Search

Abstract Background The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls. Methods Unstimulated saliva samples were collected from 229 OSCC-free and 45 OSCC subjects and evaluated for their content of 40 common oral bacteria using checkerboard DNA-DNA hybridization. DNA counts per ml saliva were determined for each species, averaged across subjects in the 2 subject groups, and significance of differences between groups determined using the Mann-Whitney test and adjusted for multiple comparisons. Diagnostic sensitivity and specificity in detection of OSCC by levels of salivary organisms were computed and comparisons made separately between a non-matched group of 45 OSCC subjects and 229 controls and a group of 45 OSCC subjects and 45 controls matched by age, gender and smoking history. Results Counts of 3 of the 40 species tested, Capnocytophaga gingivalis, Prevotella melaninogenica and Streptococcus mitis, were elevated in the saliva of individuals with OSCC (p < 0.001). When tested as diagnostic markers the 3 species were found to predict 80% of cancer cases (sensitivity) while excluding 83% of controls (specificity) in the non-matched group. Diagnostic sensitivity and specificity in the matched group were 80% and 82% respectively. Conclusion High salivary counts of C. gingivalis, P. melaninogenica and S. mitis may be diagnostic indicators of OSCC.

Background and objectiveIn patients with coronary artery disease (CAD), obesity is paradoxically associated with better survival (the 'obesity paradox'). Our objective was to determine whether this counterintuitive relationship extends to health-related quality of life (HRQOL) outcomes.DesignCross-sectional observational study.SubjectsAll adults undergoing coronary angiography residing in Alberta, Canada between January 2003 and March 2006 in the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) registry.MethodsPatients completed self-reported questionnaires 1 year after their index cardiac catheterization, including the Seattle Angina Questionnaire (SAQ) and the EuroQol 5D (EQ-5D Index). Patients were grouped into six body mass index (BMI) categories (underweight, normal, overweight, mild obesity, moderate obesity and severe obesity). An analysis of covariance was used to create risk-adjusted scores.ResultsA total of 5362 patients were included in the analysis. Obese patients were younger than normal and overweight participants, and had a higher prevalence of depression and cardiovascular risk factors. In the adjusted models, SAQ physical function scores and the EQ Index (representing overall QOL) were significantly reduced in patients with mild, moderate and severe obesity compared with patients with a normal BMI. Patients with severe obesity had both statistically and clinically significant reductions in HRQOL scores. Depressive symptoms accounted for a large proportion in variability of all HRQOL scores.ConclusionsBMI is inversely associated with physical function and overall HRQOL in CAD patients, especially in patients with severe obesity. High body weight is a modifiable risk factor; however, given the apparent obesity paradox in patients with CAD, it is critical that future studies be conducted to fully clarify the relationships between HRQOL and body composition (body fat and lean mass), nutritional state and survival outcomes.

BACKGROUND: Studies have identified prevalence rates of major depression in patients with cardiovascular disease to range from 16% to 23%, whereas 65% of patients report some symptoms after a myocardial event. Depression has been shown to be strongly related to overall poorer outcomes in patients with coronary artery disease. PURPOSE: The purpose of this pilot study was to assess the potential benefit of providing follow-up information regarding mental health resources to patients who had undergone cardiac catheterization and had reported significant levels of depression symptoms. Two methods of providing this follow-up information (personal telephone interaction and mailed-out written information) were compared. METHODS: As part of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry, patients completed baseline questionnaires, including the 10-item Center for Epidemiologic Studies Depression (CES-D) Scale. Patients reporting a score of 10 or higher were randomly assigned to one of three groups. Group A patients were contacted by mail, whereas Group B patients were contacted through a telephone follow-up call by a nurse. Both groups received information regarding community- and hospital-based mental health resources. Six weeks after the initial contact, patients in Groups A and B and those in a third control group (Group C) were called and asked to complete a repeat CES-D via telephone interview. Logistic regression modeling was used to determine the influence of the intervention on the change in depression scores from baseline to 6 weeks. RESULTS: Ninety-eight respondents had both baseline and 6-week CES-D scores. The mean age of the respondents was 64.9 years, and women constituted 27% of the sample. There was no statistically significant clinical difference between the three groups. Regression analysis demonstrated that patients who were contacted by either telephone or mail were significantly more likely to report improvement in the CES-D scores (odds ratio = 3.03, p = .03) as compared with the control group. Furthermore, respondents who were phoned reported the highest percentage of improved CES-D scores as compared with the mailed and control groups. CONCLUSIONS: This pilot study demonstrated that early recognition strategies and referral protocols that address mental health needs are effective in decreasing the reported depressive symptomatology of this high-risk population. Proactively addressing mental health issues as an integral part of the overall treatment with patients with coronary artery disease could potentially improve the health outcomes in this population. Copyright © 2009 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Several studies report that women with CAD have a poorer prognosis than men and suggest that depressive symptoms may be a contributing factor. The purpose of this study was to examine gender differences in depressive symptoms, as they relate to health-related quality of life outcomes following an AMI. METHODS: Patients with documented AMI completed a questionnaire including the Short Form 36 physical (PCS), and mental component summary (MCS) scores, and Beck Depression Inventory at baseline and at 1 year after AMI admission. RESULTS: 486 (82%) patients completed the follow-up questionnaire. Females had significantly worse PCS and MCS scores at baseline and 1-year follow-up compared to males The mean 1-year Beck scores were significantly higher (p=0.01) for females (10.02+/-8.23) compared to males (7.78+/-8.01) indicating more reported depressive symptomatology. Multivariate analyses showed significant gender-related differences in the PCS scores at 1 year, but no gender-related differences in the 1-year MCS scores. CONCLUSIONS: These results suggest that gender differences in mental health at 1 year relate to gender-related differences at 1-year depression levels. The higher level of depression in women may be a consequence of gender differences in recovery patterns from an AMI and requires further investigation. [ABSTRACT FROM AUTHOR]

