Analytical Methods for the Determination of Major Drugs Used for the Treatment of COVID-19. A Review.

At the beginning of the COVID-19 outbreak (end 2019 - 2020), therapeutic treatments based on approved drugs have been the fastest approaches to combat the new coronavirus pandemic. Nowadays several vaccines are available. However, the worldwide vaccination program is going to take a long time and its success will depend on the vaccine public's acceptance. Therefore, outside of vaccination, the repurposing of existing antiviral, anti-inflammatory and other types of drugs, have been considered an alternative medical strategy for the COVI-19 infection. Due to the broad clinical potential of the drugs, but also to their possible side effects, analytical methods are needed to monitor the drug concentrations in biological fluids and pharmaceutical products. This review deals with analytical methods developed in the period 2015 - July 2021 to detect potential drugs that, according to a literature survey, have been taken into consideration for the treatment of COVID-19. The drugs considered here have been selected on the basis of the number of articles published in the period January 2020-July 2021, using the combination of the keywords: COVID-19 and drugs or SARS-CoV-2 and drugs. A section is also devoted to monoclonal antibodies. Over the period considered, the analytical methods have been employed in a variety of real samples, such as body fluids (plasma, blood and urine), pharmaceutical products, environmental matrices and food.

Silver, copper and copper oxide nanoparticles in the fight against human viruses: progress and perspectives.

The rapid development of nanomedicine has created a high demand for silver, copper and copper oxide nanoparticles. Due to their high reactivity and potent antimicrobial activity, silver and copper-based nanomaterials have been playing an important role in the search for new alternatives for the treatment of several issues of concern, such as pathologies caused by bacteria and viruses. Viral diseases are a significant and constant threat to public health. The most recent example is the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, the object of the present review is to highlight recent progress in the biomedical uses of these metal nanoparticles for the treatment and prevention of human viral infections. We discuss the antiviral activity of AgNPs and Cu-based NPs, including their actions against SARS-CoV-2. We also discuss the toxicity, biodistribution and excretion of AgNPs and CuNPs, along with their uses in medical devices or on inert surfaces to avoid viral dissemination by fomites. The challenges and limitations of the biomedical use of these nanoparticles are presented.

Status of low-energy accelerator-based BNCT worldwide and in Argentina.

Existing and active low-energy Accelerator-Based BNCT programs worldwide will be reviewed and compared. In particular, the program in Argentina will be discussed which consists of the development of an Electro-Static-Quadrupole (ESQ) Accelerator-Based treatment facility. The facility is conceived to operate with the deuteron-induced reactions 9Be(d,n)10B and 13C(d,n)14N at 1.45 MeV deuteron energy, as neutron sources. Neutron production target development status is specified. The present status of the construction of the new accelerator development laboratory and future BNCT centre is shown.

Electrochemical preconcentration coupled with spectroscopic techniques for trace lead analysis in olive oils.

In this paper we present a novel combined electrochemical-spectroscopic approach suitable to monitor trace levels of heavy metals directly in edible oils. The method is based on the electrochemical preconcentration/extraction of the analyte from the tested real matrix by cathodic deposition onto a Pt working electrode, then transfer and anodic re-oxidation of the metallic deposit to a "clean" aqueous solution, suitable for the subsequent spectroscopic analysis. The procedure has been here focused to the determination of lead in extra virgin olive oil (EVOO), performed by applying ICP-QMS or GFAAS techniques. To this aim, the EVOO samples were mixed with proper amounts of the room temperature ionic liquid (RTIL) [P14,6,6,6]+[NTf2]-, in order to obtain a non-aqueous supporting electrolyte suitable for the electrodeposition process. The feasibility and performance of the analytical strategy were at first tested in standard solutions of Pb(II) in RTIL, produced by anodic dissolution of lead in the RTIL, as well as in olive oil samples mixed with 0.5 M RTIL and spiked with known amounts of Pb(II). The optimisation of the electrochemical parameters was achieved by applying a D-Optimal Design, properly set up to optimise the efficiency of the deposition and re-oxidation steps, quantitative recovery and measurement time. Finally, the analytical procedure was applied to the determination of Pb content in some Italian EVOOs, without any need of performing mineralization pretreatments. Data obtained with the proposed procedure satisfactorily agree with those achieved by ICP-QMS analysis after microwave digestion, being differences between the two approaches within 10%, with the advantage of reducing to half the pretreatment time, operating at room temperature and avoiding the use of aggressive solvents.

