metabolism under elevated CO2 concentrations (e[CO2]) can affect the development of the glyphosate resistance of C3 and C4 weeds. Among the chemical herbicides, glyphosate, which is a non-selective and post-emergence herbicide, is currently the most widely used herbicide in global agriculture. As a consequence, glyphosate resistant weeds, particularly in major field crops, are a widespread problem and are becoming a significant challenge to future global food production. Of particular interest here it is known that the biochemical processes involved in photosynthetic pathways of C3 and C4 plants are different, which may have relevance to their competitive development under changing environmental conditions. It has already been shown that plant anatomical, morphological, and physiological changes under e[CO2] can be different, based on (i) the plant's functional group, (ii) the available soil nutrients, and (iii) the governing water status. In this respect, C3 species are likely to have a major developmental advantage under a CO2 rich atmosphere, by being able to capitalize on the overall stimulatory effect of e[CO2]. For example, many tropical weed grass species fix CO2 from the atmosphere via the C4 photosynthetic pathway, which is a complex anatomical and biochemical variant of the C3 pathway. Thus, based on our current knowledge of CO2 fixing, it would appear obvious that the development of a glyphosate-resistant mechanism would be easier under an e[CO2] in C3 weeds which have a simpler photosynthetic pathway, than for C4 weeds. However, notwithstanding this logical argument, a better understanding of the biochemical, genetic, and molecular measures by which plants develop glyphosate resistance and how e[CO2] affects these measures will be important before attempting to innovate sustainable technology to manage the glyphosate-resistant evolution of weeds under e[CO2]. Such information will be of essential in managing weed control by herbicide use, and to thus ensure an increase in global food production in the event of increased atmospheric [CO2] levels.

We have observed significantly increased HIV infection in HIV infected macrophages in the presence of cocaine that could be due to the downregulation of BST2 restriction factor in these cells. In human inflammasome PCR array, among different involved in inflammasome formation, in HIV infected macrophages in the presence of cocaine, we have observed significant upregulation of NLRP3, AIM2 genes and downstream genes IL-1β and PTGS2. Whereas negative regulatory gene MEFV was upregulated, CD40LG and PYDC1 were significantly downregulated. Among various NOD like receptors, NOD2 was significantly upregulated in both HIV alone and HIV plus cocaine treated cells. In the downstream genes, chemokine (C-C motif) ligand 2 (CCL2), CCL7 and IL-6 were significantly up regulated in HIV plus cocaine treated macrophages. We have also observed significant ROS production (in HIV and/or cocaine treated cells) which is one of the indirect-activators of inflammasomes formation. Further, we have observed early apoptosis in HIV alone and HIV plus cocaine treated macrophages which may be resultant of inflammasome formation and cspase-1 activation. These results indicate that in case of HIV infected macrophages exposed to cocaine, increased ROS production and IL-1β transcription serve as an activators for the formation of NLRP3 and AIM2 mediated inflammasomes that leads to caspase 1 mediated apoptosis.

The human immunodeficiency virus (HIV) is a neurotropic virus. It induces neurotoxicity and subsequent brain pathologies in different brain cells. Addiction to recreational drugs remarkably affects the initiation of HIV infections and expedites the progression of acquired immunodeficiency syndrome (AIDS) associated neuropathogenesis. Symptoms of HIV-associated neurocognitive disorders (HAND) are noticed in many AIDS patients. At least 50 % of HIV diagnosed cases show one or other kind of neuropathological signs or symptoms during different stages of disease progression. In the same line, mild to severe neurological alterations are seen in at least 80 % autopsies of AIDS patients. Neurological illnesses weaken the connections between neurons causing significant altercations in synaptic plasticity. Synaptic plasticity alterations during HIV infection and recreational drug abuse are mediated by complex cellular phenomena involving changes in gene expression and subsequent loss of dendritic and spine morphology and physiology. New treatment strategies with ability to deliver drugs across blood-brain barrier (BBB) are being intensively investigated. In this context, magnetic nanoparticles (MNPs) based nanoformulations have shown significant potential for target specificity, drug delivery, drug release, and bioavailability of desired amount of drugs in non-invasive brain targeting. MNPs-based potential therapies to promote neuronal plasticity during HIV infection and recreational drug abuse are being developed.

