Long-Term Blood Pressure Reductions Following Catheter-Based Renal Denervation: A Systematic Review and Meta-Analysis.

BACKGROUND: Renal denervation is a recognized adjunct therapy for hypertension with clinically significant blood pressure (BP)-lowering effects. Long-term follow-up data are critical to ascertain durability of the effect and safety. Aside from the 36-month follow-up data available from randomized control trials, recent cohort analyses extended follow-up out to 10 years. We sought to analyze study-level data and quantify the ambulatory BP reduction of renal denervation across contemporary randomized sham-controlled trials and available long-term follow-up data up to 10 years from observational studies. METHODS: A systematic review was performed with data from 4 observational studies with follow-up out to 10 years and 2 randomized controlled trials meeting search and inclusion criteria with follow-up data out to 36 months. Study-level data were extracted and compared statistically. RESULTS: In 2 contemporary randomized controlled trials with 36-month follow-up, an average sham-adjusted ambulatory systolic BP reduction of -12.7±4.5 mm Hg from baseline was observed (P=0.05). Likewise, a -14.8±3.4 mm Hg ambulatory systolic BP reduction was found across observational studies with a mean long-term follow-up of 7.7±2.8 years (range, 3.5-9.4 years; P=0.0051). The observed reduction in estimated glomerular filtration rate across the long-term follow-up was in line with the predicted age-related decline. Antihypertensive drug burden was similar at baseline and follow-up. CONCLUSIONS: Renal denervation is associated with a significant and clinically meaningful reduction in ambulatory systolic BP in both contemporary randomized sham-controlled trials up to 36 months and observational cohort studies up to 10 years without adverse consequences on renal function.

Efficient Machine Reading Comprehension for Health Care Applications: Algorithm Development and Validation of a Context Extraction Approach.

BACKGROUND: Extractive methods for machine reading comprehension (MRC) tasks have achieved comparable or better accuracy than human performance on benchmark data sets. However, such models are not as successful when adapted to complex domains such as health care. One of the main reasons is that the context that the MRC model needs to process when operating in a complex domain can be much larger compared with an average open-domain context. This causes the MRC model to make less accurate and slower predictions. A potential solution to this problem is to reduce the input context of the MRC model by extracting only the necessary parts from the original context. OBJECTIVE: This study aims to develop a method for extracting useful contexts from long articles as an additional component to the question answering task, enabling the MRC model to work more efficiently and accurately. METHODS: Existing approaches to context extraction in MRC are based on sentence selection strategies, in which the models are trained to find the sentences containing the answer. We found that using only the sentences containing the answer was insufficient for the MRC model to predict correctly. We conducted a series of empirical studies and observed a strong relationship between the usefulness of the context and the confidence score output of the MRC model. Our investigation showed that a precise input context can boost the prediction correctness of the MRC and greatly reduce inference time. We proposed a method to estimate the utility of each sentence in a context in answering the question and then extract a new, shorter context according to these estimations. We generated a data set to train 2 models for estimating sentence utility, based on which we selected more precise contexts that improved the MRC model's performance. RESULTS: We demonstrated our approach on the Question Answering Data Set for COVID-19 and Biomedical Semantic Indexing and Question Answering data sets and showed that the approach benefits the downstream MRC model. First, the method substantially reduced the inference time of the entire question answering system by 6 to 7 times. Second, our approach helped the MRC model predict the answer more correctly compared with using the original context (F1-score increased from 0.724 to 0.744 for the Question Answering Data Set for COVID-19 and from 0.651 to 0.704 for the Biomedical Semantic Indexing and Question Answering). We also found a potential problem where extractive transformer MRC models predict poorly despite being given a more precise context in some cases. CONCLUSIONS: The proposed context extraction method allows the MRC model to achieve improved prediction correctness and a significantly reduced MRC inference time. This approach works technically with any MRC model and has potential in tasks involving processing long texts.

Salt sensitivity risk derived from nocturnal dipping and 24-h heart rate predicts long-term blood pressure reduction following renal denervation.

