Search

Abstract Diffuse pediatric-type high-grade gliomas (pedHGG), H3- and IDH-wildtype, encompass three main DNA-methylation-based subtypes: pedHGG-MYCN, pedHGG-RTK1A/B/C, and pedHGG-RTK2A/B. Since their first description in 2017 tumors of pedHGG-RTK2A/B have not been comprehensively characterized and clinical correlates remain elusive. In a recent series of pedHGG with a Gliomatosis cerebri (GC) growth pattern, an increased incidence of pedHGG-RTK2A/B (n = 18) was observed. We added 14 epigenetically defined pedHGG-RTK2A/B tumors to this GC series and provided centrally reviewed radiological, histological, and molecular characterization. The final cohort of 32 pedHGG-RTK2A/B tumors consisted of 25 pedHGG-RTK2A (78%) and seven pedHGG-RTK2B (22%) cases. The median age was 11.6 years (range, 4–17) with a median overall survival of 16.0 months (range 10.9–28.2). Seven of 11 of the newly added cases with imaging available showed a GC phenotype at diagnosis or follow-up. PedHGG-RTK2B tumors exhibited frequent bithalamic involvement (6/7, 86%). Central neuropathology review confirmed a diffuse glial neoplasm in all tumors with prominent angiocentric features in both subclasses. Most tumors (24/27 with available data, 89%) diffusely expressed EGFR with focal angiocentric enhancement. PedHGG-RTK2A tumors lacked OLIG2 expression, whereas 43% (3/7) of pedHGG-RTK2B expressed this glial transcription factor. ATRX loss occurred in 3/6 pedHGG-RTK2B samples with available data (50%). DNA sequencing (pedHGG-RTK2A: n = 18, pedHGG-RTK2B: n = 5) found EGFR alterations (15/23, 65%; predominantly point mutations) in both subclasses. Mutations in BCOR (14/18, 78%), SETD2 (7/18, 39%), and the hTERT promoter (7/19, 37%) occurred exclusively in pedHGG-RTK2A tumors, while pedHGG-RTK2B tumors were enriched for TP53 alterations (4/5, 80%). In conclusion, pedHGG-RTK2A/B tumors are characterized by highly diffuse-infiltrating growth patterns and specific radiological and histo-molecular features. By comprehensively characterizing methylation-based tumors, the chance to develop specific and effective therapy concepts for these detrimental tumors increases.

In the One Health approach, which summarizes a concept that human, animal and plant health are interdependent and linked to the ecosystems in which they exist, animal welfare assumes an important role. In addition, the Farm to Fork Strategy of the European Union recognizes animal welfare as an essential component. Transport of animals involves a number of issues related to welfare. Animals are subjected to continuous stress, not only during transit on vehicles, vessels, trains or airplanes, but also during loading and unloading operations. The handling and transport conditions have improved from basic and relatively rudimentary systems, with elements to attenuate discomfort of animals having been gradually introduced, especially for long distance transport. Despite several improvements of animal welfare standards during transportation there are still pressing issues in current EU legislation which deserve reviewing. Recently, several scientific opinions on animal welfare, including during transport, have been published by the European Food Safety Agency, following requests by the European Commission. In addition, the European Court of Auditors published its last report focused on animal welfare during transport. These reports underline the need to review current legislation governing the topic and highlight a number of outstanding issues in the European Union and in Third Countries. This article summarizes the history and current status of this complex issue. [Open Vet J 2024; 14(7.000): 1509-1525]

Abstract Medulloblastomas with extensive nodularity are cerebellar tumors characterized by two distinct compartments and variable disease progression. The mechanisms governing the balance between proliferation and differentiation in MBEN remain poorly understood. Here, we employ a multi-modal single cell transcriptome analysis to dissect this process. In the internodular compartment, we identify proliferating cerebellar granular neuronal precursor-like malignant cells, along with stromal, vascular, and immune cells. In contrast, the nodular compartment comprises postmitotic, neuronally differentiated malignant cells. Both compartments are connected through an intermediate cell stage resembling actively migrating CGNPs. Notably, we also discover astrocytic-like malignant cells, found in proximity to migrating and differentiated cells at the transition zone between the two compartments. Our study sheds light on the spatial tissue organization and its link to the developmental trajectory, resulting in a more benign tumor phenotype. This integrative approach holds promise to explore intercompartmental interactions in other cancers with varying histology.

Inductive proximity sensors are relevant in position-sensing applications in many industries but, in order to be used in harsh industrial environments, they need to be immune to electromagnetic interference (EMI). The use of conventional filters to mitigate these perturbations often compromises signal bandwidth, ranging from 100 Hz to 1.6 kHz. We have exploited recent advances in the field of artificial intelligence (AI) to study the ability of neural networks (NNs) to automatically filter out EMI features. This study offers an analysis and comparison of possible NN models (a 1D convolutional NN, a recurrent NN, and a hybrid convolutional and recurrent approach) for denoising EMI-perturbed signals and proposes a final model, which is based on gated recurrent unit (GRU) layers. This network is compressed and optimised to meet memory requirements, so that in future developments it could be implemented in application-specific integrated circuits (ASICs) for inductive sensors. The final RNN manages to reduce noise by 70% (MSEred) while occupying 2 KB of memory.

