24-h Mean Research Articles

Differential Role for the Clock Gene, BMAL1, on Kidney Function in Male versus Female Rats

Many activities of modern life, such as social visits with friends at night, long working hours, jet lag, and shift work cause circadian rhythm disturbances, which increase the risk of renal decline and eventual disease. Chronic kidney disease (CKD) is defined by decreases in glomerular filtration rate (GFR) which is higher during the daytime and lower at night in healthy individuals. Prior studies indicate that processes critical for maintaining blood pressure ( e.g. autoregulation) contribute to this time-of-day-dependence mediated by a molecular timekeeping mechanism known as the molecular circadian clock that resides in all tissues including the kidney. We hypothesized that loss of the molecular clock would impair normal kidney physiology through misalignment of functional rhythms with normal environmental patterns associated with day and night. We used a rat model of circadian disruption to interrogate our hypothesis. Male and female brain and muscle ARNT-like protein 1 knockout (BMAL1 KO) and littermate control (CON) rats aged 12-14 weeks underwent GFR measurements using FITC-labeled sinistrin clearance at two times of the day corresponding to the dark (active) and light (inactive) periods. Following GFR measurements, rats were placed in metabolic cages with food to record water intake and urine excretion over 12h active and inactive periods. Implantable telemeters were used for 24h measurement of systolic and diastolic blood pressure, locomotor activity and body temperature. Autoregulatory behavior was assessed using the isolated juxtamedullary nephron preparation to determine afferent arteriole diameter responses to changes in perfusion pressure. Diurnal measurements of GFR revealed that male BMAL1 KO rats had a significantly lower GFR in the active period as compared to CON males (1.87±0.37 vs 2.55±0.47 ml/min/100g; 2-way ANOVA, p<0.05; n=8-9). As a result, there was no diurnal variation in the KO males as seen in the CON males (Δ GFR 0.63±0.24 vs 0.04±0.21 ml/min/100g/12h CON vs KO respectively) (Sidak post-hoc, p<0.05; n=8-9) in parallel with a lack of diurnal variation in urine volume and Na excretion. Both male (n=8) and female (n=6-9) BMAL1 KO rats also displayed a significantly lower 24h mean arterial pressure (Males; 103±1 vs 107±1 mmHg, p<0.05; Females; 110±1 vs 100±2 mmHg, p<0.05) compared to CON with diurnal variation and autoregulatory reactivity preserved. Male BMAL1 KO rats consumed significantly more water compared to CON (n=5-9, 22.5±5.4 vs 14.7±4.0 mL/12h, p<0.05) concomitant with increased urine excretion (n=5-9, 13.3±6 vs 4.2±0.8 mL/12h, p<0.05) and reduced urine osmolality (n=5-7, 967±398 vs 2140±811 mmol/kg, p<0.05) regardless of time of day. Taken together these data suggest that BMAL1 is necessary for maintaining renal functional rhythms and urine concentrating ability in a sex-dependent manner. R01 DK134562 P01 HL158500. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

TYG INDEX AS PREDICTOR OF METABOLIC SYNDROME IN YOUNG TO-MIDDLE AGE STAGE I HYPERTENSIVES, UNTREATED AT THE BASELINE

Objective: Tyg index, a surrogate marker of insulin resistance, was shown to be a predictor of development of metabolic syndrome (MS) among diabetes patients and general population while the predictive value among young hypertensives is less known. The aim of the present study was to investigate the predictive capacity of tyg index for incident MS among young untreated hypertensives. Design and method: we investigated 949 young-to-middle age stage I hypertensives from the HARVEST study, mean age 32.4±8.7 years, mean BMI 24.7±3.2 kg/m2, 69.2% males, without MS at baseline. Mean 24h blood pressure (BP) at entry 130.0±10.9/81.0±8.3 mmHg. Tyg index was calculated according to the usual formula. Patients were divided into tyg quintiles:7.008-7.895, 7.896-8.199, 8.200-8.423, 8.424-8.585, >=8.586 respectively. The risk of MS was calculated by means of survival Cox analyses adjusted for several confounders. Results: Patients in the highest quintiles were significantly older 35.3±8.1 years and heavier 25.3±3.3 kg/m2 than the bottom ones (p<0.001). Also baseline metabolic parameters were worse in top quintile (serum glucose 96.2±14.1, uric acid 5.3±1.2 mg/dl, total cholesterol 212.1±35.3 mg/dl, HDL 51.8±10.2 mg/dl) in comparison to the lower ones (p<0.001 for all comparisons). Baseline 24h BP values did not differ according to Tyg quintile, while heart rate was higher in the top quintile (74.3±8.4 bpm, p<0.001). During 8.1 years of follow-up, 76.3% of subjects developed new onset MS. Again, metabolic parameters were worst in the highest tyg quintile (serum glucose 97.9±15.4 mg/dl, total cholesterol 225.9±44.7 mg/dl, and HDL 52.1±15.2 mg/dl, as was final BMI (26.2±3.6Kg/m2, p<0.001 for all comparisons). Final 24h BP did not differ according to Tyg quintile while heart rate was higher in the highest quintile (p<0.001). In multivariate Cox analysis patients in the 4th and 5th quintiles presented the highest risk of new onset MS (HR 1.51 (1.11-2.06) p=0.009; HR 1.46 (1.09-1.46)p=0.011, respectively), in comparison to the bottom quintile. Conclusions: The risk of development of metabolic syndrome was significantly increased among patients in the top tyg quintiles, confirming its predictive capacity as a surrogate marker of insulin resistance among young stage I hypertensives.

