Substances Of Interest Research Articles

Luminous Insights: Exploring Organic Fluorescent "Turn-On" Chemosensors for Metal-Ion (Cu+2, Al+3, Zn+2, Fe+3) Detection.

There are several metal ions that are vital for the growth of the environmental field as well as for the biological field but only up to the maximum limit. If they are present in excess, it could be hazardous for the human health. With the growing technology, a series of various detection techniques are employed in order to recognize those metal ions, some of them include voltammetry, electrochemical methods, inductively couples, etc. However, these techniques are expensive, time consuming, requires large storage, advanced instrumentation, and a skilled person to operate. So, here comes the need of a sensor and it is defined as a miniature device which detects the substance of interest by giving response in the form of energy change. So, from past few decades, many sensors have been formulated for detecting metal ions with some basic characteristics like selectivity, specificity, sensitivity, high accuracy, lower detection limit, and response time. Detecting various metal ions by employing chemosensors involves different techniques such as fluorescence, phosphorescence, chemiluminescence, electrochemical, and colorimetry. The fluorescence technique has certain advantages over the other techniques. This review mainly focuses on the chemosensors that show a signal in the form of fluorescence to detect Al+3, Zn+2, Cu+2, and Fe+3 ions.

MICROCHEMICAL TECHNIQUES ON BOTRYTIS CINEREA: CONTRIBUTION TO IDENTIFICATION OF PRIMARY AND SECONDARY METABOLITES

Histochemical techniques comprise several staining methods in microscopy for investigation of chemical groups or pathologies regarding tissues in plants and fungi and have been widely used for detection of groups of substances. Thereby, our work demonstrates the application of histochemical techniques recognized for detection of secondary metabolites in plants to detect substances in the fungus Botrytis cinerea. Our findings are compatible with previous reports on metabolites identified in B. cinerea, and show proteins stored in vesicular structures (0.3-0.9µm), accumulated in small groups inside of developed mycelia, and in large quantity in spores (0.2-0.7µm). Alkaloids were only detected in mycelium containing spores, not influenced by their size. Terpenoids were detected in spores, and with lighter color for mycelia vesicles. However, in younger mycelium we verified terpenoids in storage structures in the mycelia segments, demonstrating higher quantity in early development. The presence of neutral polysaccharides and terpenoids was observed around the mycelia containing younger spores and, in some storage, structures close to the spores. Our results corroborate reports on the presence of substances of the secondary metabolism in B. cinerea and could be utilized in other species of fungi to screen substances of pharmacological and nutraceutical interest.

Capturing drug use patterns at a glance: An n-ary word sufficient statistic for repeated univariate categorical values.

The efficacy of treatments for substance use disorders (SUD) is tested in clinical trials in which participants typically provide urine samples to detect whether the person has used certain substances via urine drug screenings (UDS). UDS data form the foundation of treatment outcome assessment in the vast majority of SUD clinical trials. However, existing methods to calculate treatment outcomes are not standardized, impeding comparability between studies and prohibiting reproducibility of results. We extended the concept of a binary UDS variable to multiple categories: "+" [positive for substance(s) of interest], "-" [negative for substance(s)], "o" [patient failed to provide sample], "*" [inconclusive or mixed results], and "_" [no specimens required per study design]. This construct can be used to create a standardized and sufficient representation of UDS datastreams and sufficiently collapses longitudinal records into a single, compact "word", which preserves all information contained in the original data. We developed the R software package CTNote (available on CRAN) as a tool to enable computers to parse these "words". The software package contains five groups of routines: detect a substance use pattern, account for a specific trial protocol, handle missing UDS data, measure the longest period of consecutive behavior, and count substance use events. Executing permutations of these routines result in algorithms which can define SUD clinical trial endpoints. As examples, we provide three algorithms to define primary endpoints from seminal SUD clinical trials. Representing substance use patterns as a "word" allows researchers and clinicians an "at a glance" assessment of participants' responses to treatment over time. Further, machine readable use pattern summaries are a standardized method to calculate treatment outcomes and are therefore useful to all future SUD clinical trials. We discuss some caveats when applying this data summarization technique in practice and areas of future study.