BACKGROUND: Renal denervation (RDN) has been consistently shown in recent sham-controlled clinical trials to reduce blood pressure (BP). Salt sensitivity is a critical factor in hypertension pathogenesis, but cumbersome to assess by gold-standard methodology. Twenty-four-hour average heart rate (HR) and mean arterial pressure (MAP) dipping, taken by ambulatory blood pressure monitoring (ABPM), stratifies patients into high, moderate, and low salt sensitivity index (SSI) risk categories. OBJECTIVES: We aimed to assess whether ABPM-derived SSI risk could predict the systolic blood pressure reduction at long-term follow-up in a real-world RDN patient cohort. METHODS: Sixty participants had repeat ABPM as part of a renal denervation long-term follow-up. Average time since RDN was 8.9 ±â€Š1.2 years. Based on baseline ABPM, participants were stratified into low (HR < 70 bpm and MAP dipping > 10%), moderate (HR ≥70 bpm or MAP dipping ≤ 10%), and high (HR ≥ 70 bpm and MAP dipping ≤ 10%) SSI risk groups, respectively. RESULTS: One-way ANOVA indicated a significant treatment effect ( P  = 0.03) between low ( n  = 15), moderate ( n  = 35), and high ( n  = 10) SSI risk with systolic BP reduction of 9.6 ±â€Š3.7 mmHg, 8.4 ±â€Š3.5 mmHg, and 28.2 ±â€Š9.6 mmHg, respectively. Baseline BP was not significantly different between SSI Risk groups ( P  = 0.18). High SSI risk independently correlated with systolic BP reduction ( P  = 0.02). CONCLUSIONS: Our investigation indicates that SSI risk may be a simple and accessible measure for predicting the BP response to RDN. However, the influence of pharmacological therapy on these participants is an important extraneous variable requiring testing in prospective or drug naive RDN cohorts.

Trends in blood pressure changes and hypertension prevalence in Australian adults before and during the COVID-19 pandemic.

Efforts to limit the impact of the coronavirus disease (COVID-19) pandemic led to the implementation of public health measures and reallocation of health resources. To investigate trends in blood pressure (BP), hypertension and BMI in the Australian population during the COVID-19 pandemic, data from publicly accessible health stations were analyzed. Average BP and BMI measured by the SiSU Health Station network in Australia in over 1.6 million health screenings were compared between the years 2018 and 2021. Additionally, paired trajectories for BP and BMI development before and during the COVID-19 pandemic were calculated. Comparisons between pre-COVID years and post-COVID years of 2018 versus 2020, 2019 versus 2020, 2018 versus 2021, and 2019 versus 2021 showed increases in average adjusted systolic BP of 2.0, 1.7, 2.6, and 2.3 mmHg, respectively. Paired analysis of longitudinal data showed an overall increase in the trajectory of systolic BP of 3.2 mmHg between pre- and post-COVID years. The prevalence of hypertension in users of the health stations increased by approximately 25% in the years 2020-2021. Similar trends were seen for BMI. Data from public Australian health stations indicated a strong trend toward higher BP during the COVID-19 pandemic. At the population level, BP increments have been shown to markedly increase cardiovascular disease risk. Anti-pandemic measures need to be carefully evaluated in terms of secondary public health effects and health support systems extended to effectively target cardiovascular risk.

Central stress pathways in the development of cardiovascular disease.

PURPOSE: Mental stress is of essential consideration when assessing cardiovascular pathophysiology in all patient populations. Substantial evidence indicates associations among stress, cardiovascular disease and aberrant brain-body communication. However, our understanding of the flow of stress information in humans, is limited, despite the crucial insights this area may offer into future therapeutic targets for clinical intervention. METHODS: Key terms including mental stress, cardiovascular disease and central control, were searched in PubMed, ScienceDirect and Scopus databases. Articles indicative of heart rate and blood pressure regulation, or central control of cardiovascular disease through direct neural innervation of the cardiac, splanchnic and vascular regions were included. Focus on human neuroimaging research and the flow of stress information is described, before brain-body connectivity, via pre-motor brainstem intermediates is discussed. Lastly, we review current understandings of pathophysiological stress and cardiovascular disease aetiology. RESULTS: Structural and functional changes to corticolimbic circuitry encode stress information, integrated by the hypothalamus and amygdala. Pre-autonomic brain-body relays to brainstem and spinal cord nuclei establish dysautonomia and lead to alterations in baroreflex functioning, firing of the sympathetic fibres, cellular reuptake of norepinephrine and withdrawal of the parasympathetic reflex. The combined result is profoundly adrenergic and increases the likelihood of cardiac myopathy, arrhythmogenesis, coronary ischaemia, hypertension and the overall risk of future sudden stress-induced heart failure. CONCLUSIONS: There is undeniable support that mental stress contributes to the development of cardiovascular disease. The emerging accumulation of large-scale multimodal neuroimaging data analytics to assess this relationship promises exciting novel therapeutic targets for future cardiovascular disease detection and prevention.