Background and Aims: Unique post-partum endocrine hormone oxytocin secreted during breastfeeding (BF) has amnestic, sedative properties and down-regulates stress responses. This study was done to assess the effect of BF on consumption of propofol, sevoflurane and haemodynamic stability in women., Methods: Study was conducted on 120 women aged 20-30 years of American Society of Anesthesiologists I and II physical status scheduled for tubectomy under general anaesthesia who were randomly allocated to three groups 40 of each; BF, withhold feeding (WF), and non-feeding (NF) groups. All received standard premedication. Heart rate (HR), mean arterial pressure (MAP) and state entropy (SE) values were recorded at regular intervals. All patients were induced with intravenous propofol until the SE levels dropped to 45, and dose of propofol recorded. Airway was secured with laryngeal mask airway and anaesthesia was maintained with sevoflurane in 60% N2O and O2. Sevoflurane concentration was adjusted to maintain SE between 40 and 60. End tidal concentration of sevoflurane and consumption of sevoflurane (ml) was recorded by GE Datex-Ohmeda S/5™ System. Results were analysed by analysis of variance and Chi-square test., Results: Demographic parameters were comparable. Dose of propofol and sevoflurane consumption in group BF was significantly reduced by 20% and 35%, respectively (P < 0.05) compared to group NF. Intra-operative HR and MAP were persistently low in group BF and elevated in group WF (P < 0.05)., Conclusion: BF before induction of anaesthesia decreases the consumption of propofol, sevoflurane and maintains the intra-operative haemodynamic stability, whereas withholding BF increases propofol and sevoflurane consumption with intra-operative higher HR and MAP, compared to control group.

Almost all eukaryotic mRNAs have a poly (A) tail at the 3'-end. Canonical PAPs (PAPα/γ) polyadenylate nuclear pre-mRNAs. The recent identification of the non-canonical Star-PAP revealed specificity of nuclear PAPs for pre-mRNAs, yet the mechanism how Star-PAP selects mRNA targets is still elusive. Moreover, how Star-PAP target mRNAs having canonical AAUAAA signal are not regulated by PAPα is unclear. We investigate specificity mechanisms of Star-PAP that selects pre-mRNA targets for polyadenylation. Star-PAP assembles distinct 3'-end processing complex and controls pre-mRNAs independent of PAPα. We identified a Star-PAP recognition nucleotide motif and showed that suboptimal DSE on Star-PAP target pre-mRNA 3'-UTRs inhibit CstF-64 binding, thus preventing PAPα recruitment onto it. Altering 3'-UTR cis-elements on a Star-PAP target pre-mRNA can switch the regulatory PAP from Star-PAP to PAPα. Our results suggest a mechanism of poly (A) site selection that has potential implication on the regulation of alternative polyadenylation., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Fetus in fetu (FIF) is an extremely rare congenital anomaly in the pediatric age group. It is defined by the presence of an axial skeleton and well-formed internal organs in a fetiform mass. Only about 15 cases of intracranial FIF have been reported in the literature worldwide. We report a case of temporo-occipitocervical FIF. This 7-month-old female child presented to us with occipital swelling that she had had since birth. A soft swelling was palpable in the retroauricular region with extension into the neck. A few bony parts were palpable in the swelling. Imaging was suggestive of a multiseptate mass lesion in the right occipital region with intracranial, intraspinal and extracranial components. The patient underwent exploration and excision of the extracranial mass and retromastoid suboccipital craniectomy and decompression of the intracranial component. Different parts, such as a terminal ileum, cecum, appendix, femur, humerus and vertebral body, were identified within the mass. This case meets Willis' criteria as well as 4/5 criteria stated by Spencer for the diagnosis of this condition. To the best of our knowledge, this is the first reported case of temporo-occipitocervical FIF with a well-defined embryological spectrum. This also supports Spencer's hypothesis of abnormal twinning., (© 2015 S. Karger AG, Basel.)

Spinal epidural abscess is a rare clinical entity with considerable morbidity. Even with prompt diagnosis and treatment, many patients are left with persistent residual neurological deficits. The present study details the outcome in 23 patients of primary pyogenic spinal epidural abscess, addressing the outcome following late presentation at a neurological facility. At presentation only 2 patients had relatively preserved neurological status. Eleven patients were paraplegic. All the patients underwent laminectomy and evacuation of abscess. A good functional outcome was observed in almost half of the patients, and there was a significant reduction in the number of the patients with severe disability. Factors influencing the outcome are described in this study.

