bluuebunny/crossref_metadata_2025_split huggingface dataset:
KLOTHO GENE VARIANTS (RS9536314) CORRELATES WITH DEVELOPMENT OF HYPERTENSIVE DISORDERS OF PREGNANCY AND HIGHER RATE OF MISCARRIAGE
Authors: Tunesi Francesca , Simonini Marco , Gerosa Camilla , Smid Maddalena , Citterio Lorena , Zagato Laura , Candiani Massimo , Vezzoli Giuseppe , Manunta Paolo , Lanzani Chiara Livia 
Published: May 2024

Objective:
Hypertensive disorders of pregnancy (HDP) are one of the leading causes of maternal and fetal morbidity and mortality worldwide. The incidence of HDP ranges from 4 to 25%. HDP are classified into four types: preeclampsia (PE), gestational hypertension (GH), superimposed preeclampsia, and chronic hypertension (CH). The gene Klotho (KL) is involved in several biological processes in the pathophysiology of HDP, including angiogenesis, the synthesis of antioxidant enzymes, endothelial nitric oxide generation, and endothelial dysfunction prevention. This study aims to evaluate the relationship between the incidence of HDP and the KL rs9536314 polymorphism, already associated with hypertension.

Design and method:
Most of the patients were enrolled during pregnancy in the outpatient clinic for HDP at San Raffaele Hospital; the remaining were enrolled it the outpatient clinic for hypertension at San Raffaele Hospital. A total of 142 patients were recruited: 19 PE (13.4%), 26 CH (18.3%), 39 GH (27.5%) and 58 controls (40.8%). Anamnestic interview was conducted to all of them. All patients signed informed consent and samples were taken for genotyping.

Results:
Caesarean section was more frequent in pathological pregnancy (p<0.001). Also, medically assisted procreation is more frequent in them (p<0.001). In normal pregnancies woman have a later delivery date (p<0.001). History of CH was more frequent in women with HDP than in those without (p< 0.001). KL variant with the minor allele (GG) is more prevalent in patients with normal pregnancy (p=0.01), even after adjusting for primary clinical factors like method and age of conception and mode of delivery. The same SNP also proved to be less correlated with the presence of a history of multiple miscarriage (p=0.04), which instead was positively correlated with the concomitant presence of autoimmune pathologies.

Conclusions:
The study therefore highlighted the role of the rs9536314 polymorphism of the KL gene in HDP. It suggests an association of the TT allelic variant with both the development of the hypertensive disorders of pregnancy and with the history of miscarriage. More data are needed to confirm this evidence and the potential role of Klotho protein in hypertensive disorders of pregnancy.
CLINICAL, LABORATORY AND ECHOCARDIOGRAPHIC VARIABLES ASSOCIATED WITH UNCONTROLLED RESISTANT HYPERTENSION IN WOMEN
Authors: Stevanovic Angelina , Dwklwva Milica , Smiljic Sonja , Popovic Biljana Pencic 
Published: May 2024

Objective:
High blood pressure is the most deadly risk factor for women worldwide. Resistant hypertension (RH) is defined as office and ambulatory blood pressure (BP) requiring 4 or more antihypertensive medications, whether controlled or uncontrolled. Women are at greater risk of developing resistant hypertension than men.

Design and method:
1119 resistant hypertensive patients diagnosed by ambulatory BP monitoring as true RH patients were divided into two groups: controlled RH (CRH) group, n = 489 and uncontrolled RH (URH), n = 630.
The body mass index (BMI) was calculated and all patients were evaluated for nonmodifiable risk faktors, which included age and sex, and modifiable risc factors and concomitant diseases, such as smoking, use of alcohol, Dyslipidemia, Obesity, Diabetes mellitus, Ischemic heart disease, Renal disease and Cerebrovascular disease.
Laboratory evaluation included fasting glycemia, creatinine, uric acid, lipids, microalbuminuria.
Conventional and TDI echocardiography were performed in all patients, included E/Em (ratio of diastolic velocities), left ventricular mass index (LVM) and left atrial volume index (LAVI) were calculated according to the recommendation (ASE/EACVI). Statistical analysis included bivariate logistic regression.

