Immunohistochemical field parcellation of the human hippocampus along its antero-posterior axis.

The primate hippocampus includes the dentate gyrus, cornu ammonis (CA), and subiculum. CA is subdivided into four fields (CA1-CA3, plus CA3h/hilus of the dentate gyrus) with specific pyramidal cell morphology and connections. Work in non-human mammals has shown that hippocampal connectivity is precisely patterned both in the laminar and longitudinal axes. One of the main handicaps in the study of neuropathological semiology in the human hippocampus is the lack of clear laminar and longitudinal borders. The aim of this study was to explore a histochemical segmentation of the adult human hippocampus, integrating field (medio-lateral), laminar, and anteroposterior longitudinal patterning. We provide criteria for head-body-tail field and subfield parcellation of the human hippocampus based on immunodetection of Rabphilin3a (Rph3a), Purkinje-cell protein 4 (PCP4), Chromogranin A and Regulation of G protein signaling-14 (RGS-14). Notably, Rph3a and PCP4 allow to identify the border between CA3 and CA2, while Chromogranin A and RGS-14 give specific staining of CA2. We also provide novel histological data about the composition of human-specific regions of the anterior and posterior hippocampus. The data are given with stereotaxic coordinates along the longitudinal axis. This study provides novel insights for a detailed region-specific parcellation of the human hippocampus useful for human brain imaging and neuropathology.

Granulocytic Sarcoma Mimicking Cholesteatoma: Beware the Temporal Bone in Haematological Patients.

Granulocytic sarcoma is a myeloid neoplasm that can occur in isolation or in association with acute leukaemia. The temporal bone represents a sanctuary site for myeloid progenitors: granulocytic sarcoma may develop in this location before or concomitantly with the onset of acute leukaemia. This atypical presentation with clinical and radiological data that closely mimic those of cholesteatoma often delays an accurate diagnosis. We here describe the clinical case of a 28-year-old male with granulocytic sarcoma of the external auditory canal that preceded the relapse of promyelocytic leukaemia.

Optimizing the classification of biological tissues using machine learning models based on polarized data.

Polarimetric data is nowadays used to build recognition models for the characterization of organic tissues or the early detection of some diseases. Different Mueller matrix-derived polarimetric observables, which allow a physical interpretation of a specific characteristic of samples, are proposed in literature to feed the required recognition algorithms. However, they are obtained through mathematical transformations of the Mueller matrix and this process may loss relevant sample information in search of physical interpretation. In this work, we present a thorough comparative between 12 classification models based on different polarimetric datasets to find the ideal polarimetric framework to construct tissues classification models. The study is conducted on the experimental Mueller matrices images measured on different tissues: muscle, tendon, myotendinous junction and bone; from a collection of 165 ex-vivo chicken thighs. Three polarimetric datasets are analyzed: (A) a selection of most representative metrics presented in literature; (B) Mueller matrix elements; and (C) the combination of (A) and (B) sets. Results highlight the importance of using raw Mueller matrix elements for the design of classification models.

Beyond the Pericapsular Nerve Group (PENG) Block: A Narrative Review.

The pericapsular nerve group block shows promising results in providing pain relief with a potential motor-sparing effect in hip fracture patients. In this narrative review, we analyze the published articles, and we describe the structures achieved when performing the block. We conducted a literature search to identify the articles performing the pericapsular nerve group block, in the adult or paediatric population, from November 1, 2018, to May 15, 2021. Of the 68 selected articles, 38 were considered eligible, including 1 double-blinded randomized comparative trial, 4 observational studies, and 33 case series and case reports. The technique was described in both acute and chronic pain settings, mainly performed as single shot. All studies described effective analgesia. Quadriceps weakness was experienced in some patients. It has been described as easy to perform and has a low rate of complications. It lacks, however, adequately powered randomized controlled trials to assess its clinical value and efficacy.

Permeable spaces between glenohumeral ligaments as potential gateways for rapid regional anesthesia of the shoulder.

Shoulder pain is a highly prevalent condition, often resulting in major life limitations, and requiring effective treatments. In this work, we explore the anatomical basis of a proposed approach to the regional anesthesia of the shoulder through a single injection under the subscapularis muscle. Bilateral experimental injections in shoulders from body donors (Radiolar ® and Methylene-Blue) under the subscapular muscle (n = 11) and cadaveric systematic dissections of other 35 shoulders from body donors were performed. Injectate spread was then qualitatively assessed. Long axis of permeable foramina in the anterior aspect of the shoulder joint capsule was measured in centimeters using a digital caliper. More than 40% of specimens had at least one permeable space (Weitbrech and/or Rouvière foramina) communicating the subscapular bursa and the articular space. We further demonstrate that an ultrasonography-guided injection under the subscapularis muscle allows the spread of the injectate through the anterior, inferior and posterodorsal walls of the articular capsule, the subacromial bursa, and the bicipital groove, as well as into the articular space for some injections. The odds of accidental intraarticular injection decrease when injecting with low volumes. This anatomical study provides a detailed description of foramina between glenohumeral ligaments. Furthermore, the data shown in this work supports, as a proof of concept, a safe alternative for rapid and specific blockade of terminal sensory branches innervating the shoulder joint capsule.

