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Objectives The aim of the study was to analyse the proportion of evidence-based medication displayed in pharmacies and compare it between the different linguistic regions of the country, at different times of the year to determine the amount of proven effective medications indirectly recommended to the public in different parts of Switzerland.Design This is an observational study conducted by medical doctors in the department of internal medicine at the Spitalzentrum Biel, Switzerland.Setting The observation took place from July 2019 to May 2020. From a total of 1800 pharmacies in Switzerland, 68 different pharmacies were selected across the 3 main linguistic regions and the medication on display in their windows were examined 4 times a year regarding their efficacy. The displays of medication with or without evidence-based efficacy were described using absolute numbers and proportions and compared between the different linguistic regions at different seasons using χ2.Participants There were no human or animal participants involved in this study.Primary and secondary outcome measures The primary outcome is the proportion of medication displayed in pharmacy windows with a proven effectiveness in medical literature. The secondary outcome was the variability of the primary outcome over time (seasonal changes), over the different linguistic regions of Switzerland and between chains and privately owned pharmacies.Results We examined 970 medications and found that over the whole year, there is a high proportion of non-evidence-based drugs (56,9%) displayed in pharmacies. Swiss German cantons display significantly more non-evidence-based medications in winter. We found no statistical difference for other seasons or between chains and privately owned pharmacies.Conclusion Pharmacies in Switzerland tend to display significantly more non-evidence-based drugs, thus indirectly recommending them to the public. In a time of necessary expansion of self-medication by the population, this could incite consumers to buy drugs without proven effectiveness.

Spraying various liquids (primarily aqueous solutions of various substances) is widely used in various technological processes. For most of them, high dispersibility and a narrow droplet size distribution are essential. Ultrasonic spraying allows these parameters to be achieved. However, the higher the dispersity of droplets produced by ultrasonic spraying, the lower the spray productivity. To solve this problem, we propose a method of multistage spraying, consisting of the generation of a large number of particles of large initial size (to ensure high productivity) and their subsequent destruction by propagation in a periodic ultrasonic field (to ensure small droplet sizes at high productivity). To experimentally determine the capabilities of this technique, a tubular emitter in the shape of a cylinder with a stepped-variable cross-section was designed. The configuration of the ultrasonic field inside the emitter (22.2 kHz; 182 dB) implements three-stage spraying (the number of sputtering stages corresponds to the number of anti-nodes along the emitter axis). The effectiveness of the proposed and developed technique, suitable for the generation of droplets smaller than 40 µm, with performance exceeding the known ultrasonic spray techniques by at least 10-fold, was confirmed in the course of the conducted research.

Spray technology is widely used in various industries, including medicine, food production, mechanical engineering, and nanopowder manufacturing. Achieving high dispersion and a narrow particle size distribution is crucial for many applications. Ultrasonic spraying is commonly used to achieve this. On the other hand, hydraulic nozzles provide high atomization performance. Combining these two technologies promises to offer significant benefits, but the complex processes that occur simultaneously in such a device require careful study. This work proposes a fundamental design for an acoustic-hydraulic nozzle and investigates the physical processes when a liquid is sprayed using this nozzle, both theoretically and experimentally. The study identifies the critical modes of spraying and confirms that the simultaneous use of ultrasound and hydraulic pressure can produce a fine spray (droplet size less than 50 μm vs. 150–500 μm for hydrodynamic spray) with high productivity (5–10 mL/s vs. 0.5 mL/min for ultrasonic spray). This approach has significant potential for modern industries and technologies.

