Characterization of OSL dosimeters used at the ELI-beamlines laser-driven accelerator facility.

The Extreme Light Infrastructure (ELI) Beamlines laser-driven accelerator facility is set to operate the most intense non-military laser system in the world, with ultra-high power up to 10 PW, concentrated plasma intensities of up to 1024W cm-2, and ultra-short laser pulses of the order of few femtoseconds. A robust and redundant radiation monitoring system is in place to minimise risks to personnel and general public. Beryllium oxide optically stimulated luminescence (BeO-OSL) detectors are used to monitor radiation levels in the experimental building and surrounding grounds. In fact, in recent years, BeO-OSL have become an increasingly more popular choice for personal and environmental dosimetry. At ELI Beamlines, an exhaustive and thorough characterization process of the BeO-OSLs is in place. Dosimeter responses are studied as a function of delivered air kerma and photon energies. Calibration curves are calculated. Results from the latest calibration campaign are presented.

Absolute basophil count is associated with time to recurrence in patients with high-grade T1 bladder cancer receiving bacillus Calmette-Guérin after transurethral resection of the bladder tumor.

BACKGROUND: Basophils, eosinophils and monocytes may be involved in BCG-induced immune responses and be associated with outcomes of bladder cancer patients receiving intravesical BCG. Our objective was to explore the association of baseline counts of basophils, eosinophils and monocytes with outcomes of patients with high-grade T1 bladder cancer receiving a standard course of intravesical BCG. METHODS: We retrospectively reviewed medical records of patients with primary T1 HG/G3 bladder cancer. After re-TURBT, patients were treated with a 6-week course of intravesical BCG induction followed by intravesical BCG every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months from initiation of therapy The analysis of potential risk factors for recurrence, muscle invasion and cancer-specific and overall survival was performed using univariable Cox regression models. Those factors that presented, at univariate analysis, an association with the event at a liberal p < 0.1, have been selected for the development of a multivariable model. RESULTS: A total of 1045 patients with primary T1 HG/G3 were included. A total of 678 (64.9%) recurrences, 303 (29.0%) progressions and 150 (14.3%) deaths were observed during follow-up. Multivariate analysis showed that logarithmic transformation of basophils count was associated with a 30% increment in the hazard of recurrence per unit increase of logarithmic basophils count (HR 1.30; 95% confidence interval 1.09-1.54; p = 0.0026). Basophil count modeled by quartiles was also significantly associated with time to recurrence [second vs. lower quartile HR 1.42 (1.12-1.79); p = 0.003, third vs. lower quartile HR 1.26 (1.01-1.57); p = 0.041; upper vs. lower quartile HR 1.36 (1.1-1.68); p = 0.005]. The limitations of a retrospective study are applicable. CONCLUSION: Baseline basophil count may predict recurrence in BCG-treated HG/G3 T1 bladder cancer patients. External validation is warranted.

Organization and first results of cervical cancer screening program in Mayotte, from 2010 to 2014.

OBJECTIVES: Our main goal was to report the organization of individual screening for uterus cancer in Mayotte, the last French department since 2011, and its first results. MATERIAL AND METHODS: Epidemiological and observational study describing the prior situation, the beginning of the screening with pap smears in 2010, the colposcopy consultations and the treatment of the patients by the Mayotte network for screening of cancers since 2010. RESULTS: The screening allowed an improvement of the global cover rate from 5% to 24% in 5 years. The best results concern the woman from 25 to 39 years old, with a rate that rose from 14 to 46%. CONCLUSION: This study confirms the possibility and the efficiency of a screening program on this island, which is French by law, by much closer to developing countries on many other sides.

Hibiscus syriacus Extract from an Established Cell Culture Stimulates Skin Wound Healing.

