Synergistic Antibacterial Effects of Metallic Nanoparticle Combinations

© The Author(s) 2019.Metallic nanoparticles have unique antimicrobial properties that make them suitable for use within medical and pharmaceutical devices to prevent the spread of infection in healthcare. The use of nanoparticles in healthcare is on the increase with silver being used in many devices. However, not all metallic nanoparticles can target and kill all disease-causing bacteria. To overcome this, a combination of several different metallic nanoparticles were used in this study to compare effects of multiple metallic nanoparticles when in combination than when used singly, as single elemental nanoparticles (SENPs), against two common hospital acquired pathogens (Staphylococcus aureus and Pseudomonas. aeruginosa). Flow cytometry LIVE/DEAD assay was used to determine rates of cell death within a bacterial population when exposed to the nanoparticles. Results were analysed using linear models to compare effectiveness of three different metallic nanoparticles, tungsten carbide (WC), silver (Ag) and copper (Cu), in combination and separately. Results show that when the nanoparticles are placed in combination (NPCs), antimicrobial effects significantly increase than when compared with SENPs (P < 0.01). This study demonstrates that certain metallic nanoparticles can be used in combination to improve the antimicrobial efficiency in destroying morphologically distinct pathogens within the healthcare and pharmaceutical industry.Peer reviewe

Does the Lecturer’s Innovativeness Drive VLE Adoption in Higher Education Institutes? (A Study Based on Extended UTAUT)

The focus of this study is on lecturer’s use of online technology in the higher education context. Precisely, this study aims to understand the effect of personal innovativeness in IT (PI) in determining technology adoption behavior of lecturers in the higher education institutes in Sri Lanka. In this study, the variable of personal innovativeness in IT is integrated with the UTAUT framework and thereby the causal paths which effects VLE adoption intention of individuals is examined. Literature suggests that domain-specific innovativeness is a crucial factor in determining an individual’s adoption of technological innovations. Therefore, understanding the multifaceted effects of this factor along with other significant factors can help higher education institutes to effectively endorse online technology among lectures, generating productive payoffs in the long run. The quantitative method was used for data collection, which yielded # 1253 responses through the Question Pro online survey tool. The targeted respondents were the registered lecturers in higher education institutes of Sri Lanka, selected based on simple random sampling method. Structural equation modelling (SEM) procedure was employed for data analysis using IBM SPSS (ver.21) and AMOS (Ver.26). The structural path analysis resulted in partial mediation, confirming that “lecturer’s innovativeness in IT” exerts its influence on VLE adoption intention by altering the mediators set in the study. Further, the study validated a unique set of factors that determine lecturer’s acceptance of VLE in a higher education setting

Dirhenium carbonyl compounds bearing cis-1,2-bis(diphenylphosphino)ethylene and cis-1,2-bis(diphenylphosphino)ethylene oxide ligands

Reaction of [Re2(CO)9(MeCN)] with cis-1,2-bis(diphenylphosphino)ethylene (cis-Ph2PCH=CHPPh2) in boiling benzene (80 °C) afforded two compounds, ax-[Re2(CO)9(κ1-cis-Ph2PCH=CHPPh2)] (1) and ax-[Re2(CO)9{κ1-cis-Ph2PCH=CHPh2P(O)}] (2) where the ligand is axially coordinated in a κ1 monodentate fashion through phosphorus. The close-bridged compound [Re2(CO)8(μ-κ2-cis-Ph2PCH=CHPPh2)] (3) was obtained from a similar reaction of the same ligand with [Re2(CO)8(NCMe)2] in refluxing benzene. In this case the diphosphine is equatorially coordinated to two Re atoms in a symmetrical bridging fashion. Compounds 1−3 have been characterized by IR, 1H NMR, 31P{1H} NMR spectroscopy and single crystal X-ray diffraction analyses

Dirhenium carbonyl compounds bearing cis-1,2-bis(diphenylphosphino)ethylene and cis-1,2-bis(diphenylphosphino)ethylene oxide ligands

