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Obesity in Children with Leptin Receptor Gene Polymorphisms

Acta Medica (Hradec Kralove). 2021;64(3):158-164. doi: 10.14712/18059694.2021.27.

ABSTRACT

INTRODUCTION: The study of single nucleotide polymorphisms (SNPs) of the leptin receptor gene (LEPR) based on next generation genomic sequencing (NGS) data is becoming an increasingly important aspect of diagnosis, treatment and prevention of both metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) phenotypes.

MATERIAL AND METHODS: 35 obese children 6-18 years old were examined by the NGS method with bioinformatic analysis. The main group (n = 18) was formed by children with MUO, according to the recommendations of the expert group of the National Heart, Lung, and Blood Institute. The control group (n = 17) was represented by children with MHO. Statistical methods were used: analysis of variance, Wald’s sequential analysis, Spearman’s correlation analysis, analysis of nominal data and multiple discriminant analysis.

RESULTS: 10 types of non-synonymous SNPs (rs3790435, rs1137100, rs2186248, rs70940803, rs79639154, rs1359482195, rs1137101, rs1805094, rs13306520, rs13306522) of the LEPR gene in obese children have been identified. Multiple discriminant analysis demonstrated that the following LEPR SNPs are of greatest importance in the development of MUO: rs3790435, rs13306522, rs13306520. Analysis of nominal data revealed significant differences in the groups for Copy number variation (CNV) rs3790435 of the LEPR gene. Wald’s analysis allowed us to identify 6 important predictors of MUO (І ≥ 0.5): 2 CNV rs3790435 (Relative Risk, RR = 2, Prognostic coefficient, PC = +2.76); male gender of the child (RR = 1.3, PC = +1.35); rs3790435 (RR = 1.9, PC = +2.76); hyperleptinemia more than 40.56 ng/ml (RR = 2, PC = +3); CNV rs1359482195 ≥ 3 (RR = 1.9, PC = +5.8); SNP of the LEPR gene ≥4 (RR = 3.8, PC = +5.8).

CONCLUSION: Children with the genotype rs3790435 gene LEPR had signs of MUO more often.

PMID:34779381 | DOI:10.14712/18059694.2021.27

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Serum potassium, albumin and vitamin B12 as potential oxidative stress markers of fungal peritonitis

Ann Med. 2021 Dec;53(1):2132-2141. doi: 10.1080/07853890.2021.1999489.

ABSTRACT

BACKGROUND: Biomarkers of oxidative stress (OS) have been poorly explored in fungal peritonitis (FP). Potassium is a regulator of pro-oxidants and antioxidants. Albumin and vitamin B12 (B12) are vital antioxidant agents in the circulatory system. This study aimed to investigate the antioxidative role of serum potassium, albumin and B12 in FP.

METHODS: Serum levels of potassium, albumin and B12 were retrospectively analyzed in 21 patients with a confirmed diagnosis of FP, 105 bacterial peritonitis (BP) patients and 210 patients receiving peritoneal dialysis without peritonitis.

RESULTS: Serum levels of potassium, albumin and B12 were lower in FP patients than in BP patients. Serum potassium concentration was statistically related to albumin concentration in peritonitis patients. Univariate and multivariate binary logistic regression analysis suggested that serum level of potassium and albumin were independent risk factors of FP when compared with BP. Lower potassium and B12 levels were independently associated with higher rates of technique failure in peritonitis.

CONCLUSION: These findings suggest lower serum potassium, albumin and B12 as potential oxidative stress markers of FP and raise the hypothesis that an increased level of OS could contribute to FP.KEY MESSAGESFP remains a serious complication of peritoneal dialysis (PD), with higher morbidity (1-23.8%) and mortality (2-25%), and oxidative stress plays a role in it.Our study suggested serum potassium, albumin and vitamin B12 as potential oxidative stress markers of fungal peritonitis.

