Removal of Water Binding Proteins from Dentin Increases the Adhesion Strength of Low-Hydrophilicity Dental Resins

Objectives To investigate the role of proteoglycans (PGs) on the physical properties of the dentin matrix and the bond strength of methacrylate resins with varying hydrophilicities. Methods Dentin were obtained from crowns of human molars. Enzymatic removal of PGs followed a standard protocol using 1 mg/mL trypsin (Try) for 24 h. Controls were incubated in ammonium bicarbonate buffer. Removal of PGs was assessed by visualization of glycosaminoglycan chains (GAGs) in dentin under transmission electron microscopy (TEM). The dentin matrix swelling ratio was estimated using fully demineralized dentin. Dentin wettability was assessed on wet, dry and re-wetted dentin surfaces through water contact angle measurements. Microtensile bond strength test (TBS) was performed with experimental adhesives containing 6% HEMA (H6) and 18% HEMA (H18) and a commercial dental adhesive. Data were statistically analyzed using ANOVA and post-hoc tests (α = 0.05). Results The enzymatic removal of PGs was confirmed by the absence and fragmentation of GAGs. There was statistically significant difference between the swelling ratio of Try-treated and control dentin (p \u3c 0.001). Significantly lower contact angle was found for Try-treated on wet and dry dentin (p \u3c 0.002). The contact angle on re-wet dentin was not recovered in Try-treated group (p = 0.9). Removal of PGs significantly improved the TBS of H6 (109% higher, p \u3c 0.001) and H18 (29% higher, p = 0.002) when compared to control. The TBS of commercial adhesive was not affected by trypsin treatment (p = 0.9). Significance Changing the surface energy of dentin by PGs removal improved resin adhesion, likely due to more efficient water displacement, aiding to improved resin infiltration and polymerization

The metabolic adaptation evoked by arginine enhances the effect of radiation in brain metastases

Selected patients with brain metastases (BM) are candidates for radiotherapy. A lactatogenic metabolism, common in BM, has been associated with radioresistance. We demonstrated that BM express nitric oxide (NO) synthase 2 and that administration of its substrate l-arginine decreases tumor lactate in BM patients. In a placebo-controlled trial, we showed that administration of l-arginine before each fraction enhanced the effect of radiation, improving the control of BM. Studies in preclinical models demonstrated that l-arginine radiosensitization is a NO-mediated mechanism secondary to the metabolic adaptation induced in cancer cells. We showed that the decrease in tumor lactate was a consequence of reduced glycolysis that also impacted ATP and NAD+ levels. These effects were associated with NO-dependent inhibition of GAPDH and hyperactivation of PARP upon nitrosative DNA damage. These metabolic changes ultimately impaired the repair of DNA damage induced by radiation in cancer cells while greatly sparing tumor-infiltrating lymphocytes.Fil: Marullo, Rossella. Cornell University; Estados UnidosFil: Castro, Monica. Universidad de Buenos Aires; ArgentinaFil: Yomtoubian, Shira. Cornell University; Estados UnidosFil: Nieves Calvo Vidal, M.. Cornell University; Estados UnidosFil: Revuelta, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Krumsiek, Jan. Cornell University; Estados UnidosFil: Nicholas, Andrew P.. Cornell University; Estados UnidosFil: Cresta Morgado, Pablo. Universidad de Buenos Aires; ArgentinaFil: Yang, ShaoNing. Cornell University; Estados UnidosFil: Medina, Vanina Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Roth, Berta María Cristina. Universidad de Buenos Aires; ArgentinaFil: Bonomi, Marcelo. Ohio State University; Estados UnidosFil: Keshari, Kayvan R.. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Mittal, Vivek. Cornell University; Estados UnidosFil: Navigante, Alfredo Hugo. Universidad de Buenos Aires; ArgentinaFil: Cerchietti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentin

Short-Term Changes in Respiratory Biomarkers after Swimming in a Chlorinated Pool

