Creating the HAPS Physiology Learning Outcomes: terminology, eponyms, inclusive language, core concepts, and skills.

Learning outcomes are an essential element in curriculum development because they describe what students should be able to do by the end of a course or program and they provide a roadmap for designing assessments. This article describes the development of competency-based learning outcomes for a one-semester undergraduate introductory human physiology course. Key elements in the development process included decisions about terminology, eponyms, use of the word "normal," and similar considerations for inclusivity. The outcomes are keyed to related physiology core concepts and to process skills that can be taught along with the content. The learning outcomes have been published under a Creative Commons license by the Human Anatomy and Physiology Society (HAPS) and are available free of charge on the HAPS website.NEW & NOTEWORTHY This article describes the development of competency-based learning outcomes for introductory undergraduate human physiology courses that were published and made available free of charge by the Human Anatomy and Physiology Society (HAPS). These learning outcomes can be edited and are keyed to physiology core concepts and to process skills that can be taught along with the content.

Acute adiponectin delivery is cardioprotective in the aged female rat heart.

AIM: The aged, post-menopausal female heart is characterized by reduced ischemic tolerance, and few therapies currently exist to limit ischemic damage. Adiponectin (APN), a cytokine produced in adipose tissue, limits infarct size and improves functional recovery after ischemia/reperfusion injury in adult hearts. The aim of the present study was to extend these previous studies and determine the cardioprotective efficacy of APN treatment in aged female rats. METHODS: Hearts were isolated from adult (age 6-7 months; n = 10), aged (age 23 months; n = 14) and aged ovariectomized (n = 10) female rats, and subjected to ischemia/reperfusion injury. On ischemia, hearts were infused with 9 µg of APN or vehicle. Adiponectin receptor 1, adiponectin receptor 2 and adenosine monophosphate-dependent kinase (AMPK) were assessed by western blotting, tumor necrosis factor-α and nicotinamide adenine dinucleotide phosphate oxidase levels by real time polymerase chain reaction. Non-reducing western blotting for APN multimers in visceral adipose was also carried out. RESULTS: APN infusion successfully improved post-ischemic left ventricular developed pressure (∼10-15%) and attenuated the rise in end diastolic pressure in all groups (P < 0.05). With ischemia/reperfusion injury, phospho-AMPK increased in all groups with additive effects of APN on increasing phospho-AMPK abundance in aged ovary-intact female rats only (P < 0.001). Age-associated increases in pre-ischemic tumor necrosis factor-α mRNA were unaffected by APN, whereas nicotinamide adenine dinucleotide phosphate oxidase 2 mRNA levels were attenuated by APN in adult and aged ovariectomized female rats. An age-associated decrease in cardiac adiponectin receptor 2 was observed in conjunction with elevated high molecular weight APN in adipose. CONCLUSIONS: The present data suggest that APN might be a relevant therapy for protecting the aging female heart, albeit through divergent mechanisms that are likely influenced by age-associated estrogen availability.

Estrogen receptor beta does not influence ischemic tolerance in the aged female rat heart.

INTRODUCTION: Ischemic heart disease remains the leading cause of morbidity and mortality in aged women, with a 2- to 3-fold increase in incidence following menopause. Clinical trials have failed to demonstrate cardioprotective benefit from chronic estrogen (E(2)) replacement therapy, yet protective effects of E(2) have been demonstrated in adult animal models and are mediated by the estrogen receptor (ER) subtypes ERα and ERß. AIMS: The aim of this study was to determine the effects of acute ERß activation on ischemia/reperfusion (I/R) injury in adult, aged, and aged E(2)-deficient female rats. METHODS: Hearts were isolated from adult (6 months; n = 9), aged (24 months; n = 13), and aged ovariectomized (OVX; n = 14) female Fischer 344 rats and subjected to 47 min of global I and 60 min of R. Rats were acutely treated with the ERß-agonist diarylpropionitrile (DPN; 5 µg/kg) or vehicle 45 min prior to I/R; ERß mRNA and protein levels were also assessed. RESULTS: Acute treatment with DPN had no effect on functional recovery following I/R injury in adult, aged, or aged OVX female rats. Additionally, we were unable to detect ERß mRNA or protein in the adult or aged female rat myocardium. CONCLUSIONS: Here, for the first time, our data suggest that acute ERß activation does not impact ischemic tolerance in the adult or aged female Fischer 344 rat myocardium and this likely due to a lack of detectable ERß.

