bluuebunny/crossref_metadata_2025 huggingface dataset:
Online reading habits can reveal personality traits: towards detecting psychological microtargeting
Authors: Simchon Almog , Sutton Adam , Edwards Matthew , Lewandowsky Stephan
Published: June 2023

Building on big data from Reddit, we generated two computational text models: (i) Predicting the personality of users from the text they have written and (ii) predicting the personality of users based on the text they have consumed. The second model is novel and without precedent in the literature. We recruited active Reddit users (N=1,105) of fiction-writing communities. The participants completed a Big Five personality questionnaire and consented for their Reddit activity to be scraped and used to create a machine learning model. We trained an natural language processing model [Bidirectional Encoder Representations from Transformers (BERT)], predicting personality from produced text (average performance: r=0.33). We then applied this model to a new set of Reddit users (N=10,050), predicted their personality based on their produced text, and trained a second BERT model to predict their predicted-personality scores based on consumed text (average performance: r=0.13). By doing so, we provide the first glimpse into the linguistic markers of personality-congruent consumed content.
Enhancing global preparedness during an ongoing pandemic from partial and noisy data
Authors: Klamser Pascal P , d’Andrea Valeria , Di Lauro Francesco , Zachariae Adrian , Bontorin Sebastiano , Di Nardo Antonello , Hall Matthew , Maier Benjamin F , Ferretti Luca , Brockmann Dirk , De Domenico Manlio
Published: June 2023

As the coronavirus disease 2019 spread globally, emerging variants such as B.1.1.529 quickly became dominant worldwide. Sustained community transmission favors the proliferation of mutated sub-lineages with pandemic potential, due to cross-national mobility flows, which are responsible for consecutive cases surge worldwide. We show that, in the early stages of an emerging variant, integrating data from national genomic surveillance and global human mobility with large-scale epidemic modeling allows to quantify its pandemic potential, providing quantifiable indicators for pro-active policy interventions. We validate our framework on worldwide spreading variants and gain insights about the pandemic potential of BA.5, BA.2.75, and other sub- and lineages. We combine the different sources of information in a simple estimate of the pandemic delay and show that only in combination, the pandemic potentials of the lineages are correctly assessed relative to each other. Compared to a country-level epidemic intelligence, our scalable integrated approach, that is pandemic intelligence, permits to enhance global preparedness to contrast the pandemic of respiratory pathogens such as SARS-CoV-2.
Evaluating Pre-election Polling Estimates Using a New Measure of Non-ignorable Selection Bias
Authors: West Brady T , Andridge Rebecca R
Published: June 2023

Among the numerous explanations that have been offered for recent errors in pre-election polls, selection bias due to non-ignorable partisan nonresponse bias, where the probability of responding to a poll is a function of the candidate preference that a poll is attempting to measure (even after conditioning on other relevant covariates used for weighting adjustments), has received relatively less focus in the academic literature. Under this type of selection mechanism, estimates of candidate preferences based on individual or aggregated polls may be subject to significant bias, even after standard weighting adjustments. Until recently, methods for measuring and adjusting for this type of non-ignorable selection bias have been unavailable. Fortunately, recent developments in the methodological literature have provided political researchers with easy-to-use measures of non-ignorable selection bias. In this study, we apply a new measure that has been developed specifically for estimated proportions to this challenging problem. We analyze data from 18 different pre-election polls: 9 different telephone polls conducted in 8 different states prior to the US presidential election in 2020, and nine different pre-election polls conducted either online or via telephone in Great Britain prior to the 2015 general election. We rigorously evaluate the ability of this new measure to detect and adjust for selection bias in estimates of the proportion of likely voters that will vote for a specific candidate, using official outcomes from each election as benchmarks and alternative data sources for estimating key characteristics of the likely voter populations in each context.
Impact of body mass index on disease progression and outcomes in patients with nonalcoholic fatty liver disease
Authors: Biswas Sagnik , Vaishnav Manas , Farooqui Naba , Aggarwal Arnav , Pathak Piyush , Yadav Rajni , Das Prasenjit , Elhence Anshuman , Goel Amit , Mishra Ashwani Kumar , Shalimar
Published: June 2023

Background

The relationship between body mass index (BMI) and outcomes in patients with nonalcoholic fatty liver disease (NAFLD) is not well defined. This study aimed to assess the presentations, outcomes, and development of liver-related events (LREs) and non-LREs in patients with NAFLD stratified by BMI.

Methods

Records of NAFLD patients from 2000–2022 were reviewed. Patients were categorized as lean (18.5–22.9 kg/m2), overweight (23–24.9 kg/m2), and obese (>25 kg/m2) based on BMI. Stage of steatosis, fibrosis, and NAFLD activity score were noted in the patients undergoing liver biopsy in each group.

Results

Out of 1051 NAFLD patients, 127 (12.1%) had normal BMI, 177 (16.8%) and 747 (71.1%) were overweight and obese, respectively. Median [interquartile range] BMI was 21.9 [20.6–22.5], 24.2 [23.7–24.6], and 28.3 [26.6–30.6] kg/m2 in each group, respectively. Prevalence of metabolic syndrome and dyslipidemia were significantly higher in the obese. Obese patients had significantly higher median [interquartile range] liver stiffness (6.4 [4.9–9.4] kPa) than overweight and lean subjects. A higher proportion of obese patients had significant and advanced liver fibrosis. At follow-up, there were no significant differences in the progression of liver disease, new LREs, coronary artery disease, or hypertension across the BMI groups. Overweight and obese patients were more likely to develop new-onset diabetes by follow-up. The mortality rates in the three groups were comparable (0.47, 0.68, and 0.49 per 100 person-years, respectively), with similar causes of death (liver-related vs non-liver-related).

Conclusions

Patients with lean NAFLD have similar disease severity and rates of progression as the obese. BMI is not a reliable determinant of outcomes in NAFLD patients.

