A validated dilute-and-shoot LC-MS/MS urine screening for the analysis of 95 illicit drugs and medicines: insights from clinical and forensic Brazilian cases.

Urine toxicological analysis is a relevant tool in both clinical and forensic scenarios, enabling the diagnosis of acute poisonings, elucidation of deaths, verification of substance use in the workplace, and identification of drug-facilitated crimes. For these analyses, the dilute-and-shoot technique associated with liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) is a promising alternative since it has demonstrated satisfactory results and broad applicability. This study developed and validated a comprehensive LC-MS-MS screening method to analyze 95 illicit drugs and medicines in urine samples and application to clinical and forensic Brazilian cases. The dilute-and-shoot protocol was defined through multivariate optimization studies and was set using 100 µL of sample and 300 µL of solvent. The total chromatographic run time was 7.5 minutes. The method was validated following the recommendations of the ANSI/ASB Standard 036 Guideline. The lower limits of quantification varied from 20 to 100 ng/mL. Within-run and between-run precision CVs% were lower than 20%, and bias was within ± 20%. Only four of the 95 analytes presented significant ionization suppression or enhancement (> 25%). As proof of applicability, 839 urine samples from in vivo and postmortem cases were analyzed. In total, 90.9% of the analyzed samples were positive for at least one substance, and 78 of the 95 analytes were detected. The most prevalent substances were lidocaine (40.2%), acetaminophen (38.0%), and benzoylecgonine (31.5%). The developed method proved to be an efficient and simplified alternative for analyzing 95 therapeutic and illicit drugs in urine samples. Additionally, the results obtained from sample analysis are essential to understanding the profile of Brazilian substance use, serving as a valuable database for the promotion of health and safety public policies.

Cork sheet as an efficient biosorbent for forensic toxicology: Application to vitreous humor analysis.

There is an increasing number of people affected worldwide by mental health disorders, such as depression and anxiety. One of the main courses of treatment, along with psychotherapy, is the use of psychoactive medications, like antidepressants and benzodiazepines. Also, the unprescribed use of these substances is a concerning public health issue. Hence, the analysis of psychotropic medications is mandatory in postmortem toxicology and various biological samples can be used for this detection, among them the vitreous humor (VH) stands out. Also, there is a demand for more sustainable and more efficient extraction methodologies according to green chemistry. An example is solid phase microextraction techniques (SPME), which use a solid sorbent and small solvent amounts. Biosorbents are substances of natural origin with sorptive properties, and they have been successfully used in SPME in environmental toxicology for water analysis, mainly. This study aimed to develop a sustainable, fast, cheap and simple SPME methodology using cork sheet strips as a biosorbent, to extract antidepressants, benzodiazepines and others from VH samples by liquid chromatography coupled to tandem mass spectrometry. The extraction was conducted in a 96-well plate using 200 µL of VH and optimization of relevant parameters for extraction was performed. For solvent optimization, two simplex-centroid experiments were planned for extraction and desorption and to evaluate time and pH, a Doehlert design experiment was performed. The analytical method for the determination and quantification of 17 substances was validated. The quantification limits were 5 ng/mL for all analytes and the calibration curves were linear between 5 and 30 ng/mL. This study was able to develop an efficient, cheap, simple and fast microextraction method for 17 analytes in VH, using strips of cork sheet for extraction and a 96-well plate as a container. Furthermore, this approach system could be automated for routine toxicology laboratories.

Desafios bioéticos na formação médica: uma perspectiva teleológica e axiológica / Bioethical challenges in medical schools: a teleological and axiological perspective

Resumo: Introdução: Os valores humanos e as virtudes éticas que norteiam a ação médica na sociedade contemporânea são um tema deveras importante, contudo pouco tematizado e enfatizado no processo de formação dos futuros médicos. Objetivo: Dada a suma complexidade do assunto para a formação profissional integral, haja vista a medicina ser uma ciência sobretudo humana que alia técnica e conhecimento ao bem-estar das pessoas, faz-se necessário problematizar quais os principais desafios bioéticos na formação médica sob uma perspectiva teleológica e axiológica. Métodos: Por meio de um artigo de reflexão, far-se-á uma análise sistemático-crítica conceitual das principais virtudes e dos principais valores debatidos e refletidos na tradição ética ocidental mediante cotejamento bibliográfico à luz do atual estado da arte do processo formativo médico. Resultado: A preocupação didático-pedagógica com valores e virtudes ético-morais, tais como caráter, amor, liberdade, respeito, responsabilidade, compaixão, paciência, humildade, fortaleza, prudência, justiça e coragem, entre outros, não está sendo privilegiada no ensino médico. Há um déficit nessa dimensão, dificultando o amadurecimento e a aprendizagem de práticas ético-morais indispensáveis em nosso tempo. Conclusão: O atual estágio do exercício da profissão médica, imersa num paradigma tecnicista, requer, cada vez mais, profissionais com uma formação humanista e não apenas tecnopragmática. Os desafios advindos de uma sociedade multifacetada, em constante evolução, exigem que as universidades e faculdades médicas enfoquem, precipuamente, as dimensões axiológicas e ético-morais na formação.

