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Heritability of 596 lipid species and genetic correlation with cardiovascular traits in the Busselton Family Heart Study

Gemma Cadby
Apr 1, 2020; 61:537-545
Patient-Oriented and Epidemiological Research




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Quantitative proteomics of human heart samples collected in vivo reveal the remodeled protein landscape of dilated left atrium without atrial fibrillation [Research]

Genetic and genomic research has greatly advanced our understanding of heart disease. Yet, comprehensive, in-depth, quantitative maps of protein expression in hearts of living humans are still lacking. Using samples obtained during valve replacement surgery in patients with mitral valve prolapse (MVP), we set out to define inter-chamber differences, the intersect of proteomic data with genetic or genomic datasets, and the impact of left atrial dilation on the proteome of patients with no history of atrial fibrillation (AF).  We collected biopsies from right atria (RA), left atria (LA) and left ventricle (LV) of seven male patients with mitral valve regurgitation with dilated LA but no history of AF. Biopsy samples were analyzed by high-resolution mass spectrometry (MS), where peptides were pre-fractionated by reverse phase high-pressure liquid chromatography prior to MS measurement on a Q-Exactive-HF Orbitrap instrument. We identified 7,314 proteins based on 130,728 peptides. Results were confirmed in an independent set of biopsies collected from three additional individuals. Comparative analysis against data from post-mortem samples showed enhanced quantitative power and confidence level in samples collected from living hearts. Our analysis, combined with data from genome wide association studies suggested candidate gene associations to MVP, identified higher abundance in ventricle for proteins associated with cardiomyopathies and revealed the dilated LA proteome, demonstrating differential representation of molecules previously associated with AF, in non-AF hearts. This is the largest dataset of cardiac protein expression from human samples collected in vivo. It provides a comprehensive resource that allows insight into molecular fingerprints of MVP and facilitates novel inferences between genomic data and disease mechanisms. We propose that over-representation of proteins in ventricle is consequent not to redundancy but to functional need, and conclude that changes in abundance of proteins known to associate with AF are not sufficient for arrhythmogenesis.




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Heritability of 596 lipid species and genetic correlation with cardiovascular traits in the Busselton Family Heart Study [Patient-Oriented and Epidemiological Research]

CVD is the leading cause of death worldwide, and genetic investigations into the human lipidome may provide insight into CVD risk. The aim of this study was to estimate the heritability of circulating lipid species and their genetic correlation with CVD traits. Targeted lipidomic profiling was performed on 4,492 participants from the Busselton Family Heart Study to quantify the major fatty acids of 596 lipid species from 33 classes. We estimated narrow-sense heritabilities of lipid species/classes and their genetic correlations with eight CVD traits: BMI, HDL-C, LDL-C, triglycerides, total cholesterol, waist-hip ratio, systolic blood pressure, and diastolic blood pressure. We report heritabilities and genetic correlations of new lipid species/subclasses, including acylcarnitine (AC), ubiquinone, sulfatide, and oxidized cholesteryl esters. Over 99% of lipid species were significantly heritable (h2: 0.06–0.50) and all lipid classes were significantly heritable (h2: 0.14–0.50). The monohexosylceramide and AC classes had the highest median heritabilities (h2 = 0.43). The largest genetic correlation was between clinical triglycerides and total diacylglycerol (rg = 0.88). We observed novel positive genetic correlations between clinical triglycerides and phosphatidylglycerol species (rg: 0.64–0.82), and HDL-C and alkenylphosphatidylcholine species (rg: 0.45–0.74). Overall, 51% of the 4,768 lipid species-CVD trait genetic correlations were statistically significant after correction for multiple comparisons. This is the largest lipidomic study to address the heritability of lipids and their genetic correlation with CVD traits. Future work includes identifying putative causal genetic variants for lipid species and CVD using genome-wide SNP and whole-genome sequencing data.