PMID:34779336 | DOI:10.1080/07853890.2021.1999489

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Strabismus Repair in Children with Varying Severity of Cerebral Palsy

Semin Ophthalmol. 2021 Nov 14:1-3. doi: 10.1080/08820538.2021.2003823. Online ahead of print.

ABSTRACT

OBJECTIVE: To study the success rate of strabismus surgery in patients with varying levels of severity of cerebral palsy (CP).

DESIGN: A retrospective study was conducted.

PARTICIPANTS: Sixty-four patients with varying severity of CP were included.

METHODS: All patients with different CP severity levels underwent strabismus surgery. Success was defined as any postoperative heterotropia outcome of less than 10 prism diopters in primary position. Statistical analysis was conducted using chi-square.

RESULTS: The mean age at the time of strabismus surgery was 3.1 years, and the mean follow-up was 6.0 years. The most common types of strabismus were infantile-onset exotropia in 36 patients (56%) and infantile-onset esotropia in 28 patients (44%). Surgical success was found to be better in patients with mild GMFCS (GMFCS levels 1-2) with 68% having less than 10 PD of eso or exotropia in primary gaze, as compared to patients with severe GMFCS (GMFCS levels 3-5) (38% with 10 PD of heterotropia) (P < .05; χ2). Refractive errors included myopia (27.5% in mild cases and 41.6% in severe), emmetropia (10% in mild and 8.3% in severe) and hyperopia (62.5% in mild and 50% in severe). Around 50% of the mild cases had absent binocular fusion compared to 66.6% of those with severe CP. Amblyopia was found in 62.5% of the mild cases and 54.1% of the severe cases. Nystagmus was present in 25% with mild disease and 29.1% of those with severe disease.

CONCLUSION: Restoration of good ocular alignment in patients with CP is achievable in more than half of the cases. Patients with more severe CP have poorer outcomes than those with milder palsies. There appears to be no difference in outcomes between the different types of strabismus.

PMID:34779343 | DOI:10.1080/08820538.2021.2003823

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The correlation between levels of prenatal attachment and styles coping with stress in pregnant women

J Reprod Infant Psychol. 2021 Nov 13:1-12. doi: 10.1080/02646838.2021.2001795. Online ahead of print.

ABSTRACT

BACKGROUND: Pregnancy is a very important period in the development of attachment.

OBJECTIVE: To determine the correlation between prenatal attachment levels of healthy pregnant women and their styles of coping with stress and those of high-risk pregnant women.

METHOD: This descriptive study consisted of 76 women in their third-trimester of pregnancy hospitalised at the Obstetrics and Gynaecology service at a hospital and 210 women in their third-trimester of pregnancy who were experiencing a healthy pregnancy process and admitted to the Gynaecology Outpatient Clinic for pregnancy follow-up. The data were collected with the Personal Information Form, the Prenatal Attachment Inventory and the Stress Coping Styles Scale.

RESULTS: There was a statistically significant difference between the prenatal attachment levels of healthy and high-risk pregnant women. There was a positive correlation between the prenatal attachment levels and the self-confident and optimistic approaches among the styles of coping with stress in the healthy and high-risk pregnant women .

CONCLUSION: The attachment levels of the high-risk pregnant women were higher than were those of the healthy pregnant women. As the use of the self-confident and optimistic approach styles in coping with stress increases among healthy and high-risk pregnant women, so do their prenatal attachment levels.

PMID:34779334 | DOI:10.1080/02646838.2021.2001795

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Five-year survival after elective open and endovascular aortic aneurysm repair

Scand J Surg. 2021 Nov 14:14574969211048707. doi: 10.1177/14574969211048707. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Current evidence suggests short-term survival benefit from endovascular aneurysm repair (EVAR) versus open surgical repair (OSR) in elective abdominal aortic aneurysm (AAA) procedures, but this benefit is lost during long-term follow-up. The aim of this study was to compare short- and mid-term all-cause mortality in patients with non-ruptured aneurysm treated by OSR and EVAR; and to assess the rate of complications and reinterventions, as well as to evaluate their impact on survival.

