Nevin Manimala

J Nutr. 2022 Mar 29:nxac075. doi: 10.1093/jn/nxac075. Online ahead of print.

ABSTRACT

BACKGROUND: Specialized pro-resolving mediators (SPM), synthesized from polyunsaturated fatty acids (PUFA), resolve inflammation and return damaged tissue to homeostasis. Thus, increasing metabolites of the SPM biosynthetic pathway may have potential health benefits for select clinical populations such as those with obesity that display dysregulation of SPM metabolism. However, bioavailability of SPMs and their metabolic intermediates in humans with obesity remains unclear.

OBJECTIVES: The primary objective was to determine if a marine oil supplement increased specific metabolites of the SPM biosynthetic pathway in adults with obesity. The second objective was to determine if the supplement changed the relative abundance of key immune cell populations. Finally, given the critical role of antibodies in inflammation, we determined if ex vivo CD19 + B cell antibody production was modified by marine oil intervention.

METHODS: Twenty-three subjects, median age of 56y and BMI of 33.1, consumed 2 g/d of a marine oil supplement for 28-30 days. The supplement was particularly enriched with 18-hydroxyeicosapentaenoic, 14-hydroxydocosahexaenoic, and 17-hydroxydocosahexaenoic acids. Blood was collected pre/post supplementation for plasma mass spectrometry oxylipin and fatty acid analyses, flow cytometry, and B cell isolation. Paired T-tests/Wilcoxon tests were used for statistical analyses.

RESULTS: Relative to pre-intervention, the supplement increased six different hydroxyeicosapentaenoic and hydroxydocosahexaenoic acids accompanied by changes in plasma PUFAs. Resolvin E1 and docosapentaenoic acid-derived maresin 1 levels were respectively increased 3.5 and 4.7-fold upon intervention. The supplement did not increase the concentration of D-series resolvins and had no effect on the abundance of immune cells. Ex vivo B cell IgG but not IgM levels were lowered post-supplementation.

CONCLUSIONS: A marine oil supplement increased select SPMs and their metabolic intermediates in adults with obesity. Additional studies are needed to determine if increased levels of specific SPMs control the resolution of inflammation in humans with obesity. This trial was registered at clinicaltrials.gov (NCT04701138).

PMID:35349683 | DOI:10.1093/jn/nxac075

Blood Adv. 2022 Mar 29:bloodadvances.2021006682. doi: 10.1182/bloodadvances.2021006682. Online ahead of print.

ABSTRACT

Frontline arsenic trioxide (ATO)-based treatment regimens achieve high rates of long-term relapse-free survival in treating acute promyelocytic leukemia (APL) and form the current standard of care. Refining prognostic estimates for newly diagnosed patients treated with ATO-containing regimens remains important to continue to improve outcomes and identify patients achieving suboptimal outcomes. We performed a pooled analysis of exclusively ATO-treated patients at a single academic institution and from the ALLG APML4 and Alliance C9710 studies to determine the prognostic importance of additional cytogenetic abnormalities and/or complex karyotype. We demonstrate inferior event-free survival for patients harboring complex karyotype [hazard ratio (HR): 3.74, 95% confidence interval: 1.63-8.56, P = 0.002] but not for patients harboring additional cytogenetic abnormalities (HR 2.13, 95% CI: 0.78-5.82, P = 0.142). These data support the role for full karyotypic analysis for all patients with APL and indicate a need for novel treatment strategies to overcome this adverse effect for APL harboring complex karyotype.

PMID:35349669 | DOI:10.1182/bloodadvances.2021006682

Hum Mol Genet. 2022 Mar 29:ddac061. doi: 10.1093/hmg/ddac061. Online ahead of print.

ABSTRACT

INTRODUCTION: Rheumatoid arthritis (RA) and osteoporosis (OP) are two comorbid complex inflammatory conditions with evidence of shared genetic background and causal relationships. We aimed to clarify the genetic architecture underlying RA and various OP phenotypes whilst additionally considering an inflammatory component, C-reactive protein (CRP).

MATERIAL AND METHODS: Genome-wide association study summary (GWAS) statistics were acquired from the GEFOS consortium, CHARGE consortium, and UK Biobank. Mendelian randomization (MR) was used to detect the presence of causal relationships. Colocalization analysis was performed to determine shared genetic variants between CRP and OP phenotypes. Analysis of pleiotropy between traits due to shared causal SNPs was performed using pleiotropic analysis under composite null hypothesis (PLACO).

