Identification and Antimicrobial Susceptibility Profile of Bacterial Pathogens Isolated From Wound Infections in a Teaching Hospital, Peshawar, Pakistan

Background: The resistance profile of bacteria causing wound infections may vary from time to time in a given geographical location. The key objective of this study was to determine the prevalent aerobic and or facultative anaerobic bacterial types and their antibiogram to commonly prescribed antibiotics.Methods: Pus, drainage or wound swabs from various body parts of 200 patients were aseptically collected from Khyber Teaching Hospital (KTH) and processed by standard microbiological techniques for identification of bacterial isolates and later antimicrobial susceptibility profile was determined as per Clinical and Laboratory Standard Institute (CLSI) guidelines by using Kirby-Bauer method.Results: Out of 200 clinical wound specimens processed, Staphylococcus aureus was the most common bacterial pathogen isolated (n=100, 50%), followed by Escherichia coli (n=45, 22.5%),Pseudomonas aeruginosa (n=35, 17.5%), Enterobacter species (n=14, 7%), Proteus species (n=5, 2.5%) and Morganella species (n=1, 0.5%). Staphylococcus aureus (n=100) showed highest resistance to amoxicillin (82%), followed by ofloxacin (80%), sparfloxacin (78%), ciprofloxacin (71%), levofloxacin (46%) and Gentamicin (34%). Out of 100 S. aureus isolates methicillin and vancomycin resistance was found to be in 1.5 and 2% of the isolates, respectively. Among Gram negative isolates (n=100) the vast majority were resistant to augmentin, followed by cephalosporins, quinolones and almost fairly susceptible to carbapenems, cefoperazone + sulbactam and aminoglycosides.Conclusion: There is a need for judicious use of antibiotics in clinical setup. The periodic monitoring of bacterial pathogens and their susceptibility profile is very helpful in understanding the resistance phenotypes in a given area which ultimately help physicians in selecting suitable empirical therapy

Phytotoxic characterization of crude methanolic extract of Periploca aphylla

Periploca aphylla is traditionally used in the treatment of various ailments. Phytotoxic activity of crude methanolic extract of P. aphylla was tested on the germination of wheat seeds and on the growth of the germinated seedlings. In both the field and plate studies, the extract showed inhibitory effect on the germination of the growth of root and shoot of the seedlings. The inhibition was found to be dose dependent. The higher concentration of 1000 μg/ml showed maximum inhibitory effect on the growth of root and shoots in the studies of plate as well as on fresh and dry weight of wheat plant. Similarly, the herbicidal activity is also dependent on the concentration of extract. In this study, it was found that inhibitory potential of methanolic extract of P. aphylla increased as 1000 >100 >10 μg/ml.Keywords: Phytotoxic activity, herbicidal activity, germination, plates and field studies, Perifloca aphyll

Evaluation of Antibiotics Pattern of Extended Spectrum Beta-Lactamase Producing Multi-Drug Resistant Pseudomonas aeruginosa

Background: Pseudomonas aeruginosa (Ps. aeruginosa) is considered as an opportunistic pathogen and the leading cause of morbidity and mortality in immunocompromised individuals. Globally, approximately 10-15% of the nosocomial infections are caused by Ps. aeruginosa. The Ps. aeruginosa can acquire resistance against broad-spectrum antibiotics. According to recent studies increased mortality has been observed due to infection with extended-spectrum-beta-lactamase (ESBL) producing Ps. aeruginosa strains. This study was designed to determined antibiogram of ESBL producing multi-drug resistant Ps. aeruginosa in Khyber Pakhtunkhwa.Methods: The clinical confirmed Ps. aeruginosa samples were collected according to the standard protocol, at Khyber Teaching Hospital (KTH), Peshawar. All collected samples were sub- cultured on appropriate culture media. After isolation and identification, the antibiotics susceptibility testing was performed. The detection of ESBL was carried out by the double-disc diffusion method. Carbapenemase-producing bacteria was confirmed by the modified Hodge test. Descriptive analysis was performed for statistical analysis of collected data.Results: A total of one hundred and sixty-two (n=162) Ps. aeruginosa confirmed isolates were collected, in which 59.3% were male and 40.7% were from female patients. The percentages of ESBL and carbapenemase producing Ps. aeruginosa isolates were 5.5% and 23.5%, respectively. The multidrug resistance was observed against 27.2% isolates. Among tested antibiotics highest percentages of resistance was observed against ciprofloxacin (43%) and ceftazidime (39.5%). Conclusion: We observed highest level of drug resistance in Ps. aeruginosa clinical isolates against tested antibiotics and majority of the isolates were Multi-drug resistant (MDR).Keywords: Pseudomonas; Multi-Drug Resistant; Extended Spectrum Beta Lactamases; Antibiotics Susceptibilit

