Enhancing the understanding of abstract neurophysiology concepts by first-year students at the University of La Réunion.

Teaching physiology can be challenging as students are initially required to understand basic and abstract concepts. Thus, students typically view physiology as a 'difficult' subject and place an emphasis on rote learning and memorization. Here, we attempted to address this knowledge gap by introducing a pedagogical intervention into the neurophysiology lesson plan of first-year medical and health physiology students at the University of La Réunion. This intervention aimed to better link abstract concepts (e.g. saltatory conduction) and a pathological disorder (multiple sclerosis), together with a discussion of a specific therapeutic intervention (fampridine). Students were required to complete readings (focused on neurophysiology aspects) and two online quizzes before two scheduled in-person lectures. They could also pose questions on a dedicated online forum. Thereafter, the in-person lectures discussed questions posted on the online forum, provided feedback on poorly answered questions (from the online quizzes), and dealt with questions posed by students attending classes. Student feedback regarding the pedagogic intervention was assessed by an anonymous online survey. This survey revealed that the pedagogical intervention was positively received. For example, 94% of respondents agreed the course was well developed, while 80% indicated that the pedagogical intervention was beneficial in terms of their understanding of basic and abstract neurophysiology concepts. Together, this pedagogical intervention was enthusiastically received by the students who better understood how basic nerve physiology concepts fit into the broader context, and that such an understanding can result in the development and the roll-out of unique therapeutic interventions for multiple sclerosis.

The impact of chronic stress on intracellular redox balance: A systems level analysis.

Chronic psychosocial stress is implicated in the onset and progression of noncommunicable diseases, and mechanisms underlying this relationship include alterations to the intracellular redox state. However, such changes are often investigated in isolation, with few studies adopting a system level approach. Here, male Wistar rats were exposed to 9.5 weeks of chronic unpredictable mild stress and redox status assays were subsequently performed on cardiac, hepatic, and brain tissues versus matched controls. The stressed rats displayed an anxious phenotype, with lowered plasma corticosterone levels (p = 0.04 vs. Controls) and higher plasma epinephrine concentrations (p = 0.03 vs. Controls). Our findings showed organ-specific redox profiles, with stressed rats displaying increased myocardial lipid peroxidation (p = 0.04 vs. Controls) in the presence of elevated nonenzymatic antioxidant capacity (p = 0.04 vs. Controls). Conversely, hepatic tissues of stressed rats exhibited lowered nonenzymatic antioxidant capacity (p < 0.001 vs. Controls) together with increased superoxide dismutase (SOD) activity (p = 0.05 vs. Controls). The brain displayed region-specific antioxidant perturbations, with increased SOD activity (p = 0.01 vs. Controls) in the prefrontal cortex of the stressed rats. These findings reveal distinct stress-related organ-specific vulnerability to redox perturbations and may provide novel insights into putative therapeutic targets.

Glial cell activity in cardiovascular diseases and risk of acute myocardial infarction.

Growing evidence indicates that the pathophysiological link between the brain and heart underlies cardiovascular diseases, specifically acute myocardial infarction (AMI). Astrocytes are the most abundant glial cells in the central nervous system and provide support/protection for neurons. Astrocytes and peripheral glial cells are emerging as key modulators of the brain-heart axis in AMI, by affecting sympathetic nervous system activity (centrally and peripherally). This review, therefore, aimed to gain an improved understanding of glial cell activity and AMI risk. This includes discussions on the potential role of contributing factors in AMI risk, i.e., autonomic nervous system dysfunction, glial-neurotrophic and ischemic risk markers [glial cell line-derived neurotrophic factor (GDNF), astrocytic S100 calcium-binding protein B (S100B), silent myocardial ischemia, and cardiac troponin T (cTnT)]. Consideration of glial cell activity and related contributing factors in certain brain-heart disorders, namely, blood-brain barrier dysfunction, myocardial ischemia, and chronic psychological stress, may improve our understanding regarding the pathological role that glial dysfunction can play in the development/onset of AMI. Here, findings demonstrated perturbations in glial cell activity and contributing factors (especially sympathetic activity). Moreover, emerging AMI risk included sympathovagal imbalance, low GDNF levels reflecting prothrombic risk, hypertension, and increased ischemia due to perfusion deficits (indicated by S100B and cTnT levels). Such perturbations impacted blood-barrier function and perfusion that were exacerbated during psychological stress. Thus, greater insights and consideration regarding such biomarkers may help drive future studies investigating brain-heart axis pathologies to gain a deeper understanding of astrocytic glial cell contributions and unlock potential novel therapies for AMI.