Polarimetric data-based model for tissue recognition.

We highlight the potential of a predictive optical model method for tissue recognition, based on the statistical analysis of different polarimetric indicators that retrieve complete polarimetric information (selective absorption, retardance and depolarization) of samples. The study is conducted on the experimental Mueller matrices of four biological tissues (bone, tendon, muscle and myotendinous junction) measured from a collection of 157 ex-vivo chicken samples. Moreover, we perform several non-parametric data distribution analyses to build a logistic regression-based algorithm capable to recognize, in a single and dynamic measurement, whether a sample corresponds (or not) to one of the four different tissue categories.

Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells.

Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death, has a 5-year survival rate of approximately 7-9%. The ineffectiveness of anti-PDAC therapies is believed to be due to the existence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are functionally plastic, and have exclusive tumorigenic, chemoresistant and metastatic capacities. Herein, we describe a 2D in vitro system for long-term enrichment of pancreatic CSCs that is amenable to biological and CSC-specific studies. By changing the carbon source from glucose to galactose in vitro, we force PDAC cells to utilize OXPHOS, resulting in enrichment of CSCs defined by increased CSC biomarker and pluripotency gene expression, greater tumorigenic potential, induced but reversible quiescence, increased OXPHOS activity, enhanced invasiveness, and upregulated immune evasion properties. This CSC enrichment method can facilitate the discovery of new CSC-specific hallmarks for future development into targets for PDAC-based therapies.

Proposal for a harmonized protocol for COVID-19 screening and necropsy in forensic sciences facilities.

On 31 December 2019, health authorities in the People's Republic of China informed the World Health Organization of a then limited outbreak of interstitial viral pneumonia, identified at a laboratory in the city of Wuhan. In mid-April 2020 this outbreak of COVID-19 (as the disease has been called) has aggravated and spread worldwide, causing more than 200,000 deaths and affecting especially the United States, Spain, Italy, France and the United Kingdom. Despite the severity of the outbreak, the pathological findings have not been described in detail and there are very few guidelines or protocols for conducting autopsy studies on patients who have died from COVID-19. There are currently very few histopathological case series studies on this disease. In addition, some of these studies have been performed on biopsies or surgical resection pieces from patients in whom disease was subsequently demonstrated or through minimally invasive autopsy protocols. None of the studies offer a detailed necropsy protocol. This document proposes a protocol of action for the institutes of Forensic Medicine facing the current SARS-CoV2 pandemic, which combines protection of worker safety with optimization of tissue collection.

Depolarization metric spaces for biological tissues classification.

Classification of tissues is an important problem in biomedicine. An efficient tissue classification protocol allows, for instance, the guided-recognition of structures through treated images or discriminating between healthy and unhealthy regions (e.g., early detection of cancer). In this framework, we study the potential of some polarimetric metrics, the so-called depolarization spaces, for the classification of biological tissues. The analysis is performed using 120 biological ex vivo samples of three different tissues types. Based on these data collection, we provide for the first time a comparison between these depolarization spaces, as well as with most commonly used depolarization metrics, in terms of biological samples discrimination. The results illustrate the way to determine the set of depolarization metrics which optimizes tissue classification efficiencies. In that sense, the results show the interest of the method which is general, and which can be applied to study multiple types of biological samples, including of course human tissues. The latter can be useful for instance, to improve and to boost applications related to optical biopsy.

Ultrasonography-guided anterior approach for axillary nerve blockade: An anatomical study.

Combined ultrasound (US)-guided blockade of the suprascapular and axillary nerves (ANs) has been proposed as an alternative to interscalene blockade for pain control in shoulder joint pathology or postsurgical care. This technique could help avoid respiratory complications and/or almost total upper limb palsy. Nowadays, the AN blockade is mostly performed using an in-plane caudal-to-cephalic approach from the posterior surface of the shoulder, reaching the nerve immediately after it exits the neurovascular quadrangular space (part of the spatium axillare). Despite precluding most respiratory complications, this approach has not made postsurgical pain relief any better than an interscalene blockade, probably because articular branches of the AN are not blocked.Cephalic-to-caudal methylene blue injections were placed in the first segment of the AN of six Thiel-embalmed cadavers using an US-guided anterior approach in order to compare the distribution with that produced by a posterior approach to the contralateral AN in the same cadaver. Another 21 formalin-fixed cadavers were bilaterally dissected to identify the articular branches of the AN.We found a good spread of the dye on the AN and a constant relationship of this nerve with the subscapularis muscle. The dye reached the musculocutaneous nerve, which also contributes to shoulder joint innervation. We describe the anatomical landmarks for an ultrasonography-guided anterior AN blockade and hypothesize that this anterior approach will provide better pain control than the posterior approach owing to complete blocking of the joint nerve. Clin. Anat. 33:488-499, 2020. © 2019 Wiley Periodicals, Inc.