Analytical Model for Underwater Wireless Sensor Network Energy Consumption Reduction

In an Underwater Wireless Sensor Network (UWSN), extreme energy loss is carried out by the early expiration of sensor nodes and causes a reduction in efficiency in the submerged acoustic sensor system. Systems based on clustering strategies, instead of each node sending information by itself, utilize cluster heads to collect information inside the clusters for forwarding collective information to sink. This can effectively minimize the total energy loss during transmission. The environment of UWSN is 3D architecture-based and follows a complex hierarchical clustering strategy involving its most effecting unique parameters such as propagation delay and limited transmission bandwidth. Round base clustering strategy works in rounds, where each round comprises three fundamental stages: cluster head selection, grouping or node association, and data aggregation followed by forwarding data to the sink. In UWSN, the energy consumed during the formation of clusters has been considered casually or completely evaded in the previous works. In this paper, the cluster head setup period has been considered the main contributor to extra energy utilizer. A numerical channel model is proposed to compute extra energy. It is performed by using a UWSN broad model. The results have shown that extra maximum energy consumption is approximately 12.9 percent of the system total energy consumed in information transmissions

In vivo carbon tetrachloride-induced hepatoprotective and in vitro cytotoxic activities of Garcinia hombroniana (seashore mangosteen)

Background: Garcinia hombroniana, known as "manggis hutan" (jungle mangosteen) in Malaysia, is distributed in tropical Asia, Borneo, Thailand, Andaman, Nicobar Islands, Vietnam and India. In Malaysia, its ripened crimson sour fruit rind is used as a seasoning agent in curries and culinary dishes. Its roots and leaves decoction is used against skin infections and after child birth. This study aimed to evaluate in vivo hepatoprotective and in vitro cytotoxic activities of 20% methanolic ethyl acetate (MEA) G. hombroniana bark extract. Materials and methods: In hepatoprotective activity, liver damage was induced by treating rats with 1.0 mL carbon tetrachloride (CCl4)/kg and MEA extract was administered at a dose of 50, 250 and 500 mg/kg 24 h before intoxication with CCl4. Cytotoxicity study was performed on MCF-7 (human breast cancer), DBTRG (human glioblastoma), PC-3 (human prostate cancer) and U2OS (human osteosarcoma) cell lines. 1H, 13C-NMR (nuclear magnetic resonance), and IR (infrared) spectral analyses were also conducted for MEA extract. Results: In hepatoprotective activity evaluation, MEA extract at a higher dose level of 500 mg/kg showed significant (p<0.05) potency. In cytotoxicity study, MEA extract was more toxic towards MCF-7 and DBTRG cell lines causing 78.7% and 64.3% cell death, respectively. MEA extract in 1H, 13C-NMR, and IR spectra exhibited bands, signals and J (coupling constant) values representing aromatic/phenolic constituents. Conclusions: From the results, it could be concluded that MEA extract has potency to inhibit hepatotoxicity and MCF-7 and DBTRG cancer cell lines which might be due to the phenolic compounds depicted from NMR and IR spectra

Adaptive energy efficient circular spinning protocol for dynamic cluster based UWSNs

Under Water Sensor Network (UWSN) is a novel paradigm for exploring marine environments such as offshore and mineral exploration, underwater surveillance, and sea habitat monitoring. However, a good quality underwater communication is difficult to achieve due to different constraints such as limited bandwidth, acoustic propagation issues, delays, battery replacement hitches, etc. In recent works, efficient energy-based designing and overall performance evaluation of the UWSN has become a major consideration. Cluster-based sensor networks have proven to be a successful way to increase the network's load congruency and scalability while lowering the system's total energy consumption. Usually, clustering algorithms work in three phases; cluster setup, data collection, and transmission to sink. In these types of dynamic cluster-based networks, energy consumed in cluster setup has been considered insignificant. Since these network energy consumptions are not part of data communication, we consider it extra energy consumption. In this paper, a new Energy Efficient Circular Spinning (EECS) dynamic clustering algorithm has been proposed to provide an improved cluster setup system and to minimize energy usage in re-clustering or cluster setup. Our proposed EECS mechanism suggests that system performance can improve by reducing the Cluster Head (CH) selection phase or cluster setup phase and can ultimately minimize the energy consumption of networks. It is demonstrated that by reducing the transmission of superfluous control messages during the cluster arrangement stage, approximately 21.5% to28.4% of the total network energy expended can be saved. This paper also compares the extra energy consumption, total network energy consumption, and life of the network in our proposed EECS mechanism to two different mechanisms, (1) Adaptive LEACH for UW, (2) UMOD-LEACH. The optimum value of cluster head has been calculated from energy consumption of different protocols and results show that our proposed EECS can prolong network lifetime by 21.5% and 28.4%from the above-mentioned algorithms consequently. In future, we will extend outwork for multi-hop dynamic cluster base mechanism for UW