Key messages

What is already known on this topic

What this study adds

How this study might affect research, practice, or policy
Comparing of COVID-19 response framework in the UK, USA and Indonesia: what can we learn from the psychosocial factors?
Authors: Pribadi Hendra , Atmoko Adi , Hitipeuw Imanuel , Indreswari Henny
Published: June 2023

It is possible to identify sociodemographic and psychological factors for preventing strategies COVID-19. Research on the impact of COVID-19 predominantly focuses on clinical and demographic factors, but ignores psychosocial factors. Psychosocial factors was shaped by the pandemic response include public perceptions and attitudes to the crisis, support, effective government communication and the socioeconomic impact experienced. Understanding psychosocial factors is critical for effective planning for mental health services, communications and coping with the psychological impact of the pandemic. Therefore, this study recommends considering psychosocial factors to design effective prevention strategies from the UK, USA and Indonesian response frameworks and facilitate efficient management of the pandemic.
Transvenous phrenic nerve stimulation is associated with normalization of nocturnal heart rate perturbations in patients with central sleep apnea
Authors: Baumert Mathias , Linz Dominik , McKane Scott , Immanuel Sarah
Published: June 2023

Study Objectives

To determine the effect of transvenous phrenic nerve stimulation (TPNS) on nocturnal heart rate perturbations in patients with CSA.

Methods

In this ancillary study of the remedē System Pivotal Trial, we analyzed electrocardiograms from baseline and follow-up overnight polysomnograms (PSG) in 48 CSA patients in sinus rhythm with implanted TPNS randomized to stimulation (treatment group; TPNS on) or no stimulation (control group; TPNS off). We quantified heart rate variability in the time and frequency domain. Mean change from baseline and standard error is provided.

Results

TPNS titrated to reduce respiratory events is associated with reduced cyclical heart rate variations in the very low-frequency domain across REM (VLFI: 4.12 ± 0.79% vs. 6.87 ± 0.82%, p = 0.02) and NREM sleep (VLFI: 5.05 ± 0.68% vs. 6.74 ± 0.70%, p = 0.08) compared to the control group. Further, low-frequency oscillations were reduced in the treatment arm in REM (LFn: 0.67 ± 0.03 n.u. vs. 0.77 ± 0.03 n.u., p = 0.02) and NREM sleep (LFn: 0.70 ± 0.02 n.u. vs. 0.76 ± 0.02 n.u., p = 0.03).

Conclusion

In adult patients with moderate to severe central sleep apnea, transvenous phrenic nerve stimulation reduces respiratory events and is associated with the normalization of nocturnal heart rate perturbations. Long-term follow-up studies could establish whether the reduction in heart rate perturbation by TPNS also translates into cardiovascular mortality reduction.

Clinical Trial

A Randomized Trial Evaluating the Safety and Effectiveness of the remedē® System in Patients With Central Sleep Apnea, ClinicalTrials.gov, NCT01816776
A Pilot Phase I Trial of Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells in Neonates With Hypoxic-Ischemic Encephalopathy
Authors: Cotten Charles Michael , Fisher Kimberley , Malcolm William , Gustafson Kathryn E , Cheatham Lynn , Marion Amanda , Greenberg Rachel , Kurtzberg Joanne
Published: June 2023

Hypoxic ischemic encephalopathy (HIE) in neonates causes increased mortality and long-term morbidity in surviving babies. Hypothermia (HT) has improved outcomes, however, mortality remains high with ~half of surviving babies developing neurological impairment in their first years. We previously explored the use of autologous cord blood (CB) to determine if CB cells could lessen long-term damage to the brain. However, the feasibility of CB collection from sick neonates limited the utility of this approach. Allogeneic cord tissue mesenchymal stromal cells (hCT-MSC), cryopreserved and readily available, have been shown to ameliorate brain injury in animal models of HIE. We, therefore, conducted a pilot, phase I, clinical trial to test the safety and describe the preliminary efficacy of hCT-MSC in neonates with HIE.

The study treated infants with moderate to severe HIE, treated with HT, with 1 or 2 doses of 2 million cells/kg/dose of hCT-MSC given intravenously. The babies were randomized to receive 1 or 2 doses with the first dose during HT and the second dose 2 months later. Babies were followed for survival and development with scoring of Bayley’s at 12 postnatal months.

Six neonates with moderate (4) or severe (2) HIE were enrolled. All received 1 dose of hCT-MSC during HT and 2 received a 2nd dose, 2 months later. hCT-MSC infusions were well tolerated although 5/6 babies developed low titer anti-HLA antibodies by 1 year of age. All babies survived, with average to low-average developmental assessment standard scores for ages between 12 and 17 postnatal months. Further study is warranted.
Astragaloside IV protects LO2 cells from oxidative damage caused by radiation-induced bystander effect through Akt/Nrf2 pathway
Authors: Wan Danting , Zhu Zihao , Zhou Jie , Deng Zhengzheng , Lei Pengyuan , Liu Qi , Sun Xiaoya , Huang Bo
Published: June 2023

Background

The protective effects of astragaloside IV (ASIV) on various diseases are well known, but its potential impact on radiation-induced bystander effect (RIBE) has remained unclear.

Objective

This study aimed to explore the protective mechanism of ASIV against oxidative damage caused by RIBE in LO2 cells.

Methods

To construct the RIBE model, the conditioned medium from HepG2 cells irradiated with radiation was transferred to nonirradiated LO2 cells. LY294002, a commonly used phosphatidylinositol 3-kinase/Akt pathway inhibitor, was added to LO2 cells 1 h before exposing HepG2 cells to radiation. LO2 cells were then collected for analyses after RIBE exposure.

