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Nevin Manimala Statistics

Association between Dried Fruit Intake and DNA Methylation: A Multivariable Mendelian Randomization Analysis

J Nutr Health Aging. 2023;27(11):1132-1139. doi: 10.1007/s12603-023-2030-x.

ABSTRACT

OBJECTIVES: Observational studies have reported associations between dried fruit intake and DNA methylation(DNAm). However, inherent flaws in observational study designs make them susceptible to confounding and reverse causality bias. Consequently, it is unclear whether a causal association exists. In the present study, we aimed to investigate the causal associations between dried fruit intake and DNAm.

METHODS: We performed two-sample Mendelian randomization (MR) using the IEU Open GWAS database aggregated data. Forty-three single nucleotide polymorphisms (SNPs) associated with dried fruit intake as instrumental variables (IVs) were selected as exposure. DNAm outcomes include Gran (estimated granulocyte proportions); AgeAccelGrim(GrimAge acceleration); Hannum (Hannum age acceleration); IEAA(Intrinsic epigenetic age acceleration), AgeAccelPheno( PhenoAge acceleration), and DNAmPAIadjAge (DNAm-estimated plasminogen activator inhibitor-1 levels). We used the MR pleiotropy residual sum and outlier test (MRPRESSO) and Radial-MR test to identify any level of multi-effect outliers and assessed the causal effect estimates(after removing outliers). The primary causal effects were estimated using inverse-variance weighted (IVW) method and undertook sensitivity analyses using MR methods robust to horizontal pleiotropy.The direct effects of dried fruit intake on DNAm were estimated using multivariable mendelian randomization (MVMR).

RESULTS: Leveraging two-sample MR analysis, we observed statistically significant associations between dried fruit intake with a lower AgeAccelGrim(β=-1.365, 95% confidence intervals [CI] -2.266 to -0.464, PIVW=2.985×10-3) and AgeAccelPheno (β= -1.933, 95% CI -3.068 to -0.798, PIVW=8.371×10-4). By contrast, the effects level on Gran (β=0.008, PIVW=0.430), Hannum(β=-0.430, PIVW=0.357), IEAA(β=-0.184, PIVW=0.700), and DNAmPAIadjAge (β=-1.861, PIVW=0.093) were not statistically significant. MVMR results adjusting for the potential effects of confounders showed that the causal relationship between dried fruit intake and AgeAccelGrim(β= -1.315, 95% CI -2.373 to -0.258, PIVW=1.480×10-2) and AgeAccelPheno(β= -1.595, 95% CI -2.987 to -0.202, PIVW=2.483×10-2) persisted. No significant horizontal polymorphism was found in the sensitivity analysis.

CONCLUSION: Our MR study suggested that increased dried fruit intake is associated with slower AgeAccelGrim and AgeAccelPheno. It can providing a promising avenue for exploring the beneficial effects of dried fruit intake on lifespan extension.

PMID:37997736 | DOI:10.1007/s12603-023-2030-x

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Nevin Manimala Statistics

The Joint Effect of Body Mass Index and Serum Lipid Levels on Incident Dementia among Community-Dwelling Older Adults

J Nutr Health Aging. 2023;27(11):1118-1126. doi: 10.1007/s12603-023-2027-5.

ABSTRACT

OBJECTIVES: This study aimed to explore the joint effect of body mass index (BMI) and serum lipids levels on incident dementia.

METHODS: We prospectively followed up with 1,627 dementia-free community residents aged ≥60 for 5.7 years on average. At baseline, weight, and height were measured, and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were detected in serum. Demographic characteristics were collected through questionnaires. Dementia was based on consensus diagnosis of neurologists and neuropsychologists using DSM-IV criteria. Additive Cox proportional model was used to assess the exposure-response relationship between BMI and serum lipid levels and dementia risk. Interactions and further classifications of BMI and serum lipid levels were further presented by bivariate surface models and decision-tree models.