Abstract Background Nowadays, evaluation of the efficacy and the duration of treatment, in context of monitoring patients with solid tumors, is based on the RECIST methodology. With these criteria, resistance and/or insensitivity are defined as tumor non-response which does not allow a good understanding of the diversity of the underlying mechanisms. The main objective of the OncoSNIPE® collaborative clinical research program is to identify early and late markers of resistance to treatment. Methods Multicentric, interventional study with the primary objective to identify early and / or late markers of resistance to treatment, in 600 adult patients with locally advanced or metastatic triple negative or Luminal B breast cancer, non-small-cell lung cancer or pancreatic ductal adenocarcinoma. Patients targeted in this study have all rapid progression of their pathology, making it possible to obtain models for evaluating markers of early and / or late responses over the 2-year period of follow-up, and thus provide the information necessary to understand resistance mechanisms. To explore the phenomena of resistance, during therapeutic response and / or progression of the pathology, we will use a multidisciplinary approach including high-throughput sequencing (Exome-seq and RNAseq), clinical data, medical images and immunological profile by ELISA. Patients will have long-term follow-up with different biological samples, at baseline (blood and biopsy) and at each tumoral evaluation or tumoral progression evaluated by medical imaging. Clinical data will be collected through a dedicated Case Report Form (CRF) and enriched by semantic extraction based on the French ConSoRe (Continuum Soins Recherche) initiative, a dedicated Semantic Clinical Data Warehouse (SCDW) to cancer. The study is sponsored by Oncodesign (Dijon, France) and is currently ongoing. Discussion The great diversity of intrinsic or acquired molecular mechanisms involved in resistance to treatment constitutes a real therapeutic issue. Improving understanding of mechanisms of resistance of cancer cells to anti-tumor treatments is therefore a major challenge. The OncoSNIPE cohort will lead to a better understanding of the mechanisms of resistance and will allow to explore new mechanisms of actions and to discover new therapeutic targets or strategies making it possible to circumvent the escape in different types of cancer. Trial registration Clinicaltrial.gov. Registered 16 September 2020, https://clinicaltrials.gov/ct2/show/NCT04548960?term=oncosnipe&draw=2&rank=1 and ANSM ID RCB 2017-A02018-45.

The relevance of the research is caused by the need to study the resistance of metals and their coatings to cavitation erosion in conditions of abnormally high temperatures, pressures, as well as in chemically aggressive environments in the form of acids, alkalis or aggressive gases (such as ozone). The main aim of the research is to develop specialized equipment for monitoring and detecting modes and dependencies of cavitation destruction of various metals and their coatings at abnormally high temperatures and overpressure, as well as methodology for determining (controlling) the resistance of metals and their coatings in cavitation fields. Objects: testing cavitation erosion under abnormal conditions using specially designed ultrasonic equipment for this task. Method: experimental method for studying cavitation erosion under abnormal conditions. This method is the development of the existing one regulated by the ASTM G32-10 «Standard test method for cavitation erosion». Results. To create, research and apply special materials and coatings that can ensure long-term reliable equipment operation the authors have proposed and developed a new method for monitoring the erosion resistance of metals and protective coatings under cavitation exposure in abnormal operating conditions, in terms of pressure and temperature. This method expands the capabilities of the ASTM G32-10 «Standard test method for cavitation erosion». Practical implementation of tests of cavitation erosion of metals and protective coatings under abnormal conditions will ensure the creation and application of new materials for use in various branches of human activity and industry.

Point-of-care syndromic panels allow for simultaneous and rapid detection of respiratory pathogens from nasopharyngeal swabs. The clinical performance of the QIAstat-Dx Respiratory SARS-CoV-2 panel RP2.0 (QIAstat-Dx RP2.0) and the BioFire FilmArray Respiratory panel RP2.1 (BioFire RP2.1) was evaluated for the detection of SARS-CoV-2 and other common respiratory pathogens. A total of 137 patient samples were retrospectively selected based on emergency department admission, along with 33 SARS-CoV-2 positive samples tested using a WHO laboratory developed test. The limit of detection for SARS-CoV-2 was initially evaluated for both platforms. The QIAstat-Dx RP2.0 detected SARS-CoV-2 at 500 copies/mL and had a positive percent agreement (PPA) of 85%. The BioFire RP2.1 detected SARS-CoV-2 at 50 copies/mL and had a PPA of 97%. Both platforms showed a negative percent agreement of 100% for SARS-CoV-2. Evaluation of analytical specificity from a range of common respiratory targets showed a similar performance between each platform. The QIAstat-Dx RP2.0 had an overall PPA of 82% (67–100%) in clinical samples, with differences in sensitivity depending on the respiratory target. Both platforms can be used to detect acute cases of SARS-CoV-2. While the QIAstat-Dx RP2.0 is suitable for detecting respiratory viruses within a clinical range, it has less analytical and clinical sensitivity for SARS-CoV-2 compared to the BioFire RP2.1.

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counterintuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfvén waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, α = 2 as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed >600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: preflare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that α = 1.63 ± 0.03. This is below the critical threshold, suggesting that Alfvén waves are an important driver of coronal heating.

Almaciga (Agathis philippinensis Warb.), a tropical conifer that is tapped for its resin commercially known as Manila copal, grows in many parts of the Philippines, but resin buyers prefer and pay a better price for resin from southern Palawan. The study was done to characterize almaciga resins obtained from commercial sites in Davao Oriental and Palawan (Brooke's Point and Marufinas) to explain the quality and price differences. Fresh and aged resin samples were subjected to wet chemical, thermal, and spectral analyses. Generally, the resin samples were found to be soluble in the more polar solvents although significant variations were observed for resins from various sites. Titrimetric determination revealed no significant variation in acid and saponification values, although the Brooke's Point resin had significantly lower unsaponifiable components. Predominant Fourier transform infrared spectroscopy (FTIR) absorption peaks for fresh resin include strong C=O stretch and weak = C–H stretch. Aged Palawan resins, which showed increased solubility in polar solvents, exhibited increased intensity of prominent FTIR peaks such as O–H stretch and C=O stretch. The weak peak at 1719 cm−1 seen in fresh Palawan resins was no longer observed in aged resins. DSC revealed the semi-crystalline nature of almaciga resin and melting temperatures similar to diterpenoid resin acids. This is attributed to the presence of increasing amounts of oxidized abietic acids as shown by gas chromatography-mass spectrometry (GCMS). For the Davao Oriental resins, significant amount of agatholic acid was shown, while resin acids of the abietane and pimarane type were conspicuously absent in the GC-MS spectrograms. The study found evidence that almaciga resins from Davao and Palawan differ in chemical composition and physical properties, which could explain the quality and price differences.

These science activities for elementary students focus on the external structures and functions of the human eye with hands-on object box activities based on the Montessori theory (1966) of concrete learning through manipulation of objects and focus of attention through touch. Object boxes are sets of items and corresponding cards housed in a box. Two types of object boxes are highlighted: (a) form and function analogy object boxes that describe the structures and functions of external parts of the human eye along with analogous manufactured items exhibiting the same forms and functions and (b) words with multiple meanings object boxes that present objects and two different meanings of eye-related words. These activities use analogy to help learners construct connections between previous and new learning along with developing vocabulary for better thinking and communication. (Contains 3 figures and 4 tables.)

Previously, we reported on the target cell-restricted fratricide apoptotic activity of scFvC54:sTRAIL, a fusion protein comprising human-soluble tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) genetically linked to the antibody fragment scFvC54 specific for the cell surface target antigen EGP2. In the present study, we report that the selective binding of scFvC54:sTRAIL to EGP2-positive target cells conveys an exceptionally potent pro-apoptotic effect toward neighboring tumor cells that are devoid of EGP2 expression (bystander cells). The anti-tumor bystander activity of scFvC54:sTRAIL was detectable at target-tobystander cell ratios as low as 1:100. Treatment in the presence of EGP2-blocking or TRAIL-neutralizing antibody strongly inhibited apoptosis in both target and bystander tumor cells. In the absence of target cells, bystander cell apoptosis induction was abrogated. The bystander apoptosis activity of scFvC54:sTRAIL did not require internalization, enzymatic conversion, diffusion, or communication (gap junctional intracellular communication) between target and bystander cells. Furthermore, scFvC54:sTRAIL showed no detectable signs of innocent bystander activity toward freshly isolated blood cells. Further development of this new principle is warranted for approaches where cancer cells can escape from antibody-based therapy due to partial loss of target antigen expression.

The (pro)renin-renin receptor, (P)RR has been claimed to be a novel element of the renin-angiotensin system (RAS). The function of (P)RR has been widely studied in renal and vascular pathology but the cardio-specific function of (P)RR has not been studied in detail. We therefore generated a transgenic mouse (Tg) with cardio-restricted (P)RR overexpression driven by the alpha-MHC promotor. The mRNA expression of (P)RR was ∼ 170-fold higher (P

Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay.We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults.Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia.

