Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome.

The human gut microbiome contains the largest number of bacteria in the body and has the potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, and diverse microbiome and overall health. When the gut microbiome becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, and ageing, this has a profound effect on our health and is linked to many diseases, including lifestyle diseases, metabolic diseases, inflammatory diseases, and neurological diseases. While this link in humans is largely an association of dysbiosis with disease, in animal models, a causative link can be demonstrated. The link between the gut and the brain is particularly important in maintaining brain health, with a strong association between dysbiosis in the gut and neurodegenerative and neurodevelopmental diseases. This link suggests not only that the gut microbiota composition can be used to make an early diagnosis of neurodegenerative and neurodevelopmental diseases but also that modifying the gut microbiome to influence the microbiome-gut-brain axis might present a therapeutic target for diseases that have proved intractable, with the aim of altering the trajectory of neurodegenerative and neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, and attention-deficit hyperactivity disorder, among others. There is also a microbiome-gut-brain link to other potentially reversible neurological diseases, such as migraine, post-operative cognitive dysfunction, and long COVID, which might be considered models of therapy for neurodegenerative disease. The role of traditional methods in altering the microbiome, as well as newer, more novel treatments such as faecal microbiome transplants and photobiomodulation, are discussed.

Aromas Influencing the GABAergic System.

Aromas have a powerful influence in our everyday life and are known to exhibit an array of pharmacological properties, including anxiolytic, anti-stress, relaxing, and sedative effects. Numerous animal and human studies support the use of aromas and their constituents to reduce anxiety-related symptoms and/or behaviours. Although the exact mechanism of how these aromas exert their anxiolytic effects is not fully understood, the GABAergic system is thought to be primarily involved. The fragrance emitted from a number of plant essential oils has shown promise in recent studies in modulating GABAergic neurotransmission, with GABAA receptors being the primary therapeutic target. This review will explore the anxiolytic and sedative properties of aromas found in common beverages, such as coffee, tea, and whisky as well aromas found in food, spices, volatile organic compounds, and popular botanicals and their constituents. In doing so, this review will focus on these aromas and their influence on the GABAergic system and provide greater insight into viable anxiety treatment options.

Atrial fibrillation in COVID-19: A review of possible mechanisms.

A relationship between COVID-19 infection and an increasing incidence of atrial fibrillation has been observed. However, the underlying pathophysiology as a precipitant to AF has not been reviewed. This paper will consider the possible pathological and immunological AF mechanisms as a result, of COVID-19 infection. We discuss the role myocardial microvascular pericytes expressing the ACE-2 receptor and their potential for an organ-specific cardiac involvement with COVID-19. Dysfunctional microvascular support by pericytes or endothelial cells may increase the propensity for AF via increased myocardial inflammation, fibrosis, increased tissue edema, and interstitial hydrostatic pressure. All of these factors can lead to electrical perturbances at the tissue and cellular level. We also consider the contribution of Angiotensin, pulmonary hypertension, and regulatory T cells as additional contributors to AF during COVID-19 infection. Finally, reference is given to two common drugs, corticosteroids and metformin, in COVID-19 and how they might influence AF incidence.

Effects of a health worker-led 3-month yoga intervention on blood pressure of hypertensive patients: a randomised controlled multicentre trial in the primary care setting.

BACKGROUND: Hypertension control remains a major challenge globally. A recent systematic review suggested that yoga has beneficial effects on reducing blood pressure. However, the role of yoga in hypertension management in primary health care has received little attention, and no studies have evaluated the impact of a yoga program fully delivered by health care staff on hypertension. This study, therefore, assessed the effects of a health worker-led yoga intervention on blood pressure reduction among hypertensives patients in the primary care setting. METHODS: This was a multicentric, two-arm, randomised trial conducted among hypertensive patients in seven Ayurveda Health Centres in Nepal between March 2017 and June 2018. One hundred and twenty-one participants who were on or without medications were randomised to intervention (n = 61) and wait-list control (n = 60) groups using stratified block randomisation. Participants in the intervention arm received an intervention consisting of an initial five-day structured yoga training at the centres and then a further home-based practice of yoga for five days a week for the following 90 days. Both intervention and control groups also participated in a 2-h health education session. The primary outcome of this trial was systolic blood pressure at 90-day follow-up. Data were analysed on an intention-to-treat basis using linear mixed-effects regression models. RESULTS: We included all 121 study participants (intervention/control = 61/60) in the primary analysis (52.1% males; mean ± SD age = 47.8 ± 10.8 years). The difference in systolic blood pressure between the intervention group and the control group was - 7.66 mmHg (95% CI: - 10.4, - 4.93). For diastolic blood pressure, the difference was - 3.86 mmHg (95% CI: - 6.65, - 1.06). No adverse events were reported by the participants. CONCLUSIONS: A yoga program for hypertensive patients consisting of a five-day training in health centres and 90 days of practice at home is effective for reducing blood pressure. Significant benefits for hypertensive patients could be expected if such programmes would become a part of the standard treatment practice. TRIAL REGISTRATION: This trial was prospectively registered with the Clinical Trial Registry of India [ CTRI/2017/02/007822 ] on 10/02/2017.

