Paradigm shift in drug re-purposing from Phenalenone to Phenaleno-Furanone to combat multi-drug resistant Salmonella Enterica Serovar Typhi

Over recent years, typhoid fever has gained increasing attention with several cases reporting treatment failure due to multidrug resistant (MDR) strains of Salmonella enterica serovar Typhi. While new drug development strategies are being devised to combat the threat posed by these MDR pathogens, drug repurposing or repositioning has become a good alternative. The latter is considered mainly due to its capacity for saving sufficient time and effort for pre-clinical and optimization studies. Owing to the possibility of an unsuccessful repositioning, due to the mismatch in the optimization of the drug ligand for the changed biochemical properties of “old” and “new” targets, we have chosen a “targeted” approach of adopting a combined chemical moiety-based drug repurposing. Using small molecules selected from a combination of earlier approved drugs having phenalenone and furanone moieties, we have computationally delineated a step-wise approach to drug design against MDR Salmonella. We utilized our network analysisbased pre-identified, essential chaperone protein, SicA, which regulates the folding and quality of several secretory proteins including the Hsp70 chaperone, SigE. To this end, another crucial chaperone protein, Hsp70 DnaK, was also considered due to its importance for pathogen survival under the stress conditions typically encountered during antibiotic therapies. These were docked with the 19 marketed anti-typhoid drugs along with two phenalenone-furanone derivatives, 15 non-related drugs which showed 70% similarity to phenalenone and furanone derivatives and other analogous small molecules. Furthermore, molecular dynamics simulation studies were performed to check the stability of the protein-drug complexes. Our results showed the best binding interaction and stability, under the parameters of a virtual human body environment, with XR770, a phenaleno-furanone moiety based derivative. We therefore propose XR770, for repurposing for therapeutic intervention against emerging and significant drug resistance conferred by pathogenic Salmonella strains

Frequency of Anti-HBc & HBV DNA detection in blood donors of Kerman province, Iran

Hepatitis B is a serious global infection disease and a major cause of mortality and morbidity worldwide. However, data on Occult Hepatitis B in Iran are scare. The current study assessed the frequency of Anti-HBc and HBV DNA in serum sample of healthy blood donors negative for HBsAg stratified by sex and age; and also investigated the relationship between detection of HBV-DNA and anti-HBc positivity. Since anti-HBc screening is not performed in Iranian Blood Bank, we assessed whether anti-HBc could be adopted as a screening assay for the donated blood. The study included a total of 1525 blood samples of blood donors negative for hepatitis B virus surface antigen ( 87% male with a mean age &plusmn; SD: of 31&plusmn;8yr; and 13% female with a mean age &plusmn; SD of 30&plusmn;6yr). Eight percent (121 out of 1525) of the blood samples with negative HBs-Ag were positive for Anti-HBc and were all from males. HBV-DNA was detected in 36 out of 121 anti-HBc+ specimens (29.7%). The study found a positive relation between anti-HBc positivity and detection of HBV-DNA in serum samples of HBs-Ag negative blood donors. Findings from this study suggest that, introducing anti HBc screening in Iran maybe very practical in order to limit the transmission risk of Occult Hepatitis B virus through blood transfusion.<br /

A side-effect free method for identifying cancer drug targets

Identifying efective drug targets, with little or no side efects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side efect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identifcation of efective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying efective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as efective candidates for drug development

“Impact of Mild Level Exercises on Gait, Balance, Functional Status to Prevent Fall Among Elderly In Selected Areas of Belagavi District, Karnataka – A Study Protocol”