Abstract: Introduction: Although the human values and ethical virtues that guide medical action in contemporary society constitute a very important theme, they are given little emphasis in medical training. Objective: Given the complexity of this issue in relation to comprehensive professional training, and since medicine is - an above all human - science, that combines technique and knowledge with people's well-being, it is necessary to question the main bioethical challenges in medical training from a teleological and axiological perspective. Methods: In a reflection paper, a systematic-critical conceptual analysis of the main virtues and values debated and reflected in the Western ethical tradition is conducted by means of bibliographic comparison in light of the current state of the art of the medical training process. Results: A didactic-pedagogical concern with ethical-moral values and virtues such as character, love, freedom, respect, responsibility, compassion, patience, humility, fortitude, prudence, justice and courage, is not being prioritised in medical education. There is a deficit in this dimension, making it difficult for students to mature and learn the ethical-moral practices that are indispensable in our time. Conclusion: The current stage in the exercise of the medical profession immersed in a technicalist paradigm increasingly requires professionals with a humanist and not just techno-pragmatic background. The challenges that emerge from a constantly changing and multifaceted society require universities and medical faculties to focus, above all, on the axiological and ethical-moral dimensions of training.

Asymmetric parasitic twins - Heteropagus.

BACKGROUND: Asymmetric or heteropagus conjoined twins is a rare occurrence, with an incidence of one case in 1-2 million. Conjoined twins are classified according to their symmetry, place of fusion, and grade of duplication. METHODS: We report here an extremely rare presentation of parasitic twins not described before. We describe macro and micro anatomic alterations and discuss the aspects of this peculiar presentation and the importance of prenatal diagnosis. RESULTS: The case of a twenty-three-year-old patient, with monochorionic, monoamniotic asymmetrically-conjoined twin pregnancy, discovered at 29 weeks of gestational age. We believe that this report calls attention to this presentation and the importance of prenatal care and management. The twins were delivered vaginally without life. The twins' combined weight was 1.300 gr. They were bonded in the left cervical region. CONCLUSION: This report may help to find strategies for clinical decisions in future cases. Antepartum diagnosis is important to the management, preoperative planning, and outcomes. Prenatal imaging exams like echocardiography, CT, MRI, and ultrasonography are feasible and can provide relevant information about malformation severity and prognosis.

Asymmetric parasitic twins - Heteropagus

SUMMARY BACKGROUND: Asymmetric or heteropagus conjoined twins is a rare occurrence, with an incidence of one case in 1-2 million. Conjoined twins are classified according to their symmetry, place of fusion, and grade of duplication. METHODS: We report here an extremely rare presentation of parasitic twins not described before. We describe macro and micro anatomic alterations and discuss the aspects of this peculiar presentation and the importance of prenatal diagnosis. RESULTS: The case of a twenty-three-year-old patient, with monochorionic, monoamniotic asymmetrically-conjoined twin pregnancy, discovered at 29 weeks of gestational age. We believe that this report calls attention to this presentation and the importance of prenatal care and management. The twins were delivered vaginally without life. The twins' combined weight was 1.300 gr. They were bonded in the left cervical region. CONCLUSION: This report may help to find strategies for clinical decisions in future cases. Antepartum diagnosis is important to the management, preoperative planning, and outcomes. Prenatal imaging exams like echocardiography, CT, MRI, and ultrasonography are feasible and can provide relevant information about malformation severity and prognosis.

RESUMO BACKGROUND: Gêmeos parasitas assimétricos ou heterópagos são uma ocorrência rara, com incidência de um caso em 1-2 milhões. Os gêmeos siameses são classificados de acordo com sua simetria, local de fusão e grau de duplicação. MÉTODOS: Relatamos aqui uma apresentação extremamente rara de gêmeos parasitários não descritos anteriormente. São descritas alterações macro e microscópicas e discutidos aspectos relevantes dessa malformação e da importância do diagnóstico pré-natal. RESULTADOS: Um caso de uma paciente de 23 anos de idade, com gestação monocoriônica, monoamniótica de gêmeos siameses assimétricos diagnosticada com 29 semanas de idade gestacional. Acreditamos que este relato chama a atenção para esta apresentação e para a importância do cuidado e manejo pré-natal. Os fetos nasceram de parto vaginal já sem vida, pesando em conjunto 1.300 gramas, e eram unidos pela região cervical esquerda. CONCLUSÃO: Este relato pode ajudar a encontrar estratégias para a decisão clínica em casos futuros. O diagnóstico pré-natal é fundamental para o manejo e planejamento pré-operatório. Exames de imagem como ecocardiografia, tomografia computadorizada, ressonância magnética e ultrassonografia são factíveis e podem fornecer informações-chave sobre a gravidade e prognóstico da malformação.