Identification of Umbre Orthobunyavirus as a Novel Zoonotic Virus Responsible for Lethal Encephalitis in 2 French Patients with Hypogammaglobulinemia.

BACKGROUND: Human encephalitis represents a medical challenge from a diagnostic and therapeutic point of view. We investigated the cause of 2 fatal cases of encephalitis of unknown origin in immunocompromised patients. METHODS: Untargeted metatranscriptomics was applied on the brain tissue of 2 patients to search for pathogens (viruses, bacteria, fungi, or protozoans) without a prior hypothesis. RESULTS: Umbre arbovirus, an orthobunyavirus never previously identified in humans, was found in 2 patients. In situ hybridization and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) showed that Umbre virus infected neurons and replicated at high titers. The virus was not detected in cerebrospinal fluid by RT-qPCR. Viral sequences related to Koongol virus, another orthobunyavirus close to Umbre virus, were found in Culex pipiens mosquitoes captured in the south of France where the patients had spent some time before the onset of symptoms, demonstrating the presence of the same clade of arboviruses in Europe and their potential public health impact. A serological survey conducted in the same area did not identify individuals positive for Umbre virus. The absence of seropositivity in the population may not reflect the actual risk of disease transmission in immunocompromised individuals. CONCLUSIONS: Umbre arbovirus can cause encephalitis in immunocompromised humans and is present in Europe.

Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study.

Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1-3 arose in older children (median ages 5.2-14.0 years) and had intermediate to excellent survival (5-year OS of 68.0-100%), while Group RB and MYC PB patients were much younger (median age 1.3-1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors.

Structural and Biomechanical Characterization of a Scaffold-Free Skin Equivalent Model via Biophysical Methods.

AIMS: Among in vitro skin models, the scaffold-free skin equivalent (SFSE), without exogenous material, is interesting for pharmacotoxicological studies. Our aim was to adapt in vivo biophysical methods to study the structure, thickness, and extracellular matrix of our in vitro model without any chemical fixation needed as for histology. METHODS: We evaluated 3 batches of SFSE and characterized them by histology, transmission electron microscopy (TEM), and immunofluorescence. In parallel, we investigated 3 biophysical methods classically used for in vivo evaluation, optical coherence tomography (OCT), and laser scanning microscopy (LSM) imaging devices as well as the cutometer suction to study the biomechanical properties. RESULTS: OCT allowed the evaluation of SFSE total thickness and its different compartments. LSM has a greater resolution enabling an evaluation at the cell scale and the orientation of collagen fibers. The viscoelasticity measurement by cutometry was possible on our thin skin model and might be linked with mature collagen bundles visible in TEM and LSM and with elastic fibers seen in immunofluorescence. CONCLUSION: Our data demonstrated the simplicity and sensitivity of these different in vivo biophysical devices on our thin skin model. These noninvasive tools allow to study the morphology and the biomechanics of in vitro models.

Noonan syndrome, PTPN11 mutations, and brain tumors. A clinical report and review of the literature.

Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus. He developed epilepsy 2 years later. The temporal tumor was surgically resected because of increasing crises and worsening radiological signs. Microscopy showed nodules with specific glioneuronal elements or glial nodules, leading to the diagnosis of dysembryoplastic neuroepithelial tumor (DNT). Immunohistochemistry revealed positive nuclear staining with Olig2 and pERK in small cells. SHP2 plays a key role in RAS/MAPK pathway signaling which controls several developmental cell processes and oncogenesis. An amino-acid substitution in the N-terminal SHP2 domain disrupts the self-locking conformation and leads to ERK activation. Glioneuronal tumors including DNTs and pilocytic astrocytomas have been described in NS. This report provides further support for the relation of DNTs with RASopathies and for the implication of RAS/MAPK pathways in sporadic low-grade glial tumors including DNTs. © 2017 Wiley Periodicals, Inc.

Detection of glass particles on bone lesions using SEM-EDS.

The problem of identifying the wounding agent in forensic cases is recurrent. Moreover, when several tools are involved, distinguishing the origin of lesions can be difficult. Scanning electron microscopy (SEM)/energy dispersive X-ray analysis (EDS) equipment is increasingly available to the scientific and medical community, and some studies have reported its use in forensic anthropology. However, at our knowledge, no study has reported the use of SEM-EDS in forensic cases involving glass tools, whether in case reports or experiments. We performed an experimental study on human rib fragments, on which we manually created wounds using fragments of window and mirror glass. SEM-EDS was executed on samples without any further preparation on low vacuum mode, then on the same samples after defleshing them completely by boiling them. Window and mirror glass particles were detected on experimental wounds. Both had silica in their spectra, and the opaque side of the mirror contained titanium, allowing for their identification. Boiling and defleshing the bone samples involved a loss of information in terms of the number of wounds detected as positive for glass particles and in the number of glass particles detected, for both window and mirror glass. We suggest the analysis of wounds with suspected glass particles using low vacuum mode and with no defleshment by boiling.

Infantile Hemangioma of the Posterior Fossa in a Newborn: Early Management and Long-Term Follow-up.

A 21-day-old male infant was admitted with signs of intracranial hypertension. Brain magnetic resonance imaging (MRI) revealed a voluminous mass in the posterior fossa with an intense peripheral enhancement on T1 images with gadolinium. The child was treated secondarily by surgical decompression of the posterior fossa and the lesion was biopsied. The pathological findings indicated infantile hemangioma. Treatment with oral prednisolone was initiated at 3 months, given the lack of tumor involution. Six months after corticotherapy was stopped, repeated MRIs indicated a significant reduction in tumor size and then complete disappearance. Psychometric evaluation was performed at the age of 15 years, showing heterogeneous cognitive disabilities, with verbal abilities superior to nonverbal abilities and delayed motor development. Neurological examination was normal with no focal deficit. To our knowledge, this is the first published case reporting the long-term evolution of a patient with neonatal intracerebral hemangioma. We conclude that psychometric evaluations should be part of the long-term follow-up of children who have had an intracranial capillary hemangioma.

Loss of Somatostatin Receptor Subtype 2 Promotes Growth of KRAS-Induced Pancreatic Tumors in Mice by Activating PI3K Signaling and Overexpression of CXCL16.

BACKGROUND & AIMS: The KRAS gene is mutated in most pancreatic ductal adenocarcinomas (PDAC). Expression of this KRAS oncoprotein in mice is sufficient to initiate carcinogenesis but not progression to cancer. Activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) is required for KRAS for induction and maintenance of PDAC in mice. The somatostatin receptor subtype 2 (sst2) inhibits PI3K, but sst2 expression is lost during the development of human PDAC. We investigated the effects of sst2 loss during KRAS-induced PDAC development in mice. METHODS: We analyzed tumor growth in mice that expressed the oncogenic form of KRAS (KRAS(G12D)) in pancreatic precursor cells, as well as sst2+/- and sst2-/-, and in crossed KRAS(G12D);sst2+/- and KRAS(G12D);sst2-/- mice. Pancreatic tissues and acini were collected and assessed by histologic, immunoblot, immunohistochemical, and reverse-transcription polymerase chain reaction analyses. We also compared protein levels in paraffin-embedded PDAC samples from patients vs heathy pancreatic tissues from individuals without pancreatic cancer. RESULTS: In sst2+/- mice, PI3K was activated and signaled via AKT (PKB; protein kinase B); when these mice were crossed with KRAS(G12D) mice, premalignant lesions, tumors, and lymph node metastases developed more rapidly than in KRAS(G12D) mice. In crossed KRAS(G12D);sst2+/- mice, activation of PI3K signaling via AKT resulted in activation of nuclear factor-κB (NF-κB), which increased KRAS activity and its downstream pathways, promoting initiation and progression of neoplastic lesions. We found this activation loop to be mediated by PI3K-induced production of the chemokine CXCL16. Administration of a CXCL16-neutralizing antibody to KRAS(G12D) mice reduced activation of PI3K signaling to AKT and NF-κB, blocking carcinogenesis. Levels of CXCL16 and its receptor CXCR6 were significantly higher in PDAC tissues and surrounding acini than in healthy pancreatic tissues from mice or human beings. In addition, expression of sst2 was progressively lost, involving increased PI3K activity, in mouse lesions that expressed KRAS(G12D) and progressed to PDAC. CONCLUSIONS: Based on analyses of mice, loss of sst2 from pancreatic tissues activates PI3K signaling via AKT, leading to activation of NF-κB, amplification of oncogenic KRAS signaling, increased expression of CXCL16, and pancreatic tumor formation. CXCL16 might be a therapeutic target for PDAC.