Can the introduction of an authentic learning exercise lead to the modulation of breakfast behavior in undergraduate students at University of La Réunion?

The authentic teaching and learning approach introduces real-world scenarios into the classroom to better engage Generation Z students. Considering this, we introduced an authentic learning practical exercise (breakfast meal and glycemic variation) to undergraduate biology students at the University of La Réunion (France). Here, students were initially briefed regarding the practical and subsequently determined their baseline glucose values (glucometer). They then consumed 200 mL of fruit juice together with a pain au chocolat (chocolate pastry) and subsequently recorded their glucose values at regular intervals. The last reading was done after 150 min, and they thereafter plotted such data to reveal temporal glycemic variations. During this time, the students also worked on a report to document information collected and began to supply responses to several listed questions. Three weeks after completion of the practical, we evaluated whether this intervention would lead to changes in their views regarding the nature and regularity of breakfast meal intake (employing survey questions). Our findings show that a reasonable proportion of the students indicated that the intervention did change their dietary habits, with 50% sometimes opting for an improved breakfast, whereas 10% also changed their habits albeit for only a small while. Of note, >60% of students indicated that they changed their breakfast intake habits by the end of the endocrinology module. These findings show that the beneficial effects of authentic teaching approaches may elicit relatively long-lasting changes in terms of breakfast behavioral patterns in young people and that such effects may also impact the broader society.NEW & NOTEWORTHY This study introduced an authentic learning exercise (endocrinology practical exercise) to undergraduate biology students and ascertained whether it changed their views regarding the nature and regularity of breakfast meals. Here, many altered their breakfast dietary habits, which persisted even after the completion of their module. Authentic teaching approaches can therefore trigger relatively long-lasting changes in terms of breakfast behavioral patterns in young people and may also impact the broader society.

The dual role of the hexosamine biosynthetic pathway in cardiac physiology and pathophysiology.

The heart is a highly metabolic organ with extensive energy demands and hence relies on numerous fuel substrates including fatty acids and glucose. However, oxidative stress is a natural by-product of metabolism that, in excess, can contribute towards DNA damage and poly-ADP-ribose polymerase activation. This activation inhibits key glycolytic enzymes, subsequently shunting glycolytic intermediates into non-oxidative glucose pathways such as the hexosamine biosynthetic pathway (HBP). In this review we provide evidence supporting the dual role of the HBP, i.e. playing a unique role in cardiac physiology and pathophysiology where acute upregulation confers cardioprotection while chronic activation contributes to the onset and progression of cardio-metabolic diseases such as diabetes, hypertrophy, ischemic heart disease, and heart failure. Thus although the HBP has emerged as a novel therapeutic target for such conditions, proposed interventions need to be applied in a context- and pathology-specific manner to avoid any potential drawbacks of relatively low cardiac HBP activity.

HIV-Related Myocardial Fibrosis: Inflammatory Hypothesis and Crucial Role of Immune Cells Dysregulation.

Although the underlying mechanisms driving human immunodeficiency virus (HIV)-mediated cardiovascular diseases (CVD) onset and progression remain unclear, the role of chronic immune activation as a significant mediator is increasingly being highlighted. Chronic inflammation is a characteristic feature of CVD and considered a contributor to diastolic dysfunction, heart failure, and sudden cardiac death. This can trigger downstream effects that result in the increased release of pro-coagulant, pro-fibrotic, and pro-inflammatory cytokines. Subsequently, this can lead to an enhanced thrombotic state (by platelet activation), endothelial dysfunction, and myocardial fibrosis. Of note, recent studies have revealed that myocardial fibrosis is emerging as a mediator of HIV-related CVD. Together, such factors can eventually result in systolic and diastolic dysfunction, and an increased risk for CVD. In light of this, the current review article will focus on (a) the contributions of a chronic inflammatory state and persistent immune activation, and (b) the role of immune cells (mainly platelets) and cardiac fibrosis in terms of HIV-related CVD onset/progression. It is our opinion that such a focus may lead to the development of promising therapeutic targets for the treatment and management of CVD in HIV-positive patients.

