Heart Health Begins With Community: Community-Based Research Exploring Innovative Strategies to Support First Nations Heart Health.

Background: Indigenous people have displayed their strength through their holistic practices and spiritual connection to the land. Despite overcoming the impact of discriminatory and disempowering policies within Western institutions, Indigenous people continue to experience a higher risk of cardiovascular disease, compared to the general population. To move toward improving Indigenous health outcomes, researchers need to work in partnership with communities to develop heart health strategies centred on their experienced barriers and sources of healing. We conducted a community-based explorative study in Moosonee, Ontario to explore the local community's needs and priorities regarding heart health and wellness. Methods: A convenience sample of community members and healthcare professionals were invited to participate in a sharing circle. Qualitative data were analyzed using conventional content analysis and the Indigenous method of two-eyed seeing. Results: Eight community members and 5 healthcare professionals participated in the sharing circle. Four dominant themes were identified: (1) heart health is more than metrics; (2) honouring our traumas; (3) destigmatizing care through relationship building; and (4) innovative solutions start with community. With the history of mistreatment among Indigenous people, strength-based solutions involved rebuilding clinical relationships. To bring care closer to home, digital health tools were widely accepted, but the design of these tools needs to integrate both Western and Indigenous approaches to healing. Conclusions: Indigenous health upholds the physical, emotional, psychological, and spiritual needs of an individual as being of equal importance. To improve community heart health, strategies should start by strengthening broken bonds and bridging multiple worldviews of healing.

Contexte: Les peuples autochtones tirent une grande force de leurs pratiques holistiques et de leur lien spirituel avec le territoire, et même s'ils ont surmonté les répercussions des politiques discriminatoires et marginalisantes des institutions occidentales, ils présentent encore un risque de maladies cardiovasculaires supérieur à celui de la population générale. Afin d'aider à améliorer la santé cardiovasculaire des Autochtones, les chercheurs doivent travailler avec les communautés pour mettre en place des stratégies qui tiennent compte des obstacles en matière de soins de santé et des méthodes de guérison traditionnelles. Nous avons réalisé une étude exploratoire en milieu communautaire à Moosonee (Ontario) dans le but d'explorer les besoins et les priorités de la communauté locale en matière de santé cardiovasculaire et de bien-être. Méthodologie: Des membres de la communauté et des professionnels de la santé ont été invités à participer à un cercle de partage. Les données qualitatives ont été analysées au moyen d'une analyse classique et de la méthode autochtone dite à double perspective. Résultats: Huit membres de la communauté et cinq professionnels de la santé ont participé au cercle de partage. Quatre principaux thèmes ont été abordés : 1) la santé cardiovasculaire va au-delà de ce qui se mesure; 2) il faut tenir compte des traumatismes; 3) il faut déstigmatiser les soins en nouant des relations et 4) les solutions novatrices doivent reposer sur la participation de la communauté. En raison du passé de maltraitance envers les peuples autochtones, les solutions axées sur les forces devaient permettre de restaurer la confiance envers les soins cliniques. Les outils de santé numérique, bien adaptés aux besoins de la communauté, ont été largement acceptés, mais ils doivent intégrer les méthodes de soins occidentales et autochtones. Conclusions: Selon la vision autochtone, la santé repose en parts égales sur les aspects physiques, émotionnels, psychologiques et spirituels d'une personne. L'amélioration de la santé cardiovasculaire des membres de la communauté passe donc avant tout par des stratégies qui permettent de recréer les liens qui ont été brisés et qui intèrent plusieurs visions thérapeutiques.

Access to Cardiovascular Care for Indigenous Peoples in Canada: A Rapid Review.

