Prevalence of Multidrug-Resistant Organism in ICU Burns Patients at Tertiary Care Hospital.

Burns carries a high-risk of mortality and morbidity. This with increased chances of drug-resistant infections makes the management complicated. Hence this study was conducted to find out the prevalence of multidrug-resistant organisms (MDRO) in burns patients admitted to the intensive care unit at a tertiary care hospital. A 2-year retrospective study was conducted where burn patients reporting MDRO were included. Statistical analysis was performed using SPSS version 26 where a P-value < .05 was considered statistically significant. Out of 97 patients, tissue cultures of 65 patients revealed the presence of MDRO in 27 (27.8%) patients. A male predominance (17, 63.0%) was noted with a mean age of 29.0-year-old. Fire burn (15, 55.6%) was reported to be the most common cause of burn with an average of 29.9% of Total Body Surface Area (TBSA) involved. MDR Pseudomonas aeruginosa was the commonest organism reported in 12 (44%) patients. The average length of stay (LOS) was noted to be 11.3 days with a mortality rate of 48.1% (overall, in all MDRO'S infections). Patients who reported MDRO showed a tendency for longer hospitalization with a higher risk of mortality as the TBSA increased. However, in presence of other factors in burns like higher TBSA, inhalation injury and lack of advanced skin substitute these mortality figures, and their association can be debated. Lastly, the implementation of control measures, as basic as hand hygiene, should be partaken to reduce the burden of MDR infections.

Towards a Policy Development Methodology for Human-Centred IoT Collectives.

Embedding ethical concepts into smart Internet-connected devices and making them behave in a more human-centred manner, i.e., ethically and in a socially acceptable manner, has received significant attention in the software industry. To make smart devices behave in more human-centered manners, it is important to develop a methodology for defining smart devices' key roles and mapping them with socio-ethical and administrative policies. This paper proposes a policy development methodology for making smart devices more human-centred by following its four phases i.e., concept development, defining and mapping policies, implementing the processing of policies, and deploying the devices. The suggested methodology may be used in a variety of situations where smart devices interact with people. For illustration, the proposed methodology has been applied to three different settings, including a supermarket, a children's hospital, and early learning centers, where each phase defined in the methodology has been followed. The application of the methodology to smart internet-connected devices, including robots, smart cameras, and smart speakers, has shown significant results. It has been observed that the devices behave in more human-centric ways while performing their core functions, adhering to socio-ethical policies.

Analysis of temporal changes in HIV-1 CRF01_AE gag genetic variability and CD8 T-cell epitope evolution.

Currently, little is known about the time-dependent evolution of human immunodeficiency virus-1 (HIV-1) circulating recombinant forms (CRF) 01_AE, a dominant recombinant form associated with HIV-1 epidemics worldwide. Since gag is a highly immunodominant HIV-1 protein, we performed a comparative analysis of the CRF01_AE gag protein's time-dependent changes and evolution. A total of 3105 HIV-1 CRF01_AE gag sequences representing 17 countries from the timeline 1990-2017 were obtained. The sequences' phylogenetic relationship and epidemic dynamics were analyzed through a Maximum Likelihood tree and Bayesian Skyline plot, respectively. Genomic variability was measured through Shannon entropy and time-dependent immunoevolution was analyzed using changes in proteasomal degradation pattern, cytotoxic T lymphocytes (CTL) epitopes, and Human leukocyte antigens (HLA) restriction profile. The most recent common ancestor of the HIV CRF01_AE epidemic was estimated to be 1974±1. A period of exponential growth in effective population size began in 1982, fluctuated, and then stabilized in 1999. Genetic variability (entropy) consistently increased, however, epitope variability remained comparable; the highest number of novel CTL epitopes were present in 1995-1999, which were lost over time. The spread of the HIV-1 CRF01_AE epidemic is predominant in countries within Asia. Population immunogenetic pressures in the region may have contributed to the initial changes and following adaptation/stabilization of epitope diversity within gag sequences.

The potential protective effect of the Polygonum hydropiper L against the development of fructose-induced oxidative stress and metabolic disorders in male Sprague-Dawely rats.