Towards adherence monitoring using breath or oral fluid as a matrix in a methadone maintenance treatment program for patients with a chronic heroin use disorder: issues and interpretation of the results.

Urine has been the preferred matrix for monitoring heroin and methadone adherence due to its large detection window. Drawbacks such as privacy concerns and adulteration require however other matrices. The study aims to determine if oral fluid and exhaled breath are suitable alternatives for heroin and methadone monitoring and to assess the detection time in exhaled breath. Forty-three participants, all on methadone and heroin-assisted treatment, were studied. Participants were monitored after the first and right before the second dosage of heroin. At both time points oral fluid and exhaled breath samples were collected with urine at the second time point. All samples were screened for opiates, methadone and other drugs using immunoassay and LC-MSMS. At the second time point, 98 percent of oral fluid samples and all exhaled breath samples tested positive for 6-monoacetylmorphine (6-MAM). Regarding morphine detection, the findings were reversed (100 percent in oral fluid, 98 percent in exhaled breath). Methadone-related results were 100 percent positive across all matrices, as expected. Notable is the detection of the heroin marker acetylcodeine in oral fluid and exhaled breath samples, which resulted in relatively low negative predictive value (average 54.6 percent). Oral fluid and exhaled breath are suitable alternatives for heroin and methadone maintenance monitoring. Clinicians should consider ease of collection, adulteration risk, costs, turn-around time, and the substance of interest while choosing a matrix. In addition, even in cases when medicinal heroin is used, medical professionals should be aware of the presence of acetylcodeine in these alternate matrices.

Toxicological analysis in victims of sexual and domestic violence: A retrospective study of a 3-year period (2018–2020)

This manuscript presents an epidemiological investigation carried out on abuse victims who accessed the Sexual and Domestic Violence Service (SVS&D) of IRCCS Ca’ Granda in Milan, Italy. The focal point of this research was the detection of alcohol, prescription medications, and illicit substances in victims who solicited help from the SVS&D center between 2018 and 2020. Over this three-year span, biological samples of blood and urine were procured from 207 victims, out of a patient pool of 2470. All collected samples were analyzed via High Performance Liquid Chromatography – Tandem Mass Spectrometry (HPLC-MS/MS) and Gas Chromatography – Mass Spectrometry (GC-MS).Toxicological examination results demonstrated that 43% of the cases tested positive for substances in 2018, 39% in 2019 and 60% of the cases in 2020. Overall, 45% of the victims tested resulted positive to some substance over a 3-year period, equivalent to 3.6% of the overall cases (2470 victims). Substances of toxicological interest were detected in 104 samples (out of 377, corresponding to 27.6%) belonging to 94 patients. The most detected classes of drugs were stimulants, antidepressants, benzodiazepines and antipsychotics. Moreover, BAC (Blood Alcohol Concentration) indicated positivity in 25 cases (out of 184 cases analyzed - 14% of positive cases). Based on this study's findings, we recommend broadening the range of substances evaluated in drug-facilitated sexual assaults and establishing standardized protocols for both national and international implementation. Implementing procedures would significantly enhance forensic support provided to victims of abuse seeking healthcare services post-incident.

Procesos de oxidación avanzada utilizados en el tratamiento de sustancias perfluoroalquiladas en agua

Perfluoroalkylated and polyfluoroalkylated substances (PFAS) are a large family of synthetic chemicals widely used to manufacture various commercial products. However, they are hazardous to health and the environment. These substances are very persistent and their degradation requires advanced degradation techniques. One of the most widely used technologies for this purpose is advanced oxidation processes (AOP). This study aims to evaluate the use of AOP in PFAS degradation based on their efficiency, parameters influencing each process, advantages, disadvantages, and associated research challenges. According to the results, plasma, electrochemical oxidation, sonochemical oxidation, and heterogeneous photocatalysis stand out among the AOP applied for PFAS degradation. In addition, perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) were found to be the main toxic compounds studied. In this regard, future research should focus on a wider variety of PFAS. Finally, the drawbacks associated with the application of these processes to eliminate the substances of interest were found to be an urgent need to be overcome.

Substances Detected During Coroner Postmortem Toxicology Analyses in Poisoning- and Nonpoisoning-Related Suicides.

Determining the association between drug use and suicide is complicated but can help to inform targeted suicide prevention strategies. To examine the substances prevalent in poisoning- and nonpoisoning-related suicides in Australia. This was a multiple-year, cross-sectional study of suicides from July 2013 to October 2019 in Australia with toxicology data available in a national coronial database. The cause of death was classified as poisoning related if any type of poisoning was determined by the coroner to contribute to the cause of death. Prevalence ratios (PRs) were calculated to compare substance detection in poisoning- vs nonpoisoning-related suicides. Data were analyzed from October 2021 to April 2023. All substances detected in decedents at the time of death according to toxicology reports were recorded. The most common individual substances and substance classes were identified. From these, blood concentrations of substances of interest were analyzed, and the most commonly occurring combinations of substance classes were listed. Toxicology was performed on 13 664 suicide decedents (median [IQR] age, 44 [31-57] years; 10 350 male [76%]). From these, 3397 (25%) were poisoning-related suicides (median [IQR] age, 50 [38-63] years; 2124 male [63%]). The remainder were classified as nonpoisoning-related suicides (median [IQR] age, 42 [29-55] years; 8226 male [80%]). PRs for common medicine classes being detected in poisoning-related suicides compared with nonpoisoning-related suicides were as follows: antidepressants (PR, 1.63; 95% CI, 1.54-1.73), benzodiazepines (PR, 2.01; 95% CI, 1.90-2.13), nonopioid analgesics/anti-inflammatory drugs (PR, 1.88; 95% CI, 1.78-2.00), and opioids (PR, 2.72; 95% CI, 2.58-2.87). Alcohol (as ethanol ≥0.03 g/100 mL) was almost equally prevalent in poisoning- and nonpoisoning-related deaths (PR, 1.07; 95% CI, 1.01-1.14), whereas amphetamines (PR, 0.68; 95% CI, 0.61-0.77) and cannabinoids (PR, 0.67; 95% CI, 0.60-0.74) were detected more often in nonpoisoning-related suicides. Combinations of multiple sedative agents in poisoning-related suicides were common. Both poisoning- and nonpoisoning-related suicide deaths featured a high prevalence of psychotropic medicines or potential intoxication, which suggests the association of suicide with poor mental health and substance misuse. Findings suggest that substances with a high involvement in poisoning-related suicides should be prescribed cautiously, including antidepressants that are toxic in overdose, sedatives, opioids, and potentially lethal combinations.

Copper-Catalyzed Aromatic Trifluoromethylation and the Related Transformations.

Trifluoromethylated aromatic compounds (Ar-CF3 ) are the substances of considerable interest in various industrial fields. The high lipophilicity, strong electron-withdrawing ability, and characteristic size of trifluoromethyl group are key influences in biologically active molecules. Due to these attractive properties, the benzotrifluoride structural motifs have been widely employed in the design of pharmaceuticals, agrochemicals, dyes, liquid crystals, and polymers. Therefore, the development of highly efficient methodologies for aromatic trifluoromethylation is of significant importance for wide fields of science and technology. Recently, a great deal of attention has been paid to catalytic protocols to introduce fluoroalkyl groups into aromatic rings selectively. This personal account highlights the copper-mediated aromatic trifluoromethylation and the related transformations developed by our research group.

Identification of an Unknown Substance by the Methods of Multi-Energy Pulse X-ray Tomography

The inverse problem for the non-stationary radiative transfer equation is considered, which consists in finding the attenuation coefficient according to the pulsed multi-energy X-ray exposure. For a short duration of the probing pulse, the asymptotic solution of the inverse problem is found. The problem of identifying an unknown substance by attenuation coefficients approximately found on a finite set of energy values is formulated. Algorithms for solving identification problems are proposed. The results of the numerical simulation are presented for a wide range of substances of interest in medical computed tomography.

Formulation Strategies of Nanosuspensions for Various Administration Routes.

Nanosuspensions (NSs), which are nanosized colloidal particle systems, have recently become one of the most interesting substances in nanopharmaceuticals. NSs have high commercial potential because they provide the enhanced solubility and dissolution of low-water-soluble drugs by means of their small particle sizes and large surface areas. In addition, they can alter the pharmacokinetics of the drug and, thus, improve its efficacy and safety. These advantages can be used to enhance the bioavailability of poorly soluble drugs in oral, dermal, parenteral, pulmonary, ocular, or nasal routes for systemic or local effects. Although NSs often consist mainly of pure drugs in aqueous media, they can also contain stabilizers, organic solvents, surfactants, co-surfactants, cryoprotectants, osmogents, and other components. The selection of stabilizer types, such as surfactants or/and polymers, and their ratio are the most critical factors in NS formulations. NSs can be prepared both with top-down methods (wet milling, dry milling, high-pressure homogenization, and co-grinding) and with bottom-up methods (anti-solvent precipitation, liquid emulsion, and sono-precipitation) by research laboratories and pharmaceutical professionals. Nowadays, techniques combining these two technologies are also frequently encountered. NSs can be presented to patients in liquid dosage forms, or post-production processes (freeze drying, spray drying, or spray freezing) can also be applied to transform the liquid state into the solid state for the preparation of different dosage forms such as powders, pellets, tablets, capsules, films, or gels. Thus, in the development of NS formulations, the components/amounts, preparation methods, process parameters/levels, administration routes, and dosage forms must be defined. Moreover, those factors that are the most effective for the intended use should be determined and optimized. This review discusses the effect of the formulation and process parameters on the properties of NSs and highlights the recent advances, novel strategies, and practical considerations relevant to the application of NSs to various administration routes.

Phototoxic or Photoprotective?-Advances and Limitations of Titanium (IV) Oxide in Dermal Formulations-A Review.

The widespread role of titanium (IV) oxide (TiO2) in many industries makes this substance of broad scientific interest. TiO2 can act as both a photoprotector and photocatalyst, and the potential for its role in both applications increases when present in nanometer-sized crystals. Its sunlight-scattering properties are used extensively in sunscreens. Furthermore, attempts have been made to incorporate TiO2 into dermal formulations of photolabile drugs. However, the propensity to generate reactive oxygen species (ROS) rendering this material potentially cytotoxic limits its role. Therefore, modifications of TiO2 nanoparticles (e.g., its polymorphic form, size, shape, and surface modifications) are used in an effort to reduce its photocatalytic effects. This review provides an overview of the potential risks arising from and opportunities presented by the use of TiO2 in skin care formulations.

Investigations into fentanyl precursors method classification by handheld Fourier transform infrared and Raman spectroscopy combined with multivariate statistical analysis

A goal of narcotic chemical attribution is to exploit a substance of interest for chemical forensic information and evidence. This could include determining the synthetic method used to make it and if that substance is forensically linked to any others. In most cases narcotic chemical attribution is profiling the impurities that are present, which give the substance a chemical fingerprint. One narcotic of significant concern to law enforcement and emergency responders is fentanyl due to the health risk it poses from very small amounts and its increasing prevalence in illicit drug markets. Portable handheld spectroscopic instruments have scope to become useful tools for substance identification in the field to ensure safety and to uncover possible investigative leads; however, they have limitations with interpretation of substances that have very small proportions of other components including impurities. In this study, two spectroscopic techniques, Fourier transform infrared (FTIR) and Raman spectroscopy, were applied to determine the synthetic method employed for the fentanyl precursors N-phenethyl-4-piperidone (NPP) and 4-anilino-N-phenethylpiperidine (ANPP). Principal Component Analysis (PCA) with k-nearest neighbours (k-NN) and Orthogonal Partial Least Squares - Discriminant Analysis (OPLS-DA) were used to establish classification models. The use of low-level and mid-level data fusion strategies were employed to integrate the data from the different handheld spectroscopic instruments, which allowed suitable classification of validation samples by their respective synthetic method. These results demonstrate the versatility of handheld spectroscopic instruments, with results easily being exported for data fusion analysis and the possibility for future instrument library enhancements.