Indigenous peoples in Canada are at an increased risk of cardiovascular disease compared to non-Indigenous people. Contributing factors include historical oppression, racism, healthcare biases, and disparities in terms of the social determinants of health. Access to and inequity in cardiovascular care for Indigenous peoples in Canada remain poorly studied and understood. A rapid review of the literature was performed using the PubMed/MEDLINE, Web of Science, and Indigenous Studies Portal (iPortal) databases to identify articles describing access to cardiovascular care for Indigenous peoples in Canada between 2002 and 2021. Included articles were presented narratively in the context of delays in seeking, reaching, or receiving care, or as disparities in cardiovascular outcomes, and were assessed for their successful engagement in indigenous health research using a preexisting framework. Current research suggests that gaps most prominently present as delays in receiving care and as poorer long-term outcomes. The literature is concentrated in Alberta, Manitoba, and Ontario, as well as among First Nations people, and is largely rooted in a biomedical worldview. Additional community-driven research is required to better elucidate the gaps in access to holistic cardiovascular care for Indigenous peoples in Canada. Healthcare professionals, researchers, and policymakers should reflect further upon their actions and privilege, educate themselves about historical facts and the Truth and Reconciliation Commission, tackle prevailing disparities and systemic barriers in the healthcare systems, and develop culturally safe and ethically appropriate healthcare interventions to improve the health of all Indigenous peoples in Canada.

Le risque de maladies cardiovasculaires est plus élevé chez les populations autochtones du Canada que chez les populations non autochtones. L'oppression historique, le racisme, les préjugés dans les soins de santé et les disparités quant aux déterminants sociaux de la santé sont des facteurs qui contribuent à ce phénomène. L'accès aux soins cardiovasculaires et l'équité des soins pour les personnes autochtones du Canada sont des questions peu étudiées et mal comprises. Une revue rapide de la littérature a été réalisée dans les bases de données PubMed/MEDLINE, Web of Science et Indigenous Studies Portal (iPortal) pour recenser les articles publiés entre 2002 et 2021 qui décrivent l'accès aux soins cardiovasculaires pour les peuples autochtones du Canada. Les articles retenus sont présentés de manière narrative et font état de retards dans la recherche de soins, dans l'atteinte d'un établissement de soins et dans l'obtention des soins, ou de certaines disparités quant aux résultats de santé cardiovasculaire. Ces articles ont également été évalués d'après leur intégration réussie des principes de recherche en santé autochtone à partir d'un cadre déjà établi. Selon les recherches actuelles, les écarts se manifestent principalement par des retards dans l'obtention des soins et par des résultats de santé plus défavorables à long terme. Les études publiées se concentrent surtout sur l'Alberta, le Manitoba et l'Ontario, portent principalement sur les Premières Nations et sont en grande partie abordées selon une perspective biomédicale. Des recherches plus approfondies, menées avec les communautés autochtones, sont nécessaires pour mieux comprendre les écarts dans l'accès à des soins cardiovasculaires holistiques pour les peuples autochtones du Canada. Les professionnels de la santé, les chercheurs et les décideurs politiques devraient entreprendre un processus de réflexion approfondie sur leurs actions et leurs privilèges, s'informer sur les réalités historiques ainsi que sur la Commission de vérité et réconciliation, s'attaquer aux disparités qui perdurent et aux barrières systémiques dans l'accès aux soins de santé, et mettre en place des interventions de soins culturellement sécuritaires et éthiquement adaptées, pour améliorer la santé de l'ensemble de la population autochtone du Canada.

Expanding Telemonitoring in a Virtual World: A Case Study of the Expansion of a Heart Failure Telemonitoring Program During the COVID-19 Pandemic.

BACKGROUND: To minimize the spread and risk of a COVID-19 outbreak, societal norms have been challenged with respect to how essential services are delivered. With pressures to reduce the number of in-person ambulatory visits, innovative models of telemonitoring have been used during the pandemic as a necessary alternative to support access to care for patients with chronic conditions. The pandemic has led health care organizations to consider the adoption of telemonitoring interventions for the first time, while others have seen existing programs rapidly expand. OBJECTIVE: At the Toronto General Hospital in Ontario, Canada, the rapid expansion of a telemonitoring program began on March 9, 2020, in response to COVID-19. The objective of this study was to understand the experiences related to the expanded role of a telemonitoring program under the changing conditions of the pandemic. METHODS: A single-case qualitative study was conducted with 3 embedded units of analysis. Semistructured interviews probed the experiences of patients, clinicians, and program staff from the Medly telemonitoring program at a heart function clinic in Toronto, Canada. Data were analyzed using inductive thematic analysis as well as Eakin and Gladstone's value-adding approach to enhance the analytic interpretation of the study findings. RESULTS: A total of 29 participants were interviewed, including patients (n=16), clinicians (n=9), and operational staff (n=4). Four themes were identified: (1) providing care continuity through telemonitoring; (2) adapting telemonitoring operations for a more virtual health care system; (3) confronting virtual workflow challenges; and (4) fostering a meaningful patient-provider relationship. Beyond supporting virtual visits, the program's ability to provide a more comprehensive picture of the patient's health was valued. However, issues relating to the lack of system integration and alert-driven interactions jeopardized the perceived sustainability of the program. CONCLUSIONS: With the reduction of in-person visits during the pandemic, virtual services such as telemonitoring have demonstrated significant value. Based on our study findings, we offer recommendations to proactively adapt and scale telemonitoring programs under the changing conditions of an increasingly virtual health care system. These include revisiting the scope and expectations of telemedicine interventions, streamlining virtual patient onboarding processes, and personalizing the collection of patient information to build a stronger virtual relationship and a more holistic assessment of patient well-being.

