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1.
Int J Legal Med ; 138(1): 295-299, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36609734

RESUMEN

In times of peace and except for terrorist attacks, fatalities by explosions are rare. Fireworks have deadly potential, especially self-made or illegally acquired devices. The use of professional pyrotechnics by untrained persons poses a life-threatening hazard. We present a case of devastating blunt force and blast injuries to the head and chest of a young man. After ignition of a display shell (syn. a real shell or mortar shell) without the use of a launching pipe, the device hit the man's face, nearly simultaneously followed by the explosion of the burst charge. The autopsy revealed injuries to the face and forehead as well as extensive tissue structure damage and a massive contusion with a bloody edema of the lungs. Autopsy results are supplemented with CT imaging and 3D reconstruction of the fractured mid face, as well as histological and toxicological examinations. This case of a misused display shell demonstrates both its devastating destructive potential and the corresponding and rarely observed injury pattern.


Asunto(s)
Traumatismos por Explosión , Terrorismo , Heridas no Penetrantes , Humanos , Traumatismos por Explosión/etiología , Traumatismos por Explosión/patología , Diagnóstico por Imagen , Heridas no Penetrantes/etiología , Pulmón/patología , Explosiones
2.
Aging (Albany NY) ; 15(23): 13593-13607, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38095608

RESUMEN

BACKGROUND: SARS-CoV-2 variants are constantly emerging with a variety of changes in the conformation of the spike protein, resulting in alterations of virus entry mechanisms. Solely omicron variants use the endosomal clathrin-mediated entry. Here, we investigate the influence of defined altered spike formations to study their impact on premature cellular senescence. METHODS: In our study, in vitro infections of SARS-CoV-2 variants delta (B.1.617.2) and omicron (B.1.1.529) were analyzed by using human primary small alveolar epithelial cells and human ex vivo lung slices. We confirmed cellular senescence in human lungs of COVID-19 patients. Hence, global gene expression patterns of infected human primary alveolar epithelial cells were identified via mRNA sequencing. RESULTS: Solely omicron variants of SARS-CoV-2 influenced the expression of cell cycle genes, highlighted by an increased p21 expression in human primary lung cells and human ex vivo lungs. Additionally, an upregulated senescence-associated secretory phenotype (SASP) was detected. Transcriptomic data indicate an increased gene expression of p16, and p38 in omicron-infected lung cells. CONCLUSIONS: Significant changes due to different SARS-CoV-2 infections in human primary alveolar epithelial cells with an overall impact on premature aging could be identified. A substantially different cellular response with an upregulation of cell cycle, inflammation- and integrin-associated pathways in omicron infected cells indicates premature cellular senescence.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/genética , Senescencia Celular , Células Epiteliales Alveolares
3.
Int J Obes (Lond) ; 47(11): 1088-1099, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37587162

RESUMEN

OBJECTIVE: Obesity is an independent risk factor for severe influenza virus and COVID-19 infections. There might be an interplay between adipose tissue and respiratory pathogens, although the mechanism is unknown. Proinflammatory factors secreted by the adipose tissue are often discussed to serve as indirect contributor to virus infection. However, the direct potential of adipose tissue to serve as a viral niche has not yet been investigated. METHODS: Two murine obesity models (DIO and ob/ob) were infected with influenza A virus (IAV) and monitored for 3 weeks. p.i. Lung and adipose tissue were harvested, and the viral load was analysed. Direct replication of IAV in vitro was investigated in human derived primary adipocytes and macrophages. The indirect impact of the secretory products of adipocytes during infection was analysed in a co-culture system with lung fibroblasts. Moreover, lung and adipose tissue was harvested from deceased patients infected with SARS-CoV-2 omicron variant. Additionally, replication of SARS-CoV-2 alpha, delta, and omicron variants was investigated in vitro in adipocytes and macrophages. RESULTS: Both murine obesity models presented high IAV titers compared to non-obese mice. Interestingly, adipose tissue adjacent to the lungs was a focal point for influenza virus replication in mice. We further detected IAV replication and antiviral response in human adipocytes. Co-cultivation of adipocytes and lung fibroblasts led to increased IL-8 concentration during infection. Though we observed SARS-CoV-2 in the thoracic adipose tissue of COVID-19 patients, no active replication was found in adipocytes in vitro. However, SARS-CoV-2 was detected in the macrophages and this finding was associated with increased inflammation. CONCLUSIONS: Our study revealed that thoracic adipose tissue contributes to respiratory virus infection. Besides indirect induction of proinflammatory factors during infection, adipocytes and macrophages within the tissue can directly support viral replication.