Clinical, pathological, and molecular data on desmoplastic/nodular medulloblastoma: case studies and a review of the literature.

The aim of this study was to better define the clinical and biopathological features of patients with desmoplastic/nodular medulloblastoma (DNMB) and to further characterize this subgroup. 17 children aged < 5 years, with initial DNMB treated according to the HIT-SKK protocol, were evaluated. A retrospective central radiological review, a pathological and immunohistochemical study, and array-CGH and sequencing of germline SUFU and PTCH1 genes were performed. 15 histologically reviewed cases were confirmed as DNMB including three cases of medulloblastoma with extensive nodularity. Median age at diagnosis was 26 months. Radiology showed five cases with a vermis location and one with T2 hyperintensity. All cases showed a SHH immunoprofile. A 9q deletion was found in 6 cases, a MYCN-MYCL amplification in 1 case, and a SUFU germline mutation in 1 case (/9). The presence of SUFU and PTCH1 germline mutations agreed with previous reports. At 3 years, progression-free survival and overallsurvival rates were 72 ± 15% and 85 ± 10%, respectively. The rate of recurrence was relatively high (4 patients). This may have been because chemotherapy was delayed in two cases. Age > 3 years, and residual tumor may also have been an explanation for recurrence.

Embryonal tumors with multilayered rosettes in children: the SFCE experience.

PURPOSES: The purpose of this study was to retrospectively study embryonal tumors with multilayered rosettes (ETMR), a rare new entity that gathers ETAN-TR (embryonal tumor with abundant neuropil and true rosettes), ependymoblastomas, and medulloepitheliomas, in order to improve their descriptions and try to better define therapeutic modalities. METHODS: Patients with ETMR, ETAN-TR, ependymoblastoma, and medulloepithelioma treated in SFCE centres (Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'adolescent) since 2000 were collected. Data were retrieved from clinical charts. RESULTS: Thirty-eight patients were included in the analysis. Seventeen had an ETAN-TR, 13 had a medulloepithelioma, and 8 had an ETMR. No ependymoblastoma was included. The median age at diagnosis was 31 months (range, 2.8-141 months). The predominant tumor location was supratentorial (66%); 18.4% patients had metastatic lesion. LIN28A expression was positive in 11/11 patients. Amplification of the locus 19q13.42 was positive in 10/12 patients. Thirty patients were treated according to the primitive neuroectodermal tumors of high risk (PNET-HR) protocol. The median time of follow-up was 0.9 years (range 0.1 to 15.3 years). The 1-year event-free survival (EFS) and overall survival (OS) were, respectively, 36% CI 95% (23-55) and 45% CI 95% (31-64). On multivariate analysis, complete surgical resection, radiotherapy, and high-dose chemotherapy were associated with a better overall survival with a relative risk of, respectively, 7.9 CI 95% (2.6-23.5) p < 0.0002, 41.8 CI 95% (9.4-186) p < 0.0001, and 3.5 CI 95% (1.3-9.5) p = 0.012. CONCLUSION: Prognosis of ETMR remains dismal despite multimodal therapy. LIN28A immunostaining and 19q13.42 amplification should be systematically done to secure the diagnosis. Complete surgical resection, radiotherapy, and high-dose chemotherapy are associated with better outcome.

Improving the cytological diagnosis of intraocular lymphoma from vitreous fluid.

