Cystic fibrohistiocytic tumor of the lung presenting as a solitary lesion

Cystic fibrohistiocytic tumor of the lung is a rare neoplasm. In many cases it represents a metastasis from a benign or low-grade fibrohistiocytic tumor of the skin, but occasionally it may be primary. Radiologically it usually occurs as a cystic change of multiple pulmonary nodules, and pneumothorax is the most frequent presenting symptom. We present here a 16-year-old man with recurrent right pneumothorax. The patient had no history of cutaneous fibrohistiocytic lesions. He underwent videothoracoscopic right apical segmentectomy, right lower lobe nodulectomy, and pleuroabrasion. Microscopy of the apical segmentectomy showed a cystic fibrohistiocytic tumor, whereas the nodule of the lower lobe was an intraparenchymal lymph node. The patient is alive with no tumor recurrence. The differential diagnosis includes Langerhans cell histiocytosis, lymphangioleiomyomatosis, pleuropulmonary blastoma, and metastatic endometrial stromal sarcoma. This disease usually occurs with multiple pulmonary cysts and cavitation. This case is the first reported presenting as a single lesion

Effect of different atmospheric and subatmospheric cooking techniques on qualitative properties and microstructure of artichoke heads

Quartered Violetto artichokes were cooked with different treatments (boiling, steaming, sous vide and vacuum cooking) at the same cooking value at the thermal centre. Then, the physical (moisture content, texture and colour), histological and chemical (phenolic, 5-hydroxymethylfurfural (HMF) and furan content, total antioxidant capacity) features of bracts and hearts were assessed. A deeply modified microstructure was observed in boiled and steamed samples with an evident decrease in hardness both for bracts and hearts. Lightness of two anatomical parts was decreased by all the treatments (with the exception of sous vide bracts). The highest total colour difference was recorded for steamed samples, whereas the lowest was noted for sous vide samples. Steamed and sous vide artichoke exhibited the highest total phenolic content and total antioxidant capacity. Sous vide samples exhibited the highest concentrations of HMF, 2-furan-methanol and 2,4-dihydroxy-2,5-dimetyl-3(2H)-furanone, whereas the by-product 5-metylfuraldheide was only detected in the steamed product

Academy of Emergency Medicine and Care-Society of Clinical Biochemistry and Clinical Molecular Biology consensus recommendations for clinical use of sepsis biomarkers in the emergency department.

Increasing evidence is emerging that the measurement of circulating biomarkers may be clinically useful for diagnosing and monitoring sepsis. Eight members of AcEMC (Academy of Emergency Medicine and Care) and eight members of SIBioC (Italian Society of Clinical Biochemistry and Laboratory Medicine) were identified by the two scientific societies for producing a consensus document aimed to define practical recommendations about the use of biomarkers for diagnosing of sepsis and managing antibiotic therapy in the emergency department (ED). The cumulative opinions allowed defining three grade A recommendations (i.e., highly recommended indications), entailing ordering modality (biomarkers always available on prescription), practical use (results should be interpreted according to clinical information) and test ordering defined according to biomarker kinetics. Additional grade B recommendations (i.e., potentially valuable indications) entailed general agreement that biomarkers assessment may be of clinical value in the diagnostic approach of ED patients with suspected sepsis, suggestion for combined assessment of procalcitonin (PCT) and Creactive protein (CRP), free availability of the selected biomarker(s) on prescription, adoption of diagnostic threshold prioritizing high negative predictive value, preference for more analytically sensitive techniques, along with potential clinical usefulness of measuring PCT for monitoring antibiotic treatment, with serial testing defined according to biomarker kinetics. PCT and CRP were the two biomarkers that received the largest consensus as sepsis biomarkers (grade B recommendation), and a grade B recommendation was also reached for routine assessment of blood lactate. The assessment of biomarkers other than PCT and CRP was discouraged, with exception of presepsin for which substantial uncertainty in favor or against remained

Academy of Emergency Medicine and Care-Society of Clinical Biochemistry and Clinical Molecular Biology consensus recommendations for clinical use of sepsis biomarkers in the emergency department.