RESULTS: The joint effects of TC with BMI, TG with BMI, and LDL-C with BMI on the risk of incident dementia shared a similar pattern, different from their independent exposure-response curves. The joint effect of HDL-C with BMI showed an S-surface but without statistical significance. Participants with TC<5.4 mmol/L and BMI<21 kg/m2 (Hazard Ratio(HR) 1.93, 95% Confidence Interval (CI) 1.05-3.53), TC<5.4 mmol/L and BMI≥21 kg/m2 (HR 1.73, 95% CI 1.09-2.72), and TC≥5.4 mmol/L and BMI<21 kg/m2 (HR 4.02, 95% CI 2.10-7.71) were identified to have the increased risk of incident dementia compared to those with TC≥5.4 mmol/L and BMI≥21 kg/m2. Participants with TG<1.7 mmol/L and BMI<21 kg/m2 had an increased risk of incident dementia compared to those with TG≥1.7 mmol/L and BMI≥21 kg/m2 (HR 1.98, 95%CI 1.17-3.3). Participants with LDL-C≥3.3 mmol/L and BMI<21 kg/m2 were identified to have an increased risk of incident dementia compared to those with LDL-C≥3.3 mmol/L and BMI≥21 kg/m2 (HR 3.33, 95%CI 1.64-6.78).

CONCLUSIONS: Our study showed that low BMI combined with low or high levels of serum lipids may increase the risk of dementia among older adults. This finding suggests the potential impacts of these two metabolic indexes on the risk of dementia.

PMID:37997734 | DOI:10.1007/s12603-023-2027-5

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Nevin Manimala Statistics

Adherence to Healthy and Sustainable Dietary Patterns and Long-Term Chronic Inflammation: Data from the EPIC-Potsdam Cohort

J Nutr Health Aging. 2023;27(11):1109-1117. doi: 10.1007/s12603-023-2010-1.

ABSTRACT

OBJECTIVES: We explored the prospective associations between adherence to a priori chosen dietary patterns, including EAT-Lancet (EAT-L) and Mediterranean (tMDS) diet with long-term inflammatory responses in a German population sample.

DESIGN AND SETTING: Prospective cohort study.

PARTICIPANTS: A subsample of 636 predominantly healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study who were on average 51-years old at baseline.

MEASUREMENTS: Data was collected repeatedly between 1994/1998 – 2013. At baseline (1994/1998) and 6.8-years later (2001/2005), EAT-L and tMDS scores were derived from available food frequency questionnaires. Stable high, stable low, increasing, and decreasing adherence to EAT-L and tMDS were defined as scoring above/below baseline median at baseline and 6.8-years later. Long-term chronic inflammation was assessed based on the average values of repeated measurements of two inflammatory biomarkers – chemerin and high-sensitivity C-reactive protein (hs-CRP) – in plasma samples collected between 2010/2012 and 2013. Multivariable linear regression analysis adjusted for socio-demographic and lifestyle factors at baseline and in 2010/2012 was used to assess the association between diet adherence and long-term hs-CRP and chemerin concentrations.

RESULTS: Stable high or increasing adherence to EAT-L diet compared to stable low adherence was associated with slight reduction of long-term chemerin concentrations on the long run (stable high: -4.4%; increasing: -4.0%), not reaching statistical significance. Increasing adherence to tMDS compared to stable low adherence was also associated with a minor reduction in chemerin concentrations (-3.6%). Decreasing adherence to tMDS compared stable high adherence was associated with 2.7% higher chemerin. The associations were even less pronounced when hs-CRP was used as an outcome.

CONCLUSIONS: Adherence to healthy and sustainable dietary patterns defined using existing definitions for EAT-L and tMDS were associated with minor and not statistically significant reduction in the concentrations of inflammatory biomarkers on the long run. More research is needed to explore whether following these diets may represent a suitable approach for targeted prevention in the general population.