Short term changes in the abundance of nitrifying microorganisms in a soil-plant system simultaneously exposed to copper nanoparticles and atrazine.

Copper nanoparticles (NCu) may co-exist with other pollutants in agricultural soils, such as pesticides. However, this has been little evaluated yet. Thus, possible effects of the simultaneous applications of pesticides and NCu on biogeochemical cycles are expected, for example on the nitrogen cycle. Therefore, the aim of this work was to evaluate the effect of simultaneous application of the herbicide atrazine (ATZ) and NCu on the abundance of total bacteria and nitrifying communities: ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). Moreover, the ATZ dissipation was evaluated. A soil-plant system containing ATZ at field dose (3 mg a.i. kg-1) was mixed with two doses of NCu (0.05% or 0.15% w/w). Changes in the abundance of 16S rRNA and ammonia monooxygenase (amoA) genes of AOA and AOB were evaluated by real-time quantitative PCR (qPCR) at three sampling times (1, 15 and 30 days). The residual ATZ and nitrate production were also measured. The results showed significant differences in microbial composition and abundance over the 30 days of the experiment. Particularly, an initial decrease was observed in total bacterial abundance due to the presence of ATZ and NCu respect to ATZ alone (~60%). The abundance of AOA was also remarkably reduced (~85%), but these communities gradually recovered towards the end of the experiment. Conversely, AOB abundance initially increased (>100%) and remained mainly unaltered in soil exposed to ATZ and NCu 0.15% w/w, where nitrate formation was also constant. Moreover, NCu decreased the ATZ dissipation, which was translated in a 2-fold increase on the ATZ half-life values (T1/2). This study demonstrates that the simultaneous presence of NCu and ATZ may represent a risk for the total bacteria present in soil and sensitive microorganisms such as nitrifying communities, and changes in the dissipation of the pesticide could influence this process.

Fast determination of extra-virgin olive oil acidity by voltammetry and Partial Least Squares regression.

In this paper, an approach for the detection of extra-virgin olive oil (EVOO) free-acidity, based on combination of voltammetric profiles (Voltammetry) and Partial Least Squares (PLS) multivariate regression, is described. Voltammetric measurements are performed with a 12.5 µm radius platinum microdisk, directly in the oil samples mixed with 0.5 M of the room temperature ionic liquid (RTIL) tri-hexyl(tetradecyl)phosphonium bis(trifluoromethylsulfonyl)imide, which acted as a supporting electrolyte, and allows achieving a suitable conductivity in the matrices. Multivariate regression is performed directly on full voltammetric responses recorded over a properly chosen negative potential range and scan rate, where essentially all free fatty acids, characterizing EVOOs, can be reproducibly reduced. PLS regression models are built by employing Italian EVOO samples training sets at different acidity levels (over the range 0.2% w/w - 1.5% w/w; (% w/w) represents mass percentage) and optimized by choosing the optimal complexity, in terms of number of latent variables (LVs). The free-acidity prediction is made through a multivariate model, constructed by using standards of known acidity (determined by the official volumetric titration method) and validated on an external sample set. To show the validity of the proposed method, the PLS/Voltammetry predictions of the free-acidity of a series of commercially available Italian EVOOs, ranging from 0.2 to 0.41 %w/w, are obtained and the values compared with those determined by the official titration approach. Differences found between the two methods are within 5% RSD.

The nanotechnology among US: are metal and metal oxides nanoparticles a nano or mega risk for soil microbial communities?

