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The inactive X chromosome accumulates widespread epigenetic variability with age

Clin Epigenetics. 2023 Aug 25;15(1):135. doi: 10.1186/s13148-023-01549-y.

ABSTRACT

BACKGROUND: Loss of epigenetic control is a hallmark of aging. Among the most prominent roles of epigenetic mechanisms is the inactivation of one of two copies of the X chromosome in females through DNA methylation. Hence, age-related disruption of X-chromosome inactivation (XCI) may contribute to the aging process in women.

METHODS: We analyzed 9,777 CpGs on the X chromosome in whole blood samples from 2343 females and 1688 males (Illumina 450k methylation array) and replicated findings in duplicate using one whole blood and one purified monocyte data set (in total, 991/924 females/males). We used double generalized linear models to detect age-related differentially methylated CpGs (aDMCs), whose mean methylation level differs with age, and age-related variably methylated CpGs (aVMCs), whose methylation level becomes more variable with age.

RESULTS: In females, aDMCs were relatively uncommon (n = 33) and preferentially occurred in regions known to escape XCI. In contrast, many CpGs (n = 987) were found to display an increased variance with age (aVMCs). Of note, the replication rate of aVMCs was also high in purified monocytes (94%), indicating an independence of cell composition. aVMCs accumulated in CpG islands and regions subject to XCI suggesting that they stemmed from the inactive X. In males, carrying an active copy of the X chromosome only, aDMCs (n = 316) were primarily driven by cell composition, while aVMCs replicated well (95%) but were infrequent (n = 37).

CONCLUSIONS: Our results imply that age-related DNA methylation differences at the inactive X chromosome are dominated by the accumulation of variability.

PMID:37626340 | DOI:10.1186/s13148-023-01549-y

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Lipid profiles in patients with juvenile idiopathic arthritis: a systematic literature review and meta-analysis

Lipids Health Dis. 2023 Aug 25;22(1):136. doi: 10.1186/s12944-023-01885-1.

ABSTRACT

OBJECTIVE: The purpose of this study was to comprehensively evaluate the lipid profiles in patients with juvenile idiopathic arthritis (JIA).

METHODS: The literature and relevant reviews were searched for published clinical studies on the relationship between JIA and blood lipid levels. The Newcastle-Ottawa scale (NOS) was applied to evaluate the risk and methodological value of the included case‒control and cohort studies. Standardized mean differences (SMDs) and 95% confidence intervals were derived for all variables with adequate unprocessed data. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.

RESULTS: In total, 16 studies were incorporated through screening. The analysis findings revealed that the levels of very low-density lipoprotein cholesterol [SMD=-0.411, 95% CI (-0.774~-0.048), P = 0.026], high-density lipoprotein cholesterol [SMD=-0.528, 95% CI (-0.976~-0.079), P = 0.021], and apolipoprotein A1 [SMD=-1.050, 95% CI (-1.452~-0.647), P = 0.000] in JIA patients were statistically lower than those observed in healthy controls. The level of low-density lipoprotein cholesterol [SMD = 0.202, 95% CI (0.003 ~ 0.400), P = 0.046] was significantly higher in JIA patients than in healthy controls. In JIA patients, body mass index [SMD=-0.189, 95% CI (-0.690 ~ 0.311), P = 0.459], high-density lipoprotein [SMD =-1.235, 95% CI (-2.845 ~ 0.374), P = 0.133), low-density lipoprotein [SMD = 0.616, 95% CI (-0.813 ~ 2.046), P = 0.398), triglycerides (SMD = 0.278, 95% CI (-0.182 ~ 0.738), P = 0.236], total cholesterol [SMD=-0.073, 95% CI (-0.438 ~ 0.293), P = 0.696] and apolipoprotein B levels [SMD = 0.226, 95% CI (-0.133 ~ 0.585), P = 0.217] were not significantly different from those in healthy controls.

CONCLUSIONS: The outcomes of this meta-analysis suggest that dyslipidemia is common in JIA patients compared to healthy controls. Patients with JIA have a significantly increased risk of atherosclerosis and cardiovascular disease later in life.

PMID:37626321 | DOI:10.1186/s12944-023-01885-1

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Development and evaluation of the psychometric properties of a digital questionnaire for the self-management of health and well-being in the postpartum period

BMC Pregnancy Childbirth. 2023 Aug 25;23(1):610. doi: 10.1186/s12884-023-05899-6.

ABSTRACT

BACKGROUND: Despite the fact that the Global Strategy for Women’s, Children’s and Adolescents’ Health (2016-2030) recognises the special importance of care for women during the postpartum period, thus highlighting the need to identify and measure any condition that may affect the welfare of pregnant women in any way, this is one of the most neglected stages in the health system. Given the absence in our area of global, efficient instruments, the objective of this study was to design a complete, specific measurement tool with good metric qualities in digital format for the evaluation of self-reported health and well-being during the puerperium, to conform to what was proposed by the ICHOM.

METHODS: A cross-sectional study was carried out to evaluate the psychometric characteristics of a digital measurement tool. The development of the tool was carried out in 4 steps, following the recommendations of the International Test Commission. It was tested on 280 puerperas attending primary healthcare appointments in the Basque Healthcare System (Osakidetza), and they did the newly created survey, answering all the questions that had been selected as the gold standard. The average age of the women was 34.93 (SD = 4.80). The analysis of the psychometric characteristics was based on mixed procedures of expert judgment (a focus group of healthcare professionals, an item evaluation questionnaire and interviews with users) and quantitative evaluations (EFA, CFA, and correlation with gold standard, ordinal alpha and McDonald’s omega).

RESULTS: The final version of the tool comprised 99 items that evaluate functional state, incontinence, sexuality, breastfeeding, adaptation to the role of mother and mental health, and all of these questions can be used globally or partially. It was found that the scores were valid and reliable, which gives metric guarantees for using the tool in our area.

CONCLUSIONS: The use of this comprehensive concise tool with good psychometric properties will allow women to take stock of their situation, assess if they have the necessary resources, in psychological and social terms, and work together with midwives and other healthcare professionals on the most deficient areas.

PMID:37626320 | DOI:10.1186/s12884-023-05899-6

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Web-based need-supportive parenting program to promote physical activity in secondary school students: a randomized controlled pilot trial

BMC Public Health. 2023 Aug 25;23(1):1627. doi: 10.1186/s12889-023-16528-4.

ABSTRACT

BACKGROUND: Current global trend of insufficient physical activity (PA) among children and adolescents highlights the necessity of finding effective ways to promote PA in childhood. Self-determination theory (SDT) has demonstrated efficacy as a conceptual framework for developing interventions aimed at promoting diverse health behaviours. Parents have potential to influence children’s health behaviours to a great extent, which could be enhanced from an online, self-paced training to gain knowledge on how to support children’s intrinsic motivation towards particular health behaviour. In this pilot study, we developed and tested an online SDT-informed need-supportive training for parents, enabling them to interact with their children in a way to support their intrinsic motivation towards leisure-time physical activity.

METHODS: Sixty eight students (Mage = 12.5 ± 0.72) and one parent for each child were randomly assigned to the 6-week intervention condition or control condition. Students completed psychological measures (i.e., perceptions of parents’ need-supportive behaviours, basic psychological need satisfaction and frustration, autonomous and controlled forms of motivation, as well as social cognition beliefs towards leisure-time PA) and self-reported PA pre-intervention, post-intervention, and one-month after the intervention. Repeated measures ANOVAs were conducted to test the effects of the intervention condition and time.

RESULTS: While a statistically significant intervention effect on children’s leisure-time PA was not found, students in the intervention group reported higher, albeit marginal, perceptions of intrinsic motivation (F(2, 84) = 3.095, p = 0.050) and lower perceptions of introjected regulation (F(2, 88) = 3.107, p = 0.050) and autonomy frustration (F(2, 84) = 2.987, p = 0.056) at follow-up. Contrary to expectations, children in the control group demonstrated higher perceptions of intention (F(2, 84) = 4.838, p = 0.010) and effort (F(2, 80) = 3.473, p = 0.036) towards leisure-time physical activity at follow-up. No significant changes were found in perceptions of need-supportive behaviour from parents, attitude, and perceived behavioural control.