Safety and efficacy of once-daily dexfadrostat phosphate in patients with primary aldosteronism: a randomised, parallel group, multicentre, phase 2 trial

Primary aldosteronism (PA) is caused by autonomous aldosterone overproduction and characterised by uncontrolled hypertension. There are currently no treatments that targetaldosterone synthesis. We evaluated the safety and efficacy of a novel aldosterone synthase inhibitor, dexfadrostat phosphate, in patients with PA. This multi-centre, randomised, phase 2 trial was conducted between November 2019 and May 2022 (NCT04007406; EudraCT code 2019-000919-85). Adults with PA and an office systolic blood pressure of 145-190mmHg were included. After a 2-week single-blind placebo run-in period, participants were randomised 1:1:1 to receive oral dexfadrostat phosphate 4, 8, or 12mg once daily for an 8-week double-blind treatment period, followed by a 2-week single-blind placebo withdrawal period. Randomisation was conducted centrally and stratified by centre and sex. At the beginning and end of the treatment period, 24h ambulatory systolic blood pressure (aSBP) was recorded. Blood samples were taken every 2 weeks. Primary endpoints were the change in aldosterone-to-renin ratio (ARR) and mean 24h aSBP from baseline to the end of the treatment period in the combined dose group of all participants receiving any dose of dexfadrostat phosphate. Safety endpoints were the occurrence of treatment-emergent adverse events (TEAEs) and serious adverse events over the entire study in all randomised participants who received at least one dose of dexfadrostat phosphate. In total, 35 participants received dexfadrostat phosphate and all participants completed the study. Twenty-six participants (74.3%) were male, the mean age was 51.9 years (SD 8.7), and most were White (n=32, 91.4%). The median ARR and the mean 24h aSBP significantly decreased from the beginning to the end of the treatment period in the combined dose group (ARR: 15.3 vs 0.6, least-squares mean [LSM] change in log-normal values-2.5, p<0.0001; aSBP: 142.6 vs 131.9mmHg, LSM change-10.7mmHg, p<0.0001). There were no safety concerns; all TEAEs were mild or moderate and there were no serious TEAEs. Dexfadrostat phosphate corrected the ARR and aSBP and was well tolerated in patients with PA, demonstrating the benefit of pharmacologically targeting the source of hyperaldosteronism. DAMIAN Pharma AG.

Correlation between Long-Term Exposure to Traffic Noise and Risk of Type 2 Diabetes Mellitus.

This study aimed to probe the correlation of long-term exposure to traffic noise with the risk of type 2 diabetes mellitus (T2DM). The data of 480 community residents collected from April 2017 to April 2018 were retrospectively analyzed. Exposure levels for traffic noise were defined using 24-h mean traffic noise. Logistic regression calculated the association between long-term exposure to traffic noise and the risk of T2DM. Overall, 480 enrolled participants were divided into T2DM (n = 45) and non-T2DM (n = 435) groups. Participants with T2DM were older and more likely to be male, had higher BMI, and were frequent drinkers (P < 0.001). The T2DM group displayed higher exposure to traffic noise than the non-T2DM group (P < 0.001). According to quartiles of traffic noise, all participants were categorized into four groups: Q1 (<51.5 dB), Q2 (51.5-<53.9 dB), Q3 (53.9-<58.0 dB), and Q4 (≥58.0 dB). Prevalence of T2DM was 5.4% in Q1, 7.7% in Q2, 10.3% in Q3, and 14.1% in Q4 groups. Multifactor regression analysis showed that age, BMI, drinking history, and traffic noise exposure are risk factors for T2DM (P < 0.05), whereas sex does not seem to have a significant impact on T2DM (P > 0.05). Long-term exposure to traffic noise may elevate the risk of T2DM. This suggests that long-term exposure to high levels of traffic noise can increase the incidence of diabetes mellitus, which deserves further consideration.

Protective Role of TRPC3 Gene Polymorphism (rs10518289) in Obstructive Sleep Apnea Hypopnea Syndrome Among Hypertensive Patients.

