Growing a provincial patient and family engagement network to optimize kidney care.

Patient and family engagement is crucial for a responsive health system and improves patient outcomes. However, few practical resources for purposeful engagement are available to health leaders. Over the past five years, BC Renal, the provincial kidney care network in British Columbia, developed, operationalized, and implemented a framework to enable meaningful patient and family engagement. An advisory committee, comprising patient partners and representatives from health authorities and the community, directs the outreach, resource development, and evaluation of patient and family engagement at BC Renal. Here, we describe how our network-wide patient engagement strategy was developed and expanded upon, and the progress so far. A 2022 survey reports that 95% were satisfied with the engagement opportunities, and narrative feedback suggests network members continue to adopt practical ways to collaborate more effectively. Health leaders, patient partners, and others continue to align operational and strategic activities to advance culture change in kidney care provincially.

The influence of flocculation upon global gene transcription in a yeast CYC8 mutant.

The transcriptome from a Saccharomyces cerevisiae tup1 deletion mutant was one of the first comprehensive yeast transcriptomes published. Subsequent transcriptomes from tup1 and cyc8 mutants firmly established the Tup1-Cyc8 complex as predominantly acting as a repressor of gene transcription. However, transcriptomes from tup1/cyc8 gene deletion or conditional mutants would all have been influenced by the striking flocculation phenotypes that these mutants display. In this study, we have separated the impact of flocculation from the transcriptome in a cyc8 conditional mutant to reveal those genes (i) subject solely to Cyc8p-dependent regulation, (ii) regulated by flocculation only and (iii) regulated by Cyc8p and further influenced by flocculation. We reveal a more accurate list of Cyc8p-regulated genes that includes newly identified Cyc8p-regulated genes that were masked by the flocculation phenotype and excludes genes which were indirectly influenced by flocculation and not regulated by Cyc8p. Furthermore, we show evidence that flocculation exerts a complex and potentially dynamic influence upon global gene transcription. These data should be of interest to future studies into the mechanism of action of the Tup1-Cyc8 complex and to studies involved in understanding the development of flocculation and its impact upon cell function.

Patient and Clinician Experiences With the Combination of Virtual and In-Person Chronic Kidney Disease Care Since the COVID-19 Pandemic.

Background: Following onset of the COVID-19 pandemic, chronic kidney disease (CKD) clinics in BC shifted from established methods of mostly in-person care delivery to virtual care (VC) and thereafter a hybrid of the two. Objectives: To determine strengths, weaknesses, quality-of-care delivery, and key considerations associated with VC usage to inform optimal way(s) of integrating virtual and traditional methods of care delivery in multidisciplinary kidney clinics. Design: Qualitative evaluation. Setting: British Columbia, Canada. Participants: Patients and health care providers associated with multidisciplinary kidney care clinics. Methods: Development and delivery of semi-structured interviews of patients and health care providers. Results: 11 patients and/or caregivers and 12 health care providers participated in the interviews. Participants reported mixed experiences with VC usage. All participants foresaw a future where both VC and in-person care was offered. A reported benefit of VC was convenience for patients. Challenges identified with VC included difficulty establishing new therapeutic relationships, and variable of abilities of both patients and health care providers to engage and communicate in a virtual format. Participants noted a preference for in-person care for more complex situations. Four themes were identified as considerations when selecting between in-person and VC: person's nonmedical context, support available, clinical parameters and tasks to be completed, and clinic operations. Participants indicated that visit modality selection is an individualized and ongoing process involving the patient and their preferences which may change over time. Health care provider participants noted that new workflow challenges were created when using both VC and in-person care in the same clinic session. Limitations: Limited sample size in the setting of one-on-one interviews and use of convenience sampling which may result in missing perspectives, including those already facing challenges accessing care who could potentially be most disadvantaged by implementation of VC. Conclusions: A list of key considerations, aligned with quality care delivery was identified for health care providers and programs to consider as they continue to utilize VC and refine how best to use different visit modalities in different patient and clinical situations. Further work will be needed to validate these findings and evaluate clinical outcomes with the combination of virtual and traditional modes of care delivery. Trial registration: Not registered.

