SMYD3: a new regulator of adipocyte precursor proliferation at the early steps of differentiation.

BACKGROUND: In obesity, adipose tissue undergoes a remodeling process characterized by increased adipocyte size (hypertrophia) and number (hyperplasia). The ability to tip the balance toward the hyperplastic growth, with recruitment of new fat cells through adipogenesis, seems to be critical for a healthy adipose tissue expansion, as opposed to a hypertrophic growth that is accompanied by the development of inflammation and metabolic dysfunction. However, the molecular mechanisms underlying the fine-tuned regulation of adipose tissue expansion are far from being understood. METHODS: We analyzed by mass spectrometry-based proteomics visceral white adipose tissue (vWAT) samples collected from C57BL6 mice fed with a HFD for 8 weeks. A subset of these mice, called low inflammation (Low-INFL), showed reduced adipose tissue inflammation, as opposed to those developing the expected inflammatory response (Hi-INFL). We identified the discriminants between Low-INFL and Hi-INFL vWAT samples and explored their function in Adipose-Derived human Mesenchymal Stem Cells (AD-hMSCs) differentiated to adipocytes. RESULTS: vWAT proteomics allowed us to quantify 6051 proteins. Among the candidates that most differentiate Low-INFL from Hi-INFL vWAT, we found proteins involved in adipocyte function, including adiponectin and hormone sensitive lipase, suggesting that adipocyte differentiation is enhanced in Low-INFL, as compared to Hi-INFL. The chromatin modifier SET and MYND Domain Containing 3 (SMYD3), whose function in adipose tissue was so far unknown, was another top-scored hit. SMYD3 expression was significantly higher in Low-INFL vWAT, as confirmed by western blot analysis. Using AD-hMSCs in culture, we found that SMYD3 mRNA and protein levels decrease rapidly during the adipocyte differentiation. Moreover, SMYD3 knock-down before adipocyte differentiation resulted in reduced H3K4me3 and decreased cell proliferation, thus limiting the number of cells available for adipogenesis. CONCLUSIONS: Our study describes an important role of SMYD3 as a newly discovered regulator of adipocyte precursor proliferation during the early steps of adipogenesis.

From Deutsche Zeitschrift to International journal of legal medicine-100 years of legal medicine through the lens of journal articles, Part 4: International journal of legal medicine from 1990 to 2022.

This is the fourth and final paper in a series related to the analysis of articles published in this journal during its first 100 years of activity. This article covers the time span from 1990 to 2022. It is important to note that, given the period covered by this analysis, it does not aim to provide a historical overview but rather an examination of the most recent trends in our discipline compared to the past. Between 1990 (Volume 104) and 2022 (Volume 136), 4004 articles were published in the International Journal of Legal Medicine (IJLM) across 33 volumes. This corresponds to 53% of all the articles published since the launch of the journal. When compared to the period from 1970 to 1990, some categories no longer appear to be as relevant (e.g., sexual medicine, 1 article; social medicine, 0 articles; biography, 3 articles; history, 4 articles). Conversely, the most recent period has shown an increasing importance in forensic genetics (1388 articles) and the emergence of new significant topics that merit their own classification, such as age estimation (286 articles), forensic anthropology (189 articles), forensic imaging (150 articles), and forensic entomology (90 articles).

Awareness of forensic anthropology in Switzerland: a survey among forensic practitioners, police, and prosecutors.

Forensic anthropology (FA) as a specialized discipline has been practised in multi-lingual Switzerland for over a decade. A variety of expertise regarding osteological assessments as well as facial image comparison (FIC) is provided by different centres. Nevertheless, information is lacking about the awareness of FA and its benefits for forensic investigations among forensic stakeholders. Therefore, a survey was sent to Swiss anthropologists (AN) and related professions (police officers, prosecutors, and forensic pathologists) to assess three main aspects: (1) the experience of working (biological/forensic) anthropologists within FA; (2) how FA is perceived by other professions within the legal system; and (3) identify gaps (if any) in understanding of FA with the aim to suggest avenues for improvement if necessary. The results show that awareness of FA varies by occupation and cantonal regions. In areas where close collaborations between forensic anthropologists (FAs) and other stakeholders have been formally established, be it with focus on osteological analyses or FIC, the awareness of FA competencies was superior to areas where this was not the case. An overwhelming majority of forensic actors expressed interest in continuing education related to the role of FA. These findings indicate that facilitation of communication and collaboration leads to improvement in the awareness of the competencies of FAs and their contribution to forensic investigations.