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Protecting the Heart in Obesity: Role of ACE2 and Its Partners

Rhian M. Touyz
Jan 1, 2016; 65:19-21
Commentaries




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Isha Blender opens up about loss of her son - Shares the ­heartbreaking tale in latest track ‘I Wish’

REGGAE ARTISTE Isha Blender is still coming to terms with the loss of her son, Josiah, on January 5, a mere two days after she celebrated her birthday. The daughter of legendary crooner Everton Blender said the death of a child can be one of the...




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NCEP-Defined Metabolic Syndrome, Diabetes, and Prevalence of Coronary Heart Disease Among NHANES III Participants Age 50 Years and Older

Charles M. Alexander
May 1, 2003; 52:1210-1214
Complications




heart

Heartbreak again ... Unhappy landing for ship workers, other Jamaicans

It was not the landing the Jamaicans who arrived at Kingston’s Norman Manley International Airport on Wednesday evening would want again. The 43 Jamaican ship workers of the Marella Discovery 2 were among the 115 people aboard the TUI charter flight that touched down amid the Kingston breeze and evening sunset.




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Multimodality Imaging of Inflammation and Ventricular Remodeling in Pressure-Overload Heart Failure

Inflammation contributes to ventricular remodeling after myocardial ischemia, but its role in nonischemic heart failure is poorly understood. Local tissue inflammation is difficult to assess serially during pathogenesis. Although 18F-FDG accumulates in inflammatory leukocytes and thus may identify inflammation in the myocardial microenvironment, it remains unclear whether this imaging technique can isolate diffuse leukocytes in pressure-overload heart failure. We aimed to evaluate whether inflammation with 18F-FDG can be serially imaged in the early stages of pressure-overload–induced heart failure and to compare the time course with functional impairment assessed by cardiac MRI. Methods: C57Bl6/N mice underwent transverse aortic constriction (TAC) (n = 22), sham surgery (n = 12), or coronary ligation as an inflammation-positive control (n = 5). MRI assessed ventricular geometry and contractile function at 2 and 8 d after TAC. Immunostaining identified the extent of inflammatory leukocyte infiltration early in pressure overload. 18F-FDG PET scans were acquired at 3 and 7 d after TAC, under ketamine-xylazine anesthesia to suppress cardiomyocyte glucose uptake. Results: Pressure overload evoked rapid left ventricular dilation compared with sham (end-systolic volume, day 2: 40.6 ± 10.2 μL vs. 23.8 ± 1.7 μL, P < 0.001). Contractile function was similarly impaired (ejection fraction, day 2: 40.9% ± 9.7% vs. 59.2% ± 4.4%, P < 0.001). The severity of contractile impairment was proportional to histology-defined myocardial macrophage density on day 8 (r = –0.669, P = 0.010). PET imaging identified significantly higher left ventricular 18F-FDG accumulation in TAC mice than in sham mice on day 3 (10.5 ± 4.1 percentage injected dose [%ID]/g vs. 3.8 ± 0.9 %ID/g, P < 0.001) and on day 7 (7.8 ± 3.7 %ID/g vs. 3.0 ± 0.8 %ID/g, P = 0.006), though the efficiency of cardiomyocyte suppression was variable among TAC mice. The 18F-FDG signal correlated with ejection fraction (r = –0.75, P = 0.01) and ventricular volume (r = 0.75, P < 0.01). Western immunoblotting demonstrated a 60% elevation of myocardial glucose transporter 4 expression in the left ventricle at 8 d after TAC, indicating altered glucose metabolism. Conclusion: TAC induces rapid changes in left ventricular geometry and contractile function, with a parallel modest infiltration of inflammatory macrophages. Metabolic remodeling overshadows inflammatory leukocyte signal using 18F-FDG PET imaging. More selective inflammatory tracers are requisite to identify the diffuse local inflammation in pressure overload.




