The Ospedale Maggiore, known as Ca’ Granda, was founded in 1456 by will of Francesco Sforza, Duke... more The Ospedale Maggiore, known as Ca’ Granda, was founded in 1456 by will of Francesco Sforza, Duke of Milan, and was considered for almost five centuries a model for Milanese, Italian and even European healthcare. Attracting patients from all over Europe, the Ca’ Granda distinguished itself for the introduction of new treatments and innovative health reforms. In the burial ground of the hospital still lie the bodies of the deceased patients, who came from the poorest strata of the population. The study of their remains aims to give back a general identity and a story to each of these persons as well as reconstruct a fraction of the sixteenth century population of Milano as concerns lifestyle and disease and examine practises and therapy of this exceptional hospital. It is estimated that about two million commingled bones and articulated skeletons rest in the crypt, together with other types of findings (e.g., ceramic, coins, clothing). These remains are the object of a large project ...
Il volume Una favola breve riunisce una serie di contributi scientifici che in prospettiva diacro... more Il volume Una favola breve riunisce una serie di contributi scientifici che in prospettiva diacronica affrontano il tema della salute dell'infanzia, dell'abuso sul minore e della morte prematura, dal mondo antico (greco, italico e romano) fino all'era moderna. Il volume è parte di un più ampio progetto, intitolato Mors immatura, nato nel 2017 con l'obiettivo di costruire un fecondo dialogo interdisciplinare su temi delicati e non privi di ricadute nell'attualità: archeologia, antropologia, storia del diritto e della medicina possono scrivere pagine importanti sull'infanzia, contribuendo alla formazione di una coscienza civica e di un'attenta responsabilità sociale rispetto a tematiche tuttora di grande urgenza. Una favola breve Archeologia e antropologia per la storia dell'infanzia a cura di Claudia Lambrugo.
Building the biological profile of a deceased person represents a pivotal step in order to achiev... more Building the biological profile of a deceased person represents a pivotal step in order to achieve the victim's identification. Specifically with regard to ancestry, the melanin distribution pattern in the dermal-epidermal layers has been poorly explored in the forensic field as a potential useful tool. In particular, nothing has been reported about the reliability of such method in bodies in active decay or in advanced state of decomposition. In this study fragments of skin sampled from bodies of known ancestry, both in good and in poor states of preservation, were subjected to histological analysis. We selected 15 subjects, which were divided into three groups: group A (5 white Europeans), group B (5 black Africans) and group C (5 Orientals). A double skin sample was performed on all the bodies, one from the abdomen and the other one from the right forearm. After histological processing and staining with hematoxylin and eosin (H&E) and Masson-Hamperl trichrome technique, the cutaneous melanin distribution pattern was assessed using a semi-quantitative score. The melanin distribution patterns observed both in fresh and in putrefied cadaveric skin were found to be in all cases consistent with the victims' known ancestry. Moreover no differences were observed between abdominal and forearm skin samples and all the histological findings highlighted by H&E were confirmed by the Masson-Hamperl trichrome staining. We demonstrated that the histological analysis aimed at assessing the melanin distribution pattern may be a valuable useful tool in the assessment of ancestry.
Amyloid-beta (Aβ) 42/40 ratio, tau phosphorylated at threonine-181 (p-tau), and total-tau (t-tau)... more Amyloid-beta (Aβ) 42/40 ratio, tau phosphorylated at threonine-181 (p-tau), and total-tau (t-tau) are considered core biomarkers for the diagnosis of Alzheimer’s disease (AD). The use of fully automated biomarker assays has been shown to reduce the intra- and inter-laboratory variability, which is a critical factor when defining cut-off values. The calculation of cut-off values is often influenced by the composition of AD and control groups. Indeed, the clinically defined AD group may include patients affected by other forms of dementia, while the control group is often very heterogeneous due to the inclusion of subjects diagnosed with other neurological diseases (OND). In this context, unsupervised machine learning approaches may overcome these issues providing unbiased cut-off values and data-driven patient stratification according to the sole distribution of biomarkers. In this work, we took advantage of the reproducibility of automated determination of the CSF core AD biomarkers...