Context: Adjusted survival curves are often presented in medical research articles. The most commonly used method for calculating such curves is the mean of covariates method, in which average values of covariates are entered into a proportional hazards regression equation. Use of this method is widespread despite published concerns regarding the validity of resulting curves.Objective: To compare the mean of covariates method to the less widely used corrected group prognosis method in an analysis evaluating survival in patients with and without diabetes. In the latter method, a survival curve is calculated for each level of covariates, after which an average survival curve is calculated as a weighted average of the survival curves for each level of covariates.Design, Setting, and Patients: Analysis of cohort study data from 11 468 Alberta residents undergoing cardiac catheterization between January 1, 1995, and December 31, 1996.Main Outcome Measures: Crude and risk-adjusted survival for up to 3 years after cardiac catheterization in patients with vs without diabetes, analyzed by the mean of covariates method vs the corrected group prognosis method.Results: According to the mean of covariates method, adjusted survival at 1044 days was 94.1% and 94.9% for patients with and without diabetes, respectively, with misleading adjusted survival curves that fell above the unadjusted curves. With the corrected group prognosis method, the corresponding survival values were 91.3% and 92.4%, with curves that fell more appropriately between the unadjusted curves.Conclusions: Misleading adjusted survival curves resulted from using the mean of covariates method of analysis for our data. We recommend using the corrected group prognosis method for calculating risk-adjusted curves. [ABSTRACT FROM AUTHOR]

Background: We have previously described a method for dealing with missing data in a prospective cardiac registry initiative. The method involves merging registry data to corresponding ICD-9-CM administrative data to fill in missing data 'holes'. Here, we describe the process of translating our data merging solution to ICD-10, and then validating its performance.Methods: A multi-step translation process was undertaken to produce an ICD-10 algorithm, and merging was then implemented to produce complete datasets for 1995-2001 based on the ICD-9-CM coding algorithm, and for 2002-2005 based on the ICD-10 algorithm. We used cardiac registry data for patients undergoing cardiac catheterization in fiscal years 1995-2005. The corresponding administrative data records were coded in ICD-9-CM for 1995-2001 and in ICD-10 for 2002-2005. The resulting datasets were then evaluated for their ability to predict death at one year.Results: The prevalence of the individual clinical risk factors increased gradually across years. There was, however, no evidence of either an abrupt drop or rise in prevalence of any of the risk factors. The performance of the new data merging model was comparable to that of our previously reported methodology: c-statistic = 0.788 (95% CI 0.775, 0.802) for the ICD-10 model versus c-statistic = 0.784 (95% CI 0.780, 0.790) for the ICD-9-CM model. The two models also exhibited similar goodness-of-fit.Conclusion: The ICD-10 implementation of our data merging method performs as well as the previously-validated ICD-9-CM method. Such methodological research is an essential prerequisite for research with administrative data now that most health systems are transitioning to ICD-10. [ABSTRACT FROM AUTHOR]

Abstract Background Mycobacterium tuberculosis (MTB) is a major cause of morbidity and mortality in the world. To combat against this pathogen, immune cells release cytokines including tumor necrosis factor-α (TNF-α), which is pivotal in the development of protective granulomas. Our previous results showed that Bacillus Calmette Guerin (BCG), a mycobacterium used as a model to investigate the immune response against MTB, stimulates the induction of TNF-α via mitogen-activated protein kinase (MAPK) in human blood monocytes. Since MAPK phosphatase-1 (MKP-1) is known to regulate MAPK activities, we examined whether MKP-1 plays a role in BCG-induced MAPK activation and cytokine expression. Results Primary human blood monocytes were treated with BCG and assayed for MKP-1 expression. Our results demonstrated that following exposure to BCG, there was an increase in the expression of MKP-1. Additionally, the induction of MKP-1 was regulated by p38 MAPK and extracellular signal-regulated kinase 1 and 2 (ERK1/2). Surprisingly, when MKP-1 expression was blocked by its specific siRNA, there was a significant decrease in the levels of phospho-MAPK (p38 MAPK and ERK1/2) and TNF-α inducible by BCG. Conclusions Since TNF-α is pivotal in granuloma formation, the results indicated an unexpected positive function of MKP-1 against mycobacterial infection as opposed to its usual phosphatase activity.

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting "brain fog" and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer's disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in Long COVID and ADRD are due to parallel neuroinflammation, astrocyte reactivity, hypoxia, and neurovascular injury. These neurophysiological abnormalities underpinning cognitive decline in COVID-19 can be detected by routine EEG exams. Future research will explore the value of EEG monitoring of COVID-19 patients for predicting long-term outcomes and monitoring efficacy of therapeutic interventions. HIGHLIGHTS: Abnormal intrinsic electrophysiological brain activity, such as slowing of EEG, reduced alpha wave, and epileptiform are characteristic findings in COVID-19 patients. EEG abnormalities have the potential as neural biomarkers to identify neurological complications at the early stage of the disease, to assist clinical assessment, and to assess cognitive decline risk in Long COVID patients. Similar slowing of intrinsic brain activity to that of COVID-19 patients is typically seen in patients with mild cognitive impairments, ADRD. Evidence presented supports the idea that cognitive deficits in Long COVID and ADRD are driven by overlapping neurophysiological abnormalities resulting, at least in part, from neuroinflammatory mechanisms and astrocyte reactivity. Identifying common biological mechanisms in Long COVID-19 and ADRD can highlight critical pathologies underlying brain disorders and cognitive decline. It elucidates research questions regarding cognitive EEG and mild cognitive impairment in Long COVID that have not yet been adequately investigated., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Coronary artery disease (CAD) confers increased risks of premature mortality, non-fatal morbidity, and significant impairment in functional status and health-related quality of life. Routine administration of electronic patient-reported outcome measures (PROMs) and its real time delivery to care providers is known to have the potential to inform routine cardiac care and to improve quality of care and patient outcomes. This study describes a user-centered development and evaluation of the Alberta Provincial Project for Outcomes Assessment (APPROACH) electronic Patient Reported Outcomes Measurement (e-PROM) system. This e-PROM system is an electronic system for the administration of PROMs to patients with CAD and the delivery of the summarized information to their care providers to facilitate patient-physician communication and shared decision-making. This electronic platform was designed to be accessible via web-based and hand-held devices. Heuristic and user acceptance evaluation were conducted with patients and attending care providers., Results: The APPROACH e-PROM system was co-developed with patients and care providers, research investigators, informaticians and information technology experts. Five PROMs were selected for inclusion in the online platform after consultations with patient partners, care providers, and PROMs experts: the Seattle Angina Questionnaire, Patient Health Questionnaire, EuroQOL, and Medical Outcomes Study Social Support Survey, and Self-Care of Coronary Heart Disease Inventory. The heuristic evaluation was completed by four design experts who examined the usability of the prototype interfaces. User acceptance testing was completed with 13 patients and 10 cardiologists who evaluated prototype user interfaces of the e-PROM system., Conclusion: Both patients and physicians found the APPROACH e-PROM system to be easy to use, understandable, and acceptable. The APPROACH e-PROM system provides a user-informed electronic platform designed to incorporate PROMs into the delivery of individualized cardiac care for persons with CAD., (© 2024. The Author(s).)