Sex estimation from coxal bones using deep learning in a population balanced by sex and age.

In the field of forensic anthropology, researchers aim to identify anonymous human remains and determine the cause and circumstances of death from skeletonized human remains. Sex determination is a fundamental step of this procedure because it influences the estimation of other traits, such as age and stature. Pelvic bones are especially dimorphic, and are thus the most useful bones for sex identification. Sex estimation methods are usually based on morphologic traits, measurements, or landmarks on the bones. However, these methods are time-consuming and can be subject to inter- or intra-observer bias. Sex determination can be done using dry bones or CT scans. Recently, artificial neural networks (ANN) have attracted attention in forensic anthropology. Here we tested a fully automated and data-driven machine learning method for sex estimation using CT-scan reconstructions of coxal bones. We studied 580 CT scans of living individuals. Sex was predicted by two networks trained on an independent sample: a disentangled variational auto-encoder (DVAE) alone, and the same DVAE associated with another classifier (Crecon). The DVAE alone exhibited an accuracy of 97.9%, and the DVAE + Crecon showed an accuracy of 99.8%. Sensibility and precision were also high for both sexes. These results are better than those reported from previous studies. These data-driven algorithms are easy to implement, since the pre-processing step is also entirely automatic. Fully automated methods save time, as it only takes a few minutes to pre-process the images and predict sex, and does not require strong experience in forensic anthropology.

Age assessment in unaccompanied minors: assessing uniformity of protocols across Europe.

Age assessment of migrants is crucial, particularly for unaccompanied foreign minors, a population facing legal, social, and humanitarian challenges. Despite existing guidelines, there is no unified protocol in Europe for age assessment.The Forensic Anthropology Society of Europe (FASE) conducted a comprehensive questionnaire to understand age estimation practices in Europe. The questionnaire had sections focusing on the professional background of respondents, annual assessment numbers, requesting parties and reasons, types of examinations conducted (e.g., physical, radiological), followed protocols, age estimation methods, and questions on how age estimates are reported.The questionnaire's findings reveal extensive engagement of the forensic community in age assessment in the living, emphasizing multidisciplinary approaches. However, there seems to be an incomplete appreciation of AGFAD guidelines. Commonalities exist in examination methodologies and imaging tests. However, discrepancies emerged among respondents regarding sexual maturity assessment and reporting assessment results. Given the increasing importance of age assessment, especially for migrant child protection, the study stresses the need for a unified protocol across European countries. This can only be achieved if EU Member States wholeheartedly embrace the fundamental principles outlined in EU Directives and conduct medical age assessments aligned with recognized standards such as the AGFAD guidelines.

The Impact of the COVID-19 Pandemic on Unassisted Suicide and Assisted Suicide Rates in French-Speaking Switzerland: Differences by Gender.

Aims: Most studies on the impact of COVID-19 have shown a decrease or no change in unassisted suicide rates, but effects on assisted suicide have not been studied. We aimed to estimate the association between the COVID-19 pandemic and both types of suicide. Methods: Between 2017 and 2021, 1280 assisted suicides and 535 unassisted suicides were recorded in three Swiss cantons. We conducted descriptive and time series analyses on monthly suicide rates, categorized by gender. Results: Among women, a decrease in assisted suicide rates was found during the acute phases of the pandemic. Among men, assisted suicide rates increased gradually from the onset of the pandemic. Regarding unassisted suicide rates, no significant change was observed in women, while in men, there was a decrease, which was larger at the end than at the onset. Conclusions: COVID-19 had contrasting effects on assisted and unassisted men and women suicide rates.