Whole genome sequencing of drug resistant Mycobacterium tuberculosis isolates from a high burden tuberculosis region of North West Pakistan

Tuberculosis (TB), caused by Mycobacterium tuberculosis bacteria, is a leading infectious cause of mortality worldwide, including in Pakistan. Drug resistant M. tuberculosis is an emerging threat for TB control, making it important to detect the underlying genetic mutations, and thereby inform treatment decision making and prevent transmission. Whole genome sequencing has emerged as the new diagnostic to reliably predict drug resistance within a clinically relevant time frame, and its deployment will have the greatest impact on TB control in highly endemic regions. To evaluate the mutations leading to drug resistance and to assess for evidence of the transmission of resistant strains, 81 M. tuberculosis samples from Khyber Pakhtunkhwa province (North West Pakistan) were subjected to whole genome sequencing and standard drug susceptibility testing for eleven anti-TB drugs. We found the majority of M. tuberculosis isolates were the CAS/Delhi strain-type (lineage 3; n = 57; 70.4%) and multi-drug resistant (MDR; n = 62; 76.5%). The most frequent resistance mutations were observed in the katG and rpoB genes, conferring resistance to isoniazid and rifampicin respectively. Mutations were also observed in genes conferring resistance to other first and second-line drugs, including in pncA (pyrazinamide), embB (ethambutol), gyrA (fluoroquinolones), rrs (aminoglycosides), rpsL, rrs and giB (streptomycin) loci. Whilst the majority of mutations have been reported in global datasets, we describe unreported putative resistance markers in katG, ethA (ethionamide), gyrA and gyrB (fluoroquinolones), and pncA. Analysis of the mutations revealed that acquisition of rifampicin resistance often preceded isoniazid in our isolates. We also observed a high proportion (17.6%) of pre-MDR isolates with fluoroquinolone resistance markers, potentially due to unregulated anti-TB drug use. Our isolates were compared to previously sequenced strains from Pakistan in a combined phylogenetic tree analysis. The presence of lineage 2 was only observed in our isolates. Using a cut-off of less than ten genome-wide mutation differences between isolates, a transmission analysis revealed 18 M. tuberculosis isolates clustering within eight networks, thereby providing evidence of drug-resistant TB transmission in the Khyber Pakhtunkhwa province. Overall, we have demonstrated that drug-resistant TB isolates are circulating and transmitted in North West Pakistan. Further, we have shown the usefulness of whole genome sequencing as a diagnostic tool for characterizing M. tuberculosis isolates, which will assist future epidemiological studies and disease control activities in Pakistan

Brain-protective mechanisms of autophagy associated circRNAs: Kick starting self-cleaning mode in brain cells via circRNAs as a potential therapeutic approach for neurodegenerative diseases

Altered autophagy is a hallmark of neurodegeneration but how autophagy is regulated in the brain and dysfunctional autophagy leads to neuronal death has remained cryptic. Being a key cellular waste-recycling and housekeeping system, autophagy is implicated in a range of brain disorders and altering autophagy flux could be an effective therapeutic strategy and has the potential for clinical applications down the road. Tight regulation of proteins and organelles in order to meet the needs of complex neuronal physiology suggests that there is distinct regulatory pattern of neuronal autophagy as compared to non-neuronal cells and nervous system might have its own separate regulator of autophagy. Evidence has shown that circRNAs participates in the biological processes of autophagosome assembly. The regulatory networks between circRNAs, autophagy, and neurodegeneration remains unknown and warrants further investigation. Understanding the interplay between autophagy, circRNAs and neurodegeneration requires a knowledge of the multiple steps and regulatory interactions involved in the autophagy pathway which might provide a valuable resource for the diagnosis and therapy of neurodegenerative diseases. In this review, we aimed to summarize the latest studies on the role of brain-protective mechanisms of autophagy associated circRNAs in neurodegenerative diseases (including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Spinal Muscular Atrophy, Amyotrophic Lateral Sclerosis, and Friedreich’s ataxia) and how this knowledge can be leveraged for the development of novel therapeutics against them. Autophagy stimulation might be potential one-size-fits-all therapy for neurodegenerative disease as per considerable body of evidence, therefore future research on brain-protective mechanisms of autophagy associated circRNAs will illuminate an important feature of nervous system biology and will open the door to new approaches for treating neurodegenerative diseases

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation