Influence of orthodontic treatment on temporomandibular disorders: a systematic review

Objectives: The aim of this literature systematic review was to evaluate the possible association between malocclusions, orthodontic treatment and development of temporomandibular disorders. Material and Methods: A search was carried out on PubMed-Medline database from January 2000 to August 2013 using the keywords “ orthodontics and temporomandibular disorders ”, “ orthodontics and facial pain ” and “ malocclusion and temporomandibular disorders ”. Human studies included in the study were those assessing signs and symptoms of temporomandibular disorders in relation to orthodontic treatment. Results: The search strategy resulted in 61 articles. After selection according to the inclusion/exclusion criteria 9 articles qualified for the final analysis. The articles which linked orthodontics and development of temporomandibular disorders showed very discrepant results. Some indicated that orthodontic treatment could improve signs and symptoms of temporomandibular disorders, but none of them obtained statistically significant dif ferences. Conclusions: According to the authors examined, there is no evidence for a cause-effect relationship between orthodontic treatment and temporomandibular disorders, or that such treatment might improve or prevent them. More longitudinal studies are needed to verify any possible interrelationshi

Polysialylated neuropilin-2 enhances human dendritic cell migration through the basic C-terminal region of CCL21.

Free Access at: http://glycob.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=20488940Dendritic cell (DC) migration to secondary lymphoid organs is a critical step to properly exert its role in immunity; and predominantly depends on the interaction of the chemokine receptor CCR7 with its ligands CCL21 and CCL19. Polysialic acid (PSA) has been recently reported to control CCL21-directed migration of mature DCs. Here; we first demonstrate that PSA present on human mature monocyte-derived dendritic cells did not enhance chemotactic responses to CCL19. We have also explored the molecular mechanisms underlying the selective enhancing effect of PSA on CCL21-driven chemotaxis of DCs. In this regard; we found out that prevention of DC polysialylation decreased CCL21 activation of JNK and Akt signaling pathways; both associated with CCR7-mediated chemotaxis. We also report that the enhanced PSA-mediated effect on DC migration towards CCL21 relied on the highly basic C-terminal region of this chemokine; and depended on the PSA acceptor molecule neuropilin-2 (NRP2) and on the polysialyltransferase ST8SiaIV. Altogether; our data indicate that the CCR7/CCL21/NRP2/ST8SiaIV functional axis constitutes an important guidance clue for DC targeting to lymphoid organs.This work was supported by research grant from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (FISPI0708879 to MAV).Peer reviewe

Efecto del manejo del pastoreo racional en la capacidad de carga de Brachiaria humidicola en secano sin fertilización

The effect of Voisin restricted grazing and  portion grazing upon indexes determining load capacity of Brachiaria  humidicola cv. CIAT 679 without watering and fertilizing was evaluated for 4 years on a Vertisol soil in Cauto valley. 40 cows 5/8 Holstein- 3/8 Zebu were sampled by a completely randomized design. Grazing was done “in line” using cattle yards with the same size for Voisin restricted grazing, and grazing strips for  portion grazing in which each herd fed daily out of a strip according to its avail- ability in order to increase maximum grazing consumption. Strip management in  portion grazing significantly increased grazing efficiency during both seasons compared to Voisin restricted grazing, and had a much better impact upon grazing consumption as well. Neither yield indexes nor rest time were affected; they changed according to season with a marked depletion during dry season. Annual yield average was 11,7 t dry matter ha-1, out of which only a 23% was obtained during dry season. A higher graz- ing consumption index in  portion grazing showed a 24 UGM ha-1 increase in load capacity due to rotation during rainy season compared to Voisin restricted grazing (242 vs. 218). Results clearly showed a marked effect of season and grazing consumption upon  portion grazing.Se evaluó durante 4 años el efecto de los métodos de Pastoreo Racional Voisin (PRV) y Pastoreo Porcionado en los indicadores que determinan la capacidad de carga del pasto Brachiaria humidicola cv. CIAT 679 sin riego y fertilización en un suelo Vertisol del valle del Cauto. Se utilizaron 40 vacas 5/8 Holstein-3/8 Cebú en un diseño completamente aleatorio. El pastoreo se condujo “en línea”, con cuartones de tamaño fijo en el PRV y con franjas en el Porcionado, en el que se le asignó al rebaño una porción diaria de la franja de pastoreo según disponibilidad del pasto, para incrementar su aprovechamiento. El manejo de la oferta en el Pastoreo Porcionado incrementó significativamente la intensidad de pastoreo (IP) en ambas épocas del año con respecto al PRV y ejerció un efecto favorable en el aprovechamiento del pasto (AP) al encontrarse similar tendencia. Este hecho no afectó los indi- cadores de rendimiento y tiempo de reposo, que variaron con la época del año con una marcada depresión en la seca. El promedio de rendimiento anual fue 11,7 t MS ha-1 del cual solo el 23 % se obtuvo en seca. El mayor AP en el Pastoreo Porcionado incre- mentó en 24 UGM ha-1 la capacidad de carga por rotación en la lluvia con respecto al PRV (242 vs. 218). Los resultados demuestran el efecto marcado de la época del año y del aumento del AP en el Pastoreo Porcionado durante la época de lluvia

Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed α-helix

The macrophage infectivity potentiator protein from Trypanosoma cruzi (TcMIP) is a major virulence factor secreted by the etiological agent of Chagas' disease. It is functionally involved in host cell invasion. We have determined the three-dimensional crystal structure of TcMIP at 1.7 Å resolution. The monomeric protein displays a peptidyl-prolyl cis-trans isomerase (PPlase) core, encompassing the characteristic rotamase hydrophobic active site, thus explaining the strong inhibition of TcMIP by the immunosuppressant FK506 and related drugs. In TcMIP, the twisted β-sheet of the core is extended by an extra β-strand, preceded by a long, exposed N-terminal α-helix, which might be a target recognition element. An invasion assay shows that the MIP protein from Legionella pneumophila (LpMIP), which has an equivalent N-terminal α-helix, can substitute for TcMIP. An additional exposed α-helix, this one unique to TcMIP, is located in the C-terminus of the protein. The high-resolution structure reported here opens the possibility for the design of new inhibitory drugs that might be useful for the clinical treatment of American trypanosomiasis.This work was supported by grants from Ministerio de Educación y Cultura (PB98-1631 and 2FD97-0518), CSIC and Generalitat de Catalunya (CERBA and 1999SGR188) to M.C., grant PB98-0479 to A.G. and by grant BIO2000-1659 to F.X.G.-R. P.J.B.P. and S.M.-R. acknowledge postdoctoral fellowships from FCT (Portugal). Data collection at DESY was supported by EC grants ERBFMGECT980134 and HPRI-CT-1999-00017 to EMBL-HamburgPeer Reviewe

Structures of T7 bacteriophage portal and tail suggest a viral DNA retention and ejection mechanism

Double-stranded DNA bacteriophages package their genome at high pressure inside a procapsid through the portal, an oligomeric ring protein located at a unique capsid vertex. Once the DNA has been packaged, the tail components assemble on the portal to render the mature infective virion. The tail tightly seals the ejection conduit until infection, when its interaction with the host membrane triggers the opening of the channel and the viral genome is delivered to the host cell. Using high-resolution cryo-electron microscopy and X-ray crystallography, here we describe various structures of the T7 bacteriophage portal and fiber-less tail complex, which suggest a possible mechanism for DNA retention and ejection: a portal closed conformation temporarily retains the genome before the tail is assembled, whereas an open portal is found in the tail. Moreover, a fold including a seven-bladed β-propeller domain is described for the nozzle tail protein.This work was supported by the Ministry of Science, Innovation and Universities of Spain, grants BFU 2014-54181 (to J.L.C.), BFU 2014-53550-P and BFU2017-83720-P (to M.C.), and contracts SEV-2013-0347 (to A.C.) and RYC-2011-09071 (to C.M.). We acknowledge institutional funding through the Spanish Government Centres and Units of Excellence Severo Ochoa and Maria de Maeztu awards to IRB Barcelona (SEV-2015-0500) and IBMB Structural Biology Unit (MDM-2014-0435), respectively, and from the CERCA Programme of the Catalan Government to the IRB Barcelona. This work has also been supported by the European Commission, Horizon 2020 program through iNEXT project (grant number 653706)

L-Arginine Ameliorates Defective Autophagy in GM2 Gangliosidoses by mTOR Modulation.