Gender equality has been a crosscutting issue in Horizon 2020 with three objectives: gender balance in decision-making, gender balance and equal opportunities in project teams at all levels, and inclusion of the gender dimension in research and innovation content. Between 2017 and 2022, the EU funded, in collaboration with national agencies, 13 transnational projects under "GENDER-NET Plus" that explored how to best integrate both sex and gender into studies ranging from social sciences, humanities, and health research. As the projects neared completion, forty researchers from these interdisciplinary teams met in November 2022 to share experiences, discuss challenges, and consider the best ways forward to incorporate sex and gender in research. Here, we summarize the reflections from this workshop and provide some recommendations for i) how to plan the studies (e.g., how to define sex and/or gender and their dimensions, rationale for the hypotheses, identification of data that can best answer the research question), ii) how to conduct them (e.g., adjust definitions and dimensions, perform pilot studies to ensure proper use of terminology and revise until consensus is achieved), and iii) how to analyze and report the findings being mindful of any real-world impact., Competing Interests: All authors declare no competing interests., (© 2024 The Author(s).)

Hyperactivation of the Ca2+/calmodulin-dependent phosphatase calcineurin (CN) is observed in reactive astrocytes associated with neuroinflammation and progressive degenerative diseases, like Alzheimer's disease. Apart from key transcription factors (e.g. nuclear factor of activated t cells and nuclear factor-κB) very few other CN-dependent pathways have been studied in astrocytes. The hemichannel protein, connexin 43 (Cx43) is found at high levels in astrocytes and contains a CN-sensitive Ser residue near its carboxy terminus. CN-dependent dephosphorylation of Cx43 has been reported in primary astrocytes treated with injurious stimuli, but much remains unknown about CN/Cx43 interactions in the context of neuroinflammation and disease. Western blots were used to assess total Cx43 and dephosphorylated Cx43 subtypes in rat embryonic primary astrocytes treated with a hyperactive CN fragment (ΔCN, via adenovirus), or with a proinflammatory cytokine cocktail. Under similar treatment conditions, an ethidium bromide (EtBr) uptake assay was used to assess membrane permeability. Effects of ΔCN and cytokines were tested in the presence or absence of the CN inhibitor, cyclosporin A. A connexin inhibitor, carbenoxolone was also used in EtBr assays to assess the involvement of connexins in membrane permeability. Treatment with ΔCN or cytokines increased dephosphorylated Cx43 levels in conjunction with increased membrane permeability (elevated EtBr uptake). Effects of ΔCN or cytokine treatment were blocked by cyclosporine A. Treatment-induced changes in EtBr uptake were also inhibited by carbenoxolone. The results suggest that Cx43 hemichannels could be an important mechanism through which astrocytic CN disrupts neurologic function associated with neurodegenerative disease., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aging dogs serve as a valuable preclinical model for Alzheimer's disease (AD) due to their natural age-related development of β-amyloid (Aβ) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments. We found that the frontal lobe showed accelerated atrophy with age, while the caudate nucleus remained relatively stable. Remarkably, the hippocampus increased in volume in all dogs. None of these changes were influenced by tacrolimus or Q134R treatment. Our results suggest that behavioral enrichment can prevent atrophy and increase the volume of the hippocampus but does not prevent aging-associated prefrontal cortex atrophy., (Copyright © 2024 the authors.)

Background: Alzheimer's disease (AD) is one of the multifaceted neurodegenerative diseases influenced by many genetic and epigenetic factors. Genetic factors are merely not responsible for developing AD in the whole population. The studies of genetic variants can provide significant insights into the molecular basis of Alzheimer's disease. Our research aimed to show how genetic variants interact with environmental influences in different parts of the world., Methodology: We searched PubMed and Google Scholar for articles exploring the relationship between genetic variations and global regions such as America, Europe, and Asia. We aimed to identify common genetic variations susceptible to AD and have no significant heterogeneity. To achieve this, we analyzed 35 single-nucleotide polymorphisms (SNPs) from 17 genes (ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, EPHA1, TOMM40, MS4A6A, ARID5B, SORL1, APOC1, MTHFD1L, BDNF, TFAM, and PICALM) from different regions based on previous genomic studies of AD. It has been reported that rs3865444, CD33, is the most common polymorphism in the American and European populations. From TOMM40 and APOE rs2075650, rs429358, and rs6656401, CR1 is the common investigational polymorphism in the Asian population., Conclusion: The results of all the research conducted on AD have consistently shown a correlation between genetic variations and the incidence of AD in the populations of each region. This review is expected to be of immense value in future genetic research and precision medicine on AD, as it provides a comprehensive understanding of the genetic factors contributing to the development of this debilitating disease., Competing Interests: The authors declare that they have no competing interests., (© 2024 Hossain et al.)

