Exploring the Effects of Meditation Techniques Used by Mindfulness-Based Programs on the Cognitive, Social-Emotional, and Academic Skills of Children: A Systematic Review.

There is evidence for the positive impact of mindfulness in children. However, little is known about the techniques through which mindfulness practice results in differential outcomes. Therefore, this study intended to systematically review the available evidence about the efficacy of meditation techniques used by mindfulness-based programs on cognitive, socio-emotional, and academic skills of children from 6 to 12 years of age. The review was registered on the PROSPERO database, and the literature search was conducted according to PICO criteria and PRISMA guidelines. The EBSCO databases were searched, and 29 studies were eligible: nine randomized controlled trials and 20 quasi-experimental studies. All the included randomized controlled trials were rated as having a high risk of bias. Overall, the evidence for mindfulness techniques improving cognitive and socio-emotional skills was reasonably strong. Specifically, for cognitive skills, results showed that all the interventions used "body-centered meditations" and "mindful observations." Regarding socio-emotional skills, although all the studies applied "body-centered meditations" and "mindful observations," "affect-centered meditations" were also frequent. For academic skills, just one quasi-experimental trial found improvements, thus making it difficult to draw conclusions. Further research is crucial to evaluate the unique effects of different meditation techniques on the cognitive, social-emotional, and academic skills of children. Systematic Review Registration: Identifier: RD42019126767.

Targeting Glycosylation: A New Road for Cancer Drug Discovery.

Cancer is a deadly disease that encompasses numerous cellular modifications. Among them, alterations in glycosylation are a proven reliable hallmark of cancer, with most biomarkers used in the clinic detecting cancer-associated glycans. Despite their clear potential as therapy targets, glycans have been overlooked in drug discovery strategies. The complexity associated with the glycosylation process, and lack of specific methodologies to study it, have long hampered progress. However, recent advances in new methodologies, such as glycoengineering of cells and high-throughput screening (HTS), have opened new avenues of discovery. We envision that glycan-based targeting has the potential to start a new era of cancer therapy. In this article, we discuss the promise of cancer-associated glycosylation for the discovery of effective cancer drugs.

ß3 Adrenoceptor-induced cholinergic inhibition in human and rat urinary bladders involves the exchange protein directly activated by cyclic AMP 1 favoring adenosine release.

BACKGROUND AND PURPOSE: The mechanism by which ß3 receptor agonists (e.g. mirabegron) control bladder overactivity may involve adenosine release from human and rat detrusor smooth muscle. Retrograde activation of adenosine A1 receptors reduces ACh release from cholinergic bladder nerves. ß3 -Adrenoceptors usually couple to adenylyl cyclase. Here we investigated, which of the cAMP targets, protein kinase A or the exchange protein directly activated by cAMP (EPAC) could be involved in this cholinergic inhibition of the bladder. EXPERIMENTAL APPROACH: [3 H]ACh and adenosine release from urothelium-denuded detrusor strips of cadaveric human organ donors and rats were measured by liquid scintillation spectrometry and HPLC, respectively. In vivo cystometry was also performed in urethane-anaesthetized rats. KEY RESULTS: The exchange protein directly activated by cAMP (EPAC) inhibitor, ESI-09, prevented mirabegron- and isoprenaline-induced adenosine release from human and rat detrusor strips respectively. ESI-09, but not the PKA inhibitor, H-89, attenuated inhibition of [3 H]ACh release from stimulated (10 Hz) detrusor strips caused by activating ß3 -adrenoceptors, AC (forskolin) and EPAC1 (8-CTP-2Me-cAMP). Isoprenaline-induced inhibition of [3 H]ACh release was also prevented by inhibitors of PKC (chelerythrine and Go6976) and of the equilibrative nucleoside transporter 1 (ENT1; dipyridamole and NBTI), but not by PLC inhibition with U73122. Pretreatment with ESI-09, but not with H-89, prevented the reduction of the voiding frequency caused by isoprenaline and forskolin in vivo. CONCLUSION AND IMPLICATIONS: Data suggest that ß3 -adrenoceptor-induced inhibition of cholinergic neurotransmission in human and rat urinary bladders involves activation of an EPAC1/PKC pathway downstream cAMP production resulting in adenosine outflow via ENT1.

Inhibition of cholinergic neurotransmission by ß3-adrenoceptors depends on adenosine release and A1-receptor activation in human and rat urinary bladders.