OBJECTIVES: Polygnum hydropiper L (Polygonaceae) is commonly known as smart weed. This study was designed to assess the effect of aqueous methanolic extract of P. hydropiper on oxidative stress and metabolic changes in fructose-induced hypertensive rats. METHODS: Male Sprague-Dawely rats were divided into six groups of five animals each (n = 5) and designated as normotensive group with distilled water, fructose-fed group with 10% fructose, standard control group with 10% fructose plus amlodipine (10 mg/kg) and treated groups with different doses of the aqueous methanolic extract of P. hydropiper (100, 200 and 400 mg/kg) plus 10% fructose daily for 6 weeks. Body weight gain was checked every week. Blood pressure parameters [systolic (SBP), diastolic (DBP), mean arterial pressure (MAP) and heart rate (HR)] and reactivity of extract with phenylephrine and adrenaline were measured by invasive method. Metabolic changes and oxidative stress parameters were measured from blood samples. Phytochemical analysis was also performed. KEY FINDINGS: Aqueous methanolic extract of P. hydropiper at 400 mg/kg decreased the blood pressure, heart rate, body weight and produced significant effect on metabolic and oxidative stress changes as compared to fructose-fed group. Phytochemical analysis revealed the presence of polyphenols and flavonoids in it. CONCLUSION: The present results showed that aqueous methanolic extract of P. hydropiper possesses effect on oxidative stress and metabolic changes due to polyphenols and flavonoids.

Ciprofloxacin-Loaded Gold Nanoparticles against Antimicrobial Resistance: An In Vivo Assessment.

Metallic nanoparticles, such as gold nanoparticles (AuNPs), have been extensively studied as drug delivery systems for various therapeutic applications. However, drug-loaded-AuNPs have been rarely explored in vivo for their effect on bacteria residing inside tissues. Ciprofloxacin (CIP) is a second-generation fluoroquinolone with a broad-spectrum of antibiotic properties devoid of developing bacteria resistance. This research is focused on the synthesis and physical characterization of Ciprofloxacin-loaded gold nanoparticles (CIP-AuNPs) and their effect on the colonization of Enterococcus faecalis in the liver and kidneys of mice. The successfully prepared CIP-AuNPs were stable and exerted enhanced in vitro antibacterial activity against E. faecalis compared with free CIP. The optimized CIP-AuNPs were administered (500 µg/Kg) once a day via tail vein to infected mice for eight days and were found to be effective in eradicating E. faecalis from the host tissues. Moreover, unlike CIP, CIP-AuNPs were non-hemolytic. In summary, this study demonstrated that CIP-AuNPs are promising and biocompatible alternative therapeutics for E.-faecalis-induced infections resistant to conventional drugs (e.g., beta-lactams and vancomycin) and should be further investigated.

Cardiovascular complications of systemic lupus erythematosus: impact of risk factors and therapeutic efficacy-a tertiary centre experience in an Appalachian state.

OBJECTIVES: Cardiovascular complications became a notable cause of morbidity and mortality in patients with lupus as therapeutic advancements became more efficient at managing other complications. The Appalachian community in Kentucky has a higher prevalence of traditional cardiovascular risk factors, predisposing them to cardiovascular events. Namely, the mean body mass index of the members of the Kentucky Appalachian community was reported at 33 kg/m2 and 94.3% of male members of this community use tobacco. We sought to identify risk factors that predispose patients with lupus to cardiovascular morbidities and examine the effect of immunomodulatory drugs. METHODS: We identified 20 UKHS patients having both a lupus diagnosis and experienced at least one cardiovascular event. We chose three controls matched for birth-year ±5 years to each case. In a case-control design, we analysed lupus manifestations, cardiovascular risk factors and immunosuppressive therapies. We collected Systemic Lupus Erythematosus Disease Activity Index 2000 disease activity index during the cardiovascular event. RESULTS: We identified 308 patients with lupus from among all University of Kentucky Health System patients. 20 (6.5%) of such patients with lupus were confirmed to cardiovascular complication. Of those 20, 7 (35%) had experienced myocardial infarction, 10 (50%) had experienced stroke and 4 (20%) had peripheral ischaemia. Tobacco use and male gender were the only traditional cardiovascular risk factors higher in the cases group. Hydroxychloroquine and steroids were less utilised in the cases than in the controls (70% vs 100% in hydroxychloroquine, 30% vs 82% in steroids). Venous thrombosis was found to be significantly higher in the cases. On multivariate analysis, venous thrombosis remained significant. CONCLUSION: Despite tobacco use partially explaining the increased risk of cardiovascular disease among the cases group, the higher prevalence of venous thrombosis in the cases group suggests lupus as a potential additional risk factor of cardiovascular morbidity among patients with lupus in this Appalachian community.

Effect of Flavonoid-Coated Gold Nanoparticles on Bacterial Colonization in Mice Organs.

