All-optical mapping of barrel cortex circuits based on simultaneous voltage-sensitive dye imaging and channelrhodopsin-mediated photostimulation

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Neurophotonics 2 (2015): 021013, doi:10.1117/1.NPh.2.2.021013.We describe an experimental approach that uses light to both control and detect neuronal activity in mouse barrel cortex slices: blue light patterned by a digital micromirror array system allowed us to photostimulate specific layers and columns, while a red-shifted voltage-sensitive dye was used to map out large-scale circuit activity. We demonstrate that such all-optical mapping can interrogate various circuits in somatosensory cortex by sequentially activating different layers and columns. Further, mapping in slices from whisker-deprived mice demonstrated that chronic sensory deprivation did not significantly alter feedforward inhibition driven by layer 5 pyramidal neurons. Further development of voltage-sensitive optical probes should allow this all-optical mapping approach to become an important and high-throughput tool for mapping circuit interactions in the brain.This work was supported by the World Class Institute (WCI) program of the National Research Foundation of Korea (NRF) funded by Ministry of Education, Science and Technology of Korea (MEST) (NRF) Grant No. WCI 2009-003 and by the Competitive Research Programme (CRP) of NRF (Singapore) Grant No. NRF 2008 NRF-CRP 002-082

Stem cell-based approaches in cardiac tissue engineering: controlling the microenvironment for autologous cells

Cardiovascular disease is one of the leading causes of mortality worldwide. Cardiac tissue engineering strategies focusing on biomaterial scaffolds incorporating cells and growth factors are emerging as highly promising for cardiac repair and regeneration. The use of stem cells within cardiac microengineered tissue constructs present an inherent ability to differentiate into cell types of the human heart. Stem cells derived from various tissues including bone marrow, dental pulp, adipose tissue and umbilical cord can be used for this purpose. Approaches ranging from stem cell injections, stem cell spheroids, cell encapsulation in a suitable hydrogel, use of prefabricated scaffold and bioprinting technology are at the forefront in the field of cardiac tissue engineering. The stem cell microenvironment plays a key role in the maintenance of stemness and/or differentiation into cardiac specific lineages. This review provides a detailed overview of the recent advances in microengineering of autologous stem cell-based tissue engineering platforms for the repair of damaged cardiac tissue. A particular emphasis is given to the roles played by the extracellular matrix (ECM) in regulating the physiological response of stem cells within cardiac tissue engineering platforms

Bioflavonoid luteolin prevents sFlt-1 release via HIF-1α inhibition in cultured human placenta

Preeclampsia (PE) is a serious hypertensive complication of pregnancy and is a leading cause of maternal death and major contributor to maternal and perinatal morbidity, including establishment of long-term complications. The continued prevalence of PE stresses the need for identification of novel treatments which can target prohypertensive factors implicated in the disease pathophysiology, such as soluble fms-like tyrosine kinase 1 (sFlt-1). We set out to identify novel compounds to reduce placental sFlt-1 and determine whether this occurs via hypoxia-inducible factor (HIF)-1α inhibition. We utilized a commercially available library of natural compounds to assess their ability to reduce sFlt-1 release from primary human placental cytotrophoblast cells (CTBs). Human placental explants from normotensive (NT) and preeclamptic (PE) pregnancies were treated with varying concentrations of luteolin. Protein and mRNA expression of sFlt-1 and upstream mediators were evaluated using ELISA, western blot, and real-time PCR. Of the natural compounds examined, luteolin showed the most potent inhibition of sFlt-1 release, with >95% reduction compared to vehicle-treated. Luteolin significantly inhibited sFlt-1 in cultured placental explants compared to vehicle-treated in a dose- and time-dependent manner. Additionally, significant decreases in HIF-1α expression were observed in luteolin-treated explants, suggesting a mechanism for sFlt-1 downregulation. The ability of luteolin to inhibit HIF-1α may be mediated through the Akt pathway, as inhibitors to Akt and its upstream regulator phosphatidylinositol-3 kinase (PI3K) resulted in significant HIF-1α reduction. Luteolin reduces anti-angiogenic sFlt-1 through inhibition of HIF-1α, making it a novel candidate for the treatment of PE

Increased complications of COVID-19 in people with cardiovascular disease: Role of the renin-angiotensin-aldosterone system (RAAS) dysregulation

The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID?19), has had a dramatic negative impact on public health and economies worldwide. Recent studies on COVID-19 complications and mortality rates suggest that there is a higher prevalence in cardiovascular diseases (CVD) patients. Past investigations on the associations between pre-existing CVDs and susceptibility to coronavirus infections including SARS-CoV and the Middle East Respiratory Syndrome coronavirus (MERS-CoV), have demonstrated similar results. However, the underlying mechanisms are poorly understood. This has impeded adequate risk stratification and treatment strategies for CVD patients with SARS-CoV-2 infections. Generally, dysregulation of the expression of angiotensin?converting enzyme (ACE) and the counter regulator, angiotensin?converting enzyme 2 (ACE2) is a hallmark of cardiovascular risk and CVD. ACE2 is the main host receptor for SARS-CoV-2. Although further studies are required, dysfunction of ACE2 after virus binding and dysregulation of the renin-angiotensin-aldosterone system (RAAS) signaling may worsen the outcomes of people affected by COVID-19 and with preexisting CVD. Here, we review the current knowledge and outline the gaps related to the relationship between CVD and COVID-19 with a focus on the RAAS. Improved understanding of the mechanisms regulating viral entry and the role of RAAS may direct future research with the potential to improve the prevention and management of COVID-19.Scopu

Lack of benefits for prevention of cardiovascular disease with aspirin therapy in type 2 diabetic patients - a longitudinal observational study