Contexte: Après le début de la pandémie de COVID-19, les cliniques d'insuffisance rénale chronique (IRC) de la Colombie-Britannique sont passées d'une prestation de soins traditionnelle fondée principalement sur les visites en personne à des soins en mode virtuel, puis à un modèle hybride combinant les deux méthodes. Objectifs: Déterminer les avantages et les faiblesses des soins en mode virtuel, ainsi que la qualité de la prestation des soins et les principaux facteurs à considérer relativement à l'utilization des soins en mode virtuel, afin d'informer sur les meilleurs moyens d'intégrer les méthodes virtuelles et traditionnelles de prestation des soins dans les cliniques multidisciplinaires de néphrologie. Conception: Évaluation qualitative. Cadre: Colombie-Britannique (Canada). Sujets: Patients et prestataires de soins associés à des cliniques multidisciplinaires de soins rénaux. Méthodologie: Élaboration et réalisation d'entrevues semi-structurées auprès de patients et de prestataires de soins de santé. Résultats: En tout, 11 patients et/ou soignants et 12 prestataires de soins de santé ont participé aux entrevues. Les participants ont fait état d'expériences mitigées avec les soins en mode virtuel. Tous les participants envisageaient un futur où les soins seront offerts tant en mode virtuel qu'en personne. Un des avantages mentionnés des soins en mode virtuel est la commodité pour les patients. Parmi les défis mentionnés figuraient la difficulté à établir de nouvelles relations thérapeutiques et les capacités variables des patients et des prestataires de soins de santé à établir une relation et à communiquer en mode virtuel. Les participants ont noté une préférence pour les soins en personne dans les situations plus complexes. Quatre thèmes ont été identifiés comme facteurs à prendre en compte dans le choix entre les soins virtuels ou en personne: le contexte non médical de la personne, l'aide disponible, les paramètres cliniques et les tâches à accomplir, et les opérations de la clinique. Les participants ont indiqué que le choix de la modalité pour les visites est un processus individualisé et continu impliquant le patient et ses préférences, lesquelles peuvent changer au fil du temps. Les prestataires de soins ont indiqué que le fait d'offrir à la fois des soins virtuels et en personne dans une même séance clinique créait de nouveaux défis en matière de flux de travail. Limites: La taille limitée de l'échantillon pour les entrevues individuelles et l'utilization d'un échantillonnage de commodité pourraient avoir manqué certains points de vue, notamment celui de personnes déjà confrontées à des difficultés d'accès aux soins et qui pourraient être les plus désavantagées par la mise en œuvre de soins en mode virtuel. Conclusion: Une liste de facteurs-clé à prendre en compte pour une prestation de soins de qualité a été établie à l'attention des prestataires de soins de santé et des programs qui continuent à utiliser les soins en mode virtuel, et décrit la meilleure façon d'utiliser les différentes modalités de visites dans différentes situations cliniques et pour différents patients. D'autres travaux seront nécessaires pour valider ces résultats et évaluer les résultats cliniques lorsqu'il y a combinaison des modes virtuel et traditionnel pour la prestation des soins.

Systematic analysis of tup1 and cyc8 mutants reveals distinct roles for TUP1 and CYC8 and offers new insight into the regulation of gene transcription by the yeast Tup1-Cyc8 complex.

The Tup1-Cyc8 complex in Saccharomyces cerevisiae was one of the first global co-repressors of gene transcription discovered. However, despite years of study, a full understanding of the contribution of Tup1p and Cyc8p to complex function is lacking. We examined TUP1 and CYC8 single and double deletion mutants and show that CYC8 represses more genes than TUP1, and that there are genes subject to (i) unique repression by TUP1 or CYC8, (ii) redundant repression by TUP1 and CYC8, and (iii) there are genes at which de-repression in a cyc8 mutant is dependent upon TUP1, and vice-versa. We also reveal that Tup1p and Cyc8p can make distinct contributions to commonly repressed genes most likely via specific interactions with different histone deacetylases. Furthermore, we show that Tup1p and Cyc8p can be found independently of each other to negatively regulate gene transcription and can persist at active genes to negatively regulate on-going transcription. Together, these data suggest that Tup1p and Cyc8p can associate with active and inactive genes to mediate distinct negative and positive regulatory roles when functioning within, and possibly out with the complex.

A Phase 1, Open-Label, Dose-Escalation Study of L-DOS47 in Combination With Pemetrexed Plus Carboplatin in Patients With Stage IV Recurrent or Metastatic Nonsquamous NSCLC.

Introduction: L-DOS47, a targeted urease-anti-CEACAM6 immunoconjugate, alters the acidity of the tumor microenvironment by increasing local ammonia production. In vitro, the cytotoxic effects of L-DOS47 were additive when combined with pemetrexed and carboplatin. Methods: This phase I, open-label, dose-escalation study evaluated the safety and tolerability of up to four cycles of L-DOS47 (administered on days 1, 8, and 15 of each cycle at doses ranging from 0.59 to 9.0 µg/kg) combined with pemetrexed and carboplatin in patients with stage IV nonsquamous NSCLC. Continued L-DOS47 treatment after the fourth cycle was allowed at the treating physicians' discretion. Results: A total of 14 patients received at least one dose of L-DOS47. Overall, L-DOS47 was well tolerated. Grade greater than or equal to 3 adverse events (AEs) were typically neutropenia related. Two grade greater than or equal to 3 AEs and no serious AEs were considered at least possibly related to L-DOS47. No dose-limiting toxicities were reported, so the maximum tolerated dose was not reached. The objective response rate was 41.7% with a median duration of response of 187 days. Clinical benefit was observed in 75.0% of the patients. After the first dose, L-DOS47 systemic exposure increased in a generally dose-proportional manner but decreased substantially with repeat dosing. Anti-L-DOS47 antibodies were detectable in 13 of 14 patients by cycle 2 with titers typically increasing with continued treatment. There was an apparent association between best overall response rate and highest anti-L-DOS47 antibody titer measured. Conclusions: L-DOS47 combined with standard pemetrexed and carboplatin chemotherapy is well tolerated in patients with recurrent or metastatic nonsquamous NSCLC at doses up to 9.0 µg/kg.

Immature ALS-associated mutant superoxide dismutases form variable aggregate structures through distinct oligomerization processes.

Protein misfolding and aggregation are hallmarks of many diseases, including amyotrophic lateral sclerosis (ALS). In familial ALS, aberrant self-association of mutant Cu,Zn-superoxide dismutase (SOD1) is implicated as a key contributor to disease. Mutations have the largest impacts on the stability of the most immature form of SOD1, the unmetallated, disulfide-reduced monomer (apoSH SOD1). Here we demonstrate that, despite the marginal stability of apoSH SOD1, aggregation is little correlated with the degree of protein unfolding, and multiple modes of aggregation occur, depending on the mutation and solution conditions. Light scattering and atomic force microscopy reveal two distinct mutant SOD1 behaviours: high aggregator mutants form abundant small assemblies, while low aggregator mutants form fewer, more fibre-like aggregates. Attenuated total reflectance-Fourier transform infrared spectroscopy and Thioflavin T binding show the aggregates maintain native-like anti-parallel beta structure. These results provide new evidence that ALS-associated mutations promote the aggregation of apoSH SOD1 through multiple pathways, with broad implications for understanding mechanisms of protein self-association in disease and biotechnology.

C subunit of the ATP synthase is an amyloidogenic calcium dependent channel-forming peptide with possible implications in mitochondrial permeability transition.

The c subunit is an inner mitochondrial membrane (IMM) protein encoded by three nuclear genes. Best known as an integral part of the F0 complex of the ATP synthase, the c subunit is also present in other cytoplasmic compartments in ceroid lipofuscinoses. Under physiological conditions, this 75 residue-long peptide folds into an α-helical hairpin and forms oligomers spanning the lipid bilayer. In addition to its physiological role, the c subunit has been proposed as a key participant in stress-induced IMM permeabilization by the mechanism of calcium-induced permeability transition. However, the molecular mechanism of the c subunit participation in IMM permeabilization is not completely understood. Here we used fluorescence spectroscopy, atomic force microscopy and black lipid membrane methods to gain insights into the structural and functional properties of unmodified c subunit protein that might make it relevant to mitochondrial toxicity. We discovered that c subunit is an amyloidogenic peptide that can spontaneously fold into ß-sheets and self-assemble into fibrils and oligomers in a Ca2+-dependent manner. C subunit oligomers exhibited ion channel activity in lipid membranes. We propose that the toxic effects of c subunit might be linked to its amyloidogenic properties and are driven by mechanisms similar to those of neurodegenerative polypeptides such as Aß and α-synuclein.