CONCLUSIONS: Our pilot study highlights the importance of parental training and the potential for SDT-informed interventions to support children’s intrinsic motivation towards physical activity. Further research is needed to test the intervention in other domains and combine interventions in several domains to have the highest impact.

TRIAL REGISTRATION: This pilot study is part of preparation for the main study, prospectively registered in ISRCTN registry as ISRCTN78373974 (15.12.2022). The current stage of the main study is ‘recruiting’.

PMID:37626288 | DOI:10.1186/s12889-023-16528-4

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Interrelationship between arterial hypertension, health service costs, therapeutic treatment and physical activity

BMC Prim Care. 2023 Aug 25;24(1):164. doi: 10.1186/s12875-023-02120-7.

ABSTRACT

BACKGROUND: Arterial hypertension is a high prevalence disease that increase healthcare costs and affects physical activity level. This study aimed to analyse the interrelationship between arterial hypertension, health service costs, therapeutic treatment, and physical activity in patients with cardiovascular diseases.

METHOD: Cross-sectional study that evaluated 306 patients from a hospital in Presidente Prudente-Brazil. Based on their medical diagnosis, they were classified into multiple groups to access primary care and hospital-related costs variations. Then, using data from medical records and face to face interviews, they were examined on their treatment adherence and physical activity practice. Healthcare costs were accessed using medical records. Finally, the generalised linear model was used to analyse the interrelationship between treatment adherence, physical activity, health care costs and arterial hypertension. The data were analysed with Stata/MP4 16, and a p-value of less than 5% was used to determine statistical significance.

RESULTS: The group that adhered to the arterial hypertension treatments but were physically inactive presented higher costs with consultation (US$=24.1, 95%CI = 1.90;46,3)​​ medication (US$=56.60, 95%CI = 1.65; 111.5) and total primary health care costs (US$=71.60, 95%CI = 19.2; 123.9) even after adjusting for confounding variables, meanwhile those participants that adhered to the treatments and were physical active did not present difference in healthcare cost when compared to normotensive and physical active participants.

CONCLUSION: To be adherent to hypertension treatment were related to higher health care costs meanwhile been physical activity were related to lower health care costs and the combination of both showed that be adherent and physical activity represent the same cost with health than those normotensive and active emphasizing the importance of adherence and physical activity in the hypertensive treatment.

PMID:37626283 | DOI:10.1186/s12875-023-02120-7

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Clinical outcomes of tooth-supported monolithic zirconia vs. porcelain-veneered zirconia fixed dental prosthesis, with an additional focus on the cement type: a systematic review and meta-analysis

Clin Oral Investig. 2023 Aug 26. doi: 10.1007/s00784-023-05219-4. Online ahead of print.

ABSTRACT

PURPOSE: To compare the failure rates and the prevalence of technical complications between full-coverage tooth-supported monolithic zirconia (MZ) and porcelain-veneered zirconia (PVZ) fixed dental prosthesis, based on a systematic literature review.

METHODS: An electronic search was performed in three databases, supplemented by hand searching. Several statistical methods were used.

RESULTS: Seventy-four publications reported 6370 restorations (4264 PVZ; 2106 MZ; 8200 abutment teeth; 3549 patients), followed up until 152 months. A total of 216 prostheses failed, and survival was statistically significant different between groups. PVZ had higher occurrence of complications than MZ; the difference was especially greater for either minor or major chipping. The difference in prevalence of either minor or major chipping was statistically significant for PVZ prostheses between cementation with glass ionomer and adhesive resin cement (higher), adhesive resin and resin-modified glass ionomer cement (RMGIC, higher), and between RMGIC (higher) and glass ionomer cement. For MZ the difference was significant only for minor chipping between RMGIC (higher) and adhesive resin cement. Abutment teeth to PVZ prostheses more often lost vitality. Decementation was not observed with RMGIC. Air abrasion did not seem to clinically decrease the decementation risk. The 5-year difference in the occurrence of minor or major chipping between MZ and PVZ prostheses was statistically significant, but nor for catastrophic fracture.

