Systemic therapies for salivary gland carcinomas: an overview of published clinical trials.

BACKGROUND: There is no consensus about effective systemic therapy for salivary gland carcinomas (sgcs). Our aim was summarized the clinical trials assessing the systemic therapies (ST) on sgcs. MATERIAL AND METHODS: Electronic searches were carried out through MEDLINE/pubmed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases, and gray literature. RESULTS: Seventeen different drugs were evaluated, and the most frequent histological subtype was adenoid cystic carcinoma (n=195, 45.5%). Stable disease, observed in 11 ST, achieved the highest rate in adenoid cystic carcinoma treated with sunitinib. The highest complete (11.1%) and partial response (30.5%) rates were seen in androgen receptor-positive tumors treated with leuprorelin acetate. CONCLUSIONS: Despite all the advances in this field, there is yet no effective evidence-based regimen of ST, with all the clinical trials identified showing low rates of complete and partial responses. Further, translational studies are urgently required to characterize molecular targets and effective ST.

A comprehensive resilience assessment of Mexican tree species and their relationship with drought events over the last century.

The resilience of forests to drought events has become a major natural resource sustainability concern, especially in response to climate change. Yet, little is known about the legacy effects of repeated droughts, and tree species ability to respond across environmental gradients. In this study, we used a tree-ring database (121 sites) to evaluate the overall resilience of tree species to drought events in the last century. We investigated how climate and geography affected the response at the species level. We evaluated temporal trends of resilience using a predictive mixed linear modeling approach. We found that pointer years (e.g., tree growth reduction) occurred during 11.3% of the 20th century, with an average decrease in tree growth of 66% compared to the previous period. The occurrence of pointer years was associated with negative values of the Standardized Precipitation Index (SPI, 81.6%) and Palmer Drought Severity Index (PDSI, 77.3%). Tree species differed in their resilience capacity, however, species inhabiting xeric conditions were less resistant but with higher recovery rates (e.g., Abies concolor, Pinus lambertiana, and Pinus jeffreyi). On average, tree species needed 2.7 years to recover from drought events, with extreme cases requiring more than a decade to reach pre-drought tree growth rates. The main abiotic factor related to resilience was precipitation, confirming that some tree species are better adapted to resist the effects of droughts. We found a temporal variation for all tree resilience indices (scaled to 100), with a decreasing resistance (-0.56 by decade) and resilience (-0.22 by decade), but with a higher recovery (+1.72 by decade) and relative resilience rate (+0.33 by decade). Our results emphasize the importance of time series of forest resilience, particularly by distinguishing the species-level response in the context of legacy of droughts, which are likely to become more frequent and intense under a changing climate.

CD1a+ and CD207+ cells are reduced in oral submucous fibrosis and oral squamous cell carcinoma.

BACKGROUND: The objective of this study investigated the distribution of immature dendritic cells (DCs), Langerhans cells and plasmacytoid DCs in oral submucous fibrosis (OSMF), OSMF associated with oral squamous cell carcinoma (OSMF-OSCC), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Fourteen cases of OSMF, 9 of OSMF-OSCC, 8 of OL¸ 45 of OSCC and 8 of normal epithelium were retrospectively retrieved and their diagnoses confirmed. Immunoreactions against CD1a, CD207 e CD303 were performed and the number of positive cells quantified. RESULTS: A significant decrease of CD1a+ was found in OSMF (p≤0.05), OSMF-OSCC (p ≤ 0.01), and OSCC (p ≤ 0.001) when compared to normal epithelium. For CD207+ the significance decrease was observed in OSMF-OSCC (p ≤ 0.05), and OSCC (p ≤ 0.01) when compared with normal epithelium, and in OSMF when compared with OL (p ≤ 0.05). There was no significant difference for CD303, but increased in CD303+ was observed in OSCC when compared with normal epithelium. CONCLUSION: The decrease in the number of CD1a+ and CD207+ cells may be associate to the development of oral OSCC, and in OPMDs they might be indicators of malignant transformation.