Multidrug resistance (MDR) has been a potentiator for the exploration of antibiotics. Nano drug delivery systems have opened new avenues to overcome this challenge. Although antibacterial nanocarriers are extensively realized, their effect on the bacteria residing inside the tissues and their toxicity is rarely explored. This study investigated the effects of flavonoid coated gold nanoparticles (FAuNPs) on the colonization of Enterococcus faecalis in the mouse liver and kidneys. Flavonoids were extracted from the leaves of Berberis lycium Royle and used to stabilize gold following a green synthesis approach. FAuNPs were characterized by ultraviolet-visible (UV-Vis) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), scanning transmission electron microscopy (STEM), X-ray powder diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDS). FAuNPs showed significantly higher reduction in bacterial counts in in-vitro and in-vivo in mice organs as compared to the free flavonoids owing to their biocompatibility and effectiveness.

Virtual Screening of FDA-Approved Drugs against LasR of Pseudomonas aeruginosa for Antibiofilm Potential.

Pseudomonas aeruginosa is a Gram-negative pathogenic bacterium that is present commonly in soil and water and is responsible for causing septic shock, pneumonia, urinary tract and gastrointestinal infections, etc. The multi-drug resistance (MDR) phenomenon has increased dramatically in past years and is now considered a major threat globally, so there is an urgent need to develop new strategies to overcome drug resistance by P. aeruginosa. In P. aeruginosa, a major factor of drug resistance is associated to the formation of biofilms by the LasR enzyme, which regulates quorum sensing and has been reported as a new therapeutic target for designing novel antibacterial molecules. In this study, virtual screening and molecular docking were performed against the ligand binding domain (LBD) of LasR by employing a pharmacophore hypothesis for the screening of 2373 FDA-approved compounds to filter top-scoring hit compounds. Six inhibitors out of 2373 compounds were found to have binding affinities close to that of known LasR inhibitors. The binding modes of these compounds to the binding site in LasR-LBD were analyzed to identify the key interactions that contribute to the inhibition of LasR activity. Then, 50 ns simulations of top hit compounds were performed to elucidate the stability of their binding conformations with the LasR-LBD. This study, thus concluded that sulfamerazine showed the highest binding affinity for the LasR-LBD binding pocket exhibiting strong inhibitory binding interactions during molecular dynamics (MD) simulation.

Cannabinoids and Terpenes as an Antibacterial and Antibiofouling Promotor for PES Water Filtration Membranes.

Plant phytochemicals have potential decontaminating properties, however, their role in the amelioration of hydrophobic water filtration membranes have not been elucidated yet. In this work, phytochemicals (i.e., cannabinoids (C) and terpenes (T) from C. sativa) were revealed for their antibacterial activity against different Gram-positive and Gram-negative bacteria. As such, a synergistic relationship was observed between the two against all strains. These phytochemicals individually and in combination were used to prepare polyethersulfone (PES) hybrid membranes. Membrane characterizations were carried out using scanning electron microscopy, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy. Moreover, contact angle, water retention, surface roughness, mechanical testing, and X-ray florescence analysis were also carried out. According to results, the CT-PES hybrid membrane exhibited the lowest contact angle (40°), the highest water retention (70%), and smallest average pore size (0.04 µm). The hybrid membrane also exhibited improved water flux with no surface leaching. Quantitative bacterial decline analysis of the CT-PES hybrid membranes confirmed an effective antibacterial performance against Gram-positive and Gram-negative bacteria. The results of this study established cannabinoids and terpenes as an inexpensive solution for PES membrane surface modification. These hybrid membranes can be easily deployed at an industrial scale for water filtration purposes.

Novel multiparticulate pH triggered delayed release chronotherapeutic drug delivery of celecoxib-ß-cyclodextrin inclusion complexes by using Box-Behnken design.

This study aimed to prepare novel colon targeted celecoxib-ß-cyclodextrin (CXB-ß-CD) inclusion complex loaded eudragit S 100 (ES100) microparticles for chronotherapy of rheumatoid arthritis (RA) which is an innovative approach, never reported before, for the fabrication of CXB-ß-CD complex in the form of microparticles and its colon targeting. CXB was complexed with ß-cyclodextrin by kneading technique and we evaluated the effect of ß-CD on saturation solubility of CXB. Microparticles were developed by oil-in-oil emulsion solvent evaporation technique and formulation variables (polymer conc, surfactant conc and stirring speed) were optimized by using three-factor three-level Box-Behnken design (BBD). SEM imaging revealed smooth, uniform and spherical shape microparticles. There was 7.3 fold increases in saturation solubility of CXB-ß-CD inclusion complex in distilled water as compared to pure CXB. Particle size was in the range of 50.42 µm to 238.38 µm with entrapment efficiency of 68.47% to 91.65%. Biphasic drug release pattern was found i.e initially delayed release in stomach and small intestine followed by fast release at colonic pH. Response variable results achieved from optimized formulation were very close to the response values suggested by BBD signifying the actual reliability and robustness of BBD in the fabrication of colon targeted CXB-ß-CD microparticles. The comparison of CXB-ß-CD optimized formulation with optimized formulation containing pure CXB showed increase in drug release due to enhancement of water solubility of CXB-ß-CD inclusion complex. So, it can be concluded that CXB-ß-CD loaded ES100 microparticles can be successfully fabricated with enhanced solubility for the chronotherapy of rheumatoid arthritis.