Improving the design of heart failure care from the perspective of frontline providers and administrators: A qualitative case study of a large, urban health system.

BACKGROUND: Heart failure patients often present with frailty and/or multi-morbidity, complicating care and service delivery. The Chronic Care Model (CCM) is a useful framework for designing care for complex patients. It assumes responsibility of several actors, including frontline providers and health-care administrators, in creating conditions for optimal chronic care management. This qualitative case study examines perceptions of care among providers and administrators in a large, urban health system in Canada, and how the CCM might inform redesign of care to improve health system functioning. METHODS: Sixteen semi-structured interviews were conducted between August 2014 and January 2016. Interpretive analysis was conducted to identify how informants perceive care among this population and the extent to which the design of heart failure care aligns with elements of the CCM. RESULTS: Current care approaches could better align with CCM elements. Key changes to improve health system functioning for complex heart failure patients that align with the CCM include closing knowledge gaps, standardizing treatment, improving interdisciplinary communication and improving patient care pathways following hospital discharge. CONCLUSIONS: The CCM can be used to guide health system design and interventions for frail and multi-morbid heart failure patients. Addressing care- and service-delivery barriers has important clinical, administrative and economic implications.

The Transplant Palliative Care Clinic: An early palliative care model for patients in a transplant program.

Although patients within a transplant program are awaiting or have received disease modifying or curative treatment, they are also facing advanced illness and the possibility of death. The involvement of specialized palliative care services for these patients may improve symptom management and facilitate advance care planning. However, patients in organ transplantation programs have difficulty accessing palliative care resources and often do so only sporadically in the inpatient setting. Currently, there is little access to ambulatory palliative care for these patients and there have been no descriptions of programs delivering such care in the medical literature. We outline the development and structure of a Transplant Palliative Care Clinic within the University Health Network's Multi-Organ Transplant Program, in Toronto, Canada. This information may be helpful for others aiming to provide early, integrated palliative care to patients awaiting and receiving organ transplantation.

Heterogeneity of myocardial iron distribution in response to chelation therapy in patients with transfusion-dependent anemias.

The purpose of this study is to examine the effect of different iron chelation regimens on the distribution of myocardial iron in patients with transfusion-dependent anemias. Institutional review board approval was obtained. Patients treated with iron chelation therapy who had undergone baseline and 1-year follow-up cardiac T2* MR studies in a four-year period were identified retrospectively. One hundred and eight patients (44 % male, mean age 31.6 ± 9.7 years) were included. The interventricular septum on three short-axis slices (basal, mid and apical) was divided into anterior and inferior regions of interest for T2* analysis. Cardiac iron concentration (CIC) was calculated from T2* values. Statistical analysis included analysis of variance and paired t-test, using Bonferroni adjustment in all pairwise comparisons. At baseline, T2* measurements varied significantly across all six regions (p < 0.001): lowest in the mid anteroseptum (mean 22.3 ± 10.1 ms) and highest in the apical inferoseptum (mean 26.2 ± 12.8 ms). At follow-up, T2* and CIC values improved significantly in all segments [mean change of 3.78 ms (95 % CI (2.93, 4.62), p < 0.001) and 0.23 mg/g (95 % CI (0.16, 0.29), p < 0.001), respectively]. Change in T2* values varied significantly between segments (p < 0.001) with greatest improvement in the apical inferoseptum [4.26 ms, 95 % CI (2.42, 6.11)] and least improvement in the basal anteroseptum [2.95 ms, 95 % CI (1.37, 4.54)]. The largest improvement in T2* values was noted in patients treated with deferiprone [4.96 ms, 95 % CI (2.34, 7.58)]. There was a statistically significant difference in improvement in CIC values between chelation regimens (p = 0.016). This is the first study to report heterogeneity in response to iron chelating drugs with variable segmental changes in T2* values.