Berries represent healthy dietary options and contain bioactive compounds associated with a decreased risk of diseases. Despite representing healthy food choices, these products can be contaminated by pathogenic microorganisms, including parasites. Among foodborne parasites, Giardia duodenalis, Cryptosporidium parvum, Cyclospora cayetanensis, Toxoplasma gondii, and Echinococcus multilocularis are of significant public health importance and have been recently detected in fresh berries in Europe, including Italy. Berries can be purchased fresh or frozen, and it is worrying that even frozen berries could represent a risk for the consumer. In fact, several parasites can resist freezing temperatures and have been responsible for outbreaks of infection. The aim of this study was to investigate the presence of G. duodenalis, C. parvum, C. cayetanensis, T. gondii, and E. multilocularis in frozen berries with simplex and multiplex real-time PCR protocols. A total of 108 packages of mixed frozen berries were bought from supermarkets located in a south-eastern region of Italy. The samples were tested using two simplex real-time PCR protocols targeting C. parvum and G. duodenalis, respectively, and a multiplex real-time PCR targeting C. cayetanensis, T. gondii, and E. multilocularis. None of the investigated parasites were detected in the frozen berry samples tested. This research topic is still unexplored and of great current interest. These results represent a first attempt to investigate parasitic contamination of frozen berries sold on the Italian market, but further large-scale surveys are required.

In Equids, undetected twin pregnancy represents the most important cause of abortion and is also associated with high neonatal mortality rates. Therefore, the detection and management of twin pregnancies is pivotal to allow the continuation of single pregnancies. Although pre-fixation manual crushing of one embryo is the most common management of twin pregnancies, and the impact of natural reduction has been reported in mares, very little is known about donkeys. The present study aimed to report results on the natural reduction occurrence and post-fixation manual crushing management of twin pregnancies in the Martina Franca donkey breed. Methods: Twenty-five twin pregnancies were detected at 11–13 days after ovulation. At 16 days after ovulation, twin pregnancies were classified as unilateral or bilateral and left untreated. The occurrence of natural reduction of one embryo was assessed at 20–21 days after ovulation, and post-fixation manual crushing of one embryo was performed in those cases in which natural reduction did not occur. The pregnancy rate at 28 days after ovulation and live foal rate were recorded. Result: Sixteen out of 25 twin pregnancies were unilateral and nine bilateral. At 20–21 days after ovulation, the natural reduction of one embryo occurred in 87.5% of the unilateral and in none of the bilateral twin pregnancies. The remaining twin pregnancies were treated by post-fixation manual crushing of one embryo. The 28-days-after-ovulation single embryo pregnancy rate was 93.8% for unilateral twin pregnancies and 88.9% for bilateral twin pregnancies, with an overall pregnancy rate of 92%. The live foal rate was 87%. Conclusions: The success rate of natural reduction within 20–21 days after ovulation, the 28-days-after-ovulation pregnancy rate, and the live foal rate suggest that waiting for the natural reduction of one embryo and choosing the post-fixation manual crushing of one embryo could be considered as an alternative to traditional early pre-fixation manual crushing in the Martina Franca donkey breed.

Background: In 2015, an unprecedented epidemic of microcephaly occurred in Brazil. Preliminary observations suggested involvement of cofactors in the etiopathology of Zika virus associated microcephaly. Bovine viral diarrhea virus (BVDV) was identified in fetal samples with microcephaly, originating in the state of Paraíba, and two virus sequences, obtained from the amniotic fluid collected from mothers with babies affected by Zika and microcephaly, have been characterized as two different species of BVDV, types 1 and 2. Aim: The involvement of BVDV as co-factor in the etiopathogenesis of Zika virus associated microcephaly was explored. Methods: A serological screening using an ELISA test was undertaken to detect antibodies against BVDV among patients referred to the Central laboratory of Natal, Rio Grande do Norte, encompassing microcephalic babies and their mothers, mothers and pregnant not associated with microcephaly and general patients as control group. Results: Two samples were positive, out of 382 tested, (0.52%). No specific relation with birth-defects could be established. Conclusion: The study might suggest serological evidence of the circulation of BVDV in humans. Further studies and application of improved diagnostic tests adapted to humans are necessary to clarify the epidemiological extent and impact of BVDV. [Open Vet J 2023; 13(4.000): 400-406]

Background: Pestivirus A Bovine viral diarrhea virus type 1 (BVDV-1) is an heterogeneous species within the genus, affecting cattle and other ruminants, with economic impact on livestock production. Aim: The study aimed to update the taxonomy of the Pestivirus A, Bovine viral diarrhea virus type 1 (BVDV-1) species and to verify the clustering of the strains reported as genotype 1v, originated from different countries. Methods: Recently deposited strains from China, Turkey and Iran have been evaluated by the palindromic nucleotide substitutions (PNS) genotyping method. Results: Based on secondary structure analysis of the 5'-UTR sequences, strains reported as 1v from China were clustered as sub genotype 1.7.3 (1o). Genotype 1.19 (1w) was restricted to China and genotype 1.21 (1v) was present only in Turkey and Iran. Conclusion: The application of the PNS method clarified the taxonomical status of strains, revealing the homonymy of genetically different clusters. Furthermore, these observations indicated geographic segregation in the Pestivirus A species, and confirmed the occurrence of new atypical genetic variants, with potential implications on control and prophylaxis [Open Vet J 2023; 13(7.000): 903-931]

