WHO HEARTS: A Global Program to Reduce Cardiovascular Disease Burden: Experience Implementing in the Americas and Opportunities in Canada

Globally, cardiovascular diseases (CVDs) are the leading cause of death. Viewed as a threat to the global economy, the United Nations included reducing noncommunicable diseases, including CVDs, in the 2030 sustainable development goals, and the World Health Assembly agreed to a target to reduce noncommunicable diseases 25% by the year 2025. In response, the World Health Organisation led the development of HEARTS, a technical package to guide governments in strengthening primary care to reduce CVDs. HEARTS recommends a public health and health system approach to introduce highly simplified interventions done systematically at a primary health care level and has a focus on hypertension as a clinical entry point. The HEARTS modules include healthy lifestyle counselling, evidence-based treatment protocols, access to essential medicines and technology, CVD risk-based management, team-based care, systems for monitoring, and an implementation guide. There are early positive global experiences in implementing HEARTS. Led by the Pan American Health Organisation, many national governments in the Americas are adopting HEARTS and have shown early success. Unfortunately, in Canada hypertension control is declining in women since 2010-2011 and the dramatic reductions in rates of CVD seen before 2010 have flattened when age adjusted and increased for rates that are not age adjusted, and there are marked increases in absolute numbers of Canadians with adverse CVD outcomes. Several steps that Canada could take to enhance hypertension control are outlined, the core of which is to implement a strong governmental nongovernmental collaborative strategy to prevent and control CVDs, focusing on HEARTS.     

Discovery of novel cross-protective Rickettsia prowazekii T-cell antigens using a combined reverse vaccinology and in vivo screening approach

Rickettsial agents are some of the most lethal pathogens known to man. Among them, Rickettsia prowazekii is a select agent with potential use for bioterrorism; yet, there is no anti-Rickettsia vaccine commercially available. Owing to the obligate intracellular lifestyle of rickettsiae, CD8⁺ T cells are indispensable for protective cellular immunity. Furthermore, T cells can mediate cross-protective immunity between different pathogenic Rickettsia, a finding consistent with the remarkable similarity among rickettsial genomes. However, Rickettsia T cell antigens remain unidentified. In the present study, we report an algorithm that allowed us to identify and validate four novel R. prowazekii vaccine antigen candidates recognized by CD8⁺ T cells from a set of twelve in silico-defined protein targets. Our results highlight the importance of combining proteasome-processing as well as MHC class-I-binding predictions. The novel rickettsial vaccine candidate antigens, RP778, RP739, RP598, and RP403, protected mice against a lethal challenge with Rickettsia typhi, which is indicative of cross-protective immunity within the typhus group rickettsiae. Together, our findings validate a reverse vaccinology approach as a viable strategy to identify protective rickettsial antigens and highlight the feasibility of a subunit vaccine that triggers T-cell-mediated cross-protection among diverse rickettsiae.     

Phenotype of the anti-Rickettsia CD8 T cell response suggests cellular correlates of protection for the assessment of novel antigens

The obligately intracellular bacteria Rickettsia infect endothelial cells and cause systemic febrile diseases that are potentially lethal. No vaccines are currently available and current knowledge of the effective immune response is limited. Natural and experimental rickettsial infections provide strong and cross-protective cellular immunity if the infected individual survives the acute infection. Although resistance to rickettsial infections is attributed to the induction of antigen-specific T cells, particularly CD8⁺ T cells, the identification and validation of correlates of protective cellular immunity against rickettsial infections, an important step toward vaccine validation, remains a gap in this field. Here, we show that after a primary challenge with Rickettsia typhi in the C3H mouse model, the peak of anti-Rickettsia CD8⁺ T cell-mediated responses occurs 7 days post-infection (dpi), which coincides with the beginning of rickettsial clearance. At this time point, both effector-type and memory-type CD8⁺ T cells are present, suggesting that 7 dpi is a valid time point for the assessment of CD8⁺ T cell responses of mice previously immunized with protective antigens. Based on our results, we suggest four correlates of cellular protection for the assessment of protective rickettsial antigens: (1) production of IFN-γ by antigen-experienced CD3⁺CD8⁺CD44^high cells, (2) production of Granzyme B by CD27^lowCD43^low antigen-experienced CD8⁺ T cells, (3) generation of memory-type CD8⁺ T cells [Memory Precursor Effector Cells (MPECs), as well as CD127^highCD43^low, and CD27^highCD43^low CD8⁺ T cells], and (4) generation of effector-like memory CD8⁺ T cells (CD27^lowCD43^low). We propose that these correlates could be useful for the general assessment of the quality of the CD8⁺ T cell immune response induced by novel antigens with potential use in a vaccine against Rickettsia.     

