Thallium toxicity due to audultered infusion with thallium sulfate in eight members belonging to the same family nucleus: Autopsy findings and ICP-MS analysis (inductively coupled plasma mass spectrometry) in a triple homicide

The banning of the heavy metal thallium (Tl) in many Countries, because of its toxicity, led to a remarkable reduction of the number of cases of poisoning both accidental and homicidal forcing us to better study the pharmacokinetics of this poison using new technologies. The Authors, in this work, are reporting the case of a collective thallium toxicosis caused by voluntary adulteration of an infusion with thallium sulfate, occurred in 8 members of the same familial nucleus; the administration of Prussian Blu resulted to be ineffective for 3 of these members that died at a later time. The most peculiar aspects of this rare manner of poisoning are discussed; the analytical procedures used, Inductively Coupled Plasma Mass Spectrometry (ICP-MS) in particular, resulted to be fundamental in the forensic diagnosis process of acute poisoning cause by thallium

The Italian document: decisions for intensive care when there is an imbalance between care needs and resources during the COVID-19 pandemic

Background: In early 2020, the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) published clinical ethics recommendations for the allocation of intensive care during COVID-19 pandemic emergency. Later the Italian National Institute of Health (ISS) invited SIAARTI and the Italian Society of Legal and Insurance Medicine to prepare a draft document for the definition of triage criteria for intensive care during the emergency, to be implemented in case of complete saturation of care resources. Methods: Following formal methods, including two Delphi rounds, a multidisciplinary group with expertise in intensive care, legal medicine and law developed 12 statements addressing: (1) principles and responsibilities; (2) triage; (3) previously expressed wishes; (4) reassessment and shifting to palliative care; (5) collegiality and transparency of decisions. The draft of the statements, with their explanatory comments, underwent a public consultation opened to Italian scientific or technical-professional societies and other stakeholders (i.e., associations of citizens, patients and caregivers; religious communities; industry; public institutions; universities and research institutes). Individual healthcare providers, lay people, or other associations could address their comments by e-mail. Results: Eight stakeholders (including scientific societies, ethics organizations, and a religious community), and 8 individuals (including medical experts, ethicists and an association) participated to the public consultation. The stakeholders’ agreement with statements was on average very high (ranging from 4.1 to 4.9, on a scale from 1—full disagreement to 5—full agreement). The 4 statements concerning triage stated that in case of saturation of care resources, the intensive care triage had to be oriented to ensuring life-sustaining treatments to as many patients as possible who could benefit from them. The decision should follow full assessment of each patient, taking into account comorbidities, previous functional status and frailty, current clinical condition, likely impact of intensive treatment, and the patient's wishes. Age should be considered as part of the global assessment of the patient. Conclusions: Lacking national guidelines, the document is the reference standard for healthcare professionals in case of imbalance between care needs and available resources during a COVID-19 pandemic in Italy, and a point of reference for the medico-legal assessment in cases of dispute

Evaluation of the zucker diabetic fatty (ZDF) rat as a model for human disease based on urinary peptidomic profiles

Representative animal models for diabetes-associated vascular complications are extremely relevant in assessing potential therapeutic drugs. While several rodent models for type 2 diabetes (T2D) are available, their relevance in recapitulating renal and cardiovascular features of diabetes in man is not entirely clear. Here we evaluate at the molecular level the similarity between Zucker diabetic fatty (ZDF) rats, as a model of T2D-associated vascular complications, and human disease by urinary proteome analysis. Urine analysis of ZDF rats at early and late stages of disease compared to age- matched LEAN rats identified 180 peptides as potentially associated with diabetes complications. Overlaps with human chronic kidney disease (CKD) and cardiovascular disease (CVD) biomarkers were observed, corresponding to proteins marking kidney damage (eg albumin, alpha-1 antitrypsin) or related to disease development (collagen). Concordance in regulation of these peptides in rats versus humans was more pronounced in the CVD compared to the CKD panels. In addition, disease-associated predicted protease activities in ZDF rats showed higher similarities to the predicted activities in human CVD. Based on urinary peptidomic analysis, the ZDF rat model displays similarity to human CVD but might not be the most appropriate model to display human CKD on a molecular level

Reconstructing grain-shape statistics from electron back-scatter diffraction microscopy