May Measurement Month 2019: an analysis of blood pressure screening results from Nepal.

May Measurement Month (MMM) is a global initiative to screen high blood pressure (BP) in the community and increase awareness at the population level. High BP is the leading risk factor for mortality worldwide and in Nepal. This study presents the results of the 2019 MMM in Nepal. Opportunistic BP screening was conducted in 30 out of 77 districts across Nepal and aged ≥18 years at the community and public places. BP was measured three times in a seated position. A total of 74 205 individuals participated in the study, mean age 39.9 years, and 58% were male. BP measurements for the second and third readings were available for 69 292 (93.3%) individuals. The proportion of the population that were hypertensive was 27.5% (n = 20 429). Among those hypertensives, 46.3% were aware of their hypertensive status and of these, 37.5% were on antihypertensive medication. Only 54.3% of those on antihypertensive medication had their BP controlled. Of the community screened, those self reporting to have diabetes, current tobacco users, and current alcohol drinkers were 6.7%, 23.6%, and 31.9%, respectively; 20.6% of the participants were overweight, and 6.5% were obese. Since the first BP screening campaign, MMM 2017 in Nepal, the number of participants screened has largely increased over the years. MMM's success in Nepal is through a coordinated mobilization of trained health science students and volunteers in the communities. The Nepal MMM data demonstrates that large community-based BP screening campaigns are possible in low resource settings.

Prevalence and associated factors of hypertension among veterans of the Indian Gorkha regiments living in Pokhara Metropolitan City, Nepal.

BACKGROUND: Hypertension is a major preventable risk factor for cardiovascular disease. Occupational factors such as having served or serving in armed forces may be associated with hypertension. This study aimed to assess the prevalence and factors associated with hypertension among veterans of the Indian Gorkha army living in western Nepal. METHODS: A community-based cross-sectional study was conducted among the veterans living in the Pokhara metropolitan city. Data on blood pressure (BP), anthropometric measurements, and behavioral factors were collected by face-to-face interviews using the World Health Organization's non-communicable disease risk factor surveillance (STEPS) tool. Hypertension was defined as systolic blood pressure (BP) ≥ 140 mm Hg and/or diastolic BP of ≥ 90 mm Hg or currently on antihypertensive medication. RESULTS: The age-adjusted prevalence of hypertension was 66.2 % among the study participants (317). Mean systolic and diastolic blood pressure was 144.5 mmHg (± 18.3) and 89.3mmHg (± 16.0), respectively. Among the hypertensive participants, 67 % were aware of their disease, 90 % of them were under treatment, and 14 % of the individuals who received treatment had their hypertension under control. The proportion of smokers was 12.9 % and alcohol drinker was 86.1 %. One-fourth (25.9 %) of the participants had a family history of hypertension. Veterans aged 55-64 years had higher odds (AOR: 5.3; 95 % CI: 1.8-15.9; p = 0.003) of being associated with hypertension as compared to 35-44 years. Being a current alcohol drinker (AOR: 2.5; 95 % CI: 1.4-4.5; p = 0.003), overweight (AOR: 1.9; 95 % CI: 1.0-3.5; p = 0.04), obese (AOR: 3.1; 95 % CI: 1.1-8.3; p = 0.03) and family history of hypertension (AOR: 2.9; 95 % CI: 1.5-5.8; p = 0.002) were independently associated with hypertension. CONCLUSIONS: Hypertension was prevalent in retired Nepal veterans. Hypertension was associated with a number of modifiable lifestyle and behavioral factors. Our findings suggest the need for screening, education and management of Nepal veterans for hypertension.