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Britain Must Balance a Transatlantic Heart With a European Head

19 December 2019

Robin Niblett

Director and Chief Executive, Chatham House
Returning from an EU-rooted foreign and economic policy to one which is more international in outlook will be difficult, take time, and be more costly than the new UK government currently envisages.

GettyImages-1189074470.jpg

Boris Johnson chairs the first cabinet meeting after winning a majority of 80 seats in the 2019 UK general election. Photo by Matt Dunham – WPA Pool/Getty Images.

The convincing general election win for the Conservative Party and Boris Johnson opens a new chapter in British history. On 31 January 2020, Britain will withdraw from the EU and return to its historical position as a separate European power.

Recognising the strategic significance of this change, the Queen’s speech opening the new parliament stated that 'the government will undertake the deepest review of Britain's security, defence, and foreign policy since the end of the Cold War'. But in what context?

Prime Minister Boris Johnson and other Brexit supporters have yearned for Britain to return to its exceptional trajectory. In their view, Britain can once again become a trading nation - more global in outlook and ambition than its European neighbours, freed from the shackles of an ageing and fractured European continent and its deadening regulatory hand.

This imagery makes good copy. But the 21st century does not offer Britain the same opportunities as did the 18th, 19th or early 20th centuries. This is a different world, and Britain’s position in it needs to be crafted with a sharp eye to what is possible.

Geopolitics undergoing wrenching change

This is not declinism. The UK remains an economically strong and politically influential country by relative global standards – it is currently the fifth or sixth largest economy in the world, and the second largest donor of official development assistance. It has ubiquitous cultural brands from fashion and music to the royal family, and an eminent diplomatic and security position at the heart of all of the world’s major international institutions and alliances, from NATO and the UN security council to the IMF, G7, G20 and Commonwealth. 

But Britain leaves the EU just as the geopolitical landscape is undergoing wrenching change. The United States has turned inwards, closer to its own historic norm, and is undermining the international institutions which it created alongside Britain in the 1940s. China’s international influence is on the rise alongside its vast and still growing economy, challenging traditional norms of individual freedom and public transparency.

Russia is navigating the cracks and crevices of the fracturing rules-based international order with ruthless efficiency. Sensing the change in the wind, many governments are now back-tracking on their post-Cold War transitions to more open and democratic societies.

The implications of this new context have yet to be fully internalised by those who look forward to Britain’s future outside the EU. Britain will be negotiating new trade deals in an increasingly transactional, fragmented and protectionist international economic environment. It will be trying to sell its world-class services into markets where national control over finance, law, technology and media is increasingly prized.

Making new diplomatic inroads will be no easier. The government will face strong internal and external criticism if it lends security assistance to states that are simultaneously clamping down on their citizens’ rights. With the number of military personnel in decline and investment in new equipment stretched across multiple expensive platforms, the UK could struggle to project meaningful defence cooperation to new security partners in Asia at the same time as upholding its NATO commitments and its deployments in conflict zones around the world.

Britain also opens its new global chapter at a time when it is changing domestically. There is no over-riding reason for a missionary British foreign policy – neither the economic returns or image of national glory that drove Empire, nor the existential defence of its land, interests and freedom that drove it during the Cold War.

Stretching liberal interventionism to Iraq, as Tony Blair did when he was prime minister, and to Libya as David Cameron did in 2011, has injected a deep dose of popular scepticism to the idea that Britain - with or without allies - can or should help make the world in its own image.

This more defensive mindset – epitomised by parliament’s refusal to use military force to punish President Bashar al Assad’s regime for using chemical weapons against its citizens in 2013 – will not abate soon. Especially when the new government’s political bandwidth will be stretched by fiendishly complex trade-offs between its financial promises to support domestic renewal, the imperatives of striking and implementing a new free trade agreement with the EU, and the economic consequences of leaving the single market.