Context: Falls, a frequent and preventable cause of morbidity, raise the likelihood of functional independence loss and the requirement for hospitalization and institutionalization, placing a strain on the healthcare system. The annual expenses for acute care linked to fractures from falls are estimated at $10 billion, despite the fact that the entire expenditures for acute care connected to falls remain unclear. Aims: To administer the mild level exercise programme of elderly among experimental group and to determine the effect of mild level exercise program on improvement of gait, balance and functional status of elderly among experimental group. Settings and Design: The samples from the selected rural areas of Belagavi district were selected using convenient sampling technique. A quantitative approach with post test only control group design was adopted for the study. Subjects and Methods: Elderly above the age of 60 years of selected rural areas of gokak taluka belagavi district and total 250 samples selected by using convenient sampling technique and my research approach is Quantitative Research Approach, Research deign is Post test only control group design and Sampling technique is Non-Probability; Convenient Sampling Technique respectively. Conclusions: The mild level exercise program was very much effective and the elders had great interest to learn and to do the exercises to improve their gait, balance, functional and to reduce the incidence of fall.&nbsp; Continuing nursing education programs can be conducted in hospitals and community regarding the importance of low intensity exercise program in improving gait, balance, functional status and in reducing the incidence of falls in the elderly people. &nbsp

Smart Environment Monitoring System Using Wired and Wireless Network: A Comparative Study

This chapter focuses on the implementation of a smart environment monitoring system using wired and wireless sensor networks (WSN). The goal was to develop a LabVIEW based system to monitor environmental parameters that provide inaccessible, real-time monitoring. The development of portable and efficient environment monitoring system based on LabVIEW GUI that monitors various environmental parameters such as temperature, relative humidity, Air quality and light intensity was developed. This chapter targets on both wired and wireless approach for environment monitoring. The limitations of wired network were explained by flourishing the portable system. For proceedings with the impediment and insufficiency of wired network, Arduino augmentation ascendancy, are mingled with XBee wireless sensor network. The data from the environment was sent to the sink node wirelessly through mote. Monitoring of the data was done in a personal computer (PC) through a graphical user interface made by LabVIEW. The pertinent sensor for each was connected to analog input of Arduino UNO and their values are displayed on front panel of LabVIEW. LabVIEW run time engine makes the system cost effective and facile. To reveal the effectiveness of the system, some measurement results are also predicted in this chapter

Insilico Drug Prediction and Validation of Lead candidates on Plasmodium falciparum Erythrocyte Membrane Protein 1(pfEMP1) against Malaria

Malaria is an infectious disease caused by protozoan of the genus Plasmodium. It is transmitted by bite from infected female Anopheles mosquito. Plasmodium falciparum erythrocyte membrane protein 1 (PfEmp1), an antigen that is responsible for the immune evasion of the protozoan. This protein has adhesive properties that cause the infected erythrocytes to bind to the endothelial lining of the blood vessel, thus preventing the infected cells from getting filtered by the spleen. It is found that there is an interaction between the sulphate ion on the endothelial cells and NH1, NH2 of Arg 1467 (A), NZ of Lys 1324 (A) and two bonds with N of Gly 1329 (A) on the protein. Inhibiting this interaction may prevent the evasive action. A Ligand with SO4 interactive region can be used to achieve this. Computer aided drug designing techniques were used to find a new scaffold to solve the purpose. GROMACS was used to simulate the protein-Ligand interaction. It was observed that ZINC17206599 shows the best interaction and may prove to be a promising candidate drug for Malaria. 

Impact of Mild Level Exercise Program on Incidence of Falls, Gait and Balance Among Elderly People at Selected Rural Areas of Belagavi District.

Context: Exercises that are low-intensity can aid with balance and gait. Regular low-intensity exercise is a beneficial substitute for treating balance and gait issues brought on by ageing. Objective: To assess incidence of falls, gait and balance of elderly people before and after low intensity exercise program and to assess effectiveness of low intensity exercise program on incidence of falls, gait and balance of elderly people. Setting and design: The study was conducted in selected rural areas of Belgaum district and pre experimental one group pretest post test study design was used. Materials and Methods: Population was comprised of elderly people aged 60 years and above. The sample size was 30 and non probability purposive sampling technique was used to select the samples. Berg balance scale and Performance oriented mobility assessment scale for gait was used to assess gait and balance.. Statistical Analysis used:Descriptiveand inferential statistics were used with the helpof SPSSversion 20. Results: In pretest12 (40%) of elders had incidence of fall during the one month prior to pre test and is reduced in post test as 7(23.3%) were had incidence of fall after one month to interventional program. The obtained value of ‘ t’ (29) = 6.97 for gait and ‘ t’ (29) = 2.65 for balance are found significant at 0.05 level of significance, indicating that the low intensity exercise program has helped elderly to improve their gait and balance. Conclusions: Low intensity exercise program helped elderly people to improve their gait and balance. So, such programs need to be implemented in community area to prevent incidence of fall and improve gait and balance among the elderly population