Asunto(s)
COVID-19 , Virus de la Influenza A , Gripe Humana , Humanos , Ratones , Animales , Pulmón , Tejido Adiposo , Virus de la Influenza A/fisiología , Obesidad
4.
Int J Legal Med ; 137(5): 1615-1627, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37395744

RESUMEN

Temperature-based time of death estimation using simulation methods such as the finite element method promise higher accuracy and broader applicability in nonstandard cooling scenarios than established phenomenological methods. Their accuracy depends crucially on the simulation model to capture the actual situation, which in turn hinges on the representation of the corpse's anatomy in form of computational meshes as well as on the thermodynamic parameters. While inaccuracies in anatomy representation due to coarse mesh resolution are known to have a minor impact on the estimated time of death, the sensitivity with respect to larger differences in the anatomy has so far not been studied. We assess this sensitivity by comparing four independently generated and vastly different anatomical models in terms of the estimated time of death in an identical cooling scenario. In order to isolate the impact of shape variation, the models are scaled to a reference size, and the possible impact of measurement location variation is excluded explicitly by finding measurement locations leading to minimum deviations. The thus obtained lower bound on the impact of anatomy on the estimated time of death shows, that anatomy variations lead to deviations of at least 5-10%.


Asunto(s)
Frío , Humanos , Temperatura , Análisis de Elementos Finitos , Simulación por Computador
5.
Biomolecules ; 13(3)2023 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-36979408

RESUMEN

In late 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the causative agent of coronavirus disease 2019 (COVID-19) emerged in China and spread rapidly around the world, causing an ongoing pandemic of global concern. COVID-19 proceeds with moderate symptoms in most patients, whereas others experience serious respiratory illness that requires intensive care treatment and may end in death. The severity of COVID-19 is linked to several risk factors including male sex, comorbidities, and advanced age. Apart from respiratory complications, further impairments by COVID-19 affecting other tissues of the human body are observed. In this respect, the human kidney is one of the most frequently affected extrapulmonary organs and acute kidney injury (AKI) is known as a direct or indirect complication of SARS-CoV-2 infection. The aim of this work was to investigate the importance of the protein angiotensin-converting enzyme 2 (ACE2) for a possible cell entry of SARS-CoV-2 into human kidney cells. First, the expression of the cellular receptor ACE2 was demonstrated to be decisive for viral SARS-CoV-2 cell entry in human AB8 podocytes, whereas the presence of the transmembrane protease serine 2 (TMPRSS2) was dispensable. Moreover, the ACE2 protein amount was well detectable by mass spectrometry analysis in human kidneys, while TMPRSS2 could be detected only in a few samples. Additionally, a negative correlation of the ACE2 protein abundance to male sex and elderly aged females in human kidney tissues was demonstrated in this work. Last, the possibility of a direct infection of kidney tubular renal structures by SARS-CoV-2 was demonstrated.