All this points to the fact that the most important step for Britain at the beginning of this new national chapter will be to establish an effective partnership with the EU and its member states. They face the same international risks as Britain and have as much to gain from the preservation of rules-based international behaviour. Recognising the continued interdependence between Britain and the EU will offer both sides greater leverage in a more competitive and hostile world.

A new transatlantic relationship

Once it has agreed its new relationship with the EU, Britain can turn to crafting its new relationship with the mighty United States. US-UK economic interdependence and close security ties should help discipline the bilateral economic relationship. The more difficult challenge will be for the UK to avoid falling into fissures between the US and the EU over how to manage bilateral relations with China and Russia, particularly if President Trump wins a second term.

Britain will have to get used to this difficult balancing act between its transatlantic heart and European head after Brexit. This makes it all the more important for the UK to develop new diplomatic and commercial initiatives with countries that are also struggling to cope with the current uncertain, transactional international environment.

Canada, Japan, South Korea, Australia and New Zealand can grow as bilateral economic partners and as allies in international institutions, such as the G7, OECD and WTO. They may even open a door to British engagement in regional trade arrangements such as the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CP-TPP), which do not require the same political commitments as EU membership.

Turning from an EU-rooted foreign and economic policy to one that is once again more international in outlook will be difficult, take time and be more costly than the government currently envisages. The irony is that for this to be successful requires sustained political investment by the Johnson government to build a strong relationship with the EU that it is focused on leaving.




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Immigration to the Heartland: A Profile of Immigrants in the Kansas City Region

The immigrant population in the Kansas City region has grown rapidly over the past 25 years, contributing to overall population growth in the area. This fact sheet describes immigrants in the metro area, examining their origins, industries of employment, income and poverty levels, English proficiency, educational attainment, and more.




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Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence: A Scientific Statement From the American Heart Association and the American Diabetes Association

Caroline S. Fox
Sep 1, 2015; 38:1777-1803
Scientific Statement




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Type 1 Diabetes Mellitus and Cardiovascular Disease: A Scientific Statement From the American Heart Association and American Diabetes Association

Sarah D. de Ferranti
Oct 1, 2014; 37:2843-2863
Scientific Statement




heart

Relationship of Glucose Tolerance and Plasma Insulin to the Incidence of Coronary Heart Disease: Results from Two Population Studies in Finland

Kalevi Pyörälä
Mar 1, 1979; 2:131-141
Proceedings of the Kroc Foundation International Conference on Epidemiology of Diabetes and its Macrovascular Complications




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Coronary Heart Disease Incidence and Cardiovascular Mortality in Busselton with Reference to Glucose and Insulin Concentrations

T A Welborn
Mar 1, 1979; 2:154-160
Proceedings of the Kroc Foundation International Conference on Epidemiology of Diabetes and its Macrovascular Complications




heart

Consensus Development Conference on the Diagnosis of Coronary Heart Disease in People With Diabetes: 10-11 February 1998, Miami, Florida

American Diabetes Association
Sep 1, 1998; 21:1551-1559
Consensus Development Conference Report




heart

Type 1 Diabetes Mellitus and Cardiovascular Disease: A Scientific Statement From the American Heart Association and American Diabetes Association

Sarah D. de Ferranti
Oct 1, 2014; 37:2843-2863
Scientific Statement




heart

Dalcetrapib Reduces Risk of New-Onset Diabetes in Patients With Coronary Heart Disease

Gregory G. Schwartz
May 1, 2020; 43:1077-1084
Emerging Therapies: Drugs and Regimens




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Poverty, lack of insurance can make heart failure prognosis worse, AHA says

Poverty and poor or non-existent health insurance coverage might worsen the effects of heart failure, the American Heart Association said Thursday.




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Dapagliflozin Versus Placebo on Left Ventricular Remodeling in Patients With Diabetes and Heart Failure: The REFORM Trial

OBJECTIVE

To determine the effects of dapagliflozin in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) on left ventricular (LV) remodeling using cardiac MRI.

