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Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We compared pembrolizumab with paclitaxel in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine.

Protein kinase A (PKA) has diverse functions in neurons. At rest, the subcellular localization of PKA is controlled by A-kinase anchoring proteins (AKAPs). However, the dynamics of PKA upon activation remain poorly understood. Here, we report that elevation of cyclic AMP (cAMP) in neuronal dendrites causes a significant percentage of the PKA catalytic subunit (PKA-C) molecules to be released from the regulatory subunit (PKA-R). Liberated PKA-C becomes associated with the membrane via N-terminal myristoylation. This membrane association does not require the interaction between PKA-R and AKAPs. It slows the mobility of PKA-C and enriches kinase activity on the membrane. Membrane-residing PKA substrates are preferentially phosphorylated compared to cytosolic substrates. Finally, the myristoylation of PKA-C is critical for normal synaptic function and plasticity. We propose that activation-dependent association of PKA-C renders the membrane a unique PKA-signaling compartment. Constrained mobility of PKA-C may synergize with AKAP anchoring to determine specific PKA function in neurons.

Stuttering is a speech fluency disorder, and may be associated with neuroaudiological factors linked to central auditory processing, including changes in auditory processing skills and temporal resolution.

Background Persons infected with HIV often have altered lipid profiles that may be affected by antiretroviral therapies (ART). Traditional lipid measurements may be insufficient to assess cardiovascular disease (CVD) risk in this population.Methods We report results from 39 ART-naive participants in a substudy of A5248, a single-arm study of raltegravir, emtricitabine/tenofovir administration. Samples were collected at baseline, 12, 24 and 48 weeks after ART initiation. We performed advanced lipid phenotyping using nuclear magnetic resonance spectroscopy (Liposcience, Raleigh, NC, USA) for lipid particle size and number, and examined high-density lipoprotein (HDL) function measuring reverse cholesterol transport using J774 macrophages.Results We report significant increases in total cholesterol (13 mg/dl; P<0.001) and low-density lipoprotein (LDL; 8 mg/dl; P=0.03), with no change in triglycerides and without an increase in LDL particle number (P>0.1 all time points). HDL levels were increased over baseline levels at all time points (P<0.003), but reached a peak at week 12 and subsequently declined. HDL particle numbers also increased from baseline (P<0.002) and HDL function improved at week 48 (7% increase in efflux capacity; P<0.001). Oxidized LDL (oxLDL) levels decreased by week 12, but rose subsequently, and were not different from baseline at later time points.Conclusions HDL increases were associated with increases in beneficial HDL particles and HDL cholesterol efflux capacity, which may reduce future CVD events. Persistent inflammation in these HIV+ participants, may be a cause or consequence of oxLDL levels, and may contribute to declining levels of HDL over time. Clinicaltrials.gov NCT00660972.

Hearing loss can negatively influence the communication performance of individuals, who should be evaluated with suitable material and in situations of listening close to those found in everyday life.

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The International Sociological Association’s Research Committee “Logic and Methodology” (RC33), under the direction of President Nina Baur, has begun to concentrate on sociological methodology developments in world regions other than Europe and North America. This is the first “Regional Report” to be jointly published by the BMSand this issue’s RC33 Newsletter, and it concerns Latin America.

Dichotic listening tests should be used in local languages and adapted for the population.

El artículo pretende mostrar, fundamentalmente, cómo el tema del amor se anuda a ciertos problemas generales que aborda la disciplina sociológica –incluido el problema de la vinculación social. La aproximación al tema a través de los problemas permite observar algunas diferencias en su abordaje a lo largo del tiempo. El escrito finaliza con reflexiones respecto a estas diferencias y una agenda de investigación futura.

To determine the effects of a formal auditory training program on the behavioral, electrophysiological and subjective aspects of auditory function in individuals with bilateral high-frequency hearing loss.