Increasing evidence is emerging that the measurement of circulating biomarkers may be clinically useful for diagnosing and monitoring sepsis. Eight members of AcEMC (Academy of Emergency Medicine and Care) and eight members of SIBioC (Italian Society of Clinical Biochemistry and Laboratory Medicine) were identified by the two scientific societies for producing a consensus document aimed to define practical recommendations about the use of biomarkers for diagnosing of sepsis and managing antibiotic therapy in the emergency department (ED). The cumulative opinions allowed defining three grade A recommendations (i.e., highly recommended indications), entailing ordering modality (biomarkers always available on prescription), practical use (results should be interpreted according to clinical information) and test ordering defined according to biomarker kinetics. Additional grade B recommendations (i.e., potentially valuable indications) entailed general agreement that biomarkers assessment may be of clinical value in the diagnostic approach of ED patients with suspected sepsis, suggestion for combined assessment of procalcitonin (PCT) and Creactive protein (CRP), free availability of the selected biomarker(s) on prescription, adoption of diagnostic threshold prioritizing high negative predictive value, preference for more analytically sensitive techniques, along with potential clinical usefulness of measuring PCT for monitoring antibiotic treatment, with serial testing defined according to biomarker kinetics. PCT and CRP were the two biomarkers that received the largest consensus as sepsis biomarkers (grade B recommendation), and a grade B recommendation was also reached for routine assessment of blood lactate. The assessment of biomarkers other than PCT and CRP was discouraged, with exception of presepsin for which substantial uncertainty in favor or against remained

Mammalian oocytes store proteins for the early embryo on cytoplasmic lattices

Mammalian oocytes are filled with poorly understood structures called cytoplasmic lattices. First discovered in the 1960s and speculated to correspond to mammalian yolk, ribosomal arrays, or intermediate filaments, their function has remained enigmatic to date. Here, we show that cytoplasmic lattices are sites where oocytes store essential proteins for early embryonic development. Using super-resolution light microscopy and cryoelectron tomography, we show that cytoplasmic lattices are composed of filaments with a high surface area, which contain PADI6 and subcortical maternal complex proteins. The lattices associate with many proteins critical for embryonic development, including proteins that control epigenetic reprogramming of the preimplantation embryo. Loss of cytoplasmic lattices by knocking out PADI6 or the subcortical maternal complex prevents the accumulation of these proteins and results in early embryonic arrest. Our work suggests that cytoplasmic lattices enrich maternally provided proteins to prevent their premature degradation and cellular activity, thereby enabling early mammalian development

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Unravelling integrated kinetics during spindle assembly

To ensure faithful segregation of the genetic material, during mitosis the cell assembles the mitotic spindle, a macromolecular machine made of dynamic microtubules and associated proteins. Spindle microtubules are assembled de novo by the centrosomes and through the RanGTP pathway that is sufficient for spindle self-organization. In this thesis I used a proteomics approach to study the RanGTP pathway induced microtubules and spindle self-organization and I propose that it occurs through a multi-step mechanism. I then addressed how the centrosomal and acentrosomal microtubule assembly pathways are integrated to build the bipolar spindle. My data suggest that, in small cells, centrosome maturation defines an optimal and essential balance between these two pathways due to a competition for limiting amounts of tubulin. Interestingly in big cells, I found that centrosome maturation ensures the correct positioning of each centrosome to a spindle pole and thereby assures proper centrosome segregation to the daughter cells. Finally, I present molecular insights about the interaction of the microtubule polymerase XMAP215 with its mitotic interactor TACC3.Durant la mitosi, per assegurar que el material genètic es segrega correctament, la cèl•lula construeix el fus mitòtic, una maquinària macromolecular formada de microtúbuls dinàmics i proteïnes associades. Els microtúbuls del fus són formats de novo pels centrosomes o a través de la “RanGTP pathway”, la qual és autosuficient per promoure l'autoorganització del fus mitòtic. En aquesta tesi he utilitzat tècniques de proteòmica per estudiar com la “RanGTP pathway” indueix l'autoorganització dels microtúbuls i del fus mitòtic a través d’un procés amb múltiples passos (tal i com indiquen els resultats obtinguts). Paral•lelament he estudiat com els microtúbuls formats per ambdues vies (centrosomes i “RanGTP pathway”) es coordinen per la construcció del fus bipolar. Els meus resultats suggereixen que, en cèl•lules petites, la maduració dels centrosomes defineix un equilibri òptim i essencial entre els dos sistemes, com a conseqüència de la disponibilitat limitada de tubulina. Per altra banda, en cèl•lules grans la maduració dels centrosomes condiciona la correcta localització d’aquests als pols del fus mitòtic, assegurant-ne la segregació a les dues cèl•lules filles. Finalment, exposo els detalls moleculars de la interacció entre la polimerasa de microtúbuls XMAP215 i el seu interactor mitòtic TACC3