Long-lasting reduction of Brugia timori microfilariae following a single dose of diethylcarbamazine combined with albendazole

The long-term effect of a single oral dose of 6 mg/kg bodyweight of diethylcarbamazine (DEC) combined with 400 mg albendazole (ALB) on the microfilariae (mf) of the lymphatic filarial parasite Brugia timori was studied on Alor island, Indonesia from April 2001 to April 2002. Before treatment the geometric mean of the mf density in 96 infected study subjects was 150 mf/mL night blood (range 1-5696 mf/mL). One year after treatment 69 subjects (72%) were mf-negative and the overall geometric mean mf density reduced to 3 mf/mL (0-2456 mf/mL). The reduction of mf was more pronounced 1 year after treatment compared with 6 months after treatment. It can be concluded that a single dose of DEC + ALB leads to a long-term and progressive suppression of B. timori mf for at least 1 year. Therefore, DEC+ ALB can be recommended as an effective strategy to control B. timori infection in the framework of the Global Programme to Eliminate Lymphatic Filariasis.     

The experience of Chinese bereaved persons: a preliminary study of meaning making and continuing bonds

This study explores the bereavement process of Chinese persons in Hong Kong, with the focus on how they make meaning of the death as well as how they maintain a bond with the deceased. A review of video- and audiotapes of 52 bereaved persons in bereavement counseling pointed to how these concepts are reflected in key themes that appeared throughout these interviews. The way this bereaved population found meaning in the death was reflected in how they understood the cause of death, their observations at the death moment, their understanding of the life of the deceased after the death, the life of the bereaved after the death, and the burial and mourning rituals that were followed. The continuing bond the bereaved felt with the deceased was experienced by the bereaved as either initiated by the deceased, for example by the deceased appearing in dreams or initiated by the bereaved themselves in their talking with the deceased. These 2 aspects of the bereavement process seem to be similar to those found in other societies, but the ways in which they were manifested were unique to the Chinese culture. Based on these findings, the authors conclude with implications for intervention with this bereaved population.     

Equol is more active than soy isoflavone itself to compete for binding to thromboxane A(2) receptor in human platelets

Introduction

Several dietary intervention studies examining the health effect of soy isoflavones allude to the importance of equol in establishing the cardiovascular response to soy protein. Although, the specific mechanism by which this action occurs has not been established. The aim of this study was to investigate the inhibitory effect of soy-isoflavones and the metabolite of daidzein, equol, on agonist-induced platelet responses dependent on thromboxane A₂ (TxA₂) receptor.

Material and methods

Competitive radioligand binding assay was used to screen for affinity of these compounds to the TxA₂ receptor. The effect of equol on platelet activation, evaluate through of release of the ATP, by analogs of TxA₂ was analyzed. The effect of equol on platelet aggregation was investigated with ADP, U46619 (a TxA₂ mimic) and the calcium ionophore A23187.

Results

The data showed that aglycone isoflavones and equol bind to TxA₂ receptor in the µmol/L range, whereas their glucoside derivates had very low binding activity for this receptor. Under equilibrium conditions, the following order of the relative affinity in inhibiting [³H]-SQ29585 binding was: equol > genistein > daidzein > glycitein ? genistin, daidzin, glycitin. Equol interaction was reversible and competitive for labeled-SQ29548 with not apparent decrease in the number of TxA₂ binding sites. In addition, from platelet activation studies, equol effectively inhibited ATP secretion elicited by the TxA₂ analog U46619. On the other hand, equol inhibited the platelet aggregation induced by U46619 and A23187, while it failed to inhibit that induced by ADP.

Conclusions

The aglycone isoflavones from soy, and particularly equol, have been found to have biological effects attributable to thromboxane A₂ receptor antagonism. These findings may help elucidate how dietary isoflavone modulate platelet function and explain why soy-rich foods are claimed to have beneficial effects in the prevention of thrombotic events.     

Air pollution and heart failure: Relationship with the ejection fraction

AIM: To study whether the concentrations of particulate matter in ambient air are associated with hospitaladmission due to heart failure in patients with heart failure with preserved ejection fraction and reduced ejection fraction. METHODS: We studied 353 consecutive patients admitted into a tertiary care hospital with a diagnosis of heart failure. Patients with ejection fraction of ≥ 45% were classified as having heart failure with preserved ejection fraction and those with an ejection fraction of < 45% were classified as having heart failure with reduced ejection fraction. We determined the average concentrations of different sizes of particulate matter (< 10, < 2.5, and < 1 μm) and the concentrations of gaseous pollutants (carbon monoxide, sulphur dioxide, nitrogen dioxide and ozone) from 1 d up to 7 d prior to admission. RESULTS: The heart failure with preserved ejection fraction population was exposed to higher nitrogen dioxide concentrations compared to the heart failure with reduced ejection fraction population (12.95 ± 8.22 μg/m 3 vs 4.50 ± 2.34 μg/m 3 , P < 0.0001). Multivariate analysis showed that nitrogen dioxide was a significant predictor of heart failure with preserved ejection fraction (odds ratio ranging from (1.403, 95%CI: 1.003-2.007, P = 0.04) to (1.669, 95%CI: 1.043-2.671, P = 0.03). CONCLUSION: This study demonstrates that shortterm nitrogen dioxide exposure is independently associated with admission in the heart failure with preserved ejection fraction population.