Research on the cerebrovasculature may provide insights into brain health and disease. Immunohistochemical staining is one way to visualize blood vessels, and digital pathology has the potential to revolutionize the measurement of blood vessel parameters. These tools provide opportunities for translational mouse model research. However, mouse brain tissue presents a formidable set of technical challenges, including potentially high background staining and cross-reactivity of endogenous IgG. Formalin-fixed paraffin-embedded (FFPE) and fixed frozen sections, both of which are widely used, may require different methods. In this study, we optimized blood vessel staining in mouse brain tissue, testing both FFPE and frozen fixed sections. A panel of immunohistochemical blood vessel markers were tested (including CD31, CD34, collagen IV, DP71, and VWF), to evaluate their suitability for digital pathological analysis. Collagen IV provided the best immunostaining results in both FFPE and frozen fixed murine brain sections, with highly-specific staining of large and small blood vessels and low background staining. Subsequent analysis of collagen IV-stained sections showed region and sex-specific differences in vessel density and vessel wall thickness. We conclude that digital pathology provides a useful tool for relatively unbiased analysis of the murine cerebrovasculature, provided proper protein markers are used.

Background: Exercise-associated secondary amenorrhea results in estrogen deficiency, which may lead to dysfunction in estrogen's normal cardioprotective pathways. Estrogen may be essential in a woman's endothelial adaptations to exercise. The objective of this review was to assess the association between secondary amenorrhea in physically active women and cardiovascular disease (CVD) risk., Methods and Results: A literature search was performed in January 2023 and updated in August 2023 of the Cumulative Index to Nursing and Allied Health Literature (EBSCOhost), Cochrane Library, Embase (Ovid), MEDLINE (Ovid), SPORTDiscus (EBSCOhost), and Scopus from inception to present with no date or language limitations. Citation chaining was done to screen for additional studies. Eight sources were searched for gray literature. Studies that compared physically active women with amenorrhea to physically active women with eumenorrhea aged 18 to 35 years with evidence of CVD, alterations to cardiovascular physiology, or CVD risks were included. Eighteen observational studies from 3 countries were included. Overall, the quality of evidence was good. A meta-analysis was performed. Physically active women with secondary amenorrhea had significantly lower estradiol, flow-mediated dilation, resting heart rate, systolic blood pressure, and diastolic blood pressure and higher total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol., Conclusions: Estrogen deficiency resulting from exercise-associated secondary amenorrhea in physically active women may impact cardiovascular physiology and certain CVD risk factors. The research in this area is observational; therefore, findings should be interpreted cautiously. However, as exercise-associated secondary amenorrhea is reversible and the primary prevention of CVD is important for public health, it may be important to treat secondary amenorrhea and restore estrogen levels.

Introduction: The burden of metabolic syndrome (MetS) and its components has been increasing mainly amongst male individuals. Nevertheless, clinical outcomes related to MetS (i.e., cardiovascular diseases), are worse among female individuals. Whether these sex differences in the components and sequalae of MetS are influenced by gender (i.e., psycho-socio-cultural factors)) is a matter of debate.  Therefore, the purpose of this study was to determine the association between gender-related factors and the development of MetS, and to assess if the magnitude of the associations vary by sex., Method: Data from the Colaus/PsyColaus study, a prospective population-based cohort of 6,734 middle-aged participants in Lausanne (Switzerland) (2003-2006) were used. The primary endpoint was the development of MetS as defined by the Adult Treatment Panel III of the National Cholesterol Education Program. Multivariable models were estimated using logistic regression to assess the association between gender-related factors and the development of MetS. Two-way interactions between sex,  age and gender-related factors were also tested., Results: Among 5,195 participants without MetS (mean age=51.3 ± 10.6, 56.1 % females), 27.9 % developed MetS during a mean follow-up of 10.9 years. Female sex (OR:0.48, 95 %CI:0.41-0.55) was associated with decreased risk of developing MetS. Conversely, older age, educational attainment less than university, and low income were associated with an increased risk of developing MetS. Statistically significant interaction between sex and strata of age, education, income, smoking, and employment were identified showing that the reduced risk of MetS in female individuals was attenuated in the lowest education, income, and advanced age strata. However, females who smoke and reported being employed demonstrated a decreased risk of MetS compared to males. Conversely smoking and unemployment were significant risk factors for MetS development among male adults., Conclusions: Gender-related factors such as income level and educational attainment play a greater role in the development of MetS in female than individuals. These factors represent novel modifiable targets for implementation of sex- and gender-specific strategies to achieve health equity for all people., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Purpose: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models., Methods: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics., Results: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease., Conclusion: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models' Type I error and statistical power for identifying covariates associated with DIF., (© 2023. The Author(s).)

