An unusual case of melanoma metastasis in the buccal space: learning by mistakes to distinguish it from salivary neoplasms

Background: The buccal space is an unusual location of malignancies. We report here the case of a woman with a melanoma metastasis in buccal fat pad, to evaluate the imaging features which might lead to the correct, although uncommon, diagnosis. Case presentation: A 71-year-old woman presented with a painless visible swelling of the left cheek. MRI revealed the presence of a solid lesion located in the buccal fat pad with features suggestive of malignancy. It showed T1 hyperintensity and T2 hypointensity, and restriction of diffusion. Histological examination showed neoplastic cells compatible with melanoma. Discussion: The lesion features (T1 hyperintensity and T2 hypointensity) initially lead our team to believe that there was a hemorrhagic component, possibly a residue of the biopsy. However, when associated with other malignancy features, such as low apparent diffusion coefficient (ADC) values and contrast enhancement, they should evoke the suspect of melanoma, provided that no biopsy was performed and no trauma occurred in the 3\u20137 days before

Design, Test and Analysis of a Gyrotron Cavity Mock-Up Cooled Using Mini Channels

In 2016, we have designed, built and finally tested at the FE200 facility in Le Creusot (France) a planar mock-up mimicking the water-cooled cylindrical resonance cavity of the European 170 GHz, 1 MW gyrotron to be used for electron cyclotron plasma heating in ITER. The aim of the mock-up is the characterization of the cooling capability of the cavity. A Glidcop® target is heated with an electron beam gun with resulting peak heat fluxes relevant for the full-size cavity. Underneath the target surface, whose temperature is monitored by means of a pyrometer, a set of parallel semi-circular mini-channels, with diameter of 1.5 mm, allows the flow of pressurized water, entering the mockup at ~ 9 bar and 40 °C. Several thermocouples measure the target temperature, at different distances from the heated target surface. The experimental results show that the mock-up is capable to withstand a heat fluxes of 21 MW/m2, while the cooling system keeps the heated surface below ~ 400 °C, for flow conditions comparable to those of the full-size cavity. The test results are used to first calibrate the uncertain model parameters and then, with frozen parameters, to validate a previously developed CFD model, showing good agreement with the experiment. In view of its reliability, this model might eventually be a useful tool for the simulation of the full-size gyrotron cavity operation

Cooled radiofrequency ablation technology for painful bone tumors

Bone metastases are a common cause of cancer-related debilitating pain, especially when -localized in the vertebral column and not responsive to standard treatment. In such cases, various treatment options are available; among these is Radiofrequency, whose role has been rapidly growing over the past few years. In this study, we used the innovative Osteocool RF Ablation System (Medtronic) on a patient with a painful bone metastasis localized in the 5th lumbar vertebra, with encouraging results. The radiofrequency ablation of bone metastases with palliative aim represents an excellent treatment option, as it is a minimally invasive and safe procedure, and can be repeated multiple times

Biological processes related to ribosome and mitochondrial functions might be involved in the osteochondrosis latens manifestation in gilts.

Abstract: The articular osteochondrosis (OC) is a disturbance of endochondral ossification occurring in humans and livestock animals. In pigs, OC is one of the major causes of leg weakness, leading to economic losses and reducing the animal welfare. The aim of this study was to evaluate the differential gene expression related to OC latens in femoral articular cartilage in swine. Thus, samples of MS115 5-months-old gilts, normal (control group) and affected with OC latens (affected group), were collected and submitted to histopathological and gene expression analysis. A total of 1,734 genes was differentially expressed (DE) between the two groups. Several biological processes (BP) were enriched including those already known as involved with OC, such as hypoxia, cartilage and bone development. Furthermore, new BP related to initiation of transcription and ribosome biogenesis were associated to this condition. The disruption of mitochondria and ribosome functions may contribute to the development of cartilage and bone disorders, including osteochondrosis and osteoarthritis. The activation of transcription factors (TFs), required to the cartilage and chondrocyte maturation since embrionary life, might also affect the expression of many extracellular matrix genes related to cartilage. The downregulation of TFs ATOH8 and SOX5 in the affected group would delay the chondroblast differentiation, hindering the cartilage formation and endochondral ossification. Besides the DE genes, three genes (DAG1, SC16A and SPAG9) had different isoforms expressed between the normal and affected groups. In this study, new genes and biological processes were described to be possibly involved in the manifestation of OC latens in gilts. Resumo: A osteocondrose articular (OC) é uma perturbação da ossificação endocondral que ocorre em humanos e animais de criação. Em suínos, o OC é uma das principais causas de fraqueza nas pernas, levando a perdas econômicas e reduzindo o bem-estar animal. O objetivo deste estudo foi avaliar a expressão gênica diferencial relacionada ao OC latens na cartilagem articular do fêmur em suínos. Assim, amostras de leitoas MS115 com 5 meses de idade, normais (grupo controle) e afetadas com OC latens (grupo afetado), foram coletadas e submetidas à análise histopatológica e de expressão gênica. Um total de 1.734 genes foi diferencialmente expresso (DE) entre os dois grupos. Vários processos biológicos (BP) foram enriquecidos, incluindo aqueles já conhecidos como envolvidos com CO, como hipóxia, cartilagem e desenvolvimento ósseo. Além disso, novas PA relacionadas ao início da transcrição e biogênese do ribossomo foram associadas a essa condição. O rompimento das funções das mitocôndrias e dos ribossomos pode contribuir para o desenvolvimento de doenças cartilaginosas e ósseas, incluindo osteocondrose e osteoartrite. A ativação de fatores de transcrição (TFs), necessários à maturação da cartilagem e dos condrócitos desde a vida embrionária, também pode afetar a expressão de muitos genes da matriz extracelular relacionados à cartilagem. O downregulation dos TFs ATOH8 e SOX5 no grupo afetado atrasaria a diferenciação do condroblast, dificultando a formação da cartilagem e a ossificação endocondral. Além dos genes DE, três genes (DAG1, SC16A e SPAG9) apresentaram diferentes isoformas expressas entre os grupos normal e afetado. Neste estudo, novos genes e processos biológicos foram descritos como possivelmente envolvidos na manifestação de OC latens em leitoas

