Electro-fluid dynamics of aqueous humor production: simulations and new directions.

Purpose: to theoretically investigate the role of bicarbonate ion (HCO− 3 ) on the nonpigmented transepithelial potential di erence Vm, the sodium potassium pump (Na/K) and the active secretion of aqueous humor. Methods: a three-dimensional mathematical model is proposed to isolate the roles of HCO− 3 and Na+, which are di icult to investigate experimentally. The model combines the velocity-extended Poisson-Nernst-Planck equations to describe ion electrodi usion and the Stokes equations to describe aqueous humor flow into the basolateral space adjacent to the nonpigmented ephitelial cells. Results: Computations show that Vm is close to baseline experimental measurements (on monkeys) in the range [−2.7, −2.3]mV only if HCO− 3 is included in the simulation. The model is also capable of reproducing the flow of Na+ exiting the cell and the flow of K+ entering the cell, in accordance with the physiology of the Na/K pump. The simulated Na/K ratio is 1.53, which is in very good agreement with the theoretical value of 1.5. Conclusion: Model simulations suggest that HCO− 3 inhibition may prevent physiologically correct baseline values of the nonpigmented transepithelial potential di erence and Na/K ATPase function. This may provide useful indication in the design of medications that decrease the active secretion of aqueous humor, and supports the advantage of using mathematical models as a noninvasive complement of animal models

Assessment of Cardiovascular Function in Childhood Leukemia Survivors: The Role of the Right Heart

Childhood acute lymphoblastic leukemia (ALL) survivors who underwent chemotherapy with anthracyclines have an increased cardiovascular risk. The aim of the study was to evaluate left and right cardiac chamber performances and vascular endothelial function in childhood ALL survivors. Fifty-four ALL survivors and 37 healthy controls were enrolled. All patients underwent auxological evaluation, blood pressure measurements, biochemical parameters of endothelial dysfunction, flow-mediated dilatation (FMD) of the brachial artery, mean common carotid intima-media thickness (c-IMT), antero-posterior diameter of the infra-renal abdominal aorta (APAO), and echocardiographic assessment. The ALL subjects had significantly lower FMD (p = 0.0041), higher left (p = 0.0057) and right (p = 0.0021) echocardiographic/Doppler Tei index (the non-invasive index for combined systolic and diastolic ventricular function) as compared to controls. Tricuspid annular plane excursion (TAPSE) was 16.9 +/- 1.2 mm vs. 24.5 +/- 3.7 mm, p < 0.0001. Cumulative anthracycline doses were related to TAPSE (p < 0.001). The ALL survivors treated with anthracyclines demonstrated systo/diastolic alterations of the right ventricle and reduced endothelial function compared with healthy controls. The early recognition of subclinical cardiac and vascular impairment during follow up is of utmost importance for the cardiologist to implement strategies preventing overt cardiovascular disease considering the growing number of young adults cured after childhood ALL

Multiple micronutrients and docosahexaenoic acid supplementation during pregnancy : A randomized controlled study

Maternal dietary intake during pregnancy needs to meet increased nutritional demands to maintain metabolism and to support fetal development. Docosahexaenoic acid (DHA) is essential for fetal neuro-/visual development and in immunomodulation, accumulating rapidly within the developing brain and central nervous system. Levels available to the fetus are governed by the maternal diet. In this multicenter, parallel, randomized controlled trial, we evaluated once-daily supplementation with multiple micronutrients and DHA (i.e., multiple micronutrient supplementation, MMS) on maternal biomarkers and infant anthropometric parameters during the second and third trimesters of pregnancy compared with no supplementation. Primary efficacy endpoint: change in maternal red blood cell (RBC) DHA (wt% total fatty acids) during the study. Secondary variables: other biomarkers of fatty acid and oxidative status, vitamin D, and infant anthropometric parameters at delivery. Supplementation significantly increased RBC DHA levels, the omega-3 index, and vitamin D levels. Subscapular skinfold thickness was significantly greater with MMS in infants. Safety outcomes were comparable between groups. This first randomized controlled trial of supplementation with multiple micronutrients and DHA in pregnant women indicated that MMS significantly improved maternal DHA and vitamin D status in an industrialized setting\u2014an important finding considering the essential roles of DHA and vitamin D