Purpose: Patients with coronary artery disease (CAD) experience significant angina symptoms and lifestyle changes. Revascularization procedures can result in better patient-reported outcomes (PROs) than optimal medical therapy (OMT) alone. This study evaluates the impact of response shift (RS) on changes in PROs of patients with CAD across treatment strategies., Methods: Data were from patients with CAD in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease (APPROACH) registry who completed the 16-item Canadian version of the Seattle Angina Questionnaire at 2 weeks and 1 year following a coronary angiogram. Multi-group confirmatory factor analysis (MG-CFA) was used to assess measurement invariance across treatment groups at week 2. Longitudinal MG-CFA was used to test for RS according to receipt of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical therapy (OMT) alone., Results: Of the 3116 patients included in the analysis, 443 (14.2%) received CABG, 2049(65.8%) PCI, and the remainder OMT alone. The MG-CFA revealed a partial-strong invariance across the treatment groups at 2 weeks (CFI = 0.98, RMSEA [90% CI] = 0.05 [0.03, 0.06]). Recalibration RS was detected on the Angina Symptoms and Burden subscale and its magnitude in the OMT, PCI, and CABG groups were 0.32, 0.28, and 0.53, respectively. After adjusting for RS effects, the estimated target changes were largest in the CABG group and negligible in the OMT group., Conclusion: Adjusting for RS is recommended in studies that use SAQ-CAN to assess changes in patients with CAD who have received revascularization versus OMT alone., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: The objective of this review is to assess the association between secondary amenorrhea in physically active women and cardiovascular disease risk., Introduction: It is well established that a woman's risk of cardiovascular disease greatly increases after menopause. The sharp decline in estrogen is seen as a causal factor. Exercise-induced secondary amenorrhea results in estrogen deficiency, which may lead to dysfunction in estrogen's cardioprotective pathways. Further, estrogen may be essential in a woman's endothelial adaptations to exercise. The impact of secondary amenorrhea on cardiovascular disease risk in premenopausal women is not well established., Inclusion Criteria: This review will consider studies that include physically active women experiencing amenorrhea in any country. Only studies that present evidence of cardiovascular disease, alterations to cardiovascular physiology, or data on cardiovascular risk factors (eg, lipid profile changes) will be considered. The review will consider experimental or observational epidemiological study designs., Methods: Searches will be conducted in CINAHL (EBSCOhost), the Cochrane Library, Embase (Ovid), MEDLINE (Ovid), SPORTDiscus (EBSCOhost), and Scopus from inception to present with no date or language limitations. Two independent reviewers will screen titles, abstracts, and full texts, appraise methodological quality, and extract data from studies. Where possible, studies will be pooled in a statistical meta-analysis in addition to subgroup analyses. Where pooling is not possible, the findings will be presented in narrative format. Certainty of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Review Registration: PROSPERO CRD42023360781., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 JBI.)

Introduction: Preeclampsia and gestational diabetes mellitus share risk factors such as obesity and increased maternal age, which have become more prevalent in recent decades. We examined changes in the prevalence of preeclampsia and gestational diabetes between 2005 and 2018 in Denmark and Alberta, Canada, and investigated whether the observed trends can be explained by changes in maternal age, parity, multiple pregnancy, comorbidity, and body mass index (BMI) over time., Material and Methods: This study was a register-based cohort study conducted using data from the Danish National Health Registers and the provincial health registers of Alberta, Canada. We included in the study cohort all pregnancies in 2005-2018 resulting in live-born infants and used binomial regression to estimate mean annual increases in the prevalence of preeclampsia and gestational diabetes in the two populations across the study period, adjusted for maternal characteristics., Results: The study cohorts included 846 127 (Denmark) and 706 728 (Alberta) pregnancies. The prevalence of preeclampsia increased over the study period in Denmark (2.5% to 2.9%) and Alberta (1.7% to 2.5%), with mean annual increases of 0.03 (95% confidence interval [CI] 0.02-0.04) and 0.06 (95% CI 0.05-0.07) percentage points, respectively. The prevalence of gestational diabetes also increased in Denmark (1.9% to 4.6%) and Alberta (3.9% to 9.2%), with average annual increases of 0.20 (95% CI 0.19-0.21) and 0.44 (95% CI 0.42-0.45) percentage points. Changes in the distributions of maternal age and BMI contributed to increases in the prevalence of both conditions but could not explain them entirely., Conclusions: The prevalence of both preeclampsia and gestational diabetes increased significantly from 2005 to 2018, which portends future increases in chronic disease rates among affected women. Increasing demand for long-term follow up and care will amplify the existing pressure on healthcare systems., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Calcineurin (CN) is a Ca 2+ /calmodulin-dependent protein phosphatase. In healthy tissue, CN exists mainly as a full-length (∼60 kDa) highly-regulated protein phosphatase involved in essential cellular functions. However, in diseased or injured tissue, CN is proteolytically converted to a constitutively active fragment that has been causatively-linked to numerous pathophysiologic processes. These calpain-cleaved CN fragments (∆CN) appear at high levels in human brain at early stages of cognitive decline associated with Alzheimer's disease (AD)., New Method: We developed a monoclonal antibody to ∆CN, using an immunizing peptide corresponding to the C-terminal end of the ∆CN fragment., Results: We obtained a mouse monoclonal antibody, designated 26A6, that selectively detects ∆CN in Western analysis of calpain-cleaved recombinant human CN. Using this antibody, we screened both pathological and normal human brain sections provided by the University of Kentucky's Alzheimer's Disease Research Center. 26A6 showed low reactivity towards normal brain tissue, but detected astrocytes both surrounding AD amyloid plaques and throughout AD brain tissue. In brain tissue with infarcts, there was considerable concentration of 26A6-positive astrocytes within/around infarcts, suggesting a link with anoxic/ischemia pathways., Comparison With Existing Method: The results obtained with the new monoclonal are similar to those obtained with a polyclonal we had previously developed. However, the monoclonal is an abundant tool available to the dementia research community., Conclusions: The new monoclonal 26A6 antibody is highly selective for the ∆CN proteolytic fragment and labels a subset of astrocytes, and could be a useful tool for marking insidious brain pathology and identifying novel astrocyte phenotypes., Competing Interests: Declaration of Competing Interest The monoclonal antibody, 26A6, described in this paper is part of US Patent Application No 17/325,085., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Metabolic syndrome (MetS), a cluster of 5 interconnected factors, is the main contributor to cardiovascular disease. Although sex- and gender-related elements have been linked to MetS and its components, this association has not been explored among Canadians with or without MetS. In this study, we aimed to identify sex and gender differences in characteristics of MetS in the Canadian population., Methods: This retrospective cohort study used data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) database. The CPCSSN contains de-identified electronic health records of >1.5 million Canadians (2010-2019). Individuals 35 to 75 years of age who had a primary care encounter formed the study sample (N=37,813). Multiple logistic regression models were used to estimate adjusted odds ratios for sex and gender differences among Canadians with and without MetS, which was the primary outcome variable., Results: The estimated prevalence of MetS was 41.9%. The risk of developing MetS was significantly lower among females compared with males (odds ratio 0.73, 95% confidence interval 0.70 to 0.76). However, the risk was higher in females who used antidepressants (odds ratio 1.53, 95% confidence interval 1.42 to 1.65). An equal distribution of deprivation indexes was observed between males and females with MetS, with risk slightly higher for those with material deprivation. Females were found to be the most socially deprived., Conclusions: This study provides important sex- and gender-specific differences in MetS among Canadians. Targeting sex- and gender-specific risk factors could assist in reversing the trend of adverse cardiovascular outcomes associated with MetS., (Copyright © 2023 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