AIMS: Tay-Sachs and Sandhoff diseases (GM2 gangliosidosis) are autosomal recessive disorders of lysosomal function that cause progressive neurodegeneration in infants and young children. Impaired hydrolysis catalysed by β-hexosaminidase A (HexA) leads to the accumulation of GM2 ganglioside in neuronal lysosomes. Despite the storage phenotype, the role of autophagy and its regulation by mTOR has yet to be explored in the neuropathogenesis. Accordingly, we investigated the effects on autophagy and lysosomal integrity using skin fibroblasts obtained from patients with Tay-Sachs and Sandhoff diseases. RESULTS: Pathological autophagosomes with impaired autophagic flux, an abnormality confirmed by electron microscopy and biochemical studies revealing the accelerated release of mature cathepsins and HexA into the cytosol, indicating increased lysosomal permeability. GM2 fibroblasts showed diminished mTOR signalling with reduced basal mTOR activity. Accordingly, provision of a positive nutrient signal by L-arginine supplementation partially restored mTOR activity and ameliorated the cytopathological abnormalities. INNOVATION: Our data provide a novel molecular mechanism underlying GM2 gangliosidosis. Impaired autophagy caused by insufficient lysosomal function might represent a new therapeutic target for these diseases. CONCLUSIONS: We contend that the expression of autophagy/lysosome/mTOR-associated molecules may prove useful peripheral biomarkers for facile monitoring of treatment of GM2 gangliosidosis and neurodegenerative disorders that affect the lysosomal function and disrupt autophagy

Generation of Molecular Diversity from Amino Acids. A Source for the Discovery of New TRP Channel Modulators

Trabajo presentado en el IV RECI: New Horizons in Ion Channel Research, celebrado en Cuenca (España) del 12 al 13 de febrero de 2013.Ion channels are central and challenging targets in medicinal chemistry but, because of the scarce structural knowledge, rational approaches to ion channel modulators are still rare. Moreover, the multimodal activation of some channels, like TRPs, complicates still more the scenario for rational discovery programs. Due to these facts, most strategies directed to identify ion channel modulators rely on the screening of peptide and small-molecule libraries. In this context, we have been involved in the development of synthetic pathways for the generation of diverse, chiral, highly functionalized linear and heterocyclic scaffolds from amino acids, and in the production of discrete libraries from them. The screening of these libraries on different TRP channels has allowed the discovery of some innovative hits that have progressed to hit-to-lead optimization programs. This communication will deal with the synthesis, structural characterization, and biological evaluation of a collection of β,γ–diaminoester derivatives that display significant activity at TRPV1, TRPM8 and TRPA1 channels. Compound RGM04-7, a selective.Supported by MICINN grants: Consolider-Ingenio 2010 (CSD2008-00005 and CSD2006-00015), SAF2009-09323 and BFU2009-08346, and the Generalitat Valenciana (PROMETEO/2010/046)

Prediction of poor outcome in clostridioides difficile infection: A multicentre external validation of the toxin B amplification cycle

Producción CientíficaClassification of patients according to their risk of poor outcomes in Clostridioides difficile infection (CDI) would enable implementation of costly new treatment options in a subset of patients at higher risk of poor outcome. In a previous study, we found that low toxin B amplification cycle thresholds (Ct) were independently associated with poor outcome CDI. Our objective was to perform a multicentre external validation of a PCR-toxin B Ct as a marker of poor outcome CDI. We carried out a multicentre study (14 hospitals) in which the characteristics and outcome of patients with CDI were evaluated. A subanalysis of the results of the amplification curve of real-time PCR gene toxin B (XpertTM C. difficile) was performed. A total of 223 patients were included. The median age was 73.0 years, 50.2% were female, and the median Charlson index was 3.0. The comparison of poor outcome and non–poor outcome CDI episodes revealed, respectively, the following results: median age (years), 77.0 vs 72.0 (p = 0.009); patients from nursing homes, 24.4% vs 10.8% (p = 0.039); median leukocytes (cells/μl), 10,740.0 vs 8795.0 (p = 0.026); and median PCR-toxin B Ct, 23.3 vs 25.4 (p = 0.004). Multivariate analysis showed that a PCR-toxin B Ct cut-off <23.5 was significantly and independently associated with poor outcome CDI (p = 0.002; OR, 3.371; 95%CI, 1.565–7.264). This variable correctly classified 68.5% of patients. The use of this microbiological marker could facilitate early selection of patients who are at higher risk of poor outcome and are more likely to benefit from newer and more costly therapeutic options

Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD