The development of carbon‐monoxide‐releasing molecules (CORMs) as pharmaceutical agents represents an attractive and safer alternative to administration of gaseous CO. Most CORMs developed to date ...are transition‐metal carbonyl complexes. Although such CORMs have showed promising results in the treatment of a number of animal models of disease, they still lack the necessary attributes for clinical development. Described in this Minireview are the methods used for CORM selection, to date, and how new insights into the reactivity of metal‐carbonyl complexes in vivo, together with advances in methods for live‐cell CO detection, are driving the design and synthesis of new CORMs, CORMs that will enable controlled CO release in vivo in a spatial and temporal manner without affecting oxygen transport by hemoglobin.
On target: Carbon‐monoxide‐releasing molecules (CORMs) are promising agents for the treatment of several diseases. CORMs are particularly good for enabling CO delivery in a controlled manner without affecting oxygen transport by hemoglobin. Significant progress in the methods for CO detection in live cells and the understanding of the reactivity of CORMs in vivo provides insights into CO biology and the design of safer, and more selective and efficient CORMs for clinical use.
We prospectively evaluated the efficacy and toxicity of intravenously administered colistin in 35 episodes of ventilator-associated pneumonia (VAP) due to multidrug-resistant Acinetobacter baumannii. ...Microbiological diagnosis was performed with use of quantitative culture. In 21 patients, the episodes were caused by a strain susceptible exclusively to colistin (the CO group) and were all treated with this antimicrobial intravenously. In 14 patients, the episodes were caused by strains that remained susceptible to imipenem and were treated with imipenem-cilastatin (the IM group). Acute Physiology and Chronic Health Evaluation II scores at the time of admission and Sequential Organ Failure Assessment scores at time of diagnosis were similar in both groups. VAP was considered clinically cured in 57% of cases in both groups. In-hospital mortality rates were 61.9% in the CO group and 64.2% in the IM group, and the VAP-related mortality rates were 38% and 35.7%, respectively. Four patients in the CO group and 6 in the IM group developed renal failure. Neurophysiological evaluation was performed during 12 episodes in the CO group, but it revealed no signs of neuromuscular blockade. Intravenous colistin appears to be a safe and effective alternative to imipenem for the management of VAP due to carbapenem-resistant strains of A. baumannii.
Hepatocellular carcinoma (HCC) growth relies on angiogenesis via vascular endothelial growth factor (VEGF) release. Hypoxia within tumour environment leads to intracellular stabilisation of hypoxia ...inducible factor 1 alpha (Hif1α) and signal transducer and activator of transcription (STAT3). Melatonin induces apoptosis in HCC, and shows anti-angiogenic features in several tumours. In this study, we used human HepG2 liver cancer cells as an in vitro model to investigate the anti-angiogenic effects of melatonin.
HepG2 cells were treated with melatonin under normoxic or CoCl2-induced hypoxia. Gene expression was analysed by RT-qPCR and western blot. Melatonin-induced anti-angiogenic activity was confirmed by in vivo human umbilical vein endothelial cells (HUVECs) tube formation assay. Secreted VEGF was measured by ELISA. Immunofluorescence was performed to analyse Hif1α cellular localisation. Physical interaction between Hif1α and its co-activators was analysed by immunoprecipitation and chromatin immunoprecipitation (ChIP).
Melatonin at a pharmacological concentration (1 mM) decreases cellular and secreted VEGF levels, and prevents HUVECs tube formation under hypoxia, associated with a reduction in Hif1α protein expression, nuclear localisation, and transcriptional activity. While hypoxia increases phospho-STAT3, Hif1α, and CBP/p300 recruitment as a transcriptional complex within the VEGF promoter, melatonin 1 mM decreases their physical interaction. Melatonin and the selective STAT3 inhibitor Stattic show a synergic effect on Hif1α, STAT3, and VEGF expression.
Melatonin exerts an anti-angiogenic activity in HepG2 cells by interfering with the transcriptional activation of VEGF, via Hif1α and STAT3. Our results provide evidence to consider this indole as a powerful anti-angiogenic agent for HCC treatment.
