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Nevin Manimala Statistics

A water-soluble tomato extract rich in secondary plant metabolites lowers trimethylamine-n-oxide and modulates gut microbiota: a randomized, double-blind, placebo-controlled cross-over study in overweight and obese adults

J Nutr. 2023 Jan;153(1):96-105. doi: 10.1016/j.tjnut.2022.11.009. Epub 2022 Dec 23.

ABSTRACT

BACKGROUND: Natural products rich in polyphenols have been shown to lower plasma trimethylamine-n-oxide (TMAO) known for its proatherogenic effects by modulating the intestinal microbiota.

OBJECTIVES: We aimed to determine the impact of Fruitflow, a water-soluble tomato extract, on TMAO, fecal microbiota, and plasma and fecal metabolites.

METHODS: Overweight and obese adults (n = 22, BMI 28-35 kg/m2) were included in a double-blind, placebo-controlled, cross-over study receiving 2×150 mg Fruitflow per day or placebo (maltodextrin) for 4 wk with a 6-week wash-out between interventions. Stool, blood, and urine samples were collected to assess changes in plasma TMAO (primary outcome) as well as fecal microbiota, fecal and plasma metabolites, and urine TMAO (secondary outcomes). In a subgroup (n = 9), postprandial TMAO was evaluated following a choline-rich breakfast (∼450 mg). Statistical methods included paired t-tests or Wilcoxon signed rank tests and permutational multivariate analysis of variance.

RESULTS: Fruitflow, but not placebo, reduced fasting levels of plasma (-1.5 μM, P ≤ 0.05) and urine (-19.1 μM, P ≤ 0.01) TMAO as well as plasma lipopolysaccharides (-5.3 ng/mL, P ≤ 0.05) from baseline to the end of intervention. However, these changes were significant only for urine TMAO levels when comparing between the groups (P ≤ 0.05). Changes in microbial beta, but not alpha, diversity paralleled this with a significant difference in Jaccard distance-based Principal Component (P ≤ 0.05) as well as decreases in Bacteroides, Ruminococccus, and Hungatella and increases in Alistipes when comparing between and within groups (P ≤ 0.05, respectively). There were no between-group differences in SCFAs and bile acids (BAs) in both faces and plasma but several changes within groups such as an increase in fecal cholic acid or plasma pyruvate with Fruitflow (P ≤ 0.05, respectively). An untargeted metabolomic analysis revealed TMAO as the most discriminant plasma metabolite between groups (P ≤ 0.05).

CONCLUSIONS: Our results support earlier findings that polyphenol-rich extracts can lower plasma TMAO in overweight and obese adults related to gut microbiota modulation. This trial was registered at clinicaltrials.gov as NCT04160481 (https://clinicaltrials.gov/ct2/show/NCT04160481?term= Fruitflow&draw= 2&rank= 2).

PMID:36913483 | DOI:10.1016/j.tjnut.2022.11.009

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Nevin Manimala Statistics

CDC’s Vitamin A Laboratory-External Quality Assessment Program Shows Little Change in Laboratory Performance for Multiple Nutritional Biomarkers over a 10-Year Period (2008-2017)

J Nutr. 2023 Jan;153(1):373-384. doi: 10.1016/j.tjnut.2022.11.001. Epub 2022 Dec 21.

ABSTRACT

BACKGROUND: The Vitamin A Laboratory-External Quality Assessment (VITAL-EQA) program operated by the CDC provides analytical performance assessment to low-resource laboratories conducting serum vitamins A (VIA), D (VID), B-12 (B12), and folate (FOL), as well as ferritin (FER) and CRP measurements for public health studies.

OBJECTIVES: We aimed to describe the long-term performance of VITAL-EQA participants from 2008 to 2017.

METHODS: Participating laboratories received 3 blinded serum samples biannually for duplicate analysis over 3 d. We assessed results (n = 6) for relative difference (%) from the CDC target value and imprecision (% CV) and conducted descriptive statistics on the aggregate 10-year and round-by-round data. Performance criteria were based on biologic variation and deemed acceptable (optimal, desirable, or minimal performance) or unacceptable (less than minimal performance).