PMID:37997733 | DOI:10.1007/s12603-023-2010-1

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Nevin Manimala Statistics

Association between Reduction of Muscle Mass and Faster Declines in Global Cognition among Older People: A 4-Year Prospective Cohort Study

J Nutr Health Aging. 2023;27(11):932-939. doi: 10.1007/s12603-023-2007-9.

ABSTRACT

OBJECTIVES: A few studies reported that both decrease and increase in body mass index (BMI) were associated with the development of dementia in later life. However, it is unclear what changes in body composition are associated with cognitive decline. This study investigated the longitudinal influences of changes in body composition on cognitive function among community-dwelling adults.

DESIGN, SETTING AND PARTICIPANTS: This longitudinal study included older adults aged ≥60 years without cognitive impairment who participated in National Institute for Longevity Sciences – Longitudinal Study of Aging.

MEASUREMENTS: Cognitive function was assessed using the MMSE. Body composition was measured by a dual-energy X-ray absorptiometry system. Then, BMI, fat mass index (FMI), fat-free mass index (FFMI), and muscle mass index (MMI) were calculated. The changes in body composition over 6 years (second wave to fifth wave) were calculated, and three groups were created: decreased group, decrease of >5%; stable group, change within 5%, and increased group, increase of >5%. In statistical analysis, a linear mixed model was applied by sex to investigate the influences of body composition changes on cognitive function over 4 years (fifth wave to seventh wave).

RESULTS: This study analyzed 515 participants (mean age, 67.05 years; 53.4% men). Men with decreased group in FFMI and MMI exhibited faster declines in MMSE scores than those with stable group (β [95% CI]: FFMI, -0.293 [-0.719 to -0.020]; MMI, -0.472 [-0.884 to -0.059]). In women, there was no significant association between body composition changes and cognitive functions.

CONCLUSIONS: Decrease in fat-free mass and muscle mass is associated with faster cognitive declines in men. These results suggest the importance of continuous monitoring of muscle mass to prevent cognitive decline in later life.

PMID:37997712 | DOI:10.1007/s12603-023-2007-9

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Nevin Manimala Statistics

Raising the U.S. Army Height-Weight (Body Mass Index) Standards: Quantifying Metabolic Risk

Mil Med. 2023 Nov 23:usad450. doi: 10.1093/milmed/usad450. Online ahead of print.

ABSTRACT

BACKGROUND & OBJECTIVES: The U.S. Army fell 25% short of its recruitment goal in 2022 and therefore, increasing the eligibility pool for potential recruits is of interest. Raising the body mass index (BMI) standards for eligibility presents a path to increase the recruitable population; however, there may be additional costs incurred due to attendant health risks that may be present in individuals with higher BMI.

METHODS: We filtered the 2017-2020 National Health and Nutrition Examination Survey by age (17-25 years) and BMI (up to 30 kg/m2). A k-means cluster analysis was performed on the filtered dataset for the variables used to determine metabolic syndrome. Metabolic syndrome Clusters were characterized through summary statistics and compared over clinical measurements and questionnaire responses.

RESULTS: Five distinct clusters were identified and mean BMI in two clusters (Clusters1 and 3) exceeded the current U.S. Army BMI thresholds. Of these two clusters, Cluster 1 members had metabolic syndrome. Cluster 3 members were at higher risk for metabolic syndrome compared to members of Clusters 2, 4, and 5. Mean waist circumference was slightly lower in Cluster 3 compared to Cluster 1. None of the clusters had significant differences in depression scores, poverty index, or frequency of dental visits.

CONCLUSIONS: Potential recruits from Cluster 1 have excessive health risk and may incur substantial cost to the U.S. Army if enlisted. However, potential recruits from Cluster 3 appear to add little risk and offer an opportunity to increase the pool for recruiting.

PMID:37997687 | DOI:10.1093/milmed/usad450

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Nevin Manimala Statistics

Comparing fracture resistance on bovine incisors restored by tooth fragment reattachment versus direct composite restoration techniques

Dent Traumatol. 2023 Nov 24. doi: 10.1111/edt.12909. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: Anterior teeth are prone to traumatic dental injuries (TDIs). Although a number of techniques ranging from original tooth fragment reattachment (TFR) to direct composite restoration (DCR) can be used to restore uncomplicated crown fractures, there is no consensus on which method is best. The purpose of this study was to investigate the fracture resistance of bovine incisors restored by two different techniques (TFR and DCR) in three different fracture models.