Field pea (Pisum sativum L.) is an important grain legume consumed both as human food and animal feed. However, productivity in low rainfall regions can be significantly reduced by inferior soils containing high levels of boron and/or salinity. Furthermore, powdery mildew (PM) (Erysiphe pisi) disease also causes significant yield loss in warmer regions. Breeding for tolerance to these abiotic and biotic stresses are major aims for pea breeding programs and the application of molecular markers for these traits could greatly assist in developing improved germplasm at a faster rate. The current study reports the evaluation of a near diagnostic marker, PsMlo, associated with PM resistance and boron (B) tolerance as well as linked markers associated with salinity tolerance across a diverse set of pea germplasm. The PsMlo1 marker predicted the PM and B phenotypic responses with high levels of accuracy (>80%) across a wide range of field pea genotypes, hence offers the potential to be widely adapted in pea breeding programs. In contrast, linked markers for salinity tolerance were population specific; therefore, application of these markers would be suitable to relevant crosses within the program. Our results also suggest that there are possible new sources of salt tolerance present in field pea germplasm that could be further exploited.

Alginate hydrogel/zinc oxide nanoparticles (nZnO) composite bandage was developed by freeze-dry method from the mixture of nZnO and alginate hydrogel. The developed composite bandage was porous with porosity at a range of 60%-70%. The swelling ratios of the bandages decreased with increasing concentrations of nZnO. The composite bandages with nZnO incorporation showed controlled degradation profile and faster blood clotting ability when compared to the KALTOSTAT® and control bandages without nZnO. The prepared composite bandages exhibited excellent antimicrobial activity against Escherichia coli, Staphylococcus aureus, Candida albicans, and methicillin resistant S. aureus (MRSA). Cytocompatibility evaluation of the prepared composite bandages done on human dermal fibroblast cells by Alamar assay and infiltration studies proved that the bandages have a non-toxic nature at lower concentrations of nZnO whereas slight reduction in viability was seen with increasing nZnO concentrations. The qualitative analysis of ex-vivo re-epithelialization on porcine skin revealed keratinocyte infiltration toward wound area for nZnO alginate bandages.

Background and Aims: Studies have demonstrated minimal hemodynamic variation and postoperative complications with ProSeal laryngeal mask airway (PLMA) compared to endotracheal tube (ETT). Hence, a study was conducted to compare the ventilatory parameters and airway dynamics required to maintain normocarbia and stable hemodynamics with PLMA and ETT., Material and Methods: A prospective, randomized, single blinded study was conducted on 60 patients aged 20-40 years of American society of anesthesiologists class I and II, divided into Group PLMA and Group ETT. Standard anesthesia protocol was instituted. Group PLMA received PLMA sizes as per manufacturer's recommendations and group ETT received appropriate sized cuffed ETT. Patients were initially ventilated at 14 bpm, I:E ratio 1:2, tidal volume (Vt) 6 ml/kg and later adjusted to maintain end tidal carbon dioxide (EtCO2) between 35 and 40 mmHg. Peak airway pressure (Ppeak), compliance (Compl.), Vt, airway resistance (Raw), hemodynamic parameters, oxygen saturation (SpO2) and EtCO2 were recorded throughout surgery. Postoperative complications if any, were noted., Results: Demographic parameters, Raw, EtCO2, SpO2 were comparable between groups. Ppeak was lower and Vt needed to maintain EtCO2 of 35-40 mmHg was lesser in Group PLMA. Compl was low for 5 min after insertion of PLMA. Heart rate was significantly reduced at 1 min post insertion; blood pressures were significantly lower upto 2 min after insertion and post removal in group PLMA. Incidence of cough was significantly lower in group PLMA., Conclusion: ProSeal laryngeal mask airway maintains adequate ventilation at lower Vts and minimal peak pressures, has lesser hemodynamic variations and lower incidence of postoperative cough compared to ETT.