CONCLUSION: Tooth-supported PVZ prostheses present higher failure and complication rates than MZ prosthesis. The difference in complications is striking when it comes to chipping.

CLINICAL RELEVANCE: Awareness of the outcome differences between different types of zirconia prostheses is important for clinical practice.

PMID:37626273 | DOI:10.1007/s00784-023-05219-4

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Evaluation of venous thromboembolism prophylaxis protocol in hematopoietic cell transplant patients

Bone Marrow Transplant. 2023 Aug 25. doi: 10.1038/s41409-023-02039-8. Online ahead of print.

ABSTRACT

Hematopoietic cell transplant (HCT) recipients are at risk for thromboembolic and bleeding complications. There is limited evidence regarding the optimal approach to managing venous thromboembolism (VTE) prophylaxis in hospitalized patients undergoing HCT. In this retrospective cohort study, we evaluated the incidence of bleeding and VTE events in hospitalized HCT patients who received VTE prophylaxis per our institution’s VTE Prophylaxis Protocol (VPP), with either enoxaparin 40 mg subcutaneously daily or heparin 5 000 units subcutaneously twice daily, compared to historical controls who did not receive VTE prophylaxis. The primary outcome was a composite of major bleeding events, clinically relevant non-major bleeding (CRNMB), and minor bleeding. The secondary outcome was a composite of VTE events. A total of 614 patients were evaluated, including 278 prior to and 336 after implementation of VPP. VTE prophylaxis resulted in no difference in bleeding events (15.1% in the pre-VPP group vs. 14.6% in the post-VPP group, p = 0.86) or composite of major and CRNMB events (0.72% vs. 0.30%, p = 0.59). There was a trend toward lower incidence of VTE events in the post-VPP group which did not reach statistical significance (8.6% vs. 6.0%, p = 0.20). We conclude that VTE prophylaxis does not pose additional bleeding risk in HCT patients.

PMID:37626267 | DOI:10.1038/s41409-023-02039-8

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Weight Loss After Laparoscopic Sleeve Gastrectomy in Children and Adolescents

Obes Surg. 2023 Aug 26. doi: 10.1007/s11695-023-06789-8. Online ahead of print.

ABSTRACT

PURPOSE: For children and adolescents with severe obesity, metabolic and bariatric surgery including laparoscopic sleeve gastrectomy (LSG) is increasingly used to facilitate weight loss and reduce associated medical problems. Outcomes of LSG are understudied among patients under age 15 years. We sought to examine surgical complications and weight loss outcomes among children and adolescents who underwent LSG.

MATERIALS AND METHODS: This is a single-center retrospective cohort analysis at a high-volume metropolitan children’s hospital in the northeast USA between 2011 and 2021. Weight loss was assessed at routine follow-up appointments for up to 36 months postoperatively.

RESULTS: There were 12 patients under 13 years of age (< 13), 45 from 13 up to 15 years of age (13-14), and 57 patients aged 15 years or over (≥ 15). Among all patients, 70% were female, 41% were Hispanic, and 18% were non-Hispanic Black. There were no operative mortalities. Two patients had surgical complications requiring reoperation. Follow-up beyond 6 months occurred for 62% of patients. Weight loss was evident for each group at all time points, and there was no statistically significant difference among groups at any time point. BMI Z-score reduction at 6 months was 1.53 for the < 13 group, 0.89 for the 13-14 group, and 0.86 for the ≥ 15 group and at 36 months was 1.79, 1.50, and 1.16, respectively.

CONCLUSION: These results support that LSG is a safe and effective method of achieving weight loss for young adolescents with severe obesity. Strategies to promote postoperative follow-up are needed.