Pectin engineering to modify product quality in potato.

Although processed potato tuber texture is an important trait that influences consumer preference, a detailed understanding of tuber textural properties at the molecular level is lacking. Previous work has identified tuber pectin methyl esterase (PME) activity as a potential factor impacting on textural properties, and the expression of a gene encoding an isoform of PME (PEST1) was associated with cooked tuber textural properties. In this study, a transgenic approach was undertaken to investigate further the impact of the PEST1 gene. Antisense and over-expressing potato lines were generated. In over-expressing lines, tuber PME activity was enhanced by up to 2.3-fold; whereas in antisense lines, PME activity was decreased by up to 62%. PME isoform analysis indicated that the PEST1 gene encoded one isoform of PME. Analysis of cell walls from tubers from the over-expressing lines indicated that the changes in PME activity resulted in a decrease in pectin methylation. Analysis of processed tuber texture demonstrated that the reduced level of pectin methylation in the over-expressing transgenic lines was associated with a firmer processed texture. Thus, there is a clear link between PME activity, pectin methylation and processed tuber textural properties.

Potato tuber pectin structure is influenced by pectin methyl esterase activity and impacts on cooked potato texture.

Although cooked potato tuber texture is an important trait that influences consumer preference, a detailed understanding of tuber textural properties at the molecular level is lacking. Previous work has identified tuber pectin methyl esterase activity (PME) as a potential factor impacting on textural properties. In this study, tuber PME isoform and gene expression profiles have been determined in potato germplasm with differing textural properties as assessed using an amended wedge fracture method and a sloughing assay, revealing major differences between the potato types. Differences in pectin structure between potato types with different textural properties were revealed using monoclonal antibodies specific for different pectic epitopes. Chemical analysis of tuber pectin clearly demonstrated that, in tubers containing a higher level of total PME activity, there was a reduced degree of methylation of cell wall pectin and consistently higher peak force and work done values during the fracture of cooked tuber samples, demonstrating the link between PME activity, the degree of methylation of cell wall pectin, and cooked tuber textural properties.

Discerning intra-tuber differences in textural properties in cooked Solanum tuberosum group Tuberosum and group Phureja tubers.

BACKGROUND: The textural properties of potato tubers influence their acceptability and palatability and these properties differ between varieties, groups and progeny. The aim of this study was to compare the textural properties of cooked tubers of Solanum tuberosum group Phureja with those of group Tuberosum. RESULTS: To assess intra-tuber differences, the textural properties of seven cubes from defined positions along the longitudinal axis of tubers of four Tuberosum group cultivars and three Phureja group lines were tested after cooking using an amended wedge fracture method. Tuberosum group tubers gave consistently higher peak force and work done values during fracture than the Phureja group tubers. Moreover, the values for cubes 1-6 from any tuber were not significantly different and only cube 7, from the stem end, gave higher values. Therefore, the use of any of cubes 1-6 is a valid measurement of the tuber as a whole but the central cube 4 may be most conveniently located. The dry matter content of the cubes did not influence the textural properties of the cubes, which suggested that starch swelling is not the main driving force for textural differences. Total pectin methyl esterase (PME) activity was consistently higher in cubes of the Tuberosum group cultivars over the Phureja group lines. CONCLUSION: The method developed is valid and consistent for assessing textural differences within potato germplasm. The relationship between PME activity and enhanced resistance to fracture suggests that PME may modulate pectin cohesiveness, perhaps through increasing Ca(2+)-bridges, to provide greater resistance to fracture.

Effect of global ischemia and reperfusion during ventricular fibrillation in myopathic human hearts.

