Tag: pubmed

OTJR (Thorofare N J). 2022 Nov 20:15394492221136072. doi: 10.1177/15394492221136072. Online ahead of print.

ABSTRACT

Motor vehicle crashes is a leading cause of death for Veterans. We quantified the efficacy of an Occupational Therapy Driving Intervention (OT-DI) and a Traffic Safety Education (TSE) intervention on real-world driving in combat Veterans. Via a randomized trial, we assessed 42 Veterans’ fitness-to-drive abilities using a CDS-250 driving simulator and driving records, to determine differences in simulated driving and real-world events pre- and post-interventions. The OT-DI group (vs. TSE) had fewer over-speeding errors (p < .001) and total number of driving errors (p = .002) post-intervention. At Post-Test 2, the OT-DI (vs. TSE) had a reduction in real-world speeding (p = .05). While statistically not significant, both interventions showed reductions in real-world speeding, number of violations (OT-DI: 23% and TSE: 46% decrease) and crashes (OT-DI: 25% and TSE: 50% decrease). Veterans showed early evidence of efficacy in improving their real-world fitness-to-drive abilities via an OT-DI and TSE intervention.

PMID:36408831 | DOI:10.1177/15394492221136072

Brain Behav. 2022 Nov 21:e2806. doi: 10.1002/brb3.2806. Online ahead of print.

ABSTRACT

INTRODUCTION: Studies have recognized that the loss of the blood-brain barrier (BBB) integrity is a major structural biomarker where neurodegenerative disease potentially begins. Using a combination of high-quality neuroimaging techniques, we investigated potential subtle differences in BBB permeability in mid-age healthy people, comparing carriers of the apolipoprotein E epsilon-4 (APOEε4) genotype, the biggest risk factor for late onset, non-familial AD (LOAD) with APOEε3 carriers, the population norm.

METHODS: Forty-one cognitively healthy mid-age participants (42-59) were genotyped and pseudo-randomly selected to participate in the study by a third party. Blind to genotype, all participants had a structural brain scan acquisition including gadolinium-based dynamic contrast-enhanced magnetic resonance imaging acquired using a T1-weighted 3D vibe sequence. A B1 map and T1 map were acquired as part of the multi-parametric mapping acquisition.

RESULTS: Non-significant, but subtle differences in blood-brain barrier permeability were identified between healthy mid-age APOEε4 and APOEε3 carriers, matched on age, education, and gender.

DISCUSSION: This study demonstrated a tendency toward BBB permeability in APOEε4 participants emerging from mid-age, with quantitative differences observable on a number of the measures. While the differences did not reach a statistical significance, the results from this study hint at early changes in ε4 carrier BBB that may help identify at-risk populations and facilitate the development of early interventions to change the trajectory of decline.

PMID:36408825 | DOI:10.1002/brb3.2806

Clin Pharmacol Drug Dev. 2022 Nov 21. doi: 10.1002/cpdd.1193. Online ahead of print.

ABSTRACT

Henagliflozin proline and metformin hydrochloride sustained-release tablets (HR20033) are a fixed-dose combination of the novel, highly selective, and effective sodium-glucose cotransporter-2 inhibitor henagliflozin, with a metformin sustained-release layer for the treatment of type 2 diabetes mellitus in conjunction with dietary control and exercise. The aims of this study were to investigate the effect of a high-fat diet on the pharmacokinetics of henagliflozin and metformin after a single administration of HR20033 and the effect of repeated oral administration of HR20033 on their pharmacokinetics in healthy volunteers. The food-effect clinical study involved 18 healthy subjects randomized to receive either HR20033 in the fasted condition followed by HR20033 in the fed condition or the reverse schedule, with the two doses separated by a washout period of at least 7 days. The multiple-dose clinical study was conducted on 10 healthy subjects. In the food-effect study, compared with those in the fasted condition, the area under the blood concentration curve (AUC) and peak concentration (C_max ) of henagliflozin decreased by 12.64% and 40.89%, respectively, while the AUC of metformin increased by 31.13% and C_max decreased by 7.09% in the fed state. There was no significant accumulation of HR20033 in the body after multiple oral doses. No serious adverse event was observed in either of the two clinical studies. Food did not have a clinically meaningful effect on the absorption of HR20033.

PMID:36408821 | DOI:10.1002/cpdd.1193

J Pediatr Endocrinol Metab. 2022 Nov 22. doi: 10.1515/jpem-2022-0265. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop and validate an easy-to-use screening tool for identifying adolescents at high-risk for insulin resistance (IR).