Epidemiology, clinical characteristics, household transmission, and lethality of severe acute respiratory syndrome coronavirus-2 infection among healthcare workers in Ontario, Canada.

INTRODUCTION: Protecting healthcare workers (HCWs) from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a priority to maintain a safe and functioning healthcare system. Our objective was to describe and compare the epidemiology, clinical characteristics, and lethality of SARS-CoV-2 infections among HCWs compared to non-HCWs. METHODS: Using reportable disease data at Public Health Ontario, we conducted a population-based cross-sectional study comparing demographic, exposure, and clinical variables between HCWs and non-HCWs with SARS-CoV-2 infections as of 30 September 2020. We calculated rates of infections over time and determined the frequency of within household transmissions using natural language processing based on residential address. We evaluated the risk of death using a multivariable logistic regression model adjusting for age, sex, comorbidities, symptoms, and long-term care home exposure. RESULTS: There were 7,050 (12.5%) HCW SARS-CoV-2 infections in Ontario, Canada, of whom 24.9% were nurses, 2.3% were physicians, and the remaining 72.8% other specialties, including personal support workers. Overall HCWs had an infection rate of 1,276 per 100,000 compared to non-HCWs of 346 per 100,000 (3.7 times higher). This difference decreased from a 7 times higher rate in April to no difference in September 2020. Twenty-six percent of HCWs had a household member with SARS-CoV-2 infection; 6.8% were probable acquisitions, 12.3% secondary transmissions, and 6.9% unknown direction of transmission. Death among HCWs was 0.2% compared to 6.1% of non-HCWs. The risk of death in HCWs remained significantly lower than non-HCWs after adjustment (adjusted odds ratio 0.09; 95%CI 0.05-0.17). CONCLUSION: HCWs represent a disproportionate number of diagnosed SARS-CoV-2 infections in Ontario, however this discrepancy is at least partially explained by limitations in testing earlier in the pandemic for non-HCWs. We observed a low risk of death in HCWs which could not be completely explained by other factors.

The effects of melatonin, serotonin, tryptophan and NAS on the biophysical properties of DPPC monolayers.

Melatonin is a neurohormone that has been shown to be protective in Alzheimer's diseases against amyloid-ß (Aß) toxicity, which involves interaction of Aß with neuronal membrane. Non-specific interactions of melatonin with cell membrane may play a physiological role in this process by preserving membrane fluidity. In the brain, melatonin is derived from the amino acid tryptophan through a pathway that includes serotonin and N-acetylserotonin (NAS). How these molecules affect the membrane properties is not understood. In this work, we studied interactions of melatonin and its metabolic precursors tryptophan, serotonin and NAS with dipalmitoylphosphatidylcholine (DPPC) monolayers at the air-water interface using Langmuir monolayer technique. Analysis of compression isotherms, phase transitions and compressibility moduli indicate that all four molecules alter the DPPC monolayer properties in a structure and concentration dependent manner. This effect was most pronounced for melatonin followed by NAS. Melatonin and NAS both decreased the compressibility modulus and shifted the LE/LC phase transition suggesting an increase in the membrane fluidity. Tryptophan and serotonin caused less pronounced effects on the DPPC isotherm. These differences suggest different interaction mechanisms and may be attributed to the interplay between electrostatic and hydrophobic interactions of these molecules with the zwitterionic DPPC headgroups which correlate with water solubility and oil partition coefficients (LogS and LogP) of each the four molecules. The results here demonstrate how the physiochemical properties of indoles can affect lipid membranes which may shed light on the functional significance of these important neurochemicals and the neuroprotective mechanisms of melatonin.

Reliability and validity of the Thinking Skills Inventory, a screening tool for cross-diagnostic skill deficits underlying youth behavioral challenges.