BACKGROUND Obstructive sleep apnea-hypopnea syndrome (OSAHS) presents a significant health concern, particularly among individuals with essential hypertension (EH). Understanding the genetic underpinnings of this association is crucial for effective management and intervention. We investigated the relationship between TRPC3 gene polymorphisms and susceptibility to OSAHS in patients with EH. MATERIAL AND METHODS We enrolled 373 patients with EH hospitalized at the First Affiliated Hospital of Xinjiang Medical University between April 2015 and November 2017. Patients were categorized into EH (n=74) and EH+OSAHS (n=299) groups according to the apnea-hypopnea index. Sequenom detection technology was used for TRPC3 gene single-nucleotide polymorphism genotyping, including genotypes at rs953691, rs10518289, rs2292232, rs4995894, rs951974, and rs4292355. RESULTS Sex, smoking history, alcohol history, hypertension duration, fasting blood glucose, urea, creatinine, total cholesterol, HDL-C, LDL-C, glycosylated hemoglobin, 24-h mean systolic BP, and 24-h mean diastolic BP were not significantly different between the 2 groups (P>0.05); however, age, BMI, triglyceride levels differed significantly (P<0.05). No significant difference was detected in distribution frequency of polymorphisms of TRPC3 gene between the 2 groups (P>0.05), while genotype, dominant genotype, and recessive genotype at rs10518289 and alleles at rs4292355 differed significantly (P<0.05). Logistic regression analysis showed age, BMI, and CG+GG genotypes at rs10518289 were risk factors for OSAHS in patients with EH. Interaction between TRPC3 (rs10518289) and obesity was not a risk of OSAHS with EH (P>0.05). CONCLUSIONS CC genotype of rs10518289 in the TRPC3 gene could be a protective genetic marker of OSAHS, and CG+GG genotype may be a risk genetic marker of OSAHS with EH.

Comparison of Clustering Approaches in a Multimodel Ensemble for U.S. East Coast Cold Season Extratropical Cyclones

Abstract Several clustering approaches are evaluated for 1–9-day forecasts using a multimodel ensemble that includes the GEFS, ECMWF, and Canadian ensembles. Six clustering algorithms and three clustering spaces are evaluated using mean sea level pressure (MSLP) and 12-h accumulated precipitation (APCP) for cool-season extratropical cyclones across the Northeast United States. Using the MSLP cluster membership to obtain the APCP clusters is also evaluated, along with applying clustering determined at one lead time to cluster forecasts at a different lead time. Five scenarios from each clustering algorithm are evaluated using displacement and intensity/amount errors from the scenario nearest to the MSLP and 12-h APCP analyses in the NCEP GFS and ERA5, respectively. Most clustering strategies yield similar improvements over the full ensemble mean and are similar in probabilistic skill except that 1) intensity displacement space gives lower MSLP displacement and intensity errors; and 2) Euclidean space and agglomerative hierarchical clustering, when using either full or average linkage, struggle to produce reasonably sized clusters. Applying clusters derived from MSLP to 12-h APCP forecasts is not as skillful as clustering by 12-h APCP directly, especially if several members contain little precipitation. Use of the same cluster membership for one lead time to cluster the forecast at another lead time is less skillful than clustering independently at each forecast lead time. Finally, the number of members within each cluster does not necessarily correspond with the best forecast, especially at the longer lead times, when the probability of the smallest cluster being the best scenario was usually underestimated. Significance Statement Numerical weather prediction ensembles are widely used, but more postprocessing tools are necessary to help forecasters interpret and communicate the possible outcomes. This study evaluates various clustering approaches, combining a large number of model forecasts with similar attributes together into a small number of scenarios. The 1–9-day forecasts of both sea level pressure and 12-h precipitation are used to evaluate the clustering approaches for a large number of U.S. East Coast winter cyclones, which is an important forecast problem for this region.

Abstract WP289: Insufficient Low-Frequency Blood Pressure Activity Under Orthostatic Stress Predicts Blunted Night-to-Day Blood Pressure Dipping in Patients With Ischemic Cerebrovascular Disease