Central mechanisms in sympathetic nervous dysregulation in obesity.

Cardiovascular and metabolic complications associated with excess adiposity are linked to chronic activation of the sympathetic nervous system, resulting in a high risk of mortality among obese individuals. Obesity-related positive energy balance underlies the progression of hypertension, end-organ damage, and insulin resistance, driven by increased sympathetic tone throughout the body. It is, therefore, important to understand the central network that drives and maintains sustained activation of the sympathetic nervous system in the obese state. Experimental and clinical studies have identified structural changes and altered dynamics in both grey and white matter regions in obesity. Aberrant activation in certain brain regions has been associated with altered reward circuitry and metabolic pathways including leptin and insulin signaling along with adiposity-driven systemic and central inflammation. The impact of these pathways on the brain via overactivity of the sympathetic nervous system has gained interest in the past decade. Primarily, the brainstem, hypothalamus, amygdala, hippocampus, and cortical structures including the insular, orbitofrontal, temporal, cingulate, and prefrontal cortices have been identified in this context. Although the central network involving these structures is much more intricate, this review highlights recent evidence identifying these regions in sympathetic overactivity in obesity.

Assessment of Health-Related Quality of Life Among Male Patients With Controlled and Uncontrolled Hypertension in Semi Urban India.

The burden of hypertension has been growing over recent decades. In addition to risk of stroke and cardiovascular disease development, data indicates that hypertension may also pose a hazard to the quality of life (QoL) of individuals. Patient reported outcomes such as QoL are often overlooked, with physicians and healthcare professionals not routinely evaluating or customizing treatments according to QoL. In this study we aimed to assess the QoL of hypertensive men (n = 500) undergoing treatment who visited a charitable hospital in Pune, India. Clinic blood pressure was determined and the Mini Cuestionario de Calidad de Vida en Hipertensión Arterial (MINICHAL) scale was used to assess the health-related (HR)-QoL of patients. More than half of the participants (62%) had uncontrolled hypertension, with a mean systolic blood pressure (BP) of 151 ± 12 mmHg and diastolic blood pressure of 87 ± 6 mmHg as compared to those with controlled blood pressure (mean systolic blood pressure 123 ± 6 mmHg and diastolic blood pressure 84 ± 5 mmHg; P < .01 for both). Predominantly the participants were overweight with body mass index (BMI) of those with uncontrolled hypertension being greater than those with controlled blood pressure (28.4 ± 3.3 kg/m2 vs 23.3 ± 2 kg/m2, P < .01). A reduced QoL was observed for participants with uncontrolled hypertension (overall score 41 ± 5) as compared to those with controlled blood pressure (35 ± 4, P < .001). This was evident on both the mental plane [2.8 ± 2.5 (95% CI = 2.3-3.1) vs 4.1 ± 3.2 (95% CI = 2.5-3.3)] and somatic domain [3.4 ± 3.2 (95% CI = 3.0-4.0) vs 4.7.4 ± 3.5 (95% CI = 3.1-4.5)] where the QoL was poorer (P < .001) for the uncontrolled hypertensive group. Poorer QoL was observed for people with uncontrolled hypertension. This study indicates that the QoL in patients with uncontrolled hypertension attending an outpatient clinic in India is worse than those with controlled blood pressure. Future studies need to be undertaken to ascertain whether an impaired QoL impacts the outcomes associated with high blood pressure.

Beta-blockade enhances anthracycline control of metastasis in triple-negative breast cancer.