Blood proteome of acute intracranial hemorrhage in infant victims of abusive head trauma.

Abusive head trauma (AHT) is a leading cause of mortality and morbidity in infants. While the reported incidence is close to 40 cases per 100'000 births/year, misdiagnoses are commonly observed in cases with atypical, subacute, or chronic presentation. Currently, standard clinical evaluation of inflicted intracranial hemorrhagic injury (ICH) in infants urgently requires a screening test able to identify infants who need additional investigations. Blood biomarkers characteristic of AHT may assist in detecting these infants, improving prognosis through early medical care. To date, the application of innovative omics technologies in retrospective studies of AHT in infants is rare, due also to the blood serum and cerebrospinal fluid of AHT cases being scarce and not systematically accessible. Here, we explored the circulating blood proteomes of infants with severe AHT and their atraumatic controls. We discovered 165 circulating serum proteins that display differential changes in AHT cases compared with atraumatic controls. The peripheral blood proteomes of pediatric AHT commonly reflect: (i) potentially secreted proteome from injured brain, and (ii) proteome dysregulated in the system's circulation by successive biological events following acute ICH. This study opens up a novel opportunity for research efforts in clinical screening of AHT cases.

From Deutsche Zeitschrift to International Journal of Legal Medicine-100 years of legal medicine through the lens of journal articles : Part 2: Deutsche Zeitschrift für die gesamte gerichtliche Medizin from 1948 to 1969.

The interruption of the publication of the Deutsche Zeitschrift für die gesamte gerichtliche Medizin due to the war ended with volume 39 for the years 1948/1949. Until volume 66/1969, the journal appeared unchanged under the historical title. The 912 publications contained in the 28 volumes of these two decades cover topics from the main fields of forensic medicine, but also from related and unrelated disciplines. The topic-specific analysis of the publications shows a shift of the research focus in the German institutes since the post-war period. This is most evident in the decline in the number of publications from the fields of scientific and technical criminalistics as well as forensic psychiatry and psychology. An opposite trend with a significant increase in scientific papers was observed in alcohology, forensic genetics and traffic medicine. While the evaluated publications on most topics contain new findings that are still valid today, the use of blood group characteristics for forensic purposes came to an end as a result of the introduction of DNA analysis.

From Deutsche Zeitschrift to International Journal of Legal Medicine-100 years of legal medicine through the lens of journal articles : Part 3: Zeitschrift für Rechtsmedizin-Journal of Legal Medicine from 1970 to 1990.

From volume 67 (1970) onwards, the journal appeared under the new bilingual title Zeitschrift für Rechtsmedizin-Journal of Legal Medicine. The editorial board was expanded and internationalised. From 1970 to 1990, 1416 articles were published in 36 volumes. 1036 articles were in German and 380 in English. The authors of 411 articles came from non-German-speaking countries. Compared to the periods under review in the first two parts of our article series, the proportion of papers on forensic genetics increased significantly between 1970 and 1990, with a small increase in publications on the identification of unknown dead bodies. An opposite trend was observed in the articles on forensic psychiatry and psychology, sexual medicine and social medicine. This development reflects a further sharpening of the discipline's profile.

From Deutsche Zeitschrift to International Journal of Legal Medicine-100 years of legal medicine through the lens of journal articles : Part 1: Deutsche Zeitschrift für die gesamte gerichtliche Medizin from 1922 to 1944.

From its launc h in 1922 to the end of the Second World War, the Deutsche Zeitschrift für die gesamte gerichtliche Medizin spanned 38 volumes. The 1762 papers contained in those volumes reflect contemporary interests and include many papers from peripheral fields and non-medico-legal disciplines. Publications concerned with issues outside core legal medicine fields in particular allow two distinct tendencies in the development of German institutes of legal medicine to be discerned. Firstly, there is a focus on the psychological and psychiatric aspects of the discipline. Secondly, there is tendency towards a scientific-criminalistic outlook. The fatal consequences of the Nazi seizure of power in 1933 did not spare the sciences. For legal medicine, a discipline with close links to the state, it is unsurprising that fundamental changes to the political system had a significant impact on subject matter. Leaving aside articles notable principally for their ideological content, our analysis of the 38 volumes shows that the papers examined contain new insights into many subjects, some of which are still valid today.

