Reply: Did animal offer relevant model for bevacizumab testing?

growth factor (VEGF)-blocking antibodies completely inhibit the growt

How do synchronous lung metastases influence the surgical management of children with hepatoblastoma? An update and systematic review of the literature

Approximately 20% of children with hepatoblastoma (HB) have metastatic disease at diagnosis, most frequently in the lungs. In children with HB, lung metastatic disease is associated with poorer prognosis. Its treatment has been approached with a variety of methods that integrate chemotherapy and surgical resection. The timing and feasibility of complete extirpation of lung metastases, by chemotherapy and/or metastasectomy, is crucial for the surgical treatment of the primary liver tumor, which can vary from major hepatic resections to liver transplantation (LT). In children with unresectable HB, which can be surgically treated only by LT, the persistence of unresectable metastases after neoadjuvant chemotherapy excludes the possibility of recurring to LT with consequent negative impact on patients' outcomes. Due to limited evidence and experience, there is no consensus amongst oncologists and surgeons across institutions regarding the surgical treatment for HB with synchronous metastatic lung disease. This narrative review aimed to update the current management of pulmonary metastasis in children with HB and to define its role in the decision-making strategy for the surgical approach to primary liver tumours

Antibiotic treatment-induced dysbiosis differently affects BDNF and TrkB expression in the brain and in the gut of juvenile mice

Antibiotic use during adolescence may result in dysbiosis-induced neuronal vulnerability both in the enteric nervous system (ENS) and central nervous system (CNS) contributing to the onset of chronic gastrointestinal disorders, such as irritable bowel syndrome (IBS), showing significant psychiatric comorbidity. Intestinal microbiota alterations during adolescence influence the expression of molecular factors involved in neuronal development in both the ENS and CNS. In this study, we have evaluated the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase B (TrkB) in juvenile mice ENS and CNS, after a 2-week antibiotic (ABX) treatment. In both mucosa and mucosa-deprived whole-wall small intestine segments of ABX-treated animals, BDNF and TrKB mRNA and protein levels significantly increased. In longitudinal muscle-myenteric plexus preparations of ABX-treated mice the percentage of myenteric neurons staining for BDNF and TrkB was significantly higher than in controls. After ABX treatment, a consistent population of BDNF-and TrkB-immunoreactive neurons costained with SP and CGRP, suggesting up-regulation of BDNF signaling in both motor and sensory myenteric neurons. BDNF and TrkB protein levels were downregulated in the hippocampus and remained unchanged in the prefrontal cortex of ABX-treated animals. Immunostaining for BDNF and TrkB decreased in the hippocampus CA3 and dentate gyrus subregions, respectively, and remained unchanged in the prefrontal cortex. These data suggest that dysbiosis differentially influences the expression of BDNF-TrkB in the juvenile mice ENS and CNS. Such changes may potentially contribute later to the development of functional gut disorders, such as IBS, showing psychiatric comorbidity

“Cape Fear”—A Hybrid Hillslope Plot for Monitoring Hydrological Processes

Innovative experimental field designs and methods are instrumental for dissecting hydrological processes in hillslopes. However, experimental studies at the catchment scale are rarely affordable to most research groups, and laboratory flumes are oversimplified to reproduce natural phenomena. In this work, we present the innovative “hybrid” experimental plot of Cape Fear, which features controllable water fluxes and boundary conditions, but it is directly exposed to external atmospheric agents. We demonstrate the suitability of Cape Fear to study hydrological phenomena through a feasibility test, whereby the response of the plot to a natural storm is in line with the well-known hydrological response of natural hillslopes. Future studies will address the influence of the plot geometry parameters on rill formation

ICON 2019: International Scientific Tendinopathy Symposium Consensus: Clinical Terminology