Higher plants are the source of a wide array of bioactive compounds that support skin integrity and health. Hibiscus syriacus, family Malvaceae, is a plant of Chinese origin known for its antipyretic, anthelmintic, and antifungal properties. The aim of this study was to assess the healing and hydration properties of H. syriacus ethanolic extract (HSEE). We established a cell culture from Hibiscus syriacus leaves and obtained an ethanol soluble extract from cultured cells. The properties of the extract were tested by gene expression and functional analyses on human fibroblast, keratinocytes, and skin explants. HSEE treatment increased the healing potential of fibroblasts and keratinocytes. Specifically, HSEE significantly stimulated fibronectin and collagen synthesis by 16 and 60%, respectively, while fibroblasts contractility was enhanced by 30%. These results were confirmed on skin explants, where HSEE accelerated the wound healing activity in terms of epithelium formation and fibronectin production. Moreover, HSEE increased the expression of genes involved in skin hydration and homeostasis. Specifically, aquaporin 3 and filaggrin genes were enhanced by 20 and 58%, respectively. Our data show that HSEE contains compounds capable of stimulating expression of biomarkers relevant to skin regeneration and hydration thereby counteracting molecular pathways leading to skin damage and aging.

Lysobacter capsici AZ78 produces cyclo(L-Pro-L-Tyr), a 2,5-diketopiperazine with toxic activity against sporangia of Phytophthora infestans and Plasmopara viticola.

AIMS: To investigate low molecular weight compounds produced in vitro by Lysobacter capsici AZ78 and their toxic activity against sporangia of plant pathogenic oomycetes. METHODS AND RESULTS: Assays carried out in vitro showed that L. capsici AZ78 drastically inhibits the growth of plant pathogenic oomycetes. Accordingly, the preventive application of culture filtrates of L. capsici AZ78 on grapevine and tomato plants reduced the infections, respectively, caused by Plasmopara (Pl.) viticola and Phytophthora infestans. The subsequent chemical analysis of the culture filtrates of L. capsici AZ78 by spectroscopic (essentially 1D and 2D (1)H NMR and (13)C NMR and ESI MS spectra) and optical methods led to the identification of the 2,5-diketopiperazine cyclo(L-Pro-L-Tyr) that inhibited the development of P. infestans sporangia in vitro and on tomato leaves. Furthermore, a genomic region with high sequence identity with genes coding for a hybrid polyketide synthase and nonribosomal peptide synthetase was detected in L. capsici AZ78. CONCLUSIONS: Lysobacter capsici AZ78 produces cyclo(L-Pro-L-Tyr) in vitro that was effective in killing the sporangia of P. infestans and Pl. viticola in vitro. Moreover, this low molecular weight compound prevents the occurrence of late blight lesions when applied on tomato leaves. SIGNIFICANCE AND IMPACT OF THE STUDY: The application of L. capsici AZ78 cells or its own culture filtrates effectively controls both P. infestans and Pl. viticola. Cyclo(L-Pro-L-Tyr) produced by L. capsici AZ78 is toxic against sporangia of both these oomycetes. These data enforce the potential in the use of Lysobacter members for the control of plant pathogenic oomycetes and provide the basis for the development of new low-impact fungicides based on cyclo(L-Pro-L-Tyr).

Phenazines and cancer.

Phenazines are a large group of natural and synthesised nitrogen-containing heterocycles, including more than 100 different compounds of natural origin and over 6000 synthetic compounds. Many of these compounds have been investigated as potential anti-cancer agents. Despite a large number of research publications, no recent attempt to summarise and critically evaluate the experimental findings relating to the anti-cancer activity of this class of compounds has been made. The present review fills this gap in the literature and discusses both natural and synthetic phenazines with a critical focus on in vitro, in vivo and available clinical anti-cancer activities of these compounds.

CT-guided needle biopsy performed with modified coaxial technique in the diagnosis of malignant lymphomas.

PURPOSE: The aim of was study was to evaluate the accuracy of computed tomography (CT)-guided core needle biopsy (CNB) performed by modified coaxial technique as an alternative tool to surgical biopsy in patients with suspected malignant lymphoma. MATERIALS AND METHODS: Between May 2005 and December 2008, 67 CT-guided CNB of deep lesions were performed on 64 patients with suspected malignant lymphoma. In 19 out of 64 patients (29.7%), recurrent lymphoma was suspected. A modified coaxial technique was used in all cases, and multiple samples were obtained for histological and immunohistochemical studies. RESULTS: A diagnosis of malignant lymphomas with specification of subtype according to the World Health Organization (WHO) classification was established in 41/67 cases. Other malignant neoplasms were found in 13/67, lymphoma without subtype specification was diagnosed in 7/67, whereas no conclusive diagnosis could be established in 6/67 cases. Overall diagnostic accuracy was 80.1%. In patients with a final diagnosis of malignant lymphoma, accuracy was 75.9%. No complications occurred. CONCLUSIONS: Percutaneous CT-guided CNB is a safe, effective and reliable tool in the management of lymphomas in patients without superficial lymphadenopathy and can be considered an alternative approach to surgical sampling. The modified coaxial technique represents an effective tool that has a good diagnostic accuracy value with a low complication rate.

