Reliability of Magseed® marking before neoadjuvant systemic therapy with subsequent contrast-enhanced mammography in patients with non-palpable breast cancer lesions after treatment: the MAGMA study.

PURPOSE: To assess the reliability of excising residual breast cancer lesions after neoadjuvant systemic therapy (NAST) using a previously localized paramagnetic seed (Magseed®) and the subsequent use of contrast-enhanced spectral mammography (CESM) to evaluate response. METHODS: Observational, prospective, multicenter study including adult women (> 18 years) with invasive breast carcinoma undergoing NAST between January 2022 and February 2023 with non-palpable tumor lesions at surgery. Radiologists marked tumors with Magseed® during biopsy before NAST, and surgeons excised tumors guided by the Sentimag® magnetometer. CESMs were performed before and after NAST to evaluate tumor response (Response Evaluation Criteria for Solid Tumors [RECIST]). We considered intraoperative, surgical, and CESM-related variables and histological response. RESULTS: We analyzed 109 patients (median [IQR] age of 55.0 [46.0, 65.0] years). Magseed® was retrieved from breast tumors in all surgeries (100%; 95% CI 95.47-100.0%) with no displacement and was identified by radiology in 106 patients (97.24%), a median (IQR) of 176.5 (150.0, 216.3) days after marking. Most surgeries (94.49%) were conservative; they lasted a median (IQR) of 22.5 (14.75, 40.0) min (95% CI 23.59-30.11 min). Most dissected tumor margins (93.57%) were negative, and few patients (5.51%) needed reintervention. Magseed® was identified using CESM in all patients (100%); RECIST responses correlated with histopathological evaluations of dissected tumors using the Miller-Payne response grade (p < 0.0001) and residual lesion diameter (p < 0.0001). Also 69 patients (63.3%) answered a patient's satisfaction survey and 98.8% of them felt very satisfied with the entire procedure. CONCLUSION: Long-term marking of breast cancer lesions with Magseed® is a reliable and feasible method in patients undergoing NAST and may be used with subsequent CESM.

A Worldwide Bibliometric Analysis of Published Literature Assessing Fear of COVID-19.

Many people experience intense fear of COVID-19. The purpose of this study was to provide a comprehensive visual overview of the published literature from 2020 to 2022 assessing fear of COVID-19. From 2020 to 2022, we employed the Scopus database to conduct a bibliometric analysis. We used the VOSviewer program to perform the author co-citation analysis, Mapchart to produce a worldwide map, and Wordart to make a word cloud image. From the 1769 records examined, 1654 (93.50%) were articles, with English being the most common language (96.31%). From 2020 to 2022, annual citations experienced significant growth (R2 = 99.91%; p = 0.0195). The Institut National de la Santé et de la Recherche Médicale (INSERM, France) and China led in terms of publication output (n = 36; n = 255). M. D. Griffiths authored the highest number of articles (n = 21). The most active journal was the International Journal of Environmental Research and Public Health (n = 146), and the most prevalent keyword was "human/s" (11.51%). This bibliometric analysis evaluates the quality of the research on fear of the pandemic and the crisis management of COVID-19, which can provide managers and researchers with crucial insights for future decision making.

Semisynthesis of Betaxanthins from Purified Betacyanin of Opuntia dillenii sp.: Color Stability and Antiradical Capacity.