RESULTS: Thirty-five countries reported VIA, VID, B12, FOL, FER, and CRP results from 2008-2017. The proportion of laboratories with acceptable performance ranged widely by round: VIA 48%-79% (for difference) and 65%-93% (for imprecision), VID 19%-63% and 33%-100%, B12 0%-92% and 73%-100%, FOL 33%-89% and 78%-100%, FER 69%-100% and 73%-100%, and CRP 57%-92% and 87%-100%. On aggregate, ≥60% of laboratories achieved acceptable differences for VIA, B12, FOL, FER, and CRP (only 44% for VID), and over 75% of laboratories achieved acceptable imprecision for all 6 analytes. Laboratories participating continuously in 4 rounds (2016-2017) showed generally similar performance compared to laboratories participating occasionally.

CONCLUSIONS: Although we observed little change in laboratory performance over time, on aggregate, >50% of the participating laboratories achieved acceptable performance, with acceptable imprecision being achieved more often than acceptable difference. The VITAL-EQA program is a valuable tool for low-resource laboratories to observe the state of the field and track their own performance over time. However, the small number of samples per round and the constant changes in laboratory participants make it difficult to identify long-term improvements.

PMID:36913474 | DOI:10.1016/j.tjnut.2022.11.001

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Nevin Manimala Statistics

Broadcast Television Is Not Dead: Exposure of Children to Unhealthy Food and Beverage Advertising on Television in Two Policy Environments (Ontario and Quebec). An Observational Study

J Nutr. 2023 Jan;153(1):268-278. doi: 10.1016/j.tjnut.2022.09.002. Epub 2022 Dec 21.

ABSTRACT

BACKGROUND: Food marketing can influence children’s dietary behaviors. In Canada, Quebec banned commercial advertising to children under the age of 13 y in 1980, whereas advertising to children is self-regulated by industry in the rest of the country.

OBJECTIVES: The objective of this study was to compare the extent and power of food and beverage advertising on television to children (age: 2-11 y) in two different policy environments (Ontario and Quebec).

METHODS: Advertising data for 57 selected food and beverage categories were licensed from Numerator for Toronto and Montreal (English and French markets) from January to December 2019. The 10 most popular stations for children (age: 2-11 y) and a subset of child-appealing stations were examined. Exposure to food advertisements (ads) was based on gross rating points. A content analysis of food ads was conducted, and the healthfulness of ads was assessed using Health Canada’s proposed nutrient profile model. Descriptive statistics were tabulated for the frequency of and exposure to ads.

RESULTS: On average, children were exposed to 3.7 to 4.4 food and beverage ads per day, exposure to fast-food advertising was highest (670.7-550.6 ads per year), advertising techniques were used frequently, and the majority (>90%) of advertised products were classified as unhealthy. On the top 10 stations, French children in Montreal were most exposed to unhealthy food and beverage advertising (712.3 ads per year), although they were exposed to fewer child-appealing advertising techniques compared with those in other markets. On the child-appealing stations, French children in Montreal were least exposed to food and beverage advertising (43.6 ads per year per station) and child-appealing advertising techniques compared with the other groups.

CONCLUSIONS: The Consumer Protection Act appears to positively impact exposure to child-appealing stations; yet, it does not sufficiently protect all children in Quebec and requires strengthening. Federal-level regulations restricting unhealthy advertising are needed to protect children across Canada.

PMID:36913461 | DOI:10.1016/j.tjnut.2022.09.002

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The epithelial polarity genes frazzled and GUK-holder adjust morphogen gradients to coordinate changes in cell position with cell fate specification

PLoS Biol. 2023 Mar 13;21(3):e3002021. doi: 10.1371/journal.pbio.3002021. Online ahead of print.

ABSTRACT

Morphogenetic gradients specify distinct cell populations within tissues. Originally, morphogens were conceived as substances that act on a static field of cells, yet cells usually move during development. Thus, the way cell fates are defined in moving cells remains a significant and largely unsolved problem. Here, we investigated this issue using spatial referencing of cells and 3D spatial statistics in the Drosophila blastoderm to reveal how cell density responds to morphogenetic activity. We show that the morphogen decapentaplegic (DPP) attracts cells towards its peak levels in the dorsal midline, whereas dorsal (DL) stalls them ventrally. We identified frazzled and GUK-holder as the downstream effectors regulated by these morphogens that constrict cells and provide the mechanical force necessary to draw cells dorsally. Surprisingly, GUKH and FRA modulate the DL and DPP gradient levels and this regulation creates a very precise mechanism of coordinating cell movement and fate specification.