Smart Devices and Wearable Technologies to Detect and Monitor Mental Health Conditions and Stress: A Systematic Review.

Recently, there has been an increase in the production of devices to monitor mental health and stress as means for expediting detection, and subsequent management of these conditions. The objective of this review is to identify and critically appraise the most recent smart devices and wearable technologies used to identify depression, anxiety, and stress, and the physiological process(es) linked to their detection. The MEDLINE, CINAHL, Cochrane Central, and PsycINFO databases were used to identify studies which utilised smart devices and wearable technologies to detect or monitor anxiety, depression, or stress. The included articles that assessed stress and anxiety unanimously used heart rate variability (HRV) parameters for detection of anxiety and stress, with the latter better detected by HRV and electroencephalogram (EGG) together. Electrodermal activity was used in recent studies, with high accuracy for stress detection; however, with questionable reliability. Depression was found to be largely detected using specific EEG signatures; however, devices detecting depression using EEG are not currently available on the market. This systematic review highlights that average heart rate used by many commercially available smart devices is not as accurate in the detection of stress and anxiety compared with heart rate variability, electrodermal activity, and possibly respiratory rate.

Stress Watch: The Use of Heart Rate and Heart Rate Variability to Detect Stress: A Pilot Study Using Smart Watch Wearables.

Stress is an inherent part of the normal human experience. Although, for the most part, this stress response is advantageous, chronic, heightened, or inappropriate stress responses can have deleterious effects on the human body. It has been suggested that individuals who experience repeated or prolonged stress exhibit blunted biological stress responses when compared to the general population. Thus, when assessing whether a ubiquitous stress response exists, it is important to stratify based on resting levels in the absence of stress. Research has shown that stress that causes symptomatic responses requires early intervention in order to mitigate possible associated mental health decline and personal risks. Given this, real-time monitoring of stress may provide immediate biofeedback to the individual and allow for early self-intervention. This study aimed to determine if the change in heart rate variability could predict, in two different cohorts, the quality of response to acute stress when exposed to an acute stressor and, in turn, contribute to the development of a physiological algorithm for stress which could be utilized in future smartwatch technologies. This study also aimed to assess whether baseline stress levels may affect the changes seen in heart rate variability at baseline and following stress tasks. A total of 30 student doctor participants and 30 participants from the general population were recruited for the study. The Trier Stress Test was utilized to induce stress, with resting and stress phase ECGs recorded, as well as inter-second heart rate (recorded using a FitBit). Although the present study failed to identify ubiquitous patterns of HRV and HR changes during stress, it did identify novel changes in these parameters between resting and stress states. This study has shown that the utilization of HRV as a measure of stress should be calculated with consideration of resting (baseline) anxiety and stress states in order to ensure an accurate measure of the effects of additive acute stress.

Factors affecting the fruit and vegetable intake in Nepal and its association with history of self-reported major cardiovascular events.

BACKGROUND: The World Health Organization recommends consumption of a minimum of 400 g of fruits and vegetables per day for prevention of cardiovascular disease. Low fruit and vegetable intake is associated with an increased risk of stroke by 11% and ischemic heart disease by 31%. The present study aims to explore factors affecting the fruit and vegetable intake in Nepal and its association with history of self-reported major cardiovascular events (myocardial infarction and stroke). METHOD: Data for this cross-sectional study were collected as part of the study "Community Based Management of Hypertension in Nepal" initiated in the Lekhnath Municipality in 2013. Demographic and nutrition information were collected using the WHO STEPwise approach to a surveillance tool. Descriptive statistics identified the frequency and percentage of fruit and vegetable intake. A Chi-square test examined the association between fruit and vegetable intake and history of self-reported cardiovascular events, socio-demographic and cardiovascular risk factors. Binary logistic regression analysis identified odds ratio with 95% confidence intervals between fruit and vegetable intake and history of self-reported cardiovascular events. RESULTS: The mean and median intake of fruits and vegetables were 3.3 ± 0.79 and 3 servings respectively. Of the 2815 respondents, 2% (59) reported having a history of major cardiovascular events. The adjusted odds of having a history of major cardiovascular events was 2.22 (95%CI, 1.06-4.66) for those who consumed < 3 servings compared to those who consumed ≥3 servings of fruits and vegetables a day. CONCLUSION: The respondents who consumed < 3 servings of fruits and vegetables a day had higher odds of a history of major cardiovascular events in comparison to those who consumed ≥3 servings. This finding may carry a policy recommendation for those settings where the current recommendation of having ≥5 servings of fruits and vegetables a day is not possible. Our findings also suggest that surviving a major cardiovascular event was not enough in itself to modify nutritional intake. As many Nepali consumes low amount of fruits and vegetables, appropriate measures should be taken to increase this consumption to prevent cardiovascular morbidity and mortality.