The availability of pure individual betalains in sufficient quantities which permit deeper understanding is still a challenge. This study investigates the high-yielding semisynthesis of betaxanthins using betalamic acid from a natural source (Opuntia dillenii), followed by condensation with ʟ-amino acids and further purification. Moreover, the color stability of the four synthesized individual betaxanthins, namely proline (ʟ-ProBX), alanine (ʟ-AlaBX), leucine (ʟ-LeuBX), and phenylalanine (ʟ-PheBX) betaxanthins, was investigated at different pHs. Their relative contribution to free radical scavenging was also scrutinized by TEAC and DPPH. ʟ-AlaBX and ʟ-LeuBx showed a significantly (p < 0.05) higher antioxidant activity, whereas ʟ-ProBX was the most resistant to the hydrolysis of betaxanthin and hence the least susceptible to color change. The color stability was strongly influenced by pH, with the color of ʟ-ProBX, ʟ-LeuBX, and ʟ-AlaBX at pH 6 being more stable, probably due to the easier hydrolysis under acid conditions. The semisynthesis and purification allowed us to have available remarkable quantities of pure individual betaxanthins of Opuntia dillenii for the first time, and to establish their color properties and antioxidant capacity. This study could be a step forward in the development of the best natural food colorant formulation, based on the betalain structure, which is of special interest in food technology.

Comparative study of emerging pollutants of interest in the groundwater of the volcanic islands of La Palma and El Hierro (Canary Islands).

Emerging pollutants (EPs) include a wide array of chemical compounds, as well as some microorganisms, which presence was unknown or unmeasurable until recently, or have recently started to be considered a threat towards the environment or animal and human health. No clear or homogeneous regulations exist for their measurement or control, and efforts should be made to assess their presence and offer solutions for their safe management, as well as to achieve an optimal protection of water resources. A previous study performed by our research group thoroughly studied a wide profile of EPs in El Hierro Island (Canary Islands) for the first time. Now, we present the study of the same panel of 70 EPs in La Palma Island (Canary Islands). 14 samples were collected in 2021, at different locations in La Palma island, representing seven municipalities (Los Llanos de Aridane, Santa Cruz de la Palma, El Paso, Breña Baja, Tazacorte, Barlovento and Fuencaliente) and four installation types (Piezometers/Wells, Wastewater Treatment Plant (WWTP), Water Gallery and Water Springs). High performance liquid chromatography-mass spectrometry (HPLC-MS) was performed to analyse the EP array, which included five chemical families: UV filters, UV blockers/stabilizers, parabens, Pharmaceutical Active Compounds (PhACs) and pesticides. Subsequently, a comprehensive descriptive and statistical analysis, including different tests was performed on the data obtained. Heterogeneous concentration levels of the EPs studied were found based on municipality and installation type among the island, with some of the PhACs and UV blockers/stabilizers showing very high levels, especially at Breña Baja and wastewater treatment plants (WWTPs). It is worth noting that some of the samples comprised within the WWTPs category were collected outside the treatment plant, after water has been treated, so they should not bear dangerous concentrations of any hazardous compound. The high presence of two pesticides, imidacloprid (ranging from 68.7 to 24,896.5 ng⋅L-1) and acetamiprid (ranging from 1010.7 to 5168.1 ng⋅L-1) was worth highlighting too. In addition, three EP concentration clusters were found to virtually divide the island based on mathematical percentiles of EP mean concentrations, which can help gain more insight into the contamination status of the island and measures that could be taken for their management. Finally, a comparison between La Palma results and the profile observed at El Hierro by our research group was presented. Altogether, the study performed calls for a need to take actions towards avoiding entrance of EPs in the water cycle, and not just focusing on remediation strategies once they have reached the groundwater, freshwater or soil.

Factors related to depression in adults with oral health problems in Spain (2017 to 2020).