Beta-adrenergic blockade has been associated with improved cancer survival in patients with triple-negative breast cancer (TNBC), but the mechanisms of these effects remain unclear. In clinical epidemiological analyses, we identified a relationship between beta-blocker use and anthracycline chemotherapy in protecting against TNBC progression, disease recurrence, and mortality. We recapitulated the effect of beta-blockade on anthracycline efficacy in xenograft mouse models of TNBC. In metastatic 4T1.2 and MDA-MB-231 mouse models of TNBC, beta-blockade improved the efficacy of the anthracycline doxorubicin by reducing metastatic development. We found that anthracycline chemotherapy alone, in the absence of beta-blockade, increased sympathetic nerve fiber activity and norepinephrine concentration in mammary tumors through the induction of nerve growth factor (NGF) by tumor cells. Moreover, using preclinical models and clinical samples, we found that anthracycline chemotherapy up-regulated ß2-adrenoceptor expression and amplified receptor signaling in tumor cells. Neurotoxin inhibition of sympathetic neural signaling in mammary tumors using 6-hydroxydopamine or genetic deletion of NGF or ß2-adrenoceptor in tumor cells enhanced the therapeutic effect of anthracycline chemotherapy by reducing metastasis in xenograft mouse models. These findings reveal a neuromodulatory effect of anthracycline chemotherapy that undermines its potential therapeutic impact, which can be overcome by inhibiting ß2-adrenergic signaling in the tumor microenvironment. Supplementing anthracycline chemotherapy with adjunctive ß2-adrenergic antagonists represents a potential therapeutic strategy for enhancing the clinical management of TNBC.

Associations of physical activity levels, and attitudes towards physical activity with blood pressure among adults with high blood pressure in Bangladesh.

BACKGROUND: Physical activity is important for the control of high blood pressure (hypertension). We aimed to investigate the associations of current physical activity levels, sedentary time, knowledge of and attitude towards physical activity with blood pressure in people with hypertension in a rural area in Bangladesh. METHODS: A total of 307 adults aged 30 to 75 years with hypertension were recruited from the Banshgram Union of Narial district as part of a cluster-randomized control trial. Current blood pressure was measured as the outcome variable. Associated variables included physical activity at work, travel to and from places, recreational activity, metabolic equivalent task (MET)-min, sedentary time, and awareness of and attitudes towards physical activity. Rasch analysis was used to compute a combined score from the five awareness of and attitudes towards physical activity items and categorized into 0-40 (towards negative attitude), 41-60 score (mixed attitude) and 61-100 (positive attitude). We used a generalised linear model to analyze the data. RESULTS: Participants (n = 68, 22.1%) who engaged in vigorous-intensity physical activity that causes large increases in breathing or heart rate like carrying or lifting heavy loads, digging or construction work for at least 10 minutes continuously had lower systolic blood pressure (SBP) (mean (95% confidence interval (CI)), 143.6 (140.1, 147.2)) compared to those who did not take part in a vigorous-intensity physical activity (mean (95% CI), 150 (147.6, 152.3)). MET-min less than 600 min/week was significantly associated with higher SBP 153.8 (148.1, 159.6) than MET-min 600-2999 min/week 148.0 (143.0, 152.9) and MET-min>3000 min/week 146.9 (144.5, 149.3), p = 0.001 for trend. Sitting time more than four hours a day was associated with higher DBP 91.4 (89.7, 93.0) compared to those who had sitting time less than fours a day 88.6 (87.1, 90.1). People with positive attitudes were associated with a reduced SBP of 10.6 (0.36, 20.8) mmHg and DBP 5.88 (0.47, 11.3) compared to the people who had a negative attitude towards taking part in physical activity. CONCLUSIONS: Participating in high physical activity and positive attitudes towards physical activity were associated with lower blood pressure levels. Physical activity awareness programs should be implemented to increase awareness of health benefits and increase participation in high physical activity.

Catheter-Based Renal Denervation: 9-Year Follow-Up Data on Safety and Blood Pressure Reduction in Patients With Resistant Hypertension.

BACKGROUND: Recent sham-controlled randomized clinical trials have confirmed the safety and efficacy of catheter-based renal denervation (RDN). Long-term safety and efficacy data beyond 3 years are scarce. Here, we report on outcomes after RDN in a cohort of patients with resistant hypertension with an average of ≈9-year follow-up (FU). METHODS: We recruited patients with resistant hypertension who were previously enrolled in various RDN trials applying radiofrequency energy for blood pressure (BP) lowering. All participants had baseline assessments before RDN and repeat assessment at long-term FU including medical history, automated office and ambulatory BP measurement, and routine blood and urine tests. We analyzed changes between baseline and long-term FU. RESULTS: A total of 66 participants (mean±SD, 70.0±10.3 years; 76.3% men) completed long-term FU investigations with a mean of 8.8±1.2 years post-procedure. Compared with baseline, ambulatory systolic BP was reduced by -12.1±21.6 (from 145.2 to 133.1) mm Hg (P<0.0001) and diastolic BP by -8.8±12.8 (from 81.2 to 72.7) mm Hg (P<0.0001). Mean heart rate remained unchanged. At long-term FU, participants were on one less antihypertensive medication compared with baseline (P=0.0052). Renal function assessed by estimated glomerular filtration rate fell within the expected age-associated rate of decline from 71.1 to 61.2 mL/min per 1.73 m2. Time above target was reduced significantly from 75.0±25.9% at baseline to 47.3±30.3% at long-term FU (P<0.0001). CONCLUSIONS: RDN results in a significant and robust reduction in both office and ambulatory systolic and diastolic BP at ≈9-year FU after catheter-based RDN on less medication and without evidence of adverse consequences on renal function.