Results:
Patients with URH were older (72±9.8 vs 71±10.7;p=0,01), more obese (28.0±4.0 vs 27.6±3.3;p=0.036), they also had higher prevalence of Diabetes mellitus (241(38.3%) vs 141(28.8%);p=0,001) and significantly more often in menopause or postmenopause (402(63.8%) vs 287(58.7%); p=0.046). LAVI (43.7±17.7 vs 40.2±15.0;p=0,001), LVEDV (183.3±46.3 vs 177.3±48.7;p=0,038), LVESV (82.2±24.9 vs 78.2±24.8,;p=0,007)), LVMI (116.2±23.2 vs 111.2±22.9;p=0,0003), E/Em (15.0±3.7 vs 14.5±3.8;p=0.038) and uric acid (356.3±106.7 vs 340.1±103;.p=0,028) were significantly higher in this group.
Uncontrolled RH associated with older age (0.987(0.975-0.999); p=0,032), obesity (0.968(0.936-1.000);p=0,049) and diabetes (1.467(1.132-1.901);p=0,004), but not with menopause. Having left ventricular hypertrophy (0.992(0.987-0,998);p=0,008), increased LAVI (0.991(0.984-0.999);p=0.023) and higher uric acid (1.001 (1.000-1.003), p =0.038) are also associated with URH.

Conclusions:
The prevalence of uncontrolled RH in women was high, despite optimal therapy. Hypetension remains uncontrolled in patients who are older, obese, with diabetes, left ventricular hypertrophy, and in menopause. Higher uric acid level also seems to have a negative influence on the control of the disease. High prevalence of poor blood pressure control motivates promotion of new therapeutic strategies and lifestyle changes.
COMPARISON BETWEEN WOMEN AND MEN IN THE TREATMENT OF HYPERTENSION: THE REAL-WORLD OBSERVATIONAL PROSPECTIVE DATA FROM DISCOVERY STUDY
Authors: Šabovicˇ Miso , Pejkov Hristo , Kovacˇevic´-Preradovic´ Tamara , Kušljugic´ Zumreta , Kuprešak Drasko , Jatic´ Zaim , Urinov Oybek , Caraus Alexandru , Bajraktari Gani , Gruev Ivan , Vintila Vlad Damian , Csanádi Zoltan , Batjargal Sodgerel 
Published: May 2024

Objective:
The 2023 ESH guidelines strongly emphasize the lack of data on women, both in randomized clinical trials and in real-world data. It is not known whether the considerable efforts to equalize the treatment of women and men have led to changes in routine practice, which was the main aim of our study.

Design and method:
The DISCOVERY study is a large real-world prospective observational study investigating the treatment of patients with hypertension and/or hypercholesterolemia in primary or secondary care in 10 countries in 2021 and 2022. Patients of both sexes over 18 years were included. Investigators (301 GPs, 127 internists, 271 cardiologists) treated the patients according to their usual routine. They collected data on admission and up to 12 weeks after admission so that treatment characteristics could be analyzed. The physicians were not informed about the aim (comparison of women vs. men) of the study to avoid information bias.

Results:
The study included 11,287 patients, 93.6% of whom had hypertension at baseline that was either newly diagnosed (N=2247) or previously treated (N=8280; 86.6% inadequately treated). Patients were recruited in consecutive order. Slightly more women (53.2%, mean age 62.2±11.3 years, 94% with hypertension) than men (46.8%, mean age 58.6±12.3 years, 93.2% with hypertension) were included. There were no significant differences in mean blood pressure (women 156/92mmHg, men 157/93mmHg) and in antihypertensive treatment (mainly monotherapy). There were several gender-specific differences such as age, body mass index, physical activity, smoking status and comorbidities that did not affect the results. At the second observation, blood pressure had decreased significantly (p<0.001) and consistently. Mean pressure in women was 130/80mmHg and in men 131/81mmHg. The blood pressure target < 140/90mmHg was achieved by 73.2% of women and 72.1% of men. The prescribed antihypertensive medications did not differ between women and men, being mainly single-pill combinations (71.6% for women, 71.5% for men).

Conclusions:
The study showed no differences in the treatment of hypertension between women and men under real-world conditions. The effectiveness was quite good, mainly achieved by single-pill combinations, although the treatment can still be improved.
IMPACT OF SEX ON THE ASSOCIATION BETWEEN AORTIC WAVE REFLECTION AND LEFT ATRIAL FUNCTION IN HYPERTENSIVE PATIENTS WITH RECURRENT ATRIAL FIBRILLATION
Authors: Kokhan Elizaveta , Kiyakbaev Gayrat , Kobalava Zhanna 
Published: May 2024

Objective:
Hypertension is the leading cause of atrial fibrillation (AF). However, the exact mechanism of the relation between high blood pressure and arrhythmia is still incompletely understood. Although the systolic loading sequence likely affects ventriculoatrial coupling, the data concerning the relationship between central aortic pressure and left atrial (LA) function including depending on sex is scarce.
Purpose: To assess the impact of sex on the association between aortic wave reflection parameters and LA function in patients with AF and hypertension.

Design and method:
45 men and 46 women with paroxysmal or persistent AF and hypertension were enrolled in the study. The parameters of LA size and function included in our analyses were: LA minimum volume (LAVmin), LA maximum volume (LAVmax), LA emptying fraction (LAEF), and LA expansion index (LAEI). The parameters of central aortic pressure were estimated using applanation tonometry method. All patients had sinus rhythm at the time of the study.

Results:
There were no significant differences between men and women in most clinical and demographic parameters. Both groups had similar LV mass index, but women had worse diastolic function (E/E’: 7.1 vs 9,8; p<0.001). Men and women had similar LAVmax index, however, women had worse LAEF (49 vs 39%; p=0.004) and LAEI (98 vs 64%; p=0.02).
Despite similar central systolic, diastolic pressure and pulse wave velocity, women had higher aortic augmentation index (Aix) [33 vs 25%; p<0.001], even adjusted by HR (Aix75) [34 vs 26%; p<0.001]. In a multivariate regression analysis, in men LAEF was significantly associated with height (p=0.02), weight (p=0.046), E’ (p<0.001), and E/E’ (p<0.001), whereas in women with E’ (p=0.003) and Aix75 (p=0.04), and GFR (p=0.02).

Conclusions:
Patients of both genders had similar structural patterns of LA remodeling, but women characterized by more impaired LA function parameters. As according to previous reports, women had higher wave reflection parameters (Aix and Aix75). In multiple regression analysis, only in women did LAEF significantly relate to Aix75. It might indicate a higher susceptibility of the women's LA to increased hemodynamic overload caused by wave reflection.
PROFILE OF CENTRAL AORTIC BLOOD PRESSURE, AUGMENTATION INDEX AND PULSE PRESSURE AMPLIFICATION IN PREECLAMPSIA AND UNCOMPLICATED HYPERTENSION IN PREGNANCY
Authors: Szczepaniak-chichel Ludwina , Lipski Dawid , Uruski Pawel , Tykarski Andrzej 
Published: May 2024

Objective:
The objective of our study was to assess the differences in profile of central aortic blood pressure and other pulse wave analysis parameters of arterial stiffness between healthy pregnancy, uncomplicated pregnancy hypertension (HT) and women with preeclampsia (HT+PE).