Introduction: Blunted night-to-day blood pressure (BP) dipping was common in ischemic cerebrovascular disease (ICVD). BP dipping could be influenced by baroreflex, which stabilized BP by regulating sympathovagal balance. We sought to determine the relationship between baroreflex function and BP dipping in patients with ICVD. Methods: Patients with ICVD stable for at least 3 days were enrolled. Beat-to-beat BP and ECG were monitored in 3 phases of active standing [supine (S), supine to upright (SU), upright (U), 4 min each]. Baroreflex function was evaluated by time-domain and frequency-domain baroreflex sensitivity (BRS) and by indices of sympathovagal balance [low (0.04-0.15 Hz) to high (0.15-0.4 Hz) frequency ratio (LHR) of systolic BP (SBP) and RR interval (RRI)]. BP dipping was measured as percentage with 24h ambulatory BP monitoring. SBP dipping &lt;0 was defined as reverse BP dipping. Results: Among 66 patients, mean SBP dipping was 3.54% ± 6.85%. SBP dipping was positively related to BP-LHR SU (Spearman r=0.258, p=0.036), but had no significant correlation with time-domain and frequency-domain BRS, LHR S and LHR U of BP and RRI, or RRI-LHR SU (Table 1). Lower log BP-LHR SU was indicative of less SBP dipping [β (95% CI): 6.53 (1.67-11.40), p=0.009] and the presence of reverse BP dipping [OR (95% CI): 0.11 (0.02-0.65), p=0.015], even after adjusting age, sex, vascular risk factors, 24h mean BP level, NIHSS and mRS scores (Table 2). Conclusions: Low BP-LHR SU , which suggested sympathetic underactivation of BP activity during the orthostasis-stimulated baroreflex engagement, might be a pathophysiological link between baroreflex impairment and blunted BP dipping in ICVD.

Efficacy and safety of azilsartan medoxomil in the treatment of hypertension: a systematic review and meta-analysis.

Angiotensin II receptor blockers (ARBs) are utilized for the management of hypertension and diabetes. Previous meta-analyses suggested that azilsartan medoxomil (AZL-M) improved blood pressure (BP) reduction, but there were no safety findings or suggestions for patients with hypertension or diabetes. We performed an efficacy and safety meta-analysis of randomized controlled trials (RCTs) evaluating AZL-M therapy for reducing BP in patients with hypertension. Patients with hypertension complicated by diabetes were analyzed. The relevant literature was searched in English and Chinese databases for RCTs involving AZL-M in hypertension. Efficacy variables included the change from baseline in the 24-h mean systolic/diastolic BP measured by ambulatory BP monitoring, the change from baseline in clinic systolic/diastolic BP, and responder rates. Safety variables included total adverse events (AEs), serious AEs, AEs leading to discontinuation, and AEs related to the study drug. The raw data from the included studies were utilized to calculate the odds ratio (OR) for dichotomous data and the mean difference (MD) for continuous data, accompanied by 95% confidence intervals (CIs). Statistical analysis was performed using R software. A total of 11 RCTs met the inclusion criteria, representing 7,608 patients, 5 of whom had diabetes. Pooled analysis suggested a reduction in BP among patients randomized to 40 mg of AZL-M vs. control therapy [24-h ambulatory blood pressure monitoring (ABPM) mean systolic blood pressure (SBP) (MD: -2.85 mmHg), clinic SBP (MD: -3.48 mmHg), and clinic diastolic blood pressure (DBP) (MD: -1.96 mmHg)] and for 80 mg of AZL-M vs. control therapy [24-h ABPM mean SBP (MD: -3.59 mmHg), 24-h ABPM mean DBP (MD: -2.62 mmHg), clinic SBP (MD: -4.42 mmHg), clinic DBP (MD: -3.09 mmHg), and responder rate (OR: 1.46)]. There was no difference in the reduction of risks, except for dizziness (OR: 1.56) in the 80-mg AZL-M group or urinary tract infection (OR: 1.82) in the 40-mg AZL-M group. Analysis of patients with diabetes revealed that AZL-M can provide superior management, while safety and tolerability were similar to those of control therapy. AZL-M appears to reduce BP to a greater extent than dose-control therapy and does not increase the risk of adverse events in patients with hypertension and diabetes compared with placebo. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=464284, identifier PROSPERO CRD42023464284.

Binder-type effect on the physico-mechanical, combustion and emission properties of Alstonia boonei De Wild. sawdust and Theobroma cacao L. pod biochar briquettes for energy applications.

Energy application potential from the abundant biomass residues is inadequately exploited. Over-dependence on forest trees, its negative environmental impacts, and ever-rising energy costs require alternative production technologies including briquetting. The physico-mechanical and combustion properties of binderless and bindered Alstonia boonei sawdust and Theobroma cacao (cocoa) pod briquettes, carbonized in a steel kiln (at 410±5°C, and a heating rate of 4°C/min from the ambient temperature of 25°C), piston-pressed at 9.0 MPa, were studied. The binders were starch, wax, and clay. Starch-bindered T. cacao pod briquettes recorded the maximum bulk density (640 kg/cm3), while basic density was greatest for sawdust/clay briquette (433 kg/cm3). Sawdust/wax briquette produced much Water Resistance Capacity (76.76%) with safer carbon monoxide (CO) emissions (0.67 ppm). A. boonei sawdust/starch briquettes recorded the greatest calorific value (24.023 MJ/kg), least specific fuel consumption (0.0483 kg/l), and slowest burning rate (0.0005 kg/min). All but T. cacao pod/starch and Sawdust/starch emitted CO below the safe air quality Standard of ≤ 6ppm (24h mean). Binderless sawdust, sawdust/starch and T. cacao pod/starch briquettes recorded 47.86, 20.95 and 11.40 μg/m3 particulate matter (PM2.5) respectively, which are below WHO Air Quality Standard safe for domestic uses. Binderless T. cacao pod produced more harmful CO and PM2.5 than its non-bindered A. boonei sawdust counterpart. Clay-bindered briquettes were the most durable. Briquetting, 'a waste-to-energy technology', enhances bio-residue management for domestic and industrial spaces in the global energy mix.

