Selektion av resistenta Escherichia coli vid låga antibiotikakoncentrationer i en gräsandsmodell

Enligt en erkänd hypotes, mutant selection window hypothesis, uppstår och upprätthålls antibiotikaresistens hos bakterier endast då antibiotikakoncentrationerna ligger över minimum inhibitory concentration (MIC)-värdet för en känslig, omuterad population. Det här skulle innebära att de låga antibiotikakoncentrationer man finner i miljön inte borde bidra till att upprätthålla resistens. Redan subinhibitoriska antibiotikakoncentrationer har dock visat sig ha effekt på bakterier genom att t.ex. öka mutationsfrekvensen hos bakterier, selektera för resistenta mutanter och ge upphov till nya sådana. Syftet med den här studien var att undersöka om en selektion vid låga antibiotikakoncentrationer sker också in vivo. Som modelldjur användes gräsänder inhysta i försöksrum. Änderna inokulerades med en blandning av en ciprofloxacinkänslig respektive –resistent stam av Escherichia coli och utsattes sedan under ungefär två veckor för låga koncentrationer ciprofloxacin i sin vattenmiljö. Upprepade träckprov togs och proverna spreds på selektiva plattor varvid andelen ciprofloxacinresistenta kolonier av de ursprungligen inokulerade och i träcken utsöndrade bakterierna kunde bestämmas. Studien omfattade sju försöksomgångar med olika ciprofloxacinkoncentration i varje försöksomgång; 0, 10, 20, 32, 100 ng/ml samt 1 och 10 μg/ml. I studien började det ske en selektion av ciprofloxacinresistenta bakterier vid ciprofloxacinkoncentrationen någonstans mellan 10 och 20 ng/ml. De koncentrationerna ligger över de man uppmätt i västerländska vattendrag, men under koncentrationer som uppmätts i Indien. Ciprofloxacin binder till sediment och jord och ackumuleras i växter. I vilt tillstånd utsätts alltså vattenfåglar som betar och söker föda i bottensediment, för högre koncentrationer än vad vattenkoncentrationerna indikerar. I studien användes stammar vars resistensmutationer uppkommit i labbmiljö och som innebar en kostnad för bakterierna. I en naturlig situation är det troligt att kostnaden skulle kompenseras för, vilket talar för att en selektion av resistenta bakterier skulle ske vid lägre koncentrationer än vad som iakttogs i det här försöket. Antibiotika i miljön kan tänkas selektera för resistenta bakterier.According to the mutant selection window hypothesis, antibiotic resistance in bacteria is selected for only when concentrations of antibiotics exceed the minimum inhibitory concentration (MIC) of a susceptible population. The low concentrations of antibiotics found in the environment would therefore not contribute to the occurence of resistance. How ever, subinhibitory concentrations of antibiotics have been shown to excert an effect on bacteria by e.g. increasing the mutation rate, selecting for resistant mutants and promoting the rise of new resistant mutants. In this study, the issue whether selection of resistant bacteria takes place at low concentrations of antibiotics also in vivo, was investigated using mallards as model animals. The mallards were inoculated by a mix of ciprofloxacin-resistant and –sensitive Escherichia coli and exposed to low concentrations of ciprofloxacin in their water for approximately 2 weeks. Several fecal samples were obtained over the period and spread onto selective plates in order to determine the fraction of ciprofloxacin resistant E. coli as a proportion of the total count of inoculated bacteria shedded in the fecal sample. Seven rounds were performed, each with different concentrations of ciprofloxacin; 0, 10, 20, 32, 100 ng/ml and 1 and 10 μg/ml. Selection of ciprofloxacin-resistant E.coli was observed at concentrations of 20 ng/ml and higher. These concentrations exceed those measured in waters in the industrialized parts of the world, but are lower than measured concentrations in India. Ciprofloxacin binds to particles and sediments and accumulates in plants. Free-living mallards graze and explore the sediments in aquatic environments and, hence, they are exposed to significantly higher concentrations of ciprofloxacin than suggested by the concentrations found in the water. The resistance mutations of the strains in this study were selected for in vitro in a laboratory setting and conferred a fitness cost to the bacteria. In a natural in vivo-setting, it is likely that the fitness cost would be compensated for and eliminated, which suggests that selection of resistant bacteria would occur at lower concentrations than was the case in this study. Environmental concentrations of antibiotics are thus at risk of selecting for resistant bacteria