Impact of acute stress on cortical electrical activity and cardiac autonomic coupling.

Assessment of heart rate variability (reflective of the cardiac autonomic nervous system) has shown some predictive power for stress. Further, the predictive power of the distinct patterns of cortical brain activity and - cardiac autonomic interactions are yet to be explored in the context of acute stress, as assessed by an electrocardiogram and electroencephalogram. The present study identified distinct patterns of neural-cardiac autonomic coupling during both resting and acute stress states. In particular, during the stress task, frontal delta waves activity was positively associated with low-frequency heart rate variability and negatively associated with high-frequency heart rate variability. Low high-frequency power is associated with stress and anxiety and reduced vagal control. A positive association between resting high-frequency heart rate variability and frontocentral gamma activity was found, with a direct inverse relationship of low-frequency heart rate variability and gamma wave coupling at rest. During the stress task, low-frequency heart rate variability was positively associated with frontal delta activity. That is, the parasympathetic nervous system is reduced during a stress task, whereas frontal delta wave activity is increased. Our findings suggest an association between cardiac parasympathetic nervous system activity and frontocentral gamma and delta activity at rest and during acute stress. This suggests that parasympathetic activity is decreased during acute stress, and this is coupled with neuronal cortical prefrontal activity. The distinct patterns of neural-cardiac coupling identified in this study provide a unique insight into the dynamic associations between brain and heart function during both resting and acute stress states.

Associations between health-related self-efficacy and suicidality.

BACKGROUND: Few studies have focused on exploring the association of self-efficacy and suicidal behaviour. In this study, we aim to investigate the association between health-related self-efficacy and suicidality outcomes, including lifetime/recent suicidal ideation, suicidal attempts and future intent of suicide. METHODS: A computer-assisted telephone interview (CATI) system was used to draw potential respondents aged over 15 in Taiwan via telephone numbers, which were selected by a stratified proportional randomization method according to the distribution of population size in different geographic areas of Taiwan. We obtained available information on suicide behaviours for the analysis of 2110 participants. Logistic regression was applied to investigate the independent effect of health-related self-efficacy on life-time suicidal thoughts and attempts. RESULTS: Suicidality measured as suicide ideation and attempted suicide was reported as 12.6 and 2.7% respectively in the sample. Among those with suicide ideation, 9.8% had thoughts of future suicide intent. Female gender, low education, people living alone or separated, history of psychiatric disorders, substance abuse, poor self-rated mental health and physical health were associated with suicidality factors. Low health-related self-efficacy was associated with lifetime suicide ideation, prior suicide attempt and future suicidal intent. Among those with recent suicidal ideation, low health self-efficacy was independently associated with future suicide intent after adjustment of gender, age, education, marital status, substance abuse, psychological distress, poor mental and physical health. CONCLUSION: Health-related self-efficacy was associated with suicide risks across different time points from prior ideation to future intention. Evaluation of the progress of self-efficacy in health may be long-term targets of intervention in suicide prevention strategies.

Impact of a structured yoga program on blood pressure reduction among hypertensive patients: study protocol for a pragmatic randomized multicenter trial in primary health care settings in Nepal.