An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation.

The transcription factor AP-1 plays key roles in tumorigenesis, by regulating a variety of protein-coding genes, implicated in multiple hallmarks of cancer. Among non-coding genes, no AP-1 target has been described yet in tumorigenesis. MicroRNAs (miRNAs) are negative post-transcriptional regulators of protein-coding genes. miRNA expression signatures are highly relevant in cancer and several tumor-associated miRNAs (oncomirs) play critical roles in oncogenesis. Here, we show that the miRNA miR-21, which represents the most frequently upregulated oncomir in solid tumors, is induced by AP-1 in response to RAS. By analyzing validated miR-21 targets, we have found that the tumor suppressors PTEN and PDCD4 are downregulated by RAS in an AP-1- and miR-21-dependent fashion. We further show that, given the role of PDCD4 as negative regulator of AP-1, the miR-21-mediated downregulation of PDCD4 is essential for the maximal induction of AP-1 activity in response to RAS. Our data reveal a novel mechanism of positive autoregulation of the AP-1 complex in RAS transformation and disclose the function of oncomirs as critical targets and regulators of AP-1 in tumorigenesis.

A New Flow Cytometry Technique to Identify Phaeomoniella chlamydospora Exopolysaccharides and Study Mechanisms of Esca Grapevine Foliar Symptoms.

A flow cytometry technique that unequivocally identifies some of the toxic metabolites produced by Phaeomoniella chlamydospora, one of the main fungal pathogens causing esca disease of grapevine (Vitis vinifera), was developed. Antibodies raised against exopolysaccharides (EPS)-metabolites produced by Pa. chlamydospora that have been reported to be phytotoxic-were used as antigen to immunize rats. The specificity of these antibodies was assayed by flow cytometry against Pa. chlamydospora polysaccharides and against EPS with a different structure isolated from other phytopathogenic fungi, including Phaeoacremonium aleophilum and the Botryosphaeriaceae species Neofusicoccum luteum and N. parvum. Using this method, Pa. chlamydospora polysaccharides were detected in the symptomatic leaves of esca-affected grapevines, while healthy and asymptomatic leaves from both healthy and diseased vines did not produce a binding reaction. This method potentially could be used to develop a simple kit to study the mechanisms underlying the development of esca foliar symptoms and to indirectly assess the presence of Pa. chlamydospora in grapevine material.

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia.

MicroRNAs (miRNAs) are small non-coding RNAs of 19-25 nucleotides that are involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. However, little is known about the role of miRNAs in granulopoiesis. Here, we report the expression of miRNAs in acute promyelocytic leukemia patients and cell lines during all-trans-retinoic acid (ATRA) treatment by using a miRNA microarrays platform and quantitative real time-polymerase chain reaction (qRT-PCR). We found upregulation of miR-15a, miR-15b, miR-16-1, let-7a-3, let-7c, let-7d, miR-223, miR-342 and miR-107, whereas miR-181b was downregulated. Among the upregulated miRNAs, miR-107 is predicted to target NFI-A, a gene that has been involved in a regulatory loop involving miR-223 and C/EBPa during granulocytic differentiation. Indeed, we have confirmed that miR-107 targets NF1-A. To get insights about ATRA regulation of miRNAs, we searched for ATRA-modulated transcription factors binding sites in the upstream genomic region of the let-7a-3/let-7b cluster and identified several putative nuclear factor-kappa B (NF-kappaB) consensus elements. The use of reporter gene assays, chromatin immunoprecipitation and site-directed mutagenesis revealed that one proximal NF-kappaB binding site is essential for the transactivation of the let-7a-3/let-7b cluster. Finally, we show that ATRA downregulation of RAS and Bcl2 correlate with the activation of known miRNA regulators of those proteins, let-7a and miR-15a/miR-16-1, respectively.

