Molecular Dynamics Study of Nanoribbon Formation by Encapsulating Cyclic Hydrocarbon Molecules inside Single-Walled Carbon Nanotube.

Carbon nanotubes filled with organic molecules can serve as chemical nanoreactors. Recent experimental results show that, by introducing cyclic hydrocarbon molecules inside carbon nanotubes, they can be transformed into nanoribbons or inner tubes, depending on the experimental conditions. In this paper, we present our results obtained as a continuation of our previous molecular dynamics simulation work. In our previous work, the initial geometry consisted of independent carbon atoms. Now, as an initial condition, we have placed different molecules inside a carbon nanotube (18,0): C5H5 (fragment of ferrocene), C5, C5+H2; C6H6 (benzene), C6, C6+H2; C20H12 (perylene); and C24H12 (coronene). The simulations were performed using the REBO-II potential of the LAMMPS software package, supplemented with a Lennard-Jones potential between the nanotube wall atoms and the inner atoms. The simulation proved difficult due to the slow dynamics of the H abstraction. However, with a slight modification of the parameterization, it was possible to model the formation of carbon nanoribbons inside the carbon nanotube.

IROCA-TES: Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization.

Background: Clinical audits are an important tool to objectively assess clinical protocols, procedures, and processes and to detect deviations from good clinical practice. The main aim of this project is to determine adherence to a core set of consensus- based quality indicators and then to compare the institutions in order to identify best practices. Materials and methods: We conduct a multicentre, international clinical audit of six comprehensive cancer centres in Poland, Spain, Italy, Portugal, France, and Romania as a part of the project, known as IROCATES (Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization). Results: Radiotherapy practice varies from country to country, in part due to historical, economic, linguistic, and cultural differences. The institutions developed their own processes to suit their existing clinical practice. Conclusions: We believe that this study will contribute to establishing the value of routinely performing multi-institutional clinical audits and will lead to improvement of radiotherapy practice at the participating centres.

Formation of nanoribbons by carbon atoms confined in a single-walled carbon nanotube-A molecular dynamics study.

Carbon nanotubes can serve as one-dimensional nanoreactors for the in-tube synthesis of various nanostructures. Experimental observations have shown that chains, inner tubes, or nanoribbons can grow by the thermal decomposition of organic/organometallic molecules encapsulated in carbon nanotubes. The result of the process depends on the temperature, the diameter of the nanotube, and the type and amount of material introduced inside the tube. Nanoribbons are particularly promising materials for nanoelectronics. Motivated by recent experimental results observing the formation of carbon nanoribbons inside carbon nanotubes, molecular dynamics calculations were performed with the open source LAMMPS code to investigate the reactions between carbon atoms confined within a single-walled carbon nanotube. Our results show that the interatomic potentials behave differently in quasi-one-dimensional simulations of nanotube-confined space than in three-dimensional simulations. In particular, the Tersoff potential performs better than the widely used Reactive Force Field potential in describing the formation of carbon nanoribbons inside nanotubes. We also found a temperature window where the nanoribbons were formed with the fewest defects, i.e., with the largest flatness and the most hexagons, which is in agreement with the experimental temperature range.

Application of a Machine Learning Algorithm in Generating an Evapotranspiration Data Product From Coupled Thermal Infrared and Microwave Satellite Observations.

Land surface evapotranspiration (ET) is one of the main energy sources for atmospheric dynamics and a critical component of the local, regional, and global water cycles. Consequently, accurate measurement or estimation of ET is one of the most active topics in hydro-climatology research. With massive and spatially distributed observational data sets of land surface properties and environmental conditions being collected from the ground, airborne or space-borne platforms daily over the past few decades, many research teams have started to use big data science to advance the ET estimation methods. The Geostationary satellite Evapotranspiration and Drought (GET-D) product system was developed at the National Oceanic and Atmospheric Administration (NOAA) in 2016 to generate daily ET and drought maps operationally. The primary inputs of the current GET-D system are the thermal infrared (TIR) observations from NOAA GOES satellite series. Because of the cloud contamination to the TIR observations, the spatial coverage of the daily GET-D ET product has been severely impacted. Based on the most recent advances, we have tested a machine learning algorithm to estimate all-weather land surface temperature (LST) from TIR and microwave (MW) combined satellite observations. With the regression tree machine learning approach, we can combine the high accuracy and high spatial resolution of GOES TIR data with the better spatial coverage of passive microwave observations and LST simulations from a land surface model (LSM). The regression tree model combines the three LST data sources for both clear and cloudy days, which enables the GET-D system to derive an all-weather ET product. This paper reports how the all-weather LST and ET are generated in the upgraded GET-D system and provides an evaluation of these LST and ET estimates with ground measurements. The results demonstrate that the regression tree machine learning method is feasible and effective for generating daily ET under all weather conditions with satisfactory accuracy from the big volume of satellite observations.

