Ranolazine for Symptomatic Management of Microvascular Angina.

BACKGROUND: Ranolazine is approved in the United States and Europe for chronic stable angina. Microvascular angina (MVA) is defined as angina with no obstructive coronary artery disease. STUDY QUESTION: Our objective was to assess the effectiveness of ranolazine at improving angina scores and quality of life in a Canadian cohort with severe refractory angina due to MVA. STUDY DESIGN: We administered questionnaires to 31 patients at baseline and after at least 6 weeks of ranolazine treatment. MEASURES AND OUTCOMES: Validated, clinically significant changes for each Seattle Angina Questionnaire domain and the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form were obtained from the literature. Score changes between baseline and postranolazine use were analyzed using sign test. RESULTS: Patients were mostly female (27 of 31 patients) with a median age of 57 years. After initiation of ranolazine treatment, patients experienced improvements in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form scores (80.6%; P < 0.01) and in 3 of the 4 domains of the Seattle Angina Questionnaire (physical limitation: 73.3%; P = 0.02; treatment satisfaction: 80.6%; P < 0.01; and disease perception: 77.4%; P < 0.01). Patients were less likely to have interactions with the health care system after ranolazine treatment as compared with before (35.5% vs. 93.5%; P < 0.01). CONCLUSIONS: Ranolazine significantly improves symptom control and quality of life in patients with MVA and severe refractory angina and reduces their interaction with the health care system. Given the potentially debilitating effect of chronic angina in MVA, ranolazine may be an effective treatment option.

Closing the Gender Gap Among Canadian Ophthalmology Societies.

OBJECTIVE: To evaluate gender distribution in Canadian ophthalmology societies' leadership and to determine associations between gender, academic productivity, and institutional rank. METHODS: We identified members and assessed their gender composition using publicly available updated webpages. SCOPUS database was used to gather research metrics. RESULTS: In this study, data was collected from 12 Canadian ophthalmology societies, which included 277 executive committee members. Of these, 70.5% (196) were male and 29.1% (81) were female (p < .0001). Males were significantly more prevalent in presidential leadership roles (39 males vs. 23 females, p = .02), while females were more represented in other leadership categories (77 females vs. 61 males, p = .03). The Canadian Ophthalmological Society (COS) showed an upward trend in female representation from 19.2% in 2016 to 42.3% in 2021. Research productivity showed a positive correlation with society leadership rank, with a correlation coefficient of 0.732 for the m-index (p < .001) and 0.356 for the h-index (p < .05). Academic rank was also positively correlated with society leadership rank, with a correlation coefficient of 0.536 (p < .001). There was no significant difference in h-index (12.7 ± 1.0 for males vs. 13.8 ± 1.5 for females, p = .85) or number of publications (48.6 ± 5.1 for males vs. 60.0 ± 11.3 for females, p = .83) between male and female executive members, but females had a higher m-index (0.67 ± 0.05) compared to males (0.58 ± 0.03, p < .05). In academic rank, males were more likely to be associate professors (25% vs. 5% for females, p = .0001) or instructors (14.8% vs. 6.3% for females, p = .05), while a higher proportion of females held assistant professor positions (47.5% for females vs. 30.1% for males, p = .006). CONCLUSION: In this study, we found that males were more prevalent in executive positions, particularly in presidential roles among Canadian ophthalmology societies. The gender distribution in leadership reflected the gender composition of practicing ophthalmologists in Canada. There was a positive correlation between research productivity and society rank, as well as academic position and society rank. Male and female executive members had similar h-index and number of publications, but females had a higher m-index. These findings highlight the need for continued efforts to address gender disparities in ophthalmology leadership.

A familial Alzheimer's disease associated mutation in presenilin-1 mediates amyloid-beta independent cell specific neurodegeneration.

Mutations in the presenilin (PS) genes are a predominant cause of familial Alzheimer's disease (fAD). An ortholog of PS in the genetic model organism Caenorhabditis elegans (C. elegans) is sel-12. Mutations in the presenilin genes are commonly thought to lead to fAD by upregulating the expression of amyloid beta (Aß), however this hypothesis has been challenged by recent evidence. As C. elegans lack amyloid beta (Aß), the goal of this work was to examine Aß-independent effects of mutations in sel-12 and PS1/PS2 on behaviour and sensory neuron morphology across the lifespan in a C. elegans model. Olfactory chemotaxis experiments were conducted on sel-12(ok2078) loss-of-function mutant worms. Adult sel-12 mutant worms showed significantly lower levels of chemotaxis to odorants compared to wild-type worms throughout their lifespan, and this deficit increased with age. The chemotaxis phenotype in sel-12 mutant worms is rescued by transgenic over-expression of human wild-type PS1, but not the classic fAD-associated variant PS1C410Y, when expression was driven by either the endogenous sel-12 promoter (Psel-12), a pan-neuronal promoter (Primb-1), or by a promoter whose primary expression was in the sensory neurons responsible for the chemotaxis behavior (Psra-6, Podr-10). The behavioural phenotype was also rescued by over-expressing an atypical fAD-linked mutation in PS1 (PS1ΔS169) that has been reported to leave the Notch pathway intact. An examination of the morphology of polymodal nociceptive (ASH) neurons responsible for the chemotaxis behavior also showed increased neurodegeneration over time in sel-12 mutant worms that could be rescued by the same transgenes that rescued the behaviour, demonstrating a parallel with the observed behavioral deficits. Thus, we report an Aß-independent neurodegeneration in C. elegans that was rescued by cell specific over-expression of wild-type human presenilin.

Sex, Gender, and Women's Heart Health: How Women's Heart Programs Address the Knowledge Gap.

This article aims to bridge existing knowledge gaps that impact clinical cardiovascular care and outcomes for women in Canada. The authors discuss various aspects of women's heart health, emphasizing the efficacy of multidisciplinary care in promoting women's well-being. The article also identifies the impact of national women's heart health campaigns and the value of peer support in improving outcomes. The article addresses the particular risks that women face, such as pregnancy-related complications and hormone replacement therapy, all of which are associated with cardiovascular events, and highlights the differences in ischemic symptoms between men and women. Despite improvements in acute event outcomes, challenges persist in accessing timely ambulatory care, particularly for women. Canada has responded to these challenges by introducing Women Heart Programs, which offer tailored programs, support groups, and specialized testing. However, these programs remain few in number and are found only in urban settings. Overall, this review identifies sex and gender factors related to women's heart health, underscoring the importance of specialized programs and multidisciplinary care in improving women's cardiovascular health.

Cet article vise à répondre aux incertitudes actuelles qui se répercutent sur les soins cardiovasculaires et les issues cliniques chez les femmes au Canada. Les auteurs abordent différents aspects de la santé cardiaque des femmes, mettant l'accent sur l'efficacité des soins multidisciplinaires pour améliorer le bien-être des femmes. L'article présente également l'effet des campagnes nationales sur la santé cardiaque des femmes et l'importance de l'entraide entre collègues pour améliorer les résultats. L'article traite des risques particuliers touchant les femmes, comme les complications liées à la grossesse et l'hormonothérapie substitutive, qui sont toutes associées à des événements cardiovasculaires, et il souligne les différences entre les hommes et les femmes pour ce qui est des symptômes ischémiques. Bien que des améliorations aient été observées quant à l'issue des événements aigus, des difficultés persistent sur le plan de l'accès rapide à des soins ambulatoires, surtout pour les femmes. Le Canada a répondu à ces difficultés en créant des programmes pour la santé cardiaque des femmes, qui offrent des services adaptés, des groupes de soutien et des analyses spécialisées. Cependant, ils sont encore peu nombreux et accessibles seulement en milieu urbain. Dans l'ensemble, cette analyse définit les facteurs liés au sexe et au genre qui interviennent dans la santé cardiaque des femmes, soulignant l'importance de mettre en place des programmes spécialisés et des soins multidisciplinaires pour améliorer la santé cardiovasculaire des femmes.

