Training Working Memory in Adolescents Using Serious Game Elements: Pilot Randomized Controlled Trial

Working memory capacity has been found to be impaired in adolescents with various psychological problems, such as addictive behaviors. Training of working memory capacity can lead to significant behavioral improvements, but it is usually long and tedious, taxing participants' motivation to train. This study aimed to evaluate whether adding game elements to the training could help improve adolescents' motivation to train while improving cognition. A total of 84 high school students were allocated to a working memory capacity training, a gamified working memory capacity training, or a placebo condition. Working memory capacity, motivation to train, and drinking habits were assessed before and after training. Self-reported evaluations did not show a self-reported preference for the game, but participants in the gamified working memory capacity training condition did train significantly longer. The game successfully increased motivation to train, but this effect faded over time. Working memory capacity increased equally in all conditions but did not lead to significantly lower drinking, which may be due to low drinking levels at baseline. We recommend that future studies attempt to prolong this motivational effect, as it appeared to fade over time. [Abstract copyright: ©Wouter J Boendermaker, Thomas E Gladwin, Margot Peeters, Pier JM Prins, Reinout W Wiers. Originally published in JMIR Serious Games (http://games.jmir.org), 23.05.2018.

Specific N-terminal attachment of TMTHSI linkers to native peptides and proteins for strain-promoted azide alkyne cycloaddition

The site specific attachment of the reactive TMTHSI-click handle to the N-terminus of peptides and proteins is described. The resulting molecular constructs can be used in strain-promoted azide alkyne cycloaddition (SPAAC) for reaction with azide containing proteins e.g., antibodies, peptides, nanoparticles, fluorescent dyes, chelators for radioactive isotopes and SPR-chips etc

Volumetric breast density affects performance of digital screening mammography

PURPOSE: To determine to what extent automatically measured volumetric mammographic density influences screening performance when using digital mammography (DM). METHODS: We collected a consecutive series of 111,898 DM examinations (2003-2011) from one screening unit of the Dutch biennial screening program (age 50-75 years). Volumetric mammographic density was automatically assessed using Volpara. We determined screening performance measures for four density categories comparable to the American College of Radiology (ACR) breast density categories. RESULTS: Of all the examinations, 21.6% were categorized as density category 1 ('almost entirely fatty') and 41.5, 28.9, and 8.0% as category 2-4 ('extremely dense'), respectively. We identified 667 screen-detected and 234 interval cancers. Interval cancer rates were 0.7, 1.9, 2.9, and 4.4‰ and false positive rates were 11.2, 15.1, 18.2, and 23.8‰ for categories 1-4, respectively (both p-trend < 0.001). The screening sensitivity, calculated as the proportion of screen-detected among the total of screen-detected and interval tumors, was lower in higher density categories: 85.7, 77.6, 69.5, and 61.0% for categories 1-4, respectively (p-trend < 0.001). CONCLUSIONS: Volumetric mammographic density, automatically measured on digital mammograms, impacts screening performance measures along the same patterns as established with ACR breast density categories. Since measuring breast density fully automatically has much higher reproducibility than visual assessment, this automatic method could help with implementing density-based supplemental screening

Single-crystalline PbTe film growth through reorientation

Heteroepitaxy enables the engineering of novel properties, which do not exist in a single material. Two principle growth modes are identified for material combinations with large lattice mismatch, Volmer-Weber and Stranski-Krastanov. Both lead to the formation of three-dimensional islands, hampering the growth of flat defect-free thin films. This limits the number of viable material combinations. Here, we report a distinct growth mode found in molecular beam epitaxy of PbTe on InP initiated by pre-growth surface treatments. Early nucleation forms islands analogous to the Volmer-Weber growth mode, but film closure exhibits a flat surface with atomic terracing. Remarkably, despite multiple distinct crystal orientations found in the initial islands, the final film is single-crystalline. This is possible due to a reorientation process occurring during island coalescence, facilitating high quality heteroepitaxy despite the large lattice mismatch, difference in crystal structures and diverging thermal expansion coefficients of PbTe and InP. This growth mode offers a new strategy for the heteroepitaxy of dissimilar materials and expands the realm of possible material combinations

Effect of diet with or without exercise on abdominal fat in postmenopausal women:A randomised trial

Background: We assessed the effect of equivalent weight loss with or without exercise on (intra-) abdominal fat in postmenopausal women in the SHAPE-2 study. Methods: The SHAPE-2 study is a three-armed randomised controlled trial conducted in 2012-2013 in the Netherlands. Postmenopausal overweight women were randomized to a diet (n = 97), exercise plus diet (n = 98) or control group (n = 48). Both intervention groups aimed for equivalent weight loss (6-7%) following a calorie-restricted diet (diet group) or a partly supervised intensive exercise programme (4 h per week) combined with a small caloric restriction (exercise plus diet group). Outcomes after 16 weeks are amount and distribution of abdominal fat, measured by magnetic resonance imaging (MRI) with the use of the three-point IDEAL Dixon method. Results: The diet and exercise plus diet group lost 6.1 and 6.9% body weight, respectively. Compared to controls, subcutaneous and intra-abdominal fat reduced significantly with both diet (- 12.5% and - 12.0%) and exercise plus diet (- 16.0% and - 14.6%). Direct comparison between both interventions revealed that the reduction in subcutaneous fat was statistically significantly larger in the group that combined exercise with diet: an additional 10.6 cm 2 (95%CI -18.7; - 2.4) was lost compared to the diet-only group. Intra-abdominal fat loss was not significantly larger in the exercise plus diet group (- 3.8 cm 2 , 95%CI -9.0; 1.3). Conclusions: We conclude that weight loss of 6-7% with diet or with exercise plus diet reduced both subcutaneous and intra-abdominal fat. Only subcutaneous fat statistically significantly reduced to a larger extent when exercise is combined with a small caloric restriction. Trial register: NCT01511276 (clinicaltrials.gov), prospectively registered

