Antibiotics in early life and childhood pre-B-ALL. Reasons to analyze a possible new piece in the puzzle

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer with precursor B-cell ALL (pB-ALL) accounting for~85% of the cases. Childhood pB-ALL development is infuenced by genetic susceptibility and host immune responses. The role of the intestinal microbiome in leukemogenesis is gaining increasing attention since Vicente-Dueñas’ seminal work demonstrated that the gut microbiome is distinct in mice genetically predisposed to ALL and that the alteration of this microbiome by antibiotics is able to trigger pB-ALL in Pax5 heterozygous mice in the absence of infectious stimuli. In this review we provide an overview on novel insights on the role of the microbiome in normal and preleukemic hematopoiesis, infammation, the efect of dysbiosis on hematopoietic stem cells and the emerging importance of the innate immune responses in the conversion from preleukemic to leukemic state in childhood ALL. Since antibiotics, which represent one of the most widely used medical interventions, alter the gut microbial composition and can cause a state of dysbiosis, this raises exciting epidemiological questions regarding the implications for antibiotic use in early life, especially in infants with a a preleukemic “frst hit”. Sheading light through a rigorous study on this piece of the puzzle may have broad implications for clinical practice

Flow topology of rare back flow events and critical points in turbulent channels and toroidal pipes

A study of the back flow events and critical points in the flow through a toroidal pipe at friction Reynolds number Re τ ≈ 650 is performed and compared with the results in a turbulent channel flow at Re τ ≈ 934. The statistics and topological properties of the back flow events are analysed and discussed. Conditionally-averaged flow fields in the vicinity of the back flow event are obtained, and the results for the torus show a similar streamwise wall-shear stress topology which varies considerably for the spanwise wall-shear stress when compared to the channel flow. The comparison between the toroidal pipe and channel flows also shows fewer back flow events and critical points in the torus. This cannot be solely attributed to differences in Reynolds number, but is a clear effect of the secondary flow present in the toroidal pipe. A possible mechanism is the effect of the secondary flow present in the torus, which convects momentum from the inner to the outer bend through the core of the pipe, and back from the outer to the inner bend through the pipe walls. In the region around the critical points, the skin-friction streamlines and vorticity lines exhibit similar flow characteristics with a node and saddle pair for both flows. These results indicate that back flow events and critical points are genuine features of wall-bounded turbulence, and are not artifacts of specific boundary or inflow conditions in simulations and/or measurement uncertainties in experiments.C. Chin, R. Vinuesa, R. Örlü, J. I. Cardesa, A. Noorani, P. Schlatter, and M. S. Chon

The implications of Brexit for environmental law in Scotland

This report maps the possible implications of Brexit for environmental protection in Scotland, identifying core questions as well as solutions that may be adopted, with the objective of initiating a conversation about this complex subject matter. The report has been prepared as a joint endeavour by a group of environmental law experts based at Scottish Universities. Each section was drafted by a lead author, with inputs from the rest of the group. The paper is meant for a broad audience and intentionally uses a non-technical writing style. The paper is divided in two sections. The first section addresses cross-cutting questions affecting environmental governance after Brexit, focusing on the main Brexit scenarios and their trade, competition, and law enforcement implications. This analysis identifies a series of common challenges for nvironmental law in Scotland after Brexit, which relate to: •Loss of scrutiny and enforcement powers associated with the operation of EU law and institutions; •Loss of long-term policy horizon and of the stable regulatory framework provided by EU law; •Repositioning of the UK and Scotland in international and regional environmental governance cooperation; and •Restriction/loss of access to EU funds and programmes. The second section analyses specific questions likely to emerge in elected areas of environmental law, distinguishing between different types of EU environmental legislation and the related allocation of competences within the UK. The transposition of EU environmental law into domestic law takes place in different ways. Some pieces of EU environmental law have been transposed into UK/Scottish law and configure distinctively UK/Scottish solutions. After Brexit, retaining these pieces of legislation is going to be relatively straightforward. Other pieces of EU environmental law, conversely, heavily rely upon EU processes and institutions and will no longer be applicable in their present form after Brexit. On these matters, EU powers and competences will be repatriated, raising fundamental questions concerning the allocation of powers between the UK’s central and evolved administrations. Finally, EU membership has important implications concerning the UK’s implementation of international obligations in areas such as climate change law or air pollution. In these areas, EU law is often more ambitious than the underlying international obligations. Brexit will therefore confront the UK and devolved administrations with fundamental choices regarding how to continue to comply with international obligations, and maintain and enhance their current level of commitment and ambition over time