[Adenocarcinoma of the nose after occupational exposure to wood dust: description of a case]. / Esposizione lavorativa a polvere di legno ed adenocarcinoma primitivo dei seni paranasali: descrizione di un caso.

UNLABELLED: The occupational exposure to wood dust, classified by IARC as carcinogenic certain may determine the onset of epithelial tumors of the mass graves and nasal sinuses. The symptoms of these malignancies are aspecific (nasal obstruction, rhinorrhea), the diagnosis is often delayed. CLINICAL CASE: Worker of 59 years occupied, from 1960 to 2005, in carpentry (construction of coffins), who died in 2006 for a nasal adenocarcinoma of the mass graves extended to the cranial base, initially considered intracranial cancer given the wide cranial fossae prior to the histological diagnosis. The case is emblematic to late diagnosis and long survival (the worker has survived for more than three years after TAC diagnosis of intracranial mass occurred in 2003). CONCLUSION: Extending the cranial base of a cancer of the nose and sinuses occurred in a worker exposed to wood dust is a serious critical in the system of health surveillance in the company. This rare neoplasm is a "sentinel event" that highlights a problem of underestimation of this occupational tumor and consequent failure of occupational disease complaint is therefore required a careful accounting and reporting of cases.

Primary intramedullary primitive neuroectodermal tumor (PNET)--case report and review of the literature.

Spinal primitive neuroectodermal tumors (PNET) are very rare tumors, and intramedullary localization is even less common. Indeed, amongst the 23 cases of the spinal PNET described in the literature, only eight cases had an intramedullary localization. Following the WHO 2000 classification, PNETs have been considered embryonal tumors composed of undifferentiated neuroepithelial cells with a capacity of differentiation into different cellular lines, such as astrocytic, ependymal, melanotic and muscular. They have been considered to arise from a neoplastic transformation of primitive neuroepithelial cells, thereby making their presence possible in any part of the central nervous system. The optimal treatment for these malignant tumors is not yet clear, although, over the years, radiotherapy has been considered the best treatment for spinal PNETs. The described case is that of a 38-year-old man with a primary intra-extramedullary PNET, treated by laminectomy, open biopsy and chemotherapy. The patient, 18 months after the onset of his symptomatology, died without cerebral tumor involvement.

[Intraoperative examination in neuropathology: proceedings evaluations]. / L'esame estemporaneo in neuropatologia: valutazione delle procedure tecniche.

INTRODUCTION: In the neuropathological intraoperative diagnostic is extremely important having guide lines to obtain a lot of information about the slide. In our study we have considered only the intraoperative the cases diagnosed within a month comparing the histological evaluation using the cryostat and the cytological examination of touch or smear preparation. MATERIALS AND METHODS: Our study includes 7 meningiomas, 2 metastatic carcinomas, 1 anaplastic astrocitoma, 1 mieloplaxis tumor, 1 anaplastic chordoma. For the cytological examination we have got ready 8 touch or smear preparations and we have executed 4 proceedings: stainings with Giemsa, toluidine blue and haematoxylin and eosin, after fixation with 95% alcohol and staining with haematoxylin and eosin after fixation with alcohol and a small quantity of acetic acid. For the histological examination we have got ready 8 preparations, using the cryostat. We have fixed the slides with 95% alcohol or 10% formalin and stained them with haematoxylin and eosin. In the 50% of the cases we have treated the sections with microwave at 400W. RESULTS: Two pathologists have examinated the 192 sections prepared, judging each slide considering the legibility: unsatisfactory, quite good, good and excellent. CONCLUSIONS: Considering the cytological examination, Giemsa and toluidine blue permit the best legibility of nuclear and cytoplasmatic morphological details. Legibility is worse in staining with haematoxylin and eosin. Addition of acetic acid makes variable results. In the histological slides the best result are obtained using 95% alcohol for fixing. Microwave use doesn't determine improvement.

[Petit's lumbar hernia: about a case]. / Su di un caso di ernia lombare di Petit.