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.Background Persistent tendon pain that impairs function has inconsistent medical terms that can influence choice of treatment.1 When a person is told they have tendinopathy by clinician A or tendinitis by clinician B, they might feel confused or be alarmed at receiving what they might perceive as two different diagnoses. This may lead to loss of confidence in their health professional and likely adds to uncertainty if they were to search for information about their condition. Clear and uniform terminology also assists inter-professional communication. Inconsistency in terminology for painful tendon disorders is a problem at numerous anatomical sites. Historically, the term ‘tendinitis’ was first used to describe tendon pain, thickening and impaired function (online supplementary figure S1). The term ‘tendinosis’ has also been used in a small number of publications, some of which were very influential.2 3 Subsequently, ‘tendinopathy’ emerged as the most common term for persistent tendon pain.4 5 To our knowledge, experts (clinicians and researchers) or patients have never engaged in a formal process to discuss the terminology we use. We believe that health professionals have not yet agreed on the appropriate terminology for painful tendon conditions.Peer reviewedFinal Accepted Versio

The nature and fate of natural resins in the geosphere. XII. Investigation of C-ring aromatic diterpenoids in Raritan amber by pyrolysis-GC-matrix isolation FTIR-MS

Upper Cretaceous amber from the Raritan Formation (Sayerville, New Jersey) has been investigated by Pyrolysis-GC-MS and Pyrolysis-GC-matrix isolation FTIR-MS. Results establish the existence of two distinct forms of amber in this deposit. Both forms are Class Ib ambers, but they are unambiguously differentiated on the basis of their (intact) diterpenoid composition. The presence of callitrisate in both forms, and cupraene in samples designated form 1, strongly suggest that both derive from related-but-distinct species within the Cupressaceae. In addition to callitrisate, dehydroabietate and analogous 17-nor-, 16,17-dinor- and 15,16,17-trinor- analogues of these compounds are also observed. The distributions of these products in multiple samples suggest that they are the result of biological emplacement, rather than diagenetic modification of the parent compounds. This indicates that the distributions of diterpenes observed in these samples are representative of the original bioterpenoids and, hence, are useful for chemotaxonomic analyses

Fuoriclasse. Migranti e figli di migranti (dis)persi nel sistema scolastico di un'area di frontiera.

Fuoriclasse è una pubblicazione che raccoglie l’interpretazione scientifica dei ricercatori, ricercatrici, insegnanti e formatori che sono stati parte attiva nel progetto FAMI-IMPACT FVG 2014-20, per restituire una sintesi ed una riflessione critica al termine di quattro anni di progetto strutturato in azioni di ricerca e di formazione volte a contrastare la dispersione scolastica di alunne/i con background migratorio in Friuli Venezia Giulia. Il volume riporta gli apporti della prospettiva antropologica, pedagogica e didattica con approcci qualitativi e metodologie trasversali per offrire un ripensamento sulle potenziali azioni di inclusione scolastica e sulle criticità emerse. Il titolo è dedicato a questa nuova generazione di giovani spesso italiani di fatto, ma non di diritto, che in ogni caso fanno parte della comunità di pratiche scolastiche quotidiane con cui cercano di costruire, giorno per giorno, un orizzonte di senso e di futuro sostenibile, nonostante la scuola italiana mostri una propensione quasi perversa ad escluderli, lasciandoli “fuori dalla classe”. I fuoriclasse possono essere gli alunni estranei in quanto non pienamente cittadini italiani, a causa del background migratorio, oppure gli outsider, quelli che riescono a farcela e a imporsi nonostante lo svantaggio iniziale e la situazione marginale. Le future direzioni dipenderanno soprattutto da quanto effettivamente le politiche sociali di inclusione scolastica metteranno in gioco come esercizi quotidiani di cittadinanza attiva per tutti/e, a prescindere dal background di partenza

Compound Evolutionary History of the Rhesus Macaque Mhc Class I B Region Revealed by Microsatellite Analysis and Localization of Retroviral Sequences

