Analysis and Implementation of Malicious Node in AODV Routing Protocol

The Mobile Ad-hoc Network (MANET) is constructed based on wireless medium and it is of self organizing behaviour. MANET is easy to establish and having dynamic topology. The mobile Ad-hoc networks are vulnerable to various networks attacks because MANET operational environment is open and dynamic or live. MANET uses the Routing protocols for data transfer. Two different types of Routing protocols are available: Table Driven and On Demand Routing Protocols. Malicious node is the one type of mobile node but its work is completely different compared to normal Mobile nodes. Malicious nodes have capability to change or remove Routing Information. It also sends or advertises the fake Route Request to attract user’s data. Malicious node disturbs the Network to carry correct flow of operation. It is responsible for attacks on the existing normal mobile nodes and creates receiver collision, limited transmission power, false misbehaviour etc. Malicious or selfish node carries attacks on the networks so it directly effects to the routing Performance. The objective of this work is to check Network performance in malicious environment and provide prevention for the attack. Throughput and Delay are analysed for Denial of Service (DoS) attack and prevention scenarios. Keywords: MANET, AODV, Selfish Node, DoS Attack, Routing Protocol

Morbidly adherent placenta: management is real challenge

Background: The objective of the present study was to describe management of morbidly adherent placenta with placenta previa and feto-maternal outcome.Methods: All antenatal USG diagnosed cases of morbidly adherent placenta were analyzed. The cases were managed by elective caesarean hysterectomy and non-separation of placenta at delivery. Amount of blood loss, blood transfused, ICU admission, postnatal complications and hospital stay was recorded.Results: From January 2010 to October 2018, 22 cases of morbidly adherent placenta were diagnosed on gray scale and color Doppler during antenatal ultrasound scan. Scheduled caesarean hysterectomy without attempting placental removal was done. Subtotal hysterectomy was performed in 17(77.2%) cases and total hysterectomy in remaining 5(22.8%) cases. All the patients required blood transfusion.  Seven (31.8%) patients had urinary bladder injury. One case developed DIC and One needed ventilatory support. No patient died in this series.Conclusions: Antenatal diagnosed cases of morbidly adherent placenta, avoidance of placental separation and caesarean hysterectomy results in better maternal outcome

A study on diagnosis and management of arteriovenous malformation of uterus

Background: Arteriovenous malformation is abnormal connection between an organ’s arterial and venous circulation. In acquired AVM, history of uterine procedure seems inevitable. Their clinical feature is usually vaginal bleeding. It is diagnosed by 2-D ultrasonography combined with colour doppler. Most of the time they resolve spontaneously; however, if left untreated, uterine artery embolization or hysterectomy comes in hand. The purpose of this study was to evaluate the role of TVUS and colour doppler in the diagnosis and follow-up of treated cases of uterine AVM. This study also aims to evaluate different modalities to manage uterine AVM.Methods: This was a retrospective study done at tertiary care centre from January 2018 to December 2019 to assess the presentation, treatment, and clinical pictures of patients with uterine AVM that were diagnosed with TVUS. Authors reviewed both (1) clinical data (2) ultrasound data of patients. The diagnostic criteria were “subjective” with a rich vascular network in the myometrium with the use of colour Doppler images and “objective” with a high PSV of 20 cm/sec in the vascular web.Results: Thirteen patients met the diagnostic criteria mentioned above. Out of that 100% presented with on and off bleeding per vaginum. Recent and remote history of uterine procedures were in found in 84.6% (n=11) of cases. UAE was done in 53.8% (n=7) cases. Thirty-three (33%) (n=5) cases spontaneously resolved when closely monitored with serial imaging and serum beta- HCG levels. Hysterectomy was needed in 7.4% (n=1) of patients of AVM.Conclusions: Uterine AVM occurred after unsuccessful pregnancies or uterine procedures. Triage of patients for expectant treatment, hormonal treatment vs intervention with uterine artery embolization based on their clinical status, which was supplemented by objective measurements of blood velocity measurement in the AVM, appears to be a good predictor of outcome

Giant prostatic hyperplasia: surgical treatment a rare case

We report a rare case of giant prostatic hyperplasia in an 80-year-old male patient. MRI revealed a markedly enlarged prostate measuring 814gm.We have performed suprapubic open prostatectomy (Transvesical). The adenoma was completely enucleated in one piece which was 11cm×16cm in size and weighed 504gm

Molecular Predictors of Immunophenotypic Measurable Residual Disease Clearance in Acute Myeloid Leukemia

Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT). Induction chemotherapy led to MRD- remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD-. Mutations in CEBPA, NRAS, KRAS, and NPM1 predicted high rates of MRD- remission, while mutations in TP53, SF3B1, ASXL1, and RUNX1 and karyotypic abnormalities including inv (3), monosomy 5 or 7 predicted low rates of MRD- remission. Patients with fewer individual clones were more likely to achieve MRD- remission. Among 132 patients who underwent allo-SCT, outcomes were favorable whether patients achieved early MRD- after induction or later MRD- after subsequent therapy prior to allo-SCT. As MRD conversion with chemotherapy prior to allo-SCT is rarely achieved in patients with specific baseline mutational patterns and high clone numbers, upfront inclusion of these patients into clinical trials should be considered

A Unique Modification of the Eukaryotic Initiation Factor 5A Shows the Presence of the Complete Hypusine Pathway in Leishmania donovani

Deoxyhypusine hydroxylase (DOHH) catalyzes the final step in the post-translational synthesis of an unusual amino acid hypusine (N€-(4-amino-2-hydroxybutyl) lysine), which is present on only one cellular protein, eukaryotic initiation factor 5A (eIF5A). We present here the molecular and structural basis of the function of DOHH from the protozoan parasite, Leishmania donovani, which causes visceral leishmaniasis. The L. donovani DOHH gene is 981 bp and encodes a putative polypeptide of 326 amino acids. DOHH is a HEAT-repeat protein with eight tandem repeats of α-helical pairs. Four conserved histidine-glutamate sequences have been identified that may act as metal coordination sites. A ∼42 kDa recombinant protein with a His-tag was obtained by heterologous expression of DOHH in Escherichia coli. Purified recombinant DOHH effectively catalyzed the hydroxylation of the intermediate, eIF5A-deoxyhypusine (eIF5A-Dhp), in vitro. L. donovani DOHH (LdDOHH) showed ∼40.6% sequence identity with its human homolog. The alignment of L. donovani DOHH with the human homolog shows that there are two significant insertions in the former, corresponding to the alignment positions 159-162 (four amino acid residues) and 174-183 (ten amino acid residues) which are present in the variable loop connecting the N- and C-terminal halves of the protein, the latter being present near the substrate binding site. Deletion of the ten-amino-acid-long insertion decreased LdDOHH activity to 14% of the wild type recombinant LdDOHH. Metal chelators like ciclopirox olamine (CPX) and mimosine significantly inhibited the growth of L. donovani and DOHH activity in vitro. These inhibitors were more effective against the parasite enzyme than the human enzyme. This report, for the first time, confirms the presence of a complete hypusine pathway in a kinetoplastid unlike eubacteria and archaea. The structural differences between the L. donovani DOHH and the human homolog may be exploited for structure based design of selective inhibitors against the parasite

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Synthesis, characterization and biological study of novel heterocyclic compounds

The structures of these compounds were established on the basis of analytical and spectral data. The newly synthesized compounds were evaluated for their antibacterial and antifungal activities