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We document the need to examine digital game play and app use as a context for cognitive development, particularly during middle childhood. We highlight this developmental period as 6- through 12-year olds comprise a large swath of the preadult population that plays and uses these media forms. Surprisingly, this age range remains understudied with regard to the impact of their interactive media use as compared to young children and adolescents. This gap in knowledge about middle childhood may reflect strong and widely held concerns about the effects of digital games and apps before and after this period. These concerns include concurrent and subsequent influences of game use on very young children's and adolescents' cognitive and socioemotional functioning. We highlight here what is currently known about the impact of media on young children and adolescents and what is not known about this impact in middle childhood. We then offer recommendations for the types of research that developmental scientists can undertake to examine the efficacy of digital games within the rapidly changing media ecology in which children live. We conclude with a discussion of media policies that we believe can help children benefit from their media use. Our hope is that this review will foster greater investigation of the cognitive socialization, as raised over 20 years ago by developmental psychologist and early games researcher Patricia Greenfield, that digital games serve during the middle childhood period, and childhood more generally.

We examined fourth through seventh graders' reported behaviors while playing a digital game and their reflections about those behaviors after playing. Students were randomly assigned to one of three conditions in which participants were to think about what they were learning while playing (metacognitive); about how much they liked the game (affective); or no goal (control condition). Students then were trained to think aloud as they played a coding game for 10 consecutive minutes. Following gameplay, students indicated what they learned and remembered while playing. All comments were coded for reference to cognitive processes, specific game aspects, and participants’ evaluations of the game or their gameplay. Sixth- and seventh-graders outperformed and made more references to cognitive processes than the younger students. Those in the affective condition performed worse than those in the control condition. Seventh graders referenced cognitive processes more than fourth graders during the game. Notably, across all participants reference to rules about how to play the game showed an initial spike and then immediately decreased. Overall, the findings elucidate how pre- and early adolescents may think about their game-based learning, which may inform how they use that learning outside game contexts.

N-Acyloxymethyl derivatives of pioglitazone (PIO) have been prepared and characterized as model candidates for extended-release injectable formulations. All PIO derivatives prepared are crystalline solids as determined by powder X-ray diffraction, and the solubility in aqueous media is below 1 μM at 37 °C. The melting points steadily increase from 55 °C, for the hexanoyloxymethyl derivative, to 85 °C, for the palmitoyloxymethyl derivative; inversely, the solubilities in ethyl oleate decrease as a function of increasing acyl chain length. The butyroyloxymethyl ester has a higher melting point and a lower solubility in ethyl oleate than expected from the trend. The 13C solid-state NMR spectra of the PIO homologues between the hexanoyloxymethyl derivative and stearoyloxymethyl derivative suggest a common structural motif with the acyl chains exchanging between two distinct conformations, and the rate of exchange is slower for longer chain derivatives. The butyroyloxymethyl derivative is efficiently converted to PIO in in vitrorat plasma with a half-life of <2 min at 37 oC, while the rate of enzymatic cleavage in rat plasma decreases as the ester chain length increases for the longer acyloxymethyl derivatives. The concentration of PIO in plasma increases rapidly, or “spikes,” in the hours following intramuscular (IM) injection of either the HCl salt or the butyroyloxymethyl derivative. In contrast, the more lipophilic palmitoyloxymethyl derivative provides slow growth in the PIO concentration over the first day to reach levels that remain steady for 2 weeks. On the basis of its in vivopharmacokinetic profile, as well as material and solubility properties, the PIO palmitoyloxymethyl derivative has potential as a once-monthly injectable medication to treat diabetes.

The prevalence of digital media use among children and adolescents is indisputable. One medium to which children and adolescents dedicate a sizeable portion of their time is that of the digital game. Accordingly, digital game play continues to grow as a context for cognitive development. We showcase new research and practice addressing the impact of this very popular activity on children’s and adolescents’ learning. Our goal is to stimulate new research and interest in examining the positive ramifications of digital play for development among today’s youth.