Background: The need to study the link between gender, depression, and oral health is becoming increasingly evident. This study therefore aimed to determine the prevalence and evolution over time of depression among women and men with oral health problems and to evaluate the association between depression status, lifestyle-related variables health-related variables and use of dental health services in those people. Methods: We performed a nationwide cross-sectional study on 25,631 adults with oral health problems residing in Spain from the Spanish National Health Survey 2017 and the European Health Survey of Spain 2020, including as the main variable self-reported diagnosis of depression. We analysed independent variables such as lifestyle-related variables, health-related variables, and variables related to dental health services. Sociodemographic characteristics were considered as control variables. Results: The prevalence of depression among adults with oral health problems in Spain was 7.81% (10.14% for women, 5.39% for men), with a notable decrease from 2017 to 2020 in women. Depressed women had a slightly higher percentage of filled or capped teeth, and had more covers (crowns), bridges or other types of prostheses or dentures, while men had more caries. Women also made more frequent, regular dental visits for check-ups and mouth cleaning, whereas men often needed extractions. Unfavourable associated factors in both genders were: perceiving their health as good, average, poor, or very poor, and having 1-2 and ≥ 3 comorbidities. Conversely, not being a current smoker was related to less likelihood of depression. In women only, not engaging in leisure-time physical activity produced more unfavourable associated factors. Conclusion: The prevalence of depression among adults with oral health problems in Spain from 2017 to 2020 was 7.81%, but this figure has been steadily decreasing over time. In addition, the favourable and unfavourable associated factors could help us inform health professionals and authorities in order to prevent depression and enhance the care of this population according to gender.

Methadone Requires the Co-Activation of µ-Opioid and Toll-Like-4 Receptors to Produce Extracellular DNA Traps in Bone-Marrow-Derived Mast Cells.

Methadone is an effective and long-lasting analgesic drug that is also used in medication-assisted treatment for people with opioid use disorders. Although there is evidence that methadone activates µ-opioid and Toll-like-4 receptors (TLR-4s), its effects on distinct immune cells, including mast cells (MCs), are not well characterized. MCs express µ-opioid and Toll-like receptors (TLRs) and constitute an important cell lineage involved in allergy and effective innate immunity responses. In the present study, murine bone-marrow-derived mast cells (BMMCs) were treated with methadone to evaluate cell viability by flow cytometry, cell morphology with immunofluorescence and scanning electron microscopy, reactive oxygen species (ROS) production, and intracellular calcium concentration ([Ca2+]i) increase. We found that exposure of BMMCs to 0.5 mM or 1 mM methadone rapidly induced cell death by forming extracellular DNA traps (ETosis). Methadone-induced cell death depended on ROS formation and [Ca2+]i. Using pharmacological approaches and TLR4-defective BMMC cultures, we found that µ-opioid receptors were necessary for both methadone-induced ROS production and intracellular calcium increase. Remarkably, TLR4 receptors were also involved in methadone-induced ROS production as it did not occur in BMMCs obtained from TLR4-deficient mice. Finally, confocal microscopy images showed a significant co-localization of µ-opioid and TLR4 receptors that increased after methadone treatment. Our results suggest that methadone produces MCETosis by a mechanism requiring a novel crosstalk pathway between µ-opioid and TLR4 receptors.

Effects of fentanyl and the adulterant levamisole on the rewarding and locomotor effects of methamphetamine in rats.

BACKGROUND: People who use psychostimulant substances can be exposed to unknown adulterants, such as the synthetic opioid fentanyl (FEN) and the anthelmintic cholinergic agent levamisole (LEV). This work explores the rewarding and locomotor effects of methamphetamine (METH) in combination with FEN or LEV. METHODS: We used adult male Wistar rats in the conditioned-place preference (CPP) paradigm (conditioning, extinction, and reinstatement phases) and in the open field test to study effective doses of METH, FEN, or LEV, or ineffective doses of METH+FEN or METH+LEV in combination. RESULTS: METH and LEV, at 1mg/kg METH each, and 30µg/kg FEN produced CPP. Extinction to METH- or LEV-induced CPP occurred after eight saline injections, but it took 8-26 sessions to extinguish FEN-induced CPP. A challenge dose of 0.5mg/kg METH reinstated CPP. The same occurred with 15µg/kg FEN but not with 0.5 or 1mg/kg LEV. Training animals with ineffective doses of METH (0.01mg/kg) combined with either FEN (0.3µg/kg) or LEV (0.01mg/kg) produced CPP. Sub-effective doses of METH or FEN alone did not induce reinstatement after extinction. However, animals challenged with LEV, METH+FEN, or METH+LEV mixtures did it. Combining FEN (3µg/kg) with 0.1mg/kg METH increased locomotor activity. CONCLUSION: Ineffective FEN and LEV doses mixed with METH produce effects larger than would be expected based on the effects of either drug alone. This outcome suggests a supra-additive interaction, which could increase the risk of developing a METH use disorder.