To evaluate safety and efficacy of Arthrohills oil in subjects with Musculoskeletal Pain

Musculoskeletal pain affects bones, joints, ligaments, tendons or muscles. An injury such as a fracture may cause sudden, severe pain. According to the World Health Organization (WHO), 20-33% of the world’s population has some form of chronic musculoskeletal pain, translating to 1.75 billion people globally. Outdoor patients, having chronic pain of musculoskeletal origin were advised Arthrohills oil external application locally as few drops for small joints and up to 2–3 ml for the larger joints once in a day for external application with gentle massage for 15 min up to 6 weeks were used in this study. Assessment points were Pain, Tenderness, Swelling and Joint motility. We can conclude that, effect observed in all parameters is significant. Arthohills oil was safe and effective in musculoskeletal pain

To evaluate safety and efficacy of Keshohills hair oil in subjects with mild to moderate hair fall and dandruff

Introduction - Hair fall is one of the minor diseases which is affecting approximately 1.7% of the world population and challenging task for physicians. Treating Hair issues with ayurvedic medicated oils have gained importance due to the safety and efficacy of their use. Keshohills hair oil is Ayurvedic proprietary medicine&nbsp;formulated as oil with herbs aimed at reducing hair fall and scalp dandruff. Objective - The aim of this clinical study was to evaluate the effectiveness of Keshohills hair oil&nbsp; in the management of hair fall and dandruff of the scalp in adults. Materials and Methods - &nbsp;&nbsp;50 healthy respondents were enrolled and completed the period of study positively. The 60 Second Hair Comb Test, Adherent Scalp Flaking Score, Objective Hair Assessment Questionnaire, were used in the study. Conclusion - Keshohills hair oil was effective in reducing hair loss, treating Seborrheic dermatitis

ANTIMIGRAINE ACTIVITY OF METHANOLIC EXTRACT OF ABROMA AUGUSTA L. IN LABORATORY ANIMALS

Objective: The present study aimed to evaluate of antimigraine activity of methanolic extract of Abroma augusta L. leaves in laboratory animals. Methods: The antimigraine activity was evaluated against nitroglycerine (NTG, 10 mg·kg−1, i. p.) and bradykinin (BK, 10 µg, intra-arterial) induced hyperalgesia in rats. Rats were divided randomly into six groups: normal, control, standard (sumatriptan, 42 mg·kg−1, s. c.), and Abroma augusta L. (100,200 and 400 mg·kg−1, p. o.). In the nitroglycerin (NTG) induced hyperalgesia model, rats were pre-treated with standard drug sumatriptan and Abroma augusta L. for 0, 7 and 14 d and tail flick latency were recorded separately in 0-day, 7-day and 14-day pretreatment study. Brain serotonin concentration was also estimated by HPLC method at the end of the study. In bradykinin induced hyperalgesia model the number of vocalizations were recorded as a measure of hyperalgesia in rats. Results: Abroma augusta L. showed a significant (P&lt;0.001) elevation in the tail-flick latency (at dose 400 mg·kg−1) and body weight (at doses 100, 200, and 400 mg·kg−1) in NTG-induced hyperalgesia model in rats. Further, A. augusta L. (400 mg/kg) showed a significant (P&lt;0.001) increase in brain serotonin concentration compared to NTG control group animal. It showed a significant (P&lt;0.01, P&lt;0.001) reduction in the elevated number of vocalizations at doses (200 and 400 mg·kg−1) in the bradykinin-induced hyperalgesia model in rats. Conclusion: We concluded that the methanolic extract of Aroma augusta L. possessed an anti-migraine effect in nitroglycerine and bradykinin-induced hyperalgesia model in rats