Reliability of a two-colour chewing gum test to assess masticatory performance in complete denture wearers.

The aim of this study was to test the reliability of a method to measure the masticatory performance of complete denture wearers employing a colour-mixing ability test and assessment by visual and electronic colourimetric analysis. A sample of 75 subjects was selected from patients who received new conventional complete dentures. Masticatory tests were performed using a two-colour chewing gum that was masticated for 5, 10, 20, 30 and 50 chewing cycles, performed in a random order. The mixing level of the two colours of the chewed gum was assessed visually by two independent raters based on a 5-point ordinal scale. The specimens were flattened into a 1-mm-width wafer, scanned and saved as a two-sided digital image. Each pair of images was submitted to an electronic colourimetric analysis to assess the level of colour mixture, measured by the circular variance of hue (VOH). Overall inter- and intra-rater agreements in visual analysis were 64% and 68%, respectively (almost 99% of scores ranged within ±1 point), whilst overall weighted kappa was >0.80. A proportional increase in the level of mixture occurred with increased number of chewing cycles (P < .001). Similarly, VOH and the visual analysis were highly correlated (r = -.89; P < .001). Bland-Altman plots revealed excellent agreement and extremely low systematic error between duplicated VOH measures. It was concluded that the two-colour chewing gum test is a reliable method to assess the masticatory performance in complete denture wearers using both visual and electronic colourimetric analyses.

Charge-Dependent Directed Flow in Cu+Au Collisions at sqrt[s_{NN}]=200 GeV.

We present the first measurement of charge-dependent directed flow in Cu+Au collisions at sqrt[s_{NN}]=200 GeV. The results are presented as a function of the particle transverse momentum and pseudorapidity for different centralities. A finite difference between the directed flow of positive and negative charged particles is observed that qualitatively agrees with the expectations from the effects of the initial strong electric field between two colliding ions with different nuclear charges. The measured difference in directed flow is much smaller than that obtained from the parton-hadron-string-dynamics model, which suggests that most of the electric charges, i.e., quarks and antiquarks, have not yet been created during the lifetime of the strong electric field, which is of the order of, or less than, 1 fm/c.

Dijet imbalance measurements in Au+Au and pp collisions at sqrt[s_{NN}]=200 GeV at STAR.

We report the first dijet transverse momentum asymmetry measurements from Au+Au and pp collisions at RHIC. The two highest-energy back-to-back jets reconstructed from fragments with transverse momenta above 2 GeV/c display a significantly higher momentum imbalance in heavy-ion collisions than in the pp reference. When reexamined with correlated soft particles included, we observe that these dijets then exhibit a unique new feature-momentum balance is restored to that observed in pp for a jet resolution parameter of R=0.4, while rebalancing is not attained with a smaller value of R=0.2.

The molecular mechanism of Nystatin action is dependent on the membrane biophysical properties and lipid composition.

Nystatin (Nys) is a pore forming broad-spectrum and efficient antifungal drug with significant toxicity in mammalian organisms. In order to develop a non-toxic and more effective Nys formulation, its molecular mechanism of action at the cell membrane needs to be better understood. It is widely accepted that Nys activity and toxicity depend on the presence and type of membrane sterols. Taking advantage of multiple biophysical methodologies, we now show that the formation and stabilization of Nys aqueous pores, which are associated with Nys cytotoxicity, occur in the absence of membrane sterols. Our results suggest that the Nys mechanism of action is driven by the presence of highly ordered membrane domains capable of stabilizing the Nys oligomers. Moreover, Nys pore formation is accompanied by strong Nys-induced membrane reorganization that depends on membrane lipid composition and seems to underlie the Nys cytotoxic effect. Accordingly, in membranes enriched in a gel-phase forming phospholipid, Nys incorporates within the phospholipid-enriched gel domains, where it forms pores able to expand the gel domains. In contrast, in membranes enriched in gel domain forming sphingolipids, Nys-induced pore formation occurs through the destabilization of the gel phase. These results show that the Nys mechanism of action is complex and not only dependent on membrane sterols, and provide further insight into the molecular details governing Nys activity and toxicity.