The Role of Immunometabolism in HIV-1 Pathogenicity: Links to Immune Cell Responses.

With the successful roll-out of combination antiretroviral treatment, HIV is currently managed as a chronic illness. Of note, immune activation and chronic inflammation are hallmarks of HIV-1 infection that persists even though patients are receiving treatments. Despite strong evidence linking immune activation and low-grade inflammation to HIV-1 pathogenesis, the underlying mechanisms remain less well-understood. As intracellular metabolism is emerging as a crucial factor determining the fate and activity of immune cells, this review article focuses on how links between early immune responses and metabolic reprograming may contribute to HIV pathogenicity. Here, the collective data reveal that immunometabolism plays a key role in HIV-1 pathogenesis. For example, the shift from quiescent immune cells to its activation leads to perturbed metabolic circuits that are major drivers of immune cell dysfunction and an altered phenotype. These findings suggest that immunometabolic perturbations play a key role in the onset of non-AIDS-associated comorbidities and that they represent an attractive target to develop improved diagnostic tools and novel therapeutic strategies to help blunt HIV-1 pathogenesis.

The implementation of active learning practices in a South African physiology class: a follow-up study.

Although there is increased uptake of active learning approaches in especially developed countries, this is still lagging within the African context. The current study therefore focused on the implementation of group learning at Stellenbosch University, with several modifications versus our earlier, pilot study. Students freely formed small groups at the start of a 5-wk cardiovascular physiology lecture series and were apportioned three separate assignments to complete over this period. This included three in-class group-learning sessions, while students also completed group work outside class times. The active learning element was embedded within a constructive alignment framework. Our data revealed that 75% of the students felt that the in-class sessions was a good use of their time and that they progressively improved their assignment scores, i.e., 67.5 ± 9.3%, 72.4 ± 9.8%, and 76.1 ± 9.5% for the first, second, and final ones, respectively (P < 0.0001). Moreover, the average class score for their final test (68 ± 15.1%) was higher when compared with the average class score (57.5 ± 19.4%) calculated for the previous 3 yr (P < 0.0001). This study revealed two major findings: i.e., 1) students displayed a strong positive response regarding the adoption of in-class collaborative group work, and 2) the introduction of such active learning elements correlated with improved student assignment and test scores. Based on these findings, we propose additional modifications (including a shift to more formative assessments) to ensure even greater success with the roll-out of such active learning elements within the African context.

Mobility Deviations in Adults With Human Immunodeficiency Virus: A Cross-Sectional Assessment Using Gait Analysis, Functional Performance, and Self-Report.

BACKGROUND: Little is known about how human immunodeficiency virus (HIV) affects walking biomechanics, or about associations between HIV-related gait deviations, functional performance, and self-reported outcomes. This paper reports on (1) gait biomechanics and variability in people with HIV (PWH) and (2) associations with clinical tests, self-reported function, and falls. METHODS: A cross-sectional study tested consecutively sampled PWH (n = 50) and HIV-seronegative participants ([SNP] n = 50). Participants underwent 3-dimensional gait analysis, performed clinical tests (short walk and single leg stance tests with and without dual tasking, chair-rise tests, and a physical performance battery), and completed questionnaires about function and falls. Between-group comparisons were done using analysis of covariance. Linear correlations between gait variability, clinical tests, and patient-reported outcomes were established. RESULTS: People with HIV and SNP had comparable median ages (PWH = 36.6, interquartile range [IQR] = 32.0-45.6]; SNP = 31.1, IQR = 23.2-45.1). Compared with SNP, PWH walked slower (adjusted mean difference [MD] = -0.2 meters per second [m/s], 95% confidence interval [CI] = -0.3 to -0.1) with greater variability (adjusted MD = 14.7 variability score points, 95% CI = 9.9-19.5). Moreover, PWH were slower in five-times sit-to-stand (5STS) performance (adjusted MD = 1.9 seconds, 95% CI = 1.00-2.9). Significant deviations in hip kinematics (increased flexion; adjusted MDs = 2.4°-2.8°, P = .012-.016) and knee kinematics (reduced flexion; adjusted MDs = 2.3°-3.7°, P = .007-.027) were found in PWH during dual-task (DT) walking. The PWH's 5STS moderately correlated with larger gait variability (usual pace r = -0.5; dual task r = -0.6), poorer self-reported mobility (r = 0.4) and self-care function (r = 0.5), and fear of falling (P = .003). CONCLUSIONS: People with HIV presented with biomechanical deviations suggestive of a slowed and variable gait, especially under cognitive challenges. Five-times STS may be useful to screen for gait deviations in PWH.