Case Report Radiation-induced glioblastoma in a medulloblastoma patient: A case report with molec... more Case Report Radiation-induced glioblastoma in a medulloblastoma patient: A case report with molecular features Abstract Journal Menu
Dear Editor-in-Chief, Frontotemporal dementia (FTD) is a group of clinically, pathologically, and... more Dear Editor-in-Chief, Frontotemporal dementia (FTD) is a group of clinically, pathologically, and genetically heterogeneous degenerative disorders. In up to 31% of FTD cases, a family history is described, mostly associated with mutations in progranulin (GRN), C9ORF72, and microtubule-associated protein tau (MAPT) genes, with MAPT mutations responsible for 5– 10% of all genetic cases of FTD [1]. The clinical phenotypes of MAPT mutation carriers are variable and characterized by more frequent disinhibited behavior and semantic impairment with respect to FTD patients carrying mutations in other genes. In addition, mean age at onset is lower and penetrance is almost complete [1]. Tau protein is involved in axonal transport by binding microtubules and regulating their stabilization. Six tau isoforms have been identified, deriving from alternative splicing. Most of MAPT mutations are missense mutations located in the microtubule binding domain and affecting the assembly and stabilization...
Neuronal dendritic arborizations and dendritic spines are crucial for a normal synaptic transmiss... more Neuronal dendritic arborizations and dendritic spines are crucial for a normal synaptic transmission and may be critically involved in the pathophysiology of epilepsy. Alterations in dendritic morphology and spine loss mainly in hippocampal neurons have been reported both in epilepsy animal models and in human brain tissues from patients with epilepsy. However, it is still unclear whether these dendritic abnormalities relate to the cause of epilepsy or are generated by seizure recurrence. We investigated fine neuronal structures at the level of dendritic and spine organization using Golgi impregnation, and analysed synaptic networks with immunohistochemical markers of glutamatergic (vGLUT1) and GABAergic (vGAT) axon terminals in human cerebral cortices derived from epilepsy surgery. Specimens were obtained from 28 patients with different neuropathologically defined aetiologies: type Ia and type II focal cortical dysplasia, cryptogenic (no lesion) and temporal lobe epilepsy with hipp...
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2010
The biological mechanisms associated with the development and rupture of intracranial aneurysms a... more The biological mechanisms associated with the development and rupture of intracranial aneurysms are not fully understood. To clarify the role of VEGF and the related receptors in the pathophysiology of aneurysm, immunostaining for VEGF, VEGFR1 and VEGFR2 was performed on specimens from six unruptured aneurysms and on two specimens of normal arteries wall as a control. The results were correlated with NO concentration of CSF collected during surgery from 8 patients affected by unruptured aneurysms and in 11 control patients. The immunohistochemical data showed a different pattern of VEGF/VEGFR1/VEGFR2 in aneurysms when compared with control. The results of this preliminary study suggest an imbalance of VEGF, VEGFR1 and VEGFR2, and the interaction of VEGF and NO in the pathophysiology of unruptured aneurysms. Our data support the hypothesis of aneurysm formation associated with a loss of expression of VEGFR1, moderate expression of VEGFR2 and high concentration of nitrate.
The biological mechanisms associated with the development and rupture of intracranial aneurysms a... more The biological mechanisms associated with the development and rupture of intracranial aneurysms are not fully understood. To clarify the role of VEGF and the related receptors in the pathophysiology of aneurysm, immunostaining for VEGF, VEGFR1 and VEGFR2 was performed on specimens from six unruptured aneurysms and on two specimens of normal arteries wall as a control. The results were correlated with NO concentration of CSF collected during surgery from 8 patients affected by unruptured aneurysms and in 11 control patients. The immunohistochemical data showed a different pattern of VEGF/VEGFR1/VEGFR2 in aneurysms when compared with control. The results of this preliminary study suggest an imbalance of VEGF, VEGFR1 and VEGFR2, and the interaction of VEGF and NO in the pathophysiology of unruptured aneurysms. Our data support the hypothesis of aneurysm formation associated with a loss of expression of VEGFR1, moderate expression of VEGFR2 and high concentration of nitrate.
