Crescentic Glomerulonephritis in IgA Multiple Myeloma: A Case Report

Background: There are few reports of glomerulonephritis (GN) with crescents and a rapidly progressive course that lead to a diagnosis of a previously unsuspected B-cell dyscrasia. Case Presentation: We report a case of rapidly progressive GN: the patient showed no evidence of etiology at the time of biopsy and was diagnosed as IgA multiple myeloma (MM) during investigation based on a renal biopsy. He presented diffuse proliferative and exudative GN and marked plasma cell infiltration of the kidney. Conclusion: The present case raises the possibility that proliferative GN with crescents may be a rare mode of presentation of MM

Development and Validation of a Multi-Pollutant Method for the Analysis of Polycyclic Aromatic Hydrocarbons, Synthetic Musk Compounds and Plasticizers in Atmospheric Particulate Matter (PM₂.₅)

[Abstract] Exposure to atmospheric particulate matter (PM) associated pollutants is a global concern due to the risk posed in human health after inhalation. In this study, a simple and sensitive multi-residue method is developed for the analysis of 50 organic pollutants, comprising 18 polycyclic aromatic hydrocarbons (PAHs), 12 phthalate esters (PAEs), 12 organophosphorus flame retardants (OPFRs), 6 synthetic musk compounds (SMCs) and 2 bisphenols in PM₂.₅ samples. The method consists of three cycles of ultrasonic assisted solvent extraction and vortex (UASE + vortex), followed by a vortex-assisted dispersive solid phase extraction (d-SPE) clean-up and a final determination step by using programmed temperature vaporization-gas chromatography-tandem mass spectrometry (PTV-GC-MS/MS). Experimental conditions concerning clean-up adsorbents (alumina, silica gel and Florisil®) and filters (glass fibre, PTFE and nylon), as well as PTV-GC-MS/MS conditions were studied. In addition, the use of SRM (selected reaction monitoring) mode in MS-MS, as well as matrix-matched calibration together with labelled subrogate standards, resulted in successfully validation results for most of the compounds due to the high sensitivity, minimization of matrix effects and recovering losses compensation. The proposed method was validated in terms of linearity, limits of detection and quantification (LODs and LOQs), analytical recoveries by analysing a spiked composite sample (PM₂.₅) at three spiking levels and intra-day and inter-day precision. Moreover, an urban particulate matter standard reference material (SRM 1648a) was analysed to assess PAHs determination accuracy. Furthermore, applicability of the method was proved by analysing 12 PM₂.₅ samples from an industrial area. Among all studied pollutants, bisphenol A (BPA) was the most predominant with an average concentration of 5000 pg m⁻³, followed by bis(2-ethylhexyl) phthalate (DEHP) and diisobutyl phthtalate (DiBP) with 1990 pg m⁻³ and 632 pg m⁻³, respectively. Concerning OPFRs, average concentrations between 345 – 253 pg m⁻³ were found for triphenyl phosphine oxide (TPPO), tris(chloropropyl) phosphate (TCPP), tri-iso-butyl phosphate (TiBP) and tris(2-butoxyethyl) phosphate (TBOEP). Finally, the highest PAHs levels were found for 5-6 ring-number PAHs (Σ5-6 rings PAHs) with an average concentration of 2680 pg m⁻³, while only 2 SMCs were quantitated accounting for 17.5 pg m⁻³ by average.This work was supported by the Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (Programa Estatal de I+D+i Orientada a los Retos de la Sociedad, ref: RTI 2018-101116-B-I00) and the Xunta de Galicia (Programa de Consolidación y Estructuración de Unidades de Investigación Competitivas ref: ED431C 2017/28-2017-2020). Joel Sánchez-Piñero acknowledges the Xunta de Galicia and the European Union (European Social Fund - ESF) for a predoctoral grant (ED481A-2018/164). The Laboratorio de Medio Ambiente de Galicia (LMAG) of the Subdirección Xeral de Meteoroloxía e Cambio Climático (Xunta de Galicia) is also acknowledged for providing the samples used in the present research workXunta de Galicia; ED431C 2017/28-2017-2020Xunta de Galicia; ED481A-2018/16

Phthalates, organotin compounds and per-polyfluoroalkyl substances in semiconfined areas of the Spanish coast: occurrence, sources and risk assessment

Postprint3,25

Pore dimensions and the role of occupancy in unitary conductance of Shaker K channels

