Nevin Manimala

Clin Lab. 2023 Jan 1;69(1). doi: 10.7754/Clin.Lab.2022.221031.

ABSTRACT

BACKGROUND: HAdV-36 leads to adipocyte proliferation of adipose tissue through E4orf1 gene, leading to the development of obesity and related diseases. We aimed to investigate the presence and any association of HAdV-36 in non-alcoholic fatty liver disease (NAFLD) patients Methods: The patient group was composed of 116 patients; 30 obese patients with NAFLD (BMI > 30 kg/m2), 30 patients with Diabetes Mellitus (DM)+NAFLD (BMI > 30 kg/m2), 16 patients with NAFLD (BMI < 30 kg/m2), and operated obese group with NAFLD (BMI > 30 kg/m2). The control group comprised 81 non-obese healthy adults. Liver adipose tissue samples were obtained in 30 operated NAFLD patients. HAdV-36-DNA, HAdV-36 neutralizing antibodies, serum lipid, and adipokine levels were analyzed.

RESULTS: HAdV-36 neutralizing antibodies (HAdV-36 Ab-positive) were detected in 10/116 and 2/81 participants in the study and control groups, respectively; the difference was statistically significant (p < 0.005). LDL, total cholesterol but not adipokine levels were found to be significantly higher in HadV-36 Ab-positive patients (p < 0.05). While HAdV-36 was identified as a risk factor with OR = 4.11 in univariate analyses, there was no significant difference in binary logistic regression analysis. HAdV-36-DNA was detected in the adipose tissue samples of two patients.

CONCLUSIONS: We suggest that the presence of HAdV-36 may lead to the development of obesity with the increase in adipose tissue, and diseases such as hyperlipidemia, NAFLD, DM, and metabolic syndrome may develop on the basis of chronic inflammation caused by obesity. Thus, HAdV-36 may be a plausible risk factor for the development of NAFLD.

PMID:36649529 | DOI:10.7754/Clin.Lab.2022.221031

Clin Lab. 2023 Jan 1;69(1). doi: 10.7754/Clin.Lab.2022.220342.

ABSTRACT

BACKGROUND: The CURB-65 scoring system is a simple tool for assessment and prognosis prediction for community-acquired pneumonia (CAP) patients. However, the variations in the performance of CURB-65 in young and elderly patients, underestimation, or overestimation of the severity have often been reported. It is worth noting that the application of biomarkers is helpful for improving the accuracy of the scoring system. In recent years, more and more reports and studies paid attention to procalcitonin (PCT) in respiratory infectious diseases, and its clinical value has attracted increasing attention. The study aimed at investigating the effectiveness of the CURB-65 score combined with PCT in predicting admission of CAP patients to intensive care units (ICU).

METHODS: We conducted a retrospective study. We analyzed data from 520 non-immune individuals over the age of 18 in this study. All patients received blood indicators measurement and CURB-65 score calculation on admission. The primary outcome used to assess the probability of a CAP patient was who would get a bed in general ward or ICU. Receiver operating characteristic curves (ROC) were used to evaluate the sensitivity and specificity of the CURB-65 model and PCT combined CURB-65 augmented model in predicting the main outcomes.

RESULTS: After analyzing the data from 520 patients, we found that the probability of entering the ICU was 22.1% (115/520). The AUC of Combination 1 (PCT&CURB-65 scores), Combination 2 (WBC&CURB-65 scores), Combination 3 (hs-CRP&CURB-65 scores) and Combination 4 (D-dimer&CURB-65 scores) for predicting CAP patients entering the ICU was 0.92 (95% CI 0.88 – 0.95), 0.91 (95% CI 0.87 – 0.94), 0.89 (95% CI 0.85 – 0.92), and 0.90 (95% CI 0.87 – 0.94), respectively, with statistically significant differences (p = 0.00); the sensitivities were 0.83, 0.82, 0.77 and 0.77, respectively, and the specificities were 0.92, 0.84, 0.90 and 0.91, respectively. PCT was superior to other indexes to improve the sensitivity and specificity of the CURB-65 score.