1289-1295Reaction of [Re2(CO)9(MeCN)] with cis-1,2-bis(diphenylphosphino)ethylene (cis-Ph2PCH=CHPPh2) in boiling benzene (80 °C) afforded two compounds, ax-[Re2(CO)9(κ1-cis-Ph2PCH=CHPPh2)] (1) and ax-[Re2(CO)9{κ1-cis- Ph2PCH=CHPh2P(O)}] (2) where the ligand is axially coordinated in a κ1 monodentate fashion through phosphorus. The close-bridged compound eq-[Re2(CO)8(μ-κ2-cis-Ph2PCH=CHPPh2)] (3) is obtained from a similar reaction of the same ligand with [Re2(CO)8(NCMe)2] in refluxing benzene. In this case the diphosphine is equatorially coordinated to two Re atoms in a symmetrical bridging fashion. Compounds 1−3 have been characterized by IR, 1H NMR, 31P{1H} NMR spectroscopy and single crystal X-ray diffraction analyses

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

One Health investigation of the first human rabies death linked to a clinically suspected rabid bull calf in Bangladesh

Rabies is a fatal and neglected zoonotic disease that remains endemic in Bangladesh. Most human cases result from dog bites, and it is not uncommon for livestock to be bitten by dogs. This report presents the first known clinically diagnosed human rabies case in Bangladesh associated with exposure to infected livestock. The case involved a 65-year-old male farmer from rural Bangladesh who died of clinically diagnosed rabies after a minor, unrecognized exposure to a bull calf suspected of having rabies. The man suffered very little hand injuries while feeding the calf, which had been showing progressive neurological symptoms consistent with rabies. Despite medical advice, he did not receive post-exposure prophylaxis (PEP), largely due to negligence. Thirty-four days after the exposure, the man began to exhibit early symptoms of rabies, including limb weakness, neck and back pain, anxiety, and early signs of hydrophobia. The illness quickly progressed to the classic features of furious rabies, such as severe hydrophobia, aerophobia, confusion, and agitation. He died 41 days after the initial exposure. This case triggered fear and panic in the local community, reflecting a broader lack of awareness about rabies, particularly its transmission from non-traditional hosts like livestock. The incident highlights the severe consequences of inadequate awareness and delayed or missed PEP following potential rabies exposure. It emphasizes the urgent need to raise public awareness about all possible transmission routes, ensure timely access to PEP for both humans and animals, stray dog vaccination and strengthen public-veterinary health collaboration in Bangladesh

Combining RNA interference and kinase inhibitors against cell signalling components involved in cancer

BACKGROUND: The transcription factor activator protein-1 (AP-1) has been implicated in a large variety of biological processes including oncogenic transformation. The tyrosine kinases of the epidermal growth factor receptor (EGFR) constitute the beginning of one signal transduction cascade leading to AP-1 activation and are known to control cell proliferation and differentiation. Drug discovery efforts targeting this receptor and other pathway components have centred on monoclonal antibodies and small molecule inhibitors. Resistance to such inhibitors has already been observed, guiding the prediction of their use in combination therapies with other targeted agents such as RNA interference (RNAi). This study examines the use of RNAi and kinase inhibitors for qualification of components involved in the EGFR/AP-1 pathway of ME180 cells, and their inhibitory effects when evaluated individually or in tandem against multiple components of this important disease-related pathway. METHODS: AP-1 activation was assessed using an ME180 cell line stably transfected with a beta-lactamase reporter gene under the control of AP-1 response element following epidermal growth factor (EGF) stimulation. Immunocytochemistry allowed for further quantification of small molecule inhibition on a cellular protein level. RNAi and RT-qPCR experiments were performed to assess the amount of knockdown on an mRNA level, and immunocytochemistry was used to reveal cellular protein levels for the targeted pathway components. RESULTS: Increased potency of kinase inhibitors was shown by combining RNAi directed towards EGFR and small molecule inhibitors acting at proximal or distal points in the pathway. After cellular stimulation with EGF and analysis at the level of AP-1 activation using a β-lactamase reporter gene, a 10–12 fold shift or 2.5–3 fold shift toward greater potency in the IC(50 )was observed for EGFR and MEK-1 inhibitors, respectively, in the presence of RNAi targeting EGFR. CONCLUSION: EGFR pathway components were qualified as targets for inhibition of AP-1 activation using RNAi and small molecule inhibitors. The combination of these two targeted agents was shown to increase the efficacy of EGFR and MEK-1 kinase inhibitors, leading to possible implications for overcoming or preventing drug resistance, lowering effective drug doses, and providing new strategies for interrogating cellular signalling pathways

