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There are unexplained geographical variations in the incidence of kidney cancer with the high rates reported in Baltic countries, as well as eastern and central Europe. Having access to a large and well-annotated collection of “tumor/non-tumor” pairs of kidney cancer patients from the Czech Republic, Romania, Serbia, UK, and Russia, we aimed to analyze the morphology of non-neoplastic renal tissue in nephrectomy specimens. By applying digital pathology, we performed a microscopic examination of 1012 frozen non-neoplastic kidney tissues from patients with renal cell carcinoma. Four components of renal parenchyma were evaluated and scored for the intensity of interstitial inflammation and fibrosis, tubular atrophy, glomerulosclerosis, and arterial wall thickening, globally called chronic renal parenchymal changes. Moderate or severe changes were observed in 54 (5.3%) of patients with predominance of occurrence in Romania (OR = 2.67, CI 1.07–6.67) and Serbia (OR = 4.37, CI 1.20–15.96) in reference to those from Russia. Further adjustment for comorbidities, tumor characteristics, and stage did not change risk estimates. In multinomial regression model, relative probability of non-glomerular changes was 5.22 times higher for Romania and Serbia compared to Russia. Our findings show that the frequency of chronic renal parenchymal changes, with the predominance of chronic interstitial nephritis pattern, in kidney cancer patients varies by country, significantly more frequent in countries located in central and southeastern Europe where the incidence of kidney cancer has been reported to be moderate to high. The observed association between these pathological features and living in certain geographic areas requires a larger population-based study to confirm this association on a large scale.

International audience; Toll-like receptor 9 (TLR9) recognizes bacterial, viral or cell damage-associated DNA, which initiates innate immune responses. We have previously shown that TLR9 expression is downregulated in several viral induced cancers including HPV16-induced cervical neoplasia. Findings supported that downregulation of TLR9 expression is involved in loss of anti-viral innate immunity allowing an efficient viral replication. Here we investigated the role of TLR9 in altering the growth of transformed epithelial cells. Re-introducing TLR9 under the control of an exogenous promoter in cervical or head and neck cancer patient-derived cells reduced cell proliferation, colony formation and prevented independent growth of cells under soft agar. Neither TLR3, 7, nor the TLR adapter protein MyD88 expression had any effect on cell proliferation, indicating that TLR9 has a unique role in controlling cell growth. The reduction of cell growth was not due to apoptosis or necrosis, yet we observed that cells expressing TLR9 were slower in entering the S-phase of the cell cycle. Microarray-based gene expression profiling analysis highlighted a strong interferon (IFN) signature in TLR9-expressing head and neck cancer cells, with an increase in IFN-type I and IL-29 expression (IFN-type III), yet neither IFN-type I nor IL-29 production was responsible for the block in cell growth. We observed that the protein half-life of p16(INK4a) was increased in TLR9-expressing cells. Taken together, these data show for the first time that TLR9 affects the cell cycle by regulating p16(INK4a) post-translational modifications and highlights the role of TLR9 in the events that lead to carcinogenesis

Background and objectives Central venous catheterization of the internal jugular vein is a commonly performed invasive procedure associated with a significant morbidity and even mortality. Ultrasound-guided methods have shown to significantly improve the success of the technique and are recommended by various scientific societies, including the American Society of Anesthesiologists. The aim of this report is to describe an innovative ultrasound-guided central line placement of the internal jugular vein. Technique The authors describe an innovative ultrasound-guided central line placement of the internal jugular vein based on an oblique approach – the “Syringe-Free” approach. This technique allows immediate progression of the guide wire in the venous lumen, while maintaining a real-time continuous ultrasound image. Conclusions The described method adds to the traditional oblique technique the possibility of achieving a continuous real-time ultrasound-guided venipuncture and a guide wire insertion that does not need removing the probe from the puncture field, while having a single operator performing the whole procedure.

Observation of benthic photoautotrophs on sediment surfaces shows a single algal layer without distinction between photosynthetic groups. Until now it has not been possible to distinguish between benthic photosynthetic microorganisms, i.e. cyanobacteria and diatoms, at μm to mm scales using a single nondisruptive system. Chlorophyll autofluorescence can be used to distinguish different photoautotrophic groups if the correct excitation light is applied. Using this principle, a nonintrusive technique was developed to study the spatial distribution of benthic cyanobacteria and diatoms. By means of a charge coupled device camera, diatoms and cyanobacteria could be identified by blue light (470 nm) excitation and amber light (600 nm) excitation, respectively. By this approach, diatom or cyanobacterial dominance could be easily distinguished using the blue over amber ratio. We applied this method successfully to (mixed) laboratory cultures as well as natural photosynthetic microbial mats. Cultures of the diatom Nitzschia capitellata and the cyanobacterium Geitlerinema sp. showed close correlation between autofluorescence and cell abundance. This simple and cheap imaging system allows fast observations of the fine-scale (μm-mm) spatial heterogeneities of live benthic microbial photoautotrophs both in culture and natural photosynthetic biofilms structure (e.g., microphytobenthos and photosynthetic microbial mats).

Marine sedimentary habitats generally have their highest microbial activity in the top few centimeters. Where light reaches the sediments, benthic oxygenic photoautotrophs grow and the organic matter released is decomposed in a series ofdifferent metabolic pathways by heterotrophic prokaryotes. If grazing pressure is low (or absent), as found more often in extreme environments such as hot springs, high salinity environments and sediments with periodic desiccation, hotosynthetic microbial mats may be formed. Microbial mats are permanently vertically laminated microbial communities, with the top photosynthetic layer composed of cyanobacteria and benthic eukaryotic microalgae (such as diatoms). Much work has been doneregarding the physico-chemical parameters structuring the microbial activity, but to my knowledge there are no reports on microscale (µm to mm) abundance distributions of viruses, prokaryotes and oxygenic photoautotrophs in benthic systems. It is, however, essential to collect samples at the scale relevant for microbial activity. Moreover, it is important to improve our understanding of which underlying factors, other than bottom-up (e.g. physico-chemical variables such as organic matter, light, temperature), regulate the spatial distribution of key members of benthic ecosystems.In this thesis, I show that viruses and prokaryotes in a tidal sediment from Dunstaffnage Bay, Scotland, distribute heterogeneously both at horizontal and vertical mm scale. Furthermore, it was also shown that the dynamic viral activity over time contributed to the microscale heterogeneity observed (Chapter 2). To be able to examine microscale distributions of viruses and prokaryotes in photosynthetic microbial mats an improved method for extracting viruses and prokaryotes from thesemats with their high load of organic matter was developed (Chapter 3). The method also provided better results when applied to the sediment. Furthermore, the newly developed method could be successfully combined with flow cytometry, thereby providing a fast and accurate method that can help opening the research field of viral ecology in microbial mats. Application of this method to intertidal microbial mats from the Wadden Sea island Schiermonnikoog, The Netherlands, also showed microscaleheterogeneity in prokaryotic and viral abundances, the latter amongst the highest recorded (1.5 ± 1.5 x 1010 viruses g-1) in natural benthic habitats (Chapter 5). Viral and prokaryotic abundances were related to the depth of the oxygenicphotoautotrophic layer between the sampled periods (November 2012, April, and July 2013). Microscale observation and distinction of the two main oxygenic photoautotrophic groups (cyanobacteria and diatoms) in microbial mats was possibledue to the development of a new, fast and non-intrusive, method using photoautotrophic group-specific autofluorescence imaging (Chapter 4). Applying the method in the field displayed patchy populations of cyanobacteria and diatoms at the µm to mm spatial scale. These findings will have implications on the localproductivity, as cyanobacteria have different productivity rates from diatoms. Considering that grazing pressure is typically low in microbial mats, I have focused on other factors (viruses and fungi) that may affect variability in (microscale) spatial and temporal distribution of the major groups of oxygenic photoautotrophs.The high viral abundances found in the microbial mats indicated that viruses could be significant players in the mats as potential mortality agents for prokaryotes and oxygenic photoautotrophs (Chapter 5), with particularly high abundances in the photosynthetic layer compared to the heterotrophic layers below. The fungus Emericellopsis sp. was found to affect the spatial distribution of oxygenic photoautotrophs by degrading benthic cyanobacteria and diatoms, during summer and autumn (Chapter 6). Consequently, small (2 - 5 cm) ring-like clearings in the photosynthetic microbial mat occurred that were re-colonised firstly by the diatoms. Fungal activity thus influenced not only oxygenic photoautotrophic speciesdistribution and diversity (via degradation), but also succession and subsequently is expected to have an effect on the productivity of the photosynthetic microbial mat.Overall, it was observed that microbes (prokaryotes and oxygenicphotoautotrophs) in microbial mats and intertidal sediments can be distributed at µm to mm scales. Mortality agents, such as viruses and fungi, were found relevant underlying factors for the observed microscale spatial distributions. Based on thesefindings more research on interactions between these mortality agents (viruses and fungi) and the dominant benthic microbial groups is desired. This would improve our understanding of their role in species diversity and succession, as well as the extentto which these mortality factors affect biogeochemical cycling within the microbial mats.

PubMed: 26787795, Background: Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. Methods: We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. Results: The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl-1 and increased to 9.8 (1.8) g dl-1 after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). Conclusions: Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl-1), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold. © 2016 The Author. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.