Magnetite (Fe3O4) is the most commonly and extensively explored magnetic nanoparticles (MNPs) for drug-targeting and imaging in the field of biomedicine. Nevertheless, its potential application as safe and effective drug-carrier for CNS (Central Nervous System) anomalies is very limited. Previous studies have shown an entangled epidemic of opioid use and HIV infection and increased neuropathogenesis. Opiate such as morphine, heroine, etc. are used frequently as recreational drugs. Existing treatments to alleviate the action of opioid are less effective at CNS level due to impermeability of therapeutic molecules across brain barriers. Thus, development of an advanced nanomedicine based approach may pave the way for better treatment strategies. We herein report magnetic nanoformulation of a highly selective and potent morphine antagonist, CTOP (D-Pen-Cys-Tyr-DTrp-Orn-Thr-Pen-Thr-NH2), which is impenetrable to the brain. MNPs, synthesized in size range from 25 to 40 nm, were characterized by Transmission electron microscopy and assembly of MNPs-CTOP nanoformulations were confirmed by FTIR spectroscopy and fluorescent detection. Flow-cytometry analysis showed that biological efficacy of this nanoformulation in prevention of morphine induced apoptosis in peripheral blood mononuclear cells remains equivalent to that of free CTOP. Similarly, confocal microscopy reveals comparable efficacy of free and MNPs bound CTOP in protecting modulation of neuronal dendrite and spine morphology during morphine exposure and morphine-treated HIV infection. Further, typical transmigration assay showed increased translocation of MNPs across in vitro blood-brain barrier upon exposure of external magnetic force where barrier integrity remains unaltered. Thus, the developed nanoformulation could be effective in targeting brain by application of external magnetic force to treat morphine addiction in HIV patients.

MicroRNAs (miRNAs), the post-transcriptional regulators of gene expression, play key roles in modulating many cellular processes. The changes in the expression profiles of several specific miRNAs affect the interactions between miRNA and their targets in various illnesses, including addiction, HIV, cancer etc. The presence of anti-HIV-1 microRNAs (which regulate the level of infectivity of HIV-1) have been validated in the cells which are the primary targets of HIV infection. Drugs of abuse impair the intracellular innate anti-HIV mechanism(s) in monocytes, contributing to cell susceptibility to HIV infection. Emerging evidence has implicated miRNAs are differentially expressed in response to chronic morphine treatment. Activation of mu opioid receptors (MOR) by morphine is shown to down regulate the expression of anti-HIV miRNAs. In this review, we summarize the results which demonstrate that several drugs of abuse related miRNAs have roles in the mechanisms that define addiction, and how they interact with HIV.

The human immunodeficiency virus 1 (HIV-1) still remains one of the leading life-threatening diseases in the world. The introduction of highly active antiretroviral therapy has significantly reduced disease morbidity and mortality. However, most of the drugs have variable penetrance into viral reservoir sites, including gut-associated lymphoid tissue (GALT). Being the largest lymphoid organ, GALT plays a key role in early HIV infection and host-pathogen interaction. Many different treatment options have been proposed to eradicate the virus from GALT. However, it becomes difficult to deliver traditional drugs to the GALT because of its complex physiology. In this regard, we developed a polymer-based Pluronic nanocarrier containing anti-HIV drug called efavirenz (EFV) targeting Microfold cells (M-cells) in the GALT. M-cells are specialized epithelial cells that are predominantly present in the GALT. In this work, we have exploited this paracellular transport property of M-cells for targeted delivery of Pluronic nanocarrier tagged EFV, bioconjugated with anti-M-cell-specific antibodies to the GALT (nanodrug). Preliminary characterization showed that the nanodrug (EFV-F12-COOH) is of 140 nm size with 0.3 polydispersion index, and the zeta potential of the particles was -19.38±2.2 mV. Further, drug dissolution study has shown a significantly improved sustained release over free drugs. Binding potential of nanodrug with M-cell was also confirmed with fluorescence microscopy and in vitro uptake and release studies. The anti-HIV activity of the nanodrug was also significantly higher compared to that of free drug. This novel formulation was able to show sustained release of EFV and inhibit the HIV-1 infection in the GALT compared to the free drug. The present study has potential for our in vivo targeted nanodrug delivery system by combining traditional enteric-coated capsule technique via oral administration.