Asunto(s)
COVID-19 , Anciano , Femenino , Humanos , Masculino , Enzima Convertidora de Angiotensina 2 , Riñón/metabolismo , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , SARS-CoV-2/metabolismo
6.
Int J Legal Med ; 137(2): 427-435, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36565316

RESUMEN

The age of majority, which corresponds to the age of 18 years in most European countries, plays a crucial role for a large number of legal decisions. Accordingly, an increasing number of requests by authorities to forensic age estimation experts comprise the question of whether the age of 18 years has been reached by an individual. In recent years, novel study data suggested that magnetic resonance imaging (MRI) of the knee might likewise allow for the determination of majority beyond reasonable doubt. However, the data basis, especially concerning the distal femoral epiphysis (DFE), is still poor. For this reason, 392 routine MRI cases of the knee (204 males and 188 females of a Western Caucasian population, aged between 12 and 25 years) were retrospectively analyzed. T1-weighted and water-selective fat-saturated PD/T2-weighted sequences, generated at 1.5 and 3.0 T clinical MR scanners, were available. Ossification stages of the DFE were determined by means of the classification system by Vieth et al. (Eur Radiol 2018; 28:3255-3262). Both the intra-observer agreement and inter-observer agreement were found to be "very good" (κ = 0.899 and κ = 0.830). The present study confirmed that MRI of the DFE is suitable to determine majority in both sexes when stage 6 is present as the study revealed minimum ages above the age of 18 years for this stage (20.40 years in males and 20.60 years in females). Accordingly, the data represent a strong support for the so far existing database. Hence, the investigation of the knee using routine MRI appears to become a realistic alternative for forensic age estimation practice in the near future.


Asunto(s)
Determinación de la Edad por el Esqueleto , Osteogénesis , Masculino , Femenino , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Estudios Retrospectivos , Determinación de la Edad por el Esqueleto/métodos , Imagen por Resonancia Magnética/métodos , Epífisis/diagnóstico por imagen , Antropología Forense
7.
Int J Legal Med ; 137(2): 601-607, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36547700

RESUMEN

The reconstruction of traffic accidents involving powered two-wheelers (PTWs) frequently proves to be a challenging task. A case in which a fatal head-on crash of a PTW with a small truck where only minor vehicles damage was observed but resulted in isolated fatal chest trauma is discussed here. External examination of the corpse revealed two lacerations on the back, at the first glance implying sharp trauma. Based on the accident traces, the technical expert assumed an emergency break of the PTW rider resulting in a rotation of the PTW in terms of a wheelie on the front wheel. The first contact between the PTW rider and the tail end of the small truck probably occurred with the upper side of the helmet, and then, the back handle of the PTW caused the stab-like injuries followed by compression of the rider between the small truck or asphalt and the PTW. Based on the few accident traces available, neither a reconstruction of the pre-impact velocity nor a detailed reconstruction of the PTW rider kinematics was possible. However, using an interdisciplinary approach, the principal collision position as well as the injury mechanisms could be reconstructed.


Asunto(s)
Laceraciones , Traumatismos Torácicos , Humanos , Accidentes de Tránsito , Motocicletas , Vehículos a Motor
8.
Sci Rep ; 12(1): 20147, 2022 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-36418341

RESUMEN

In a previous article a new algorithm for fully automatic 'CT histogram based Fat Estimation and quasi-Segmentation' (CFES) was validated on synthetic data, on a special CT phantom, and tested on one corpse. Usage of said data in FE-modelling for temperature-based death time estimation is the investigation's number one long-term goal. The article presents CFES's results on a human corpse sample of size R = 32, evaluating three different performance measures: the τ-value, measuring the ability to differentiate fat from muscle, the anatomical fat-muscle misclassification rate D, and the weighted distance S between the empirical and the theoretical grey-scale value histogram. CFES-performance on the sample was: D = 3.6% for weight exponent α = 1, slightly higher for α ≥ 2 and much higher for α ≤ 0. Investigating τ, S and D on the sample revealed some unexpected results: While large values of τ imply small D-values, rising S implies falling D and there is a positive linear relationship between τ and S. The latter two findings seem to be counter-intuitive. Our Monte Carlo analysis detected a general umbrella type relation between τ and S, which seems to stem from a pivotal problem in fitting Normal mixture distributions.