36 páginas, 3 figuras, 5 tablas.[BACKGROUND]: Swimming in chlorinated pools involves exposure to disinfection by-products (DBPs) and has been associated with impaired respiratory health.[OBJECTIVES]: We evaluated short-term changes in several respiratory biomarkers to explore mechanisms of potential lung damage related to swimming pool exposure.[METHODS]: We measured lung function and biomarkers of airway inflammation (fractional exhaled nitric oxide –FeNO- and 8 cytokines and 1 growth factor (VEGF) in exhaled breath condensate), oxidative stress (8-isoprostane in exhaled breath condensate), and lung permeability (surfactant protein D -SPD- and the Clara cell secretory protein -CC16- in serum) in 48 healthy non-smoking adults before and after swimming for 40 min in a chlorinated indoor swimming pool. We measured trihalomethanes in exhaled breath as a marker of individual exposure to DBPs. Energy expenditure during swimming, atopy and CC16 genotype (rs3741240) was also determined.[RESULTS]: Median serum CC16 levels increased from 6.01 to 6.21 μg/L (average increase 3.3%, paired Wilcoxon test p = 0.03), regardless of atopic status and CC16 genotype. This increase was explained both by energy expenditure and different markers of DBP exposure in multivariate models. FeNO was unchanged overall but tended to decrease among atopics. We found no significant changes in lung function, SP-D, 8-isoprostane, 8 cytokines and VEGF.[CONCLUSIONS]: A slight increase in serum CC16, a marker of lung epithelium permeability, was detected in healthy adults after swimming in an indoor chlorinated pool. Exercise and DBP exposure explained this association, without involving inflammatory mechanisms. Further research is needed to confirm the results, establish the clinical relevance of short-term serum CC16 changes, and evaluate the long-term health impacts.Work funded by the projects SAF2005-07643-C03-01; CP06/00341; CP01/3058; SAF2007-62719, FISCP06/00341 and FI06/00651.Peer reviewe

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum

Registro español de nutrición enteral domiciliaria del año 2009; Grupo NADYA-SENPE

Objetivo: Describir las características de la Nutrición Enteral Domiciliaria (NED) en España, registrada por el grupo NADYA-SENPE durante el año 2009. Material y métodos: Recopilación y análisis descriptivo de los datos del registro de NED del grupo NADYASENPE desde el 1 de enero al 31 de diciembre de 2009. Resultados: Se registraron 6.540 pacientes, 5,11% más que en el año anterior y 6.649 episodios de NED (3.135 en mujeres, 47,93%) pertenecientes a 32 centros hospitalarios. Siendo 6.238 (95,38%) mayores de 14 años. La edad media en los menores de 14 años fue de 3,67 ± 2,86 y de 72,10 ± 16,89 en los mayores de 14 años. La enfermedad de base que se registró con más frecuencia fue la neurológica en 2.732 (41,77%) ocasiones, seguida de la neoplasia en 1838; 28,10%. La vía de acceso se registró en 1.123 (17,17%) de los episodios, siendo más frecuente la administración por sonda nasogástrica 562 (50,04%). El tiempo medio de tratamiento nutricional fue de 323 días (10,77 meses). Finalizaron 606 episodios de NED, siendo el motivo más frecuentes el fallecimiento del enfermo, lo que aconteció en 295 (48,68%) ocasiones y el paso a alimentación oral en 219 (36,14%). Los pacientes mantenían una actividad normal en 2162 episodios de NED (32,55%) y en 2468 (37,13%) hacían vida “cama-sillón”. El grado de dependencia fue “total” en 2598 (39,07%) de los episodios registrado. El suministro de la fórmula nutricional se realizó desde el hospital en 4.183 (62,91%) casos y por la farmacia de referencia en 2.262 (el 34,02%) y el material fungible se suministró desde el hospital en 3.531 (53,11%) de los casos. Conclusiones: El número de pacientes con NED registrados es superior al del año 2008, continuando con el incremento progresivo desde el inicio del registro. Las características de los mismos mantiene el mismo perfil que en años anteriores con pequeñas variaciones.Objective: To describe the Home Enteral Nutrition Characteristics (HEN) recorded by the group NADYASENPE during 2009. Material and methods: collection and analysis of the data voluntary recorded in the HEN registry from the NADYASENPE group from January 1st to December 31st. Results: 6.540 HEN patients were registered, 5.11% more than the previous year and 6,649 episodes (3,135 in women, 47,93%) from 32 different hospitals. 6,238 of them (95,38%) were over 14 years. The mean age of the patients under 14 yr was 3,67 ± 2,86 and it was 72,10 ± 16,89 in those over 14 yr group. The base illness registered more frequently was the neurological disorders in 2,732 (41,77%) patients, followed by cancer patients in 1,838; 28,10%. The enteral access route was registered in 1,123 (17,17%) of the episodes, being more frequent the administration by nasogastric tube 562 (50,04%). The mean length of nutritional treatment by episode was 323 days (10,77 months). 606 episodes of HEN ended, being the principal reasons for discontinuing treatment the patient death in 295 (48,68%) occasions. The transition to oral feeding occurred in 219 (36,14%) cases. Patients maintained normal activity in 2162 (32,55%) HEN episodes and 2,468 (37,13%) cases were living “bedcouch”. The level of dependence was “total” in 2,598 (39,07%) of the episodes recorded. The nutritional formula was provided by the hospital in 4,183 (62,91%) cases and by the reference pharmacy in 2,262 (el 34,02%). Consumables were provided by the hospital in 3,531 (53,11%) cases. Conclusions: The number of HEN patients recorded increased from the year 2008, continuing the gradual growth increase since the start of registration. The characteristics of the patients remain in the same profile as in previous years

Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program

Altres ajuts: This work was supported by the Obra Social "La Caixa" (to M. Esteller).Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease

Where myth and archaeology meet: Discovering the Gorgon Medusa's Lair.

Here we report the discovery of ceramic fragments that form part of a Gorgoneion, a ceramic image representation of the Gorgon Medusa. The fragments were found in a deep part of Gorham's Cave, well known to ancient mariners as a natural shrine, between the 8th and 2nd century BCE. We discuss the context of this discovery, both within the inner topography of the cave itself, and also the broader geographical context. The discovery is situated at the extreme western end of the Mediterranean Sea, where it meets the Atlantic Ocean. The location was known to ancient mariners as the northern Pillar of Herakles, which marked the end of the known world. We relate the discovery, and its geographical and chronological context, to Greek legends that situated the lair of the Gorgon sisters at a location which coincides with the physical attributes and geographical position of Gorham's Cave. We thus provide, uniquely, a geographical and archaeological context to the myth of Perseus and the slaying of the Gorgon Medusa

Reporting randomised clinical trials of analgesics after traumatic or orthopaedic surgery is inadequate: a systematic review

Background Several randomised clinical trials (RCTs) of analgesics in postoperative pain after traumatic or orthopaedic surgery (TOS) have been published, but no studies have assessed the quality of these reports. We aimed to examine the quality of reporting RCTs on analgesics for postoperative pain after TOS. Methods Reports of RCTs assessing analgesics in postoperative pain after TOS were systematically searched from electronic databases. The quality of reports was assessed using the CONSORT checklist (scoring range from 0 to 22). The quality was considered poor when scoring was 12 or lesser. The publication year and the impact factor of journals were recorded. Results A total of 92 reports of RCTs were identified and 69 (75%) scored 12 or lesser in CONSORT checklist (range 5-17). The mean (SD) CONSORT score of all reports was 10.6 (2.7). Missing CONSORT items included primary and secondary outcome measures (11%), the specific objectives and hypothesis definition (12%), the sample size calculation (12%), the dates defining the periods of recruitment (12%), the discussion of external validity of findings (14%), the allocation sequence generation (24%), and the interpretation of potential bias or imprecision of results (25%). There was a little improvement in CONSORT scores over time (r = 0.62; p < 0.001) and with impact factor of journals (r = 0.30; p < 0.001). Conclusion Quality of reporting RCTs on analgesics after TOS is poor. Reporting of those RCTs should be improved according to methodological standard checklists in the next years