First drug-checking study at an electronic festival and fentanyl detection in the central region of Mexico.

BACKGROUND: Perception of drug adulteration has increased in Mexico, but there is little research on adulterants and toxicity. The aim of this study was to identify drug composition in an electronic music outdoor festival nearby Mexico City. METHODS: The participants completed a questionnaire with demographic data, harm reduction strategies, drug-use patterns, history, and the drug they expected to find. We took a small sample of each substance and prepared it for drug checking. A two-section drug testing station was placed within the grounds of the festival. Interaction with participants occurred at the front part. Drug checking was conducted at the rear part. The service was free of charge, voluntary and confidential. Forty persons aged 22 to 48 years participated (mode = 28), of which 92.5% were male, most (82.5%) were single. Through the Substance Analysis Program of "ReverdeSer Collective," we conducted the testing with the attendants that provided 51 drug samples, following ethical and biosafety protocols. We used colorimetry, Fourier Transform Infrared Spectroscopy, and fentanyl immunoassay strips for sample analysis. RESULTS: Substances of choice among attendants were psychostimulants (MDMA and other amphetamine-like drugs) and hallucinogens. Most samples contained what the users expected plus adulterants. Main adulterants were methylene-dioxy-ethyl-amphetamine, methylene-dioxy-propyl-amphetamine, hydroxyamphetamine, and the selective serotonin reuptake inhibitor venlafaxine. Fentanyl was present in 2 out of 4 cocaine samples and in 14 of the 22 confirmed MDMA samples. CONCLUSIONS: Some of the adulterants found pose serious health risks, especially fentanyl, amphetamine-like substances, and venlafaxine. Therefore, it is urgent to monitor these adulterants at electronic music festivals and to implement prevention, treatment, and harm reduction public policies. Naloxone distribution and drug-assisted therapies should be part of government programs in Mexico.

Prevalence and Associated Factors of Depression among Adults Suffering from Migraine in Spain.

Considering the significance of migraine and the limited amount of research conducted on its association with depression in population-based studies in Spain, this study aimed to determine the prevalence and change of depression from 2017 to 2020 among adults with migraine in Spain and to analyze the sociodemographic and health-related variables linked to depression in migraine sufferers. A cross-sectional study on 5329 adults with migraine from the Spanish National Health Survey 2017 and the European Health Survey in Spain 2020 was performed. Binary logistic regression was used to examine the factors related to depression. A total of 26.32% of people with migraine suffered from depression. No significant changes in that prevalence between 2017 and 2020 were observed. The risk factors associated with depression included being between the ages of 25 and 44 (p = 0.018), being separated or divorced (p = 0.033), being unemployed (p < 0.001), not engaging in recreational physical activity (p = 0.016), perceiving one's health as average, poor, or very poor (p < 0.001), experiencing moderate to severe pain in daily activities (p = 0.011, p = 0.004, p < 0.001, respectively), and having 1-2 or ≥3 chronic conditions (p = 0.003, p < 0.001, respectively). Conversely, being married (p = 0.001) and alcohol consumption (p = 0.007) were identified as protective factors.

Temporal Evolution and Associated Factors of Adherence to Mammography Screening among Women in Spain: Results from Two National Health Surveys (2017-2020).

Ensuring equity in cancer screening is recommended by the European Commission. Despite the fact that breast cancer screening is a free population-based program in Spain, there remains considerable variation in the adherence to screening rate among population groups. This study was designed to describe the adherence of breast cancer screening in women in Spain, to evaluate the evolution in the period from 2017 to 2020, and to determine the variables that influence choosing to undergo breast cancer screening. A nationwide cross-sectional study with 7220 females aged 50-69 years from the 2017 Spanish National Health Survey and the 2020 European Health Survey for Spain was performed. We investigated mammography uptake rates, with socio-demographic factors, lifestyle habits, and health-related characteristics as independent variables. Multivariable logistic regression was used to identify the associated factors of mammography adherence. Of the women, 78% had undergone mammography in the previous two years, and there was a significant decrease in the uptake rate for breast cancer screening from 2017 (81.23%) to 2020 (74.68%) (p < 0.001). Educational level, marital status, residential location, nationality, smoking status, alcohol consumption, and leisure-time physical activity were all associated factors of mammography uptake.