BACKGROUND: Hypertension control remains a major global challenge. The behavioral approaches recommended for blood pressure reduction are stress reduction, increased exercise and healthy dietary habits. Some study findings suggest that yoga has a beneficial effect in reducing blood pressure. However, the role of yoga on blood pressure has received little attention in existing health care practices in developing countries. This study will be conducted in primary health care facilities in Nepal to assess the effectiveness of a pragmatic yoga intervention to complement standard practice in further reducing blood pressure. METHODS: This will be multicentric, two arms, randomized, nonblinded, pragmatic trial. It will be conducted in seven District Ayurveda Health Centers (DAHCs) in Nepal between July 2017 and June 2018. The study participants will consist of hypertensive patients with or without antihypertensive medication attending to the outpatient department (OPD). One hundred and forty participants will be randomized to treatment or control groups by using a stratified block randomization. At the study site, the treatment arm participants will receive an intervention consisting of five days of structured yoga training and practice of the same package at home with a recommendation of five days a week for the following 90 days. Both the intervention and control groups will receive two hours of health education on lifestyle modifications. The primary outcome of this trial will be the change in systolic blood pressure and it will be assessed after 90 days of the intervention. DISCUSSION: This study will establish the extent to which a yoga intervention package can help reduce blood pressure in hypertensive patients. If proven effective, study findings may be used to recommend the governing bodies and other stakeholders for the integration of yoga in the national healthcare system for the treatment and control of hypertension. TRIAL REGISTRATION: Clinical Trial Registry- India (CTRI); CTRI Reg. No- CTRI/2017/02/007822 . Registered on 10/02/2017.

Self-efficacy reduces the impact of social isolation on medical student's rural career intent.

BACKGROUND: Social isolation in medical students is a subjective experience that may influence medical career decision making. Rural self-efficacy has been shown to influence rural career intentions following a rural clinical placement, however its impact on social isolation during a rural clinical placement has not been previously modeled. The objective of this study is to explore whether self-perception of social isolation is associated with rural career intent in rural medical students. Secondly, to determine whether self-efficacy influences the association between social isolation and rural career intent. METHODS: 2015 data, from a cross-sectional survey of the National Federation of Rural Australian Medical Educators (FRAME) study. Among 619 medical students attending rural clinical schools (RCS), rural career intent was assessed. This included intended rural location for either postgraduate medical specialist or generalist training or completion of that training. Self-efficacy beliefs in rural medical practice were based on a validated scale consisting of six questions. Social isolation was measured asking students whether they felt socially isolated during their RCS placement. RESULTS: 31.3% of surveyed students self-reported feeling socially isolated during their rural placement. Social isolation was associated with reduced rural career intent after controlling for gender, rural background, RCS preference, RCS support and wellbeing. In step-wise logistic regression the association between social isolation and rural intent disappeared with the inclusion of rural self-efficacy. CONCLUSIONS: Social isolation during a rural clinical placement is commonly reported and is shown to reduce rural career intent. High levels of rural clinical self-efficacy reduce the effects of social isolation on future rural workforce intentions.

FTO associations with obesity and telomere length.

This review examines the biology of the Fat mass- and obesity-associated gene (FTO), and the implications of genetic association of FTO SNPs with obesity and genetic aging. Notably, we focus on the role of FTO in the regulation of methylation status as possible regulators of weight gain and genetic aging. We present a theoretical review of the FTO gene with a particular emphasis on associations with UCP2, AMPK, RBL2, IRX3, CUX1, mTORC1 and hormones involved in hunger regulation. These associations are important for dietary behavior regulation and cellular nutrient sensing via amino acids. We suggest that these pathways may also influence telomere regulation. Telomere length (TL) attrition may be influenced by obesity-related inflammation and oxidative stress, and FTO gene-involved pathways. There is additional emerging evidence to suggest that telomere length and obesity are bi-directionally associated. However, the role of obesity risk-related genotypes and associations with TL are not well understood. The FTO gene may influence pathways implicated in regulation of TL, which could help to explain some of the non-consistent relationship between weight phenotype and telomere length that is observed in population studies investigating obesity.

The benefit of exercise training in pulmonary hypertension: a clinical review.

Pulmonary hypertension (PH) is a clinical condition characterised by raised pulmonary artery pressure, which results in increased right ventricular afterload and dyspnoea. This is accompanied by reduced exercise capacity, quality of life and, eventually, death. An increasing range of targeted medications has transformed the treatment of pulmonary arterial hypertension, a specific type of PH. Supervised exercise training is recommended as part of a multifaceted management plan for PH. However, many questions remain regarding how exercise training improves exercise capacity and quality of life. The optimal exercise regimen (frequency, timing, duration and intensity) also remains unclear. This review provides an update on the pathophysiology of exercise impairment in PH, suggests mechanisms by which exercise may improve symptoms and function and offers evidence-based recommendations regarding the frequency and intensity of an exercise programme for patients with PH.