RESEARCH DESIGN AND METHODS

We randomized 56 patients with T2DM and HF with LV systolic dysfunction to dapagliflozin 10 mg daily or placebo for 1 year, on top of usual therapy. The primary end point was difference in LV end-systolic volume (LVESV) using cardiac MRI. Key secondary end points included other measures of LV remodeling and clinical and biochemical parameters.

RESULTS

In our cohort, dapagliflozin had no effect on LVESV or any other parameter of LV remodeling. However, it reduced diastolic blood pressure and loop diuretic requirements while increasing hemoglobin, hematocrit, and ketone bodies. There was a trend toward lower weight.

CONCLUSIONS

We were unable to determine with certainty whether dapagliflozin in patients with T2DM and HF had any effect on LV remodeling. Whether the benefits of dapagliflozin in HF are due to remodeling or other mechanisms remains unknown.




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Blood Pressure Variability and Risk of Heart Failure in ACCORD and the VADT

OBJECTIVE

Although blood pressure variability is increasingly appreciated as a risk factor for cardiovascular disease, its relationship with heart failure (HF) is less clear. We examined the relationship between blood pressure variability and risk of HF in two cohorts of type 2 diabetes participating in trials of glucose and/or other risk factor management.

RESEARCH DESIGN AND METHODS

Data were drawn from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Veterans Affairs Diabetes Trial (VADT). Coefficient of variation (CV) and average real variability (ARV) were calculated for systolic (SBP) and diastolic blood pressure (DBP) along with maximum and cumulative mean SBP and DBP during both trials.

RESULTS

In ACCORD, CV and ARV of SBP and DBP were associated with increased risk of HF, even after adjusting for other risk factors and mean blood pressure (e.g., CV-SBP: hazard ratio [HR] 1.15, P = 0.01; CV-DBP: HR 1.18, P = 0.003). In the VADT, DBP variability was associated with increased risk of HF (ARV-DBP: HR 1.16, P = 0.001; CV-DBP: HR 1.09, P = 0.04). Further, in ACCORD, those with progressively lower baseline blood pressure demonstrated a stepwise increase in risk of HF with higher CV-SBP, ARV-SBP, and CV-DBP. Effects of blood pressure variability were related to dips, not elevations, in blood pressure.

CONCLUSIONS

Blood pressure variability is associated with HF risk in individuals with type 2 diabetes, possibly a consequence of periods of ischemia during diastole. These results may have implications for optimizing blood pressure treatment strategies in those with type 2 diabetes.




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In Politics, Aim for the Heart, Not the Head

In 1935, researchers from Columbia University fanned out around the city of Allentown, Pa., and handed out leaflets ahead of local and state elections. What residents did not know was that they were part of an experiment in political persuasion -- an experiment whose results came to mind last week...




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Soul of woman embraces heart of man / Sandy Ross.

This book is a biography of Sandy and her great grand fathers life journey, through an inspirational spiritual connection, involving cellular memory and genetic DNA. It entails a story of forced assimilation on a culture, still not identified in the countries constitution. Survival, deception, manipulation and confusion regarding Colonisation. This is on a scale of mass deception from a democracy that claims, equality and equity to all. The letter of Patent making South Australia a Province in 1836, shows that Consciousness Raising is evolving through the resilience and visualisation of the' Original peoples' of this ancient land, seen through the eyes of Sandy.




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Aligning to aliveness : a simple guide to heart-centred living / Robert Beno.




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Teacher : one woman's struggle to keep the heart in teaching / Gabbie Stroud.

Stroud, G. J. (Gabrielle J.), 1977-




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Heart of the grass tree / Molly Murn.

Grandmothers -- Death -- Fiction.




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A manual for heartache / Cathy Rentzenbrink.

Rentzenbrink, Cathy -- Family.




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Finding the heart of the nation : the journey of the Uluru Statement towards voice, treaty and truth / Thomas Mayor.