Meta-research evaluating redundancy and use of systematic reviews when planning new studies in health research:a scoping review

BACKGROUND: Several studies have documented the production of wasteful research, defined as research of no scientific importance and/or not meeting societal needs. We argue that this redundancy in research may to a large degree be due to the lack of a systematic evaluation of the best available evidence and/or of studies assessing societal needs. OBJECTIVES: The aim of this scoping review is to (A) identify meta-research studies evaluating if redundancy is present within biomedical research, and if so, assessing the prevalence of such redundancy, and (B) to identify meta-research studies evaluating if researchers had been trying to minimise or avoid redundancy. ELIGIBILITY CRITERIA: Meta-research studies (empirical studies) were eligible if they evaluated whether redundancy was present and to what degree; whether health researchers referred to all earlier similar studies when justifying and designing a new study and/or when placing new results in the context of earlier similar trials; and whether health researchers systematically and transparently considered end users’ perspectives when justifying and designing a new study. SOURCES OF EVIDENCE: The initial overall search was conducted in MEDLINE, Embase via Ovid, CINAHL, Web of Science, Social Sciences Citation Index, Arts & Humanities Citation Index, and the Cochrane Methodology Register from inception to June 2015. A 2nd search included MEDLINE and Embase via Ovid and covered January 2015 to 26 May 2021. No publication date or language restrictions were applied. CHARTING METHODS: Charting methods included description of the included studies, bibliometric mapping, and presentation of possible research gaps in the identified meta-research. RESULTS: We identified 69 meta-research studies. Thirty-four (49%) of these evaluated the prevalence of redundancy and 42 (61%) studies evaluated the prevalence of a systematic and transparent use of earlier similar studies when justifying and designing new studies, and/or when placing new results in context, with seven (10%) studies addressing both aspects. Only one (1%) study assessed if the perspectives of end users had been used to inform the justification and design of a new study. Among the included meta-research studies evaluating whether redundancy was present, only two of nine health domains (medical areas) and only two of 10 research topics (different methodological types) were represented. Similarly, among the included meta-research studies evaluating whether researchers had been trying to minimise or avoid redundancy, only one of nine health domains and only one of 10 research topics were represented. CONCLUSIONS THAT RELATE TO THE REVIEW QUESTIONS AND OBJECTIVES: Even with 69 included meta-research studies, there was a lack of information for most health domains and research topics. However, as most included studies were evaluating across different domains, there is a clear indication of a high prevalence of redundancy and a low prevalence of trying to minimise or avoid redundancy. In addition, only one meta-research study evaluated whether the perspectives of end users were used to inform the justification and design of a new study. SYSTEMATIC REVIEW REGISTRATION: Protocol registered at Open Science Framework: https://osf.io/3rdua/ (15 June 2021). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13643-022-02096-y

Тепловой расходомер

Полезная модель относится к области измерительной техники, а именно к тепловым устройствам для измерения расхода жидких или газообразных сред, и может быть использована в химической, электронной, энергетической и других отраслях промышленности

Evaluation of the Trivedi Effect®- Energy of Consciousness Energy Healing Treatment on the Physical, Spectral, and Thermal Properties of Zinc Chloride