The comparative effects of Resveratrol and Curcumin in combination with photodynamic therapy.

Background and aim: Photodynamic therapy, PDT, is a promising option among the local treatments with oncolytic potential. Although the basic principle is simple, its intricate mechanisms allow for a broad range of optimization methods. The purpose of this study was to assess the effects of Resveratrol and Curcumin as adjuvants of PDT on experimental tumors. Methods: Sixty-six Wistar male rats were divided into 11 groups: control, Curcumin (CUR), Resveratrol (RES) alone or followed by irradiation (IR) (CUR+IR and RES+IR, respectively), 5,10,15,20-tetra-sulphonato-phenyl-porphyrin (TSPP), TSPP+IR (PDT), and CUR or RES administered prior to or after PDT (CUR+TSPP+IR, RES+TSPP+IR, TSPP+IR+CUR, TSPP+IR+RES). Results: Both CUR and RES significantly decreased lipid peroxidation, while RES also showed an increase in glutathione (GSH) levels, especially when it was administered before PDT (p<0.01). Both antioxidants decreased cyclooxygenase (COX)2 expression, to a minimum when they administered prior to PDT (p<0.001 and p<0.01) while nitric oxide synthase (NOS)2 expression diminished in the combined regimen, particularly in RES associated with PDT. CUR and RES induced similar changes in terms of cell death, but CUR seemed to be more efficient on tumor necrosis and showed a higher apoptotic index when was administered after PDT (p<0.001). Conclusion: Both RES and CUR in association with PDT decreased oxidative stress, diminished the COX2 and NOS2 expressions and increased cell death by positively influencing the necrotic rate and apoptotic index, particularly when CUR was administered after PDT. The results show that CUR is a promising class to study in PDT optimization and further invites to exploit its promises.

Quality-by-design in pharmaceutical development: From current perspectives to practical applications.

Current pharmaceutical research directions tend to follow a systematic approach in the field of applied research and development. The concept of quality-by-design (QbD) has been the focus of the current progress of pharmaceutical sciences. It is based on, but not limited, to risk assessment, design of experiments and other computational methods and process analytical technology. These tools offer a well-organized methodology, both to identify and analyse the hazards that should be handled as critical, and are therefore applicable in the control strategy. Once implemented, the QbD approach will augment the comprehension of experts concerning the developed analytical technique or manufacturing process. The main activities are oriented towards the identification of the quality target product profiles, along with the critical quality attributes, the risk management of these and their analysis through in silico aided methods. This review aims to offer an overview of the current standpoints and general applications of QbD methods in pharmaceutical development.

Pharmacological options in treating SASR-CoV-2 infection/COVID-19 / [Farmakoterápiás lehetoségek SARS-CoV-2-fertozés/COVID­19-betegség esetén]

There is currently no proven effective therapy for COVID-19. Here we discuss the drugs most investigated for the treatment of the disease. All the listed therapies are experimental at this stage. However, due to the severe healthcare effects of the pandemic and the potentially fatal outcome of COVID-19 patients treated in the intensive care units, their off-label use should none-the-less be considered. Orv Hetil. 2020; 161(17): 685­688.

Practical aspects of intensive care for critically ill COVID-19 patients requiring respiratory support / [Kritikus állapotú, légzéstámogatást igénylo COVID­19-fertozött beteg ellátásának gyakorlati szempontjai]

In December 2019, a novel outbreak of pneumonia was reported in Wuhan city, China. Initially, the zoonitic infection spread from human to human, causing a pandemic. This viral disease (COVID-19) can appear in a variety of forms, from asymptomatic through the spectrum of mild symptoms to severe respiratory failure, requiring intensive care. Caring for this latter group of patients puts a significant burden on health care. The purpose of this summary is to present the practical aspects of intensive care for patients requiring respiratory support and mechanical ventilation. Orv Hetil. 2020; 161(17): 678­684.