Results

The study found that ASIV significantly improved cell proliferation and promoted the recovery of mitochondrial membrane potential while reducing the rate of apoptosis. Western blot analyses demonstrated that ASIV upregulated B-cell lymphoma 2 and downregulated B-cell lymphoma 2-related X protein and cleaved-caspase 3. Measurement of reactive oxygen species, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels showed that ASIV effectively restored the oxidative stress state induced by RIBE. Additionally, immunofluorescence and western blots analyses confirmed that ASIV enhanced the translocation of Nrf2 to the nucleus and activated downstream nicotinamide adenine dinucleotide phosphate: quinine oxidoreductase 1 and heme oxygenase 1. Importantly, Akt pathway inhibitor repressed ASIV-induced activation of Nrf2 and its protective effect against RIBE.

Conclusion

This study demonstrates that ASIV protects LO2 cells against oxidative damage caused by RIBE through activation of the Akt/Nrf2 pathway.
AS160 expression, but not AS160 Serine‐588, Threonine‐642, and Serine‐704 phosphorylation, is essential for elevated insulin‐stimulated glucose uptake by skeletal muscle from female rats after acute exercise
Authors: Wang Haiyan , Zheng Amy , Arias Edward B. , Kwak Seong Eun , Pan Xiufang , Duan Dongsheng , Cartee Gregory D.
Published: June 2023

One exercise session can increase subsequent insulin‐stimulated glucose uptake (ISGU) by skeletal muscle in both sexes. We recently found that muscle expression and phosphorylation of key sites of Akt substrate of 160 kDa (AS160; also called TBC1D4) are essential for the full‐exercise effect on postexercise‐ISGU (PEX‐ISGU) in male rats. In striking contrast, AS160's role in increased PEX‐ISGU has not been rigorously tested in females. Our rationale was to address this major knowledge gap. Wild‐type (WT) and AS160‐knockout (KO) rats were either sedentary or acutely exercised. Adeno‐associated virus (AAV) vectors were engineered to express either WT‐AS160 or AS160 mutated on key serine and threonine residues (Ser588, Thr642, and Ser704) to alanine to prevent their phosphorylation. AAV vectors were delivered to the muscle of AS160‐KO rats to determine if WT‐AS160 or phosphorylation‐inactivated AS160 would influence PEX‐ISGU. AS160‐KO rats have lower skeletal muscle abundance of the GLUT4 glucose transporter protein. This GLUT4 deficit was rescued using AAV delivery of GLUT4 to determine if eliminating muscle GLUT4 deficiency would normalize PEX‐ISGU. The novel results were as follows: (1) AS160 expression was required for greater PEX‐ISGU; (2) rescuing muscle AS160 expression in AS160‐KO rats restored elevated PEX‐ISGU; (3) AS160's essential role for the postexercise increase in ISGU was not attributable to reduced muscle GLUT4 content; and (4) AS160 phosphorylation on Ser588, Thr642, and Ser704 was not essential for greater PEX‐ISGU. In conclusion, these novel findings revealed that three phosphosites widely proposed to influence PEX‐ISGU are not required for this important outcome in female rats.
PROGNOSTIC VALUE OF MICRORNA-126-3P FOR CARDIOVASCULAR EVENTS IN A GENERAL POPULATION
Authors: Martinez-Arroyo Olga , Ortega Ana , Flores-Chova Ana , Sanchez-Garcia Belen , Garcia-Garcia Ana B. , Chaves Felipe J. , Martin-Escudero Juan C , Redon Josep , Cortés Raquel
Published: June 2023

Objective:

Endothelial dysfunction is a forerunner of atherosclerosis, leading to cardiovascular disease, and albuminuria is a marker of endothelial dysfunction. Measurement of circulating levels of microRNAs is emerging as potential biomarkers for cardiovascular disease. We aimed to estimate the predictive value of a plasma microRNAs signature associated with albuminuria in the incidence of cardiovascular events.

Design and method:

The first study phase was to identify the plasma miRNAs associated with albuminuria in patients with HTN and controls. In a second step, a predictive model of miRNAs to assess the risk to develop CV events was analyzed in a retrospective study of the general population (HORTEGA Follow-up Study), on those who did not have previous CVD and had complete basal information on relevant covariates. Plasma miRNAs quantified in hypertensive patients by next generation sequencing were validated in a cohort of patients and controls by real-time quantitative PCR. The microRNAs associated with albuminuria were tested and their prognostic value for cardiovascular event incidence were analyzed on a retrospective, population-based study using Cox proportional hazard models.

Results:

A plasma microRNA profile was identified in the discovery cohort (n = 48) associated with albuminuria and three microRNAs (miR-126-3p, miR-1260b and miR-374a-5p) were confirmed in the validation cohort (n = 98). The microRNA signature discriminates urinary albumin excretion at baseline (n = 1025), and predicts the incidence of cardiovascular events and coronary heart disease and stroke in a general population retrospective study within a 14-year follow-up (n = 926). Thus, high miR-126-3p levels were associated with a shorter time free of both cardiovascular events (HR = 1.48, (1.36–1.62), p < 0.0001), as well as coronary artery disease and stroke combined (HR = 2.49, (2.19–2.83), p < 0.0001) (Figure).

Conclusions:

An increased plasma microRNAs profile was identified in hypertensive patients with albuminuria. Increased miR-126-3p emerges as a prognostic marker for cardiovascular events in a long-term general population. Further studies will assess the potential role of miR-126-3p as a guide for the status of endothelial dysfunction.
PREDICTION OF CAROTID INTIMA MEDIA THICKNESS AND STIFFNESS IN ADOLESCENCE AND YOUNG ADULTHOOD FROM FOUR BLOOD PRESSURE PARAMETERS AND RESTING HEART RATE
Authors: Neuhauser Hannelore , Büschges Julia , Schmidt-Trucksäss Arno
Published: June 2023

Objective:

Childhood blood pressure (BP) is associated with hard outcomes and intermediate markers of cardiovascular disease several decades later but studies on more short-termed outcomes are scarce and and it is unclear whether different BP parameters are all predictive. This study investigates the association of four BP parameters and resting heart rate (RHR) at age 3 - 17 years with three carotid markers one decade later with population-based data.