Alzheimer’s disease (AD) is increasingly recognized as a highly heterogeneous disorder occurring ... more Alzheimer’s disease (AD) is increasingly recognized as a highly heterogeneous disorder occurring under distinct clinical and neuropathological phenotypes. Despite the molecular determinants of such variability not being well defined yet, microglial cells may play a key role in this process by releasing distinct pro- and/or anti-inflammatory cytokines, potentially affecting the expression of the disease. We carried out a neuropathological and biochemical analysis on a series of AD brain samples, gathering evidence about the heterogeneous involvement of microglia in AD. The neuropathological studies showed differences concerning morphology, density and distribution of microglial cells among AD brains. Biochemical investigations showed increased brain levels of IL-4, IL-6, IL-13, CCL17, MMP-7 and CXCL13 in AD in comparison with control subjects. The molecular profiling achieved by measuring the brain levels of 25 inflammatory factors known to be involved in neuroinflammation allowed a ...
Bone taphonomy is a widely investigated topic; however, few data are available concerning marine ... more Bone taphonomy is a widely investigated topic; however, few data are available concerning marine bone taphonomy, especially on remains recovered from great depths and with short post-mortem intervals. To date, few studies have evaluated the bony changes which occur in seawater compared to samples with different post-mortem histories, and none through a comparative analysis of different approaches. To this purpose, this pilot study aims to examine the influence of seawater on bone preservation compared to other depositional contexts by multiple perspectives. Forty-nine human bone samples (femurs or tibiae) recovered from different environments (sea water, fresh water, outdoor, burial in coffin) were compared by macroscopic, microscopic and bone densitometric approaches. In order to investigate organic and inorganic components, undecalcified and decalcified histology of thin sections was performed. The analyses revealed a well-preserved bone tissue both macroscopically (92%) and micro...
The Ospedale Maggiore, known as Ca’ Granda, was founded in 1456 by will of Francesco Sforza, Duke... more The Ospedale Maggiore, known as Ca’ Granda, was founded in 1456 by will of Francesco Sforza, Duke of Milan, and was considered for almost five centuries a model for Milanese, Italian and even European healthcare. Attracting patients from all over Europe, the Ca’ Granda distinguished itself for the introduction of new treatments and innovative health reforms. In the burial ground of the hospital still lie the bodies of the deceased patients, who came from the poorest strata of the population. The study of their remains aims to give back a general identity and a story to each of these persons as well as reconstruct a fraction of the sixteenth century population of Milano as concerns lifestyle and disease and examine practises and therapy of this exceptional hospital. It is estimated that about two million commingled bones and articulated skeletons rest in the crypt, together with other types of findings (e.g., ceramic, coins, clothing). These remains are the object of a large project ...
Il volume Una favola breve riunisce una serie di contributi scientifici che in prospettiva diacro... more Il volume Una favola breve riunisce una serie di contributi scientifici che in prospettiva diacronica affrontano il tema della salute dell'infanzia, dell'abuso sul minore e della morte prematura, dal mondo antico (greco, italico e romano) fino all'era moderna. Il volume è parte di un più ampio progetto, intitolato Mors immatura, nato nel 2017 con l'obiettivo di costruire un fecondo dialogo interdisciplinare su temi delicati e non privi di ricadute nell'attualità: archeologia, antropologia, storia del diritto e della medicina possono scrivere pagine importanti sull'infanzia, contribuendo alla formazione di una coscienza civica e di un'attenta responsabilità sociale rispetto a tematiche tuttora di grande urgenza. Una favola breve Archeologia e antropologia per la storia dell'infanzia a cura di Claudia Lambrugo.
