Nevin Manimala

Eur J Clin Nutr. 2023 Aug 4. doi: 10.1038/s41430-023-01315-6. Online ahead of print.

ABSTRACT

BACKGROUND: Epigenetic studies have reported relationships between dietary nutrient intake and methylation levels. However, genetic variants that may affect DNA methylation (DNAm) pattern, called methylation quantitative loci (mQTL), are usually overlooked in these analyses. We investigated whether mQTL change the relationship between dietary nutrient intake and leukocyte DNAm levels with an example of estimated fatty acid intake and ATP-binding cassette transporter A1 (ABCA1).

METHODS: A cross-sectional study on 231 participants (108 men, mean age: 62.7 y) without clinical history of cancer and no prescriptions for dyslipidemia. We measured leukocyte DNAm levels of 8 CpG sites within ABCA1 gene by pyrosequencing method and used mean methylation levels for statistical analysis. TaqMan assay was used for genotyping a genetic variant of ABCA1 (rs1800976). Dietary fatty acid intake was estimated with a validated food frequency questionnaire and adjusted for total energy intake by using residual methods.

RESULTS: Mean ABCA1 DNAm levels were 5% lower with the number of minor alleles in rs1800976 (CC, 40.6%; CG, 35.9%; GG, 30.6%). Higher dietary n-3 PUFA intake was associated with lower ABCA1 DNAm levels (1st (ref) vs. 4th, β [95% CI]: -2.52 [-4.77, -0.28]). After controlling for rs180076, the association between dietary n-3 PUFA intake and ABCA1 DNAm levels was attenuated, but still showed an independent association (1st (ref) vs. 4th, β [95% CI]: -2.00 [-3.84, -0.18]). The interaction of mQTL and dietary n-3 PUFA intake on DNAm levels was not significant.

CONCLUSIONS: This result suggested that dietary n-3 PUFA intake would be an independent predictor of DNAm levels in ABCA1 gene after adjusting for individual genetic background. Considering mQTL need to broaden into other genes and nutrients for deeper understanding of DNA methylation, which can contribute to personalized nutritional intervention.

PMID:37542202 | DOI:10.1038/s41430-023-01315-6

Abdom Radiol (NY). 2023 Aug 4. doi: 10.1007/s00261-023-04010-z. Online ahead of print.

ABSTRACT

PURPOSE: To assess diagnostic performance of MR defecographic findings in diagnosis of dyssynergic defecation (DD).

METHODS: This retrospective study included 46 patients with chronic constipation who met the Rome IV criteria for diagnosis of present or absent DD and underwent MRI between Jan 2015 and June 2020. Patients were divided into DD group (n = 24) and non-DD group (n = 22). Nine parameters were analyzed by two radiologists: anorectal angle (ARA) and M line at rest, defecation, and change between 2 phases; anal canal width; prominent puborectalis muscle; abnormal evacuation. Receiver operating characteristic (ROC) curves were plotted to extract the optimal cut-offs and area under the curve (AUC). Multivariate analysis was performed.

RESULTS: Seven findings showed statistically significant difference between DD and non-DD groups. M line at defecation had highest odds ratio, followed by ARA change, ARA at defecation, M line change, prominent puborectalis muscle, abnormal evacuation and anal canal width, respectively. ARA change and prominent puborectalis muscle had highest specificity (95.5% and 100%, respectively). The optimal cut-offs of ARA at defecation, ARA change, M line at defecation, M line change and anal canal width were 122°, 1.5°, 3.25 cm, 1.9 cm and 8.5 mm, respectively. Multivariate logistic regression revealed two significant findings in differentiating between DD and non-DD, including M line at defecation (OR 23.31, 95% CI 3.10-175.32) and ARA at defecation (OR 13.63, 95% CI 1.94-95.53) with sensitivity, specificity, PPV, NPV and AUC of 79.2%, 95.5%, 95%, 80.8% and 0.87(95% CI 0.78-0.97), respectively.

CONCLUSION: MR defecography has high diagnostic performance in diagnosis of DD. Although M line and ARA at defecation are two significant findings on multivariate analysis, ARA change less than 1.5 degrees and prominent puborectalis muscle have good specificity in DD diagnosis.