Specialist training in Fiji: Why do graduates migrate, and why do they remain? A qualitative study

<p>Abstract</p> <p>Background</p> <p>Specialist training was established in the late 1990s at the Fiji School of Medicine. Losses of graduates to overseas migration and to the local private sector prompted us to explore the reasons for these losses from the Fiji public workforce.</p> <p>Methods</p> <p>Data were collected on the whereabouts and highest educational attainments of the 66 Fiji doctors who had undertaken specialist training to at least the diploma level between 1997 and 2004. Semistructured interviews focusing on career decisions were carried out with 36 of these doctors, who were purposively sampled to include overseas migrants, temporary overseas trainees, local private practitioners and public sector doctors.</p> <p>Results</p> <p>120 doctors undertook specialist training to at least the diploma level between 1997 and 2004; 66 of the graduates were Fiji citizens or permanent residents; 54 originated from other countries in the region. Among Fiji graduates, 42 completed a diploma and 24 had either completed (21) or were enrolled (3) in a master's programme. Thirty-two (48.5%) were working in the public sectors, four (6.0%) were temporarily training overseas, 30.3% had migrated overseas and the remainder were mostly in local private practice. Indo-Fijian ethnicity and non-completion of full specialist training were associated with lower retention in the public sectors, while gender had little impact. Decisions to leave the public sectors were complex, with concerns about political instability and family welfare predominating for overseas migrants, while working conditions not conducive to family life or frustrations with career progression predominated for local private practitioners. Doctors remaining in the public sectors reported many satisfying aspects to their work despite frustrations, though 40% had seriously considered resigning from the public service and 60% were unhappy with their career progression.</p> <p>Conclusion</p> <p>Overall, this study provides some support for the view that local or regional postgraduate training may increase retention of doctors. Attention to career pathways and other sources of frustration, in addition to encouragement to complete training, should increase the likelihood of such programmes' reaching their full potentials.</p

Developmental Sex Differences in Nicotinic Currents of Prefrontal Layer VI Neurons in Mice and Rats

There is a large sex difference in the prevalence of attention deficit disorder; yet, relatively little is known about sex differences in the development of prefrontal attention circuitry. In male rats, nicotinic acetylcholine receptors excite corticothalamic neurons in layer VI, which are thought to play an important role in attention by gating the sensitivity of thalamic neurons to incoming stimuli. These nicotinic currents in male rats are significantly larger during the first postnatal month when prefrontal circuitry is maturing. The present study was undertaken to investigate whether there are sex differences in the nicotinic currents in prefrontal layer VI neurons during development.Using whole cell recording in prefrontal brain slice, we examined the inward currents elicited by nicotinic stimulation in male and female rats and two strains of mice. We found a prominent sex difference in the currents during the first postnatal month when males had significantly greater nicotinic currents in layer VI neurons compared to females. These differences were apparent with three agonists: acetylcholine, carbachol, and nicotine. Furthermore, the developmental sex difference in nicotinic currents occurred despite male and female rodents displaying a similar pattern and proportion of layer VI neurons possessing a key nicotinic receptor subunit.This is the first illustration at a cellular level that prefrontal attention circuitry is differently affected by nicotinic receptor stimulation in males and females during development. This transient sex difference may help to define the cellular and circuit mechanisms that underlie vulnerability to attention deficit disorder