Surgical Coaching: Patient Perspectives Regarding Surgeon Coaches in the Operating Room.

BACKGROUND: Surgical coaching programs have been introduced as platforms for ongoing professional development amongst independently practicing surgeons. While there is a plethora of evidence regarding the effectiveness of surgical coaching for practicing staff surgeons, patients' opinions regarding surgical coaching are largely unknown. OBJECTIVES: To determine patients' baseline attitudes and opinions about the hypothetical situation of their treating surgeon having a surgical coach present during their upcoming operation, and to determine patients' baseline knowledge and prior exposure to surgical coaching. DESIGN AND SETTING: This study was conducted at a tertiary hospital in Vancouver, Canada. Patients on the surgical waitlist of 2 independently practicing Otolaryngologists within the subspeciality of Neurotology were invited to participate in the study. Participants engaged in a semi-structured interview to discuss their opinions and knowledge of physician coaches and to learn about surgical coaching. The interview was conducted based on a pre-set script. RESULTS: Of the 100 patients approached, 70 consented to participate. Forty-three (61%) participants identified as female, and the mean age was 56±15 years. Initially, 84% of participants (n = 59) consented to the hypothetical presence of a surgical coach. Post-discussion, this number increased to 95.7% (n = 67, p = 0.04). Prior participant exposure to coaching related to employment, education, athletics, or music was high (90%, n = 63). Younger participants between 25 and 45 years of age were more amenable to the presence of a surgical coach compared to participants >66 years of age (p = 0.01). After the interview, 55 (79%) participants were interested in learning more about surgical coaching. CONCLUSION: Many patients were unaware of the rationale and importance of surgical coaching programs for practicing staff surgeons. Most patients, especially younger patients, were amenable to the presence of a surgical coach during their surgery, and this number increased in all age categories with patient education about surgical coaching.

Neuroligin Plays a Role in Ethanol-Induced Disruption of Memory and Corresponding Modulation of Glutamate Receptor Expression.

Exposure to alcohol causes deficits in long-term memory formation across species. Using a long-term habituation memory assay in Caenorhabditis elegans, the effects of ethanol on long-term memory (> 24 h) for habituation were investigated. An impairment in long-term memory was observed when animals were trained in the presence of ethanol. Cues of internal state or training context during testing did not restore memory. Ethanol exposure during training also interfered with the downregulation of AMPA/KA-type glutamate receptor subunit (GLR-1) punctal expression previously associated with long-term memory for habituation in C. elegans. Interestingly, ethanol exposure alone had the opposite effect, increasing GLR-1::GFP punctal expression. Worms with a mutation in the C. elegans ortholog of vertebrate neuroligins (nlg-1) were resistant to the effects of ethanol on memory, as they displayed both GLR-1::GFP downregulation and long-term memory for habituation after training in the presence of ethanol. These findings provide insights into the molecular mechanisms through which alcohol consumption impacts memory.

One-Year Prospective Follow-up of Women With INOCA and MINOCA at a Canadian Women's Heart Centre.

BACKGROUND: Many women with cardiac chest pain and ischemia or myocardial infarction have no obstructive coronary artery disease (INOCA or MINOCA). Studies suggest that these patients have a decreased quality of life and are at increased risk of cardiovascular events. Our study reports 1-year quality of life, frequency of angina, and outcomes following entry into a multidisciplinary Women's Heart Centre (WHC). METHODS: Patients with INOCA and MINOCA completed questionnaires on baseline demographics and clinical presentation. At 1-year, frequency of chest pain, quality of life, depression and anxiety symptoms, and cardiovascular outcomes were reported and compared with baseline. RESULTS: A total of 154 women with nonobstructive coronary artery disease were included in this study (112 patients with INOCA and 42 with MINOCA). Median age was 59 years, and the most common referral was for chest pain (94% in INOCA and 66% in MINOCA). At baseline, 64% of patients with INOCA and 43% of patients with MINOCA did not have specific diagnoses. Following investigations in the WHC, 71.4% of patients with INOCA established a new or a changed diagnosis (most common was coronary microvascular dysfunction at 68%), whereas 60% of patients with MINOCA established new or changed diagnoses (the most common of which was coronary vasospasm at 60%). At 1-year, participants had significantly decreased chest pain, improved quality of life, and improved mental health. CONCLUSIONS: A multidisciplinary WHC significantly increases the yield of a specific diagnosis in patients with INOCA and MINOCA. Further, attending a WHC could significantly improve the clinical and psychological outcomes of women with INOCA and MINOCA.