The influence of the transposed stomach through the posterior mediastinum on the respiratory forced expiratory volume and forced vital capacity in patients with resected esophageal cancer.

Although the use of the posterior mediastinum and the stomach as a reconstruction option after esophagectomy has large acceptance all over the world, there are concerns about the potential respiratory impairment it could cause. We prospectively studied 35 patients regarding the forced expiratory volume and vital capacity. The patients were studied preoperatively and between the 45th and 60th postoperative days. The value of both parameters decreased, although they were still within normal clinical ranges. We concluded that this type of reconstruction does not harm the patients regarding the respiratory flow rates.

Genetic parameter estimates for prenatal and postnatal mortality in Nellore cattle.

The aim of this study was to estimate genetic parameters for prenatal (PRE) and postnatal (POS) mortality in Nellore cattle. A total of 13 141 (PRE) and 17 818 (POS) records from Nellore females were used. PRE and POS were recorded using binary scale scores: a score of '1' was given to calves that were born alive (PRE) and those that were alive at weaning (POS), and a score of '0' was given to calves that were not alive at or around birth (PRE), as well as to those weighed at birth but not at weaning (POS). The relationship matrix included 698 sires, 107 paternal grandsires and 69 maternal grandsires. Data were analysed using Bayesian inference and a sire-maternal grandsire threshold model, including contemporary groups as random effects, and the classes of dam age at the beginning of mating season (for PRE), and dam age at calving and birthweight (linear covariable) (for POS), as fixed effects. For both traits, the covariance between direct and maternal effects (rD,M ) was estimated (rD,M ≠ 0) or fixed at zero (rD,M  = 0). PRE and POS rates were 3.00 and 4.04%, respectively. Estimates of direct and maternal heritability were 0.07 and 0.17, respectively, for PRE, and 0.02 and 0.07, respectively, for POS, assuming rD,M  = 0. For rD,M  ≠ 0, these estimates were 0.07 and 0.12, respectively, for PRE, and 0.03 and 0.07, respectively, for POS. The correlation estimates between direct and maternal effects were -0.71 (PRE) and -0.33 (POS). PRE and POS show low genetic variability, indicating that these traits probably suffer major environmental influences. Additionally, our study shows that the maternal genetic component affects preweaning calf mortality twice as much (or more) as the direct genetic component. A large number of offspring per sire is necessary in progeny tests to genetically decrease calf mortality.

Measurement of the Transverse Single-Spin Asymmetry in p

We present the measurement of the transverse single-spin asymmetry of weak boson production in transversely polarized proton-proton collisions at sqrt[s]=500 GeV by the STAR experiment at RHIC. The measured observable is sensitive to the Sivers function, one of the transverse-momentum-dependent parton distribution functions, which is predicted to have the opposite sign in proton-proton collisions from that observed in deep inelastic lepton-proton scattering. These data provide the first experimental investigation of the nonuniversality of the Sivers function, fundamental to our understanding of QCD.

Beam Energy Dependence of the Third Harmonic of Azimuthal Correlations in Au+Au Collisions at RHIC.