Design and method:

4,607 14- to 28-year old participants of the nationwide German pediatric cohort KiGGS had semi–automated sonography with measurements of carotid intima media thickness (CIMT), lumen diameter (LD) and distensibility coefficient (DC) at their 11-year follow–up. We investigated associations of both baseline and follow-up systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), pulse pressure (PP) and RHR, with CIMT and LD > = 90th percentile and DC > = 10th percentile in logistic regression models. Percentiles were computed by sex and age. Analyses were adjusted for a cardiovascular risk score from added z-scores of body mass index, triglycerides, total-/HDL-cholesterol-ratio and HbA1c.

Results:

In longitudinal analyses SBP, DBP, MAP and RHR were significantly associated with all measures of subclinical atherosclerosis 11 years later, with similar, however weak, effect estimates, e.g. an OR of 1.19 (CI 1.09 - 1.31) for a one standard deviation increase in SBP with elevated CIMT. Cross–sectionally, the strongest association was found for MAP with reduced DC (OR 1.76; CI 1.60 - 1.94). For PP not all of these associations were significant. RHR was associated with elevated LD and reduced DC and inversely associated with elevated CIMT. Associations were similar when adjusting for the composite cardiovascular risk score.

Conclusions:

This study fills a gap between previous findings of an association between childhood BP and adverse effects in the vasculature in mid-adulthood, several decades later, by giving evidence for the association already after one decade. While individual risk prediction based of single BP measurements in this study is only weak, its robustness and consistency over five haemodynamic parameters and three subclinical atherosclerosis measures underscore the importance of preventing high blood pressure already early in the life course.
A PROOF-OF-PRINCIPLE EPIGENOME-WIDE ASSOCIATION STUDY OF PLASMA RENIN AND ALDOSTERONE CONCENTRATION IN A GHANAIAN POPULATION: THE RODAM STUDY
Authors: Linden Eva L. van der , Born Bert -Jan van den , Henneman Peter , Agyemang Charles
Published: June 2023

Objective:

The epigenetic regulation of the renin-angiotensin-aldosterone system (RAAS) potentially plays a role in the pathophysiology underlying the high burden of hypertension in sub-Saharan Africans (SSA). In this first epigenome-wide association study (EWAS) of plasma renin and aldosterone concentrations, we explored the association between DNA methylation and concentrations of renin and aldosterone.

Design and method:

Epigenome-wide DNA methylation was measured using the Illumina 450k array on whole blood samples of 68 Ghanaian participants of the Research on Obesity and Diabetes among African Migrants Study (RODAM). Differentially methylated positions (DMPs) were assessed for plasma renin and aldosterone concentration using linear regression models adjusted for age, sex, body mass index, diabetes mellitus, hypertension, and technical covariates. Additionally, we extracted methylation loci previously associated with hypertension, kidney function, or that were annotated to RAAS-related genes, and associated these with renin and aldosterone concentration.

Results:

We identified one epigenome-wide significant DMP associated with renin, and ten DMPs associated with aldosterone. Top DMPs were annotated to the PTPRN2, SKIL, and KCNT1 genes, which have been reported in relation to cardiometabolic risk factors, atherosclerosis, and sodium-potassium handling. Moreover, EWAS loci previously associated with hypertension, kidney function, or RAAS-related genes, were also associated with renin and aldosterone concentration.

Conclusions:

In this first EWAS on RAAS hormones, we identified DMPs associated with renin and aldosterone in a SSA population. These findings are a first step in understanding the role of DNA methylation in regulation of the RAAS in general, and in a SSA population specifically. The results of this proof-of-principle study will inform new analyses including a larger sample size and a new methylation array (Illumina Infinium MethylationEPIC), which will we use to replicate these initial findings. This will help to further establish the role of DNA methylation and the RAAS system in the hypertension burden in SSA populations.
FOLLOW-UP OF VASCULAR LESIONS IN FIBROMUSCULAR DYSPLASIA. NO EVIDENCE FOR PROGRESSION YET
Authors: Leeuw Peter W. de , Zelis Piet , Kleijnen Bianca , Schutten Monica , Kroon Abraham
Published: June 2023

Objective:

It is currently unknown whether the vascular lesions in patients with fibromuscular dysplasia (FMD) are progressive in time. Therefore, repeat CT-angiography (CTA) is often necessary to evaluate possible evolution of the abnormalites. It would be unjustified to frequently expose patients to this diagnostic modality with its drawbacks (radiation, contrast material) if the vascular lesions turn out to be stable.

The aim of our study was to explore whether vascular FMD lesions (unifocal or multifocal, with or without aneurysms) change in terms of extensiveness or localization over a period of a few years.

Design and method:

To qualify for the present study, patients had to be diagnosed with FMD in any vascular bed and both the diagnostic and the follow-up CTA had to be performed at the same institution using the same imaging protocol. Patients who had been referred by other hospitals and were followed in our own clinic were excluded from the analysis. On both the basal and the follow-up CTA, we assessed the number of lesions, the site of lesions, and the presence or absence of aneurysms.

Results:

A total of 161 patients had both a diagnostic and a follow-up CTA at our own clinic. Their mean age at diagnosis was 49 + 11 years (range 19-76) and 63% of the patients had been detected during a work-up for hypertension. On average, FMD was diagnosed nine years after the initial diagnosis of hypertension had been made. In the remainder of the patients, FMD was diagnosed after the patient had experienced a dissection (coronary, carotid).

Follow-up CTA after two years was available in 111 patients and after three years in 50 patients. In only three patients we found new vascular lesions after a period of two years. In all the others, the pattern of lesions remained constant.