MATERIALS AND METHODS: Sixty extracted bovine lower incisors were randomly divided into three groups (n = 20). Angle, oblique, or transverse sections of all the teeth in a group were prepared by using a disk. The cut surfaces were scanned, and the cross-sectional areas (CSA) of the enamel and dentin were measured. Half the teeth in each group were restored by DCR (n = 10) and the other half by TFR (n = 10). The forces required to fracture the restored teeth were then measured using a Universal testing machine, and the fracture modes were analyzed (cohesive, adhesive, or mixed).

RESULTS: No statistically significant differences between the TFR and DCR restorations were detected for total and enamel CSAs in any of the restoration shapes (p > .067). The fracture forces required to break DCT angle and transverse restorations were significantly greater than for the corresponding shapes restored with TFR (p < .033). However, the difference in the forces needed to fracture oblique section restorations by DCR or TFR was not statistically significant (p = .239), despite a similar trend (143.4 ± 51 N and 120.9 ± 25 N, respectively).

CONCLUSION: This study revealed that a greater force is required to fracture teeth restored by the DCT than by the TFR technique, especially for a transverse section. This demonstrates that restoring a fractured tooth provides a superior outcome compared to reattaching the fractured fragment.

PMID:37997669 | DOI:10.1111/edt.12909

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Nevin Manimala Statistics

An Association Between Pediatric Bronchiolitis and Atopic Dermatitis: A Multi-Institutional Electronic Medical Records Database Study From Taiwan

Clin Pediatr (Phila). 2023 Nov 24:99228231214087. doi: 10.1177/00099228231214087. Online ahead of print.

ABSTRACT

Atopic dermatitis (AD) is triggered by many environmental factors. We sought to determine the relationship between birth weight, infectious diseases, and AD. This retrospective cohort study analyzed data from the CGR Database for the period 2004 through 2015 in Taiwan. All diseases were classified using the International Classification of Disease codes. Logistic regression adjusted for birth weights and comorbidities were analyzed by SAS (version 9.4). P < .05 were considered statistically significant. In children with AD, bronchiolitis was significantly associated with the development of AD, whether the patients were aged < 2 years (odds ratio [OR] = 1.497; P = .014) or ≥ 2 years (OR = 1.882; P = .022). There was also no difference in the association between AD and different birth weights. We conclude that AD is associated with a previous history of bronchiolitis in children, regardless of age (less than or greater than 2 years).

PMID:37997661 | DOI:10.1177/00099228231214087

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Nevin Manimala Statistics

Association of GNB3, ACE polymorphisms with POAG and NTG

Ophthalmic Genet. 2023 Nov 24:1-5. doi: 10.1080/13816810.2023.2283415. Online ahead of print.

ABSTRACT

PURPOSE: Primary open-angle glaucoma (POAG) represents the most prevalent form of glaucoma and stands as a foremost contributor to irreversible vision impairment on a global scale. Despite notable strides made in comprehending the genetic underpinnings of POAG, investigations within the context of Russia remain constrained.

METHODS: The study cohort comprised a total of 235 individuals, with 135 of them exhibiting various forms of glaucoma encompassing both POAG and (NTG, while the remaining 100 individuals served as control subjects. Each participant underwent a comprehensive ocular examination to ascertain their ocular health status. Genotyping of the relevant single nucleotide polymorphisms (SNPs) was carried out using the Taq Man genotyping assay. Specifically, the two SNPs under scrutiny were GNB3 rs5443 gene and ACE rs4646994. Statistical analysis was performed to evaluate the association of these SNPs with glaucoma risk.

RESULTS: The presence of the T allele of rs5443 was found to be associated with NTG (p = .004). However, no statistically significant correlation was identified between this SNP and POAG (p = .88).