We present results from a harmonic decomposition of two-particle azimuthal correlations measured with the STAR detector in Au+Au collisions for energies ranging from sqrt[s_{NN}]=7.7 to 200 GeV. The third harmonic v_{3}^{2}{2}=⟨cos3(ϕ_{1}-ϕ_{2})⟩, where ϕ_{1}-ϕ_{2} is the angular difference in azimuth, is studied as a function of the pseudorapidity difference between particle pairs Δη=η_{1}-η_{2}. Nonzero v_{3}^{2}{2} is directly related to the previously observed large-Δη narrow-Δϕ ridge correlations and has been shown in models to be sensitive to the existence of a low viscosity quark gluon plasma phase. For sufficiently central collisions, v_{3}^{2}{2} persist down to an energy of 7.7 GeV, suggesting that quark gluon plasma may be created even in these low energy collisions. In peripheral collisions at these low energies, however, v_{3}^{2}{2} is consistent with zero. When scaled by the pseudorapidity density of charged-particle multiplicity per participating nucleon pair, v_{3}^{2}{2} for central collisions shows a minimum near sqrt[s_{NN}]=20 GeV.

Centrality and Transverse Momentum Dependence of Elliptic Flow of Multistrange Hadrons and ϕ Meson in Au+Au Collisions at √[sNN]=200 GeV.

We present high precision measurements of elliptic flow near midrapidity (|y|<1.0) for multistrange hadrons and ϕ meson as a function of centrality and transverse momentum in Au+Au collisions at center of mass energy √[sNN]=200 GeV. We observe that the transverse momentum dependence of ϕ and Ω v2 is similar to that of π and p, respectively, which may indicate that the heavier strange quark flows as strongly as the lighter up and down quarks. This observation constitutes a clear piece of evidence for the development of partonic collectivity in heavy-ion collisions at the top RHIC energy. Number of constituent quark scaling is found to hold within statistical uncertainty for both 0%-30% and 30%-80% collision centrality. There is an indication of the breakdown of previously observed mass ordering between ϕ and proton v2 at low transverse momentum in the 0%-30% centrality range, possibly indicating late hadronic interactions affecting the proton v2.

Effect of reduced glutathione (GSH) in canine sperm cryopreservation: In vitro and in vivo evaluation.

The aim of this study was to compare the in vitro and in vivo efficiency of different concentrations (0, 10 and 20 mM) of reduced glutathione supplemented to the extender for canine semen cryopreservation. Six normospermic dogs were used and each ejaculate was divided in 3 experimental groups, according to GSH concentration (GSH-0, GSH-10 and GSH-20 Groups). After thawing, samples were evaluated by sperm motility by computer-assisted sperm analysis (CASA), flow cytometric evaluation of plasma and acrosome membrane integrity, mitochondrial membrane potential and activity, chromatin susceptibility to acid-induced denaturation, and measurement of spontaneous and induced production of thiobarbituric acid reactive substances (TBARS). In vivo tests were carried out with GSH-0 and GSH-10 groups, for which six bitches were inseminated with semen cryopreserved in extender without GSH or containing 10 mM GSH. Intrauterine insemination was performed by cervical catheterization on the 5th and 6th days after the LH surge, detected by serum progesterone and LH assays. In the CASA evaluation, GSH-20 group had the lowest total and progressive motility and lower percentage of sperm with rapid and slow speed. Groups treated with glutathione showed lower percentage of acrosome damage, but higher percentage of plasma membrane injury. GSH-20 group had higher percentage of sperm with low mitochondrial activity and higher concentration of induced TBARS. Both groups (GSH-0 and GSH-10) had positive pregnancies. In conclusion, 20 mM GSH supplementation to canine cryopreservation extender promoted sperm damage, especially to mitochondrial activity. However, addition of 10 mM GSH resulted in acrosome protection, preserving fertility rate.

Diallel analysis to choose parents for black bean (Phaseolus vulgaris L.) breeding.