Fatal diving: could it be an immersion pulmonary edema? Case report.

Immersion pulmonary edema is a rare, underrecognized, and potentially lethal pathology developing during scuba diving and other immersion-related activities (swimming or apnoea). Physiopathology is complex and not fully understood, but its mechanisms involve an alteration of the alveolo-capillary barrier caused by transcapillary pressure elevation during immersion, leading to an accumulation of fluid and blood in the alveolar space. Diagnosis remains a challenge for clinicians and forensic practionner. The symptoms begin during ascent, with cough, frothy sputum, and hemoptysis. Auscultation reveals signs of pulmonary edema. Pulmonary CT scan, which is the radiological exam of choice, shows ground glass opacities and interlobular thickening, eventually demonstrating a patterned distribution, likely in the anterior segments of both lungs. Apart from the support of vital functions, there is no specific treatment and hyperbaric oxygen therapy is not systematically recommended. We present a case of fatal IPE occurring in a recreational diver who unfortunately died shortly after his last dive. Diagnosis was made after complete forensic investigations including post-mortem-computed tomography, complete forensic autopsy, histological examination, and toxicological analysis.

Fatal Ogilvie's syndrome after hip surgery and review of the literature.

Ogilvie's syndrome refers to a massive dilation of the colon without mechanical obstruction. Although this syndrome is well-known in the clinical literature and may sometimes be encountered as a complication of abdominal, pelvic, or hip surgery, it has only been reported sporadically in the forensic literature. We present the case of a forensic autopsy carried out on a patient whose death was related to cecal necrosis with acute peritonitis due to Ogilvie's syndrome following hip surgery. This diagnosis was based on clinical data, post-mortem imagery, autopsy findings, histological analysis, post-mortem chemistry, and microbiological analysis. A review of the literature and possible physiopathology of this disease are performed, while focusing on medico-legal perspectives.

[Management of domestic violence by primary care physician]. / Prise en charge de la violence domestique par le médecin de premier recours.

Domestic violence is a public health problem. It would affect more than a third of women and a quarter of men in Switzerland and has a significantly impact on their physical and mental health as well as their family and socio-professional relationships. The primary care physician plays a key role in the detection and the management of victims of domestic violence. This article recalls this role and explains the methods of taking care of these victims.

La violence domestique constitue un problème de santé publique. Elle toucherait en Suisse plus d'un tiers des femmes et un quart des hommes, et a un impact considérable sur leur santé physique et mentale ainsi que sur leurs relations familiales et socioprofessionnelles. Le médecin de premier recours joue un rôle primordial dans la détection et la prise en charge des victimes de violences domestiques. Cet article rappelle ce rôle et explique les modalités de prise en charge de ces victimes.

Tympanal bone fracture in forensic practice.

A tympanal bone fracture is an uncommon complication of head trauma and is mostly associated with a mandibular or petrous bone fracture. Upon reviewing the medicolegal literature, we could not find any publications on this topic. Tympanal bone fracture may lead to chronic complications (including external auditory canal stenosis and conductive hearing loss), with an important impact in both the medical and judiciary fields (e.g., chronic disabilities with loss of income). We decided to investigate the prevalence and mechanisms of tympanal bone fractures by means of a retrospective observational study on living victims who underwent head computed tomography after blunt head trauma and clinical forensic investigation at our center. We selected 159 cases of living victims with blunt head trauma (following an assault, traffic accident, or work accident) between January 2016 and December 2020. Re-examination of head imaging revealed 12 cases of tympanal bone fracture. Seven individuals showed cranial fractures involving the petrous bone (on the same side as the tympanal bone fracture). Three individuals had a temporomandibular fracture after a fall with chin impact. Only two victims exhibited an isolated tympanal bone fracture.

