PET-CT has low specificity for mediastinal staging of non-small-cell lung cancer in an endemic area for tuberculosis: a diagnostic test study (LACOG 0114).

BACKGROUND: The present study aims to assess the performance of 18F-FDG PET-CT on mediastinal staging of non-small cell lung cancer (NSCLC) in a location with endemic granulomatous infectious disease. METHODS: Diagnostic test study including patients aged 18 years or older with operable stage I-III NSCLC and indication for a mediastinal lymph node biopsy. All patients underwent a 18F-FDG PET-scan before invasive mediastinal staging, either through mediastinoscopy or thoracotomy, which was considered the gold-standard. Surgeons and pathologists were blinded for scan results. Primary endpoint was to evaluate sensitivity, specificity and positive and negative predictive values of PET-CT with images acquired in the 1st hour of the exam protocol, using predefined cutoffs of maximal SUV, on per-patient basis. RESULTS: Overall, 85 patients with operable NSCLC underwent PET-CT scan followed by invasive mediastinal staging. Mean age was 65 years, 49 patients were male and 68 were white. One patient presented with active tuberculosis and none had HIV infection. Using any SUV_max > 0 as qualitative criteria for positivity, sensitivity and specificity were 0.87 and 0.45, respectively. Nevertheless, even when the highest SUV cut-off was used (SUV_max ≥5), specificity remained low (0.79), with an estimated positive predictive value of 54%. CONCLUSIONS: Our findings are in line with the most recent publications and guidelines, which recommend that PET-CT must not be solely used as a tool to mediastinal staging, even in a region with high burden of tuberculosis. TRIAL REGISTRATION: The LACOG 0114 study was registered at ClinicalTrials.gov , before study initiation, under identifier NCT02664792.

Methylphenidate induces state-dependency of social recognition learning: Central components.

Methylphenidate (MPH) is a widely prescribed drug for the treatment of attention-deficit hyperactivity disorder. Findings in the literature suggest that the effects of MPH on memory may result from increased extracellular levels of norepinephrine (NE) and dopamine (DA). Here, we report that the systemic administration of MPH before the acquisition phase in a social discrimination task impaired the retrieval of the social recognition memory (SRM), but made it state-dependent: another administration of MPH before the retention test recovered the SRM. We observed that the induction of state dependency by MPH relies on the ventromedial prefrontal cortex (vmPFC), but not on the CA1 region of the hippocampus (CA1). Also, the inhibitors of NE and DA, nisoxetine and GBR12909, respectively, restored the SRM when infused into the vmPFC. Only the GBR12909 was able to restore the SRM in the CA1, whereas nisoxetine could not restore and even caused an impairment on memory retrieval when infused alone before the retention test. The data suggest that the state-dependence of SRM induced by MPH depends on an influence of both catecholamines on the vmPFC, while NE inhibits the retrieval of SRM on the hippocampus.

Design and optimization of biocompatible polycaprolactone/poly (l-lactic-co-glycolic acid) scaffolds with and without microgrooves for tissue engineering applications.

This study investigated the effects of smooth and microgrooved membrane blends, with different polycaprolactone (PCL)/ poly(lactic-co-glycolic acid) (PLGA) ratios on the viability, proliferation, and adhesion of different mammalian cell types. The polymer matrices with and without microgrooves, obtained by solvent casting, were characterized by field-emission scanning electron microscopy, atomic force microscopy, contact angle and Young's modulus. Blend characterization showed an increase in roughness and stiffness of membranes with 30% PLGA, without any effect on the contact angle value. Pure PCL significantly decreased the viability of Vero, HaCaT, RAW 264.7, and human fetal lung and gingival fibroblast cells, whereas addition of increasing concentrations of PLGA led to a reduced cytotoxicity. Increased proliferation rates were observed for all cell lines. Fibroblasts adhered efficiently to smooth membranes of the PCL70/PLGA30 blend and pure PLGA, compared to pure PCL and silicone. Microgrooved membranes promoted similar cell adhesion for all groups. Microstructured membranes (15 and 20-µm wide grooves) promoted suitable orientation of fibroblasts in both PCL70/PLGA30 and pure PLGA, as compared to pure PCL. Neuronal cells of the dorsal root ganglion exhibited an oriented adhesion to all the tested microgrooved membranes. Data suggest a satisfactory safety profile for the microgrooved PCL70/PLGA30 blend, pointing out this polymer combination as a promising biomaterial for peripheral nerve regeneration when cell orientation is required. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1522-1534, 2018.

Extinction memory is facilitated by methylphenidate and regulated by dopamine and noradrenaline receptors.

Extinction is defined as the learned inhibition of retrieval and is the mainstay of exposure therapy, which is widely used to treat drug addiction, phobias and fear disorders. The psychostimulant, methylphenidate (MPH) is known to increase extracellular levels of noradrenaline and dopamine by blocking their reuptake and studies have demonstrated that MPH can modulate hippocampal physiology and/or functions including long-term potentiation (LTP), learning and memory. However, the influence of MPH on fear extinction memory has been insufficiently studied. Here we investigate the effect of MPH infused into the CA1 region of the hippocampus on extinction memory in animals normally incapable of showing contextual fear conditioning (CFC) extinction because of weak training, and the possible mechanisms through which it acts during this process. For this, male Wistar rats with infusion cannulae stereotaxically implanted in the CA1 region were submitted to a weak extinction protocol in a CFC apparatus. Animals that received intra-CA1 infusion of MPH (12.5µg/side) 20min before the extinction training (Ext Tr) expressed less freezing behavior than Veh-treated animals during both Ext Tr and extinction retention Test (Ext Test). Additionally, the administration of MPH+Timolol (1µg/side) or MPH+SCH23390 (1.5µg/side) intra-CA1 20min before the Ext Tr blocked the enhancing effect of the MPH on extinction learning. These results suggest that MPH in the CA1 region of the hippocampus is able to induce the consolidation of extinction memory and this process occurs through both ß-adrenergic and D1/D5 dopaminergic receptors.