The effect of lack of global coronary perfusion on myocardial activation rate, wavebreak, and its temporal progression during human ventricular fibrillation (VF) is not known. We tested the hypothesis that global myocardial ischemia decreases activation rate and spatiotemporal organization during VF in myopathic human hearts, while increasing wavebreak, and that a short duration of reperfusion can restore these spatiotemporal changes to baseline levels. The electrograms were acquired during VF in a human Langendorff model using global mapping consisting of two 112-electrode arrays placed on the epicardium and endocardium simultaneously. We found that global myocardial ischemia results in slowing of the global activation rate (combined endo and epi), from 4.89+/-0.04 Hz. to 3.60+/-0.04 Hz. during the 200 s of global ischemia (no coronary flow) (P<0.01) in eight myopathic hearts. Two minutes of reperfusion contributed to reversal of the slowing with activation rate value increasing close to VF onset (4.72+/-0.04 Hz). In addition, during the period of ischemia, an activation rate gradient between the endocardium (3.76+/-0.06 Hz) and epicardium (3.45+/-0.06 Hz) was observed (P<0.01). There was a concomitant difference in wavebreak index (that provides a normalized parameterization of phase singularities) between the epicardium (11.29+/-2.7) and endocardium (3.25+/-2.7) during the 200 s of ischemia (P=0.02). The activation rate, gradient, and wavebreak changes were reversed by short duration (2 min) of reperfusion. Global myocardial ischemia of 3 min leads to complex spatiotemporal changes during VF in myopathic human hearts; these changes can be reversed by a short duration of reperfusion.

Strawberry polyphenols are equally cytotoxic to tumourigenic and normal human breast and prostate cell lines.

The cytotoxic effects of strawberry polyphenols were investigated on normal cells and tumour cells derived from the same patient. A human prostate epithelial cell line (P21) and two tumour cell lines (P21 tumour cell line 1 and 2) derived from the same patient, and a normal human breast epithelial cell line (B42) and a tumour line derived from it (B42 clone 16) were used. A polyphenol-rich extract derived from strawberry or anthocyanin or tannin-rich sub-fractions were applied to the cell lines in doses varying from 50 to 1.5 microg/ml. The strawberry extract was cytotoxic with doses of approximately 5 microg/ml causing a 50% reduction in cell survival in both the normal and the tumour lines. The extracts were also cytotoxic to peripheral blood human lymphocytes stimulated with phytohaemagglutinin but higher levels (>20 microg/ml for 50% reduction in cell survival) were required. After fractionation of the strawberry sample, the cytotoxicity was retained in the tannin-rich fraction and this fraction was considerably more toxic to all cells (normal or tumour cell lines or lymphocytes) than the anthocyanin-rich fraction. Established prostate (LNCaP and PC-3) and breast (MCF-7) tumour cell lines were more resistant to the strawberry extract with concentrations of 50 microg/ml required for 50% reduction in cell survival, which is similar to levels in previous studies on the antiproliferative effects of berry extracts. Although these concentrations are much greater than possible physiological levels, they are comparable to those reported in other studies. From these findings, we conclude that there is little evidence to assume that polyphenols from strawberry have a differential cytotoxic effect on tumour cells relative to comparable normal cells from the same tissue derived from the same patient.

Berry extracts exert different antiproliferative effects against cervical and colon cancer cells grown in vitro.

Polyphenol-rich berry extracts were screened for their antiproliferative effectiveness using human cervical cancer (HeLa) cells grown in microtiter plates. Rowan berry, raspberry, lingonberry, cloudberry, arctic bramble, and strawberry extracts were effective but blueberry, sea buckthorn, and pomegranate extracts were considerably less effective. The most effective extracts (strawberry > arctic bramble > cloudberry > lingonberry) gave EC 50 values in the range of 25-40 microg/(mL of phenols). These extracts were also effective against human colon cancer (CaCo-2) cells, which were generally more sensitive at low concentrations but conversely less sensitive at higher concentrations. The strawberry, cloudberry, arctic bramble, and the raspberry extracts share common polyphenol constituents, especially the ellagitannins, which have been shown to be effective antiproliferative agents. However, the components underlying the effectiveness of the lingonberry extracts are not known. The lingonberry extracts were fractionated into anthocyanin-rich and tannin-rich fractions by chromatography on Sephadex LH-20. The anthocyanin-rich fraction was considerably less effective than the original extract, whereas the antiproliferative activity was retained in the tannin-rich fraction. The polyphenolic composition of the lingonberry extract was assessed by liquid chromatography-mass spectrometry and was similar to previous reports. The tannin-rich fraction was almost entirely composed of procyanidins of linkage type A and B. Therefore, the antiproliferative activity of lingonberry was caused predominantly by procyanidins.