Expansion of GARP-Expressing CD4+CD25-FoxP3+ T Cells and SATB1 Association with Activation and Coagulation in Immune Compromised HIV-1-Infected Individuals in South Africa.

Although antiretroviral treatment lowers the burden of human immunodeficiency virus (HIV)-related disease, it does not always result in immunological recovery. This manifests as persistent chronic inflammation, immune activation or exhaustion that can promote the onset of co-morbidities. As the exact function of regulatory T (Treg) cells in HIV remains unclear, this cross-sectional study investigated three expression markers (Forkhead box protein P3 [FOXP3], glycoprotein A repetitions predominant [GARP], special AT-rich sequence binding protein 1 [SATB1]) and compared their expansion between CD4+CD25- and CD4+CD25++ T cells. Age-matched study subjects were recruited (Western Cape, South Africa) and sub-divided: HIV-negative subjects (n = 12), HIV-positive naïve treated (n = 22), HIV-positive treated based on CD4 count cells/µL (CD4 > 500 and CD4 < 500) (n = 34) and HIV-treated based on viral load (VL) copies/mL (VL < 1000 and VL > 1000) (n = 34). Markers of immune activation (CD38) and coagulation (CD142) on T cells (CD8) were assessed by flow cytometry together with FOXP3, GARP and SATB1 expression on CD4+CD25- and CD4+CD25++ T cells. Plasma levels of interleukin-10 (IL-10; anti-inflammatory marker), IL-6 (inflammatory marker) and D-dimer (coagulation marker) were assessed. This study revealed three major findings in immuno-compromised patients with virological failure (CD4 < 500; VL > 1000): (1) the expansion of the unconventional Treg cell subset (CD4+CD25-FOXP3+) is linked with disease progression markers; (2) increased GARP expression in the CD4+CD25- and CD4+CD25++ subsets; and (3) the identification of a strong link between CD4+CD25-SATB1+ cells and markers of immune activation (CD8+CD38+) and coagulation (CD8+CD142+ and D-dimer).

The effects of physical activity on adipokines in individuals with overweight/obesity across the lifespan: A narrative review.

This narrative review summarizes current knowledge on the effects of physical activity (PA) on adipokine levels in individuals with overweight and obesity. Approximately 90 investigations including randomized control, cross-sectional and longitudinal studies that reported on the effects of a single session of PA (acute) or long-term PA (chronic) on adipokine levels in individuals with overweight/obesity were reviewed. The findings support the notion that there is consensus on the benefits of chronic exercise training-regardless of the mode (resistance vs. aerobic), intensity and cohort (healthy vs. diabetes)-on adipokine levels (such as tumour necrosis factor-alpha, interleukin-6, adiponectin, visfatin, omentin-1 and leptin). However, several confounding factors (frequency, intensity, time and type of exercise) can alter the magnitude of the effects of an acute exercise session. Available evidence suggests that PA, as a part of routine lifestyle behaviour, improves obesity complications by modulating adipokine levels. However, additional research is needed to help identify the most effective interventions to elicit the most beneficial changes in adipokine levels in individuals with overweight/obesity.

The Impact of Sugar-Sweetened Beverage Consumption on the Liver: A Proteomics-based Analysis.