Postmortem coronary artery calcium score in cases of myocardial infarction.

Sudden cardiac death (SCD) related to atherosclerotic coronary artery disease (ACAD) resulting in myocardial infarction is the most prevalent cause of death in western countries. In clinical practice, coronary artery calcium score (CACS) is considered an independent predictor of coronary events, closely related to atherosclerotic burden and is quantified radiologically by the Agatston score being calculated through computed tomography. Postmortem computed tomography (PMCT) allows the visualization and quantification of coronary calcifications before the autopsy. However, it was reported that some patients who died from severe ACAD had a zero CACS in PMCT. In this study, a retrospective evaluation of CACS in adult's myocardial infarction cases related to ACAD, with available CACS and histological slides of coronary arteries, was performed in order to gain a deeper understanding of coronary calcifications and their role in myocardial infarction cases. The CACS was calculated by using the software Smartscore 4.0 after the radiological examination on a 64-row CT unit using a specific cardiac protocol. Thirty-six cases were identified out of 582 autopsies, recorded during a 2-year study period (29 men, 7 women; age 56.3 ± 11.7). CACS was 0-10 in 5 cases (5 men, 44.8 ± 13.7), 11-100 in 8 cases (6 men, 2 women, 53.1 ± 7.7), 101-400 in 13 cases (11 men, 2 women, 57.4 ± 9.6), and > 400 in 10 cases (9 men, 1 woman, 63.1 ± 11.9). Coronary thrombosis was found in 28 cases, histologically identified as plaque erosions in 6 cases and as plaque ruptures in 22 cases. Statistical analyses showed that CACS increases significantly with age (p-value < 0.05) and does not show significant correlation with gender, body weight, body mass index, and heart weight. CACS was significantly higher in plaque ruptures than in plaque erosions (p-value < 0.01). Zero or low CACS on unenhanced PMCT cannot exclude the presence of myocardial infarction related to ACAD. This paradoxical discrepancy between imaging and autopsy findings can be explained considering the histological aspect of fatal coronary plaques.

Immunohistochemical renal expression of aquaporin 2, arginine-vasopressin, vasopressin receptor 2, and renin in saltwater drowning and freshwater drowning.

The diagnosis of drowning is considered one of the most difficult in forensic medicine. Due to the paucity of signs, it is a classical diagnosis by exclusion. For this reason, specific immunohistochemical markers would be useful. Far too little has been done to analyze in-depth the differences between SWD and FWD. We focused on the renal immunohistochemical expression of aquaporin 2, AVP, V2R, and renin in cases of drowning. This study has two purposes: (1) to better understand the differences between saltwater drowning (SWD) and freshwater drowning (FWD), which may indicate different pathophysiology and (2) to eventually identify markers useful for the diagnosis of drowning. We retrospectively investigated 10 cases of SWD gathered from the Institute of Legal Medicine in Genoa (Italy), and 10 cases of FWD from the University Center of Legal Medicine in Geneva (Switzerland). As a control group, we investigated 10 cases of death by gunshot to the head. A strong expression of AQP2 and AVP was significantly (p < 0.05) more evident in cases of SWD than in FWD and control cases. Regarding the V2R, no statistically significant differences were found between the studied groups. The renin tubular expression was particularly intense (p < 0.05) both in SWD and in FWD compared controls. According to our results, AQP2 and AVP represent potential useful markers for the differential diagnosis between SWD and other causes of death, including FWD. Renin may be a useful marker in the diagnosis of drowning but it does not allow for differentiation between FWD and SWD.

Inside the lungs of COVID-19 disease.

In the setting of the coronavirus disease 2019 (COVID-19) pandemic, only few data regarding lung pathology induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is available, especially without medical intervention interfering with the natural evolution of the disease. We present here the first case of forensic autopsy of a COVID-19 fatality occurring in a young woman, in the community. Diagnosis was made at necropsy and lung histology showed diffuse alveolar damage, edema, and interstitial pneumonia with a geographically heterogeneous pattern, mostly affecting the central part of the lungs. This death related to COVID-19 pathology highlights the heterogeneity and severity of central lung lesions after natural evolution of the disease.