RESULTS: MR analysis was suggestive of horizontal pleiotropy between RA and OP traits. RA was a significant causal risk factor for CRP (β = 0.027, 95%CI = 0.016 to 0.038). There was no evidence of CRP → OP causal relationship, but horizontal pleiotropy was apparent. Colocalization established shared genomic regions between CRP and OP including GCKR and SERPINA1 genes. Pleiotropy arising from shared causal SNPs revealed through the colocalization analysis were all confirmed by PLACO. These genes were found to be involved in the same molecular function ‘protein binding’ (GO:0005515) associated with RA, OP and CRP.

DISCUSSION: We identified three major components explaining the epidemiological relationship among RA, OP and inflammation: (1) Pleiotropy explains a portion of the shared genetic relationship between RA and OP, albeit polygenically; (2) RA contributes to CRP elevation; (3) CRP, which is influenced by RA, demonstrated pleiotropy with OP.

PMID:35349660 | DOI:10.1093/hmg/ddac061

Diabetes Care. 2022 Apr 1;45(4):1013-1024. doi: 10.2337/dc21-1705.

ABSTRACT

BACKGROUND: Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted.

PURPOSE: To conduct an updated systematic review and meta-analysis of plasma, serum, and urine metabolite markers and incident type 2 diabetes.

DATA SOURCES: We searched PubMed and Embase until 6 March 2021.

STUDY SELECTION: We selected prospective observational studies where investigators used high-throughput techniques to investigate the relationship between plasma, serum, or urine metabolites and incident type 2 diabetes.

DATA EXTRACTION: Baseline metabolites per-SD risk estimates and 95% CIs for incident type 2 diabetes were extracted from all eligible studies.

DATA SYNTHESIS: A total of 61 reports with 71,196 participants and 11,771 type 2 diabetes cases/events were included in the updated review. Meta-analysis was performed for 412 metabolites, of which 123 were statistically significantly associated (false discovery rate-corrected P < 0.05) with type 2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain, aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and energy-related metabolites (mannose, trehalose, and pyruvate), acylcarnitines (C4-DC, C4-OH, C5, C5-OH, and C8:1), the majority of glycerolipids (di- and triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides included in meta-analysis were associated with higher risk of type 2 diabetes (hazard ratio 1.07-2.58). Higher levels of glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines were associated with lower type 2 diabetes risk (hazard ratio 0.69-0.90).

LIMITATIONS: Substantial heterogeneity (I2 > 50%, τ2 > 0.1) was observed for some of the metabolites.

CONCLUSIONS: Several plasma and serum metabolites, including amino acids, lipids, and carbohydrates, are associated with type 2 diabetes risk.

PMID:35349649 | DOI:10.2337/dc21-1705

Brief Bioinform. 2022 Mar 30:bbac139. doi: 10.1093/bib/bbac139. Online ahead of print.

NO ABSTRACT

PMID:35349641 | DOI:10.1093/bib/bbac139

Brain. 2022 Mar 10:awab365. doi: 10.1093/brain/awab365. Online ahead of print.