Deficits in a range of skill domains (including executive functioning, emotion regulation, social cognition and language/communication) are associated with disrupted youth behavior and functioning across mental health diagnoses. The identification of skill deficits are important for effective treatment planning, particularly for personalized interventions. While there are multiple ways to assess these skills, parent/caregiver reports represent an important information source. To date, no single, brief measure has been developed that gathers parent/caregiver ratings across this range of constructs. We have developed a short caregiver-report questionnaire (the Thinking Skills Inventory; TSI), to screen for skill deficits. Here, we examine the reliability and validity of this rating scale in 384 youth who were consecutively referred for neuropsychiatric evaluation. A primary caregiver completed the TSI as well as other established measures. Exploratory and confirmatory factor analyses support five subscales on the TSI: Attention and Working Memory, Language and Communication, Emotion Regulation, Cognitive Flexibility, and Social Thinking Skills. The subscales showed moderate to high internal consistency (Cronbach's alphas range from 0.84 to 0.91). Correlations with established caregiver-report measures confirm their convergent and discriminant validity, and associations with multiple clinical diagnoses and cross-diagnostic aggressive behavior further support the utility of the scale for our intended purpose. In sum, this free, brief measure is a valid and reliable way to identify variation in skill domains relevant to a range of psychopathology. The TSI may be useful in youth mental health settings to assist with treatment planning and to inform referral for further evaluation.

Walk the Line: How Successful Are Efforts to Maintain Monogamy in Intimate Relationships?

Monogamy, typically defined as sexual and romantic exclusivity to one partner, is a near-universal expectation in committed intimate relationships in Western societies. Attractive alternative partners are a common threat to monogamous relationships. However, little is known about how individuals strive to protect their relationships from tempting alternatives, particularly those embedded in one's social network. The current exploratory study was guided by the Investment Model, which states that satisfaction, investments, and perceived alternatives to a relationship predict commitment, which in turn predicts relationship longevity. The study aimed to identify relationship and extradyadic attraction characteristics associated with monogamy maintenance efforts, specifically relationship commitment, as predicted by the Investment Model. The efficacy of monogamy maintenance efforts was assessed via sexual and emotional infidelity measures at a 2-month follow-up. U.S. adults in heterosexual intimate relationships (N = 287; 50.2% male; M age = 34.5 years; M relationship length = 87 months) were recruited online to complete the survey study. Through structural equation modelling, the Investment Model structure was replicated, and relationship commitment predicted use of relationship-enhancing efforts as well as self-monitoring/derogation efforts. Individuals who experienced reciprocated attraction used significantly more avoidance and self-monitoring/derogation efforts than did those who experienced unreciprocated attraction. Ultimately, monogamy maintenance efforts did not significantly predict success in maintaining monogamy at follow-up. These findings have important research, educational, and clinical implications relating to relationship longevity.

Youth Depression Screening with Parent and Self-Reports: Assessing Current and Prospective Depression Risk.

Few studies have examined the incremental validity of multi-informant depression screening approaches. In response, we examined how recommendations for using a multi-informant approach may vary for identifying concurrent or prospective depressive episodes. Participants included 663 youth (AgeM = 11.83; AgeSD = 2.40) and their caregiver who independently completed youth depression questionnaires, and clinical diagnostic interviews, every 6 months for 3 years. Receiver operating characteristic (ROC) analyses showed that youth-report best predicted concurrent episodes, and that both youth and parent-report were necessary to adequately forecast prospective episodes. More specifically, youth-reported negative mood symptoms and parent-reported anhedonic symptoms incrementally predicted future depressive episodes. Findings were invariant to youth's sex and age, and results from person and variable-centered analyses suggested that discrepancies between informants were not clinically meaningful. Implications for future research and evidence-based decision making for depression screening initiatives are discussed.

Characteristics of Child Psychiatric Outpatients at Highest Risk for Suicidal Thoughts and Behaviors.