The authors are surgeons of Moscati Hospital in Aversa (CE)-Italy, and one of them is a Radiologist in the same hospital; they describe a rare case of lumbar hernia, the Petits hernia and describe the anatomical aspects of parietals hernias. Subsequently they describe the diagnostics aspects and then the surgicals treatments. In this case-report the authors describe the surgical operation to use one prolene-net to close the parietal breach. The most important aspect, that the authors emphsasize, is the absolute importance of careful clinic examination to diagnose it. This work is completed with some pictures that show it; some pictures are made in operatory-room during the surgical treatment and some of them are TC images.

Non-Hodgkin's lymphoma in the gluteal region: a case report.

The infiltration of the skeletal muscles on the part of lymphomatous cells is rarely reported and only histological examination can reveal it. Based on a review of the literature, it is the purpose of this study to describe a rare case of non-Hodgkin's lymphoma with muscular invasion, characterized by voluminous swelling in the left gluteal region, in a female aged 60 years who was completely asymptomatic. Biopsy and immunohistochemistry alone allowed us to diagnose non-Hodgkin's lymphoma. It is the purpose of this study to document the existence of NHL with musculoskeletal localization, emphasizing the morphological features and the site, as well as hypothesizing that wide-margin surgery can constitute a valid therapeutic aid for such extralymphonodal forms, that are particularly large and with a single localization.

Multiple osteoid osteoma. A clinical case.

Osteoid osteoma is a benign tumor occurring frequently during the growth years. It may be found in any of the skeletal segments, and it is often present as an isolated neoformation. In some rare cases it may involve more than one segment or it may be multicentric. The authors report their experience with a case of double localization of metachronous osteoid osteoma.

RNA expression bcl-w, a new related protein Bcl-2 family, and caspase-3 in isolated sertoli cells from pre-pubertal rat testes.

Apoptosis has a major role in molding the embryo, in the maintenance of tissue homeostasis, and in the defense against pathogens, while its disgregulation is strongly implicated in cancer as well as in autoimmune and degenerative diseases. The opposite action of anti-apoptotic proteins (Bcl-2 family) and pro-apoptotic proteins (p53, Bax, Bak) regulates the activation of caspases that are the effectors proteases of the cell suicide. Bcl-W is a pro-survival protein, recently discovered, related to the Bcl-2 family. The presence of Bcl-W is fundamental for spermatogenesis in rats. Caspases are cysteine-dependent aspartate-specific proteases, and their over-expression can result in apoptotic cell death. Normally, caspases exist in cells as inactive pro-enzymes and can be activated by 2 distinct mechanisms: the FADD/caspase 8 cascade, and the Apaf-1/caspase 9 cascade. These 2 mechanisms are used extensively by cells for the activation of the effectors caspases: caspase 3, caspase 6, and/or caspase 7. Bcl-W and caspases might have a pivotal role in maintenance of Sertoli cells integrity. In this study, we demonstrate that both Bcl-W mRNA and caspase 3 mRNA are expressed in isolated Sertoli cells of pre-puberal rat testes. This finding might be crucial in clarifying whether Sertoli cells die by an apoptotic mechanism. Further studies are required to understand whether the expression of Bcl-W and caspases is different before and after puberty in rat testis and/or in pathological conditions, that lead to an increased cell apoptosis.

[A new technique for foetal brain fixation and extraction]. / Una nuova procedura per la fissazione ed estrazione dell'encefalo fetale.

We performed a new technique for foetal brain fixation and extraction that offers a remarkable reduction in sampling time facilitates specimen handling while conserving high quality. With the new fixation method, it is possible to obtain samples adequate for macroscopic and microscopic observations and immunohistochemical analysis. The technique involves the creation of an ex vacuo phenomenon in the subarachnoideal space prior to injecting the fixative solution. In this manner, the solution is homogenously distributed. Ease, reproducibility and the possibility of standardizing the procedure are the principal advantages. Low costs, reduced wording time and less need for human resources are other advantages. Histologically, we obtained, quickly, high quality slides with routine and immunohistochemical stains. Disadvantages of the technique derive from the use of formaldehyde and glacial acetic acid, rather than water to wash the samples; thus one must work in a well ventilated area, with gloves, protective glasses and an adequate lab coat to avoid skin and respiratory tract damage.