Practical aspects of anesthetic and perioperative care for COVID-19 patients / [A COVID­19-fertozött betegek anesztéziájának és perioperatív ellátásának gyakorlati szempontjai]

Caring for those affected by the coronavirus outbreak of December 2019 imposed a heavy burden on healthcare systems. Not only because some patients require intensive care, but because patients with any form of the disease may need surgical intervention. Managing these cases is a major challenge for anesthesiologists. The purpose of this summary is to present the practical aspects of anesthetic and perioperative care for patients requiring surgical treatment. Orv Hetil. 2020; 161(17): 692­695.

Airway management of coronavirus-infected patients / [Légútbiztosítás koronavírus-fertozött betegekben]

The coronavirus pandemic is a serious challenge for healthcare workers worldwide. The virus is spread through the air by droplets of moisture when people cough or sneeze and it has a very high virulence. Procedures generating airway aerosols are dangerous for every participant of patient care. The serious form of coronavirus infection can cause progressive respiratory failure. The best treatment is early endotracheal intubation and invasive mechanical ventilation. Intubation is an aerosol-generating process and thus carries the risk of contamination. Additionally the airway management of this patient population is usually difficult. The goal of this article is to give a practice-based overview of the peculiarities of airway management in coronavirus-infected patients with special regard to infection control and patient safety considerations. Orv Hetil. 2020; 161(17): 696­703.

Organ replacement therapy and life-supporting treatment modalities in critically ill COVID-19 patients / [Emelt szintu szervtámogató és életfenntartó kezelések kritikus állapotú COVID­19-fertozött betegeken]

In critically ill COVID-19 patients, the failure of the cardiorespiratory system can be due to one of the following: (1) cytokine storm, haemophagocytosis ­ septic shock, (2) unmanageable hypoxemia, (3) isolated organ failure or as part of multi-organ failure. Herein we give an overview of the therapeutic options for treating or preventing these disease states. In recent years, CytoSorb-haemoperfusion to remove cytokines has shown promising results in the treatment of septic shock. Inhalational nitric oxide (iNO), inhalational epoprostenol and veno-venous extracorporeal membrane oxygenation (ECMO) are options in severe hypoxemia that is unresponsive to conventional mechanical ventilation. Renal failure is a frequent component of the multi-organ failure usually seen with disease progression and necessitates starting one of the available continuous renal replacement modalities. Orv Hetil. 2020; 161(17): 704­709.

Intrahospital resuscitation of COVID-19 patients / [A COVID­19-betegek kórházon belüli újraélesztésének speciális szempontjai]

The coronavirus pandemic is a serious challenge for healthcare workers worldwide. The virus is spread through the air by droplets of moisture when people cough or sneeze and it has a very high virulence. Procedures generating airway aerosols are dangerous for every participant of patient care. Mortality of COVID-19 is above 10%, thus cardiopulmonary resuscitation is an often needed intervention in this patient group. Resuscitation is an aerosol-generating process and thus carries the risk of contamination. The goal of this article is to give a practice-based overview of the specialities of cardiopulmonary resuscitation in coronavirus-infected patients. Orv Hetil. 2020. 161(17): 710­712.

The in vivo modulatory effects of Cornus mas extract on photodynamic therapy in experimental tumors.

BACKGROUND: Photodynamic therapy (PDT) is a treatment of cancer due to its ability to induce cell death, oxidative stress and acute inflammatory reaction in targeted sites. To optimize the effect of PDT the addition of some compounds with supplementary cytotoxic effect on tumor cells was tried. METHODS: The study was performed on 35 Wistar male albino rats with Walker 256 carcinosarcoma. The animals were randomly assigned in seven groups (n = 5) and treated as follows: group 1 - control; group 2 - Cornus mas (CM) extract 15 mg/kg b.w., administered for 7 days; group 3 - CM extract administered for 7 days followed by irradiation (CM + IR); group 4 - one dose of tetra-p-sulfonato-phenyl-porphyrin (TSPP) 10 mg/kg b.w.; group 5 - TSPP + IR; group 6 - CM extract administered daily for 7 days before TSPP and IR (CM + TSPP + IR); group 7 - TSPP + IR followed by CM administered for 7 days (TSPP + IR + CM). RESULTS: The results showed that MDA and GSSG levels increased after PDT in parallel with the increasing of COX-2 expression and DNA damage. Apoptotic and necrotic index enhanced in TSPP + IR, effect improved by CM association before PDT. CM + TSPP + IR regimen also induced more intense inflammatory reactions, increased COX-2 expression, determined DNA damage, apoptosis and necrosis, compared to the TSPP + IR + CM group. Both combined therapeutic regimens reduced MDA levels in tumor tissue, especially CM + TSPP + IR and increased the antioxidant defense and iNOS expression. CONCLUSIONS: Our results demonstrated that CM associated before PDT had beneficial effects in PDT and may represent a promising option in PDT strategies.