Electrocardiogram QRS duration and associations with telomere length: A cross-sectional analysis in Australian rural diabetic and non-diabetic population.

Prolonged electrocardiogram QRS durations are often present in aging populations. Shorter telomere length is considered a biomarker of cellular aging. Decreased telomere length has been associated with coronary artery risk, and ventricular remodeling. However, the association between telomeres and cardiac conduction abnormalities, such as increased QRS duration are not well understood. A retrospective cross-sectional population was obtained from the CSU Diabetes Screening Research Initiative database where 273 participants had both ECG-derived QRS duration and DNA to permit leukocyte telomere length (LTL) determination. Telomere length was determined using the monochrome multiplex quantitative PCR method to measure mean relative LTL. Resting 12-lead electrocardiograms were obtained from each subject using a Welch Allyn PC-Based ECG system. Relative LTL was moderately negatively associated with QRS duration in type 2 diabetes mellitus (T2DM) patients (R2=0.055), compared to controls (R2=0.010). In general linear models with no adjustments a significant interaction between QRS duration and LTL is observed for a combined population of T2DM and non-diabetics. When we compared T2DM to non-diabetics, we found that T2DM increased the effect size for relative LTL on QRS duration in comparison to controls. Hence, for each 0.1 unit of relative LTL attrition, QRS duration in T2DM patients increased by 3.24ms (95% CI, -63.00 to -1.84), compared to 1.65ms in controls (95% CI, -40.44 to 7.40). In summary we have observed an association between LTL in a rural aging mixed population of T2DM and non-diabetes. We have observed an unadjusted association between QRS duration and LTL in T2DM. We noted that the control group demonstrated no such association. This highlights the complexity of T2DM when exploring disease phenotype-telomere interactions.

The influence of rural clinical school experiences on medical students' levels of interest in rural careers.

BACKGROUND: Australian Rural Clinical School (RCS) programmes have been designed to create experiences that positively influence graduates to choose rural medical careers. Rural career intent is a categorical evaluation measure and has been used to assess the Australian RCS model. Predictors for rural medical career intent have been associated with extrinsic values such as students with a rural background. Intrinsic values such as personal interest have not been assessed with respect to rural career intent. In psychology, a predictor of the motivation or emotion for a specific career or career location is the level of interest. Our primary aims are to model over one year of Australian RCS training, change in self-reported interest for future rural career intent. Secondary aims are to model student factors associated with rural career intent while attending an RCS. METHODS: The study participants were medical students enrolled in a RCS in the year 2013 at the University of New South Wales (UNSW) and who completed the newly developed self-administered UNSW Undergraduate Destinations Study (UDS) questionnaire. Data were collected at baseline and after one year of RCS training on preferred location for internship, work and intended specialty. Interest for graduate practice location (career intent) was assessed on a five-variable Likert scale at both baseline and at follow-up. A total of 165 students completed the UDS at baseline and 150 students after 1 year of follow-up. RESULTS: Factors associated with intent to practise in a rural location were rural background (χ2 = 28.4, P < 0.001), two or more previous years at an RCS (χ2 = 9.0, P = 0.003), and preference for a rural internship (χ2 = 17.8, P < 0.001). At follow-up, 41% of participants who originally intended to work in a metropolitan location at baseline changed their preference and indicated a preference for a rural location. The level of interest in intended practice location was significantly higher for those intending to work in a rural area than those with intention to work in a metropolitan (urban area) location (t = -3.1, P = 0.002). Initial rural career location intention was associated with increased interest levels after 1 year of follow-up (paired t = -2.3, P = 0.02). CONCLUSION: When evaluating the success of RCS outcomes with respect to rural workforce destination, both rural practice intentions and level of interest are key factors related to projected career destination. RCS experience can positively influence practice intent (toward rural practice) and interest levels (toward greater interest in rural practice).

Assessment of Registered Clinical Trial Designs: Comparison of L-Arginine and/or L-Citrulline Interventions for Hypertension.