The RanGTP Pathway: From Nucleo-Cytoplasmic Transport to Spindle Assembly and Beyond

The small GTPase Ran regulates the interaction of transport receptors with a number of cellular cargo proteins. The high affinity binding of the GTP-bound form of Ran to import receptors promotes cargo release, whereas its binding to export receptors stabilizes their interaction with the cargo. This basic mechanism linked to the asymmetric distribution of the two nucleotide-bound forms of Ran between the nucleus and the cytoplasm generates a switch like mechanism controlling nucleo-cytoplasmic transport. Since 1999, we have known that after nuclear envelope breakdown (NEBD) Ran and the above transport receptors also provide a local control over the activity of factors driving spindle assembly and regulating other aspects of cell division. The identification and functional characterization of RanGTP mitotic targets is providing novel insights into mechanisms essential for cell division. Here we review our current knowledge on the RanGTP system and its regulation and we focus on the recent advances made through the characterization of its mitotic targets. We then briefly review the novel functions of the pathway that were recently described. Altogether, the RanGTP system has moonlighting functions exerting a spatial control over protein interactions that drive specific functions depending on the cellular context

From meiosis to mitosis - the sperm centrosome defines the kinetics of spindle assembly after fertilization in Xenopus

Bipolar spindle assembly in the vertebrate oocyte relies on a self-organization chromosome-dependent pathway. Upon fertilization, the male gamete provides a centrosome, and the first and subsequent embryonic divisions occur in the presence of duplicated centrosomes that act as dominant microtubule organizing centres (MTOCs). The transition from meiosis to embryonic mitosis involves a necessary adaptation to integrate the dominant chromosome-dependent pathway with the centrosomes to form the bipolar spindle. Here, we took advantage of the Xenopus laevis egg extract system to mimic in vitro the assembly of the first embryonic spindle and investigate the respective contributions of the centrosome and the chromosome-dependent pathway to the kinetics of the spindle bipolarization. We found that centrosomes control the transition from the meiotic to the mitotic spindle assembly mechanism. By defining the kinetics of spindle bipolarization, the centrosomes ensure their own positioning to each spindle pole and thereby their essential correct inheritance to the two first daughter cells of the embryo for the development of a healthy organism.T.C. was supported by a Formación de Personal Investigador (FPI) fellowship (Ministerio de Economıa y Competitividad) [grant number BES-2010-031355]. This work was supported by the Ministerio de Economıa y Competitividad [grant numbers ́ BFU2009-10202 and BFU2012-37163]. We acknowledge the support of the Spanish Ministerio de Economıa y Competitividad programme ́ ‘Centro de Excelencia Severo Ochoa 2013–2017’ [grant number SEV-2012-0208

The sequential activation of the mitotic microtubule assembly pathways favors bipolar spindle formation

Centrosome maturation is the process by which the duplicated centrosomes recruit pericentriolar components and increase their microtubule nucleation activity before mitosis. The role of this process in cells entering mitosis has been mostly related to the separation of the duplicated centrosomes and thereby to the assembly of a bipolar spindle. However, spindles can form without centrosomes. In fact, all cells, whether they have centrosomes or not, rely on chromatin-driven microtubule assembly to form a spindle. To test whether the sequential activation of these microtubule assembly pathways, defined by centrosome maturation and nuclear envelope breakdown, plays any role in spindle assembly, we combined experiments in tissue culture cells and Xenopus laevis egg extracts with a mathematical model. We found that interfering with the sequential activation of the microtubule assembly pathways compromises bipolar spindle assembly in tissue culture cells but not in X. laevis egg extracts. Our data suggest a novel function for centrosome maturation that determines the contribution of the chromosomal microtubule assembly pathway and favors bipolar spindle formation in most animal cells in which tubulin is in limiting amounts.T.C. was supported by Formación de Personal Investigador (FPI) Fellowship BES-2010-031355. This work was supported by Spanish ministry grants BFU2009-10202 and BFU2012-37163. We acknowledge support of the Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa 2013-2017, SEV-2012-0208