Study on vascular mechanisms underlying the hypotensive effect of Sorghum halepense (L.) Pers.

Sorghum halepense L (Poaceae), ordinarily it is known as Johnson grass and locally as baru. This study was designed to find the vascular mechanisms underlying the hypotensive activity of S. halepense. In this study, effect of S. halepense seed extract/fractions on various blood pressure parameters were evaluated in normal and fructose induced hypertensive rats by invasive technique. Possible underlying hypotensive mechanism of active fraction was determined by using various pharmacological inhibitors. S. halepense extract/fractions vasorelaxant effect were also evaluated on rat aorta rings in organ bath and various intracellular signaling pathway inhibitors were used for determination of underlying mechanisms. S. halepense extract/fractions produced blood pressure lowering effect with most significant effect by its aqueous soluble fraction at dose of 10mg/kg. This effect was attenuated by pretreatment of atropine. Aqueous soluble fraction produced endothelium dependent vasorelaxation in rat aortic rings that was inhibited by pretreatment of atropine after phenylephrine induced contraction. The vasorelaxant effect of aqueous soluble fraction was attenuated by potassium channel blockers and also produced inhibitory effect on calcium entry through calcium channels. It also suppressed phenylephrine induced contraction like verapamil. By HPLC analysis found vanillic acid and naringinin in it. In conclusion, aqueous soluble fraction of S.halepense possess phytoconstituents which may be responsible for hypotensive and vasorelaxant effect of Sorghum halepense.

Clinical Outcome of Ampullary Carcinoma: Single Cancer Center Experience.

INTRODUCTION: Ampullary cancers represent a subset of periampullary cancers, comprising only 0.2% all gastrointestinal cancers. Localized disease is primarily managed by a surgical intervention, called pancreaticoduodenectomy (PD), followed in many cases by the administration of adjuvant chemotherapy (CT) or chemoradiation therapy (CRT). However, there are no clear evidence-based guidelines to aid in selecting both the modality and regimen of adjuvant therapy for resected Ampullary carcinoma. METHODS: We retrospectively analyzed 54 patients at KU Cancer Center, who had undergone endoscopic resection or pancreaticoduodenectomy (PD) for Ampullary cancer from June 2006 to July 2016. We obtained patients' baseline characteristics, clinical presentation, pathology, treatment modality, recurrence pattern, and survival outcomes. The time-to-events data were compared using Kaplan-Meier methods. A univariate and multivariate Cox proportional hazards regression was performed to evaluate factors associated with overall survival (OS) and generate hazard ratios (HR). RESULTS: The mean age of the 54 patients was 68 (37-90). 38 (70%) were males and 16 (30%) were females. Most of the patients were Caucasian (76%). Approximately half of all patients had a history of smoking, 20% had alcohol abuse, and 13% had pancreatitis. Among the 54 patients with localized cancers, 9 (16%) were treated definitively with nonoperative therapies, usually due to a prohibitive comorbidity profile, performance status, or unresectable tumor. 45 out of 54 patients (83%) underwent surgery. Of the 45 patients who underwent surgery, 18 patients (40% of the study cohort) received adjuvant therapy due to concerns for advanced disease as determined by the treating physician. 13 patients (24%) received adjuvant CT and 5 patients (9.2%) received CRT. The remaining 27 patients (50%) underwent surgery alone. The median OS for the entire study cohort was 30 months. When compared to surgery alone, adjuvant therapy with either CT or CRT had no statistically significant difference in terms of progression-free survival (p=0.56) or overall survival (p=0.80). In univariate Cox proportional hazards regression analysis, high-risk features like peripancreatic extension (16%) and perineural invasion (26%) were found to be associated with poor OS. Lymph node metastasis (29%) did not significantly affect OS (HR 1.42, 95% CI [0.73-1.86]; p=0.84). Lymphovascular invasion (29%) was not associated with poor OS (HR 1.22, 95% CI [0.52, 2.96]; p=0.76). In multivariate Cox regression analysis, only age group>70 years was significantly associated with OS , while other factors, including the receipt of adjuvant therapy, lymph nodes, positive margin, and lymphovascular, perineural, and peripancreatic involvement, were not significantly associated with OS. These results are likely due to small sample size. CONCLUSIONS: Despite numerous advances in both cancer care and research, efforts in rare malignancies such as Ampullary cancer remain very challenging with a clear lack of an evidence-based standard of care treatment paradigm. Although adding adjuvant therapies such as chemotherapy or chemoradiotherapy is likely to improve survival in high-risk disease, there is no standardized regimen for the treatment of Ampullary cancer. More research is required to elucidate whether statistically and clinically relevant differences exist that may warrant a change in the current adjuvant treatment strategies.