Selective neuronal death following exposure to methylenedioxypyrovalerone is accompanied by an inhibition of NMDA receptor NR2B subunit expression.

In a previous study, methylenedioxypyrovalerone (MDPV), a designer drug of the cathinone family, caused selective enhancement of Caspase3 immunoreactive (Casp3+) apoptotic cells in the nucleus accumbens (NAc) of 7­day­old mice. To further elaborate on the mechanism underlying MDPV­elicited apoptosis, here, we investigated the appearance of Casp3+ cells in developing neural tube explants of E12.5 mice, following MDPV treatment in vitro. Apoptotic cells appeared in large number in the pallium as radial progenitor cells and multipolar neurons, and in the subpallium including the future NAc, both in control and MDPV treated specimens. MDPV did not cause gross morphological changes in the neural tube or in the abundance of Casp3+ cells, based on a visual impression, though quantification was not attempted. We also studied the changes in NMDA receptor (NMDAR) protein subunits NR1 and NR2B in the NAc of 7­day­old MDPV treated and control mice, using western blotting of tissue obtained by selective dissection. In MDPV treated animals, expression of NR2B was lower than in the control animals, whereas expression of NR1 did not differ significantly from controls. The findings indicate that, during early postembryonic development, downregulation of the NR2B receptor subunit (at this time predominant in the NMDAR) is accompanied by a decreased viability of neurons. Decreased viability is expressed, in this case, as enhanced susceptibility to stimulation by MDPV - essentially a robust dopaminergic agent, potently affecting the neurons of the NAc. The findings are likely relevant to dopaminergic/NMDAR interactions and a potential pro­survival role of the NR2B subunit in critical phases of neural development.

Effects of Cariprazine, Aripiprazole, and Olanzapine on Mouse Fibroblast Culture: Changes in Adiponectin Contents in Supernatants, Triglyceride Accumulation, and Peroxisome Proliferator-Activated Receptor-γ Expression.

Background and Objectives: The use of the dopamine-partial agonist subclass (also termed dopamine stabilizers) of atypical antipsychotics for the treatment of negative schizophrenia symptoms and some mood disorders has increased recently. Similar to other second-generation antipsychotics (SGAs), aripiprazole (ARI) and cariprazine (CAR) also influence food intake, but the peripheral effects of these drugs on adipose-tissue homeostasis, including adipokine secretion as well as lipo- and adipogenesis, are not fully elucidated. In this study, we explored the adipocyte-related mechanisms induced by second-generation antipsychotics (SGAs), leading to changes in peripheral signals involved in energy homeostasis. Materials and Methods: CAR, a new SGA, was compared with ARI and olanzapine (OLA), using cell cultures to study adipogenesis, and the expression levels of peroxisome proliferator-activated receptor-γ (PPAR-γ) was measured in adipocytes derived from mouse fibroblasts, by western blotting on days 7, 14, and 21 postinduction. The triglyceride (TG) content of the cells was also evaluated on day 15 using Oil Red O staining, and the adiponectin (AN) content in the cell culture supernatants was quantified on days 7 and 15 by enzyme-linked immunosorbent assay. Cells were treated with two concentrations of ARI (0.5 and 20 µg/mL), OLA (1 and 20 µg/mL), and CAR (0.1 and 2 µg/mL). Results: Both concentrations of ARI and OLA, as well as the lower concentration of CAR, significantly increased the TG contents. The AN levels in the supernatants were significantly increased by the higher concentration of ARI on days 7 and 15 (p < 0.05). Although PPAR-γ levels were not significantly affected by ARI and OLA, the lower concentration of CAR induced a significant time-dependent decrease in PPAR-γ expression (p < 0.05). Conclusions: The in vitro adipogenesis considered from TG accumulation, AN secretion, and PPAR-γ expression was differently influenced by ARI, CAR, and OLA. Understanding the adipocyte-related mechanisms of antipsychotics could contribute to understanding their weight-influencing effect.

[Open transgastric necrosectomy for extended walled-off pancreas necrosis]. / Kiterjedt, demarkált pancreas necrosis sebészi kezelése transgastricus necrectomiával.