CONCLUSIONS: Procalcitonin improves the accuracy and sensitivity of the CURB-65 score in predicting the probability of CAP patients entering the ICU, and PCT was superior to other indexes to improve the sensitivity and specificity of the CURB-65 score.

PMID:36649520 | DOI:10.7754/Clin.Lab.2022.220342

Clin Lab. 2023 Jan 1;69(1). doi: 10.7754/Clin.Lab.2022.220105.

ABSTRACT

BACKGROUND: Blood ammonia detection is used for the diagnosis or differential diagnosis of various hepatitis virus infections, severe liver cirrhosis, and hepatic encephalopathy. It is also one of the important indexes reflecting liver coma, Reyes syndrome, and other diseases. However, blood ammonia changes rapidly with time. If samples are not sent and detected in time, the results will be wrong, resulting in clinical misdiagnosis and life danger to patients. The purpose of this paper is to explore the change of blood ammonia with time and establish its reference interval.

METHODS: For this study, 228 healthy patients (111 males and 117 females) were selected who underwent physical examination at the Health Management Center of the Second Xiangya Hospital of Central South University from April to May 2021. The blood ammonia detection kit (colorimetric method) produced by Roche Diagnostics GmbH of Germany was used for detection on the Roche cobas c702 automatic biochemical analyzer. After eliminating outliers from the obtained test results, they were grouped according to gender and age, and SPSS 26.0 software was employed to statistically analyze the blood ammonia test results.

RESULTS: The differences in blood ammonia levels at each detection time were statistically significant (p < 0.05). The differences in blood ammonia levels between male and female subjects at 1 hour, 2 hours, and 3 hours were statistically significant (p < 0.05), but all ages saw no statistically significant difference in blood ammonia levels between segments (p > 0.05). The blood ammonia levels of each detection time and different genders showed a normal distribution. Therefore, it is necessary to take the 95% (X ± 1.96S) results of both sides as the reference interval according to the detection time and gender, and establish the reference intervals. The 1-hour blood ammonia reference interval for healthy men in Changsha is 15.8 – 47.5 μmol/L, for healthy women it is 12.4 – 39.6 μmol/L; the 2-hour blood ammonia reference interval for healthy men is 22.3 – 56.5 μmol/L, and for healthy women it is 19.1 – 48.0 μmol/L; the reference interval of 3-hours blood ammonia for healthy men is 27.9 – 65.7 μmol/L, and for healthy women it is 24.6 – 56.7 μmol/L.

CONCLUSIONS: There are differences in blood ammonia levels between men and women at different detection times in Changsha. A reference interval suitable for blood ammonia in healthy individuals in the region should be established according to the detection time and gender, so as to provide better relevant evidence for clinical diagnosis.

PMID:36649513 | DOI:10.7754/Clin.Lab.2022.220105

Clin Lab. 2023 Jan 1;69(1). doi: 10.7754/Clin.Lab.2022.211124.

ABSTRACT

BACKGROUND: Presently, several classification methods are based on diffuse large B-cell lymphoma (DLBCL), but its clinical application has not yet been testified in Asian populations.

METHODS: Twenty-five DLBCL patients were subjected to second-generation gene sequencing (NGS), and retrospective analysis of clinical features of the patients was to explore genotyping and survival prognosis biomarkers.