Effect of high-amylose rice "Hoshinishiki" on postprandial glucose levels measured by continuous glucose monitoring in patients with diabetes.

We examined the effect of consuming Hoshinishiki, a type of high-amylose rice, on postprandial glucose as measured by continuous glucose monitoring in diabetes patients. A single-blinded clinical trial involving 11 hospitalized patients diagnosed with type 1 or type 2 diabetes was performed. The patients consumed high-amylose rice for 2 days (days 2 and 4 of the study) and control rice for 2 days (days 1 and 3 of the study). Linear mixed models were used to test the effects on the 24-h mean glucose levels, time in range (TIR), incremental area under the curve of glucose levels at 2 h after meals, the average glucose levels at 1, 2, and 3 h after meals, and the maximum glucose levels within 3 h. The results showed that the consumption of high-amylose rice led to significantly lower 24-h mean glucose levels, levels at 2 and 3 h after a meal, and postprandial glucose peak levels within 3 h, as well as significantly higher TIR. A similar trend was observed when the analysis was restricted to patients with type 2 diabetes. These results suggest that high-amylose rice may be a more beneficial staple food for glycemic control than regular rice.

Early time-restricted eating improves markers of cardiometabolic health but has no impact on intestinal nutrient absorption in healthy adults

Early time-restricted eating (eTRE) improves aspects of cardiometabolic health. Although the circadian system appears to regulate nutrient absorption, little is known about the effects of eTRE on intestinal absorption. In this randomized crossover trial, 16 healthy adults follow a controlled, weight maintenance diet for 9days, consuming all calories between 0800 and 1400 (eTRE schedule) or 0800 and 2000 (control schedule). We measure the energy content of the diet, stool, and urine with bomb calorimetry and calculate intestinal energy absorption. The eTRE schedule is more effective than the control eating schedule for improving markers of cardiometabolic health, including 24-h mean glucose concentrations and glycemic variability, assessed as the mean amplitude of glycemic excursions. However, eTRE has no effect on intestinal energy and macronutrient absorption, gastrointestinal transit time, colonic hydrogen gas production, or stool microbial composition, suggesting eTRE does not impact gastrointestinal function. This trial is registered (ClinicalTrials.gov: NCT04877262).

Ambient temperature and the occurrence of intradialytic hypotension in patients receiving hemodialysis.

Intradialytic hypotension (IDH) is a common hemodialysis complication causing adverse outcomes. Despite the well-documented associations of ambient temperatures with fluid removal and pre-dialysis blood pressure (BP), the relationship between ambient temperature and IDH has not been adequately studied. We conducted a cohort study at a tertiary hospital in southern Taiwan between 1 January 2016 and 31 October 2021. The 24-h pre-hemodialysis mean ambient temperature was determined using hourly readings from the weather station closest to each patient's residence. IDH was defined using Fall40 [systolic BP (SBP) drop of ≥40mmHg] or Nadir90/100 (SBP <100 if pre-dialysis SBP was ≥160, or SBP <90mmHg). Multivariate logistic regression with generalizing estimating equations and mediation analysis were utilized. The study examined 110400 hemodialysis sessions from 182 patients, finding an IDH prevalence of 11.8% and 10.4% as per the Fall40 and Nadir90/100 criteria, respectively. It revealed a reverse J-shaped relationship between ambient temperature and IDH, with a turning point around 27°C. For temperatures under 27°C, a 4°C drop significantly increased the odds ratio of IDH to 1.292 [95% confidence interval (CI) 1.228 to 1.358] and 1.207 (95% CI 1.149 to 1.268) under the Fall40 and Nadir90/100 definitions, respectively. Lower ambient temperatures correlated with higher ultrafiltration, accounting for about 23% of the increased IDH risk. Stratified seasonal analysis indicated that this relationship was consistent in spring, autumn and winter. Lower ambient temperature is significantly associated with an increased risk of IDH below the threshold of 27°C, irrespective of the IDH definition. This study provides further insight into environmental risk factors for IDH in patients undergoing hemodialysis.

Morning blood pressure surge and intracranial atherosclerotic plaque characteristics: a high-resolution magnetic resonance vessel wall imaging study.