Is There a Shared Etiology of Olfactory Impairments in Normal Aging and Neurodegenerative Disease?

As we age, our olfactory function declines. In addition to occurring in normal aging, more rapid decrement of olfactory decline has been associated with several neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). It has been argued that since olfactory deficits occur less frequently or are absent in diseases such as progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy, olfactory deficits can be used for differential diagnoses of AD and PD. The purpose of this review is to provide a survey of current knowledge about the molecular bases and differential patterns of olfactory deficits present in normal aging, AD, and PD. As substantial research has been conducted in this area, the majority of the content of this review focuses on articles published in the past decade. We hypothesize that olfactory deficits in normal aging, AD, and PD may have different underlying causes, and propose the use of model organisms with small, tractable nervous systems and/or easy to manipulate genomes to further investigate the cellular mechanisms responsible for these deficits.

Recent Developments in Sex-Related Differences in Presentation, Prognosis, and Management of Coronary Artery Disease.

Coronary artery disease (CAD) is the most prevalent type of heart disease among women and men. Sex-related differences in the presentation, prognosis, and management of patients with CAD has been increasingly studied. Compared with men, women are more likely to present with multiple comorbidities, have a higher prevalence of psychological risk factors, and present with atypical symptoms. These factors, along with delays in seeking medical attention, might contribute to sex-related treatment differences in women with stable angina and acute coronary syndrome. This review article highlights recent evidence examining sex-related differences in stable CAD patients with obstructive CAD, nonobstructive CAD, as well as myocardial infarction.

Yield of Cardiac Magnetic Resonance Imaging in Patients With Acute Coronary Syndrome and No Obstructive Coronary Artery Disease.

PURPOSE: Ten percent to 25% of women and 6%-10% of men with acute coronary syndrome (ACS) are found to have no obstructive coronary artery disease (CAD) on coronary computed tomography angiogram or invasive coronary angiography. The etiology of presentation is often unclear. We examined the diagnostic yield of cardiac magnetic resonance imaging (CMR) in patients with signs and symptoms suggestive of an ACS and no obstructive CAD. METHODS: We retrospectively studied patients with signs and symptoms suggestive of an ACS and no obstructive CAD on coronary computed tomography angiogram or invasive coronary angiography who had CMR performed at St. Paul's Hospital, British Columbia, Canada, from 2013 to 2015. No obstructive CAD was defined as <50% stenosis in any epicardial artery. We compared CMR diagnostic yield in troponin-positive and troponin-negative patients and determined the etiology of presentation in each category. We also examined gender differences. RESULTS: Ninety-eight patients met inclusion criteria. The average age was 55.8 years, 70% were female, and 60% were troponin positive upon presentation. Abnormal CMR was observed in 35.7% of patients, yielding a diagnosis in 27.9% of females and 53.5% of males (P = 0.02). Troponin-positive patients had a significantly higher prevalence of an abnormal CMR than did troponin-negative patients (44.1% vs. 23.1%; P = 0.03). Myocarditis was more common in troponin-positive patients (25.4% vs. 2.6%; P = 0.002). CONCLUSIONS: Forty-four percent of patients with positive troponin and with signs and symptoms suggestive of an ACS, no obstructive CAD on invasive coronary angiography or coronary computed tomography angiogram, and unclear diagnosis had abnormalities on CMR that identified the diagnosis. CMR should be considered in patients with positive troponin values when the etiology for their presentation is unclear.