Bioactive Compounds Produced by Endophytic Microorganisms Associated with Bryophytes-The "Bryendophytes".

The mutualistic coexistence between the host and endophyte is diverse and complex, including host growth regulation, the exchange of substances like nutrients or biostimulants, and protection from microbial or herbivore attack. The latter is commonly associated with the production by endophytes of bioactive natural products, which also possess multiple activities, including antibacterial, insecticidal, antioxidant, antitumor, and antidiabetic properties, making them interesting and valuable model substances for future development into drugs. The endophytes of higher plants have been extensively studied, but there is a dearth of information on the biodiversity of endophytic microorganisms associated with bryophytes and, more importantly, their bioactive metabolites. For the first time, we name bryophyte endophytes "bryendophytes" to elaborate on this important and productive source of biota. In this review, we summarize the current knowledge on the diversity of compounds produced by endophytes, emphasizing bioactive molecules from bryendophytes. Moreover, the isolation methods and biodiversity of bryendophytes from mosses, liverworts, and hornworts are described.

A step towards harmonising human biomonitoring study setup on European level: Materials provided and lessons learnt in HBM4EU.

Internal exposure of the human body to potentially harmful chemical substances can be assessed by Human Biomonitoring (HBM). HBM can be used to generate conclusive data that may provide an overview of exposure levels in entire or specific population groups. This knowledge can promote the understanding of potential risks of the substances of interest or help monitoring the success of regulatory measures taken on the political level. Study planning and design are key elements of any epidemiologic study to generate reliable data. In the field of HBM, this has been done using differing approaches on various levels of population coverage so far. Comparison and combined usage of the resulting data would contribute to understanding exposure and its factors on a larger scale, however, the differences between studies make this a challenging and somewhat limited endeavour. This article presents templates for documents that are required to set up an HBM study, thus facilitating the generation of harmonised HBM data as a step towards standardisation of HBM in Europe. They are designed to be modular and adaptable to the specific needs of a single study while emphasising minimum requirements to ensure comparability. It further elaborates on the challenges encountered during the process of creating these documents during the runtime of the European Joint Programme HBM4EU in a multi-national expert team and draws up lessons learnt in the context of knowledge management.

Prerequisite for Imputing Non-detects among Airborne Samples in OSHA's IMIS Databank: Prediction of Sample's Volume.

The US Integrated Management Information System (IMIS) contains workplace measurements collected by Occupational Safety and Health Administration (OSHA) inspectors. Its use for research is limited by the lack of record of a value for the limit of detection (LOD) associated with non-detected measurements, which should be used to set censoring point in statistical analysis. We aimed to remedy this by developing a predictive model of the volume of air sampled (V) for the non-detected results of airborne measurements, to then estimate the LOD using the instrument detection limit (IDL), as IDL/V. We obtained the Chemical Exposure Health Data from OSHA's central laboratory in Salt Lake City that partially overlaps IMIS and contains information on V. We used classification and regression trees (CART) to develop a predictive model of V for all measurements where the two datasets overlapped. The analysis was restricted to 69 chemical agents with at least 100 non-detected measurements, and calculated sampling air flow rates consistent with workplace measurement practices; undefined types of inspections were excluded, leaving 412,201/413,515 records. CART models were fitted on randomly selected 70% of the data using 10-fold cross-validation and validated on the remaining data. A separate CART model was fitted to styrene data. Sampled air volume had a right-skewed distribution with a mean of 357 l, a median (M) of 318, and ranged from 0.040 to 1868 l. There were 173,131 measurements described as non-detects (42% of the data). For the non-detects, the V tended to be greater (M = 378 l) than measurements characterized as either 'short-term' (M = 218 l) or 'long-term' (M = 297 l). The CART models were complex and not easy to interpret, but substance, industry, and year were among the top three most important classifiers. They predicted V well overall (Pearson correlation (r) = 0.73, P < 0.0001; Lin's concordance correlation (rc) = 0.69) and among records captured as non-detects in IMIS (r = 0.66, P < 0.0001l; rc = 0.60). For styrene, CART built on measurements for all agents predicted V among 569 non-detects poorly (r = 0.15; rc = 0.04), but styrene-specific CART predicted it well (r = 0.87, P < 0.0001; rc = 0.86). Among the limitations of our work is the fact that samples may have been collected on different workers and processes within each inspection, each with its own V. Furthermore, we lack measurement-level predictors because classifiers were captured at the inspection level. We did not study all substances that may be of interest and did not use the information that substances measured on the same sampling media should have the same V. We must note that CART models tend to over-fit data and their predictions depend on the selected data, as illustrated by contrasting predictions created using all data vs. limited to styrene. We developed predictive models of sampled air volume that should enable the calculation of LOD for non-detects in IMIS. Our predictions may guide future work on handling non-detects in IMIS, although it is advisable to develop separate predictive models for each substance, industry, and year of interest, while also considering other factors, such as whether the measurement evaluated long-term or short-term exposure.

