Pluripotent and Multipotent Stem Cells Display Distinct Hypoxic miRNA Expression Profiles

MicroRNAs are reported to have a crucial role in the regulation of self-renewal and differentiation of stem cells. Hypoxia has been identified as a key biophysical element of the stem cell culture milieu however, the link between hypoxia and miRNA expression in stem cells remains poorly understood. We therefore explored miRNA expression in hypoxic human embryonic and mesenchymal stem cells (hESCs and hMSCs). A total of 50 and 76 miRNAs were differentially regulated by hypoxia (2% O2) in hESCs and hMSCs, respectively, with a negligible overlap of only three miRNAs. We found coordinate regulation of precursor and mature miRNAs under hypoxia suggesting their regulation mainly at transcriptional level. Hypoxia response elements were located upstream of 97% of upregulated hypoxia regulated miRNAs (HRMs) suggesting hypoxia-inducible-factor (HIF) driven transcription. HIF binding to the candidate cis-elements of specific miRNAs under hypoxia was confirmed by Chromatin immunoprecipitation coupled with qPCR. Role analysis of a subset of upregulated HRMs identified linkage to reported inhibition of differentiation while a downregulated subset of HRMs had a putative role in the promotion of differentiation. MiRNA-target prediction correlation with published hypoxic hESC and hMSC gene expression profiles revealed HRM target genes enriched in the cytokine:cytokine receptor, HIF signalling and pathways in cancer. Overall, our study reveals, novel and distinct hypoxia-driven miRNA signatures in hESCs and hMSCs with the potential for application in optimised culture and differentiation models for both therapeutic application and improved understanding of stem cell biology

May Measurement Month 2017: an analysis of blood pressure screening results from the United Arab Emirates-Northern Africa and Middle East

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. United Arab Emirates has a young population, but cardiovascular disease (CVD) is the commonest cause of death (40%). Myocardial infarction and stroke occurs at least a decade earlier than in western countries. Previous screening in our young population showed that 85% of the population had at least one CVD risk factor and about 62% of them were unaware of it. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. Screening was held in 23 sites such as mosques, sports, and men's/ladies' clubs, airports, parks, shopping malls, work places as well as their residences, and in the public areas of hospitals or outpatient clinics. A total of 6193 individuals were screened during MMM17. The mean age was 39.2 ± 13.1 years. After multiple imputation, 1867 (30.2%) had hypertension. Of individuals not receiving anti-hypertensive medication, 813 (15.8%) were hypertensive. Of 1054 individuals receiving anti-hypertensive medication, 427 (40.6%) had uncontrolled BP. MMM17 was a useful screening model as it makes BP measurement easily accessible. Eight hundred and thirteen (16%) possibly new hypertensives were uncovered and 427(40.6%) of those on treatment for hypertension were found to be uncontrolled. These results suggest that opportunistic screening can identify significant numbers with raised BP

Low-friction self-centering droplet propulsion and transport using a Leidenfrost herringbone-ratchet structure

A fundamental limitation to the ability to transport sessile droplets is frictional forces arising from surface adhesion. This can be overcome by using the Leidenfrost effect on a heated substrate to levitate the droplet on a cushion of vapor. By structuring the surface under the droplet, the flow of vapor below the droplet can be controlled and this can be used to induce preferential droplet propulsion in a particular direction. However, while propulsion can be induced, the dramatic reduction in frictional forces leads to instability and it is difficult to control droplet motion when transporting droplets along a defined path. Here, we present a self-propulsion and self-centering concept using the principles of negative feedback to enable a droplet to be transported along a defined path. In our implementation, we use a combined herringbone and ratchet design, which provides the ability to control droplet position without compromising on speed. This intrinsic self-centering and correction via negative feedback offers the potential to design paths and tracks for droplets to follow, without the need for walls

Maximizing Happiness in Graphs of Bounded Clique-Width

Clique-width is one of the most important parameters that describes structural complexity of a graph. Probably, only treewidth is more studied graph width parameter. In this paper we study how clique-width influences the complexity of the Maximum Happy Vertices (MHV) and Maximum Happy Edges (MHE) problems. We answer a question of Choudhari and Reddy '18 about parameterization by the distance to threshold graphs by showing that MHE is NP-complete on threshold graphs. Hence, it is not even in XP when parameterized by clique-width, since threshold graphs have clique-width at most two. As a complement for this result we provide a $n^{\mathcal{O}(\ell \cdot \operatorname{cw})}$ algorithm for MHE, where $\ell$ is the number of colors and $\operatorname{cw}$ is the clique-width of the input graph. We also construct an FPT algorithm for MHV with running time $\mathcal{O}^*((\ell+1)^{\mathcal{O}(\operatorname{cw})})$, where $\ell$ is the number of colors in the input. Additionally, we show $\mathcal{O}(\ell n^2)$ algorithm for MHV on interval graphs.Comment: Accepted to LATIN 202

Phenytoin versus Leviteracetam for seizure prophylaxis after brain injury - A meta analysis