METHODS: The medical records of the non-ruptured AAA patients undergoing OSR or EVAR between 1 January 2011 and 31 December 2019 at Tartu University Hospital, Estonia, were retrospectively reviewed. We gathered survival data from the national registry (mean follow-up period was 3.7 ± 2.3 years).

RESULTS: A total of 225 non-ruptured AAA patients were treated operatively out of whom 95 (42.2%) were EVAR and 130 (57.8%) were OSR procedures. The difference in estimated all-cause mortality between the OSR and EVAR groups at day 30 was statistically irrelevant (2.3% vs 0%; p = 0.140), but OSR patients showed statistically significantly higher 5 year survival compared with EVAR patients (75.3% vs 50.0%, p = 0.002). Complication and reintervention rates for the EVAR and OSR groups did not differ statistically (26.3% vs 16.9%, p = 0.122; 10.5% vs 11.5%, p = 0.981, respectively). Multivariate analysis revealed that greater aneurysm diameter (p = 0.012), EVAR procedure (p = 0.016), male gender (p = 0.023), and cerebrovascular diseases (p = 0.028) were independently positively associated with 5-year mortality.

CONCLUSIONS: Thirty-day mortality, and complication and reintervention rates for EVAR and OSR after elective AAA repair were similar. Although the EVAR procedure is an independent risk factor for 5-year mortality, higher age and greater proportion of comorbidities among EVAR patients may influence not only the choice of treatment modality, but also prognosis.

PMID:34779283 | DOI:10.1177/14574969211048707

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Improved anti-inflammatory effect of curcumin by designing self-emulsifying drug delivery system

Drug Dev Ind Pharm. 2021 Nov 14:1-11. doi: 10.1080/03639045.2021.2001486. Online ahead of print.

ABSTRACT

Purpose of present study was to prepare and evaluate self-emulsifying drug delivery system (SEDDS) of curcumin (Cur) to enhance its solubility and percentage release for the evaluation of anti-inflammatory effect. Curcumin loaded SEDDS formulation was prepared, and zones of self-emulsification were recognized by dilution method for the construction of phase diagram. Lauroglycol FCC, Tween 80 (surfactant), and Transcutol HP (co-surfactant) were selected based on their solubility and highest emulsion region in phase diagram. Thermodynamic stability of Cur-SEDDS was calculated through globule size, zeta potential, polydispersity index (PDI), viscosity and pH. Cur-SEDDS were also characterized by encapsulation efficiency (EE %), FT-IR, in vitro release, and in vivo anti-inflammatory effect. Results revealed that droplet size of Cur-SEDDS was 19.77 ± 0.03 nm with their PDI 0.22 ± 0.19, zeta potential -19.33 ± 0.94 and viscosity 25.68 ± 0.86 cp. EE % of Cur-SEDDS was found to be 94.99 ± 0.38%, percentage release 65.83% compared with pure curcumin powder. The designed formulation possesses significant anti-inflammatory activity in paw edema when compared with positive control in carrageenan induced rat paw edema assay. Newly developed Cur-SEDDS with enhanced curcumin solubility, percentage release and better anti-inflammatory action may be an alternative source of oral delivery of curcumin.

PMID:34779318 | DOI:10.1080/03639045.2021.2001486

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Aortic Valve ReplAcemenT versus Conservative Treatment in Asymptomatic SeveRe Aortic Stenosis: The AVATAR Trial

Circulation. 2021 Nov 13. doi: 10.1161/CIRCULATIONAHA.121.057639. Online ahead of print.