ABSTRACT

At present, no research criteria exist for the diagnosis of prodromal behavioural variant frontotemporal dementia (bvFTD), though early detection is of high research importance. Thus, we sought to develop and validate a proposed set of research criteria for prodromal bvFTD, termed ‘mild behavioural and/or cognitive impairment in bvFTD’ (MBCI-FTD). Participants included 72 participants deemed to have prodromal bvFTD; this comprised 55 carriers of a pathogenic mutation known to cause frontotemporal lobar degeneration, and 17 individuals with autopsy-confirmed frontotemporal lobar degeneration. All had mild behavioural and/or cognitive changes, as judged by an evaluating clinician. Based on extensive clinical workup, the prodromal bvFTD group was divided into a Development Group (n = 22) and a Validation Group (n = 50). The Development Group was selected to be the subset of the prodromal bvFTD group for whom we had the strongest longitudinal evidence of conversion to bvFTD, and was used to develop the MBCI-FTD criteria. The Validation Group was the remainder of the prodromal bvFTD group and was used as a separate sample on which to validate the criteria. Familial non-carriers were included as healthy controls (n = 165). The frequencies of behavioural and neuropsychiatric features, neuropsychological deficits, and social cognitive dysfunction in the prodromal bvFTD Development Group and healthy controls were assessed. Based on sensitivity and specificity analyses, seven core features were identified: apathy without moderate-severe dysphoria, behavioural disinhibition, irritability/agitation, reduced empathy/sympathy, repetitive behaviours (simple and/or complex), joviality/gregariousness, and appetite changes/hyperorality. Supportive features include a neuropsychological profile of impaired executive function or naming with intact orientation and visuospatial skills, reduced insight for cognitive or behavioural changes, and poor social cognition. Three core features or two core features plus one supportive feature are required for the diagnosis of possible MBCI-FTD; probable MBCI-FTD requires imaging or biomarker evidence, or a pathogenic genetic mutation. The proposed MBCI-FTD criteria correctly classified 95% of the prodromal bvFTD Development Group, and 74% of the prodromal bvFTD Validation Group, with a false positive rate of <10% in healthy controls. Finally, the MBCI-FTD criteria were tested on a cohort of individuals with prodromal Alzheimer’s disease, and the false positive rate of diagnosis was 11-16%. Future research will need to refine the sensitivity and specificity of these criteria, and incorporate emerging biomarker evidence.

PMID:35349636 | DOI:10.1093/brain/awab365

PLoS One. 2022 Mar 29;17(3):e0265757. doi: 10.1371/journal.pone.0265757. eCollection 2022.

ABSTRACT

Globalization boosts the process of market predictions in the pursuit of economic growth. When economic, political, and social forces gain traction by promoting policies and the climate favoring globalization, entrepreneurial results reach out. Policymakers are still searching for a context within which regional policies can be structured to foster long-term entrepreneurship opportunities. The literature on entrepreneurial phenomena is incomplete and uncertain as to how globalization forces establish a nonlinear mechanism to promote the entrepreneurial process. This study provides the basic context for identifying globalization forces to create a nonlinear effect on the entrepreneurial process in order to address this problem. The results propose that policymakers strengthen the social and political dimension of globalization to increase opportunities-based entrepreneurship.

PMID:35349596 | DOI:10.1371/journal.pone.0265757

PLoS One. 2022 Mar 29;17(3):e0261686. doi: 10.1371/journal.pone.0261686. eCollection 2022.

ABSTRACT

BACKGROUND: Disordered mineral metabolism reverses incompletely after kidney transplantation in numerous patients. Post-transplantation bone disease is a combination of pre-existing chronic kidney disease and mineral disorder and often evolving osteoporosis. These two frequently overlapping conditions increase the risk of post-transplantation fractures.

MATERIAL AND METHODS: We studied the prevalence of low bone volume in bone biopsies obtained from kidney transplant recipients who were biopsied primarily due to the clinical suspicion of persistent hyperparathyroidism between 2000 and 2015 at the Hospital District of Helsinki and Uusimaa. Parameters of mineral metabolism, results of dual-energy x-ray absorptiometry scans, and the history of fractures were obtained concurrently. One hundred nine bone biopsies taken at a median of 31 (interquartile range, IQR, 18-70) months after transplantation were included in statistical analysis. Bone turnover was classified as high in 78 (72%) and normal/low in 31 (28%) patients. The prevalence of low bone volume (n = 47, 43%) was higher among patients with low/normal turnover compared to patients with high turnover [18 (58%) vs. 29 (37%), P = 0.05]. Thirty-seven fragility fractures in 23 (21%) transplant recipients corresponding to fracture incidence 15 per 1000 person-years occurred during a median follow-up 9.1 (IQR, 6.3-12.1) years. Trabecular bone volume did not correlate with incident fractures. Accordingly, low bone mineral density at the lumbar spine correlated with low trabecular bone volume, but not with incident fractures. The cumulative corticosteroid dose was an important determinant of low bone volume, but not of incident fractures.

CONCLUSIONS: Despite the high prevalence of trabecular bone loss among kidney transplant recipients, the number of fractures was limited. The lack of association between trabecular bone volume and fractures suggests that the bone cortical compartment and quality are important determinants of bone strength and post-transplantation fracture.

PMID:35349587 | DOI:10.1371/journal.pone.0261686

PLoS One. 2022 Mar 29;17(3):e0265716. doi: 10.1371/journal.pone.0265716. eCollection 2022.