BACKGROUND: L-Arginine (Arg) is an essential amino acid and a precursor for the synthesis of vascular nitric oxide, while L-Citrulline is a non-essential amino acid substrate for increasing L-arginine. Both L-arginine and L-Citrulline in translational studies may acutely lower the blood pressure. Current meta-analysis for L-arginine or L-Citrulline interventions in blood pressure have identified significant heterogeneity. Clinical trial evidence for L-arginine or L-Citrulline in chronic blood pressure reduction in the general population requires an examination of trial designs, as not all translational studies may have influenced vascular reactivity. Our aims are to explore whether L-arginine and L-citrulline intervention trials in chronic blood pressure consider standardized end points relevant to the general adult populations. METHODS: A step-wise search on clinicaltrials.gov, the U.S. Library of Medicine registry for clinical trials, was performed including the following keyword search parameters: "completed" "L-Citrulline" "L-arginine" trial", and "adults", involving "blood pressure" reduction as a primary end point in adult humans. RESULTS: Of the forty-four completed trials, only five were included for analysis. Following the careful evaluation of trial design, we observed heterogeneity across participant inclusion criteria (population sample size, age range, sex), interventional design (dosages, duration), and primary outcomes, measured with respect to changes in diastolic or systolic blood pressure. CONCLUSION: In conclusion, there is a lack of robust trial design evidence to suggest that L-arginine or L-Citrulline, based on current RCTs in the general population, have an overall positive effect on vascular endothelial reactivity and a beneficial chronic blood pressure-lowering effect. Indeed, conclusions drawn from human meta-analysis studies have been heterogenous between studies, which may be attributed to study design heterogeneity, including differences in sample population, age, and blood pressure at the time of entry. Inconsistencies in the study design poses a challenge for systematic reviews and meta-analysis to accurately assess the effect size and impact of L-arginine or L-citrulline on both systolic and diastolic blood pressure.

A complementary medicine student-led telehealth clinic: evaluating learning & teaching perceptions.

OBJECTIVES: This study evaluates a multi-centered complementary medicine (CM) student-led telehealth clinic during the COVID-19 pandemic. Likert and qualitative responses explore student and educator learning and teaching perceptions of the implementation of a successful telehealth clinic. RESULTS: 51 students and 17 educators completed the survey. Respondents agreed that support from educators (90%) and orientation (70%) assisted effective performance. Over 90% (93%) of all respondents supported telehealth in student-led clinics, whilst 87% encountered barriers such as technical and infrastructure issues. Respondents agreed that telehealth practice skills improved in case history taking (90%), treatment (90%) and building patient rapport (60%). Respondents (61%) disagreed that physical examination was effectively performed, and 100% of respondents agreed telehealth was a valuable learning experience. This study is the first to explore student and educator perceptions of telehealth in an Australian University multi-centered CM student-led clinic. To be successful in an educational environment, students and educators require digital literacy and adequate telehealth practice infrastructure. Whilst some in-person practice skills are transferable to telehealth, educators need to adapt curriculum to ensure counselling and physical examination skills are specifically taught for virtual consultations. Telehealth in clinical practice requires continued investigation and educational development.

The influence of aortic stiffness on carotid stiffness: computational simulations using a human aorta carotid model.

Increased aortic and carotid stiffness are independent predictors of adverse cardiovascular events. Arterial stiffness is not uniform across the arterial tree and its accurate assessment is challenging. The complex interactions and influence of aortic stiffness on carotid stiffness have not been investigated. The aim of this study was to evaluate the effect of aortic stiffness on carotid stiffness under physiological pressure conditions. A realistic patient-specific geometry was used based on magnetic resonance images obtained from the OsiriX library. The luminal aortic-carotid model was reconstructed from magnetic resonance images using 3D Slicer. A series of aortic stiffness simulations were performed at different regional aortic areas (levels). By applying variable Young's modulus to the aortic wall under two pulse pressure conditions, one could examine the deformation, compliance and von Mises stress between the aorta and carotid arteries. An increase of Young's modulus in an aortic area resulted in a notable difference in the mechanical properties of the aortic tree. Regional deformation, compliance and von Mises stress changes across the aorta and carotid arteries were noted with an increase of the aortic Young's modulus. Our results indicate that increased carotid stiffness may be associated with increased aortic stiffness. Large-scale clinical validation is warranted to examine the influence of aortic stiffness on carotid stiffness.