ABSTRACT

Background: Surgical aortic valve replacement (SAVR) represents a class I indication in symptomatic patients with severe aortic stenosis (AS). However, indications for early SAVR in asymptomatic patients with severe AS and normal left ventricular function remain debated. Methods: The Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR) trial is an investigator-initiated international prospective randomized controlled trial that evaluated the safety and efficacy of early SAVR in the treatment of asymptomatic patients with severe AS, according to common criteria (valve area ≤1 cm2 with aortic jet velocity >4 m/s or a mean trans-aortic gradient ≥40 mm Hg), and with normal LV function. Negative exercise testing was mandatory for inclusion. The primary hypothesis was that early SAVR would reduce the primary composite endpoint of all-cause death, acute myocardial infarction, stroke or unplanned hospitalization for heart failure, as compared to a conservative strategy according to guidelines. The trial was designed as event-driven to reach a minimum of 35 prespecified events. The study was performed in 9 centers in 7 European countries. Results: Between June 2015 and September 2020, 157 patients (mean age 67 years, 57 % men) were randomly allocated to early surgery (n=78) or conservative treatment (n=79). Follow-up was completed in May 2021. Overall median follow-up was 32 months: 28 months in the early surgery group and 35 months in the conservative treatment group. There was a total of 39 events, 13 in early surgery and 26 in conservative treatment group. In the early surgery group, 72 patients (92.3 %) underwent SAVR with operative mortality of 1.4 %. In an intention-to-treat analysis, patients randomized to early surgery had a significantly lower incidence of primary composite endpoint than those in the conservative arm (HR 0.46, 95 % CI 0.23-0.90, p=0.02). There was no statistical difference in secondary endpoints, including all-cause mortality, first heart failure hospitalizations, major bleeding or thromboembolic complications, but trends were consistent with the primary outcome. Conclusions: In asymptomatic patients with severe AS, early surgery reduced a primary composite of all-cause death, acute myocardial infarction, stroke or unplanned hospitalization for heart failure compared with conservative treatment. This randomized trial provides preliminary support for early SAVR once AS becomes severe, regardless of symptoms.

PMID:34779220 | DOI:10.1161/CIRCULATIONAHA.121.057639

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Intravenous Thrombolysis Before Mechanical Thrombectomy for Acute Ischemic Stroke: A Meta-Analysis

J Am Heart Assoc. 2021 Nov 15:e022303. doi: 10.1161/JAHA.121.022303. Online ahead of print.

ABSTRACT

Background Whether intravenous thrombolysis before mechanical thrombectomy provides additional benefit for functional outcome in acute ischemic stroke remains uncertain. We performed a meta-analysis to compare the outcomes of direct mechanical thrombectomy (dMT) to mechanical thrombectomy with bridging using intravenous thrombolysis (bridging therapy [BT]) in patients with acute ischemic stroke. Methods and Results We performed a literature search in the PubMed, Excerpta Medica database, and Cochrane Central Register of Controlled Trials from January 1, 2003, to April 26, 2021. We included randomized clinical trials and observational studies that reported the 90-day functional outcome in patients with acute ischemic stroke undergoing dMT compared with BT. The 12 included studies (3 randomized controlled trials and 9 observational studies) yielded 3924 participants (mean age, 68.0 years [SD, 13.1 years]; women, 44.2%; 1887 participants who received dMT and 2037 participants who received BT). A meta-analysis of randomized controlled trial and observational data revealed similar 90-day functional independence (odds ratio [OR], 1.04; 95% CI, 0.90-1.19), mortality (OR, 1.03; 95% CI, 0.78-1.36), and successful recanalization (OR, 0.93; 95% CI, 0.76-1.14) for patients treated with dMT or BT. Compared with those in the BT group, patients in the dMT group were less likely to experience symptomatic intracranial hemorrhage (OR, 0.68; 95% CI, 0.51-0.91; P=0.008) or any intracranial hemorrhage (OR, 0.71; 95% CI, 0.61-0.84; P<0.001). Conclusions In this meta-analysis of patients with acute ischemic stroke, we found no significant differences in 90-day functional outcome or mortality between dMT and BT, but a lower rate of symptomatic intracranial hemorrhage for dMT. These findings support the use of dMT without intravenous thrombolysis bridging therapy. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: 42021234664.

