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Fluoride exposure is widespread, with drinking water commonly containing natural and artificially added sources of the ion. Ingested fluoride undergoes absorption across the gastric and intestinal epithelia. Previous studies have reported adverse gastrointestinal effects with high levels of fluoride exposure. Here, we examined the effects of fluoride on the transepithelial ion transport and resistance of three intestinal epithelia. We used the Caco-2 cell line as a model of human intestinal epithelium, and rat and mouse colonic epithelia for purposes of comparison. Fluoride caused a concentration-dependent decline in forskolin-induced Cl- secretion and transepithelial resistance of Caco-2 cell monolayers, with an IC50 for fluoride of about 3 mM for both parameters. In the presence of 5 mM fluoride, transepithelial resistance fell exponentially with time, with a t1/2 of about 7 hours. Subsequent imaging by immunofluorescence and scanning electron microscopy showed structural abnormalities in Caco-2 cell monolayers exposed to fluoride. The Young's modulus of the epithelium was not affected by fluoride, although proteomic analysis revealed changes in expression of a number of proteins, particularly those involved in cell-cell adhesion. In line with its effects on Caco-2 cell monolayers, fluoride, at 5 mM, also had profound effects on Cl- secretion and transepithelial resistance of both rat and mouse colonic epithelia. Our results show that treatment with fluoride has major effects on the structure, function, and proteome of intestinal epithelia, but only at concentrations considerably higher than those likely to be encountered in vivo, when much lower fluoride doses are normally ingested on a chronic basis.

Meningiomas are intracranial tumors originating from arachnoidal cells. Multiple intracranial meningiomas are rare and occur when two or more lesions occur either simultaneously or sequentially in different locations. We described a case of multiple meningothelial meningioma post forensic autopsy.

Cremation has seen a constant increase in popularity all around the world. Because of its extensively destructive nature, however, a series of medico-legal issues arise concerning identification, forensic autopsy, external examination, histological, toxicological and genetic exams to be performed not in the immediacy of death. The aim of this study is to compare the international legislation on cremation, seeking the response of various countries to their medico-legal issues. Several affinities but also some differences were found. Similarities include the need for a certificate by a medical examiner excluding any medico-legal issues and non-natural causes of death and the expression of consent to cremation given by the deceased when still alive otherwise by relatives. Significant differences were found in German law, which provides for a second medical examination prior to cremation and in Italian law providing for the medical examiner to collect biological samples from the body and store them for a minimum of ten years for any future purpose of justice. The Italian approach could give a plausible solution to the medico-legal issues raised by cremation with the imperative premise, however, we need to look deeply into its privacy and consent implications, cost–benefits rate, sample collection and storage protocol.