On average, compared to non-referred youth, child psychiatric outpatients show elevated rates of suicidal thoughts and behaviors (STBs), which are predictors of completed suicide. Determining the psychopathology features that associate with highest risk for STBs among youth outpatients may yield opportunities for targeted prevention/intervention. Yet, outpatient studies are limited and have not systematically examined comorbidity and dimensional psychopathology. In 758 youth, aged 6-18, consecutively referred for neuropsychiatric evaluation, we examined the extent to which diagnostic groups, comorbid subgroups and dimensional symptoms associated with STBs. After controlling for comorbidity, mood, anxiety and conduct disorders associated with elevated STB risk. Regarding dimensions, symptoms of depression, aggression and psychosis all contributed to higher STB risk. Although ADHD (as a diagnosis or dimension) did not associate with elevated STB risk independently, ADHD that was comorbid with other conditions did. Suicide prevention/intervention efforts should be investigated in youth outpatients with the highest risk for STBs.

Effect of Varying Concentrations of Docosahexaenoic Acid on Amyloid Beta (1⁻42) Aggregation: An Atomic Force Microscopy Study.

Healthcare has advanced significantly, bringing with it longer life expectancies and a growing population of elders who suffer from dementia, specifically Alzheimer's disease (AD). The amyloid beta (Aß) peptide has been implicated in the cause of AD, where the peptides undergo a conformational change and form neurotoxic amyloid oligomers which cause neuronal cell death. While AD has no cure, preventative measures are being designed to either slow down or stop the progression of this neurodegenerative disease. One of these measures involves dietary supplements with polyunsaturated fatty acids such as docosahexaenoic acid (DHA). This omega-3 fatty acid is a key component of brain development and has been suggested to reduce the progression of cognitive decline. However, different studies have yielded different results as to whether DHA has positive, negative, or no effects on Aß fibril formation. We believe that these discrepancies can be explained with varying concentrations of DHA. Here, we test the inhibitory effect of different concentrations of DHA on amyloid fibril formation using atomic force microscopy. Our results show that DHA has a strong inhibitory effect on Aß1⁻42 fibril formation at lower concentrations (50% reduction in fibril length) than higher concentrations above its critical micelle concentration (70% increase in fibril length and three times the length of those at lower concentrations). We provide evidence that various concentrations of DHA can play a role in the inhibitory effects of amyloid fibril formation in vitro and help explain the discrepancies observed in previous studies.

Intraoperative use of dexmedetomidine is associated with decreased overall survival after lung cancer surgery.

BACKGROUND AND AIMS: The aim is to evaluate the association between the use of intraoperative dexmedetomidine with an increase in recurrence-free survival (RFS) and overall survival (OS) after nonsmall cell lung cancer (NSCLC) surgery. MATERIAL AND METHODS: This was a propensity score-matched (PSM) retrospective study. Single academic center. The study comprised patients with Stage I through IIIa NSCLC. Patients were excluded if they were younger than 18 years. Primary outcomes of the study were RFS and OS. RFS and OS were evaluated using univariate and multivariate Cox proportional hazards models after PSM (n = 251/group) to assess the association between intraoperative dexmedetomidine use and the primary outcomes. The value of P < 0.05 was considered statistically significant. RESULTS: After PSM and adjusting for significant covariates, the multivariate analysis demonstrated no association between the use of dexmedetomidine and RFS (hazard ratio [HR] [95% confidence interval (CI)]: HR = 1.18, 95% CI: 0.91-1.53; P = 0.199). The multivariate analysis also demonstrated an association between the administration of dexmedetomidine and reduced OS (HR = 1.28, 95% CI: 1.03-1.59; P = 0.024). CONCLUSIONS: This study demonstrated that the intraoperative use of dexmedetomidine to NSCLC patients was not associated with a significant impact on RFS and but worsening OS. A randomized controlled study should be conducted to confirm the results of this study.

Study of Cardiovascular Outcomes in Renal Transplantation: A Prospective, Multicenter Study to Determine the Incidence of Cardiovascular Events in Renal Transplant Recipients in Ontario, Canada.