Graphene-based nanocomposites: synthesis and their theranostic applications.

Graphene, the mother of all carbon materials, has unlocked a new era of biomedical nanomaterials due to its exceptional biocompatibility, physicochemical and mechanical properties. It is a single atom thick, nanosized, two-dimensional structure and provides high surface area with adjustable surface chemistry to form hybrids. The present article provides a comprehensive review of ever-expanding application of graphene nanomaterials with different inorganic and organic materials in drug delivery and theranostics. Methods of preparation of nanomaterials are elaborated and biological and physicochemical characteristics of biomedical relevance are also discussed. Graphene form nanomaterials with metallic nanoparticles offer multiscale application. First, graphene act as a platform to attach nanoparticles and provide excellent mechanical strength. Second, graphene improves efficacy of metallic nanoparticles in diagnostic, biosensing, therapeutic and drug delivery application. Graphene-based polymeric nanocomposites find wider application in drug delivery with flexibility to incorporate hydrophilic, hydrophobic, sensitive and macromolecules. In addition, grapheme quantum dots and graphene hybrids with inorganic nanocrystal and carbon nanotubes hybrids have shown interesting properties for diagnosis and therapy. Finally, we have pointed out research trends that may be more common in future for graphene-based nanomaterials.

Use of colistin for the treatment of multi drug resistant isolates in neonates.

OBJECTIVE: To determine the impact of using colistin for multidrug-resistant organisms in neonates. METHODS: This retrospective study was conducted at the Shifa International Hospital, Islamabad, Pakistan, and comprised microbiological data of babies from January 2010 to October 2012.The data was reviewed to identify the babies infected with multidrug-resistant organisms and who had received colistin therapy. SPSS 16 was used for data analysis. RESULTS: Of the 30 neonates, 24(80%) were males and 6(20%) were females. Besides, 16(53.3%) neonates were preterm babies (< 37 weeks gestation). Two or more risk factors for multidrug-resistant organisms were present in 13(44%) babies. Mechanical ventilation was found in 26(87%) neonates and prior prolonged use of antibiotics in 7(23%). The commonest pathogen isolated was Acinetobacter, in 22(73%) cases. All isolates were susceptible to colistin but pan-resistant to multiple antibiotics, including cephalosporins, amikacin, meropenem and piperacillin/tazobactam. Colistin therapy was used for bacteraemia in 2(7%) cases, clinical sepsis 18(60%), pneumonia 2(7%) and tracheitis 8(26.7%). Moreover, 15(50%) neonates received both intravenous and aerosolised colistin while 9(30%) received aerosolised therapy alone. CONCLUSIONS: Colistin therapy was well tolerated in neonates for the treatment of multidrug-resistant organisms.

Novel nanoparticulate systems for lung cancer therapy: an updated review.

Lung cancer is the leading cause of cancer-related deaths in the world. Conventional therapy for lung cancer is associated with lack of specificity and access to the normal cells resulting in cytotoxicity, reduced cellular uptake, drug resistance and rapid drug clearance from the body. The emergence of nanotechnology has revolutionized the treatment of lung cancer. The focus of nanotechnology is to target tumor cells with improved bioavailability and reduced toxicity. In the recent years, nanoparticulate systems have extensively been exploited in order to overcome the obstacles in treatment of lung cancer. Nanoparticulate systems have shown much potential for lung cancer therapy by gaining selective access to the tumor cells due to surface modifiability and smaller size. In this review, various novel nanoparticles (NPs) based formulations have been discussed in the treatment of lung cancer. Nanotechnology is expected to grow fast in future, and it will provide new avenues for the improved treatment of lung cancer. This review article also highlights the characteristics, recent advances in the designing of NPs and therapeutic outcomes.