In this study, conducted in two different seasons, we aimed to choose parents to obtain promising segregating populations for the extraction of black bean (Phaseolus vulgaris L.) lines that are superior in terms of disease resistance, plant architecture, and grain yield. Twelve parents were arranged in two groups to compose a partial diallel in a 5 x 7 scheme. Group 1 was composed of parents with black grains and erect plant architecture, while group 2 was composed of parents that had carioca grains and were resistant to the main fungal diseases that occur in the common bean. The following traits were evaluated: severity of angular leaf spot (ALS), plant architecture (PAG), and grain yield (YIELD). The data were analyzed according to a partial diallel model using parents and F1 hybrids. In the genetic control of ALS and PAG, additive effects were predominant, while for YIELD, additive effects were predominant in one season and dominance effects were in another season, because it is a more complex trait than ALS and PAG. For YIELD, we observed an interaction between general combining ability and specific combining ability between seasons. The genes that control ALS, PAG, and YIELD were in eight of the 12 parents evaluated in the diallel. The cultivar 'BRS Estilo' is suitable to use as a parent in common bean breeding in terms of ALS, PAG and YIELD. Recurrent selection is the most recommended option for simultaneously breeding for PAG, YIELD, and resistance to angular leaf spot in bean culture.

Morphoagronomic characterization and genetic diversity of a common bean RIL mapping population derived from the cross Rudá x AND 277.

Recombinant inbred lines (RILs) are a valuable resource for building genetic linkage maps. The presence of genetic variability in the RILs is essential for detecting associations between molecular markers and loci controlling agronomic traits of interest. The main goal of this study was to quantify the genetic diversity of a common bean RIL population derived from a cross between Rudá (Mesoamerican gene pool) and AND 277 (Andean gene pool). This population was developed by the single seed descent method from 500 F2 plants until the F10 generation. Seven quantitative traits were evaluated in the field in 393 RILs, the parental lines, and five control cultivars. The plants were grown using a randomized block design with additional controls and three replicates. Significant differences were observed among the RILs for all evaluated traits (P < 0.01). A comparison of the RILs and parental lines showed significant differences (P < 0.01) for the number of days to flowering (DFL) and to harvest (DH), productivity (PROD) and mass of 100 beans (M100); however, there were no significant differences for plant architecture, degree of seed flatness, or seed shape. These results indicate the occurrence of additive x additive epistatic interactions for DFL, DH, PROD, and M100. The 393 RILs were shown to fall into 10 clusters using Tocher's method. This RIL population clearly contained genetic variability for the evaluated traits, and this variability will be crucial for future studies involving genetic mapping and quantitative trait locus identification and analysis.

Observation of Charge Asymmetry Dependence of Pion Elliptic Flow and the Possible Chiral Magnetic Wave in Heavy-Ion Collisions.

We present measurements of π(-) and π(+) elliptic flow, v(2), at midrapidity in Au+Au collisions at √[s(NN)]=200, 62.4, 39, 27, 19.6, 11.5, and 7.7 GeV, as a function of event-by-event charge asymmetry, A(ch), based on data from the STAR experiment at RHIC. We find that π(-) (π(+)) elliptic flow linearly increases (decreases) with charge asymmetry for most centrality bins at √[s(NN)]=27 GeV and higher. At √[s(NN)]=200 GeV, the slope of the difference of v(2) between π(-) and π(+) as a function of A(ch) exhibits a centrality dependence, which is qualitatively similar to calculations that incorporate a chiral magnetic wave effect. Similar centrality dependence is also observed at lower energies.

Azimuthal Anisotropy in U+U and Au+Au Collisions at RHIC.

Collisions between prolate uranium nuclei are used to study how particle production and azimuthal anisotropies depend on initial geometry in heavy-ion collisions. We report the two- and four-particle cumulants, v_{2}{2} and v_{2}{4}, for charged hadrons from U+U collisions at sqrt[s_{NN}]=193 GeV and Au+Au collisions at sqrt[s_{NN}]=200 GeV. Nearly fully overlapping collisions are selected based on the energy deposited by spectators in zero degree calorimeters (ZDCs). Within this sample, the observed dependence of v_{2}{2} on multiplicity demonstrates that ZDC information combined with multiplicity can preferentially select different overlap configurations in U+U collisions. We also show that v_{2} vs multiplicity can be better described by models, such as gluon saturation or quark participant models, that eliminate the dependence of the multiplicity on the number of binary nucleon-nucleon collisions.