Metal nanoparticles and metal oxides nanoparticles (MNPs/MONPs) have been widely included in a great diversity of products and industrial applications and they are already a part of our everyday life. According to estimation studies, their production is expected to increase exponentially in the next few years. Consequently, soil has been suggested as the main sink of MNPs/MONPs once they are deliberately or accidentally released into the environment. The potential negative perturbations that may result on soil microbial communities and ecological processes are resulting in concerns. Several nano-toxicological studies of MNPs/MONPs, reported so far, have focused on aquatic organisms, animals, and soil invertebrates. However, during recent years, the studies have been oriented to understand the effects of MNPs/MONPs on microbial communities and their interaction with soil components. The studies have suggested that MNPs/MONPs are one of the most toxic type to soil biota, amongst different types of nanomaterials. This may threaten soil health and fertility, since microbial communities are known to support important biological processes and ecosystem services such as the nutrient cycling, whereby their protection against the environmental pollution is imperative. Therefore, in this review we summarize the actual knowledge available from the last five years (2013-2018) and gaps about the potential negative, positive or neutral effects produced on soil by different classes of MNPs/MONPs. A particular emphasis has been placed on the associated soil microorganisms and biological processes. Finally, perspectives about future research are discussed.

Electrochemical preparation of standard solutions of Pb(II) ions in ionic liquid for analysis of hydrophobic samples: The olive oil case.

In this paper we present an electrochemical approach to prepare standard solutions of metal ions in a room temperature ionic liquid (IL), which can find useful application for analysis in hydrophobic matrices. The method, developed here for the case of lead ions, is based on the galvanostatic dissolution of a lead anode dipped directly in a suitable IL, namely tri-hexyl(tetradecyl)phosphonium bis (trifluoromethylsulfonyl) imide ([P14,6,6,6]+[NTf2]-). After each oxidation step, the metal dissolution process in the IL solutions was monitored by cyclic voltammetric measurements at a glassy carbon disk electrode. The results indicated that the peak current relevant to the reduction of the electro-generated Pb(II) increased linearly while increasing the oxidation time. By varying the oxidation time from 200 to 6000s, a set of Pb(II)/[P14,6,6,6]+[NTf2]- solutions at concentrations ranging between 10 and 300µgg-1 was prepared. To validate the efficiency of the electrochemical procedure to produce metal ion standard solutions, the Pb content was quantified by developing a microwave digestion procedure specifically suitable for the IL medium, followed by ICP-QMS analysis in the digested standards. The results indicated a satisfactory agreement between concentrations found by ICP-QMS and calculated from electrochemical data, with a coulometric efficiency of Pb(II) generation in ionic liquid ≥95.6%. Finally, the applicability of the Pb(II)/IL solutions as standards for analyses in hydrophobic media was tested by determining, by ICP-QMS, the Pb content in an extra-virgin olive oil spiked with known amounts of a Pb(II)/IL standard. Satisfactory Pb recoveries, ≥96%, were measured.

A novel electroanalytical approach based on the use of a room temperature ionic liquid for the determination of olive oil acidity.

In this paper, a novel voltammetric/amperometric approach for the direct determination of free acidity (FFA, expressed as mass percentage of free oleic acid) in olive oil samples is presented. The method is based on the reduction processes occurring at a platinum microdisk electrode involving the free fatty acids present in the matrices. To overcome problems related to the low conductivity of the samples investigated, olive oils were mixed with suitable amounts of the room temperature ionic liquid (RTIL), tri-hexyl(tetradecyl)phosphonium bis (trifluoromethylsulfonyl) imide ([P14,6,6,6]+[NTf2]-), which acted as a supporting electrolyte. Conditions for a reliable quantification of the acids were preliminarily investigated by performing voltammetric and chronoamperometric measurements in RTIL solutions containing oleic acid at different concentrations. Oleic acid (OA) was chosen as a model compound as it is the main component of the FFA content in olive oils. In order to establish the effect of oxygen on the electroanalytical responses, the reduction process of OA was investigated under both deoxygenated and oxygenated conditions. It was found that, in both situations, the current arising from the electrode process of OA depended linearly on the OA concentration over a wide range varying from 0.1% to 8% OA (w/w). This range includes FFA values which can be found on all categories of commercially available oil samples, including extra-virgin, virgin and lampante oils. Voltammetric and chronoamperometric experiments were also performed in oil/RTIL samples artificially acidified (extra-virgin olive oils with known addition of oleic acid) and in natural olive oils from some commercial categories. The results obtained indicated that the electrochemical procedure developed was satisfactory in terms of both sensitivity and detection limits. The reliability of the proposed approach for the detection of FFA was finally assessed by comparison of the voltammetric/chronoamperometric values with those obtained by the official method for quantification of olive oil acidity, which is an acid/base volumetric titration.