Conclusions:

Over a period of two to three years, vascular FMD lesions do not seem to progress in most patients. If repeat CTA scanning is considered, one should respect at least this time period.
AT1R BLOCKADE PROMOTES TRANSFER OF HYPERTENSION BY RENAL CD11C+F4/80+ MACROPHAGES
Authors: Araos Patricio , Cortés Sut’yam , Campos Rafael , Reyes Javier , Figueroa Steffany M. , Fuenzalida María José , Pacheco Rodrigo , Amador Cristián
Published: June 2023

Objective:

The immune system participates in arterial hypertension (AHT) induced by Angiotensin II (AngII). dendritic cells (DCs)-CD11c+ and macrophages (Mo) are abundant in the kidney. However, new subpopulations of CD11c+ cells with Mo characteristics have been described, presenting an F4/80+ phenotype. Additionally, recent studies have shown a controversial role of the type 1 AngII receptor (AT1R) in CD11c+ cells. In this context, it is unknown whether Mo CD11c+-F4/80+ modifies their phenotype during AngII-induced inflammatory kidney damage, and whether this promotes AHT in an AT1R-dependent manner.

The goal was evaluate whether renal Mo CD11c+-F4/80+ (rMo) modify their phenotype in AHT by AngII and determine whether their transfer to normotensive animals promotes AHT in an AT1R-dependent manner.

Design and method:

Male C57BI/6 mice (8 - 10 weeks, n = 6) were infused with AngII (490 ng/kg/min), AngII+Losartan (LOS; 20mg/kg/day, in drinking water), or vehicle for 14 -days. Systolic blood pressure (SBP) was measured by photoplestimography, DCs-CD11c+-F4/80- and rMo infiltrate were evaluated in cortex and medulla by flow cytometry. These cells were isolated and transferred to normotensive recipients, whose SBP was measured for 7-days (n = 3 - 5). Finally, the rMo were stimulated in vitro with AngII (100nM-24h) to analyze the abundance of mRNAs (Nox2, Sgk1, ENaC and AT1R; qRT-PCR). The data correspond to the mean ± standard deviation.

Results:

AngII increased SBP (AngII 134.7 ± 6.9 vs. Vehicle (Vh) 114.5 ± 7.8mmHg;p < 0.001) and promoted DCs-CD11c+F4/80- (AngII = 45.6 ± 11.9% vs. Vh = 31.7 ± 6.7%; p < 0.05) and Mo-CD11c+F4/80+ (AngII = 66.1 ± 8.4% vs. Vh = 55.6 ± 5.1%; p < 0.05) infiltration in renal medulla, and that was prevented by LOS (p < 0.05). We did not observe statistical differences in cortex. Interestingly, rMo transfer from AngII animals did not induce AHT in healthy recipient animals after 24h (Basal = 106.8 ± 2.3 vs.112.4 ± 4.9 mmHg;ns), compared to DCs-CD11c+-F4/80- (Basal = 110.0 ± 8.3 vs.132.0 ± 14.3mmHg;p < 0.05). However, the rMo of AngII+LOS animals increased SBP healthy recipients with respect to their baseline (basal = 109 ± 5.6 vs. 123 ± 8.0mmHg;p < 0.05). The rMo and DCs of hypertensive animals showed an increase in the abundance of AT1R (p < 0.05) compared to vehicle rMo.

Conclusions:

Pharmacological blockade of AT1R in vivo would have a differential effect on rMo, transferring AHT to normotensive animals. These findings suggest that subpopulations of renal CD11c+ cells have a differential role in AHT.
SUBCLINICAL TARGET ORGAN DAMAGE IN A SAMPLE OF CHILDREN WITH SOLITARY FUNCTIONING KIDNEY. A PRELIMINARY OBSERVATIONAL STUDY
Authors: Tagetti Angela , Cattazzo Filippo , Marcon Denise , Romano Simone , Bortolotti Stefano , Minuz Pietro , Brugnara Milena , Fava Cristiano
Published: June 2023

Objective:

Solitary Functioning Kidney (SFK) is a condition characterized by a single-functioning kidney. Children bearing this condition are exposed to an increased risk of subclinical organ damage (SOD) due to the compensatory hyperfiltration in the remaining kidney and increased peripheral blood pressure (pBP) values. The aim of the present study was to assess the impact of traditional (pBP) and novel (central systolic blood pressure, cSBP) cardiovascular risk factors on SOD in children and adolescents with solitary functional kidney.

Design and method:

Carotid ultrasonography was performed to measure carotid Intima-Media Thickness (cIMT), an index of subclinical atherosclerosis. Arterial stiffness was assessed by measuring carotid Distensibility Coefficient (cDC) and carotid-femoral Pulse Wave Velocity (PWV). Cardiac mass and remodeling were analyzed using transthoracic echocardiography. Central and peripheral (both office and ambulatory) BP measurements, as well as biochemical data from blood and urine samples were collected.

Results:

Forty-eight SFK children and adolescents were included, of whom 45.5% were hypertensive at the Ambulatory Blood Pressure Monitoring. Twenty-four patients had increased cIMT and RWT while 8.4% and 8.9% demonstrated a reduction of cDC and an increase of PWV. Two patients had a left ventricular mass index (LVMi) above the 95th percentile. cSBP correlated with all vascular indices measured (cIMT r = 0.43; cDC r = -0.33; PWV r = 0.42, p < 0.05) and with LVMi (r = 0.41; p = 0.005). Office pSBP correlated with cDC (r = -0.31; p = 0.03), PWV (r = 0.42 and p = 0.004) and LVMi (r = 0.33; p = 0.02). Regarding ABPM measurements, daytime systolic BP correlated with all vascular indices (cIMT r = 0.34, cDC r = -0.31, PWV r = 0.39 p < 0.005) but not with echocardiographic ones. No correlation was found between cardiovascular parameters and the estimated glomerular filtration rate or the urinary albumin to creatinine ratio.

Conclusions:

Our data show a high prevalence of subclinical atherosclerosis and cardiac remodeling in children and adolescents with SFK. A lesser proportion of patients presented an increased arterial stiffening. cSBP more than pBP (office or ambulatory) associates with SOD. Children with SFK could bear a greater cardiovascular risk pointing out the importance of early preventive efforts.
PHARMACOLOGICAL AND INTERVENTIONAL TREATMENT OF RESISTANT HYPERTENSION. A NETWORK META-ANALYSIS
Authors: Schmidt Bernhard , Barbosa Clara Vollmer , Lang Hannah , Melk Anette , Tian Zhejia
Published: June 2023

Objective:

Resistant hypertension is associated with a high risk of cardiovascular disease, chronic kidney disease and mortality. Yet, its management is still challenging. This study aims to establish the comparative effectiveness of pharmacologic and interventional treatments by conducting a network meta-analysis.

Design and method:

We systematically searched MEDLINE, Cochrane Register of Controlled Trials (CENTRAL) and Web of Science Core Collection in March 2022. Randomized controlled trials comparing treatment options as add-on therapy for management of resistant hypertension were included. Outcomes were blood pressure changes, measured in the office and in 24h ABPM. We applied a frequentist random effects model to perform a network meta-analysis combining placebo medication and sham procedure as the reference comparator.

Results:

From 4771 records, 24 studies met our inclusion criteria with 3458 included patients in total. 12 active treatment alternatives were analyzed. Among all comparators, spironolactone had the highest-ranking probability and was considered as the most effective treatment to reduce office systolic blood pressure (-13.30 mmHg [-17.89; -8.72]; P < 0.0001) and 24h systolic blood pressure (-8.46 mmHg [-12.54; -4.38]; P < 0.0001) in patients with resistant hypertension.

Conclusions:

Among all pharmacologic and interventional treatments, spironolactone has been found to be most effective in reducing office and 24h systolic blood pressure as an add-on therapy for resistant hypertension. Our study provides an evidence-based and valid reference in clinical decision-making.
A HYPERADRENERGIC STATE IN HYPERTENSION IS ASSOCIATED WITH MOOD DISTURBANCE AND IMPAIRED STRESS-MODULATED VASOMOTOR RESPONSES
Authors: Farukh Bushra , Faconti Luca , McNally Ryan , Moulton Calum , Young Allan , Chowienczyk Phil
Published: June 2023

Objective:

Increasing evidence suggests a high prevalence of affective disorders in hypertension, however, the physiological associations remain unclear. Noradrenergic activation in the central and peripheral nervous systems is a putative mechanism that may explain the link between both conditions. Here, we investigate whether these stress-sensitive co-morbidities may be dependent on basal noradrenergic activity and whether vascular responses to centrally acting stimuli vary according to noradrenergic activity.

Design and method:

We examined the relation of affective disorders and stress-mediated vascular responses to plasma concentrations of normetanephrine (NMN), a measure of noradrenergic activity, in subjects with primary hypertension. Subjects on antidepressant medication, alpha- and beta-blockers were excluded. The Patient Health Questionnaire (PHQ-9), the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDSSR-16), and Generalised Anxiety Disorder-7 (GAD-7) questionnaires were used for the evaluation of symptoms of depression and anxiety. Forearm blood flow (strain gauge plethysmography) was used to assess vascular responses to mental stress (Stroop colour-word test) and slow breathing (by biofeedback), interventions that respectively increase or decrease noradrenergic activity in the pre-frontal cortex and locus coeruleus.

Results:

100 subjects (53% male) with (mean ± SD) age 43.4 ± 10.9 years were recruited. 88% of subjects were treated with anti-hypertensive medications and 4% had type 2 diabetes. 31% and 34% of the study population scored moderate to severe depression for PHQ-9 and QIDSSR-16 respectively indicating significant mood disturbance. Scores representing low mood and high anxiety were 2-3-fold higher for hypertensive subjects in the highest compared to lowest NMN tertiles (PHQ-9: 9.2 ± 5.8 vs 3.8 ± 2.7, P < 0.001; QIDSSR-16: 12.3 ± 4.9 vs 4.5 ± 3.5, P = 0.003; GAD-7: 9.0 ± 5.5 vs 4.6 ± 3.8, P = 0.003). Forearm vasodilator responses to mental stress and vasoconstrictor responses to slow breathing were attenuated in those with high compared to low NMN (28.3 ± 21% vs. 47.1 ± 30% increases for mental stress and 3.7 ± 21% vs. 18.6 ± 15% decreases for slow breathing for highest vs. lowest tertiles of NMN, both P < 0.01).

Conclusions:

A hyperadrenergic state in hypertension is associated with mood disturbance and impaired stress-modulated vasomotor responses. This association may be mediated by chronic stress impinging on pathways regulating central arousal and peripheral sympathetic nerve activity.
CAN SERUM CONSENTRATION MEASUREMENTS OF ANTIHYPERTENSIVE DRUGS IMPROVE BLOOD PRESSURE CONTROL? A MULTICENTER DOUBLE BLINDED RANDOMIZED CONTROLLED TRIAL
Authors: Halvorsen Lene Vernås , Søraas Camilla Lund , Larstorp Anne Cecilie K. , Bergland Ola Undrum , Brobak Karl Marius , Aune Arleen , Olsen Eirik , Rognstad Stine , Heimark Sondre , Aarskog Nikolai Ravn , Hjørnholm Ulla , Kjær Vibeke Nordheim , Elmula Fadl Elmula M. Fadl , Solbu Marit Dahl , Gerdts Eva , Mo Rune , Opdal Mimi Stokke , Rostrup Morten , Kjeldsen Sverre Erik , Høieggen Aud
Published: June 2023

Objective:

Drug concentration in urine or serum using liquid chromatography coupled to mass-spectrometry (UHPLC-MS/MS) may disclose non-adherence. Whether this direct method will improve adherence is still unknown. In this multicenter randomized controlled trial with a double-blinded approach, we aimed to investigate if measurements and standardized information about serum concentrations of antihypertensive drugs (therapeutic drug monitoring (TDM)), could improve blood pressure (BP) control in documented non-adherent hypertensive patients.