Asunto(s)
Adiposidad , Humanos , Algoritmos , Cadáver , Tomografía Computarizada por Rayos X
9.
Virchows Arch ; 481(2): 139-159, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35364700

RESUMEN

The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ findings, limitations or current studies, and open questions. This article summarizes published literature and the consented experience of the nationwide network of clinical, neuro-, and forensic pathologists from 27 German autopsy centers with more than 1200 COVID-19 autopsies. The autopsy tissues revealed that SARS-CoV-2 can be found in virtually all human organs and tissues, and the majority of cells. Autopsies have revealed the organ and tissue tropism of SARS-CoV-2, and the morphological features of COVID-19. This is characterized by diffuse alveolar damage, combined with angiocentric disease, which in turn is characterized by endothelial dysfunction, vascular inflammation, (micro-) thrombosis, vasoconstriction, and intussusceptive angiogenesis. These findings explained the increased pulmonary resistance in COVID-19 and supported the recommendations for antithrombotic treatment in COVID-19. In contrast, in extra-respiratory organs, pathological changes are often nonspecific and unclear to which extent these changes are due to direct infection vs. indirect/secondary mechanisms of organ injury, or a combination thereof. Ongoing research using autopsies aims at answering questions on disease mechanisms, e.g., focusing on variants of concern, and future challenges, such as post-COVID conditions. Autopsies are an invaluable tool in medicine and national and international interdisciplinary collaborative autopsy-based research initiatives are essential.


Asunto(s)
COVID-19 , Autopsia , Humanos , Pulmón/patología , Pandemias , SARS-CoV-2
10.
Int J Legal Med ; 136(3): 777-784, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34962588

RESUMEN

Determining majority plays a key role for forensic age diagnostics in living individuals. Recent data suggest that magnetic resonance imaging (MRI) of the proximal tibial epiphysis (PTE) may be a suitable alternative or at least an additional tool to clarify whether an individual has reached majority. However, the reference data situation is still sparse. Hence, the present dual center study retrospectively analyzed routine MRI of the knee in 413 cases (214 males and 199 females) of a Western Caucasian population aged between 12 and 25 years. MRI was performed at 1.5 and 3.0 T clinical scanners using T1- and T2-weighted sequences. The classification system by Vieth et al. (Eur Radiol 2018; 28:3255-3262) was applied for determining the ossification stages of the PTE. Intra-observer agreement was "very good" (κ = 0.931), and inter-observer agreement was "good" (κ = 0.798). Minimum ages above the age of 18 years were observed with the final stage (stage 6) in either sex (20.27 years in males and 18.55 years in females). The results are not in contradiction with the previous data and can be considered a strong and valuable support of the so far existing database. Therefore, the investigation of the PTE using routine MRI (either at 1.5 or 3.0 T) could be taken into consideration for application in forensic age estimation practice in near future.


Asunto(s)
Determinación de la Edad por el Esqueleto , Epífisis , Adolescente , Adulto , Determinación de la Edad por el Esqueleto/métodos , Niño , Epífisis/anatomía & histología , Epífisis/diagnóstico por imagen , Femenino , Antropología Forense , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Osteogénesis , Estudios Retrospectivos , Tibia/anatomía & histología , Tibia/diagnóstico por imagen , Adulto Joven
11.
Insects ; 12(4)2021 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-33800533

RESUMEN

Skeletonization is often perceived as an indicator of long post-mortem intervals. The finding of feeding larvae of first colonizers, on the other hand, indicates days. We present a case in which both findings were present. Larvae of Phormia regina, aged 9 days, and skeletonization of the head and part of the thorax were both found on an unidentified female body. Identification of dentures eventually led to resolution of the case and a confession, which settled the seeming contradiction in favor of forensic entomology.