Mayor, Thomas -- Travel -- Australia.




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Spiral movements of the apex of the exposed mammalian heart.

United Kingdom, c.1939.




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Spiral movements of the apex of the exposed mammalian heart.

United Kingdom, c.1939.




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Starling's law of the heart. Reel 1.

[1946?]




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Starling's law of the heart. Reel 2.

[1946?]




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The diagnosis, prevention, & treatment of diseases of the heart, and of aneurism : with observations on rheumatism / by J.J. Furnivall.

London : J. Churchill, 1845.




heart

Did Christ die of a broken heart?

[Edinburgh] : [publisher not identified], [1862]




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The effects of rheumatic fever on the heart / by G. A. Gibson.

[Edinburgh?] : [publisher not identified], [1901?]




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The effects of venesection in renewing and increasing the heart's action under certain circumstances / by John Reid.

Edinburgh : printed by J. Stark, [1836?]




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The electro-motive changes in heart-block / by G. A. Gibson.

London : British Medical Journal, 1906.




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Ranking the Top 10 worst playoff heartbreaks in Bruins history

Is the Bruins' most recent exit from the Stanley Cup Playoffs also their most heartbreaking? Joe Haggerty counts down the biggest playoff disappointments, including way too many losses against the B's archrivals, the Montreal Canadiens.




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Manual of valvular heart disease

9781496310125 paperback




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Heart burn. / design : Biman Mullick.

London : Cleanair, Smoke-free Environment (33 Stillness Rd, London, SE23 1NG), [198-?]




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दिल की जलन। = Heart burn. / design : Biman Mullick.

London : Cleanair (33 Stillness Rd, London, SE23 1NG), [1989?]




heart

Dila jalana = Heart burn. / design : Biman Mullick.

London : Cleanair (33 Stillness Rd, London, SE23 1NG), [198-?]




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Hārtabarna = Heart burn. / design : Biman Mullick.

London : Cleanair (33 Stillness Rd, London, SE23 1NG), [198-?]




heart

Ha gubin wadnahaaga! = Heart burn. / design : Biman Mullick.

London : Cleanair (33 Stillness Rd, London, SE23 1NG), [198-?]




heart

Hārta jbalē = Heart burn. / design : Biman Mullick.

London : Cleanair (33 Stillness Rd, London, SE23 1NG), [198-?]




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Cardiologist worries heart patients denying themselves care over pandemic fears

A St. John's cardiologist says public health restrictions put in place under the COVID-19 pandemic, while justified, may be harming cardiac patients whose procedures have been postponed indefinitely as well as heart patients who are avoiding hospitals.



  • News/Canada/Nfld. & Labrador

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Heartbreak & triumph: Tancredi, Wilkinson reflect on Olympic soccer journey

Melissa Tancredi and Rhian Wilkinson were pillars of the Team Canada for nearly two decades. Together, they've lived the highs and lows of the women's national soccer program - from the awe of their first Games in Beijing 2008, the heartbreak and redemption in London 2012, and finally, solidifying Canada's reputation as a soccer world power in Rio 2016. It's been a rollercoaster they'd ride over and over again.




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Tampa mayor offers lighthearted apology to star QB Tom Brady

Mayor Jane Castor has issued a letter of apology after Tampa didn't exactly give the best of welcomes to one of its newest and most famous residents when NFL superstar Tom Brady was ejected from a downtown park while working out.



  • Sports/Football/NFL

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Ten years later hearts are changing - North Africa

After 10 years in North Africa, an OM worker sees a change in the hearts of neighbours and friends.




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Wounded feet, healed heart - Moldova

Their desire to help leads a Love Moldova outreach team to a woman whose loss of her toes leads to the salvation of her soul.




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A transformed heart

An Albanian man's heart is forever changed after suffering a heart attack and meeting Jesus in his recuperation.