Cajal-Retzius neurons are required for the development of the human hippocampal fissure.

Cajal-Retzius neurons (CRN) are the main source of Reelin in the marginal zone of the developing neocortex and hippocampus (HC). They also express the transcription factor p73 and are complemented by later-appearing GABAergic Reelin+ interneurons. The human dorsal HC forms at gestational week 10 (GW10), when it develops a rudimentary Ammonic plate and incipient dentate migration, although the dorsal hippocampal fissure (HF) remains shallow and contains few CRN. The dorsal HC transforms into the indusium griseum (IG), concurrently with the rostro-caudal appearance of the corpus callosum, by GW14-17. Dorsal and ventral HC merge at the site of the former caudal hem, which is located at the level of the future atrium of the lateral ventricle and closely connected with the choroid plexus. The ventral HC forms at GW11 in the temporal lobe. The ventral HF is wide open at GW14-16 and densely populated by large numbers of CRNs. These are in intimate contact with the meninges and meningeal blood vessels, suggesting signalling through diverse pathways. At GW17, the fissure deepens and begins to fuse, although it is still marked by p73/Reelin+ CRNs. The p73KO mouse illustrates the importance of p73 in CRN for HF formation. In the mutant, Tbr1/Reelin+ CRNs are born in the hem but do not leave it and subsequently disappear, so that the mutant cortex and HC lack CRN from the onset of corticogenesis. The HF is absent, which leads to profound architectonic alterations of the HC. To determine which p73 isoform is important for HF formation, isoform-specific TAp73- and DeltaNp73-deficient embryonic and early postnatal mice were examined. In both mutants, the number of CRNs was reduced, but each of their phenotypes was much milder than in the global p73KO mutant missing both isoforms. In the TAp73KO mice, the HF of the dorsal HC failed to form, but was present in the ventral HC. In the DeltaNp73KO mice, the HC had a mild patterning defect along with a shorter HF. Complex interactions between both isoforms in CRNs may contribute to their crucial activity in the developing brain.

Identifying small pelvic inclusions through SEM technology.

Tiny calcified structures may be occasionally recovered during excavation of human skeletal remains. Since taphonomic processes may displace these structures from their topographical relation with neighbouring organs or bones, differential diagnoses may pose a major challenge to the archeologist and/or anthropologist. Enteroliths, kidney stones or gallstones, phleboliths, calcified ganglia, or sesamoid bones account for most of such calcified tiny structures. In addition to their pure medical/paleopathological interest, some remains may be related to diet, to chronic haemolytic conditions, and/or to infections or chronic intestinal diseases. We here describe the technical procedures carried out to confirm or refute the identification of a sesamoid bone. The object in question was a small (5 × 3 × 2 mm) calcified structure that appeared over the right coxal bone of an 18th century individual buried in the church Nuestra Señora de La Concepción, in Santa Cruz de Tenerife (Canary Islands). For comparative purposes we also analyzed kidney stones and gallstones from modern individuals. As shown in this study, scanning electron microscope (SEM) analysis is the preferred method to establish a precise differential diagnosis in these cases.

A Radial Glia Fascicle Leads Principal Neurons from the Pallial-Subpallial Boundary into the Developing Human Insula.