Reconstructing the three-dimensional (3D) size and shape distribution of randomly oriented grains using only images of cross sections remains an important challenge. Even for ellipsoids, a solution is only possible when they are solids of revolution, and may still be numerically unstable. Here we show that crystallographic orientation data, for example from electron back-scatter diffraction (EBSD), provides enough additional information to obtain moments of the 3D grain distribution, provided grain shapes can be assumed to align with crystal axes. We show that this moment method can give an average 3D grain size and shape (with error estimate) which is rigorous for ellipsoids and a good approximation for cuboidal grains, indicating that it may be a useful technique for polycrystalline materials in general. High throughput image analysis and EBSD now make the necessary sample sizes practical. We illustrate by applying the method to a basaltic rock specimen

“Self stabbing sucide”: 116 casi occorsi nella città di Milano dal 1993 al 2016

Introduzione Mentre molti omicidi nel Mondo sono compiuti con armi da taglio, i suicidi realizzati con siffatta modalit\ue0 lesiva sono rari accadimenti, comprovati nello 0,5-0,7% di tutti i casi di autosoppressione; in genere, sui corpi si osserva una sola ferita mortale, per quanto possano esserne eccezionalmente osservate anche molte, che sollevano la necessit\ue0 di stabilire se trattasi di modalit\ue0 realmente suicida piuttosto che omicida. In questi casi, ulteriori informazioni per configurare l\u2019esatta natura dell\u2019accadimento, sono desumibili dall\u2019anamnesi della vittima, dai dati circostanziali e di sopralluogo, nonch\ue9 dalle caratteristiche delle lesioni e dalla loro localizzazione. In questo studio, presentiamo l\u2019analisi dei casi di suicidio con armi da taglio, occorsi a Milano in 24 anni. Materiali e metodi Sono stati analizzati retrospettivamente 23417 verbali di autopsia redatti tra il 1993 e il 2016 presso la Sezione di medicina legale dell\u2019Universit\ue0 degli Studi di Milano estrapolando da 4022 suicidi totali, solo quelli realizzati con armi da taglio. Su questi casi, abbiamo approfondito lo studio delle caratteristiche delle vittime, della distribuzione e del numero delle lesioni autoinferte e delle caratteristiche dell\u2019arma feritrice. Risultati Abbiamo desunto 116 casi di suicidio con armi da taglio di cui: 103 realizzati con modalit\ue0 semplice e 13 con modalit\ue0 complessa, che hanno visto maggiormente coinvolti maschi italiani di et\ue0 compresa tra 41-e 50 anni, affetti da patologie psichiatriche, che si sono uccisi nella propria abitazione utilizzando, prevalentemente, coltelli da cucina. Le lesioni sono risultate monodistrettuali e localizzate agli arti superiori o al torace. In tutti i casi osservati, la morte, per la presenza di lesioni \u201cda assaggio\u201d a profondit\ue0 variabile, mancanza di segni di lotta, sangue limitato all\u2019area circostante il corpo e per la direzionalit\ue0 delle lesioni, da destra a sinistra, con il gomito piegato a 90 gradi verso il corpo, \ue8 stata attribuita, anche nel caso dei suicidi complessi, a shock emorragico da azione suicida. Conclusioni Gli inusuali suicidi compiuti con armi da taglio richiedono un approccio forense completo basato su un approfondito esame della scena del crimine durante il sopralluogo giudiziario, un\u2019accurata raccolta dei dati anamnestico-circostanziali e degli esiti autoptici i quali, unitamente alle indagini tossicologiche, possono rappresentare strumenti fondamentali per esprimersi motivatamente su un giudizio di accadimento omicida piuttosto che suicida

Activation of the spinal and brainstem locomotor networks during free treadmill stepping in rats lacking dopamine transporter