For cleanup of animal fat before GCanalysis of organochlorine pesticides and polychlorinated biphenyls, freezing‐lipid filtration with solid‐phase extraction and matrix solid‐phase dispersion were evaluated to replace the official Brazilian methodology that uses preparative alumina column chromatography. General drawbacks associated with this last technique, such as the use of large amounts of solvent, laborious and time‐consuming procedure could be avoided by using these alternative approaches. Experiments were carried out to study the performance by using different combinations of sorbents and elution solvents. Efficiency of alternative extraction methods in terms of fat removal and recovery capability was monitored by gravimetry, TLC, and GCwith electron capture detection. Freezing‐lipid filtration with solid‐phase extraction afforded better clean up efficiency with recoveries in a range of 54.5 to 103.6% with the relative standard deviation of less than 10% for all compounds under investigation.

•Central auditory processing disorder was detected in all the individuals in the study group.•The study group had worse performance with a statistically significant difference.•The changes especially are in auditory closure and temporal processing as compared to the control group.

Summary We addressed the question how temperature elevation inhibits Mayaro virus replication inAedes albopictus infected cells. The morphology and macromolecular changes induced by temperature, infection and high serum concentration were investigated in these cells. Cells incubated with 2 and 10% serum at 28°C disclosed an intense vacuolization and inhibition of [35S]methionine incorporation in a time-dependent manner. 34 and 50 kDa viral structural proteins were detected 24 h after infection. In contrast, an inhibition of viral proteins synthesis occurred when infected cells were kept at 37°C (heat-shock conditions). Total cellular RNA was isolated from mock and infected cells incubated at 28 or 37°C. Northern blot analysis with a Mayaro genomic probe coding for viral structural proteins showed a decrease in the amount of viral 26S RNA in stressed cells when compared to those kept at 28°C. Taken together, these results suggest that the inhibition of viral proteins synthesis in response to temperature elevation is associated with a decrease in the amount of subgenomic 26S RNA.

Literature has shown that, even with the conservative nontraumatic surgical techniques, early repairing surgeries induce changes in the upper dental arch morphologic characteristics in patients with cleft lip and palate. The evaluation of unoperated adult cleft patients enables us to exclude the influence of treatment, emphasizing the morphologic characteristics inherent to the presence of the cleft and its functional counterbalances, that is, the morphologic pattern imposed by cleft. In this study, the maxillary dental casts of 31 unoperated adult complete bilateral cleft lip and palate patients (20 men and 11 women) were compared to a noncleft sample matched for gender. Intercanine, inter–first premolar, inter–second premolar and inter–first molar arch widths measurements as well as arch length were measured from xerox copies taken of the models. The findings indicate the presence of premaxillary prognathism and a progressive increase in the constriction of the dental arches. This constriction of the maxillary segments, even in the absence of surgical intervention, is a result of the absence of an intact palate between the two maxillary processes. Although gender significantly influenced the size of the maxillary arches in the noncleft patients, similar differences were not observed in the cleft group. It seems that the presence of the cleft in itself has the greater influence on the morphologic characteristics of the maxillary arch than gender.

We aimed to evaluate the incidence of pancreatic alterations in Crohn's disease using endoscopic ultrasound (EUS) and to correlate the number of alterations with current clinical data.

The aim of this study was to analyse patient-reported outcomes of reduction mammoplasty among Brazilian women.

To better understand the natural history, management, and outcome of pneumothoraces in HIV-infected patients, we reviewed hospital charts and chest radiographs of HIV-infected adults discharged from the University of Maryland Medical Center over a 6-year period. Sixty pneumothoraces occurred in 39 patients. Twenty-three pneumothoraces resulted from trauma and 37 were spontaneous. Thirty-two (86%) of the spontaneous pneumothoraces occurred in patients with Pneumocystis carinii pneumonia (PCP). Eighty percent of the traumatic pneumothoraces in patients who did not have PCP resolved. Patients who had pneumothorax as well as PCP were more difficult to manage and had a poorer outcome (50% mortality) than those who did not have PCP (25% mortality).