PMID:36913435 | DOI:10.1371/journal.pbio.3002021

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Leaving no one behind in health: Financial hardship to access health care in Ethiopia

PLoS One. 2023 Mar 13;18(3):e0282561. doi: 10.1371/journal.pone.0282561. eCollection 2023.

ABSTRACT

BACKGROUND: Financial hardship (of health care) is a global and a national priority area. All people should be protected from financial hardship to ensure inclusive better health outcome. However, financial hardship of healthcare has not been well studied in Ethiopia in general and in Debre Tabor town in particular. Therefore, this study aimed to assess the incidence of financial hardship of healthcare and associated factors among households in Debre Tabor town.

METHODS: Community based cross sectional study was conducted, from May 24/2022 to June 17/2022, on 423 (selected through simple random sampling) households. Financial hardship was measured through catastrophic (using 10% threshold level) and impoverishing (using $1.90 poverty line) health expenditures. Patient perspective bottom up and prevalence based costing approach were used. Indirect cost was estimated through human capital approach. Bi-variable and multiple logistic regressions were used.

RESULTS: The response rate was 95%. The mean household annual healthcare expenditure was Ethiopian birr 12050.64 ($227.37). About 37.1% (95%CI: 32, 42%) of the households spend catastrophic health expenditure with a 10% threshold level and 10.4% of households were impoverished with $1.90 per day poverty line. Being old, with age above 60, (AOR: 4.21, CI: 1.23, 14.45), being non-insured (AOR: 2.19, CI: 1.04, 4.62), chronically ill (AOR: 7.20, CI: 3.64, 14.26), seeking traditional healthcare (AOR: 2.63, CI: 1.37. 5.05) and being socially unsupported (AOR: 2.77, CI: 1.25, 6.17) were statistically significant factors for catastrophic health expenditure.

CONCLUSION: The study showed that significant number of households was not yet protected from financial hardship of healthcare. The financial hardship of health care is stronger among the less privileged populations: non-insured, the chronically diseased, the elder and socially unsupported. Therefore, financial risk protection strategies should be strengthened by the concerned bodies.

PMID:36913429 | DOI:10.1371/journal.pone.0282561

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Nevin Manimala Statistics

Relationship between fall history and toe grip strength in older adults with knee osteoarthritis in Japan: A cross-sectional study

PLoS One. 2023 Mar 13;18(3):e0282944. doi: 10.1371/journal.pone.0282944. eCollection 2023.

ABSTRACT

BACKGROUND: Knee osteoarthritis (KOA), one of the most common musculoskeletal diseases in older adults, is associated with a high incidence of falls. Similarly, toe grip strength (TGS) is associated with a history of falls in older adults; however, the relationship between TGS and falls in older adults with KOA who are at risk of falling is not known. Therefore, this study aimed to determine if TGS is associated with a history of falls in older adults with KOA.

METHODS: The study participants, older adults with KOA scheduled to undergo unilateral total knee arthroplasty (TKA), were divided into two groups: non-fall (n = 256) and fall groups (n = 74). Descriptive data, fall-related assessments, modified Fall Efficacy Scale (mFES), radiographic data, pain, and physical function including TGS were evaluated. The assessment was conducted on the day before performing TKA. Mann-Whitney and chi-squared tests were performed to compare the two groups. Multiple logistic regression analysis was performed to determine the association of each outcome with the presence or absence of falls.

RESULTS: Mann-Whitney U test revealed that the fall group had statistically significantly lower height, TGS on the affected and unaffected sides, and mFES. Multiple logistic regression analysis revealed that the incidence of fall history is associated with TGS on the affected side; the weaker the affected TGS of the KOA, the more likely the individual is to fall.

CONCLUSIONS: Our results indicate that TGS on the affected side is related to a history of falls in older adults with KOA. The significance of evaluating TGS among patients with KOA in routine clinical practice was demonstrated.