RESULTS: The prevalent mutant genes in DLBCL patients cover myeloid differentiation factor 88 (MyD88) (40%), TP53 (32%), B-cell translocation gene 2 (BTG2) (28%), PIM1 (28%), and CREB-binding protein (CREBBP) (24%) in this study. The classical International Prognostic Index (IPI) scores were associated with progression-free survival (PFS) (HR: 7.52, 95% CI 1.51 – 37.6, p = 0.00393) via univariate analysis. Furthermore, patients with ETS-variant gene 6 (ETV6) (HR: 5.1, 95% CI 0.927 – 28.1, p = 0.0371), platelet-derived growth factor receptor A (PDGFRA) (HR: 4.29, 95% CI 0.824 – 22.3, p = 0.0594), platelet-derived growth factor receptor B (PDGFRB) (HR: 10.8, 95% CI 0.979 – 119, p = 0.0149) was distinctively correlated with poor PFS except for the IPI score. Nevertheless, the mutation of PDGFRA/B gene was not distinct in further multivariate analysis (PFS: HR: 2.72, 95% CI 0.52 – 14.23, p = 0.2369). Additionally, better survival prognosis was in DLBCL patients who did not progress within 12 months (POD12). Ultimately, caspase recruitment domain 11 (CARD11) gene mutations were enriched in patients with primary intranodal tumors, but the prognostic relevance was not discovered.

CONCLUSIONS: ETV6 and platelet-derived growth factor receptor (PDGFR)A/B gene mutations are supposed to be potential biomarkers for the prognosis of DLBCL patients via the statistical analysis of this small sample, and POD12 is also expected to be an effective endpoint for efficacy assessment.

PMID:36649512 | DOI:10.7754/Clin.Lab.2022.211124

Clin Lab. 2023 Jan 1;69(1). doi: 10.7754/Clin.Lab.2022.220304.

ABSTRACT

BACKGROUND: A D-dimer assay can be used to reduce unnecessary imaging when ruling out venous thromboembolism (VTE) in the Emergency Department (ED), thus potentially reducing patient visit times and costs.

METHODS: This was a cross-sectional retrospective data analysis of an academic medical center ED visits between January 1 and June 30, 2019. ED visit length and VTE diagnostic cost were compared for visits with and without a D-dimer assay. The total sample size was 106 adult ED patients who were not at high risk of VTE and, of these, 27 encounters included D-dimer testing and 79 encounters did not. Outcomes were measured using independent samples t-tests to compare ED visit length and VTE diagnostic cost for ED visits with and without D-dimer tests.

RESULTS: D-dimer testing had a moderate effect upon ED visit length, but it did not correspond to differences in ED visit length or VTE diagnostic cost.

CONCLUSIONS: D-dimer testing was not statistically significant in improving the ED visit length or the VTE diagnostic cost compared to imaging studies for suspected VTE cases in the ED.

PMID:36649503 | DOI:10.7754/Clin.Lab.2022.220304

Clin Lab. 2023 Jan 1;69(1). doi: 10.7754/Clin.Lab.2022.220357.

ABSTRACT

BACKGROUND: The aim is to verify the therapeutic effect and possible mechanism of human umbilical cord Wharton’s jelly-derived transplantation of mesenchymal stem cells (UMSCs) on CCl4-induced hepatic fibrosis rats through in vivo studies and to explore the regulatory mechanism of UMSCs on fibrosis of hepatic stellate cells (HSCs) through in vitro experiments.

METHODS: In vivo experiment: Rats were randomly divided into blank control group and hepatic fibrosis group. During the entire trial, the blank control group received subcutaneous injection of normal saline, while in the hepatic fibrosis group received injections of 50% CCl4-olive oil subcutaneously for 10 weeks to establish the rat model of liver fibrosis. Hepatic fibrosis rats were then randomly and evenly divided into umbilical cord mesenchymal stem cell (UMSC) group, bone marrow mesenchymal stem cell (BMSC) group, UMSC-culture medium (CM) group, and control group. Rats in each group were infused with the following substances through the caudal vein as follows: 1 mL UMSCs (2 × 106/mL) in UMSC group, 1 mL BMSCs (2 × 106/mL) in BMSC group, 1 mL UMSCs-CM in CM group, and 1 mL saline in control group. Rats of each group were closely observed (weight, hair condition, activity, appetite, diarrhea, etc.), venous blood samples were collected, the number of white blood cells and lymphocytes were measured, and liver function indicators (ALT, AST, TBIL, ALB) were determined. Three weeks later, rat liver specimens were taken, HE stained, pathological changes were examined and quantified. In vitro experiments: HSCs were seeded in 6-well plates at 1.0 × 105/mL, with a serum-free medium for 24 hours. Then, 2 mL of UMSCs-CM was added in the study group, while an equal amount of complete medium was added to the control group. RT-PCR was used to detect TGF-β1, Collagen-I, TIMP-2 mRNA expression in HSCs, and western blot was used to detect TGF-β1 protein expression in HSCs.