Study protocol for approach bias retraining for nicotine addiction among dual combustible and electronic cigarette users

BackgroundElectronic cigarette (ECIG) use has become a popular method for nicotine delivery. Combustible cigarette (CC) cessation or reduction are the primary reasons for ECIG uptake among adults. Yet, most CC smokers who initiate ECIG use do not fully transition from CC to ECIG, despite intending to quit CC completely. Retraining approach bias, or the approach action tendency toward stimuli related to the substance of interest, has been effective in alcohol and CC use treatments. However, approach bias retraining for both CC and (ECIG) users has not been explored. Therefore, the objective of the study is to evaluate the initial efficacy of approach bias retraining among dual CC and ECIG users. MethodsEligible dual CC/ECIG using adults (N = 90) will complete a phone-screener, baseline assessment, 4 treatment sessions over 2 weeks, ecological momentary assessments (EMAs) post-intervention, and follow-ups at 4- and 6-week post-intervention. Participants will be assigned to one of three conditions at baseline: (1) CC + ECIG retraining; (2) CC only retraining; and (3) sham retraining. Participants will engage in a self-guided quit attempt to abstain from all nicotine products starting at treatment session 4. ConclusionsThe study may lead to a more effective treatment for at-risk nicotine users while simultaneously isolating explanatory mechanisms. The findings should guide advances in the theoretical conceptualization of nicotine addiction for dual users and mechanisms involved in maintaining and abstaining from CC and ECIG, and provide initial effect size data for a brief intervention, thus providing necessary data for a large-scale follow-up trial.Clinical Trials ID: NCT05306158

Comparison of the Determination of Some Antihypertensive Drugs in Clinical Human Plasma Samples by Solvent Front Position Extraction and Precipitation Modes.

The determination of the selected antihypertensive drugs in human plasma samples with the novel solvent front position extraction (SFPE) technique is presented. The SFPE procedure combined with LC-MS/MS analysis was used for the first time to prepare a clinical sample containing the drugs mentioned above from different therapeutic groups. The effectiveness of our approach was compared with the precipitation method. The latter technique is usually used to prepare biological samples in routine laboratories. During the experiments, the substances of interest and the internal standard were separated from other matrix components using a prototype horizontal chamber for thin-layer chromatography/high-performance thin-layer chromatography (TLC/HPTLC) with a moving pipette powered by a 3D mechanism, which distributed the solvent on the adsorbent layer. Detection of the six antihypertensive drugs was performed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in multiple reaction monitoring (MRM) mode. Results obtained by SFPE were very satisfactory (linearity R2 ≥ 0.981; %RSD ≤ 6%; LOD and LOQ were in the range of 0.06-9.78 ng/mL and 0.17-29.64 ng/mL, respectively). The recovery was in the range of 79.88-120.36%. Intra-day and inter-day precision had a percentage coefficient of variation (CV) in the range of 1.10-9.74%. The procedure is simple and highly effective. It includes the automation of TLC chromatogram development, which significantly reduced the number of manual operations performed, the time of sample preparation and solvent consumption.