12.
Cancer Rep (Hoboken) ; 4(4): e1366, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33719186

RESUMEN

BACKGROUND: In patients diagnosed with cervical cancer, the purpose of lymphadenectomy is the removal of lymph nodes for diagnosis and potential treatment of metastasized tumor cells. It is unclear if afferent lymphatic vessels harbor tumor cells and, thus, may pose additional risk for recurrence or progression if not removed. AIM: In this feasibility study, we analyzed the lymphatic vessels afferent to sentinel lymph node (SLN) using a highly sensitive and specific molecular marker for cervical cancer cells. METHODS AND RESULTS: Twenty patients diagnosed with cervical cancer of FIGO stage IA1 to IIB2 underwent laparoscopic SLN removal. Labeling was done using patent blue and the afferent lymphatic vessels were harvested from the parametric tissue and frozen at -80°C. HPV DNA type was evaluated in the primary tumor. Lymphatic vessels afferent to the sentinel lymph nodes were analyzed for the presence of viral oncogene transcripts of the respective HPV type. In one of 18 patients, all with tumor stage ≤IBI and pN0 by conventional histopathology, HPV mRNA could be detected in two of four lymphatic vessels, whereas at least one of the lymphatic vessel biopsies of both patients with tumors ˃4 cm and pN1 status was HPV mRNA positive. No clinical correlation with recurrence after a median follow-up of 9 years was noticed. CONCLUSION: HPV mRNA indicative of disseminated tumor cells could be detected in lymphatic vessels. The relevance of harvesting lymphatic vessels afferent to SLN in order to increase oncologic safety will have to be investigated in a future prospective study.


Asunto(s)
Escisión del Ganglio Linfático/métodos , Metástasis Linfática/patología , Vasos Linfáticos/patología , Ganglio Linfático Centinela/cirugía , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Estudios de Factibilidad , Femenino , Humanos , Vasos Linfáticos/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Ganglio Linfático Centinela/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía
13.
Elife ; 102021 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-33781385

RESUMEN

Clinical observations indicate that COVID-19 is a systemic disease. An investigation of the viral distribution within the human body and its correlation with tissue damage can aid in understanding the pathophysiology of SARS-CoV-2 infection. We present a detailed mapping of the viral RNA in 61 tissues and organs of 11 deceased patients with COVID-19. The autopsies were performed within the early postmortem interval (between 1.5 and 15 hr, mean: 5.6 hr) to minimize the bias due to viral RNA and tissue degradation. Very high viral loads (>104copies/ml) were detected in most patients' lungs, and the presence of intact viral particles in the lung tissue could be verified by transmission electron microscopy. Interestingly, viral RNA was detected throughout various extrapulmonary tissues and organs without visible tissue damage. The dissemination of SARS-CoV-2-RNA throughout the body supports the hypothesis that there is a maladaptive host response with viremia and multiorgan dysfunction.


Since the discovery of the new coronavirus that causes COVID-19, scientists have been scrambling to understand the different features of the virus. While a lot more is now known about SARS-CoV-2, several key questions have proved more difficult to answer. For example, it remained unclear where the virus travels to in the body and causes the most harm. To help answer this question, Deinhardt-Emmer, Wittschieber et al. performed postmortem examinations on 11 patients who had recently died of COVID-19. After sampling 61 different organs and tissues from each patient, several tests were used to detect traces of SARS-CoV-2. The experiments showed that the largest pool of SARS-CoV-2 was present in the lungs, where it had caused severe damage to the alveolae, the delicate air sacs at the end of the lungs' main air tubes. Small amounts of the virus were also detected in other organs and tissues, but no severe tissue damage was seen. In addition, Deinhardt-Emmer, Wittschieber et al. found that each patient had increased levels of some of the proteins involved in inflammation and blood clotting circulating their bloodstream. This suggests that the inflammation caused by SARS-CoV-2 leads to an excessive immune reaction throughout the entire body. This research provides important new insights into which areas of the body are most impacted by SARS-CoV-2. These findings may help to design more effective drug treatments that target the places SARS-CoV-2 is most likely to accumulate and help patients fight off the infection at these regions.