Design and method:

Patients were > = 18 years old with eGFR >30 mL/min/1.73m2, prescribed > = 2 antihypertensive agents and on a stable treatment regimen for at least 4 weeks. Experienced pharmacologists assessed adherence status based on serum drug concentrations, dose and patient-reported time since last intake of the drugs. Patients received no information regarding use of blood samples to screen for non-adherence. The ethics committee approved the study. All patients signed written informed consent.

Non-adherent patients with a systolic daytime ambulatory BP (ABPM) > = 135 mmHg were randomized 1:1 to TDM-intervention or not. The number of visits during 6 months follow-up were equal in both groups and antihypertensive medication regimens remained unchanged. Standardized TDM-information was given to the intervention-group at baseline and after 1 and 3 months. The control group remained uninformed about serum drug measurements until after completion of the study. Life style advice and information on necessity of BP treatment, how to remember to take medications and potential hypertension mediated end-organ damage were given to both groups.

Investigators and patients were masked for BPs, and separate personnel measuring BPs were blinded to randomization group.

Results:

From 2017 to 2022, 606 patients (52.3%) of 1159 patients investigated had uncontrolled HT. The non-adherent patients were younger (57.8 vs 64.0 years, p < 0.001), duration of hypertension was shorter (12 vs 16 years, p = 0.024) and daytime diastolic ABPM (90 vs 84 mmHg, p < 0.001) and heart rate (76 vs 70 bpm, p < 0.001) were higher. Uncontrolled and non-adherent patients were enrolled into the subsequent randomized study performed with a double-blinded approach.

Conclusions:

There was no difference in the primary end-point, daytime systolic ABPM at 3 months, between TDM and control group (-6.7 vs -7.3 mmHg, p = 0.897).
TESTOSTERONE INDUCES POSTMENOPAUSAL HYPERTENSIVE HYPERTROPHY THROUGH INHIBITING THE ACTIVATION OF AMPK- FOXO1/MURF1 SIGNALING PATHWAY
Authors: Zhu Lulu
Published: June 2023

Objective:

It has been found that relative elevated level of testosterone could exacerbates postmenopausal hypertensive left ventricular hypertrophy(PM-HTN-LVH), but the mechanisms responsible are unknown. Moreover, MuRF1, a muscle-specific E3 ubiquitin ligase in the ubiquitination process, was newly identified as a negative regulatory factor of myocardial and muscle tissue in exerting a protective functions on the cardiomyocyte hypertrophy. There are little study to certify whether MuRF1 took part in testosterone-induced PM-HTN-LVH.

Design and method:

Femal spontaneously hypertensive rats (SHR) were ovariectomized (OVX group) or sham-operated (Sham group) at 12 weeks and then the OVX group were intramuscularly injected the testosterone (T 2.85 mg/kg/ quaque omni die im) (OVX+T group) or vehicle (OVX+ vehicle group) for 4 weeks. Futher, Cultured cardiomyocytes were respectively stimulated with different concentration gradients of testosterone for 24h, then measured the expression of myosin heavy chain (MHC) and MuRF1, as well as the phosphorylation levels of AMPK(p-AMPK) and Forkhead box O 1 (p-FOXO1), were separately measured using western blot.

Results:

After 4 weeks of testosterone supplementation, SHR heart exhibited significant increments in the heart weight/tibial length and the levels of IVST, LVPWT, LVM and the expression of MHC, and have a lower expression of the MuRF1, p-AMPK and p-FOXO1 in the OVX+T group, compared with OVX group and Sham group. Moreover, the expression level of p-AMPK and p-FOXO1 in the heart were at least twice as many as gastrocnemius muscle among the three group, but the MuRF1 was equivalent between heart and gastrocnemius muscle. In vivo, after the treatment of different gradients of testosterone for 24h, the protein expression of MHC showed an S-shaped growth trend and MuRF1, p-AMPK and p-FOXO1 presented with reverse S-shaped reduction along with increasing of testosterone concentration, peaking at 10-6M testosterone.

Conclusions:

The present study demonstrates that testosterone induces PM-HTN-LVH by modulating the atrophy related AMPK-FOXO1/MuRF1 signaling pathway in vitro and vivo. Increased the heart expression of MuRF1 by activation of AMPK may reverse testosterone-mediated PM-HTN-LVH, which might cause little change of MuRF1 expression in the skeletal muscle resulting in the muscle atrophy.
PULSE WAVE VELOCITY AND BLOOD PRESSURE VARIABILITY AS PROGNOSTIC INDICATORS IN VERY ELDERLY PATIENTS WITH DECOMPENSATED CHRONIC CONDITIONS
Authors: Sierra Alejandro De La , Sierra Cristina , Murillo Marcos , Aiello Francesco , Mateu Aina , Almagro Pedro
Published: June 2023

Objective:

There is scarce evidence of the prognostic importance of hemodynamic measures, such as blood pressure (BP), BP variability and arterial stiffness in the very elderly population with advanced chronic conditions. We aimed to evaluate the prognostic importance of 24-hour BP, BP variability and arterial stiffness in a cohort of very elderly patients admitted to the hospital due to a decompensated chronic disease.