Background: In most cases, palliative care is prescribed to adults diagnosed with cancer. The definition of the most suitable therapy for an effective sedation in terminal cancer patients still represents one of the most challenging goals in medical practice. Due to their poor health, the correct dosing of drugs used for deep palliative sedation in terminal cancer patients, often already on polypharmacological therapy, can be extremely complicated, also considering possible drug-to-drug interactions that could lead to an increased risk of overdose and/or incongruous administration with fatal outcomes. The case of a terminal cancer patient is presented, focusing on the “adequacy” of administered therapy. Materials and Methods: A young male, affected by Ewing sarcoma, attending a palliative care at his own home, died soon after midazolam administration. Toxicological and histological analyses were performed on body fluids and organ fragments. Results and Discussion: Morphological reliefs evidenced a neoplastic mass, composed of lobulated tissue with a lardy, pinkish-gray consistency, extending from the pleural surface to the lung parenchyma, also present at the sacrum region (S1–S5), at the anterior mediastinum level, occupying the entire left pleural cavity, and infiltrating the ipsilateral lung. Metastatic lesions diffused to rachis and lumbar structures. The brain presented edema and congestion. Toxicological analyses evidenced blood midazolam concentrations in the range of 0.931–1.690 µg/mL, while morphine was between 0.266 and 0.909 µg/mL. Death was attributed to cardiorespiratory depression because of a synergic action between morphine and midazolam. The pharmacological interaction between midazolam and morphine is discussed considering the clinical situation of the patient. The opportunity to proceed with midazolam administration is discussed starting from guidelines recommendation. Finally, professional liability outlines are highlighted.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Universidade Federal de Uberlândia Ressaltar os processos criativos nas aulas de arte como acontecimentos importantes para a transformação e construção de pensamentos e emoções dos alunos, observando o papel e a formação do professor de arte e sua inserção nesse processo, são objetivos desta pesquisa. Para alcançar os objetivos mencionados, observamos na formação do professor de arte bases importantes a partir das quais surgiram metodologias e dinâmicas de aula que intervieram na realidade de cada escola usada como ambiente deste estudo que, por sua vez, utilizou-se do corpo em ação (performativa) como uma das premissas para a observação do que denominamos “fluxo criativo”. Nesse sentido, buscaram-se experiências de processos criativos usando a pesquisa-ação com alunos do ensino regular, níveis fundamental e médio, da educação pública (prefeitura e estado). Adotando como procedimento técnico a observação participante, apresentaram-se ainda concepções sobre corpo, arte e experiência que permitiram perceber o corpo enquanto instrumento da “experiência em arte” e conectá-las aos sentidos da percepção como forma de lidar com sensações estéticas. Ao trabalhar com alunos em níveis diferentes de aprendizagem na sala de aula, abordaram-se as inteligências e como alcançá-las através da percepção. Por meio de experimentos práticos com o ensino na área de arte, pretendeu-se valorizar aulas que respeitassem as inteligências dos alunos buscando alcançá-los através de um trabalho que proporcionasse o autoconhecimento como produto em confluência com a área da arteterapia. Para tanto, experiências foram propostas com a inteligência emocional, promovendo respeito às diferenças, ressaltando a proposta do professor como interlocutor do processo criativo em arte em que “fluxos criativos” afetaram os sujeitos envolvidos a ponto de transformá-los através da apreciação e fruição na prática performativa. Hacer hincapié en los procesos creativos en las clases de arte como eventos importantes para la transformación y la construcción de los pensamientos y emociones de los estudiantes, señalando la función y la formación de los profesores de arte y su lugar en el proceso, son objetivos de esta investigación. Para lograr estos objetivos, se observa la formación del profesor de arte principales bases de la que surgió metodologías y dinámica de clases que tomaron parte en la realidad de cada escuela se utiliza como medio de este estudio que, a su vez, se utiliza el cuerpo en acción (performativa) como una de las premisas para la observación de lo que llamamos "flujo creativo". En este sentido, trataron de procesos creativos experimentos utilizando la investigación-acción con los estudiantes regulares, nivel de primaria y secundaria, la educación pública (ciudad y estado). La adopción de la observación participante como procedimiento técnico, todavía tenía ideas sobre el arte corporal y la experiencia que les permite percibir el cuerpo como un instrumento de la "experiencia en el arte" y conectarlos a los sentidos de percepción como una forma de hacer frente a las sensaciones estéticas. Cuando se trabaja con los estudiantes en los diferentes niveles de aprendizaje en el aula, dirigida a las inteligencias y cómo llegar a ellos a través de la percepción. A través de experimentos prácticos con la enseñanza en el área de arte, tenía la intención de realzar las lecciones de respetar la inteligencia de los estudiantes que buscan llegar a ellos a través de un trabajo que proporcionaría auto-conocimiento como confluencia producto con el campo de la terapia del arte. Por lo tanto, se propusieron experimentos con la inteligencia emocional, la promoción del respeto a las diferencias, tomando nota de la propuesta del maestro como un socio del proceso creativo en el arte que "flujo creativo" afectó a los involucrados como para transformarlos través de la apreciación y el disfrute en la práctica performativa. Dissertação (Mestrado)

The study reports the evolution of the demyelinization process based on cholesterol ([CHOL]) levels quantified in median nerve samples and collected at different times-from death from both right and left wrists. The statistical data show that the phenomenon evolves differently in the right and left nerves. Such a difference can reasonably be attributed to a different multicenter evolution of the demyelinization. For data analysis, the enrolled subjects were grouped by similar postmortem intervals (PMIs), considering 3 intervals: PMI < 48 hours, 48 hours < PMI < 78 hours, and PMI > 78 hours. Data obtained from tissue dissected within 48 hours of death allowed for a PMI estimation according to the following equations: PMI = 0.000 + 0.7623 [CHOL]right (R = 0.581) for the right wrist and PMI = 0.000 + 0.8911 [CHOL]left (R = 0.794) for the left wrist.At present, this correlation cannot be considered to be definitive because of the limitation of the small size of the samples analyzed, because the differences in the sampling time and the interindividual and intraindividual variation may influence the demyelinization process.