Indexación: Web of Science; Scopus.K channels mediate the selective passage of K+ across the plasma membrane by means of intimate interactions with ions at the pore selectivity filter located near the external face. Despite high conservation of the selectivity filter, the K+ transport properties of different K channels vary widely, with the unitary conductance spanning a range of over two orders of magnitude. Mutation of Pro475, a residue located at the cytoplasmic entrance of the pore of the small-intermediate conductance K channel Shaker (Pro475Asp (P475D) or Pro475Gln (P475Q)), increases Shaker's reported. 20-pS conductance by approximately six-and approximately threefold, respectively, without any detectable effect on its selectivity. These findings suggest that the structural determinants underlying the diversity of K channel conductance are distinct from the selectivity filter, making P475D and P475Q excellent probes to identify key determinants of the K channel unitary conductance. By measuring diffusion-limited unitary outward currents after unilateral addition of 2 M sucrose to the internal solution to increase its viscosity, we estimated a pore internal radius of capture of 0.82 for all the three Shaker variants (wild type, P475D, and P475Q). This estimate is consistent with the internal entrance of the Kv1.2/2.1 structure if the effective radius of hydrated K+ is set to 4 A. Unilateral exposure to sucrose allowed us to estimate the internal and external access resistances together with that of the inner pore. We determined that Shaker resistance resides mainly in the inner cavity, whereas only similar to 8% resides in the selectivity filter. To reduce the inner resistance, we introduced additional aspartate residues into the internal vestibule to favor ion occupancy. No aspartate addition raised the maximum unitary conductance, measured at saturating [K+], beyond that of P475D, suggesting an similar to 200-pS conductance ceiling for Shaker. This value is approximately one third of the maximum conductance of the large conductance K (BK) channel (the K channel of highest conductance), reducing the energy gap between their K+ transport rates to similar to 1 kT. Thus, although Shaker's pore sustains ion translocation as the BK channel's does, higher energetic costs of ion stabilization or higher friction with the ion's rigid hydration cage in its narrower aqueous cavity may entail higher resistance.http://jgp.rupress.org/content/146/2/13

Occurrence of organotin compounds in waters of the spanish coast under the European Water Framework Directive

Organotin compounds (OTCs), such as tributyltin (TBT), are persistent organic pollutants that are present in water samples (surface water, river water, sea water, waste water, etc.) because of anthropogenic activities (antifouling agents in ship paints, biocides in polymers, etc.). The toxicity and endocrine disruption potential of these chemicals have been demonstrated even at very low levels (<1 ng L−1) (Devos et al. 2012). Due to the extensive presence of OTCs in all environmental media as well as their adverse effects on human health and biota, quantitative and qualitative determination of those com-pounds in complex environmental matrices has become a matter of great concern, mainly butyl and phenyl-substituted. Also, these compounds are included in the list of priority substances according to the EU Directive 2013/39/EU amending Directives 2000/60/EC and 2008/105/EC as regards priority substances in the field of water policy. This directive specifies annual average environmental quality standard (AA-EQS) of 0.2 ng L−1 TBT and a maximum allowable environmental quality standard (MAC-EQS) of 1.5 ng L−1 TBT for all surface waters. Samples were collected in two semiconfined coastal areas, one of them an area with high industrial and port activities (Ría de Vigo) and the other one with high touristic and agricultural activity (Mar Menor).The sampling campaigns were performed in spring and autumn of 2015. The levels of MBT, DBT, TBT, MPhT, DPhT and TPhT in the seawater samples were analyzed by HS-SPME-GC–QqQMS/ MS method (Moscoso-Pérez et al. 2015). MPhT, DPhT and TPhT were not detected in any sample at levels higher than LOQ. For butylated compounds, MBT, DBT and TBT were detected in 100% of the analyzed samples in the Mar Menor. In the Vigo estuary, MBT has been detected in 83.3% of the samples, the DBT in 75% and the TBT in 88%. The TBT is present in 92% of the total of 39 analyzed samples, being detected in 100% of the samples of the Mar Menor and in 88% of the samples of the Ría de Vigo. These levels are similar than those detected in other locations, and lower than the detected in ports near the coast of Gijón characterized by a great maritime traffic (Centineo et al. 2004).Program of Consolidation and Structuring of Units of Competitive Investigation of the University System of Galicia (Xunta de Galicia) potentially cofinanced by ERDF in the frame of the operative Program of Galicia 2007-2013 (reference: GRC2013-047) and by the Ministry of Economy and Competitiveness (IMPACTA, project reference: CTM2013-48194-C3-2-R, and ARPA-ACUA, project reference: CTM2016-77945-C3-3-R)

Laparoscopic versus open colectomy for acute complicated diverticulitis: a comparative study of outcomes - a systematic review

Acute complicated diverticulitis presents a more severe form of diverticular illness frequently needing urgent medical intervention and possibly surgical therapy. The aim of this review is to gather conclusive evidence from the literature comparing laparoscopic techniques to open and conservative ones in order to determine the most effective treatment plan for complicated diverticulitis. Online databases like PubMed, Google Scholar, Cochrane, Elsevier and many others were systematically searched according to an inclusion criterion to obtain a total of 13 studies to be included in the review. 8/13 studies presented short term outcomes while 5/13 studies concluded with long term outcomes following index surgeries. Based on the end results, it can be concluded that laparoscopic surgery, in particular laparoscopic colon resection is superior to other techniques in treating complicated diverticulitis in terms of fewer short-term complications, low mortality rate better quality of life with few recurrence rates. However, other approaches have their own advantages and can be given priority based on the unique presentation of each case. The clinicians are advised to make informed decisions keeping in view all the patient and disease associated aspects

Nasopharyngeal Colonization and Invasive Disease Are Enhanced by the Cell Wall Hydrolases LytB and LytC of Streptococcus pneumoniae