AIMS: To improve the cytological diagnosis of retinal lymphoma on vitreous fluid using improved cell collection and systematic analyses. METHODS AND RESULTS: Since October 2010, we have developed and optimized in our department a method with which to perform the diagnosis of retinal lymphoma. The vitreous sample was collected in a tube containing RPMI-1640 medium, decomplemented fetal bovine serum, and gentamicin. The transport and technical steps were performed at 4°C. Systematically, cytological examination with May-Grünwald-Giemsa staining and immunocytochemistry (mainly anti-CD3, anti-CD20 and anti-CD68 antibodies) were performed on cytospins. Whenever possible, determination of B-cell clonality, flow cytometry and determination of the interleukin (IL)-10/IL-6 ratio were performed. From October 2010 to June 2013, with this optimized protocol, 38 vitreous cytological samples from 32 patients were analysed, and a final diagnosis was possible, avoiding a biopsy, in all cases except one. CONCLUSION: The preservation of vitreous fluid cells on culture medium led to the diagnosis of retinal lymphoma in 10 of 12 cases, and exclusion of this diagnosis in 26 cases. This protocol may be applied even when the delay in shipping from the surgery to the pathology departments exceeds 1 h.

A comparative immunohistochemistry study of diagnostic tools in salivary gland tumors: usefulness of mammaglobin, gross cystic disease fluid protein 15, and p63 cytoplasmic staining for the diagnosis of mammary analog secretory carcinoma?

BACKGROUND: Mammary analog secretory carcinoma (MASC) of the salivary gland has been recently described according to morphological, immunohistochemical, and molecular (ETV6-NTRK3 translocation) similarities with the mammary secretory carcinoma. The most important differential diagnostic considerations of MASC are low-grade adenocarcinoma not otherwise specified (NOS), cystadenocarcinoma, and acinic cell carcinoma (AciCC). These tumors may share an overlapping morphology with MASC, and additional immunohistochemical studies are required to reinforce the diagnosis. Mammaglobin, GCDFP-15, and p63 staining have been reported in MASC. Our study was designed to check the specificity of these antibodies in MASC compared to other frequent tumors of salivary glands. METHODS: A series of 62 salivary gland tumors [10 MASCs, 5 adenocarcinomas NOS and 2 cystadenocarcinomas with MASC features and without ETV6 rearrangement, one low-grade cribriform cystadenocarcinoma (LGCCC), 9 AciCCs, 10 MECs, 10 adenoid cystic carcinomas (AdeCCs), 5 polymorphous low-grade adenocarcinomas (PLGAs), and 10 pleomorphic adenomas (PAs)] was analyzed by immunohistochemistry with mammaglobin, GCDFP-15, and p63 antibodies. RESULTS: Positivity for mammaglobin was observed in all MASCs, cystadenocarcinomas, LGCCC, and PLGAs, in some adenocarcinomas NOS, PAs, and MECs, rarely in AciCCs and never in AdeCCs. Positivity for GCDFP-15 was observed in most of the tumor types except in AdeCCs. Interestingly, cytoplasmic positivity for p63 was observed in most of MASCs and PLGAs while rarely in adenocarcinomas NOS and PAs, and never in the other tumor types. CONCLUSION: Our study revealed the usefulness of mammaglobin and p63 cytoplasmic staining to define which tumors are worth to be screened for ETV6 rearrangement.

Ephrin-B1 is a novel specific component of the lateral membrane of the cardiomyocyte and is essential for the stability of cardiac tissue architecture cohesion.

RATIONALE: Cardiac tissue cohesion relying on highly ordered cardiomyocytes (CM) interactions is critical because most cardiomyopathies are associated with tissue remodeling and architecture alterations. OBJECTIVE: Eph/ephrin system constitutes a ubiquitous system coordinating cellular communications which recently emerged as a major regulator in adult organs. We examined if eph/ephrin could participate in cardiac tissue cyto-organization. METHODS AND RESULTS: We reported the expression of cardiac ephrin-B1 in both endothelial cells and for the first time in CMs where ephrin-B1 localized specifically at the lateral membrane. Ephrin-B1 knock-out (KO) mice progressively developed cardiac tissue disorganization with loss of adult CM rod-shape and sarcomeric and intercalated disk structural disorganization confirmed in CM-specific ephrin-B1 KO mice. CMs lateral membrane exhibited abnormal structure by electron microscopy and notably increased stiffness by atomic force microscopy. In wild-type CMs, ephrin-B1 interacted with claudin-5/ZO-1 complex at the lateral membrane, whereas the complex disappeared in KO/CM-specific ephrin-B1 KO mice. Ephrin-B1 deficiency resulted in decreased mRNA expression of CM basement membrane components and disorganized fibrillar collagen matrix, independently of classical integrin/dystroglycan system. KO/CM-specific ephrin-B1 KO mice exhibited increased left ventricle diameter and delayed atrioventricular conduction. Under pressure overload stress, KO mice were prone to death and exhibited striking tissue disorganization. Finally, failing CMs displayed downregulated ephrin-B1/claudin-5 gene expression linearly related to the ejection fraction. CONCLUSIONS: Ephrin-B1 is necessary for cardiac tissue architecture cohesion by stabilizing the adult CM morphology through regulation of its lateral membrane. Because decreased ephrin-B1 is associated with molecular/functional cardiac defects, it could represent a new actor in the transition toward heart failure.