In the one health approach, which summarizes the concept that human, animal, and plant health are interdependent and linked to the ecosystems in which they exist, animal welfare assumes an important role. In addition, the Farm to Fork Strategy of the European Union recognizes animal welfare as an essential component. Transport of animals involves a number of issues related to welfare. Animals are subjected to continuous stress, not only during transit on vehicles, vessels, trains, or airplanes, but also during loading and unloading operations. The handling and transport conditions have improved from basic and relatively rudimentary systems, with elements to attenuate the discomfort of animals having been gradually introduced, especially for long-distance transport. Despite several improvements in animal welfare standards during transportation there are still pressing issues in current EU legislation which deserve reviewing. Recently, several scientific opinions on animal welfare, including during transport, have been published by the European Food Safety Agency, following requests by the European Commission. In addition, the European Court of Auditors published its last report focused on animal welfare during transport. These reports underline the need to review current legislation governing the topic and highlight a number of outstanding issues in the European Union and in Third Countries. This article summarizes the history and current status of this complex issue. [ABSTRACT FROM AUTHOR]

Abstract Mesenchymal tumors of the central nervous system (CNS) include numerous entities, with different pathological features and biological behavior. Mesenchymal non-meningothelial tumors are rare and comprise neoplasms that are exclusive to the CNS or show peculiar features when occurring in the CNS compared with other sites. Within this group there are three new entities, classified on the basis of specific molecular alterations and included in the 5th edition of the WHO Classification of CNS Tumors: primary intracranial sarcoma; DICER1-mutant; CIC-rearranged sarcoma; intracranial mesenchymal tumor, FET::CREB fusion-positive. These tumors often show variable morphology, making diagnosis very challenging, although the implementation of molecular techniques has led to better characterization and more precise identification of these entities. However, many molecular alterations have yet to be discovered and some recently reported CNS tumors are currently missing an appropriate classification. Herein, we report the case of a 43-year-old man who presented with an intracranial mesenchymal tumor. Histopathological examination showed a wide spectrum of peculiar morphological features and a non-specific immunohistochemical profile. Whole transcriptome sequencing revealed the presence of a novel genetic rearrangement involving COX14 and PTEN genes, which has never been reported before in any other neoplasm. The tumor did not cluster in any defined methylation class of the brain tumor classifier, but resulted in a calibrated score of 0.89 for the methylation class “Sarcoma, MPNST-like”, when analyzed by the sarcoma classifier. Our study is the first to report about this tumor with unique pathological and molecular features, characterized by a novel rearrangement between COX14 and PTEN genes. Other studies are necessary in order to define it as a new entity or as a novel rearrangement involving recently described and incompletely characterized CNS mesenchymal tumors.

Inductive proximity sensors are relevant in position-sensing applications in many industries but, in order to be used in harsh industrial environments, they need to be immune to electromagnetic interference (EMI). The use of conventional filters to mitigate these perturbations often compromises signal bandwidth, ranging from 100 Hz to 1.6 kHz. We have exploited recent advances in the field of artificial intelligence (AI) to study the ability of neural networks (NNs) to automatically filter out EMI features. This study offers an analysis and comparison of possible NN models (a 1D convolutional NN, a recurrent NN, and a hybrid convolutional and recurrent approach) for denoising EMI-perturbed signals and proposes a final model, which is based on gated recurrent unit (GRU) layers. This network is compressed and optimised to meet memory requirements, so that in future developments it could be implemented in application-specific integrated circuits (ASICs) for inductive sensors. The final RNN manages to reduce noise by 70% (MSEred) while occupying 2 KB of memory. [ABSTRACT FROM AUTHOR]

Berries represent healthy dietary options and contain bioactive compounds associated with a decreased risk of diseases. Despite representing healthy food choices, these products can be contaminated by pathogenic microorganisms, including parasites. Among foodborne parasites, Giardia duodenalis, Cryptosporidium parvum, Cyclospora cayetanensis, Toxoplasma gondii, and Echinococcus multilocularis are of significant public health importance and have been recently detected in fresh berries in Europe, including Italy. Berries can be purchased fresh or frozen, and it is worrying that even frozen berries could represent a risk for the consumer. In fact, several parasites can resist freezing temperatures and have been responsible for outbreaks of infection. The aim of this study was to investigate the presence of G. duodenalis, C. parvum, C. cayetanensis, T. gondii, and E. multilocularis in frozen berries with simplex and multiplex real-time PCR protocols. A total of 108 packages of mixed frozen berries were bought from supermarkets located in a south-eastern region of Italy. The samples were tested using two simplex real-time PCR protocols targeting C. parvum and G. duodenalis, respectively, and a multiplex real-time PCR targeting C. cayetanensis, T. gondii, and E. multilocularis. None of the investigated parasites were detected in the frozen berry samples tested. This research topic is still unexplored and of great current interest. These results represent a first attempt to investigate parasitic contamination of frozen berries sold on the Italian market, but further large-scale surveys are required. [ABSTRACT FROM AUTHOR]

The Mediterranean Sea is considered a “litmus paper” of pollution risks for any parameter, including faecal contamination. Giardia duodenalis is one of the most important protozoan parasites responsible for diarrhoea in a wide range of hosts, including humans, domestic and wild animals, worldwide. The degree of contamination related to the protozoan's resistant forms on land, and the consequent transport through rivers from point sources to the sea are important aspects to better understand the processes involved in the microbiological pollution of aquatic ecosystems. However, land-sea transfer routes and the complex transmission patterns often remain neglected. This contribution deals with the contamination by G. duodenalis of the Mediterranean Sea through its inhabitants (shellfish, marine mammals, fishes), and provides data on the origin of such contamination on land from humans and animals to soil, fresh produce and waters; this scenario allows to understand the long journey of the protozoan following the drainage basins (i.e., natural watersheds) from the mainland towards the final destination. The Mediterranean Sea contamination is also explained in the light of the Giardia survival in water and the effects of climatic change with the related consequences. Addressing faecal contamination threats in the Mediterranean Sea is a difficult task, but a number of mitigation measures need to be implemented and/or in some countries even applied. Effective management must become a priority in the agenda of policy makers of all Mediterranean Countries for the implementation of successful measures and can only be applied in the perspective of the One Health approach.