Background. The effects of hypoxia on renin secretion and renin gene expression have been controversial. In recent studies, we have demonstrated that acute hypoxia of 6 h duration caused a marked stimulation of renin secretion and renal renin gene expression. This hypoxia-induced stimulation of the renin–angiotensin system might contribute, for example, to the progression of chronic renal failure and to the development of hypertension in the sleep-apnoea syndrome. For this reason, we were interested in the more chronic effects of hypoxia on renal renin gene expression and its possible regulation.Methods. Male rats were exposed to chronic normobaric hypoxia (10% O2) for 2 and 4 weeks. Additional groups of rats were treated with an endothelin ETA receptor antagonist, LU135252, or a NO donor, molsidomine, respectively. Systolic blood pressure and right ventricular pressures were measured. Renal renin, endothelin-1 and endothelin-3 gene expression were quantitated using RNAase protection assays.Results. During chronic hypoxia, haematocrit increased to 72±2%, and right ventricular pressure increased by a mean of 26 mmHg. Renal renin gene expression was halved during 4 weeks of chronic hypoxia. This decrease was reversed by endothelin receptor blockade (105 or 140% of baseline values after treatment for weeks 3–4 or 1–4). Furthermore, there was a trend of increasing renal endothelin-1 gene expression (to 173% of baseline values) after 4 weeks of hypoxia. Systolic blood pressure increased moderately during 4 weeks of chronic hypoxia from 129±2 to 150±4 mmHg. This blood pressure increase was higher in rats treated for 4 weeks with an endothelin receptor antagonist (196±11 mmHg).Conclusions. Chronic hypoxia (in contrast to acute hypoxia) suppresses renal renin gene expression. This inhibition presumably is mediated by endothelins.

Background:There is evidence from in vitro studies to suggest that the genes of platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) are, like the erythropoietin gene, regulated by oxygen tension. Hypoxia-induced stimulation of, for example, PDGF or VEGF might be involved in the pathogenesis of acute or chronic renal failure and in renal ‘inflammatory’ diseases (glomerulonephritis, vasculitis, allograft rejection). Methods:Male Wistar rats were exposed to chronic normobaric hypoxia (10% O2, 90% N2) for 4 weeks. Additional groups of rats were treated with the endothelin receptor antagonist LU13525 and the NO donor molsidomine. Renal mRNA levels of PDGF-A, PDGF-B, and VEGF were semiquantitated using RNase protection assays. Results:Renal gene expression of PDGF-A and PDGF-B was neither affected by 2 or 4 weeks of hypoxia nor by concomitant treatment with LU135252 or molsidomine. Chronic hypoxia did also not change VEGF gene expression; however, concomitant treatment with LU135252 increased all VEGF subtypes (188, 164, 120). Conclusions:The findings of the present study suggest that renal PDGF and VEGF gene expression in vivo during chronic hypoxia for 2 and 4 weeks is not sensitive to tissue hypoxia in contrast to cell culture experiments. During chronic hypoxia with concomitant blockade of endothelin receptors, all VEGF subtypes were increased, suggesting an inhibitory action of endothelins with regard to renal VEGF gene expression.

Middle childhood remains a privileged albeit understudied developmental period in studies examining child–computer interactions, particularly as it pertains to digital game play. Middle childhood also is marked by increasing digital game play, arguably the most common form of child–computer interactions during this developmental period. For example, children between the ages of 6 and 8 play digital games 60–90 min per day and 47% of 3rd to 8th grade teachers reported using digital games in their classrooms several times a week (Vega & Robb, 2019). Surprisingly, how content learning and cognition may be facilitated through digital gaming remains sparsely investigated among children during this period. In the studies that do examine the linkages between game play and content learning or cognition, research methodologies vary markedly. The goal of this narrative review is to help bring greater cohesion to the research literature, which often spans many disciplines. This review emphasizes the games, measurement of outcomes, and research designs that have been used to examine content learning and cognitive skills among children ages 6 to 12 in the context of digital games.

To evaluate the feasibility and accuracy of multiplane transesophageal Doppler echocardiographic assessment of the severity of aortic stenosis in mechanically ventilated patients using modified transgastral views of the left ventricular outflow tract and the aortic valve.

Endothelin1, 2 and 3 ET1, 2, 3 have suppressive effects on the renin system in different experimental in vitro models, whereas a modulation of renin secretion or renin gene expression by endothelins ETs in in vivo studies has not so far been found. In a recent study we observed a significant stimulation of the renin system by acute hypoxia over 6 h in rats. In the study reported here, we investigated the more chronic effects of hypoxia 10 O2for 4 weeks on renin gene expression and the influence of the ET system on its regulation. Renin mRNA levels decreased after 2 weeks of hypoxia to 76 of control and after 4 weeks to 49 of control p < 0.05. Concomitant administration of the ETAreceptor antagonist LU135252 led to a significant increase in renin gene expression compared to control or hypoxia alone. ET1 mRNA increased to 120 after 2 weeks and 173 after 4 weeks of hypoxia NS, while ET3 was not affected by hypoxia. We therefore conclude that ETs have a suppressive effect on renal renin gene expression in the setting of chronic hypoxia in rats in vivo.