METHODS: Α total of 1,053 adolescents (554 females), aged 12.5 to 17.5 years with complete data on glucose and insulin levels were included. Body mass index (BMI), fat mass index (FMI) and the homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. VO₂max was predicted using 20 m multi-stage fitness test. The population was randomly separated into two cohorts for the development (n=702) and validation (n=351) of the index, respectively. Factors associated with high HOMA-IR were identified by Spearman correlation in the development cohort; multiple logistic regression was performed for all identified independent factors to develop a score index. Finally, receiver operating characteristic (ROC) analysis was performed in the validation cohort and was used to define the cut-off values that could identify adolescents above the 75th and the 95th percentile for HOMA-IR.

RESULTS: BMI and VO₂max significantly identified high HOMA-IR in males; and FMI, TV watching and VO₂max in females. The HELENA-IR index scores range from 0 to 29 for males and 0 to 43 for females. The Area Under the Curve, sensitivity and specificity for identifying males above the 75th and 95th of HOMA-IR percentiles were 0.635 (95%CI: 0.542-0.725), 0.513 and 0.735, and 0.714 (95%CI: 0.499-0.728), 0.625 and 0.905, respectively. For females, the corresponding values were 0.632 (95%CI: 0.538-0.725), 0.568 and 0.652, and 0.708 (95%CI: 0.559-0.725), 0.667 and 0.617, respectively. Simple algorithms were created using the index cut-off scores.

CONCLUSIONS: Paediatricians or physical education teachers can use easy-to-obtain and non-invasive measures to apply the HELENA-IR score and identify adolescents at high risk for IR, who should be referred for further tests.

PMID:36408818 | DOI:10.1515/jpem-2022-0265

Sports Biomech. 2022 Nov 21:1-14. doi: 10.1080/14763141.2022.2140701. Online ahead of print.

ABSTRACT

To investigate the effects of bike fitting compared to qualitative-based riding posture recommendations on comfort, fatigue, and pain in amateur cyclists. This was a randomised controlled parallel trial of 162 amateur cyclists divided into two groups: bike fitting group (BFG) – participants received a bike fitting session based on 3D kinematic assessments; and a control group (QG) – participants who received a handout containing qualitative-based cycling posture recommendations. Primary outcomes were perceived comfort (FEEL Scale), perceived fatigue (OMNI Scale), and perceived pain (numeric rating pain scale, NRPS). Outcomes were assessed at baseline, when the interventions were delivered, and after 15 days. Intention-to-treat analyses were conducted using student t-tests between pre and post intervention on both groups. All dependent variables from BFG displayed significant statistical difference between both groups post-intervention (p < 0.05). FEEL Scale and OMNI Scale results showed the highest changes of all variables under analysis (mean differences of 3.12 and 3.95 points, respectively); while the body parts with more reduction in riding pain were Groin and Back (mean differences of 1.68 and 1.35, respectively). In conclusion, 3D kinematic bikefit demonstrated superior improvements over riding pain, comfort and fatigue compared to qualitative riding posture recommendations.

PMID:36408812 | DOI:10.1080/14763141.2022.2140701

Proteomics Clin Appl. 2022 Nov 21:e2200062. doi: 10.1002/prca.202200062. Online ahead of print.

ABSTRACT

PURPOSE: Colorectal cancer (CAC) has been reported as the second leading cause of cancer death worldwide. The 5-year annual survival is around 50%, mainly due to late diagnosis, striking necessity for early detection. This study aims to identify autoantibody in patients’ sera for early screening of cancer.

EXPERIMENTAL DESIGN: The study used a high-density human proteome array with approximately 17,000 recombinant proteins. Screening of sera from healthy individuals, CAC from Indian origin, and CAC from middle-east Asia origin were performed. Bio-statistical analysis was performed to identify significant autoantibodies altered. Pathway analysis is performed to explore the underlying mechanism of the disease.

RESULTS: The comprehensive proteomic analysis revealed dysregulation of 15 panels of proteins including CORO7, KCNAB1, WRAP53, NDUFS6, KRT30, and COLGALT2. Further biological pathway analysis for the top dysregulated autoantigenic proteins revealed perturbation in important biological pathways such as ECM degradation and cytoskeletal remodeling etc. CONCLUSIONS AND CLINICAL RELEVANCE: : The generation of an autoimmune response against cancer-linked pathways could be linked to the screening of the disease. The process of immune surveillance can be detected at an early stage of cancer. Moreover, AAbs can be easily extracted from blood serum through the least invasive test for disease screening. This article is protected by copyright. All rights reserved.

PMID:36408811 | DOI:10.1002/prca.202200062

Thorac Cancer. 2022 Nov 21. doi: 10.1111/1759-7714.14730. Online ahead of print.

ABSTRACT

OBJECTIVES: This study investigated whether radiomic features extracted from radial-probe endobronchial ultrasound (radial EBUS) images can assist in decision-making for subsequent clinical management in cases with indeterminate pathologic results.

