Cyclic strain upregulates VEGF and attenuates proliferation of vascular smooth muscle cells

OBJECTIVE:Vascular smooth muscle cell (VSMC) hypertrophy and proliferation occur in response to strain-induced local and systemic inflammatory cytokines and growth factors which may contribute to hypertension, atherosclerosis, and restenosis. We hypothesize VSMC strain, modeling normotensive arterial pressure waveforms in vitro, results in attenuated proliferative and increased hypertrophic responses 48 hrs post-strain.METHODS:Using Flexcell Bioflex Systems we determined the morphological, hyperplastic and hypertrophic responses of non-strained and biomechanically strained cultured rat A7R5 VSMC. We measured secretion of nitric oxide, key cytokine/growth factors and intracellular mediators involved in VSMC proliferation via fluorescence spectroscopy and protein microarrays. We also investigated the potential roles of VEGF on VSMC strain-induced proliferation.RESULTS:Protein microarrays revealed significant increases in VEGF secretion in response to 18 hours mechanical strain, a result that ELISA data corroborated. Apoptosis-inducing nitric oxide (NO) levels also increased 43% 48 hrs post-strain. Non-strained cells incubated with exogenous VEGF did not reproduce the antimitogenic effect. However, anti-VEGF reversed the antimitogenic effect of mechanical strain. Antibody microarrays of strained VSMC lysates revealed MEK1, MEK2, phospo-MEK1T385, T291, T298, phospho-Erk1/2T202+Y204/T185+T187, and PKC isoforms expression were universally increased, suggesting a proliferative/inflammatory signaling state. Conversely, VSMC strain decreased expression levels of Cdk1, Cdk2, Cdk4, and Cdk6 by 25-50% suggesting a partially inhibited proliferative signaling cascade.CONCLUSIONS:Subjecting VSMC to cyclic biomechanical strain in vitro promotes cell hypertrophy while attenuating cellular proliferation. We also report an upregulation of MEK and ERK activation suggestive of a proliferative phenotype. Hhowever, the proliferative response appears to be aborogated by enhanced antimitogenic cytokine VEGF, NO secretion and downregulation of Cdk expression. Although exogenous VEGF alone is not sufficient to promote the quiescent VSMC phenotype, we provide evidence suggesting that strain is a necessary component to induce VSMC response to the antimitogenic effects of VEGF. Taken together these data indicate that VEGF plays a critical role in mechanical strain-induced VSMC proliferation and vessel wall remodeling. Whether VEGF and/or NO inhibit signaling distal to Erk 1/2 is currently under investigation.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Family-centred music therapy with preterm infants and their parents in the Neonatal Intensive Care Unit (NICU) in Colombia – A mixed-methods study

This article reports a mixed-methods study of Music Therapy (MT) with preterm infants and their parents in a neonatal intensive care unit (NICU) in Colombia. The aim was to find out whether live MT during kangaroo care had an effect on the physiological outcomes of the neonates and would help parents to decrease their anxiety levels and improve parent–infant bonding. The participants were 36 medically stable neonates born between the 28th and 34th week of gestation and their parents. The quantitative data collection included heart rate, oxygen saturation, weight gain, length of hospitalization and re-hospitalization rate. The assessment measures for anxiety and bonding were the State-Trait Anxiety Inventory (STAI) and the Mother-to-Infant-Bonding Scale (MIBS). Thematic analysis was used to analyse the qualitative data collected with semi-structured interviews and questionnaires. The quantitative results showed statistically significant improvements in maternal state-anxiety (p = .007) and in the babies weight gain per day during the intervention period (p = .036). Positive trends were found regarding the babies’ length of hospitalization and re-hospitalization rate. Both parents improved their scores with the MIBS, but this was not statistically significant. The qualitative analysis showed that MT was important for parental well-being, for bonding and for fostering the development of the neonates. Interacting musically with their babies helped parents to experience feelings of connectedness and to distract themselves from their difficulties and from the noisy hospital environment

Sensitivity and Specificity of Multiple Kato-Katz Thick Smears and a Circulating Cathodic Antigen Test for Schistosoma mansoni Diagnosis Pre- and Post-repeated-Praziquantel Treatment

Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This ‘gold standard’ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings

Does mass drug administration for the integrated treatment of neglected tropical diseases really work? Assessing evidence for the control of schistosomiasis and soil-transmitted helminths in Uganda

This paper was one of four papers commissioned to review the role of social sciences in NTD control by TDR, the Special Programme for Research and Training on Tropical Diseases, which is executed by WHO and co-sponsored by UNICEF, UNDP, the World Bank and WHO.This article has been made available through the Brunel Open Access Publishing Fund.Background: Less is known about mass drug administration [MDA] for neglected tropical diseases [NTDs] than is suggested by those so vigorously promoting expansion of the approach. This paper fills an important gap: it draws upon local level research to examine the roll out of treatment for two NTDs, schistosomiasis and soil-transmitted helminths, in Uganda. Methods: Ethnographic research was undertaken over a period of four years between 2005-2009 in north-west and south-east Uganda. In addition to participant observation, survey data recording self-reported take-up of drugs for schistosomiasis, soil-transmitted helminths and, where relevant, lymphatic filariasis and onchocerciasis was collected from a random sample of at least 10% of households at study locations. Data recording the take-up of drugs in Ministry of Health registers for NTDs were analysed in the light of these ethnographic and social survey data. Results: The comparative analysis of the take-up of drugs among adults revealed that although most long term residents have been offered treatment at least once since 2004, the actual take up of drugs for schistosomiasis and soil-transmitted helminths varies considerably from one district to another and often also within districts. The specific reasons why MDA succeeds in some locations and falters in others relates to local dynamics. Issues such as population movement across borders, changing food supply, relations between drug distributors and targeted groups, rumours and conspiracy theories about the 'real' purpose of treatment, subjective experiences of side effects from treatment, alternative understandings of affliction, responses to social control measures and historical experiences of public health control measures, can all make a huge difference. The paper highlights the need to adapt MDA to local circumstances. It also points to specific generalisable issues, notably with respect to health education, drug distribution and more effective use of existing public health legislation. Conclusion: While it has been an achievement to have offered free drugs to so many adults, current standard practices of monitoring, evaluation and delivery of MDA for NTDs are inconsistent and inadequate. Efforts to integrate programmes have exacerbated the difficulties. Improved assessment of what is really happening on the ground will be an essential step in achieving long-term overall reduction of the NTD burden for impoverished communities.This article is available through the Brunel Open Access Publishing Fund