Melatonin induces apoptosis in many different cancer cell lines, including hepatocellular carcinoma cells. However, the responsible pathways have not been clearly elucidated. A member of the forkhead ...transcription factors' family, FoxO3a, has been implicated in the expression of the proapoptotic protein Bim (a Bcl-2-interacting mediator of cell death). In this study, we used human HepG2 liver cancer cells as an in vitro model to investigate whether melatonin treatment induces Bim through regulation by the transcription factor FoxO3a.
Cytotoxicity of melatonin was compared in HepG2 hepatoblastoma cells and primary human hepatocytes. Proapoptotic Bim expression was analysed by reverse transcriptase-polymerase chain reaction and western blot. Reporter gene assays and chromatin immunoprecipitation assays were performed to analyse whether FoxO3a transactivates the Bim promoter. Small interfering RNA (siRNA) was used to study the role of FoxO3a in Bim expression. Immunofluorescence was performed to analyse FoxO3a localisation in HepG2 cells.
Melatonin treatment induces apoptosis in HepG2 cells, but not in primary human hepatocytes. The proapoptotic effect was mediated by increased expression of the BH3-only protein Bim. During melatonin treatment, we observed increased transcriptional activity of the forkhead-responsive element and could demonstrate that FoxO3a binds to a specific sequence within the Bim promoter. Furthermore, melatonin reduced phosphorylation of FoxO3a at Thr(32) and Ser(253), and induced its increased nuclear localisation. Moreover, silencing experiments with FoxO3a siRNA prevented Bim upregulation.
This study shows that melatonin can induce apoptosis in HepG2 hepatocarcinoma cells through the upregulation of proapoptotic Bim mediated by nuclear translocation and activation of the transcription factor FoxO3a.
An “on site” bioremediation program was designed and implemented in soil polluted with polycyclic aromatic hydrocarbons (PAHs), especially naphthalene. We began by characterizing the soil's physical ...and chemical properties. A microbiological screening corroborated the presence of microorganisms capable of metabolizing PAHs. We then analyzed the viability of bioremediation by developing laboratory microcosms and pilot scale studies, to optimize the costs and time associated with remediation. The treatment assays were based on different types of biostimulants, such as a slow or fast-release fertilizer, combined with commercial surfactants. Once the feasibility of the biostimulation was confirmed, a real-scale bioremediation program was undertaken in 900 m3 of contaminated soil. The three-step design reduced PAH contamination by 94.4% at the end of treatment (161 days). The decrease in pollutants was concomitant with the selection of autochthonous bacteria capable of degrading PAHs, with Bacillus and Pseudomonas the most abundant genera.
•A three-step bioremediation program was designed for a polluted soil with PAHs.•Biostimulation was based in applying nutrient plus surfactants, watering and aeration.•Microcosm and pilot scale studies allowed the selection of the best treatment.•Bioremediation of 900 m3 of contaminated soil showed a final reduction of 94.4% PAHs.•Autochthonous Bacillus and Pseudomonas were the bacterial genera with highest representation.
PAH-polluted soil underwent biostimulation at the microcosms and pilot-scale to optimize subsequent field-scale bioremediation.
In hospitals, operating rooms are energy-intensive spaces, due to the high flow of outside air required to achieve the necessary indoor air quality. Operating rooms demand ventilation continuously, ...despite periods of low daily surgical activity. However, by controlling ventilation during inactive periods in the operating room, significant energy savings can be achieved, avoiding penalties on IAQ levels. This paper evaluates the energy savings achieved by introducing ventilation flow control and regulation systems in operating rooms of hospitals located in different climatic zones within Spain. In addition, emissions and economic savings have also been evaluated. Two control and regulation strategies of the air flow to be supplied and extracted in the operating rooms, during periods of inactivity, are studied and include regulation by schedule and regulation by occupancy. Data from a 900-bed university hospital center are used as a reference to evaluate the average occupancy of the operating rooms, and the energy consumption, thus validating the model for calculating the demand of a typical operating room. The energy savings for the regulation by occupancy are 37.5%, and the regulation by schedule are 40% of the annual demand, with respect to an operating room working permanently.