Stagnating rates of blood pressure control in Australia: insights from opportunistic screening of 10 046 participants of the May Measurement Month campaigns.

BACKGROUND: Raised blood pressure (BP) remains the single most important modifiable risk factor contributing to cardiovascular and all-cause mortality in Australia and worldwide. May Measurement Month , a global BP measurement and screening campaign initiated by the International Society of Hypertension and carried out in Australia since its inception in 2017, aimed at obtaining standardized BP measurements from members of the community to increase awareness of high BP and its associated risks. METHOD: Adults participants (≥18 years) were recruited through opportunistic sampling across Australia during the month of May in 2017, 2018 and 2019. Trained volunteers recorded BP readings in a standardized manner and collected data on demographic, lifestyle factors and comorbidities. Hypertension was defined as SBP of at least 140 mmHg, or DBP of at least 90 mmHg, or taking antihypertensive medication. Data were collated centrally and analysis was carried out using regression models to evaluate the associations between BP and participant characteristics. RESULTS: A total of 10 046 participants were screened, of whom 3097 (31.0%) had hypertension, only 48.5% were aware of their condition and 44.4% were taking antihypertensive medication. Of those taking antihypertensive medication, 53.2% were controlled to less than 140/90 mmHg, whereas the remaining 46.8% of participants had BP of at least 140/90 mmHg suggestive of inadequately treated hypertension. CONCLUSION: Consecutive data obtained over a 3-year period in Australia demonstrated stagnating awareness, treatment and control rates with the latter two being substantially lower than global rates and those in other high-income countries. Concerted efforts from all stakeholders will be required to help overcome the unacceptably poor rates of BP treatment and control in Australia.

Current Applications of Robot-Assisted Ultrasound Examination.

Despite advances in miniaturization and automation, the need for expert acquisition of a full echocardiogram, including Doppler, has restricted access in remote areas. Recent developments in robotics, teleoperation, and upgraded telecommunications infrastructure may provide a solution to this deficiency. Robot-assisted teleoperated ultrasound examination can aid medical diagnosis in remote locations and may improve health inequalities between rural and urban settings. This review aimed to analyze the status of teleoperated robotic systems for ultrasound examinations, evaluate clinical and preclinical applications, identify limitations, and outline future directions for clinical use. Overall, robot-assisted teleoperated ultrasound is feasible and safe in the reported clinical and preclinical studies, with the robots able to follow the hand movements performed by sonographers and researchers from a distance or in local networks. Moreover, multiple types of ultrasound examinations have been performed in remote areas, with a high success rate nearly comparable to that of conventional sonography. The studies showed that although a low-bandwidth link can be used to control a robot, the bandwidth requirements for real-time transmission of video and ultrasound images are significantly higher. Furthermore, if haptic feedback is implemented, the bandwidth requirements are increased. Haptically enabled systems that improve robotic control are necessary for accelerating the introduction to clinical use. Haptic feedback and enhanced front-end interface control for remote users are vital aspects required for clinical application. The incorporation of artificial intelligence through either aiding in window acquisition (knowledge of anatomical landmarks to adjust scanning planes) or through measurement and disease identification is yet to be researched. However, it has the potential to lead to dramatic advances. A new generation of robots is in development, and several projects in the preclinical stage reveal a promising future to overcome the shortage of health professionals in remote areas.

Stress and social isolation, and its relationship to cardiovascular risk in young adults with intellectual disability.