Zinc chloride has the importance in pharmaceutical/nutraceutical industries for the prevention and treatment of several diseases. The objective of the current study was to investigate the impact of The Trivedi Effect®-Energy of Consciousness Healing Treatment (Biofield Energy Healing Treatment) on physical, structural, and thermal properties of zinc chloride using PXRD, PSD, FT-IR, UV-vis, TGA, and DSC analysis. Zinc chloride was divided into two parts. One part was denoted as the control without any, while the other part was defined as the Trivedi Effect® Treated sample, which received the Trivedi Effect® Treatment remotely from eighteen renowned Biofield Energy Healers. The PXRD analysis revealed that the crystallite size and relative intensities of the PXRD peaks significantly altered in the treated sample compared with the control sample. The crystallite size of treated sample was decreased by 4.19% compared with the control sample. The particle size at d10 and d50 of the Biofield Energy Treated sample decreased by 4.72% and 2.70%, respectively compared with the control sample. But, the particle size of the treated sample increased at d90 by 0.83 compared with the control sample. Consequently, the surface area was increased by 3.22% in the treated sample compared with the control sample. The FT-IR spectroscopic analysis revealed that Zn-Cl stretching in the control and treated sample was at 520 cm-1 and 521 cm-1, respectively. The UV-vis analysis exhibited that the wavelength of the maximum absorbance of the control and treated samples was at 196.4 and 196.2 nm, respectively. The TGA thermograms revealed two steps of the thermal degradation and the weight loss of the treated sample was significantly reduced by 22.54% in the 1st step of degradation compared with the control sample. The DSC analysis showed that the enthalpy of decomposition was significantly increased by 34.9% in the treated sample (89.17 J/g) compared with the control sample (66.10 J/g). Overall, DSC and TGA analysis indicated that the thermal stability of the treated sample was increased compared with the control sample. The current study anticipated that The Trivedi Effect®-Energy of Consciousness Healing Treatment might lead to generate a new polymorphic form of zinc chloride, which would be more soluble, stable, and higher absorption rate compared with the control sample. Hence, the treated zinc chloride could be very useful to design the various forms of nutraceuticals and pharmaceutical formulation which might be providing a better therapeutic response against inflammatory diseases, immunological disorders, aging, stress, cancer, etc. https://www.trivedieffect.com/science/evaluation-of-the-trivedi-effect-energy-of-consciousness-energy-healing-treatment-on-the-physical-spectral-and-thermal-properties-of-zinc-chloride http://www.sciencepublishinggroup.com/journal/paperinfo?journalid=118&doi=10.11648/j.ajls.20170501.1

Liquid Chromatography – Mass Spectrometry (LC-MS) Analysis of Withania somnifera (Ashwagandha) Root Extract Treated with the Energy of Consciousness

Withania somnifera (ashwagandha) root extract is very popular ancient herbal medicine. The objective of the study was to characterize and evaluate the impact of The Trivedi Effect®-Biofield Energy Healing Treatment (Energy of Consciousness) on phytoconstituents present in the ashwagandha root extract using LC-MS. Ashwagandha root extract was divided into two parts. One part was denoted as the control, while the other part was defined as The Trivedi Effect® - Biofield Energy Treated sample, which received Energy of Consciousness Healing Treatment remotely from eighteen renowned Biofield Energy Healers. The LC-MS analysis of the control and treated samples showed a very close retention time (Rt), indicated that the polarity of the phytoconstituents present in the root extract are same. The numbers of peaks observed in the total ion chromatograms were 28 and 29 in the control and treated samples, respectively. The change in the peak height% of the phytoconstituents in the treated sample was altered significantly within the range of -50.91% to 118.12% compared with the control sample. Similarly, the change in the peak area% of most of the phytoconstituents in the treated ashwagandha was significantly altered within the range of -54.95% to 66.95% compared with the control sample. An additional peak was appeared in the treated sample at Rt of 5.72 minutes, which was not found in the control sample. The LC-MS spectra indicated the presence of possible withanolides like -hydroxy-2,3-dihydro-withanolide F, withanolide A, withaferine A, withanone, withanolide D, ixocarpalactone A, withanolide S, thiowithanolide, etc. in both the samples. The peak are percentage (%) was altered in the identified withanolides, but withanolide sulfoxide was increased significantly by 12.44% in the treated sample compared with the control sample. These results indicated that The Trivedi Effect® - Biofield Energy Treatment might have an impact on the intrinsic physicochemical properties of the phytoconstituents present in the ashwagandha root extract. This could be the probable cause of alteration in the peak height, peak area, and appearance of a new peak in the treated sample. As a result, the concentrations of the phytoconstituents altered in the treated sample compared with the control sample. The treated ashwagandha root extract would be helpful for designing better pharmaceutical/nutraceutical formulations which might be providing a better therapeutic response against autoimmune diseases, nervous and sexual disorders, infectious diseases, antiaging, diabetes, cancer, ulcer, immunological disorders, stress, arthritis, etc. Source: https://www.trivedieffect.com/science/liquid-chromatography-mass-spectrometry-lc-ms-analysis-of-withania-somnifera-ashwagandha-root-extract-treated-with-the-energy-of-consciousness http://www.sciencepublishinggroup.com/journal/paperinfo?journalid=398&doi=10.11648/j.ajqcms.20170101.1

Effect of the Energy of Consciousness (The Trivedi Effect®) on Withania somnifera Root Extract Using Gas Chromatography – Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy

Withania somnifera (Ashwagandha) root extract is very popular ancient herbal medicine. The objective of the study was to characterize and evaluate the impact of The Trivedi Effect® - Energy of Consciousness Healing Treatment (Biofield Energy Healing) on phytoconstituents present in the ashwagandha root extract using GC-MS and NMR. Ashwagandha root extract was divided into two parts. One part was denoted as the control, while the other part was defined as The Trivedi Effect® - Biofield Energy Treated sample, which received The Trivedi Effect® - Energy of Consciousness Healing Treatment remotely from eighteen renowned Biofield Energy Healers. The GC-MS data indicated that the peak height and peak area of The Trivedi Effect® treated sample were found to be altered compared with the control sample. The peak height of the phytoconstituents present in the treated ashwagandha sample was altered significantly in the range of -8.32% to 89.25% compared with the control sample. Similarly, the peak area of the treated sample was altered significantly in the range of - 4.28% to 216.30% compared with the control sample. Overall, the change in the peak area% of the treated sample was significantly altered in the range of -18.29% to 170.18% compared with the control sample. The GC-MS and NMR analysis results identified the presence of withanolides such as glyco-withanolides, alkaloids, and sugars in the root extract in both the sample. The peak area of 2,3,4,5-tetrahydropyridazine (1), methyl ethyl sulfoxide (2), 5,6-dihydro-2-methyl-4(H)pyran-3,4-dione (4), diethoxy-2-methyl-propane (5), 2,3,4,5-tetrahydroxy-tetrahydro-pyran (6), and 3,4-dimethyl-2(3H)-furanone (7) were significantly increased by 170.18%, 58.21%, 7.74%, 139.50%, 23.16%, and 45.63%, respectively in the treated sample compared with the control sample. On the contrary, the peak area% of 2-hydroxy-γ-butyrolactone (3) was decreased by - 14.96% in the treated ashwagandha compared with the control sample. From the results, it can be hypothesized that The Trivedi Effect® - Biofield Energy Treatment might have the impact on the intrinsic physicochemical properties of the phytoconstituents present in the ashwagandha root extract and responsible for the alteration in the relative peak height/area of treated sample compared with the control sample. As a result, the concentrations of the phytoconstituents assumed to be increased in treated sample compared with the control sample. This treated ashwagandha root extract would be helpful for designing better nutraceutical/pharmaceutical formulations which might be providing a better therapeutic response against autoimmune diseases, nervous and sexual disorders, infectious diseases, antiaging, diabetes, cancer, immunological disorders, stress, arthritis, etc. Source: https://www.trivedieffect.com/science/effect-of-the-energy-of-consciousness-the-trivedi-effect-on-withania-somnifera-root-extract-using-gas-chromatography-mass-spectrometry-and-nuclear-magnetic-resonance-spectroscopy http://www.sciencepublishinggroup.com/journal/paperinfo?journalid=320&doi=10.11648/j.jdmp.20170302.1

The challenges of applying planetary boundaries as a basis for strategic decision-making in companies with global supply chains

YesThe Planetary Boundaries (PB) framework represents a significant advance in specifying the ecological constraints on human development. However, to enable decision-makers in business and public policy to respect these constraints in strategic planning, the PB framework needs to be developed to generate practical tools. With this objective in mind, we analyse the recent literature and highlight three major scientific and technical challenges in operationalizing the PB approach in decision-making: first, identification of thresholds or boundaries with associated metrics for different geographical scales; second, the need to frame approaches to allocate fair shares in the 'safe operating space' bounded by the PBs across the value chain and; third, the need for international bodies to co-ordinate the implementation of the measures needed to respect the Planetary Boundaries. For the first two of these challenges, we consider how they might be addressed for four PBs: climate change, freshwater use, biosphere integrity and chemical pollution and other novel entities. Four key opportunities are identified: (1) development of a common system of metrics that can be applied consistently at and across different scales; (2) setting 'distance from boundary' measures that can be applied at different scales; (3) development of global, preferably open-source, databases and models; and (4) advancing understanding of the interactions between the different PBs. Addressing the scientific and technical challenges in operationalizing the planetary boundaries needs be complemented with progress in addressing the equity and ethical issues in allocating the safe operating space between companies and sectors