Rhabdomyoblastic Differentiation in Head and Neck Malignancies Other Than Rhabdomyosarcoma

Rhabdomyosarcoma is a relatively common soft tissue sarcoma that frequently affects children and adolescents and may involve the head and neck. Rhabdomyosarcoma is defined by skeletal muscle differentiation which can be suggested by routine histology and confirmed by immunohistochemistry for the skeletal muscle-specific markers myogenin or myoD1. At the same time, it must be remembered that when it comes to head and neck malignancies, skeletal muscle differentiation is not limited to rhabdomyosarcoma. A lack of awareness of this phenomenon could lead to misdiagnosis and, subsequently, inappropriate therapeutic interventions. This review focuses on malignant neoplasms of the head and neck other than rhabdomyosarcoma that may exhibit rhabdomyoblastic differentiation, with an emphasis on strategies to resolve the diagnostic dilemmas these tumors may present. Axiomatically, no primary central nervous system tumors will be discussed.info:eu-repo/semantics/publishedVersio

Poor prognostic clinicopathologic features correlate with VEGF expression but not with PTEN expression in squamous cell carcinoma of the larynx

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the relationship between expression of vascular endothelial growth factor (VEGF) and phosphatase and tensin homolog deleted in chromosome ten (PTEN), angiogenesis and clinicopathological parameters of squamous cell carcinoma of the larynx.</p> <p>Methods</p> <p>We examined immunohistochemical expression of VEGF and PTEN and CD34 for microvessel density (MVD) in sections of formalin-fixed, paraffin embedded tissue blocks of 140 patients with squamous cell carcinoma of the larynx. The intensity of VEGF and PTEN staining and the proportion of cells staining were scored.</p> <p>Results</p> <p>The tumor grade was not significantly related to PTEN expression, but it was to VEGF expression (p = 0.400; p = 0.015, respectively). While there was no significant relationship between PTEN expression and tumor size and cartilage invasion (p = 0.311, p = 0.128), there was a significant relationship between the severity of VEGF expression and tumor size (p = 0.006) and lymph node metastasis (p = 0.048) but not cartilage invasion (p = 0.129). MVD was significantly higher in high-grade tumors (p = 0.003) but had no significant relationship between MVD, lymph node metastasis, and cartilage invasion (p = 0.815, p = 0.204). There was also no significant relationship between PTEN and VEGF expression (p = 0.161) and between PTEN and VEGF expression and the MVD (p = 0.120 and p = 0.175, respectively).</p> <p>Conclusions</p> <p>Increased VEGF expression may play an important role in the outcome of squamous cell carcinoma of the larynx. PTEN expression was not related to VEGF expression and clinicopathological features of squamous cell carcinoma of the larynx.</p

Oral acantholytic squamous cell carcinoma shares clinical and histological features with angiosarcoma

<p>Abstract</p> <p>Background</p> <p>acantholytic squamous cell carcinomas (ASCC) and intraoral angiosarcoma share similar histopathological features. Aim of this study was to find marker for a clear distinction.</p> <p>Methods</p> <p>Four oral acantholytic squamous cell carcinomas and one intraoral angiosarcoma are used to compare the eruptive intraoral growth-pattern, age-peak, unfavourable prognosis and slit-like intratumorous spaces in common histological staining as identical clinical and histopathological features. Immunohistochemical staining for pancytokeratin, cytokeratin, collagen type IV, γ2-chain of laminin-5, endothelial differentiation marker CD31 and CD34, F VIII-associated antigen, Ki 67-antigen, β-catenin, E-cadherin, α-smooth-muscle-actin and Fli-1 were done.</p> <p>Results</p> <p>Cytokeratin-immunoreactive cells can be identified in both lesions. The large vascularization of ASCC complicates the interpretation of vascular differential markers being characteristic for angiosarcoma. Loss of cell-cell-adhesion, monitored by loss of E-cadherin and β-catenin membrane-staining, are indetified as reasons for massive expression of invasion-factor ln-5 in ASCC and considered responsible for unfavourable prognosis of ASCC. Expression of Fli-1 in angiosarcoma and cellular immunoreaction for ln-5 in ASCC are worked out as distinguishing features of both entities.</p> <p>Conclusion</p> <p>Fli-1 in angiosarcoma and ln-5 in ASCC are distinguishing features.</p