Modeling and determination of directionality of the kerf in epifluorescence sharp bone trauma analysis.

Characteristics of sharp bone trauma can be extremely useful to determine the origin of cut marks and to provide information regarding the context of death. Using human ribs and clavicle bones, this study analyzes the characteristics of bone kerfs made by different bladed implements, thanks to epifluorescence macroscopy. This technique, which is a nondestructive tool that uses autofluorescence of bones, documents bone damage precisely with high resolution. Both qualitative and quantitative criteria are analyzed. Our results identify unique class characteristics on bone lesions, allowing modeling kerf depending on the weapon, regardless of the type of bone that is wounded. Moreover, we demonstrate for the first time microscopic criteria of directionality, using fluorescence excitation. Orientation of cracks, flakes, and lateral pushing back especially helps in determining the tip and the end of the lesion, leading to the position of the aggressor. Kerf wall characteristics and striation location are also very useful. Epifluorescence macroscopy could be a new tool of choice in anthropology through cut mark analysis in establishing how the blade was used and providing details about the blow.

Embryonal tumor with multilayered rosettes: diagnostic tools update and review of the literature.

Embryonal tumor with multilayered rosettes (ETMR), including embryonal tumor with abundant neuropil and true rosettes (ETANTR), and ependymoblastoma (EBL) constitute a distinct entity of the primitive neuroectodermal tumor (PNET) family. The presence of a focal amplification at chromosome region 19q13.42 associated with an up-regulation of the oncogenic miRNA cluster C19MC suggests that they may represent a histological spectrum of a single biological entity. Their histopathological spectrum is wide, including medulloepithelioma, their location may be supra- or infra-tentorial, their prognosis is poor. Recent data on molecular subgroups of PNETs have led to new insights on diagnosis and treatment of these tumors. Subsequently, LIN28A immunoexpression was identified as a highly specific marker for ETMR. In this study, we report 4 cases diagnosed initially as ETANTR with CGH-array data, including 19q13.42 gain with absence of other amplicons, particularly of the MYC gene family, and inconstant gain of whole chromosome 2. Immunohistochemical positive expression of LIN28A and absence of Olig2 expression were observed. We summarize the literature on ETMR, pointing out on the nosological evolution of this entity and the findings on genetic hallmarks of this particular tumor. Our results emphasize the usefulness of immunohistochemistry as a highly sensitive and fast diagnostic tool for ETMR and for genetic data, especially for 19q13.42 locus. Biological features may offer new therapeutic options for these embryonal tumors that do not usually respond to conventional treatments of PNETs.

[National network of paediatric central nervous system tumours reviewing by the Groupe d'Étude de Neuropathologie Oncologique Pediatrique (GENOP)]. / Réseau de relecture des tumeurs pédiatriques du système nerveux central par le Groupe d'étude de neuropathologie oncologique pédiatrique (GENOP).

Diagnosis of paediatric tumours of the central nervous system is often difficult because WHO classification criteria are mainly defined for adults tumours and do not always apply to their paediatric counterparts. These tumours are rare (400 cases/year among more than 50 pathological subtypes per year in France). Pathological diagnosis may be a challenge for a general pathologist with a too low number of paediatric cases in his recruitment. Hence, a reference group of paediatric neuropathologists was formed (GENOP) on the behalf of the comité "Tumeurs Cérébrales" de la Société Française de lutte contre les Cancers de l'Enfant. This network is supported by the Institut National du Cancer (INCa). GENOP aim is to structure a centralised review of paediatric central nervous system tumours in order to harmonise neuropathological diagnosis at the national level and enhance patients care. Cases assessed during the last 3 years led GENOP to better identify tumours subtypes for which there is a diagnostic challenge. A set of immunohistochemical or molecular specialised techniques was developed, leading to an increased diagnostic accuracy. It allowed a better distinction between diffuse and circumscribed glioma, a better recognition of glioneuronal differentiation and a better subtyping of embryonal tumours such as medulloblastomas. Inter-observer agreement varied according to the tumour subtypes.