Differential signature of the centrosomal MARK4 isoforms in glioma

Background: MAP/microtubule affinity-regulating kinase 4 (MARK4) is a serine-threonine kinase expressed in two spliced isoforms, MARK4L and MARK4S, of which MARK4L is a candidate for a role in neoplastic transformation. Methods: We performed mutation analysis to identify sequence alterations possibly affecting MARK4 expression. We then investigated the MARK4L and MARK4S expression profile in 21 glioma cell lines and 36 tissues of different malignancy grades, glioblastoma-derived cancer stem cells (GBM CSCs) and mouse neural stem cells (NSCs) by real-time PCR, immunoblotting and immunohistochemistry. We also analyzed the sub-cellular localisation of MARK4 isoforms in glioma and normal cell lines by immunofluorescence. Results: Mutation analysis rules out sequence variations as the cause of the altered MARK4 expression in glioma. Expression profiling confirms that MARK4L is the predominant isoform, whereas MARK4S levels are significantly decreased in comparison and show an inverse correlation with tumour grade. A high MARK4L/MARK4S ratio also characterizes undifferentiated cells, such as GBM CSCs and NSCs. Accordingly, only MARK4L is expressed in brain neurogenic regions. Moreover, while both MARK4 isoforms are localised to the centrosome and midbody in glioma and normal cells, the L isoform exhibits an additional nucleolar localisation in tumour cells. Conclusions: The observed switch towards MARK4L suggests that the balance between the MARK4 isoforms is carefully guarded during neural differentiation but may be subverted in gliomagenesis. Moreover, the MARK4L nucleolar localisation in tumour cells features this MARK4 isoform as a nucleolus-associated tumour marker

Microbiome preterm birth DREAM challenge: Crowdsourcing machine learning approaches to advance preterm birth research

Every year, 11% of infants are born preterm with significant health consequences, with the vaginal microbiome a risk factor for preterm birth. We crowdsource models to predict (1) preterm birth (PTB; <37 weeks) or (2) early preterm birth (ePTB; <32 weeks) from 9 vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from public raw data via phylogenetic harmonization. The predictive models are validated on two independent unpublished datasets representing 331 samples from 148 pregnant individuals. The top-performing models (among 148 and 121 submissions from 318 teams) achieve area under the receiver operator characteristic (AUROC) curve scores of 0.69 and 0.87 predicting PTB and ePTB, respectively. Alpha diversity, VALENCIA community state types, and composition are important features in the top-performing models, most of which are tree-based methods. This work is a model for translation of microbiome data into clinically relevant predictive models and to better understand preterm birth

Success Factors for Effective Knowledge Sharing in Community-based Question-Answering

Nowadays, people increasingly seek information and ask for help on Question and Answer (Q&amp;A) sites. The enormous success of Stack Exchange , a constantly growing network of Q&amp;A sites, attests this increasing trend. The success of Q&amp;A mainly depends on the will of their members to provide good quality answers to others’ questions. We investigate the success factors of Q&amp;A that is those factors that foster effective knowledge creation and sharing. In particular, we focus those factors that can be acted upon by contributors when writing a question

GitHub Discussions: An exploratory study of early adoption

Discussions is a new feature of GitHub for asking questions or discussing topics outside of specific Issues or Pull Requests. Before being available to all projects in December 2020, it had been tested on selected open source software projects. To understand how developers use this novel feature, how they perceive it, and how it impacts the development processes, we conducted a mixed-methods study based on early adopters of GitHub discussions from January until July 2020. We found that: (1) errors, unexpected behavior, and code reviews are prevalent discussion categories; (2) there is a positive relationship between project member involvement and discussion frequency; (3) developers consider GitHub Discussions useful but face the problem of topic duplication between Discussions and Issues; (4) Discussions play a crucial role in advancing the development of projects; and (5) positive sentiment in Discussions is more frequent than in Stack Overflow posts. Our findings are a first step towards data-informed guidance for using GitHub Discussions, opening up avenues for future work on this novel communication channel

"Parque Pachacamac" - LIMA - PERU - Concorso Internazionale ristretto di progettazione paesaggistica, urbana e architettonica - Progetto Menzione Speciale "On the Shores of the Myth"

Il progetto riguarda un parco lineare a protezione di una futura area di scavo archeologico di 150 Ha alla periferia di Lima. Il parco ha un doppio scopo, di inquadrare l'area di scavo e proteggere i quartieri vicini dalla polvere. Il progetto si è distinto per la capacità di rammendare i tessuti della città esistente, e di fornire tre logiche sistemiche integrate riguardanti rispettivamente : il ciclo delle materie inerti a scala metropolitana, il ciclo locale di gestione delle acque, la circolarità di competenze e valori sociali