Dopamine is extremely important for the multiple functions of the brain and spinal cord including locomotor behavior. Extracellular dopamine levels are controlled by the membrane dopamine transporter (DAT), and animals lacking DAT (DAT-KO) are characterized by hyperdopaminergia and several alterations of locomotion including hyperactivity. Neuronal mechanisms of such altered locomotor behavior are still not fully understood. We believe that in hyperdopaminergic animals both the spinal and brain neuronal networks involved in locomotion are modified. Using the c-fos technique, we studied activated neuronal networks of the spinal cord and two brainstem structures related to locomotor control and being under the strong dopaminergic influence, the cuneiform nucleus (CnF) and ventrolateral periaqueductal gray (VLPAG), in wild-type (DAT-WT) and DAT-KO rats. In the spinal cord, most c-fos-positive cells were located in the dorsal laminae II-IV and in the central gray matter (laminae V-VI). No differences were revealed for the central areas. As for the dorsal areas, in the DAT-WT group, labeled cells mostly occupied the lateral region, whereas, in the DAT-KO group, c-fos-positive cells were observed in both medial and lateral regions in some animals or in the medial regions in some animals. In the brainstem of the DAT-WT group, approximately the same number of labeled cells were found in the CnF and VLPAG, but in the DAT-KO group, the VLPAG contained a significantly smaller number of c-fos-positive cells compared to the CnF. Thereby, our work indicates an imbalance in the sensorimotor networks located within the dorsal horns of the spinal cord as well as a disbalance in the activity of brainstem networks in the DAT-deficient animals

Angiotensin converting enzyme inhibitor therapy in children with Alport syndrome: effect on urinary albumin, TGF-β, and nitrite excretion

BACKGROUND: Angiotensin converting enzyme inhibitors are routinely prescribed to patients with chronic kidney disease because of their known renoprotective effects. We evaluated the effect of short-term therapy with the angiotensin converting enzyme inhibitor, enalapril, in early Alport syndrome, defined as disease duration less than 10 years and a normal glomerular filtration rate. METHODS: 11 children with early Alport syndrome were investigated. Two consecutive early morning urine specimens were collected at the start of the study for measurement of urinary creatinine, total protein, albumin, TGF-β, and nitrite excretion. Patients were treated with enalapril, ≅ 0.2 mg/kg/day, once a day for 14 days. Two early morning urine specimens were collected on days 13 and 14 of enalapril treatment and two weeks later for measurement of urinary creatinine, total protein, albumin, TGF-β, and nitrite excretion. RESULTS: Prior to treatment, urinary excretion of transforming growth factor-β and nitrite, the major metabolite of nitric oxide, was within normal limits in all patients. Administration of enalapril for 2 weeks did not alter urinary albumin, transforming growth factor-β, or nitrite excretion. CONCLUSION: These findings suggest that early Alport syndrome represents a disease involving exclusively intrinsic glomerular barrier dysfunction. At this stage of the illness, there is no evidence of angiotensin II-mediated proteinuria or increased production of transforming growth factor-β and, therefore, routine treatment with an angiotensin converting enzyme inhibitor may not be warranted

A Molecular Signature of Proteinuria in Glomerulonephritis

Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 “albumin-regulated genes” differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n = 25) could be distinguished from those of control subjects (n = 6) based solely upon the expression of these 231 “albumin-regulated genes.” The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that all forms of primary glomerulonephritis (n = 33) can be distinguished from controls (n = 21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis

Medico-legal assessment of personal damage in older people: report from a multidisciplinary consensus conference

Ageing of the global population represents a challenge for national healthcare systems and healthcare professionals, including medico-legal experts, who assess personal damage in an increasing number of older people. Personal damage evaluation in older people is complex, and the scarcity of evidence is hindering the development of formal guidelines on the subject. The main objectives of the first multidisciplinary Consensus Conference on Medico-Legal Assessment of Personal Damage in Older People were to increase knowledge on the subject and establish standard procedures in this field. The conference, organized according to the guidelines issued by the Italian National Institute of Health (ISS), was held in Bologna (Italy) on June 8, 2019 with the support of national scientific societies, professional organizations, and stakeholders. The Scientific Technical Committee prepared 16 questions on 4 thematic areas: (1) differences in injury outcomes in older people compared to younger people and their relevance in personal damage assessment; (2) pre-existing status reconstruction and evaluation; (3) medico-legal examination procedures; (4) multidimensional assessment and scales. The Scientific Secretariat reviewed relevant literature and documents, rated their quality, and summarized evidence. During conference plenary public sessions, 4 pairs of experts reported on each thematic area. After the last session, a multidisciplinary Jury Panel (15 members) drafted the consensus statements. The present report describes Conference methods and results, including a summary of evidence supporting each statement, and areas requiring further investigation. The methodological recommendations issued during the Conference may be useful in several contexts of damage assessment, or to other medico-legal evaluation fields