ABSTRACT

BACKGROUND: Inadequate complementary feeding is a major cause of childhood malnutrition. Malnutrition caused by insufficient complementary feeding accounts for more than one-third of all under-five mortality whereas appropriate feeding practices are critical for improving nutritional status and ensuring child survival. Thus, the objective of this study was to assess the prevalence of appropriate complementary feeding practices among mothers having 6-23 months children, from Feb.-march 2020 and associated factors in Shashemene Town, Oromia, Ethiopia.

METHODS: From February to March of 2020, a community-based cross-sectional survey was conducted. 536 mothers with children aged 6 to 23 months were chosen for the study using a two-stage sampling procedure. Data was collected by Face-to-face interviews during home-to-home visits with mothers who had children aged 6-23 months, using a structured questionnaire on the main complementary feeding indicators. The Statistical Package for the Social Sciences (SPSS) software was used to analyze the data. Logistic regression was used to identify factors associated with appropriate complementary feeding practice, with statistical significance set at probability value < 0.05.

RESULTS: The proportion of children aged 6-23 months who met the criteria for complementary food introduction, minimum meal frequency, minimum dietary diversity, minimum acceptable diet, and appropriate complementary feeding practices was 67.9 percent, 61.7 percent, 42.5 percent, 41.7 percent, and 30 percent, respectively. Child age 12-17 and 18-23 months were the independent factors associated with appropriate complementary feed practice [adjusted odd ratio (AOR): 2.32, 95 percent confidence interval (CI): (1.40-3.82)]. ** 1.91 (1.10-3.32) **. Socioeconomic status: mothers in the wealth index of the household, second, third, and fourth, [AOR: 4.27,95 percent, CI (1.8-10.22) ** 4.02(2.23-9.94) ** 7.02(3.27-15.1) **], number of antenatal care visits greater than or equal to four [AOR: 2.57,95 percent, CI: (1.3-5.05)] **, information sources [AOR: 3.5,95 percent, CI: (1.45-8.26) **].

CONCLUSION: This study found that children aged 6-23 months had a low level of appropriate complementary feeding practice. Mothers with children aged 6-11 months, the number of antenatal care (ANC) visits, socioeconomic status, sources of information, mothers’ knowledge, and positive attitude were all associated with appropriate feeding practices. As a result, nutritional education/counseling intervention on child feeding practices was suggested.

PMID:35349586 | DOI:10.1371/journal.pone.0265716

PLoS One. 2022 Mar 29;17(3):e0265483. doi: 10.1371/journal.pone.0265483. eCollection 2022.

ABSTRACT

WHO supports the harnessing of mobile technologies to improve access to smoking cessation services. As such, this study evaluated the effectiveness of smoking cessation services provided by community pharmacists using PharmQuit compared with standard care. The study was a prospective, multicenter, randomized controlled trial that included 156 participants who were 18 years or older and smoked at least one cigarette daily for a month, were ready to quit, willing to participate, and had a smartphone. The study was performed at seven community pharmacies in three provinces in Thailand. Participants were allocated to the intervention (n = 78) and control groups (n = 78). Both groups received the usual smoking cessation services with pharmacotherapy and counseling from community pharmacists for 6 months. The intervention group received PharmQuit as an additional service. Both groups were scheduled for follow-up visits on days 7, 14, 30, 60, 120, and 180. The primary outcome was continuous abstinence rate on day 180. The secondary outcomes included 7-day point abstinence rate, number of cigarettes smoked per day, exhaled carbon monoxide levels, adherence rate to the program, and satisfaction with PharmQuit. An analysis using the intent-to-treat principle was performed. Smoking cessation rates and the number of cigarettes smoked per day were significantly higher during the follow-up visits in both groups (p < 0.05). However, there were no statistically significant differences between the two groups. The adherence rate to the smoking cessation program was higher in the intervention group than in the control group (74 days vs. 60 days, p > 0.05). The results showed the benefits of the contribution of community pharmacists. Although the inclusion of PharmQuit did not yield better results than pharmacists’ counselling alone, it may help obtain better adherence to smoking cessation programs. Trial registration: Thai Clinical Trials Registry: TCTR20200925004 on September 25, 2020 -retrospectively registered, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=6841.

PMID:35349576 | DOI:10.1371/journal.pone.0265483