BACKGROUND: Renal transplant recipients (RTRs) are at significantly higher risk for morbidity and mortality compared with the general population, largely attributed to cardiovascular disease (CVD). Previous estimates of CVD events have come from health care databases and retrospective studies. OBJECTIVE: The objective of this study was to prospectively determine the prevalence of risk factors and incidence of CVD events in a Canadian cohort of RTRs. DESIGN: Study of Cardiovascular Outcomes in Renal Transplantation (SCORe) was a prospective, longitudinal, multicenter observational study. SETTING: Adult RTRs were recruited from 6 participating transplant sites in Ontario, Canada. PATIENTS: Eligible patients were those receiving a living or deceased donor renal transplant. Patients who received simultaneous transplant of any other organ were excluded. MEASUREMENTS: Primary outcomes included myocardial infarction (MI) defined by American College of Cardiology (ACC-MI) criteria, and major adverse cardiac events (MACE), defined as cardiovascular (CV) death, ACC-MI, coronary revascularization, and nonhemorrhagic stroke. CV events were adjudicated by a single, independent cardiologist. METHODS: CV and transplant-specific risk factors that predict MACE and ACC-MI were identified by stepwise regression analysis using the Cox proportional hazards model. RESULTS: A total of 1303 patients enrolled across 6 transplant centers were followed for 4.5 ± 1.6 years (mean ± SD). Incidence of MACE was 7.0%, with significant independent predictors/risk factors including age, diabetes, coronary revascularization, nonhemorrhagic stroke, and renal replacement therapy (RRT). ACC-MI incidence was 4.0%, with significant independent predictors/risk factors including age, coronary revascularization, and duration of RRT in excess of the median value (2.91 years). LIMITATIONS: Patients were recruited from a single province, so may not reflect the experience of RTRs in other areas of Canada. CONCLUSIONS: Using a prospective design and rigorous methodology, this study found that the incidence of CV events after renal transplantation was elevated relative to the general Canadian population and was comparable with that reported in patient registries, thus helping validate the utility of retrospective analysis in this field. SCORe highlights the importance of monitoring RTRs for traditional cardiac and transplant-specific CV risk factors to help prevent CV morbidity and mortality. Further research is needed to investigate a broader range of potential risk factors and their combined effects on incident CV events.

CONTEXTE: Les receveurs d'une greffe rénale présentent un risque significativement plus élevé de morbidité et de mortalité que l'ensemble de la population, ceci est en grande partie attribuable aux maladies cardiovasculaires. Les estimations antérieures du nombre d'événements cardiovasculaires proviennent des bases de données du système de santé et des résultats d'études rétrospectives. OBJECTIF DE L'ÉTUDE: L'étude visait à mesurer de manière prospective la prévalence des facteurs de risque et l'incidence des événements cardiovasculaires dans une cohorte de patients receveurs d'une greffe rénale au Canada. TYPE D'ÉTUDE: L'étude SCORe consistait en une étude observationnelle longitudinale menée de façon prospective au sein de plusieurs centres hospitaliers. CADRE DE L'ÉTUDE: Les patients adultes receveurs d'une greffe rénale ont été recrutés dans six hôpitaux de la province de l'Ontario, au Canada. PATIENTS: Les patients qui avaient reçu une greffe rénale provenant d'un donneur vivant ou décédé ont été inclus dans l'étude. Les patients qui avaient reçu une greffe simultanée de tout autre organe ont été exclus. MESURES: Les principaux critères retenus incluaient un infarctus du myocarde répondant aux critères établis par l'American College of Cardiology (ACC-MI), des événements cardiaques majeurs indésirables (MACE) tels que le décès d'origine cardiovasculaire, l'ACC-MI, la revascularisation coronarienne et l'AVC non hémorragique. Ces événements cardiovasculaires ont été constatés par un cardiologue indépendant. MÉTHODOLOGIE: Les facteurs de risque, cardiovasculaires ou spécifiques à la transplantation, qui permettent de prédire les MACE et l'ACC-MI ont été identifiés à l'aide du modèle de risques proportionnels de Cox pour l'analyse de régression en étapes. RÉSULTATS: Les 1 303 patients recrutés au sein des six centres hospitaliers ont été suivis sur une moyenne de 1,6 an (SD ± 4,5). L'incidence de MACE était de 7,0%, avec des indicateurs prévisionnels indépendants et des facteurs de risque significatifs incluant l'âge, le diabète, la revascularisation coronarienne, l'AVC non hémorragique et la thérapie de remplacement rénale. L'incidence d'ACC-MI était de 4,0%, avec des indicateurs prévisionnels indépendants et des facteurs de risque significatifs incluant l'âge, la revascularisation coronarienne et une durée pour la thérapie de remplacement rénal excédant la valeur médiane (2,91 ans). LIMITES DE L'ÉTUDE: Les patients ont été recrutés dans une seule province, les résultats sont susceptibles de ne pas être représentatifs de la situation des receveurs d'une greffe rénale ailleurs au Canada. CONCLUSIONS: Grâce à un plan d'étude prospectif et à une méthodologie rigoureuse, nous avons déterminé que l'incidence des événements cardiovasculaires chez les receveurs d'une greffe rénale a été plus élevée que dans la population canadienne en général. Nous avons également constaté qu'elle était comparable à l'incidence rapportée dans les registres de patients, ce qui vient confirmer l'utilité des études rétrospectives dans ce domaine. Les résultats obtenus lors de l'étude SCORe mettent en lumière l'importance de faire un suivi auprès des receveurs d'une greffe rénale afin de détecter les facteurs de risque cardiovasculaires ou spécifiques à l'intervention, et ainsi aider à prévenir la mortalité et la morbidité liées aux maladies cardiovasculaires. D'autres recherches sont nécessaires afin d'examiner un plus large éventail de facteurs de risques potentiels et leurs effets concomitants sur les événements cardiovasculaires.

Recent Progress in Alzheimer's Disease Research, Part 3: Diagnosis and Treatment.

The field of Alzheimer's disease (AD) research has grown exponentially over the past few decades, especially since the isolation and identification of amyloid-ß from postmortem examination of the brains of AD patients. Recently, the Journal of Alzheimer's Disease (JAD) put forth approximately 300 research reports which were deemed to be the most influential research reports in the field of AD since 2010. JAD readers were asked to vote on these most influential reports. In this 3-part review, we review the results of the 300 most influential AD research reports to provide JAD readers with a readily accessible, yet comprehensive review of the state of contemporary research. Notably, this multi-part review identifies the "hottest" fields of AD research providing guidance for both senior investigators as well as investigators new to the field on what is the most pressing fields within AD research. Part 1 of this review covers pathogenesis, both on a molecular and macro scale. Part 2 review genetics and epidemiology, and part 3 covers diagnosis and treatment. This part of the review, diagnosis and treatment, reviews the latest diagnostic criteria, biomarkers, imaging, and treatments in AD.

Recent Progress in Alzheimer's Disease Research, Part 1: Pathology.

The field of Alzheimer's disease (AD) research has grown exponentially over the past few decades, especially since the isolation and identification of amyloid-ß from postmortem examination of the brains of AD patients. Recently, the Journal of Alzheimer's Disease (JAD) put forth approximately 300 research reports which were deemed to be the most influential research reports in the field of AD since 2010. JAD readers were asked to vote on these most influential reports. In this 3-part review, we review the results of the 300 most influential AD research reports to provide JAD readers with a readily accessible, yet comprehensive review of the state of contemporary research. Notably, this multi-part review identifies the "hottest" fields of AD research providing guidance for both senior investigators as well as investigators new to the field on what is the most pressing fields within AD research. Part 1 of this review covers pathogenesis, both on a molecular and macro scale. Part 2 review genetics and epidemiology, and part 3 covers diagnosis and treatment. This part of the review, pathology, reviews amyloid-ß, tau, prions, brain structure, and functional changes with AD and the neuroimmune response of AD.

Recent Progress in Alzheimer's Disease Research, Part 2: Genetics and Epidemiology.

This is the second part of a three-part review series reviewing the most important advances in Alzheimer's disease (AD) research since 2010. This review covers the latest research on genetics and epidemiology. Epidemiological and genetic studies are revealing important insights into the etiology of, and factors that contribute to AD, as well as areas of priority for research into mechanisms and interventions. The widespread adoption of genome wide association studies has provided compelling evidence of the genetic complexity of AD with genes associated with such diverse physiological function as immunity and lipid metabolism being implicated in AD pathogenesis.