This final chapter of the Canadian Women's Heart Health Alliance "ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women" presents ATLAS highlights from the perspective of current status, challenges, and opportunities in cardiovascular care for women. We conclude with 12 specific recommendations for actionable next steps to further the existing progress that has been made in addressing these knowledge gaps by tackling the remaining outstanding disparities in women's cardiovascular care, with the goal to improve outcomes for women in Canada., (© 2023 The Authors.)

Despite significant progress in medical research and public health efforts, gaps in knowledge of women's heart health remain across epidemiology, presentation, management, outcomes, education, research, and publications. Historically, heart disease was viewed primarily as a condition in men and male individuals, leading to limited understanding of the unique risks and symptoms that women experience. These knowledge gaps are particularly problematic because globally heart disease is the leading cause of death for women. Until recently, sex and gender have not been addressed in cardiovascular research, including in preclinical and clinical research. Recruitment was often limited to male participants and individuals identifying as men, and data analysis according to sex or gender was not conducted, leading to a lack of data on how treatments and interventions might affect female patients and individuals who identify as women differently. This lack of data has led to suboptimal treatment and limitations in our understanding of the underlying mechanisms of heart disease in women, and is directly related to limited awareness and knowledge gaps in professional training and public education. Women are often unaware of their risk factors for heart disease or symptoms they might experience, leading to delays in diagnosis and treatments. Additionally, health care providers might not receive adequate training to diagnose and treat heart disease in women, leading to misdiagnosis or undertreatment. Addressing these knowledge gaps requires a multipronged approach, including education and policy change, built on evidence-based research. In this chapter we review the current state of existing cardiovascular research in Canada with a specific focus on women., (© 2023 The Authors.)

The impact of the presence or absence of sex hormones on women's health is woefully underresearched. Fundamentally, women's bodies are now understood to spend considerable time under widely fluctuating hormonal influences, including puberty, pregnancy, peripartum, and menopause, and a woman's vessels are therefore preset for functional and physiological alterations based on levels of sex hormones. However, our understanding of the influences of sex hormones on the regulation of a multitude of biological and physiological processes has not translated into the development and/or collection or analyses of data on therapeutic treatments and/or outcomes in the context of women's disease management., (© 2023 The Authors.)

Background: Cardiovascular diseases (CVDs) are the leading cause of premature death for Canadian women, which may be due partly to a lack of awareness of the presentation of acute coronary events in emergency departments (EDs). To address an identified gap in women's cardiovascular care, we sought to describe the clinical and comorbid factors of women who, following discharge from an ED, suffered a myocardial infarction (MI)., Methods: Descriptive analyses were completed on a cohort of women who presented to an ED in Alberta, Canada, between January 1, 2010 and December 31, 2020, were discharged, and within 30 days of their index ED visit, were admitted to the hospital with an MI. The cohort was explored for clinical and comorbid data, ED visits pre-MI, type of MI, and presenting complaint/ primary diagnosis for the index ED visit., Results: 1380 women were included in this analysis with a mean age of 67 (standard deviation ±13) years. The frequencies of hypertension, diabetes, and dyslipidemia among the youngest women, aged 18-45 years, were 47.5%, 31.3%, and 48.8%, respectively. Women across all ages demonstrated a high prevalence of traditional CVD risk factors, and 22% of women presented to an ED 2 or more times within the 30 days pre-MI., Conclusions: Regardless of their age, the women in this cohort had notable CVD risk factors. Future research is required to better understand the phenomenon of women presenting multiple times to an ED pre-MI. Research is needed on life-stage-specific factors of women presenting to EDs pre-MI, to help reduce MI incidence., (© 2023 The Authors.)