Design and method:
In a prospective longitudinal study we have examined 241 pregnant women admitted between 2017 and 2023 to outpatient clinic and gave their consent to participate. On monthly visits throughout pregnancy, and 6-8 weeks, 6 months and 1 year postpartum on each occasion after at least 10 min rest brachial blood pressure was measured (OMRON®-705I) and assessment of aortic central blood pressure (AoBP), augmentation index (AIx, AIx75HR) and pulse pressure amplification (PPAmpl) was performed with applanation tonometry method (SphygmoCor® PVx) by a single investigator. Pharmacotherapy in hypertensive patients was managed in accordance with ESH/ESC guidelines.

Results:
We have recruited 201 women with hypertension (145 chronic; 56 pregnancy induced) and 40 normotensive pregnant controls. Preeclampsia developed in 49 of women with hypertension (HT+PE), on average in 32,8 week of gestation(range:20-39w.g.). Profiles of assessed central pulse wave analysis parameters are presented in Figure 1. Significant differences between the groups (p< 0.05) are marked on the graphs. Mean brachial BP was maintained below < 140/90 mmHg in each subgroup throughout pregnancy with antihypertensive treatment.

Conclusions:
AoSP was significantly lower in normotensive than in HT patients through whole pregnancy. In preeclampsia from 6thmonth AoSP was significantly higher and rising until delivery while in uncomplicated HT it was stable until 9thmonth. AIx was lower and PPAmpl higher in control group than in hypertensive patients through whole pregnancy however only in 4th and 6thmonth difference reached statistical significance. There is a turning point in trends of both -AIx and PPAmpl in preeclamptic patients, although in opposite direction, in between 23-26w.g.,at least a month before PE recognition. In addition there is significant difference between preeclamptic and uncomplicated HT in PPAmpl in 27-31w.g. and opposite trend between the groups in direction of changes of this parameter onwards. Observation of AIx and PPAmpl profile in pregnancy could be useful in earlier prediction of preeclampsia.
COMPARATIVE ASSESSMENT OF ECHOCARDIOGRAPHY INDICATORS IN PREGNANT WOMEN DEPENDING ON THE FORM OF ARTERIAL HYPERTENSION
Authors: Mokhinur Sadulloeva , Zakirova Feruza , Kuchkarov Husniddin , Jabborova Nafisakhon , Yenaliyeva Diana , Hazratkulov Rustam 
Published: May 2024

Objective:
To identify the features of hemodynamic parameters in pregnant women with pre-existed/chronic arterial hypertension (CAH) and gestational arterial hypertension (GAH).

Design and method:
Study included 61 pregnant women with arterial hypertension. Women were divided into 2 groups: I group included women with CAH (n=31) and II group included women with GAH (n=30) according to the 2018 ESC during pregnancy. All women underwent a medical history taking, BP measurement, ECG, EchoCG, 24-hour BP monitoring. Statistical analysis of obtained data was carried out using STATISTICA 13 program.

Results:
Analysis showed, CAH was more common in women whose average age exceeded 30 years, while GAH in those under 30 years of age (32.7±4.8 years and 27.2±5.7 years, in groups I and II, p=0.0001). They also differed in number of pregnancies 3.3±1.2 and 2.5±1.35, p 0.0174 and births 2.7±1.05 and 2.13±1.0, p 0.0341. Groups had similar SBP values 153.8±16.4 mmHg and 150.2±8.1 mmHg, p 0.2840, but differed in DBP 96.4±7.6 mmHg and 88.6±5.9 mmHg, p 0.0002. Statistically significant high DBP rates in I group, in our opinion, are associated with greater activation of renin-angiotensin-aldosterone system in CAH, whereas in GAH, hormonal and immunological mechanisms are more important. EchoCG indicators were within normal values, but had own characteristics. So in I group, IVST was 0.98±0.14 cm; PWT was 0.93±0.12 cm; LV mass was 166.96±49.6 g; LV index mass was 90.97±22.94; EDV was 108.45±23.72 ml; EF was 64.9±4.9%. In II group IVST was 0.94±0.12 cm, p 0.2364; PWT was 0.92±0.10 cm, p 0, 7254, LV mass was 154.1±30.8 g, p 0.2304; LV index mass was 82.56±17.14, p 0.1110; EDV was 102.63±17.42 ml, p 0.2805; EF was 65.6±3.8%, p 0.5839. Among women included in the study, there were no women with left ventricular diastolic dysfunction in both groups, E/A = 1.3±0.2.