PMID:37626262 | DOI:10.1007/s11695-023-06789-8

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Diagnostic accuracy of diastolic pressure ratio using a pressure microcatheter for intracoronary physiological assessment

Heart Vessels. 2023 Aug 26. doi: 10.1007/s00380-023-02301-5. Online ahead of print.

ABSTRACT

Recently, instantaneous wave-free ratio (iFR) has emerged as an alternative to the fractional flow reserve (FFR) for intracoronary physiological assessment. Although all diastolic resting indices are reportedly identical to the iFR, limited data exist on diastolic pressure ratio (dPR) measured using a microcatheter (dPRmicro). This study aimed to evaluate the diagnostic accuracy of dPRmicro compared to FFR measured using a microcatheter (FFRmicro) in real-world practice for intracoronary physiological assessment. This was a single-center, retrospective, observational study. We identified 103 consecutive suspected angina pectoris patients (107 lesions) who underwent dPRmicro and FFRmicro measurement using the Navvus® catheter at Takasaki Heart Hospital from March 2019 to June 2019. A total of 103 lesions in 103 patients were finally included in the study. The mean FFRmicro and dPRmicro values were 0.80 and 0.88, respectively. With an FFRmicro ≤ 0.80, the dPRmicro showed a diagnostic accuracy of 79.6%, sensitivity of 74.6%, specificity of 87.5%, positive predictive value of 90.4%, and negative predictive value of 68.6%. The area under the receiver operating characteristic (ROC) curve was 0.894 (95% confidence interval, 0.833-0.956), and the optimal cut-off value for dPRmicro derived from the ROC analysis was 0.90. dPRmicro and FFRmicro values were discordant in 21/103 cases (20.4%). As a multivariable logistic regression analysis was performed, the male sex (vs. female) had a statistically significant association with a dPRmicro-FFRmicro discordance (OR 4.91; 95% CI, 1.04-23.0; P = 0.044). No other factors were found to be significantly associated with the discordance. In conclusion, dPRmicro measured using a microcatheter had good diagnostic accuracy and correlation with FFRmicro, hence, it can be useful for making revascularization decisions. However, re-studies in larger populations will be needed to better understand the properties of diastolic resting index measured using a microcatheter in clinical settings.

PMID:37626238 | DOI:10.1007/s00380-023-02301-5

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Cap-assisted endoscopic mucosal resection as a salvage technique for challenging colorectal laterally spreading tumors

Surg Endosc. 2023 Aug 25. doi: 10.1007/s00464-023-10347-9. Online ahead of print.

ABSTRACT

BACKGROUND: Cap-assisted endoscopic mucosal resection (EMR-c) has emerged as a potential alternative to standard piecemeal wide-field EMR (WF-EMR) for the resection of laterally spreading tumors (LSTs). However, clear indications for this technique are still lacking. Our objective was to investigate the performance of salvage EMR-c after WF-EMR failure in the resection of large colorectal LSTs.

METHODS: The data of consecutive patients undergoing WF-EMR for large colorectal LSTs (2015-2021) were analyzed in this single-center, retrospective, observational study. In the event of a WF-EMR failure, the procedure was switched to EMR-c in the same session. The efficacy of the two techniques was evaluated in terms of complete endoscopic resection, R0 resection, and recurrence rate. Safety was also assessed.

RESULTS: Overall, the data from 81 WF-EMRs were collected. Eighteen cases of WF-EMR failure were switched to EMR-c in the same session and complete endoscopic resection was achieved in 17/18 patients (94.4%). No statistically significant difference was observed between WF-EMR and salvage EMR-c in terms of macroscopic radicality (P = 0.40) and R0 resection (P = 0.12). However, recurrence was more common with EMR-c (44.4% vs. 23.5%; P = 0.05), as were adverse events, particularly intraprocedural bleeding (27.8% vs. 7.9%; P = 0.04).

CONCLUSION: EMR-c is an effective salvage technique for challenging colorectal LSTs following WF-EMR failure. Due to the elevated risk of adverse events associated with this procedure, careful patient selection, endoscopic expertise, and close follow-up are strongly recommended.

PMID:37626237 | DOI:10.1007/s00464-023-10347-9