Background: In 2015, an unprecedented epidemic of microcephaly occurred in Brazil. Preliminary observations suggested the involvement of cofactors in the etiopathology of Zika virus-associated microcephaly. Bovine viral diarrhea virus (BVDV) was identified in fetal samples with microcephaly, originating in the state of Paraíba, and two virus sequences, obtained from the amniotic fluid collected from mothers with babies affected by Zika and microcephaly, have been characterized as two different species of BVDV, types 1 and 2. Aim: The involvement of BVDV as a co-factor in the etiopathogenesis of Zika virus-associated microcephaly was explored. Methods: A serological screening using an ELISA test was undertaken to detect antibodies against BVDV among patients referred to the Central Laboratory of Natal, Rio Grande do Norte, encompassing microcephalic babies and their mothers, mothers and pregnants not associated with microcephaly and general patients as a control group. Results: Two samples were positive out of 382 tested (0.52%). No specific relation with birth defects could be established. Conclusions: The study might suggest serological evidence of BVDV in humans. Further studies and the application of improved diagnostic tests adapted to humans are necessary to clarify the epidemiological extent and impact of BVDV. [ABSTRACT FROM AUTHOR]

Background: Pestivirus A Bovine viral diarrhea virus type 1 (BVDV-1) is a heterogeneous species within the genus, affecting cattle and other ruminants, with economic impact on livestock production. Aim: The study aimed to update the taxonomy of the Pestivirus A, BVDV-1 species and to verify the clustering of the strains reported as genotype 1v, originating from different countries. Methods: Recently deposited strains from China, Turkey, and Iran have been evaluated by the palindromic nucleotide substitutions (PNS) genotyping method. Results: Based on secondary structure analysis of the 5'-UTR sequences, strains reported as 1v from China were clustered as sub genotype 1.7.3 (1o). Genotype 1.19 (1w) was restricted to China and genotype 1.21 (1v) was present only in Turkey and Iran. Conclusion: The application of the PNS method clarified the taxonomical status of strains, revealing the homonymy of genetically different clusters. Furthermore, these observations indicated geographic segregation in the Pestivirus A species, and confirmed the occurrence of new atypical genetic variants, with potential implications on control and prophylaxis. [ABSTRACT FROM AUTHOR]

Simple Summary: In Equids, twin pregnancy is an unwanted event, and the traditional management of twin pregnancies involves the early, pre-fixation, manual crushing of one embryo before the 16th day after ovulation when the two embryos are still mobile. However, due to the high percentage of natural reduction of one embryo in unilaterally fixed twins, early post-fixation manual crushing management can also be proposed, allowing the time for natural reduction occurrence. The present study aimed to report data about managing twin pregnancies through natural reduction and post-fixation manual crushing in the Martina Franca donkey breed. The natural reduction of one embryo occurred at 20–21 days after ovulation in 87.5% of unilateral twin pregnancies, with 12.5% of cases requiring post-fixation manual crushing, and none of the bilateral twin pregnancies requiring manual crushing. The single embryo pregnancy rate at 28 days after ovulation was 93.8% for unilateral twin pregnancies and 88.9% for bilateral twin pregnancies, with an overall pregnancy rate of 92%. The live foal rate was 87%. Taken together, the results showed that waiting for the natural reduction of one embryo and using post-fixation manual crushing can be a practical option for the management of twin pregnancy in donkeys. In Equids, undetected twin pregnancy represents the most important cause of abortion and is also associated with high neonatal mortality rates. Therefore, the detection and management of twin pregnancies is pivotal to allow the continuation of single pregnancies. Although pre-fixation manual crushing of one embryo is the most common management of twin pregnancies, and the impact of natural reduction has been reported in mares, very little is known about donkeys. The present study aimed to report results on the natural reduction occurrence and post-fixation manual crushing management of twin pregnancies in the Martina Franca donkey breed. Methods: Twenty-five twin pregnancies were detected at 11–13 days after ovulation. At 16 days after ovulation, twin pregnancies were classified as unilateral or bilateral and left untreated. The occurrence of natural reduction of one embryo was assessed at 20–21 days after ovulation, and post-fixation manual crushing of one embryo was performed in those cases in which natural reduction did not occur. The pregnancy rate at 28 days after ovulation and live foal rate were recorded. Result: Sixteen out of 25 twin pregnancies were unilateral and nine bilateral. At 20–21 days after ovulation, the natural reduction of one embryo occurred in 87.5% of the unilateral and in none of the bilateral twin pregnancies. The remaining twin pregnancies were treated by post-fixation manual crushing of one embryo. The 28-days-after-ovulation single embryo pregnancy rate was 93.8% for unilateral twin pregnancies and 88.9% for bilateral twin pregnancies, with an overall pregnancy rate of 92%. The live foal rate was 87%. Conclusions: The success rate of natural reduction within 20–21 days after ovulation, the 28-days-after-ovulation pregnancy rate, and the live foal rate suggest that waiting for the natural reduction of one embryo and choosing the post-fixation manual crushing of one embryo could be considered as an alternative to traditional early pre-fixation manual crushing in the Martina Franca donkey breed. [ABSTRACT FROM AUTHOR]