CONCLUSION: This study provides evidence of an association between the T allele of rs5443 and a reduced susceptibility NTG within the Russian population. These observations augment the comprehension of the genetic underpinnings of glaucoma and hold potential implications for the prospective development of targeted therapeutic interventions.

PMID:37997634 | DOI:10.1080/13816810.2023.2283415

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Nevin Manimala Statistics

Clinical Characteristics and Treatment Experiences of Pediatric Acute Mastoiditis and Its Complications at the University Tertiary Care Center in the 10-Year Prevaccinal Period

Ear Nose Throat J. 2023 Nov 24:1455613231212828. doi: 10.1177/01455613231212828. Online ahead of print.

ABSTRACT

Introduction: We aim to provide an overview of the clinical characteristics and treatment of pediatric acute mastoiditis (AM) and its complications in the prevaccinal pneumococcal period. Materials and methods: Retrospective case series. An analysis of pediatric patients with AM treated at a university tertiary care center from 2008 to 2018 was performed. Results: The research included 121 children, and 27.3% of them had some form of complication. The mean age at presentation of AM was 3.7 years (range = 0-18 years). The most common extracranial complication of AM was a subperiosteal abscess (n = 25, 75.8%) and the most common intracranial complication was meningoencephalitis (n = 2, 6%). The most common pathogen isolated in the complicated AM was Streptococcus pneumoniae (n = 17, 51.5%). A total of 60% of patients reported antibiotic use before hospital admission, mostly third-generation cephalosporins (37.5%). There was a statistically significant difference between age group and occurrence of complications (P = .001). Females had complications more frequently than males (P = .035). There were no statistically significant differences in levels of inflammatory parameters (C-reactive protein and leukocyte count) between patients with or without complications (P = .373 and P = .124; respectively). All patients with complications of AM were surgically treated. Mortality was 0% and all children completely recovered. Conclusion: Extracranial and intracranial complications of AM required surgical treatment and extended antibiotic therapy. Inflammation parameters did not have a predictive role in identifying children with complications of AM. Further investigations will determine whether the introduction of the mandatory pneumococcal vaccine in our country has led to a reduction in the incidence of AM and its complications.

PMID:37997632 | DOI:10.1177/01455613231212828

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Nevin Manimala Statistics

Model validation and selection in metabolic flux analysis and flux balance analysis

Biotechnol Prog. 2023 Nov 24:e3413. doi: 10.1002/btpr.3413. Online ahead of print.

ABSTRACT

13C-Metabolic Flux Analysis (13C-MFA) and Flux Balance Analysis (FBA) are widely used to investigate the operation of biochemical networks in both biological and biotechnological research. Both methods use metabolic reaction network models of metabolism operating at steady state so that reaction rates (fluxes) and the levels of metabolic intermediates are constrained to be invariant. They provide estimated (MFA) or predicted (FBA) values of the fluxes through the network in vivo, which cannot be measured directly. These fluxes can shed light on basic biology and have been successfully used to inform metabolic engineering strategies. Several approaches have been taken to test the reliability of estimates and predictions from constraint-based methods and to compare alternative model architectures. Despite advances in other areas of the statistical evaluation of metabolic models, such as the quantification of flux estimate uncertainty, validation and model selection methods have been underappreciated and underexplored. We review the history and state-of-the-art in constraint-based metabolic model validation and model selection. Applications and limitations of the χ2 -test of goodness-of-fit, the most widely used quantitative validation and selection approach in 13C-MFA, are discussed, and complementary and alternative forms of validation and selection are proposed. A combined model validation and selection framework for 13C-MFA incorporating metabolite pool size information that leverages new developments in the field is presented and advocated for. Finally, we discuss how adopting robust validation and selection procedures can enhance confidence in constraint-based modeling as a whole and ultimately facilitate more widespread use of FBA in biotechnology.

PMID:37997613 | DOI:10.1002/btpr.3413