Observation of Transverse Spin-Dependent Azimuthal Correlations of Charged Pion Pairs in p

We report the observation of transverse polarization-dependent azimuthal correlations in charged pion pair production with the STAR experiment in p^{↑}+p collisions at RHIC. These correlations directly probe quark transversity distributions. We measure signals in excess of 5 standard deviations at high transverse momenta, at high pseudorapidities η>0.5, and for pair masses around the mass of the ρ meson. This is the first direct transversity measurement in p+p collisions.

Genetic variability analysis of Zymomonas mobilis strains from the UFPEDA microorganisms collection.

Zymomonas mobilis is a Gram-negative bacterium that has drawn attention in the bioethanol industry. Besides bioethanol, this bacterium also produces other biotechnological products such as levans, which show antitumor activity. Molecular studies involving Z. mobilis have advanced to the point that allows us to characterize interspecies genetic diversity and understand their metabolism, and these data are essential for better utilization of this species. In this study, the genetic diversity of 24 strains from the Microorganisms Collection of Departamento de Antibióticos (UFPEDA) from Universidade Federal de Pernambuco were characterized. The methods used were amplified ribosomal DNA restriction analysis and diversity analysis of the internally transcribed 16S-23S rDNA spacer region (ISR). These analyses revealed low genetic variability of the 16S rDNA gene. These data confirm that these isolates are, or are closely related to, Z. mobilis. Moreover, the analysis of the ISR confirmed the genetic variability of strains deposited in the UFPEDA collection of microorganisms and grouped these strains into ten ribotypes, which can be used in the future for breeding programs and for the preservation of biodiversity. Furthermore, this study characterized the genetic variability between the UFPEDA 205/ ZAP, UFPEDA 98/AG11, and ZAG strains, which were obtained by spheroplast fusion among them. The data also indicate that there is genetic variability among the UFPEDA 202/CP4 and UFPEDA 633/ ZM4 strains, demonstrating that these important Z. mobilis strains are distinct, as suggested in previous studies.

Comparison of idiopathic achalasia and Chagas' disease esophagopathy at the light of high-resolution manometry.

The comparison between idiopathic achalasia (IA) and Chagas' disease esophagopathy (CDE) may evaluate if treatment options and their outcomes can be accepted universally. This study aims to compare IA and CDE at the light of high-resolution manometry. We studied 86 patients with achalasia: 45 patients with CDE (54% females, mean age 55 years) and 41 patients with IA (58% females, mean age 49 years). All patients underwent high-resolution manometry. Upper esophageal sphincter parameters were similar (basal pressure CDE = 72 ± 45 mmHg, IA = 82 ± 57 mmHg; residual pressure CDE = 9.9 ± 9.9 mmHg, IA = 9.8 ± 7.5 mmHg). In the body of the esophagus, the amplitude was higher in the IA group than the CDE group at 3 cm (CDE = 15 ± 14 mm Hg, IA = 42 ± 52 mmHg, P = 0.003) and 7 cm (CDE = 16 ± 15 mmHg, IA = 36 ± 57 mmHg, P = 0.04) above the lower esophageal sphincter (LES). The LES basal pressure (CDE = 17 ± 16 mmHg, IA = 40 ± 22 mmHg, P < 0.001) and residual pressure (CDE = 12 ± 11 mmHg, IA = 27 ± 13 mmHg, P < 0.001) were also higher in the IA group. Our results show that: (i) there is no difference in regards to the upper esophageal sphincter; (ii) higher pressures of the esophageal body are noticed in patients with IA; and (iii) basal and residual pressures of the LES are lower in patients with CDE. Our results did not show expressive manometric differences between IA and CDE. Some differences may be attributed to a more pronounced esophageal dilatation in patients with CDE.