Abstract Background Pediatric low-grade gliomas (pLGGs), particularly incompletely resected supratentorial tumours, can undergo progression after surgery. However to date, there are no predictive biomarkers for progression. Here, we aimed to identify pLGG-specific microRNA signatures and evaluate their value as a prognostic tool. Methods We identified and validated supratentorial incompletey resected pLGG-specific microRNAs in independent cohorts from four European Pediatric Neuro-Oncology Centres. Results These microRNAs demonstrated high accuracy in differentiating patients with or without progression. Specifically, incompletely resected supratentorial pLGGs with disease progression showed significantly higher miR-1248 combined with lower miR-376a-3p and miR-888-5p levels than tumours without progression. A significant (p

Embryonal tumors are a heterogenous group of neoplasms mostly defined by recurrent genetic driver events. They have been, previously, broadly classified as either medulloblastoma or supratentorial primitive neuroectodermal tumors (PNETs). However, the application of DNA methylation/gene expression profiling in large series of neoplasms histologically defined as PNET, revealed tumors, which showed genetic events associated with glial tumors. These findings led to the definitive removal of the term “PNET” in the 2016 World Health Organization (WHO) classification of CNS tumors. Moreover, further studies on a large scale of methylation profiling have allowed the identification of new molecular-defined entities and have largely influenced the 5th edition of the WHO classification of CNS tumors (WHO CNS5) for both medulloblastomas and other CNS embryonal tumors. The importance of molecular characteristics in CNS embryonal tumors is well represented by the identification of different molecular groups and subgroups in medulloblastoma. So, in the CNS5, the emerged group 3 and group 4 belong to the classification, and the four molecular and morphologic types are now combined into a unique section. Among other embryonal tumors, two new recognized entities are introduced in CNS5: CNS neuroblastoma, FOXR2-activated, and CNS tumor with BCOR internal tandem duplication (ITD). Embryonal tumor with multilayered rosettes (ETMR), already present in the previous classification now has a revised nomenclature as a result of the new DICER1 alteration, additional to the formerly known C19MC. Regarding atypical teratoid/rhabdoid tumor (AT/RT), three molecular subgroups are recognized in CNS5. The combination of histopathological and molecular features reflects the complexity of all these tumors and gives critical information in terms of prognosis and therapy. This encourages the use of a layered diagnostic report with the integrated diagnosis at the top, succeeded by layers including the histological, molecular, and other essential details.

Abstract Seminal plasma (SP) of donkey stallions was evaluated using various oxidative stress parameters as well as protease and protease inhibitor activities. SP was obtained by nine donkey stallions. In addition, one donkey stallion with non-obstructive azoospermia was enrolled in this study. Free radical scavenging activity (FRSA), the ferric reducing ability of plasma (FRAP), total antioxidant capacity (TAC), and total thiol level (TTL) were highly correlated with each other and with the protease inhibitor activity. However, only FRAP, TAC, and the nitrate/nitrite concentration (NOx) were significantly correlated with sperm concentration, production, and kinetics. Protease inhibitor activity was highly correlated with sperm concentration and production; however, it did not correlate with sperm kinetics. The azoospermic stallion produced a lower amount of semen than the normospermic stallions and its SP showed a lower antioxidant activity when evaluated with FRAP, TAC, and TTL as well as a higher NOx and a lower protease inhibitor activity. In conclusion, the evaluation of SP oxidative profile by FRAP, TAC, and NOx may provide reliable information on donkey sperm quality whereas protease inhibitor activity may play a role as a marker of the sperm concentration in this species.

Abstract Two cases of cutaneous myiasis diagnosed in 2018 in Emilia‐Romagna region (northern Italy) were reported. The first one, described in a domestic cat Felis silvestris catus L. (Carnivora: Felidae) and caused by Calliphora vicina Robineau‐Desvoidy (Diptera: Calliphoridae), was the first one of this type ever reported in Italy in cats. The second one was described in a domestic dog Canis lupus familiaris L. (Carnivora: Canidae) and caused by Lucilia sericata (Meigen) (Diptera: Calliphoridae) and was unusual because it occurred in absence of lesions. An extensive literature search on cutaneous myiasis in these two domestic animal species was performed in order to draw attention to predisposing conditions and risk factors.

Persistent mortality rates of medulloblastoma (MB) and severe side effects of the current therapies require the definition of the molecular mechanisms that contribute to tumor progression. Using cultured MB cancer stem cells and xenograft tumors generated in mice, we show that low expression of miR‐326 and its host gene β‐arrestin1 (ARRB1) promotes tumor growth enhancing the E2F1 pro‐survival function. Our models revealed that miR‐326 and ARRB1 are controlled by a bivalent domain, since the H3K27me3 repressive mark is found at their regulatory region together with the activation‐associated H3K4me3 mark. High levels of EZH2, a feature of MB, are responsible for the presence of H3K27me3. Ectopic expression of miR‐326 and ARRB1 provides hints into how their low levels regulate E2F1 activity. MiR‐326 targets E2F1 mRNA, thereby reducing its protein levels; ARRB1, triggering E2F1 acetylation, reverses its function into pro‐apoptotic activity. Similar to miR‐326 and ARRB1 overexpression, we also show that EZH2 inhibition restores miR‐326/ARRB1 expression, limiting E2F1 pro‐proliferative activity. Our results reveal a new regulatory molecular axis critical for MB progression.