Asunto(s)
Autopsia , COVID-19/patología , SARS-CoV-2/aislamiento & purificación , Anciano , Anciano de 80 o más Años , COVID-19/sangre , COVID-19/inmunología , COVID-19/terapia , Causas de Muerte , Comorbilidad , Femenino , Humanos , Inflamación/sangre , Inflamación/inmunología , Pulmón/patología , Pulmón/virología , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , ARN Viral/sangre , Carga Viral
14.
Histopathology ; 78(5): 727-737, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33067892

RESUMEN

AIMS: Haemophagocytosis in the bone marrow of patients who have succumbed to coronavirus disease 19 (COVID-19) has not been widely studied. The aims of the present study were to perform morphological analyses and morphometry of haemophagocytosis in the bone marrow of patients with severe COVID-19, and to correlate the findings with the clinical course of the disease. METHODS AND RESULTS: In this single-centre study performed at the University Hospital Jena, bone marrow specimens of 15 deceased patients who had experienced a severe course of COVID-19 were sampled from the vertebral column during autopsy. Slides of the bone marrow were stained with routine stains or immunohistochemically, and further examined for haemophagocytosis by the use of light microscopy. To substantiate the morphological findings, additional slides were stained for CD163 and morphometry was performed. In all bone marrow samples, an increase in cellularity was found. Haemophagocytes with erythrophagocytosis were detected in 67% of the deceased patients. In tissues with low numbers of haemophagocytes or ill-defined haemophagocytes, an increase in iron deposits was frequently seen. Morphological findings were then correlated with several important clinical data, and the HScore (probability of having a reactive hemophagocytic syndrome) was calculated to posthumously confirm the diagnosis of secondary haemophagocytic lymphohistiocytosis. The median duration of disease and the hospitalisation time were lower in patients with haemophagocytosis (n = 10) than in patients without haemophagocytosis (n = 5). In addition, patients with haemophagocytes showed increased inflammatory parameters 2-5 days prior to death, in contrast to patients without haemophagocytes. CONCLUSIONS: Haemophagocytosis is a common finding in the bone marrow of deceased individuals with severe COVID-19, and may indicate fatal severe acute respiratory syndrome coronavirus 2 infections.


Asunto(s)
COVID-19/virología , Linfohistiocitosis Hemofagocítica/virología , SARS-CoV-2/fisiología , Anciano , Anciano de 80 o más Años , Autopsia , Médula Ósea/patología , Médula Ósea/virología , COVID-19/complicaciones , COVID-19/patología , Femenino , Hospitalización , Humanos , Inmunohistoquímica , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/patología , Masculino , Persona de Mediana Edad
15.
ESC Heart Fail ; 7(5): 2305-2317, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32619089

RESUMEN

AIMS: Dendritic cells (DCs) are central mediators of adaptive immunity, and there is growing evidence of their role in myocardial inflammatory disease. We hypothesized that plasmacytoid and myeloid DCs are involved in the mechanisms of myocarditis and analysed these two main subtypes in human myocarditis subjects, as well as in a murine model of experimental autoimmune myocarditis (EAM). METHODS AND RESULTS: Circulating DCs were analysed by flow cytometry in patients with acute myocarditis, dilated cardiomyopathy, and controls. Myocardial biopsies were immunostained for the presence of DCs and compared with non-diseased controls. In a mouse model of acute myocarditis induced through synthetic cardiac myosine peptide injection, effects of immunomodulation including DC inhibition through MCS-18 versus placebo treatment were tested at the peak of inflammation (Day 21), as well as 1 week later (partial recovery). Circulatory pDCs and mDCs were significantly reduced in myocarditis patients compared with controls (P < 0.01 for both) and remained so even after 6 months of follow-up. Human myocarditis biopsies showed accumulation of pDCs (two-fold CD304+/three-fold CD123+, all P < 0.05) compared with controls. Myocardial pDCs and mDCs accumulated in EAM (P for both <0.0001). MCS-18 treatment reduced pDC levels (P = 0.009), reduced myocardial inflammation (myocarditis score reduction from 2.6 to 1.8, P = 0.026), and improved ejection fraction (P = 0.03) in EAM at Day 21 (peak of inflammation). This effect was not observed during the partial recovery of inflammation on Day 28. CONCLUSIONS: Circulating DCs are reduced in human myocarditis and accumulate in the inflamed myocardium. MCS-18 treatment reduces DCs in EAM, leading to amelioration of inflammation and left ventricular remodelling during the acute phase of myocarditis. Our data further elucidate the role of DCs and their specific subsets in acute inflammatory cardiomyopathies.