Umami compounds are a determinant of the flavor of potato (Solanum tuberosum L.).

Vegetable flavor is an important factor in consumer choice but a trait that is difficult to assess quantitatively. The purpose of this study was to assess the levels of the major umami compounds in boiled potato tubers, in cultivars previously assessed for sensory quality. The free levels of the major umami amino acids, glutamate and aspartate, and the 5'-nucleotides, GMP and AMP, were measured in potato samples during the cooking process. Tubers were sampled at several time points during the growing season. The levels of both glutamate and 5'-nucleotides were significantly higher in mature tubers of two Solanum phureja cultivars compared with two Solanum tuberosum cultivars. The equivalent umami concentration was calculated for five cultivars, and there were strong positive correlations with flavor attributes and acceptability scores from a trained evaluation panel, suggesting that umami is an important component of potato flavor.

Antiproliferative activity is predominantly associated with ellagitannins in raspberry extracts.

Raspberry extracts enriched in polyphenols, but devoid of organic acids, sugars and vitamin C, were prepared by sorption to C18 solid phase extraction matrices and tested for their ability to inhibit the proliferation of human cervical cancer (HeLa) cells in vitro. The raspberry extract reduced proliferation in a dose-dependent manner whether this was judged by cell number or measurements of cell viability. However, measurements based on cell viability were more accurate and gave an EC(50) value of 17.5 microg/ml gallic acid equivalents (GAE) at day 4 of culture. Raspberry extracts were fractionated by sorption to Sephadex LH-20 into an unbound fraction, which was obviously enriched in anthocyanins, and a bound fraction. The unbound anthocyanin-enriched fraction was much less effective in reducing proliferation then the original extract and gave an EC(50) value estimated at 67 microg/ml. The LH-20 bound fraction was more effective than the original raspberry extract (EC(50)=13 microg/ml) suggesting that the main anti-proliferative agents were retained in the bound fraction. Analysis of the original extract, the unbound and the LH20 bound fractions by LC-MS confirmed that the unbound fraction was enriched in anthocyanins and the bound fraction primarily contained ellagitannins. The ellagitannin-rich bound fraction had the highest antioxidant capacity as measured by the ferric reducing antioxidant potential (FRAP) assay. The mechanism by which the ellagitannins inhibit proliferation of cancer cells is discussed.

Increased ventricular repolarization heterogeneity in patients with ventricular arrhythmia vulnerability and cardiomyopathy: a human in vivo study.

Increased repolarization heterogeneity can provide the substrate for reentrant ventricular arrhythmias in animal models of cardiomyopathy. We hypothesized that ventricular repolarization heterogeneity is also greater in patients with cardiomyopathy and ventricular arrhythmia vulnerability (inducible ventricular tachycardia or positive microvolt T wave alternans, VT/TWA) compared with a similar patient population without ventricular arrhythmia vulnerability (no VT/TWA). Endocardial and epicardial repolarization heterogeneity was measured in patients with (n = 12) and without (n = 10) VT/TWA by using transvenous 26-electrode catheters placed along the anteroseptal right ventricular endocardium and left ventricular epicardium. Local activation times (AT), activation-recovery intervals (ARI), and repolarization times (RT) were measured from unipolar electrograms. Endocardial RT dispersion along the apicobasal ventricle was greater (P < 0.005) in patients with VT/TWA than in those without VT/TWA because of greater ARI dispersion (P < 0.005). AT dispersion was similar between the two groups. Epicardial RT dispersion along the apicobasal ventricle was greater (P < 0.05) in patients with VT/TWA than in those without VT/TWA because of greater ARI dispersion (P < 0.05). AT dispersion was similar between the two groups. A plot of AT as a function of ARI revealed an inverse linear relationship for no VT/TWA such that progressively later activation was associated with progressively shorter ARI. The AT-ARI relationship was nonlinear in VT/TWA. In conclusion, patients with cardiomyopathy and VT/TWA have greater endocardial and epicardial repolarization heterogeneity than those without VT/TWA without associated conduction slowing. The steep repolarization gradients in VT/TWA may provide the substrate for functional conduction block and reentrant ventricular arrhythmias.