Background: Current standard therapy for seizure prophylaxis in Neuro-surgical patients involves the use of Phenytoin (PHY). However, a new drug Levetiracetam (LEV) is emerging as an alternate treatment choice. We aimed to conduct a meta-analysis to compare these two drugs in patients with brain injury.Methods: An electronic search was performed in using Pubmed, Embase, and CENTRAL. We included studies that compared the use of LEV vs. PHY for seizure prophylaxis for brain injured patients (Traumatic brain injury, intracranial hemorrhage, intracranial neoplasms, and craniotomy). Data of all eligible studies was extracted on to a standardized abstraction sheet. Data about baseline population characteristics, type of intervention, study design and outcome was extracted. Our primary outcome was seizures.Results: The literature search identified 2489 unduplicated papers. Of these 2456 papers were excluded by reading the abstracts and titles. Another 25 papers were excluded after reading their complete text. We selected 8 papers which comprised of 2 RCTs and 6 observational studies. The pooled estimate\u27s Odds Ratio 1.12 (95% CI = 0.34, 3.64) demonstrated no superiority of either drug at preventing the occurrence of early seizures. In a subset analysis of studies in which follow up for seizures lasted either 3 or 7 days, the effect estimate remained insignificant with an odds ratio of 0.96 (95% CI = 0.34, 2.76). Similarly, 2 trials reporting seizure incidence at 6 months also had insignificant pooled results while comparing drug efficacy. The pooled odds ratio was 0.96 (95% CI = 0.24, 3.79).Conclusions: Levetiracetam and Phenytoin demonstrate equal efficacy in seizure prevention after brain injury. However, very few randomized controlled trials (RCTs) on the subject were found. Further evidence through a high quality RCT is highly recommended

Post-neonatal Mortality, Morbidity, and Developmental Outcome after Ultrasound-Dated Preterm Birth in Rural Malawi: A Community-Based Cohort Study

Using data collected as a follow-up to a randomized trial, Melissa Gladstone and colleagues show that during the first two years of life, infants born preterm in southern Malawi are disadvantaged in terms of mortality, growth, and development

Combination therapy in hypertension: An update

Meticulous control of blood pressure is required in patients with hypertension to produce the maximum reduction in clinical cardiovascular end points, especially in patients with comorbidities like diabetes mellitus where more aggressive blood pressure lowering might be beneficial. Recent clinical trials suggest that the approach of using monotherapy for the control of hypertension is not likely to be successful in most patients. Combination therapy may be theoretically favored by the fact that multiple factors contribute to hypertension, and achieving control of blood pressure with single agent acting through one particular mechanism may not be possible. Regimens can either be fixed dose combinations or drugs added sequentially one after other. Combining the drugs makes them available in a convenient dosing format, lower the dose of individual component, thus, reducing the side effects and improving compliance. Classes of antihypertensive agents which have been commonly used are angiotensin receptor blockers, thiazide diuretics, beta and alpha blockers, calcium antagonists and angiotensin-converting enzyme inhibitors. Thiazide diuretics and calcium channel blockers are effective, as well as combinations that include renin-angiotensin-aldosterone system blockers, in reducing BP. The majority of currently available fixed-dose combinations are diuretic-based. Combinations may be individualized according to the presence of comorbidities like diabetes mellitus, chronic renal failure, heart failure, thyroid disorders and for special population groups like elderly and pregnant females

Predictors of dizziness in older persons: a 10-year prospective cohort study in the community

BACKGROUND: The current diagnosis-oriented approach of dizziness does not suit older patients. Often, it is difficult to identify a single underlying cause, and when a diagnosis is made, therapeutic options may be limited. Identification of predictors of dizziness may provide new leads for the management of dizziness in older patients. The aim of the present study was to investigate long-term predictors of regular dizziness in older persons. METHODS: Population-based cohort study of 1,379 community-dwelling participants, aged ≥60 years, from the Longitudinal Aging Study Amsterdam (LASA). Regular dizziness was ascertained during face-to-face medical interviews during 7- and 10-year follow-up. We investigated 26 predictors at baseline from six domains: socio-demographic, medical history, medication, psychological, sensory, and balance/gait. We performed multivariate logistic regression analyses with presence of regular dizziness at 7- and 10-year follow-up as dependent variables. We assessed the performance of the models by calculating calibration and discrimination. RESULTS: Predictors of regular dizziness at 7-year follow-up were living alone, history of dizziness, history of osteo/rheumatoid arthritis, use of nitrates, presence of anxiety or depression, impaired vision, and impaired function of lower extremities. Predictors of regular dizziness at 10-year follow-up were history of dizziness and impaired function of lower extremities. Both models showed good calibration (Hosmer-Lemeshow P value of 0.36 and 0.31, respectively) and acceptable discrimination (adjusted AUC after bootstrapping of 0.77 and 0.71). CONCLUSIONS: Dizziness in older age was predicted by multiple factors. A multifactorial approach, targeting potentially modifiable predictors (e.g., physical exercise for impaired function of lower extremities), may add to the current diagnosis-oriented approach. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2318-14-133) contains supplementary material, which is available to authorized users