The chronic obstructive pulmonary disease has become a disease of public health importance. Among the various risk factors, smoking remains the main culprit. In addition to airway obstruction, the presence of intrinsic positive end expiratory pressure, respiratory muscle dysfunction contributes to the symptoms of the patient. Perioperative management of these patients includes identification of modifiable risk factors and their optimisation. Use of regional anaesthesia alone or in combination with general anaesthesia improves pulmonary functions and reduces the incidence of post-operative pulmonary complications.

Background: Field pea (Pisum sativum L.) is a cool-season grain legume that is cultivated world-wide for both human consumption and stock-feed purposes. Enhancement of genetic and genomic resources for field pea will permit improved understanding of the control of traits relevant to crop productivity and quality. Advances in second-generation sequencing and associated bioinformatics analysis now provide unprecedented opportunities for the development of such resources. The objective of this study was to perform transcriptome sequencing and characterisation from two genotypes of field pea that differ in terms of seed and plant morphological characteristics., Results: Transcriptome sequencing was performed with RNA templates from multiple tissues of the field pea genotypes Kaspa and Parafield. Tissue samples were collected at various growth stages, and a total of 23 cDNA libraries were sequenced using Illumina high-throughput sequencing platforms. A total of 407 and 352 million paired-end reads from the Kaspa and Parafield transcriptomes, respectively were assembled into 129,282 and 149,272 contigs, which were filtered on the basis of known gene annotations, presence of open reading frames (ORFs), reciprocal matches and degree of coverage. Totals of 126,335 contigs from Kaspa and 145,730 from Parafield were subsequently selected as the reference set. Reciprocal sequence analysis revealed that c. 87% of contigs were expressed in both cultivars, while a small proportion were unique to each genotype. Reads from different libraries were aligned to the genotype-specific assemblies in order to identify and characterise expression of contigs on a tissue-specific basis, of which 87% were expressed in more than one tissue, while others showed distinct expression patterns in specific tissues, providing unique transcriptome signatures., Conclusion: This study provided a comprehensive assembled and annotated transcriptome set for field pea that can be used for development of genetic markers, in order to assess genetic diversity, construct linkage maps, perform trait-dissection and implement whole-genome selection strategies in varietal improvement programs, as well to identify target genes for genetic modification approaches on the basis of annotation and expression analysis. In addition, the reference field pea transcriptome will prove highly valuable for comparative genomics studies and construction of a finalised genome sequence.

Objective: The aim of this trial was to evaluate the bleeding after dental extractions among patients on uninterrupted antiplatelet therapy., Materials and Methods: A total of 190 patients under oral antiplatelet drugs requiring extraction of a single molar tooth were randomly assigned to two groups. Group A consisted of 95 patients on uninterrupted antiplatelet therapy and Group B consisted of 95 patients who have discontinued antiplatelet medication 5 days prior to extraction. The bleeding time of all patients was checked prior to extraction. The surgical procedure involved simple extraction of a single molar tooth under local anesthesia. The extraction socket was sutured with 3-0 silk. Pressure pack with gauze was given for 1 h. Bleeding after 1 h, 24 h, 48 h, and 5 days were compared between two groups. Chi-square test was used to compare the variables. P < 0.05 was taken as significant., Results: None of the patients in either group had any significant uncontrollable bleeding after extraction., Conclusion: Hence, we recommend routine single tooth extractions in patients on long-term antiplatelet medication, without interruption or alteration of their medication. Such patients do not have an increased risk of prolonged or excessive postoperative bleeding.

Background: Although highly active antiretroviral therapy (HAART) has significantly reduced the morbidity and mortality in HIV patients, virus continues to reside in the central nervous system (CNS) reservoir. Hence, a complete eradication of virus remains a challenge. HIV productively infects microglia/macrophages, but astrocytes are generally restricted to HIV infection. The relative importance of the possible replication blocks in astrocytes, however, is yet to be delineated. A recently identified restriction factor, sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1), restricts HIV infection in resting CD4(+)T cells and in monocyte-derived dendritic cells. However, SAMHD1 expression and HIV-1 restriction activity regulation in the CNS cells are unknown. Though, certain miRNAs have been implicated in HIV restriction in resting CD4(+)T cells, their role in the CNS HIV restriction and their mode of action are not established. We hypothesized that varying SAMHD1 expression would lead to restricted HIV infection and host miRNAs would regulate SAMHD1 expression in astrocytes., Results: We found increased SAMHD1 expression and decreased miRNA expression (miR-181a and miR-155) in the astrocytes compared to microglia. We report for the first time that miR-155 and miR-181a regulated the SAMHD1 expression. Overexpression of these cellular miRNAs increased viral replication in the astrocytes, through SAMHD1 modulation. Reactivation of HIV replication was accompanied by decrease in SAMHD1 expression., Conclusions: Here, we provide a proof of concept that increased SAMHD1 in human astrocytes is in part responsible for the HIV restriction, silencing of which relieves this restriction. At this time, this concept is of theoretical nature. Further experiments are needed to confirm if HIV replication can be reactivated in the CNS reservoir.