The treatment of metal‐laden industrial effluents by reverse osmosis is gaining in popularity worldwide due to its high performance. However, this process generates a polymetallic concentrate ...(retentate) stream in need of efficient post‐treatment prior to environmental discharge. This paper presents results on the bioremediation (in batch mode) of a metal‐laden, arsenic‐dominated retentate using Shewanella sp. O23S as inoculum. The incubation of the retentate for 14 days under anoxic conditions resulted in the following removal yields: As (8%), Co (11%), Mo (3%), Se (62%), Sb (30%) and Zn (40%). The addition of 1 mmol l−1 cysteine increased the removal rate as follows: As (27%), Co (80%), Mo (78%), Se (88%), Sb (83%) and Zn (90%). The contribution of cysteine as a source of H2S to enhancing the removal yield was confirmed by its addition after 7 days of incubations initially lacking it. Additionally, the cysteine‐sourced H2S was confirmed by its capture onto headspace‐mounted Pb‐acetate test strips that were analysed by X‐ray diffraction. We show that real metal‐laden industrial effluents can be treated to medium‐to‐high efficiency using a biological system (naturally sourced inocula) and inexpensive reagents (yeast extract, lactate and cysteine).
Significance and Impact of the Study: This study provides evidence of the medium‐to‐high removal of metals and metalloids present in real industrial effluents by using naturally sourced metal‐resistant bacterial inocula. Apart from the applied research significance, the coupling of cysteine degradation to metal removal sheds light into the microbially driven natural attention of industrial pollution in specific geochemical settings. The results warrant the scaling up of the process to treat larger effluent volumes and potentially recover valuable metals in the form of metal sulphides.
ABSTRACT
Even though the electromagnetic counterpart AT2017gfo to the binary neutron star merger GW170817 is powered by the radioactive decay of r-process nuclei, only few tentative identifications ...of light r-process elements have been made so far. One of the major limitations for the identification of heavy nuclei is incomplete or missing atomic data. While substantial progress has been made on lanthanide atomic data over the last few years, for actinides there has been less emphasis, with the first complete set of opacity data only recently published. We perform atomic structure calculations of neodymium (Z = 60) as well as the corresponding actinide uranium (Z = 92). Using two different codes flexible atomic code (fac) and hartree–fock-relativistic (hfr) for the calculation of the atomic data, we investigate the accuracy of the calculated data (energy levels and electric dipole transitions) and their effect on kilonova opacities. For the fac calculations, we optimize the local central potential and the number of included configurations and use a dedicated calibration technique to improve the agreement between theoretical and available experimental atomic energy levels (AELs). For ions with vast amounts of experimental data available, the presented opacities agree quite well with previous estimations. On the other hand, the optimization and calibration method cannot be used for ions with only few available AELs. For these cases, where no experimental nor benchmarked calculations are available, a large spread in the opacities estimated from the atomic data obtained with the various atomic structure codes is observed. We find that the opacity of uranium is almost double the neodymium opacity.
Widespread purpura annularis telangiectodes following mRNA SARS‐CoV‐2 vaccine Falkenhain‐López, D.; Gutiérrez‐Collar, C.; Arroyo‐Andrés, J. ...
JEADV. Journal of the European Academy of Dermatology and Venereology/Journal of the European Academy of Dermatology and Venereology,
November 2021, Letnik:
35, Številka:
11
Journal Article
Despite the wide application of adherence as a concept, the definition, evaluation and improvement of the adherence to treatment by patients with chronic obstructive pulmonary disease (COPD) still ...present some challenges. First, it is necessary to clearly define the concepts of treatment adherence, compliance and persistence. Second, it is critical to consider the various methods of evaluating and quantifying adherence when interpreting adherence studies. In addition, the advantages and disadvantages of the different ways of measuring treatment adherence should be taken into account. Another subject of some debate is the number of variables associated with COPD treatment adherence. Adherence is a complex concept that goes beyond the dosage or the use of inhalation devices, and a number of variables are involved in determining adherence, from the clinical aspects of the disease to the patient's confidence in the doctor's expertise and the level of social support experienced by the patient. Notably, despite these challenges, the importance of adherence has been well established by clinical trials and routine clinical practice. The available evidence consistently shows the substantial impact that a lack of adherence has on the control of the disease and its long-term prognosis. For these reasons, the correct evaluation of therapeutic adherence should be a key objective in clinical interviews of patients. In recent years, various initiatives for improving adherence have been explored. All these initiatives have been based on patient education. Therefore, health care professionals should be aware of the issues pertaining to adherence and take the opportunity to educate patients each time they contact the health care system.
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