Asunto(s)
Cardiomiopatía Dilatada , Miocarditis , Animales , Células Dendríticas , Humanos , Inflamación , Ratones , Miocardio
16.
Leukemia ; 34(3): 771-786, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31690822

RESUMEN

The proximal DNA damage response kinase ATM is frequently inactivated in human malignancies. Germline mutations in the ATM gene cause Ataxia-telangiectasia (A-T), characterized by cerebellar ataxia and cancer predisposition. Whether ATM deficiency impacts on tumor initiation or also on the maintenance of the malignant state is unclear. Here, we show that Atm reactivation in initially Atm-deficient B- and T cell lymphomas induces tumor regression. We further find a reduced T cell abundance in B cell lymphomas from Atm-defective mice and A-T patients. Using T cell-specific Atm-knockout models, as well as allogeneic transplantation experiments, we pinpoint impaired immune surveillance as a contributor to cancer predisposition and development. Moreover, we demonstrate that Atm-deficient T cells display impaired proliferation capacity upon stimulation, due to replication stress. Altogether, our data indicate that T cell-specific restoration of ATM activity or allogeneic hematopoietic stem cell transplantation may prevent lymphomagenesis in A-T patients.


Asunto(s)
Linfoma/inmunología , Linfocitos T/inmunología , Alelos , Animales , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proliferación Celular , Etopósido/farmacología , Trasplante de Células Madre Hematopoyéticas , Linfoma/metabolismo , Ratones , Ratones Noqueados , Linfocitos T/metabolismo , Trasplante Homólogo , Resultado del Tratamiento
17.
Forensic Sci Int ; 290: 189-195, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30081326

RESUMEN

Temperature based death time estimation (TDE) is severely limited in situations where body core temperature has almost decreased to ambient temperature. The TDE method of Marshall/Hoare and Henßge (MHH) defines a lower bound TK for body core temperature below which the time p.m. should be stated to be >10h only. A recent study (Potente et al., 2017 [10]) established a new method, called variance-bias-tradeoff (VBT) complementing MHH in constructing a right-side-half-infinite 97.5%-confidence interval for such 'near equilibrium'-situations. It seemingly proved the validity for all body core temperatures T

Asunto(s)
Intervalos de Confianza , Modelos Estadísticos , Cambios Post Mortem , Temperatura Corporal , Medicina Legal/métodos , Humanos , Temperatura
18.
Rofo ; 190(12): 1152-1158, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29913524

RESUMEN

PURPOSE: In forensic odontology the comparison between antemortem and postmortem panoramic radiographs (PRs) is a reliable method for person identification. The purpose of this study was to improve and automate identification of unknown people by comparison between antemortem and postmortem PR using computer vision. MATERIALS AND METHODS: The study includes 43 467 PRs from 24 545 patients (46 % females/54 % males). All PRs were filtered and evaluated with Matlab R2014b including the toolboxes image processing and computer vision system. The matching process used the SURF feature to find the corresponding points between two PRs (unknown person and database entry) out of the whole database. RESULTS: From 40 randomly selected persons, 34 persons (85 %) could be reliably identified by corresponding PR matching points between an already existing scan in the database and the most recent PR. The systematic matching yielded a maximum of 259 points for a successful identification between two different PRs of the same person and a maximum of 12 corresponding matching points for other non-identical persons in the database. Hence 12 matching points are the threshold for reliable assignment. CONCLUSION: Operating with an automatic PR system and computer vision could be a successful and reliable tool for identification purposes. The applied method distinguishes itself by virtue of its fast and reliable identification of persons by PR. This Identification method is suitable even if dental characteristics were removed or added in the past. The system seems to be robust for large amounts of data. KEY POINTS: · Computer vision allows an automated antemortem and postmortem comparison of panoramic radiographs (PRs) for person identification.. · The present method is able to find identical matching partners among huge datasets (big data) in a short computing time.. · The identification method is suitable even if dental characteristics were removed or added.. CITATION FORMAT: · Heinrich A, Güttler F, Wendt S et al. Forensic Odontology: Automatic Identification of Persons Comparing Antemortem and Postmortem Panoramic Radiographs Using Computer Vision. Fortschr Röntgenstr 2018; 190: 1152 - 1158.