PMID:36913410 | DOI:10.1371/journal.pone.0282944

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First passage time analysis of spatial mutation patterns reveals sub-clonal evolutionary dynamics in colorectal cancer

PLoS Comput Biol. 2023 Mar 13;19(3):e1010952. doi: 10.1371/journal.pcbi.1010952. Online ahead of print.

ABSTRACT

The signature of early cancer dynamics on the spatial arrangement of tumour cells is poorly understood, and yet could encode information about how sub-clones grew within the expanding tumour. Novel methods of quantifying spatial tumour data at the cellular scale are required to link evolutionary dynamics to the resulting spatial architecture of the tumour. Here, we propose a framework using first passage times of random walks to quantify the complex spatial patterns of tumour cell population mixing. First, using a simple model of cell mixing we demonstrate how first passage time statistics can distinguish between different pattern structures. We then apply our method to simulated patterns of mutated and non-mutated tumour cell population mixing, generated using an agent-based model of expanding tumours, to explore how first passage times reflect mutant cell replicative advantage, time of emergence and strength of cell pushing. Finally, we explore applications to experimentally measured human colorectal cancer, and estimate parameters of early sub-clonal dynamics using our spatial computational model. We infer a wide range of sub-clonal dynamics, with mutant cell division rates varying between 1 and 4 times the rate of non-mutated cells across our sample set. Some mutated sub-clones emerged after as few as 100 non-mutant cell divisions, and others only after 50,000 divisions. The majority were consistent with boundary driven growth or short-range cell pushing. By analysing multiple sub-sampled regions in a small number of samples, we explore how the distribution of inferred dynamics could inform about the initial mutational event. Our results demonstrate the efficacy of first passage time analysis as a new methodology in spatial analysis of solid tumour tissue, and suggest that patterns of sub-clonal mixing can provide insights into early cancer dynamics.

PMID:36913406 | DOI:10.1371/journal.pcbi.1010952

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Modeling in higher dimensions to improve diagnostic testing accuracy: Theory and examples for multiplex saliva-based SARS-CoV-2 antibody assays

PLoS One. 2023 Mar 13;18(3):e0280823. doi: 10.1371/journal.pone.0280823. eCollection 2023.

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has emphasized the importance and challenges of correctly interpreting antibody test results. Identification of positive and negative samples requires a classification strategy with low error rates, which is hard to achieve when the corresponding measurement values overlap. Additional uncertainty arises when classification schemes fail to account for complicated structure in data. We address these problems through a mathematical framework that combines high dimensional data modeling and optimal decision theory. Specifically, we show that appropriately increasing the dimension of data better separates positive and negative populations and reveals nuanced structure that can be described in terms of mathematical models. We combine these models with optimal decision theory to yield a classification scheme that better separates positive and negative samples relative to traditional methods such as confidence intervals (CIs) and receiver operating characteristics. We validate the usefulness of this approach in the context of a multiplex salivary SARS-CoV-2 immunoglobulin G assay dataset. This example illustrates how our analysis: (i) improves the assay accuracy, (e.g. lowers classification errors by up to 42% compared to CI methods); (ii) reduces the number of indeterminate samples when an inconclusive class is permissible, (e.g. by 40% compared to the original analysis of the example multiplex dataset) and (iii) decreases the number of antigens needed to classify samples. Our work showcases the power of mathematical modeling in diagnostic classification and highlights a method that can be adopted broadly in public health and clinical settings.

PMID:36913381 | DOI:10.1371/journal.pone.0280823

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Poor outcomes among critically ill HIV-positive patients at hospital discharge and post-discharge in Guinea, Conakry: A retrospective cohort study

PLoS One. 2023 Mar 13;18(3):e0281425. doi: 10.1371/journal.pone.0281425. eCollection 2023.

ABSTRACT

INTRODUCTION: Optimal management of critically ill HIV-positive patients during hospitalization and after discharge is not fully understood. This study describes patient characteristics and outcomes of critically ill HIV-positive patients hospitalized in Conakry, Guinea between August 2017 and April 2018 at discharge and 6 months post-discharge.