In humans, the single polymorphic B locus of the major histocompatibility complex is linked to the microsatellite MIB. In rhesus macaques, however, haplotypes are characterized by the presence of unique combinations of multiple B genes, which may display different levels of polymorphism. The aim of the study was to shed light on the evolutionary history of this highly complex region. First, the robustness of the microsatellite MIB-linked to almost half of the B genes in rhesus macaques (Mamu-B)–for accurate B haplotyping was studied. Based on the physical map of an established haplotype comprising 7 MIB loci, each located next to a certain Mamu-B gene, two MIB loci, MIB1 and MIB6, were investigated in a panel of MHC homozygous monkeys. MIB1 revealed a complex genotyping pattern, whereas MIB6 analysis resulted in the detection of one or no amplicon. Both patterns are specific for a given B haplotype, show Mendelian segregation, and even allow a more precise haplotype definition than do traditional typing methods. Second, a search was performed for retroelements that may have played a role in duplication processes as observed in the macaque B region. This resulted in the description of two types of duplicons. One basic unit comprises an expressed Mamu-B gene, adjacent to an HERV16 copy closely linked to MIB. The second type of duplicon comprises a Mamu-B (pseudo)gene, linked to a truncated HERV16 structure lacking its MIB segment. Such truncation seems to coincide with the loss of B gene transcription. Subsequent to the duplication processes, recombination between MIB and Mamu-B loci appears to have occurred, resulting in a hyperplastic B region. Thus, analysis of MIB in addition to B loci allows deciphering of the compound evolutionary history of the class I B region in Old World monkeys

Neutralising reactivity against SARS-CoV-2 delta and omicron variants by vaccination and infection history.

BACKGROUND: The continuous emergence of SARS-CoV-2 variants of concern (VOC) with immune escape properties, such as Delta (B.1.617.2) and Omicron (B.1.1.529), questions the extent of the antibody-mediated protection against the virus. Here we investigated the long-term antibody persistence in previously infected subjects and the extent of the antibody-mediated protection against B.1, B.1.617.2 and BA.1 variants in unvaccinated subjects previously infected, vaccinated naïve and vaccinated previously infected subjects. METHODS: Blood samples collected 15 months post-infection from unvaccinated (n=35) and vaccinated (n=41) previously infected subjects (Vo' cohort) were tested for the presence of antibodies against the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens using the Abbott, DiaSorin, and Roche immunoassays. The serum neutralising reactivity was assessed against B.1, B.1.617.2 (Delta), and BA.1 (Omicron) SARS-CoV-2 strains through micro-neutralisation. The antibody titres were compared to those from previous timepoints, performed at 2- and 9-months post-infection on the same individuals. Two groups of naïve subjects were used as controls, one from the same cohort (unvaccinated n=29 and vaccinated n=20) and a group of vaccinated naïve healthcare workers (n=61). RESULTS: We report on the results of the third serosurvey run in the Vo' cohort. With respect to the 9-month time point, antibodies against the S antigen significantly decreased (P=0.0063) among unvaccinated subjects and increased (P<0.0001) in vaccinated individuals, whereas those against the N antigen decreased in the whole cohort. When compared with control groups (naïve Vo' inhabitants and naïve healthcare workers), vaccinated subjects that were previously infected had higher antibody levels (P<0.0001) than vaccinated naïve subjects. Two doses of vaccine elicited stronger anti-S antibody response than natural infection (P<0.0001). Finally, the neutralising reactivity of sera against B.1.617.2 and BA.1 was 4-fold and 16-fold lower than the reactivity observed against the original B.1 strain. CONCLUSIONS: These results confirm that vaccination induces strong antibody response in most individuals, and even stronger in previously infected subjects. Neutralising reactivity elicited by natural infection followed by vaccination is increasingly weakened by the recent emergence of VOCs. While immunity is not completely compromised, a change in vaccine development may be required going forward, to generate cross-protective pan-coronavirus immunity in the global population

Characterization of Leishmania spp. causing cutaneous leishmaniasis in Manaus, Amazonas, Brazil

In the State of Amazonas, American tegumentary leishmaniasis is endemic and presents a wide spectrum of clinical variability due to the large diversity of circulating species in the region. Isolates from patients in Manaus and its metropolitan region were characterized using monoclonal antibodies and isoenzymes belonging to four species of the parasite: Leishmania (Viannia) guyanensis, 73% (153/209); Leishmania (Viannia) braziliensis, 14% (30/209); Leishmania (Leishmania) amazonensis, 8% (17/209); and Leishmania (Viannia) naiffii, 4% (9/209). The most prevalent species was L. (V.) guyanensis. The principal finding of this study was the important quantity of infections involving more than one parasite species, representing 14% (29/209) of the total. The findings obtained in this work regarding the parasite are further highlighted by the fact that these isolates were obtained from clinical samples collected from single lesions