Rare type of calvarial defects seen in patients with neurofibromatosis type-1 (NF1) is presented. The issues of pathogenesis and management are discussed. Two cases of NF1 with skull defects in the region of the lambdoid suture are reported. The possible etiological basis and nature of these type of defects and management issues are discussed. The calvarial skull defects in the lambdoid suture region are rare defects in NF1 patients. The possible reason of the progressive nature of these type of lesions can be the cerebrospinal fluid pulsations behaving like "growing skull fractures," especially when not associated with structural lesions. It leads to progressive enlargement of the small congenital defects in the region of the lambdoid suture and abnormal susceptibility of bones for resorption. For these defects, conservative management is suggested due to its progressive nature and high chances of operative treatment failure.

Background: HIV-associated neurocognitive disorder (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occurs in approximately 50% of HIV infected individuals. In the United States, the prevalence of cigarette smoking ranges from 35-70% in HIV-infected individuals compared to 20% in general population. Cognitive impairment in heavy cigarette smokers has been well reported. However, the synergistic effects of nicotine and HIV infection and the underlying mechanisms in the development of HAND are unknown., Results: In this study, we explored the role of nicotine in the progression of HAND using SK-N-MC, a neuronal cell line. SK-N-MC cells were infected with HIV-1 in the presence or absence of nicotine for 7 days. We observed significant increase in HIV infectivity in SK-N-MC treated with nicotine compared to untreated HIV-infected neuronal cells. HIV and nicotine synergize to significantly dysregulate the expression of synaptic plasticity genes and spine density; with a concomitant increase of HDAC2 levels in SK-N-MC cells. In addition, inhibition of HDAC2 up-regulation with the use of vorinostat resulted in HIV latency breakdown and recovery of synaptic plasticity genes expression and spine density in nicotine/HIV alone and in co-treated SK-N-MC cells. Furthermore, increased eIF2 alpha phosphorylation, which negatively regulates eukaryotic translational process, was observed in HIV alone and in co-treatment with nicotine compared to untreated control and nicotine alone treated SK-N-MC cells., Conclusions: These results suggest that nicotine and HIV synergize to negatively regulate the synaptic plasticity gene expression and spine density and this may contribute to the increased risk of HAND in HIV infected smokers. Apart from disrupting latency, vorinostat may be a useful therapeutic to inhibit the negative regulatory effects on synaptic plasticity in HIV infected nicotine abusers.

Background: Gut damage resulting in microbial translocation (MT) is considered a major cause of immune activation (IA) in HIV infection, but data in children are limited, particularly in the absence of antiretroviral therapy., Methods: Sixty perinatally HIV-infected, antiretroviral therapy-naive children, aged 2-12 years, were evaluated for plasma levels of lipopolysaccharide, DNA sequences encoding bacterial 16 second ribosomal DNA (16S rDNA) and soluble CD14 concurrently with markers of CD4 and CD8 T-cell IA and immune exhaustion (IE), CD4 counts, and plasma viral load. At study entry, participants were classified into immune categories (ICs): IC1 (CD4% > 25), IC2 (CD4% 15-25), and IC3 (CD4% < 15). Age-matched HIV-uninfected children served as controls. Data were evaluated at study entry and at 12 months., Results: Levels of MT, IA, and IE were increased in patients as compared with controls, were highest in patients in IC3 group, and did not change over 12 months. MT products lipopolysaccharide and 16S rDNA correlated with each other and each correlated with plasma viral load, soluble CD14, and T-cell IA and IE. There was a correlation of IA with IE. CD4 counts and percentage were inversely correlated with MT products and underlying CD4 activation., Conclusions: In a natural history cohort of HIV-infected children not on therapy, MT was more pronounced in the most severely immunocompromised patients and was associated with IA. Strategies to reduce MT may help to reduce IA and prevent CD4 depletion.