PMID:37542178 | DOI:10.1007/s00261-023-04010-z

Eye (Lond). 2023 Aug 4. doi: 10.1038/s41433-023-02668-9. Online ahead of print.

ABSTRACT

BACKGROUND/ AIMS: To describe the visual outcomes in eyes with dropped nucleus during phacoemulsification surgery.

SETTING: Singapore National Eye Centre (SNEC).

DESIGN: Retrospective chart review of prospectively reported cases of dropped nucleus.

METHODS: The clinical charts of all cases of dropped nucleus (Jan 2001 to Dec 2016) were retrospectively reviewed for patient demographics, surgeon type, stage of surgery, timing of pars plana vitrectomy (PPV), and complications. Visual success was defined as best corrected visual acuity (BCVA) ≥ 20/40 at last review. Final risk factors affecting visual success were identified using multivariate logistic regression analysis.

RESULTS: Incidence of dropped nucleus following cataract surgery was 0.17% (n = 292). Duration of follow-up was 25.5 months (mean), 18.5 months (median). There was a statistically significant difference in dropped nucleus rate between Residents (0.3%) and Faculty (0.14%) (x² = 38.2, P < 0.001), but ensuing major complications rates were similar. PPV was performed in 251 eyes (87.2%). At final examination, 202 cases (85.2%) achieved BCVA 20/40 or better, after excluding patients with co-existing ocular pathology. Timing of vitrectomy (delayed vs same-day) did not influence the final visual success (x² = 0.969, p = 0.51). Risk factors for poor visual outcomes included age >70 years, absence of intraocular lens (IOL) implant, and presence of major complications.

CONCLUSION: Overall incidence of dropped nucleus in SNEC was 0.17%, with BCVA of 20/40 or better in 85.2% cases. Visual prognosis was influenced by patient’s age, presence of IOL implant or additional major complications.

PMID:37542173 | DOI:10.1038/s41433-023-02668-9

J Perinatol. 2023 Aug 4. doi: 10.1038/s41372-023-01729-x. Online ahead of print.

ABSTRACT

OBJECTIVE: Extremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital.

STUDY DESIGN: Blinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age.

RESULTS: We assessed 1452 EP infants and 183 TR infants. TR-based thresholds showed higher overall EP impairment than Bayley norm-based thresholds (O.R. = 1.86; [95% CI 1.56-2.23], especially for severe impairment (36% vs. 24%; p ≤ 0.001). Difficulty recruiting TR patients at 2 years extended the study by 14 months and affected their demographics.

CONCLUSION: Impairment rates among EP infants appear to be substantially underestimated from Bayley III norms. These rates may be best assessed by comparison with healthy term infants followed with minimal attrition from birth in the same centers.

GOV ID: Term Reference (under the Generic Database Study): NCT00063063.

PMID:37542155 | DOI:10.1038/s41372-023-01729-x

Evid Based Dent. 2023 Aug 4. doi: 10.1038/s41432-023-00916-1. Online ahead of print.

ABSTRACT

DATA SOURCES: Five scientific databases were electronically searched: PubMed, EMBASE, OpenGrey, Web of Science and Cochrane Library. The search was conducted until 17 February 2022 without any restriction on date of publication but was restricted to English language. Relevant studies were also screened for related publications. The aim of this systematic review and meta-analysis was to evaluate the effectiveness of regenerative endodontic procedures (REPs) in mature and immature permanent teeth with necrotic pulp and to evaluate if the success rate was affected by the stage of root development.

STUDY SELECTION: Types of studies: all of the included studies were randomised controlled trials (RCTs).

TYPES OF PARTICIPANTS: people with necrotic permanent teeth (immature or mature) treated with regenerative endodontic procedures. Types of interventions: regenerative endodontic procedures. Language: RCTs published in English.

EXCLUSION CRITERIA: Types of studies: (1) case reports, (2) retrospective cohort trials, (3) prospective cohort trials, (4) animal trials, (5) in-vitro trials, (6) non-randomised trials.

POPULATION: primary teeth. Types of interventions: no details about the clinical procedures. Follow-up period: <6 months.

DATA EXTRACTION AND SYNTHESIS: The titles and abstracts of the RCTs identified by the search strategies were independently screened by two reviewers. After the initial screening, the full text of the relevant trials were reassessed against the inclusion and exclusion criteria. Discrepancies and disagreements were resolved by consensus after including a third reviewer.