To investigate the relationship between morning blood pressure surge (MBPS) and intracranial atherosclerotic plaque burden and vulnerability. A total of 267 ischaemic stroke patients were retrospectively analysed. Sleep-trough and prewaking MBPS were calculated from ambulatory blood pressure monitoring (ABPM). Plaque characteristics, including intraplaque haemorrhage (IPH), maximum wall thickness (max WT), and stenosis degree, were obtained from high-resolution MR vessel wall imaging (HR-vwMRI). Linear and logistic regression were used to detect the association. Subjects with the top tertile of sleep-trough MBPS (≥15.1 mmHg) had a lower prevalence (9.1% vs. 19.6%, P = .029) of severe stenosis (≥70%) than others. Subjects within the top tertile of prewaking MBPS (≥7.6 mmHg) had a lower percentage of IPH (27.3% vs. 40.4%, P = .035) than others. After adjusting for stroke risk factors (age, sex, diabetes, hyperlipidaemia, hyperhomocysteinaemia, smoking, and family stroke history) and 24-h mean systolic blood pressure, 10 mmHg sleep-trough MBPS increment was associated with 0.07mm max WT reduction, and the top tertile MBPS group was associated with a lower chance of severe stenosis (odd ratio = 0.407, 95% CI, 0.175-0.950). Additionally, an increased prewaking MBPS is associated with a lower incidence of IPH, with OR = 0.531 (95% CI, 0.296-0.952). Subgroup analysis demonstrated that the positive findings could only be seen in non-diabetic subjects. Increment of MBPS is negatively associated with intracranial atherosclerotic plaque burden and vulnerability, and this relationship remains significant in the non-diabetic subgroup. This study provided evidence that MBPS was associated with the intracranial atherosclerotic plaque burden and vulnerability on HR-vwMRI.

Improvement of spatial-temporal urban heat island study based on local climate zone framework: A case study of Hangzhou, China

Large-scale long-period urban heat island (UHI) intensity (UHII) prediction with high spatiotemporal resolutions, satisfactory accuracy, and calculation efficiency is crucial and challenging for UHI mitigation studies. This study proposes a framework combining an urban weather generator (UWG), local climate zone (LCZ), deep-learning method, and Python automatic cyclical calculation to obtain hourly UHII throughout one year and over a total of 1920 blocks in Hangzhou City. The spatial-averaged hourly UHII are between −2 °C and 6 °C in more than 96 % time, and those at 0 °C–1 °C contribute to 43.80 % of the total time. Spring gives the most intense nocturnal UHII, while winter has the weakest one. A significant diurnal UCI phenomenon could accompany the strong nocturnal UHI phenomenon. From the synthetic (based on seasonal data) 24-h curves, mean UHII and UCII (average of the positive and negative values, respectively) drop by approximately 25 % in winter compared to spring. Spatially, UHII is higher in the central regions with compact buildings but significantly lower in the high-vegetation-coverage regions. Based on LCZ framework, LCZ 1 (compact high-rise configurations) has the highest UHII, independent of examined periods. UHII relations to building coverage, vegetation ratio, and building height are individually quantified. The building coverage has the highest influence on annual UHII, with a correlation coefficient as high as 0.76. Results indicate that, for UHI mitigation purposes, the percentage of compact high-rise configurations (LCZ 1) in the urban area shall be limited, and the vegetation ratio is better to be greater than 20 %.

The association of exhaled nitric oxide with air pollutants in young infants of asthmatic mothers

BackgroundExhaled nitric oxide is a marker of airway inflammation. Air pollution induces airway inflammation and oxidative stress. Little is known about the impact of air pollution on exhaled nitric oxide in young infants.MethodsThe Breathing for Life Trial recruited pregnant women with asthma into a randomised controlled trial comparing usual clinical care versus inflammometry-guided asthma management in pregnancy. Four hundred fifty-seven infants from the Breathing for Life Trial birth cohort were assessed at six weeks of age. Exhaled nitric oxide was measured in unsedated, sleeping infants. Its association with local mean 24-h and mean seven-day concentrations of ozone, nitric oxide, nitrogen dioxide, carbon monoxide, sulfur dioxide, ammonia, particulate matter less than 10 μm (PM10) and less than 2.5 μm (PM2.5) in diameter was investigated. The air pollutant data were sourced from local monitoring sites of the New South Wales Air Quality Monitoring Network. The association was assessed using a ‘least absolute shrinkage and selection operator’ (LASSO) approach, multivariable regression and Spearman’s rank correlation.ResultsA seasonal variation was evident with higher median exhaled nitric oxide levels (13.6 ppb) in warmer months and lower median exhaled nitric oxide levels (11.0 ppb) in cooler months, P = 0.008. LASSO identified positive associations for exhaled nitric oxide with 24-h mean ammonia, seven-day mean ammonia, seven-day mean PM10, seven-day mean PM2.5, and seven-day mean ozone; and negative associations for eNO with seven-day mean carbon monoxide, 24-h mean nitric oxide and 24-h mean sulfur dioxide, with an R-square of 0.25 for the penalized coefficients. These coefficients selected by LASSO (and confounders) were entered in multivariable regression. The achieved R-square was 0.27.ConclusionIn this cohort of young infants of asthmatic mothers, exhaled nitric oxide showed seasonal variation and an association with local air pollution concentrations.

