Tractography of developing white matter of the internal capsule and corpus callosum in very preterm infants

To investigate in preterm infants associations between Diffusion Tensor Imaging (DTI) parameters of the posterior limb of the internal capsule (PLIC) and corpus callosum (CC) and age, white matter (WM) injury and clinical factors. In 84 preterm infants DTI was performed between 40-62 weeks postmenstrual age on 3 T MR. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) values and fibre lengths through the PLIC and the genu and splenium were determined. WM injury was categorised as normal/mildly, moderately and severely abnormal. Associations between DTI parameters and age, WM injury and clinical factors were analysed. A positive association existed between FA and age at imaging for fibres through the PLIC (r = 0.48 p < 0.001) and splenium (r = 0.24 p < 0.01). A negative association existed between ADC and age at imaging for fibres through the PLIC (r = -0.65 p < 0.001), splenium (r = -0.35 p < 0.001) and genu (r = -0.53 p < 0.001). No association was found between DTI parameters and gestational age, degree of WM injury or categorical clinical factors. These results indicate that in our cohort of very preterm infants, at this young age, the development of the PLIC and CC is ongoing and independent of the degree of prematurity or WM injury.Neuro Imaging Researc

Molecular pathways involved in the synergistic interaction of the PKCβ inhibitor enzastaurin with the antifolate pemetrexed in non-small cell lung cancer cells

Conventional regimens have limited impact against non-small cell lung cancer (NSCLC). Current research is focusing on multiple pathways as potential targets, and this study investigated molecular mechanisms underlying the combination of the PKCβ inhibitor enzastaurin with the multitargeted antifolate pemetrexed in the NSCLC cells SW1573 and A549. Pharmacologic interaction was studied using the combination-index method, while cell cycle, apoptosis induction, VEGF secretion and ERK1/2 and Akt phosphorylation were studied by flow cytometry and ELISAs. Reverse transcription–PCR, western blot and activity assays were performed to assess whether enzastaurin influenced thymidylate synthase (TS) and the expression of multiple targets involved in cancer signaling and cell cycle distribution. Enzastaurin-pemetrexed combination was highly synergistic and significantly increased apoptosis. Enzastaurin reduced both phosphoCdc25C, resulting in G2/M checkpoint abrogation and apoptosis induction in pemetrexed-damaged cells, and GSK3β and Akt phosphorylation, which was additionally reduced by drug combination (−58% in A549). Enzastaurin also significantly reduced pemetrexed-induced upregulation of TS expression, possibly through E2F-1 reduction, whereas the combination decreased TS in situ activity (>50% in both cell lines) and VEGF secretion. The effects of enzastaurin on signaling pathways involved in cell cycle control, apoptosis and angiogenesis, as well as on the expression of genes involved in pemetrexed activity provide a strong experimental basis to their evaluation as pharmacodynamic markers in clinical trials of enzastaurin-pemetrexed combination in NSCLC patients

Sensing and adhesion are adaptive functions in the plant pathogenic xanthomonads

<p>Abstract</p> <p>Background</p> <p>Bacterial plant pathogens belonging to the <it>Xanthomonas </it>genus are tightly adapted to their host plants and are not known to colonise other environments. The host range of each strain is usually restricted to a few host plant species. Bacterial strains responsible for the same type of symptoms on the same host range cluster in a pathovar. The phyllosphere is a highly stressful environment, but it provides a selective habitat and a source of substrates for these bacteria. Xanthomonads colonise host phylloplane before entering leaf tissues and engaging in an invasive pathogenic phase. Hence, these bacteria are likely to have evolved strategies to adapt to life in this environment. We hypothesised that determinants responsible for bacterial host adaptation are expressed starting from the establishment of chemotactic attraction and adhesion on host tissue.</p> <p>Results</p> <p>We established the distribution of 70 genes coding sensors and adhesins in a large collection of xanthomonad strains. These 173 strains belong to different pathovars of <it>Xanthomonas </it>spp and display different host ranges. Candidate genes are involved in chemotactic attraction (25 genes), chemical environment sensing (35 genes), and adhesion (10 genes). Our study revealed that candidate gene repertoires comprised core and variable gene suites that likely have distinct roles in host adaptation. Most pathovars were characterized by unique repertoires of candidate genes, highlighting a correspondence between pathovar clustering and repertoires of sensors and adhesins. To further challenge our hypothesis, we tested for molecular signatures of selection on candidate genes extracted from sequenced genomes of strains belonging to different pathovars. We found strong evidence of adaptive divergence acting on most candidate genes.</p> <p>Conclusions</p> <p>These data provide insight into the potential role played by sensors and adhesins in the adaptation of xanthomonads to their host plants. The correspondence between repertoires of sensor and adhesin genes and pathovars and the rapid evolution of sensors and adhesins shows that, for plant pathogenic xanthomonads, events leading to host specificity may occur as early as chemotactic attraction by host and adhesion to tissues.</p

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Review of High-Temperature Recovery of Rare Earth (Nd/Dy) from Magnet Waste

Rare-earth metals, particularly neodymium, dysprosium, and praseodymium are becoming increasingly important in the transition to a green economy due to their essential role in permanent magnet applications such as in electric motors and generators. With the increasingly limited rare-earth supply and complexity of processing Nd, Dy, and Pr from primary ores, recycling of rare-earth based magnets has become a necessary option to manage supply and demand. Depending on the form of the starting material (sludge or scrap), there are different routes that can be used to recover neodymium from secondary sources, ranging from hydrometallurgical (based on its primary production process), electrochemical to pyrometallurgical. Pyrometallurgical routes provide solution in cases where water is scarce and generation of waste is to be limited. This paper presents a systematic review of previous studies on the high-temperature (pyrometallurgical) recovery of rare earths from magnets. The features and conditions at which the recycling processes had been studied are mapped and evaluated technically. The review also highlights the reaction mechanisms, behaviors of the rare-earth elements, and the formation of intermediate compounds in high-temperature recycling processes. Recommendations for further scientific research to enable the development of recovery of the rare-earth and magnet recycling are also presented

Fetal and postnatal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta-analysis of animal experiments.

Publication status: PublishedFunder: ZonMw; doi: http://dx.doi.org/10.13039/501100001826BACKGROUND: The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development and health remains unclear. OBJECTIVES: Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes. METHODS: A systematic search was conducted in Pubmed and Embase from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta-analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in case of 10 comparisons or more per subgroup. RESULTS: We included 37 articles (n= 3133 offspring from n=716 litters, containing n= 51 comparisons) in this review, mostly (95%) on rodent models and 6% pig models. Follow-up of offspring ranged from birth to two years of age. Thirty four of the included articles could be included in the meta-analysis. No significant effects in the overall meta-analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details. CONCLUSION: This systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non-human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date