RESULTS: Following the initial electronic and manual searches, a total of 3766 articles were initially identified. This was reduced to 2739 articles after duplicates were removed. However, after the initial screening phase, 35 articles were considered potentially relevant and qualified for full-text scrutiny. Out of the 35 articles, only 27 were considered eligible for inclusion. The differences in the success rate and the asymptomatic rate between the mature and immature permanent teeth with necrotic pulp were not statistically significant. However, the differences between the two groups were statistically significant in the rate of positive response to electrical pulp testing.

CONCLUSIONS: Based on the results of this systematic review and meta-analysis, the authors concluded that REPs are an effective therapy and can achieve high success rates for both mature and immature necrotic permanent teeth. It was also concluded that the REPs were more successful in regaining vitality responses for mature compared with immature permanent teeth with necrotic pulps.

PMID:37542112 | DOI:10.1038/s41432-023-00916-1

Sci Rep. 2023 Aug 4;13(1):12677. doi: 10.1038/s41598-023-39856-2.

ABSTRACT

Anesthesia for laparoscopic sleeve gastrectomy and perioperative management remains a challenge. Several clinical studies indicate that opioid-free anesthesia (OFA) may be beneficial, but there is no consensus on the most optimal anesthesia technique in clinical practice. The aim of our study was to assess the potential benefits and risks of intraoperative OFA compared to multimodal analgesia (MMA) with remifentanil infusion. In a prospective, randomized study, we analyzed 59 patients’ data. Primary outcome measures were oxycodone consumption and reported pain scores (numerical rating scale, NRS) at 1, 6, 12, and 24th hours after surgery. Postoperative sedation on the Ramsay scale, nausea and vomiting on the PONV impact scale, desaturation episodes, pruritus, hemodynamic parameters, and hospital stay duration were also documented and compared. There were no significant differences in NRS scores or total 24-h oxycodone requirements. In the first postoperative hour, OFA group patients needed an average of 4.6 mg of oxycodone while the MMA group 7.72 mg (p = 0.008, p < 0.05 statistically significant). The PONV impact scale was significantly lower in the OFA group only in the first hour after the operation (p = 0.006). Patients in the OFA group required higher doses of ephedrine 23.67 versus 15.69 mg (p = 0.039) and more intravenous fluids 1160 versus 925.86 ml (p = 0.007). The mode of anesthesia did not affect the pain scores or the total dose of oxycodone in the first 24 postoperative hours. Only in the first postoperative hour were an opioid-sparing effect and reduction of PONV incidence seen in the OFA group when compared with remifentanil-based anesthesia. However, patients in the OFA group showed significantly greater hemodynamic lability necessitating higher vasopressor doses and more fluid volume.

PMID:37542100 | DOI:10.1038/s41598-023-39856-2

Sci Rep. 2023 Aug 4;13(1):12655. doi: 10.1038/s41598-023-39719-w.

ABSTRACT

The postpartum period is a crucial starting point for the delivery of family planning services. To date, there are numerous primary studies in Ethiopia on postpartum contraceptive use and related factors. However, the results of key variables are inconsistent, making it difficult to use the results to advance the service dimensions of postpartum contraceptive use in the country. Therefore, this systematic review and meta-analysis was required to summarize this inconsistency and compile the best available evidence on the impact of maternal educational status, antenatal care and menstrual resumption on postpartum contraceptive use in Ethiopia. PubMed, Google Scholar, Scopus, Science Direct, and the repositories of online research institutes were searched. Data were extracted with Microsoft Excel and analyzed with the statistical software STATA (version 14). Data on the study area, design, population, sample size, and observed frequency were extracted using the Joanna Briggs Institute tool. To obtain the pooled effect size, a meta-analysis was performed using a weighted inverse variance random effects model. Cochran’s Q X² test, and I² statistics were used to test for heterogeneity, estimate the total quantity, and measure the variability attributed to heterogeneity. A mixed-effects meta-regression analysis was performed to identify possible sources of heterogeneity. To examine publication bias, the Eggers regression test and the Beggs correlation test were used at a p-value threshold of 0.001. Of the 654 articles reviewed, 18 studies met the inclusion criteria and were included in this meta-analysis. Overall, the final analysis includes 11,263 study participants. In Ethiopia, postpartum contraceptive use correlated significantly with maternal educational status (OR = 3.121:95% CI 2.127-4.115), antenatal care follow-up (OR = 3.286; 95% CI 2.353-4.220), and return of the mother’s menses (OR = 3.492; 95% CI 1.843-6.615). A uniform meta-regression was performed based on publication year (p = 0.821), sample size (p = 0.989), and city of residence (p = 0.104), which revealed that none of these factors are significant. The use of postpartum contraceptives was found to be better among mothers who are educated, attended antenatal appointments, and resumed their menstrual cycle. Based on our research, we strongly recommended that antenatal care use and maternal educational accessibility need to improve. For family planning professionals, removing barriers to menstruation resumption should be a key priority.