Objective: Mental health issues are closely associated with symptoms and outcomes of cardiovascular diseases (CVDs). The magnitude of this problem is alarmingly high in low and middle-income countries (LMICs). This systematic review and meta-analysis aimed to examine the effectiveness of psychosocial interventions on mental health outcomes among patients with CVDs living in LMICs., Methods: This review includes Randomized controlled trials (RCTs) and quasi-experimental studies conducted on adult patients who had a CVD and/or hypertension and located in LMICs. Studies published in English between 2010 and March, 2021 and which primarily reported mental health outcomes of resilience, self-efficacy, Quality of life (QoL), depression and anxiety were included. Studies were screened, extracted and critically appraised by two independent reviewers. Meta-analysis was conducted for RCTs and narrative summaries were conducted for all other studies. PRISMA guidelines were followed for reporting review methods and findings., Results: 109 studies included in this review reported educational, nursing, behavioral and psychological, spiritual, relaxation, and mindfulness interventions provided by multidisciplinary teams. 14 studies reported self-efficacy, 70 reported QoL, 62 reported one or both of anxiety and depression, and no study was found that reported resilience as an outcome in this population. Pooled analysis showed improvements in self-efficacy and QoL outcomes. The majority of studies showed improvement in outcomes, though the quality of the included studies varied., Conclusion: Patients with CVDs in LMICs may experience improved mental health through the use of diverse psychosocial interventions. Evaluations are needed to investigate whether the impact of interventions on mental health are sustained over time., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Evidence suggests that intensive care unit (ICU) survivors often suffer long-term complications such as post-intensive care syndrome (PICS) and post-traumatic stress disorder (PTSD) from critical illness and ICU stay. PICS and PTSD affect both ICU survivors and their families, which overburdens the healthcare systems. Lack of evidence on the comparative psychometric properties of assessment tools is a major barrier in evidence-based screening for post-ICU symptomatology and health-related quality of life., Objectives: We aimed to identify existing tools for screening PTSD and PICS in ICU survivors and their families and to examine evidence on the validity, reliability, sensitivity, and specificity of existing tools, as reflected in published peer-reviewed studies., Method: A scoping review based on literature searches (CINAHL, MEDLINE, EMBASE, PsycINFO, Scopus, Health and Psychosocial Instruments, Dissertations and Theses Global, and Google Scholar) and predefined eligibility criteria was conducted according to current scoping review guidelines., Findings: We identified 44 studies reporting on the development and assessment of psychometric properties of PICS/PTSD in ICU survivors or families globally. We identified five tools addressing all three aspects of PICS manifestations, one tool for both physical and mental aspects of PICS, and fivefive tools for quality-of-life assessment in ICU survivors. Altogether, 25 tools assess only one aspect of PICS: five for cognitive impairment, seven for physical impairment, and 13 for mental health impairment and PTSD in ICU survivors. However, only two tools were found for PICS-family assessment. Other findings include (i) unclear validity and often limited feasibility of tools, (ii) low diagnostic accuracy of cognitive assessment tools, and (iii) evidence of appropriate psychometric properties and feasibility of psychological health assessment tools., Conclusion: These results have implications for the selection and implementation of the assessment methods as a means for promoting meaningful patient-centred clinical outcomes to minimise long-term sequelae, reduce the rate of rehospitalisation, and optimise recovery after ICU discharge., Competing Interests: Conflict of interest The authors have no conflict of interest to disclose., (Copyright © 2022 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Provider communication training is effective for increasing HPV vaccination rates among U.S. adolescents. However, such trainings often rely on in-person meetings, which can be burdensome for providers and costly to implement. To evaluate the feasibility of Checkup Coach, an app-based coaching intervention, to improve provider communication about HPV vaccination. In 2021, we offered Checkup Coach to providers in 7 primary care clinics in a large integrated delivery system. Participating providers (n = 19) attended a 1-h interactive virtual workshop that taught 5 high-quality practices for recommending HPV vaccination. Providers then had 3 months of access to our mobile app, which offered ongoing communication assessments, tailored tips for addressing parents' concerns, and a dashboard of their clinic's HPV vaccination coverage. Online surveys assessed pre-/post-intervention changes in providers' perceptions and communication behaviors. Compared to baseline, more providers reported high-quality HPV vaccine recommendation practices at 3-month follow-up (47% vs. 74%, p < .05). Providers' knowledge, self-efficacy, and shared commitment to improving HPV vaccination also improved (all p < .05). Although we found improvements in several other cognitions after the workshop, these changes did not retain statistical significance at 3 months. About three-quarters (78%) of providers used the mobile app, logging 2.3 sessions on average. Most providers agreed the app was easy to use (mean = 4.7/5.0), a convenient way to get vaccination data (mean = 4.6/5.0), and a tool they would recommend (mean = 4.3/5.0). Our app-based coaching intervention demonstrated feasibility and warrants additional evaluation as a novel mode for training providers to improve their HPV vaccine communication., (© Society of Behavioral Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Women vs men have major differences in terms of risk-factor profiles, social and environmental factors, clinical presentation, diagnosis, and treatment of cardiovascular disease. Women are more likely than men to experience health issues that are complex and multifactorial, often relating to disparities in access to care, risk-factor prevalence, sex-based biological differences, gender-related factors, and sociocultural factors. Furthermore, awareness of the intersectional nature and relationship of sociocultural determinants of health, including sex and gender factors, that influence access to care and health outcomes for women with cardiovascular disease remains elusive. This review summarizes literature that reports on under-recognized sex- and gender-related risk factors that intersect with psychosocial, economic, and cultural factors in the diagnosis, treatment, and outcomes of women's cardiovascular health., (© 2023 The Authors.)

Brain aging is a naturally occurring process resulting in the decline of cognitive functions and increased vulnerability to develop age-associated disorders. Fluctuation in lipid species is crucial for normal brain development and function. However, impaired lipid metabolism and changes in lipid composition in the brain have been increasingly recognized to play a crucial role in physiological aging, as well as in several neurodegenerative diseases. In the last decades, the role of sexual dimorphism in the vulnerability to develop age-related neurodegeneration has increased. However, further studies are warranted for detailed assessment of how age, sex, and additional non-biological factors may influence the lipid changes in brains. The aim of this work is to address the presence of sex differences in the brain lipid changes that occur along aging, and in the two most common age-related neurodegenerative disorders (Alzheimer's and Parkinson's diseases). We included the studies that assessed lipid-related alterations in the brain of both humans and experimental models. Additionally, we explored the influence of sex on lipid-lowering therapies. We conclude that sex exerts a notable effect on lipid modifications occurring with age and neurodegeneration, and in lipid-reducing interventions. Therefore, the application of sex as an experimental variable is strongly encouraged for future research in the field of precision medicine approach., (© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Background Gender-related factors are psycho-socio-cultural characteristics and are associated with adverse clinical outcomes in acute myocardial infarction, independent of sex. Whether sex- and gender-related factors contribute to the substantial heterogeneity in hospital length of stay (LOS) among patients with non-ST-segment-elevation myocardial infarction remains unknown. Methods and Results This observational cohort study combined and analyzed data from the GENESIS-PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome study), EVA (Endocrine Vascular Disease Approach study), and VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI [Acute Myocardial Infarction] Patients study) cohorts of adults hospitalized across Canada, the United States, Switzerland, Italy, Spain, and Australia for non-ST-segment-elevation myocardial infarction. In total, 5219 participants were assessed for eligibility. Sixty-three patients were excluded for missing LOS, and 2938 were excluded because of no non-ST-segment-elevation myocardial infarction diagnosis. In total, 2218 participants were analyzed (66% women; mean±SD age, 48.5±7.9 years; 67.8% in the United States). Individuals with longer LOS (51%) were more likely to be White race, were more likely to have diabetes, hypertension, and a lower income, and were less likely to be employed and have completed secondary education. No univariate association between sex and LOS was observed. In the adjusted multivariable model, age (0.62 d/10 y; P <0.001), unemployment (0.63 days; P =0.01), and some of countries included relative to Canada (Italy, 4.1 days; Spain, 1.7 days; and the United States, -1.0 days; all P <0.001) were independently associated with longer LOS. Medical history mediated the effect of employment on LOS. No interaction between sex and employment was observed. Longer LOS was associated with increased 12-month all-cause mortality. Conclusions Older age, unemployment, and country of hospitalization were independent predictors of LOS, regardless of sex. Individuals employed with non-ST-segment-elevation myocardial infarction were more likely to experience shorter LOS. Sociocultural factors represent a potential target for improvement in health care expenditure and resource allocation.