Asunto(s)
Inteligencia Artificial , Odontología Forense/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Radiografía Panorámica/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Niño , Conjuntos de Datos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
19.
Int J Legal Med ; 132(2): 563-577, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29335777

RESUMEN

Post-mortem body cooling is the foundation of temperature-based death time estimations (TDE) in homicide cases. Forensic science generally provides two types of p.m. body cooling models, the phenomenological and the physical models. Since both of them have to implement important individual parameters like the quantity of abdominal fat explicitly or implicitly, a more exact quantification and localization of abdominal fat is a desideratum in TDE. Particularly for the physical models, a better knowledge of the abdominal fat distribution could lead to relevant improvements in TDEs. Modern imaging methods in medicine like computed tomography (CT) are opening up the possibility to register the quantity and spatial distribution of body fat in individual cases with unprecedented precision. Since a CT-scan of an individual's abdominal region can comprise 1000 slices as an order of magnitude, it is evident that their evaluation for body fat quantification and localization needs fully automated algorithms. The paper at hand describes the development and validation of such an algorithm called "CT-histogram-based fat estimation and quasi-segmentation" (CFES). The approach can be characterized as a weighted least squares method dealing with the gray value histogram of single CT-slices only. It does not require any anatomical a priori information nor does it perform time-consuming feature detection on the CT-images. The processing result consists in numbers quantifying the amount of abdominal body fat and of muscle-, organ-, and connective tissue. As a by-product, CFES generates a quasi-segmentation of the slices processed differentiating fat from muscle-, organ-, and connective tissue. The tool is validated on synthetic data and on CT-data of a special phantom. It was also applied on a CT-scan of a dead body, where it produced anatomically plausible results.


Asunto(s)
Grasa Abdominal/diagnóstico por imagen , Algoritmos , Fantasmas de Imagen , Tomografía Computarizada por Rayos X , Adulto , Temperatura Corporal , Patologia Forense , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Cambios Post Mortem
20.
Insects ; 8(2)2017 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-28524106

RESUMEN

Differences in growth rate of forensically important dipteran larvae make species determination an essential requisite for an accurate estimation of time since colonization of the body. Interspecific morphological similarities, however, complicate species determination. Muscle attachment site (MAS) patterns on the inside of the cuticula of fly larvae are species specific and grow proportionally with the animal. The patterns can therefore be used for species identification, as well as age estimation in forensically important dipteran larvae. Additionally, in species where determination has proven to be difficult-even when employing genetic methods-this easy and cheap method can be successfully applied. The method was validated for a number of Calliphoridae, as well as Sarcophagidae; for Piophilidae species, however, the method proved to be inapt. The aim of this article is to assess the utility of the MAS method for applications in forensic entomology. Furthermore, the authors are currently engineering automation for pattern acquisition in order to expand the scope of the method. Automation is also required for the fast and reasonable application of MAS for species determination. Using filters on digital microscope pictures and cross-correlating them within their frequency range allows for a calculation of the correlation coefficients. Such pattern recognition permits an automatic comparison of one larva with a database of MAS reference patterns in order to find the correct, or at least the most likely, species. This facilitates species determination in immature stages of forensically important flies and economizes time investment, as rearing to adult flies will no longer be required.

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