RESULTS: In vivo experiment: Compared with the control group, after the transplantation, the activity status (weight, spirit, appetite, movement, hair, diarrhea, etc.) of rats in the UMSC group, BMSC group, and CM group were improved. The liver function indexes of these groups, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were significantly decreased (p < 0.05), while albumin (ALB) levels were mildly but not significantly increased (p > 0.05). The Knodell score (reflecting the degree of liver inflammation) and Chevallier score (reflecting the degree of liver fibrosis) of liver specimens in pathological examination were also significantly reduced, and the difference in the quantitative scores of those indexes was statistically significant (p < 0.05). There was no statistically significant difference in the number of venous white blood cells and lymphocytes, liver function indexes (ALT, AST, TBIL, ALB), Knodell score, and Chevallier score of liver samples among the UMSC group, BMSC group, and CM group. In vitro experiments: After treatment with UMSCs-CM, the expression of TGF-β1, Collagen-I, and TIMP-2 mRNA in HSCs was significantly down-regulated compared with that of the control group (treated with complete medium), and it gradually decreased with the extension of the treatment time. Compared with the control group, the expression of TGF-β1 protein in the HSCs of the experimental group was down-regulated, and this effect was time-dependent, specifically, the control group (2.49 ± 0.43) > the experimental group at 48 hours (1.98 ± 0.26) > the experimental group at 72 hours (1.62 ± 0.20) (F = 7.796, p < 0.05).

CONCLUSIONS: In rats with liver fibrosis, transplantation of UMSCs can improve liver function and reduce the inflammatory activity and fibrosis of the liver, possibly through the paracrine mechanism. UMSCs inhibit HSCs fibrosis through a paracrine mechanism, which is time-dependent, possibly by targeting TGF-β1 and its downstream gene products.

PMID:36649501 | DOI:10.7754/Clin.Lab.2022.220357

Scand J Occup Ther. 2023 Jan 17:1-8. doi: 10.1080/11038128.2022.2164350. Online ahead of print.

ABSTRACT

BACKGROUND: The Self-Assessment of Modes Questionnaire (SAMQ) is developed to help therapists identify their preferred use of modes when interacting with clients in clinical practice. A Danish translation of the SAMQ has been developed (D-SAMQ). To provide a robust instrument for occupational therapy practice and research, evaluation of the psychometric properties of the D-SAMQ is needed.

OBJECTIVES: The study aims to evaluate test-retest reliability, measurement error and content validity in terms of cultural relevance of the D-SAMQ.

MATERIAL AND METHODS: Danish occupational therapists were recruited to represent diverse clinical settings and to work with various age groups. The D-SAMQ consists of 20 clinical cases. A repeated measures design was employed with evaluation of content validity at the second timepoint. The Content Validity Index and Kappa statistics were employed.

RESULTS: In most cases (n = 12, 60%) agreement (test-retest reliability and measurement error) was moderate or strong. Also, there was a moderate (n = 6 cases, 30%), strong (n = 4 cases, 20%) or almost perfect agreement (n = 10 cases, 50%) on the cultural relevance of the cases.

CONCLUSIONS: Acceptable test-retest reliability, measurement error and content validity were found. The SAMQ may support occupational therapists to adapt their therapeutic style to meet the needs of the clients.

PMID:36649478 | DOI:10.1080/11038128.2022.2164350

Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2213264120. doi: 10.1073/pnas.2213264120. Epub 2023 Jan 17.

