IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis

Myeloproliferation, myelofibrosis, and neoangiogenesis are the 3 major intrinsic pathophysiologic features of myeloid metaplasia with myelofibrosis (MMM). The myeloproliferation is characterized by an increased number of circulating CD34+ progenitors with the prominent amplification of dystrophic megakaryocytic (MK) cells and myeloid metaplasia in the spleen and liver. The various biologic activities of interleukin 8 (IL-8) in hematopoietic progenitor proliferation and mobilization as well as in neoangiogenesis prompted us to analyze its potential role in MMM. We showed that the level of IL-8 chemokine is significantly increased in the serum of patients and that various hematopoietic cells, including platelets, participate in its production. In vitro inhibition of autocrine IL-8 expressed by CD34+ cells with either a neutralizing or an antisense anti-IL-8 treatment increases the proliferation of MMM CD34(+)-derived cells and stimulates their MK differentiation. Moreover, addition of neutralizing anti-IL-8 receptor (CXC chemokine receptor 1 [CXCR1] or 2 [CXCR2]) antibodies to MMM CD34+ cells cultured under MK liquid culture conditions increases the proliferation and differentiation of MMM CD41+ MK cells and restores their polyploidization. Our results suggest that IL-8 and its receptors participate in the altered MK growth that features MMM and open new therapeutic prospects for this still incurable disease.     

Screening for autism spectrum disorders: state of the art in Europe

A large number of studies have reported on the validity of autism spectrum disorder (ASD) screening procedures. An overall understanding of these studies’ findings cannot be based solely on the level of internal validity of each, since screening instruments might perform differently according to certain factors in different settings. Europe has led the field with the development of the first screening tool and first prospective screening study of autism. This paper seeks to provide an overview of ASD screening studies and ongoing programmes across Europe, and identify variables that have influenced the outcomes of such studies. Results show that, to date, over 70,000 children have been screened in Europe using 18 different screening procedures. Differences among findings across studies have enabled us to identify ten factors that may influence screening results. Although it is impossible to draw firm conclusions as to which screening procedure is most effective, this analysis might facilitate the choice of a screening method that best fits a specific scenario, and this, in turn, may eventually improve early ASD detection procedures.     

Sympathetic nerve tissue in milky spots of the human greater omentum

Omental milky spots (OMSs), small lymphoid structures positioned in the greater omentum, are involved in peritoneal immune homeostasis and the formation of omental metastases. Sympathetic nerve activity is known to regulate immune function in other lymphoid organs (e.g. spleen and lymph nodes) and to create a favourable microenvironment for various tumour types. However, it is still unknown whether OMSs receive sympathetic innervation. Therefore, the aim of this study was to establish whether OMSs of the adult human greater omentum receive sympathetic innervation. A total of 18 OMSs were isolated from five omenta, which were removed from 3% formaldehyde-perfused cadavers (with a median age of 84 years, ranging from 64 to 94). OMSs were embedded in paraffin, cut and stained with a general (PGP9.5) and sympathetic nerve marker (TH and DBH), and evaluated by bright field microscopy. A T-cell, B-cell, and macrophage staining was performed to confirm OMS identity. In 50% of the studied OMSs, sympathetic nerve fibres were observed at multiple levels of the same OMS. Nerve fibres were represented as dots or elongated structures and often observed in relation to small vessels and occasionally as individual structures residing between lymphoid cells. The current study shows that 50% of the investigated OMSs contain sympathetic nerve fibres. These findings may contribute to our understanding of neural regulation of peritoneal immune response and the involvement of OMSs in omental metastases.     

Predictors of natural mentoring relationships and students’ adjustment to college

Little research exists that examines natural mentoring relationships (NMRs) during the college transition. We examine the role of parental attachment and help-seeking behaviors in students’ development of new NMRs and the role NMRs have on students’ outcomes. Included in the study were 215 first-year students at a large, urban, private university. Participants completed surveys at the beginning (Time 1) and at the end (Time 2) of the school year. We used structural equation modeling to test a hypothesized model that included predictors (i.e., attachment to parents and help-seeking behaviors) of NMRs and social and academic adjustment in college. Findings show a path relationship connecting the attachment to parents to help-seeking behaviors, and then to the number of reported NMRs. Help-seeking behaviors mediated the association between attachment and NMRs. The number of NMRs is associated with higher social adjustment, but not academic adjustment by the end of students’ first year of college. Based on these results, we discuss the theoretical implications of newly formed NMRs and provide guidance for institutional interventions targeting first-year college students to assist with transition challenges.     