METHODS: A total of 494 patients who underwent radial EBUS biopsy for lung nodules between January 2017 and December 2018 were allocated to our training set. For the validation set, 229 patients with radial EBUS biopsy results from January 2019 to April 2020 were used. A multivariate logistic regression analysis was used for feature selection and prediction modeling.

RESULTS: In the training set, 157 (67 benign and 90 malignant) of 212 patients pathologically diagnosed as indeterminate were analyzed. In the validation set, 213 patients were diagnosed as indeterminate, and 158 patients (63 benign and 95 malignant) were included in the analysis. The performance of the radiomics-added model, which considered satellite nodules, linear arc, shape, patency of vessels and bronchi, echogenicity, spiculation, C-reactive protein, and minimum histogram, was 0.929 for the training set and 0.877 for the validation set, whereas the performance of the model without radiomics was 0.910 and 0.891, respectively.

CONCLUSION: Although the next diagnostic step for indeterminate lung biopsy results remains controversial, integrating various factors, including radiomic features from radial EBUS, might facilitate decision-making for subsequent clinical management.

PMID:36408780 | DOI:10.1111/1759-7714.14730

Biometrics. 2022 Nov 21. doi: 10.1111/biom.13785. Online ahead of print.

ABSTRACT

I discuss the assumptions needed for identification of average treatment effects and local average treatment effects in instrumented difference-in-differences (IDID), and the possible trade-offs between assumptions of standard IV and those needed for the new proposal IDID, in one- and two-sample settings. I also discuss the interpretation of the estimands identified under monotonicity. I conclude by suggesting possible extensions to the estimation method, by outlining a strategy to use data-adaptive estimation of the nuisance parameters, based on recent developments.

PMID:36408762 | DOI:10.1111/biom.13785

Pharmacogenomics. 2022 Nov 21. doi: 10.2217/pgs-2022-0123. Online ahead of print.

ABSTRACT

Aim: To investigate the influence of CYP3A5 and IL-10 polymorphisms on tarcolimus metabolism and renal function for renal transplantation recipients at a stable period. Methods: CYP3A5 and IL-10 polymorphisms, together with other clinical factors, were collected for 149 renal transplantation patients at postoperative stable period. Statistics analysis was performed to explore key factors affecting tarcolimus metabolism. Results: CYP3A5 6986A >G and IL-10 -819C >T significantly impacted tacrolimus metabolism (p < 0.001). CYP3A5 6986A >G G allele and IL-10 -819C >T T allele were associated with poorer tacrolimus metabolic capability. Patients with various tacrolimus metabolism rates presented little difference in renal functions at stable period. Conclusion: Genotyping of CYP3A5 and IL-10 might benefit the precision dosage of tacrolimus for renal transplantation recipients.

PMID:36408735 | DOI:10.2217/pgs-2022-0123

Mol Oncol. 2022 Nov 21. doi: 10.1002/1878-0261.13345. Online ahead of print.

ABSTRACT

Epigenome-wide gene-gene (G×G) interactions associated with non-small cell lung cancer (NSCLC) survival may provide insights into molecular mechanisms and therapeutic targets. Hence, we proposed a three-step analytic strategy to identify significant and robust G×G interactions that are relevant to NSCLC survival. In the first step, among 49 billion pairs of DNA methylation probes, we identified 175,775 G×G interactions with P_Bonferroni ≤0.05 in the discovery phase of epigenomic analysis; among them, 15,534 were confirmed with P≤0.05 in the validation phase. In the second step, we further performed a functional validation for these G×G interactions at the gene expression level by way of a two-phase (discovery and validation) transcriptomic analysis, and confirmed 25 significant G×G interactions enriched in the 6p21.33 and 6p22.1 regions. In the third step, we identified two G×G interactions using the trans-omics analysis, which had significant (P≤0.05) epigenetic cis-regulation of transcription and robust G×G interactions at both the epigenetic and transcriptional levels. These interactions were cg14391855×cg23937960 (β_interaction =0.018, P=1.87×10^-12 ), which mapped to RELA×HLA-G (β_interaction =0.218, P=8.82×10^-11 ), and cg08872738×cg27077312 (β_interaction =-0.010, P=1.16×10^-11 ), which mapped to TUBA1B×TOMM40 (β_interaction =-0.250, P=3.83×10^-10 ). A trans-omics mediation analysis revealed that 20.3% of epigenetic effects on NSCLC survival were significantly (P=0.034) mediated through transcriptional expression. These statistically significant trans-omics G×G interactions can also discriminate patients with high risk of mortality. In summary, we identified two G×G interactions at both the epigenetic and transcriptional levels, and our findings may provide potential clues for precision treatment of NSCLC.

PMID:36408734 | DOI:10.1002/1878-0261.13345