The direct detrusor relaxant effect of ß3-adrenoceptor agonists as a primary mechanism to improve overactive bladder symptoms has been questioned. Among other targets, activation of ß3-adrenoceptors downmodulate nerve-evoked acetylcholine (ACh) release, but there is insufficient evidence for the presence of these receptors on bladder cholinergic nerve terminals. Our hypothesis is that adenosine formed from the catabolism of cyclic AMP in the detrusor may act as a retrograde messenger via prejunctional A1 receptors to explain inhibition of cholinergic activity by ß3-adrenoceptors. Isoprenaline (1 µM) decreased [3H]ACh release from stimulated (10 Hz, 200 pulses) human (-47 ± 5%) and rat (-38 ± 1%) detrusor strips. Mirabegron (0.1 µM, -53 ± 8%) and CL316,243 (1 µM, -37 ± 7%) mimicked isoprenaline (1 µM) inhibition, and their effects were prevented by blocking ß3-adrenoceptors with L748,337 (30 nM) and SR59230A (100 nM), respectively, in human and rat detrusor. Mirabegron and isoprenaline increased extracellular adenosine in the detrusor. Blockage of A1 receptors with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 100 nM) or the equilibrative nucleoside transporters (ENT) with dipyridamole (0.5 µM) prevented mirabegron and isoprenaline inhibitory effects. Dipyridamole prevented isoprenaline-induced adenosine outflow from the rat detrusor, and this effect was mimicked by the ENT1 inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI, 30 µM). Cystometry recordings in anesthetized rats demonstrated that SR59230A, DPCPX, dipyridamole, and NBTI reversed the decrease in the voiding frequency caused by isoprenaline (0.1-1,000 nM). Data suggest that inhibition of cholinergic neurotransmission by ß3-adrenoceptors results from adenosine release via equilibrative nucleoside transporters and prejunctional A1-receptor stimulation in human and rat urinary bladder.

An exploratory study of the Work Ability Index (WAI) and its components in a group of computer workers.

OBJECTIVE: The objective of this paper is to present a study on the assessment of the work ability of a group of aged computers workers. The study was developed with the goal of creating a decision making framework oriented towards the maintenance of the health and working ability of aged workers. PARTICIPANTS: Fifty computer workers participated in this study. They were administrative secretaries and computer technicians working mainly with office computers. METHODS: The method used to assess the work ability was the Work Ability Index (WAI). RESULTS: 78% of the participants had good or excellent work ability and only 2% a poor one. The average WAI score was 40.5 (SD=5.761; min=27; max=49). This study confirms the decrease in work ability of workers while aging. The group overall work ability was slightly higher than the reference values develop by the Finnish Institute of Occupational Health. CONCLUSIONS: The assessment of work ability is fundamental to make age-friendly workplaces. WAI is one tool designed to perform such assessment. The results obtained could assist the early identification of situations where employees are struggling with their work ability, thus helping to prioritize ergonomic interventions devoted to improve the working conditions, and allowing the continued employment of aging workers on their current job.

[Small cell lung cancer--state of the art and future perspectives]. / Carcinoma do pulmão de pequenas células--Estado da arte e perspectivas futuras.

Lung cancer is the leading cause of cancer-related death in Portugal. Almost 3500 Portuguese are expected to be diagnosed with lung cancer in 2006; approximately 20% will have small cell lung cancer (SCLC). At presentation, 25% to 30% of patients will have local or regional disease, classified as limited stage disease. The concurrent chemovalidation therapy is the best choice. Once daily thoracic radiation therapy to doses in the range of 50 Gy to 60 Gy would reflect an accepted standard of care in daily practice. Because of the increase toxicity associated with hyper fractionated radiation, this approach is often limited to select patients. Etoposide plus cisplatin are synergistic, well tolerated and result in equal or superior survival compared with other regimens. This is the standard regimen for concomitant therapy in limited stage and for extensive disease SCLC. Despite good chemo sensitivity and radio sensitivity, the prognosis of SCLC is very poor because of the early development of resistance and the associated high tendency to recurrence, making second line treatment of SCLC a problem of real medical relevance. Topotecan now offers an effective and well tolerated monosubstance for second line therapy of recurrent SCLC. There has been a significant increase in median survival for patients with SCLC receiving topotecan plus symptomatic therapy versus symptomatic therapy. The efficacy of this drug is comparable to the efficacy of the three-drug combination CAV. The tolerability can be improved by means of toxicity-adapted dosing. In elderly and in patients with performance status 2, topotecan is also well tolerated and has good efficacy. Initial studies into weekly administration also demonstrate good efficacy. The combination of topotecan with cranial radiotherapy is well tolerated and effective in the treatment of cerebral metastases of SCLC. New classes of agents, such as antiangiogenic agents including bevacizumab, small molecule tyrosine kinase inhibitors and thalidomide are being evaluated with chemotherapy for patients with extensive stage SCLC.