Association between short-term exposure to ambient air pollution and upper respiratory tract infection in Kunshan.

The health effects of air pollution have become a major public health problem. Studies on the relationship between short-term exposure to air pollutants and upper respiratory tract infection (URTI) related clinic visits and expenditures were scarce. From January 1, 2019, to December 31, 2021, we included all the URTI cases that turned to 11 public hospitals in Kunshan, and summarized individual medical cost. Daily meteorological factors and 24-h mean concentrations of four common air pollutants, including particulate matter with an aerodynamic diameter less than 2.5μm (PM2.5) and 10μm (PM10), sulfur dioxide (SO2), and nitrogen dioxide (NO2), were consecutively recorded. Generalized additive regression model was adopted to quantify the associations between each air pollutant and the daily clinic visits of URTI cases. We further calculated attributable number (AN) and attributable fraction, and performed sensitivity analysis by gender, age, and season. A total of 934,180 cases were retrieved during the study period. PM2.5, PM10, SO2, and NO2 showed significant associations with hospital visits and expenditures due to URTI. Relative risks for them were 1.065 (95% confidence interval [CI] 1.055, 1.076), 1.045 (95% CI 1.037, 1.052), 1.098 (95% CI 1.038, 1.163), and 1.098 (95% CI 1.085, 1.111) on lag 0-5days, respectively. Thirty-one thousand four hundred fifty-five (95% CI 27,457, 35,436) cases could be ascribed to increased NO2 and accounted for 3.37% (95% CI 2.94%, 3.79%) of all clinic visits. Sensitivity analyses indicated that the effects of air pollution were generally consistent for male and female. PM2.5, PM10, and NO2 had stronger associations among people aged ≤ 18years, followed by those aged 19-64years and ≥ 65years. The association strengths of air pollution varied seasonally. Short-term exposure to ambient air pollutants had significant associations with clinic visits and expenditures owing to URTI. Children and adolescents appeared to be more susceptible to adverse health effects of air pollution. NO2 may be a priority when formulating pollution control measures.

The 24-h profile of the DNA repair enzyme 8-oxoguanine glycosylase 1 (OGG1) is associated with age, TNF-α, and waist circumference in healthy adults

It is unknown how the DNA repair enzyme OGG1 relates to healthy aging in humans, in particular to inflammaging, that is associated with increased levels of TNF-α. This study aimed (1) to investigate how 24-h profiles for OGG1 change during healthy aging and (2) to analyze the relationship of OGG1 with TNF-α, central body fat, cortisol and oxidative DNA/RNA damage. In a cross-sectional study in 20 healthy older and 20 young women, salivary levels of OGG1, TNF-α, cortisol and oxidative DNA/RNA damage were quantified by ELISAs every 4 h for a 24-h period. Trunk circumferences were taken as measures of central body fat. Older women, compared to young women, exhibited significantly lower protein levels of OGG1 throughout the whole 24-h period, a 2.5 times lower 24-h mean level for OGG1 (P < 0.00001) and loss of 24-h variation of OGG1. Both age groups demonstrated significant 24-h variation for TNF-alpha, cortisol and oxidative damage. The 24-h mean level for TNF-α was more than twice as high in older compared to young women (P = 0.011). Regression analysis detected that age, TNF-α and waist circumference were negative significant predictors of OGG1, explaining 56% of variance of OGG1 (P < 0.00001), while levels of cortisol and oxidative damage were no predictors of OGG1. Results indicate a strong decrease of protein levels of OGG1 and a loss of 24-h variation during natural cellular aging. The negative relationship, found between OGG1 and TNF-α and between OGG1 and waist circumference, suggests involvement of proinflammatory processes in DNA repair.

Abstract 17563: Serial ABPM, Antihypertensive Drug Treatment, and Pregnancy Outcomes in Women With Hypertension Found Early During Pregnancy