Cardiometabolic complications such as the metabolic syndrome and Type 2 Diabetes Mellitus (T2DM) are major causes of global morbidity and mortality. As sugar-sweetened beverages (SSBs) are implicated in this process, this study aimed to obtain greater mechanistic insights. Male Wistar rats (~200 g) were gavaged with a local SSB every day for a period of six months while the control group was gavaged with an iso-volumetric amount of water. Experimental dosages were calculated according to the surface area-to-volume ratio and were equivalent to 125 mL/day (in human terms). A proteomic analysis was performed on isolated liver samples and thereafter, markers of endoplasmic reticulum (ER) stress, antioxidant/oxidant capacity, calcium regulation, and mitochondrial functionality were assessed. These data show that SSB consumption resulted in (a) the induction of mild hepatic ER stress; (b) altered hepatic mitochondrial dynamics; and (c) perturbed calcium handling across mitochondria-associated ER membranes. Despite significant changes in markers of ER stress, the antioxidant response and calcium handling (proteomics data), the liver is able to initiate adaptive responses to counteract such stressors. However, the mitochondrial data showed increased fission and decreased fusion that may put the organism at risk for developing insulin resistance and T2DM in the longer term.

Chronic stress and endothelial dysfunction: mechanisms, experimental challenges, and the way ahead.

Although chronic stress is an important risk factor for cardiovascular diseases (CVD) onset, the underlying mechanisms driving such pathophysiological complications remain relatively unknown. Here, dysregulation of innate stress response systems and the effects of downstream mediators are strongly implicated, with the vascular endothelium emerging as a primary target of excessive glucocorticoid and catecholamine action. Therefore, this review article explores the development of stress-related endothelial dysfunction by focusing on the following: 1) assessing the phenomenon of stress and complexities surrounding this notion, 2) discussing mechanistic links between chronic stress and endothelial dysfunction, and 3) evaluating the utility of various preclinical models currently employed to study mechanisms underlying the onset of stress-mediated complications such as endothelial dysfunction. The data reveal that preclinical models play an important role in our efforts to gain an increased understanding of mechanisms underlying stress-mediated endothelial dysfunction. It is our understanding that this provides a good foundation going forward, and we propose that further efforts should be made to 1) more clearly define the concept of stress and 2) standardize protocols of animal models with specific guidelines to better indicate the mental complications that are simulated.

Student response to a cooperative learning element within a large physiology class setting: lessons learned.

Physiology students grapple with large amounts of subject content and hence memorize facts to pass examinations. In parallel, students display limited critical-thinking and creative skills, integration abilities, and/or a deeper engagement with subject content. This study aimed to assess the feasibility of introducing active learning methods (cooperative learning) in a relatively large class to final-year undergraduate physiology students (Bachelor of Science stream) at Stellenbosch University in South Africa. An assignment designed to enhance active and engaged learning was made available to the students (n = 225) during the second week of a 5-wk cardiovascular physiology series of lectures. Students were instructed to freely form working groups (n = 3/group) and the assignment was due by the end of the module. Student groups were expected and encouraged to continuously work on the assignment (outside class time). Three cooperative learning slots were also created during class time, with the lecturer and postgraduate students acting as guides. After the module, students anonymously completed an electronic questionnaire. This study revealed three major findings in terms of implementing cooperative learning in large classes within a South African context, i.e., 1) relatively good reception by students with some indication of group work; 2) it is logistically feasible in relatively large classes, although adequate support is crucial; and 3) additional measures need to be adopted to ensure its success.

The Combination Effect of Aspalathin and Phenylpyruvic Acid-2-O-ß-D-glucoside from Rooibos against Hyperglycemia-Induced Cardiac Damage: An In Vitro Study.