Hypertension (HTN) is a critical primary modifiable risk factor for the development of cardiovascular diseases, with recognized sex-based differences. While sex refers to one's biological genetic makeup and attributes, gender encompasses the individual's psycho-socio-cultural characteristics, including their environment and living conditions. The impact of each gendered variable may differ amongst men and women with respect to HTN. Applying a sex and gender-based lenses to inform our understanding of HTN has the potential to unveil important contributors of HTN-related cardiovascular outcomes. For instance, increased life stressors, work related anxiety and depression, typically have more pronounced effect on women than men with HTN. The impact of social surrounding including marital status and social support on HTN also differs amongst men and women. While married men are less likely to have higher blood pressure, single women, and those who never married are less likely to have HTN. Additionally, the beneficial role of social support is more pronounced in more historically marginalized cultural groups compared to majority. Finally, socioeconomic status, including education level and income have a linear and inverse relationship in blood pressure control in more resource-rich countries. The aim of this review is to summarize how sex and gender interact in shaping the clinical course of HTN demonstrating the importance of both sex and gender in HTN risk and its treatment. Hence, when investigating the role of gendered factors in HTN it is imperative to consider cultural, and social settings. In this narrative we found that employment and education play a significant role in manifestation and control of HTN particularly in women., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Sharing health data for research purposes across international jurisdictions has been a challenge due to privacy concerns. Two privacy enhancing technologies that can enable such sharing are synthetic data generation (SDG) and federated analysis, but their relative strengths and weaknesses have not been evaluated thus far. In this study we compared SDG with federated analysis to enable such international comparative studies. The objective of the analysis was to assess country-level differences in the role of sex on cardiovascular health (CVH) using a pooled dataset of Canadian and Austrian individuals. The Canadian data was synthesized and sent to the Austrian team for analysis. The utility of the pooled (synthetic Canadian + real Austrian) dataset was evaluated by comparing the regression results from the two approaches. The privacy of the Canadian synthetic data was assessed using a membership disclosure test which showed an F1 score of 0.001, indicating low privacy risk. The outcome variable of interest was CVH, calculated through a modified CANHEART index. The main and interaction effect parameter estimates of the federated and pooled analyses were consistent and directionally the same. It took approximately one month to set up the synthetic data generation platform and generate the synthetic data, whereas it took over 1.5 years to set up the federated analysis system. Synthetic data generation can be an efficient and effective tool for enabling multi-jurisdictional studies while addressing privacy concerns., (© 2023. The Author(s).)

Background: Rural Canadian populations face many challenges due to their geographical isolation, including inaccessible and inequitable primary health care. Specifically, pregnant women are at risk of not receiving prenatal care (PNC) due to physical and social barriers. Inadequate PNC can have detrimental effects on both maternal and neonatal health outcomes. Nurse practitioners (NPs) are an essential group of alternative primary care providers who can provide specialized care, including PNC, to these underserved populations., Objective: The purpose of this narrative review was to identify existing NP-led rural PNC programs in other health care systems to support maternal and neonatal outcomes., Methods: A systematic search was performed to identify articles published between 2002 and 2022 on CINAHL (EBSCO host) and MEDLINE (OVID). Literature was excluded if (1) the context was based in urban centers; (2) the study focused on specialized obstetrical/gynecological-based care; or (3) the study was published in a language other than English. The literature was assessed and synthesized into a narrative review., Results: The initial search identified 34 potentially relevant articles. Five broad themes were identified, including (1) barriers to care; (2) mobile health clinics; (3) collaborative or tiered models of care; (4) telemedicine; and (5) NPs as essential primary care providers., Conclusions: The introduction of a collaborative NP-led approach to rural Canadian settings has the potential to address barriers to PNC and provide efficient, equitable, and inclusive health care., Competing Interests: No competing financial interests exist. The authors certify that the submission is original work and is not under review at any other publication., (© Monica Kneller et al., 2023; Published by Mary Ann Liebert, Inc.)

Cardiovascular diseases represent the leading cause of mortality and morbidity worldwide, and age is an important risk factor. Preclinical models provide supportive evidence toward age-related cardiac changes, as well as allow for the study of pathological aspects of the disease. In the present work, we evaluated the electrocardiogram (ECG) recording in the O. degus during the aging process in both females and males. Taking into account the age and sex, our study provides the normal ranges for the heart rate, duration and voltage of the ECG waves and intervals, as well as electrical axis deviation. We found that the QRS complex duration and QTc significantly increased with age, whereas the heart rate significantly decreased. On the other hand, the P wave, PR and QTc segments durations, S wave voltage and electrical axis were found to be significantly different between males and females. The heart rhythm was also altered in aged animals, resulting in an increased incidence of arrhythmias, especially in males. Based on these results, we suggest that this rodent model could be useful for cardiovascular research, including impacts of aging and biological sex.