PURPOSE: Stress produces many physiological changes, some of which may contribute to the development of cardiovascular disease (CVD). Individuals with intellectual disability (ID) are exposed to multiple and stressful challenges everyday which may put them at increased cardiovascular risk. This current study aimed to establish whether adults with ID experience higher levels of subjective stress and encounter different stressors (including social isolation) than the general population, and whether there is a relationship between stress and cardiometabolic profile in this population. METHODS: Adults with ID (n = 35) aged 18-45 years completed the Subjective Stress Survey, and underwent a physiological assessment to measure blood pressure, metabolic profile and subclinical CVD risk factors, and were compared to a control group (n = 29). Multiple regression was used to investigate whether cardiometabolic parameters were predicative of SSS scores. RESULTS: Findings showed adults with ID have higher perceived stress levels (total score ID: 21.3 ± 11.4 vs control: 13.9 ± 9.0, p = 0.006), which is elicited by unique stressors, when compared to people without ID. Stress was strongly associated with increased social isolation (r = -0.38, p = 0.002) and with obesity in females with mild ID (r = 0.72). Regression showed that arterial stiffness was predictive of total SSS score (p = 0.038). CONCLUSIONS: Adults with ID aged 18-45 years report higher levels of perceived stress when compared to people without ID.Implications for RehabilitationReducing stress in this young population may prevent development of arterial stiffness, and consequently lower the risk of cardiometabolic morbidity and mortality.There are unique targets for stress management in young adults with intellectual disability, including supporting decision-making and improving self-efficacy.Improving community integration and reducing social isolation may decrease perceived stress in young adults with intellectual disability.

Mental health and quality of life during weight loss in females with clinically severe obesity: a randomized clinical trial.

The purpose of this investigation was to explore the effects of dietary weight loss intervention, with and without the addition of exercise on health-related quality of life, depressive symptoms, and anxiety. As part of the EMPOWER study for women, sixty premenopausal women (BMI of 40.4 ± 6.7) were randomized to energy restriction only (ER) or to exercise plus energy restriction (EXER) for 12 months. Health-related quality of life was assessed using the SF-36, depressive symptoms were assessed using the Beck Depression Inventory II (BDI), and anxiety symptoms using the Spielberger state and trait anxiety questionnaire. All measures were completed at baseline, 3, 6 and 12 months. At 12 months, there were significant (p < 0.05) group-by-time interactions favouring the EXER group for five of the eight domains and the mental component summary score. At 12 months, a significant group-by-time interaction favouring the EXER group is reported for both state and trait anxiety (p = .005 and p = .001, respectively). At 12 months, there was a significant group-by-time interaction for depressive symptoms favouring EXER (p < 0.05). Within-group changes for BDI scores were improved at all follow-up time points in the EXER group. Exercise training confers an additional benefit to energy restriction in the absence of additional weight loss at 12 months for health-related quality of life, depressive symptoms, and state and trait anxiety scores when compared to energy restriction only. Exercise and an energy-restricted diet improve health-related quality of life and mental health. Exercise may protect mental health without further weight loss for women with severe obesity.

A randomised preclinical trial of adrenaline use during cardiac arrest in mice.

Background: Adrenaline is routinely administered during cardiac arrest resuscitation. Using a novel murine model of cardiac arrest, this study evaluates the effects of adrenaline use on survival and end-organ injury. Methods: A total of 58 mice, including cardiac arrest (CA) and sham (SHAM) groups received intravenous potassium chloride either as a bolus (CA) or slow infusion (SHAM), inducing ECG-confirmed asystole (in CA only) for 4-minutes prior to intravenous adrenaline (+ADR;250 ul,32 ug/ml) or saline (-ADR;250 ul) and manual chest compressions (300 BPM) for 4-minutes. Mice with return of spontaneous circulation (ROSC) were assessed at 24- or 72-h timepoints. Results: Among animals that underwent CA, rates of ROSC (n = 21 (95 %) vs n = 14 (82 %), P = 0.18) and survival to the planned endpoint (n = 11 (50 %) vs n = 12 (71 %), P = 0.19) were similar when comparing those treated with (CA+ADR) and without (CA-ADR) adrenaline. However, in CA animals that initially achieved ROSC, subsequent mortality was approximately 3-fold greater with adrenaline treatment (48 % vs 14 %, P = 0.042). Among SHAM animals, adrenaline use had no impact on survival rates or other endpoints. Greater myocardial injury occurred in CA+ADR vs CA-ADR, with increased Hs-Troponin levels measured at 24- (26.0 ± 0.9 vs 9.4 ± 5.3 ng/mL, P = 0.015) and 72-h (20.9 ± 8.3 vs 5.0 ± 2.4 ng/mL, P = 0.012), associated with increased expression of pro-inflammatory and fibrotic genes within cardiac and renal tissue. Conclusion: Adrenaline did not improve ROSC or overall survival but following successful ROSC, its use resulted in 3-fold greater mortality rates. Adrenaline was also associated with increased myocardial injury, end-organ inflammation, and fibrosis. These findings underscore the need for further preclinical evaluation of alternate pharmacologic adjuncts for cardiopulmonary resuscitation that improve survival and limit end-organ injury.