ABSTRACT

Adaptive immunity is driven by specific binding of hypervariable receptors to diverse molecular targets. The sequence diversity of receptors and targets are both individually known but because multiple receptors can recognize the same target, a measure of the effective “functional” diversity of the human immune system has remained elusive. Here, we show that sequence near-coincidences within T cell receptors that bind specific epitopes provide a new window into this problem and allow the quantification of how binding probability covaries with sequence. We find that near-coincidence statistics within epitope-specific repertoires imply a measure of binding degeneracy to amino acid changes in receptor sequence that is consistent across disparate experiments. Paired data on both chains of the heterodimeric receptor are particularly revealing since simultaneous near-coincidences are rare and we show how they can be exploited to estimate the number of epitope responses that created the memory compartment. In addition, we find that paired-chain coincidences are strongly suppressed across donors with different human leukocyte antigens, evidence for a central role of antigen-driven selection in making paired chain receptors public. These results demonstrate the power of coincidence analysis to reveal the sequence determinants of epitope binding in receptor repertoires.

PMID:36649423 | DOI:10.1073/pnas.2213264120

Circ Cardiovasc Interv. 2023 Jan;16(1):e012350. doi: 10.1161/CIRCINTERVENTIONS.122.012350. Epub 2023 Jan 17.

ABSTRACT

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used as a treatment option for unprotected left main stem artery (unprotected left main stem percutaneous intervention) disease. However, whether patient outcomes have improved over time is uncertain.

METHODS: Using the United Kingdom national PCI database, we studied all patients undergoing unprotected left main stem percutaneous intervention between 2009 and 2017. We excluded patients who presented with ST-segment-elevation, cardiogenic shock, and with an emergency indication for PCI.

RESULTS: Between 2009 and 2017, in the study-indicated population, 14 522 unprotected left main stem percutaneous intervention procedures were performed. Significant temporal changes in baseline demographics were observed with increasing patient age and comorbid burden. Procedural complexity increased over time, with the number of vessels treated, bifurcation PCI, number of stents used, and use of intravascular imaging and rotational atherectomy increased significantly through the study period. After adjustment for baseline differences, there were significant temporal reductions in the occurrence of peri-procedural myocardial infarction (P<0.001 for trend), in-hospital major adverse cardiac or cerebrovascular events (P<0.001 for trend), and acute procedural complications (P<0.001 for trend). In multivariable analysis examining the associates of in-hospital major adverse cardiac or cerebrovascular events, while age per year (odds ratio, 1.02 [95% CIs, 1.01-1.03]), female sex (odds ratio, 1.47 [1.19-1.82]), 3 or more stents (odds ratio, 1.67 [05% [1.02-2.67]), and patient comorbidity were associated with higher rates of in-hospital major adverse cardiac or cerebrovascular events, by contrast use of intravascular imaging (odds ratio, 0.56 [0.45-0.70]), and year of PCI (odds ratio, 0.63 [0.46-0.87]) were associated with lower rates of in-hospital major adverse cardiac or cerebrovascular events.

CONCLUSIONS: Despite trends for increased patient and procedural complexity, in-hospital patient outcomes have improved after unprotected left main stem percutaneous intervention over time.

PMID:36649390 | DOI:10.1161/CIRCINTERVENTIONS.122.012350

Res Comput Mol Biol. 2022 May;13278:86-106. doi: 10.1007/978-3-031-04749-7_6. Epub 2022 Apr 29.

ABSTRACT

Principal component analysis (PCA) is a widely used dimensionality reduction technique in machine learning and multivariate statistics. To improve the interpretability of PCA, various approaches to obtain sparse principal direction loadings have been proposed, which are termed Sparse Principal Component Analysis (SPCA). In this paper, we present ThreSPCA, a provably accurate algorithm based on thresholding the Singular Value Decomposition for the SPCA problem, without imposing any restrictive assumptions on the input covariance matrix. Our thresholding algorithm is conceptually simple; much faster than current state-of-the-art; and performs well in practice. When applied to genotype data from the 1000 Genomes Project, ThreSPCA is faster than previous benchmarks, at least as accurate, and leads to a set of interpretable biomarkers, revealing genetic diversity across the world.

PMID:36649383 | PMC:PMC9836035 | DOI:10.1007/978-3-031-04749-7_6