A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP

A female offspring of consanguineous parents, showed features of Wiskott-Aldrich syndrome (WAS), including recurrent infections, eczema, thrombocytopenia, defective T cell proliferation and chemotaxis, and impaired natural killer cell function. Cells from this patient had undetectable WAS protein (WASP), but normal WAS sequence and messenger RNA levels. WASP interacting protein (WIP), which stabilizes WASP, was also undetectable. A homozygous c.1301C>G stop codon mutation was found in the WIPF1 gene, which encodes WIP. Introduction of WIP into the patient’s T cells restored WASP expression. These findings indicate that WIP deficiency should be suspected in patients with features of WAS in whom WAS sequence and mRNA levels are normal

The involvement of muscle-related genes in the occurrence of scrotal hernia in pigs.

Abstract: The incidence of scrotal hernia is still a problem in the swine production, leading to economic losses and reducing the animal welfare. Although some QTLs and candidate genes have already been associated to scrotal hernia, the genetic mechanisms and genes controlling this pathology remain to be clarified. Therefore, this study aimed to identify genes involved in the scrotal hernia occurrence in pigs. Thus, two experiments were performed: 1) RNA-Seq analysis of the inguinal ring tissue from eight 60-days-old Landrace pigs (4 healthy and 4 affected with scrotal hernia) that were sequenced in the Illumina HiSeq 2500 and 2) quantitative PCR (qPCR) of 8 candidate genes chosen from the inguinal ring transcriptome in 18 MS115 30-days-old pigs (9 normal and 9 affected with scrotal hernia). Based on the differentially expressed (DE) genes in this transcriptome, some candidate genes related to muscle development biological processes (BP), including the muscle structure (ACTA1), intracellular transport (RYR1, MYBPC1), cell adhesion (COL13A1) and apoptosis (MAP1LC3) were found. The expression profile of the DE genes was consistent with the anatomical alterations related to the scrotal hernia development, such as the weakness of the inguinal canal and non-obliteration of the processus vaginalis. In the qPCR analysis, the MYH1 was the only DE gene identified. The downregulation of the MYH1gene might be one of the possible causes of scrotal hernia in swine since its expression had already been reduced in 30-days-old affected pigs. Therefore, the DE genes identified in our study related to muscle development bioprocesses are possibly involved in the occurrence of scrotal hernia in pigs. Resumo: A incidência de hérnia escrotal ainda é um problema na produção de suínos, levando a perdas econômicas e reduzindo o bem-estar animal. Embora alguns QTLs e genes candidatos já tenham sido associados à hérnia escrotal, os mecanismos genéticos e os genes que controlam esta patologia ainda precisam ser esclarecidos. Portanto, este estudo teve como objetivo identificar genes envolvidos na ocorrência de hérnia escrotal em suínos. Assim, foram realizadas duas experiências: 1) Análise de RNA-Seq do tecido anelar inguinal de oito suínos Landrace com 60 dias de idade (4 saudáveis ??e 4 afetados com hérnia escrotal) que foram sequenciados no Illumina HiSeq 2500 e 2) PCR quantitativa (qPCR) de 8 genes candidatos escolhidos do transcriptoma do anel inguinal em 18 porcos MS115 com 30 dias de idade (9 normais e 9 afetados com hérnia escrotal). Com base nos genes diferencialmente expressos (DE) neste transcriptoma, alguns genes candidatos relacionaram-se aos processos biológicos (BP) de desenvolvimento muscular, incluindo a estrutura muscular (ACTA1), transporte intracelular (RYR1, MYBPC1), adesão celular (COL13A1) e apoptose ( MAP1LC3) foram encontrados. O perfil de expressão dos genes DE foi consistente com as alterações anatômicas relacionadas ao desenvolvimento da hérnia escrotal, como a fraqueza do canal inguinal e a não obliteração do processo vaginal. Na análise qPCR, o MYH1 foi o único gene DE identificado. O downregulation do gene MYH1 pode ser uma das possíveis causas de hérnia escrotal em suínos, uma vez que sua expressão já havia sido reduzida em suínos afetados com 30 dias de idade. Portanto, os genes DE identificados em nosso estudo relacionados a bioprocessos de desenvolvimento muscular estão possivelmente envolvidos na ocorrência de hérnia escrotal em suínos

Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern

Background: Recent in-vitro data have shown that the activity of monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies according to the variant of concern (VOC). No studies have compared the clinical efficacy of different mAbs against Omicron VOC. Methods: The MANTICO trial is a non-inferiority randomised controlled trial comparing the clinical efficacy of early treatments with bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in outpatients aged 50 or older with mild-to-moderate SARS-CoV-2 infection. As the patient enrolment was interrupted for possible futility after the onset of the Omicron wave, the analysis was performed according to the SARS-CoV-2 VOC. The primary outcome was coronavirus disease 2019 (COVID-19) progression (hospitalisation, need of supplemental oxygen therapy, or death through day 14). Secondary outcomes included the time to symptom resolution, assessed using the product-limit method. Kaplan-Meier estimator and Cox proportional hazard model were used to assess the association with predictors. Log rank test was used to compare survival functions. Results: Overall, 319 patients were included. Among 141 patients infected with Delta, no COVID-19 progression was recorded, and the time to symptom resolution did not differ significantly between treatment groups (Log-rank Chi-square 0.22, p 0.90). Among 170 patients infected with Omicron (80.6% BA.1 and 19.4% BA.1.1), two COVID-19 progressions were recorded, both in the bamlanivimab/etesevimab group, and the median time to symptom resolution was 5 days shorter in the sotrovimab group compared with the bamlanivimab/etesevimab and casirivimab/imdevimab groups (HR 0.53 and HR 0.45, 95% CI 0.36-0.77 and 95% CI 0.30-0.67, p<0.01). Conclusions: Our data suggest that, among adult outpatients with mild-to-moderate SARS-CoV-2 infection due to Omicron BA.1 and BA.1.1, early treatment with sotrovimab reduces the time to recovery compared with casirivimab/imdevimab and bamlanivimab/etesevimab. In the same population, early treatment with casirivimab/imdevimab may maintain a role in preventing COVID-19 progression. The generalisability of trial results is substantially limited by the early discontinuation of the trial and firm conclusions cannot be drawn. Funding: This trial was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The VOC identification was funded by the ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic) project, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement number 101016167. Clinical trial number: NCT05205759

Systematic review and meta-analysis of in vitro efficacy of antibiotic combination therapy against carbapenem-resistant Gram-negative bacilli.

The superiority of combination therapy for carbapenem-resistant Gram-negative bacilli (CR-GNB) infections remains controversial. In vitro models may predict the efficacy of antibiotic regimens against CR-GNB. A systematic review and meta-analysis was performed including pharmacokinetic/pharmacodynamic (PK/PD) and time-kill (TK) studies examining the in vitro efficacy of antibiotic combinations against CR-GNB [PROSPERO registration no. CRD42019128104]. The primary outcome was in vitro synergy based on the effect size (ES): high, ES ≥ 0.75, moderate, 0.35ES0.75; low, ES ≤ 0.35; and absent, ES = 0). A network meta-analysis assessed the bactericidal effect and re-growth rate (secondary outcomes). An adapted version of the ToxRTool was used for risk-of-bias assessment. Over 180 combination regimens from 136 studies were included. The most frequently analysed classes were polymyxins and carbapenems. Limited data were available for ceftazidime/avibactam, ceftolozane/tazobactam and imipenem/relebactam. High or moderate synergism was shown for polymyxin/rifampicin against Acinetobacter baumannii [ES = 0.91, 95% confidence interval (CI) 0.44-1.00], polymyxin/fosfomycin against Klebsiella pneumoniae (ES = 1.00, 95% CI 0.66-1.00) and imipenem/amikacin against Pseudomonas aeruginosa (ES = 1.00, 95% CI 0.21-1.00). Compared with monotherapy, increased bactericidal activity and lower re-growth rates were reported for colistin/fosfomycin and polymyxin/rifampicin in K. pneumoniae and for imipenem/amikacin or imipenem/tobramycin against P. aeruginosa. High quality was documented for 65% and 53% of PK/PD and TK studies, respectively. Well-designed in vitro studies should be encouraged to guide the selection of combination therapies in clinical trials and to improve the armamentarium against carbapenem-resistant bacteria