Increased estrogen receptor ß in adipose tissue is associated with increased intracellular and reduced circulating adiponectin protein levels in aged female rats.

BACKGROUND: Obesity and associated metabolic and cardiovascular disease risk are correlated with reduced circulating adiponectin (APN) levels. Metabolic and cardiovascular disease risk is also increased after menopause and may be linked to disturbances in estrogen receptor (ER) signaling in adipose. OBJECTIVE: We hypothesized that age-associated estrogen (E(2))-deficiency alters the ERα/ß ratio in adipose tissue and increases risk for metabolic disease via APN-ac activated mechanisms. METHODS: Visceral adipose was isolated from adult (6 months) and aged (24 months) female Fisher 344 rats (n = 5-6/group) with ovaries intact or removed by surgical ovariectomy (OVX) and subjected to western blotting. RESULTS: Notably, weight was greatest in aged OVX rats (P < 0.01) and associated with a 2-fold increase in ERß protein versus adult intact rats (P < 0.001). ER levels were increased in aged OVX versus adult OVX rats. Intra-adipocyte APN was also increased in aged OVX rats versus all groups (P < 0.01), whereas circulating APN levels decreased in aged OVX versus adult OVX rats (P < 0.05). Endoplasmic reticulum protein of 44 kDa (Erp44) levels remained the same (P = 0.09). Adiponectin receptor-1 (AdipoR1) and peroxisome proliferator-activated receptor-α (PPAR-α) were also unchanged. AdipoR2, PPAR-γ, and phosphorylated adenosine monophosphate-dependant kinase (pAMPK) to total AMPK ratio all decreased with age (P < 0.05). CONCLUSIONS: Collectively, these data suggested that age-associated increases in ERß paired with decreased PPAR-γ levels might predispose E(2)-deficient postmenopausal women for increased adiposity and associated metabolic and cardiovascular disease risk. Reduced circulating APN and AdipoR2 levels might contribute to age and E(2)-deficiency linked disease progression.

Rapid estrogen receptor-alpha activation improves ischemic tolerance in aged female rats through a novel protein kinase C epsilon-dependent mechanism.

The effects of estrogen deficiency on the loss of cardioprotection with advancing age are complex and poorly understood. A major focus of the current study was to uncover a cardioprotective role for rapid, nongenomic estrogen receptor (ER) signaling in the aged female myocardium. We hypothesized that selective ERalpha activation in aged females would reduce infarct size in part, through reversal of age-associated reductions in mitochondrial protein kinase Cepsilon (PKCepsilon). Hearts isolated from adult (6 month old) and aged (23-24 months old) female F344 rats with ovaries removed (n = 20 per group) were subjected to ischemia/reperfusion (47 min global ischemia). Rats were injected sc with the ERalpha agonist propylpyrazole triol (PPT) or vehicle 45 min before heart isolation (5 microg/kg). Infarct size was greatest in aged vs. adult ovariectomized rats, significantly reduced by PPT, and the protection reversed by prior administration of the ER inhibitor ICI 182,780 (3 mg/kg). Increased ERalpha particulate targeting occurred after PPT in conjunction with reversal of age-related reductions in nuclear PKCepsilon, mitochondrial PKCepsilon and pAkt (P < 0.05). PPT also increased mRNA levels for the PKCepsilon anchoring protein, receptor for activated C kinase2 (RACK2; P < 0.05). Our data suggest, for the first time, that selective ERalpha activation reduces ischemic injury in the aged, estrogen-deficient heart through a mechanism involving nongenomic redistribution of ERalpha and PKCepsilon activation. A novel feed-forward transcriptional mechanism to potentially enhance PKCepsilon-RACK2 interactions was also observed. Collectively, our findings may provide key insight into developing targeted therapeutic interventions in postmenopausal women to reduce ischemia/reperfusion injury, including selective ERalpha mimetics.