Abstract We compared GABAergic function and neuronal excitability in the hippocampal tissue of seven sporadic MTLE patients with a patient carrying a SCN1A loss‐of‐function mutation. All had excellent outcome from anterior temporal lobectomy, and neuropathological study always showed characteristic hippocampal sclerosis (Hs). Compared to MTLE patients, there was a more severe impairment of GABAergic transmission, due to the lower GABAergic activity related to the NaV1.1 loss‐of‐function, in addition to the typical GABA‐current rundown, a hallmark of sporadic MTLE. Our results give evidence that a pharmacological rescuing of the GABAergic dysfunction may represent a promising strategy for the treatment of these patients.

Background: Classical swine fever virus (CSFV), species member of the family Flaviviridae, is generally considered restricted to domestic and wild suids. Circulation of CFSV has been detected in cattle herds in China and India. Natural infection appeared associated with clinical signs in some cases. Aim: Secondary structures of the internal ribosome entry site (IRES) in the 5’ untranslated region (UTR) were used for genomic characterization of bovine strains. Methods: Sequences have been compared to representative CSFV strains isolated from pigs, vaccines and contaminants from porcine cell lines and an ovine strain isolated in Spain. Results: Observed sequences from cattle showed genetic relatedness with live attenuated vaccine strains used in pigs. Sequence characteristics of the Chinese strain S171 resulted genetically distant from previously reported CSFV genotypes, suggesting a new outgroup in the species, described for the first time and named CSFV-d. Other Chinese strains were genetically closely related to CSFV genotype a2 (Alfort type) pig strains. Indian strains, reported from the states of Tamil Nadu and Meghalaya, were genetically closely related to CSFV genotype a1 (Brescia type) and a5 pig strains, respectively. Conclusion: These preliminary observations are new and relevant in countries where CSFV control and eradication strategies are applied.

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children and among the subtypes, Group 3 MB has the worst outcome. Here, we perform an in vivo, patient-specific screen leading to the identification of Otx2 and c-MYC as strong Group 3 MB inducers. We validated our findings in human cerebellar organoids where Otx2/c-MYC give rise to MB-like organoids harboring a DNA methylation signature that clusters with human Group 3 tumors. Furthermore, we show that SMARCA4 is able to reduce Otx2/c-MYC tumorigenic activity in vivo and in human cerebellar organoids while SMARCA4 T910M, a mutant form found in human MB patients, inhibits the wild-type protein function. Finally, treatment with Tazemetostat, a EZH2-specific inhibitor, reduces Otx2/c-MYC tumorigenesis in ex vivo culture and human cerebellar organoids. In conclusion, human cerebellar organoids can be efficiently used to understand the role of genes found altered in cancer patients and represent a reliable tool for developing personalized therapies.

Recent advances in genetic and molecular characterization of telomere maintenance mechanisms (TMMs) highlighted their strong relationship with cancer pathogenesis; neoplastic cells rely on two mechanisms to maintain telomere length and escape from replicative senescence: (a) reactivation of telomerase expression and (b) activation of alternative lengthening of telomere (ALT). Our aims are to describe the role of telomere maintenance in the context of recently published literature regarding pediatric brain cancers and to discuss the emerging therapeutic strategies to target telomerase-positive and ALT-positive tumors. In this review, we illustrate the incidence of TMM via telomerase or ALT and discuss the importance of analyzing telomere length and ALT-associated genetic alterations in certain histological/molecular subtypes of pediatric brain tumors, as potential therapeutic biomarkers. Telomerase-dependent TMM is a common mechanism in SHH-medulloblastomas and ependymomas, which could potentially benefit from antitelomerase therapies, while ALT-dependent TMM is more frequently activated in α-thalassemia/mental retardation syndrome X-linked/H3.3-mutated pediatric high-grade gliomas, metastatic medulloblastomas, and choroid plexus tumors, which could potentially be treated with ALT-targeted drugs. Conversely, pediatric low-grade gliomas lack both mechanisms of telomere maintenance, and anti-TMM therapies do not appear to be a promising strategy for these tumors.

The management of patients with Central Nervous System (CNS) malignancies relies on the appropriate classification of these tumors. Recently, the World Health Organization (WHO) has published new criteria underlining the importance of an accurate molecular characterization of CNS malignancies, in order to integrate the information generated by histology. Next generation sequencing (NGS) allows single step sequencing of multiple genes, generating a comprehensive and specific mutational profile of the tumor tissue. We developed a custom NGS-based multi-gene panel (Glio-DNA panel) for the identification of the correct glioma oncotype and the detection of its essential molecular aberrations. Specifically, the Glio-DNA panel targets specific genetic and chromosomal alterations involving ATRX chromatin remodeler (ATRX), cyclin dependent kinase inhibitor 2A (CDKN2A), isocitrate dehydrogenase (NADP+) 1 (IDH1) and the telomerase reverse transcriptase (TERT) promoter while also recognizing the co-deletion of 1p/19q, loss of chromosome 10 and gain of chromosome 7. Furthermore, the Glio-DNA panel also evaluates the methylation level of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter that predicts temozolomide efficacy. As knowledge of the mutational landscape of each glioma is mandatory to define a personalized therapeutic strategy, the Glio-DNA panel also identifies alterations involving “druggable” or “actionable” genes. To test the specificity of our panel, we used two reference mutated DNAs verifying that NGS allele frequency measurement was highly accurate and sensitive. Subsequently, we performed a comparative analysis between conventional techniques - such as immunohistochemistry or fluorescence in situ hybridization - and NGS on 60 diffuse glioma samples that had been previously characterized. The comparison between conventional testing and NGS showed high concordance, suggesting that the Glio-DNA panel may replace multiple time-consuming tests. Finally, the identification of alterations involving different actionable genes matches glioma patients with potential targeted therapies available through clinical trials. In conclusion, our analysis demonstrates NGS efficacy in simultaneously detecting different genetic alterations useful for the diagnosis, prognosis and treatment of adult patients with diffuse glioma.