Amiodarone is a potent anti-arrhythmic drug with a well-known potential chronic pulmonary toxicity. We describe a case of acute pulmonary toxicity (APT) induced by amiodarone in a 57 year old patient submitted to a perfusion of 900 mg in just 6 hours, to control an auricular flutter with rapid ventricular response. During the administration, the patient developed hemodynamic instability and oxygen dessaturation that led to an electrical cardioversion with return of sinus rhythm. Still, the patient continued in progressive respiratory deterioration with acute bilateral infiltrates on chest x-ray and apparent normal cardiac filling pressures confirmed by echocardiography. Anon-cardiogenic pulmonar edema progressing to clinico-physiological ARDS criteria was diagnosed. Expeditive therapeutic measures were undertaken, namely by initiation of non-invasive positive airway pressure support, that attained a good result.Albeit rare, amiodarone-induced APT might have severe consequences, namely progression to ALI/ARDS with a high mortality index.As it is a frequently prescribed drug, there should be a high clinical suspicion towards this phenomenon, allowing precocious therapeutic measures to be taken in a timely fashion to prevent the associated unfavorable outcome.

Objectives To estimate the diagnostic accuracy of magnetic resonance imaging (MRI) in detecting additional lesions and contralateral cancer not identified using conventional imaging in primary breast cancer. Methods We have conducted a systematic review and meta- analyses to estimate diagnostic accuracy indices and the impact of MRI on surgical management. Results Fifty articles were included (n =10,811 women). MRI detected additional disease in 20% of women and in the contralateral breast in 5.5%. The summary PPV of ipsilateral additional disease was 67% (95% CI 59-74%). For contralateral breast, the PPV was 37% (95% CI 27-47%). For ipsilateral lesions, MRI devices =1.5 Tesla (T) had higher PPV (75%, 95% CI 64-83%) than MRI with

The signal peptide-less FGF gene family prototype, FGF1 is released in response to temperature stress in vitro as a latent reducing agent-sensitive homodimer non-covalently complexed with the extravesicular p40 domain of p65 synaptotagmin (Syt)1. Because FGF1 is well recognized as an angiogenesis factor in vivo and angiogenesis is known to be induced by hypoxia, we examined the release of FGF1 and p40 Syt1 under conditions of hypoxia and temperature stress using a chemostatic microcarrier cell culture system. We report that like the pathway used by FGF1 and p40 Syt1 release under temperature stress, hypoxia also induces the release of FGF1 and p40 Syt1 with similar kinetic and pharmacologic properties including the requirement for functional cysteine residues. Lastly, FGF1 and p40 Syt1 release in response to hypoxia and temperature stress is sensitive to lipoxygenase and cyclooxygenase inhibitors suggesting that arachidonic acid metabolism may play an important role in the mechanism of FGF1 releas...

Unlike vascular endothelial growth factor (VEGF)-A, the effect of VEGF-C on tumor angiogenesis, vascular permeability, and leukocyte recruitment is not known. To this end, we quantified in vivo growth and vascular function in tumors derived from two VEGF-C-overexpressing (VC+) and mock-transfected cell lines (T241 fibrosarcoma and VEGF-A-/- embryonic stem cells) grown in murine dorsal skinfold chambers. VC+ tumors grew more rapidly than mock-transfected tumors and exhibited parallel increases in tumor angiogenesis. Furthermore, VEGF-C overexpression elevated vascular permeability in T241 tumors, but not in VEGF-A-/- tumors. Surprisingly, unlike VEGF-A, VEGF-C did not increase leukocyte rolling or adhesion in tumor vessels. Administration of VEGF receptor (VEGFR)-2 neutralizing antibody DC101 reduced vascular density and permeability of both VC+ and mock-transduced T241 tumors. These data suggest that VEGFR-2 signaling is critical for tumor angiogenesis and vascular permeability and that VEGFR-3 signaling does not compensate for VEGFR-2 blockade. An alternate VEGFR, VEGFR-1 or neuropilin-1, may modulate adhesion of leukocytes to tumor vessels.

Texto completo. Acesso restrito. p. 197 – 202 Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-02-20T20:15:27Z No. of bitstreams: 1 11111.pdf: 428419 bytes, checksum: 68002842252cfdce13a7eebeed9770fc (MD5) Approved for entry into archive by Fatima Cleômenis Botelho Maria (botelho@ufba.br) on 2013-02-21T13:39:41Z (GMT) No. of bitstreams: 1 11111.pdf: 428419 bytes, checksum: 68002842252cfdce13a7eebeed9770fc (MD5) Made available in DSpace on 2013-02-21T13:39:41Z (GMT). No. of bitstreams: 1 11111.pdf: 428419 bytes, checksum: 68002842252cfdce13a7eebeed9770fc (MD5) Previous issue date: 1984 Plasma levels of estradiol and progesterone were investigated in women using daily vaginal pills containing 1 mg norethindrone and 50 mcg mestranol. Of 13 treatment cycles in ten women using one vaginal pill daily, six were ovulatory and seven anovulatory. All 12 cycles in ten women using two vaginal pills daily were anovulatory. Salvador