Measurement of Noradrenaline and Serotonin Metabolites With Internal Jugular Vein Sampling: An Indicator of Brain Monoamine Turnover in Depressive Illness and Panic Disorder.

In research spanning three decades we have estimated brain monoamine turnover (approximately equating with synthesis rate) with sampling from the internal jugular veins and measurement of trans-cerebral plasma monoamine metabolite concentration gradients. Here we report indices of brain noradrenaline and serotonin turnover in patients with major depressive illness (MDD) and panic disorder (PD). Brain noradrenaline turnover was assessed from the combined flux into the internal jugular veins of the metabolites dihydroxyphenylglycol (DHPG) and 3-hydroxy-4-methoxyphenylglycol (MHPG), and brain serotonin turnover from the overflow of the primary metabolite, 5-hydroxyindole acetic acid (5HIAA). Comparison was made with matched healthy research participants. In both MD and PD the estimate of brain noradrenaline turnover provided by metabolite overflow was unremarkable. In contrast, in both patient groups the estimate of brain serotonin turnover provided by 5HIAA overflow was increased 3-4-fold (P < 0.01). This neurotransmitter abnormality was normalized in MDD and PD in clinical remission, during selective serotonin reuptake blocker (SSRI) dosing. We cannot be sure if the brain serotonergic abnormality we find in MDD and PD is causal or a correlate. Measurements in PD were not made during a panic attack. The increased estimated serotonin turnover here may possibly be a substrate for panic attacks; serotonergic raphe nuclei participate in anxiety responses in experimental animals. It is puzzling that the findings were identical in MDD and PD, although it may be pertinent that these psychiatric diagnoses are commonly comorbid. It is unlikely that activation of brain serotonergic neurons is driving the sympathetic nervous activation present, which contributes to cardiovascular risk, persistent sympathetic activation in MDD and episodic activation in PD during panic attacks. We have previously demonstrated that the mechanism of activation of human central sympathetic outflow in other contexts (hypertension, heart failure) is activation of noradrenergic brainstem neurons projecting to the hypothalamus and amygdala.

A Global Longitudinal Study Examining Social Restrictions Severity on Loneliness, Social Anxiety, and Depression.

Purpose: Social restrictions and government-mandated lockdowns implemented worldwide to kerb the SARS-CoV-2 virus disrupted our social interactions, behaviours, and routines. While many studies have examined how the pandemic influenced loneliness and poor mental health, such as depression, almost none have focussed on social anxiety. Further, how the change in social restrictions affected change in mental-health and well-being has not yet been explored. Methods: This is a longitudinal cohort study in community dwellers who were surveyed across three timepoints in the first six months of the pandemic. We measured loneliness, social anxiety, depression, and social restrictions severity that were objectively coded in a sample from Australia, United States, and United Kingdom (n = 1562) at each time point. Longitudinal data were analysed using a multivariate latent growth curve model. Results: Loneliness reduced, depression marginally reduced, and social anxiety symptoms increased as social restrictions eased. Specific demographic factors (e.g., younger age, unemployment, lower wealth, and living alone) all influenced loneliness, depression, and social anxiety at baseline. No demographic factors influenced changes for loneliness; we found that those aged over 25 years reduced faster on depression, while those younger than 25 years and unemployed increased faster on social anxiety over time. Conclusion: We found evidence that easing social restrictions brought about additional burden to people who experienced higher social anxiety symptoms. As country-mandated lockdown and social restrictions eased, people are more likely report higher social anxiety as they readjust into their social environment. Mental health practitioners are likely to see higher levels of social anxiety in vulnerable communities even as social restrictions ease.