Building the biological profile of a deceased person represents a pivotal step in order to achiev... more Building the biological profile of a deceased person represents a pivotal step in order to achieve the victim's identification. Specifically with regard to ancestry, the melanin distribution pattern in the dermal-epidermal layers has been poorly explored in the forensic field as a potential useful tool. In particular, nothing has been reported about the reliability of such method in bodies in active decay or in advanced state of decomposition. In this study fragments of skin sampled from bodies of known ancestry, both in good and in poor states of preservation, were subjected to histological analysis. We selected 15 subjects, which were divided into three groups: group A (5 white Europeans), group B (5 black Africans) and group C (5 Orientals). A double skin sample was performed on all the bodies, one from the abdomen and the other one from the right forearm. After histological processing and staining with hematoxylin and eosin (H&E) and Masson-Hamperl trichrome technique, the cutaneous melanin distribution pattern was assessed using a semi-quantitative score. The melanin distribution patterns observed both in fresh and in putrefied cadaveric skin were found to be in all cases consistent with the victims' known ancestry. Moreover no differences were observed between abdominal and forearm skin samples and all the histological findings highlighted by H&E were confirmed by the Masson-Hamperl trichrome staining. We demonstrated that the histological analysis aimed at assessing the melanin distribution pattern may be a valuable useful tool in the assessment of ancestry.
Amyloid-beta (Aβ) 42/40 ratio, tau phosphorylated at threonine-181 (p-tau), and total-tau (t-tau)... more Amyloid-beta (Aβ) 42/40 ratio, tau phosphorylated at threonine-181 (p-tau), and total-tau (t-tau) are considered core biomarkers for the diagnosis of Alzheimer’s disease (AD). The use of fully automated biomarker assays has been shown to reduce the intra- and inter-laboratory variability, which is a critical factor when defining cut-off values. The calculation of cut-off values is often influenced by the composition of AD and control groups. Indeed, the clinically defined AD group may include patients affected by other forms of dementia, while the control group is often very heterogeneous due to the inclusion of subjects diagnosed with other neurological diseases (OND). In this context, unsupervised machine learning approaches may overcome these issues providing unbiased cut-off values and data-driven patient stratification according to the sole distribution of biomarkers. In this work, we took advantage of the reproducibility of automated determination of the CSF core AD biomarkers...
Case Report Radiation-induced glioblastoma in a medulloblastoma patient: A case report with molec... more Case Report Radiation-induced glioblastoma in a medulloblastoma patient: A case report with molecular features Abstract Journal Menu
Dear Editor-in-Chief, Frontotemporal dementia (FTD) is a group of clinically, pathologically, and... more Dear Editor-in-Chief, Frontotemporal dementia (FTD) is a group of clinically, pathologically, and genetically heterogeneous degenerative disorders. In up to 31% of FTD cases, a family history is described, mostly associated with mutations in progranulin (GRN), C9ORF72, and microtubule-associated protein tau (MAPT) genes, with MAPT mutations responsible for 5– 10% of all genetic cases of FTD [1]. The clinical phenotypes of MAPT mutation carriers are variable and characterized by more frequent disinhibited behavior and semantic impairment with respect to FTD patients carrying mutations in other genes. In addition, mean age at onset is lower and penetrance is almost complete [1]. Tau protein is involved in axonal transport by binding microtubules and regulating their stabilization. Six tau isoforms have been identified, deriving from alternative splicing. Most of MAPT mutations are missense mutations located in the microtubule binding domain and affecting the assembly and stabilization...
Neuronal dendritic arborizations and dendritic spines are crucial for a normal synaptic transmiss... more Neuronal dendritic arborizations and dendritic spines are crucial for a normal synaptic transmission and may be critically involved in the pathophysiology of epilepsy. Alterations in dendritic morphology and spine loss mainly in hippocampal neurons have been reported both in epilepsy animal models and in human brain tissues from patients with epilepsy. However, it is still unclear whether these dendritic abnormalities relate to the cause of epilepsy or are generated by seizure recurrence. We investigated fine neuronal structures at the level of dendritic and spine organization using Golgi impregnation, and analysed synaptic networks with immunohistochemical markers of glutamatergic (vGLUT1) and GABAergic (vGAT) axon terminals in human cerebral cortices derived from epilepsy surgery. Specimens were obtained from 28 patients with different neuropathologically defined aetiologies: type Ia and type II focal cortical dysplasia, cryptogenic (no lesion) and temporal lobe epilepsy with hipp...