Design and method:

We studied 249 patients older than 80 (66% women), admitted due to a chronic disease decompensation (60% congestive heart failure). During admission, 24-hour brachial and central BP, BP and heart rate variabilities, aortic pulse wave velocity and BP variability ratio were determined through non-invasive 24-hour monitoring. The primary outcome was 1-year mortality. Secondary outcome was the composite of 1-year mortality or readmission.

Results:

Increased arterial stiffness (aortic pulse wave velocity and BP variability ratio) was associated with 1-year mortality. For each standard deviation (SD) increase in aortic pulse wave velocity and BP variability ratio, mortality increased 3.3 times and 31%, respectively, after adjustments for clinical confounders and BP. Increased BP variability (38% increase for each SD change) and reduced heart rate variability (32% increase for each SD change) also predicted 1-year mortality in fully adjusted models. No association was found between 24-hour BP (either brachial or aortic) and 1-year mortality.

Conclusions:

Increased aortic stiffness and BP and heart rate variabilities predict 1-year mortality in very elderly patients with decompensated chronic conditions. Measurements of such estimates could be useful in the prognostic evaluation of this specific population.
SUBPOPULATIONS OF LYMPHOCYTES AND MONOCYTES IN PATIENTS` VENOUS BLOOD WITH ATRIAL FIBRILLATION OR ATRIAL FLUTTER ASSOCIATED WITH HYPERTENSION
Authors: Ilchyshyna Olena , Sychov Oleg , Talaieva Tetiana , Stasyshena Oksana
Published: June 2023

Objective:

The most common reason of arrhythmia onset nowadays is hypertensive desease. The aim of the study is to compare the subpopulations of lymphocytes (LCTs) and monocytes (MCTs) in blood of patients (pts) with paroxysmal and persistent forms of AF or atrial flutter (AFL) associated with arterial hypertension.

Design and method:

The study involved 103 patients with atrial fibrillation and flutter that occurred on the backdround of hypertension. Depending on the form of arrhythmia, patients were divided into three main groups: group I – with paroxysmal form of atrial fibrillation, group II – with a persistent form of atrial fibrillation, group III – with a persistent form of atrial flutter. The control groups included patients with hypertension, but without these arrhythmias and healthy individuals who entered groups IV and V, respectively. The lymphocytes and monocytes subpopulation in peripheral blood was assessed by flow cytometry.

Results:

Analyzing the lymphocyte subpopulations in peripheral blood of patients with atrial fibrillation and flutter (groups I, II and III), it was found that the number of cells with cytotoxic activity (NK and NKT) in both absolute count and percentage values was significantly higher than in healthy individuals. A statistically significant decrease of T-regulatory cells number was found in patients with arrhythmias compared to control groups (p < 0.05). In patients with AF and AFL associated with hypertension, compared to patients with hypertension without these rhythm disturbances or healthy individuals, there is an increased number of classical and intermediate monocytes subpopulations.

Conclusions:

1. In patients with atrial fibrillation or atrial flutter associated with hypertension, compared to patients with hypertension without these rhythm disturbances or healthy people, there is an increased number of classical and intermediate monocytes fraction and a decreased content of T-regulatory cells in peripheral blood, an increased number of cells with cytotoxic activity (NK and NKT) compared to healthy individuals. These changes can be one of the factors for the activation of systemic and local inflammatory processes that can lead to fibrosis in the myocardium and the associated electrical and structural remodeling typical for AF and AFL.
RAS BLOCKERS PLUS CCB COMBINATIONS ON HOMA-IR, HOMA-B, HOMA-S AND QUICKI INDICES IN PREDIABETIC HYPERTENSIVE PATIENTS, A RANDOMIZED 12-WEEK OPEN-LABEL COMPARATIVE STUDY
Authors: Liontos Angelos , Biros Dimitrios , Papagiannopoulos Christos , Veliani Cornelia , Tsiakas Ilias , Christaki Eirini , Elisaf Moses , Liberopoulos Evangelos , Milionis Haralampos , Liamis Georgios
Published: June 2023

Objective:

Hypertensive patients often suffer from other metabolism related comorbidities characterized by insulin resistance (e.g., diabetes mellitus, metabolic syndrome). Dual combination treatment is advised with current treatment guidelines for the management of Hypertension. ARB or ACE-i plus CCB combinations are considered to have a beneficial effect on glucose homeostasis. We present comparative data of the effect of delapril/manidipine versus telmisartan/amlodipine versus valsartan/amlodipine combination treatments, in HOMA-IR, HOMA-B, HOMA-S and QUICKI indices before and after a 12-week treatment, in hypertensive prediabetic patients.

Design and method:

Data were collected from 158 patients from the outpatient clinic for patients with lipid disorders, hypertension and diabetes of our hospital, during the period 2014-2018. A total of 53 patients was randomized in the delapril/manidipine (DEL/MANI) group 30/10 mg per day while 51 patients had been randomized in the group of telmisartan/amlodipine (TEL/AMLO) 80/5mg per day and 54 patients in the valsartan/amlodipine (VAL/AMLO) 160/5 mg per day. All patients successfully completed the study. Baseline characteristics are presented in Table 1A.

Results:

The resulting alternations in HOMA-IR, HOMA-B, HOMA-S, QUICKI, before and after the 12-week treatment are presented on Table 1B for all treatment groups.

Conclusions:

comparison between the treatment groups showed a statistically significant difference in the change of HOMA-IR (from the beginning of treatment to its end) between the TEL/AMLO treatment group and the DEL/MANI treatment group (p-value<0.05), with increased insulin sensitivity in the TEL/AMLO group. Furthermore, HOMA-B was significantly increased in the DEL/MANI group compared with the TEL/AMLO group (p<0.05). No other significant changes were evident. Patients in the TEL/AMLO group had significantly lower insulin resistance as shown by the HOMA-IR index compared with the patients that received VAL/AMLO (p <0.001). Furthermore, QUICKI index was significantly increased in the TEL/AMLO group compared with the VAL/AMLO group (p<0.01).