Activation of pro-oncogenic pathways in colorectal hyperplastic polyps.

BACKGROUND: In contrast to sessile serrated adenomas and traditional serrated adenomas which are associated with a significant cancer risk, the role of hyperplastic polyps (HP) in colorectal carcinogenesis as well as the molecular mechanisms underlying their development remain controversial and still need to be clarified. Several reports suggest that a subset of HP may represent precursor lesions of some colorectal cancers. However, biomarkers are needed to identify the subset of HP that may have a malignant potential. The hormone precursor, progastrin (PG) has been involved in colon carcinogenesis and is known to activate pro-oncogenic pathways such as the ERK or the STAT3 pathway. We therefore analyzed PG expression and the activation of these signaling factors in HP. METHODS: We retrospectively analyzed PG expression as well as the phosphorylation of ERK and STAT3 by immunohistochemistry in HP from 48 patients. RESULTS: Mean percentages of epithelial cells positive for PG or phospho-ERK were respectively, 31% and 33% in HP and were significantly higher in these lesions compared to normal colon (3%, p=0.0021 and 7%, p=0.0008, respectively). We found a significant correlation between PG and phospho-ERK expression in HP with ERK activation significantly stronger in lesions with high progastrin expression (p=0.015). In contrast, STAT3 was not significantly activated in HP compared to normal colon and we did not observe a significant correlation with PG expression. CONCLUSIONS: HP overexpressing PG that have the highest activation of the ERK pathway might reflect less latent lesions that might have a malignant potential.

Deciphering the elusive nature of sharp bone trauma using epifluorescence macroscopy: a comparison study multiplexing classical imaging approaches.

Characterization of sharp-force trauma on human bones can be extremely useful in providing information regarding the nature and context of death. Nevertheless, in the identification of weapons used to cause sharp-force trauma and analysis of bone wounds, challenging tasks still remain. Current analysis attempting to dissect bone wound characteristics varied quite a lot and mixed different criteria, thus leading sometimes to conflicting results. In this context, the aim of our study is to clarify qualitative aspects of cut marks induced by sharp weapons on human bones. For that purpose, we analyzed bone samples via an original approach based on bone autofluorescence with an epifluorescence macroscope and compared it to previous existing methods. In this study, we used bone sections from human clavicles on which three different kinds of lesions were manually implemented, using different weapons. The bone wounds were analyzed by three different methodologies, light microscopy, scanning electron microscopy (SEM), and micro-computed tomography, and were compared with epifluorescence macroscopy. We paid attention more significantly to the aspect of walls and floor of the kerf, so as to conclude on the nature and distinguish between weapons used. Among all technologies used in this study, the most precise and efficient methods were epifluorescence macroscopy and SEM. Nonetheless, epifluorescence macroscopy is faster, cheaper, and more accessible than SEM. More significantly, this technique, which has the potential to accurately document the nature of the damage, is nondestructive, and could thus be highly useful in forensic science as anthropology.

MR, (18)F-FDG, and (18)F-AV45 PET correlate with AD PSEN1 original phenotype.

We report the case of a 37-year-old man suffering from insidious visual agnosia and spastic paraparesis due to a PSEN1 mutation. His mother was diagnosed with Alzheimer disease after a biopsy. He was assessed by multimodal neuroimaging, including new in vivo positron emission tomography amyloid imaging (F-AV45). His data were compared with those from healthy participants and patients with sporadic predemential Alzheimer disease. He exhibited posterior cortical thickness reduction, posterior hypometabolism, and increased amyloid ligand uptake in the posterior cortex and the striatum. We show that F-AV45 positron emission tomography allows visualization of the unusual pattern of amyloid deposits that co-localize with cortical atrophy in this genetic form of Alzheimer disease.