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2010
The biological mechanisms associated with the development and rupture of intracranial aneurysms a... more The biological mechanisms associated with the development and rupture of intracranial aneurysms are not fully understood. To clarify the role of VEGF and the related receptors in the pathophysiology of aneurysm, immunostaining for VEGF, VEGFR1 and VEGFR2 was performed on specimens from six unruptured aneurysms and on two specimens of normal arteries wall as a control. The results were correlated with NO concentration of CSF collected during surgery from 8 patients affected by unruptured aneurysms and in 11 control patients. The immunohistochemical data showed a different pattern of VEGF/VEGFR1/VEGFR2 in aneurysms when compared with control. The results of this preliminary study suggest an imbalance of VEGF, VEGFR1 and VEGFR2, and the interaction of VEGF and NO in the pathophysiology of unruptured aneurysms. Our data support the hypothesis of aneurysm formation associated with a loss of expression of VEGFR1, moderate expression of VEGFR2 and high concentration of nitrate.
The biological mechanisms associated with the development and rupture of intracranial aneurysms a... more The biological mechanisms associated with the development and rupture of intracranial aneurysms are not fully understood. To clarify the role of VEGF and the related receptors in the pathophysiology of aneurysm, immunostaining for VEGF, VEGFR1 and VEGFR2 was performed on specimens from six unruptured aneurysms and on two specimens of normal arteries wall as a control. The results were correlated with NO concentration of CSF collected during surgery from 8 patients affected by unruptured aneurysms and in 11 control patients. The immunohistochemical data showed a different pattern of VEGF/VEGFR1/VEGFR2 in aneurysms when compared with control. The results of this preliminary study suggest an imbalance of VEGF, VEGFR1 and VEGFR2, and the interaction of VEGF and NO in the pathophysiology of unruptured aneurysms. Our data support the hypothesis of aneurysm formation associated with a loss of expression of VEGFR1, moderate expression of VEGFR2 and high concentration of nitrate.
Alzheimer’s disease (AD) is increasingly recognized as a highly heterogeneous disorder occurring ... more Alzheimer’s disease (AD) is increasingly recognized as a highly heterogeneous disorder occurring under distinct clinical and neuropathological phenotypes. Despite the molecular determinants of such variability not being well defined yet, microglial cells may play a key role in this process by releasing distinct pro- and/or anti-inflammatory cytokines, potentially affecting the expression of the disease. We carried out a neuropathological and biochemical analysis on a series of AD brain samples, gathering evidence about the heterogeneous involvement of microglia in AD. The neuropathological studies showed differences concerning morphology, density and distribution of microglial cells among AD brains. Biochemical investigations showed increased brain levels of IL-4, IL-6, IL-13, CCL17, MMP-7 and CXCL13 in AD in comparison with control subjects. The molecular profiling achieved by measuring the brain levels of 25 inflammatory factors known to be involved in neuroinflammation allowed a ...
Bone taphonomy is a widely investigated topic; however, few data are available concerning marine ... more Bone taphonomy is a widely investigated topic; however, few data are available concerning marine bone taphonomy, especially on remains recovered from great depths and with short post-mortem intervals. To date, few studies have evaluated the bony changes which occur in seawater compared to samples with different post-mortem histories, and none through a comparative analysis of different approaches. To this purpose, this pilot study aims to examine the influence of seawater on bone preservation compared to other depositional contexts by multiple perspectives. Forty-nine human bone samples (femurs or tibiae) recovered from different environments (sea water, fresh water, outdoor, burial in coffin) were compared by macroscopic, microscopic and bone densitometric approaches. In order to investigate organic and inorganic components, undecalcified and decalcified histology of thin sections was performed. The analyses revealed a well-preserved bone tissue both macroscopically (92%) and micro...
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