Psychological impact of COVID-19 and determinants among Spanish university students.

Background: University students are a vulnerable population and faced a significant psychological impact from the COVID-19 pandemic. Therefore, this study aimed to determine the level of fear of COVID-19 among university students and to evaluate the possible relationship between fear of COVID-19 and socio-demographic, health-related determinants, variables related to the COVID-19 and variables related to the psychological impact of the COVID-19 pandemic. Methods: We conducted a cross-sectional study between December 2020 and December 2021 on a sample of 950 university students from two universities in southern Spain. Participants completed a form that collected socio-demographic, health-related and COVID-related variables, a validated questionnaire related to the psychological impact of the COVID-19 pandemic and the fear of COVID Scale (FCV-19S). Descriptive, inferential, and multivariable linear regression analyzes were conducted. Results: The mean FCV-19S score was 14.86 ± 5.16 points. The factors identified as predictors of FCV-19S were being female (p < 0.001), holding religious beliefs (p = 0.04), living in towns with over 10,000 inhabitants (p < 0.01), living with someone vulnerable to COVID-19 (p = 0.02), watching TV to keep informed about COVID-19 (p < 0.01), believing in a low probability of surviving if infected with COVID-19 (p < 0.001), having a higher level of death anxiety (p < 0.001) and suffering from insomnia (p < 0.001). Conclusion: An average fear of COVID-19 score of 14.86 ± 5.16 points has been found among university students in Spain. These findings can aid in identifying specific factors contributing to fear of COVID-19 and in developing coping strategies to alleviate the stress of the pandemic.

Xylazine potentiates the lethal but not the rewarding effects of fentanyl in mice.

BACKGROUND: Fentanyl is commonly laced with xylazine. People who use this combination report heightened effects, but it also increases death risk. Although no medication has been approved to counteract overdoses produced by fentanyl and xylazine, naloxone is frequently used. This paper studies the preclinical rewarding and lethal effects of fentanyl combined with xylazine and the efficacy of yohimbine or naloxone to prevent death. METHODS: Male Swiss Webster mice were treated with (in mg/kg, i.p.) xylazine (0.3, 1, 3, or 5.6), fentanyl (0.01, 0.3, or 0.1), or 1 xylazine plus 0.01 (non-effective) or 0.1 (effective) fentanyl doses during the conditioned-place preference (CPP) test. In addition, independent groups received (in mg/kg, i.p.): xylazine (31.6, 60, 74.2, or 100), fentanyl (3.1 or 10), or both substances at two doses: 31.6 xylazine + 3.1 fentanyl, or 60 xylazine + 10 fentanyl to analyze lethal effects. We determined whether yohimbine or naloxone (each medication tested at 10 or 30mg/kg) could prevent the lethality produced by fentanyl/xylazine combinations. Female mice were also tested in key experiments. RESULTS: Xylazine neither induced CPP nor altered fentanyl's rewarding effects. In contrast, lethality was potentiated when fentanyl was combined with xylazine. Naloxone, but not yohimbine, effectively prevented the lethality of the fentanyl/xylazine combinations. CONCLUSIONS: At the doses tested, xylazine does not increase the rewarding effect of fentanyl on the CPP in male mice but potentiates the risk of fatal overdose in male and female mice. A high naloxone dose prevents death induced by coadministration of fentanyl and xylazine in both sexes.

The Resurgence of Hallucinogen Drugs in Clinical Research.