AIMS: In severe acute pancreatitis the timing of necrosectomy is ideally should be postponed 4-6 weeks after the onset of the disease when the walled-of pancreatic necrosis (WOPN) has developed. The authors present their experience with open transgastric necrosectomy for extended WOPN. PATIENTS AND METHODS: The authors performed 17 (12 male, 5 female with a mean age of 61.6 ± 15.1 years) open transgastric necrosectomies for extended WOPN in a period of 1, January 2012 and 31, December 2017. Before the operations conservative and semiconservative therapy was used for an average of 74.6 ± 83.1 days. The mean size of the WOPNs was 13.8 ± 5.2 cm with localisation of the retrocolic and retroduodenal regions. All necroses were septic. RESULTS: Complications related to the operation were not observed. The mean time of hospitalization after the surgery was 11.6 ± 12.8 days. The mortality rate was 5.9%. Late operation or other interventions for pseudocyst or pancreas fistula formation was not performed. Two patients needed endoscopic dilatation with lavage in the early postoperative period because of fever. New diabetes mellitus was not observed but worsening of previously existed diabetes developed in 6.3% of the cases. CONCLUSIONS: The open transgastric necrosectomy is safe and effective for extended WOPN. The advantage of this type of necrosectomy is the prevention of pancreatic pseudocyst and fistula formation.

Kinetics of dopamine release from poly(aspartamide)-based prodrugs.

Preparation of novel biocompatible and biodegradable polymer-based prodrugs that can be applied in complex drug delivery systems is one of the most researched fields in pharmaceutics. The kinetics of the drug release strongly depends on the physicochemical parameters of prodrugs as well as environmental properties, therefore precise kinetical description is crucial to design the appropriate polymer prodrug formula. The aim of the present study was to investigate the dopamine release from different poly(aspartamide) based dopamine drug conjugates in different environments and to work out a kinetic description which can be extended to describe drug release in similar systems. Poly(aspartamide) was conjugated with different amounts of dopamine. In order to alter the solubility of the conjugates, 2-aminoethanol was also grafted to the main chain. Chemical structure as well as physical properties such as solubility, lipophilicity measurements and thermogravimetric analysis has been carried out. Kinetics of dopamine release from the macromolecular prodrugs which has good water solubility has been studied and compared in different environments (phosphate buffer, Bromelain and α-Chymotrypsin). It was found that the kinetics of release in those solutions can be satisfactorily described by first order reaction rate. For poorly-soluble conjugates, the release of dopamine was considered as a result of coupling of diffusion and chemical reaction. Besides the time dependence of dopamine cleavage, a practical quantity, the half-life of the release of loading capacity has been introduced and evaluated. It was found, that dopamine containing macromolecular prodrugs exhibit prolonged release kinetics and the quantitative description of the kinetics, including the most important physical parameters provides a solid base for future pharmaceutical and medical studies. STATEMENT OF SIGNIFICANCE: Poly(aspartamide) based polymer-drug conjugates are promising for controlled and prolonged drug delivery due to their biocompatibility and biodegradability. In this study different poly(aspartamide) based dopamine conjugates were synthesized which can protect dopamine from deactivation in the human body. Since there is no satisfying kinetics description for drug release from covalent polymer-drug conjugates in the literature, dopamine release was investigated in different environments and a complete kinetical description was worked out. This study demonstrates that poly(aspartamide) is able to protect conjugated dopamine from deactivation and provide prolonged release in alkaline pH as well as in the presence of different enzymes. Furthermore, detailed kinetical descriptions were demonstrated which can be used in case of other covalent polymer-drug conjugates.

Chronic fluoxetine treatment induces lipid accumulation but does not alter the expression of Pref-1 in rat adipose tissue.

This study aims to investigate the effects of chronic fluoxetine (FLX) treatment on preadipocyte factor-1 (Pref-1) expression in subcutaneous, visceral and brown adipose tissues, and on the size of vacuoles in a dipocytes obtained from the perirenal regions in rats. Twenty-eight Wistar rats were treated with FLX at two different doses and fourteen animals received vehicle. After 40 days of treatment, the subcutaneous, perirenal and interscapular adipose tissues were collected. Pref-1 expression was examined using an immunohistochemical method and the vacuolar area was measured in stained sections. In the low dose FLX group, the size of vacuoles increased both in male and female animals. The high dose of FLX also induced a significant increase of vacuole size, but only in male animals. Neither of the two doses of FLX has significantly affected the Pref-1 expression in any type of adipose tissue.