Long-term acquired everolimus resistance in pancreatic neuroendocrine tumours can be overcome with novel PI3K-AKT-mTOR inhibitors

Background:The mTOR-inhibitor everolimus improves progression-free survival in advanced pancreatic neuroendocrine tumours (PNETs). However, adaptive resistance to mTOR inhibition is described.Methods:QGP-1 and BON-1, two human PNET cell lines, were cultured with increasing concentrations of everolimus up to 22 weeks to reach a dose of 1 μM everolimus, respectively, 1000-fold and 250-fold initial IC 50. Using total DNA content as a measure of cell number, growth inhibitory dose-response curves of everolimus were determined at the end of resistance induction and over time after everolimus withdrawal. Response to ATP-competitive mTOR inhibitors OSI-027 and AZD2014, and PI3K-mTOR inhibitor NVP-BEZ235 was studied. Gene expression of 10 PI3K-Akt-mTOR pathway-related genes was evaluated using quantitative real-time PCR (RT-qPCR).Results:Long-term everolimus-treated BON-1/R and QGP-1/R showed a significant reduction in everolimus sensitivity. During a drug holiday, gradual return of everolimus sensitivity in BON-1/R and QGP-1/R led to complete reversal of resistance after 10-12 weeks. Treatment with AZD2014, OSI-027 and NVP-BEZ235 had an inhibitory effect on cell proliferation in both sensitive and resistant cell lines. Gene expression in BON-1/R revealed downregulation of MTOR, RICTOR, RAPTOR, AKT and HIF1A, whereas 4EBP1 was upregulated. In QGP-1/R, a downregulation of HIF1A and an upregulation of ERK2 were observed.Conclusions:Long-term everolimus resistance was induced in two human PNET cell lines. Novel PI3K-AKT-mTOR pathway-targeting drugs can overcome everolimus resistance. Differential gene expression profiles suggest different mechanisms of everolimus resistance in BON-1 and QGP-1

Visually guided inspiration breath-hold facilitated with nasal high flow therapy in locally advanced lung cancer

Background and purpose Reducing breathing motion in radiotherapy (RT) is an attractive strategy to reduce margins and better spare normal tissues. The objective of this prospective study (NCT03729661) was to investigate the feasibility of irradiation of non-small cell lung cancer (NSCLC) with visually guided moderate deep inspiration breath-hold (IBH) using nasal high-flow therapy (NHFT). Material and methods Locally advanced NSCLC patients undergoing photon RT were given NHFT with heated humidified air (flow: 40 L/min with 80% oxygen) through a nasal cannula. IBH was monitored by optical surface tracking (OST) with visual feedback. At a training session, patients had to hold their breath as long as possible, without and with NHFT. For the daily cone beam CT (CBCT) and RT treatment in IBH, patients were instructed to keep their BH as long as it felt comfortable. OST was used to analyze stability and reproducibility of the BH, and CBCT to analyze daily tumor position. Subjective tolerance was measured with a questionnaire at 3 time points. Results Of 10 included patients, 9 were treated with RT. Seven (78%) completed the treatment with NHFT as planned. At the training session, the mean BH length without NHFT was 39 s (range 15-86 s), and with NHFT 78 s (range 29-223 s) (p = .005). NHFT prolonged the BH duration by a mean factor of 2.1 (range 1.1-3.9s). The mean overall stability and reproducibility were within 1 mm. Subjective tolerance was very good with the majority of patients having no or minor discomfort caused by the devices. The mean inter-fraction tumor position variability was 1.8 mm (-1.1-8.1 mm;SD 2.4 mm). Conclusion NHFT for RT treatment of NSCLC in BH is feasible, well tolerated and significantly increases the breath-hold duration. Visually guided BH with OST is stable and reproducible. We therefore consider this an attractive patient-friendly approach to treat lung cancer patients with RT in BH

Природный и антропогенный факторы формирования и развития культурного ландшафта Форосского парка

Цель данной статьи: на примере небольшой территории Южного берега Крыма – парка в пгт. Форос и прилегающей к нему местности – показать роль и место культурного ландшафта в формировании человеком исторического геокультурного пространства

Subclinical thyroid dysfunction and cognitive decline in old age

&lt;p&gt;Background: Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).&lt;/p&gt; &lt;p&gt;Methods: Prospective longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) &#60;0.45 mU/L or &#62;4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests.&lt;/p&gt; &lt;p&gt;Results: Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up.&lt;/p&gt; &lt;p&gt;Conclusion: We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.&lt;/p&gt

Subclinical thyroid dysfunction and cognitive decline in old age

&lt;p&gt;Background: Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).&lt;/p&gt; &lt;p&gt;Methods: Prospective longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) &#60;0.45 mU/L or &#62;4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests.&lt;/p&gt; &lt;p&gt;Results: Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up.&lt;/p&gt; &lt;p&gt;Conclusion: We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.&lt;/p&gt