The article discusses the relationship which nuclear hormone receptors (NHR) have with the renin-angiotensin-aldosterone system (RAAS). Research which has been completed which found a close relationship between the RAAS and NHR is discussed. The role that NHRs play in the RAAS and the human body as a whole is mentioned.

Background: To assist the development of new anti-cancer drugs, it is important to identify biomarkers of treatment efficacy in the preclinical phases of drug development. In order to improve the predictivity of preclinical experiments, more realistic animal models are needed, for example, tumors xenografted directly on the prostate gland of rodents., Purpose: To characterize the in-vivo metabolism of healthy rat prostate and of an orthotopic human prostate cancer model using proton magnetic resonance spectroscopy (MRS)., Material and Methods: The highly metastatic and hormone-independent PC3-MM2 human prostate cancer model was implanted into the ventral prostate lobe of three Nude rats. Healthy Nude (n = 6) and Sprague-Dawley (n = 6) rats were also studied for interspecies comparison of normal prostate metabolism. Magnetic resonance imaging and short echo-time (TE 11.2 ms) single voxel PRESS spectroscopy were performed on dorsal (DP) and ventral (VP) prostate as well as tumor at 4.7 T. The metabolic content and volume of dorsal and ventral lobes were characterized as a function of species and age., Results: Slightly lower total creatine (tCr)/water (11.3 ± 2.6 vs. 15.3 ± 3.0, NS), but significantly higher Inositol (Ins)/water (18.9 ± 1.9 vs. 6.6 ± 3.3, P < 0.003) and total choline (tCho)/water (15.0 ± 2.1 vs. 5.6 ± 1.1, P < 0.00007) were observed within healthy DP lobes with respect to VP lobes. No significant variation in metabolic content was seen in healthy DP and VP lobes of Nude rats as a function of age, and no species dependence was observed in their metabolic content. For the orthotopic PC3-MM2 tumor, implanted in VP, the tCr/water ratio was significantly lower (3.1 ± 0.9) than neighboring DP (12.8 ± 1.8, P < 0.00003) and healthy VP (15.3 ± 3.0, P < 0.00006). For Ins, the metabolite ratio in PC3-MM2 was close to that of healthy VP (4.3 ± 2.8 vs. 6.6 ± 3.3, p = NS), but much lower than in neighboring DP (19.1 ± 1.3, P < 0.00005). A similar trend was also observed for tCho, where metabolite ratios in PC3-MM2, healthy VP and neighboring DP were 3.5 ± 0.9, 5.6 ± 1.1, and 15.9 ± 0.8, respectively., Conclusion: The in-vivo MRS study of healthy prostate and orthotopic prostate cancer is feasible in rats. Such baseline data could be important when following the modifications in metabolism, including during anti-cancer drug development protocols or following radiotherapy.

Early imaging or blood biomarkers of tumor response is needed to customize anti-tumor therapy on an individual basis. This study evaluates the sensitivity and relevance of five potential MRI biomarkers. Sixty nude rats were implanted with human glioma cells (U-87 MG) and randomized into three groups: one group received an anti-angiogenic treatment (Sorafenib), a second a cytotoxic drug [1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU (Carmustine)] and a third no treatment. The tumor volume, apparent diffusion coefficient (ADC) of water, blood volume fraction (BVf), microvessel diameter (vessel size index, VSI) and vessel wall integrity (contrast enhancement, CE) were monitored before and during treatment. Sorafenib reduced tumor CE as early as 1 day after treatment onset. By 4 days after treatment onset, tumor BVf was reduced and tumor VSI was increased. By 14 days after treatment onset, ADC was increased and the tumor growth rate was reduced. With BCNU, ADC was increased and the tumor growth rate was reduced 14 days after treatment onset. Thus, the estimated MRI parameters were sensitive to treatment at different times after treatment onset and in a treatment-dependent manner. This study suggests that multiparametric MR monitoring could allow the assessment of new anti-tumor drugs and the optimization of combined therapies., (Copyright © 2010 John Wiley & Sons, Ltd.)