Logic circuit prototypes for three-terminal magnetic tunnel junctions with mobile domain walls.

Spintronic computing promises superior energy efficiency and nonvolatility compared to conventional field-effect transistor logic. But, it has proven difficult to realize spintronic circuits with a versatile, scalable device design that is adaptable to emerging material physics. Here we present prototypes of a logic device that encode information in the position of a magnetic domain wall in a ferromagnetic wire. We show that a single three-terminal device can perform inverter and buffer operations. We demonstrate one device can drive two subsequent gates and logic propagation in a circuit of three inverters. This prototype demonstration shows that magnetic domain wall logic devices have the necessary characteristics for future computing, including nonlinearity, gain, cascadability, and room temperature operation.

Nanoscale transport of charge-transfer states in organic donor-acceptor blends.

Charge-transfer (CT) states, bound combinations of an electron and a hole on separate molecules, play a crucial role in organic optoelectronic devices. We report direct nanoscale imaging of the transport of long-lived CT states in molecular organic donor-acceptor blends, which demonstrates that the bound electron-hole pairs that form the CT states move geminately over distances of 5-10 nm, driven by energetic disorder and diffusion to lower energy sites. Magnetic field dependence reveals a fluctuating exchange splitting, indicative of a variation in electron-hole spacing during diffusion. The results suggest that the electron-hole pair of the CT state undergoes a stretching transport mechanism analogous to an 'inchworm' motion, in contrast to conventional transport of Frenkel excitons. Given the short exciton lifetimes characteristic of bulk heterojunction organic solar cells, this work confirms the potential importance of CT state transport, suggesting that CT states are likely to diffuse farther than Frenkel excitons in many donor-acceptor blends.

Present status of accelerator-based BNCT: Focus on developments in Argentina.

In this work we provide some information on the present status of accelerator-based BNCT (AB-BNCT) worldwide and subsequently concentrate on the recent accelerator technology developments in Argentina.

Relationship between salt consumption measured by 24-h urine collection and blood pressure in the adult population of Vitória (Brazil).

High salt intake is related to an increase in blood pressure and development of hypertension. However, currently, there are no national representative data in Brazil using the gold standard method of 24-h urine collection to measure sodium consumption. This study aimed to determine salt intake based on 24-h urine collection in a sample of 272 adults of both genders and to correlate it with blood pressure levels. We used a rigorous protocol to assure an empty bladder prior to initiating urine collection. We excluded subjects with a urine volume <500 mL, collection period outside of an interval of 23-25 h, and subjects with creatinine excretion that was not within the range of 14.4-33.6 mg/kg (men) and 10.8-25.2 mg/kg (women). The mean salt intake was 10.4±4.1 g/day (d), and 94% of the participants (98% of men and 90% of women) ingested more than the recommended level of 5 g/d. We found a positive association between salt and body mass index (BMI) categories, as well as with salt and blood pressure, independent of age and BMI. The difference in systolic blood pressure reached 13 mmHg between subjects consuming less than 6 g/d of salt and those ingesting more than 18 g/d. Subjects with hypertension had a higher estimated salt intake than normotensive subjects (11.4±5.0 vs 9.8±3.6 g/d, P<0.01), regardless of whether they were under treatment. Our data indicate the need for interventions to reduce sodium intake, as well the need for ongoing, appropriate monitoring of salt consumption in the general population.