Introduction: Few data are available on serial ambulatory blood pressure monitoring (ABPM) throughout pregnancyand antihypertensive drug treatment required for good blood pressure (BP) control in hypertensivepregnant women. Hypothesis: Evaluation of BP control, antihypertensive drug treatment intensity, and pregnancy outcomes in patients with hypertension (HTN) found early during pregnancy. Methods: We studied 49 consecutive pregnant patients (mean age 33.4±4.8 years, BMI before pregnancy24.5±3.7 kg/m2) referred for office HTN found early during pregnancy who gave birth to 50 children (1 twin pregnancy) in 2011-2015. Gestational HTN was previouslydiagnosed in 39 women, and 9 women had a history of previous miscarriage or stillbirth, with multipleprevious pregnancies lost in some patients. ABPM was repeated at 5-10-15-20-25-30-33-35-37 weeksof pregnancy. We calculated overall antihypertensive treatment intensity in standard daily drug doses per patient (standard doses: labetalol 200 mg, methyldopa 750 mg, metoprolol 50 mg, nifedipine 20mg, verapamil 120 mg). Statistical analysis was performed using ANOVA. Results: All children were born alive (24 vaginal delivery, 26 cesarean section) and are well at follow-up.Gestational age was 38.0±2.5 (range 29-40) weeks, and birth weight was 3215±653g (range 955-4200). Preeclampsia/eclampsia occurred in 10/3 patients. Four patients had normal BP values by ABPM throughout pregnancy and did not receive antihypertensive drugs. Most patients were treatedwith labetalol and methyldopa. Throughout pregnancy, BP remainedwell controlled (24h mean SBP/DBP 120.3-126.0/75.3-77.1 mmHg), the number of treated patientsincreased from 25 at 5 weeks to 42 at 25-35 weeks, and the average number of daily antihypertensivedrug doses in treated pts increased from 1.82 at 5 weeks to 2.98 at 37 weeks. Conclusions: Serial ABPM-guided antihypertensive drug treatment started early during pregnancywas associated with favorable outcomes. The number of patients requiring treatment increased throughout the pregnancy. No physiological BP fall atthe end of 1 st trimester was observed. Our findings help estimate the expected treatment intensity required in pregnant patients with preexisting hypertension.

Blood pressure in atrial fibrillation and in sinus rhythm during ambulatory blood pressure monitoring: data from the TEMPLAR project

The coexistence of hypertension and atrial fibrillation (AF) is common and accounts for a worse prognosis. Uncertainties exist regarding blood pressure (BP) measurements in AF patients by automated oscillometric devices. The Microlife WatchBP 03 AFIB ambulatory BP monitoring (ABPM) device including an AF algorithm with each measurement was used in 430 subjects aged >65 years referred for ABPM and with assumed paroxysmal AF to perform intra-individual comparisons of BP during both AF-indicated and sinus rhythm. Only subjects with >30% of measurements indicating AF and episodes >30 min for assumed AF and for sinus rhythm were included. Mean age was 78 ± 7 years, 43% were male, 77% hypertensive, and 72% were treated. Compared to sinus rhythm, 24-h mean arterial pressure was similar (87.2 ± 9.5 vs 87.5 ± 10.6 mm Hg, p = 0.47), whereas 24-h systolic BP tended to be lower (123.6 ± 13.9 vs 124.7 ± 16.1 mm Hg, p = 0.05) and night-time diastolic BP higher (64.6 ± 10.9 vs 63.3 ± 10.4 mm Hg, p = 0.01) in assumed AF. Diastolic (not systolic) BP variability was higher in AF (p < 0.001). Results were similar with heart rates <90 and ≥90 bpm. In conclusion, this is the first study to use intra-individual comparisons of averaged BP during an ABPM in assumed paroxysmal AF and sinus rhythm. Our results imply that ABPM is feasible and informative also in patients with AF. We also suggest that an AF detection algorithm offers a new approach to evaluate the reliability of averaged BP values in AF compared to SR during an ABPM.

Comparison between visit-to-visit office and 24-h blood pressure variability in treated hypertensive patients.

In any treated hypertensive patient office blood pressure (BP) values may differ between visits and this variability (V) has an adverse prognostic impact. However, little information is available on visit-to-visit 24-h BPV. In 1114 hypertensives of the ELSA and PHYLLIS trials we compared visit-to-visit office and 24-h mean BPV by coefficient of variation (CV) of the mean systolic (S) and diastolic (D) BP obtained from yearly measurements during a 3-4 year treatment period. Visit-to-visit BPV during daytime and night-time were also compared. Twenty-four-hour SBP-CV was about 20% less than office SBP-CV ( P < 0.0001). SBP-CV was considerably greater for the night-time than for the daytime period (20%, P < 0.0001). Results were similar for DBP and in males and females, older and younger patients, patients under different antihypertensive drugs or with different baseline or achieved BP values. In the group as a whole and in subgroups there was significant correlations between office and 24-h BP-CV but the correlation coefficients was weak, indicating that office SBP or DBP CV accounted for only about 1-4% of 24-h SBP or DBP-CV values. Twenty-four-hour mean BP across visits is more stable than across visit office BP. Visit-to-visit office and 24-h BPV are significantly related to each other, but correlation coefficients are low, making visit-to-visit office BP variations poorly predictive of the concomitant 24-h BP variations and thus of on-treatment ambulatory BP stability.