Recent evidence shows that rooibos compounds, aspalathin and phenylpyruvic acid-2-O-ß-D-glucoside (PPAG), can independently protect cardiomyocytes from hyperglycemia-related reactive oxygen species (ROS). While aspalathin shows more potency by enhancing intracellular antioxidant defenses, PPAG acts more as an anti-apoptotic agent. Thus, to further understand the protective capabilities of these compounds against hyperglycemia-induced cardiac damage, their combinatory effect was investigated and compared to metformin. An in vitro model of H9c2 cardiomyocytes exposed to chronic glucose concentrations was employed to study the impact of such compounds on hyperglycemia-induced damage. Here, high glucose exposure impaired myocardial substrate utilization by abnormally enhancing free fatty acid oxidation while concomitantly suppressing glucose oxidation. This was paralleled by altered expression of genes involved in energy metabolism including acetyl-CoA carboxylase (ACC), 5' AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor-alpha (PPARα). The combination treatment improved myocardial substrate metabolism, maintained mitochondrial membrane potential, and attenuated various markers for oxidative stress including nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and glutathione content. It also showed a much-improved effect by ameliorating DNA damage when compared to metformin. The current study demonstrates that rooibos compounds offer unique cardioprotective properties against hyperglycemia-induced and potentially against diabetes-induced cardiac damage. These data also support further exploration of rooibos compounds to better assess the cardioprotective effects of different bioactive compound combinations.

Citrus fruit-derived flavonoid naringenin and the expression of hepatic organic cation transporter 1 protein in diabetic rats treated with metformin.

Naringenin possesses many pharmacological effects and may modulate metformin disposition. The purpose of this study was to evaluate the role of naringenin on hepatic expression of organic cation transporter 1 (OCT1) protein and its associated effects on metformin-associated hyperlactataemia in diabetes. Forty-nine male Sprague Dawley rats randomly assigned to seven groups (n = 7) were orally treated daily with 3.0 mL/kg body-weight (BW) of distilled water (group 1) or 60 mg/kg BW of naringenin (groups 2 and 5) or 250 mg/kg BW of metformin (groups 3 and 6), respectively, dissolved in distilled water. Similarly, group 7 was given metformin and naringenin. Groups 4, 5, 6 and 7 were administered intraperitoneally with streptozotocin at a single dose of 60 mg/kg BW to induce diabetes. Glucose tolerance tests were performed. The animals were killed after 8 weeks of treatment, blood was collected, and livers excised for further biochemical analysis. Lowered body-weight, increased polydipsia and reduced hepatic glycogen concentrations were observed in diabetic rats compared to controls. Naringenin only significantly decreased plasma lactate levels, while metformin only or with naringenin significantly increased plasma lactate levels in diabetic compared to non-treated diabetic animals. Metformin only but not naringenin significantly increased plasma lactate levels in non-diabetic compared to control rats. Furthermore, naringenin with or without metformin but not metformin only significantly increased hepatic organic cation transporter 1 (OCT1) expression in diabetic compared to non-treated diabetic rats. Contrastingly, metformin only but not naringenin significantly increased hepatic OCT1 expression in non-diabetic rats compared to controls. Diabetic rats treated with metformin exhibited significantly increased plasma metformin concentrations compared to non-diabetic but naringenin significantly dropped this parameter. Conversely, hepatic metformin concentrations were significantly lower in diabetic rats treated with metformin compared to non-diabetic rats but significantly increased when naringenin was added. These results suggest that naringenin ameliorated hyperglycaemia-induced reduction in hepatic OCT1 expression leading to metformin accumulation and increased lactic acid production.

HIV-related cardiovascular diseases: the search for a unifying hypothesis.

Although the extensive rollout of antiretroviral (ARV) therapy resulted in a longer life expectancy for people living with human immunodeficiency virus (PLHIV), such individuals display a relatively increased occurrence of cardiovascular diseases (CVD). This health challenge stimulated significant research interests in the field, leading to an improved understanding of both lifestyle-related risk factors and the underlying mechanisms of CVD onset in PLHIV. However, despite such progress, the precise role of various risk factors and mechanisms underlying the development of HIV-mediated CVD still remains relatively poorly understood. Therefore, we review CVD onset in PLHIV and focus on 1) the spectrum of cardiovascular complications that typically manifest in such persons and 2) underlying mechanisms that are implicated in this process. Here, the contributions of such factors and modulators and underlying mechanisms are considered in a holistic and integrative manner to generate a unifying hypothesis that includes identification of the core pathways mediating CVD onset. The review focuses on the sub-Saharan African context, as there are relatively high numbers of PLHIV residing within this region, indicating that the greater CVD risk will increasingly threaten the well-being and health of its citizens. It is our opinion that such an approach helps point the way for future research efforts to improve treatment strategies and/or lifestyle-related modifications for PLHIV.