PMID:34779235 | DOI:10.1161/JAHA.121.022303

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Metabolic Factors Mediate the Association Between Serum Uric Acid to Serum Creatinine Ratio and Cardiovascular Disease

J Am Heart Assoc. 2021 Nov 15:e023054. doi: 10.1161/JAHA.121.023054. Online ahead of print.

ABSTRACT

Background The serum uric acid/serum creatinine ratio (SUA/SCr), which represents renal function-normalized SUA, is associated with diverse adverse outcomes. The aim of this study was to investigate the association between SUA/SCr and cardiovascular disease (CVD), and determine whether and to what extent this association is mediated by cardiometabolic factors. Methods and Results This prospective study enrolled 96 378 participants from the Kailuan study without stroke and myocardial infarction at baseline (2006). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses were conducted to separately explore the mediating effects of cardiometabolic factors on the association between SUA/SCr and CVD. During median follow up of 11.01 years, 6315 (6.55%) individuals developed incident CVD. After adjustment for potential confounders, the highest quartile of SUA/SCr was associated with the highest risk of CVD (HR, 1.15; 95% CI, 1.07-1.23), stroke (HR, 1.16; 95% CI, 1.07-1.26), ischemic stroke (HR, 1.12; 95% CI, 1.02-1.22), and hemorrhagic stroke (HR, 1.36; 95% CI, 1.11-1.65), but not with myocardial infarction (HR, 1.07; 95% CI, 0.92-1.25). The association was consistent across different degrees of kidney function and glucose tolerance statuses. Additionally, the association between high SUA/SCr and CVD was partially mediated by triglycerides (30.74%), body mass index (BMI) (19.52%), total cholesterol (15.06%), hs-CRP (high-sensitivity C-reactive protein) (13.06%), diastolic blood pressure (11.75%), and blood glucose (-16.38%). Conclusions SUA/SCr and CVD were positively associated. Furthermore, this association was partially mediated through blood lipids, BMI, blood pressure, hs-CRP, and blood glucose.

PMID:34779219 | DOI:10.1161/JAHA.121.023054

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Regulation of the Enzymatic Activities of Lysozyme by the Surface Ligands of Ultrasmall Gold Nanoclusters: The Role of Hydrophobic Interactions

Langmuir. 2021 Nov 15. doi: 10.1021/acs.langmuir.1c02719. Online ahead of print.

ABSTRACT

Nanomaterials for biological applications would inevitably encounter and interact with biomolecules, which have a profound impact on the properties, functions, and even fates of both nanomaterials and biomolecules. Among the biomolecules, lysozyme (Lys) is of great importance in defending the bacterial intruder and maintaining health. Here, the interactions between fluorescent gold nanoclusters (AuNCs) (∼2 nm) capped with different surface ligands and Lys were thoroughly investigated. Fluorescence spectroscopic studies showed that dihydrolipoic acid (DHLA)-capped and glutathione (GSH)-capped AuNCs both quenched the intrinsic fluorescence of Lys by different quenching mechanisms. Agarose gel electrophoresis and zeta-potential assays showed that statistically one DHLA-AuNC could bind one Lys, while one GSH-AuNC could bind 3-4 Lys, providing new examples for the concept of a “protein complex”. Activity assays indicated that DHLA-AuNCs heavily inhibited the enzymatic activity of Lys, while GSH-AuNCs had little effect. By synchronous fluorescence and circular dichroism spectroscopic studies, it was deduced that both AuNCs would interact with Lys by electrostatic attractions due to the distinct surface charges, and then DHLA-AuNCs would further interact with Lys by hydrophobic interactions, probably due to the hydrophobic carbon chain of DHLA and the hydrophobic side chains of amino acid residues in Lys, which was proved by the significant secondary structure changes caused by DHLA-AuNCs. Meanwhile, conformational changes induced by GSH-AuNCs with zwitterionic ligands were neglectable. Therefore, this work provided a comprehensive study of the consequences and mechanisms of the interactions between Lys and AuNCs, which was essential for the design and better use of nanomaterials as biological agents.

PMID:34779209 | DOI:10.1021/acs.langmuir.1c02719