Since the dawn of civilization, ancient cultures have utilized hallucinogens from plants and fungi in the context of religious and healing practices. Recently, their use has expanded to other cultures. Hallucinogens are natural or synthetic substances that alter the perception of reality at nontoxic doses, producing intense psychological and physiological effects. The initial research on hallucinogens began in the 1950s. However, their non-medical use, studies without proper controls, and negative social opinion resulted in legal restrictions that limited their use for clinical and preclinical research for more than two decades. A renewed interest in studying hallucinogens as potential therapeutic agents for treating different psychiatric conditions has recently re-emerged. This review summarizes the effects of main hallucinogen drugs and their therapeutic potential. Classic hallucinogens such as LSD, dimethyltryptamine, psilocin, and mescaline have chemical structures similar to serotonin and directly activate 5-hydroxy-tryptamine (5-HT2A) receptors. Ketamine is a dissociative anesthetic with antagonist effects at the glutamatergic N-methyl-D-aspartate receptor, indirectly activating 5-HT2A receptors. Ketamine has rapid antidepressant effects and reduces suicidal ideation, but its effects are short-lasting. Other hallucinogens are under study. It is necessary to continue this research with a more rigorous methodology and include studying the long-term effects of psychedelics use.

Amphetamine-type Stimulants: Novel Insights into their Actions and use Patterns.

This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.

Fentanyl and other New Psychoactive Synthetic Opioids. Challenges to Prevention and Treatment.

Synthetic opioids have played a significant role in the current opioid crisis in the United States (U.S.) and Canada and are a matter of concern worldwide. New psychoactive opioids (NPOs) are classified in the internationally recognized new psychoactive substances (NPSs) category. This group comprises compounds that may have been synthesized decades ago but appeared only recently in the illicit drug market. Such is the case of fentanyl, fentanyl analogs, and non-fentanyl opioids. Most NPOs have effects similar to morphine, including euphoria and analgesia, and can produce fatal respiratory depression. Here, we present an overview of the systemic and molecular effects of main NPOs, their classification, and their pharmacological properties. We first review the fentanyl group of NPOs, including the four compounds of clinical use (fentanyl, alfentanil, sufentanil, and remifentanil) and the veterinary drug carfentanil. We also provide essential information on non-medical fentanyl analogs and other synthetic opioids such as brorphine, etonitazene, and MT-45, used as adulterants in commonly misused drugs. This paper also summarizes the scarce literature on the use of NPOs in Mexico. It concludes with a brief review of the challenges to prevention and treatment posed by NPOs and some recommendations to face them.

Brain-Derived Neurotrophic Factor (BDNF) and First-Episode Psychosis. A longitudinal one-year prognosis study.

The brain-derived neurotrophic factor (BDNF) is a neurotrophin that has been linked to the schizophrenia neurodevelopmental hypothesis.

Fentanyl and other New Psychoactive Synthetic Opioids. Challenges to Prevention and Treatment

ABSTRACT Synthetic opioids have played a significant role in the current opioid crisis in the United States (U.S.) and Canada and are a matter of concern worldwide. New psychoactive opioids (NPOs) are classified in the internationally recognized new psychoactive substances (NPSs) category. This group comprises compounds that may have been synthesized decades ago but appeared only recently in the illicit drug market. Such is the case of fentanyl, fentanyl analogs, and non-fentanyl opioids. Most NPOs have effects similar to morphine, including euphoria and analgesia, and can produce fatal respiratory depression. Here, we present an overview of the systemic and molecular effects of main NPOs, their classification, and their pharmacological properties. We first review the fentanyl group of NPOs, including the four compounds of clinical use (fentanyl, alfentanil, sufentanil, and remifentanil) and the veterinary drug carfentanil. We also provide essential information on non-medical fentanyl analogs and other synthetic opioids such as brorphine, etonitazene, and MT-45, used as adulterants in commonly misused drugs. This paper also summarizes the scarce literature on the use of NPOs in Mexico. It concludes with a brief review of the challenges to prevention and treatment posed by NPOs and some recommendations to face them.