METHODS: We carried out a retrospective observational cohort study using routine clinical data. Analytic statistics were used to describe characteristics and outcomes.

RESULTS: 401 patients were hospitalized during the study period, 230 (57%) were female, median age was 36 (IQR: 28-45). At admission, 229 patients (57%) were on ART, median CD4 was 64 cells/mm3, 166 (41%) had a VL >1000 copies/ml, and 97 (24%) had interrupted treatment. 143 (36%) patients died during hospitalisation. Tuberculosis was the major cause of death for 102 (71%) patients. Of 194 patients that were followed after hospitalization a further 57 (29%) were lost-to-follow-up (LTFU) and 35 (18%) died, 31 (89%) of which had a TB diagnosis. Of all patients who survived a first hospitalisation, 194 (46%) were re-hospitalised at least once more. Amongst those LTFU, 34 (59%) occurred immediately after hospital discharge.

CONCLUSION: Outcomes for critically ill HIV-positive patients in our cohort were poor. We estimate that 1-in-3 patients remained alive and in care 6 months after their hospital admission. This study shows the burden of disease on a contemporary cohort of patients with advanced HIV in a low prevalence, resource limited setting and identifies multiple challenges in their care both during hospitalisation as well as during and after re-transitioning to ambulatory care.

PMID:36913379 | DOI:10.1371/journal.pone.0281425

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Comparative evaluation of saliva and nasopharyngeal swab for SARS-CoV-2 detection using RT-qPCR among COVID-19 suspected patients at Jigjiga, Eastern Ethiopia

PLoS One. 2023 Mar 13;18(3):e0282976. doi: 10.1371/journal.pone.0282976. eCollection 2023.

ABSTRACT

BACKGROUND: Nasopharyngeal swab (NPS) remains the recommended sample type for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) diagnosis. However, the collection procedure causes discomfort and irritation to the patients, lowering the quality of the sample and exposing healthcare workers to risk. Furthermore, there is also a shortage of flocked swabs and personnel protective equipment in low-income settings. Therefore, this necessitates an alternative diagnostic specimen. The purpose of this study was to evaluate the performance of saliva against NPS for SARS-CoV-2 detection using RT-qPCR among COVID-19 suspected patients at Jigjiga, Eastern Ethiopia.

METHODS: Comparative cross-sectional study was conducted from June 28 to July 30, 2022. A total of 227 paired saliva and NPS samples were collected from 227 COVID-19 suspected patients. Saliva and NPS samples were collected and transported to the Somali Regional Molecular Laboratory. Extraction was conducted using DaAn kit (DaAn Gene Co., Ltd China). Veri-Q RT-qPCR was used for amplification and detection (Mico BioMed Co, Ltd, Republic of Korea). The data were entered into Epi-data version 4.6 and analyzed using SPSS 25. McNemar’s test was used to compare the detection rate. Agreement between NPS and saliva was performed using Cohen’s Kappa. The mean and median of cycle threshold values were compared using paired t-tests and the correlation between cycle threshold values was measured using Pearson correlation coefficient. P value < 0.05 was considered statistically significant.

RESULTS: The overall positivity rate of SARS-CoV-2 RNA was 22.5% (95% CI 17-28%). Saliva showed higher sensitivity (83.8%, 95% CI, 73-94.5%) than NPS (68.9%, 95% CI 60.8-76.8%). The specificity of saliva was 92.6% (95% CI, 80.6% – 100%) compared to NPS (96.7%, 95% CI, 87% – 100%). The positive, negative, and overall percent agreement between NPS and saliva was 83.8%, 92.6%, and 91.2% respectively (κ = 0.703, 95% CI 0.58-0.825, P = 0.00). The concordance rate between the two samples was 60.8%. NPS showed a higher viral load than saliva. There was low positive correlation between the cycle threshold values of the two samples (r = 0.41, 95% CI -1.69 to -0.98, P >0.05).

CONCLUSION: Saliva showed a higher detection rate for SARS-CoV-2 molecular diagnosis than NPS and there was significant agreement between the two specimens. Therefore, saliva could be suitable and easily obtainable alternative diagnostic specimen for SARS-CoV-2 molecular diagnosis.

PMID:36913377 | DOI:10.1371/journal.pone.0282976