* Context.--Standards for pathology reporting of cancer are foundational to national and international benchmarking, epidemiology, and clinical trials, with international standards for pathology reporting of cancer being undertaken through the International Collaboration on Cancer Reporting (ICCR). Objective.--To develop standardized templates for brain tumor diagnostic pathology reporting. Design.--As a response to the 2016 updated 4th edition of the WHO (World Health Organization) Classification of Tumours of the Central Nervous System (2016 CNS WHO), an expert ICCR committee developed data sets to facilitate reporting of brain tumors that are classified histologically and molecularly by the 2016 CNS WHO; as such, this represents the first combined histologic and molecular ICCR data set, and required a novel approach with 3 highly related data sets that should be used in an integrated manner. Results.--The current article and accompanying ICCR Web site describe reporting data sets for central nervous system tumors in the hope that they provide easy-to-use and highly reproducible means to issue diagnostic reports in consort with the 2016 CNS WHO. Conclusions.--The consistent use of these templates will undoubtedly prove useful for patient care, clinical trials, epidemiologic studies, and monitoring of neuro-oncologic care around the world. (Arch Pathol Lab Med. 2020;144:196-206; doi: 10.5858/arpa.2018-0565-OA), The value of a structured or synoptic approach to cancer reporting, leading to improvement in the quality and completeness of pathology cancer reports, has been recognized through many studies (1-4) [...]

Bovine viral diarrhea virus (BVDV) and classical swine fever virus (CSFV) are members of the genus Pestivirus that cause disease in wild and domestic animals and are responsible for extensive economic losses of livestock and biological industry. BVDV is also a significant laboratory contaminant. Currently, no effective antiviral therapeutics are available to control their infection. Ginsenosides, as major pharmacological ingredients in the plants of ginseng, have various biological activities. In the present work, the antiviral activity of 9 ginsenosides and 3 other saponins from Araliaceae plants was investigated against Pestivirus. Ginsenoside Rb2 and Rb3 showed low cytotoxicity and obvious antiviral effect. They were able to inhibit the replication and proliferation of BVDV and CSFV. In addition, our results suggest that the possible antiviral mechanism of Rb2 might be related to its ability to affect the translation of these viruses. Obtained results suggest that ginsenoside Rb2 and Rb3 have a potential for effective treatment against Pestivirus infection.

Pediatric high-grade gliomas represent a heterogeneous group of tumors with a wide variety of molecular features. We performed whole exome sequencing and methylation profiling on matched primary and recurrent tumors from four pediatric patients with hemispheric high-grade gliomas. Genetic analysis showed the presence of some variants shared between primary and recurrent tumors, along with other variants exclusive of primary or recurrent tumors. NSD1 variants, all novel and not previously reported, were present at high frequency in our series (100%) and were all shared between the samples, independently of primary or recurrence. For every variant, in silico prediction tools estimated a high probability of altering protein function. The novel NSD1 variant (c.5924T > A; p.Leu1975His) was present in one in four cases at recurrence, and in two in four cases at primary. The novel NSD1 variant (c.5993T > A; p.Met1998Lys) was present in one in four cases both at primary and recurrence, and in one in four cases only at primary. The presence of NSD1 mutations only at recurrence may suggest that they can be sub-clonal, while the presence in both primary and recurrence implies that they can also represent early and stable events. Furthermore, their presence only in primary, but not in recurrent tumors, suggest that NSD1 mutations may also be influenced by treatment.

Poultry red mites (Dermanyssus gallinae) are primarily ectoparasites of laying hens but also parasitize synanthropic birds in urban contexts. This mite can occasionally attack mammals, including humans, and cause mild to severe dermatitis. Attacks by zoonotic Mesostigmata mites are currently an increasing but still neglected problem of urban life. The authors present two cases of dermanyssosis involving two health workers at a hospital, linked to air conditioning outdoor units colonized by pigeons. Videos that describe the environmental contamination by D. gallinae and show where the infestation originated are presented. In addition, the authors update the literature of all urban cases, which, to date, reports over 240 clinical cases, mostly in private homes but also in public buildings. Dermatitis due to these mites is often unrecognized and, therefore, misdiagnosed. This report describes how the two cases herein reported were rapidly resolved thanks to the close cooperation between veterinary parasitologists and allergologists. It is crucial to raise awareness of the problem among general practitioners and specialists. In addition, the authors suggest a reconsideration of urban architectural choices that increase the public health risk posed by dermanyssosis and other diseases related to synanthropic birds.