Immunohistochemical expression of P-selectin, SP-A, HSP70, aquaporin 5, and fibronectin in saltwater drowning and freshwater drowning.

The diagnosis of drowning is one of the most difficult in forensic medicine. The aim of this study was to analyze pulmonary tissue reactions in death by drowning. In particular, we focused on the immunohistochemical expression of P-selectin, SP-A, HSP70, AQP-5, and fibronectin to investigate our expression in drowning and to understand whether there are differences between saltwater drowning (SWD) and freshwater drowning (FWD), which may indicate a different pathophysiology. We retrospectively investigated 10 cases of SWD (Mediterranean Sea) from the Institute of Legal Medicine of Genoa (Italy), and 10 cases of FWD (Lake of Geneva) from the University Center of Legal Medicine of Geneva (Switzerland). As control group, we examined 10 cases of death by acute external bleeding, characterized by minimal respiratory distress. As compared with controls, in SWD cases, the results showed a decrease of SP-A expression with membrane patterns. Furthermore, we observed a greater SP-A expression with granular pattern in drowning cases without statistically significant difference between SWD and FWD. For the markers AQP-5, HSP70, fibronectin, and P-selectin, no statistically significant differences were found between SWD, FWD, and controls.

Intimomedial mucoid arterial degeneration, a rare arterial disorder of forensic significance.

The body of a 43-year-old African woman with a history of aortic aneurysm and hypertension was forensically investigated after her sudden death. The cause of death was related to a cardiac tamponade due to a ruptured aneurysm of the ascending aorta. Post-mortem gross examination showed an abnormal whitish discoloration of the intima with fibrous thickening of the aortic wall. Several arteries (left main and circumflex coronaries, carotid, renal and iliac arteries) showed similar features. Upon histological examination, the aortic aneurysm as well as the other arteries sampled showed mucoid degeneration, excess mucopolysaccharides and pools of mucin inside the intima and the media associated with collagen and elastic fiber destruction and loss of smooth muscle cells. This pattern strongly suggested the diagnosis of intimomedial mucoid degeneration (IMMD), a rare arterial disorder consisting of a progressive deposition of mucin into the intima and media, with a strong prevalence in middle-aged black African females with high blood pressure. In addition to the typical features of IMMD, histological examination of the ascending aorta showed a thickening of the adventita with sparse mixed inflammatory infiltrates and fibrosis, suggesting an additional chronic infectious aortitis. No infectious agent was detected. The body of literature on IMMD is reviewed and the origin of death is discussed in this case report.

Molecular tissue changes in early myocardial ischemia: from pathophysiology to the identification of new diagnostic markers.

Diagnosing early myocardial ischemia (the initial 4 to 6 h after interruption of blood flow to part of the myocardium) remains a challenge for clinical and forensic pathologists. Several immunohistochemical markers have been proposed for improving postmortem detection of early myocardial ischemia; however, no single marker appears to be both sufficiently specific as well as sensitive. This review summarizes the diverse categories of molecular tissue markers that have been investigated in human autopsy samples with acute myocardial infarction as well as in the well-established and widely used in vivo animal model of early myocardial ischemia (permanent ligation of the coronary artery). Recently identified markers appearing during the initial 2 h of myocardial ischemia are highlighted. Among them, only six were tested for specificity (C5b-9, hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, heart fatty acid binding protein, connexin 43, and JunB). Despite the discovery of several potentially promising markers (in terms of early expression and specificity), many of them remain to be tested and validated for application in routine diagnostics in clinical and forensic pathology. In particular, research investigating the postmortem stability of these markers is required before any might be implemented into routine diagnostics. Establishing a standardized panel of immunohistochemical markers may be more useful for improving sensitivity and specificity than searching for a single marker.