The human insular lobe, in the depth of the Sylvian fissure, displays three main cytoarchitectonic divisions defined by the differentiation of granular layers II and IV. These comprise a rostro-ventral agranular area, an intermediate dysgranular area, and a dorso-caudal granular area. Immunohistochemistry in human embryos and fetuses using antibodies against PCNA, Vimentin, Nestin, Tbr1, and Tb2 reveals that the insular cortex is unique in that it develops far away from the ventricular zone (VZ), with most of its principal neurons deriving from the subventricular zone (SVZ) of the pallial-subpallial boundary (PSB). In human embryos (Carnegie stage 16/17), the rostro-ventral insula is the first cortical region to develop; its Tbr1+ neurons migrate from the PSB along the lateral cortical stream. From 10 gestational weeks (GW) onward, lateral ventricle, ganglionic eminences, and PSB grow forming a C-shaped curvature. The SVZ of the PSB gives rise to a distinct radial glia fiber fascicle (RGF), which courses lateral to the putamen in the external capsule. In the RGF, four components can be established: PF, descending from the prefrontal PSB to the anterior insula; FP, descending from the fronto-parietal PSB toward the intermediate insula; PT, coursing from the PSB near the parieto-temporal junction to the posterior insula, and T, ascending from the temporal PSB and merging with components FP and PT. The RGF fans out at different dorso-ventral and rostro-caudal levels of the insula, with descending fibers predominating over ascending ones. The RGF guides migrating principal neurons toward the future agranular, dysgranular, and granular insular areas, which show an adult-like definition at 32 GW. Despite the narrow subplate, and the absence of an intermediate zone except in the caudal insula, most insular subdivisions develop into a 6-layered isocortex, possibly due to the well developed outer SVZ at the PSB, which is particularly prominent at the level of the dorso-caudal insula. The small size of the initial PSB sector may, however, determine the limited surface expansion of the insula, which is in contrast to the exuberant growth of the opercula deriving from the adjacent frontal-parietal and temporal VZ/SVZ.

Cryptogenetic liver cirrhosis and prothrombotic mutations - A mere association?

Thrombin activation and microthrombosis of intrahepatic portal venules is a common feature in liver cirrhosis, due in part to relative protein C deficiency and altered coagulation-anticoagulation-fibrinolysis balance. Extension of this microthrombotic process to larger portal vessels explains the increased incidence of portal vein thrombosis in liver cirrhosis. Thrombin not only leads to thrombosis, but also activates liver stellate cells and promotes fibrogenesis. Also, ischemia associated with thrombosis up-regulates the expression and secretion of growth factors involved in fibrogenesis. The coincidence in a given patient of prothrombotic mutations, such as factor V Leiden or PAI-1 polymorphisms, can accelerate the fibrogenetic process. We hereby present two cases of liver cirrhosis in which etiologic evaluation was negative except for the finding of a factor V Leiden mutation in one case and the 4G/5G PAI polymorphism in the second case. These observations support the hypothesis that these mutations may be involved in the etiology of some cases of cirrhosis, or, at least, accelerate the evolution of the disease. It is therefore convenient to search for the presence of prothrombotic mutations in patients with cryptogenetic cirrhosis.

Cartilage-derived tumor in a prehispanic individual from La Gomera (Canary Islands).

We present the case of a left tibia with an outgrowth at its distal metaphyseal/epiphyseal end, composed of cancellous bone, surrounding a destructive process that, on radiological examination, reaches the tibiotalar joint surface. The cancellous bone of the outgrowth is well preserved and is in continuity with intramedullary cancellous bone. The tibia belonged to a prehispanic adult individual, probably male, from La Gomera, in the Canary Archipelago. The antiquity of the sample is unknown, but radiocarbon dating of other samples ranges from 1600 to1800 years BP. The lesion is suggestive of a cartilage-derived tumor, most likely a chondrosarcoma. Other etiologic possibilities are also discussed, including osteochondroma, enchondroma, chondromyxoid fibroma or chondroblastoma.

Cortical hypoplasia and ventriculomegaly of p73-deficient mice: Developmental and adult analysis.

Trp73, a member of the p53 gene family, plays a crucial role in neural development. We describe two main phenotypic variants of p73 deficiency in the brain, a severe one characterized by massive apoptosis in the cortex leading to early postnatal death and a milder, non-/low-apoptosis one in which 50% of pups may reach adulthood using an intensive-care breeding protocol. Both variants display the core triad of p73 deficiency: cortical hypoplasia, hippocampal malformations, and ventriculomegaly. We studied the development of the neocortex in p73 KO mice from early embryonic life into advanced age (25 months). Already at E14.5, the incipient cortical plate of the p73 KO brains showed a reduced width. Examination of adult neocortex revealed a generalized, nonprogressive reduction by 10-20%. Area-specific architectonic landmarks and lamination were preserved in all cortical areas. The surviving adult animals had moderate ventricular distension, whereas pups of the early lethal phenotypic variant showed severe ventriculomegaly. Ependymal cells of wild-type ventricles strongly express p73 and are particularly vulnerable to p73 deficiency. Ependymal denudation by apoptosis and reduction of ependymal cilia were already evident in young mice, with complete absence of cilia in older animals. Loss of p73 function in the ependyma may thus be one determining factor for chronic hydrocephalus, which leads to atrophy of subcortical structures (striatum, septum, amygdala). p73 Is thus involved in a variety of CNS activities ranging from embryonic regulation of brain size to the control of cerebrospinal fluid homeostasis in the adult brain via maintenance of the ependyma.