‘Do i care?’ young adults' recalled experiences of early adolescent overweight and obesity: a qualitative study

<p>Objective: Individual behaviour change to reduce obesity requires awareness of, and concern about, weight. This paper therefore describes how young adults, known to have been overweight or obese during early adolescence, recalled early adolescent weight-related awareness and concerns. Associations between recalled concerns and weight-, health- and peer-related survey responses collected during adolescence are also examined.</p> <p>Design: Qualitative semi-structured interviews with young adults; data compared with responses to self-report questionnaires obtained in adolescence.</p> <p>Participants: A total of 35 participants, purposively sub-sampled at age 24 from a longitudinal study of a school year cohort, previously surveyed at ages 11, 13 and 15. Physical measures during previous surveys allowed identification of participants with a body mass index (BMI) indicative of overweight or obesity (based on British 1990 growth reference) during early adolescence. Overall, 26 had been obese, of whom 11 had BMI99.6th centile, whereas 9 had been overweight (BMI=95th–97.9th centile).</p> <p>Measures: Qualitative interview responses describing teenage life, with prompts for school-, social- and health-related concerns. Early adolescent self-report questionnaire data on weight-worries, self-esteem, friends and victimisation (closed questions).</p> <p>Results: Most, but not all recalled having been aware of their overweight. None referred to themselves as having been obese. None recalled weight-related health worries. Recollection of early adolescent obesity varied from major concerns impacting on much of an individual's life to almost no concern, with little relation to actual severity of overweight. Recalled concerns were not clearly patterned by gender, but young adult males recalling concerns had previously reported more worries about weight, lower self-esteem, fewer friends and more victimisation in early adolescence; no such pattern was seen among females. Conclusion: The popular image of the unhappy overweight teenager was not borne out. Many obese adolescents, although well aware of their overweight recalled neither major dissatisfaction nor concern. Weight-reduction behaviours are unlikely in such circumstances.</p&gt

SEIS: Insight's Seismic Experiment for Internal Structure of Mars.

By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars' surface the SEIS (Seismic Experiment for Internal Structure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01 Hz to 50 Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1 sps and a continuous compound VBB/SP vertical axis at 10 sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking's Mars seismic monitoring by a factor of ∼ 2500 at 1 Hz and ∼ 200 000 at 0.1 Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars' surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of M w ∼ 3 at 40 ∘ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution.Electronic supplementary materialThe online version of this article (10.1007/s11214-018-0574-6) contains supplementary material, which is available to authorized users

A geophysical study of Mesquite Valley: Nevada-California border

This paper reports the results of a geophysical investigation of a sedimentary basin, Mesquite Valley, and its surrounding area in the Basin and Range province of the western United States. Mesquite Valley is located about 40 km south-southwest of Las Vegas, Nevada, and straddles the border between Nevada and California (Figure 1). It is surrounded on three sides by mountains in which Paleozoic sedimentary rocks and Precambrian granites and gneisses crop out (Figure 1) [Burchfiel et al., 1974; Durchfiel and Davis, 1971; Hewett, 1956]. Unlike most basins in the Basin and Range province, however, there are no clearly active, range-bounding normal faults, and, in general, the surrounding topography is more subdued than in the regions farther west or north

A Broadly Applicable Strategy for Entry into Homogeneous Nickel(0) Catalysts from Air-Stable Nickel(II) Complexes

A series of air-stable nickel complexes of the form L[subscript 2]Ni(aryl) X (L = monodentate phosphine, X = Cl, Br) and LNi(aryl)X (L = bis-phosphine) have been synthesized and are presented as a library of precatalysts suitable for a wide variety of nickel-catalyzed transformations. These complexes are easily synthesized from low-cost NiCl[subscript 2]·6H[subscript 2]O or NiBr[subscript 2]·3H[subscript 2]O and the desired ligand followed by addition of 1 equiv of Grignard reagent. A selection of these complexes were characterized by single-crystal X-ray diffraction, and an analysis of their structural features is provided. A case study of their use as precatalysts for the nickel-catalyzed carbonyl-ene reaction is presented, showing superior reactivity in comparison to reactions using Ni(cod)[subscript 2]. Furthermore, as the precatalysts are all stable to air, no glovebox or inert-atmosphere techniques are required to make use of these complexes for nickel-catalyzed reactions.National Institute of General Medical Sciences (U.S.) (GM63755)National Science Foundation (U.S.). Graduate Research Fellowshi