Background: Classical swine fever virus (CSFV), species member of the family Flaviviridae, is generally considered restricted to domestic and wild suids. The circulation of CFSV has been detected in cattle herds in China and India. Natural infection appeared associated with clinical signs in some cases. Aim: The secondary structures of the internal ribosome entry site in the 5' untranslated region (UTR) were used for the genomic characterization of bovine strains. Methods: Sequences have been compared to the representative CSFV strains isolated from pigs, vaccines, and contaminants from porcine cell lines and an ovine strain isolated in Spain. Results: The observed sequences from cattle showed a genetic relatedness with live-attenuated vaccine strains used in pigs. Sequence characteristics of the Chinese strain S171 are genetically distant from the previously reported CSFV genotypes, suggesting a new outgroup in the species, described for the first time, and named CSFV-d. Other Chinese strains were genetically closely related to CSFV genotype a2 (Alfort type) pig strains. Indian strains, reported from the states of Tamil Nadu and Meghalaya, were genetically closely related to CSFV genotype a1 (Brescia type) and a5 pig strains, respectively. Conclusion: These preliminary observations are new and relevant in countries, where CSFV control and eradication strategies are applied. [ABSTRACT FROM AUTHOR]

Avoiding radio communication blackouts during atmospheric entry is crucial to a space mission and can be life-saving. A novel ray-tracing algorithm, called Blackout Ray Tracer (BORAT), based on a Snell's law solver, is introduced to analyze the signal behavior during reentry using geometrical optics for nonmagnetized and magnetized plasma. The ray-tracing analysis is performed on Knapp's case fluid simulations provided by the University of Stuttgart. The effect of an applied magnetic field on ray tracing is discussed and visualized using radiation patterns. The results suggest that a sufficiently strong magnetic field is promising to mitigate radio communication blackouts. [ABSTRACT FROM AUTHOR]

In 2015, a young female Alpine chamois (Rupicapra rupicapra rupicapra), originated from the Aosta Valley Region, Northernwestern Italy, was conferred to the National Reference Center for Wild Animal Diseases for pathologic examinations. Histological analysis revealed a severe meningoencephalitis characterized by lymphocytic and plasmacellular infiltration, gliosis, perivascular cuffs and leptomeningitis at the level of brain and brain stem. Laboratory investigations included polymerase chain reaction, sequencing and characterization by phylogenetic analysis and evaluation of the internal ribosome entry site (IRES) secondary structure in the 5’ untranslated region. These tests identified the pathological agent as border disease virus (BDV), a known health risk in domestic small ruminants. Genetic characteristics of the isolated strains, closely related to ovine and caprine strain sequences from neighbouring regions of Piedmont, France and Switzerland, suggested geographic segregation and micro-evolutive steps within the species.

Abstract Childhood medulloblastomas (MB) are heterogeneous and are divided into four molecular subgroups. The provisional non-wingless-activated (WNT)/non-sonic hedgehog-activated (SHH) category combining group 3 and group 4 represents over two thirds of all MBs, coupled with the highest rates of metastases and least understood pathology. The molecular era expanded our knowledge about molecular aberrations involved in MB tumorigenesis, and here, we review processes leading to non-WNT/non-SHH MB formations. The heterogeneous group 3 and group 4 MBs frequently harbor rare individual genetic alterations, yet the emerging profiles suggest that infrequent events converge on common, potentially targetable signaling pathways. A mutual theme is the altered epigenetic regulation, and in vitro approaches targeting epigenetic machinery are promising. Growing evidence indicates the presence of an intermediate, mixed signature group along group 3 and group 4, and future clarifications are imperative for concordant classification, as misidentifying patient samples has serious implications for therapy and clinical trials. To subdue the high MB mortality, we need to discern mechanisms of disease spread and recurrence. Current preclinical models do not represent the full scale of group 3 and group 4 heterogeneity: all of existing group 3 cell lines are MYC-amplified and most mouse models resemble MYC-activated MBs. Clinical samples provide a wealth of information about the genetic divergence between primary tumors and metastatic clones, but recurrent MBs are rarely resected. Molecularly stratified treatment options are limited, and targeted therapies are still in preclinical development. Attacking these aggressive tumors at multiple frontiers will be needed to improve stagnant survival rates.

Despite the economic and animal welfare importance of the Poultry Red Mite Dermanyssus gallinae, its genetic structure has been studied in a scattered way so far. The prophylaxis and control of such a globally distributed ectoparasite can be significantly improved by understanding its genetic population structure (composition in species and intraspecific variants). The present study aims to establish a rigorous framework for characterizing the neutral genetic structure of D. gallinae based on a literature review combined with an integrative analysis of the data available in GenBank on population-level nucleotide sequence diversity supplemented by a new dataset. The integrative analysis was conducted on sequence data extracted from GenBank coupled with new sequences of two fragments of the mitochondrial gene encoding Cytochrome Oxidase I (CO1) as well as of an intron of the nuclear gene encoding Tropomyosin (Tpm) from several PRM populations sampled from European poultry farms. Emphasis was placed on using the mitochondrial gene encoding CO1 on which the main universal region of DNA barcoding in animals is located. The species D. gallinae sensu lato is a species complex, encompassing at least two cryptic species, i.e., not distinguishable by morphological characters: D. gallinae sensu stricto and D. gallinae L1. Only D. gallinae s.s. has been recorded among the populations sampled in poultry farms worldwide. Current knowledge suggests they are structured in three mitochondrial groups (haplogroups A, B, and C). Haplogroup A is cosmopolitan, and the other two present slightly contrasted distributions (B rather in the northern part of Europe, C most frequently found in the southern part). Recent data indicate that a dynamic geographic expansion of haplogroup C is underway in Europe. Our results also show that NUMT (nuclear mitochondrial DNA) pseudogenes have generated artifactual groups (haplogroups E and F). It is important to exclude these artifact groups from future analyses to avoid confusion. We provide an operational framework that will promote consistency in the analysis of subsequent results using the CO1 fragment and recommendations for future analyses.