Characterization of Cardiac Sympathetic Nervous System and Inflammatory Activation in HFpEF Patients.

We have shown that systemic and cardiac sympathetic activation is present in heart failure with preserved ejection fraction (HFpEF) patients. Conversely, whereas systemic inflammatory activation was also detected in HFpEF, we did not detect local myocardial release of inflammatory cytokines. Activation of the sympathetic system correlated with both hemodynamic and demographic factors that characteristically cluster together in HFpEF. Together these data suggest that there may be a role for antiadrenergic therapies in certain HFpEF patients. The study does not implicate locally derived cytokines in the myocardial biology of HFpEF, although systemic sources may contribute to the global pathophysiology of HFpEF.

Poorer Self-Reported Physical Health and Higher Anxiety Trait in Young Adults With Previous Coarctation Repair.

BACKGROUND: Little is known about the impact of a coarctation repair on the functional outcomes of young adults. This study aimed to determine (1) the functional and mental health status in young adults with previous coarctation repair, and (2) the impact of late hypertension on their quality of life. METHODS: A cross-sectional study using validated self-reported questionnaires (Short Form 36 version 2 [SF-36v2], Beck Depression Inventory [BDI], and State-Trait Anxiety Inventory [STAI]) was performed in 54 patients aged 15-47 years with previous paediatric coarctation repair. Questionnaire scores were compared to healthy age- and gender-matched controls. Patients' previously published 24-hour blood pressure monitoring results were included. RESULTS: Late hypertension was present in 64% (34/54) at a mean of 29±8 years after coarctation repair. SF-36v2 mean physical component summary score was significantly lower in coarctation patients compared with controls (53.1±6.8 vs 56.0±4.7, p=0.02), but there was no significant difference in mean mental component summary score (p=0.2). SF-36v2 mean role emotional score tended to be associated with 10 mmHg increases in mean 24-hour systolic blood pressure (regression coefficient 4.3 p=0.06). STAI mean trait anxiety score tended to be higher in coarctation patients compared with controls (36.6±9.0 vs 33.5±7.8, p=0.06). There was no significant difference in BDI scores between patients and controls. CONCLUSIONS: Young adults with previous coarctation repair report poorer physical health and tended towards higher anxiety trait compared to healthy controls. Strategies to improve self-reported physical health and anxiety should be explored. Long-term assessment of quality of life outcomes in coarctation patients is warranted.

MicroRNA-132 may be associated with blood pressure and liver steatosis-preliminary observations in obese individuals.

Recent findings in experimental models have shown that the microRNA miR-132 (mir-132) is an important regulator of liver homeostasis and lipid metabolism. We aimed to assess miR-132 expression in liver and fat tissues of obese individuals and examine its association with blood pressure (BP) and hepatic steatosis. We examined obese individuals undergoing bariatric surgery for weight loss (n = 19). Clinical and demographic information was obtained. Quantitative PCR was performed to determine tissue expression of miR-132 in liver and subcutaneous and visceral fat biopsies obtained during bariatric surgery. Liver biopsies were read by a single liver pathologist and graded for steatosis, inflammation and fibrosis. Participants (aged 39 ± 8.1 years) had a body mass index (BMI) of 42 ± 4.5 kg/m2 and presented with 2.2 ± 1.2 metabolic abnormalities. Supine BP was 127 ± 16/74 ± 11 mmHg. Hepatic and visceral fat expression of miR-132 were correlated (r = 0.59, P = 0.033). There was no correlation between subcutaneous and visceral expression of miR-132 (r = -0.31, P = 0.20). Hepatic and visceral fat miR-132 expression were associated with BMI (r = 0.62 and r = 0.68, P = 0.049 respectively) and degree of liver steatosis (r = 0.60 and r = 0.55, P < 0.05, respectively). Subcutaneous fat miRNA-132 expression was correlated to office systolic BP (r = 0.46, P < 0.05), several aspects of 24 h BP (24 h systolic BP: r = 0.52; day systolic BP: r = 0.59, P < 0.05 for all), plasma triglycerides (r = 0.51, P < 0.01) and liver enzymes (ALT: r = -0.52; AST: r = -0.48, P < 0.05 for all). We found an association between miR-132 and markers of cardiovascular and metabolic disease. Reduction of miR-132 may be a target for the regulation of liver lipid homeostasis and control of obesity-related blood pressure.