Conclusions:
Preliminary results show that women with CAH have an older age and higher DBP compared with pregnant women with HAG. The next stage of the study will be a comparative assessment of development of such end points as preeclampsia and eclampsia in pregnant women with CAH and GAH.
Pars Plana Vitrectomy With External Drainage for Nonexudative Retinal Detachment
Authors: Scupola Andrea , Fossataro Claudia , Sammarco Maria Grazia , Fossataro Federica , Savino Gustavo , Rizzo Stanislao 
Published: May 2024

Purpose:
To describe a surgical technique for retinal detachment with undetected retinal breaks, which combines pars plana vitrectomy and external subretinal fluid (SRF) drainage.

Methods:
In this retrospective observational study, patients with a diagnosis of retinal detachment with undetected retinal breaks were enrolled. Standard three-port 25-gauge (G) core and peripheral pars plana vitrectomy was performed. Perfluorocarbon liquid was injected into the vitreous cavity to obtain posterior retinal flattening. Trans-scleral 27-G needle external drainage was performed approximately at 8 mm from limbus to drain SRF subconjunctivally. Prophylactic peripheral endolaser was performed on 360°. Sulfur hexafluoride 20% was used as tamponade.

Results:
In 14 of 15 patients, complete SRF drainage was obtained. In only one case, SRF did not leak out in the subconjunctival space. Neither intraoperative nor postsurgical complications were recorded. Flat retina with no SRF was observed in all samples, and no retinal detachment relapses were reported at each follow-up.

Conclusion:
External drainage combined with pars plana vitrectomy may represent a valid and safe option to drain SRF in retinal detachment cases with undetected retinal breaks. The advantages of the technique include the absence of dispersion of retinal pigment epithelium cells in the vitreous chamber, prompt dry retina, and low risk of postoperative retinal folds.
Investigating neuroepigenetic alterations in chronic low back pain with positron emission tomography
Authors: Yoo Chi-Hyeon , Rani Nisha , Shen Shiqian , Loggia Marco L. , Gaynor Kate , Moore Katelyn E. , Bagdasarian Frederick A. , Lin Yu-Shiuan , Edwards Robert R. , Price Julie C. , Hooker Jacob M. , Wey Hsiao-Ying 
Published: May 2024

Abstract
Epigenetics has gained considerable interest as potential mediators of molecular alterations that could underlie the prolonged sensitization of nociceptors, neurons, and glia in response to various environmental stimuli. Histone acetylation and deacetylation, key processes in modulating chromatin, influence gene expression; elevated histone acetylation enhances transcriptional activity, whereas decreased acetylation leads to DNA condensation and gene repression. Altered levels of histone deacetylase (HDAC) have been detected in various animal pain models, and HDAC inhibitors have demonstrated analgesic effects in these models, indicating HDACs' involvement in chronic pain pathways. However, animal studies have predominantly examined epigenetic modulation within the spinal cord after pain induction, which may not fully reflect the complexity of chronic pain in humans. Moreover, methodological limitations have previously impeded an in-depth study of epigenetic changes in the human brain. In this study, we employed [11C]Martinostat, an HDAC-selective radiotracer, positron emission tomography to assess HDAC availability in the brains of 23 patients with chronic low back pain (cLBP) and 11 age-matched and sex-matched controls. Our data revealed a significant reduction of [11C]Martinostat binding in several brain regions associated with pain processing in patients with cLBP relative to controls, highlighting the promising potential of targeting HDAC modulation as a therapeutic strategy for cLBP.
Inflammation-based markers, especially the uric acid/albumin ratio, are associated with non-dipper pattern in newly diagnosed treatment-naive hypertensive patients
Authors: Toprak Kenan , Özen Kaya , Karataş Mesut , Dursun Ayten 
Published: May 2024