<p>Abstract</p> <p>Background</p> <p>The risk-benefit ratio of aspirin therapy in prevention of cardiovascular disease (CVD) remains contentious, especially in type 2 diabetes. This study examined the benefit and harm of low-dose aspirin (daily dose < 300 mg) in patients with type 2 diabetes.</p> <p>Methods</p> <p>This is a longitudinal observational study with primary and secondary prevention cohorts based on history of CVD at enrolment. We compared the occurrence of primary composite (non-fatal myocardial infarction or stroke and vascular death) and secondary endpoints (upper GI bleeding and haemorrhagic stroke) between aspirin users and non-users between January 1995 and July 2005.</p> <p>Results</p> <p>Of the 6,454 patients (mean follow-up: median [IQR]: 4.7 [4.4] years), usage of aspirin was 18% (n = 1,034) in the primary prevention cohort (n = 5731) and 81% (n = 585) in the secondary prevention cohort (n = 723). After adjustment for covariates, in the primary prevention cohort, aspirin use was associated with a hazard-ratio of 2.07 (95% CI: 1.66, 2.59, p < 0.001) for primary endpoint. There was no difference in CVD event rate in the secondary prevention cohort. Overall, aspirin use was associated with a hazard-ratio of 2.2 (1.53, 3.15, p < 0.001) of GI bleeding and 1.71 (1.00, 2.95, p = 0.051) of haemorrhagic stroke. The absolute risk of aspirin-related GI bleeding was 10.7 events per 1,000 person-years of treatment.</p> <p>Conclusion</p> <p>In Chinese type 2 diabetic patients, low dose aspirin was associated with a paradoxical increase in CVD risk in primary prevention and did not confer benefits in secondary prevention. In addition, the risk of GI bleeding in aspirin users was rather high.</p

A clinical prediction model for hospitalized COPD exacerbations based on “treatable traits”

10.2147/COPD.S194922International Journal of COPD14719-72

On the correspondence between surface UV observations and TOMS determinations of surface UV: a potential method for quality evaluating world surface UV observations

A comparison of erythemally weighted surface UV irradiance observations with similar NASA TOMS surface UV determinations is described. Comparisons are made for two observation periods: the Robertson-Berger (R-B) meter period from 1974 to the late 1980s and the current period from 1996 to the present when more sophisticated UVB-1 instruments were used. The more primitive R-B meter observations that comprised the fi rst U.S. UV network are seen to drift downward with respect to those of the TOMS. While the UVB-1 observations did not appear to drift, a substantial bias is noted to exist between the TOMS and the UVB-1 stations collecting observations; the TOMS estimations tend to be higher. A portion of the bias may be attributed to errors in calibration, total ozone, and cosine response of the surface instrumentation. Unaccounted aerosol effects, although not considered to be large in the TOMS estimations, present another source of error. Comparisons are fi rst done for all sky conditions and then for clear sky conditions. The biases typically agree for all sky conditions within the uncertainties of the surface instruments' calibrations, liberally defi ned as ± 5%, implying that the TOMS cloud correction scheme performs reasonably well. Snow cover severely impacts the TOMS observations, giving considerably higher estimations. The biases for clear sky conditions ranged from 15% to 19% with no obvious drifts between the satellite and surface observations. The variation in the biases among stations is within the calibration uncertainties of the instruments, but the absolute bias is unexpectedly large. The standard deviations of the clear sky comparisons among all stations are steady at 4.8% ± 0.7%. A plot of the TOMS/UVB-1 ratio versus TOMS cloud refl ectivity observations is noisy, but qualitatively suggestive of a possible slight increase (~ 5% or greater) over the range of clear to overcast skies. The results from these comparisons is believed to be relevant to a WMO goal of uniformly assuring the quality of UV observations made by networks in many countries. The results for clear sky comparisons suggest that a satellite observing system such as TOMS, which provides global coverage daily, might partially serve as a fi rst-order check to quality assure UV observations being made by networks worldwide. Future research should concentrate on determining the causes of the large differences seen between the UVB-1 and TOMS and the range of uncertainties, using a larger array of stations

Estimated marine fish landings (in tonnes)in India during 2002 and 2003

Estimated marine fishing landing in India during 2002 and 2003 is 2.59 and 2.58 millon tonnes respectively. Gear wise landing were also estimated during this period

Mechanical thrombectomy: can it be safely delivered out of hours in the UK?

BACKGROUND: Mechanical thrombectomy was approved by NICE as a treatment for stroke in 2016. However, most of the evidence is from studies conducted during working hours. Only few centres in the UK perform thrombectomies out-of-hours. The Royal Stoke University Hospital (RSUH) has offered thrombectomies over 24 h (24/7) since 2010. The aim of this service review is to compare the outcomes for patients treated in regular working hours to those treated outside normal working hours within this unit. METHODS: This retrospective service analysis includes all patients treated with mechanical thrombectomy at RSUH since the start of the service in January 2010 to June 2019. Data on key demographics, timings, procedural complications, and long-term outcomes including death and disability at 90 days were collected. In-hours was defined as the time between 8:00-17:00 h, Monday to Friday; out-of-hours was defined as any time outside this period. RESULTS: In total, 516 mechanical thrombectomies were performed in this time period; data were available on 501 of these. Successful recanalization (TICI 2b/3) was achieved in 86% of patients. By 90 days 96 (19%) had died and 234 (47%) were functionally independent (modified Rankin Scale score ≤ 2). 211 (42%) of the procedures were performed in-hours and 290 (58%) out-of-hours. Door-to-CT and door-to-groin times were significantly longer out-of-hours than in-hours, but thrombectomy duration was significantly shorter. There were no significant differences in complications and short- and long-term outcomes. CONCLUSION: Mechanical thrombectomy was delivered safely and effectively 24/7 in this UK hospital, with no difference in clinical outcomes