A long-term psychiatric 40 years-old male patient was found dead at 9:00 a.m. in the clinic where he lived. Death was caused by traumatic injuries, which the sanitary staff imputed to a fall. Nurses declared that the patient refused having breakfast, whereas at autopsy the stomach contained 350 g of whitish semifluid material. Using both shotgun and gel-based proteomics, we demonstrated that the chyme contained partly digested milk- and bread-derived proteins, eaten during a recent breakfast. The conflict between evidence and assertions of the attending sanitary staff prompted the Legal Authority to undertake detailed investigations to ascertain facts and possible responsibilities. The herein characterization provides insights in the in vivo mechanisms of gastric breakdown of food proteins in a real meal. β-lactoglobulin was partially resistant to gastric digestion as confirmed by Western blot analysis, in contrast to caseins and wheat gluten proteins, which had been degraded by gastric fluids. In addition to a complex pattern of gastric proteins (e.g., mucin-5AC, pepsin A-3, pepsinogen C, gastric lipase, gastrokine-2, trefoil factors), chyme contained intact proteins and variably sized food-derived polypeptides arising from peptic and nonpeptic proteolytic cleavage as well as heterodimeric disulfide-cross-linked peptides. These findings suggest that the current analytical workflows offer only a partial picture of the real complexity of the human "digestome".

Post-mortem morphological modifications in median nerve samples collected at different times after death were studied in subjects with known circumstances and times of death. Histological analyses were performed by light and electron microscopy on single fiber and on transversal sections. Results of morphological observations evidenced the progressive disappearance of myelin over time according to a process similar to Wallerian degeneration occurring in vivo. Electron microscope analysis of transversal sections evidenced four steps through which post-mortal myelin degradation proceeded, from the initial structure modification (after 12 h from death) to the complete collapse and the simultaneous appearance of dropsy bumps toward the axon (after 48 h from death). The post-mortal demyelinization process can reasonably be thought to have a multifocal origin. Post-mortem alterations of nerve fibers do not evolve simultaneously and in a uniform manner in all the fibers of the same nerve, where different factors come into play, particularly fiber gauge.

Gender differences in substance use/abuse have been the focus of research in the last 15 years. Initiation, use patterns, acceleration of disease course, and help-seeking patterns are known to be influenced by gender differences with regard to biological, psychological, cultural and socioeconomic factors. This paper presents a systematic review of published data on gender differences in the use/abuse of psychoactive and psychotic drugs, focusing on the importance of a multidisciplinary approach. The basis for this paper was obtained by Medline searches using the search terms "human" and "gender", combined with individual drug names or "drugs of abuse". The reference lists of these papers were further checked for other relevant studies. The gender difference in drug abuse is more evident in adults than in adolescents (13-19 years): adult men are 2-3 times more likely than women to develop drug abuse/dependence disorders and approximately 4 times as likely to have an alcohol use disorder. Such prevalence rates have not been observed in adolescents. Differences between men and women involve: (i) the biological response to the drug, (ii) the progression to drug dependence, and (iii) the comorbid psychiatric diagnoses, which may be due to both sociocultural factors and innate biological differences. A crucial role played by ovarian hormones (oestrogens and progesterone) has been documented in both human and animal model studies. Epidemiological data on how particular psychobiological and physiological characteristics in females influence vulnerability to both drug addiction and toxicological consequences of drugs are still in their infancy. Significant gaps remain in our knowledge, which are primarily attributable to the lack of empirical data that only a systematic and multidisciplinary approach to the topic can generate. The introduction of gender into forensic toxicological evaluations may help elucidate the relationship between the body's absorption of abused drugs (alone or in combination) and the onset of intoxications, both lethal and none.

Cholesterol levels in the median nerve were studied at various post-mortem intervals (PMIs). Single median nerve samples were collected from the wrists of 36 subjects during forensic autopsies of subjects with known circumstances and times of death. Although the absolute values varied, increments in cholesterol concentration were recorded. Subsequently, 16 subjects who did not suffer of any neurological and/or metabolic diseases with known times and circumstances of death were enrolled. For each enrolled subject, two samples were collected from the wrist at an interval of approximately two hours (t1 and t2). The obtained results revealed a gradual increase in cholesterol level with increasing time since death. The cholesterol concentration data obtained for each subject at t1 and t2 were correlated with the time since death, a linear interpolation was applied, and the PMI was back-calculated. Similar trends were obtained for the samples collected at similar PMIs; thus, three groups were considered: PMI78h. Good correlation coefficients were obtained, especially for the first group (R(2)=0.9362) for which the PMI could be calculated with an error that ranged from -4 to 5.9h. Although it requires further confirmation via analyses of larger numbers of samples, the method proposed here can currently be applied to PMI determinations.