PMID:37542086 | DOI:10.1038/s41598-023-39719-w

Cell Tissue Bank. 2023 Aug 4. doi: 10.1007/s10561-023-10105-0. Online ahead of print.

ABSTRACT

Biomaterials capable of managing wounds should have essential features like providing a natural microenvironment for wound healing and as support material for stimulating tissue growth. Eggshell membrane (ESM) is a highly produced global waste due to increased egg consumption. The unique and fascinating properties of ESM allow their potential application in tissue regeneration. The wound healing capacity of bone marrow-derived mesenchymal stem cells (BM-MSCs), ESM, and their combination in rabbits with full-thickness skin defect (2 × 2 cm²) was evaluated. Twenty-five clinically healthy New Zealand White rabbits were divided into five groups of five animals each, with group A receiving no treatment (control group), group B receiving only fibrin glue (FG), group C receiving FG and ESM as a dressing, group D receiving FG and BM-MSCs, and group E receiving a combination of FG, ESM, and BM-MSCs. Wound healing was assessed using clinical, macroscopical, photographic, histological, histochemical, hematological, and biochemical analysis. Macroscopic examination of wounds revealed that healing was exceptional in group E, followed by groups D and C, compared to the control group. Histopathological findings revealed improved quality and a faster rate of healing in group E compared to groups A and B. In addition, healing in group B treated with topical FG alone was nearly identical to that in control group A. However, groups C and D showed improved and faster recovery than control groups A and B. The macroscopic, photographic, histological, and histochemical evaluations revealed that the combined use of BM-MSCs, ESM, and FG had superior and faster healing than the other groups.

PMID:37542003 | DOI:10.1007/s10561-023-10105-0

Eur J Cancer. 2023 Jul 5;191:112965. doi: 10.1016/j.ejca.2023.112965. Online ahead of print.

ABSTRACT

PURPOSE: The safety and objective clinical responses were observed in the phase I study using adjuvant autologous tumour-infiltrating lymphocytes (TILs) following concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients.

METHODS AND MATERIALS: One hundred fifty-six patients with stage III-IVb and pretreatment Epstein-Barr virus DNA levels of ≥4000 copies/ml were randomly assigned to receive CCRT combined with TIL infusion (n = 78) or CCRT alone (n = 78). All patients received CCRT and patients assigned to the TIL group received TIL infusion within 1 week after CCRT. The primary endpoint was investigator-assessed progression-free survival (PFS) at 3 years.

RESULTS: After a median follow-up of 62.3 months, no significant difference was observed in the 3-year PFS rate between the CCRT plus TIL infusion group and CCRT alone group (75.6% versus 74.4%, hazard ratios, 1.08; 95% confidence intervals, 0.62-1.89). TIL infusion was safe without grade 3 or 4 adverse events and all the high-grade adverse effects were associated with myelosuppression caused by CCRT. Exploratory analysis showed that a potential survival benefit was observed with TILs in patients with lower levels of circulating CD8+TIM3+ cells, serum IL-8 or PD-L1. The infused TIL products in patients with favourable outcomes were associated with increased transcription of interferon-γ and a series of inflammatory related genes and a lower exhausted score.

CONCLUSION: The primary objective of prolonging PFS with CCRT plus TILs in high-risk NPC patients was not met. These findings may provide evidence for the design of future trials investigating the combination of TILs plus immune checkpoint inhibitors based on CCRT in high-risk NPC patients.

TRIAL REGISTRATION NUMBER: NCT02421640.

PMID:37540921 | DOI:10.1016/j.ejca.2023.112965