Prescription – Pollution – Poo – Pandemics - Priorities : Neuraminidase Inhibitors from an Environmental Resistance Development Perspective

The natural Influenza A virus (IAV) host is waterfowl. Human IAV is treated with neuraminidase inhibitors (NAIs), which are stockpiled worldwide in case of an IAV pandemic. As the drugs escape regular waste water treatment, they can be detected in river waters. We hypothesize that exposure of low pathogenic avian IAV (LPAIV) infecting Mallards to NAIs in the water promotes development of resistance that can persist in the absence of drugs. Dissemination of resistance genes to humans pose a health risk, particularly if incorporated into a pandemic IAV. To test the hypothesis, LPAIVs of both NA phylogenetic groups were assessed in an in vivo Mallard model by inoculation and exposure of birds to NAI in their water. In previous work in the model, the oseltamivir-resistant H275Y mutation emerged in H1N1 in response to oseltamivir exposure and persisted without drug pressure. In this thesis, a H7N9 was exposed to oseltamivir and a H1N1 and H4N2 to zanamivir and peramivir. Furthermore, a H1N1 with the H275Y mutation was exposed to zanamivir in order to assess the additional development of zanamivir resistance and the persistence of the H275Y mutation in the presence of zanamivir. Several substitutions reducing drug susceptibility emerged; I222T in H7N9, V116A, A138V, T157I, R152K and D199G in H1N1 exposed to zanamivir, H275N and E119G in H4N2 exposed to zanamivir and 275Y in H4N2 exposed to peramivir. None of the tested zanamivir-induced substitutions persisted in the absence of drug, indicating lower risk of circulation of these substitutions in the wild as compared to oseltamivir. There is a risk of NAI resistance emerging in LPAIVs of Mallards exposed to NAIs in the water. Zanamivir appears to be the best option from an environmental perspective. Drug concentrations in the Mallard model are mostly higher than the concentrations detected in rivers, but are in the same magnitude regarding OC and an H1N1 LPAIV. Given the importance of NAIs as the first line of defence in the event of a pandemic, this is of public health concern. Surveillance of LPAIV in waterfowl, prudent use of NAIs and waste water treatment improvements are important measures to mitigate the risk

Prescription – Pollution – Poo – Pandemics - Priorities : Neuraminidase Inhibitors from an Environmental Resistance Development Perspective

The natural Influenza A virus (IAV) host is waterfowl. Human IAV is treated with neuraminidase inhibitors (NAIs), which are stockpiled worldwide in case of an IAV pandemic. As the drugs escape regular waste water treatment, they can be detected in river waters. We hypothesize that exposure of low pathogenic avian IAV (LPAIV) infecting Mallards to NAIs in the water promotes development of resistance that can persist in the absence of drugs. Dissemination of resistance genes to humans pose a health risk, particularly if incorporated into a pandemic IAV. To test the hypothesis, LPAIVs of both NA phylogenetic groups were assessed in an in vivo Mallard model by inoculation and exposure of birds to NAI in their water. In previous work in the model, the oseltamivir-resistant H275Y mutation emerged in H1N1 in response to oseltamivir exposure and persisted without drug pressure. In this thesis, a H7N9 was exposed to oseltamivir and a H1N1 and H4N2 to zanamivir and peramivir. Furthermore, a H1N1 with the H275Y mutation was exposed to zanamivir in order to assess the additional development of zanamivir resistance and the persistence of the H275Y mutation in the presence of zanamivir. Several substitutions reducing drug susceptibility emerged; I222T in H7N9, V116A, A138V, T157I, R152K and D199G in H1N1 exposed to zanamivir, H275N and E119G in H4N2 exposed to zanamivir and 275Y in H4N2 exposed to peramivir. None of the tested zanamivir-induced substitutions persisted in the absence of drug, indicating lower risk of circulation of these substitutions in the wild as compared to oseltamivir. There is a risk of NAI resistance emerging in LPAIVs of Mallards exposed to NAIs in the water. Zanamivir appears to be the best option from an environmental perspective. Drug concentrations in the Mallard model are mostly higher than the concentrations detected in rivers, but are in the same magnitude regarding OC and an H1N1 LPAIV. Given the importance of NAIs as the first line of defence in the event of a pandemic, this is of public health concern. Surveillance of LPAIV in waterfowl, prudent use of NAIs and waste water treatment improvements are important measures to mitigate the risk