French national addictovigilance follow-up of zolpidem between 2014 and 2020: evolution of drug abuse, misuse and dependence before and after the regulatory change.

Since the appearance of zolpidem on the market, the occurrence of serious cases of abuse, misuse and dependence have come to the attention of authorities. In view of the increase in the number and severity of cases among zolpidem users and the predominant presence of zolpidem in falsified prescriptions, the French Health Authorities implemented part of the narcotics regulation for zolpidem in April 2017. The objective of this article was to describe the evolution of the abuse, dependence and misuse of zolpidem. We used three data sources: (i) zolpidem is a reimbursable and strictly prescription drug in France. Medic'AM is a public database that indicates the number of tablets reimbursed each month in France for each reimbursable drug. This database has been analyzed as a proxy of the exposure of the French population to zolpidem; (ii) all French cases of drug dependence or abuse reported by health professionals (regulatory obligation) and (iii) an epidemiological tool based on the surveillance of falsified prescriptions over two periods: the 3-year period before the regulatory measure (2014-16) and the 3-year period after the regulatory measure (2018-20). This regulatory change had two immediate consequences: a sharp decline in falsified prescriptions and a decrease of ∼57% between the two study periods in the zolpidem reimbursement data. Markers of problematic consumption remained after the regulatory change with worsening cases, particularly for people who were genuinely dependent and/or had comorbidities or misusers for whom zolpidem was the substance of interest, whose proportion increased significantly in the addictovigilance notification system, from 43.6% (N = 107) to 59.3% (N = 127) (P < 0.01). Further monitoring is needed in light of these persistent markers of problematic consumption.

Optimal Designs for Antoine’s Equation: Compound Criteria and Multi-Objective Designs via Genetic Algorithms

Antoine’s Equation is commonly used to explain the relationship between vapour pressure and temperature for substances of industrial interest. This paper sets out a combined strategy to obtain optimal designs for the Antoine Equation for D- and I-optimisation criteria and different variance structures for the response. Optimal designs strongly depend not only on the criterion but also on the response’s variance, and their efficiency can be strongly affected by a lack of foresight in this selection. Our approach determines compound and multi-objective designs for both criteria and variance structures using a genetic algorithm. This strategy provides a backup for the experimenter providing high efficiencies under both assumptions and for both criteria. One of the conclusions of this work is that the differences produced by using the compound design strategy versus the multi-objective one are very small.

From the Nobel prize for physiology to the new training and competitive paradigm of competitive swimming

Nitric - monoxide is recognized as a molecule with a very simple structure, considered for a long time as an extremely toxic substance. Yet, due to the possibility of endogenous biosynthesis and the variety of biological actions it possesses, today it is considered as paracrine substance of exceptional pharmacological, physiological and pathophysiological interest. Bearing in mind the numerous negative ecological and health effects that it has on the human environment on a daily basis, extremely large initial efforts have been made for decades to suppress it to a certain extent.. However, the discoveries that, in the eighties of the last century, led to new scientific advances in the fields of chemistry, physiology and medicine, led to a stunning conclusion - that the survival of the most dominant species on Earth mostly depends on its (bio)synthesis. Depending on the concentration, it performs a dual role in the vasculature, since in lower concentrations it has the function of an extremely powerful vasodilator, while in the case of high concentrations it performs the role of cytotoxin and cytostatic, thereby contributing to the body's defense against parasitic infections and tumors. Maintaining its availability in the endothelium is crucial for the normal functioning of the cardiovascular system. The Nobel Prize, which was awarded in 1998. for the discovery of the signaling role of nitric oxide in the human body, opened up a series of specific questions, which primarily relate to the place and role of this molecule in various biochemical processes that constantly occur in the human body under different conditions. Accordingly, the theoretical and empirical issues of the role of nitric oxide in swimming, training, and the general health of swimmers (athletes) in water are the subject of this paper.