Diagnóstico tardío de carcinoma oculto de vesícula biliar por implante en puerto laparoscópico / Late diagnosis of occult gallbladder carcinoma by an implant in a laparoscopic trocar site

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Nuclear matter from effective quark-quark interaction.

We study neutron matter and symmetric nuclear matter with the quark-meson model for the two-nucleon interaction. The Bethe-Bruckner-Goldstone many-body theory is used to describe the correlations up to the three hole-line approximation with no extra parameters. At variance with other nonrelativistic realistic interactions, the three hole-line contribution turns out to be non-negligible and to have a substantial saturation effect. The saturation point of nuclear matter, the compressibility, the symmetry energy, and its slope are within the phenomenological constraints. Since the interaction also reproduces fairly well the properties of the three-nucleon system, these results indicate that the explicit introduction of the quark degrees of freedom within the considered constituent quark model is expected to reduce the role of three-body forces.

Effectiveness of vitamin A in the prevention of complications of prematurity.

BACKGROUND: To assess the effectiveness of vitamin A supplementation in very low birth weight (VLBW) infants to prevent complications of prematurity. METHODS: This was a retrospective cohort study to determine the effectiveness of vitamin A in preventing complications of prematurity in VLBW infants. Vitamin A was delivered intramuscularly at a dose of 5000 IU, three times weekly during the first 28 days of life. RESULTS: Of the 187 eligible VLBW infants, we excluded from the analysis (due to death or transfer to another hospital), 16 infants weighing <1000 g and 17 weighing 1000-1500 g. Sixty VLBW infants received the vitamin supplement. We observed no differences between the groups in the duration of oxygen therapy or in the risk of bronchopulmonary dysplasia. The risk of sepsis was up to three times higher among the infants who were given the vitamin A supplement. CONCLUSION: Given the increased risk of sepsis in patients weighing >1000 g, the risk associated with repeated intramuscular injections of vitamin A and the modest clinical results described, we do not believe the universal administration of vitamin A to VLBW infants to be justified as prophylaxis for bronchopulmonary dysplasia.

Functional mapping of the circuits involved in the expression of contextual fear responses in socially defeated animals.

In this study, we have aimed at outlining the neural systems underlying the expression of contextual fear to social defeat. First, we have developed an experimental procedure, where defeated animals could express, without the presence of a dominant aggressive male, robust and reliable conditioned fear responses to the context associated with social defeat. Next, by examining the pattern of Fos expression, we have been able to outline a brain circuit comprising septal and amygdalar sites, as well as downstream hypothalamic paths, putatively involved in the expression of contextual fear to social threat. Of particular relevance, we have found that exposure to a defeat-associated context results in a striking Fos up-regulation in the dorsomedial part of the dorsal premammillary nucleus (PMDdm). To further understand the role of the PMDdm in the circuit organizing conditioned fear to social threats, we have been able to observe that pharmacological blockade of the PMDdm reduced fear responses to a social defeat-associated context. Next, we observed that pharmacological blockade of the dorsomedial part of the periaqueductal gray, one of the main targets of the PMDdm, produced an even higher reduction of conditioned fear in defeated intruders, and appears as an important node for the expression of contextual defensive responses to social threats. The present results help to elucidate the basic organization of the neural circuits underlying contextual conditioned responses to social defeat, and reveal that they share at least part of the same circuit involved in innate responses to social defeat to an aggressive conspecific.

Accelerator-based BNCT.

The activity in accelerator development for accelerator-based BNCT (AB-BNCT) both worldwide and in Argentina is described. Projects in Russia, UK, Italy, Japan, Israel, and Argentina to develop AB-BNCT around different types of accelerators are briefly presented. In particular, the present status and recent progress of the Argentine project will be reviewed. The topics will cover: intense ion sources, accelerator tubes, transport of intense beams, beam diagnostics, the (9)Be(d,n) reaction as a possible neutron source, Beam Shaping Assemblies (BSA), a treatment room, and treatment planning in realistic cases.