Objective
Physiologically, at night, blood pressure (BP) is expected to decrease by at least 10% in hypertensive individuals. The absence of this decrease, called non-dipper hypertension, is associated with increased end-organ damage and cardiovascular mortality and morbidity in hypertensive individuals. It is known that increased inflammatory process plays an important role in the etiopathogenesis of non-dipper hypertension pattern. In recent years, it has been shown that inflammation-based markers (IBMs) obtained by combining various inflammation-related hematological and biochemical parameters in a single fraction have stronger predictive value than single inflammatory parameters. However, until now, there has not been a study investigating the relationship of these markers with dipper/non-dipper status in newly diagnosed hypertensive patients.

Methods
Based on ambulatory BP monitoring, 217 dipper and 301 non-dipper naive hypertensive subjects were included in this study. All subjects’ IBM values were compared between dipper and non-dipper hypertensive individuals.

Results
IBMs [C-reactive protein/albumin ratio (CAR), monocyte/high-density lipoprotein cholesterol ratio (MHR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio, systemic immune-inflammation index (SII), uric acid/albumin ratio (UAR)] were significantly higher in the non-dipper group. CAR, MHR, NLR, SII, and UAR were determined as independent predictors for non-dipper pattern (P < 0.05, for all). Also, UAR’s diagnostic performance for non-dipper pattern was found to be superior to other IBMs (area under the curve: 0.783, 95% confidence interval: 0.743–0.822; P < 0.001).

Conclusion
These findings suggest an association between elevated IBMs, particularly UAR, and the non-dipper hypertension pattern observed in our study.
Changes in corneal epithelial irregularity following treatment with artificial tears
Authors: Tan Jacqueline , Chidi-Egboka Ngozi , Jia Tianni , Showyin Jared , Stapleton Fiona 
Published: May 2024

Significance
Dry eye sufferers have a highly irregular corneal epithelial surface compared with those without dry eye. This study demonstrated that corneal epithelial thickness irregularity can be significantly reduced after as little as 48 hours following treatment with regular use of topical ocular lubricants.

Purpose
This study aimed to compare changes in corneal epithelial thickness irregularity factor (EIF) and ocular symptoms in a population with symptoms of dry eye before and up to 4 weeks after treatment with two commercially available lubricating eye drops versus saline.

Methods
We conducted a prospective single-center, investigator-masked, randomized, parallel-group dispensing study. Participants with moderate to severe symptoms of dry eye (Ocular Surface Disease Index score >23 at baseline) were enrolled and randomly assigned to receive either 0.15% hyaluronic acid + hydroxypropyl guar, 0.2% hyaluronic acid, or saline (16 in each group). Corneal epithelial thickness measurements were obtained along vertical and horizontal CASIA SS-1000 Optical Coherence Tomography scans at baseline and after 48 hours, 2 weeks, and 4 weeks. The Ocular Surface Disease Index questionnaire was administered at baseline, 2 weeks, and 4 weeks.

Results
Forty-eight participants (male-to-female ratio, 17:31) completed the study. Horizontal EIF was significantly lower at all follow-up visits compared with baseline (p=0.001), but there were no significant differences between study eye drops (p=0.34). No significant difference in vertical EIF was observed over time (p=0.32) or between eye drops (p=0.08). Ocular symptoms significantly improved after 2 and 4 weeks of treatment compared with baseline (p<0.001), but no differences were observed between eye drops (p=0.46).

Conclusions
All treatments were effective for reducing EIF along the horizontal meridian 48 hours after initiation of treatment, and improvements were maintained for 4 weeks. Improvements in ocular symptoms were observed with all study treatments.