Although highly active antiretroviral therapy (HAART) has resulted in remarkable decline in the morbidity and mortality in AIDS patients, controlling HIV infections still remain a global health priority. HIV access to the CNS serves as the natural viral preserve because most antiretroviral (ARV) drugs possess inadequate or zero delivery across the brain barriers. Thus, development of target-specific, effective, safe, and controllable drug-delivery approach is an important health priority for global elimination of AIDS progression. Emergence of nanotechnology in medicine has shown exciting prospect for development of novel drug delivery systems to administer the desired therapeutic levels of ARV drugs in the CNS. Neuron-resuscitating and/or antidependence agents may also be delivered in the brain through nanocarriers to countercheck the rate of neuronal degradation during HIV infection. Several nanovehicles such as liposomes, dendrimers, polymeric nanoparticles, micelles, and solid lipid nanoparticles have been intensively explored. Recently, magnetic nanoparticles and monocytes/macrophages have also been used as carrier to improve the delivery of nanoformulated ARV drugs across the blood-brain barrier. Nevertheless, more rigorous research homework has to be elucidated to sort out the shortcomings that affect the target specificity, delivery, release, and/or bioavailability of desired amount of drugs for treatment of neuroAIDS., (Copyright © 2014 John Wiley & Sons, Ltd.)

The blood-brain barrier (BBB) is considered as the primary impediment barrier for most drugs. Delivering therapeutic agents to the brain is still a big challenge to date. In our study, a dual mechanism, receptor mediation combined with external non-invasive magnetic force, was incorporated into ferrous magnet-based liposomes for BBB transmigration enhancement. The homogenous magnetic nanoparticles (MNPs), with a size of ∼10 nm, were synthesized and confirmed by TEM and XRD respectively. The classical magnetism assay showed the presence of the characteristic superparamagnetic property. These MNPs encapsulated in PEGylated fluorescent liposomes as magneto-liposomes (MLs) showed mono-dispersion, ∼130 ± 10 nm diameter, by dynamic laser scattering (DLS) using the lipid-extrusion technique. Remarkably, a magnetite encapsulation efficiency of nearly 60% was achieved. Moreover, the luminescence and hydrodynamic size of the MLs was stable for over two months at 4 ° C. Additionally, the integrity of the ML structure remained unaffected through 120 rounds of circulation mimicking human blood fluid. After biocompatibility confirmation by cytotoxicity evaluation, these fluorescent MLs were further embedded with transferrin and applied to an in vitro BBB transmigration study in the presence or absence of external magnetic force. Comparing with magnetic force- or transferrin receptor-mediated transportation alone, their synergy resulted in 50-100% increased transmigration without affecting the BBB integrity. Consequently, confocal microscopy and iron concentration in BBB-composed cells further confirmed the higher cellular uptake of ML particles due to the synergic effect. Thus, our multifunctional liposomal magnetic nanocarriers possess great potential in particle transmigration across the BBB and may have a bright future in drug delivery to the brain.

Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and miR-155, which are integral to HIV replication, and immune activation. Using miRNA isolation and analysis, RNA interference, quantitative real time PCR, and reporter assays we explored the effects of cocaine on miR-155 and miR-20 in the context of HIV infection. Here we demonstrate using monocyte-derived dendritic cells (MDCCs) that cocaine significantly inhibited miR-155 and miR-20a expression in a dose dependent manner. Cocaine and HIV synergized to lower miR-155 and miR-20a in MDDCs by 90%. Cocaine treatment elevated LTR-mediated transcription and PU.1 levels in MDCCs. But in context of HIV infection, PU.1 was reduced in MDDCs regardless of cocaine presence. Cocaine increased DC-SIGN and and decreased CD83 expression in MDDC, respectively. Overall, we show that cocaine inhibited miR-155 and prevented maturation of MDDCs; potentially, resulting in increased susceptibility to HIV-1. Our findings could lead to the development of novel miRNA-based therapeutic strategies targeting HIV infected cocaine abusers.