Background: Streptococcus pneumoniae is a common colonizer of the human nasopharynx and one of the major pathogens causing invasive disease worldwide. Dissection of the molecular pathways responsible for colonization, invasion, and evasion of the immune system will provide new targets for antimicrobial or vaccine therapies for this common pathogen. Methodology/Principal Findings: We have constructed mutants lacking the pneumococcal cell wall hydrolases (CWHs) LytB and LytC to investigate the role of these proteins in different phases of the pneumococcal pathogenesis. Our results show that LytB and LytC are involved in the attachment of S. pneumoniae to human nasopharyngeal cells both in vitro and in vivo. The interaction of both proteins with phagocytic cells demonstrated that LytB and LytC act in concert avoiding pneumococcal phagocytosis mediated by neutrophils and alveolar macrophages. Furthermore, C3b deposition was increased on the lytC mutant confirming that LytC is involved in complement evasion. As a result, the lytC mutant showed a reduced ability to successfully cause pneumococcal pneumonia and sepsis. Bacterial mutants lacking both LytB and LytC showed a dramatically impaired attachment to nasopharyngeal cells as well as a marked degree of attenuation in a mouse model of colonization. In addition, C3b deposition and phagocytosis was more efficient for the double lytB lytC mutant and its virulence was greatly impaired in both systemic and pulmonary models of infection. Conclusions/Significance: This study confirms that the CWHs LytB and LytC of S. pneumoniae are essential virulence factor

pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation

Cancer; Mechanisms of diseaseCàncer; Mecanismes de la malaltiaCáncer; Mecanismos de la enfermedadThe human transcriptome contains thousands of small open reading frames (sORFs) that encode microproteins whose functions remain largely unexplored. Here, we show that TINCR lncRNA encodes pTINCR, an evolutionary conserved ubiquitin-like protein (UBL) expressed in many epithelia and upregulated upon differentiation and under cellular stress. By gain- and loss-of-function studies, we demonstrate that pTINCR is a key inducer of epithelial differentiation in vitro and in vivo. Interestingly, low expression of TINCR associates with worse prognosis in several epithelial cancers, and pTINCR overexpression reduces malignancy in patient-derived xenografts. At the molecular level, pTINCR binds to SUMO through its SUMO interacting motif (SIM) and to CDC42, a Rho-GTPase critical for actin cytoskeleton remodeling and epithelial differentiation. Moreover, pTINCR increases CDC42 SUMOylation and promotes its activation, triggering a pro-differentiation cascade. Our findings suggest that the microproteome is a source of new regulators of cell identity relevant for cancer.Work in the Abad lab is supported by VHIO, Fero Foundation, La Caixa Foundation, Asociación Española Contra el Cancer (AECC), La Mutua Foundation and by grants from the Spanish Ministry of Science and Innovation (SAF2015-69413-R; RTI2018-102046-B-I00). M.A. was recipient of a Ramón y Cajal contract from the Spanish Ministry of Science and Innovation (RYC-2013-14747). O.B. is recipient of a FPI-AGAUR fellowship from Generalitat de Catalunya. We also acknowledge funding from grant PGC2018-094091-B-I00 from the Spanish Government

The Antares Collaboration : Contributions to the 34th International Cosmic Ray Conference (ICRC 2015, The Hague)

The ANTARES detector, completed in 2008, is the largest neutrino telescope in the Northern hemisphere. Located at a depth of 2.5 km in the Mediterranean Sea, 40 km off the Toulon shore, its main goal is the search for astrophysical high energy neutrinos. In this paper we collect the 21 contributions of the ANTARES collaboration to the 34th International Cosmic Ray Conference (ICRC 2015). The scientific output is very rich and the contributions included in these proceedings cover the main physics results, ranging from steady point sources, diffuse searches, multi-messenger analyses to exotic physics

Status and Recent Results of the Acoustic Neutrino Detection Test System AMADEUS

The AMADEUS system is an integral part of the ANTARES neutrino telescope in the Mediterranean Sea. The project aims at the investigation of techniques for acoustic neutrino detection in the deep sea. Installed at a depth of more than 2000m, the acoustic sensors of AMADEUS are based on piezo-ceramics elements for the broad-band recording of signals with frequencies ranging up to 125kHz. AMADEUS was completed in May 2008 and comprises six "acoustic clusters", each one holding six acoustic sensors that are arranged at distances of roughly 1m from each other. The clusters are installed with inter-spacings ranging from 15m to 340m. Acoustic data are continuously acquired and processed at a computer cluster where online filter algorithms are applied to select a high-purity sample of neutrino-like signals. 1.6 TB of data were recorded in 2008 and 3.2 TB in 2009. In order to assess the background of neutrino-like signals in the deep sea, the characteristics of ambient noise and transient signals have been investigated. In this article, the AMADEUS system will be described and recent results will be presented.Comment: 7 pages, 8 figures. Proceedings of ARENA 2010, the 4th International Workshop on Acoustic and Radio EeV Neutrino Detection Activitie