Immunity against selected piscine flagellates

This discussion is on immune response to Amyloodinium ocellatum, Cryptobia salmositica, Trypanoplasma borreli and Trypanosoma carassii. Piscidin and histone-like proteins enhance innate resistance to Amyloodinium. Fish that are naturally resistant to Cryptobia and Trypanoplasma can be bred. Cryptobia resistance in charr is controlled by a dominant Mendelian locus and protection is via the Alternative Pathway of Complement Activation. Studies on Cryptobia-tolerant charr may lead to production of transgenic Cryptobia-tolerant salmon. Innate response to T. borreli is associated with NO in macrophages. Transferrin regulates resistance and carp have been bred for transferrin genotypes. Recovered fish are protected from homologous challenge, and complement fixing antibodies are crucial in protection. Studies on antigens in T. carassii may lead to a vaccine. There are two vaccines against cryptobiosis; a single dose of the attenuated vaccine protects salmonids. On challenge fish inoculated with the metalloprotease-DNA vaccine do not have the disease and they recover faster.     

Anti-citrullinated heat shock protein 90 antibodies identified in bronchoalveolar lavage fluid are a marker of lung-specific immune responses

Previous work has demonstrated a correlation between serum anti-citrullinated HSP90 antibodies and rheumatoid arthritis-associated interstitial lung disease (RA-ILD). To further investigate this potential pathogenic relationship, we used ELISA-based techniques to assess anti-citrullinated HSP90 antibody profiles in bronchoalveolar lavage fluid (BALF) of patients with different stages of RA-ILD. 9/21 RA-derived BALF specimens demonstrated IgG and/or IgA antibodies targeting citrullinated HSP90 proteins/peptides, highlighting disease specific responses (with a predilection for RA-ILD) that did not occur in IPF patients (0/5) or healthy control subjects (0/5). Comparison of antibody profiles between BALF and matching serum specimens revealed various recognition patterns favoring predominant production of anti-citrullinated HSP90 antibodies within the lung microenvironment—further supporting the connection between this antibody specificity and parenchymal lung disease. Equally important, qualitative as well as quantitative differences in anti-citrullinated HSP90 profiles between BALF and serum indicate that the lung plays a direct role in shaping the immune repertoire of RA/RA-ILD.     

Plasma chemistry reference values in the gyr falcon (Falco rusticolus)

Blood samples were collected from 102 clinically healthy gyr falcons (Falco rusticolus) over a time period of approximately 3 years as part of routine examination procedures. Standard blood chemistry analyses were carried out to establish normal reference values for the species. Plasma chemistry analyses included alkaline phosphatase (ALP), amylase, blood urea nitrogen, bile acids, calcium, cholesterol, creatinine, creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), glucose, phosphate, iron, total protein, total bilirubin, and uric acid. Reference intervals were determined using a quantile approach with 90 % confidence intervals of the limits. Juveniles and adults differ in ALT, creatinine, AST, glucose, LDH, and uric acid. Sexes differ in ALP, CK, AST, and phosphorus. This study provides valuable information on the plasma biochemistry values for gyr falcons that may help in the medical management of this endangered and commonly used falconry species.     

Invasive Breast Carcinoma with Neuroendocrine Differentiation: A Single-Center Analysis of Clinical Features and Prognosis

Introduction Invasive breast cancer with neuroendocrine differentiation is a rare subtype of breast malignancy. Due to frequent changes in the definition of these lesions, the correct diagnosis, estimation of exact prevalence, and clinical behaviour of this entity may be challenging. The aim of this study was to evaluate the prevalence, clinical features, and outcomes in a large cohort of patients with breast cancer with neuroendocrine differentiation. Patients Twenty-seven cases of breast cancer with neuroendocrine differentiation have been included in this analysis. Twenty-one cases were identified by systematic immunohistochemical re-evaluation of 465 breast cancer specimens using the neuroendocrine markers chromogranin A and synaptophysin, resulting in a prevalence of 4.5%. A further six cases were identified by a review of clinical records. Results Median age at the time of diagnosis was 61 years. 70% of patients had T2 – 4 tumors and 37% were node-positive. The most common immunohistochemical subtype was HR-positive/HER2-negative (85%). 93% were positive for synaptophysin and 48% for chromogranin A. Somatostatin receptor type 2A status was positive in 12 of 24 analyzed tumors (50%). Neuroendocrine-specific treatment with somatostatin analogues was administered in two patients. The 5-year survival rate was 70%. Conclusions Breast cancer with neuroendocrine differentiation is mostly HR-positive/HER2-negative and the diagnosis is made at a higher TNM stage than in patients with conventional invasive breast carcinoma. Moreover, breast cancer with neuroendocrine differentiation was found to be associated with impaired prognosis in several retrospective trials. Due to somatostatin receptor 2A expression, somatostatin receptor-based imaging can be used and somatostatin receptor-targeted therapy can be offered in selected cases. Key words: neuroendocrine neoplasia of the breast, invasive breast cancer with neuroendocrine differentiation, neuroendocrine breast cancer, neuroendocrine markers, somatostatin receptor 2A