Modulation of fructokinase activity of potato (Solanum tuberosum) results in substantial shifts in tuber metabolism.

Potato plants (Solanum tuberosum L. cvs Desiree and Record) transformed with sense and antisense constructs of a cDNA encoding the potato fructokinase StFK1 exhibited altered transcription of this gene, altered amount of protein and altered enzyme activities. Measurement of the maximal catalytic activity of fructokinase revealed a 2-fold variation in leaf (from 90 to 180% of wild type activity) and either a 10- or 30-fold variation in tuber (from 10 or 30% to 300% in Record and Desiree, respectively) activity. The comparative effect of the antisense construct in leaf and tuber tissue suggests that this isoform is only a minor contributor to the total fructokinase activity in the leaf but the predominant isoform in the tuber. Antisense inhibition of the fructokinase resulted in a reduced tuber yield; however, its overexpression had no impact on this parameter. The modulation of fructokinase activity had few, consistent effects on carbohydrate levels, with the exception of a general increase in glucose content in the antisense lines, suggesting that this enzyme is not important for the control of starch synthesis. However, when metabolic fluxes were estimated, it became apparent that the transgenic lines display a marked shift in metabolism, with the rate of redistribution of radiolabel to sucrose markedly affected by the activity of fructokinase. These data suggest an important role for fructokinase, acting in concert with sucrose synthase, in maintaining a balance between sucrose synthesis and degradation by a mechanism independent of that controlled by the hexose phosphate-mediated activation of sucrose phosphate synthase.

Effects of folic acid fortification and multivitamin therapy on homocysteine and vitamin B(12) status in cardiac transplant recipients.

BACKGROUND: Hyperhomocysteinemia is a frequent finding after cardiac transplantation, but increased folate intake induces a decrease in total homocysteine concentrations. In 1998, food in Canada was fortified nationwide with folic acid. We assessed the impact of routine folate fortification on homocysteine concentrations in our cardiac transplant population. METHODS: In 18 subjects, we measured total homocysteine (tHcy), serum folate, and cobalamin concentrations in 1997 (before folate fortification) and in 1998 (after fortification). We repeated the analysis after specific multivitamin supplementation for 10 weeks. RESULTS: We found a significant decrease in baseline tHcy concentrations and in folate concentrations between 1997 and 1998. However, we also found a decrease in serum cobalamin concentrations. We found a correlation between decreased cobalamin concentrations and the methionine synthase A2756G genotype, but not with other common polymorphisms associated with homocysteine metabolism. After multivitamin supplementation, we observed a trend toward further decrease in tHcy concentrations and a significant increase in serum folate and cobalamin concentrations. Finally, we measured serum methylmalonic acid concentrations, an index of tissue cobalamin status. We did not find a correlation between increased methylmalonic acid concentrations and decreased serum cobalamin, perhaps related to the confounding effect of altered renal status on methylmalonic acid excretion. CONCLUSIONS: National folate fortification was associated with decreased tHcy and increased folate concentrations in our cardiac transplant population. Additional administration of vitamin supplements induced a further decrease in tHcy and an increase in folate. Finally, folate fortification unveiled cobalamin deficiency in some patients, associated with the methionine synthase A2756G mutation.

Animal spare parts? A Canadian public consultation on xenotransplantation.

Xenotransplantation, or the use of animal cells, tissues and organs for humans, has been promoted as an important solution to the worldwide shortage of organs. While scientific studies continue to be done to address problems of rejection and the possibility of animal-to-human virus transfer, socio-ethical and legal questions have also been raised around informed consent, life-long monitoring, animal welfare and animal rights, and appropriate regulatory practices. Many calls have also been made to consult publics before policy decisions are made. This paper describes the Canadian public consultation process on xenotransplantation carried out by the Canadian Public Health Association in an arm's length process from Health Canada, the ministry overseeing government health policy and regulation. Focusing on six citizen for a conducted around the country patterned after the citizen jury deliberative approach, the paper describes the citizen panelists' recommendations to hold off on proceeding with clinical trials and the rationales behind this recommendation. The consultation process is discussed in the context of constructive technology assessment, a framework which argues for broader input into earlier stages of technology innovation, particularly at the technology design stage.